#!/usr/bin/env python3
# Papillary Carcinoma Thyroid - Exam Notes PDF Generator
# Color palette: Deep teal headings, coral subheadings, amber highlights, black body text
# Font: Liberation Sans (falls back to Helvetica in reportlab)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import mm, pt
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont
import os

# ── Font registration ──────────────────────────────────────────────────────────
FONT_DIR = "/usr/share/fonts/truetype/liberation"
fonts_registered = False
try:
    pdfmetrics.registerFont(TTFont("LiberationSans", f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LiberationSans-Bold", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFont(TTFont("LiberationSans-Italic", f"{FONT_DIR}/LiberationSans-Italic.ttf"))
    pdfmetrics.registerFontFamily(
        "LiberationSans",
        normal="LiberationSans",
        bold="LiberationSans-Bold",
        italic="LiberationSans-Italic",
    )
    BASE_FONT = "LiberationSans"
    BASE_BOLD = "LiberationSans-Bold"
    BASE_ITALIC = "LiberationSans-Italic"
    fonts_registered = True
except Exception as e:
    print(f"Font registration failed: {e}. Using Helvetica.")
    BASE_FONT = "Helvetica"
    BASE_BOLD = "Helvetica-Bold"
    BASE_ITALIC = "Helvetica-Oblique"

# ── Color Palette (Teal/Coral/Amber) ──────────────────────────────────────────
C_H1_BG     = colors.HexColor("#0D5C6E")   # deep teal - H1 background
C_H1_FG     = colors.HexColor("#FFFFFF")   # white text on H1
C_H2_FG     = colors.HexColor("#B03A2E")   # deep coral/crimson for H2
C_H2_BG     = colors.HexColor("#FDECEA")   # very light rose for H2 bg
C_H3_FG     = colors.HexColor("#7D5A00")   # dark amber/gold for H3
C_H3_BG     = colors.HexColor("#FFF8E1")   # pale yellow for H3 bg
C_HIGHLIGHT = colors.HexColor("#FFF3CD")   # soft amber highlight
C_PEARL_BG  = colors.HexColor("#E8F4F8")   # light teal background for pearls
C_PEARL_FG  = colors.HexColor("#000000")   # 100% black for pearl text
C_BODY      = colors.HexColor("#000000")   # 100% black body text
C_CAUTION   = colors.HexColor("#C0392B")   # 100% red for cautions/doses
C_DOSE      = colors.HexColor("#1A6E25")   # 100% green for doses
C_TABLE_HDR = colors.HexColor("#0D5C6E")   # teal table header
C_TABLE_ALT = colors.HexColor("#EAF4F7")   # alternating row
C_RULE      = colors.HexColor("#0D5C6E")   # horizontal rule
C_FLOWCHART_HDR = colors.HexColor("#1A4E6E")
C_FLOWCHART_BG  = colors.HexColor("#EBF5FB")
C_FLOWCHART_BOX = colors.HexColor("#D0EAF5")
C_VIVA_BG   = colors.HexColor("#F0FFF0")
C_VIVA_Q    = colors.HexColor("#145A32")

PAGE_W, PAGE_H = A4
MARGIN = 16 * mm
BODY_SIZE = 10.5
BODY_LEADING = 15.5
CELL_LEADING = 13

# ── Styles ─────────────────────────────────────────────────────────────────────
def make_styles():
    s = {}

    s["h1"] = ParagraphStyle("h1",
        fontName=BASE_BOLD, fontSize=13, leading=17,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceAfter=4*pt, spaceBefore=10*pt,
        leftIndent=6, rightIndent=6,
        borderPad=(4, 6, 4, 6),
    )
    s["h2"] = ParagraphStyle("h2",
        fontName=BASE_BOLD, fontSize=11.5, leading=15,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceAfter=3*pt, spaceBefore=8*pt,
        leftIndent=4, borderPad=(3, 5, 3, 5),
    )
    s["h3"] = ParagraphStyle("h3",
        fontName=BASE_BOLD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceAfter=2*pt, spaceBefore=6*pt,
        leftIndent=4, borderPad=(2, 4, 2, 4),
    )
    s["body"] = ParagraphStyle("body",
        fontName=BASE_FONT, fontSize=BODY_SIZE, leading=BODY_LEADING,
        textColor=C_BODY, spaceAfter=2*pt, spaceBefore=0,
        alignment=TA_JUSTIFY,
    )
    s["bullet"] = ParagraphStyle("bullet",
        fontName=BASE_FONT, fontSize=BODY_SIZE, leading=BODY_LEADING,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10,
        spaceAfter=1*pt,
    )
    s["sub_bullet"] = ParagraphStyle("sub_bullet",
        fontName=BASE_FONT, fontSize=10, leading=14,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10,
        spaceAfter=1*pt,
    )
    s["pearl"] = ParagraphStyle("pearl",
        fontName=BASE_BOLD, fontSize=10.5, leading=14,
        textColor=C_PEARL_FG, backColor=C_PEARL_BG,
        spaceAfter=3*pt, spaceBefore=3*pt,
        leftIndent=8, rightIndent=8,
        borderPad=(3, 6, 3, 6),
    )
    s["caution"] = ParagraphStyle("caution",
        fontName=BASE_BOLD, fontSize=10.5, leading=14,
        textColor=C_CAUTION, backColor=colors.HexColor("#FFF0F0"),
        spaceAfter=2*pt, spaceBefore=2*pt,
        leftIndent=8, borderPad=(2, 5, 2, 5),
    )
    s["cell"] = ParagraphStyle("cell",
        fontName=BASE_FONT, fontSize=10, leading=CELL_LEADING,
        textColor=C_BODY,
    )
    s["cell_bold"] = ParagraphStyle("cell_bold",
        fontName=BASE_BOLD, fontSize=10, leading=CELL_LEADING,
        textColor=C_BODY,
    )
    s["cell_hdr"] = ParagraphStyle("cell_hdr",
        fontName=BASE_BOLD, fontSize=10, leading=CELL_LEADING,
        textColor=colors.white,
    )
    s["viva_q"] = ParagraphStyle("viva_q",
        fontName=BASE_BOLD, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_VIVA_Q, backColor=C_VIVA_BG,
        spaceAfter=1*pt, spaceBefore=4*pt,
        leftIndent=6, borderPad=(2, 5, 2, 5),
    )
    s["viva_a"] = ParagraphStyle("viva_a",
        fontName=BASE_FONT, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_BODY, leftIndent=12,
        spaceAfter=3*pt,
    )
    s["center"] = ParagraphStyle("center",
        fontName=BASE_FONT, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_BODY, alignment=TA_CENTER,
    )
    s["center_bold"] = ParagraphStyle("center_bold",
        fontName=BASE_BOLD, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_BODY, alignment=TA_CENTER,
    )
    s["title"] = ParagraphStyle("title",
        fontName=BASE_BOLD, fontSize=16, leading=20,
        textColor=C_H1_FG, backColor=C_H1_BG,
        alignment=TA_CENTER, spaceAfter=6*pt,
        borderPad=(8, 10, 8, 10),
    )
    s["subtitle"] = ParagraphStyle("subtitle",
        fontName=BASE_FONT, fontSize=10.5, leading=14,
        textColor=colors.HexColor("#666666"),
        alignment=TA_CENTER, spaceAfter=4*pt,
    )
    s["flowchart_box"] = ParagraphStyle("flowchart_box",
        fontName=BASE_FONT, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER,
    )
    s["flowchart_bold"] = ParagraphStyle("flowchart_bold",
        fontName=BASE_BOLD, fontSize=10, leading=13,
        textColor=C_FLOWCHART_HDR, alignment=TA_CENTER,
    )
    return s

def rule(story, color=C_RULE, thickness=0.7):
    story.append(HRFlowable(width="100%", thickness=thickness, color=color, spaceAfter=4*pt, spaceBefore=2*pt))

def h1(story, text, S):
    story.append(Spacer(1, 4*pt))
    story.append(Paragraph(text, S["h1"]))

def h2(story, text, S):
    story.append(Spacer(1, 2*pt))
    story.append(Paragraph(text, S["h2"]))

def h3(story, text, S):
    story.append(Paragraph(text, S["h3"]))

def body(story, text, S):
    story.append(Paragraph(text, S["body"]))

def bullet(story, items, S, sub=False):
    key = "sub_bullet" if sub else "bullet"
    for item in items:
        story.append(Paragraph(f"• {item}", S[key]))

def pearl(story, text, S):
    story.append(Paragraph(f"★ {text}", S["pearl"]))

def caution(story, text, S):
    story.append(Paragraph(f"⚠ {text}", S["caution"]))

def spacer(story, h=4):
    story.append(Spacer(1, h*pt))

# ── Table helpers ──────────────────────────────────────────────────────────────
def make_table(data, col_widths, S, alt_rows=True):
    table_data = []
    for r_idx, row in enumerate(data):
        new_row = []
        for c_idx, cell in enumerate(row):
            if isinstance(cell, str):
                style = S["cell_hdr"] if r_idx == 0 else S["cell"]
                new_row.append(Paragraph(cell, style))
            else:
                new_row.append(cell)
        table_data.append(new_row)

    t = Table(table_data, colWidths=col_widths, repeatRows=1)
    cmds = [
        ("BACKGROUND", (0, 0), (-1, 0), C_TABLE_HDR),
        ("TEXTCOLOR",  (0, 0), (-1, 0), colors.white),
        ("FONTNAME",   (0, 0), (-1, 0), BASE_BOLD),
        ("FONTSIZE",   (0, 0), (-1, -1), 10),
        ("LEADING",    (0, 0), (-1, -1), CELL_LEADING),
        ("ROWBACKGROUNDS", (0, 1), (-1, -1), [colors.white, C_TABLE_ALT] if alt_rows else [colors.white]),
        ("BOX",        (0, 0), (-1, -1), 0.6, C_RULE),
        ("INNERGRID",  (0, 0), (-1, -1), 0.4, colors.HexColor("#CCCCCC")),
        ("TOPPADDING", (0, 0), (-1, -1), 4),
        ("BOTTOMPADDING", (0, 0), (-1, -1), 4),
        ("LEFTPADDING", (0, 0), (-1, -1), 5),
        ("RIGHTPADDING", (0, 0), (-1, -1), 5),
        ("VALIGN",     (0, 0), (-1, -1), "TOP"),
    ]
    t.setStyle(TableStyle(cmds))
    return t

# ── Flowchart builder ──────────────────────────────────────────────────────────
def flowchart(story, title, boxes, S, col_widths=None):
    """Build a simple top-down flowchart using a table with arrows."""
    spacer(story, 4)
    # Title bar
    story.append(Paragraph(title, S["h3"]))
    spacer(story, 2)
    w = PAGE_W - 2 * MARGIN
    box_w = w * 0.75
    avail = col_widths or [box_w]

    flow_data = []
    for i, box in enumerate(boxes):
        if isinstance(box, tuple):
            label, style_key = box
        else:
            label, style_key = box, "flowchart_box"
        bg = C_FLOWCHART_BOX if style_key == "flowchart_box" else colors.HexColor("#C8E6FA")
        p = Paragraph(label, S[style_key])
        row = [p]
        flow_data.append((row, bg))

    rows = []
    bgs = []
    arrows = []
    for i, (row, bg) in enumerate(flow_data):
        rows.append(row)
        bgs.append(bg)
        if i < len(flow_data) - 1:
            arrows.append(i)

    # interleave with arrow rows
    final_rows = []
    final_bgs = []
    for i, (row, bg) in enumerate(zip(rows, bgs)):
        final_rows.append(row)
        final_bgs.append(bg)
        if i < len(rows) - 1:
            final_rows.append([Paragraph("&#x25BC;", S["center"])])
            final_bgs.append(colors.white)

    t = Table(final_rows, colWidths=[box_w], repeatRows=0)
    cmds = [
        ("BOX",         (0, 0), (-1, -1), 0.5, C_RULE),
        ("TOPPADDING",  (0, 0), (-1, -1), 5),
        ("BOTTOMPADDING",(0,0), (-1, -1), 5),
        ("LEFTPADDING", (0, 0), (-1, -1), 8),
        ("RIGHTPADDING",(0, 0), (-1, -1), 8),
        ("ALIGN",       (0, 0), (-1, -1), "CENTER"),
        ("VALIGN",      (0, 0), (-1, -1), "MIDDLE"),
    ]
    for i, bg in enumerate(final_bgs):
        cmds.append(("BACKGROUND", (0, i), (0, i), bg))
    t.setStyle(TableStyle(cmds))

    # center the flowchart
    outer = Table([[t]], colWidths=[w])
    outer.setStyle(TableStyle([
        ("ALIGN", (0,0), (-1,-1), "CENTER"),
        ("TOPPADDING", (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
        ("RIGHTPADDING", (0,0), (-1,-1), 0),
    ]))
    story.append(outer)
    spacer(story, 4)


# ══════════════════════════════════════════════════════════════════════════════
#   CONTENT BUILDER
# ══════════════════════════════════════════════════════════════════════════════
def build_content(story, S):
    W = PAGE_W - 2*MARGIN

    # ── TITLE ──────────────────────────────────────────────────────────────────
    story.append(Paragraph("PAPILLARY CARCINOMA OF THE THYROID", S["title"]))
    story.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS  |  Sources: Scott-Brown's OHN&S, KJ Lee's Essential Otolaryngology, "
        "Bailey & Love's Surgery, Robbins Pathology, DeVita Oncology",
        S["subtitle"]
    ))
    rule(story)
    spacer(story, 2)

    # ── 1. DEFINITION ──────────────────────────────────────────────────────────
    h1(story, "1.  DEFINITION", S)
    bullet(story, [
        "Papillary thyroid carcinoma (PTC) is a MALIGNANT EPITHELIAL TUMOUR showing follicular cell differentiation "
        "with characteristic nuclear features (ground-glass nuclei, nuclear grooves, pseudo-inclusions).",
        "It is the MOST COMMON thyroid malignancy - accounts for ~80% of all thyroid cancers.",
        "Also the COMMONEST PAEDIATRIC thyroid malignancy.",
        "Carries EXCELLENT prognosis, especially in young patients.",
    ], S)
    pearl(story, "PEARL: Diagnosis of PTC rests on nuclear morphology - NOT papillary architecture alone. "
          "(Scott-Brown's OHN&S, 8th ed.)", S)
    spacer(story, 4)

    # ── 2. APPLIED ANATOMY ─────────────────────────────────────────────────────
    h1(story, "2.  APPLIED ANATOMY", S)
    bullet(story, [
        "Thyroid lies in anterior neck, C5-T1 level; enclosed in pretracheal fascia.",
        "Two lobes + isthmus; pyramidal lobe present in 40-50% (remnant of thyroglossal duct).",
        "Blood supply: Superior thyroid artery (1st branch of ECA) + Inferior thyroid artery (from thyrocervical trunk of subclavian).",
        "Venous drainage: Superior/Middle thyroid veins -> IJV; Inferior thyroid vein -> brachiocephalic vein.",
        "Lymphatics: Rich intraglandular lymphatic plexus; drain to central compartment (Level VI) and lateral "
          "cervical nodes (Levels II-V) - explaining PTC's lymphotropic behaviour.",
        "RLN (recurrent laryngeal nerve): closely related to inferior thyroid artery - at risk in surgery.",
        "External branch of SLN: runs with superior thyroid vessels - at risk during superior pole ligation.",
        "Parathyroid glands (4): 2 superior (related to posterior thyroid at junction of upper/middle thirds) + "
          "2 inferior (variable - related to inferior thyroid artery) - at risk in thyroidectomy.",
    ], S)

    # Anatomy summary table
    data = [
        ["Structure", "Relation / Clinical Significance"],
        ["RLN", "Runs in tracheoesophageal groove; at risk in thyroid surgery -> hoarseness if injured"],
        ["External branch SLN", "Runs with superior thyroid pedicle -> loss of high-pitched voice if injured"],
        ["Parathyroid glands", "4 glands closely adherent -> hypocalcaemia if devascularised"],
        ["Trachea", "Posterior to isthmus -> compression/deviation by large tumour"],
        ["Carotid sheath", "Lateral to thyroid -> invaded in advanced PTC (T4b disease)"],
    ]
    story.append(make_table(data, [W*0.3, W*0.7], S))
    spacer(story, 4)

    # ── 3. EMBRYOLOGY ──────────────────────────────────────────────────────────
    h1(story, "3.  EMBRYOLOGY", S)
    bullet(story, [
        "Thyroid develops from ENDODERM of floor of pharynx (foramen caecum) at 4th week of gestation.",
        "Descends along thyroglossal duct -> reaches final position by 7th week.",
        "Thyroglossal duct normally obliterates -> remnant forms pyramidal lobe or thyroglossal cyst.",
        "Parafollicular C-cells (calcitonin-secreting) arise from NEURAL CREST (ultimo-branchial body / 4th pharyngeal pouch).",
        "Follicular cells (give rise to PTC) derive from ENDODERMAL thyroid precursor cells.",
        "Ectopic thyroid tissue can occur anywhere along thyroglossal duct tract (lingual thyroid, intratracheal).",
    ], S)
    spacer(story, 4)

    # ── 4. PHYSIOLOGY ──────────────────────────────────────────────────────────
    h1(story, "4.  PHYSIOLOGY (Relevant Points)", S)
    bullet(story, [
        "Follicular cells synthesize T3 (triiodothyronine) and T4 (thyroxine) under TSH stimulation.",
        "TSH (thyroid stimulating hormone) binds TSHR -> activates adenylate cyclase -> cAMP -> thyroid hormone synthesis.",
        "T3/T4 feedback inhibits hypothalamic TRH and pituitary TSH (negative feedback).",
        "Iodine uptake via Na+/I- symporter (NIS) - exploited by radioactive iodine (RAI) therapy in PTC.",
        "PTC is NON-FUNCTIONAL - does NOT produce excess hormones; presents euthyroid.",
        "Post-thyroidectomy: lifelong thyroxine required; TSH suppression used in high-risk PTC to reduce recurrence.",
        "Thyroglobulin (Tg): produced by follicular cells; used as TUMOUR MARKER for PTC surveillance post-surgery.",
    ], S)
    spacer(story, 4)

    # ── 5. AETIOLOGY & RISK FACTORS ────────────────────────────────────────────
    h1(story, "5.  AETIOLOGY & RISK FACTORS", S)

    h2(story, "A. Radiation Exposure (STRONGEST established risk)", S)
    bullet(story, [
        "Ionising radiation - childhood neck irradiation (most important modifiable risk factor).",
        "Chernobyl nuclear accident (1986) -> marked increase in PTC in children of Belarus/Ukraine.",
        "Latency period: ~10-20 years after radiation exposure.",
        "Results predominantly in RET/PTC gene rearrangements.",
    ], S)

    h2(story, "B. Genetic / Molecular Factors", S)
    bullet(story, [
        "BRAF V600E mutation: MOST COMMON genetic event in PTC (~50% of cases).",
        "RET/PTC rearrangements: common in radiation-induced PTC.",
        "RAS mutations, NTRK1 rearrangements also implicated.",
        "MAPK pathway activation: central to malignant transformation (altered in ~70% of PTC).",
    ], S)
    caution(story, "CAUTION: BRAF V600E mutation = negative prognostic marker -> associated with higher "
            "extrathyroidal invasion, LN metastasis, recurrence risk. (KJ Lee's Essential ORL)", S)

    h2(story, "C. Other Risk Factors", S)
    data = [
        ["Risk Factor", "Notes"],
        ["Female sex", "3x more common in women; F:M = 3:1"],
        ["Age", "Peak 40-50 yrs (women); 50-60 yrs (men); but occurs at all ages"],
        ["Familial syndromes", "FAP (familial adenomatous polyposis), Cowden syndrome, Gardner syndrome"],
        ["Iodine status", "Adequate iodine -> PTC more common; iodine deficiency -> follicular Ca more common"],
        ["Prior thyroid disease", "Hashimoto thyroiditis: association noted (chronic lymphocytic stimulation)"],
        ["Obesity / hormonal", "Possible links; not fully established"],
    ]
    story.append(make_table(data, [W*0.35, W*0.65], S))
    spacer(story, 4)

    # ── 6. CLASSIFICATION / VARIANTS ───────────────────────────────────────────
    h1(story, "6.  CLASSIFICATION / HISTOLOGICAL VARIANTS", S)

    h2(story, "A. WHO Classification of Thyroid Tumours (Key PTC Variants)", S)
    data = [
        ["Variant", "Features", "Prognosis"],
        ["Classical / Conventional PTC", "Papillae + ground-glass nuclei; most common", "Good"],
        ["Papillary Microcarcinoma", "< 10 mm; incidental; controversial management", "Excellent"],
        ["Follicular variant (FVPTC)", "Follicular architecture + PTC nuclei; EFVPTC reclassified as NIFTP", "Good"],
        ["Tall-cell variant", "Cells ht > 2x width; columnar; > 30% tall cells", "Poor - aggressive"],
        ["Columnar-cell variant", "Columnar cells; nuclear stratification", "Poor - aggressive"],
        ["Diffuse sclerosing variant", "Diffuse involvement + dense fibrosis + psammoma bodies", "Intermediate"],
        ["Solid variant", "Solid growth pattern; post-Chernobyl children", "Intermediate"],
        ["Hobnail variant", "Apically placed nuclei; micropapillary features", "Poor - aggressive"],
        ["Cribriform-morular variant", "Associated with FAP; APC gene mutation", "Variable"],
        ["Hurthle cell (oncocytic) variant", "Oxyphil cells; may be RAI-resistant", "Variable"],
    ]
    story.append(make_table(data, [W*0.32, W*0.44, W*0.24], S))
    pearl(story, "KEY: Tall-cell, columnar-cell, and hobnail variants are HIGH-RISK/AGGRESSIVE variants. "
          "Encapsulated follicular variant (non-invasive) now reclassified as NIFTP (non-malignant). "
          "(Scott-Brown's OHN&S)", S)
    spacer(story, 4)

    # ── 7. CLINICAL FEATURES ───────────────────────────────────────────────────
    h1(story, "7.  CLINICAL FEATURES", S)

    h2(story, "A. History", S)
    bullet(story, [
        "PAINLESS neck swelling / thyroid nodule - most common presentation.",
        "Duration: usually months; slow-growing.",
        "Dysphagia, dysphonia (hoarseness), dyspnea: suggest advanced disease / RLN involvement.",
        "Rapid enlargement: may suggest anaplastic transformation.",
        "Cervical lymphadenopathy: nodal metastasis (30% at presentation).",
        "History of radiation exposure (childhood, neck, chest).",
        "Family history of thyroid cancer or related syndromes.",
        "Prior thyroid disease (Hashimoto, MNG).",
        "Euthyroid state: no hyperthyroid or hypothyroid symptoms.",
        "Paediatric patients: higher rate of LN metastases (up to 60%) at presentation.",
    ], S)

    h2(story, "B. Physical Examination", S)
    bullet(story, [
        "THYROID NODULE: firm, non-tender; moves on swallowing (thyroid origin).",
        "Hard, irregular, fixed nodule: suggests malignancy / extrathyroidal extension.",
        "Cervical lymphadenopathy (Level VI central nodes first, then Levels II-V lateral).",
        "Cystic lymph nodes in neck: characteristic of PTC nodal metastasis.",
        "Tracheal deviation: large tumour / extrathyroidal extension.",
        "Pemberton's sign: facial plethora on raising arms (superior mediastinal compression - rare).",
        "Vocal cord palsy: test voice; indirect laryngoscopy MANDATORY pre-operatively.",
        "Look for: Berry's sign (loss of carotid pulsation -> carotid invasion, late sign).",
    ], S)
    spacer(story, 4)

    # ── 8. INVESTIGATIONS ──────────────────────────────────────────────────────
    h1(story, "8.  INVESTIGATIONS", S)

    h2(story, "A. Laboratory", S)
    data = [
        ["Test", "Expected Finding / Significance"],
        ["TFTs (TSH, free T3, T4)", "Usually NORMAL (PTC is non-functional); TSH suppressed -> lower malignancy risk"],
        ["Thyroglobulin (Tg)", "Pre-op: may be elevated; POST-op: KEY TUMOUR MARKER for recurrence surveillance"],
        ["Anti-Tg antibodies", "Can interfere with Tg assay; must test simultaneously"],
        ["Serum Calcium + PTH", "Pre-op baseline; important if parathyroids at risk"],
        ["Calcitonin", "To exclude medullary thyroid carcinoma in the differential"],
        ["CBC, LFTs, renal", "Pre-operative workup"],
        ["BRAF mutation testing", "On FNA/surgical specimen; prognostication and targeted therapy planning"],
    ]
    story.append(make_table(data, [W*0.35, W*0.65], S))

    h2(story, "B. Imaging", S)
    data = [
        ["Modality", "Use / Findings in PTC"],
        ["USG Neck (FIRST LINE)", "Nodule characterization; size, echogenicity, margins, calcifications, vascularity. "
         "ACR TIRADS / ATA risk classification. Evaluate lymph nodes."],
        ["USG features of malignancy", "Hypoechoic; microcalcifications (psammoma bodies); irregular margins; "
         "taller-than-wide shape; increased vascularity; no halo"],
        ["FNAC (USG-guided)", "GOLD STANDARD for diagnosis. Bethesda System for reporting. "
         "Bethesda V/VI -> malignant."],
        ["CT Neck/Chest", "Assess extrathyroidal extension, retrosternal goitre, mediastinal nodes, lung metastases. "
         "AVOID iodinated contrast pre-RAI (delays RAI by 4-8 weeks)."],
        ["MRI Neck", "Better soft tissue delineation; recurrent disease; tracheal/oesophageal invasion."],
        ["Radioiodine scan (I-131/I-123)", "POST-thyroidectomy for RAI ablation planning; detects residual/metastatic "
         "functioning thyroid tissue. NOT used for pre-op diagnosis (PTC may not concentrate I-131 well)."],
        ["18F-FDG PET-CT", "RAI-negative, Tg-positive recurrence; aggressive variants; distant metastases workup."],
        ["Indirect Laryngoscopy", "MANDATORY pre-op to assess vocal cord mobility (RLN function)."],
    ]
    story.append(make_table(data, [W*0.28, W*0.72], S))

    h2(story, "C. Pathology / Cytology - Bethesda System", S)
    data = [
        ["Bethesda Category", "Diagnosis", "Malignancy Risk", "Management"],
        ["I",   "Non-diagnostic",                  "1-4%",    "Repeat FNA"],
        ["II",  "Benign",                           "0-3%",    "Clinical follow-up"],
        ["III", "AUS/FLUS",                         "5-15%",   "Repeat FNA / molecular testing"],
        ["IV",  "Follicular neoplasm",              "15-30%",  "Lobectomy"],
        ["V",   "Suspicious for malignancy",        "60-75%",  "Near-total thyroidectomy"],
        ["VI",  "Malignant",                        "97-99%",  "Total thyroidectomy"],
    ]
    story.append(make_table(data, [W*0.06, W*0.28, W*0.18, W*0.48], S))
    spacer(story, 4)

    # ── 9. DIAGNOSIS ───────────────────────────────────────────────────────────
    h1(story, "9.  DIAGNOSIS", S)

    h2(story, "A. Histopathological Diagnosis (Definitive)", S)
    bullet(story, [
        "NUCLEAR FEATURES (light microscopy) - defining criteria:",
    ], S)
    bullet(story, [
        "Ground-glass / 'Orphan Annie eye' nuclei - optically clear, empty appearance.",
        "Intranuclear cytoplasmic inclusions (pseudo-inclusions) - invagination of cytoplasm.",
        "Nuclear grooves ('coffee bean' appearance) - longitudinal nuclear grooves.",
        "Nuclear enlargement, crowding and overlap ('basket of eggs').",
        "Margination of chromatin to nuclear membrane.",
    ], S, sub=True)
    bullet(story, [
        "ARCHITECTURAL FEATURES:",
    ], S)
    bullet(story, [
        "Papillae with fibrovascular stalks lined by cuboidal epithelium.",
        "Psammoma bodies: laminated calcified concentric rings (almost PATHOGNOMONIC for PTC).",
        "Multiloculated cystic change; colloid contents.",
        "Lymphatic invasion (blood vessel invasion uncommon in smaller lesions).",
    ], S, sub=True)
    pearl(story, "PEARL: Diagnosis of PTC is based on nuclear morphology - papillary architecture is NOT required. "
          "Psammoma bodies are almost NEVER found in follicular or medullary Ca. (Robbins Pathology)", S)

    h2(story, "B. Cytological Diagnosis (FNAC - Bethesda)", S)
    bullet(story, [
        "USG-guided FNAC: gold standard pre-op investigation.",
        "Cytology shows: Orphan Annie nuclei, nuclear grooves, pseudo-inclusions, papillary fragments.",
        "Ground-glass nuclei less prominent in FNA and frozen sections.",
        "Molecular testing (BRAF, RAS, RET/PTC): improves diagnosis of indeterminate nodules.",
    ], S)
    spacer(story, 4)

    # ── 10. DIFFERENTIAL DIAGNOSIS ─────────────────────────────────────────────
    h1(story, "10.  DIFFERENTIAL DIAGNOSIS", S)
    data = [
        ["Condition", "Distinguishing Features"],
        ["Follicular adenoma", "Benign; FNA cannot reliably differentiate from follicular Ca; "
         "requires capsular/vascular invasion on histology"],
        ["Follicular carcinoma", "Follicular architecture; NO PTC nuclear features; "
         "vascular/capsular invasion on histology; rare LN mets; blood-borne spread"],
        ["Medullary thyroid carcinoma", "C-cell origin; elevated calcitonin; amyloid in stroma; "
         "calcitonin immunostaining positive; part of MEN2"],
        ["Hashimoto thyroiditis", "Can show nuclear clearing mimicking PTC; but absence of true "
         "papillae, pseudo-inclusions; anti-TPO antibodies elevated"],
        ["Graves' disease", "Hyperthyroidism; diffuse goitre; nuclear changes can mimic PTC on histology"],
        ["Metastatic carcinoma to thyroid", "Rare; primary sites: kidney (clear cell), breast, lung, colon"],
        ["Anaplastic thyroid Ca", "Rapidly growing, aggressive; undifferentiated cells; poor prognosis"],
        ["Multinodular goitre", "Benign multinodular; USG and FNAC differentiates"],
        ["Lymphoma of thyroid", "Associated with Hashimoto; lymphoid markers positive"],
    ]
    story.append(make_table(data, [W*0.32, W*0.68], S))
    spacer(story, 4)

    # ── 11. STAGING ────────────────────────────────────────────────────────────
    h1(story, "11.  STAGING", S)

    h2(story, "A. TNM Staging (AJCC 8th Edition - 2017)", S)
    bullet(story, [
        "AGE is the MOST IMPORTANT prognostic factor in PTC - incorporated into staging.",
        "Patients < 55 years: Stage I (distant mets -> Stage II only).",
        "Patients >= 55 years: Stage I-IVB based on T, N, M.",
    ], S)
    data = [
        ["Stage", "Age < 55 yrs", "Age >= 55 yrs"],
        ["I",   "Any T, Any N, M0",    "T1-T2, N0/NX, M0"],
        ["II",  "Any T, Any N, M1",    "T1-T2, N1 OR T3, N0/NX, M0"],
        ["III", "Not applicable",      "T3, N1 OR T4a, any N, M0"],
        ["IVA", "Not applicable",      "T4b, any N, M0"],
        ["IVB", "Not applicable",      "Any T, any N, M1"],
    ]
    story.append(make_table(data, [W*0.12, W*0.38, W*0.5], S))

    h2(story, "B. T Staging (Primary Tumour)", S)
    data = [
        ["T Stage", "Definition"],
        ["T1a", "Tumour <= 1 cm (microcarcinoma), confined to thyroid"],
        ["T1b", "Tumour > 1 cm but <= 2 cm, confined to thyroid"],
        ["T2",  "Tumour > 2 cm but <= 4 cm, confined to thyroid"],
        ["T3a", "Tumour > 4 cm, confined to thyroid"],
        ["T3b", "Gross extrathyroidal extension into strap muscles only"],
        ["T4a", "Extends to subcutaneous soft tissue, larynx, trachea, oesophagus, or RLN"],
        ["T4b", "Extends to prevertebral fascia, carotid artery, or mediastinal vessels"],
    ]
    story.append(make_table(data, [W*0.12, W*0.88], S))

    h2(story, "C. ATA Risk Stratification (Post-operative - for RAI decision)", S)
    data = [
        ["Risk", "Criteria", "Recurrence Risk"],
        ["Low", "Intrathyroidal PTC; no vascular invasion; no LN mets or < 5 micro LN mets (<0.2cm); "
         "no RAI-avid mets", "< 5%"],
        ["Intermediate", "Minor extrathyroidal extension; vascular invasion; > 5 LN mets or LN > 0.2 cm; "
         "aggressive histology; RAI-avid disease outside thyroid bed", "5-20%"],
        ["High", "Gross extrathyroidal extension; incomplete resection; distant mets; "
         "Tg out of proportion to scan; LN > 3 cm", "> 20%"],
    ]
    story.append(make_table(data, [W*0.15, W*0.65, W*0.2], S))
    pearl(story, "PEARL: In PTC < 55 yrs, even with distant metastasis -> Stage II only (not Stage IV). "
          "This explains the excellent prognosis in young patients. (AJCC 8th Ed.)", S)
    spacer(story, 4)

    # ── 12. MANAGEMENT ─────────────────────────────────────────────────────────
    h1(story, "12.  MANAGEMENT", S)

    # Flowchart - diagnostic workup
    flowchart(story, "DIAGNOSTIC FLOWCHART - Thyroid Nodule / Suspected PTC", [
        ("Thyroid Nodule Detected (clinical / incidental)", "flowchart_bold"),
        ("USG Neck: TIRADS / ATA risk classification + node assessment", "flowchart_box"),
        ("USG-guided FNAC (if >= 1 cm or high-risk features)", "flowchart_box"),
        ("Bethesda Reporting: Categories I-VI", "flowchart_box"),
        ("Bethesda V/VI -> Malignant -> Pre-op workup: CT, indirect laryngoscopy, staging", "flowchart_box"),
        ("MDT Discussion -> Management Decision", "flowchart_bold"),
    ], S)

    h2(story, "A. Surgical Management (MAINSTAY)", S)

    h3(story, "i. Extent of Surgery", S)
    data = [
        ["Situation", "Recommended Surgery"],
        ["Low-risk PTC (unifocal, <= 1 cm, intrathyroidal, no LN mets)", "Thyroid lobectomy (acceptable; some guidelines)"],
        ["PTC > 4 cm or bilateral or extrathyroidal extension or high-risk features",
         "Total / Near-total thyroidectomy"],
        ["PTC with clinical LN metastasis (N1)", "Total thyroidectomy + appropriate neck dissection"],
        ["Standard approach (most PTC)", "Total thyroidectomy +/- neck dissection based on LN status"],
    ]
    story.append(make_table(data, [W*0.38, W*0.62], S))

    h3(story, "ii. Neck Dissection", S)
    data = [
        ["Type", "Indication"],
        ["Central neck dissection (Level VI)", "cN1a disease (clinically/US positive central nodes); "
         "some advocate prophylactic in high-risk cases (controversial)"],
        ["Lateral neck dissection (Levels II-V)", "cN1b disease (clinically/US positive lateral nodes); "
         "modified radical neck dissection (MRND)"],
        ["Prophylactic central neck dissection", "Controversial - may reduce reoperations but increases "
         "hypoparathyroidism risk"],
    ]
    story.append(make_table(data, [W*0.35, W*0.65], S))
    caution(story, "CAUTION: Elective central neck dissection is CONTROVERSIAL in clinically N0 PTC - "
            "discuss in MDT. (Scott-Brown's OHN&S 8th ed.)", S)

    h3(story, "iii. Minimally Invasive Approaches", S)
    bullet(story, [
        "Video-assisted thyroidectomy (VAT): small incision; good cosmesis.",
        "Robotic thyroidectomy (transaxillary/retroauricular): scarless neck approaches.",
        "TOETVA (transoral endoscopic thyroidectomy via vestibular approach): no external scar.",
        "Reserved for carefully selected patients by experienced centres.",
    ], S)

    h2(story, "B. Radioactive Iodine (RAI) Therapy", S)
    bullet(story, [
        "Uses NIS (Na+/I- symporter) in thyroid follicular cells to concentrate I-131.",
        "INDICATIONS: High-risk and intermediate-risk PTC post-thyroidectomy; remnant ablation.",
        "NOT routinely recommended for low-risk PTC (unifocal, intrathyroidal, < 1-2 cm, no LN mets).",
        "Pre-RAI preparation: withdraw thyroxine (TSH > 30 mIU/L) OR use recombinant TSH (rhTSH).",
        "Low iodine diet for 1-2 weeks before RAI.",
    ], S)
    data = [
        ["RAI Dose", "Indication"],
        ["1.1 GBq (30 mCi)", "Remnant ablation (low-risk intermediate disease)"],
        ["3.7-5.5 GBq (100-150 mCi)", "Adjuvant therapy (intermediate/high-risk)"],
        ["5.5-7.4 GBq (150-200 mCi)", "Treatment of known metastatic disease"],
    ]
    story.append(make_table(data, [W*0.38, W*0.62], S))
    caution(story, "AVOID iodinated CT contrast pre-RAI therapy - iodine loading delays RAI by 4-8 weeks. "
            "Use MRI or non-contrast CT instead.", S)

    h2(story, "C. TSH Suppression Therapy (Medical)", S)
    bullet(story, [
        "Levothyroxine (T4) given post-thyroidectomy for two purposes: (1) hormone replacement, "
          "(2) TSH suppression to reduce tumour recurrence.",
        "TSH drives follicular cell growth -> suppressing TSH reduces residual PTC growth.",
    ], S)
    data = [
        ["Risk Group", "TSH Target"],
        ["High-risk (persistent disease)", "< 0.1 mIU/L (full suppression)"],
        ["Intermediate-risk", "0.1-0.5 mIU/L"],
        ["Low-risk (free of disease)", "0.5-2.0 mIU/L (low-normal range)"],
    ]
    story.append(make_table(data, [W*0.45, W*0.55], S))
    pearl(story, "PEARL: TSH suppression carries risks of atrial fibrillation, osteoporosis (esp. post-menopausal women). "
          "Degree of suppression should be tailored to risk. (ATA Guidelines 2015, updated 2023)", S)

    h2(story, "D. External Beam Radiotherapy (EBRT)", S)
    bullet(story, [
        "Indications: Unresectable gross residual disease not amenable to RAI; palliation of bone mets.",
        "NOT routine; reserved for selected high-risk cases with extrathyroidal extension / tracheal invasion.",
    ], S)

    h2(story, "E. Targeted Therapy (Tyrosine Kinase Inhibitors)", S)
    bullet(story, [
        "For RADIOIODINE-REFRACTORY metastatic PTC (rare).",
        "Sorafenib (multikinase inhibitor): FDA-approved for progressive RAI-refractory DTC.",
        "Lenvatinib: approved; shows higher PFS than sorafenib in trials.",
        "BRAF inhibitors (vemurafenib, dabrafenib): for BRAF V600E+ refractory PTC.",
        "RET inhibitors (selpercatinib): for RET fusion-positive thyroid cancers.",
    ], S)

    # Flowchart - Management
    flowchart(story, "MANAGEMENT FLOWCHART - Confirmed PTC", [
        ("Confirmed PTC (FNA / Intra-op frozen section)", "flowchart_bold"),
        ("Total Thyroidectomy +/- Neck Dissection (Central +/- Lateral based on N status)", "flowchart_box"),
        ("Post-op: ATA Risk Stratification (Low / Intermediate / High)", "flowchart_box"),
        ("RAI Ablation (Intermediate/High risk) + TSH Suppression with Levothyroxine", "flowchart_box"),
        ("Surveillance: Tg + Anti-Tg levels + USG Neck (every 6-12 months x 2 years, then annual)", "flowchart_box"),
        ("Biochemical/Structural recurrence? -> Further workup (PET-CT, I-131 scan) + Reoperation / RAI / TKI", "flowchart_box"),
    ], S)
    spacer(story, 4)

    # ── 13. COMPLICATIONS ──────────────────────────────────────────────────────
    h1(story, "13.  COMPLICATIONS", S)

    h2(story, "A. Surgical Complications", S)
    data = [
        ["Complication", "Detail / Management"],
        ["RLN injury (unilateral)", "Hoarseness; most common nerve injury. Majority are temporary (neuropraxia). "
         "Permanent in < 1% by experienced surgeon."],
        ["RLN injury (bilateral)", "Bilateral vocal cord palsy -> stridor, respiratory distress -> emergency tracheostomy"],
        ["Hypocalcaemia / Hypoparathyroidism", "MOST COMMON post-total thyroidectomy complication. Transient in most. "
         "Permanent in 1-3%. Treat: Calcium 1g TDS + Calcitriol 0.25-0.5 mcg BD. MONITOR calcium 6-hourly post-op."],
        ["Haemorrhage / haematoma", "Rare but serious -> neck haematoma can cause airway compression -> re-exploration"],
        ["Wound infection / seroma", "Uncommon; managed with antibiotics/drainage"],
        ["Chyle leak", "Left lateral neck dissection -> thoracic duct injury -> chylous fistula"],
        ["Tracheomalacia", "Rare; long-standing tracheal compression -> airway collapse post thyroid removal"],
    ]
    story.append(make_table(data, [W*0.33, W*0.67], S))
    caution(story, "CAUTION: Post-total thyroidectomy - check calcium 6-hourly. Tingling + perioral numbness = "
            "early hypocalcaemia. Chvostek's / Trousseau's sign if severe. Treat EARLY.", S)

    h2(story, "B. RAI Complications", S)
    bullet(story, [
        "Radiation thyroiditis / sialadenitis (parotid/submandibular swelling, dry mouth, taste changes).",
        "Transient bone marrow suppression at high doses.",
        "Increased risk of secondary malignancies (leukaemia, salivary gland tumours) at cumulative high doses.",
        "Pulmonary fibrosis: high-dose RAI for lung metastases.",
        "Teratogenicity: contraindicated in pregnancy; avoid pregnancy for 6-12 months after RAI.",
    ], S)

    h2(story, "C. Disease Complications", S)
    bullet(story, [
        "Cervical lymph node recurrence: most common site of recurrence in PTC.",
        "Distant metastases: lung (most common), bone, brain, liver.",
        "Tracheal invasion: cough, haemoptysis, stridor.",
        "Oesophageal invasion: dysphagia.",
        "Anaplastic transformation: rare; very poor prognosis.",
    ], S)
    spacer(story, 4)

    # ── 14. PROGNOSIS ──────────────────────────────────────────────────────────
    h1(story, "14.  PROGNOSIS", S)
    bullet(story, [
        "EXCELLENT overall: 10-year survival > 95% (Robbins Pathology); > 90% in most series.",
        "Lymph node metastases in young patients do NOT significantly worsen survival.",
        "Prognostic factors (worsening outcomes):",
    ], S)
    bullet(story, [
        "Age > 55 years (STRONGEST prognostic factor in AJCC 8th ed.)",
        "Male sex",
        "Tumour size > 4 cm",
        "Extrathyroidal extension (especially gross T4 disease)",
        "Distant metastases (lung, bone)",
        "Aggressive histological variants (tall-cell, columnar, hobnail)",
        "BRAF V600E mutation",
        "Incomplete surgical resection (R1/R2)",
        "Vascular invasion",
    ], S, sub=True)
    data = [
        ["Stage (AJCC 8th ed.)", "Approximate 10-Year Survival"],
        ["Stage I (< 55 yrs, M0)", "> 98%"],
        ["Stage II (< 55 yrs, M1 or >= 55 yrs)", "~90%"],
        ["Stage III (>= 55 yrs, selected)", "~70%"],
        ["Stage IVA/IVB (advanced)", "~50%"],
    ]
    story.append(make_table(data, [W*0.45, W*0.55], S))
    pearl(story, "PEARL: PTC is one of the few cancers where lymph node metastasis in young patients does NOT "
          "significantly affect survival. However, macroscopic nodal disease may increase recurrence rate. "
          "(KJ Lee's ORL + Scott-Brown's)", S)
    spacer(story, 4)

    # ── 15. FOLLOW-UP ──────────────────────────────────────────────────────────
    h1(story, "15.  FOLLOW-UP", S)
    data = [
        ["Time Point", "Investigation", "Action"],
        ["6-12 wks post-op", "TFTs, serum calcium, Tg + anti-Tg", "Dose-adjust levothyroxine; manage hypocalcaemia"],
        ["6-12 months post-RAI", "Neck USG + serum Tg + anti-Tg", "Baseline structural / biochemical response"],
        ["Annually x 5 years", "Neck USG + Tg + anti-Tg", "Monitor for structural recurrence"],
        ["Every 1-2 yrs (long-term)", "Tg + anti-Tg; USG if indicated", "Low-risk patients with undetectable Tg: low-intensity surveillance"],
        ["Tg rising / suspicious USG", "Neck USG + CT/MRI; I-131 whole body scan or PET-CT", "Reoperative surgery / re-RAI / TKI"],
    ]
    story.append(make_table(data, [W*0.22, W*0.33, W*0.45], S))
    bullet(story, [
        "Stimulated Tg (after rhTSH or T4 withdrawal): used to detect residual / recurrent disease.",
        "Detectable Tg on T4 therapy in low-risk patient: re-evaluate with stimulated Tg + USG.",
        "Anti-Tg antibodies: must be measured with every Tg; if present and rising, suggests recurrence "
          "(antibodies can falsely suppress Tg assay).",
        "Adjust TSH suppression level as risk decreases over time (avoid overtreatment).",
    ], S)
    spacer(story, 4)

    # ── 16. RECENT ADVANCES ────────────────────────────────────────────────────
    h1(story, "16.  RECENT ADVANCES", S)
    data = [
        ["Advance", "Detail"],
        ["NIFTP Reclassification (2016)", "Non-invasive follicular thyroid neoplasm with papillary-like nuclear features - "
         "reclassified as NON-MALIGNANT; avoids overtreatment of low-risk lesions."],
        ["Molecular Testing (ThyroSeq, Afirma GSC)", "Genomic classifiers for indeterminate FNA nodules (Bethesda III/IV); "
         "improves specificity and avoids unnecessary surgery."],
        ["Active Surveillance (for microcarcinoma)", "Japan Kuma Hospital data: 2/3 of papillary microcarcinoma "
         "(<10mm) never progress; selected patients monitored without surgery."],
        ["Lenvatinib / Sorafenib", "VEGFR inhibitors - approved for RAI-refractory progressive DTC. "
         "SELECT trial (lenvatinib): PFS benefit vs placebo."],
        ["BRAF / MEK inhibitors", "Dabrafenib + Trametinib: for BRAF V600E-mutant advanced PTC; "
         "FDA breakthrough designation."],
        ["RET inhibitors (Selpercatinib, Pralsetinib)", "For RET fusion-positive thyroid cancers (Phase I/II trials show "
         "high response rates)."],
        ["Liquid biopsy", "Circulating tumour DNA (ctDNA) - emerging role in disease monitoring, "
         "detecting recurrence before structural imaging. (PMID 37882489)"],
        ["Robotic / Transoral thyroidectomy", "Scarless approaches gaining ground in selected centres; "
         "oncologically equivalent to open surgery."],
        ["Reduced RAI in low-risk PTC", "Multiple RCTs and meta-analyses support de-escalation or omission of "
         "RAI ablation in truly low-risk PTC (ATA 2015 revised guidelines)."],
    ]
    story.append(make_table(data, [W*0.3, W*0.7], S))
    spacer(story, 4)

    # ── 17. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(story, "17.  VIVA QUESTIONS & ANSWERS", S)

    vivas = [
        ("Q1: What is the MOST COMMON thyroid malignancy?",
         "Papillary carcinoma (~80% of all thyroid cancers). Also the most common in children."),
        ("Q2: What are the characteristic nuclear features of PTC?",
         "Orphan Annie eye nuclei (ground-glass, optically clear), intranuclear pseudo-inclusions, nuclear grooves "
         "(coffee-bean appearance), nuclear crowding and overlap."),
        ("Q3: What is psammoma body? Its significance in PTC?",
         "Concentrically laminated calcified structures within papillae. Almost pathognomonic for PTC - "
         "NEVER (almost) found in follicular or medullary carcinoma."),
        ("Q4: What is the most important prognostic factor in PTC?",
         "Age > 55 years (per AJCC 8th edition). In patients < 55 yrs even distant mets = Stage II only."),
        ("Q5: What is BRAF mutation? Its significance?",
         "BRAF V600E mutation is the MOST COMMON genetic event in PTC (~50%). It is a NEGATIVE prognostic marker - "
         "associated with extrathyroidal invasion, LN mets, recurrence, and RAI resistance."),
        ("Q6: What is NIFTP?",
         "Non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Previously classified as "
         "encapsulated follicular variant of PTC (EFVPTC). In 2016, reclassified as non-malignant to prevent overtreatment."),
        ("Q7: What is the role of Thyroglobulin in PTC?",
         "Tg is the KEY TUMOUR MARKER for post-operative surveillance. After total thyroidectomy, Tg should be "
         "undetectable. Rising Tg indicates recurrence. Must always measure with anti-Tg antibodies."),
        ("Q8: What is the difference between central and lateral neck dissection in PTC?",
         "Central neck dissection (Level VI): for cN1a disease (positive central nodes). "
         "Lateral neck dissection (Levels II-V): for cN1b disease (positive lateral cervical nodes). "
         "Prophylactic central neck dissection remains controversial."),
        ("Q9: What is the indication for RAI in PTC?",
         "Intermediate and high-risk PTC post-total thyroidectomy. Not recommended for low-risk unifocal intrathyroidal "
         "PTC < 1-2 cm without LN mets. Pre-RAI: withdraw T4 (TSH > 30) or use rhTSH."),
        ("Q10: What is the most common complication after total thyroidectomy?",
         "Transient hypocalcaemia (hypoparathyroidism). Permanent in 1-3%. "
         "Other important: RLN injury (hoarseness/stridor). Monitor calcium 6-hourly post-op."),
        ("Q11: What targeted therapy is used for RAI-refractory PTC?",
         "Lenvatinib and Sorafenib (multikinase inhibitors targeting VEGFR, RET, FGFR). "
         "BRAF V600E+: dabrafenib + trametinib. RET fusions: selpercatinib or pralsetinib."),
        ("Q12: Why is LN metastasis in young PTC patients not a poor prognostic sign?",
         "PTC has an unusual biology - microscopic LN mets in young patients < 55 yrs do not significantly affect "
         "10-year survival. However, macroscopic (bulky) nodal disease may increase recurrence risk. "
         "This is in contrast to most other malignancies. (Scott-Brown's + Bailey & Love's)"),
    ]

    for q, a in vivas:
        story.append(Paragraph(q, S["viva_q"]))
        story.append(Paragraph(a, S["viva_a"]))

    spacer(story, 4)

    # ── 18. CLINICAL PEARLS ────────────────────────────────────────────────────
    h1(story, "18.  CLINICAL PEARLS", S)
    pearls_list = [
        "PTC is diagnosed by NUCLEAR morphology - NOT papillary architecture. Nuclear features can diagnose PTC even in follicular-patterned lesions.",
        "Orphan Annie eye nuclei + nuclear grooves + pseudo-inclusions = HALLMARK of PTC on FNA.",
        "Psammoma bodies on FNA = almost diagnostic of PTC in a thyroid nodule.",
        "Age > 55 = WORST prognostic factor in AJCC 8th ed. staging for PTC.",
        "BRAF V600E mutation in ~50% PTC = negative prognosis + possible targeted therapy.",
        "AVOID iodinated CT contrast pre-RAI therapy (delays RAI by 4-8 weeks due to iodine loading).",
        "Pre-operative INDIRECT LARYNGOSCOPY is MANDATORY before thyroid surgery - document vocal cord mobility.",
        "Most common post-total thyroidectomy complication = HYPOCALCAEMIA. Monitor calcium 6-hourly post-op.",
        "Thyroglobulin = key post-op tumour marker. Must ALWAYS measure simultaneously with anti-Tg antibodies.",
        "Papillary microcarcinoma (< 10 mm): many never progress; active surveillance is an option in selected patients.",
        "Central neck dissection is CONTROVERSIAL for clinically N0 disease - discuss in MDT.",
        "Cystic lymph node in lateral neck of young person = PTC nodal metastasis until proven otherwise.",
        "Lymph node mets in PTC < 55 yrs = does NOT significantly worsen 10-year survival (unlike most cancers).",
        "Post-op TSH suppression: degree tailored to risk - full suppression for high-risk, low-normal for low-risk (avoid AF + osteoporosis).",
        "NIFTP (2016): encapsulated non-invasive follicular variant of PTC reclassified as BENIGN to prevent overtreatment.",
    ]
    for p in pearls_list:
        pearl(story, p, S)
    spacer(story, 4)

    # ── 19. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(story, "19.  KEY POINTS SUMMARY  (Quick Revision)", S)
    summary_data = [
        ["TOPIC", "KEY POINT"],
        ["Definition", "Malignant follicular cell tumour with papillary nuclear features; 80% of all thyroid Ca"],
        ["Most common", "Most common thyroid malignancy AND most common paediatric thyroid malignancy"],
        ["Gender/Age", "F:M = 3:1; Peak 40-50 yrs (women); all ages affected"],
        ["Top risk factor", "Ionising radiation (childhood); BRAF V600E mutation most common molecular event"],
        ["Presentation", "Painless thyroid nodule; euthyroid; 30% have LN mets at presentation"],
        ["Diagnosis", "USG -> FNAC (Bethesda V/VI) -> histology (nuclear features: Orphan Annie, grooves, inclusions, psammoma bodies)"],
        ["Lymph spread", "Lymphotropic - lateral neck nodes; cystic nodes; LN mets do NOT worsen survival in young"],
        ["Staging", "AJCC 8th ed.: Age-based; < 55 yrs: Stage I (M0) or Stage II (M1) only"],
        ["Prognostic factor", "Age > 55, extrathyroidal extension, distant mets, BRAF+, aggressive variant"],
        ["Surgery", "Total thyroidectomy (standard); lobectomy for selected low-risk; neck dissection for cN1 disease"],
        ["RAI", "Post-op for intermediate/high risk; NOT for low-risk; RAI dose 30-200 mCi based on risk"],
        ["Medical", "Levothyroxine (TSH suppression + replacement); targeted TKI for RAI-refractory cases"],
        ["Surveillance", "Tg + anti-Tg + USG at 6-12 months, then annually"],
        ["Prognosis", "10-year survival > 95%; excellent in young patients"],
        ["Recent advance", "NIFTP reclassification; molecular testing (ThyroSeq); active surveillance for microcarcinoma; Lenvatinib/TKI"],
    ]
    story.append(make_table(summary_data, [W*0.25, W*0.75], S))

    spacer(story, 6)
    story.append(Paragraph(
        "References: Scott-Brown's Otorhinolaryngology Head & Neck Surgery 8th ed. | KJ Lee's Essential Otolaryngology 11th ed. | "
        "Bailey & Love's Surgery 28th ed. | Robbins & Kumar Basic Pathology | ATA Guidelines 2015 (Updated 2023) | "
        "AJCC Cancer Staging Manual 8th ed. | PubMed PMID: 37882489, 38115346",
        S["subtitle"]
    ))


# ══════════════════════════════════════════════════════════════════════════════
#   MAIN
# ══════════════════════════════════════════════════════════════════════════════
def main():
    outpath = "/home/daytona/workspace/ptc-notes/Papillary_Ca_Thyroid_ExamNotes.pdf"
    doc = SimpleDocTemplate(
        outpath,
        pagesize=A4,
        leftMargin=MARGIN,
        rightMargin=MARGIN,
        topMargin=16*mm,
        bottomMargin=16*mm,
        title="Papillary Carcinoma of the Thyroid - Exam Notes",
        author="Orris Medical AI",
        subject="ENT/Surgery - Thyroid Oncology - KNRUHS",
    )
    S = make_styles()
    story = []
    build_content(story, S)
    doc.build(story)
    print(f"PDF generated: {outpath}")

if __name__ == "__main__":
    main()

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_ptc.py'

#!/usr/bin/env python3
# Coagulation Pathway - Exam Notes PDF
# NEW Color Palette: Deep purple headings, forest green subheadings, gold H3,
#                    warm beige backgrounds -- distinct from PTC teal/coral theme

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1  # 1 point in ReportLab units

# ── Font registration ──────────────────────────────────────────────────────────
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("LiberationSans", f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LiberationSans-Bold", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFont(TTFont("LiberationSans-Italic", f"{FONT_DIR}/LiberationSans-Italic.ttf"))
    pdfmetrics.registerFontFamily(
        "LiberationSans",
        normal="LiberationSans",
        bold="LiberationSans-Bold",
        italic="LiberationSans-Italic",
    )
    BASE_FONT = "LiberationSans"
    BASE_BOLD = "LiberationSans-Bold"
    BASE_ITALIC = "LiberationSans-Italic"
except Exception:
    BASE_FONT = "Helvetica"
    BASE_BOLD = "Helvetica-Bold"
    BASE_ITALIC = "Helvetica-Oblique"

# ── NEW Color Palette: Purple / Forest Green / Gold ───────────────────────────
C_H1_BG     = colors.HexColor("#3B1F6E")   # deep purple
C_H1_FG     = colors.HexColor("#FFFFFF")
C_H2_FG     = colors.HexColor("#1A5C2A")   # forest green
C_H2_BG     = colors.HexColor("#EAF5EB")   # pale green bg
C_H3_FG     = colors.HexColor("#7A5200")   # dark gold
C_H3_BG     = colors.HexColor("#FFF8E7")   # pale gold bg
C_BODY      = colors.HexColor("#000000")
C_TABLE_HDR = colors.HexColor("#3B1F6E")   # purple table header
C_TABLE_ALT = colors.HexColor("#F0EBF9")   # pale lavender alt row
C_PEARL_BG  = colors.HexColor("#EAF5EB")   # light green pearl bg
C_PEARL_FG  = colors.HexColor("#000000")
C_CAUTION   = colors.HexColor("#C0392B")
C_DOSE_FG   = colors.HexColor("#1A5C2A")
C_HIGHLIGHT = colors.HexColor("#FFF3CD")
C_RULE      = colors.HexColor("#3B1F6E")
C_FC_BOX    = colors.HexColor("#D8CCF0")   # lavender flowchart box
C_FC_HDR    = colors.HexColor("#3B1F6E")
C_VIVA_BG   = colors.HexColor("#F0EBF9")
C_VIVA_Q    = colors.HexColor("#3B1F6E")

PAGE_W, PAGE_H = A4
MARGIN = 16 * mm
BODY_SIZE = 10.5
BODY_LEADING = 15.5
CELL_LEADING = 13

# ── Styles ─────────────────────────────────────────────────────────────────────
def make_styles():
    s = {}
    s["title"] = ParagraphStyle("title",
        fontName=BASE_BOLD, fontSize=15, leading=19,
        textColor=C_H1_FG, backColor=C_H1_BG,
        alignment=TA_CENTER, spaceAfter=4*pt, borderPad=(8,10,8,10))
    s["subtitle"] = ParagraphStyle("subtitle",
        fontName=BASE_FONT, fontSize=10, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3*pt)
    s["h1"] = ParagraphStyle("h1",
        fontName=BASE_BOLD, fontSize=12.5, leading=16,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceAfter=3*pt, spaceBefore=8*pt,
        leftIndent=5, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2",
        fontName=BASE_BOLD, fontSize=11, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceAfter=2*pt, spaceBefore=6*pt,
        leftIndent=4, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3",
        fontName=BASE_BOLD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceAfter=2*pt, spaceBefore=4*pt,
        leftIndent=4, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body",
        fontName=BASE_FONT, fontSize=BODY_SIZE, leading=BODY_LEADING,
        textColor=C_BODY, spaceAfter=2*pt, alignment=TA_JUSTIFY)
    s["bullet"] = ParagraphStyle("bullet",
        fontName=BASE_FONT, fontSize=BODY_SIZE, leading=BODY_LEADING,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=1*pt)
    s["sub_bullet"] = ParagraphStyle("sub_bullet",
        fontName=BASE_FONT, fontSize=10, leading=14,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=1*pt)
    s["pearl"] = ParagraphStyle("pearl",
        fontName=BASE_BOLD, fontSize=10.5, leading=14,
        textColor=C_PEARL_FG, backColor=C_PEARL_BG,
        spaceAfter=3*pt, spaceBefore=2*pt,
        leftIndent=8, rightIndent=8, borderPad=(3,6,3,6))
    s["caution"] = ParagraphStyle("caution",
        fontName=BASE_BOLD, fontSize=10.5, leading=14,
        textColor=C_CAUTION, backColor=colors.HexColor("#FFF0F0"),
        spaceAfter=2*pt, spaceBefore=2*pt, leftIndent=8, borderPad=(2,5,2,5))
    s["cell"] = ParagraphStyle("cell",
        fontName=BASE_FONT, fontSize=10, leading=CELL_LEADING, textColor=C_BODY)
    s["cell_bold"] = ParagraphStyle("cell_bold",
        fontName=BASE_BOLD, fontSize=10, leading=CELL_LEADING, textColor=C_BODY)
    s["cell_hdr"] = ParagraphStyle("cell_hdr",
        fontName=BASE_BOLD, fontSize=10, leading=CELL_LEADING, textColor=colors.white)
    s["viva_q"] = ParagraphStyle("viva_q",
        fontName=BASE_BOLD, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_VIVA_Q, backColor=C_VIVA_BG,
        spaceAfter=1*pt, spaceBefore=4*pt, leftIndent=6, borderPad=(2,5,2,5))
    s["viva_a"] = ParagraphStyle("viva_a",
        fontName=BASE_FONT, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_BODY, leftIndent=12, spaceAfter=3*pt)
    s["center"] = ParagraphStyle("center",
        fontName=BASE_FONT, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_BODY, alignment=TA_CENTER)
    s["center_bold"] = ParagraphStyle("center_bold",
        fontName=BASE_BOLD, fontSize=10.5, leading=BODY_LEADING,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    s["fc_box"] = ParagraphStyle("fc_box",
        fontName=BASE_FONT, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    return s

def rule(story, color=C_RULE):
    story.append(HRFlowable(width="100%", thickness=0.6, color=color, spaceAfter=3*pt, spaceBefore=2*pt))

def h1(story, text, S): story.append(Spacer(1,3*pt)); story.append(Paragraph(text, S["h1"]))
def h2(story, text, S): story.append(Spacer(1,2*pt)); story.append(Paragraph(text, S["h2"]))
def h3(story, text, S): story.append(Paragraph(text, S["h3"]))
def body(story, text, S): story.append(Paragraph(text, S["body"]))
def sp(story, h=4): story.append(Spacer(1, h*pt))

def bullet(story, items, S, sub=False):
    k = "sub_bullet" if sub else "bullet"
    for item in items:
        story.append(Paragraph(f"• {item}", S[k]))

def pearl(story, text, S):
    story.append(Paragraph(f"★ {text}", S["pearl"]))

def caution(story, text, S):
    story.append(Paragraph(f"⚠ {text}", S["caution"]))

def make_table(data, col_widths, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for ci, cell in enumerate(row):
            if isinstance(cell, str):
                st = S["cell_hdr"] if ri == 0 else S["cell"]
                nr.append(Paragraph(cell, st))
            else:
                nr.append(cell)
        rows.append(nr)
    t = Table(rows, colWidths=col_widths, repeatRows=1)
    cmds = [
        ("BACKGROUND",    (0,0), (-1,0),  C_TABLE_HDR),
        ("TEXTCOLOR",     (0,0), (-1,0),  colors.white),
        ("FONTNAME",      (0,0), (-1,0),  BASE_BOLD),
        ("FONTSIZE",      (0,0), (-1,-1), 10),
        ("LEADING",       (0,0), (-1,-1), CELL_LEADING),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [colors.white, C_TABLE_ALT] if alt else [colors.white]),
        ("BOX",           (0,0), (-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0), (-1,-1), 0.4, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING",   (0,0), (-1,-1), 5),
        ("RIGHTPADDING",  (0,0), (-1,-1), 5),
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
    ]
    t.setStyle(TableStyle(cmds))
    return t

def flowchart(story, title, boxes, S):
    sp(story, 3)
    story.append(Paragraph(title, S["h3"]))
    sp(story, 2)
    W = PAGE_W - 2*MARGIN
    bw = W * 0.78
    rows = []
    bgs = []
    for i, box in enumerate(boxes):
        if isinstance(box, tuple):
            txt, bold = box
        else:
            txt, bold = box, False
        st = S["center_bold"] if bold else S["fc_box"]
        bg = colors.HexColor("#C8B8E8") if bold else C_FC_BOX
        rows.append([Paragraph(txt, st)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["center"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",           (0,0), (-1,-1), 0.5, C_RULE),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 8),
        ("RIGHTPADDING",  (0,0), (-1,-1), 8),
        ("ALIGN",         (0,0), (-1,-1), "CENTER"),
        ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ]
    for i, bg in enumerate(bgs):
        cmds.append(("BACKGROUND", (0,i), (0,i), bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([
        ("ALIGN", (0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",   (0,0),(-1,-1),0),
        ("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",  (0,0),(-1,-1),0),
        ("RIGHTPADDING", (0,0),(-1,-1),0),
    ]))
    story.append(outer)
    sp(story, 5)


# ══════════════════════════════════════════════════════════════════════════════
#   CONTENT
# ══════════════════════════════════════════════════════════════════════════════
def build(story, S):
    W = PAGE_W - 2*MARGIN

    # TITLE
    story.append(Paragraph("COAGULATION PATHWAY", S["title"]))
    story.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS  |  Sources: Goldman-Cecil Medicine, Miller's Anesthesia, "
        "Sabiston Surgery, Bailey & Love, Robbins Pathology, Tietz Laboratory Medicine",
        S["subtitle"]))
    rule(story)
    sp(story, 2)

    # ── 1. DEFINITION & OVERVIEW ───────────────────────────────────────────────
    h1(story, "1.  DEFINITION & OVERVIEW", S)
    bullet(story, [
        "HAEMOSTASIS: Physiological process that stops bleeding after vascular injury while maintaining blood fluidity.",
        "COAGULATION: Series of enzymatic reactions converting soluble fibrinogen -> insoluble fibrin clot.",
        "COAGULATION CASCADE: Sequential activation of clotting factors (zymogens) in an amplifying waterfall sequence.",
        "THROMBOSIS: Pathological coagulation - unwanted clot formation within intact vessels.",
        "Coagulation factors: plasma glycoproteins, mostly synthesised in the LIVER; circulate as inactive ZYMOGENS.",
        "Activated form denoted by lowercase 'a' suffix (e.g., Factor X -> Factor Xa).",
        "Calcium (Ca2+) and phospholipid membrane surfaces are ESSENTIAL cofactors at each step.",
    ], S)
    pearl(story, "PEARL: Coagulation cascade = Haemostasis (physiological) vs Thrombosis (pathological). "
          "Thrombin is the CENTRAL enzyme of the entire cascade. (Goldman-Cecil Medicine)", S)
    sp(story, 4)

    # ── 2. PHYSIOLOGY OF HAEMOSTASIS ──────────────────────────────────────────
    h1(story, "2.  PHYSIOLOGY OF HAEMOSTASIS", S)
    h2(story, "Four Sequential Phases", S)
    data = [
        ["Phase", "Process", "Key Components"],
        ["1. Vascular spasm",
         "Immediate vasoconstriction on vessel injury",
         "Smooth muscle contraction; endothelin; catecholamines"],
        ["2. Primary haemostasis",
         "Platelet plug formation (platelet-vessel wall interaction)",
         "vWF, collagen, GPIb receptor, GPIIb/IIIa, ADP, thromboxane A2"],
        ["3. Secondary haemostasis",
         "Coagulation cascade -> fibrin clot reinforces platelet plug",
         "Coagulation factors I-XIII; Ca2+; phospholipid; thrombin"],
        ["4. Fibrinolysis",
         "Gradual clot dissolution after healing",
         "Plasminogen -> Plasmin; tPA; uPA; D-dimers"],
    ]
    story.append(make_table(data, [W*0.2, W*0.38, W*0.42], S))
    sp(story, 4)

    # ── 3. COAGULATION FACTORS ────────────────────────────────────────────────
    h1(story, "3.  COAGULATION FACTORS (Quick Reference)", S)
    data = [
        ["Factor", "Name", "Pathway", "Note"],
        ["I",    "Fibrinogen",              "Common",   "Converted to fibrin by thrombin"],
        ["II",   "Prothrombin",             "Common",   "Vit K-dependent; activated -> thrombin (IIa)"],
        ["III",  "Tissue Factor (TF)",      "Extrinsic","Released by damaged endothelium/monocytes"],
        ["IV",   "Calcium (Ca2+)",          "All",      "Essential cofactor at every step"],
        ["V",    "Labile Factor",           "Common",   "Cofactor in prothrombinase complex"],
        ["VII",  "Stable Factor",           "Extrinsic","Vit K-dependent; shortest half-life (~6 hrs)"],
        ["VIII", "Anti-haemophilic A",      "Intrinsic","Deficient in Haemophilia A; cofactor for IXa"],
        ["IX",   "Christmas Factor",        "Intrinsic","Vit K-dependent; deficient in Haemophilia B"],
        ["X",    "Stuart-Prower Factor",    "Common",   "Vit K-dependent; final activator in both pathways"],
        ["XI",   "Plasma Thromboplastin Antecedent", "Intrinsic", "Deficient in Haemophilia C"],
        ["XII",  "Hageman Factor",          "Intrinsic","Contact activation; deficiency = prolonged aPTT without bleeding"],
        ["XIII", "Fibrin Stabilising Factor","Common",  "Cross-links fibrin; activated by thrombin"],
        ["vWF",  "von Willebrand Factor",   "Primary",  "Platelet adhesion to collagen; carrier for FVIII"],
    ]
    story.append(make_table(data, [W*0.08, W*0.26, W*0.17, W*0.49], S))
    caution(story, "Vitamin K-dependent factors: II, VII, IX, X, Protein C, Protein S. "
            "Warfarin inhibits Vitamin K -> reduces all these factors. Factor VII (shortest t1/2) depletes first -> PT prolonged first.", S)
    sp(story, 4)

    # ── 4. COAGULATION PATHWAYS ───────────────────────────────────────────────
    h1(story, "4.  COAGULATION PATHWAYS", S)

    h2(story, "A. Classic Cascade Model (Laboratory / In Vitro Model)", S)
    bullet(story, [
        "Classically divided into: EXTRINSIC pathway + INTRINSIC pathway -> converge on COMMON pathway.",
        "Both pathways culminate in activation of Factor X -> prothrombinase complex -> thrombin -> fibrin.",
        "This is an OVERSIMPLIFICATION - does not fully reflect in vivo haemostasis (Miller's Anesthesia, 10e).",
        "Remains the basis for standard coagulation TESTS (PT tests extrinsic; aPTT tests intrinsic).",
    ], S)

    h2(story, "B. Extrinsic Pathway (Tissue Factor / TF Pathway)", S)
    bullet(story, [
        "TRIGGER: Vascular injury -> subendothelial TISSUE FACTOR (TF/Factor III) exposed to blood.",
        "TF + circulating Factor VIIa -> TF:VIIa complex (extrinsic tenase).",
        "TF:VIIa complex activates:",
    ], S)
    bullet(story, [
        "Factor X -> Xa (directly)",
        "Factor IX -> IXa (cross-activation of intrinsic pathway)",
    ], S, sub=True)
    bullet(story, [
        "Inhibited by TFPI (tissue factor pathway inhibitor) - limits initial burst.",
        "Tests: PROTHROMBIN TIME (PT) / INR measures extrinsic pathway.",
        "NOW considered the PRIMARY/MAJOR initiator of in vivo coagulation.",
    ], S)

    h2(story, "C. Intrinsic Pathway (Contact Activation Pathway)", S)
    bullet(story, [
        "TRIGGER: Contact of blood with negatively charged surfaces (collagen, glass, kaolin).",
        "Factor XII (Hageman) activated -> XIIa.",
        "XIIa activates Factor XI -> XIa.",
        "XIa activates Factor IX -> IXa.",
        "IXa + Factor VIIIa + Ca2+ + phospholipid = INTRINSIC TENASE COMPLEX.",
        "Intrinsic tenase activates Factor X -> Xa (amplification of extrinsic pathway signal).",
        "Role: AMPLIFICATION system - propagates thrombin generation initiated by TF pathway.",
        "Tests: aPTT (activated partial thromboplastin time) measures intrinsic pathway.",
        "NOTE: Factor XII, prekallikrein, HMWK deficiency -> prolonged aPTT but NO bleeding (these factors less important in vivo).",
    ], S)

    h2(story, "D. Common Pathway", S)
    bullet(story, [
        "Factor Xa + Factor Va + Ca2+ + phospholipid = PROTHROMBINASE COMPLEX.",
        "Prothrombinase complex: Prothrombin (II) -> Thrombin (IIa) [THROMBIN BURST].",
        "THROMBIN actions (central role):",
    ], S)
    bullet(story, [
        "Cleaves fibrinopeptides A and B from fibrinogen -> Fibrin monomers.",
        "Fibrin monomers polymerise -> Fibrin strands (soluble fibrin).",
        "Activates Factor XIII -> XIIIa (transglutaminase).",
        "XIIIa cross-links fibrin strands -> INSOLUBLE FIBRIN CLOT (stable clot).",
        "Activates platelets, Factors V, VIII, XI (positive feedback amplification).",
        "Activates Protein C (negative feedback - anticoagulant).",
    ], S, sub=True)

    # Flowchart
    flowchart(story, "COAGULATION CASCADE - Classic Model (Flowchart)", [
        ("EXTRINSIC PATHWAY                        INTRINSIC PATHWAY", True),
        ("Tissue Injury -> TF exposed              Contact with collagen/surface", False),
        ("TF + VIIa -> TF:VIIa complex             XII -> XIIa -> XI -> XIa -> IX -> IXa", False),
        ("Activates X -> Xa    Activates IX -> IXa (cross-link)     IXa + VIIIa + Ca2+ + PL (intrinsic tenase) -> Xa", False),
        ("COMMON PATHWAY: Xa + Va + Ca2+ + PL = Prothrombinase Complex", True),
        ("Prothrombin (II) -> THROMBIN (IIa)", False),
        ("Fibrinogen (I) -> Fibrin monomers -> Fibrin polymer", False),
        ("Factor XIIIa (activated by thrombin) -> Cross-linked insoluble FIBRIN CLOT", True),
    ], S)
    sp(story, 2)

    # ── 5. CELL-BASED MODEL (MODERN VIEW) ─────────────────────────────────────
    h1(story, "5.  CELL-BASED MODEL OF COAGULATION (Modern / In Vivo)", S)
    data = [
        ["Phase", "Location", "Events"],
        ["INITIATION",
         "TF-bearing cells (fibroblasts, smooth muscle)",
         "TF:FVIIa -> activates FX -> FXa; FXa + FVa -> small amount thrombin (thrombin spark). "
         "TFPI limits this phase."],
        ["AMPLIFICATION",
         "Platelet surface",
         "Thrombin spark activates platelets; activates FV, FVIII, FXI. "
         "Platelets adhere, release granules (ADP, thromboxane A2, vWF)."],
        ["PROPAGATION",
         "Activated platelet surface",
         "IXa:VIIIa (intrinsic tenase) -> massive FXa generation. "
         "FXa:FVa (prothrombinase) -> THROMBIN BURST -> fibrin clot."],
    ]
    story.append(make_table(data, [W*0.2, W*0.3, W*0.5], S))
    pearl(story, "PEARL: Cell-based model explains WHY Factor XII deficiency does not cause bleeding: "
          "the TF (extrinsic) pathway is the PRIMARY initiator in vivo. "
          "(Sabiston Surgery, 7th ed. / Miller's Anesthesia, 10e)", S)
    sp(story, 4)

    # ── 6. NATURAL ANTICOAGULANT SYSTEMS ──────────────────────────────────────
    h1(story, "6.  NATURAL ANTICOAGULANT SYSTEMS (Inhibitors of Coagulation)", S)
    data = [
        ["System", "Mechanism", "Clinical Relevance"],
        ["TFPI (Tissue Factor Pathway Inhibitor)",
         "Inhibits TF:VIIa complex AND FXa directly. Enhanced by Protein S. "
         "Limits initiation phase of coagulation.",
         "Deficiency -> hypercoagulable state"],
        ["Antithrombin (AT / AT-III)",
         "Serine protease inhibitor. Inhibits Thrombin (IIa), FXa, FIXa, FXIa. "
         "Works on endothelial surface via heparan sulfate proteoglycans.",
         "Heparin works by binding AT -> accelerates AT activity 1000x. "
         "AT deficiency -> DVT/PE risk."],
        ["Protein C + Protein S",
         "Thrombin binds thrombomodulin on endothelium -> activates Protein C (APC). "
         "APC + Protein S (cofactor) -> inactivates FVa and FVIIIa -> reduces thrombin generation.",
         "Both Vit K-dependent. Deficiency -> hypercoagulable state. "
         "APC resistance (Factor V Leiden) = most common inherited thrombophilia."],
        ["Fibrinolytic system",
         "Plasminogen -> Plasmin (by tPA/uPA). Plasmin degrades fibrin -> D-dimers, FDPs. "
         "PAI-1 inhibits tPA (antifibrinolytic). alpha2-antiplasmin inhibits plasmin.",
         "tPA used therapeutically (thrombolysis in MI, stroke). "
         "D-dimer elevated in DVT, PE, DIC."],
        ["Thrombomodulin",
         "Endothelial receptor; binds thrombin -> removes thrombin from procoagulant reactions; "
         "complex activates Protein C.",
         "Natural anticoagulant on intact endothelium."],
    ]
    story.append(make_table(data, [W*0.22, W*0.44, W*0.34], S))
    sp(story, 4)

    # ── 7. FIBRINOLYSIS ────────────────────────────────────────────────────────
    h1(story, "7.  FIBRINOLYSIS", S)
    bullet(story, [
        "Gradual dissolution of fibrin clot after wound healing - regulated, delayed process.",
        "Plasminogen (inactive) -> PLASMIN (active) via:",
    ], S)
    bullet(story, [
        "tPA (tissue plasminogen activator) - from endothelium; more relevant to intravascular fibrinolysis.",
        "uPA (urokinase plasminogen activator) - extravascular fibrinolysis; cell migration.",
    ], S, sub=True)
    bullet(story, [
        "Plasmin degrades cross-linked fibrin -> FIBRIN DEGRADATION PRODUCTS (FDPs) + D-DIMERS.",
        "D-dimer: specific product of cross-linked fibrin breakdown - used clinically to screen for DVT/PE/DIC.",
        "Inhibitors of fibrinolysis: PAI-1 (inhibits tPA), alpha2-antiplasmin (inhibits plasmin), TAFI.",
        "Antifibrinolytic drugs: Tranexamic acid, aminocaproic acid - inhibit plasminogen binding to fibrin.",
    ], S)
    sp(story, 4)

    # ── 8. COAGULATION TESTS ──────────────────────────────────────────────────
    h1(story, "8.  INVESTIGATIONS / COAGULATION TESTS", S)
    data = [
        ["Test", "Pathway Tested", "Normal Range", "Detects / Used For"],
        ["PT (Prothrombin Time)",
         "Extrinsic + Common (VII, X, V, II, I)",
         "11-14 sec",
         "Liver disease, Warfarin monitoring, Vit K deficiency, DIC. Factor VII first to fall."],
        ["INR (International Normalised Ratio)",
         "Extrinsic",
         "0.8-1.2 (normal); 2-3 (therapeutic anticoagulation)",
         "Standardised PT. Target INR 2-3 for AF/DVT; 2.5-3.5 for mechanical valves."],
        ["aPTT (activated Partial Thromboplastin Time)",
         "Intrinsic + Common (XII, XI, IX, VIII, X, V, II, I)",
         "25-35 sec",
         "Haemophilia A (FVIII) and B (FIX), Heparin monitoring, Lupus anticoagulant, DIC."],
        ["TT (Thrombin Time)",
         "Common pathway (fibrinogen -> fibrin)",
         "14-16 sec",
         "Fibrinogen deficiency, dysfibrinogenaemia, heparin effect, DIC."],
        ["Platelet count",
         "Primary haemostasis",
         "150,000-400,000 /uL",
         "Thrombocytopenia (ITP, DIC, TTP). Bleeding risk if < 50,000/uL for surgery."],
        ["Bleeding time / PFA-100",
         "Primary haemostasis + platelet function",
         "BT: 2-7 min",
         "vWD, platelet function disorders, aspirin effect."],
        ["D-dimer",
         "Fibrinolysis",
         "< 0.5 mg/L (< 500 ng/mL)",
         "DVT/PE screening (high sensitivity, low specificity). Elevated in DIC, infection, pregnancy."],
        ["Fibrinogen",
         "Common pathway",
         "1.5-4.0 g/L",
         "DIC (falls), acute phase reactant (rises in inflammation). Critical if < 1.0 g/L."],
        ["TEG / ROTEM",
         "Global coagulation (whole blood)",
         "Graphical analysis",
         "Perioperative/trauma coagulopathy; guides blood product therapy."],
    ]
    story.append(make_table(data, [W*0.18, W*0.22, W*0.18, W*0.42], S))
    caution(story, "IMPORTANT: PT measures extrinsic pathway (Factor VII mainly). aPTT measures intrinsic pathway "
            "(Factors VIII, IX - Haemophilia). Both share common pathway factors (X, V, II, I). "
            "Factor XIII deficiency: normal PT + aPTT but abnormal clot solubility test.", S)
    sp(story, 4)

    # ── 9. CLINICAL APPLICATIONS: COAGULOPATHIES ──────────────────────────────
    h1(story, "9.  CLINICAL APPLICATIONS - COAGULOPATHIES", S)
    data = [
        ["Disorder", "Defect", "PT", "aPTT", "Clinical Feature / Treatment"],
        ["Haemophilia A",
         "Factor VIII deficiency (X-linked recessive)",
         "Normal", "Prolonged",
         "Deep muscle/joint bleeds (haemarthrosis). Tx: FVIII concentrate / recombinant FVIII."],
        ["Haemophilia B (Christmas disease)",
         "Factor IX deficiency (X-linked recessive)",
         "Normal", "Prolonged",
         "Same as Haemophilia A clinically. Tx: FIX concentrate."],
        ["von Willebrand Disease (vWD)",
         "vWF deficiency/dysfunction",
         "Normal", "Normal or prolonged",
         "Most common inherited bleeding disorder. Mucocutaneous bleeds. Tx: Desmopressin (DDAVP), vWF concentrate."],
        ["Vitamin K deficiency",
         "Reduced II, VII, IX, X, Protein C, S",
         "Prolonged", "Prolonged",
         "Malabsorption, liver disease, prolonged antibiotics, neonates. Tx: Vit K, FFP."],
        ["Warfarin therapy",
         "Inhibits Vit K-dependent factors (VKOR inhibition)",
         "Prolonged", "Prolonged",
         "INR monitoring. Reversal: Vit K, Prothrombin Complex Concentrate (PCC), FFP."],
        ["Liver failure",
         "Reduced synthesis of all factors except FVIII (produced by endothelium)",
         "Prolonged", "Prolonged",
         "Also dysfibrinogenaemia, low platelet count (hypersplenism), high D-dimer (DIC)."],
        ["DIC (Disseminated Intravascular Coagulation)",
         "Widespread clot activation -> consumption of all factors + platelets",
         "Prolonged", "Prolonged",
         "Low fibrinogen, high D-dimer, low platelets, schistocytes. Treat underlying cause; FFP, cryoprecipitate, platelets."],
        ["Factor V Leiden (APC resistance)",
         "Mutant FV resistant to Protein C inactivation",
         "Normal", "Normal or slightly prolonged",
         "Most common hereditary thrombophilia; DVT/PE risk. Tx: Anticoagulation."],
    ]
    story.append(make_table(data, [W*0.2, W*0.23, W*0.07, W*0.08, W*0.42], S))
    sp(story, 4)

    # ── 10. MANAGEMENT OVERVIEW ───────────────────────────────────────────────
    h1(story, "10.  MANAGEMENT", S)
    h2(story, "A. Medical Management of Bleeding Disorders", S)
    data = [
        ["Drug / Agent", "Mechanism", "Use"],
        ["Fresh Frozen Plasma (FFP)",
         "Contains all coagulation factors",
         "Acute coagulopathy, warfarin reversal, DIC, liver failure"],
        ["Prothrombin Complex Concentrate (PCC / Beriplex)",
         "Contains concentrated Vit K-dependent factors II, VII, IX, X",
         "Rapid warfarin reversal; emergency surgery; DOAC reversal (4-factor PCC)"],
        ["Cryoprecipitate",
         "Concentrated: Fibrinogen, FVIII, vWF, FXIII, fibronectin",
         "Hypofibrinogenaemia (< 1.0 g/L), DIC, haemophilia A, vWD"],
        ["Factor concentrates",
         "Recombinant or plasma-derived specific factors",
         "FVIII (Haemophilia A), FIX (Haemophilia B), vWF, FXIII"],
        ["Desmopressin (DDAVP)",
         "Releases vWF + FVIII from endothelial cells (Weibel-Palade bodies)",
         "Mild Haemophilia A, vWD (Type 1), platelet dysfunction. Dose: 0.3 mcg/kg IV."],
        ["Tranexamic acid",
         "Antifibrinolytic - inhibits plasminogen activation",
         "Trauma (CRASH-2 trial), surgical haemostasis, menorrhagia. Dose: 1g IV or oral."],
        ["Vitamin K (phytomenadione)",
         "Restores synthesis of Vit K-dependent factors",
         "Warfarin reversal (1-10 mg IV/oral depending on urgency)"],
        ["Heparin (UFH)",
         "Binds Antithrombin -> 1000x increase in AT activity -> inhibits thrombin + FXa",
         "DVT/PE treatment, cardiac surgery, dialysis. Monitor: aPTT (target 60-100 sec)."],
        ["LMWH (enoxaparin, dalteparin)",
         "Anti-FXa predominant effect via AT",
         "DVT prophylaxis/treatment, ACS. Monitor: anti-Xa levels (if needed, e.g., renal impairment)."],
        ["Warfarin",
         "Inhibits Vit K epoxide reductase -> reduces II, VII, IX, X, Protein C, S",
         "AF, DVT, mechanical valves. Target INR 2-3 (3-4 for metallic valves)."],
        ["DOACs (dabigatran, rivaroxaban, apixaban)",
         "Dabigatran: direct thrombin inhibitor. Rivaroxaban/apixaban: direct FXa inhibitor.",
         "AF, DVT/PE. No routine monitoring. Reversal: idarucizumab (dabigatran), andexanet alfa (FXa inhibitors)."],
    ]
    story.append(make_table(data, [W*0.22, W*0.38, W*0.4], S))

    h2(story, "B. Surgical Management", S)
    bullet(story, [
        "Surgical haemostasis: direct pressure, ligation, electrocautery, argon beam coagulator.",
        "Topical haemostatic agents: Gelfoam (gelatin sponge), Surgicel (oxidised cellulose), "
          "fibrin glue (thrombin + fibrinogen), bone wax.",
        "Cell salvage (intraoperative): autologous blood recovery to reduce transfusion.",
        "Massive transfusion protocol (MTP): ratio FFP:Platelets:pRBC = 1:1:1 in major haemorrhage.",
        "Surgical correction of underlying cause (e.g., splenectomy in refractory ITP, liver transplant for end-stage liver failure).",
    ], S)
    caution(story, "CRASH-2 TRIAL: Tranexamic acid within 3 hours of trauma -> reduces all-cause mortality. "
            "Give early - benefit lost if given > 3 hours after injury.", S)
    sp(story, 4)

    # ── 11. COMPLICATIONS ─────────────────────────────────────────────────────
    h1(story, "11.  COMPLICATIONS", S)
    data = [
        ["Complication", "Key Features"],
        ["Thrombosis / Thromboembolism",
         "DVT -> PE (most common VTE). Arterial thrombosis -> MI, stroke. "
         "Risk factors: Virchow's triad (stasis, endothelial injury, hypercoagulability)."],
        ["DIC (Disseminated Intravascular Coagulation)",
         "Simultaneous bleeding + clotting. Triggered by sepsis, trauma, obstetric complications, malignancy. "
         "Consumptive coagulopathy: low platelets, fibrinogen, elevated D-dimer, PT/aPTT both prolonged."],
        ["Haemorrhage",
         "From factor deficiency, platelet dysfunction, anticoagulant excess. "
         "Assess bleeding site: mucocutaneous (platelet/vWF problem) vs deep tissue/joints (factor deficiency)."],
        ["Heparin-induced thrombocytopaenia (HIT)",
         "Immune-mediated; anti-heparin-PF4 antibodies -> paradoxical THROMBOSIS despite low platelets. "
         "Stop heparin; switch to argatroban or fondaparinux."],
        ["Antiphospholipid syndrome (APS)",
         "Lupus anticoagulant + anticardiolipin antibodies -> paradoxical thrombosis + recurrent pregnancy loss. "
         "Prolonged aPTT in lab but thrombotic in vivo."],
        ["Overdose of anticoagulants",
         "Heparin: reverse with protamine sulphate (1mg per 100 units heparin). "
         "Warfarin: reverse with Vit K + PCC/FFP. "
         "DOACs: specific reversal agents (idarucizumab, andexanet alfa)."],
    ]
    story.append(make_table(data, [W*0.28, W*0.72], S))
    sp(story, 4)

    # ── 12. VIVA QUESTIONS ────────────────────────────────────────────────────
    h1(story, "12.  VIVA QUESTIONS & ANSWERS", S)
    vivas = [
        ("Q1: What initiates the coagulation cascade in vivo?",
         "TISSUE FACTOR (TF/Factor III) released by damaged endothelium/subendothelial fibroblasts. "
         "TF + circulating Factor VIIa -> TF:VIIa complex = primary initiator. "
         "(NOT contact activation/Factor XII - that is laboratory artefact)"),
        ("Q2: What is the role of thrombin in coagulation?",
         "Thrombin (Factor IIa) is the CENTRAL enzyme. It: "
         "(1) Converts fibrinogen to fibrin monomers. "
         "(2) Activates Factor XIII (cross-links fibrin). "
         "(3) Activates Platelets. "
         "(4) Positive feedback: activates Factors V, VIII, XI. "
         "(5) Negative feedback: activates Protein C (anticoagulant)."),
        ("Q3: What is the difference between PT and aPTT?",
         "PT: tests EXTRINSIC pathway (TF + Factors VII, X, V, II, I) -> prolonged in Vit K deficiency, warfarin, liver disease. "
         "aPTT: tests INTRINSIC pathway (Factors XII, XI, IX, VIII, X, V, II, I) -> prolonged in Haemophilia A/B, heparin. "
         "Both prolonged: DIC, liver failure, common pathway defects."),
        ("Q4: Name the Vitamin K-dependent coagulation factors.",
         "Factors II (prothrombin), VII, IX, X, Protein C, Protein S. "
         "Mnemonic: 1972 (I, IX, VII, II) + Proteins C and S. "
         "Warfarin inhibits Vit K epoxide reductase -> reduces all these."),
        ("Q5: What is Factor V Leiden?",
         "Point mutation (Arg506Gln) in Factor V gene -> FV resistant to inactivation by Activated Protein C (APC resistance). "
         "MOST COMMON hereditary thrombophilia (5% of Caucasians). "
         "Presents with DVT, PE. Treat with anticoagulation."),
        ("Q6: What is DIC and how does it present?",
         "Disseminated Intravascular Coagulation: systemic activation of coagulation -> consumption of factors and platelets. "
         "Simultaneously: bleeding (from depletion) AND thrombosis (microthrombi in small vessels). "
         "Labs: low platelets, low fibrinogen, elevated D-dimer, schistocytes, prolonged PT + aPTT. "
         "Causes: sepsis (most common), trauma, obstetric emergency, malignancy."),
        ("Q7: How does heparin work?",
         "Heparin binds Antithrombin (AT-III) -> conformational change -> increases AT activity ~1000-fold. "
         "AT then rapidly inactivates Thrombin (IIa) and Factor Xa. "
         "UFH also inhibits IXa, XIa. LMWH predominantly inhibits FXa. "
         "Monitored with aPTT (UFH) or anti-Xa levels (LMWH)."),
        ("Q8: What is the cell-based model of coagulation?",
         "Modern (in vivo) model: Three phases - INITIATION (on TF-bearing cells), "
         "AMPLIFICATION (on activated platelets), PROPAGATION (on platelet surface -> thrombin burst). "
         "Explains why Factor XII deficiency does not cause bleeding, and why platelets are central to coagulation."),
        ("Q9: What are D-dimers? When are they elevated?",
         "D-dimers: specific fragments produced when Factor XIIIa-cross-linked fibrin is degraded by plasmin. "
         "Elevated in: DVT, PE, DIC, surgery/trauma, pregnancy, malignancy, MI, infection. "
         "High sensitivity (> 95%) but low specificity for DVT/PE. "
         "Used to RULE OUT DVT/PE (if negative, DVT/PE very unlikely)."),
        ("Q10: What is the antidote for warfarin overdose?",
         "Urgent reversal: Prothrombin Complex Concentrate (PCC/Beriplex) + IV Vitamin K 5-10 mg. "
         "Non-urgent: Oral Vitamin K 1-5 mg (takes 6-12 hours). "
         "Last resort: Fresh Frozen Plasma (FFP - large volumes needed). "
         "Monitor INR after reversal."),
    ]
    for q, a in vivas:
        story.append(Paragraph(q, S["viva_q"]))
        story.append(Paragraph(a, S["viva_a"]))
    sp(story, 4)

    # ── 13. KEY POINTS SUMMARY ────────────────────────────────────────────────
    h1(story, "13.  KEY POINTS SUMMARY  (Quick Revision)", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Haemostasis phases", "Vascular spasm -> Primary (platelet plug) -> Secondary (coagulation cascade) -> Fibrinolysis"],
        ["Extrinsic pathway", "TF + VIIa = PRIMARY in vivo initiator; measured by PT/INR"],
        ["Intrinsic pathway", "Contact activation (XII -> XI -> IX -> VIII); AMPLIFICATION; measured by aPTT"],
        ["Common pathway", "X -> Xa + Va = Prothrombinase -> Thrombin (IIa) -> Fibrinogen -> Fibrin -> cross-link by XIIIa"],
        ["Thrombin (IIa)", "CENTRAL enzyme: makes fibrin, activates platelets + FVIII + FV + XIII, activates Protein C"],
        ["Vit K factors", "II, VII, IX, X, Protein C, Protein S. Warfarin inhibits all. Factor VII falls first (shortest t1/2)."],
        ["PT", "Tests: Extrinsic + Common (VII, X, V, II, I). Prolonged: warfarin, liver disease, Vit K deficiency."],
        ["aPTT", "Tests: Intrinsic + Common (XII, XI, IX, VIII, X, V, II, I). Prolonged: Haemophilia A/B, heparin."],
        ["Anticoagulants", "AT-III (inhibits IIa + Xa), Protein C/S (inactivates FVa + FVIIIa), TFPI (inhibits TF:VIIa)"],
        ["Fibrinolysis", "Plasminogen -> Plasmin (by tPA/uPA) -> degrades fibrin -> D-dimers. Inhibited by tranexamic acid."],
        ["D-dimer", "Specific fibrin degradation product. High sensitivity for DVT/PE but low specificity."],
        ["Haemophilia A/B", "FVIII (A) / FIX (B) deficiency; X-linked recessive; prolonged aPTT; deep bleeds"],
        ["DIC", "Consumptive coagulopathy: low platelets + fibrinogen, high D-dimer, prolonged PT + aPTT; schistocytes"],
        ["Heparin MOA", "Binds AT-III -> 1000x acceleration of AT -> inhibits thrombin + FXa"],
        ["Recent advances", "Cell-based model, DOACs (direct thrombin/FXa inhibitors), ROTEM/TEG, specific reversal agents (idarucizumab)"],
    ]
    story.append(make_table(data, [W*0.25, W*0.75], S))

    sp(story, 5)
    story.append(Paragraph(
        "References: Goldman-Cecil Medicine 2-Vol Set | Miller's Anesthesia 10th ed. | Sabiston Surgery 21st ed. | "
        "Bailey & Love's Surgery 28th ed. | Robbins Pathology | Tietz Laboratory Medicine 7th ed. | "
        "Barash Clinical Anesthesia 9th ed. | AJCC / ATA / ASH Guidelines",
        S["subtitle"]))


# ── MAIN ──────────────────────────────────────────────────────────────────────
def main():
    outpath = "/home/daytona/workspace/ptc-notes/Coagulation_Pathway_ExamNotes.pdf"
    doc = SimpleDocTemplate(
        outpath, pagesize=A4,
        leftMargin=MARGIN, rightMargin=MARGIN,
        topMargin=15*mm, bottomMargin=15*mm,
        title="Coagulation Pathway - Exam Notes",
        author="Orris Medical AI",
        subject="Physiology/Surgery - Coagulation - KNRUHS",
    )
    S = make_styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"PDF generated: {outpath}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Coagulation Pathway - FOCUSED ENT PG Exam Notes (5-6 pages max)
# Color palette: Indigo / Warm Orange / Sage Green (new theme, distinct from purple and teal)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1

FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib", f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFont(TTFont("LibI", f"{FONT_DIR}/LiberationSans-Italic.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB", italic="LibI")
    NM, BD, IT = "Lib", "LibB", "LibI"
except Exception:
    NM, BD, IT = "Helvetica", "Helvetica-Bold", "Helvetica-Oblique"

# ── Palette: Indigo / Orange / Sage ──────────────────────────────────────────
C_H1_BG  = colors.HexColor("#1E3A5F")   # dark navy-indigo
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#B84800")   # deep burnt orange
C_H2_BG  = colors.HexColor("#FFF0E6")   # pale peach
C_H3_FG  = colors.HexColor("#2E6B3E")   # sage green
C_H3_BG  = colors.HexColor("#EAF5ED")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1E3A5F")
C_ALT    = colors.HexColor("#EBF0F7")
C_PEARL  = colors.HexColor("#E8F2FF")
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#1E3A5F")
C_VQ_BG  = colors.HexColor("#EBF0F7")
C_VQ_FG  = colors.HexColor("#1E3A5F")
C_FC_BOX = colors.HexColor("#D0DCF0")
C_FC_HDR = colors.HexColor("#1E3A5F")

M = 15*mm
W_PAGE, H_PAGE = A4
BSIZE = 10.5
BLEAD = 15.5
CLEAD = 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BSIZE, leading=BLEAD,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BSIZE, leading=BLEAD,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CLEAD, textColor=C_BODY)
    s["cellb"] = ParagraphStyle("cellb", fontName=BD, fontSize=9.5, leading=CLEAD, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CLEAD, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BLEAD,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BLEAD,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st, t, S): st.append(Paragraph(t, S["h1"]))
def h2(st, t, S): st.append(Paragraph(t, S["h2"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st, t, S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st, t, S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for cell in row:
            if isinstance(cell, str):
                st = S["cellh"] if ri == 0 else S["cell"]
                nr.append(Paragraph(cell, st))
            else:
                nr.append(cell)
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    cmds = [
        ("BACKGROUND",   (0,0),(-1,0), C_TH),
        ("FONTNAME",     (0,0),(-1,0), BD),
        ("FONTSIZE",     (0,0),(-1,-1), 9.5),
        ("LEADING",      (0,0),(-1,-1), CLEAD),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",          (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",    (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 5),
        ("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",       (0,0),(-1,-1), "TOP"),
    ]
    t.setStyle(TableStyle(cmds))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 3)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = W_PAGE - 2*M
    bw = W * 0.80
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        style = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#B8C8E8") if bold else C_FC_BOX
        rows.append([Paragraph(txt, style)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",          (0,0),(-1,-1), 0.5, C_RULE),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 6),
        ("RIGHTPADDING", (0,0),(-1,-1), 6),
        ("ALIGN",        (0,0),(-1,-1), "CENTER"),
        ("VALIGN",       (0,0),(-1,-1), "MIDDLE"),
    ]
    for i, bg in enumerate(bgs):
        cmds.append(("BACKGROUND",(0,i),(0,i), bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([
        ("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
    ]))
    st.append(outer)
    sp(st, 4)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = W_PAGE - 2*M

    # TITLE
    st.append(Paragraph("COAGULATION PATHWAY", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  Sources: Goldman-Cecil, Miller's Anesthesia, "
        "Sabiston Surgery, Bailey & Love, Robbins Pathology",
        S["sub"]))
    rule(st)
    sp(st, 2)

    # ── 1. DEFINITION ──────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "HAEMOSTASIS: Physiological process to arrest bleeding after vascular injury while maintaining blood fluidity.",
        "COAGULATION CASCADE: Sequential enzymatic activation of clotting factors (zymogens) culminating in "
          "insoluble fibrin clot formation.",
        "Coagulation factors: Plasma proteins (mostly liver-synthesised); circulate as inactive ZYMOGENS; "
          "activated form denoted by suffix 'a' (e.g., X -> Xa).",
        "Ca2+ (Factor IV) and platelet phospholipid surface are essential cofactors at every step.",
    ], S)
    sp(st, 4)

    # ── 2. PATHWAYS OF COAGULATION ─────────────────────────────────────────────
    h1(st, "2.  PATHWAYS OF COAGULATION", S)

    h2(st, "A. Extrinsic Pathway  (Tissue Factor / TF Pathway) -- PRIMARY in vivo initiator", S)
    bl(st, [
        "TRIGGER: Vascular injury -> subendothelial TISSUE FACTOR (TF / Factor III) exposed to blood.",
        "TF + circulating Factor VIIa -> TF:VIIa complex (Extrinsic Tenase).",
        "TF:VIIa activates: Factor X -> Xa (direct) AND Factor IX -> IXa (cross-activates intrinsic pathway).",
        "Limited quickly by TFPI (Tissue Factor Pathway Inhibitor).",
        "TESTED BY: Prothrombin Time (PT) / INR.",
    ], S)

    h2(st, "B. Intrinsic Pathway  (Contact Activation) -- AMPLIFICATION system", S)
    bl(st, [
        "TRIGGER: Contact of blood with negatively charged surfaces (collagen, glass, kaolin).",
        "XII -> XIIa -> XI -> XIa -> IX -> IXa.",
        "IXa + Factor VIIIa + Ca2+ + phospholipid = INTRINSIC TENASE COMPLEX -> activates X -> Xa.",
        "Role in vivo: amplifies thrombin generation initiated by extrinsic pathway.",
        "TESTED BY: aPTT (activated partial thromboplastin time).",
        "NOTE: Factor XII deficiency -> prolonged aPTT but NO clinical bleeding.",
    ], S)

    h2(st, "C. Common Pathway", S)
    bl(st, [
        "Xa + Va + Ca2+ + phospholipid = PROTHROMBINASE COMPLEX.",
        "Prothrombinase: Prothrombin (II) -> THROMBIN (IIa)  [THROMBIN BURST].",
        "Thrombin cleaves fibrinopeptides A + B from Fibrinogen -> Fibrin monomers.",
        "Fibrin monomers polymerise -> Factor XIIIa (activated by thrombin) cross-links fibrin -> STABLE INSOLUBLE CLOT.",
    ], S)
    pearl(st, "THROMBIN (IIa) is the CENTRAL enzyme: makes fibrin, activates platelets, activates FV/FVIII/XIII "
          "(positive feedback), and activates Protein C (negative feedback). (Goldman-Cecil Medicine)", S)

    # Main Cascade Flowchart
    flowchart(st, "COAGULATION CASCADE FLOWCHART", [
        ("EXTRINSIC PATHWAY                           |         INTRINSIC PATHWAY", True),
        ("Tissue injury -> TF exposed                 |   Surface contact: XII -> XIIa -> XI -> XIa", False),
        ("TF + VIIa -> TF:VIIa complex                |   IXa + VIIIa + Ca2+ + PL = Intrinsic Tenase", False),
        ("Activates X -> Xa  (also IX -> IXa)         |   Xa generated", False),
        ("COMMON PATHWAY:  Xa + Va + Ca2+ + PL  =  PROTHROMBINASE COMPLEX", True),
        ("Prothrombin (II)  ->  THROMBIN (IIa)", False),
        ("Fibrinogen (I)  ->  Fibrin monomers  ->  Fibrin polymer", False),
        ("Factor XIII -> XIIIa (activated by Thrombin) -> Cross-linked STABLE FIBRIN CLOT", True),
    ], S)
    sp(st, 2)

    # ── 3. VITAMIN K-DEPENDENT FACTORS ─────────────────────────────────────────
    h1(st, "3.  VITAMIN K-DEPENDENT FACTORS", S)
    bl(st, [
        "Factors II, VII, IX, X, Protein C, Protein S -- all Vitamin K-dependent.",
        "Warfarin inhibits Vitamin K epoxide reductase (VKOR) -> reduces all these factors.",
        "Factor VII has SHORTEST half-life (~6 hrs) -> PT prolonged FIRST with warfarin.",
    ], S)
    caut(st, "Mnemonic: 1972 -> Factors I (prothrombin=II), IX, VII, II + Protein C + Protein S.", S)
    sp(st, 4)

    # ── 4. NATURAL ANTICOAGULANTS ──────────────────────────────────────────────
    h1(st, "4.  NATURAL ANTICOAGULANT SYSTEMS", S)
    data = [
        ["System", "Mechanism", "Clinical Note"],
        ["TFPI",
         "Inhibits TF:VIIa and FXa -- limits initiation phase",
         "Deficiency -> hypercoagulable state"],
        ["Antithrombin-III (AT-III)",
         "Inhibits Thrombin, FXa, FIXa. Acts on endothelial heparan sulfate surface. "
         "Heparin binds AT-III -> 1000x acceleration",
         "AT-III deficiency -> DVT/PE risk. Basis of heparin therapy."],
        ["Protein C + Protein S",
         "Thrombin + thrombomodulin -> activates Protein C. "
         "Activated Protein C + Protein S (cofactor) -> inactivates FVa and FVIIIa",
         "Both Vit K-dependent. Deficiency -> thrombosis. "
         "Factor V Leiden = APC resistance (most common hereditary thrombophilia)."],
        ["TFPI + thrombomodulin",
         "Intact endothelium continuously suppresses coagulation",
         "Endothelial injury removes all these brakes -> coagulation activates"],
    ]
    st.append(tbl(data, [W*0.2, W*0.45, W*0.35], S))
    sp(st, 4)

    # ── 5. FIBRINOLYSIS ────────────────────────────────────────────────────────
    h1(st, "5.  FIBRINOLYSIS (Clot Dissolution)", S)
    bl(st, [
        "Plasminogen -> PLASMIN (by tPA from endothelium, or uPA).",
        "Plasmin degrades cross-linked fibrin -> FIBRIN DEGRADATION PRODUCTS (FDPs) + D-DIMERS.",
        "D-dimer: specific marker of fibrin breakdown; used to screen DVT/PE/DIC.",
        "Fibrinolysis inhibitors: PAI-1 (inhibits tPA), alpha2-antiplasmin (inhibits plasmin).",
        "Antifibrinolytic drugs: Tranexamic acid, Aminocaproic acid -- inhibit plasminogen -> fibrin binding.",
    ], S)
    sp(st, 4)

    # ── 6. COAGULATION TESTS ──────────────────────────────────────────────────
    h1(st, "6.  COAGULATION TESTS  (Investigations)", S)
    data = [
        ["Test", "Pathway", "Normal", "Prolonged in"],
        ["PT / INR",
         "Extrinsic + Common\n(VII, X, V, II, I)",
         "11-14 sec\nINR 0.8-1.2",
         "Warfarin, Vit K deficiency, liver disease, DIC, FVII deficiency"],
        ["aPTT",
         "Intrinsic + Common\n(XII, XI, IX, VIII, X, V, II, I)",
         "25-35 sec",
         "Haemophilia A (FVIII) and B (FIX), Heparin therapy, Lupus anticoagulant, DIC"],
        ["TT (Thrombin Time)",
         "Common only\n(Fibrinogen -> Fibrin)",
         "14-16 sec",
         "Hypofibrinogenaemia, dysfibrinogenaemia, heparin effect, DIC"],
        ["D-dimer",
         "Fibrinolysis",
         "< 0.5 mg/L",
         "DVT, PE, DIC, surgery, malignancy, pregnancy. High sensitivity, low specificity."],
        ["Platelet count",
         "Primary haemostasis",
         "150-400 x10^9/L",
         "ITP, DIC, TTP, heparin-induced (HIT). Surgical risk if < 50 x10^9/L."],
        ["Fibrinogen",
         "Common pathway",
         "1.5-4.0 g/L",
         "DIC (consumed), liver failure. Critical if < 1.0 g/L -> replace with cryoprecipitate."],
    ]
    st.append(tbl(data, [W*0.13, W*0.22, W*0.15, W*0.5], S))
    caut(st, "Both PT and aPTT prolonged = DIC / liver failure / common pathway defect / Vit K deficiency / "
         "supratherapeutic warfarin + heparin together.", S)
    sp(st, 4)

    # ── 7. KEY CLINICAL DISORDERS ─────────────────────────────────────────────
    h1(st, "7.  KEY CLINICAL DISORDERS (Relevant to ENT/Surgical Practice)", S)
    data = [
        ["Disorder", "Defect / Cause", "PT", "aPTT", "Management"],
        ["Haemophilia A",
         "FVIII deficient\n(X-linked recessive)",
         "Normal", "Long",
         "FVIII concentrate\nDDAVP (mild cases)"],
        ["Haemophilia B",
         "FIX deficient\n(X-linked recessive)",
         "Normal", "Long",
         "FIX concentrate"],
        ["von Willebrand Disease",
         "vWF deficiency\n(most common inherited)",
         "Normal", "Normal/long",
         "DDAVP 0.3 mcg/kg IV\nvWF concentrate"],
        ["Vit K deficiency /\nWarfarin overdose",
         "Reduced II,VII,IX,X\nVKOR inhibition",
         "Long", "Long",
         "Vit K (IV/oral)\nPCC (urgent)\nFFP"],
        ["Liver failure",
         "Reduced all factors\nexcept FVIII",
         "Long", "Long",
         "Vit K, FFP\nCryoprecipitate\nPlatelet transfusion"],
        ["DIC",
         "Consumption of all\nfactors + platelets",
         "Long", "Long",
         "Treat cause\nFFP + Cryo + Platelets"],
    ]
    st.append(tbl(data, [W*0.19, W*0.21, W*0.07, W*0.07, W*0.46], S))
    sp(st, 4)

    # ── 8. PERIOPERATIVE MANAGEMENT (Anticoagulation) ─────────────────────────
    h1(st, "8.  PERIOPERATIVE MANAGEMENT OF ANTICOAGULATION", S)

    h2(st, "A. Common Anticoagulants and Reversal", S)
    data = [
        ["Drug", "Mechanism", "Monitor", "Reversal"],
        ["Heparin (UFH)",
         "Binds AT-III -> inhibits IIa + FXa",
         "aPTT (target 60-100 sec)",
         "Protamine sulphate 1mg per 100 units heparin"],
        ["LMWH (enoxaparin)",
         "Anti-FXa predominant via AT-III",
         "Anti-Xa level (if needed)",
         "Partial reversal: Protamine. No complete antidote."],
        ["Warfarin",
         "Inhibits VKOR -> reduces II,VII,IX,X,\nProtein C+S",
         "INR (target 2-3 or 2.5-3.5 for valves)",
         "Urgent: PCC (Beriplex) + Vit K 5-10mg IV\nNon-urgent: oral Vit K 1-5 mg"],
        ["DOACs (dabigatran,\nrivaroxaban, apixaban)",
         "Dabigatran: direct thrombin inhibitor\nRivaroxaban/Apixaban: direct FXa inhibitor",
         "No routine monitoring",
         "Dabigatran: idarucizumab (Praxbind)\nFXa inhibitors: andexanet alfa\nPCC if specific antidote unavailable"],
    ]
    st.append(tbl(data, [W*0.16, W*0.28, W*0.2, W*0.36], S))

    h2(st, "B. Blood Products", S)
    data = [
        ["Product", "Contains", "Indication"],
        ["FFP (Fresh Frozen Plasma)",
         "All coagulation factors",
         "Acute coagulopathy, warfarin reversal (if PCC unavailable), DIC, liver failure"],
        ["Cryoprecipitate",
         "Fibrinogen, FVIII, vWF, FXIII, fibronectin (concentrated)",
         "Fibrinogen < 1.0 g/L (DIC, liver failure), Haemophilia A, vWD"],
        ["Platelet concentrate",
         "Platelets",
         "Count < 50 x10^9/L pre-surgery; < 100 x10^9/L for intracranial/ophthalmic surgery"],
        ["PCC (Prothrombin\nComplex Concentrate)",
         "Concentrated II, VII, IX, X\n(3-factor or 4-factor)",
         "URGENT warfarin reversal, DOAC reversal, emergency surgery in anticoagulated patient"],
        ["Tranexamic acid",
         "Antifibrinolytic: inhibits plasminogen activation",
         "Surgical haemostasis, trauma (within 3 hrs - CRASH-2), tonsillectomy bleeding"],
    ]
    st.append(tbl(data, [W*0.2, W*0.35, W*0.45], S))
    caut(st, "Pre-op ENT surgery: Stop warfarin 5 days before; bridge with LMWH if high risk. "
         "Stop aspirin 7 days before elective surgery. DOACs: stop 24-48 hrs (48-72 hrs if renal impairment).", S)
    sp(st, 4)

    # ── 9. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "9.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What initiates coagulation in vivo?",
         "Tissue Factor (TF/Factor III) + Factor VIIa -> TF:VIIa complex. "
         "This is the PRIMARY in vivo initiator (extrinsic pathway). NOT Factor XII contact activation."),
        ("Q2: What is the role of Thrombin?",
         "Thrombin (IIa) is the central enzyme: (1) Converts fibrinogen -> fibrin; "
         "(2) Activates Factor XIII (cross-links fibrin); "
         "(3) Activates Platelets; (4) Positive feedback: activates FV, FVIII, FXI; "
         "(5) Negative feedback: activates Protein C."),
        ("Q3: PT vs aPTT -- what does each test?",
         "PT: Extrinsic + Common pathway (Factor VII, X, V, II, I). Prolonged: warfarin, Vit K deficiency, liver disease. "
         "aPTT: Intrinsic + Common (Factors XII, XI, IX, VIII, X, V, II, I). Prolonged: Haemophilia A/B, heparin. "
         "BOTH prolonged: DIC, liver failure, common pathway defect."),
        ("Q4: Name Vitamin K-dependent coagulation factors.",
         "Factors II, VII, IX, X + Protein C + Protein S. "
         "Factor VII has shortest half-life (~6 hrs) -> PT prolonged first with warfarin."),
        ("Q5: How does heparin work?",
         "Binds Antithrombin-III (AT-III) -> conformational change -> increases AT activity ~1000-fold. "
         "AT-III then rapidly inhibits Thrombin (IIa) and Factor Xa. "
         "UFH monitored by aPTT (target 60-100 sec). Reversed by protamine sulphate."),
        ("Q6: What is D-dimer? When is it elevated?",
         "Specific fragment from plasmin degradation of cross-linked fibrin (Factor XIIIa-stabilised). "
         "Elevated in: DVT, PE, DIC, surgery, malignancy, pregnancy, sepsis. "
         "High sensitivity for DVT/PE (if negative -> excludes DVT/PE); low specificity."),
        ("Q7: How do you manage a warfarin patient needing urgent ENT surgery?",
         "URGENT: PCC (Beriplex/Octaplex) + Vitamin K 5-10 mg IV -> reverses within 30-60 min. "
         "Check INR before and 30 min after PCC. "
         "FFP as alternative if PCC unavailable (large volumes needed). "
         "Elective: stop warfarin 5 days pre-op; bridge with LMWH if high VTE risk."),
        ("Q8: What is DIC?",
         "Disseminated Intravascular Coagulation = systemic coagulation activation -> consumption of all factors and platelets. "
         "Presents with simultaneous BLEEDING + THROMBOSIS. "
         "Labs: low platelets, low fibrinogen, high D-dimer, schistocytes, prolonged PT + aPTT. "
         "Causes: sepsis, trauma, obstetric emergency, malignancy. "
         "Treatment: treat underlying cause + FFP + cryoprecipitate + platelets."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 4)

    # ── 10. KEY POINTS SUMMARY ────────────────────────────────────────────────
    h1(st, "10.  KEY POINTS SUMMARY", S)
    data = [
        ["POINT", "FACT"],
        ["Primary initiator in vivo", "Tissue Factor (TF) + VIIa -> extrinsic pathway. NOT Factor XII."],
        ["Central enzyme", "Thrombin (IIa): makes fibrin, activates platelets, positive + negative feedback"],
        ["Extrinsic pathway", "TF + VIIa -> Xa; TESTED by PT/INR"],
        ["Intrinsic pathway", "XII->XI->IX + VIII -> Xa; AMPLIFICATION; TESTED by aPTT"],
        ["Common pathway", "Xa + Va -> Prothrombinase -> Thrombin -> Fibrin -> XIIIa -> stable clot"],
        ["Vit K factors", "II, VII, IX, X, Protein C, S. Warfarin inhibits all. FVII falls first."],
        ["Natural anticoagulants", "TFPI (limits TF:VIIa), AT-III (inhibits IIa+Xa), Protein C+S (inactivates FVa+FVIIIa)"],
        ["PT prolonged", "Warfarin, Vit K deficiency, liver disease, FVII deficiency, DIC"],
        ["aPTT prolonged", "Haemophilia A (FVIII) / B (FIX), heparin, lupus anticoagulant, DIC"],
        ["D-dimer elevated", "DVT, PE, DIC, surgery, malignancy - high sensitivity, low specificity"],
        ["Heparin reversal", "Protamine sulphate (1mg per 100 units UFH)"],
        ["Warfarin reversal", "Urgent: PCC + Vit K IV. Non-urgent: oral Vit K."],
        ["Fibrinolysis", "Plasmin (from tPA/uPA) degrades fibrin -> D-dimers + FDPs. Tranexamic acid inhibits this."],
        ["DIC labs", "Low platelets + low fibrinogen + high D-dimer + prolonged PT and aPTT + schistocytes"],
    ]
    st.append(tbl(data, [W*0.3, W*0.7], S))

    sp(st, 5)
    st.append(Paragraph(
        "References: Goldman-Cecil Medicine | Miller's Anesthesia 10e | Sabiston Surgery | "
        "Bailey & Love's Surgery 28e | Robbins Pathology | Tietz Laboratory Medicine",
        S["sub"]))


# ── MAIN ──────────────────────────────────────────────────────────────────────
def main():
    out = "/home/daytona/workspace/ptc-notes/Coagulation_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Coagulation Pathway - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG - Coagulation")
    S = styles()
    st = []
    build(st, S)
    doc.build(st)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# ENT Manifestations in Thyroid Disease - Focused ENT PG Exam Notes
# NEW Palette: Burgundy/wine headings, teal-blue subheadings, olive H3
# Distinct from: teal/coral (PTC), purple/green (coag), navy/orange (coag v2)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFont(TTFont("LibI", f"{FONT_DIR}/LiberationSans-Italic.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB", italic="LibI")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Burgundy / Teal-Blue / Olive ────────────────────────────────────
C_H1_BG  = colors.HexColor("#6B0F1A")   # deep burgundy/wine
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#005F73")   # rich teal-blue
C_H2_BG  = colors.HexColor("#E8F6F8")   # pale teal
C_H3_FG  = colors.HexColor("#4A5E00")   # olive green
C_H3_BG  = colors.HexColor("#F3F7E4")   # pale olive
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#6B0F1A")
C_ALT    = colors.HexColor("#FAEAEA")   # pale rose alt rows
C_PEARL  = colors.HexColor("#E8F6F8")   # teal pearl bg
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#6B0F1A")
C_VQ_BG  = colors.HexColor("#F3EEF5")
C_VQ_FG  = colors.HexColor("#6B0F1A")
C_FC_BOX = colors.HexColor("#D4EAF0")
C_FC_HDR = colors.HexColor("#005F73")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st, t, S): st.append(Paragraph(t, S["h1"]))
def h2(st, t, S): st.append(Paragraph(t, S["h2"]))
def h3(st, t, S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st, t, S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st, t, S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for cell in row:
            if isinstance(cell, str):
                nr.append(Paragraph(cell, S["cellh"] if ri == 0 else S["cell"]))
            else:
                nr.append(cell)
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,0), C_TH),
        ("FONTNAME",     (0,0),(-1,0), BD),
        ("FONTSIZE",     (0,0),(-1,-1), 9.5),
        ("LEADING",      (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",          (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",    (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",   (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",       (0,0),(-1,-1), "TOP"),
    ]))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 3)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = WP - 2*M
    bw = W * 0.82
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        styl = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#B8D4DC") if bold else C_FC_BOX
        rows.append([Paragraph(txt, styl)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",(0,0),(-1,-1),0.5,C_RULE),
        ("TOPPADDING",(0,0),(-1,-1),4),("BOTTOMPADDING",(0,0),(-1,-1),4),
        ("LEFTPADDING",(0,0),(-1,-1),6),("RIGHTPADDING",(0,0),(-1,-1),6),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]
    for i, bg in enumerate(bgs): cmds.append(("BACKGROUND",(0,i),(0,i),bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([
        ("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
    ]))
    st.append(outer); sp(st, 4)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("ENT MANIFESTATIONS IN THYROID DISEASE", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Cummings Otolaryngology 7e, Scott-Brown's OHN&S 8e, Bailey & Love 28e, Goldman-Cecil Medicine",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. INTRODUCTION ────────────────────────────────────────────────────────
    h1(st, "1.  INTRODUCTION", S)
    bl(st, [
        "Thyroid disorders are the MOST COMMON endocrine disorders seen in ENT practice.",
        "The thyroid gland is anatomically intimate with key ENT structures: larynx, trachea, oesophagus, "
          "RLN, SLN, and cervical lymphatics.",
        "Both HYPO- and HYPERTHYROIDISM produce distinct ENT manifestations.",
        "Thyroid MASSES (goitre, malignancy) cause compressive ENT symptoms.",
        "Post-treatment complications (surgery, RAI, radiotherapy) also produce ENT sequelae.",
    ], S)
    sp(st, 4)

    # ── 2. CLASSIFICATION ──────────────────────────────────────────────────────
    h1(st, "2.  CLASSIFICATION OF ENT MANIFESTATIONS", S)
    data = [
        ["Category", "Conditions", "ENT Relevance"],
        ["Hypothyroidism",
         "Hashimoto thyroiditis, post-surgical, iodine deficiency, post-RAI, post-RT",
         "Hearing loss, hoarseness, macroglossia, middle ear effusion, vertigo, dysphagia"],
        ["Hyperthyroidism / Thyrotoxicosis",
         "Graves' disease, toxic MNG, toxic adenoma",
         "Proptosis/orbitopathy, tremor of voice, sensorineural hearing loss, tinnitus, anxiety/palpitations"],
        ["Thyroid Mass / Goitre",
         "MNG, malignant thyroid tumours, Riedel's thyroiditis",
         "Tracheal compression/deviation, dysphagia, dysphonia (RLN), stridor, cervical LN"],
        ["Post-treatment",
         "Post-thyroidectomy, post-RT to neck",
         "RLN palsy, hypoparathyroidism, hypothyroidism, tracheomalacia, wound complications"],
        ["Congenital",
         "Congenital hypothyroidism, Pendred syndrome",
         "Sensorineural hearing loss, goitre, speech delay, macroglossia"],
    ]
    st.append(tbl(data, [W*0.18, W*0.3, W*0.52], S))
    sp(st, 4)

    # ── 3. HYPOTHYROIDISM - ENT MANIFESTATIONS ────────────────────────────────
    h1(st, "3.  HYPOTHYROIDISM -- ENT MANIFESTATIONS", S)

    h2(st, "A. Ear", S)
    bl(st, [
        "SENSORINEURAL HEARING LOSS (SNHL): bilateral, symmetric, progressive; worsens with severity of hypothyroidism. "
          "Mechanism: mucopolysaccharide deposits in cochlear structures, reduced endolymph resorption.",
        "CONDUCTIVE HEARING LOSS: due to oedema of Eustachian tube mucosa -> middle ear effusion (glue ear).",
        "MIDDLE EAR EFFUSION (GLUE EAR): myxoedematous mucous in middle ear; common, especially in children.",
        "TINNITUS: occurs in conjunction with hearing loss.",
        "VERTIGO: experienced in 2/3 of hypothyroid patients; usually mild, brief attacks; "
          "ENG changes may be absent. (Cummings ORL 7e)",
    ], S)
    pearl(st, "PEARL: Hypothyroidism is a REVERSIBLE cause of sensorineural hearing loss and middle ear effusion. "
          "ALWAYS check TFTs in a child with bilateral glue ear or unexplained SNHL. (Cummings ORL 7e)", S)

    h2(st, "B. Nose and Throat", S)
    bl(st, [
        "HOARSENESS: gradual, progressive; due to mucopolysaccharide infiltration of vocal cord submucosa "
          "-> thickened, oedematous cords. Voice becomes low-pitched, husky, slow.",
        "MACROGLOSSIA: enlarged tongue from myxoedematous deposits -> affects speech, swallowing; "
          "may cause obstructive sleep apnoea (OSA).",
        "DYSPHAGIA: oropharyngeal dysphagia from macroglossia + pharyngeal oedema.",
        "NASAL OBSTRUCTION: mucosal oedema of nasal mucosa -> rhinitis-like symptoms, blocked nose.",
        "SLEEP DISORDERED BREATHING / OSA: macroglossia + pharyngeal myxoedema + obesity -> upper airway obstruction.",
        "PERIORBITAL OEDEMA: myxoedematous periorbital puffiness (non-pitting); characteristic facies.",
        "LOSS OF LATERAL EYEBROW (Hertoghe's sign): outer 1/3 eyebrow loss; classical sign.",
    ], S)

    h2(st, "C. Congenital Hypothyroidism (Cretinism)", S)
    bl(st, [
        "Congenital SNHL - if untreated leads to deaf-mutism.",
        "Macroglossia, large protruding tongue.",
        "Delayed speech and language development.",
        "Neonatal goitre in endemic areas.",
        "Pendred Syndrome: autosomal recessive; biallelic SLC26A4 mutation -> sensorineural hearing loss + goitre + "
          "abnormal perchlorate discharge test; Mondini cochlear dysplasia on imaging.",
    ], S)
    pearl(st, "PENDRED SYNDROME: Most common syndromic cause of congenital hearing loss with goitre. "
          "Mutation: SLC26A4 (pendrin). Features: SNHL (often prelingual), goitre, abnormal perchlorate test, "
          "enlarged vestibular aqueduct on CT temporal bone. (Cummings ORL)", S)

    h2(st, "D. Post-RT / Post-Laryngectomy Hypothyroidism", S)
    bl(st, [
        "Hypothyroidism after neck irradiation (for H&N cancer, laryngectomy + RT): onset 4 months - 1 year.",
        "Risk factors: high radiation dose, combined surgery + RT, no midline shielding.",
        "Monitor TFTs every 3-6 months in first year, then annually, after neck RT + laryngectomy. (Cummings ORL 7e)",
        "Hypothyroidism post-treatment -> WORSENS voice, swallowing, hearing if not treated.",
    ], S)
    sp(st, 4)

    # ── 4. HYPERTHYROIDISM -- ENT MANIFESTATIONS ──────────────────────────────
    h1(st, "4.  HYPERTHYROIDISM / THYROTOXICOSIS -- ENT MANIFESTATIONS", S)

    h2(st, "A. Graves' Ophthalmopathy (Thyroid Eye Disease -- TED)", S)
    bl(st, [
        "MOST IMPORTANT ENT/orbital manifestation of Graves' disease.",
        "Occurs in 25-50% of Graves' patients; may precede, coincide, or follow thyrotoxicosis.",
        "Mechanism: TSH receptor antibodies (TRAb) + T-cell mediated inflammation of orbital fibroblasts "
          "-> glycosaminoglycan deposition -> orbital tissue expansion.",
    ], S)
    data = [
        ["Clinical Feature", "Detail"],
        ["Proptosis (exophthalmos)",
         "MOST COMMON sign; bilateral (though often asymmetric). Due to expanded orbital contents. "
         "Measured by Hertel exophthalmometer (normal < 20 mm; significant if > 22 mm or > 2mm asymmetry)."],
        ["Lid retraction / Lid lag",
         "Upper lid retraction: Dalrymple's sign (white sclera visible above iris). "
         "Lid lag on downgaze: von Graefe's sign. Due to sympathetic overactivity + fibrosis."],
        ["Periorbital / conjunctival oedema",
         "Chemosis (conjunctival oedema), periorbital puffiness, redness."],
        ["Restricted ocular motility",
         "Diplopia due to extraocular muscle fibrosis (inferior rectus most commonly involved). "
         "Restricted upgaze most common complaint."],
        ["Exposure keratopathy",
         "Corneal exposure from proptosis + incomplete lid closure -> corneal ulceration."],
        ["Optic neuropathy (dysthyroid)",
         "MOST SERIOUS complication: apical crowding by enlarged muscles compresses optic nerve. "
         "Presents with reduced visual acuity, colour vision changes, RAPD. EMERGENCY - requires decompression."],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))
    caut(st, "CLINICAL ACTIVITY SCORE (CAS): Scores activity (0-7) to guide treatment. "
         "CAS >= 3 = active disease -> steroids + orbital RT. "
         "Optic neuropathy = EMERGENCY -> IV methylprednisolone + urgent orbital decompression surgery.", S)

    h2(st, "B. Ear", S)
    bl(st, [
        "SENSORINEURAL HEARING LOSS: reported in hyperthyroidism; likely vascular mechanism (cochlear ischaemia).",
        "TINNITUS: pulsatile tinnitus from increased cardiac output and hyperdynamic circulation.",
        "Increased bone resorption in hyperthyroidism may affect temporal bone density.",
    ], S)

    h2(st, "C. Voice / Larynx", S)
    bl(st, [
        "VOICE TREMOR: fine tremor of laryngeal muscles -> tremulous voice in thyrotoxicosis.",
        "Voice may be HIGH-PITCHED due to sympathetic overactivity of laryngeal muscles.",
        "In Graves' disease: thyroid enlargement may compress/stretch the RLN -> hoarseness (rare, usually in large goitre).",
    ], S)

    h2(st, "D. Subacute (De Quervain's) Thyroiditis - ENT Features", S)
    bl(st, [
        "Painful thyroid swelling with REFERRED OTALGIA (pain radiates to ear) -- ENT presentation.",
        "Pain worse on turning head; associated with fever, malaise, dysphagia.",
        "Transient thyrotoxicosis followed by hypothyroidism.",
        "Can mimic peritonsillar abscess or deep neck infection in ENT clinic.",
        "Treatment: NSAIDs / steroids; self-limiting.",
    ], S)
    pearl(st, "PEARL: Referred otalgia + painful neck swelling in a febrile patient = consider De Quervain's thyroiditis. "
          "Pain radiates to ear via Arnold's nerve (X) or Jacobson's nerve (IX). (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 5. GOITRE / THYROID MASS -- COMPRESSIVE ENT FEATURES ─────────────────
    h1(st, "5.  GOITRE / THYROID MASS -- COMPRESSIVE ENT SYMPTOMS", S)
    data = [
        ["Structure Compressed", "Symptom / Sign", "Clinical Note"],
        ["Trachea",
         "Dyspnoea, stridor (inspiratory or biphasic), tracheal deviation",
         "Intrathoracic (retrosternal) goitre -> Pemberton's sign: facial plethora/stridor on raising arms. "
         "CT neck/chest to assess tracheal compression before surgery."],
        ["Oesophagus",
         "Dysphagia (especially solids), globus sensation",
         "Posterior goitre more likely to compress oesophagus. Barium swallow / OGD if needed."],
        ["Recurrent Laryngeal Nerve (RLN)",
         "Hoarseness, dysphonia, bovine cough",
         "Suggests malignant invasion (RLN compression by benign goitre is uncommon). "
         "MANDATES indirect laryngoscopy + CT staging. May indicate PTC or anaplastic Ca."],
        ["Superior Laryngeal Nerve (SLN) external branch",
         "Loss of high pitch, vocal fatigue",
         "More subtle than RLN. Affects cricothyroid muscle."],
        ["Cervical sympathetic chain",
         "Horner syndrome: ptosis, miosis, anhidrosis",
         "Suggests advanced malignant invasion (T4b disease)."],
        ["Internal jugular vein / subclavian",
         "Facial/neck oedema, distended neck veins",
         "Superior vena cava (SVC) syndrome in massive retrosternal goitre or advanced malignancy."],
        ["Cervical lymph nodes",
         "Cervical lymphadenopathy",
         "PTC: lymphotropic; lateral neck nodes Level II-V. Central compartment Level VI first."],
    ]
    st.append(tbl(data, [W*0.22, W*0.28, W*0.5], S))

    # Compression flowchart
    flowchart(st, "APPROACH TO COMPRESSIVE THYROID SYMPTOMS", [
        ("Patient with Goitre + Compressive Symptoms (dyspnoea, dysphagia, hoarseness)", True),
        ("History: Duration, rate of growth, weight loss, pain, radiation exposure, family history", False),
        ("Examination: Goitre size, nodule, LN, vocal cord assessment (indirect laryngoscopy)", False),
        ("Investigations: TFTs, USG neck, FNAC (if nodule), CT neck/chest (if retrosternal / airway concern)", False),
        ("Indirect Laryngoscopy: MANDATORY - assess vocal cord mobility (RLN function)", False),
        ("MDT decision: Surgery (thyroidectomy +/- neck dissection) vs Medical / RAI vs Observation", True),
    ], S)
    sp(st, 2)

    # ── 6. POST-THYROIDECTOMY ENT COMPLICATIONS ───────────────────────────────
    h1(st, "6.  POST-THYROIDECTOMY ENT COMPLICATIONS", S)
    data = [
        ["Complication", "Mechanism", "ENT Feature / Management"],
        ["RLN injury (unilateral)",
         "Neuropraxia or transection of RLN during thyroid surgery",
         "Hoarseness, breathy voice, aspiration. Laryngoscopy: immobile vocal cord. "
         "Most recover in 3-6 months (if neuropraxia). Permanent: medialisation thyroplasty / injection."],
        ["RLN injury (bilateral)",
         "Both RLNs damaged (rare)",
         "Bilateral vocal cord palsy -> stridor, severe airway obstruction -> EMERGENCY tracheostomy. "
         "Subglottic airway severely compromised."],
        ["SLN (external branch) injury",
         "Damaged during superior pole ligation",
         "Loss of high pitch, vocal fatigue, reduced projection. Cricothyroid paralysis. "
         "Cricothyroid vibrissae reduced. Affects professional voice users significantly."],
        ["Hypoparathyroidism",
         "Devascularisation of parathyroid glands",
         "Hypocalcaemia -> perioral tingling, Chvostek's sign, Trousseau's sign, laryngospasm, tetany. "
         "Monitor calcium post-op 6-hourly. Treat: Ca gluconate IV + calcitriol + oral calcium."],
        ["Tracheomalacia",
         "Chronic tracheal compression -> cartilaginous rings weakened",
         "Airway collapse post-thyroid removal. Rare. Presents immediately post-extubation with "
         "severe stridor. Management: re-intubation, tracheostomy if severe."],
        ["Wound haematoma",
         "Post-op bleeding into neck",
         "Airway compression. EMERGENCY: bedside wound opening to decompose, then formal re-exploration. "
         "Drain insertion + close monitoring for first 24 hrs."],
        ["Chyle leak",
         "Thoracic duct injury (left lateral neck dissection)",
         "Chylous fistula: milky drainage day 2-3, especially after fatty meal. "
         "Conservative: low-fat diet, pressure dressing, octreotide. Surgical ligation if fails."],
        ["Post-RT hypothyroidism",
         "Radiation damage to thyroid after neck RT",
         "Insidious onset; worsens voice/swallowing/hearing. Check TFTs every 3-6 months. "
         "Treat: levothyroxine replacement."],
    ]
    st.append(tbl(data, [W*0.22, W*0.25, W*0.53], S))
    caut(st, "EMERGENCY: Bilateral RLN palsy + stridor post-thyroidectomy = immediate tracheostomy. "
         "Neck haematoma causing airway compromise = OPEN THE WOUND AT THE BEDSIDE IMMEDIATELY.", S)
    sp(st, 4)

    # ── 7. PENDRED SYNDROME (Special Topic for ENT PG) ────────────────────────
    h1(st, "7.  PENDRED SYNDROME  (Key ENT-Endocrine Syndrome)", S)
    data = [
        ["Feature", "Detail"],
        ["Definition",       "Autosomal recessive syndrome: SNHL + goitre + abnormal perchlorate discharge test"],
        ["Gene",             "SLC26A4 (encodes pendrin - anion transporter); chromosome 7q31"],
        ["Hearing loss",     "Bilateral SNHL; often congenital/prelingual; progressive. Enlarged vestibular aqueduct (EVA) on CT."],
        ["Cochlear anomaly", "Mondini dysplasia (incomplete cochlear partition type II) on CT temporal bones"],
        ["Goitre",           "Diffuse or nodular; from defective thyroid iodide organification; may be euthyroid"],
        ["Perchlorate test", "Abnormal perchlorate discharge > 10% (confirms defective organification)"],
        ["Thyroid function", "Usually euthyroid; subclinical hypothyroidism possible; frank hypothyroidism in ~50%"],
        ["Management",       "Hearing aids / cochlear implantation for SNHL. Thyroxine for hypothyroidism. Avoid iodine-depleted diet."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    pearl(st, "PENDRED SYNDROME = 2nd most common cause of congenital SNHL after Connexin 26 (GJB2) mutation. "
          "Triad: SNHL + Goitre + Abnormal perchlorate test. CT temporal bone: enlarged vestibular aqueduct. (Cummings ORL)", S)
    sp(st, 4)

    # ── 8. INVESTIGATIONS ─────────────────────────────────────────────────────
    h1(st, "8.  INVESTIGATIONS", S)
    data = [
        ["Investigation", "Purpose"],
        ["TFTs (TSH, free T4, T3)", "First-line; TSH most sensitive. TSH low -> hyperthyroidism; high -> hypothyroidism."],
        ["Anti-TPO, anti-Tg antibodies", "Hashimoto thyroiditis diagnosis; risk of hypothyroidism."],
        ["TRAb (TSH receptor antibodies)", "Graves' disease diagnosis and monitoring."],
        ["USG neck (thyroid + LN)", "Thyroid nodule characterisation; goitre size; lymphadenopathy assessment."],
        ["FNAC (USG-guided)", "Cytological diagnosis of thyroid nodule. Bethesda classification."],
        ["CT neck/chest", "Retrosternal goitre; tracheal compression; malignancy staging. Avoid iodinated contrast if RAI planned."],
        ["Indirect / Video laryngoscopy", "MANDATORY pre-op. Vocal cord mobility assessment (RLN function)."],
        ["Pure Tone Audiogram + Tympanometry", "Hearing loss type (SNHL vs conductive); middle ear effusion (type B tympanogram)."],
        ["ABR / ASSR", "Threshold estimation in children with hypothyroid hearing loss; pre-cochlear implant workup."],
        ["CT temporal bones", "Pendred syndrome: enlarged vestibular aqueduct, Mondini dysplasia."],
        ["Perchlorate discharge test", "Pendred syndrome: abnormal if > 10% iodide discharge after perchlorate."],
        ["Hertel exophthalmometry", "Measure proptosis in Graves' ophthalmopathy. Normal < 20 mm."],
        ["MRI orbits", "Graves' ophthalmopathy: assess extraocular muscle enlargement, optic nerve compression."],
        ["Radioiodine (I-123) scan", "Post-thyroidectomy RAI planning; toxic goitre differentiation."],
    ]
    st.append(tbl(data, [W*0.32, W*0.68], S))
    sp(st, 4)

    # ── 9. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "9.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What are the ENT manifestations of hypothyroidism?",
         "Ear: SNHL (bilateral, progressive), conductive HL (middle ear effusion from ET oedema), vertigo, tinnitus. "
         "Nose/throat: hoarseness (myxoedematous VC thickening), macroglossia, nasal obstruction, dysphagia, OSA. "
         "Eyes: periorbital myxoedema, loss of lateral eyebrows (Hertoghe's sign)."),
        ("Q2: What is Pendred syndrome?",
         "Autosomal recessive; SLC26A4 mutation. "
         "Triad: bilateral SNHL (congenital, progressive) + Goitre + Abnormal perchlorate discharge test (> 10%). "
         "CT: enlarged vestibular aqueduct (EVA) + Mondini cochlear dysplasia. "
         "2nd most common genetic cause of congenital SNHL."),
        ("Q3: What is Graves' ophthalmopathy and its most serious complication?",
         "Thyroid Eye Disease (TED): TSH receptor antibody-mediated orbital fibroblast activation "
         "-> glycosaminoglycan deposition -> proptosis, lid retraction, restricted EOM, chemosis. "
         "Most serious complication: Dysthyroid optic neuropathy - apical compression of optic nerve "
         "-> reduced VA, colour vision changes, RAPD. EMERGENCY: IV methylprednisolone + orbital decompression."),
        ("Q4: What are the ENT features of a large thyroid goitre?",
         "Compressive: tracheal deviation/compression (stridor, dyspnoea), dysphagia (oesophageal compression), "
         "hoarseness (RLN compression - suggests malignancy), Pemberton's sign (retrosternal goitre). "
         "Malignant features: hoarseness + fixed hard nodule + rapid growth + LN metastases."),
        ("Q5: What is Pemberton's sign?",
         "Facial congestion, plethora, and inspiratory stridor on raising both arms above the head. "
         "Indicates superior mediastinal compression / retrosternal goitre causing SVC/tracheal obstruction. "
         "POSITIVE Pemberton's = indication for urgent thyroidectomy."),
        ("Q6: What are the post-thyroidectomy ENT complications and their management?",
         "RLN injury (unilateral) -> hoarseness; most recover; permanent -> thyroplasty. "
         "RLN injury (bilateral) -> emergency tracheostomy. "
         "Hypoparathyroidism -> hypocalcaemia -> laryngospasm/tetany; IV Ca gluconate + calcitriol. "
         "SLN injury -> loss of high pitch; affects cricothyroid. "
         "Tracheomalacia -> airway collapse post-extubation; tracheostomy. "
         "Haematoma -> airway compression -> OPEN WOUND AT BEDSIDE."),
        ("Q7: What is De Quervain's thyroiditis and its ENT features?",
         "Subacute granulomatous thyroiditis (likely viral). "
         "ENT: painful neck swelling + referred otalgia (via Arnold's/Jacobson's nerve), fever, dysphagia. "
         "Transient thyrotoxicosis phase followed by hypothyroidism. Self-limiting. "
         "Treatment: NSAIDs / prednisolone. Mimics peritonsillar abscess or deep neck infection."),
        ("Q8: How does hypothyroidism cause hearing loss?",
         "SNHL: mucopolysaccharide deposits in spiral ligament, stria vascularis, Reissner's membrane. "
         "Reduced endolymph resorption. Cochlear blood flow reduced. "
         "Conductive HL: Eustachian tube oedema -> middle ear effusion (glue ear). "
         "KEY: Hypothyroid HL is REVERSIBLE with thyroxine replacement - important clinical point."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 4)

    # ── 10. KEY POINTS SUMMARY ────────────────────────────────────────────────
    h1(st, "10.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Hypothyroid - Ear",
         "Bilateral progressive SNHL + Middle ear effusion (glue ear from ET oedema) + Vertigo + Tinnitus. "
         "REVERSIBLE with thyroxine. Check TFTs in bilateral glue ear."],
        ["Hypothyroid - Voice",
         "Progressive hoarseness: myxoedematous vocal cord thickening -> low-pitched, husky voice"],
        ["Hypothyroid - Oral",
         "Macroglossia -> dysphagia, OSA, speech change. Periorbital myxoedema. Hertoghe's sign."],
        ["Pendred Syndrome",
         "SLC26A4 mutation; SNHL + Goitre + Abnormal perchlorate test; Enlarged vestibular aqueduct on CT"],
        ["Post-RT Hypothyroid",
         "After neck RT + laryngectomy; monitor TFTs every 3-6 months in year 1; then annually"],
        ["Graves' Ophthalmopathy",
         "Proptosis (Hertel > 22mm), lid retraction, EOM restriction, diplopia. "
         "Optic neuropathy = EMERGENCY -> IV steroids + orbital decompression"],
        ["Pemberton's Sign",
         "Facial plethora + stridor on arm raising = retrosternal goitre compressing SVC/trachea"],
        ["Goitre compression",
         "Trachea -> stridor; Oesophagus -> dysphagia; RLN -> hoarseness (= suspect malignancy); "
         "Sympathetic chain -> Horner syndrome"],
        ["RLN injury post-op",
         "Unilateral: hoarseness; Bilateral: EMERGENCY tracheostomy"],
        ["Hypoparathyroidism post-op",
         "Hypocalcaemia -> perioral tingling, Chvostek's, Trousseau's, laryngospasm. IV Ca gluconate + calcitriol"],
        ["De Quervain's thyroiditis",
         "Referred otalgia + painful thyroid swelling + fever. Mimics deep neck infection. NSAIDs/steroids."],
        ["Neck haematoma post-op",
         "OPEN WOUND AT BEDSIDE if airway compromise -> formal re-exploration in OT"],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))

    sp(st, 5)
    st.append(Paragraph(
        "References: Cummings Otolaryngology H&N Surgery 7th ed. | Scott-Brown's OHN&S 8th ed. | "
        "Bailey & Love's Surgery 28th ed. | Goldman-Cecil Medicine | Harrison's Internal Medicine 22nd ed.",
        S["sub"]))


# ── MAIN ─────────────────────────────────────────────────────────────────────
def main():
    out = "/home/daytona/workspace/ptc-notes/ENT_Thyroid_Manifestations.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="ENT Manifestations in Thyroid Disease - Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    st = []
    build(st, S)
    doc.build(st)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Carcinoma Maxilla (Maxillary Sinus Carcinoma) - Focused ENT PG Exam Notes
# NEW Palette: Charcoal-green headings, deep amber subheadings, dusty blue H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Charcoal Green / Deep Amber / Dusty Blue ──────────────────────
C_H1_BG  = colors.HexColor("#1C3B2A")   # dark forest charcoal-green
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#A05000")   # deep amber
C_H2_BG  = colors.HexColor("#FFF5E6")   # pale amber
C_H3_FG  = colors.HexColor("#1A4A6E")   # dusty steel blue
C_H3_BG  = colors.HexColor("#EAF1F8")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1C3B2A")
C_ALT    = colors.HexColor("#EAF3ED")   # pale green alt
C_PEARL  = colors.HexColor("#FFF5E6")   # pale amber pearl
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#1C3B2A")
C_VQ_BG  = colors.HexColor("#EAF1F8")
C_VQ_FG  = colors.HexColor("#1C3B2A")
C_FC_BOX = colors.HexColor("#D2E8D8")
C_FC_HDR = colors.HexColor("#1C3B2A")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for cell in row:
            if isinstance(cell, str):
                nr.append(Paragraph(cell, S["cellh"] if ri==0 else S["cell"]))
            else:
                nr.append(cell)
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTNAME",      (0,0),(-1,0), BD),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 3)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = WP - 2*M
    bw = W * 0.82
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        styl = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#B2D4BE") if bold else C_FC_BOX
        rows.append([Paragraph(txt, styl)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",(0,0),(-1,-1),0.5,C_RULE),
        ("TOPPADDING",(0,0),(-1,-1),4),("BOTTOMPADDING",(0,0),(-1,-1),4),
        ("LEFTPADDING",(0,0),(-1,-1),6),("RIGHTPADDING",(0,0),(-1,-1),6),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]
    for i, bg in enumerate(bgs): cmds.append(("BACKGROUND",(0,i),(0,i),bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([
        ("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
    ]))
    st.append(outer); sp(st, 4)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("CARCINOMA OF THE MAXILLA  (Maxillary Sinus Carcinoma)", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e, Cummings ORL 7e, KJ Lee's Essential ORL, Bailey & Love 28e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION ──────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "Carcinoma of the maxilla = malignant tumour arising from the MAXILLARY ANTRUM (sinus) and/or maxillary bone.",
        "Accounts for 50-70% of all paranasal sinus malignancies.",
        "Most common histological type: SQUAMOUS CELL CARCINOMA (SCC) - 40-50%.",
        "Paranasal sinus malignancies overall: < 5% of all H&N cancers; incidence 0.5-1.0 per 100,000.",
        "Often presents LATE due to the expansile nature of the maxillary sinus masking early symptoms.",
    ], S)
    sp(st, 4)

    # ── 2. APPLIED ANATOMY ─────────────────────────────────────────────────────
    h1(st, "2.  APPLIED ANATOMY", S)
    bl(st, [
        "Maxillary sinus (antrum of Highmore): largest PNS; pyramidal shape; opens into middle meatus via "
          "ostium on medial wall.",
        "WALLS of maxillary sinus:",
    ], S)
    data = [
        ["Wall", "Structure", "Clinical Significance if Invaded"],
        ["Roof (= orbital floor)", "Thin bone; contains infraorbital nerve", "Diplopia, infraorbital anaesthesia, proptosis"],
        ["Floor (= hard palate / alveolus)", "Related to upper molar teeth roots", "Loosening of teeth, oro-antral fistula, palatal swelling"],
        ["Medial wall (= lateral nasal wall)", "Nasal cavity", "Nasal obstruction, epistaxis (EARLIEST symptom)"],
        ["Anterior wall", "Facial soft tissue, canine fossa", "Facial swelling, cheek numbness, facial asymmetry"],
        ["Posterior wall", "Pterygopalatine fossa, pterygoid plates", "Trismus (pterygoid muscle invasion), pain radiating to ear"],
        ["Lateral wall", "Zygoma, buccal sulcus", "Cheek fullness, buccal sulcus mass"],
    ]
    st.append(tbl(data, [W*0.18, W*0.27, W*0.55], S))
    pearl(st, "PEARL: Ohngren's line = imaginary plane from medial canthus to angle of mandible divides maxillary sinus. "
          "SUPRASTRUCTURE (above line) = worse prognosis (close to orbit, skull base, pterygoids). "
          "INFRASTRUCTURE (below line) = better prognosis. (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 3. AETIOLOGY & RISK FACTORS ────────────────────────────────────────────
    h1(st, "3.  AETIOLOGY & RISK FACTORS", S)
    data = [
        ["Risk Factor", "Cancer Type", "Detail"],
        ["HARDWOOD dust (oak, beech, mahogany)",
         "Adenocarcinoma (intestinal type)",
         "900x increased risk. Latency ~40 yrs. Prescribed occupational disease (UK). "
         "Furniture workers, High Wycombe area. African mahogany = most carcinogenic."],
        ["SOFTWOOD dust",
         "SCC",
         "Lower risk than hardwood but implicated in SCC of maxillary sinus"],
        ["NICKEL compounds",
         "SCC",
         "250-fold increased risk. Latency 18-36 years. Nickel refinery workers."],
        ["CHROMIUM / polycyclic hydrocarbons",
         "SCC",
         "Occupational inhalation. Synergistic with smoking."],
        ["SMOKING",
         "SCC",
         "Predominant risk factor for SCC; synergistic with wood dust."],
        ["HPV (types 6 and 11)",
         "SCC (via inverted papilloma)",
         "~10% of inverted papillomas undergo malignant transformation to SCC."],
        ["Aflatoxin, mustard gas, thorotrast",
         "Various",
         "Historical/occupational exposures. Thorotrast (thorium dioxide paint) - watch dial workers."],
        ["Radiation",
         "Sarcoma (post-RT)",
         "Previous radiotherapy to head and neck; latency years."],
        ["Leather industry, textile workers",
         "Adenocarcinoma",
         "Lower risk than woodworkers but documented association."],
    ]
    st.append(tbl(data, [W*0.28, W*0.22, W*0.5], S))
    caut(st, "NO evidence that chronic sinusitis predisposes to sinus cancer. "
         "Incidence of chronic sinusitis in Ca maxilla = same as general population. (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 4. CLASSIFICATION / HISTOLOGY ──────────────────────────────────────────
    h1(st, "4.  CLASSIFICATION / HISTOLOGICAL TYPES", S)
    data = [
        ["Type", "Frequency", "Key Features"],
        ["Squamous Cell Carcinoma (SCC)",
         "40-50% (MOST COMMON)",
         "Arises from respiratory epithelium. Smoking main risk. "
         "Moderately aggressive. Cervical LN mets 10-25%."],
        ["Adenocarcinoma (intestinal type)",
         "13-19%",
         "Wood dust exposure. Ethmoid > maxillary. Locally aggressive; LN mets common. "
         "5-yr survival ~50%."],
        ["Adenocarcinoma (non-intestinal)",
         "Less common",
         "Relatively better prognosis. Glandular origin."],
        ["Adenoid Cystic Carcinoma (ACC)",
         "6-10%",
         "Minor salivary gland origin. Maxillary sinus most common. "
         "HIGH perineural invasion. Slow but relentless growth. Long latency to recurrence. "
         "5-yr survival 73-90% but 15-yr falls to 40%."],
        ["Olfactory Neuroblastoma (Esthesioneuroblastoma)",
         "< 5%",
         "Olfactory epithelium origin. Kadish staging (A-D). Radiosensitive. "
         "Bimodal age peak (2nd and 6th decades)."],
        ["SNUC (Sinonasal Undifferentiated Carcinoma)",
         "Rare",
         "Highly aggressive; > 80% present as T4. Rapid growth. "
         "Trimodality treatment needed."],
        ["Mucosal Melanoma",
         "Rare",
         "Aggressive; worse prognosis than cutaneous melanoma."],
        ["Lymphoma (NK/T-cell)",
         "Rare",
         "Previously 'lethal midline granuloma'. EBV-associated."],
        ["Rhabdomyosarcoma",
         "Children",
         "Most common paediatric sinonasal malignancy."],
    ]
    st.append(tbl(data, [W*0.28, W*0.14, W*0.58], S))
    sp(st, 4)

    # ── 5. CLINICAL FEATURES ───────────────────────────────────────────────────
    h1(st, "5.  CLINICAL FEATURES", S)
    h2(st, "A. Early Features (Infrastructure - below Ohngren's line)", S)
    bl(st, [
        "NASAL OBSTRUCTION: unilateral, progressive; earliest symptom.",
        "EPISTAXIS: unilateral; blood-stained nasal discharge.",
        "DENTAL SYMPTOMS: loosening of upper molar teeth, ill-fitting denture.",
        "ORO-ANTRAL FISTULA: communication between oral cavity and antrum.",
        "PALATAL SWELLING: medial wall expansion into palate.",
        "FACIAL SWELLING over cheek (anterior wall).",
        "CHEEK ANAESTHESIA / PAIN: infraorbital nerve involvement.",
    ], S)
    h2(st, "B. Late Features (Suprastructure - above Ohngren's line / advanced)", S)
    bl(st, [
        "PROPTOSIS / DIPLOPIA: roof (orbital floor) invasion.",
        "EPIPHORA: nasolacrimal duct obstruction.",
        "INFRAORBITAL NERVE ANAESTHESIA: V2 involvement.",
        "TRISMUS: pterygoid plate/muscle invasion (posterior wall) -> severe limitation of jaw opening.",
        "EAR PAIN (referred otalgia): posterior wall -> pterygopalatine fossa -> auriculotemporal nerve (V3).",
        "HEADACHE: skull base invasion.",
        "CERVICAL LYMPHADENOPATHY: usually jugulodigastric or submandibular nodes; late finding.",
        "CHEEK / SKIN FIXITY: anterior wall invasion with skin involvement (T4).",
    ], S)
    pearl(st, "PEARL: TRISMUS = pterygoid involvement = LATE/advanced disease -> poor prognosis, "
          "often unresectable. Infraorbital anaesthesia is an early sign of roof involvement (V2). "
          "Any unilateral nasal obstruction in an adult = biopsy + imaging until proven otherwise. (Cummings ORL)", S)

    # Symptom direction flowchart
    flowchart(st, "SYMPTOMS BY WALL INVOLVED (Spread Directions)", [
        ("MAXILLARY SINUS  --  Tumour spreads in all directions", True),
        ("Medial wall -> Nasal cavity: obstruction, epistaxis, discharge", False),
        ("Floor -> Hard palate / alveolus: loose teeth, oro-antral fistula, palatal swelling", False),
        ("Roof (orbital floor) -> Orbit: proptosis, diplopia, epiphora, infraorbital anaesthesia", False),
        ("Anterior wall -> Face: cheek swelling, skin involvement", False),
        ("Posterior wall -> Pterygoids / PPF: TRISMUS, referred ear pain, V3 symptoms", False),
        ("Superior / skull base -> Cribriform plate / brain: headache, anosmia, CNS symptoms (LATE)", True),
    ], S)
    sp(st, 2)

    # ── 6. STAGING ─────────────────────────────────────────────────────────────
    h1(st, "6.  STAGING  (AJCC/UICC 8th Edition - TNM)", S)
    h2(st, "A. T Staging - Maxillary Sinus", S)
    data = [
        ["T Stage", "Description"],
        ["T1", "Tumour limited to antral mucosa; NO erosion or destruction of bone"],
        ["T2", "Tumour causes erosion/destruction of bone (except posterior wall); extends into hard palate and/or middle nasal meatus"],
        ["T3", "Tumour invades any of: posterior wall maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses"],
        ["T4a (Moderately advanced local)", "Tumour invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses"],
        ["T4b (Very advanced local)", "Tumour invades orbital apex, dura, brain, middle cranial fossa, cranial nerves other than V2, nasopharynx, clivus"],
    ]
    st.append(tbl(data, [W*0.12, W*0.88], S))

    h2(st, "B. N and M Staging", S)
    data = [
        ["Stage", "Description"],
        ["N0", "No regional LN metastasis"],
        ["N1", "Single ipsilateral LN <= 3 cm, ENE-"],
        ["N2a", "Single ipsilateral LN > 3 cm but <= 6 cm, ENE-"],
        ["N2b", "Multiple ipsilateral LNs, all <= 6 cm, ENE-"],
        ["N2c", "Bilateral or contralateral LNs, all <= 6 cm, ENE-"],
        ["N3a", "Any LN > 6 cm, ENE-"],
        ["N3b", "Any LN, ENE+"],
        ["M1", "Distant metastasis"],
    ]
    st.append(tbl(data, [W*0.12, W*0.88], S))

    h2(st, "C. Ohngren's Classification (Practical / Prognostic)", S)
    data = [
        ["Division", "Location", "Prognosis / Reason"],
        ["Infrastructure",
         "Below Ohngren's line (medial canthus to angle of mandible). "
         "Involves floor, medial wall, anterior wall.",
         "BETTER prognosis. Amenable to surgical resection (infrastructure maxillectomy). "
         "Away from orbit and skull base."],
        ["Suprastructure",
         "Above Ohngren's line. "
         "Involves roof, posterior wall, pterygoid plates.",
         "WORSE prognosis. Proximity to orbit, skull base, cavernous sinus, pterygoids. "
         "Trismus + orbital invasion = poor resectability."],
    ]
    st.append(tbl(data, [W*0.18, W*0.40, W*0.42], S))
    caut(st, "Cervical LN metastasis occurs in only 10% at presentation but develops in 25-35% during disease course. "
         "Submandibular and jugulodigastric nodes most commonly involved. (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 7. INVESTIGATIONS ──────────────────────────────────────────────────────
    h1(st, "7.  INVESTIGATIONS", S)
    data = [
        ["Investigation", "Purpose / Findings"],
        ["Nasal endoscopy + BIOPSY", "ESSENTIAL first step. Visualise tumour; punch biopsy for histology. "
          "Endoscopic biopsy preferred over Caldwell-Luc approach."],
        ["CT SCAN - PNS + Neck (FIRST-LINE imaging)",
         "Bony erosion, extent of invasion, wall involvement, orbital floor, skull base. "
         "Best for bony detail. CT neck for lymph node assessment."],
        ["MRI - Face / skull base (COMPLEMENTARY)",
         "Soft tissue extent, perineural invasion (ACC), orbital, dural, brain involvement. "
         "Distinguishes tumour from retained secretions (CT cannot). MANDATORY for T4 disease."],
        ["PET-CT",
         "Distant metastases, occult nodal disease, response to CRT, restaging. "
         "Not routine for initial staging in all centres."],
        ["Orthopantomogram (OPG)",
         "Dental root involvement, mandible, alveolar destruction."],
        ["Chest X-ray / CT chest",
         "Lung metastases (distant mets in 17-25%)."],
        ["Biopsy",
         "DEFINITIVE diagnosis. Endoscopic-guided punch biopsy. "
         "Avoid trans-facial route (risks seeding). Tissue for IHC (esp. for lymphoma, melanoma, ACC)."],
        ["Ophthalmology assessment",
         "Formal assessment of visual acuity, EOM, fundoscopy when orbital involvement suspected."],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))
    sp(st, 4)

    # ── 8. MANAGEMENT ──────────────────────────────────────────────────────────
    h1(st, "8.  MANAGEMENT", S)
    h2(st, "A. Principles", S)
    bl(st, [
        "MDT approach: ENT/head and neck surgeon, oncologist, radiologist, prosthodontist, maxillofacial surgeon.",
        "Surgery + radiotherapy (combined modality) is the STANDARD of care for resectable disease.",
        "Chemotherapy: mainly for unresectable disease, organ preservation protocols, or metastatic disease.",
        "Prognosis is best when resection achieves CLEAR MARGINS (R0 resection).",
    ], S)

    h2(st, "B. Surgical Management", S)
    data = [
        ["Procedure", "Indication", "Structures Removed"],
        ["Medial maxillectomy",
         "Tumours of medial wall / nasal cavity, limited disease",
         "Medial wall of maxilla, lateral nasal wall"],
        ["Infrastructure maxillectomy",
         "T1-T2; infrastructure tumours (below Ohngren's line)",
         "Floor of maxillary sinus, hard palate, alveolus. Orbital floor preserved."],
        ["Total maxillectomy",
         "T2-T3; full sinus involvement",
         "All 6 walls of maxillary sinus. Orbital floor preserved if not invaded. "
         "Weber-Ferguson incision approach."],
        ["Extended total maxillectomy\n(radical maxillectomy)",
         "T3-T4a; suprastructure involvement",
         "Total maxillectomy + orbital floor exenteration OR ethmoidectomy + pterygoid resection"],
        ["Orbital exenteration",
         "Tumour invading orbital fat / extraocular muscles / apex",
         "Removal of orbital contents. Only if no other option. Significant morbidity."],
        ["Endoscopic resection",
         "Selected early T1-T2 tumours; medial/inferior wall",
         "FESS-based; increasing role in experienced centres; less morbidity."],
        ["Neck dissection",
         "N+ disease clinically; some advocate elective ND for high-risk T3-T4",
         "MRND or selective neck dissection (Levels I-III most common for maxillary Ca)"],
    ]
    st.append(tbl(data, [W*0.23, W*0.27, W*0.5], S))

    h2(st, "C. Radiotherapy", S)
    bl(st, [
        "POST-OPERATIVE RT (adjuvant): standard after total/radical maxillectomy.",
        "Dose: 50-66 Gy to tumour bed + 44-50 Gy to elective neck fields.",
        "Indications for post-op RT: positive margins (R1/R2), perineural invasion, T3-T4, LN involvement.",
        "PRIMARY RT (definitive): for unresectable tumours or patient unfit for surgery.",
        "TECHNIQUES: IMRT (intensity-modulated RT) preferred to reduce dose to orbit, optic nerves, parotid.",
    ], S)

    h2(st, "D. Chemotherapy", S)
    bl(st, [
        "NOT used as sole treatment for resectable disease.",
        "INDUCTION chemotherapy (TPF: taxane + cisplatin + 5-FU): organ preservation, downstage before surgery.",
        "CONCURRENT chemoradiotherapy (cisplatin-based): unresectable disease; post-op high-risk cases.",
        "CETUXIMAB (anti-EGFR): alternative if platinum ineligible.",
        "TARGETED therapy / immunotherapy (pembrolizumab, nivolumab): recurrent/metastatic SCC of H&N.",
    ], S)

    flowchart(st, "MANAGEMENT FLOWCHART - Carcinoma Maxilla", [
        ("Suspected Maxillary Ca: Nasal endoscopy + Biopsy (histology)", True),
        ("Staging: CT PNS + neck AND MRI face/skull base + CXR; PET-CT if advanced", False),
        ("MDT Discussion: Resectable vs Unresectable?", True),
        ("RESECTABLE: Surgery (total/radical maxillectomy +/- neck dissection) + Post-op RT (50-66 Gy)", False),
        ("UNRESECTABLE / INOPERABLE: Concurrent CRT (cisplatin + RT) or Palliative RT + supportive care", False),
        ("Reconstruction: Prosthetic obturator (immediate) / Microvascular free flap (ALT / fibula) (delayed)", False),
        ("Follow-up: Clinical + endoscopy + CT/MRI 3-monthly (yr 1-2), then 6-monthly (yr 3-5)", True),
    ], S)
    sp(st, 2)

    h2(st, "E. Reconstruction", S)
    bl(st, [
        "PROSTHETIC OBTURATOR: immediate; restores oral function, speech, swallowing after maxillectomy.",
        "MICROVASCULAR FREE FLAP: ALT (anterolateral thigh) or fibula free flap for soft tissue + bone.",
        "Temporal flap: for smaller defects.",
        "Orbital prosthesis: after exenteration.",
        "Dental rehabilitation: important QoL aspect; implants after healing/RT.",
    ], S)
    sp(st, 4)

    # ── 9. COMPLICATIONS ───────────────────────────────────────────────────────
    h1(st, "9.  COMPLICATIONS", S)
    data = [
        ["Complication", "Note"],
        ["Recurrence (LOCAL)",
         "Most common cause of treatment failure. 50-70% recur locally. "
         "CT/MRI at 3 months post-treatment as baseline; then surveillance imaging."],
        ["Orbital involvement / blindness",
         "Tumour progression into orbit or radiation injury to optic nerve/retina."],
        ["Trismus",
         "Pterygoid invasion by tumour OR post-RT fibrosis of pterygoid muscles. "
         "Physiotherapy, jaw-opening exercises; trismus splints."],
        ["Osteoradionecrosis (ORN)",
         "Radiation necrosis of maxillary bone. Risk with dental extraction post-RT. "
         "Prevention: dental assessment pre-RT; avoid extractions for 1 year post-RT."],
        ["Oro-antral / oro-nasal fistula",
         "Post-surgical; managed with obturator initially; surgical closure."],
        ["Cranial nerve deficits",
         "V2 (infraorbital anaesthesia, facial numbness), V3 (trismus), III/IV/VI (diplopia from orbital invasion)."],
        ["Distant metastases",
         "Lungs, bone, brain (17-25% overall). Chemotherapy / best supportive care."],
        ["Chyle leak",
         "If neck dissection performed on left side (thoracic duct injury)."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))
    sp(st, 4)

    # ── 10. PROGNOSIS ──────────────────────────────────────────────────────────
    h1(st, "10.  PROGNOSIS", S)
    data = [
        ["Factor", "Impact on Prognosis"],
        ["Overall 5-yr survival", "~50% for all paranasal sinus malignancies collectively"],
        ["Infrastructure (below Ohngren's)", "Better prognosis (~50-60% 5-yr survival)"],
        ["Suprastructure (above Ohngren's)", "Worse prognosis (~25-35% 5-yr survival)"],
        ["T1-T2 disease", "5-yr survival 60-80%"],
        ["T4 disease", "5-yr survival < 20-30%"],
        ["Clear surgical margins (R0)", "Best outcomes; incomplete resection = poor prognosis"],
        ["Perineural invasion (ACC)", "High recurrence rate; 15-yr survival 40% despite good 5-yr"],
        ["Cervical LN involvement", "Significantly worsens prognosis"],
        ["SNUC / Mucosal melanoma", "Very poor prognosis; aggressive biology"],
        ["Wood-worker adenocarcinoma", "Relatively BETTER prognosis than other adenocarcinomas"],
    ]
    st.append(tbl(data, [W*0.33, W*0.67], S))
    sp(st, 4)

    # ── 11. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "11.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What is Ohngren's line and its significance?",
         "Imaginary line from medial canthus of eye to angle of mandible. "
         "INFRASTRUCTURE (below) = floor, anterior, medial walls -> better prognosis, easier to resect. "
         "SUPRASTRUCTURE (above) = roof, posterior wall, pterygoids -> worse prognosis, proximity to orbit and skull base."),
        ("Q2: What is the most common site of paranasal sinus malignancy?",
         "Maxillary sinus (50-70%), followed by nasal cavity (15-30%), then ethmoid sinus (10-20%). "
         "Most common histology: Squamous cell carcinoma (40-50%)."),
        ("Q3: What occupational exposure causes sinonasal adenocarcinoma?",
         "HARDWOOD dust (oak, beech, African mahogany) - 900-fold increased risk. "
         "Latency ~40 years. Intestinal-type adenocarcinoma. Prescribed occupational disease in UK. "
         "NICKEL exposure -> SCC (250-fold risk). SOFTWOOD dust -> SCC."),
        ("Q4: What is the clinical significance of trismus in Ca maxilla?",
         "Trismus = invasion of PTERYGOID MUSCLES/PLATES (posterior wall). "
         "Indicates ADVANCED disease (T3-T4). Signifies involvement of infratemporal fossa. "
         "Significantly worsens prognosis and resectability. "
         "T4b = orbital apex + dura + brain + clivus + carotid = unresectable."),
        ("Q5: What is the surgical approach for Ca maxilla?",
         "WEBER-FERGUSON incision (lateral rhinotomy extended to upper lip) provides best exposure for total maxillectomy. "
         "Infrastructure maxillectomy for T1-T2 infraorbital disease. "
         "Radical maxillectomy + orbital exenteration for suprastructure T4 with orbital invasion. "
         "Endoscopic approach: selected early lesions in experienced centres."),
        ("Q6: What are the ENT features of Ca maxilla by wall?",
         "Medial wall: nasal obstruction + epistaxis (earliest). "
         "Floor: loose teeth, palatal swelling, oro-antral fistula. "
         "Roof: proptosis, diplopia, epiphora, infraorbital anaesthesia. "
         "Anterior: cheek swelling, skin invasion. "
         "Posterior: TRISMUS (pterygoid), referred ear pain (auriculotemporal nerve V3)."),
        ("Q7: What is adenoid cystic carcinoma of the maxillary sinus?",
         "Minor salivary gland origin. 6-10% of sinonasal malignancies. "
         "HALLMARK: perineural invasion -> facial pain, nerve deficits. "
         "Slow but relentless growth; high late recurrence rate. "
         "5-yr survival 73-90% but 15-yr survival falls to 40%. "
         "Maxillary sinus most common site. Patients often present with long history of facial pain."),
        ("Q8: What imaging is used and why are BOTH CT and MRI needed?",
         "CT PNS+Neck: BONY DETAIL - erosion, wall destruction, nodal size. Best for bone. "
         "MRI face/skull base: SOFT TISSUE - perineural spread, orbital contents, dural invasion, "
         "distinguishes tumour from retained secretions (CT cannot differentiate). "
         "Both together are complementary and MANDATORY for accurate staging."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 4)

    # ── 12. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(st, "12.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Definition",     "Malignant tumour of maxillary antrum; 50-70% of all PNS malignancies; SCC most common (40-50%)"],
        ["Ohngren's line",  "Medial canthus to angle of mandible; infra = better prognosis; supra = worse prognosis"],
        ["Earliest symptom","Unilateral nasal obstruction + epistaxis (medial wall involvement)"],
        ["Late symptoms",   "Trismus (pterygoid = posterior wall), proptosis (orbital floor), cheek skin involvement"],
        ["Trismus",         "= Posterior wall / pterygoid invasion = T3-T4 = ADVANCED disease = POOR prognosis"],
        ["Key risk factors", "Hardwood dust -> adenocarcinoma (900x risk); Nickel -> SCC (250x risk); Smoking -> SCC; HPV -> SCC via inverted papilloma"],
        ["Staging",         "AJCC 8th ed: T1 (mucosa only) -> T4b (orbital apex / dura / brain / clivus)"],
        ["Imaging",         "CT (bony erosion) + MRI (soft tissue / perineural / dura) -- BOTH required together"],
        ["Management",      "Surgery (total/radical maxillectomy) + post-op RT = standard for resectable. Weber-Ferguson incision."],
        ["Unresectable",    "Concurrent CRT (cisplatin + RT); T4b = palliative intent"],
        ["ACC special note", "Perineural invasion; high late recurrence; long facial pain history before diagnosis"],
        ["Prognosis",       "Overall 5-yr ~50%; infra > supra; R0 margin = best outcome; SNUC/melanoma = worst"],
        ["Reconstruction",  "Prosthetic obturator (immediate) + free flap (ALT/fibula) for larger defects"],
        ["Follow-up",       "CT/MRI at 3 months post-Rx as baseline; then 3-monthly (yr 1-2), 6-monthly (yr 3-5)"],
    ]
    st.append(tbl(data, [W*0.23, W*0.77], S))

    sp(st, 5)
    st.append(Paragraph(
        "References: Scott-Brown's OHN&S 8th ed. (Vol 2, Ch 7) | Cummings ORL H&N Surgery 7th ed. (Ch 94) | "
        "KJ Lee's Essential Otolaryngology 11th ed. | Bailey & Love's Surgery 28th ed. | AJCC Cancer Staging 8th ed.",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Ca_Maxilla_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Carcinoma Maxilla - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Branchial Cyst - Focused ENT PG Exam Notes (5-6 pages)
# NEW Palette: Slate-blue headings, deep rose subheadings, warm ochre H3
# Distinct from all previous themes

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Slate-Blue / Deep Rose / Warm Ochre ─────────────────────────────
C_H1_BG  = colors.HexColor("#1E3A5F")   # same deep navy as coag notes? No - use slate-teal
C_H1_BG  = colors.HexColor("#2C4A6E")   # slate-blue (lighter than PTC teal, different from navy)
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#992244")   # deep rose/raspberry
C_H2_BG  = colors.HexColor("#FEF0F4")   # pale rose
C_H3_FG  = colors.HexColor("#7A5500")   # warm ochre/dark gold
C_H3_BG  = colors.HexColor("#FFF8EC")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#2C4A6E")
C_ALT    = colors.HexColor("#EDF2F8")   # pale slate alt row
C_PEARL  = colors.HexColor("#FEF0F4")   # rose pearl bg
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#2C4A6E")
C_VQ_BG  = colors.HexColor("#EDF2F8")
C_VQ_FG  = colors.HexColor("#2C4A6E")
C_FC_BOX = colors.HexColor("#D0DCF0")
C_FC_HDR = colors.HexColor("#2C4A6E")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for cell in row:
            if isinstance(cell, str):
                nr.append(Paragraph(cell, S["cellh"] if ri==0 else S["cell"]))
            else:
                nr.append(cell)
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTNAME",      (0,0),(-1,0), BD),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 3)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = WP - 2*M
    bw = W * 0.82
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        styl = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#B8C8DC") if bold else C_FC_BOX
        rows.append([Paragraph(txt, styl)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",(0,0),(-1,-1),0.5,C_RULE),
        ("TOPPADDING",(0,0),(-1,-1),4),("BOTTOMPADDING",(0,0),(-1,-1),4),
        ("LEFTPADDING",(0,0),(-1,-1),6),("RIGHTPADDING",(0,0),(-1,-1),6),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]
    for i, bg in enumerate(bgs): cmds.append(("BACKGROUND",(0,i),(0,i),bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([
        ("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
    ]))
    st.append(outer); sp(st, 4)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("BRANCHIAL CYST  (Branchial Cleft Anomaly)", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e, Cummings ORL 7e, Bailey & Love 28e, Robbins Pathology",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION ──────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "A BRANCHIAL CYST is a congenital cystic remnant arising from incomplete obliteration of the "
          "branchial (pharyngeal) cleft apparatus during embryological development.",
        "Part of a spectrum: CYST (no surface communication) -> SINUS (opens to ONE surface, "
          "skin or pharynx) -> FISTULA (opens to BOTH surfaces).",
        "Second branchial cleft anomalies: MOST COMMON = 90-95% of all branchial cleft anomalies.",
        "Present most commonly in young adults (20-40 years); may present at any age.",
    ], S)
    sp(st, 4)

    # ── 2. EMBRYOLOGY ──────────────────────────────────────────────────────────
    h1(st, "2.  EMBRYOLOGY  (Key for Exam)", S)
    bl(st, [
        "Pharyngeal (branchial) arches: 5 pairs of mesodermal condensations (arches 1, 2, 3, 4, 6) "
          "separated by ectodermal CLEFTS externally and endodermal POUCHES internally.",
        "Normally: 2nd arch (Reichert's cartilage) grows caudally to cover clefts 2, 3, 4 -> fuses "
          "with epicardial ridge -> obliterates the CERVICAL SINUS OF HIS.",
        "FAILURE of obliteration -> ectoderm trapped -> forms branchial cyst/sinus/fistula.",
        "CERVICAL SINUS OF HIS = temporary space between 2nd arch and epicardial ridge. "
          "Its persistence -> 2nd branchial cleft cyst.",
        "1st branchial cleft: gives rise to external auditory canal (EAC). Failure -> 1st BCC near EAC.",
        "3rd/4th cleft anomalies: communicate with pyriform sinus (hypopharynx) internally.",
    ], S)
    pearl(st, "PEARL: 2nd arch fails to cover 3rd + 4th clefts -> cervical sinus of His persists "
          "-> trapped ectoderm -> branchial cyst. This explains why 2nd BCC is 90-95% of all cases. "
          "(Cummings ORL / Langman's Embryology)", S)
    sp(st, 4)

    # ── 3. CLASSIFICATION ──────────────────────────────────────────────────────
    h1(st, "3.  CLASSIFICATION OF BRANCHIAL CLEFT ANOMALIES", S)
    data = [
        ["Type", "Frequency", "Location", "Internal Opening", "Key Feature / Nerve at Risk"],
        ["1st Branchial\nCleft Anomaly",
         "< 5%",
         "Near EAC, below tragus, parotid region, upper neck",
         "External auditory canal",
         "WORK TYPE 1: ectodermal EAC duplication; near tragus. "
         "WORK TYPE 2: ecto + mesodermal; deep to parotid. "
         "FACIAL NERVE (CN VII) at risk during excision."],
        ["2nd Branchial\nCleft Anomaly",
         "90-95%\n(MOST COMMON)",
         "Anterior border of SCM, Level II-III (angle of mandible). "
         "Deep to platysma, superficial to carotid sheath.",
         "Tonsillar fossa (palatine tonsil bed)",
         "Fistula tract passes BETWEEN internal and external carotid arteries. "
         "Over CN IX (glossopharyngeal), CN XII (hypoglossal), "
         "under stylohyoid ligament to tonsillar fossa."],
        ["3rd Branchial\nCleft Anomaly",
         "~2-3%",
         "Medial edge of SCM, Level III, lower neck",
         "Pyriform sinus (via thyrohyoid membrane)",
         "Tract passes LATERAL to common carotid, medial/posterior to internal carotid, "
         "over CN XII, under CN IX -> through thyrohyoid membrane -> pyriform sinus. "
         "May present as recurrent thyroiditis (left lobe)."],
        ["4th Branchial\nCleft Anomaly",
         "Very rare",
         "Lower neck, may extend into mediastinum",
         "Pyriform sinus (apex)",
         "Tract descends into mediastinum, loops around aortic arch (left) or subclavian (right), "
         "ascends to pyriform sinus. "
         "Presents as recurrent thyroiditis or suppurative thyroiditis."],
    ]
    st.append(tbl(data, [W*0.14, W*0.1, W*0.2, W*0.17, W*0.39], S))
    pearl(st, "PEARL: 2nd BCC fistula tract = between ICA and ECA, over CN IX, under CN XII, "
          "under stylohyoid ligament -> tonsillar fossa. "
          "3rd/4th BCC -> pyriform sinus opening (IMPORTANT diagnostic and surgical point). "
          "(Scott-Brown's OHN&S / Cummings ORL)", S)
    sp(st, 4)

    # ── 4. PATHOLOGY ───────────────────────────────────────────────────────────
    h1(st, "4.  PATHOLOGY", S)
    h2(st, "A. Macroscopy", S)
    bl(st, [
        "Well-circumscribed cystic swelling; 2-5 cm diameter (may be larger).",
        "Smooth, fluctuant, transilluminant (unless infected).",
        "Unilocular; thin wall; contents: clear watery fluid OR turbid/mucinous fluid OR cholesterol crystals.",
        "Infected cyst: thick, fibrotic wall; turbid contents; surrounded by inflammatory adhesions.",
    ], S)
    h2(st, "B. Microscopy  (Robbins Pathology)", S)
    bl(st, [
        "Lined by STRATIFIED SQUAMOUS EPITHELIUM (most common) or pseudostratified columnar epithelium.",
        "Cyst wall contains LYMPHOID TISSUE with PROMINENT GERMINAL CENTRES (key diagnostic feature).",
        "Contents: desquamated squamous cells, keratin, granular debris, cholesterol crystals.",
        "Malignant transformation: RARE. Most cystic SCCs in neck are metastatic from UADT, NOT primary BCCs.",
    ], S)
    caut(st, "CAUTION: Lymphoid tissue with germinal centres in cyst wall = DIAGNOSTIC HALLMARK "
         "of branchial cyst. Branchial cleft cysts usually do NOT undergo malignant transformation. "
         "Cystic SCC in neck of adult > 40 yrs = METASTATIC until proven otherwise. (Robbins Pathology)", S)
    sp(st, 4)

    # ── 5. CLINICAL FEATURES ───────────────────────────────────────────────────
    h1(st, "5.  CLINICAL FEATURES", S)
    h2(st, "A. History", S)
    bl(st, [
        "Age: 20-40 years (peak); can present in childhood or middle age.",
        "Gradual painless lateral neck swelling (most common presentation).",
        "Sudden enlargement after URTI: inflammation -> rapid cyst expansion.",
        "Recurrent infection of cyst: repeated episodes of painful neck swelling and tenderness.",
        "Sinus/fistula: persistent intermittent discharge from pit on anterior neck (along SCM).",
        "Dysphagia or stridor: rare; large cysts compressing adjacent structures.",
        "FISTULA: mucoid discharge from small pit on the skin along anterior border of SCM.",
    ], S)
    h2(st, "B. Physical Examination", S)
    bl(st, [
        "LOCATION: Anterior border of SCM at junction of upper and middle thirds "
          "(Level II); deep to platysma.",
        "Smooth, spherical, fluctuant, non-tender swelling.",
        "TRANSILLUMINANT (unless infected/haemorrhaged into).",
        "Moves laterally (not vertically like thyroglossal cyst).",
        "NOT pulsatile (unlike carotid body tumour); NOT compressible (unlike vascular malformation).",
        "Fistulous opening: tiny pit discharging mucoid fluid at anterior SCM border (lower third).",
        "In infection: warm, tender, erythematous; may fluctuate; trismus if deep extension.",
        "Bailey's classification (position relative to SCM anterior border): Types 1-4.",
    ], S)
    pearl(st, "BAILEY'S CLASSIFICATION of 2nd Branchial Cyst position: "
          "Type 1 = Superficial to deep cervical fascia, anterior to SCM. "
          "Type 2 = Deep to deep cervical fascia, anterior to carotid sheath (MOST COMMON). "
          "Type 3 = Between carotid vessels extending to pharyngeal wall. "
          "Type 4 = Medial to carotid sheath, pharyngeal wall. (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 6. DIFFERENTIAL DIAGNOSIS ──────────────────────────────────────────────
    h1(st, "6.  DIFFERENTIAL DIAGNOSIS  (Lateral Neck Swelling)", S)
    data = [
        ["Condition", "Distinguishing Features"],
        ["Lymph node (reactive/infective)",
         "Multiple nodes, tender, associated with URTI, resolves with antibiotics. USG: solid, hilum present."],
        ["Lymphoma",
         "Rubbery nodes, may be multiple levels, constitutional symptoms (B symptoms), "
         "biopsy shows lymphomatous cells."],
        ["Metastatic SCC (cystic LN)",
         "Age > 40 yrs, smoker, alcohol use. Thick-walled cyst on CT. PET-CT for primary. "
         "MOST IMPORTANT differential in adults."],
        ["Cystic metastasis from PTC",
         "Thyroid nodule present or history of thyroid cancer. USG thyroid + FNAC cyst."],
        ["Carotid body tumour (paraganglioma)",
         "Pulsatile, transmitted pulsation, at carotid bifurcation. "
         "Positive 'Lyre sign' on angiography (splaying of ICA/ECA)."],
        ["Cystic hygroma / lymphatic malformation",
         "Children; brilliantly transilluminant; multilocular; soft; invaginates around structures."],
        ["Parotid tail / salivary gland cyst",
         "Overlaps with 1st BCC; related to parotid gland. Salivary amylase in aspirate."],
        ["Thyroglossal cyst",
         "MIDLINE; moves on tongue protrusion and swallowing. "
         "NOT lateral - easy distinction from 2nd BCC."],
        ["Dermoid / epidermoid cyst",
         "Doughy, non-fluctuant; no lymphoid tissue on histology."],
        ["Cervical abscess / deep neck space infection",
         "Fever, trismus, dysphagia, unwell. Septic picture."],
    ]
    st.append(tbl(data, [W*0.3, W*0.7], S))
    caut(st, "CRITICAL: In a patient > 40 years, smoker/drinker with cystic lateral neck mass = "
         "METASTATIC SCC until proven otherwise. Perform panendoscopy + directed biopsies. "
         "Do NOT simply excise as 'branchial cyst' without excluding malignancy. (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 7. INVESTIGATIONS ──────────────────────────────────────────────────────
    h1(st, "7.  INVESTIGATIONS", S)
    data = [
        ["Investigation", "Purpose / Findings"],
        ["USG Neck (FIRST-LINE)",
         "Cystic nature confirmed; thin-walled, anechoic with posterior enhancement (classic). "
         "If infected: thick wall, internal echoes, septae. 'Beak' pointing medially on USG "
         "suggests sinus/fistula -> warrants CT/MRI."],
        ["FNAC (Fine Needle Aspiration Cytology)",
         "Confirms cystic fluid; shows squamous cells, cholesterol crystals, lymphocytes. "
         "Send for cytology + biochemistry. If suspicious cells -> urgent investigation."],
        ["CT Neck with contrast",
         "Defines extent; relation to carotid vessels; sinus/fistula tract; lymph nodes. "
         "Classic: thin-walled, low-density homogenous mass anterolateral to carotid. "
         "Infected BCC: thick-walled, heterogenous, septated."],
        ["MRI Neck",
         "High T2 signal, low T1 (clear fluid); perineural spread; relation to CN VII (1st BCC). "
         "Better soft tissue detail than CT."],
        ["Barium swallow / pharyngoscopy",
         "3rd/4th BCC: look for pyriform sinus opening (fistula). "
         "Contrast study to delineate fistula tract."],
        ["Panendoscopy",
         "Rule out pyriform sinus fistula for 3rd/4th BCCs. "
         "Exclude primary UADT malignancy in adults with cystic neck mass."],
        ["Thyroid scan (if 4th BCC suspected)",
         "4th BCC may present as suppurative thyroiditis; thyroid scan shows focal hyperperfusion."],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))
    sp(st, 4)

    # ── 8. MANAGEMENT ──────────────────────────────────────────────────────────
    h1(st, "8.  MANAGEMENT", S)
    h2(st, "A. Surgical Excision (DEFINITIVE TREATMENT)", S)
    bl(st, [
        "COMPLETE SURGICAL EXCISION of cyst, sinus tract or fistula = treatment of choice.",
        "TIMING: Elective surgery when UNINFECTED. Infection should be treated first "
          "(antibiotics +/- I&D if necessary) -> excision after 6-8 weeks in quiescent phase.",
        "Excision in infected field = HIGH recurrence risk + facial nerve injury risk.",
    ], S)

    h2(st, "B. Surgical Technique for 2nd Branchial Cyst", S)
    bl(st, [
        "Transverse cervical skin crease incision at level of cyst.",
        "Dissect cyst free from carotid sheath; preserve IJV, carotid arteries, CN IX, CN XII.",
        "Fistula tract: traced BETWEEN ICA and ECA, over CN IX, CN XII, under stylohyoid ligament "
          "-> tonsillar fossa (divided at tonsillar fossa).",
        "May need SECOND incision (step-ladder incision) to trace fistula superiorly.",
        "Complete removal including fistula tract to prevent recurrence.",
    ], S)

    h2(st, "C. Surgical Considerations by Type", S)
    data = [
        ["Type", "Special Surgical Considerations"],
        ["1st BCC",
         "CN VII (facial nerve) at risk - IDENTIFY AND PRESERVE throughout. "
         "May require superficial parotidectomy for access. "
         "Approach: parotidectomy incision. Two incisions (step-ladder) if fistula extends to EAC."],
        ["2nd BCC (most common)",
         "Tract between ICA and ECA; over CN IX and CN XII; under stylohyoid ligament -> tonsillar fossa. "
         "Two transverse incisions may be needed for long fistula. Tonsillectomy may aid upper dissection."],
        ["3rd BCC",
         "Tract passes via thyrohyoid membrane -> pyriform sinus. "
         "Identify pyriform sinus opening endoscopically (cauterise/close). "
         "Careful dissection near carotid bifurcation and vagus nerve."],
        ["4th BCC",
         "Endoscopic cauterisation of pyriform sinus opening is preferred (avoids open surgery). "
         "Open surgery complex due to mediastinal tract. "
         "Repeated recurrences may need thyroid lobectomy (if left lobe involved)."],
    ]
    st.append(tbl(data, [W*0.16, W*0.84], S))

    # Management flowchart
    flowchart(st, "MANAGEMENT FLOWCHART - Branchial Cyst", [
        ("Lateral neck cyst: USG + FNAC (confirm cystic; rule out malignancy)", True),
        ("Age < 40 yrs, no risk factors: Branchial Cyst likely -> CT Neck for anatomy", False),
        ("Age > 40 yrs, smoker/drinker: Exclude metastatic SCC -> CT + PET-CT + Panendoscopy first", False),
        ("Infected cyst? -> Antibiotics +/- I&D -> Wait 6-8 weeks -> Excise when quiescent", False),
        ("ELECTIVE SURGICAL EXCISION: Complete removal of cyst + entire fistula/sinus tract", True),
        ("1st BCC: Preserve CN VII | 2nd BCC: Between ICA/ECA, over CN IX + CN XII | 3rd/4th: Pyriform sinus tract", False),
        ("Follow-up: Wound check at 2 weeks; histology review; recurrence surveillance at 6 months", True),
    ], S)
    sp(st, 2)

    h2(st, "D. Non-surgical options (limited role)", S)
    bl(st, [
        "SCLEROTHERAPY (OK-432 / bleomycin): limited evidence; more useful for lymphatic malformations.",
        "ASPIRATION alone: high recurrence rate; NOT recommended as definitive treatment.",
        "ANTIBIOTICS: for acute infection; not definitive treatment for the cyst itself.",
    ], S)
    sp(st, 4)

    # ── 9. COMPLICATIONS ───────────────────────────────────────────────────────
    h1(st, "9.  COMPLICATIONS", S)
    h2(st, "A. Of the Disease", S)
    bl(st, [
        "Recurrent infection: most common complication; worsens with each episode (fibrosis, adhesions).",
        "Abscess formation: requires I&D + antibiotics before definitive surgery.",
        "Spontaneous rupture: may create sinus tract.",
        "Fistula formation: to skin or pharynx.",
        "MALIGNANT TRANSFORMATION: extremely rare; 'branchiogenic carcinoma' - controversial entity. "
          "Most 'cystic SCCs' in neck = METASTATIC from UADT primary.",
    ], S)
    h2(st, "B. Of Surgery", S)
    data = [
        ["Complication", "Relevance"],
        ["Recurrence",
         "MOST COMMON. Occurs if excision is incomplete (cyst wall left) or infected field surgery. "
         "Rate: 3-15% in uninfected; much higher if operated during infection."],
        ["CN VII injury (1st BCC)",
         "Facial nerve palsy; IDENTIFY nerve before dissection of 1st BCC in parotid."],
        ["CN IX / CN XII injury",
         "Glossopharyngeal / hypoglossal nerve damage during 2nd BCC dissection. "
         "Results in dysphagia, tongue deviation."],
        ["Vagus nerve / sympathetic chain injury",
         "Horner syndrome; voice change; bradycardia."],
        ["Haemorrhage from carotid / IJV",
         "Careful dissection required; major vessel injury uncommon but serious."],
        ["Wound infection / seroma",
         "Common minor complications; managed conservatively."],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))
    sp(st, 4)

    # ── 10. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "10.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What is a branchial cyst and what is its embryological origin?",
         "A branchial cyst is a congenital cystic remnant from incomplete obliteration of the pharyngeal "
         "(branchial) cleft apparatus. 2nd branchial cleft anomaly (90-95%): failure of 2nd arch to grow "
         "caudally -> cervical sinus of His persists -> trapped ectoderm -> branchial cyst. "
         "Classically presents in young adults (20-40 yrs) as painless lateral neck swelling."),
        ("Q2: What is the difference between a branchial cyst, sinus and fistula?",
         "CYST: no communication with any surface. "
         "SINUS: communicates with ONE surface only (skin OR pharynx). "
         "FISTULA: communicates with BOTH surfaces (skin AND pharynx). "
         "Second BCC fistula: external opening at anterior SCM (lower third); "
         "internal opening at tonsillar fossa."),
        ("Q3: What is the course of the 2nd branchial fistula tract?",
         "External opening: anterior border of SCM (lower neck). "
         "Tract passes: deep to platysma, superiorly between ICA and ECA, "
         "OVER CN IX (glossopharyngeal) and CN XII (hypoglossal), "
         "UNDER stylohyoid ligament -> palatine TONSILLAR FOSSA (internal opening). "
         "Surgically important: must dissect carefully around ICA/ECA and CN IX/XII."),
        ("Q4: What is Bailey's classification of 2nd branchial cyst?",
         "Type 1: Superficial to deep cervical fascia, anterior to SCM. "
         "Type 2 (MOST COMMON): Deep to deep cervical fascia, anterior to carotid sheath. "
         "Type 3: Between ICA and ECA extending to pharyngeal wall. "
         "Type 4: Medial to carotid sheath, adjacent to pharyngeal wall."),
        ("Q5: How do you distinguish a branchial cyst from metastatic cystic SCC in neck?",
         "Age and risk factors: < 40 yrs, no smoking/alcohol -> likely BCC. "
         "> 40 yrs, smoker, alcohol -> METASTATIC SCC until proven otherwise. "
         "Imaging: thin-walled cyst (BCC) vs thick-walled, septated, infiltrative (metastatic SCC). "
         "FNAC: squamous debris + lymphocytes (BCC) vs malignant squamous cells. "
         "Panendoscopy + PET-CT to find primary in suspicious cases."),
        ("Q6: What are the histological features of a branchial cyst?",
         "Lining: stratified squamous or pseudostratified columnar epithelium. "
         "WALL: contains LYMPHOID TISSUE with PROMINENT GERMINAL CENTRES (key feature). "
         "Cyst contents: cholesterol crystals, desquamated cells, granular debris. "
         "Size: 2-5 cm; smooth wall. (Robbins Pathology / Cummings ORL)"),
        ("Q7: When should you NOT operate on a branchial cyst immediately?",
         "During ACTIVE INFECTION: surgery in infected field = high recurrence + nerve injury risk. "
         "Management: Antibiotics (IV if severe) +/- incision and drainage if fluctuant abscess. "
         "Wait 6-8 weeks after infection resolves -> then ELECTIVE excision in quiescent state."),
        ("Q8: What nerve is at risk in 1st branchial cleft cyst excision?",
         "FACIAL NERVE (CN VII): 1st BCC lies in parotid region, close to or through parotid. "
         "Work Type 2 is particularly close to facial nerve trunk or its branches. "
         "Must use facial nerve monitoring and formal parotidectomy approach. "
         "Distinguish from preauricular sinus/cyst (which is NOT a true 1st BCC and less related to CN VII)."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 4)

    # ── 11. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(st, "11.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Definition",      "Congenital cystic remnant of branchial cleft; cyst = no opening, sinus = 1 opening, fistula = 2 openings"],
        ["Most common",     "2nd branchial cleft cyst = 90-95% of all branchial anomalies"],
        ["Embryology",      "Failure of 2nd arch to obliterate cervical sinus of His -> trapped ectoderm"],
        ["Age / sex",       "Presents 20-40 yrs; equal sex incidence; may enlarge after URTI"],
        ["Location",        "Anterior border of SCM at Level II-III (angle of mandible); superficial to carotid sheath"],
        ["Histology",       "Squamous/columnar lining + LYMPHOID TISSUE WITH GERMINAL CENTRES in wall (diagnostic)"],
        ["Bailey Types",    "Type 2 most common: deep to deep cervical fascia, anterior to carotid sheath"],
        ["2nd BCC fistula tract", "Between ICA + ECA; over CN IX + CN XII; under stylohyoid ligament -> tonsillar fossa"],
        ["1st BCC",         "Near EAC / parotid; CN VII at risk; Work Type 1 (ecto) / Type 2 (ecto + meso)"],
        ["3rd/4th BCC",     "Pyriform sinus opening; may present as recurrent thyroiditis (left lobe)"],
        ["Key DD",          "Metastatic cystic SCC in neck: age > 40 + smoker/drinker = malignancy until proven otherwise"],
        ["Investigation",   "USG (first line) -> FNAC -> CT neck; panendoscopy if 3rd/4th or adult suspicious mass"],
        ["Treatment",       "Complete surgical excision; wait 6-8 weeks if infected; NOT during active infection"],
        ["Complications",   "Recurrence (incomplete excision or infected field), CN VII (1st BCC), CN IX/XII (2nd BCC)"],
        ["Malignant change", "Extremely rare; most cystic SCCs in neck are METASTATIC, not primary branchiogenic carcinoma"],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))

    sp(st, 5)
    st.append(Paragraph(
        "References: Scott-Brown's OHN&S 8th ed. | Cummings ORL H&N Surgery 7th ed. | "
        "Bailey & Love's Surgery 28th ed. | Robbins & Kumar Pathologic Basis of Disease | "
        "Langman's Medical Embryology",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Branchial_Cyst_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Branchial Cyst - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Craniopharyngioma - Focused ENT/Neurosurgery PG Exam Notes (5-6 pages)
# NEW Palette: Deep teal-green headings, rich plum subheadings, copper H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Teal-Green / Plum / Copper ──────────────────────────────────────
C_H1_BG  = colors.HexColor("#0B4D4D")   # deep teal-green
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#6B1A4A")   # deep plum/magenta
C_H2_BG  = colors.HexColor("#FBF0F6")   # pale lavender-rose
C_H3_FG  = colors.HexColor("#7A3E00")   # copper/burnt sienna
C_H3_BG  = colors.HexColor("#FFF3E8")   # pale peach-copper
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#0B4D4D")
C_ALT    = colors.HexColor("#E6F3F3")   # pale teal alt row
C_PEARL  = colors.HexColor("#E6F3F3")   # teal pearl
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#0B4D4D")
C_VQ_BG  = colors.HexColor("#FBF0F6")
C_VQ_FG  = colors.HexColor("#0B4D4D")
C_FC_BOX = colors.HexColor("#CCE8E8")
C_FC_HDR = colors.HexColor("#0B4D4D")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for cell in row:
            if isinstance(cell, str):
                nr.append(Paragraph(cell, S["cellh"] if ri==0 else S["cell"]))
            else:
                nr.append(cell)
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTNAME",      (0,0),(-1,0), BD),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 3)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = WP - 2*M
    bw = W * 0.82
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        styl = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#9ED0D0") if bold else C_FC_BOX
        rows.append([Paragraph(txt, styl)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",(0,0),(-1,-1),0.5,C_RULE),
        ("TOPPADDING",(0,0),(-1,-1),4),("BOTTOMPADDING",(0,0),(-1,-1),4),
        ("LEFTPADDING",(0,0),(-1,-1),6),("RIGHTPADDING",(0,0),(-1,-1),6),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]
    for i, bg in enumerate(bgs): cmds.append(("BACKGROUND",(0,i),(0,i),bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([
        ("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
    ]))
    st.append(outer); sp(st, 4)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("CRANIOPHARYNGIOMA", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e, Bradley & Daroff Neurology, "
        "Grainger & Allison Radiology, Cummings ORL 7e, KJ Lee's ORL",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION ──────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "Craniopharyngioma is a BENIGN (WHO Grade I) but locally aggressive epithelial tumour "
          "arising from RATHKE'S POUCH remnants along the craniopharyngeal duct (pituitary stalk).",
        "Most common SUPRASELLAR tumour in CHILDREN.",
        "Comprises 1-3% of all intracranial tumours; 2-5% of CNS tumours.",
        "BIMODAL age distribution: Peak 1 at 5-15 years; Peak 2 at 50-60 years.",
        "Despite benign histology: significant morbidity from proximity to optic chiasm, "
          "hypothalamus, pituitary, and 3rd ventricle.",
    ], S)
    sp(st, 4)

    # ── 2. EMBRYOLOGY / APPLIED ANATOMY ────────────────────────────────────────
    h1(st, "2.  EMBRYOLOGY & APPLIED ANATOMY", S)
    h2(st, "A. Embryology", S)
    bl(st, [
        "RATHKE'S POUCH: ectodermal evagination of the primitive stomodeum (roof of primitive mouth) "
          "that ascends to form the ANTERIOR PITUITARY (adenohypophysis).",
        "Craniopharyngeal duct: connects Rathke's pouch to the roof of the pharynx.",
        "Normally obliterates completely by 7-8 weeks gestation.",
        "Failure of obliteration -> epithelial cell rests persist along the pituitary stalk -> "
          "craniopharyngioma arises from squamous cell remnants of these rests.",
        "Location follows the craniopharyngeal duct: nasopharynx -> sphenoid -> sella -> suprasellar.",
    ], S)
    h2(st, "B. Applied Anatomy", S)
    bl(st, [
        "Suprasellar cistern: where most craniopharyngiomas develop.",
        "Critical neighbouring structures:",
    ], S)
    data = [
        ["Adjacent Structure", "Clinical Effect if Compressed"],
        ["Optic chiasm (above pituitary)", "BITEMPORAL HEMIANOPIA (most common visual defect)"],
        ["Optic nerves", "Unilateral visual loss, optic atrophy"],
        ["Pituitary gland / stalk", "Hypopituitarism: growth hormone deficiency (most common), hyperprolactinaemia (stalk compression), pan-hypopituitarism"],
        ["Hypothalamus", "Diabetes insipidus (DI), obesity, sleep disturbances, temperature dysregulation"],
        ["3rd ventricle", "Obstructive hydrocephalus -> raised ICP -> headache, vomiting, papilloedema"],
        ["Cavernous sinus", "CN III, IV, VI palsies, V1/V2 sensory loss (rare, large tumours)"],
        ["Internal carotid arteries", "Encasement -> stroke risk (large/invasive tumours)"],
    ]
    st.append(tbl(data, [W*0.3, W*0.7], S))
    pearl(st, "PEARL: Craniopharyngioma is the most common suprasellar mass in CHILDREN. "
          "Bitemporal hemianopia + short stature (GH deficiency) + raised ICP in a child "
          "= craniopharyngioma until proven otherwise. (Scott-Brown's OHN&S / Cummings ORL)", S)
    sp(st, 4)

    # ── 3. CLASSIFICATION / PATHOLOGY ──────────────────────────────────────────
    h1(st, "3.  CLASSIFICATION  &  PATHOLOGY", S)
    data = [
        ["Feature", "ADAMANTINOMATOUS Type (Classic)", "PAPILLARY Type"],
        ["Frequency",    "90% of all craniopharyngiomas",   "10% of all craniopharyngiomas"],
        ["Age group",    "CHILDREN and young adults (5-15 yrs); also adults",
                         "ADULTS ONLY (peak 40-55 yrs); rare in children"],
        ["Molecular",    "CTNNB1 (beta-catenin) mutation in 92-94% of cases; Wnt signalling pathway",
                         "BRAF V600E mutation in ~95% of cases"],
        ["Gross appearance",
         "Multilobulated, mixed CYSTIC + SOLID. "
         "Cysts contain dark viscous 'motor oil' / 'machinery oil' fluid (cholesterol-rich). "
         "CALCIFICATION in ~75% (sand-like or gravel-like). "
         "Irregular margins; microscopic finger-like extensions into surrounding brain.",
         "Often SOLID; smoother surface; any cysts contain CLEAR fluid. "
         "RARELY calcifies. Distinct from adamantinomatous type."],
        ["Microscopy",
         "Stratified squamous epithelium with: peripheral PALISADING of nuclei, "
         "central STELLATE RETICULUM (cobweb-like loosening), "
         "nodules of WET KERATIN (ghost cells - keratinised cells without nuclei - PATHOGNOMONIC). "
         "Resembles ameloblastoma of jaw.",
         "TRUE non-keratinising squamous epithelium over fibrovascular cores. "
         "GOBLET CELLS may be present. NO wet keratin. NO stellate reticulum."],
        ["Calcification",  "Common (~75%); visible on CT (sand or gravel-like)",
                           "Rare; less visible on CT"],
        ["Prognosis",      "Higher recurrence; more adherent to critical structures",
                           "Slightly less recurrent; better demarcated"],
    ]
    st.append(tbl(data, [W*0.16, W*0.42, W*0.42], S))
    pearl(st, "WET KERATIN = PATHOGNOMONIC for Adamantinomatous Craniopharyngioma. "
          "Differs from DRY keratin (epidermoid/dermoid cysts). "
          "Diagnostic even without viable epithelium on biopsy. (Bradley & Daroff Neurology)", S)
    sp(st, 4)

    # ── 4. CLINICAL FEATURES ───────────────────────────────────────────────────
    h1(st, "4.  CLINICAL FEATURES", S)
    h2(st, "A. Triad of Presentations", S)
    bl(st, [
        "1. RAISED INTRACRANIAL PRESSURE (ICP): headache, vomiting, papilloedema.",
        "2. VISUAL DISTURBANCES: bitemporal hemianopia, visual loss, optic atrophy.",
        "3. ENDOCRINE / HYPOTHALAMIC DYSFUNCTION: growth failure, delayed puberty, DI, obesity.",
    ], S)
    h2(st, "B. Detailed Clinical Features by System", S)
    data = [
        ["System", "Symptoms / Signs", "Mechanism"],
        ["RAISED ICP",
         "Headache (morning, postural), nausea/vomiting, papilloedema, diplopia (CN VI palsy - false localising sign)",
         "Tumour enlargement + obstructive hydrocephalus (3rd ventricle blocked)"],
        ["VISUAL",
         "Bitemporal hemianopia (MOST COMMON; fibres from nasal retinae cross at chiasm). "
         "Unilateral visual loss. Optic atrophy (pale disc on fundoscopy). Diplopia.",
         "Optic chiasm compression. Optic nerve compression. CN VI palsy from raised ICP."],
        ["ENDOCRINE (PITUITARY)",
         "SHORT STATURE / GROWTH FAILURE: GH deficiency (most common hormone deficit). "
         "Delayed puberty: LH/FSH deficiency. "
         "Amenorrhoea, reduced libido. "
         "Hypothyroidism (TSH deficiency). "
         "Secondary adrenal insufficiency (ACTH deficiency). "
         "Hyperprolactinaemia (stalk effect: loss of dopamine inhibition).",
         "Compression/damage to pituitary gland and stalk."],
        ["HYPOTHALAMIC",
         "DIABETES INSIPIDUS (DI): polyuria, polydipsia, dilute urine (central DI - ADH deficiency). "
         "OBESITY / hyperphagia (hypothalamic involvement). "
         "Somnolence, temperature dysregulation. "
         "BEHAVIOURAL CHANGES, memory impairment.",
         "Direct hypothalamic involvement by tumour or post-surgical damage."],
        ["NEUROLOGICAL",
         "Personality change, cognitive decline, memory loss. "
         "Seizures (rare). "
         "Cranial nerve palsies (CN III, IV, VI, V - large tumours).",
         "Frontal lobe involvement, temporal lobe involvement, cranial nerve compression."],
    ]
    st.append(tbl(data, [W*0.17, W*0.42, W*0.41], S))
    caut(st, "SHORT STATURE in a child: always consider craniopharyngioma. "
         "GH deficiency is the MOST COMMON endocrine deficit. "
         "DI (central) = hypothalamic involvement = hallmark of hypothalamic craniopharyngioma.", S)
    sp(st, 4)

    # ── 5. INVESTIGATIONS ──────────────────────────────────────────────────────
    h1(st, "5.  INVESTIGATIONS", S)
    h2(st, "A. Imaging (Key for Exam)", S)
    data = [
        ["Investigation", "Findings in Craniopharyngioma"],
        ["MRI Brain (INVESTIGATION OF CHOICE)",
         "MIXED cystic + solid suprasellar mass. "
         "T1: cyst may show HIGH signal (short T1) due to proteinaceous / cholesterol content ('motor oil'). "
         "T2: cysts bright; solid areas intermediate. "
         "Contrast: ENHANCEMENT of solid component and cyst wall. "
         "No enhancement of cyst cavity. Optic chiasm draped over tumour. "
         "Pituitary gland often seen SEPARATELY below the mass. "
         "MR spectroscopy: high LIPID PEAKS."],
        ["CT Brain (for CALCIFICATION)",
         "CALCIFICATION in 75% (adamantinomatous) - sand-like or gravel-like; highly characteristic. "
         "Papillary type: rarely calcifies. "
         "Hyperdense cyst contents (proteinaceous). "
         "Hydrocephalus if 3rd ventricle blocked."],
        ["Skull X-ray (historical)",
         "Suprasellar calcification (60-80% visible). "
         "Enlarged sella turcica. "
         "Features of raised ICP (copper-beaten skull in children, sutural diastasis)."],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))

    h2(st, "B. Endocrine Assessment", S)
    data = [
        ["Test", "Purpose"],
        ["Serum GH + IGF-1",       "GH deficiency (most common; low IGF-1)"],
        ["LH, FSH, testosterone/oestradiol", "Gonadotropin deficiency"],
        ["TSH + free T4",           "Central hypothyroidism (low/normal TSH + low T4)"],
        ["ACTH + morning cortisol", "Secondary adrenal insufficiency (life-threatening if missed)"],
        ["Prolactin",               "Often mildly elevated (stalk effect); very high = prolactinoma"],
        ["Serum sodium + osmolality + urine osmolality", "Diabetes insipidus: serum Na high, serum osm high, urine dilute (< 300 mOsm/kg)"],
        ["Water deprivation test",  "Confirm central DI; differentiate from nephrogenic DI and psychogenic polydipsia"],
    ]
    st.append(tbl(data, [W*0.38, W*0.62], S))

    h2(st, "C. Ophthalmological Assessment", S)
    bl(st, [
        "Visual acuity, colour vision, visual field testing (Humphrey / Goldman perimetry).",
        "Fundoscopy: optic atrophy (pale disc), papilloedema.",
        "Formal neuro-ophthalmology assessment mandatory pre-operatively.",
    ], S)

    h2(st, "D. Other", S)
    bl(st, [
        "Bone age X-ray: assessment of growth retardation in children.",
        "Growth velocity chart: below 3rd percentile -> investigate.",
        "EEG: if seizures suspected.",
    ], S)
    sp(st, 4)

    # ── 6. DIFFERENTIAL DIAGNOSIS ──────────────────────────────────────────────
    h1(st, "6.  DIFFERENTIAL DIAGNOSIS  (Suprasellar Mass)", S)
    data = [
        ["Condition", "Distinguishing Features"],
        ["Pituitary macroadenoma",
         "Adults; sellar mass extending into suprasellar; no calcification; no 'motor oil' cysts. "
         "Endocrine: excess hormone (GH -> acromegaly; ACTH -> Cushing's; Prolactin -> amenorrhoea)."],
        ["Rathke cleft cyst",
         "No calcification (key distinction from craniopharyngioma). "
         "Simple cyst; no solid components; no wet keratin. MRI signal variable (mucoid contents)."],
        ["Optic pathway / hypothalamic glioma",
         "Children; expands optic nerves and chiasm (not compresses from outside). "
         "NF-1 association. T2 bright on MRI. No calcification. No 'motor oil'."],
        ["Germinoma",
         "Adolescent males; pineal or suprasellar; DI common. "
         "AFP + beta-hCG tumour markers elevated. Radiosensitive."],
        ["Meningioma (suprasellar)",
         "Adults; dural tail; enhances homogenously; calcification possible but no cysts."],
        ["Arachnoid cyst",
         "CSF signal on all MRI sequences; no enhancement; no solid component; no calcification."],
        ["Hypothalamic hamartoma",
         "Isointense to grey matter; sessile or pedunculated; no enhancement; presents with "
         "precocious puberty + gelastic (laughing) seizures."],
        ["Epidermoid / dermoid cyst",
         "DWI restriction (epidermoid). Dermoid: fat signal. "
         "DRY keratin (not wet keratin). No calcification pattern of craniopharyngioma."],
        ["Langerhans cell histiocytosis",
         "Loss of posterior pituitary bright spot on T1 MRI. "
         "DI + lytic bone lesions. Infundibular thickening."],
    ]
    st.append(tbl(data, [W*0.27, W*0.73], S))
    sp(st, 4)

    # ── 7. MANAGEMENT ──────────────────────────────────────────────────────────
    h1(st, "7.  MANAGEMENT", S)
    h2(st, "A. Surgical Management (PRIMARY TREATMENT)", S)
    bl(st, [
        "GOAL: Maximal safe resection while preserving visual function, hypothalamic function "
          "and quality of life.",
        "TOTAL RESECTION (GTR): best for cure but associated with HIGH MORBIDITY "
          "(hypothalamic damage -> obesity, DI, cognitive problems).",
        "SUBTOTAL RESECTION + RADIOTHERAPY: increasingly favoured to reduce hypothalamic damage.",
        "Philosophy shift: from radical excision (high morbidity) to LIMITED surgery + RT "
          "(better QoL outcomes).",
    ], S)
    data = [
        ["Surgical Approach", "Indication / Advantage"],
        ["TRANSSPHENOIDAL (endoscopic extended)",
         "For purely sellar or small suprasellar tumours; intrasellar component. "
         "Endoscopic endonasal approach (EEA): gaining prominence for sellar + retrochiasmatic tumours. "
         "Less morbidity; no brain retraction; good access to stalk and diaphragma sellae."],
        ["TRANSCRANIAL - Pterional craniotomy",
         "For large suprasellar tumours; retrochiasmatic / retrosellar extension; "
         "tumours involving anterior fossa. Most common traditional approach."],
        ["Subfrontal / frontal interhemispheric",
         "Retrochiasmatic tumours; tumours in 3rd ventricle."],
        ["Transcallosal / transventricular",
         "Intraventricular tumours; hydrocephalus; 3rd ventricular craniopharyngiomas."],
        ["Combined endoscopic + craniotomy",
         "For complex large tumours requiring multi-corridor approach."],
    ]
    st.append(tbl(data, [W*0.3, W*0.7], S))

    h2(st, "B. Radiotherapy", S)
    bl(st, [
        "ADJUVANT RT after subtotal resection: reduces recurrence significantly.",
        "LINAC (Linear Accelerator) radiosurgery: LINAC reduces recurrence 5-fold for "
          "craniopharyngioma (Scott-Brown's OHN&S).",
        "STEREOTACTIC RADIOSURGERY (Gamma Knife / CyberKnife): for small residual solid tumours; "
          "< 3 cm from optic chiasm required for safety.",
        "PROTON BEAM THERAPY: better dose conformity; preferred in children to reduce "
          "radiation to developing brain.",
        "FRACTIONATED EXTERNAL BEAM RT: for larger residual tumours near optic chiasm.",
        "PRIMARY RT alone: in unfit patients or those refusing surgery.",
    ], S)

    h2(st, "C. Intracystic Therapy (for cystic predominant tumours)", S)
    bl(st, [
        "INTRACYSTIC BLEOMYCIN: chemotherapy instilled directly into cyst via Ommaya reservoir; "
          "shrinks cyst; NOT widely accepted (significant neurotoxicity risk).",
        "INTRACYSTIC P32 (Phosphorus-32): radioactive isotope instilled into cyst; reduces cyst size.",
        "INTRACYSTIC INTERFERON-ALPHA: emerging therapy; less toxic than bleomycin.",
        "These experimental intracystic therapies have NOT gained widespread acceptance. (Scott-Brown's OHN&S)",
    ], S)

    h2(st, "D. Targeted Therapy (Recent Advance)", S)
    bl(st, [
        "BRAF V600E inhibitors (vemurafenib, dabrafenib): for PAPILLARY craniopharyngioma "
          "(95% harbour BRAF V600E mutation); dramatic responses reported in case series.",
        "CTNNB1 / Wnt pathway inhibitors: under investigation for adamantinomatous type.",
        "These are being evaluated in clinical trials for recurrent/unresectable disease.",
    ], S)

    h2(st, "E. Management of Complications", S)
    data = [
        ["Complication", "Management"],
        ["Hydrocephalus",
         "VP shunt OR 3rd ventriculostomy (ETV) before definitive surgery if raised ICP severe."],
        ["Diabetes Insipidus",
         "DESMOPRESSIN (DDAVP): intranasal 10-20 mcg BD or oral 0.1-0.2 mg TDS. "
         "Monitor fluid balance + serum sodium strictly (risk of hyponatraemia if over-treated)."],
        ["GH deficiency",
         "Recombinant GH therapy (somatropin) in children after tumour control confirmed. "
         "Monitor for tumour recurrence; theoretically GH could stimulate residual tumour."],
        ["Pan-hypopituitarism",
         "Hydrocortisone (life-saving; must be given first before thyroid replacement). "
         "Levothyroxine for hypothyroidism. Sex steroids for puberty/libido."],
        ["Obesity / hypothalamic damage",
         "Dietary management, exercise, GLP-1 receptor agonists (emerging). "
         "Methylphenidate for cognitive fatigue (some centres)."],
        ["Visual loss",
         "Urgent decompression of optic chiasm if acute visual deterioration. "
         "Ophthalmology follow-up; low-vision aids."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))

    # Management Flowchart
    flowchart(st, "MANAGEMENT FLOWCHART - Craniopharyngioma", [
        ("Suspected Craniopharyngioma: MRI Brain + CT Brain (calcification)", True),
        ("Full endocrine assessment + Formal visual field testing + Ophthalmology review", False),
        ("Hydrocephalus present? -> VP shunt / ETV first if raised ICP", False),
        ("MDT: Neurosurgeon + Endocrinologist + Ophthalmologist + Radiation Oncologist", True),
        ("Surgical resection: Transsphenoidal (small/sellar) OR Transcranial pterional (large suprasellar)", False),
        ("Subtotal resection (to preserve hypothalamus) + Post-op RT (LINAC / Gamma Knife / Proton beam)", False),
        ("Endocrine replacement: Hydrocortisone FIRST -> T4 -> DDAVP -> GH -> Sex steroids", False),
        ("Surveillance: MRI 3-6 monthly (yr 1-2); annual long-term; endocrine review 6-monthly", True),
    ], S)
    sp(st, 2)
    sp(st, 4)

    # ── 8. COMPLICATIONS & PROGNOSIS ───────────────────────────────────────────
    h1(st, "8.  COMPLICATIONS & PROGNOSIS", S)
    h2(st, "A. Complications", S)
    data = [
        ["Complication", "Detail"],
        ["Recurrence",    "Most common cause of treatment failure. Local recurrence even after GTR (~20-40%). "
                          "Close MRI surveillance essential."],
        ["Pan-hypopituitarism", "Common post-op; requires lifelong hormone replacement."],
        ["Diabetes Insipidus", "Occurs in 80-90% post-surgery. Permanent in majority."],
        ["Hypothalamic obesity", "Major long-term morbidity; irreversible hypothalamic damage; "
                                  "severe obesity, poor QoL."],
        ["Visual deterioration", "From surgical trauma to chiasm or incomplete decompression."],
        ["Cognitive impairment", "Memory problems, personality change; especially with hypothalamic involvement."],
        ["Radiation complications", "Radiation necrosis (rare), optic neuropathy, pituitary damage, "
                                     "secondary malignancy (very long-term)."],
        ["Vascular injury", "Carotid artery or anterior communicating artery damage during surgery."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))

    h2(st, "B. Prognosis", S)
    bl(st, [
        "10-year OVERALL SURVIVAL: 70-90% with modern treatment.",
        "Despite good survival: HIGH MORBIDITY from hypothalamic damage + endocrine deficits + cognitive issues.",
        "QUALITY OF LIFE is a major concern; hypothalamic involvement = major determinant of QoL.",
        "Recurrence rate: 20-50% after subtotal resection alone; significantly reduced with adjuvant RT.",
        "GTR (gross total resection): lower recurrence but higher morbidity from hypothalamic damage.",
        "Papillary type: slightly better; BRAF inhibitors may improve outcomes.",
        "Children: better survival but greater endocrine and cognitive morbidity.",
    ], S)
    caut(st, "HYPOTHALAMIC DAMAGE = most feared complication of surgery. "
         "Results in morbid obesity, DI, cognitive decline, poor QoL. "
         "Modern approach: LIMITED resection + RT to preserve hypothalamus. (Scott-Brown's OHN&S)", S)
    sp(st, 4)

    # ── 9. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "9.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What is craniopharyngioma and what is its origin?",
         "Benign (WHO Grade I) epithelial tumour arising from Rathke's pouch remnants. "
         "Most common suprasellar tumour in children. 1-3% of all intracranial tumours. "
         "Bimodal: peak 1 = 5-15 yrs; peak 2 = 50-60 yrs."),
        ("Q2: What are the two types of craniopharyngioma and their key differences?",
         "Adamantinomatous (90%): children + adults; CTNNB1/beta-catenin mutation; "
         "mixed cystic + solid; calcification (75%); WET KERATIN (pathognomonic); 'motor oil' cysts; "
         "peripheral palisading + stellate reticulum. "
         "Papillary (10%): adults only (40-55 yrs); BRAF V600E mutation (95%); "
         "usually solid; clear cyst fluid if present; no calcification; no wet keratin."),
        ("Q3: What is 'wet keratin' and why is it important?",
         "Wet keratin = ghost cells: keratinised cells without nuclei (anucleate squames). "
         "Unique to adamantinomatous craniopharyngioma. "
         "Differs from DRY keratin (epidermoid/dermoid cysts). "
         "DIAGNOSTIC even without viable epithelium on small biopsy. (Bradley & Daroff Neurology)"),
        ("Q4: What is the typical triad of craniopharyngioma presentation?",
         "1. RAISED ICP: headache, vomiting, papilloedema. "
         "2. VISUAL: bitemporal hemianopia (optic chiasm compression). "
         "3. ENDOCRINE: short stature (GH deficiency), delayed puberty, DI (polyuria/polydipsia)."),
        ("Q5: What does the MRI show in craniopharyngioma?",
         "Suprasellar mixed cystic + solid mass. "
         "T1: cyst - HIGH signal (cholesterol/protein = 'motor oil'). "
         "T2: cysts bright. Solid/wall: enhances with contrast. "
         "CT: CALCIFICATION (75%) - sand/gravel-like (adamantinomatous). "
         "Pituitary seen SEPARATELY below the mass. Optic chiasm draped over lesion."),
        ("Q6: What is the most common endocrine deficit in craniopharyngioma?",
         "GROWTH HORMONE (GH) deficiency - most common. "
         "Presents as short stature, growth failure in children. "
         "Low IGF-1. Requires GH stimulation tests (insulin tolerance test / glucagon test). "
         "Treat with recombinant somatropin after tumour control."),
        ("Q7: What is central DI and how is it managed?",
         "Central DI = hypothalamic damage -> ADH (vasopressin) deficiency -> "
         "polyuria (> 3 L/day), polydipsia, dilute urine (osm < 300 mOsm/kg), hypernatraemia. "
         "Management: DESMOPRESSIN (DDAVP) - intranasal or oral. "
         "Monitor fluid balance + serum sodium strictly."),
        ("Q8: What is the modern management approach to craniopharyngioma?",
         "Shift from RADICAL EXCISION (high hypothalamic morbidity) to "
         "LIMITED/SUBTOTAL RESECTION + ADJUVANT RADIOTHERAPY. "
         "LINAC radiosurgery reduces recurrence 5-fold. "
         "Endoscopic transsphenoidal for sellar/retrochiasmatic tumours; "
         "pterional craniotomy for large suprasellar lesions. "
         "Papillary type: BRAF V600E inhibitors (vemurafenib/dabrafenib) - emerging targeted therapy."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 4)

    # ── 10. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(st, "10.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Definition",      "Benign (WHO Grade I) epithelial tumour from Rathke's pouch remnants; most common suprasellar tumour in children"],
        ["Bimodal age",     "Peak 1: 5-15 yrs (children); Peak 2: 50-60 yrs (adults)"],
        ["Types",           "Adamantinomatous (90%): CTNNB1 mutation, calcified, 'motor oil' cysts, wet keratin. Papillary (10%): BRAF V600E, adults, solid, no calcification"],
        ["Wet keratin",     "PATHOGNOMONIC for adamantinomatous type; ghost cells; unique - NOT seen in epidermoid/dermoid"],
        ["Triad",           "Raised ICP + Bitemporal hemianopia + Endocrine deficit (GH deficiency most common)"],
        ["DI",              "Central DI = hypothalamic involvement; ADH deficiency; DDAVP treatment"],
        ["Key imaging",     "CT: calcification (75%). MRI: mixed cystic/solid suprasellar mass; cyst T1 bright ('motor oil'); pituitary seen separate"],
        ["Bitemporal hemianopia", "Optic chiasm compression; nasal retinal fibres cross at chiasm -> temporal field loss bilaterally"],
        ["Surgery",         "Pterional craniotomy (large suprasellar) OR Endoscopic transsphenoidal (sellar/small). Modern: limited resection + RT"],
        ["Radiotherapy",    "LINAC reduces recurrence 5-fold. Proton beam preferred in children. Gamma Knife for small residual."],
        ["Endocrine replacement", "ORDER: Hydrocortisone FIRST (life-saving) -> T4 -> DDAVP -> GH -> Sex steroids"],
        ["Prognosis",       "10-yr survival 70-90%; HIGH MORBIDITY from hypothalamic damage (obesity, DI, cognitive decline)"],
        ["Targeted therapy", "Papillary type: BRAF V600E inhibitors (vemurafenib/dabrafenib); Adamantinomatous: CTNNB1/Wnt inhibitors under investigation"],
        ["Key DD",          "Pituitary adenoma (no calcification, no cysts), Rathke cleft cyst (no calcification, simple), Germinoma (AFP/hCG positive), Optic glioma (NF-1)"],
    ]
    st.append(tbl(data, [W*0.23, W*0.77], S))

    sp(st, 5)
    st.append(Paragraph(
        "References: Scott-Brown's OHN&S 8th ed. | Bradley & Daroff Neurology in Clinical Practice | "
        "Grainger & Allison Diagnostic Radiology | Cummings ORL 7th ed. | KJ Lee's Essential ORL | "
        "Langman's Medical Embryology",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Craniopharyngioma_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Craniopharyngioma - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

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#!/usr/bin/env python3
# Mandible Fracture - Focused ENT/Maxillofacial PG Exam Notes (5-6 pages)
# NEW Palette: Charcoal-purple headings, forest-teal subheadings, amber-gold H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Charcoal-Purple / Forest-Teal / Amber-Gold ──────────────────────
C_H1_BG  = colors.HexColor("#3D2060")   # rich charcoal-purple
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#155A4A")   # forest teal
C_H2_BG  = colors.HexColor("#EDF6F3")   # pale mint
C_H3_FG  = colors.HexColor("#7A5500")   # amber-gold
C_H3_BG  = colors.HexColor("#FFF8E6")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#3D2060")
C_ALT    = colors.HexColor("#F0ECF8")   # pale purple alt row
C_PEARL  = colors.HexColor("#EDF6F3")   # teal pearl bg
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#3D2060")
C_VQ_BG  = colors.HexColor("#EDF6F3")
C_VQ_FG  = colors.HexColor("#3D2060")
C_FC_BOX = colors.HexColor("#D8CCEE")
C_FC_HDR = colors.HexColor("#3D2060")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = []
        for cell in row:
            nr.append(Paragraph(cell, S["cellh"] if ri==0 else S["cell"]))
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 2)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = WP - 2*M
    bw = W * 0.84
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        styl = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#B8A8D8") if bold else C_FC_BOX
        rows.append([Paragraph(txt, styl)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",(0,0),(-1,-1),0.5,C_RULE),
        ("TOPPADDING",(0,0),(-1,-1),3),("BOTTOMPADDING",(0,0),(-1,-1),3),
        ("LEFTPADDING",(0,0),(-1,-1),5),("RIGHTPADDING",(0,0),(-1,-1),5),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]
    for i, bg in enumerate(bgs): cmds.append(("BACKGROUND",(0,i),(0,i),bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0)]))
    st.append(outer); sp(st, 3)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("MANDIBLE FRACTURE", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Schwartz's Surgery 11e, Cummings ORL 7e, Scott-Brown's OHN&S 8e, "
        "Bailey & Love 28e, AO/ASIF Principles",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION ──────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "A mandibular fracture is a disruption in the continuity of the mandibular bone "
          "resulting from trauma, pathological processes, or iatrogenic causes.",
        "MOST COMMON fractured facial bone after nasal bones.",
        "The mandible is a ring-like structure: force applied at one point often creates "
          "BILATERAL or REMOTE fractures (the 'ring' concept).",
        "85% are displaced due to the pull of attached muscles of mastication.",
        "Dental occlusion is the primary clinical and therapeutic guide for all mandible fractures.",
    ], S)
    sp(st, 3)

    # ── 2. APPLIED ANATOMY ────────────────────────────────────────────────────
    h1(st, "2.  APPLIED ANATOMY", S)
    h2(st, "A. Anatomical Regions", S)
    data = [
        ["Region", "Definition", "Frequency"],
        ["Condyle",
         "Head of mandible; articulates with glenoid fossa (TMJ). Subcondylar = below condylar neck.",
         "26-36% (MOST COMMON)"],
        ["Angle",
         "Junction of body and ramus; inferior to 3rd molar. Lines of weakness due to impacted M3.",
         "25-31%"],
        ["Body",
         "Horizontal tooth-bearing portion between mental foramen and angle.",
         "15-22%"],
        ["Parasymphysis",
         "Between the two canines (distal to symphysis but anterior to mental foramen).",
         "14-20%"],
        ["Symphysis",
         "Midline; fusion point of two embryonic halves; thick bone, less common fracture site.",
         "7-15%"],
        ["Ramus",
         "Vertical portion; well-protected by muscles (masseter laterally, pterygoid medially).",
         "3-5%"],
        ["Coronoid process",
         "Attachment of temporalis; protected by zygoma; rare fracture site.",
         "< 1%"],
        ["Alveolar process",
         "Tooth-bearing ridge; may fracture independently or with body fracture.",
         "< 3%"],
    ]
    st.append(tbl(data, [W*0.18, W*0.60, W*0.22], S))

    h2(st, "B. Muscle Displacement Forces", S)
    bl(st, [
        "ELEVATOR muscles (close jaw): Masseter, medial pterygoid, temporalis -> pull ramus superiorly.",
        "DEPRESSOR muscles (open jaw): Digastric, geniohyoid, mylohyoid -> pull symphysis/body inferiorly.",
        "LATERAL PTERYGOID: protrusion of condyle; pulls condylar head anteriorly and medially on fracture.",
        "Muscle pull determines whether a fracture is FAVOURABLE or UNFAVOURABLE (see below).",
    ], S)
    pearl(st,
        "PEARL: Angle fracture = WEAK POINT because: (1) impacted 3rd molar reduces bone stock, "
        "(2) thin bone between roots of M3 and sigmoid notch, (3) oblique line acts as stress riser. "
        "Condyle = most common fracture site due to transmission of force along the mandibular axis. "
        "(Schwartz's Surgery 11e)", S)
    sp(st, 3)

    # ── 3. CLASSIFICATION ─────────────────────────────────────────────────────
    h1(st, "3.  CLASSIFICATION", S)
    h2(st, "A. By Anatomical Site (Dingman & Natvig / Kazanjian & Converse)", S)
    bl(st, [
        "Condyle | Subcondylar | Coronoid | Ramus | Angle | Body | Parasymphysis | Symphysis | Alveolar",
        "MOST COMMON sites: Condyle (26-36%) > Angle (25-31%) > Body (15-22%).",
    ], S)

    h2(st, "B. By Favourability of Fracture Line", S)
    data = [
        ["Type", "Definition", "Effect of Muscles"],
        ["FAVOURABLE\n(Horizontally favourable)",
         "Fracture line runs such that muscle pull RESISTS displacement: "
         "Line runs from posterior-superior to anterior-inferior (medially) or "
         "posteroinferior to anterosuperior.",
         "Muscles hold fragments together. "
         "MORE STABLE. Less surgical urgency."],
        ["UNFAVOURABLE\n(Horizontally unfavourable)",
         "Fracture line runs such that muscle pull CAUSES displacement: "
         "Line runs from anterior-superior to posterior-inferior.",
         "Muscles DISPLACE fragments. "
         "LESS STABLE. Requires early fixation."],
        ["VERTICALLY\nFAVOURABLE",
         "Fracture line from buccal to lingual such that masseter/pterygoid hold fragments.",
         "Less lateral displacement."],
        ["VERTICALLY\nUNFAVOURABLE",
         "Fracture line allows medial or lateral override of fragments.",
         "Greater lateral displacement; harder to reduce."],
    ]
    st.append(tbl(data, [W*0.18, W*0.46, W*0.36], S))

    h2(st, "C. By Fracture Character", S)
    data = [
        ["Type", "Description"],
        ["Simple (closed)", "No communication with external environment or oral cavity."],
        ["Compound (open)", "Communication with external environment (skin or oral mucosa). MOST MANDIBLE FRACTURES are compound (due to dentition and mucosa)."],
        ["Comminuted", "Multiple fragments; high-energy trauma; difficult fixation."],
        ["Greenstick", "Incomplete; periosteum intact; CHILDREN only (flexible bones)."],
        ["Pathological", "Fracture through diseased bone: tumour, cyst (dentigerous), osteomyelitis, osteoporosis."],
        ["Atrophic / Edentulous", "Severely resorbed edentulous mandible; poor bone stock; healing difficult."],
        ["Condylar subcondylar", "Below condylar head; special management (closed vs open controversial)."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    sp(st, 3)

    # ── 4. CLINICAL FEATURES ──────────────────────────────────────────────────
    h1(st, "4.  CLINICAL FEATURES", S)
    h2(st, "A. History", S)
    bl(st, [
        "Mode of injury: RTA, assault (commonest), fall, sports, industrial, gunshot.",
        "Pain: localized to fracture site; worsened by jaw movement.",
        "Malocclusion: patient notices inability to bite normally (teeth not fitting together).",
        "Paraesthesia / numbness: inferior alveolar nerve (IAN) / mental nerve distribution "
          "(lower lip, chin) = pathognomonic of body/parasymphysis fracture.",
        "Trismus: difficulty / inability to open mouth (pain, muscle spasm, coronoid impingement).",
        "Drooling of saliva; difficulty swallowing; dysarthria.",
        "Airway: bilateral parasymphysis / body fractures -> posterior tongue displacement -> "
          "acute airway compromise (EMERGENCY).",
    ], S)
    h2(st, "B. Physical Examination - Signs", S)
    data = [
        ["Sign", "Significance"],
        ["Malocclusion",
         "CARDINAL SIGN of mandible fracture. Change in bite = displaced fracture until proven otherwise. "
         "Premature contact on one side; anterior open bite (bilateral condyle fractures)."],
        ["Step deformity / irregularity",
         "Palpable step on inferior border of mandible at fracture site. "
         "Visible gap between teeth at fracture site."],
        ["Paraesthesia lower lip / chin",
         "Inferior alveolar nerve (IAN) injury at body / parasymphysis fracture. "
         "Mental nerve exits at mental foramen (between premolars)."],
        ["Trismus",
         "Limited mouth opening due to pain, muscle spasm or coronoid impingement."],
        ["Sublingual haematoma",
         "Ecchymosis in floor of mouth = VIRTUALLY DIAGNOSTIC of mandible fracture."],
        ["Abnormal mobility",
         "Bimanual palpation: movement at fracture site with manipulation."],
        ["Deviation of chin on opening",
         "Unilateral condyle fracture: chin deviates TOWARD injured side on opening (pterygoid pull)."],
        ["Anterior open bite",
         "Bilateral condyle fractures: posterior teeth in contact; anterior teeth apart."],
        ["Facial asymmetry / bruising",
         "Soft tissue contusion, swelling at angle or body."],
    ]
    st.append(tbl(data, [W*0.27, W*0.73], S))
    caut(st,
        "AIRWAY ALERT: Bilateral parasymphysis or body fractures cause posterior displacement of "
        "tongue base -> acute airway obstruction. ATLS protocol first; early intubation / surgical "
        "airway if needed before fracture management. (Schwartz's Surgery 11e)", S)
    sp(st, 3)

    # ── 5. INVESTIGATIONS ─────────────────────────────────────────────────────
    h1(st, "5.  INVESTIGATIONS", S)
    data = [
        ["Investigation", "Details / Use"],
        ["OPG (Orthopantomogram)\nFIRST-LINE INVESTIGATION",
         "Single panoramic view of entire mandible. "
         "Shows fracture site, displacement, involvement of tooth roots and IAN canal. "
         "Best for: body, angle, ramus, condyle. "
         "Limitation: poor for symphysis (burnout artefact), cannot assess condylar head well."],
        ["PA Mandible (Posteroanterior view)",
         "Shows mediolateral displacement. "
         "Complements OPG. Combined OPG + PA = standard radiological assessment."],
        ["Lateral oblique views (right and left)",
         "Good for body and angle fractures. "
         "Alternative when OPG not available."],
        ["CT scan (Axial + Coronal + 3D reformat)",
         "GOLD STANDARD for complex/comminuted fractures, condylar fractures, polytrauma. "
         "3D CT: best pre-operative planning. "
         "Defines fragment displacement, relation to IAN canal, tooth roots, articular surface."],
        ["Dental occlusion assessment",
         "Angle's classification: Class I (normal), II (mesial), III (distal). "
         "Restoring pre-injury occlusion = primary treatment goal."],
        ["CBCT (Cone Beam CT)",
         "Lower radiation; excellent for condylar fractures and dentoalveolar injuries. "
         "Increasingly used for mandible fractures."],
    ]
    st.append(tbl(data, [W*0.27, W*0.73], S))
    pearl(st,
        "PEARL: OPG + PA mandible = standard radiological pair for mandible fracture. "
        "CT + 3D reformat for condylar fractures, comminuted fractures, polytrauma, "
        "and pre-op surgical planning. (Schwartz's Surgery 11e)", S)
    sp(st, 3)

    # ── 6. MANAGEMENT ─────────────────────────────────────────────────────────
    h1(st, "6.  MANAGEMENT", S)
    h2(st, "A. Initial / Emergency Management", S)
    bl(st, [
        "ATLS protocol: airway, breathing, circulation first.",
        "Airway: chin lift, jaw thrust; suction blood/clots; "
          "bilateral symphysis fractures -> tongue stitch (through-and-through tongue suture) + "
          "manual anterior traction of anterior segment.",
        "Haemorrhage control: external pressure, packing, ligation if needed.",
        "IV access, IV fluids, analgesia, antibiotics (compound fracture: penicillin/amoxicillin).",
        "Soft diet; oral hygiene; temporary immobilisation with head bandage (Barton bandage).",
        "Tetanus prophylaxis (compound/contaminated fractures).",
    ], S)

    h2(st, "B. Definitive Treatment - Principles", S)
    bl(st, [
        "THREE GOALS: (1) Restore dental occlusion, (2) Anatomical reduction of fracture, "
          "(3) Stable fixation + soft tissue repair. (Schwartz's Surgery 11e)",
        "TIMING: Within 24-48 hours ideally; up to 5-7 days acceptable if soft tissues permit.",
        "CLOSED TREATMENT: for minimally displaced fractures, intact occlusion, condylar fractures "
          "(if no displacement/dislocation).",
        "OPEN TREATMENT (ORIF): displaced fractures, compound fractures, unfavourable fracture lines, "
          "failed closed treatment, edentulous mandible, comminuted, pathological.",
    ], S)

    h2(st, "C. Closed Treatment - Intermaxillary Fixation (IMF)", S)
    bl(st, [
        "ARCH BARS (Erich arch bars): stainless steel bars wired to maxillary and mandibular teeth "
          "-> rubber bands / wires close jaw in occlusion = IMF. GOLD STANDARD closed method.",
        "Duration: 4-6 weeks (varies by site; condylar = shorter to prevent TMJ ankylosis).",
        "IMF SCREWS (bone screws in maxilla + mandible): faster alternative to arch bars; "
          "useful for patients with good dentition.",
        "BARTON BANDAGE: external crepe bandage support; used as temporary measure only.",
        "Complications of IMF: pulmonary aspiration risk (jaw wired shut), poor oral hygiene, "
          "nutritional compromise, TMJ stiffness.",
    ], S)

    h2(st, "D. Open Reduction Internal Fixation (ORIF)", S)
    data = [
        ["Method", "Details"],
        ["Champy Technique\n(Functionally Stable Fixation)",
         "Single MONOCORTICAL miniplate placed along the 'ideal lines of osteosynthesis' "
         "(Champy's lines) on the tension surface of the mandible. "
         "For angle: plate along external oblique ridge. "
         "For body: two miniplates - one along alveolar margin, one along inferior border. "
         "Advantages: less invasive, less IAN risk, quicker. No prolonged IMF needed. "
         "Limitation: not for comminuted or severely displaced fractures."],
        ["AO/ASIF Rigid Fixation",
         "BICORTICAL compression plates / reconstruction plates. "
         "For severely displaced, comminuted, edentulous, and gunshot fractures. "
         "Provides rigid fixation; allows early mobilisation. "
         "Requires careful placement away from IAN canal and tooth roots."],
        ["Lag screw fixation",
         "Single or double cortical screws creating interfragmentary compression. "
         "Used for symphysis/parasymphysis fractures as adjunct to plates."],
        ["Reconstruction plate",
         "Large load-bearing plate; for comminuted, pathological, or post-resection defects. "
         "Placed along inferior border; spans entire defect."],
        ["External fixation",
         "Percutaneous pins + connecting bar. "
         "For contaminated/gunshot fractures; edentulous mandible; infected non-union. "
         "Temporary stabilisation pending definitive repair."],
    ]
    st.append(tbl(data, [W*0.23, W*0.77], S))

    h2(st, "E. Special Situations", S)
    data = [
        ["Situation", "Management"],
        ["Condylar fracture (unilateral, minimal displacement)",
         "CLOSED TREATMENT preferred: soft diet + physiotherapy. "
         "IMF for 2-3 weeks then active jaw exercise. "
         "Key: EARLY MOBILISATION to prevent TMJ ankylosis. (Schwartz's Surgery 11e)"],
        ["Condylar fracture (displaced / dislocated / bilateral)",
         "OPEN REDUCTION if: dislocation into middle cranial fossa, "
         "lateral extracapsular displacement, failed closed treatment, "
         "foreign body in joint, or bilateral + Class III malocclusion."],
        ["Condylar fracture in children",
         "ALWAYS closed treatment. Remodelling potential is excellent. "
         "Early mobilisation essential. Growth disturbance if condyle damaged."],
        ["Angle fracture with impacted M3",
         "Remove the tooth in the fracture line if it interferes with reduction, "
         "infected, or periodontally compromised. Champy plate along external oblique ridge."],
        ["Edentulous mandible",
         "Atrophic bone: poor healing, high non-union risk. "
         "Dentures as splints + IMF, OR reconstruction plate (inferior border). "
         "Bone graft for severe atrophy. Hyperbaric oxygen adjunct (irradiated bone)."],
        ["Paediatric fracture",
         "Greenstick / incomplete: closed treatment, soft diet. "
         "Avoid damage to developing tooth buds. "
         "Absorbable plates available for children to avoid second surgery."],
    ]
    st.append(tbl(data, [W*0.27, W*0.73], S))

    # Management flowchart
    flowchart(st, "MANAGEMENT FLOWCHART - Mandible Fracture", [
        ("ATLS: Airway secured, haemorrhage controlled, polytrauma excluded", True),
        ("OPG + PA mandible; CT for complex/condylar/polytrauma", False),
        ("Assess: displaced/undisplaced? Favourable/unfavourable? Dentition? Site?", False),
        ("UNDISPLACED / FAVOURABLE: Closed Rx - soft diet, IMF (arch bars / IMF screws) 4-6 weeks", False),
        ("DISPLACED / UNFAVOURABLE: ORIF - Champy miniplates (angle/body) OR AO plates (comminuted)", True),
        ("CONDYLAR: Closed (most) | Open ORIF (dislocated, bilateral, failed closed)", False),
        ("Post-op: Antibiotics, oral hygiene, soft diet; early jaw physiotherapy to prevent TMJ ankylosis", True),
    ], S)
    sp(st, 2)

    # ── 7. COMPLICATIONS ──────────────────────────────────────────────────────
    h1(st, "7.  COMPLICATIONS", S)
    data = [
        ["Complication", "Cause / Management"],
        ["MALOCCLUSION (most common early)",
         "Inadequate reduction or relapse. Reassess with occlusal splint; revision ORIF if needed."],
        ["INFECTION / OSTEOMYELITIS",
         "Compound nature of most mandible fractures; tooth in fracture line; delayed treatment. "
         "IV antibiotics; debridement; sequestrectomy; remove infected hardware; bone graft later."],
        ["NON-UNION",
         "Inadequate fixation; infection; poor bone quality (edentulous, irradiated, osteoporotic). "
         "Re-fixation + bone graft (iliac crest or rib); hyperbaric oxygen."],
        ["MALUNION",
         "Fracture heals in incorrect position -> malocclusion, facial asymmetry. "
         "Osteotomy and re-fixation."],
        ["IAN / MENTAL NERVE INJURY",
         "Inferior alveolar nerve injury at body/angle fracture OR iatrogenic during ORIF. "
         "Lower lip / chin paraesthesia. Usually neurapraxia; most recover. Microsurgical repair if lacerated."],
        ["TMJ ANKYLOSIS",
         "Condylar fracture + prolonged immobilisation -> fibrous/bony ankylosis of TMJ. "
         "PREVENTION: early mobilisation. Rx: condylectomy + interpositional arthroplasty + aggressive physiotherapy."],
        ["HARDWARE FAILURE / PLATE EXPOSURE",
         "Plate fracture, screw loosening; plate exposure through thin mucosa (angle). "
         "Remove hardware after union; revision fixation if before union."],
        ["TOOTH LOSS / DAMAGE",
         "Extraction of teeth in fracture line; devitalised teeth post-trauma. "
         "Dental implants / prosthetics after union."],
        ["FACIAL ASYMMETRY (late)",
         "Condylar growth disturbance in children; malunion in adults. "
         "Orthognathic surgery for correction."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))
    caut(st,
        "TMJ ANKYLOSIS = feared long-term complication of condylar fractures. "
        "Key prevention: NEVER immobilise condylar fractures for > 3 weeks; "
        "start active physiotherapy as soon as possible. "
        "Once ankylosis established: gap arthroplasty or total TMJ replacement required.", S)
    sp(st, 3)

    # ── 8. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "8.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: Why is the angle of the mandible the second most common fracture site?",
         "Three reasons: (1) Impacted/erupting 3rd molar reduces bone stock and creates a stress riser; "
         "(2) Thin bone between molar roots and sigmoid notch; "
         "(3) Junction of body and ramus - anatomically weak. "
         "Condyle is MOST COMMON overall due to force transmission along mandibular axis."),
        ("Q2: What is a favourable vs unfavourable mandible fracture?",
         "FAVOURABLE: fracture line oriented such that muscle pull resists displacement (holds fragments). "
         "UNFAVOURABLE: muscle pull causes/worsens displacement. "
         "VERTICALLY UNFAVOURABLE: allows mediolateral override. "
         "Unfavourable fractures require ORIF; favourable may be treated closed."),
        ("Q3: What is sublingual haematoma and what does it indicate?",
         "Ecchymosis/bruising in the floor of the mouth (sublingual region). "
         "VIRTUALLY DIAGNOSTIC of mandible fracture. "
         "Due to tearing of sublingual or submental vessels at fracture site. "
         "Combined with trismus + malocclusion = classic triad."),
        ("Q4: How does a unilateral condylar fracture present?",
         "Chin deviates toward the INJURED SIDE on opening (lateral pterygoid of normal side pulls unopposed). "
         "Ipsilateral premature contact. Malocclusion with ipsilateral posterior open bite. "
         "Contralateral cross-bite. Unilateral trismus. Anterior open bite in bilateral fractures."),
        ("Q5: What is the Champy technique of fixation?",
         "Functionally stable fixation using single MONOCORTICAL MINIPLATE placed along "
         "Champy's 'ideal lines of osteosynthesis' on the tension surface. "
         "Angle: plate on external oblique ridge. "
         "Body: two plates (alveolar + inferior border). "
         "Advantages: no IMF needed, less IAN risk, lower morbidity. "
         "Limitation: not for comminuted fractures."),
        ("Q6: When is ORIF indicated in condylar fractures?",
         "Indications: (1) Dislocation into middle cranial fossa, "
         "(2) Lateral extracapsular displacement, "
         "(3) Bilateral condyle + inability to establish occlusion, "
         "(4) Failed closed treatment, "
         "(5) Foreign body in TMJ. "
         "Closed treatment preferred for: unilateral, non/minimally displaced condylar fractures - "
         "especially in children (remodelling potential). (Schwartz's Surgery 11e)"),
        ("Q7: What are the complications of arch bar / IMF?",
         "Pulmonary aspiration risk (jaw wired shut, cannot vomit safely - wire cutters MUST be at bedside). "
         "Poor oral hygiene -> periodontal disease, caries. "
         "Nutritional compromise (liquid diet only). "
         "TMJ stiffness / ankylosis if prolonged. "
         "Pressure necrosis of gingival mucosa. Needle-stick injury to surgeon."),
        ("Q8: What is the significance of a tooth in the fracture line?",
         "Tooth in fracture line = technically compound fracture (communicates via periodontal membrane). "
         "Risk of infection / osteomyelitis if tooth left. "
         "Decision: RETAIN if tooth is vital, intact, aiding reduction, and no periodontal disease; "
         "REMOVE if mobile, fractured, infected, interfering with reduction, or in gunshot injury."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 3)

    # ── 9. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(st, "9.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Most common site",     "Condyle (26-36%) most common; Angle (25-31%) 2nd; Body (15-22%) 3rd"],
        ["Ring concept",         "Force at one point -> bilateral/remote fracture; parasymphysis blow -> bilateral condyle fractures"],
        ["Cardinal sign",        "MALOCCLUSION = most important sign; sublingual haematoma = virtually diagnostic"],
        ["IAN injury sign",      "Lower lip + chin paraesthesia = inferior alveolar nerve injured (body/parasymphysis fracture)"],
        ["Favourable fracture",  "Muscle pull holds fragments together; may treat closed"],
        ["Unfavourable fracture", "Muscle pull displaces fragments; needs ORIF"],
        ["Investigation",        "OPG + PA mandible first-line; CT 3D for complex/condylar/polytrauma"],
        ["Angle's classification", "Class I = normal occlusion; Class II = mesial (mandible back); Class III = distal (mandible forward)"],
        ["IMF",                  "Arch bars + wires / IMF screws; 4-6 weeks; wire cutters at bedside (aspiration risk)"],
        ["Champy technique",     "Monocortical miniplate along tension/osteosynthesis line; no IMF needed; lower morbidity"],
        ["Condylar fracture",    "Closed Rx (most); ORIF for dislocation into MCF, lateral displacement, bilateral + malocclusion; CHILDREN = always closed"],
        ["Angle fracture + M3",  "Remove M3 if infected/mobile/interfering; Champy plate on external oblique ridge"],
        ["TMJ ankylosis",        "Most feared condylar complication; PREVENT with early mobilisation < 3 weeks"],
        ["Non-union Rx",         "Re-fixation + bone graft + antibiotics; hyperbaric O2 for irradiated/compromised bone"],
        ["Paediatric",           "Greenstick; always closed; absorbable plates; watch for growth disturbance"],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))

    sp(st, 4)
    st.append(Paragraph(
        "References: Schwartz's Principles of Surgery 11th ed. | Cummings ORL H&N Surgery 7th ed. | "
        "Scott-Brown's OHN&S 8th ed. | Bailey & Love's Surgery 28th ed. | "
        "AO/ASIF Principles of Fracture Management in the Craniomaxillofacial Skeleton",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Mandible_Fracture_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Mandible Fracture - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

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Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_mandible_fracture.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_mandible_fracture.py'

#!/usr/bin/env python3
# Videofluoroscopy (VFSS) - Focused ENT PG Exam Notes (5-6 pages)
# NEW Palette: Midnight blue headings, deep crimson subheadings, teal-green H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Midnight Blue / Deep Crimson / Teal-Green ───────────────────────
C_H1_BG  = colors.HexColor("#0D1B3E")   # midnight blue
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#9B1B30")   # deep crimson
C_H2_BG  = colors.HexColor("#FEF2F4")   # pale rose
C_H3_FG  = colors.HexColor("#0B5940")   # deep teal-green
C_H3_BG  = colors.HexColor("#EAF5F1")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#0D1B3E")
C_ALT    = colors.HexColor("#E8EBF4")   # pale midnight alt row
C_PEARL  = colors.HexColor("#EAF5F1")   # teal pearl bg
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#0D1B3E")
C_VQ_BG  = colors.HexColor("#E8EBF4")
C_VQ_FG  = colors.HexColor("#0D1B3E")
C_FC_BOX = colors.HexColor("#C5CBE0")
C_FC_HDR = colors.HexColor("#0D1B3E")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = [Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

# Normal Swallow Phases Box
def phases_box(st, S):
    W = WP - 2*M
    phases = [
        ("ORAL PREPARATORY",
         "Voluntary. Food chewed, mixed with saliva -> bolus formed. "
         "Lips sealed; buccinator contracts; tongue moulds bolus. "
         "Duration: variable (depends on food texture)."),
        ("ORAL TRANSIT",
         "Voluntary. Tongue tip elevates to hard palate -> pushes bolus posteriorly. "
         "Tongue propels bolus to posterior oral cavity -> triggers pharyngeal swallow. "
         "Duration: ~1 sec."),
        ("PHARYNGEAL",
         "INVOLUNTARY (reflex). Triggered at tonsillar fauces / posterior tongue. "
         "Sequence: velopharyngeal closure -> laryngeal elevation + closure (epiglottic tilt) "
         "-> UOS relaxation (cricopharyngeus) -> pharyngeal peristalsis -> bolus enters oesophagus. "
         "Duration: ~1 sec. AIRWAY PROTECTED throughout."),
        ("OESOPHAGEAL",
         "Involuntary peristalsis propels bolus to stomach. "
         "Upper oesophageal sphincter (UOS/cricopharyngeus) relaxes -> bolus enters. "
         "Lower oesophageal sphincter (LOS) relaxes to receive bolus. "
         "Duration: 8-20 sec."),
    ]
    sp(st, 2)
    col1 = W * 0.22
    col2 = W * 0.78
    rows = [[Paragraph("PHASE", S["cellh"]), Paragraph("KEY EVENTS", S["cellh"])]]
    for ph, desc in phases:
        rows.append([Paragraph(ph, S["cell"]), Paragraph(desc, S["cell"])])
    t = Table(rows, colWidths=[col1, col2], repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),("LEADING",(0,0),(-1,-1), CL),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    st.append(t); sp(st, 3)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("VIDEOFLUOROSCOPY (VFSS) OF SWALLOWING", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e Vol 2, Cummings ORL 7e, "
        "Logemann (1993), IDDSI Framework",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION ─────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "Videofluoroscopy Swallowing Study (VFSS) = a RECORDED RADIOGRAPHIC (X-ray) study of "
          "the swallowing structures, their movement and coordination during deglutition.",
        "Also called: MODIFIED BARIUM SWALLOW (MBS) study, Dynamic Swallowing Study.",
        "Originally described by LOGEMANN (1983/1993) as a standardised diagnostic procedure "
          "for oropharyngeal dysphagia.",
        "GOLD STANDARD investigation for oropharyngeal dysphagia and aspiration assessment.",
        "Dynamic (real-time) assessment: tracks radio-opaque bolus from oral cavity to "
          "upper oesophagus. Differs from traditional (static) barium swallow.",
        "Provides both SAFETY (aspiration risk) and EFFICIENCY (bolus clearance) information.",
    ], S)
    sp(st, 3)

    # ── 2. PHYSIOLOGY OF NORMAL SWALLOWING ────────────────────────────────────
    h1(st, "2.  PHYSIOLOGY OF NORMAL SWALLOWING  (Applied Anatomy)", S)
    h2(st, "The 4 Phases of Deglutition", S)
    phases_box(st, S)

    h2(st, "Key Structures Visualised on VFSS", S)
    bl(st, [
        "ORAL CAVITY: lips, tongue, floor of mouth, hard palate, soft palate (velum).",
        "PHARYNX: oropharynx, hypopharynx; posterior pharyngeal wall; tonsillar pillars.",
        "LARYNX: epiglottis, arytenoids, true and false vocal folds.",
        "UPPER OESOPHAGEAL SPHINCTER (UOS): cricopharyngeus muscle (C5/C6 level); "
          "relaxes to allow bolus entry.",
        "OESOPHAGUS: proximal oesophagus visible on lateral view.",
        "AIRWAY: trachea and laryngeal vestibule (site of aspiration assessment).",
    ], S)
    pearl(st,
        "PHARYNGEAL PHASE = MOST CRITICAL for airway protection. "
        "Sequence: velopharyngeal closure -> hyoid/larynx elevation -> "
        "epiglottic inversion -> vocal fold adduction -> UOS relaxation -> pharyngeal peristalsis. "
        "Failure at any step -> PENETRATION or ASPIRATION. (Cummings ORL / Scott-Brown's)", S)
    sp(st, 3)

    # ── 3. INDICATIONS ────────────────────────────────────────────────────────
    h1(st, "3.  INDICATIONS FOR VFSS", S)
    data = [
        ["Category", "Specific Indications"],
        ["Neurological",
         "CVA / stroke (most common cause of oropharyngeal dysphagia). "
         "Parkinson's disease. Motor neurone disease (ALS). "
         "Multiple sclerosis. Traumatic brain injury. "
         "Myasthenia gravis. Guillain-Barre syndrome."],
        ["Head & Neck Cancer (ENT)",
         "Post-laryngectomy / partial laryngectomy. "
         "Post-pharyngectomy / glossectomy. "
         "Post-chemo-radiotherapy (CRT) for HNC. "
         "Post-oral cavity / oropharynx surgery. "
         "Pre-operative swallowing baseline assessment."],
        ["Structural / ENT causes",
         "Cricopharyngeal dysfunction / achalasia (failure of UOS to relax). "
         "Zenker's diverticulum (posterior pharyngeal wall pouching). "
         "Cervical osteophytes impinging on pharynx. "
         "Postcricoid web. Laryngeal cleft. Laryngomalacia."],
        ["Paediatric",
         "Feeding difficulties / failure to thrive. "
         "Laryngeal cleft, tracheo-oesophageal fistula (post-repair). "
         "Recurrent aspiration pneumonia. "
         "Cerebral palsy, Down syndrome. "
         "Radiologist's presence is BEST PRACTICE for paediatric VFSS."],
        ["Other",
         "Unexplained aspiration pneumonia. "
         "Recurrent chest infections. "
         "Assessment of swallowing after prolonged intubation / tracheostomy. "
         "Monitoring response to swallowing therapy."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    sp(st, 3)

    # ── 4. PROCEDURE ──────────────────────────────────────────────────────────
    h1(st, "4.  PROCEDURE", S)
    h2(st, "A. Team", S)
    bl(st, [
        "SPEECH AND LANGUAGE THERAPIST (SLT): primary assessor; directs bolus trials; "
          "interprets swallowing function; recommends therapy.",
        "RADIOLOGIST / RADIOGRAPHER: operates fluoroscopy equipment; monitors radiation dose.",
        "Physician / Surgeon may be present; nurse/physiotherapist for complex patients.",
        "Paediatric VFSS: radiologist presence = BEST PRACTICE. (Scott-Brown's OHN&S)",
    ], S)

    h2(st, "B. Patient Preparation", S)
    bl(st, [
        "NO FASTING required before VFSS.",
        "Patient positioned in their USUAL EATING/DRINKING position (sitting upright or at angle).",
        "Clinical Swallowing Examination (CSE / bedside assessment) MUST be performed before "
          "VFSS to confirm suitability and direct content of examination.",
        "Calibration: metal coin or ring of known diameter taped to chin for biomechanical measurements.",
        "Suction equipment available in case of gross aspiration.",
    ], S)

    h2(st, "C. Contrast Agent", S)
    bl(st, [
        "BARIUM SULPHATE: most commonly used radio-opaque contrast; mixed with food/liquid.",
        "IOTROLAN / water-soluble contrast: if fistula, perforation or aspiration risk is very high "
          "(barium pneumonitis risk with large volume aspiration).",
        "Test boluses given in INCREASING VOLUME to minimise aspiration risk.",
        "Multiple CONSISTENCIES tested (IDDSI framework):",
    ], S)
    data = [
        ["IDDSI Level", "Consistency", "Example"],
        ["Level 0", "Thin liquid (water)",    "Water, juice"],
        ["Level 1", "Slightly thick",          "Nectar-like"],
        ["Level 2", "Mildly thick",             "Yoghurt-drink"],
        ["Level 3", "Liquidised",               "Smooth puree"],
        ["Level 4", "Pureed",                   "Smooth mash"],
        ["Level 5", "Minced & moist",           "Minced meat"],
        ["Level 6", "Soft & bite-sized",        "Soft fish"],
        ["Level 7", "Regular / easy to chew",   "Normal diet"],
    ]
    st.append(tbl(data, [W*0.14, W*0.36, W*0.50], S))

    h2(st, "D. Views / Planes", S)
    bl(st, [
        "LATERAL VIEW (primary): lips anteriorly to C7 inferiorly. "
          "Assesses oral, pharyngeal, and proximal oesophageal phases; aspiration into trachea.",
        "ANTEROPOSTERIOR (AP) VIEW: symmetry of bolus flow, laterality of residue, "
          "vocal fold abduction. Aspiration harder to see (trachea overlies oesophagus).",
        "OBLIQUE VIEW: additional detail on bolus transport through pharynx into oesophagus.",
        "OESOPHAGEAL SCREEN: all patients should have oesophageal phase assessed "
          "(35% have simultaneous pharyngeal + oesophageal disorders). (Scott-Brown's OHN&S)",
    ], S)

    h2(st, "E. Compensatory Strategies Trialled During VFSS", S)
    bl(st, [
        "CHIN TUCK (chin-down posture): widens valleculae -> delays pharyngeal swallow -> reduces aspiration.",
        "HEAD TILT (to stronger side): directs bolus to stronger side of pharynx.",
        "HEAD ROTATION (to weaker/damaged side): closes ipsilateral pyriform sinus -> "
          "directs bolus to stronger side.",
        "EFFORTFUL SWALLOW: increases tongue base retraction -> better pharyngeal clearance.",
        "SUPRAGLOTTIC SWALLOW: voluntary breath-hold before swallow -> adducts VFs -> protects airway.",
        "MULTIPLE SWALLOWS / LIQUID CHASE: clears residue in valleculae or pyriform sinuses.",
        "TEXTURE MODIFICATION: change consistency to safer level (e.g., thicken liquids).",
    ], S)
    sp(st, 3)

    # ── 5. ANALYSIS / FINDINGS ────────────────────────────────────────────────
    h1(st, "5.  ANALYSIS OF VFSS FINDINGS", S)
    h2(st, "A. Penetration-Aspiration Scale (Rosenbek et al., 1996)", S)
    data = [
        ["Score", "Description"],
        ["1", "Material does not enter airway."],
        ["2", "Material enters airway, remains above vocal folds; ejected."],
        ["3", "Material enters airway, remains above vocal folds; NOT ejected (silent penetration)."],
        ["4", "Material contacts vocal folds; ejected."],
        ["5", "Material contacts vocal folds; NOT ejected."],
        ["6", "Material passes below vocal folds; ejected into larynx or out."],
        ["7", "Material passes below vocal folds; NOT ejected despite effort."],
        ["8", "Material passes below vocal folds; NO effort to eject (SILENT ASPIRATION)."],
    ]
    st.append(tbl(data, [W*0.1, W*0.9], S))

    h2(st, "B. Key Findings Assessed", S)
    data = [
        ["Finding", "Definition / Significance"],
        ["ASPIRATION",
         "Entry of material BELOW the vocal folds into the trachea. "
         "PRE-swallow aspiration: material enters airway before swallow reflex triggers. "
         "INTRA-swallow: during swallow. POST-swallow: after bolus passes (residue spills over). "
         "SILENT ASPIRATION (PAS 8): no cough, no protective response; highest risk."],
        ["PENETRATION",
         "Material enters laryngeal vestibule (above vocal folds) but does NOT pass below. "
         "PAS 2-5. May or may not be ejected. Less dangerous than aspiration."],
        ["RESIDUE",
         "Bolus material remaining after swallow attempt: in valleculae (base of tongue) "
         "or pyriform sinuses (cricopharyngeal dysfunction). "
         "Indicates impaired clearance; risk of post-swallow aspiration."],
        ["ORAL TRANSIT TIME",
         "Time from lip closure to triggering of pharyngeal swallow. Prolonged in oral phase disorders."],
        ["PHARYNGEAL TRANSIT TIME",
         "Time from pharyngeal swallow trigger to UOS closure. "
         "Prolonged in pharyngeal weakness or cricopharyngeal dysfunction."],
        ["HYOLARYNGEAL EXCURSION",
         "Anterior and superior movement of hyoid and larynx during swallow. "
         "Reduced -> UOS fails to open adequately -> residue in pyriform sinuses."],
        ["UOS (CRICOPHARYNGEAL) OPENING",
         "Width and duration of UOS opening. "
         "Reduced opening -> dysphagia, pyriform residue -> cricopharyngeal myotomy indicated."],
        ["ANATOMICAL ABNORMALITIES",
         "Zenker's diverticulum, cricopharyngeal bar, cervical osteophytes, "
         "pharyngeal pouch, webs, fistulae, post-surgical changes."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    pearl(st,
        "PEARL: SILENT ASPIRATION (PAS 8 = no cough, no response to aspiration) occurs in "
        "up to 40% of stroke patients. Clinical bedside assessment CANNOT detect silent aspiration. "
        "VFSS is the ONLY reliable method to detect and quantify aspiration. (Logemann / Cummings ORL)", S)
    sp(st, 3)

    # ── 6. VFSS vs FEES ───────────────────────────────────────────────────────
    h1(st, "6.  VFSS vs FEES  (Fibreoptic Endoscopic Evaluation of Swallowing)", S)
    data = [
        ["Feature", "VFSS", "FEES"],
        ["Principle",
         "Fluoroscopic X-ray; radio-opaque bolus tracked",
         "Flexible nasendoscope positioned in pharynx; direct visual assessment"],
        ["Gold standard for",
         "OROPHARYNGEAL DYSPHAGIA and ASPIRATION (gold standard)",
         "Laryngopharyngeal anatomy, secretion management, pharyngeal residue"],
        ["Phases assessed",
         "ALL 4 phases: oral prep, oral transit, pharyngeal, oesophageal",
         "PHARYNGEAL phase primarily; oral and oesophageal phases NOT seen"],
        ["Aspiration detection",
         "YES - direct visualisation of bolus entering trachea",
         "YES - but 'white-out' (lens covered by bolus) obscures peak of swallow"],
        ["Radiation",
         "YES - ionising radiation; 3 min = 2 cervical spine X-rays",
         "NO - no radiation; safe for repeated/prolonged use"],
        ["Bedside use",
         "NO - radiology dept; patient must be mobile/stable",
         "YES - bedside, ICU, clinic, ward"],
        ["Oral phase assessment",
         "YES - tongue, lip, palate movement visible",
         "NO - oral phase not visible"],
        ["Laryngeal sensitivity",
         "Cannot assess",
         "CAN assess (FEESST = FEES + Sensory Testing with air puff to arytenoids)"],
        ["Secretion management",
         "Limited - barium coats structures",
         "EXCELLENT - directly visualises secretion pooling/aspiration"],
        ["Structural pathology",
         "YES - Zenker's, web, osteophyte, fistula",
         "YES - direct mucosal view; vocal fold palsy; tumour"],
        ["Paediatric use",
         "Preferred - more complete assessment; radiologist present",
         "Possible but less comfortable for infants"],
        ["Disadvantages",
         "Radiation; needs radiology dept; barium taste/texture different from real food; "
         "limited mucosa/sensation assessment",
         "White-out at swallow peak; no oral phase; no oesophageal view; "
         "discomfort; risk of epistaxis/laryngospasm"],
    ]
    st.append(tbl(data, [W*0.18, W*0.41, W*0.41], S))
    caut(st,
        "VFSS CANNOT replace FEES and vice versa - they are COMPLEMENTARY. "
        "VFSS: best for complete swallowing assessment and aspiration quantification. "
        "FEES: best for bedside, secretion management, laryngeal/pharyngeal anatomy, "
        "sensitivity testing. Combined approach recommended for complex patients. (Scott-Brown's OHN&S)", S)
    sp(st, 3)

    # ── 7. CONTRAINDICATIONS & LIMITATIONS ───────────────────────────────────
    h1(st, "7.  CONTRAINDICATIONS & LIMITATIONS", S)
    h2(st, "Contraindications", S)
    bl(st, [
        "PREGNANCY: radiation exposure to fetus.",
        "GROSS ASPIRATION (relative): proceed very cautiously; use small volumes; "
          "suction must be available; consider FEES instead.",
        "Medically UNSTABLE patient: cannot safely attend radiology department.",
        "NIL BY MOUTH for non-dysphagia reasons (pre-anaesthetic): cannot perform.",
        "Inability to cooperate: cannot maintain position or follow instruction "
          "(severe cognitive impairment, agitation).",
        "Known allergy to radio-opaque contrast (rare but potentially life-threatening).",
    ], S)

    h2(st, "Limitations", S)
    bl(st, [
        "RADIATION: ionising; limit duration; minimise repeat studies. "
          "(3 min VFSS = 2 cervical spine X-rays radiation dose).",
        "Barium ALTERS food/fluid properties: does not behave exactly as normal food/fluid.",
        "CONTROLLED setting: may not reflect patient's real-life eating and drinking.",
        "Cannot assess mucosal detail, sensation, or laryngopharyngeal secretions well.",
        "Variability between swallows (especially semi-solids): stability can differ.",
        "Equipment-dependent: needs fluoroscopy suite + trained SLT + radiographer.",
        "Cost: high equipment + staff costs.",
    ], S)
    sp(st, 3)

    # ── 8. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "8.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What is a VFSS and why is it called the gold standard?",
         "VFSS = videofluoroscopy swallowing study = recorded real-time X-ray of swallowing "
         "structures during deglutition. Gold standard because: (1) assesses ALL 4 phases of "
         "swallowing dynamically, (2) quantifies aspiration and penetration using PAS, "
         "(3) identifies silent aspiration (missed on bedside assessment in up to 40% of strokes), "
         "(4) allows trial of compensatory strategies in real time. (Logemann / Scott-Brown's OHN&S)"),
        ("Q2: What is silent aspiration and why is it clinically important?",
         "Silent aspiration = entry of material below vocal folds WITHOUT any protective response "
         "(no cough, no throat clear, PAS score = 8). Clinically important: "
         "cannot be detected on bedside clinical swallowing examination. "
         "Leads to recurrent aspiration pneumonia, lung abscess, respiratory failure. "
         "VFSS is the only reliable method to detect it."),
        ("Q3: Name the 4 phases of swallowing and which is assessed best by VFSS.",
         "1. Oral preparatory (voluntary - bolus formation). "
         "2. Oral transit (voluntary - tongue propels bolus). "
         "3. Pharyngeal (involuntary - airway protection, UOS opens, pharyngeal peristalsis). "
         "4. Oesophageal (involuntary - peristalsis to stomach). "
         "VFSS assesses ALL 4. Pharyngeal phase most critical for airway safety. "
         "FEES cannot assess oral or oesophageal phases."),
        ("Q4: What is the Penetration-Aspiration Scale (PAS)?",
         "8-point scale by Rosenbek et al. (1996) rating depth of airway invasion and patient response. "
         "Score 1 = no airway entry. Score 2-5 = penetration (above VFs). "
         "Score 6-7 = aspiration (below VFs) with ejection attempt. "
         "Score 8 = SILENT ASPIRATION (below VFs, no response). "
         "Higher scores = greater severity and airway risk."),
        ("Q5: What compensatory strategies can be trialled during VFSS?",
         "1. Chin tuck: widens valleculae, delays swallow reflex, reduces pre-swallow aspiration. "
         "2. Head rotation to weaker side: closes ipsilateral pyriform sinus, directs bolus to stronger side. "
         "3. Effortful swallow: increases tongue base retraction, improves pharyngeal clearance. "
         "4. Supraglottic swallow: voluntary breath-hold -> VF adduction before swallow. "
         "5. Multiple swallows / liquid chase: clears pyriform residue. "
         "6. Texture modification (thicken liquids / soften solids)."),
        ("Q6: What are the key differences between VFSS and FEES?",
         "VFSS: gold standard; all 4 phases; radiation; radiology dept needed; "
         "best for aspiration quantification and oral phase assessment. "
         "FEES: bedside; no radiation; direct mucosal/secretion view; "
         "pharyngeal phase only; white-out at swallow peak; "
         "can assess laryngeal sensitivity (FEESST). "
         "They are COMPLEMENTARY, not interchangeable."),
        ("Q7: What is cricopharyngeal dysfunction and how does it appear on VFSS?",
         "Cricopharyngeus = upper oesophageal sphincter; failure to relax = "
         "CRICOPHARYNGEAL ACHALASIA / dysfunction. "
         "VFSS findings: persistent 'cricopharyngeal bar' (posterior indentation at C5/C6 on lateral view), "
         "pyriform sinus residue after swallow, delayed or absent UOS opening, "
         "bolus fails to pass into oesophagus. "
         "Treatment: cricopharyngeal myotomy / botulinum toxin injection / endoscopic stapler diverticulotomy."),
        ("Q8: What are the contraindications to VFSS?",
         "1. Pregnancy (radiation). "
         "2. Medically unstable - cannot attend radiology. "
         "3. Gross aspiration (relative) - use small volumes, suction ready; consider FEES. "
         "4. NIL by mouth (non-dysphagia reason). "
         "5. Inability to cooperate (severe dementia, agitation). "
         "6. Known contrast allergy. "
         "(Scott-Brown's OHN&S Vol 2)"),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 3)

    # ── 9. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(st, "9.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Full name",         "Videofluoroscopy Swallowing Study (VFSS) = Modified Barium Swallow (MBS)"],
        ["Coined by",         "LOGEMANN (1983) - first standardised diagnostic procedure for oropharyngeal dysphagia"],
        ["Gold standard for", "Oropharyngeal dysphagia and aspiration assessment"],
        ["Phases assessed",   "ALL 4: oral preparatory, oral transit, pharyngeal, oesophageal (vs FEES = pharyngeal only)"],
        ["Key advantage",     "Detects SILENT ASPIRATION (PAS 8) - missed in up to 40% of stroke patients on bedside exam"],
        ["PAS",               "Penetration-Aspiration Scale 1-8; PAS 8 = silent aspiration (no response, below VFs)"],
        ["Contrast agent",    "Barium sulphate; water-soluble if fistula/perforation; small volumes, increasing incrementally"],
        ["Primary view",      "LATERAL plane (lips to C7); AP for symmetry; oblique for upper oesophagus"],
        ["Team",              "SLT (primary) + Radiologist/Radiographer; paediatric = radiologist essential"],
        ["IDDSI",             "International Dysphagia Diet Standardisation Initiative: 8-level food/drink texture framework"],
        ["Cricopharyngeal bar", "Persistent posterior indentation at C5/C6 on VFSS = UOS dysfunction; Rx: myotomy or Botox"],
        ["Chin tuck",         "Widens valleculae + delays pharyngeal trigger -> reduces pre-swallow aspiration"],
        ["VFSS vs FEES",      "VFSS: all phases, radiation, radiology. FEES: bedside, no radiation, pharyngeal only, secretions"],
        ["Radiation dose",    "3 min VFSS = 2 cervical spine X-rays; not contraindicated but minimise duration"],
        ["Contraindications", "Pregnancy, medically unstable, nil by mouth (non-dysphagia), inability to cooperate, contrast allergy"],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))

    sp(st, 4)
    st.append(Paragraph(
        "References: Scott-Brown's OHN&S 8th ed. Vol 2 | Cummings ORL H&N Surgery 7th ed. | "
        "Logemann JA (1993) Manual for Videofluoroscopic Study of Swallowing | "
        "Rosenbek PAS Scale (1996) | IDDSI Framework (2017)",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Videofluoroscopy_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Videofluoroscopy Swallowing Study - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_vfss.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_vfss.py'

#!/usr/bin/env python3
# Foreign Body in Airway - Focused ENT PG Exam Notes (5-6 pages)
# NEW Palette: Deep olive-green headings, saffron-orange subheadings, steel-blue H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Deep Olive-Green / Saffron-Orange / Steel-Blue ──────────────────
C_H1_BG  = colors.HexColor("#2E4A1E")   # deep olive-green
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#B84A00")   # saffron-orange
C_H2_BG  = colors.HexColor("#FFF5EC")   # pale saffron
C_H3_FG  = colors.HexColor("#1A3E5C")   # steel-blue
C_H3_BG  = colors.HexColor("#EAF1F8")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#2E4A1E")
C_ALT    = colors.HexColor("#EBF1E6")   # pale olive alt row
C_PEARL  = colors.HexColor("#EAF1F8")   # steel-blue pearl bg
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_RULE   = colors.HexColor("#2E4A1E")
C_VQ_BG  = colors.HexColor("#EBF1E6")
C_VQ_FG  = colors.HexColor("#2E4A1E")
C_FC_BOX = colors.HexColor("#C8D8B8")
C_FC_HDR = colors.HexColor("#2E4A1E")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    s["ctr"] = ParagraphStyle("ctr", fontName=NM, fontSize=10, leading=13,
        textColor=C_BODY, alignment=TA_CENTER)
    s["ctrb"] = ParagraphStyle("ctrb", fontName=BD, fontSize=10, leading=13,
        textColor=C_FC_HDR, alignment=TA_CENTER)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = [Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

def flowchart(st, title, boxes, S):
    sp(st, 2)
    st.append(Paragraph(title, S["h2"]))
    sp(st, 2)
    W = WP - 2*M
    bw = W * 0.84
    rows, bgs = [], []
    for i, box in enumerate(boxes):
        bold = isinstance(box, tuple)
        txt = box[0] if bold else box
        styl = S["ctrb"] if bold else S["ctr"]
        bg = colors.HexColor("#A8C890") if bold else C_FC_BOX
        rows.append([Paragraph(txt, styl)])
        bgs.append(bg)
        if i < len(boxes)-1:
            rows.append([Paragraph("&#x25BC;", S["ctr"])])
            bgs.append(colors.white)
    t = Table(rows, colWidths=[bw])
    cmds = [
        ("BOX",(0,0),(-1,-1),0.5,C_RULE),
        ("TOPPADDING",(0,0),(-1,-1),3),("BOTTOMPADDING",(0,0),(-1,-1),3),
        ("LEFTPADDING",(0,0),(-1,-1),5),("RIGHTPADDING",(0,0),(-1,-1),5),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]
    for i, bg in enumerate(bgs): cmds.append(("BACKGROUND",(0,i),(0,i),bg))
    t.setStyle(TableStyle(cmds))
    outer = Table([[t]], colWidths=[W])
    outer.setStyle(TableStyle([("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0)]))
    st.append(outer); sp(st, 3)


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("FOREIGN BODY IN THE AIRWAY", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Schwartz's Surgery 11e, Cummings ORL 7e, "
        "Scott-Brown's OHN&S 8e, Bailey & Love 28e, APLS / ALSG Guidelines",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION ─────────────────────────────────────────────────────────
    h1(st, "1.  DEFINITION", S)
    bl(st, [
        "Foreign body (FB) aspiration = inadvertent inhalation of a solid or semisolid object "
          "into the larynx, trachea or bronchial tree.",
        "A PAEDIATRIC EMERGENCY: most common in children 6 months to 3 years "
          "(peak at 1-2 years).",
        "Third most common cause of accidental death in children under 1 year.",
        "Can also occur in adults: elderly (poor dentition, reduced cough reflex, sedation), "
          "neurologically impaired, intoxicated, or following dental procedures.",
        "AIRWAY FB = LIFE-THREATENING: complete obstruction -> death within minutes if untreated.",
    ], S)
    sp(st, 3)

    # ── 2. AETIOLOGY / TYPES OF FOREIGN BODY ─────────────────────────────────
    h1(st, "2.  AETIOLOGY & TYPES OF FOREIGN BODY", S)
    h2(st, "A. Predisposing Factors", S)
    bl(st, [
        "CHILDREN: immature swallowing coordination; lack of molar teeth (unable to chew properly); "
          "tendency to put objects in mouth; playing while eating; crying/laughing while eating.",
        "ADULTS: elderly (poor dentition, reduced gag/cough reflex); "
          "sedation / general anaesthesia; alcohol intoxication; neurological disease "
          "(stroke, Parkinson's, bulbar palsy); dental procedures (loose crowns, drill bits).",
        "Iatrogenic: broken dental instruments, loose tooth during intubation, suction catheter tips.",
    ], S)

    h2(st, "B. Common Foreign Bodies by Type", S)
    data = [
        ["Category", "Examples", "Key Characteristics"],
        ["ORGANIC / VEGETABLE\n(most common)",
         "PEANUTS (most common), seeds, popcorn, sunflower seeds, beans, carrot pieces",
         "Swell with moisture -> harder to remove. "
         "PEANUT OIL is highly irritant -> causes severe reactive bronchitis, "
         "chemical pneumonitis. Most dangerous vegetable FB. "
         "Cannot see on X-ray (radiolucent)."],
        ["INORGANIC / METALLIC",
         "Coins (oesophagus > airway), pins (safety/sewing), screws, "
         "metal toy parts, pen caps",
         "RADIOPAQUE on X-ray - can be seen directly. "
         "Sharp objects (open safety pins) risk mucosal laceration on removal."],
        ["PLASTIC",
         "Toy parts, pen tops, button batteries",
         "Radiolucent; may be missed on plain X-ray. "
         "BUTTON BATTERIES = extreme emergency: liquefactive necrosis within 2 hours."],
        ["FOOD",
         "Fish bones, meat, hot dogs, grapes (children)",
         "Grapes/hot dogs = smooth round -> complete occlusion risk. "
         "Fish bones = sharp, may embed in larynx/pyriform sinus."],
    ]
    st.append(tbl(data, [W*0.17, W*0.33, W*0.50], S))
    caut(st,
        "PEANUT = most common and most dangerous airway FB in children. "
        "Peanut oil causes chemical bronchitis + mucosal oedema -> progressive inflammation. "
        "BUTTON BATTERY = surgical emergency: electrochemical reaction causes liquefactive "
        "tissue necrosis within 2 hours; must be removed IMMEDIATELY. (Schwartz's Surgery 11e)", S)
    sp(st, 3)

    # ── 3. SITES OF LODGEMENT & ANATOMY ──────────────────────────────────────
    h1(st, "3.  SITES OF LODGEMENT & APPLIED ANATOMY", S)
    data = [
        ["Site", "Frequency", "Why / Anatomical Reason"],
        ["RIGHT MAIN BRONCHUS\n(MOST COMMON)",
         "Most common in adults and children",
         "Wider diameter, more vertical (less acute angle with trachea: ~25 degrees vs left ~45 degrees). "
         "Greater airflow on right. FB follows path of least resistance."],
        ["RIGHT LOWER LOBE BRONCHUS",
         "Most common lobar site",
         "Continuation of right main bronchus; steep angulation draws FB downward."],
        ["LEFT MAIN BRONCHUS",
         "Less common",
         "Narrower, more horizontal angle. FB less likely to enter."],
        ["TRACHEA",
         "~10-15%",
         "Mobile FB ('asthmatoid wheeze' / 'audible slap') - "
         "moves with respiration; audible at mouth as click."],
        ["LARYNX (supraglottis/glottis)",
         "~5-10%",
         "MOST DANGEROUS SITE: complete obstruction -> acute asphyxia. "
         "Presents with sudden severe stridor, aphonia, cyanosis."],
        ["Bilateral bronchi",
         "Rare",
         "Usually large tracheal objects that then impact at carina."],
    ]
    st.append(tbl(data, [W*0.20, W*0.14, W*0.66], S))
    pearl(st,
        "RIGHT MAIN BRONCHUS = most common site of FB lodgement (adult + child). "
        "Anatomical reasons: wider calibre + more vertical angle (25 degrees vs left 45 degrees) + "
        "greater airflow. Exception: when patient is supine/right lateral, right vs left may be equal. "
        "(Schwartz's Surgery 11e / Cummings ORL)", S)
    sp(st, 3)

    # ── 4. CLINICAL FEATURES ─────────────────────────────────────────────────
    h1(st, "4.  CLINICAL FEATURES", S)
    h2(st, "A. Classic History - Three Stages (Jackson's Stages)", S)
    data = [
        ["Stage", "Name", "Features"],
        ["Stage 1\n(ACUTE)",
         "Initial impact",
         "SUDDEN onset: violent choking episode, paroxysmal coughing, gagging, possible cyanosis. "
         "Occurs at time of FB inhalation. "
         "Stridor (laryngeal/tracheal FB) or wheeze (bronchial FB). "
         "May be WITNESSED by parents/carers. Duration: minutes to hours."],
        ["Stage 2\n(ASYMPTOMATIC)",
         "Quiescent phase",
         "FB becomes lodged; mucosal reflexes fatigue. "
         "SYMPTOM-FREE INTERVAL: child appears well; no respiratory distress. "
         "DANGEROUS - leads to false reassurance and missed/delayed diagnosis. "
         "Duration: hours to weeks."],
        ["Stage 3\n(COMPLICATIONS)",
         "Obstructive/inflammatory",
         "FB causes progressive: obstructive emphysema, atelectasis, recurrent pneumonia, "
         "lung abscess, bronchiectasis. "
         "Symptoms return: chronic cough, recurrent LRTI, wheeze, haemoptysis, fever. "
         "May be mistaken for asthma, URTI, or bronchiolitis."],
    ]
    st.append(tbl(data, [W*0.12, W*0.16, W*0.72], S))

    h2(st, "B. Signs by Site of FB", S)
    data = [
        ["Location", "Symptoms", "Signs"],
        ["LARYNGEAL",
         "Sudden stridor, hoarseness (dysphonia), aphonia, croupy cough, "
         "severe respiratory distress, choking, cyanosis",
         "Inspiratory stridor. Marked suprasternal/intercostal recession. "
         "Cyanosis. Unable to phonate. ACUTE EMERGENCY."],
        ["TRACHEAL",
         "'Asthmatoid wheeze', cough, mild distress. "
         "Audible SLAP sound (FB moves during inspiration/expiration)",
         "Bilateral wheeze. 'AUDITORY SLAP' - palpable thud on chest wall. "
         "'PALPATORY THUD'. Mobile FB."],
        ["RIGHT MAIN BRONCHUS",
         "Unilateral wheeze, cough, recurrent LRTI on right side",
         "REDUCED breath sounds on right. "
         "UNILATERAL WHEEZE (localised). "
         "HYPERRESONANCE on right (air trapping / obstructive emphysema). "
         "Mediastinal SHIFT to LEFT on expiration (check expiratory film)."],
        ["BRONCHIAL (subacute)",
         "Persistent cough, recurrent pneumonia same lobe, "
         "failure to improve with antibiotics",
         "Focal signs: decreased breath sounds, dullness (atelectasis) or "
         "hyperresonance (air trapping). "
         "Clubbing (late - bronchiectasis)."],
    ]
    st.append(tbl(data, [W*0.17, W*0.38, W*0.45], S))
    caut(st,
        "STAGE 2 (asymptomatic/quiescent phase) = most dangerous: "
        "child appears well after initial choking episode. "
        "Do NOT be falsely reassured. If witnessed choking -> INVESTIGATE regardless of current symptoms. "
        "Delayed diagnosis leads to obstructive pneumonia, bronchiectasis, abscess.", S)
    sp(st, 3)

    # ── 5. INVESTIGATIONS ────────────────────────────────────────────────────
    h1(st, "5.  INVESTIGATIONS", S)
    data = [
        ["Investigation", "Findings / Role"],
        ["CHEST X-RAY PA (Inspiratory)\nFIRST-LINE",
         "RADIOPAQUE FB: directly visible (coins, metal objects - 10-15% of airway FBs). "
         "RADIOLUCENT FB (most common): indirect signs only. "
         "Normal CXR does NOT exclude FB. "
         "Indirect signs: (see below)"],
        ["CHEST X-RAY Expiratory\n(KEY for bronchial FB)",
         "OBSTRUCTIVE EMPHYSEMA / AIR TRAPPING: affected side FAILS to deflate on expiration "
         "(normal side deflates). "
         "Mediastinal shift AWAY from affected side on expiration. "
         "Most important indirect sign on plain CXR."],
        ["DECUBITUS (lateral) film\n(Paediatric alternative)",
         "Child unable to cooperate with expiratory film. "
         "FB side DEPENDENT: normal lung deflates (gravity), "
         "FB-side FAILS to deflate. "
         "Mediastinal shift to normal (upper) side."],
        ["CXR Indirect Signs\n(Radiolucent FB)",
         "1. Unilateral HYPERINFLATION / air trapping (ball-valve effect). "
         "2. Mediastinal shift AWAY from FB side on expiration. "
         "3. ATELECTASIS / collapse (complete obstruction). "
         "4. Consolidation / pneumonia (secondary infection). "
         "5. Shift of trachea (tracheal FB)."],
        ["CT Chest\n(if CXR inconclusive)",
         "Detects radiolucent FBs, localises exactly. "
         "Virtual bronchoscopy reconstructions. "
         "Identifies complications (abscess, bronchiectasis). "
         "Not always needed if strong clinical suspicion -> go to bronchoscopy."],
        ["Fluoroscopy",
         "Real-time assessment of chest expansion asymmetry. "
         "Demonstrates PARADOXICAL mediastinal movement. "
         "Historical - largely replaced by CT."],
        ["RIGID BRONCHOSCOPY\n(DIAGNOSTIC + THERAPEUTIC)",
         "DEFINITIVE investigation AND treatment. "
         "Performed under GA. Directly visualises + removes FB. "
         "Preferred over flexible bronchoscopy for FB removal in all cases."],
    ]
    st.append(tbl(data, [W*0.27, W*0.73], S))
    pearl(st,
        "KEY RADIOLOGY: Expiratory CXR shows FB side HYPERINFLATED (fails to collapse) "
        "= ball-valve obstruction (air enters on inspiration past FB, "
        "FB blocks air exit on expiration). "
        "NORMAL INSPIRATORY CXR does NOT exclude airway FB. (Schwartz's Surgery 11e)", S)
    sp(st, 3)

    # ── 6. MANAGEMENT ────────────────────────────────────────────────────────
    h1(st, "6.  MANAGEMENT", S)

    h2(st, "A. EMERGENCY - Complete Airway Obstruction (Conscious Patient)", S)
    bl(st, [
        "ASK: 'Are you choking?' -> If EFFECTIVE cough: ENCOURAGE coughing; do NOT interfere.",
        "If INEFFECTIVE cough / unable to speak / cyanotic:",
    ], S)

    data = [
        ["Age Group", "First Aid Sequence"],
        ["INFANT\n(< 1 year)",
         "1. 5 BACK BLOWS: face-down over forearm; heel of hand between shoulder blades. "
         "2. 5 CHEST THRUSTS: face-up; 2 fingers on lower sternum; NOT abdominal thrusts. "
         "Alternate back blows and chest thrusts. "
         "DO NOT USE ABDOMINAL THRUSTS (Heimlich) in infants < 1 year - risk of abdominal/liver injury."],
        ["CHILD\n(1 year - puberty)",
         "1. 5 BACK BLOWS: lean forward; heel of hand between shoulder blades. "
         "2. 5 ABDOMINAL THRUSTS (HEIMLICH MANOEUVRE): stand behind, fist above umbilicus, "
         "sharp upward thrust. "
         "Alternate until FB expelled or child loses consciousness."],
        ["ADULT",
         "5 BACK BLOWS followed by 5 ABDOMINAL THRUSTS (HEIMLICH). "
         "If pregnant or obese: CHEST THRUSTS instead of abdominal. "
         "Alternate until FB expelled."],
        ["UNCONSCIOUS (any age)",
         "Call for help / ambulance. "
         "Start CPR (chest compressions create pressure to dislodge FB). "
         "If FB visible in mouth: FINGER SWEEP to remove. "
         "NEVER blind finger sweep (may push FB deeper). "
         "Hospital: laryngoscopy + Magill forceps extraction."],
    ]
    st.append(tbl(data, [W*0.16, W*0.84], S))

    h2(st, "B. Hospital Management - Stable / Incomplete Obstruction", S)
    bl(st, [
        "ADMIT: all cases of suspected airway FB regardless of current symptom status.",
        "Oxygen therapy; monitoring; IV access; nil by mouth.",
        "Do NOT perform blind finger sweeps or Heimlich in cooperative child - "
          "may dislodge a partially impacted FB and cause complete obstruction.",
        "RIGID BRONCHOSCOPY under GENERAL ANAESTHESIA = DEFINITIVE TREATMENT.",
        "Timing: URGENT if symptomatic; SEMI-URGENT (within hours) if stable.",
        "Senior anaesthetist + ENT/thoracic surgeon team present.",
    ], S)

    h2(st, "C. Rigid Bronchoscopy - Key Points", S)
    bl(st, [
        "RIGID BRONCHOSCOPE (Storz/Hollinger): preferred for FB removal in all ages; "
          "provides ventilation + suction + excellent optical access + forceps working channel.",
        "OPTICAL FORCEPS: preferred grasping instrument; "
          "alligator, rat-tooth, peanut forceps based on FB type.",
        "Anaesthesia: spontaneous ventilation (traditional) or controlled TIVA; "
          "avoid paralysis as cough reflex helps dislodge FB.",
        "PEANUT: grasp with peanut forceps; keep airway open during removal "
          "(enlarged due to moisture - may be tight).",
        "SHARP FB (open safety pin): CLOSE PIN before withdrawal "
          "using modified forceps; sharp end TRAILING.",
        "EPINEPHRINE INJECTION into mucosa if FB retained long-term: "
          "reduces bleeding during removal. (Schwartz's Surgery 11e)",
        "FLEXIBLE BRONCHOSCOPY: useful for diagnosis and for retrieving FBs in distal/lobar bronchi "
          "where rigid scope cannot reach; less ideal as primary tool.",
        "POST-BRONCHOSCOPY: monitor; repeat CXR; intensive physiotherapy; "
          "antibiotics if secondary pneumonia.",
    ], S)

    # Management Flowchart
    flowchart(st, "MANAGEMENT FLOWCHART - Airway Foreign Body", [
        ("Suspected/witnessed FB aspiration: assess airway patency immediately", True),
        ("COMPLETE OBSTRUCTION: Back blows + Abdominal/Chest thrusts (Heimlich) by age group", False),
        ("Unconscious: CPR + visible FB removal; HOSPITAL: laryngoscopy + Magill forceps", False),
        ("PARTIAL / NO OBSTRUCTION: O2, nil by mouth, IV access, CXR (PA + Expiratory)", False),
        ("Strong suspicion (witnessed choking + unilateral signs): proceed to rigid bronchoscopy", True),
        ("RIGID BRONCHOSCOPY under GA: optical forceps removal; ventilation maintained throughout", False),
        ("Post-op: CXR, chest physio, antibiotics if secondary infection, monitor for complications", True),
    ], S)
    sp(st, 2)

    # ── 7. COMPLICATIONS ─────────────────────────────────────────────────────
    h1(st, "7.  COMPLICATIONS", S)
    data = [
        ["Complication", "Mechanism / Management"],
        ["Acute asphyxia / death",
         "Complete laryngeal/tracheal obstruction; most fatal in first few minutes. "
         "Back blows + Heimlich + CPR; emergency laryngoscopy / tracheostomy."],
        ["Obstructive emphysema",
         "Ball-valve effect: air enters past FB, cannot exit. "
         "Hyperinflation -> mediastinal shift -> cardiorespiratory compromise."],
        ["Atelectasis / Collapse",
         "Complete obstruction -> absorption collapse of lobe/segment. "
         "Resolves after FB removal; physio."],
        ["Aspiration pneumonia",
         "Infection distal to FB; secondary to retained secretions. "
         "Antibiotics (amoxicillin-clavulanate); remove FB urgently."],
        ["Lung abscess",
         "Suppurative infection distal to long-standing FB. "
         "Prolonged antibiotics + FB removal + surgical drainage if needed."],
        ["Bronchiectasis",
         "Chronic infection / inflammation -> permanent bronchial wall destruction. "
         "Irreversible; late complication of delayed diagnosis. "
         "Lobectomy if localised."],
        ["Bronchoscopy complications",
         "Hypoxia, laryngospasm, bronchospasm, haemorrhage, airway trauma, "
         "pneumothorax, oesophageal perforation (rare). "
         "Anaesthetist + surgeon must be experienced."],
        ["Chemical bronchitis\n(peanut)",
         "Peanut oil -> severe reactive bronchitis + mucosal oedema within hours. "
         "Early removal essential; steroids/adrenaline nebulisers post-removal."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    sp(st, 3)

    # ── 8. VIVA QUESTIONS ────────────────────────────────────────────────────
    h1(st, "8.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: Why is the right main bronchus the most common site for FB lodgement?",
         "Three anatomical reasons: "
         "(1) WIDER DIAMETER than left main bronchus. "
         "(2) More VERTICAL angle with trachea (~25 degrees vs left ~45 degrees). "
         "(3) Greater AIRFLOW on right side. "
         "FB follows the path of least resistance and greatest airflow. "
         "Exception: equal risk in supine/right lateral patients. (Schwartz's Surgery)"),
        ("Q2: Describe Jackson's three stages of airway FB.",
         "Stage 1 (Acute): sudden choking, violent cough, gagging, stridor/wheeze - FB impacts. "
         "Stage 2 (Quiescent): FB lodges, reflexes fatigue -> SYMPTOM-FREE INTERVAL. "
         "DANGEROUS - false reassurance, leads to delayed diagnosis. "
         "Stage 3 (Complication): obstructive emphysema, atelectasis, pneumonia, abscess, bronchiectasis."),
        ("Q3: What is the X-ray sign of a bronchial FB and why does it occur?",
         "EXPIRATORY FILM: unilateral HYPERINFLATION (air trapping) on affected side = "
         "BALL-VALVE OBSTRUCTION. "
         "FB allows air IN on inspiration (airways dilate) but BLOCKS exit on expiration (airways narrow). "
         "Mediastinal shift to the NORMAL side on expiration. "
         "In infants: decubitus film (dependent normal lung deflates; FB-side fails to deflate)."),
        ("Q4: What is the first aid management of FB choking in a child vs infant?",
         "INFANT (< 1 year): 5 back blows + 5 CHEST THRUSTS (NOT abdominal - liver/organ injury risk). "
         "CHILD (> 1 year): 5 back blows + 5 ABDOMINAL THRUSTS (Heimlich). "
         "Alternate until FB expelled or loss of consciousness -> CPR. "
         "NEVER blind finger sweep."),
        ("Q5: Why is peanut the most dangerous vegetable FB?",
         "1. RADIOLUCENT - not visible on plain X-ray; diagnosis easily missed. "
         "2. SWELLS with moisture - enlarges after lodgement, harder to remove. "
         "3. PEANUT OIL is highly irritant - causes severe reactive bronchitis, "
         "mucosal oedema, chemical pneumonitis within hours. "
         "4. Crumbles easily - fragments on removal attempts. "
         "Requires EARLY URGENT rigid bronchoscopy."),
        ("Q6: What are the principles of rigid bronchoscopy for FB removal?",
         "Performed under GA; spontaneous ventilation preferred (cough helps). "
         "Rigid scope provides: ventilation, suction, optical access, forceps channel. "
         "Optical forceps (rat-tooth, alligator, peanut forceps) based on FB type. "
         "SHARP FB (open safety pin): close pin before extraction; sharp end trailing. "
         "PEANUT: inject epinephrine if long-retained (reduces mucosal bleeding). "
         "Post-op: CXR + physiotherapy + antibiotics if secondary infection."),
        ("Q7: What are the complications of long-standing (delayed diagnosis) airway FB?",
         "ATELECTASIS -> PNEUMONIA -> LUNG ABSCESS -> BRONCHIECTASIS (irreversible). "
         "Chemical bronchitis (peanut oil). Obstructive emphysema with mediastinal shift. "
         "Late complications require prolonged antibiotics, physiotherapy, "
         "and possibly surgical lobectomy for localised bronchiectasis."),
        ("Q8: What is the difference in management of laryngeal vs bronchial FB?",
         "LARYNGEAL FB (EMERGENCY): complete obstruction -> acute asphyxia. "
         "Immediate back blows + Heimlich. If unconscious: CPR. "
         "Hospital: direct laryngoscopy + Magill forceps / rigid laryngoscope. "
         "Emergency tracheostomy/cricothyrotomy if laryngoscopy fails. "
         "BRONCHIAL FB (semi-urgent): incomplete obstruction; stable patient. "
         "Admit, O2, CXR, nil by mouth -> elective urgent RIGID BRONCHOSCOPY under GA."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 3)

    # ── 9. KEY POINTS SUMMARY ────────────────────────────────────────────────
    h1(st, "9.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Age",              "Peak 1-2 years; boys > girls; 3rd most common accidental death < 1 year"],
        ["Most common FB",   "PEANUT (most common vegetable/food FB); most common overall = organic/vegetable"],
        ["Most common site", "RIGHT MAIN BRONCHUS (wider, more vertical, greater airflow)"],
        ["Laryngeal FB",     "Most dangerous site: complete obstruction -> acute asphyxia -> death"],
        ["Jackson's stages", "Stage 1: acute choking. Stage 2: QUIESCENT (asymptomatic - dangerous). Stage 3: complications"],
        ["Tracheal FB sign", "'Auditory slap' / 'palpatory thud' - FB moves with respiration; bilateral wheeze"],
        ["CXR indirect sign","Expiratory film: unilateral air trapping (fails to deflate) = BALL-VALVE effect; mediastinal shift away"],
        ["Decubitus film",   "For infants: dependent normal side deflates; FB-side fails to deflate"],
        ["Infant first aid", "5 back blows + 5 CHEST THRUSTS (NOT Heimlich - liver injury risk < 1 year)"],
        ["Child/adult",      "5 back blows + 5 ABDOMINAL THRUSTS (Heimlich); alternate until expelled"],
        ["Gold standard Rx", "RIGID BRONCHOSCOPY under GA + optical forceps removal"],
        ["Peanut danger",    "Radiolucent + swells + oil causes chemical bronchitis + crumbles = most dangerous"],
        ["Button battery",   "EXTREME EMERGENCY: liquefactive necrosis within 2 hours; remove IMMEDIATELY"],
        ["Safety pin removal","CLOSE pin before extraction; sharp end trailing to avoid mucosal laceration"],
        ["Late complications","Atelectasis -> Pneumonia -> Abscess -> BRONCHIECTASIS (irreversible); may need lobectomy"],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))

    sp(st, 4)
    st.append(Paragraph(
        "References: Schwartz's Principles of Surgery 11th ed. | Cummings ORL H&N Surgery 7th ed. | "
        "Scott-Brown's OHN&S 8th ed. | Bailey & Love's Surgery 28th ed. | "
        "APLS (Advanced Paediatric Life Support) Guidelines | ALSG Protocols",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/ForeignBody_Airway_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Foreign Body in Airway - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Piperacillin - Focused ENT PG Exam Notes (5-6 pages)
# NEW Palette: Rich burgundy headings, deep teal subheadings, warm amber H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Rich Burgundy / Deep Teal / Warm Amber ──────────────────────────
C_H1_BG  = colors.HexColor("#5C1230")   # rich burgundy
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#0D4D4D")   # deep teal
C_H2_BG  = colors.HexColor("#E8F5F5")   # pale teal
C_H3_FG  = colors.HexColor("#7A4800")   # warm amber
C_H3_BG  = colors.HexColor("#FFF6E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#5C1230")
C_ALT    = colors.HexColor("#F5E8EE")   # pale burgundy alt row
C_PEARL  = colors.HexColor("#E8F5F5")   # teal pearl bg
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#155A1A")   # dark green for doses
C_DOSE_BG= colors.HexColor("#EAF5EB")
C_RULE   = colors.HexColor("#5C1230")
C_VQ_BG  = colors.HexColor("#F5E8EE")
C_VQ_FG  = colors.HexColor("#5C1230")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S): st.append(Paragraph(f"♥ {t}", S["dose"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = [Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("PIPERACILLIN  (& Piperacillin-Tazobactam)", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Lippincott Pharmacology 8e, Bailey & Love 28e, "
        "Harriet Lane Handbook 23e, Goldman-Cecil Medicine, Goodman & Gilman",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. INTRODUCTION / CLASSIFICATION ──────────────────────────────────────
    h1(st, "1.  INTRODUCTION & CLASSIFICATION", S)
    data = [
        ["Property", "Detail"],
        ["Drug class",        "Beta-lactam antibiotic; UREIDOPENICILLIN (extended-spectrum / antipseudomonal penicillin)"],
        ["Chemical name",     "Piperacillin sodium; MW 539.5 Da"],
        ["Subclass of",       "Semi-synthetic penicillin; derived from ampicillin with piperazine side chain"],
        ["Commercial forms",  "Piperacillin alone (parenteral only; historical). "
                              "PIPERACILLIN-TAZOBACTAM (Pip-Taz; trade name: TAZOCIN, ZOSYN) = "
                              "standard clinical formulation (4:1 ratio)."],
        ["Route",             "INTRAVENOUS (IV) or Intramuscular (IM) ONLY. NOT orally bioavailable "
                              "(acid-labile; destroyed by gastric acid)."],
        ["Bactericidal action","YES - concentration-INDEPENDENT, TIME-DEPENDENT killing "
                              "(efficacy depends on time drug concentration stays above MIC)."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))
    sp(st, 3)

    # ── 2. PENICILLIN CLASS OVERVIEW (for context) ────────────────────────────
    h1(st, "2.  PENICILLIN CLASS - SPECTRUM OVERVIEW", S)
    data = [
        ["Penicillin Subclass", "Examples", "Spectrum / Key Organisms"],
        ["Natural penicillins",
         "Penicillin G (IV), Penicillin V (oral)",
         "Streptococci, Treponema pallidum, Neisseria meningitidis, Clostridium. "
         "Narrow spectrum."],
        ["Aminopenicillins\n(extended spectrum)",
         "Ampicillin, Amoxicillin",
         "+ Gram-negatives: H. influenzae, E. coli, Salmonella, Shigella, Proteus mirabilis. "
         "NOT Pseudomonas."],
        ["Antistaphylococcal\n(penicillinase-resistant)",
         "Cloxacillin, Dicloxacillin, Nafcillin, Methicillin",
         "MSSA (beta-lactamase producing Staph aureus). "
         "NOT Pseudomonas. NOT MRSA."],
        ["Antipseudomonal\nUreidopenicillins",
         "PIPERACILLIN, Ticarcillin",
         "Broadest spectrum penicillin. "
         "+ Pseudomonas aeruginosa, Klebsiella, Enterobacter, Bacteroides (with tazobactam). "
         "See Section 3 for full spectrum."],
    ]
    st.append(tbl(data, [W*0.22, W*0.22, W*0.56], S))
    sp(st, 3)

    # ── 3. MECHANISM OF ACTION ────────────────────────────────────────────────
    h1(st, "3.  MECHANISM OF ACTION", S)
    bl(st, [
        "Piperacillin is a BETA-LACTAM antibiotic: contains the 4-membered beta-lactam ring "
          "fused to a thiazolidine ring with a ureidopiperazine R side chain.",
        "Mechanism: INHIBITS BACTERIAL CELL WALL SYNTHESIS by binding to "
          "PENICILLIN-BINDING PROTEINS (PBPs) = transpeptidases / carboxypeptidases "
          "that catalyse the final cross-linking (transpeptidation) of peptidoglycan chains.",
        "PBP binding -> PREVENTS transpeptidation of peptidoglycan -> "
          "weakened cell wall -> osmotic lysis -> BACTERICIDAL effect.",
        "Piperacillin's ureidopiperazine side chain gives it greater affinity for PBPs of "
          "GRAM-NEGATIVE organisms (including Pseudomonas) compared to ampicillin.",
        "TIME-DEPENDENT killing: efficacy correlates with the duration that free drug "
          "concentration remains ABOVE the MIC (minimum inhibitory concentration). "
          "Optimised by prolonged infusion (extended or continuous infusion strategies).",
        "BACTERICIDAL: activates autolysins (murein hydrolases) that destroy bacterial cell wall. "
          "Activity requires actively dividing bacteria (static phase less sensitive).",
    ], S)
    pearl(st,
        "PEARL: Piperacillin is TIME-DEPENDENT, not concentration-dependent. "
        "Clinical implication: giving the same daily dose as a prolonged infusion "
        "(e.g. 4-hour or continuous infusion) achieves better T > MIC than bolus dosing. "
        "Key for PHARMACODYNAMIC optimisation in severe infections. (Lippincott Pharmacology)", S)
    sp(st, 3)

    # ── 4. ANTIMICROBIAL SPECTRUM ─────────────────────────────────────────────
    h1(st, "4.  ANTIMICROBIAL SPECTRUM", S)
    h2(st, "A. Piperacillin Alone", S)
    data = [
        ["Category", "Organisms Covered"],
        ["Gram-POSITIVE\n(moderate coverage)",
         "Streptococcus pyogenes (Group A Strep), S. pneumoniae, "
         "Enterococcus faecalis (variable), viridans streptococci. "
         "NOTE: MRSA - NOT covered. Staph aureus (MSSA) - variable (piperacillinase susceptible)."],
        ["Gram-NEGATIVE\n(broad coverage)",
         "Pseudomonas aeruginosa (KEY; hallmark of piperacillin). "
         "E. coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter spp., "
         "Haemophilus influenzae, Neisseria gonorrhoeae, Morganella, Serratia."],
        ["ANAEROBES\n(variable)",
         "Bacteroides fragilis (variable; better with tazobactam). "
         "Clostridium, Fusobacterium, Peptostreptococcus."],
        ["NOT covered",
         "MRSA, VRSA, MRSE (methicillin-resistant organisms). "
         "Stenotrophomonas maltophilia (intrinsic resistance to piperacillin). "
         "Some beta-lactamase-producing strains (covered by adding tazobactam)."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))

    h2(st, "B. Piperacillin-Tazobactam (Pip-Taz) - Extended Spectrum", S)
    bl(st, [
        "TAZOBACTAM = beta-lactamase inhibitor (penicillanic acid sulphone). "
          "Irreversibly inhibits class A and some class C beta-lactamases.",
        "Combined with piperacillin in 4:1 ratio -> extends spectrum to cover "
          "BETA-LACTAMASE PRODUCING organisms.",
        "ADDITIONAL coverage with Pip-Taz vs piperacillin alone:",
    ], S)
    bl(st, [
        "Beta-lactamase-producing Staph aureus (MSSA).",
        "Most Enterobacterales (E. coli, Klebsiella) producing TEM/SHV beta-lactamases.",
        "Bacteroides fragilis and most anaerobes.",
        "H. influenzae, Moraxella catarrhalis (beta-lactamase producers).",
        "ESBL-producing organisms: VARIABLE - some strains may be covered; check sensitivity.",
        "NOT: MRSA, VRE, Stenotrophomonas, carbapenem-resistant organisms (KPC, NDM).",
    ], S, sub=True)
    pearl(st,
        "PIPERACILLIN vs PIP-TAZ: Piperacillin alone covers Pseudomonas but NOT "
        "beta-lactamase producers (easily inactivated). "
        "Adding TAZOBACTAM restores activity against most beta-lactamase producing organisms "
        "while maintaining anti-Pseudomonal activity. "
        "Pip-Taz is the standard clinical formulation. (Lippincott Pharmacology / Bailey & Love)", S)
    sp(st, 3)

    # ── 5. PHARMACOKINETICS ───────────────────────────────────────────────────
    h1(st, "5.  PHARMACOKINETICS", S)
    data = [
        ["Parameter", "Piperacillin", "Tazobactam"],
        ["Bioavailability (oral)", "NEGLIGIBLE - acid labile; IV/IM only", "IV only (combined with piperacillin)"],
        ["Protein binding",       "~16-21% (relatively low)",             "~31%"],
        ["Volume of distribution","0.24 L/kg; widely distributed to tissues, lung, bile, "
                                   "bone, peritoneal fluid, wound fluid",  "Similar distribution to piperacillin"],
        ["CSF penetration",       "POOR in normal meninges; "
                                   "improves with inflamed meninges (limited use for meningitis)", "Poor"],
        ["Metabolism",            "Minimal hepatic metabolism; "
                                   "small amount hydrolysed to desethyl-piperacillin (active)",     "Minimal"],
        ["Excretion",             "Primarily RENAL: glomerular filtration + tubular secretion. "
                                   "70-80% excreted unchanged in urine. Also biliary excretion (20%).", "Primarily renal (68% unchanged in urine)"],
        ["Half-life (t1/2)",      "0.7-1.2 hours (normal renal function)",  "0.7-1.0 hours"],
        ["Renal impairment",      "DOSE REDUCTION required if CrCl < 40 mL/min", "Adjust with piperacillin"],
        ["Dialysis",              "Removed by haemodialysis (30-50%); supplement post-HD dose", "Removed by haemodialysis"],
    ]
    st.append(tbl(data, [W*0.22, W*0.44, W*0.34], S))
    sp(st, 3)

    # ── 6. CLINICAL USES / INDICATIONS ───────────────────────────────────────
    h1(st, "6.  CLINICAL USES & INDICATIONS", S)
    h2(st, "A. General Indications (Pip-Taz)", S)
    data = [
        ["Indication", "Notes"],
        ["Hospital-acquired pneumonia (HAP) / VAP",
         "Covers gram-negatives including Pseudomonas; "
         "used in combination with aminoglycoside (gentamicin/amikacin) for synergy. "
         "(Bailey & Love / Schwartz's Surgery)"],
        ["Septicaemia / bacteraemia",
         "Broad-spectrum empirical therapy in febrile neutropenia (with amikacin). "
         "Covers gram-negative bacteraemia including Pseudomonas."],
        ["Intra-abdominal infections",
         "Peritonitis, complicated appendicitis, bowel perforation. "
         "Covers gram-negatives + anaerobes (Bacteroides fragilis)."],
        ["Urinary tract infections (complicated)",
         "Pyelonephritis, urosepsis; covers Pseudomonas and resistant gram-negatives."],
        ["Skin & soft tissue infections",
         "Necrotising fasciitis, diabetic foot infections, infected pressure sores. "
         "Polymicrobial coverage."],
        ["Febrile neutropenia",
         "Standard empirical therapy (pip-taz + aminoglycoside). "
         "Broad gram-negative + Pseudomonas coverage essential."],
        ["Osteomyelitis / septic arthritis",
         "When gram-negative or polymicrobial infection suspected."],
        ["Gynaecological infections",
         "Pelvic inflammatory disease, septic abortion, postpartum endometritis."],
    ]
    st.append(tbl(data, [W*0.30, W*0.70], S))

    h2(st, "B. ENT-Specific Indications", S)
    data = [
        ["ENT Indication", "Rationale for Pip-Taz"],
        ["Deep neck space infections (Ludwig's angina, parapharyngeal / retropharyngeal abscess)",
         "Polymicrobial (Strep, anaerobes, gram-negatives). "
         "Pip-taz covers entire spectrum; used with metronidazole in some protocols. "
         "Standard choice in most ENT centres."],
        ["Otogenic intracranial complications (brain abscess, sigmoid sinus thrombosis)",
         "Gram-negative coverage (Pseudomonas, Proteus) + anaerobes. "
         "Combined with metronidazole + ceftriaxone or used alone."],
        ["Malignant (necrotising) otitis externa",
         "Pseudomonas aeruginosa = causative organism in 90%+. "
         "IV pip-taz or ciprofloxacin. First-line anti-pseudomonal agent."],
        ["Rhinosinusitis - complicated (orbital / intracranial extension)",
         "Polymicrobial; gram-negatives. Broad-spectrum IV antibiotics required."],
        ["Post-laryngectomy / post-operative ENT wound infection",
         "Hospital-acquired wound infection; Pseudomonas, gram-negatives."],
        ["Tracheitis / ventilator-associated tracheobronchitis",
         "Pip-taz + aminoglycoside for Pseudomonas-suspected infection."],
    ]
    st.append(tbl(data, [W*0.35, W*0.65], S))
    sp(st, 3)

    # ── 7. DOSAGE ─────────────────────────────────────────────────────────────
    h1(st, "7.  DOSAGE & ADMINISTRATION", S)
    dose(st,
        "PIPERACILLIN-TAZOBACTAM (doses based on piperacillin component): "
        "ADULTS: 4g/0.5g (4.5g vial) IV every 6-8 hours (q6h or q8h). "
        "Severe/Pseudomonas: 4.5g IV q6h (= 18g/day). "
        "Extended infusion: 4.5g over 4 HOURS q8h (optimises T > MIC - preferred in ICU). "
        "CHILDREN (> 2 months): 100 mg/kg/dose q8h IV (max 4g/dose). "
        "NEONATES: 100 mg/kg/dose q8h (adjust by gestational age - Harriet Lane). "
        "Renal impairment: CrCl 20-40: 4.5g q8h; CrCl < 20: 4.5g q12h. "
        "Haemodialysis: 4.5g q12h + 2.25g after each HD session.", S)
    bl(st, [
        "Reconstitution: Dilute in 50-250 mL NS or D5W; infuse over 30 min (standard) "
          "or 4 hours (extended infusion).",
        "Stability: stable 12 hours at room temperature; 3 days refrigerated after reconstitution.",
        "NOT compatible with aminoglycosides in the same infusion line (inactivation occurs).",
        "Piggyback IV administration; separate line or flush line before aminoglycoside.",
    ], S)
    sp(st, 3)

    # ── 8. RESISTANCE ────────────────────────────────────────────────────────
    h1(st, "8.  MECHANISMS OF RESISTANCE", S)
    data = [
        ["Mechanism", "Detail / Examples"],
        ["Beta-lactamase production\n(MOST COMMON)",
         "Gram-positive: secreted extracellularly (staphylococcal penicillinase). "
         "Gram-negative: secreted into periplasmic space. "
         "Hydrolysis of beta-lactam ring -> loss of bactericidal activity. "
         "TAZOBACTAM inhibits class A (TEM, SHV, CTX-M) and some class C beta-lactamases. "
         "NOT carbapenemases (KPC, NDM, OXA-48) = not covered by pip-taz. (Lippincott Pharmacology)"],
        ["ESBL production",
         "Extended-spectrum beta-lactamases: hydrolysable beta-lactams including pip-taz. "
         "ESBL-producing E. coli, Klebsiella = pip-taz may FAIL clinically even if "
         "in-vitro sensitive. Carbapenem preferred for ESBL infections."],
        ["AmpC beta-lactamases\n(class C, inducible)",
         "Chromosome-mediated; inducible by 3rd-gen cephalosporins / pip-taz. "
         "Enterobacter, Citrobacter, Serratia, Morganella (ESCPM group). "
         "Tazobactam POOR inhibitor of AmpC -> resistance."],
        ["Reduced outer membrane\npermeability / porin loss",
         "Loss of OprD porin in P. aeruginosa -> reduced uptake of drug. "
         "Intrinsic resistance mechanism in some P. aeruginosa strains."],
        ["Efflux pumps",
         "MexAB-OprM and other multidrug efflux systems in P. aeruginosa actively "
         "pump piperacillin out of the bacterial cell."],
        ["Altered PBPs",
         "Modified PBPs have reduced affinity for piperacillin. "
         "MRSA: mecA gene -> PBP2a (low affinity for all beta-lactams) -> "
         "piperacillin/pip-taz CANNOT treat MRSA."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))
    caut(st,
        "CRITICAL: Pip-Taz does NOT cover MRSA, VRE, ESBL-producing organisms (clinically), "
        "carbapenem-resistant organisms (CRO), or Stenotrophomonas. "
        "For MRSA: add vancomycin/teicoplanin. For ESBL: use meropenem/imipenem. "
        "(Lippincott Pharmacology 8e)", S)
    sp(st, 3)

    # ── 9. ADVERSE EFFECTS ────────────────────────────────────────────────────
    h1(st, "9.  ADVERSE EFFECTS & DRUG INTERACTIONS", S)
    h2(st, "A. Adverse Effects", S)
    data = [
        ["Effect", "Detail / Frequency"],
        ["HYPERSENSITIVITY REACTIONS\n(MOST IMPORTANT)",
         "Rash, urticaria (most common, ~3%). "
         "Anaphylaxis (< 0.05%): IgE-mediated; LIFE-THREATENING. "
         "Cross-reactivity with OTHER PENICILLINS (< 5% with cephalosporins; < 1% with carbapenems). "
         "ALWAYS ask allergy history before prescribing. "
         "Serum sickness (type III) - rare."],
        ["Neurotoxicity",
         "SEIZURES (high doses, renal impairment, intrathecal use). "
         "Encephalopathy, myoclonus. Most common in ICU patients with renal failure."],
        ["Haematological",
         "THROMBOCYTOPENIA (dose-dependent; common in prolonged therapy). "
         "Neutropenia, eosinophilia. "
         "COAGULOPATHY: platelet dysfunction (inhibits ADP-induced aggregation); "
         "elevated PT/INR (especially at high doses or with hepatic disease). "
         "Coombs-positive haemolytic anaemia (rare)."],
        ["GI effects",
         "Nausea, vomiting, diarrhoea. "
         "C. DIFFICILE COLITIS: prolonged use disrupts bowel flora; "
         "any broad-spectrum antibiotic risk. Monitor for watery diarrhoea + WBC rise."],
        ["Hepatotoxicity",
         "Transient elevation of LFTs (ALT, AST, bilirubin). "
         "Cholestatic jaundice (rare). Monitor LFTs in prolonged courses."],
        ["HYPONATRAEMIA",
         "Pip-taz contains 2.84 mEq Na per gram piperacillin. "
         "High sodium load with full-dose therapy -> monitor serum sodium "
         "in fluid-restricted patients (cardiac, renal)."],
        ["Electrolyte disturbances",
         "HYPOKALAEMIA (renal potassium wasting from non-reabsorbable anion effect). "
         "Hypernatraemia (sodium load). Monitor electrolytes."],
        ["Injection site reactions",
         "Phlebitis, pain at IV site. Thrombophlebitis with peripheral IV."],
        ["Pseudomembranous colitis",
         "Clostridium difficile. Stop pip-taz; start oral vancomycin or fidaxomicin."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))

    h2(st, "B. Drug Interactions", S)
    data = [
        ["Drug", "Interaction"],
        ["AMINOGLYCOSIDES\n(gentamicin, amikacin)",
         "SYNERGISTIC antibacterial effect (especially against Pseudomonas). "
         "PHYSICAL INCOMPATIBILITY: do NOT mix in same IV infusion. "
         "Administer via separate lines or flush between drugs."],
        ["WARFARIN / anticoagulants",
         "Pip-taz may increase INR (platelet dysfunction + intestinal flora changes). "
         "Monitor INR closely; adjust warfarin dose."],
        ["VECURONIUM / neuromuscular blockers",
         "Piperacillin prolongs neuromuscular blockade. "
         "Monitor in ICU patients on neuromuscular blocking agents."],
        ["METHOTREXATE",
         "Pip-taz reduces renal tubular secretion of methotrexate -> "
         "METHOTREXATE TOXICITY. Avoid combination; if necessary, monitor MTX levels closely."],
        ["PROBENECID",
         "Reduces tubular secretion of piperacillin -> increases pip-taz serum levels "
         "(clinical benefit possible; not routinely used)."],
        ["VALPROATE / VALPROIC ACID",
         "Piperacillin may reduce valproate levels (mechanism: impairs enterohepatic recirculation). "
         "Monitor valproate levels; increase dose if needed. Risk of SEIZURES."],
    ]
    st.append(tbl(data, [W*0.25, W*0.75], S))
    sp(st, 3)

    # ── 10. VIVA QUESTIONS ────────────────────────────────────────────────────
    h1(st, "10.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What class of antibiotic is piperacillin and what is its mechanism of action?",
         "UREIDOPENICILLIN (antipseudomonal, extended-spectrum penicillin) = beta-lactam antibiotic. "
         "MOA: binds PENICILLIN-BINDING PROTEINS (PBPs = transpeptidases) -> inhibits peptidoglycan "
         "cross-linking -> weakened cell wall -> osmotic lysis -> BACTERICIDAL. "
         "TIME-DEPENDENT killing: efficacy depends on T > MIC (not peak concentration)."),
        ("Q2: Why is piperacillin always given as piperacillin-tazobactam clinically?",
         "Piperacillin alone is hydrolysed by bacterial beta-lactamases (class A, C) -> rapidly inactivated. "
         "TAZOBACTAM = beta-lactamase inhibitor; irreversibly inhibits beta-lactamases -> "
         "protects piperacillin from degradation. "
         "Combined (4:1 ratio): extends spectrum to beta-lactamase-producing organisms "
         "(MSSA, most Enterobacterales, B. fragilis) while retaining Pseudomonas coverage."),
        ("Q3: What is the key organism covered by piperacillin that other penicillins miss?",
         "PSEUDOMONAS AERUGINOSA. "
         "Piperacillin's ureidopiperazine side chain provides affinity for PBPs of P. aeruginosa. "
         "No other penicillin subclass covers Pseudomonas reliably. "
         "Also: Klebsiella, Enterobacter, Bacteroides (with tazobactam), Serratia, Morganella."),
        ("Q4: Why is piperacillin NOT orally bioavailable?",
         "ACID-LABILE: the beta-lactam ring is hydrolysed by gastric acid -> "
         "drug destroyed before absorption. "
         "Must be given IV or IM. This is true of all antipseudomonal penicillins. "
         "In contrast, amoxicillin is acid-stable (oral bioavailability 70-90%)."),
        ("Q5: What are the ENT-specific indications for pip-taz?",
         "1. DEEP NECK SPACE INFECTIONS (Ludwig's angina, parapharyngeal/retropharyngeal abscess): "
         "polymicrobial (strep + anaerobes + gram-negatives). "
         "2. MALIGNANT OTITIS EXTERNA: Pseudomonas aeruginosa in 90%+ of cases. "
         "3. Otogenic intracranial complications: brain abscess, sigmoid sinus thrombosis. "
         "4. Complicated sinusitis with orbital/intracranial extension. "
         "5. Post-operative ENT wound infections."),
        ("Q6: What organisms does pip-taz NOT cover?",
         "MRSA (methicillin-resistant Staph aureus): mecA gene -> PBP2a -> resistant to ALL beta-lactams. "
         "VRE (vancomycin-resistant Enterococcus). "
         "ESBL-producing E. coli/Klebsiella (clinically unreliable despite in-vitro sensitivity). "
         "Carbapenem-resistant organisms (KPC, NDM, OXA-48 producers). "
         "Stenotrophomonas maltophilia (intrinsic resistance). "
         "Atypicals (Mycoplasma, Chlamydia, Legionella) - no cell wall."),
        ("Q7: What is the most important adverse effect of piperacillin to know?",
         "1. HYPERSENSITIVITY: rash (3%), anaphylaxis (< 0.05%) - life-threatening; IgE-mediated. "
         "Cross-react with other penicillins. Always take allergy history. "
         "2. THROMBOCYTOPENIA: dose-dependent; common with prolonged IP-TAZ in ICU. "
         "3. HYPONATRAEMIA: 2.84 mEq Na/g piperacillin = high sodium load. "
         "4. HYPOKALAEMIA: renal K+ wasting. "
         "5. C. DIFFICILE colitis with prolonged use. "
         "6. SEIZURES: high dose + renal failure. "
         "7. VALPROATE interaction: reduces valproate levels -> seizure risk."),
        ("Q8: What is extended infusion of pip-taz and why is it used?",
         "Extended infusion = 4.5g IV over 4 HOURS (vs standard 30-min bolus). "
         "Based on TIME-DEPENDENT pharmacodynamics: longer infusion time -> "
         "more time drug concentration remains above MIC (T > MIC) -> better bacterial killing. "
         "Particularly useful for: resistant organisms with higher MICs, "
         "ICU/critically ill patients, Pseudomonas infections. "
         "Studies show improved clinical outcomes vs bolus dosing for MDR organisms."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 3)

    # ── 11. KEY POINTS SUMMARY ───────────────────────────────────────────────
    h1(st, "11.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Class",             "UREIDOPENICILLIN (antipseudomonal, extended-spectrum penicillin); beta-lactam"],
        ["MOA",               "Binds PBPs -> inhibits peptidoglycan transpeptidation -> cell wall lysis -> bactericidal"],
        ["Killing kinetics",  "TIME-DEPENDENT: T > MIC determines efficacy; extended infusion optimises this"],
        ["Route",             "IV or IM ONLY (acid-labile; NOT oral)"],
        ["Key organism",      "PSEUDOMONAS AERUGINOSA (hallmark); also Klebsiella, Enterobacter, anaerobes (with Taz)"],
        ["Clinical form",     "Pip-Taz (piperacillin 4g + tazobactam 0.5g) = TAZOCIN/ZOSYN; 4:1 ratio"],
        ["Tazobactam role",   "Beta-lactamase inhibitor -> extends spectrum to beta-lactamase producing organisms"],
        ["Adult dose",        "4.5g IV q6-8h; severe infections q6h; extended infusion: 4.5g over 4h q8h"],
        ["Renal adjustment",  "Required if CrCl < 40 mL/min; supplement post-haemodialysis"],
        ["NOT covered",       "MRSA, VRE, ESBL (clinically), carbapenem-resistant organisms, Stenotrophomonas"],
        ["Resistance",        "Beta-lactamase (most common); ESBL; AmpC; efflux pumps; porin loss; altered PBPs"],
        ["Key ADR",           "Anaphylaxis (IgE); thrombocytopenia; hyponatraemia (high Na load); hypokalaemia; seizures (renal failure)"],
        ["Drug interaction",  "Aminoglycosides: synergy BUT incompatible in same line. Valproate: reduces levels -> seizures. Methotrexate: toxicity."],
        ["ENT use",           "Deep neck infections (Ludwig's), malignant OE (Pseudomonas), otogenic intracranial complications"],
        ["Not for",           "Oral use; MRSA infections; ESBL infections; primary meningitis treatment"],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))

    sp(st, 4)
    st.append(Paragraph(
        "References: Lippincott Illustrated Reviews Pharmacology 8th ed. | "
        "Bailey & Love's Surgery 28th ed. | Harriet Lane Handbook 23rd ed. | "
        "Goodman & Gilman's Pharmacology 13th ed. | Goldman-Cecil Medicine 26th ed. | "
        "BNF 86 (British National Formulary)",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Piperacillin_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Piperacillin - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_piperacillin.py'

#!/usr/bin/env python3
# Chemotherapy in Head and Neck Cancer - Focused ENT PG Exam Notes (5-6 pages)
# NEW Palette: Dark indigo headings, deep amber subheadings, forest green H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Dark Indigo / Deep Amber / Forest Green ─────────────────────────
C_H1_BG  = colors.HexColor("#1A1A5E")   # dark indigo
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#B35A00")   # deep amber
C_H2_BG  = colors.HexColor("#FFF6E8")
C_H3_FG  = colors.HexColor("#1A5C2A")   # forest green
C_H3_BG  = colors.HexColor("#EAF5EC")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1A1A5E")
C_ALT    = colors.HexColor("#EBEBF8")
C_PEARL  = colors.HexColor("#EAF5EC")
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#1A1A5E")
C_VQ_BG  = colors.HexColor("#EBEBF8")
C_VQ_FG  = colors.HexColor("#1A1A5E")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S): st.append(Paragraph(f"♥ {t}", S["dose"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = [Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("CHEMOTHERAPY IN HEAD AND NECK CANCERS", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e Vol 1 & Vol 2, Cummings ORL 7e, "
        "Key Trials: VA Laryngeal, RTOG 91-11, RTOG 9501, EORTC 22931, EXTREME, KEYNOTE-048",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. ROLE OF CHEMOTHERAPY IN HNC ────────────────────────────────────────
    h1(st, "1.  ROLE OF CHEMOTHERAPY IN HEAD AND NECK CANCER", S)
    bl(st, [
        "Chemotherapy is regularly employed in HNC management but has NOT changed CURE RATES "
          "of locally advanced HNC when used alone. (Scott-Brown's OHN&S)",
        "KEY ROLES: "
          "(1) RADIOSENSITISATION when given concurrently with RT (chemoradiation = CRT). "
          "(2) ORGAN PRESERVATION: avoids laryngectomy/pharyngectomy. "
          "(3) Reduces DISTANT METASTASES. "
          "(4) PALLIATIVE treatment of recurrent/metastatic disease.",
        "Most HNCs = SQUAMOUS CELL CARCINOMA (HNSCC); HPV-positive (oropharynx) vs HPV-negative "
          "differ in biology, prognosis, and response to treatment.",
        "CISPLATIN = most active single agent against HNSCC (cornerstone of all regimens).",
        "Performance status (ECOG/WHO) is critical in deciding appropriateness of chemotherapy.",
    ], S)
    pearl(st,
        "PEARL: Chemotherapy in HNC does NOT improve cure rates alone. "
        "Its main value is as a RADIOSENSITISER (concurrent CRT) and for ORGAN PRESERVATION. "
        "Concurrent CRT = standard of care for locally advanced HNSCC. (Scott-Brown's OHN&S)", S)
    sp(st, 3)

    # ── 2. CHEMOTHERAPY STRATEGIES ────────────────────────────────────────────
    h1(st, "2.  CHEMOTHERAPY STRATEGIES", S)
    data = [
        ["Strategy", "Definition", "Role in HNC / Evidence"],
        ["INDUCTION\n(Neoadjuvant)\nChemotherapy",
         "Chemotherapy given BEFORE definitive surgery or RT. "
         "Intention: reduce tumour bulk, improve local/distant control, enable organ preservation.",
         "VA Laryngeal Study (1991): Cisplatin/5-FU x 3 cycles then RT. "
         "85% response rate. NO survival benefit vs surgery+RT BUT 64% laryngeal preservation. "
         "RTOG 91-11: concurrent CRT SUPERIOR to induction CT for organ preservation and locoregional control. "
         "TPF (Taxane-Platinum-5FU) > PF (Cisplatin-5FU) for OS/PFS in phase III trials. "
         "Role remains CONTROVERSIAL; case-by-case basis. (Level 1 evidence)"],
        ["CONCURRENT\nCHEMORADIATION\n(CRT) - STANDARD",
         "Chemotherapy given SIMULTANEOUSLY with RT. "
         "Synergistic: chemo radiosensitises; RT enhances drug delivery.",
         "RTOG 9501 + EORTC 22931: adjuvant CRT in HIGH-RISK post-op patients improved 5yr survival by 13%. "
         "Indications: extracapsular spread (ECS), positive margins, perineural invasion, N2/N3 nodes. "
         "ECS + positive margins = STRONGEST indications (post-hoc analysis). "
         "Drug: CISPLATIN 100 mg/m2 q3w (standard); or 40 mg/m2 weekly."],
        ["ADJUVANT\nChemotherapy",
         "Chemotherapy given AFTER curative surgery or RT in high-risk patients. "
         "Intention: eradicate micrometastatic disease.",
         "Randomised trials do NOT show significant survival benefit for adjuvant CT alone. "
         "REPLACED by concurrent CRT in high-risk settings. "
         "(Level 1 evidence - Scott-Brown's OHN&S)"],
        ["PALLIATIVE\nChemotherapy",
         "For recurrent and/or metastatic disease with no curative intent. "
         "Performance status-dependent.",
         "Cisplatin/carboplatin + 5-FU: response rate ~40%; median OS 6-12 months. "
         "Carboplatin preferred (less toxic) in palliative setting vs cisplatin. "
         "EXTREME trial: Cisplatin + 5-FU + Cetuximab = improved response + short-term OS "
         "vs Cisplatin + 5-FU alone. Standard 1st-line R/M HNSCC (pre-immunotherapy). "
         "Now REPLACED by KEYNOTE-048 pembrolizumab-based regimens."],
    ]
    st.append(tbl(data, [W*0.17, W*0.28, W*0.55], S))
    sp(st, 3)

    # ── 3. KEY CHEMOTHERAPY AGENTS ────────────────────────────────────────────
    h1(st, "3.  KEY CHEMOTHERAPY AGENTS IN HNSCC", S)
    data = [
        ["Agent", "Class / MOA", "Use in HNC / Doses / Key Toxicities"],
        ["CISPLATIN\n(GOLD STANDARD)",
         "Platinum alkylating agent. "
         "Cross-links DNA strands -> inhibits DNA replication -> apoptosis.",
         "CONCURRENT CRT: 100 mg/m2 IV q3 weeks (3 cycles with RT) OR 40 mg/m2 weekly. "
         "Induction: PF (cisplatin 100 + 5-FU 1000 mg/m2/day x4). "
         "TOXICITIES: NEPHROTOXICITY (dose-limiting; requires aggressive IV hydration + mannitol), "
         "Nausea/vomiting (severe; requires ondansetron + dexamethasone), "
         "Ototoxicity (sensorineural hearing loss - irreversible; audiogram before each cycle), "
         "Peripheral neuropathy (cumulative), Myelosuppression, Hypomagnesaemia."],
        ["CARBOPLATIN",
         "Platinum compound; less reactive than cisplatin. "
         "DNA cross-links; less protein binding.",
         "Used when cisplatin not tolerated (renal impairment, hearing loss, poor PS). "
         "AUC 5-6 (Calvert formula) q3w. "
         "TOXICITIES: MYELOSUPPRESSION (dose-limiting; less nephrotoxic/ototoxic than cisplatin). "
         "Thrombocytopenia > neutropenia. Less nausea. Preferred in palliative setting."],
        ["5-FLUOROURACIL\n(5-FU)",
         "Antimetabolite; inhibits thymidylate synthase -> blocks DNA synthesis. "
         "S-phase specific.",
         "Combination regimens: PF (cisplatin + 5-FU), TPF (docetaxel + cisplatin + 5-FU). "
         "Given as continuous infusion 96-120 hours. "
         "TOXICITIES: Mucositis (severe; dose-limiting), diarrhoea, myelosuppression, "
         "hand-foot syndrome (infusional), cardiac toxicity (coronary spasm - rare)."],
        ["DOCETAXEL\n(Taxane)",
         "Taxane; stabilises microtubules -> inhibits cell division. "
         "M-phase specific.",
         "TPF regimen (induction): Docetaxel 75 mg/m2 + Cisplatin 75 mg/m2 + 5-FU 750 mg/m2/d x5. "
         "TPF > PF in terms of OS/PFS for locally advanced HNSCC (level 1 evidence). "
         "TOXICITIES: Myelosuppression (neutropenia), fluid retention, neuropathy, "
         "nail changes, hypersensitivity (premedicate with dexamethasone)."],
        ["PACLITAXEL",
         "Taxane; same mechanism as docetaxel. "
         "Different formulation (Cremophor vs nab-paclitaxel).",
         "Weekly paclitaxel + carboplatin (alternative induction). "
         "TOXICITIES: Neuropathy (dose-limiting), myelosuppression, "
         "hypersensitivity (premedicate with steroids + antihistamine)."],
        ["METHOTREXATE",
         "Antimetabolite; inhibits dihydrofolate reductase -> blocks purine/pyrimidine synthesis.",
         "Single agent: recurrent/metastatic disease (low-cost, modest activity). "
         "Response rate ~15-20%. Weekly low-dose IV. "
         "TOXICITIES: Mucositis, myelosuppression, hepatotoxicity, nephrotoxicity "
         "(ensure adequate renal function; leucovorin rescue for high-dose MTX)."],
        ["BLEOMYCIN",
         "Glycopeptide antibiotic; DNA strand breaks via free radical generation.",
         "Historical use (PVB regimen). NOW RARELY USED in HNC. "
         "TOXICITIES: PULMONARY FIBROSIS (cumulative; dose-limiting - irreversible), "
         "Skin reactions (hyperpigmentation, scleroderma), fever."],
    ]
    st.append(tbl(data, [W*0.14, W*0.22, W*0.64], S))
    sp(st, 3)

    # ── 4. KEY REGIMENS ───────────────────────────────────────────────────────
    h1(st, "4.  KEY REGIMENS & LANDMARK TRIALS", S)
    data = [
        ["Regimen", "Drugs", "Trial / Indication / Result"],
        ["PF",
         "Cisplatin 100 mg/m2 d1 + 5-FU 1000 mg/m2/day x4d q3w",
         "VA Laryngeal Study (1991): induction PF x3 -> RT. Organ preservation (64%) without survival cost. "
         "Historic significance: first demonstrated organ preservation in larynx cancer."],
        ["TPF\n(standard induction)",
         "Docetaxel 75 + Cisplatin 75 + 5-FU 750 mg/m2/d x5 q3w",
         "TAX323 (Europe) / TAX324 (USA): TPF > PF for OS, PFS, locoregional failure, distant failure "
         "in locally advanced HNSCC. CURRENT STANDARD induction regimen. High toxicity."],
        ["Concurrent Cisplatin-RT\n(post-op adjuvant)",
         "Cisplatin 100 mg/m2 q3w x3 concurrent with RT",
         "RTOG 9501 + EORTC 22931: adjuvant CRT after surgery in high-risk (ECS, +margins) "
         "= improved locoregional control + 13% improvement in 5yr OS. "
         "ECS + positive margins = KEY INDICATIONS."],
        ["EXTREME\n(R/M 1st line)",
         "Cisplatin + 5-FU + Cetuximab q3w (6 cycles) -> Cetuximab maintenance",
         "EXTREME trial (Vermorken 2008): Cetuximab + PF vs PF alone. "
         "Improved OS (10.1 vs 7.4 months) and response rate (36% vs 20%). "
         "Standard 1st-line R/M HNSCC until pembrolizumab superseded it."],
        ["KEYNOTE-048\n(immunotherapy 1st line)",
         "Pembrolizumab alone OR Pembrolizumab + Cisplatin + 5-FU",
         "Pembrolizumab monotherapy: superior OS in PD-L1 CPS >= 1 and CPS >= 20. "
         "Pembro + chemo: superior OS vs EXTREME in all-comers. "
         "NOW STANDARD 1st-line R/M HNSCC (replaced EXTREME in most guidelines)."],
        ["Cetuximab-RT\n(organ preservation)",
         "Cetuximab 400 mg/m2 loading + 250 mg/m2 weekly concurrent with RT",
         "Bonner trial: Cetuximab-RT vs RT alone in LA HNSCC - "
         "improved OS (49 vs 29 months) and locoregional control. "
         "Alternative to cisplatin-RT for cisplatin-ineligible patients "
         "(though recent trials suggest cisplatin superior for HPV+ patients)."],
    ]
    st.append(tbl(data, [W*0.16, W*0.22, W*0.62], S))
    sp(st, 3)

    # ── 5. TARGETED THERAPY & IMMUNOTHERAPY ──────────────────────────────────
    h1(st, "5.  TARGETED THERAPY & IMMUNOTHERAPY", S)
    h2(st, "A. EGFR Targeted Therapy", S)
    bl(st, [
        "EGFR (Epidermal Growth Factor Receptor) = 170 kDa transmembrane protein; "
          "overexpressed in 80-90% of HNSCC -> promotes cell proliferation, survival, metastasis.",
        "EGFR signalling: ligand binding -> receptor dimerisation -> autophosphorylation "
          "-> RAS-MAPK + PI3K-AKT + STAT pathways -> cell proliferation, angiogenesis.",
    ], S)
    data = [
        ["Agent", "Type", "Target", "Use / Key Trial"],
        ["CETUXIMAB\n(Erbitux)",
         "Chimeric IgG1 monoclonal antibody",
         "EGFR extracellular domain",
         "1. Concurrent with RT (Bonner trial): LA HNSCC, cisplatin-ineligible. "
         "2. EXTREME regimen: 1st-line R/M HNSCC (+ cisplatin + 5-FU). "
         "3. Monotherapy: platinum-refractory R/M HNSCC (10-13% response). "
         "SE: acneiform rash (surrogate of response), hypomagnesaemia, infusion reactions."],
        ["PANITUMUMAB",
         "Fully human IgG2 monoclonal antibody",
         "EGFR",
         "R/M HNSCC in combination with chemotherapy. Less immunogenic than cetuximab. "
         "SE: similar to cetuximab (rash, hypomagnesaemia)."],
        ["ERLOTINIB\nGEFITINIB",
         "Small molecule tyrosine kinase inhibitors (TKIs)",
         "EGFR intracellular TK domain",
         "Limited activity in HNSCC as monotherapy. "
         "Unlike NSCLC, no activating EGFR mutations drive HNSCC. "
         "Not standard of care. (Scott-Brown's OHN&S)"],
    ]
    st.append(tbl(data, [W*0.14, W*0.17, W*0.14, W*0.55], S))

    h2(st, "B. Immune Checkpoint Inhibitors (Immunotherapy)", S)
    data = [
        ["Agent", "Target", "Indication / Trial"],
        ["PEMBROLIZUMAB\n(Keytruda)",
         "Anti-PD-1 monoclonal antibody",
         "KEYNOTE-048: 1st-line R/M HNSCC (with or without cisplatin+5-FU). "
         "Monotherapy superior OS in PD-L1 CPS >= 1. "
         "CURRENT STANDARD 1st-line R/M HNSCC. "
         "SE: immune-related AEs: pneumonitis, colitis, hepatitis, endocrinopathies, skin reactions."],
        ["NIVOLUMAB\n(Opdivo)",
         "Anti-PD-1 monoclonal antibody",
         "CheckMate-141: 2nd-line R/M HNSCC after platinum failure. "
         "Improved OS vs investigator's choice (7.5 vs 5.1 months). "
         "FDA-approved for platinum-refractory R/M HNSCC."],
        ["DURVALUMAB\nATEZOLIZUMAB",
         "Anti-PD-L1 antibodies",
         "Under investigation in combination with CRT for locally advanced HNSCC. "
         "Not yet standard of care."],
    ]
    st.append(tbl(data, [W*0.17, W*0.18, W*0.65], S))

    h2(st, "C. Mechanism of Radiosensitisation", S)
    bl(st, [
        "Chemotherapy radiosensitises tumours through multiple mechanisms (Scott-Brown's OHN&S):",
    ], S)
    bl(st, [
        "Inhibits tumour repopulation between RT fractions.",
        "Preferentially kills HYPOXIC CELLS (normally radioresistant).",
        "Inhibits REPAIR of sublethal radiation damage.",
        "Sterilises MICROMETASTATIC disease outside RT fields.",
        "Decreases tumour mass -> improved blood supply -> reoxygenation -> more radiosensitive.",
        "Fractionated RT also enhances drug delivery (reduces tumour mass -> better vascularity).",
    ], S, sub=True)
    caut(st,
        "CISPLATIN TOXICITY CHECKLIST before each cycle: "
        "Serum creatinine (eGFR > 50 mL/min), audiogram (ototoxicity), "
        "FBC (neutrophils > 1.5, platelets > 100), Mg2+ levels. "
        "Severe ototoxicity or nephrotoxicity = SWITCH TO CARBOPLATIN.", S)
    sp(st, 3)

    # ── 6. RECURRENT / METASTATIC HNC ────────────────────────────────────────
    h1(st, "6.  RECURRENT & METASTATIC HNSCC - MANAGEMENT", S)
    bl(st, [
        "Locoregional recurrence in up to 50% of locally advanced HNC. "
          "Prognosis poor: median OS < 1 year without treatment.",
        "Salvage surgery: best outcomes in those with smaller volume recurrence, "
          "longer disease-free interval, fewer comorbidities.",
        "Re-irradiation +/- chemotherapy: consider if adequate interval since prior RT "
          "(risk of severe late toxicity).",
        "DISTANT METASTASES: chemotherapy as palliative treatment; "
          "does NOT significantly extend survival; shared decision-making essential.",
        "FITNESS/PERFORMANCE STATUS is the MOST IMPORTANT factor for chemotherapy decision. "
          "ECOG 0-1: full-dose therapy; ECOG 2: reduced-dose; ECOG 3-4: best supportive care.",
    ], S)
    dose(st,
        "1st-LINE R/M HNSCC (current standard, KEYNOTE-048): "
        "PD-L1 CPS >= 1: PEMBROLIZUMAB alone (preferred, less toxicity) or "
        "Pembrolizumab + Cisplatin/Carboplatin + 5-FU. "
        "CPS < 1 / cisplatin-eligible: Pembrolizumab + Cisplatin + 5-FU. "
        "2nd-LINE after platinum failure: NIVOLUMAB (CheckMate-141) or cetuximab monotherapy. "
        "Platinum-sensitive: re-challenge with Cisplatin/Carboplatin + 5-FU. "
        "Elderly/poor PS: Methotrexate weekly (single agent; low cost; modest activity).", S)
    sp(st, 3)

    # ── 7. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "7.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What is the role of chemotherapy in head and neck cancer?",
         "Chemotherapy does NOT improve cure rates of locally advanced HNC when used alone. "
         "Its key roles are: (1) RADIOSENSITISATION in concurrent CRT (main use). "
         "(2) ORGAN PRESERVATION (avoids laryngectomy/pharyngectomy). "
         "(3) Reduces distant metastases. (4) Palliative therapy for R/M disease. "
         "(Scott-Brown's OHN&S)"),
        ("Q2: What is the VA Laryngeal Cancer Study and its significance?",
         "VA (Veterans Affairs) Laryngeal Cancer Study (1991): "
         "Randomised stage III/IV larynx cancer to: "
         "(A) Induction cisplatin/5-FU x3 + RT vs (B) Surgery + RT. "
         "85% chemotherapy response rate. NO survival difference between arms. "
         "64% laryngeal preservation in chemo arm. "
         "SIGNIFICANCE: First major trial showing larynx can be preserved with chemotherapy "
         "without compromising survival = birth of ORGAN PRESERVATION concept."),
        ("Q3: What did the RTOG 91-11 trial show?",
         "RTOG 91-11: 547 patients with stage III/IV larynx cancer randomised to: "
         "(1) Induction cisplatin/5-FU then RT, (2) CONCURRENT cisplatin-RT, (3) RT alone. "
         "RESULT: Concurrent CRT was SUPERIOR for organ preservation and locoregional control "
         "vs induction CT or RT alone. No significant OS difference. "
         "CONCLUSION: Concurrent CRT = standard of care for larynx preservation."),
        ("Q4: What are the indications for adjuvant concurrent CRT post-surgery in HNC?",
         "High-risk features (RTOG 9501 + EORTC 22931): "
         "ABSOLUTE: (1) Extracapsular spread (ECS) of nodal disease - STRONGEST indication. "
         "(2) Positive surgical margins - STRONGEST indication. "
         "RELATIVE: (3) Perineural invasion. (4) Lymphovascular invasion. "
         "(5) T4 primary. (6) N2/N3 nodal disease. "
         "Concurrent cisplatin + RT = 13% improvement in 5yr OS for high-risk patients."),
        ("Q5: What is the EXTREME trial and what is current 1st-line treatment for R/M HNSCC?",
         "EXTREME trial (Vermorken 2008): Cetuximab + Cisplatin + 5-FU vs Cisplatin + 5-FU. "
         "Response: 36% vs 20%; OS: 10.1 vs 7.4 months. First regimen to improve OS in R/M HNSCC. "
         "NOW SUPERSEDED: KEYNOTE-048 (2019) showed PEMBROLIZUMAB alone or with "
         "chemo superior to EXTREME in R/M HNSCC. "
         "Current standard: Pembrolizumab-based regimen (PD-L1 CPS-guided)."),
        ("Q6: How does cisplatin sensitise tumours to radiotherapy?",
         "Multiple mechanisms: (1) Inhibits tumour repopulation between RT fractions. "
         "(2) Kills hypoxic cells (normally radioresistant). "
         "(3) Inhibits repair of sublethal radiation damage. "
         "(4) Reduces tumour mass -> improved vascularity -> reoxygenation -> more radiosensitive. "
         "(5) Sterilises micrometastatic disease outside RT fields. (Scott-Brown's OHN&S)"),
        ("Q7: What is cetuximab and what is its role in HNC?",
         "Cetuximab = chimeric IgG1 monoclonal antibody against EGFR extracellular domain. "
         "EGFR overexpressed in 80-90% of HNSCC. Cetuximab blocks EGFR -> inhibits proliferation. "
         "Uses in HNC: (1) Concurrent with RT (Bonner trial) - alternative to cisplatin. "
         "(2) EXTREME regimen - 1st-line R/M (now replaced by pembrolizumab). "
         "(3) Monotherapy for platinum-refractory R/M HNSCC (10-13% response). "
         "SE: acneiform rash (correlates with response), hypomagnesaemia, infusion reactions."),
        ("Q8: What are the key toxicities of cisplatin in HNC treatment?",
         "1. NEPHROTOXICITY (dose-limiting): require IV hydration (1L NS pre+post); "
         "mannitol diuresis; monitor creatinine; avoid NSAIDs/aminoglycosides. "
         "2. OTOTOXICITY: irreversible SNHL; audiogram before each cycle; "
         "switch to carboplatin if significant hearing loss. "
         "3. Nausea/vomiting (severe): ondansetron + dexamethasone + NK1 antagonist. "
         "4. HYPOMAGNESAEMIA (common; may persist after treatment). "
         "5. Peripheral neuropathy (cumulative). "
         "6. Myelosuppression (less than carboplatin)."),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 3)

    # ── 8. KEY POINTS SUMMARY ─────────────────────────────────────────────────
    h1(st, "8.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Role of chemo",       "Radiosensitisation + organ preservation; does NOT improve cure rates alone"],
        ["Gold standard drug",  "CISPLATIN: most active single agent against HNSCC"],
        ["Induction regimen",   "TPF (Docetaxel + Cisplatin + 5-FU) > PF (Cisplatin + 5-FU) for OS/PFS (TAX323/TAX324)"],
        ["Organ preservation",  "VA Laryngeal Study: induction cisplatin/5-FU -> RT = 64% larynx preservation, no OS difference"],
        ["Concurrent CRT",      "RTOG 91-11: concurrent cisplatin-RT superior to induction CT or RT alone for larynx preservation"],
        ["Adjuvant CRT",        "RTOG 9501 + EORTC 22931: ECS + positive margins = strongest indications; 13% OS benefit"],
        ["Cisplatin dose (CRT)", "100 mg/m2 IV q3w x3 cycles concurrent with RT (standard)"],
        ["Cisplatin toxicity",   "Nephrotoxicity, ototoxicity (irreversible SNHL), vomiting, hypomagnesaemia, neuropathy"],
        ["EXTREME trial",       "Cetuximab + Cisplatin + 5-FU: first to improve OS in R/M HNSCC (10.1 vs 7.4 months)"],
        ["Current R/M standard","KEYNOTE-048: PEMBROLIZUMAB (anti-PD-1) +/- chemo = new 1st-line for R/M HNSCC"],
        ["Cetuximab",           "Anti-EGFR monoclonal antibody; Bonner trial: concurrent with RT in LA HNSCC; SE: acneiform rash"],
        ["EGFR",                "Overexpressed in 80-90% HNSCC; target for cetuximab/panitumumab; TKIs (erlotinib) less active"],
        ["Adjuvant chemo alone", "NOT recommended (no survival benefit); concurrent CRT preferred"],
        ["Palliative chemo",     "Carboplatin/cisplatin + 5-FU (40% RR); median OS 6-12 months; performance status key"],
        ["HPV+ oropharynx",      "Better prognosis; higher sensitivity to CRT; current trials exploring de-escalation strategies"],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))

    sp(st, 4)
    st.append(Paragraph(
        "References: Scott-Brown's OHN&S 8th ed. Vol 1 & Vol 2 | Cummings ORL 7th ed. | "
        "VA Laryngeal Study (NEJM 1991) | RTOG 91-11 (Forastiere 2003) | "
        "RTOG 9501 + EORTC 22931 (Cooper/Bernier 2004) | "
        "EXTREME (Vermorken NEJM 2008) | KEYNOTE-048 (Burtness Lancet 2019) | "
        "Bonner (NEJM 2006) | TAX323/TAX324 trials",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Chemo_HNC_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Chemotherapy in Head & Neck Cancer - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Mucormycosis of Maxilla - Focused ENT PG Exam Notes (5-6 pages)
# NEW Palette: Dark chocolate-brown headings / steel teal subheadings / olive-gold H3
# Distinct from all previous PDFs

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# ── Palette: Dark Chocolate-Brown / Steel Teal / Olive-Gold ──────────────────
C_H1_BG  = colors.HexColor("#3B1A0A")   # dark chocolate-brown
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#1A4A5C")   # steel teal
C_H2_BG  = colors.HexColor("#E6F2F6")
C_H3_FG  = colors.HexColor("#5C4A00")   # olive-gold
C_H3_BG  = colors.HexColor("#F8F3E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#3B1A0A")
C_ALT    = colors.HexColor("#F5EDEA")
C_PEARL  = colors.HexColor("#E6F2F6")
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#3B1A0A")
C_VQ_BG  = colors.HexColor("#F5EDEA")
C_VQ_FG  = colors.HexColor("#3B1A0A")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=3, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9.5, leading=13,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=12, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=3, leftIndent=4, borderPad=(4,6,4,6))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=2, leftIndent=3, borderPad=(3,5,3,5))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,4,2,4))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1, alignment=TA_JUSTIFY)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=13, firstLineIndent=-10, spaceAfter=1)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=25, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=7, rightIndent=7, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=7, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=BL,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S): st.append(Paragraph(f"♥ {t}", S["dose"]))

def tbl(data, cw, S, alt=True):
    rows = []
    for ri, row in enumerate(data):
        nr = [Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("MUCORMYCOSIS OF THE MAXILLA", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: KJ Lee's Essential Otolaryngology 11e, "
        "Medical Microbiology 9e (Murray), Scott-Brown's OHN&S 8e, "
        "Grainger & Allison Radiology 6e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. INTRODUCTION ────────────────────────────────────────────────────────
    h1(st, "1.  INTRODUCTION & DEFINITION", S)
    bl(st, [
        "MUCORMYCOSIS (= Zygomycosis) = opportunistic, life-threatening ANGIOINVASIVE fungal "
          "infection caused by fungi of the order MUCORALES (class Zygomycetes). "
          "(KJ Lee's Essential Otolaryngology)",
        "Most common clinical form affecting the maxilla and paranasal sinuses = "
          "RHINOCEREBRAL MUCORMYCOSIS (also called Rhinoorbitalcerebral Mucormycosis / ROCM). "
          "Begins in nasal cavity and paranasal sinuses; spreads to orbit and brain.",
        "HALLMARK: ANGIOINVASION by hyphae -> vascular thrombosis -> ischaemic necrosis "
          "-> characteristic BLACK ESCHAR (necrotic tissue). This distinguishes it from "
          "other fungal infections.",
        "Infections are RARE but RAPIDLY PROGRESSIVE and FATAL if not promptly treated. "
          "Mortality rates 70-100% without aggressive intervention. (Medical Microbiology 9e)",
        "India had the highest global burden during COVID-19 pandemic (COVID-associated "
          "mucormycosis / CAM) driven by corticosteroid use + uncontrolled DM.",
    ], S)
    pearl(st,
        "PEARL: Mucormycosis = TRIAD OF: (1) Susceptible host (DKA/immunocompromised). "
        "(2) Angioinvasion by non-septate hyphae at right angles. "
        "(3) Ischaemic necrosis / black eschar. "
        "Causative term: Mucorales fungi are UNIQUE in that they grow optimally in "
        "ACIDIC + HIGH GLUCOSE + HIGH IRON environment = explains DKA predisposition. (KJ Lee)", S)
    sp(st, 3)

    # ── 2. AETIOLOGY / MYCOLOGY ────────────────────────────────────────────────
    h1(st, "2.  AETIOLOGY - CAUSATIVE ORGANISMS", S)
    data = [
        ["Organism", "Key Features"],
        ["Rhizopus arrhizus\n(= R. oryzae)\n[MOST COMMON]",
         "Most common cause of human mucormycosis overall. "
         "Produces KETONE REDUCTASE = grows optimally in acidic/high-glucose environment (DKA). "
         "Rhizoids (root-like structures) present - helps identify genus. "
         "Sporangiophores arise at nodes adjacent to rhizoids. (Medical Microbiology 9e)"],
        ["Mucor spp.",
         "Second most common. Sporangiophores arise between rhizoids (unlike Rhizopus). "
         "No rhizoids present in some species."],
        ["Rhizomucor spp.",
         "Thermotolerant; recovered from dung and soil. "
         "Causes invasive disease in hospitalised/immunocompromised patients."],
        ["Lichtheimia\n(formerly Absidia) spp.",
         "Sporangiophores arise between nodes. "
         "Associated with disseminated mucormycosis in haematology patients."],
        ["Cunninghamella spp.",
         "Particularly aggressive; high mortality. "
         "Associated with pulmonary and disseminated forms in BMT patients."],
        ["Apophysomyces\nelegans",
         "Common in INDIA and tropical regions; important in post-traumatic skin infections "
         "and in immunocompetent hosts. Accounts for significant proportion of Indian cases."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    h3(st, "Microscopic Morphology (Histopathology - KEY EXAM POINT)", S)
    bl(st, [
        "Hyphae = BROAD (10-20 microns wide), RIBBON-LIKE, ASEPTATE or pauci-septate (sparsely septate). "
          "Width > 10 microns: distinguishes Mucorales from Aspergillus (3-5 microns, regularly septate).",
        "Branching pattern = IRREGULAR, at RIGHT ANGLES (90 degrees, haphazard). "
          "Contrast: Aspergillus = regular dichotomous branching at ACUTE ANGLES (45 degrees).",
        "Walls are THIN; stain weakly with GMS (Grocott Methenamine Silver) and other fungal stains. "
          "H&E stain is often MORE SENSITIVE (highlights cytoplasm).",
        "ANGIOINVASION: hyphae invade blood vessel walls -> thrombus formation -> tissue infarction.",
        "Tissue reaction: suppurative inflammation + necrosis; giant cell reaction uncommon.",
    ], S)
    sp(st, 3)

    # ── 3. PREDISPOSING FACTORS ────────────────────────────────────────────────
    h1(st, "3.  PREDISPOSING FACTORS / RISK FACTORS", S)
    data = [
        ["Risk Factor", "Mechanism / Detail"],
        ["DIABETIC KETOACIDOSIS\n(DKA) [MOST COMMON\nin rhinocerebral form]",
         "HIGH GLUCOSE + ACIDIC pH: (1) Inhibits neutrophil chemotaxis and phagocytosis. "
         "(2) Mucorales enzyme KETONE REDUCTASE thrives in acidic/high-glucose environment. "
         "(3) ABNORMAL TRANSFERRIN BINDING in DM: free iron available for fungal growth. "
         "(4) Transferrin normally bacteriostatic (binds iron); in DM it is dysfunctional. "
         "Rhinocerebral form predominates in DKA. (KJ Lee's Otolaryngology)"],
        ["Haematologic malignancy\n(leukaemia, lymphoma)",
         "Neutropenia (< 500/uL) = most critical immune defect. "
         "Neutrophils are the primary defence against Mucorales. "
         "Pulmonary form more common in haematology patients."],
        ["Bone marrow transplant\n(BMT) / Solid organ\ntransplant",
         "Prolonged neutropenia + high-dose immunosuppression. "
         "Voriconazole prophylaxis (given for Aspergillus) = Mucorales are intrinsically "
         "RESISTANT to voriconazole -> breakthrough mucormycosis."],
        ["Corticosteroids",
         "Impairs neutrophil and macrophage function. "
         "COVID-19 pandemic: high-dose dexamethasone + uncontrolled DM "
         "-> surge in COVID-Associated Mucormycosis (CAM) cases, especially in India."],
        ["DEFEROXAMINE therapy\n(iron-chelation therapy)",
         "Deferoxamine acts as a SIDEROPHORE for Rhizopus spp.: "
         "provides iron directly to the fungus -> enhances growth and pathogenicity. "
         "Used in dialysis patients (iron overload/aluminium toxicity). "
         "Contraindicated in patients at risk. (KJ Lee's Otolaryngology)"],
        ["Renal failure\n/ Dialysis",
         "Deferoxamine use + uraemia -> immune dysfunction."],
        ["HIV / AIDS",
         "Advanced HIV with CD4 < 200 + concomitant neutrophil dysfunction."],
        ["Malnutrition /\nProtein deficiency",
         "Impaired innate immunity; common in developing world context."],
        ["Trauma / Burns",
         "Primary cutaneous mucormycosis after contaminated wounds; immunocompetent hosts."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    sp(st, 3)

    # ── 4. PATHOGENESIS ────────────────────────────────────────────────────────
    h1(st, "4.  PATHOGENESIS", S)
    bl(st, [
        "Sporangiospores inhaled from environment (ubiquitous in soil, decaying vegetation) "
          "-> deposited in nasal cavity / paranasal sinuses.",
        "In IMMUNOCOMPETENT host: macrophages and neutrophils phagocytose and destroy spores. "
          "In IMMUNOCOMPROMISED: spores germinate -> hyphae.",
        "ANGIOINVASION: hyphae penetrate vessel walls of maxillary sinus / nasal cavity "
          "-> vascular thrombosis -> ISCHAEMIC NECROSIS of surrounding tissue.",
        "Rapid spread along neurovascular bundles: sinus -> orbit -> cavernous sinus -> brain. "
          "Perineural and perivascular invasion are hallmarks (KJ Lee's Otolaryngology).",
        "Iron plays critical role: transferrin (iron-binding protein) is normally fungistatic; "
          "in DKA/uraemia, transferrin is dysfunctional -> free iron available -> promotes hyphal growth.",
        "ACIDOSIS further disrupts neutrophil function and favours Mucorales growth "
          "(ketone reductase system).",
    ], S)
    sp(st, 3)

    # ── 5. CLINICAL FEATURES ──────────────────────────────────────────────────
    h1(st, "5.  CLINICAL FEATURES - RHINOCEREBRAL / MAXILLARY FORM", S)
    h2(st, "A. Stages of Spread", S)
    data = [
        ["Stage / Site", "Clinical Features"],
        ["Stage 1:\nNasal / Sinus\n(EARLIEST)",
         "Fever, nasal congestion, rhinorrhoea (serosanguinous or blood-stained). "
         "Headache, facial pain (maxillary sinus involvement). "
         "Nasal endoscopy: pale / greyish nasal mucosa -> progresses to BLACK ESCHAR "
         "(pathognomonic: necrotic black turbinate / septum = 'black turbinate sign'). "
         "Unilateral involvement is characteristic early sign."],
        ["Stage 2:\nOrbital Extension",
         "Periorbital oedema, proptosis (exophthalmos). "
         "Chemosis (conjunctival oedema), ophthalmoplegia (CN III, IV, VI palsy). "
         "Vision loss (central retinal artery thrombosis / optic nerve involvement). "
         "PAINFUL OPHTHALMOPLEGIA = key clinical sign of orbital involvement."],
        ["Stage 3:\nCavernous Sinus\nThrombosis",
         "Bilateral symptoms (contralateral spread via cavernous sinus). "
         "Multiple cranial nerve palsies (CN III, IV, V1, V2, VI). "
         "Fever, sepsis, headache worsening."],
        ["Stage 4:\nIntracranial Extension",
         "Altered consciousness, seizures, focal neurological deficits. "
         "Frontal lobe / basal ganglia infarction. "
         "Meningitis (RARE; may occur). "
         "FATAL if reaches brain: mortality approaches 100% with CNS involvement."],
        ["Maxilla-specific\nFeatures",
         "PALATAL NECROSIS: black eschar on hard palate (pathognomonic). "
         "Loose / discoloured teeth, alveolar necrosis. "
         "Oroantral fistula formation. "
         "Cheek swelling / infra-orbital numbness (V2 involvement). "
         "Trismus (pterygoid involvement)."],
    ]
    st.append(tbl(data, [W*0.20, W*0.80], S))
    h2(st, "B. General Clinical Features (Mnemonic: PROVEN)", S)
    bl(st, [
        "P - Palatal/Paranasal necrosis (black eschar on palate = PATHOGNOMONIC)",
        "R - Rhinorrhoea (serosanguinous) + facial pain/headache",
        "O - Orbital involvement: proptosis, ophthalmoplegia, chemosis",
        "V - Vision loss (central retinal artery thrombosis)",
        "E - Extension to cavernous sinus and brain",
        "N - Necrotic black turbinate / nasal mucosa (endoscopy finding)",
    ], S)
    caut(st,
        "BLACK ESCHAR on nasal mucosa or hard palate in a DIABETIC patient = "
        "MUCORMYCOSIS until proven otherwise. Emergency biopsy, antifungal therapy, "
        "and surgical debridement must be initiated immediately. "
        "ANY DELAY IS FATAL. Mortality doubles with each 6-hour delay. (KJ Lee's Otolaryngology)", S)
    sp(st, 3)

    # ── 6. DIAGNOSIS ──────────────────────────────────────────────────────────
    h1(st, "6.  DIAGNOSIS", S)
    h2(st, "A. Clinical + Endoscopic Assessment", S)
    bl(st, [
        "Nasal endoscopy: FIRST-LINE investigation. "
          "Look for pale/grey/black discolouration of nasal mucosa, turbinates, septum. "
          "Biopsy of abnormal-looking tissue = mandatory even if mucosa appears viable.",
        "Tissue biopsy: PARAMOUNT for rapid diagnosis. 85% sensitivity, 100% specificity "
          "with multiple biopsies. (KJ Lee's Otolaryngology)",
        "Oral examination: hard palate for black eschar, teeth for loosening, alveolar necrosis.",
    ], S)
    h2(st, "B. Histopathology (GOLD STANDARD)", S)
    bl(st, [
        "SILVER STAIN (GMS = Grocott Methenamine Silver): "
          "silver deposits in fungal cell wall; very sensitive. PREFERRED stain. "
          "Also: Calcofluor white stain (fluorescence microscopy).",
        "H&E stain: shows fungal cytoplasm; may have high false negatives "
          "(cytoplasm sparse at growing tips).",
        "Histology findings: broad (> 10 micron), aseptate/pauci-septate hyphae, "
          "right-angle branching, angioinvasion, vessel thrombosis, tissue necrosis.",
        "KOH preparation: rapid bedside test; shows broad aseptate hyphae.",
        "Culture: Sabouraud Dextrose Agar (SDA); grey-brown woolly colonies within 12-18 hrs. "
          "Do NOT wait for culture - empirical treatment must be started immediately. "
          "Culture absence does NOT rule out disease. (KJ Lee's Otolaryngology)",
    ], S)
    h2(st, "C. Imaging", S)
    data = [
        ["Modality", "Findings / Role"],
        ["CT SINUSES\n(NON-CONTRAST)\n[1st-line imaging]",
         "Unilateral soft tissue mucosal thickening in nasal cavity/sinuses (early). "
         "Sinus opacification (non-specific). "
         "WORRISOME: soft tissue emphysema, bony erosion (late-phase finding). "
         "Periantral fat stranding / obliteration (maxillary involvement). "
         "Orbital floor erosion, palatal defect. (KJ Lee's Otolaryngology)"],
        ["MRI WITH CONTRAST\n(GADOLINIUM)\n[Modality of choice for\nsoft tissue extension]",
         "'BLACK TURBINATE SIGN': absent gadolinium enhancement of sinonasal mucosa on T1/T2 "
         "= highly suggestive of mucosal necrosis from angioinvasion (pathognomonic on MRI). "
         "Extrasinus invasion: enhances with Gd. "
         "Orbital extension: proptosis, extraconal fat infiltration. "
         "Cavernous sinus: T1 enhancement, cavernous sinus thrombosis. "
         "Intracranial: infarcts (DWI restriction), meningeal enhancement. (KJ Lee)"],
        ["CT CHEST",
         "If disseminated disease suspected: consolidation, nodules, halo sign, "
         "air-crescent sign (5-12.5% of cases); cavitation 26-40%. (Grainger & Allison)"],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    sp(st, 3)

    # ── 7. MANAGEMENT ─────────────────────────────────────────────────────────
    h1(st, "7.  MANAGEMENT - TRIPLE APPROACH", S)
    pearl(st,
        "MANAGEMENT TRIAD: (1) CORRECT UNDERLYING CONDITION (DKA, immunosuppression). "
        "(2) EARLY AGGRESSIVE SURGICAL DEBRIDEMENT (remove all necrotic tissue). "
        "(3) SYSTEMIC ANTIFUNGAL THERAPY (amphotericin B as first choice). "
        "ALL THREE must be done simultaneously - any one alone is insufficient. (KJ Lee)", S)

    h2(st, "A. Correction of Predisposing Condition", S)
    bl(st, [
        "CONTROL DIABETIC KETOACIDOSIS: aggressive IV insulin + fluid/electrolyte correction. "
          "This is a POSITIVE PROGNOSTICATOR (reversible immunosuppression). (KJ Lee)",
        "Reduce / stop immunosuppression where clinically feasible "
          "(steroids, deferoxamine, cytotoxic agents).",
        "MDT approach: endocrinologist (diabetes control), haematologist, "
          "infectious disease specialist, ICU.",
        "G-CSF / GM-CSF: cytokine therapy to reduce neutropenic days; "
          "widely used in haematology patients (KJ Lee's Otolaryngology).",
    ], S)

    h2(st, "B. Surgical Debridement", S)
    bl(st, [
        "EARLY, AGGRESSIVE, REPEATED surgical debridement of all necrotic tissue. "
          "Most important surgical intervention.",
        "ENDOSCOPIC approach: functional endoscopic sinus surgery (FESS) + "
          "maxillectomy as needed. Resection of necrotic turbinates, ethmoid, "
          "maxillary antrum, orbital floor, palate.",
        "MEDIAL MAXILLECTOMY / INFRASTRUCTURE MAXILLECTOMY: when palate and alveolus involved.",
        "TOTAL MAXILLECTOMY: for extensive maxillary involvement with cheek/infratemporal spread.",
        "ORBITAL EXENTERATION: if orbit invaded with loss of vision "
          "(controversial; some advocate if vision already lost).",
        "Hyperbaric oxygen (HBO): adjunctive; increases tissue oxygen -> impairs fungal growth. "
          "Evidence limited but used in some centres.",
        "Repeat debridement every 24-48 hours until margins are clear of disease.",
    ], S)

    h2(st, "C. Antifungal Therapy", S)
    dose(st,
        "FIRST-LINE: AMPHOTERICIN B = antifungal of choice for mucormycosis. "
        "CONVENTIONAL deoxycholate AmB: 1 mg/kg/day IV. "
        "LIPOSOMAL AmB (Ambisome): 5 mg/kg/day IV - PREFERRED: less nephrotoxic, "
        "better CNS penetration, improved survival in retrospective studies. "
        "Duration: minimum 6-12 weeks; continue until clinical resolution + "
        "radiological clearance + immune reconstitution. (KJ Lee's Otolaryngology)", S)
    data = [
        ["Antifungal", "Role / Notes"],
        ["LIPOSOMAL AMPHOTERICIN B\n(Ambisome) 5 mg/kg/day IV\n[DRUG OF CHOICE]",
         "Polyene macrolide; binds ergosterol in fungal membrane -> pore formation -> cell lysis. "
         "Active against ALL Mucorales. "
         "PREFERRED over conventional AmB: less nephrotoxicity, better CNS penetration. "
         "Monitor: daily creatinine, K+, Mg2+; infusion-related reactions (fever, rigors - "
         "premedicate with paracetamol + diphenhydramine)."],
        ["CONVENTIONAL AmB\n(deoxycholate) 1 mg/kg/day",
         "Equally effective but higher nephrotoxicity. "
         "Use when liposomal not available (cost). "
         "Requires hydration: 500 mL NS pre + post infusion; monitor renal function daily."],
        ["POSACONAZOLE\n(oral / IV)",
         "Triazole with activity against Mucorales and Aspergillus. "
         "Used as STEP-DOWN THERAPY after initial IV amphotericin response, "
         "or as SALVAGE therapy (AmB refractory). "
         "Also used for prophylaxis in high-risk haematology patients."],
        ["ISAVUCONAZOLE\n(oral / IV)",
         "Newer triazole; FDA-approved for mucormycosis (2015). "
         "Used as salvage or when amphotericin not tolerated. "
         "Good oral bioavailability; less drug interactions than posaconazole."],
        ["VORICONAZOLE",
         "NOT effective against Mucorales - INTRINSIC RESISTANCE. "
         "Active against Aspergillus. "
         "Voriconazole prophylaxis in BMT -> breakthrough mucormycosis. "
         "NEVER use for mucormycosis. (KJ Lee's Otolaryngology)"],
        ["ECHINOCANDINS\n(caspofungin)",
         "Limited activity alone; sometimes used as COMBINATION with AmB. "
         "Experimental; some synergy data in vitro."],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))
    caut(st,
        "VORICONAZOLE = CONTRAINDICATED for Mucorales: Mucorales are intrinsically resistant. "
        "Patients on voriconazole prophylaxis (BMT) are uniquely at risk for "
        "BREAKTHROUGH MUCORMYCOSIS. Switch immediately to amphotericin B. "
        "DEFEROXAMINE is also contraindicated in at-risk patients (acts as siderophore for Rhizopus). "
        "(KJ Lee's Otolaryngology / Medical Microbiology 9e)", S)
    sp(st, 3)

    # ── 8. PROGNOSIS ──────────────────────────────────────────────────────────
    h1(st, "8.  PROGNOSIS & PROGNOSTIC FACTORS", S)
    data = [
        ["Factor", "POOR Prognosis", "GOOD Prognosis"],
        ["Underlying disease", "Haematologic malignancy, prolonged neutropenia", "DKA (reversible)"],
        ["Extent of disease",  "Intracranial / bilateral / palatal/facial involvement", "Limited sinonasal only"],
        ["Neutrophil count",   "Severe neutropenia < 500/uL at diagnosis", "Neutrophil recovery"],
        ["Mental status",      "Altered consciousness", "Alert, GCS 15"],
        ["Treatment",         "Delayed diagnosis / surgery; conventional AmB only", "Early surgery + liposomal AmB"],
        ["Biomarkers",        "CRP >= 5.5 mg/dL; renal/liver failure", "Normal CRP, normal organ function"],
        ["Overall mortality", "70-100% (all forms); 25% rhinocerebral if treated early", "DKA form: 25-50% with optimal care"],
    ]
    st.append(tbl(data, [W*0.18, W*0.41, W*0.41], S))
    bl(st, [
        "50% overall mortality for all-cause acute invasive fungal sinusitis (largest systematic review). "
          "(KJ Lee's Otolaryngology)",
        "Rhinocerebral form with intracranial extension: near 100% mortality.",
        "Rhinocerebral form limited to sinuses + orbit with early aggressive treatment: "
          "25-50% survival.",
        "Positive prognosticators: reversible immunosuppression (DKA), surgical resection, "
          "liposomal amphotericin B. (KJ Lee's Otolaryngology)",
    ], S)
    sp(st, 3)

    # ── 9. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "9.  HIGH-YIELD VIVA QUESTIONS", S)
    vivas = [
        ("Q1: What is mucormycosis and what is its hallmark?",
         "Mucormycosis = opportunistic angioinvasive fungal infection by order Mucorales "
         "(Rhizopus arrhizus most common). "
         "HALLMARK = ANGIOINVASION by broad, aseptate, right-angle-branching hyphae -> "
         "vascular thrombosis -> ischaemic necrosis -> BLACK ESCHAR. "
         "Rhinocerebral form is most common in DKA patients. (KJ Lee / Medical Microbiology 9e)"),
        ("Q2: Why is DKA the most common predisposing factor?",
         "(1) HIGH GLUCOSE + ACIDIC pH impairs neutrophil chemotaxis and phagocytosis. "
         "(2) Mucorales enzyme KETONE REDUCTASE grows optimally in acidic, high-glucose conditions. "
         "(3) ABNORMAL TRANSFERRIN in DM: normally transferrin is fungistatic (binds iron); "
         "in DKA it is dysfunctional -> FREE IRON available -> enhances fungal growth. "
         "(4) Acidosis further impairs innate immune function. (KJ Lee's Otolaryngology)"),
        ("Q3: What are the histopathological features of mucormycosis?",
         "BROAD (> 10 micron) RIBBON-LIKE, ASEPTATE (or pauci-septate) hyphae. "
         "BRANCHING at RIGHT ANGLES (90 degrees), irregular/haphazard pattern. "
         "CONTRAST with Aspergillus: narrow (3-5 micron), regularly septate, "
         "dichotomous branching at ACUTE ANGLES (45 degrees). "
         "H&E: angioinvasion, vessel thrombosis, ischaemic necrosis. "
         "SILVER STAIN (GMS): most sensitive for fungal cell wall. "
         "Hyphae walls THIN, weakly GMS-positive; better seen on H&E. (Medical Microbiology 9e)"),
        ("Q4: What is the BLACK TURBINATE SIGN and where is it seen?",
         "BLACK TURBINATE SIGN on MRI: "
         "ABSENCE of gadolinium (Gd) enhancement of sinonasal mucosa on T1-weighted MRI "
         "= highly suggestive of mucosal necrosis from angioinvasion by Mucorales. "
         "Normally inflamed mucosa enhances with Gd; necrotic non-perfused mucosa does NOT. "
         "Clinically, 'black eschar' (black necrotic turbinate/palate) = pathognomonic finding "
         "on endoscopy/oral examination. (KJ Lee's Otolaryngology)"),
        ("Q5: What is the drug of choice and why is voriconazole contraindicated?",
         "DRUG OF CHOICE: LIPOSOMAL AMPHOTERICIN B (Ambisome) 5 mg/kg/day IV. "
         "Polyene binds ergosterol -> fungicidal. Active against ALL Mucorales. "
         "Liposomal preferred: less nephrotoxicity + better CNS penetration + improved survival. "
         "VORICONAZOLE = CONTRAINDICATED: Mucorales are INTRINSICALLY RESISTANT to voriconazole. "
         "Voriconazole prophylaxis in BMT patients leaves them unprotected against Mucorales -> "
         "BREAKTHROUGH MUCORMYCOSIS. (KJ Lee's Otolaryngology)"),
        ("Q6: Why is deferoxamine a risk factor?",
         "DEFEROXAMINE = iron-chelating agent used in dialysis patients (iron overload). "
         "Deferoxamine acts as a SIDEROPHORE for Rhizopus spp.: "
         "the iron-deferoxamine complex is preferentially taken up by Rhizopus as an iron source "
         "-> directly ENHANCES FUNGAL GROWTH and pathogenicity. "
         "Deferoxamine should be avoided/stopped in any patient suspected of mucormycosis. "
         "(KJ Lee's Otolaryngology / Medical Microbiology 9e)"),
        ("Q7: What is the surgical management of maxillary mucormycosis?",
         "EARLY AGGRESSIVE SURGICAL DEBRIDEMENT = cornerstone of surgical management. "
         "Goal: remove ALL necrotic tissue with clear margins. "
         "Options: (1) Endoscopic debridement (early / limited disease). "
         "(2) Medial maxillectomy / infrastructure maxillectomy (palatal/alveolar involvement). "
         "(3) Total maxillectomy (extensive maxillary disease). "
         "(4) Orbital exenteration (orbital involvement with visual loss). "
         "Repeat debridement every 24-48h until margins clear. "
         "Hyperbaric oxygen: adjunctive (limited evidence)."),
        ("Q8: What are the prognostic factors in mucormycosis?",
         "POOR PROGNOSIS: intracranial/bilateral/facial involvement, haematologic malignancy, "
         "neutropenia < 500/uL, altered consciousness, CRP >= 5.5 mg/dL, delayed treatment. "
         "GOOD PROGNOSIS: DKA (reversible immunosuppression), early surgery, liposomal AmB. "
         "Overall mortality: 50% for AIFS (systematic review). "
         "DKA form with early treatment: 25-50% survival. "
         "Intracranial extension: near 100% mortality. (KJ Lee's Otolaryngology)"),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a, S["va"]))
    sp(st, 3)

    # ── 10. SUMMARY TABLE ─────────────────────────────────────────────────────
    h1(st, "10.  KEY POINTS SUMMARY", S)
    data = [
        ["TOPIC", "KEY POINT"],
        ["Definition",       "Angioinvasive fungal infection; order Mucorales; hallmark = vascular thrombosis + black eschar"],
        ["Organism",         "Rhizopus arrhizus (most common); also Mucor, Rhizomucor, Lichtheimia, Cunninghamella, Apophysomyces"],
        ["Hyphae",           "BROAD (> 10 micron), ASEPTATE/pauci-septate, RIGHT-ANGLE branching (90 deg) - key exam point"],
        ["vs Aspergillus",   "Aspergillus: narrow (3-5 micron), regularly septate, acute-angle branching (45 deg)"],
        ["Top risk factor",  "DKA (rhinocerebral form); neutropenia (pulmonary form); corticosteroids"],
        ["DKA mechanism",    "Ketone reductase + dysfunctional transferrin + impaired neutrophils + acidosis"],
        ["Deferoxamine risk","Acts as siderophore for Rhizopus -> enhances fungal iron uptake -> contraindicated"],
        ["Voriconazole",     "CONTRAINDICATED (intrinsic resistance); breakthrough mucormycosis in BMT patients"],
        ["Pathognomonic sign","Black eschar on hard palate / nasal turbinate (angioinvasion + necrosis)"],
        ["Black turbinate sign","Absent gadolinium enhancement on MRI T1 = mucosal necrosis from angioinvasion"],
        ["Histology stain",  "GMS (silver stain) = most sensitive; H&E for angioinvasion; KOH for rapid bedside"],
        ["Drug of choice",   "LIPOSOMAL AmB 5 mg/kg/day IV (preferred); conventional AmB 1 mg/kg/day (alternative)"],
        ["Step-down",        "Posaconazole or isavuconazole (oral/IV) after initial response to AmB"],
        ["Surgery",          "Early aggressive debridement; medial/total maxillectomy; repeat q24-48h until clear"],
        ["Prognosis",        "50% mortality overall; near 100% with intracranial extension; DKA form best prognosis"],
    ]
    st.append(tbl(data, [W*0.22, W*0.78], S))

    sp(st, 4)
    st.append(Paragraph(
        "References: KJ Lee's Essential Otolaryngology 11th ed. | "
        "Medical Microbiology 9th ed. (Murray et al.) | "
        "Scott-Brown's OHN&S 8th ed. | Grainger & Allison Diagnostic Radiology 6th ed. | "
        "Robbins & Cotran Pathology 10th ed. | Fitzpatrick's Dermatology 9th ed.",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Mucormycosis_Maxilla_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=14*mm, bottomMargin=14*mm,
        title="Mucormycosis of Maxilla - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

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Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_mucormycosis.py'

#!/usr/bin/env python3
# Chemotherapy in HNC - v2 SIMPLIFIED, POINT-WISE, TABULAR
# NEW Palette: Deep forest green headings / warm rust subheadings / dark navy H3
# Easy-to-read student-friendly layout

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette: Deep Forest Green / Warm Rust / Dark Navy
C_H1_BG  = colors.HexColor("#1C4A1C")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#8B2500")
C_H2_BG  = colors.HexColor("#FFF0EA")
C_H3_FG  = colors.HexColor("#0D2B5C")
C_H3_BG  = colors.HexColor("#EAF0FF")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1C4A1C")
C_ALT    = colors.HexColor("#EAF5EA")
C_PEARL  = colors.HexColor("#EAF0FF")
C_CAUT   = colors.HexColor("#C0392B")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#1C4A1C")
C_VQ_BG  = colors.HexColor("#EAF5EA")
C_VQ_FG  = colors.HexColor("#1C4A1C")
C_NUM_BG = colors.HexColor("#1C4A1C")

M = 14*mm
WP, HP = A4
BS, BL, CL = 10.5, 15.5, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=6, spaceAfter=3, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10, leading=13,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=3, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["body"] = ParagraphStyle("body", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, spaceAfter=1)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=15,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["blb"] = ParagraphStyle("blb", fontName=BD, fontSize=BS, leading=15,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=1)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=1, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellb"] = ParagraphStyle("cellb", fontName=BD, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=3, leftIndent=5, borderPad=(2,4,2,4))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=11, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, bold=False, sub=False):
    key = "sbl" if sub else ("blb" if bold else "bl")
    for i in items: st.append(Paragraph(f"• {i}", S[key]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S): st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S): st.append(Paragraph(f"♥ {t}", S["dose"]))

def tbl(data, cw, S, alt=True, hcols=None):
    if hcols is None: hcols = list(range(len(data[0])))
    rows = []
    for ri, row in enumerate(data):
        nr = [Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
        rows.append(nr)
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT] if alt else [colors.white]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.35, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    return t

# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("CHEMOTHERAPY IN HEAD & NECK CANCERS", S["title"]))
    st.append(Paragraph(
        "10-Mark Easy Study Notes  |  KNRUHS ENT PG  |  "
        "Scott-Brown's OHN&S 8e, Cummings ORL 7e, KJ Lee 11e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── QUICK FACTS BOX ───────────────────────────────────────────────────────
    h1(st, "QUICK FACTS - READ FIRST", S)
    data = [
        ["What you MUST know", "Answer"],
        ["Most common HNC histology",   "Squamous Cell Carcinoma (HNSCC) - 90%+"],
        ["Most active single drug",     "CISPLATIN - backbone of all regimens"],
        ["Does chemo cure HNC alone?",  "NO - chemo does NOT improve cure rates alone"],
        ["Main role of chemo in HNC",   "RADIOSENSITISER (given with RT) + organ preservation"],
        ["Standard concurrent drug",    "Cisplatin 100 mg/m2 IV every 3 weeks x3 cycles"],
        ["Best organ preservation trial","RTOG 91-11 - concurrent CRT best for larynx"],
        ["1st-line R/M HNSCC today",    "PEMBROLIZUMAB (anti-PD1) +/- chemotherapy (KEYNOTE-048)"],
        ["HPV+ oropharynx",             "Better prognosis; higher chemo-RT sensitivity"],
    ]
    st.append(tbl(data, [W*0.38, W*0.62], S))
    sp(st, 4)

    # ── 1. ROLES OF CHEMOTHERAPY ──────────────────────────────────────────────
    h1(st, "1.  WHAT DOES CHEMOTHERAPY DO IN HNC?", S)
    data = [
        ["Role", "When Used", "Goal"],
        ["RADIOSENSITISATION\n(MOST IMPORTANT)",
         "Concurrent with RT (chemoradiation)",
         "Chemo makes tumour cells more sensitive to radiation -> better killing"],
        ["ORGAN PRESERVATION",
         "Induction chemo before RT",
         "Shrink tumour first -> avoid surgery (save larynx/pharynx)"],
        ["REDUCE DISTANT\nMETASTASES",
         "Concurrent / induction",
         "Kill cancer cells that have spread outside RT field"],
        ["PALLIATION",
         "Recurrent or metastatic disease",
         "Control symptoms, improve quality of life (NOT cure)"],
    ]
    st.append(tbl(data, [W*0.28, W*0.28, W*0.44], S))
    pearl(st,
        "KEY POINT: Chemo ALONE does not cure HNC. "
        "Its power is in COMBINATION with radiotherapy (chemoradiation = CRT). "
        "Concurrent CRT is the standard of care for locally advanced HNSCC.", S)
    sp(st, 4)

    # ── 2. CHEMOTHERAPY STRATEGIES SIMPLIFIED ─────────────────────────────────
    h1(st, "2.  THE 4 CHEMOTHERAPY STRATEGIES", S)
    data = [
        ["Strategy", "Simple Explanation", "Key Trial", "Result"],
        ["INDUCTION\n(Neoadjuvant)\nChemo FIRST",
         "Give chemo BEFORE surgery/RT\nShrink tumour first",
         "VA Laryngeal Study\n(1991)",
         "85% tumour response\n64% larynx saved\nSame survival as surgery"],
        ["CONCURRENT\nCHEMO-RT\n(CRT)\n[STANDARD]",
         "Give chemo AT THE SAME TIME as RT\nChemo = radiosensitiser",
         "RTOG 91-11\nRTOG 9501\nEORTC 22931",
         "Best organ preservation\n13% better 5yr survival\n(high-risk post-op)"],
        ["ADJUVANT\nChemo AFTER",
         "Give chemo AFTER surgery/RT\nKill remaining cells",
         "Multiple RCTs",
         "NO survival benefit alone\nReplaced by concurrent CRT"],
        ["PALLIATIVE\nChemo",
         "For spread/recurrent disease\nNot curable",
         "EXTREME trial\nKEYNOTE-048",
         "Median survival 6-12 months\nPembrolizumab now standard"],
    ]
    st.append(tbl(data, [W*0.17, W*0.27, W*0.22, W*0.34], S))
    sp(st, 4)

    # ── 3. DRUGS TABLE ────────────────────────────────────────────────────────
    h1(st, "3.  KEY DRUGS AT A GLANCE", S)
    data = [
        ["Drug", "How it Works (Simple)", "Main Use in HNC", "Key Side Effects"],
        ["CISPLATIN\n(STAR DRUG)",
         "Damages DNA -> cancer cell death",
         "Concurrent CRT standard\n100 mg/m2 q3w OR 40 mg/m2 weekly",
         "NEPHROTOXICITY (kidney)\nOTOTOXICITY (hearing loss)\nSevere vomiting\nNeuropathy\nHypomagnesaemia"],
        ["CARBOPLATIN",
         "Same as cisplatin (less harsh)",
         "When cisplatin not tolerated\n(renal failure, hearing loss)",
         "THROMBOCYTOPENIA (platelets)\nLess nephrotoxic\nLess vomiting"],
        ["5-FLUOROURACIL\n(5-FU)",
         "Blocks DNA building blocks\n-> prevents cell division",
         "Combination regimens\n(PF, TPF) as infusion",
         "MUCOSITIS (mouth sores)\nDiarrhoea\nHand-foot syndrome\nCardiac spasm (rare)"],
        ["DOCETAXEL\n(Taxane)",
         "Freezes cell division\nmachinery (microtubules)",
         "TPF induction regimen\n75 mg/m2 q3w",
         "Neutropenia\nFluid retention\nNeuropathy\nNail changes"],
        ["PACLITAXEL\n(Taxane)",
         "Same as docetaxel",
         "Weekly + carboplatin\nalternative induction",
         "Neuropathy (main)\nNeutropenia\nHypersensitivity"],
        ["METHOTREXATE",
         "Blocks folate pathway\n-> stops cell growth",
         "Single agent in recurrent/\nmetastatic (cheap, low activity)",
         "Mucositis\nMyelosuppression\nHepatotoxicity"],
        ["CETUXIMAB\n(Targeted)",
         "Antibody blocks EGFR\non cancer cell surface",
         "With RT (Bonner trial)\nWith chemo in R/M (EXTREME)",
         "Acne-like rash (=good sign)\nHypomagnesaemia\nInfusion reaction"],
        ["PEMBROLIZUMAB\n(Immunotherapy)",
         "Releases brakes on your\nimmune system (anti-PD1)",
         "1st-line R/M HNSCC\n(KEYNOTE-048 standard)",
         "Immune reactions:\npneumonitis, colitis,\nthyroid problems"],
    ]
    st.append(tbl(data, [W*0.14, W*0.22, W*0.26, W*0.38], S))
    sp(st, 4)

    # ── 4. LANDMARK TRIALS TABLE ──────────────────────────────────────────────
    h1(st, "4.  LANDMARK TRIALS - EASY SUMMARY", S)
    data = [
        ["Trial", "What They Did", "What They Found", "Why It Matters"],
        ["VA LARYNGEAL\nSTUDY (1991)",
         "Stage III/IV larynx cancer\nInduction cisplatin+5-FU x3\nthen RT  vs  Surgery+RT",
         "Same survival in both groups\n64% kept their larynx",
         "FIRST trial showing you can\nSAVE the larynx with chemo\nwithout losing survival"],
        ["RTOG 91-11\n(2003)",
         "3 groups:\n(1) Induction chemo then RT\n(2) Concurrent cisplatin-RT\n(3) RT alone",
         "Concurrent CRT was BEST\nfor organ preservation\nand locoregional control",
         "Concurrent CRT = GOLD\nSTANDARD for larynx\norgan preservation"],
        ["RTOG 9501 +\nEORTC 22931\n(2004)",
         "After surgery in high-risk\npatients:\nAdjuvant cisplatin+RT\nvs RT alone",
         "Cisplatin+RT better:\n+13% in 5yr survival\nBetter local control",
         "Indications for adjuvant CRT:\nExtracapsular spread (ECS)\nPositive margins - KEY!"],
        ["TAX 323/324\n(TPF trials)",
         "Induction TPF\nvs\nInduction PF",
         "TPF better: OS, PFS,\nlocal + distant control",
         "TPF = standard induction\nif induction used today"],
        ["EXTREME\n(2008)",
         "R/M HNSCC:\nCetuximab+Cisplatin+5FU\nvs Cisplatin+5FU alone",
         "Cetuximab added:\nResponse 36% vs 20%\nOS 10.1 vs 7.4 months",
         "First drug to beat\ncisplatin+5FU in R/M\n(now replaced by pembro)"],
        ["KEYNOTE-048\n(2019)",
         "R/M HNSCC:\nPembrolizumab alone\nor Pembro+chemo\nvs EXTREME regimen",
         "Pembro alone: better OS\nif PD-L1 CPS >= 1\nPembro+chemo beats EXTREME",
         "CURRENT STANDARD\n1st-line R/M HNSCC\n(replaced EXTREME)"],
        ["BONNER TRIAL\n(2006)",
         "Cetuximab+RT\nvs RT alone\n(locally advanced)",
         "Cetuximab+RT: OS\n49 vs 29 months\nBetter local control",
         "Option for patients\nwho CANNOT have cisplatin\n(cisplatin-ineligible)"],
    ]
    st.append(tbl(data, [W*0.16, W*0.24, W*0.26, W*0.34], S))
    sp(st, 4)

    # ── 5. CISPLATIN - KEY EXAM FOCUS ─────────────────────────────────────────
    h1(st, "5.  CISPLATIN - EVERYTHING YOU NEED TO KNOW", S)
    h2(st, "How it Works", S)
    bl(st, [
        "PLATINUM compound - forms cross-links in DNA strands",
        "Cross-linked DNA cannot be copied -> cancer cell CANNOT divide -> dies",
        "BACTERICIDAL-type action: KILLS cells (not just stops them)",
        "Also RADIOSENSITISES: helps radiation damage cells more effectively",
    ], S)
    h2(st, "How it Radiosensitises (5 Ways to Remember)", S)
    data = [
        ["Mechanism", "Simple Meaning"],
        ["Stops tumour repopulation", "Cancer cells cannot regrow between RT fractions"],
        ["Kills hypoxic cells",       "Low-oxygen cells are usually radiation-resistant; cisplatin kills them"],
        ["Blocks radiation repair",   "Cancer cells cannot fix the radiation damage"],
        ["Shrinks tumour",            "Better blood supply -> more oxygen -> more radiosensitive"],
        ["Kills micrometastases",     "Destroys spread cells outside the RT field"],
    ]
    st.append(tbl(data, [W*0.35, W*0.65], S))
    h2(st, "Side Effects Checklist (Before Each Cycle)", S)
    data = [
        ["Side Effect", "What to Check / Do"],
        ["NEPHROTOXICITY (MAIN)", "Creatinine / eGFR > 50 mL/min before each cycle\nHydrate: 1 L NS before + 1 L NS after\nMonitor urine output\nSwitch to carboplatin if kidney impaired"],
        ["OTOTOXICITY (HEARING LOSS)", "Audiogram before each cycle\nHigh-frequency SNHL - IRREVERSIBLE\nSwitch to carboplatin if significant loss"],
        ["NAUSEA/VOMITING", "Severe (grade 3-4)\nGive: Ondansetron + Dexamethasone + NK1 antagonist (aprepitant)"],
        ["HYPOMAGNESAEMIA", "Check Mg2+ levels; common and may persist after treatment\nReplace IV/oral magnesium"],
        ["MYELOSUPPRESSION", "FBC: Neutrophils > 1.5 x10^9/L, Platelets > 100 x10^9/L before cycle"],
        ["NEUROPATHY", "Cumulative peripheral neuropathy (tingling/numbness hands+feet)\nDose-reduce or stop if severe"],
    ]
    st.append(tbl(data, [W*0.28, W*0.72], S))
    dose(st,
        "CISPLATIN DOSE: Concurrent CRT = 100 mg/m2 IV day 1, 22, 43 (q3w x3 cycles). "
        "OR 40 mg/m2 weekly (less toxic, similar efficacy, commonly used in India). "
        "CARBOPLATIN dose: AUC 5-6 by Calvert formula when cisplatin not suitable.", S)
    sp(st, 4)

    # ── 6. REGIMENS TABLE ─────────────────────────────────────────────────────
    h1(st, "6.  COMMON REGIMENS - QUICK TABLE", S)
    data = [
        ["Regimen Name", "Drugs", "When Used"],
        ["PF",
         "Cisplatin 100 mg/m2 day 1\n+ 5-FU 1000 mg/m2/day x4 days\nq3 weekly",
         "Historic induction\n(VA Laryngeal study)\nNow replaced by TPF"],
        ["TPF\n(STANDARD INDUCTION)",
         "Docetaxel 75 + Cisplatin 75\n+ 5-FU 750 mg/m2/day x5\nq3 weekly",
         "Induction chemo if used\nSuperior to PF (TAX323/324)\nHigh toxicity - needs G-CSF"],
        ["CONCURRENT\nCISPLATIN-RT",
         "Cisplatin 100 mg/m2 q3w x3\n(OR 40 mg/m2 weekly)\nconcurrent with RT",
         "STANDARD post-op adjuvant\nHigh-risk features:\nECS or positive margins"],
        ["EXTREME",
         "Cetuximab + Cisplatin\n+ 5-FU q3w x6\nthen Cetuximab maintenance",
         "R/M HNSCC 1st line\n(historic, now replaced\nby KEYNOTE-048 regimen)"],
        ["KEYNOTE-048\n(CURRENT STD)",
         "PEMBROLIZUMAB alone\nOR Pembro + Cisplatin + 5-FU",
         "1st-line R/M HNSCC\nPD-L1 CPS >= 1: pembro alone\nAll others: pembro + chemo"],
        ["CETUXIMAB-RT\n(Bonner)",
         "Cetuximab 400 mg/m2 loading\nthen 250 mg/m2 weekly\nwith RT",
         "Locally advanced HNSCC\nCisplatin-INELIGIBLE patients"],
    ]
    st.append(tbl(data, [W*0.18, W*0.32, W*0.50], S))
    sp(st, 4)

    # ── 7. EGFR + IMMUNOTHERAPY SIMPLIFIED ────────────────────────────────────
    h1(st, "7.  TARGETED THERAPY & IMMUNOTHERAPY (SIMPLE)", S)
    h2(st, "EGFR - Why It Matters in HNC", S)
    bl(st, [
        "EGFR = a protein on cancer cell surface that tells cells to GROW",
        "Overexpressed in 80-90% of HNSCC -> cancer grows fast",
        "Block EGFR -> stop growth signal -> slower tumour growth",
    ], S)
    data = [
        ["Drug", "Type", "Blocks Where?", "Use"],
        ["CETUXIMAB\n(Erbitux)",
         "Monoclonal antibody\n(chimeric IgG1)",
         "EGFR outside the cell\n(extracellular domain)",
         "With RT (Bonner) OR\nwith chemo in R/M (EXTREME)\nMonotherapy in platinum-refractory"],
        ["PANITUMUMAB",
         "Fully human antibody",
         "EGFR extracellular",
         "R/M HNSCC combinations\nLess allergic than cetuximab"],
        ["ERLOTINIB /\nGEFITINIB",
         "Small molecule TKI\n(tyrosine kinase inhibitor)",
         "EGFR inside the cell\n(intracellular domain)",
         "Limited activity in HNSCC\nNOT standard of care"],
    ]
    st.append(tbl(data, [W*0.16, W*0.20, W*0.26, W*0.38], S))

    h2(st, "Immunotherapy - How It Works (Simple)", S)
    bl(st, [
        "Cancer cells wear a 'DISGUISE' (PD-L1 protein) that hides them from your immune system",
        "Pembrolizumab/Nivolumab = ANTI-PD1 antibodies = REMOVE THE DISGUISE",
        "Once disguise removed: YOUR OWN T-CELLS attack and kill the cancer",
        "Works best when tumour has HIGH PD-L1 expression (measured by CPS score)",
    ], S)
    data = [
        ["Drug", "Target", "Key Trial", "Indication"],
        ["PEMBROLIZUMAB\n(Keytruda)",
         "Anti-PD1\n(blocks PD-1\non T-cells)",
         "KEYNOTE-048\n(2019)",
         "1st-line R/M HNSCC\nPD-L1 CPS >= 1: alone\nAll: with chemo\nCURRENT STANDARD"],
        ["NIVOLUMAB\n(Opdivo)",
         "Anti-PD1",
         "CheckMate-141\n(2016)",
         "2nd-line R/M HNSCC\nAfter platinum failure\nOS 7.5 vs 5.1 months"],
    ]
    st.append(tbl(data, [W*0.18, W*0.17, W*0.18, W*0.47], S))
    caut(st,
        "SIDE EFFECTS OF IMMUNOTHERAPY = 'Immune-related Adverse Events (irAEs)': "
        "Pneumonitis (lung), Colitis (bowel), Hepatitis (liver), Thyroiditis (thyroid), "
        "Skin rash. Treat with STEROIDS (prednisolone). Can be severe/life-threatening.", S)
    sp(st, 4)

    # ── 8. WHEN TO USE WHAT - FLOWCHART TABLE ─────────────────────────────────
    h1(st, "8.  WHEN TO USE WHICH TREATMENT? (DECISION GUIDE)", S)
    data = [
        ["Clinical Situation", "Treatment of Choice", "Key Drug(s)"],
        ["Locally advanced HNSCC\nPost-op HIGH RISK\n(ECS or +ve margins)",
         "ADJUVANT Concurrent CRT",
         "Cisplatin 100 mg/m2 q3w x3\n+ RT 60-66 Gy"],
        ["Locally advanced HNSCC\nLarynx/Pharynx\nOrgan preservation goal",
         "CONCURRENT CRT\n(RTOG 91-11 standard)",
         "Cisplatin 100 mg/m2 q3w x3\n+ RT 70 Gy"],
        ["Same but CANNOT have\ncisplatin (renal/hearing)",
         "CETUXIMAB + RT\n(Bonner protocol)",
         "Cetuximab 400 -> 250 mg/m2\nweekly + RT"],
        ["Induction chemo\n(if used - controversial)",
         "TPF x3 cycles then\nassess for CRT or surgery",
         "Docetaxel + Cisplatin + 5-FU"],
        ["Recurrent/Metastatic\n1st line (CURRENT STD)",
         "PEMBROLIZUMAB\n(PD-L1 CPS guided)",
         "CPS >= 1: Pembro alone\nAll: Pembro + Cisplatin + 5-FU"],
        ["R/M 2nd line\n(after platinum failure)",
         "NIVOLUMAB\nor cetuximab monotherapy",
         "Nivolumab 3 mg/kg q2w\n(CheckMate-141)"],
        ["Poor performance\nstatus (ECOG 3-4)",
         "Best supportive care\n(palliative / hospice)",
         "Avoid aggressive chemo\nMethotrexate weekly if any"],
    ]
    st.append(tbl(data, [W*0.28, W*0.30, W*0.42], S))
    sp(st, 4)

    # ── 9. VIVA Q&A ───────────────────────────────────────────────────────────
    h1(st, "9.  VIVA QUESTIONS & CRISP ANSWERS", S)
    vivas = [
        ("Q1: What is the main role of chemotherapy in HNC?",
         "Chemo does NOT cure HNC alone. Main roles:\n"
         "1. RADIOSENSITISER - makes tumour sensitive to radiation (MOST IMPORTANT)\n"
         "2. Organ preservation (avoid laryngectomy)\n"
         "3. Reduce distant metastases\n"
         "4. Palliation in recurrent/metastatic disease"),
        ("Q2: Name the VA Laryngeal study and its significance.",
         "VA Laryngeal Cancer Study (1991) - NEJM\n"
         "Design: Induction cisplatin/5-FU x3 -> RT  vs  Surgery + RT\n"
         "Result: Same survival; 64% larynx preservation in chemo arm\n"
         "Significance: FIRST proof that larynx can be saved with chemo without losing survival"),
        ("Q3: What did RTOG 91-11 show?",
         "3 arms: (1) Induction CT + RT, (2) Concurrent cisplatin-RT, (3) RT alone\n"
         "Result: Concurrent CRT = BEST for organ preservation and locoregional control\n"
         "Conclusion: Concurrent CRT = STANDARD OF CARE for larynx preservation"),
        ("Q4: When do you give adjuvant CRT? What are the indications?",
         "After surgery in HIGH-RISK patients (RTOG 9501 + EORTC 22931)\n"
         "STRONGEST indications: (1) Extracapsular spread (ECS) of nodes\n"
         "                       (2) Positive surgical margins\n"
         "Other indications: Perineural invasion, LVI, T4, N2/N3\n"
         "Benefit: 13% improvement in 5yr overall survival"),
        ("Q5: What is EXTREME trial? Is it still the standard?",
         "EXTREME (2008): Cetuximab + Cisplatin + 5-FU vs Cisplatin + 5-FU in R/M HNSCC\n"
         "Result: Response 36% vs 20%; OS 10.1 vs 7.4 months (cetuximab better)\n"
         "NOW REPLACED: KEYNOTE-048 (2019) showed PEMBROLIZUMAB superior to EXTREME\n"
         "Current standard: Pembrolizumab +/- chemo (PD-L1 CPS guided)"),
        ("Q6: How does cisplatin radiosensitise tumours?",
         "5 mechanisms:\n"
         "1. Blocks tumour repopulation between RT fractions\n"
         "2. Kills hypoxic (radiation-resistant) cells\n"
         "3. Prevents repair of radiation-induced DNA damage\n"
         "4. Shrinks tumour -> better oxygenation -> more radiosensitive\n"
         "5. Kills micrometastases outside RT field"),
        ("Q7: What are the important cisplatin toxicities?",
         "1. NEPHROTOXICITY: check creatinine before each cycle; hydrate aggressively\n"
         "2. OTOTOXICITY: irreversible SNHL; audiogram before each cycle\n"
         "3. NAUSEA/VOMITING: severe; ondansetron + dexamethasone + NK1 antagonist\n"
         "4. HYPOMAGNESAEMIA: monitor and replace Mg2+\n"
         "5. NEUROPATHY: cumulative peripheral neuropathy"),
        ("Q8: What is cetuximab and when is it used?",
         "Cetuximab = chimeric IgG1 monoclonal antibody; blocks EGFR (overexpressed in 80-90% HNSCC)\n"
         "Uses: (1) With RT (Bonner trial) = when CISPLATIN CANNOT be given\n"
         "       (2) EXTREME regimen = R/M HNSCC 1st line (now historic)\n"
         "       (3) Monotherapy = platinum-refractory R/M HNSCC\n"
         "Side effect: Acneiform rash = MARKER OF RESPONSE (good sign)"),
    ]
    for q, a in vivas:
        st.append(Paragraph(q, S["vq"]))
        st.append(Paragraph(a.replace("\n","<br/>"), S["va"]))
    sp(st, 4)

    # ── 10. FINAL MEMORY AID ──────────────────────────────────────────────────
    h1(st, "10.  MEMORY AIDS & QUICK REVISION", S)
    data = [
        ["Remember This", "Key Point"],
        ["CISPLATIN = STAR DRUG",      "Backbone of ALL HNC chemo regimens; most active single agent"],
        ["CRT > Induction CT",          "RTOG 91-11: concurrent CRT beats induction CT for organ preservation"],
        ["ECS + +ve margins -> CRT",    "Strongest indications for post-op adjuvant CRT (RTOG 9501/EORTC 22931)"],
        ["TPF > PF",                    "Induction: docetaxel-cisplatin-5FU superior to cisplatin-5FU (TAX323/324)"],
        ["EXTREME -> KEYNOTE-048",      "Pembrolizumab replaced cetuximab+chemo as 1st-line R/M standard"],
        ["Cetuximab = when no cisplatin","Bonner trial: cetuximab+RT for cisplatin-ineligible patients"],
        ["Rash with cetuximab = GOOD",  "Acneiform rash = surrogate marker of EGFR response"],
        ["Vori not for Mucor",          "Not relevant here - but remember voriconazole fails Mucorales"],
        ["Chemo toxicity checklist",    "Creatinine (nephro) + Audiogram (oto) + FBC (myelo) + Mg2+ before each cycle"],
        ["PD-L1 CPS >= 1",              "Pembrolizumab monotherapy preferred (KEYNOTE-048)"],
        ["CPS < 1",                     "Pembrolizumab + Cisplatin + 5-FU (all-comers benefit)"],
        ["ECOG 3-4",                    "Best supportive care only; aggressive chemo harmful"],
    ]
    st.append(tbl(data, [W*0.35, W*0.65], S))

    sp(st, 3)
    st.append(Paragraph(
        "Sources: Scott-Brown's OHN&S 8e | Cummings ORL 7e | KJ Lee Essential ORL 11e | "
        "VA Laryngeal Study NEJM 1991 | RTOG 91-11 (Forastiere 2003) | "
        "RTOG 9501/EORTC 22931 (Cooper/Bernier 2004) | "
        "TAX323/324 | EXTREME (Vermorken NEJM 2008) | "
        "KEYNOTE-048 (Burtness Lancet 2019) | Bonner NEJM 2006",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Chemo_HNC_Easy_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Chemotherapy in HNC - Easy Notes - ENT PG",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Chemo HNC v3 - BULLET-POINT STYLE, minimal tables, student-friendly
# Palette: Deep plum headings / teal subheadings / golden H3

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 12: Deep plum / Steel teal / Gold
C_H1_BG  = colors.HexColor("#3D1052")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#0A4D5C")
C_H2_BG  = colors.HexColor("#E5F4F8")
C_H3_FG  = colors.HexColor("#6B4800")
C_H3_BG  = colors.HexColor("#FFF8E5")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#3D1052")
C_ALT    = colors.HexColor("#F2EAF8")
C_PEARL  = colors.HexColor("#E5F4F8")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#3D1052")
C_VQ_BG  = colors.HexColor("#F2EAF8")
C_VQ_FG  = colors.HexColor("#3D1052")
C_NUM    = colors.HexColor("#3D1052")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    # numbered point - bold label + normal text
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=12, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))

# numbered point: "1. <bold label> - normal text"
def pt(st, num, label, text, S):
    st.append(Paragraph(f"<b>{num}. {label}</b> - {text}", S["pt"]))

# plain bullet
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items:
        st.append(Paragraph(f"&#x2022; {i}", S[k]))

def pearl(st,t,S): st.append(Paragraph(f"&#9733; {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"&#9888; {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"&#x2665; {t}", S["dose"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("CHEMOTHERAPY IN HEAD & NECK CANCERS", S["title"]))
    st.append(Paragraph(
        "Simple Exam Notes  |  KNRUHS ENT PG  |  "
        "Scott-Brown's OHN&S 8e, Cummings ORL 7e, KJ Lee 11e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. BASICS ─────────────────────────────────────────────────────────────
    h1(st, "1.  THE BASICS - WHAT YOU MUST KNOW FIRST", S)
    bl(st, [
        "<b>Most HNC</b> = Squamous Cell Carcinoma (HNSCC) - 90%+",
        "<b>Chemotherapy ALONE does NOT cure HNC</b> - this is the single most important fact",
        "<b>Chemotherapy WORKS</b> when combined with Radiotherapy (= Chemoradiation / CRT)",
        "<b>Most active drug</b> = CISPLATIN - used in almost every regimen",
        "<b>HPV-positive oropharynx cancer</b> - better prognosis, responds well to CRT",
    ], S)
    pearl(st,
        "KEY CONCEPT: Chemo's main job in HNC is to be a RADIOSENSITISER - "
        "it makes cancer cells more sensitive to radiation so RT kills them better. "
        "This is why concurrent chemoradiation is the standard of care.", S)
    sp(st, 4)

    # ── 2. ROLES OF CHEMO ─────────────────────────────────────────────────────
    h1(st, "2.  4 ROLES OF CHEMOTHERAPY IN HNC", S)
    pt(st, "1", "Radiosensitisation",
       "Give chemo WITH radiotherapy at the same time. "
       "Chemo makes tumour cells sensitive to radiation -> better killing. "
       "This is the MOST IMPORTANT role.", S)
    pt(st, "2", "Organ Preservation",
       "Give chemo BEFORE surgery to shrink the tumour. "
       "If tumour responds well - surgery can be avoided. "
       "Example: Save the larynx instead of doing laryngectomy.", S)
    pt(st, "3", "Reducing Distant Metastases",
       "Chemo kills cancer cells that have spread beyond the radiation field. "
       "Used in concurrent and induction settings.", S)
    pt(st, "4", "Palliation",
       "For recurrent or metastatic disease where cure is not possible. "
       "Goal: control symptoms and improve quality of life. "
       "Median survival in this setting = 6-12 months.", S)
    sp(st, 4)

    # ── 3. STRATEGIES ─────────────────────────────────────────────────────────
    h1(st, "3.  THE 4 CHEMOTHERAPY STRATEGIES", S)

    h2(st, "A. Induction (Neoadjuvant) Chemotherapy - Chemo BEFORE RT/Surgery", S)
    bl(st, [
        "Given BEFORE definitive treatment (RT or surgery)",
        "Goal: shrink tumour first, then do RT or surgery",
        "Helps preserve organs (e.g. larynx, pharynx)",
        "<b>VA Laryngeal Study (1991)</b>: Induction cisplatin + 5-FU x3 cycles, then RT",
    ], S)
    bl(st, [
        "85% tumour response rate",
        "64% of patients kept their larynx",
        "Same survival as surgery + RT group",
        "SIGNIFICANCE: First proof of organ preservation concept",
    ], S, sub=True)
    bl(st, [
        "<b>Standard regimen today</b> = TPF (Docetaxel + Cisplatin + 5-FU) - better than old PF",
        "Role is CONTROVERSIAL today - used case by case, not routine",
    ], S)
    sp(st, 2)

    h2(st, "B. Concurrent Chemoradiation (CRT) - Chemo DURING RT - STANDARD", S)
    bl(st, [
        "Chemo given AT THE SAME TIME as radiotherapy",
        "This is the <b>CURRENT STANDARD OF CARE</b> for locally advanced HNSCC",
        "<b>How chemo radiosensitises (5 mechanisms)</b>:",
    ], S)
    bl(st, [
        "Stops tumour cells from repopulating between RT fractions",
        "Kills hypoxic cells (radiation can't kill them - chemo can)",
        "Blocks repair of radiation-induced DNA damage",
        "Shrinks tumour -> better blood supply -> more oxygen -> more radiosensitive",
        "Kills micrometastases outside the RT field",
    ], S, sub=True)
    bl(st, [
        "<b>RTOG 91-11 Trial</b>: 3 arms - induction chemo then RT / concurrent CRT / RT alone",
    ], S)
    bl(st, [
        "Concurrent CRT was BEST for organ preservation and locoregional control",
        "Conclusion: Concurrent CRT = standard for larynx organ preservation",
    ], S, sub=True)
    bl(st, [
        "<b>RTOG 9501 + EORTC 22931</b>: Adjuvant CRT after surgery in high-risk patients",
    ], S)
    bl(st, [
        "13% improvement in 5-year survival with concurrent CRT",
        "STRONGEST indications: Extracapsular spread (ECS) of nodes + Positive margins",
        "Other indications: perineural invasion, lymphovascular invasion, N2/N3, T4",
    ], S, sub=True)
    dose(st,
        "CISPLATIN DOSE for concurrent CRT: 100 mg/m2 IV on Day 1, 22, 43 (every 3 weeks x3). "
        "Alternative: 40 mg/m2 weekly (less toxic, similar efficacy - widely used in India). "
        "CARBOPLATIN (AUC 5-6) when cisplatin cannot be used (renal impairment, hearing loss).", S)
    sp(st, 2)

    h2(st, "C. Adjuvant Chemotherapy - Chemo AFTER Surgery", S)
    bl(st, [
        "Given after curative surgery in high-risk patients",
        "Goal: eradicate microscopic residual disease",
        "Randomised trials: <b>NO significant survival benefit</b> from adjuvant chemo alone",
        "Has been REPLACED by concurrent CRT (adjuvant CRT) in high-risk settings",
        "Level 1 evidence against using chemo alone after surgery (Scott-Brown's OHN&S)",
    ], S)
    sp(st, 2)

    h2(st, "D. Palliative Chemotherapy - For R/M HNSCC", S)
    bl(st, [
        "For RECURRENT or METASTATIC disease - no curative intent",
        "Performance status is the MOST IMPORTANT factor before giving palliative chemo",
        "ECOG 0-1: full-dose therapy / ECOG 2: reduced dose / ECOG 3-4: supportive care only",
        "<b>Old standard: EXTREME regimen</b> (Cetuximab + Cisplatin + 5-FU)",
    ], S)
    bl(st, [
        "EXTREME trial (2008): response 36% vs 20%; OS 10.1 vs 7.4 months",
        "First regimen to beat cisplatin + 5-FU in R/M HNSCC",
    ], S, sub=True)
    bl(st, [
        "<b>NEW STANDARD: KEYNOTE-048 (2019)</b> - PEMBROLIZUMAB replaced EXTREME",
    ], S)
    bl(st, [
        "PD-L1 CPS >= 1: Pembrolizumab alone - superior OS vs EXTREME",
        "All patients: Pembrolizumab + Cisplatin + 5-FU - superior to EXTREME",
        "Pembrolizumab alone is preferred (less toxic, equal/better efficacy)",
    ], S, sub=True)
    sp(st, 4)

    # ── 4. KEY DRUGS ──────────────────────────────────────────────────────────
    h1(st, "4.  KEY DRUGS - POINT BY POINT", S)

    h2(st, "CISPLATIN - The Most Important Drug", S)
    bl(st, [
        "<b>Class</b>: Platinum alkylating agent",
        "<b>Mechanism</b>: Forms DNA cross-links -> DNA cannot be copied -> cancer cell dies",
        "<b>Action</b>: Bactericidal / cytotoxic + radiosensitiser",
        "<b>Use</b>: Concurrent CRT (100 mg/m2 q3w) and induction regimens",
        "<b>Toxicities to know</b>:",
    ], S)
    bl(st, [
        "NEPHROTOXICITY (dose-limiting) - check creatinine before each cycle; hydrate with 1L NS pre + post",
        "OTOTOXICITY - irreversible SNHL - audiogram before each cycle - switch to carboplatin if impaired",
        "Nausea/vomiting - severe - needs ondansetron + dexamethasone + NK1 antagonist",
        "Hypomagnesaemia - monitor and replace Mg2+ regularly",
        "Peripheral neuropathy - cumulative, can be dose-limiting",
        "Myelosuppression - check FBC (neutrophils > 1.5, platelets > 100 before cycle)",
    ], S, sub=True)
    caut(st,
        "Before each cisplatin cycle check: Creatinine (eGFR > 50) + Audiogram + "
        "FBC (neutrophils, platelets) + Serum Mg2+. "
        "If nephrotoxicity or ototoxicity develops - SWITCH TO CARBOPLATIN.", S)
    sp(st, 2)

    h2(st, "CARBOPLATIN", S)
    bl(st, [
        "Same mechanism as cisplatin but less reactive",
        "LESS nephrotoxic and less ototoxic than cisplatin",
        "DOSE: AUC 5-6 by Calvert formula",
        "Dose-limiting toxicity = THROMBOCYTOPENIA (low platelets) - not kidneys",
        "Preferred in palliative setting and when cisplatin contraindicated",
    ], S)
    sp(st, 2)

    h2(st, "5-FLUOROURACIL (5-FU)", S)
    bl(st, [
        "Antimetabolite - blocks thymidylate synthase -> stops DNA synthesis",
        "Given as continuous infusion (96-120 hours)",
        "Used in PF and TPF induction regimens",
        "Key toxicity: MUCOSITIS (mouth sores) - dose-limiting, severe",
        "Also: diarrhoea, hand-foot syndrome, rare cardiac toxicity (coronary spasm)",
    ], S)
    sp(st, 2)

    h2(st, "DOCETAXEL (Taxane)", S)
    bl(st, [
        "Stabilises microtubules -> cells cannot divide -> death",
        "Part of TPF induction regimen (75 mg/m2)",
        "TPF is SUPERIOR to PF for OS and PFS (TAX323/TAX324 trials)",
        "Toxicities: neutropenia, fluid retention, neuropathy, nail changes",
        "Requires G-CSF (granulocyte colony stimulating factor) prophylaxis",
    ], S)
    sp(st, 2)

    h2(st, "METHOTREXATE", S)
    bl(st, [
        "Antimetabolite - inhibits dihydrofolate reductase",
        "Single agent in recurrent/metastatic disease (cheap option)",
        "Response rate ~15-20% only",
        "Toxicities: mucositis, myelosuppression, hepatotoxicity, nephrotoxicity",
    ], S)
    sp(st, 4)

    # ── 5. TARGETED THERAPY ───────────────────────────────────────────────────
    h1(st, "5.  TARGETED THERAPY - CETUXIMAB & EGFR", S)

    h2(st, "EGFR - Why It Matters", S)
    bl(st, [
        "EGFR (Epidermal Growth Factor Receptor) = growth signal protein on cancer cell surface",
        "Overexpressed in <b>80-90% of HNSCC</b> -> drives rapid cell growth",
        "Blocking EGFR = stops growth signal = slower tumour growth",
    ], S)
    sp(st, 2)

    h2(st, "CETUXIMAB (Erbitux)", S)
    bl(st, [
        "Chimeric IgG1 monoclonal antibody against EGFR extracellular domain",
        "Blocks EGFR -> stops cancer growth signalling",
        "<b>Use 1</b>: With radiotherapy (<b>Bonner trial</b>) - for locally advanced HNSCC",
    ], S)
    bl(st, [
        "Bonner trial: Cetuximab + RT vs RT alone -> OS 49 vs 29 months",
        "OPTION when cisplatin cannot be given (cisplatin-ineligible patients)",
    ], S, sub=True)
    bl(st, [
        "<b>Use 2</b>: EXTREME regimen - R/M HNSCC 1st line (now replaced by pembrolizumab)",
        "<b>Use 3</b>: Monotherapy in platinum-refractory R/M HNSCC (10-13% response)",
        "<b>Key side effect</b>: Acneiform (acne-like) rash - severity correlates with response",
        "Also: hypomagnesaemia, infusion reactions (premedicate with antihistamine + steroid)",
    ], S)
    sp(st, 4)

    # ── 6. IMMUNOTHERAPY ──────────────────────────────────────────────────────
    h1(st, "6.  IMMUNOTHERAPY (CHECKPOINT INHIBITORS)", S)

    h2(st, "How It Works (Simple)", S)
    bl(st, [
        "Cancer cells display <b>PD-L1 protein</b> on their surface as a disguise",
        "PD-L1 binds PD-1 on T-cells -> tells T-cells: 'I am not cancer, ignore me'",
        "Anti-PD1 drugs block this interaction -> T-cells recognize and attack cancer",
        "Works best when tumour has high PD-L1 expression (measured by CPS = Combined Positive Score)",
    ], S)
    sp(st, 2)

    h2(st, "PEMBROLIZUMAB (Keytruda) - Current Standard", S)
    bl(st, [
        "Anti-PD1 monoclonal antibody",
        "<b>KEYNOTE-048 trial (2019)</b>: Pembro vs EXTREME in R/M HNSCC",
    ], S)
    bl(st, [
        "PD-L1 CPS >= 1: Pembrolizumab alone = superior OS to EXTREME",
        "All patients: Pembrolizumab + Cisplatin + 5-FU = superior to EXTREME",
        "CURRENT 1ST-LINE STANDARD for R/M HNSCC",
    ], S, sub=True)
    bl(st, [
        "Side effects = Immune-Related Adverse Events (irAEs):",
    ], S)
    bl(st, [
        "Pneumonitis, Colitis, Hepatitis, Thyroiditis, Skin rash",
        "Treat with high-dose steroids (prednisolone 1-2 mg/kg/day)",
        "Can be life-threatening if not recognised early",
    ], S, sub=True)
    sp(st, 2)

    h2(st, "NIVOLUMAB (Opdivo)", S)
    bl(st, [
        "Anti-PD1 monoclonal antibody",
        "<b>CheckMate-141 trial</b>: 2nd-line R/M HNSCC after platinum failure",
        "OS 7.5 vs 5.1 months (vs investigator's choice)",
        "FDA approved for platinum-refractory R/M HNSCC",
    ], S)
    sp(st, 4)

    # ── 7. LANDMARK TRIALS TABLE (one table is justified here) ────────────────
    h1(st, "7.  LANDMARK TRIALS SUMMARY  (Table)", S)
    data = [
        ["Trial (Year)", "Design", "Key Result", "Conclusion"],
        ["VA Laryngeal\nStudy (1991)",
         "Induction cisplatin+5-FU\nthen RT vs Surgery+RT",
         "Same survival; 64%\nlarynx preserved",
         "Organ preservation possible\nwithout losing survival"],
        ["RTOG 91-11\n(2003)",
         "Concurrent CRT vs\nInduction CT+RT vs RT alone",
         "Concurrent CRT BEST for\norgan preservation",
         "Concurrent CRT = standard\nfor larynx preservation"],
        ["RTOG 9501 +\nEORTC 22931 (2004)",
         "Post-op adjuvant\ncisplatin+RT vs RT",
         "+13% 5yr OS in high-risk\nECS / positive margins",
         "Adjuvant CRT for ECS\nand positive margins"],
        ["TAX 323/324",
         "TPF vs PF induction",
         "TPF: better OS, PFS,\nlocal + distant control",
         "TPF = standard induction\nif induction used"],
        ["EXTREME (2008)",
         "Cetuximab+cisplatin+5FU\nvs cisplatin+5FU (R/M)",
         "OS 10.1 vs 7.4 months\nResponse 36% vs 20%",
         "First to beat cisplatin+5FU\nin R/M (now replaced)"],
        ["KEYNOTE-048\n(2019)",
         "Pembrolizumab alone or\n+chemo vs EXTREME (R/M)",
         "Pembro alone better if\nCPS>=1; Pembro+chemo\nbeats EXTREME overall",
         "CURRENT 1st-line standard\nR/M HNSCC"],
        ["Bonner (2006)",
         "Cetuximab+RT vs RT alone\n(locally advanced)",
         "OS 49 vs 29 months\nbetter local control",
         "Option when cisplatin\nnot possible"],
    ]
    st.append(tbl(data, [W*0.16, W*0.25, W*0.26, W*0.33], S))
    sp(st, 4)

    # ── 8. VIVA Q&A ───────────────────────────────────────────────────────────
    h1(st, "8.  VIVA QUESTIONS & ANSWERS", S)

    vivas = [
        ("Q1. What is the role of chemotherapy in head and neck cancer?",
         [
             "Chemo does NOT improve cure rates alone in HNC",
             "Main role = RADIOSENSITISATION: given concurrently with RT to sensitise tumour cells",
             "Organ preservation: induction chemo to shrink tumour and avoid surgery",
             "Reduces distant metastases when given concurrently",
             "Palliation: controls symptoms in recurrent/metastatic disease",
         ]),
        ("Q2. Describe the VA Laryngeal Cancer Study and its significance.",
         [
             "VA (Veterans Affairs) Laryngeal Study, 1991 - NEJM",
             "Stage III/IV larynx cancer: Induction cisplatin/5-FU x3 -> RT  vs  Surgery + RT",
             "Result: 85% chemo response rate; 64% larynx preserved; NO survival difference",
             "Significance: FIRST major trial proving larynx can be saved with chemo-RT",
             "Birth of the ORGAN PRESERVATION concept in HNC",
         ]),
        ("Q3. What did the RTOG 91-11 trial show?",
         [
             "Three arms: (1) Induction CT + RT, (2) Concurrent cisplatin-RT, (3) RT alone",
             "Concurrent CRT = BEST for organ preservation and locoregional control",
             "No overall survival difference between the three arms",
             "Conclusion: Concurrent CRT = gold standard for larynx organ preservation",
         ]),
        ("Q4. When do you give adjuvant concurrent CRT after surgery?",
         [
             "RTOG 9501 + EORTC 22931 identified indications",
             "STRONGEST: Extracapsular spread (ECS) of lymph nodes",
             "STRONGEST: Positive surgical margins",
             "Others: Perineural invasion, lymphovascular invasion, N2/N3, T4 disease",
             "Benefit: 13% improvement in 5-year overall survival with adjuvant cisplatin-RT",
         ]),
        ("Q5. How does cisplatin radiosensitise tumours?",
         [
             "Stops tumour repopulation between radiotherapy fractions",
             "Kills hypoxic cells which are normally resistant to radiation",
             "Prevents repair of radiation-induced DNA damage",
             "Shrinks tumour -> better vascularity -> more oxygenation -> more radiosensitive",
             "Kills micrometastatic cells outside the radiation field",
         ]),
        ("Q6. What are the toxicities of cisplatin?",
         [
             "Nephrotoxicity (dose-limiting): check creatinine before cycle; hydrate aggressively",
             "Ototoxicity: irreversible SNHL; audiogram before each cycle",
             "Severe nausea/vomiting: ondansetron + dexamethasone + NK1 antagonist",
             "Hypomagnesaemia: monitor and replace Mg2+",
             "Peripheral neuropathy: cumulative, may require dose reduction",
         ]),
        ("Q7. What is EXTREME trial? Is it still the standard?",
         [
             "EXTREME trial (2008): Cetuximab + Cisplatin + 5-FU vs Cisplatin + 5-FU in R/M HNSCC",
             "Result: Response 36% vs 20%; OS 10.1 vs 7.4 months - cetuximab improved outcomes",
             "EXTREME was first regimen to improve OS in R/M HNSCC",
             "NOW REPLACED: KEYNOTE-048 (2019) showed pembrolizumab is superior",
             "Current 1st-line R/M HNSCC = Pembrolizumab +/- chemotherapy",
         ]),
        ("Q8. What is cetuximab and when is it used?",
         [
             "Chimeric IgG1 monoclonal antibody targeting EGFR extracellular domain",
             "EGFR overexpressed in 80-90% of HNSCC",
             "Use 1: With RT (Bonner trial) - when cisplatin cannot be given (cisplatin-ineligible)",
             "Use 2: EXTREME regimen for R/M HNSCC (now historic - replaced by pembrolizumab)",
             "Use 3: Monotherapy in platinum-refractory R/M HNSCC (10-13% response)",
             "Key SE: Acneiform rash = surrogate marker of response (rash = better outcome)",
         ]),
    ]
    for q, points in vivas:
        st.append(Paragraph(q, S["vq"]))
        bl(st, points, S)
        sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Scott-Brown's OHN&S 8e | Cummings ORL 7e | KJ Lee 11e | "
        "NEJM VA 1991 | RTOG 91-11 Forastiere 2003 | RTOG9501/EORTC22931 Cooper/Bernier 2004 | "
        "EXTREME Vermorken NEJM 2008 | KEYNOTE-048 Burtness Lancet 2019 | Bonner NEJM 2006",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Chemo_HNC_BulletStyle_ENT_PG.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Chemotherapy in HNC - Bullet Notes - ENT PG",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Carotid Body Tumour - ENT PG Exam Notes (5-6 pages)
# Bullet-point style, minimal tables
# NEW Palette: Deep teal-navy headings / burnt sienna subheadings / olive H3

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 13: Deep Teal-Navy / Burnt Sienna / Olive
C_H1_BG  = colors.HexColor("#0C3347")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#8B3A00")
C_H2_BG  = colors.HexColor("#FFF3EA")
C_H3_FG  = colors.HexColor("#4A5C00")
C_H3_BG  = colors.HexColor("#F3F8E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#0C3347")
C_ALT    = colors.HexColor("#E5F2FA")
C_PEARL  = colors.HexColor("#E5F2FA")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#0C3347")
C_VQ_BG  = colors.HexColor("#E5F2FA")
C_VQ_FG  = colors.HexColor("#0C3347")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=12, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def pt(st, num, label, text, S):
    st.append(Paragraph(f"<b>{num}. {label}</b> - {text}", S["pt"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items:
        st.append(Paragraph(f"&#x2022; {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"&#9733; {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"&#9888; {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"&#x2665; {t}", S["dose"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("CAROTID BODY TUMOUR (PARAGANGLIOMA)", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Bailey & Love's Surgery 28e, Scott-Brown's OHN&S 8e, "
        "Cummings ORL 7e, KJ Lee 11e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. BASICS / INTRODUCTION ──────────────────────────────────────────────
    h1(st, "1.  BASICS - WHAT IS A CAROTID BODY TUMOUR?", S)
    bl(st, [
        "<b>Carotid body tumour (CBT)</b> = a PARAGANGLIOMA arising from chemoreceptor cells "
          "of the carotid body",
        "Also called: <b>Chemodectoma</b> (older term), <b>Glomus caroticum</b>",
        "Part of a wider family of paragangliomas: carotid body, glomus jugulare, "
          "glomus vagale, glomus tympanicum",
        "The carotid body = a <b>chemoreceptor organ</b> that detects changes in blood O2, "
          "CO2, and pH -> signals brainstem to adjust breathing and heart rate",
        "Location: nestled in the <b>carotid bifurcation</b> (where common carotid artery "
          "divides into internal and external carotid arteries)",
        "Tumour arises from <b>chemoreceptor (glomus) cells</b> on the <b>medial side</b> "
          "of the carotid bulb -> adheres to carotid wall",
        "Classification: <b>Neuroendocrine tumour</b> of neural crest origin "
          "(APUD cell lineage)",
    ], S)
    pearl(st,
        "KEY FACT: Carotid body tumour = CHEMODECTOMA = PARAGANGLIOMA. "
        "It arises at the carotid bifurcation from chemoreceptor cells. "
        "Most are BENIGN (only ~5-10% malignant) but surgery is still risky "
        "due to proximity to major vessels and cranial nerves. (Bailey & Love 28e)", S)
    sp(st, 4)

    # ── 2. EPIDEMIOLOGY ───────────────────────────────────────────────────────
    h1(st, "2.  EPIDEMIOLOGY & AETIOLOGY", S)
    bl(st, [
        "<b>Rare tumour</b> - uncommon in general population",
        "<b>Peak age</b>: Fifth decade (40-50 years); slight female preponderance",
        "<b>Higher incidence at HIGH ALTITUDES</b>: chronic hypoxia -> carotid body "
          "hyperplasia -> increased tumour risk (e.g. Andean populations of Peru, Mexico)",
        "<b>Sporadic vs Familial</b>:",
    ], S)
    bl(st, [
        "SPORADIC: majority of cases; unilateral; no family history",
        "FAMILIAL: ~10% of cases; often BILATERAL (up to 38% bilateral in familial form)",
        "Familial = autosomal dominant inheritance",
        "Associated with SUCCINATE DEHYDROGENASE (SDH) gene mutations",
    ], S, sub=True)
    bl(st, [
        "<b>SDH gene mutations</b>: SDH complex = part of mitochondrial respiratory chain (Complex II)",
    ], S)
    bl(st, [
        "SDHB mutation: associated with malignant paragangliomas (higher risk of metastasis)",
        "SDHD mutation: most common in familial CBT; paternally imprinted (only father's gene expressed)",
        "SDHC, SDHA: less common",
        "Genetic testing (SDH gene panel) recommended in all CBT patients, especially young/bilateral",
    ], S, sub=True)
    bl(st, [
        "<b>Association with PHAEOCHROMOCYTOMA</b>: especially in familial cases "
          "(same SDH mutation affects adrenal medulla). "
          "Always screen for phaeochromocytoma before surgery (urinary catecholamines / "
          "plasma metanephrines). (Bailey & Love 28e)",
        "<b>Multiple Endocrine Neoplasia (MEN)</b>: associated with MEN2A/2B (RET proto-oncogene), "
          "von Hippel-Lindau (VHL), and NF1 (neurofibromatosis type 1)",
    ], S)
    sp(st, 4)

    # ── 3. PATHOLOGY ──────────────────────────────────────────────────────────
    h1(st, "3.  PATHOLOGY", S)
    h2(st, "Macroscopic Features", S)
    bl(st, [
        "Well-defined, encapsulated, firm, reddish-brown mass",
        "Highly vascular tumour - bleeds profusely when cut",
        "Situated at carotid bifurcation, adherent to carotid wall",
        "Surrounded by a fibrous adventitial sheath",
    ], S)
    h2(st, "Microscopic Features", S)
    bl(st, [
        "<b>Zellballen pattern</b> (= characteristic): clusters of chief cells (Type I cells) "
          "surrounded by sustentacular cells (Type II), arranged in rounded nests separated by "
          "fibrovascular stroma. 'Zellballen' = German for 'cell balls'",
        "Chief cells (Type I): large, polygonal, contain neurosecretory granules "
          "(catecholamines) - stain with chromogranin, synaptophysin",
        "Sustentacular cells (Type II): spindle-shaped, peripheral supporting cells; "
          "stain with S-100",
        "Rich vascular network (sinusoidal) between cell nests",
        "IHC stains: Chromogranin A (+), Synaptophysin (+), S-100 (+) in sustentacular cells, "
          "Neuron-specific enolase (NSE) (+)",
        "<b>Malignancy</b>: cannot be determined by histology alone; malignancy = "
          "presence of METASTASES (lymph nodes, distant). "
          "Only 5-10% of CBTs are truly malignant.",
    ], S)
    sp(st, 4)

    # ── 4. CLINICAL FEATURES ──────────────────────────────────────────────────
    h1(st, "4.  CLINICAL FEATURES", S)
    h2(st, "Symptoms", S)
    bl(st, [
        "Long history of a <b>slowly enlarging, painless lump</b> at the carotid bifurcation "
          "(anterior triangle of neck, level II/III)",
        "Often present for months to years before diagnosis",
        "Dysphagia if large (pharyngeal compression)",
        "Hoarseness (vagus nerve involvement)",
        "Syncope or dizziness (carotid sinus stimulation by the tumour = <b>carotid sinus syndrome</b>)",
        "Pulsatile tinnitus (if glomus tympanicum/jugulare component)",
        "About <b>one-third</b> of patients present with a pharyngeal mass pushing the "
          "tonsil medially and anteriorly (Bailey & Love 28e)",
    ], S)
    h2(st, "Signs - Classic Examination Findings", S)
    bl(st, [
        "Mass at <b>level of carotid bifurcation</b> (angle of mandible / upper anterior triangle)",
        "<b>Firm, rubbery consistency</b>",
        "<b>PULSATILE</b> mass (transmitted pulsations from carotid)",
        "<b>Mobile side to side BUT NOT up and down</b> - this is the CLASSIC FINDING "
          "(Fontaine's sign): tumour is held by carotid vessels -> moves horizontally but "
          "cannot move vertically. This distinguishes CBT from lymph node.",
        "<b>Bruit</b> may be heard over the mass on auscultation",
        "<b>Can be partially emptied by firm compression</b> then slowly refills pulsatilely",
        "In parapharyngeal space: tonsil displaced medially and anteriorly on oropharyngeal exam",
    ], S)
    bl(st, [
        "Cranial nerve deficits (in large tumours or invasive disease):",
    ], S)
    bl(st, [
        "CN IX (glossopharyngeal): dysphagia",
        "CN X (vagus): hoarseness, weak cough",
        "CN XI (accessory): shoulder weakness",
        "CN XII (hypoglossal): tongue deviation (towards affected side)",
        "Horner's syndrome: ptosis, miosis, anhidrosis (sympathetic chain involvement)",
    ], S, sub=True)
    caut(st,
        "NEVER BIOPSY a suspected carotid body tumour - neither open biopsy NOR "
        "fine-needle aspiration (FNAC). "
        "Risk: massive haemorrhage, embolism, or tumour seeding. "
        "Diagnosis is clinical + radiological. Tissue diagnosis = surgical excision only. "
        "(Bailey & Love 28e)", S)
    sp(st, 4)

    # ── 5. INVESTIGATIONS ─────────────────────────────────────────────────────
    h1(st, "5.  INVESTIGATIONS", S)
    h2(st, "Imaging (Most Important)", S)
    bl(st, [
        "<b>Duplex (Doppler) Ultrasound</b>: First-line investigation. "
          "Shows vascular mass at carotid bifurcation with internal vascularity. "
          "Can assess splaying of internal and external carotid arteries.",
        "<b>CT Angiography (CTA)</b>: "
          "Excellent for showing tumour size, extent, relationship to carotid vessels, "
          "bony involvement. 'Splaying of ICA and ECA' = pathognomonic CT finding.",
        "<b>MRI / MR Angiography</b>: "
          "Best for soft tissue detail. "
          "Classic appearance: 'SALT AND PEPPER' pattern on T2-weighted MRI "
          "(multiple flow voids from vessels = pepper; high T2 signal = salt). "
          "MRA shows feeding vessels and relation to ICA/ECA. (Bailey & Love 28e)",
        "<b>Conventional Angiography (DSA - Digital Subtraction Angiography)</b>: "
          "Gold standard for vascular anatomy. "
          "Shows 'LYRE SIGN' (LYREBIRD SIGN): splaying of ICA and ECA by tumour "
          "with tumour blush between the two vessels - pathognomonic. "
          "Also used for pre-operative embolisation.",
        "<b>Octreotide scan / MIBG scan</b>: if functional tumour or bilateral disease suspected; "
          "useful for identifying multi-focal paragangliomas.",
        "<b>PET-CT (68Ga-DOTATATE)</b>: best for detecting synchronous/metachronous paragangliomas "
          "and metastatic disease in hereditary cases.",
    ], S)
    h2(st, "Biochemical Tests (To Rule Out Functional Tumour)", S)
    bl(st, [
        "Most CBTs are <b>NON-FUNCTIONAL</b> (do not secrete catecholamines)",
        "But always screen: 24-hour urinary catecholamines (adrenaline, noradrenaline, "
          "dopamine, VMA) OR plasma metanephrines",
        "<b>Functional CBT</b>: headache, hypertension, sweating, palpitations (rare)",
        "MUST rule out phaeochromocytoma before surgery (hypertensive crisis risk under GA)",
        "Serum chromogranin A: elevated in most paragangliomas (tumour marker)",
    ], S)
    h2(st, "Genetic Testing", S)
    bl(st, [
        "Offered to all patients with CBT",
        "SDH gene panel (SDHB, SDHC, SDHD, SDHA) for hereditary assessment",
        "SDHB mutation = higher malignancy risk -> closer surveillance needed",
    ], S)
    sp(st, 4)

    # ── 6. SHAMBLIN CLASSIFICATION ────────────────────────────────────────────
    h1(st, "6.  SHAMBLIN CLASSIFICATION", S)
    bl(st, [
        "The <b>Shamblin classification</b> determines surgical difficulty and resectability "
          "of carotid body tumours based on their relationship to the carotid vessels. "
          "(Bailey & Love 28e)",
    ], S)
    data = [
        ["Type", "Description", "Surgery / Risk"],
        ["Type I\n(Localised)",
         "Small tumour\nLess than 180 degrees of carotid vessel\nEasily dissected away from vessel",
         "Easy surgical excision\nLow complication rate\nMinimal vessel manipulation"],
        ["Type II\n(Adherent)",
         "Moderate tumour\nSurrounds vessel by MORE than 180 degrees\nAdherent to carotid wall",
         "Difficult dissection\nHigher risk of vessel injury\nMay need partial vessel repair"],
        ["Type III\n(Encasing)",
         "Large tumour\nCOMPLETELY ENCASES carotid vessels\nMost challenging",
         "Highest risk of:\nStroke, cranial nerve injury\nMay need carotid resection\n+ vein graft reconstruction"],
    ]
    st.append(tbl(data, [W*0.12, W*0.48, W*0.40], S))
    sp(st, 4)

    # ── 7. MANAGEMENT ─────────────────────────────────────────────────────────
    h1(st, "7.  MANAGEMENT", S)
    h2(st, "A. Pre-operative Preparation", S)
    bl(st, [
        "Biochemical screen to rule out functional tumour / phaeochromocytoma",
        "Complete imaging workup (MRI + CTA + angiography)",
        "Genetic testing and counselling",
        "<b>Pre-operative EMBOLISATION</b> (24-48 hours before surgery):",
    ], S)
    bl(st, [
        "Reduces intra-operative blood loss significantly",
        "Embolise feeding vessels from external carotid branches (ascending pharyngeal artery, "
          "occipital artery, superior thyroid artery)",
        "Performed by interventional radiology via conventional angiography",
        "Risk of embolisation itself: stroke, cranial nerve palsy (small risk)",
    ], S, sub=True)
    bl(st, [
        "Cross-clamp test / carotid occlusion test (balloon test occlusion): if carotid "
          "sacrifice anticipated (Type III), assess contralateral blood flow adequacy",
        "Neurophysiology monitoring setup if needed",
    ], S)
    h2(st, "B. Surgery - Mainstay of Treatment", S)
    bl(st, [
        "<b>Surgical excision = treatment of choice</b> for fit patients",
        "Approach: Transcervical approach through anterior triangle of neck",
        "Sub-adventitial dissection (Malan's dissection): plane between tumour and "
          "adventitia of carotid vessels - KEY TECHNIQUE to avoid vessel injury",
        "Principles:",
    ], S)
    bl(st, [
        "Identify and protect CN IX, X, XI, XII and sympathetic chain throughout",
        "Control external carotid artery first (less important), then dissect ICA",
        "Type I and II: tumour can be peeled off vessels with careful dissection",
        "Type III: may require carotid arteriotomy, resection and vein graft interposition "
          "(saphenous vein graft or prosthetic graft)",
        "Vascular surgery standby essential for large tumours",
        "Heparinisation prior to carotid clamping",
    ], S, sub=True)
    bl(st, [
        "<b>Complications of surgery</b>:",
    ], S)
    bl(st, [
        "Stroke (most feared): from ICA injury or clamp ischaemia - rate ~2-5%",
        "Cranial nerve injury: CN XII (most common - tongue deviation), "
          "CN X (hoarseness), CN IX, Horner's syndrome",
        "Haemorrhage from carotid vessels",
        "Wound haematoma",
        "Higher complications in Type III tumours",
    ], S, sub=True)
    h2(st, "C. Radiotherapy", S)
    bl(st, [
        "<b>Radiotherapy does NOT cure the tumour</b>",
        "Can <b>arrest or slow growth</b> - used for disease control",
        "Indications: inoperable tumours, elderly/unfit patients, residual/recurrent disease, "
          "malignant paraganglioma with metastases",
        "Stereotactic radiosurgery (Gamma Knife / CyberKnife): increasingly used for "
          "intracranial extension and glomus jugulare",
    ], S)
    h2(st, "D. Observation (Active Surveillance)", S)
    bl(st, [
        "For elderly/frail patients with slow-growing small tumours",
        "Regular surveillance with MRI every 1-2 years",
        "Surgery avoided if risk of complications outweighs tumour growth risk",
        "CBTs have a very slow growth rate (average 0.8-1 cm/year)",
    ], S)
    dose(st,
        "MANAGEMENT SUMMARY: Young, fit patient + Type I/II = Surgery (pre-op embolisation 24-48h before). "
        "Type III = Surgery + vascular team + possible carotid reconstruction. "
        "Elderly/frail/unfit = Radiotherapy OR active surveillance. "
        "Malignant/metastatic = Radiotherapy + chemotherapy (limited evidence) + SDH-targeted therapy.", S)
    sp(st, 4)

    # ── 8. DIFFERENTIAL DIAGNOSIS ─────────────────────────────────────────────
    h1(st, "8.  DIFFERENTIAL DIAGNOSIS OF LATERAL NECK MASS AT CAROTID BIFURCATION", S)
    bl(st, [
        "<b>Lymph node</b> (reactive, metastatic, lymphoma): most common neck mass; "
          "moves in all directions; not pulsatile",
        "<b>Branchial cyst</b>: anterior to SCM at angle of jaw; transilluminates; "
          "fluctuant; younger age",
        "<b>Carotid artery aneurysm</b>: pulsatile, expansile; confirm with duplex US + CTA",
        "<b>Vagal paraganglioma</b> (glomus vagale): higher up, near jugular foramen; "
          "displaces carotid anteriorly rather than splaying ICA/ECA",
        "<b>Schwannoma / neurofibroma</b>: spindle-shaped on MRI; moves side to side; "
          "Tinel's sign occasionally",
        "<b>Salivary gland tumour</b> (deep lobe parotid): higher, near angle of jaw; "
          "MRI shows parotid origin",
        "<b>Lipoma</b>: soft, non-pulsatile, fluctuant",
        "<b>Laryngocoele</b>: emerges through thyrohyoid membrane; "
          "increases with Valsalva/blowing",
    ], S)
    sp(st, 4)

    # ── 9. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "9.  VIVA QUESTIONS & ANSWERS", S)
    vivas = [
        ("Q1. What is a carotid body tumour? Where does it arise?",
         [
             "Carotid body tumour = paraganglioma / chemodectoma",
             "Arises from chemoreceptor (glomus) cells of the carotid body at the carotid bifurcation",
             "Carotid body = chemoreceptor organ detecting blood O2, CO2, and pH changes",
             "Tumour arises on the MEDIAL side of the carotid bulb -> adherent to carotid wall",
             "Usually benign; only 5-10% develop true malignancy (defined by metastases)",
         ]),
        ("Q2. Describe the classic clinical features of CBT on examination.",
         [
             "Painless, slowly enlarging mass at level of carotid bifurcation",
             "Firm, rubbery, pulsatile lump",
             "MOBILE SIDE TO SIDE but NOT up and down - CLASSIC SIGN (Fontaine's sign)",
             "Bruit audible over the mass",
             "Can be partially compressed and slowly refills pulsatilely",
             "One-third: pharyngeal mass with medial tonsil displacement",
         ]),
        ("Q3. What is the Shamblin classification?",
         [
             "Describes surgical difficulty based on relationship to carotid vessels",
             "Type I: localised, < 180 degrees - easy excision",
             "Type II: adherent, > 180 degrees - difficult dissection",
             "Type III: completely encases vessels - highest risk; may need carotid resection + graft",
         ]),
        ("Q4. What is the LYRE sign and SALT AND PEPPER sign?",
         [
             "LYRE SIGN (on conventional angiography / CTA): splaying of ICA and ECA "
               "by the carotid body tumour between them, like a lyre/harp shape - PATHOGNOMONIC",
             "SALT AND PEPPER sign (on T2 MRI): multiple signal voids from vessels (=pepper) "
               "mixed with high T2 signal (=salt) - characteristic of paragangliomas",
         ]),
        ("Q5. Why is biopsy contraindicated in CBT?",
         [
             "FNAC and open biopsy are both CONTRAINDICATED",
             "Reasons: risk of massive haemorrhage (highly vascular tumour)",
             "Risk of tumour seeding and carotid injury",
             "Diagnosis is confirmed clinically + radiologically",
             "Tissue diagnosis only obtained at definitive surgical excision",
         ]),
        ("Q6. What is the role of pre-operative embolisation?",
         [
             "Performed 24-48 hours before surgery by interventional radiology",
             "Embolises feeding vessels (ascending pharyngeal, occipital, superior thyroid arteries)",
             "Reduces intra-operative blood loss significantly",
             "Makes tumour softer and easier to dissect",
             "Small risk: stroke, cranial nerve palsy from embolisation itself",
         ]),
        ("Q7. What genetic mutations are associated with familial CBT?",
         [
             "SUCCINATE DEHYDROGENASE (SDH) gene mutations - most important",
             "SDH complex = Complex II of mitochondrial respiratory chain",
             "SDHD: most common in familial CBT; paternally imprinted; bilateral tumours",
             "SDHB: higher risk of malignant paraganglioma and metastasis",
             "SDHC, SDHA: less common",
             "Also: VHL (von Hippel-Lindau), RET (MEN2), NF1 (neurofibromatosis)",
             "Association with PHAEOCHROMOCYTOMA - always screen before surgery",
         ]),
        ("Q8. What are the complications of surgical excision of CBT?",
         [
             "STROKE: most feared complication; from ICA injury or clamp ischaemia (~2-5%)",
             "Cranial nerve injury: CN XII (most common -> tongue deviation), "
               "CN X (hoarseness), CN IX (dysphagia), Horner's syndrome",
             "Major haemorrhage: ICA/ECA injury",
             "Wound haematoma",
             "Complications increase with Shamblin type (Type III = highest risk)",
             "Radiotherapy: option for inoperable/elderly to arrest growth (not curative)",
         ]),
    ]
    for q, points in vivas:
        st.append(Paragraph(q, S["vq"]))
        bl(st, points, S)
        sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Bailey & Love's Short Practice of Surgery 28e | "
        "Scott-Brown's OHN&S 8e | KJ Lee's Essential Otolaryngology 11e | "
        "Cummings ORL 7e | Goldman-Cecil Medicine 26e",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/CarotidBodyTumour_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Carotid Body Tumour - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Jet Ventilation - ENT PG Exam Notes (5-6 pages)
# Bullet-point style, minimal tables
# NEW Palette 14: Dark slate-blue / deep magenta / burnt gold

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 14: Dark slate-blue / deep magenta / burnt gold
C_H1_BG  = colors.HexColor("#1E2D5C")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#7A0050")
C_H2_BG  = colors.HexColor("#FCE8F4")
C_H3_FG  = colors.HexColor("#6B4000")
C_H3_BG  = colors.HexColor("#FFF6E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1E2D5C")
C_ALT    = colors.HexColor("#EAF0FF")
C_PEARL  = colors.HexColor("#EAF0FF")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#1E2D5C")
C_VQ_BG  = colors.HexColor("#EAF0FF")
C_VQ_FG  = colors.HexColor("#1E2D5C")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    s["va"] = ParagraphStyle("va", fontName=NM, fontSize=10, leading=BL,
        textColor=C_BODY, leftIndent=12, spaceAfter=3)
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def pt(st, num, label, text, S):
    st.append(Paragraph(f"<b>{num}. {label}</b> - {text}", S["pt"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items:
        st.append(Paragraph(f"&#x2022; {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"&#9733; {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"&#9888; {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"&#x2665; {t}", S["dose"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


# ════════════════════════════════════════════════════════════════════════════════
def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("JET VENTILATION IN ENT / AIRWAY SURGERY", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Notes  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e Vol 1, Cummings ORL 7e, "
        "Miller's Anaesthesia 10e, KJ Lee 11e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. DEFINITION & OVERVIEW ──────────────────────────────────────────────
    h1(st, "1.  WHAT IS JET VENTILATION?", S)
    bl(st, [
        "<b>Jet ventilation</b> = a technique of delivering high-velocity pulses of gas "
          "(oxygen +/- anaesthetic) through a narrow-bore cannula or injector needle "
          "to ventilate the lungs WITHOUT a conventional endotracheal tube",
        "Provides ventilation while keeping the airway <b>clear and accessible</b> for the surgeon",
        "First described in the 1960s for rigid bronchoscopy; now widely used in ENT, "
          "airway surgery, and as an emergency rescue technique",
        "<b>Key advantage</b>: tube-free airway = unobstructed surgical field for laryngoscopy, "
          "microlaryngeal surgery, tracheal surgery, and laser surgery",
        "Considered in two main contexts in ENT:",
    ], S)
    bl(st, [
        "<b>Elective</b>: microlaryngoscopy, laser laryngeal surgery, tracheal procedures, "
          "bronchoscopy (planned technique for access)",
        "<b>Emergency</b>: cannot-intubate cannot-oxygenate (CICO) scenario "
          "via transtracheal needle cricothyrotomy",
    ], S, sub=True)
    pearl(st,
        "COMMON MISCONCEPTION: Jet ventilation does NOT work by the Venturi effect. "
        "It works primarily by FRICTION (entrainment of surrounding gas via friction). "
        "There are 6 postulated mechanisms of gas exchange in jet ventilation. "
        "(Scott-Brown's OHN&S 8e)", S)
    sp(st, 4)

    # ── 2. MECHANISMS OF GAS EXCHANGE ─────────────────────────────────────────
    h1(st, "2.  MECHANISMS OF GAS EXCHANGE IN JET VENTILATION", S)
    bl(st, [
        "The jet stream entrains surrounding gas and moves it into the lungs. "
          "Six proposed mechanisms (Scott-Brown's OHN&S 8e):",
    ], S)
    pt(st, "1", "Convective / Bulk Flow",
       "The high-velocity jet pushes a bulk mass of gas into the airways. "
       "This is the main mechanism at lower frequencies.", S)
    pt(st, "2", "Laminar Flow in Small Airways",
       "Gas moves in an orderly layered pattern in smaller peripheral airways, "
       "facilitating gas exchange even when tidal volumes are small.", S)
    pt(st, "3", "Pendelluft",
       "'Swinging air' - gas moves between lung regions with different compliance/resistance "
       "during each breath cycle, enhancing mixing and gas exchange.", S)
    pt(st, "4", "Cardiogenic Mixing",
       "Heartbeat-induced movement and vibration of lung parenchyma "
       "causes gas mixing in the alveoli.", S)
    pt(st, "5", "Molecular Diffusion",
       "At high frequencies, bulk convection decreases but molecular diffusion "
       "between gas molecules in airways becomes increasingly important for CO2/O2 exchange.", S)
    pt(st, "6", "Taylor-type Dispersion",
       "Interaction between convective flow and radial molecular diffusion "
       "in the airways creates an enhanced axial gas transport phenomenon.", S)
    sp(st, 4)

    # ── 3. TYPES OF JET VENTILATION ───────────────────────────────────────────
    h1(st, "3.  TYPES / CLASSIFICATION OF JET VENTILATION", S)
    h2(st, "A. By FREQUENCY", S)
    bl(st, [
        "<b>Low-Frequency Jet Ventilation (LFJV)</b>:",
    ], S)
    bl(st, [
        "Rate: 10-150 breaths/min (0.17-2.5 Hz)",
        "Delivered via manual or simple automatic injector (e.g. Manujet / Sanders injector)",
        "Simpler equipment; lower cost",
        "RISK: no pressure alarm on simple devices -> all deaths in one UK survey "
          "occurred with LFJV devices that had no pressure alarm (Cook & Alexander 2008)",
        "Gas exchange primarily by bulk/convective flow",
    ], S, sub=True)
    bl(st, [
        "<b>High-Frequency Jet Ventilation (HFJV)</b>:",
    ], S)
    bl(st, [
        "Rate: 60-600 breaths/min (1-10 Hz); defined as > 1 Hz (60 breaths/min)",
        "Requires a dedicated HFJV machine (e.g. Monsoon, Acutronic)",
        "Has pressure monitoring, pause pressure alarm, and safety cut-off",
        "SAFER: automatic cycling stops if airway pressure exceeds alarm threshold "
          "-> prevents breath stacking",
        "Gas exchange by multiple mechanisms (all 6 listed above)",
        "Preferred for laryngeal and airway surgery",
    ], S, sub=True)
    bl(st, [
        "<b>Superimposed HFJV (SHFJV)</b>: combines HFJV with LFJV simultaneously. "
          "Shown to improve end-expiratory volumes. Used in some specialist centres.",
    ], S)
    sp(st, 3)
    h2(st, "B. By POSITION / DELIVERY SITE", S)
    bl(st, [
        "<b>Supraglottic Jet Ventilation</b>:",
    ], S)
    bl(st, [
        "Jet cannula placed ABOVE the vocal cords (proximal to laryngoscope tip)",
        "Entrained gas passes through glottis into trachea",
        "SAFER: less risk of barotrauma; preferred for most ENT procedures",
        "Requires patent airway below cannula for expiration",
        "Cummings ORL: preferable to place cannula proximal to end of laryngoscope "
          "-> decreases risk of pneumothorax/pneumomediastinum",
    ], S, sub=True)
    bl(st, [
        "<b>Subglottic / Transglottic Jet Ventilation</b>:",
    ], S)
    bl(st, [
        "Jet cannula passed through the cords into the subglottis/trachea",
        "More reliable gas delivery; useful when supraglottic anatomy difficult",
        "Risk of barotrauma higher; cannula may obstruct surgical field",
        "NOT recommended in children: risk of air trapping and barotrauma",
    ], S, sub=True)
    bl(st, [
        "<b>Transtracheal Jet Ventilation (TTJV)</b>:",
    ], S)
    bl(st, [
        "Needle/cannula placed directly through cricothyroid membrane or trachea",
        "Used in EMERGENCY: cannot-intubate cannot-oxygenate (CICO) scenario",
        "Wide-bore needle (14-16G) through cricothyroid membrane + jet injector",
        "Highest risk of barotrauma (pneumothorax, surgical emphysema) if airway not patent",
        "Transtracheal route = MAJOR independent risk factor for complications "
          "(Jaquet series; Scott-Brown's OHN&S)",
        "1% pneumothorax rate; 8.4% surgical emphysema (Bougain series of 643 TTJV episodes)",
    ], S, sub=True)
    sp(st, 4)

    # ── 4. TECHNICAL PARAMETERS ───────────────────────────────────────────────
    h1(st, "4.  TECHNICAL PARAMETERS", S)
    bl(st, [
        "<b>Driving Pressure</b>: up to 4 bar (4000 mbar / 400 kPa). "
          "Higher pressure -> higher tidal volume but higher barotrauma risk",
        "<b>Frequency</b>: 60-600 breaths/min for HFJV; typically 100-200 bpm used in practice",
        "<b>Inspiratory:Expiratory (I:E) ratio</b>: typically 1:2 to 1:3 to allow full expiration "
          "and prevent air trapping (breath stacking)",
        "<b>Pause Pressure</b>: sensed in last 10 ms of expiratory pause. "
          "If pause pressure alarm threshold exceeded -> machine STOPS cycling "
          "-> prevents breath stacking / barotrauma. CRITICAL safety feature. (Scott-Brown's)",
        "<b>FiO2</b>: pure oxygen (100%) or oxygen-air mix. "
          "With laser surgery: use lowest possible FiO2 (30-40%) to reduce fire risk",
        "<b>Cannula size</b>: typically 13-14G for adult transtracheal; "
          "smaller gauge for subglottic depending on setup",
    ], S)
    sp(st, 4)

    # ── 5. CLINICAL INDICATIONS ───────────────────────────────────────────────
    h1(st, "5.  INDICATIONS IN ENT / AIRWAY SURGERY", S)
    h2(st, "Elective ENT Indications", S)
    bl(st, [
        "<b>Microlaryngoscopy / Direct Laryngoscopy</b>: "
          "tube-free laryngeal view for vocal cord surgery, biopsy, laser treatment. "
          "Jet via supraglottic route = clear operating field",
        "<b>CO2 Laser Laryngeal Surgery</b>: "
          "ETT is a fire hazard in oxygen-rich environment with laser. "
          "Jet ventilation eliminates endotracheal tube -> reduces laser fire risk. "
          "Also: use lowest FiO2 possible (Cummings ORL 7e)",
        "<b>Laryngeal papillomatosis (RRP)</b>: "
          "jet ventilation allows access but RISK: propelling HPV particles, blood, "
          "papilloma fragments distally into bronchi. (Cummings ORL 7e)",
        "<b>Subglottic / tracheal stenosis</b>: "
          "when ETT cannot pass through narrow segment; jet maintains oxygenation "
          "while surgeon dilates or resects stenosis",
        "<b>Laryngotracheal reconstruction / tracheal surgery</b>",
        "<b>Rigid bronchoscopy</b>: Sanders injector through side port of rigid bronchoscope",
        "<b>Laryngeal / tracheal foreign body removal</b>: "
          "tube-free access with maintained oxygenation",
        "<b>Paediatric airway endoscopy</b>: jet may be used but subglottic route "
          "NOT recommended in children (air trapping risk)",
    ], S)
    h2(st, "Emergency Indication - CICO Scenario", S)
    bl(st, [
        "<b>Cannot-Intubate Cannot-Oxygenate (CICO)</b> = life-threatening airway emergency",
        "Transtracheal jet ventilation via needle cricothyrotomy = temporising oxygenation "
          "while definitive airway (surgical cricothyrotomy / tracheostomy) secured",
        "Steps: identify cricothyroid membrane -> 14-16G cannula at 45 deg caudally "
          "-> confirm tracheal placement (aspiration of air) -> connect jet injector "
          "-> ventilate at 1-second bursts, WATCH CHEST RISE AND FALL",
        "LIMITATION: CO2 retention occurs after 30-45 minutes (cannot support ventilation long-term)",
        "Expiration must be passive through the upper airway - if upper airway OBSTRUCTED "
          "-> CANNOT USE TTJV (gas traps -> barotrauma)",
    ], S)
    caut(st,
        "CRITICAL SAFETY RULE: Jet ventilation in the presence of AIRWAY OUTFLOW OBSTRUCTION "
        "= CATASTROPHIC. Gas goes in but cannot exit -> breath stacking -> "
        "tension pneumothorax, pneumomediastinum, surgical emphysema. "
        "Always confirm upper airway is PATENT before using supraglottic or transtracheal jet. "
        "(Scott-Brown's OHN&S 8e / Cummings ORL 7e)", S)
    sp(st, 4)

    # ── 6. ADVANTAGES & DISADVANTAGES ─────────────────────────────────────────
    h1(st, "6.  ADVANTAGES & DISADVANTAGES", S)
    h2(st, "Advantages", S)
    bl(st, [
        "Tube-free airway = unobstructed surgical field for laryngeal/tracheal surgery",
        "Eliminates endotracheal tube fire hazard with CO2 laser",
        "Provides ventilation without needing a secured, sealed airway",
        "Allows paralysis without coughing/gagging (clean operative field)",
        "HFJV machines have pressure alarms preventing barotrauma",
        "Can be used via rigid bronchoscope (Sanders injector) during bronchoscopy",
        "Life-saving rescue technique in CICO emergencies",
    ], S)
    h2(st, "Disadvantages / Risks", S)
    bl(st, [
        "<b>BAROTRAUMA</b>: pneumothorax, pneumomediastinum, surgical emphysema "
          "(especially TTJV and in airway obstruction)",
        "<b>Hypoxia</b> (SpO2 < 90%): most common complication (Hu series: 47/58 complications were hypoxia)",
        "<b>Hypercarbia</b> (CO2 > 60 mmHg): CO2 retention is common, especially LFJV at lower rates",
        "<b>Air trapping / breath stacking</b>: if expiration inadequate; leads to raised intrathoracic pressure",
        "<b>Mucosal drying</b>: high-flow dry gas desiccates laryngeal and tracheal mucosa",
        "<b>Gastric distension</b>: entrainment of gas into oesophagus and stomach especially in small patients",
        "<b>Particle dispersal</b>: in laryngeal papillomatosis - HPV particles propelled distally",
        "<b>Aspiration risk</b>: no cuff to seal airway; blood/secretions can be blown distally",
        "Higher BMI patients require increased driving pressure",
        "Risk factors for complication: high BMI, ASA 3/4, cardiac history, "
          "previous laryngeal surgery, longer case, laser use (Hu series, 839 patients)",
    ], S)
    sp(st, 4)

    # ── 7. COMPARISON TABLE (one table - justified for comparison) ─────────────
    h1(st, "7.  JET VENTILATION vs CONVENTIONAL INTUBATION  (Comparison)", S)
    data = [
        ["Feature", "Jet Ventilation", "Conventional ETT"],
        ["Surgical access",     "EXCELLENT - tube-free larynx",  "Limited - tube in field"],
        ["Laser fire risk",     "LOW (no tube; low FiO2 possible)", "HIGH (PVC tube flammable)"],
        ["Airway seal",         "NONE - open system",             "SECURE - cuffed tube"],
        ["CO2 control",         "POOR (especially LFJV)",         "EXCELLENT"],
        ["Aspiration protection","NONE",                          "Good (cuffed tube)"],
        ["Barotrauma risk",     "HIGH if outflow obstruction",    "Lower (pressure limited)"],
        ["Equipment",           "Special injector / HFJV machine","Standard anaesthetic circuit"],
        ["Learning curve",      "Steeper; needs experience",      "Familiar to all anaesthetists"],
        ["Best for",            "Laryngeal / tracheal surgery, CICO rescue", "Most other surgeries"],
    ]
    st.append(tbl(data, [W*0.22, W*0.39, W*0.39], S))
    sp(st, 4)

    # ── 8. VIVA QUESTIONS ─────────────────────────────────────────────────────
    h1(st, "8.  VIVA QUESTIONS & ANSWERS", S)
    vivas = [
        ("Q1. What is jet ventilation and how does it work?",
         [
             "High-velocity pulses of gas delivered through a narrow-bore cannula WITHOUT an ETT",
             "Does NOT work by Venturi effect - works primarily by FRICTION (entrainment)",
             "6 mechanisms: (1) Bulk/convective flow, (2) Laminar flow in small airways, "
               "(3) Pendelluft, (4) Cardiogenic mixing, (5) Molecular diffusion, (6) Taylor dispersion",
             "Provides ventilation with tube-free surgical access to the larynx/airway",
         ]),
        ("Q2. Classify jet ventilation by frequency and by position.",
         [
             "By FREQUENCY: Low-frequency (10-150 bpm, Manujet/Sanders) vs "
               "High-frequency (60-600 bpm, HFJV machine, e.g. Monsoon)",
             "By POSITION: Supraglottic (above cords - safest) / Subglottic (through cords) / "
               "Transtracheal (through cricothyroid membrane - emergency use)",
             "Superimposed HFJV = LFJV + HFJV combined (improved end-expiratory volumes)",
         ]),
        ("Q3. What are the ENT indications for jet ventilation?",
         [
             "Microlaryngoscopy and direct laryngoscopy (tube-free field)",
             "CO2 laser laryngeal surgery (eliminates ETT fire hazard)",
             "Laryngeal papillomatosis (access, but risk of HPV dispersal)",
             "Subglottic/tracheal stenosis (ETT cannot pass)",
             "Laryngotracheal reconstruction and tracheal surgery",
             "Rigid bronchoscopy (Sanders injector via scope side port)",
             "Emergency: CICO scenario via transtracheal needle cricothyrotomy",
         ]),
        ("Q4. Why is jet ventilation used with CO2 laser laryngeal surgery?",
         [
             "Conventional ETT = FIRE HAZARD in oxygen-rich environment with laser",
             "PVC/silicone tubes can ignite when hit by CO2 laser beam",
             "Jet ventilation ELIMINATES the endotracheal tube from the field",
             "Additionally: use lowest possible FiO2 (30-40%) to further reduce fire risk",
             "Allows clear laryngeal access and unobstructed laser delivery",
         ]),
        ("Q5. What is PAUSE PRESSURE and why is it important?",
         [
             "Pause pressure = airway pressure sensed in the LAST 10 MILLISECONDS of the expiratory pause",
             "If pause pressure exceeds the alarm threshold -> HFJV machine STOPS cycling automatically",
             "This prevents BREATH STACKING (gas in without adequate expiration)",
             "Breath stacking -> rising intrathoracic pressure -> pneumothorax/barotrauma",
             "Pause pressure alarm is a CRITICAL SAFETY FEATURE of HFJV machines",
             "Deaths in one UK survey occurred only with LFJV devices (no pressure alarm)",
         ]),
        ("Q6. What are the complications of jet ventilation?",
         [
             "BAROTRAUMA: pneumothorax, pneumomediastinum, surgical emphysema "
               "(most dangerous if airway outflow obstruction present)",
             "Hypoxia (SpO2 < 90%): most common complication in published series",
             "Hypercarbia (CO2 retention): especially with LFJV",
             "Breath stacking / air trapping (inadequate expiration time)",
             "Mucosal drying from high-flow dry gas",
             "Gastric distension in small patients",
             "HPV/blood particle dispersal in laryngeal papillomatosis",
             "Risk factors: high BMI, ASA 3-4, cardiac disease, previous laryngeal surgery",
         ]),
        ("Q7. When is jet ventilation CONTRAINDICATED or dangerous?",
         [
             "AIRWAY OUTFLOW OBSTRUCTION: gas cannot exit -> catastrophic breath stacking",
             "Examples: large obstructing laryngeal mass, ball-valve lesion, "
               "inadequate muscle relaxation, severe laryngotracheal stenosis",
             "Severe lung disease (bullae, emphysema): barotrauma risk",
             "When used transtracheally and upper airway is completely obstructed",
             "Children: subglottic/transtracheal jet NOT recommended (air trapping risk)",
             "Obesity (high BMI): needs higher driving pressure; higher complication risk",
         ]),
        ("Q8. How is transtracheal jet ventilation performed in a CICO emergency?",
         [
             "CICO = Cannot Intubate Cannot Oxygenate = life-threatening emergency",
             "Step 1: Identify cricothyroid membrane (between thyroid and cricoid cartilages)",
             "Step 2: Insert 14-16G IV cannula at 45 degrees caudally through membrane",
             "Step 3: Aspirate air to confirm tracheal placement",
             "Step 4: Connect to manual jet injector (Manujet) or high-pressure oxygen",
             "Step 5: Ventilate with 1-second bursts, watch for chest rise and fall",
             "LIMITATION: Only a temporising measure (CO2 rises after 30-45 min)",
             "Definitive airway (surgical cricothyrotomy / tracheostomy) must be secured",
             "DANGER: if upper airway is obstructed, DO NOT use TTJV (gas cannot exit)",
         ]),
    ]
    for q, points in vivas:
        st.append(Paragraph(q, S["vq"]))
        bl(st, points, S)
        sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Scott-Brown's OHN&S 8e Vol 1 (Ch.31) | Cummings ORL 7e | "
        "Miller's Anaesthesia 10e | KJ Lee Essential ORL 11e | "
        "Cook & Alexander UK Survey 2008 | Hu et al. 839-case series | "
        "Jaquet et al. 734-case series | Bougain et al. 643 TTJV series",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/JetVentilation_ENT_PG_Exam.pdf"
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Jet Ventilation - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    S = styles()
    story = []
    build(story, S)
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# CSF - ENT PG Exam Notes (5-6 pages, bullet-point style)
# Palette 15: Deep forest-green / warm rust-brown / dark violet

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 15: Deep forest-green (#1A4A2A) / warm rust-brown (#7A2E00) / dark violet (#3D0A5C)
C_H1_BG  = colors.HexColor("#1A4A2A")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#7A2E00")
C_H2_BG  = colors.HexColor("#FFF0E6")
C_H3_FG  = colors.HexColor("#3D0A5C")
C_H3_BG  = colors.HexColor("#F3EAFC")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1A4A2A")
C_ALT    = colors.HexColor("#EAF5EE")
C_PEARL  = colors.HexColor("#EAF5EE")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#1A4A2A")
C_VQ_BG  = colors.HexColor("#F3EAFC")
C_VQ_FG  = colors.HexColor("#3D0A5C")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items:
        st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    # ── TITLE ─────────────────────────────────────────────────────────────────
    st.append(Paragraph("CEREBROSPINAL FLUID (CSF) - ENT PG EXAM NOTES", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Cummings ORL 7e (Ch.48), Scott-Brown's OHN&S 8e Vol 1 & 2, "
        "Costanzo Physiology 7e, KJ Lee Essential ORL 11e",
        S["sub"]))
    rule(st); sp(st, 2)

    # ── 1. PHYSIOLOGY OF CSF ──────────────────────────────────────────────────
    h1(st, "1.  PHYSIOLOGY OF CSF", S)
    h2(st, "Production", S)
    bl(st, [
        "<b>Site:</b> Choroid plexus of lateral, 3rd and 4th ventricles (mainly lateral ventricles)",
        "<b>Rate:</b> 500 mL/day (0.35 mL/min). Total CSF volume in adults = 90-150 mL "
          "(brain + cord + ventricles combined); turns over 3-4 times per day",
        "<b>Mechanism:</b> Active secretion by choroid plexus epithelial cells "
          "(Na+, Cl-, HCO3- and water secreted INTO CSF; K+ absorbed FROM CSF into blood). "
          "Not simple ultrafiltration",
        "Choroid plexus barrier = 3 layers: capillary endothelium + basement membrane, "
          "neuroglial membrane, and choroid plexus epithelial cells",
    ], S)
    h2(st, "Circulation", S)
    bl(st, [
        "Lateral ventricles -> 3rd ventricle (via foramina of Monro) -> "
          "4th ventricle (via aqueduct of Sylvius) -> subarachnoid space (via foramina of Luschka and Magendie) "
          "-> circulates around brain and spinal cord",
        "Intracranial pressure (ICP) normally 10-15 mmHg (70-180 mmH2O at lumbar puncture)",
    ], S)
    h2(st, "Absorption", S)
    bl(st, [
        "<b>Site:</b> Arachnoid granulations (Pacchionian bodies) in the superior sagittal sinus - "
          "one-way bulk flow from CSF to venous blood",
        "Minor routes: lymphatics of cranial nerves, spinal nerve roots",
        "Absorption is PRESSURE-DEPENDENT: increases when ICP rises (self-regulating system)",
    ], S)
    h2(st, "Composition of Normal CSF (vs Blood)", S)
    data = [
        ["Parameter",         "CSF",              "Blood/Serum"],
        ["Colour",            "Crystal clear / colourless", "Red (cells) / yellow (serum)"],
        ["Pressure",          "70-180 mmH2O",     "Venous: ~10 mmHg"],
        ["Protein",           "15-45 mg/dL",      "6000-8000 mg/dL"],
        ["Glucose",           "45-80 mg/dL (60-70% of blood glucose)", "70-110 mg/dL"],
        ["Cells (WBC)",       "< 5 cells/mm3 (lymphocytes)", "4000-11000/mm3"],
        ["Chloride",          "120-130 mEq/L (HIGHER than blood)", "95-106 mEq/L"],
        ["Specific gravity",  "1.003-1.008",      "1.025-1.030"],
        ["pH",                "7.31-7.34",         "7.35-7.45"],
        ["Beta-2 transferrin","PRESENT (unique)",  "Absent in nasal secretions/tears"],
    ]
    st.append(tbl(data, [W*0.30, W*0.35, W*0.35], S))
    pearl(st,
        "CLINICAL PEARL: Beta-2 transferrin (tau protein) is present ONLY in CSF, "
        "aqueous humour, and perilymph. It is ABSENT from nasal secretions, tears, "
        "saliva, and blood. It is the GOLD STANDARD biochemical test to confirm CSF leak. "
        "(Cummings ORL 7e Ch.48)", S)
    sp(st, 4)

    # ── 2. CSF RHINORRHOEA ────────────────────────────────────────────────────
    h1(st, "2.  CSF RHINORRHOEA", S)
    h2(st, "Definition", S)
    bl(st, [
        "Leakage of CSF through a defect in the skull base / dura into the nasal cavity "
          "or nasopharynx, presenting as clear watery nasal discharge",
        "Always indicates a communication between subarachnoid space and sinonasal tract",
        "Risk of life-threatening ASCENDING MENINGITIS (retrograde contamination) - "
          "Pneumococcal meningitis most common",
    ], S)
    h2(st, "Causes / Aetiology", S)
    bl(st, [
        "<b>Traumatic (most common, ~80%):</b>",
    ], S)
    bl(st, [
        "Accidental head trauma: anterior skull base fracture (cribriform plate, "
          "fovea ethmoidalis, posterior wall of frontal sinus, sella)",
        "Iatrogenic / surgical: FESS (most common iatrogenic cause), "
          "anterior skull base surgery, endoscopic sinus surgery, "
          "transsphenoidal hypophysectomy, middle turbinate resection (Cummings ORL)",
        "60-70% close spontaneously within 1 week of trauma; "
          "most remainder close by 3 months",
    ], S, sub=True)
    bl(st, [
        "<b>Spontaneous / Non-traumatic (~20%):</b>",
    ], S)
    bl(st, [
        "Idiopathic (benign intracranial hypertension / empty sella / "
          "lateral lamella of cribriform plate long = Keros Type 3 = higher risk)",
        "Meningocele / meningoencephalocele through skull base defect "
          "(dura protrudes under constant CSF pressure through a bony dehiscence)",
        "Raised ICP (hydrocephalus, idiopathic intracranial hypertension - BIH / pseudotumour cerebri)",
        "Skull base erosion: pituitary tumour, meningioma, nasopharyngeal carcinoma, "
          "cholesteatoma extending to skull base",
    ], S, sub=True)
    bl(st, [
        "<b>Congenital:</b> persistent craniopharyngeal canal, basal encephalocele",
    ], S)
    h2(st, "Clinical Features", S)
    bl(st, [
        "Unilateral, clear, watery nasal discharge - profuse, intermittent or constant",
        "Increases on leaning forward (Valsalva, straining, coughing)",
        "<b>Halo sign / Ring sign / Target sign:</b> clear halo around blood stain on white gauze/paper "
          "(CSF separates out to periphery due to lower specific gravity) - BEDSIDE TEST",
        "Salty taste (CSF glucose taste)",
        "History of trauma, previous sinus/skull base surgery, or headache suggestive of raised ICP",
        "COMPLICATIONS: Ascending meningitis (pneumococcal most common), brain abscess, "
          "pneumocephalus, tension pneumocephalus",
    ], S)
    h2(st, "Investigation / Diagnosis", S)
    h3(st, "Biochemical Tests (confirm CSF)", S)
    bl(st, [
        "<b>Beta-2 transferrin assay (GOLD STANDARD):</b> immunofixation electrophoresis; "
          "detected only in CSF (and aqueous humour, perilymph). "
          "Highly sensitive and specific; requires only a small sample (0.5 mL)",
        "<b>Beta-trace protein (beta-TP):</b> prostaglandin-D synthase; also specific for CSF; "
          "results available faster than beta-2 transferrin in some labs",
        "<b>Glucose test (unreliable):</b> glucose > 30 mg/dL in nasal fluid suggestive but "
          "not specific (nasal secretions may contain glucose in diabetics / inflamed mucosa)",
        "<b>Halo test / Ring test:</b> simple bedside screening only, not diagnostic",
    ], S)
    h3(st, "Imaging (localise the defect)", S)
    bl(st, [
        "<b>High-Resolution CT (HRCT) Skull Base:</b> 1 mm coronal sections "
          "(or coronal reformats from axial data). Shows bony dehiscence, fracture. "
          "FIRST-LINE imaging for localisation. ~80% accuracy",
        "<b>MR Cisternography:</b> non-invasive; heavily T2-weighted with fat suppression "
          "and reversal. Identifies CSF signal in sinuses/nose. Shows meningocele / "
          "meningoencephalocele. Complements CT (soft tissue detail where CT shows bony detail)",
        "<b>CT Cisternography:</b> intrathecal radiopaque contrast (metrizamide) + CT. "
          "~80% accuracy. Only if active leak present at time of imaging",
        "<b>Radionuclide cisternography:</b> In-111 DTPA or Tc-99m DTPA intrathecal + nasal pledgets "
          "assayed for tracer. Limited by poor spatial resolution; high false-positive rate; "
          "not used as sole test",
        "<b>Intrathecal Fluorescein:</b> 0.1 mL of 10% fluorescein in 10 mL patient's own CSF, "
          "infused slowly over 30 minutes intrathecally. Endoscopic identification intraoperatively "
          "(greenish hue of CSF). Dose-dependent risk of seizures; NOT FDA-approved. "
          "(Keerl et al. - 420 administrations; safe at low dose 50 mg or less, Cummings ORL)",
        "<b>CT/MR Fusion:</b> hybrid imaging combining bony detail of CT with soft tissue of MRI. "
          "Best anatomical road-map for surgical planning",
    ], S)
    sp(st, 4)

    # ── 3. MANAGEMENT OF CSF RHINORRHOEA ─────────────────────────────────────
    h1(st, "3.  MANAGEMENT OF CSF RHINORRHOEA", S)
    h2(st, "Conservative (initial)", S)
    bl(st, [
        "Bed rest with head elevation (30 degrees)",
        "Avoid straining, nose-blowing, sneezing (open-mouthed sneezing advised)",
        "Avoid NSAIDs (impair platelet function; bleeding increases leak)",
        "Lumbar drain (continuous or intermittent): reduces ICP and CSF flow "
          "to allow spontaneous healing; especially for post-traumatic leaks",
        "Acetazolamide: carbonic anhydrase inhibitor, reduces CSF production; "
          "adjunct in raised ICP cases",
        "60-70% of traumatic leaks close within 1 week conservatively",
    ], S)
    caut(st,
        "PROPHYLACTIC ANTIBIOTICS are NOT recommended for uncomplicated traumatic CSF rhinorrhoea "
        "- evidence shows no reduction in meningitis risk and risk of selecting resistant organisms. "
        "Treat infection if it occurs.", S)
    h2(st, "Surgical - Endoscopic Repair (FESS approach)", S)
    bl(st, [
        "<b>Approach of choice:</b> Endoscopic Endonasal approach (EEA) - "
          "minimally invasive, no facial incision, excellent visualisation, "
          "success rate 80-95%",
        "<b>Steps:</b> Identify defect endoscopically (intraoperative fluorescein helps) -> "
          "remove mucosa 5 mm around defect -> place graft -> seal",
        "<b>Grafts used (layered closure):</b>",
    ], S)
    bl(st, [
        "Free mucosal graft (middle turbinate mucosa, nasal septum)",
        "Fat graft (abdominal fat) - fills dead space",
        "Fascia lata or temporalis fascia",
        "Bone (ethmoid bone, septal bone) as underlay rigid layer",
        "Biosynthetic dural substitutes (DuraGen, DuraSeal)",
        "Tissue glue (fibrin glue) to seal over the graft",
        "Nasal packing for 5-7 days post-repair",
    ], S, sub=True)
    bl(st, [
        "<b>Multilayer closure technique (Bath Plug / Gasket seal / Nasoseptal flap "
          "for large defects):</b> underlay dural substitute + overlay free mucosal or "
          "fascia graft + fibrin glue",
        "<b>Success rate:</b> 80-90% first attempt; 90-95% with repeat surgery",
        "Lumbar drain for 3-5 days post-operatively reduces pressure during healing",
    ], S)
    h2(st, "Surgical - Extracranial / Intracranial Routes", S)
    bl(st, [
        "<b>Extracranial (non-endoscopic):</b> external ethmoidectomy, "
          "sublabial transsphenoidal (for sphenoid sinus leaks), "
          "osteoplastic flap (frontal sinus)",
        "<b>Intracranial / transcranial:</b> craniotomy for large defects, "
          "meningoencephalocele, failed endoscopic repair, anterior skull base tumour, "
          "multiple or posterior fossa defects",
        "<b>CSF diversion:</b> lumboperitoneal or ventriculoperitoneal shunt for "
          "persistent leak (<1%) with underlying subclinical hydrocephalus or "
          "raised ICP (Scott-Brown's OHN&S 8e)",
    ], S)
    sp(st, 4)

    # ── 4. CSF OTORRHOEA ─────────────────────────────────────────────────────
    h1(st, "4.  CSF OTORRHOEA", S)
    h2(st, "Definition & Mechanism", S)
    bl(st, [
        "Leakage of CSF through the temporal bone into the middle ear / external ear canal",
        "If tympanic membrane intact: CSF drains via Eustachian tube -> nasopharynx "
          "(presents as CSF rhinorrhoea, not otorrhoea)",
        "If tympanic membrane perforated: CSF drains through the perforation into EAC -> "
          "presents as OTORRHOEA (clear watery discharge from ear)",
    ], S)
    h2(st, "Causes", S)
    bl(st, [
        "<b>Traumatic:</b> temporal bone fractures (longitudinal or transverse "
          "with tegmen disruption and TM perforation)",
        "<b>Iatrogenic:</b> translabyrinthine surgery (acoustic neuroma), "
          "cochlear implantation, mastoid surgery - air cell tracts anterior to IAM, "
          "around jugular bulb, subluxed stapes all potential conduits (Scott-Brown's OHN&S 8e)",
        "<b>Spontaneous:</b> tegmen dehiscence with meningocele/meningoencephalocele, "
          "idiopathic intracranial hypertension, cholesteatoma eroding tegmen",
        "<b>Congenital:</b> Mondini deformity (cochlear malformation), "
          "enlarged cochlear aqueduct / vestibular aqueduct",
    ], S)
    h2(st, "Gusher at Stapedectomy (Special Case)", S)
    bl(st, [
        "Abnormal communication between CSF and perilymph space",
        "Occurs in X-linked stapes gusher (POU3F4 mutation) and Mondini deformity",
        "Opening the oval window -> profuse CSF gush from middle ear",
        "<b>Management:</b> Do NOT pack tightly (creates tension pneumocephalus). "
          "Use fat graft + temporalis fascia over oval window; "
          "consider lumbar drain to reduce ICP; abort stapedectomy if uncontrolled",
    ], S)
    h2(st, "Management of CSF Otorrhoea", S)
    bl(st, [
        "<b>Traumatic (most close spontaneously):</b> "
          "head elevation, avoid straining, no ear instrumentation, "
          "lumbar drain if persistent (>7 days)",
        "<b>Surgical (post-mastoid/translabyrinthine):</b> "
          "bone wax, muscle/fat/fascia obliteration of air cell tracts; "
          "pack Eustachian tube orifice + fill middle ear cleft with fat; "
          "lumbar drain for a few days post-operatively (Scott-Brown's OHN&S)",
        "<b>Persistent leak (<1%):</b> consider lumboperitoneal or "
          "ventriculoperitoneal shunt if subclinical hydrocephalus suspected",
        "Meningitis risk (1-5% after VS surgery) - associated with CSF otorrhoea/rhinorrhoea; "
          "treat immediately if suspected",
    ], S)
    sp(st, 4)

    # ── 5. COMPARISON TABLE ────────────────────────────────────────────────────
    h1(st, "5.  CSF RHINORRHOEA vs CSF OTORRHOEA  (Comparison)", S)
    data = [
        ["Feature",          "CSF Rhinorrhoea",                      "CSF Otorrhoea"],
        ["Site of leak",     "Anterior/central skull base: "
                             "cribriform plate, fovea ethmoidalis, "
                             "sphenoid sella, frontal sinus",
                                                                      "Temporal bone: tegmen tympani / "
                                                                      "mastoid, oval/round window"],
        ["Common cause",     "Head trauma, iatrogenic FESS, "
                             "spontaneous (BIH)",                     "Temporal bone fracture, "
                                                                      "translabyrinthine surgery"],
        ["Presentation",     "Clear watery unilateral nasal discharge", "Clear watery ear discharge "
                                                                      "(if TM perforated)"],
        ["TM status",        "Normal (no ear finding)",               "TM may be perforated / intact "
                                                                      "(if intact -> nasal drip)"],
        ["Halo sign",        "Positive on nasal gauze",               "Positive on ear gauze"],
        ["Main imaging",     "HRCT + MR cisternography of skull base", "HRCT temporal bone + MRI brain"],
        ["Surgical repair",  "Endoscopic endonasal (EEA) - gold standard", "Mastoid / middle cranial "
                                                                      "fossa approach"],
        ["Meningitis risk",  "Pneumococcal most common",              "Same; 1-5% post-VS surgery"],
    ]
    st.append(tbl(data, [W*0.22, W*0.39, W*0.39], S))
    sp(st, 4)

    # ── 6. VIVA Q&A ───────────────────────────────────────────────────────────
    h1(st, "6.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. What is beta-2 transferrin and why is it important?", S)
    bl(st, [
        "Also called tau protein or carbohydrate-deficient transferrin",
        "Present ONLY in CSF, aqueous humour, and perilymph - absent from nasal secretions, "
          "tears, saliva, and blood",
        "GOLD STANDARD biochemical test to confirm CSF leak - highly specific and sensitive",
        "Immunofixation electrophoresis on nasal fluid / ear fluid sample",
        "Requires only 0.5 mL of fluid; can be sent to lab even if sample is small",
        "Only limitation: not available 24/7 in all centres; takes time",
    ], S); sp(st, 2)

    vq(st, "Q2. What is the difference between meningocele and meningoencephalocele?", S)
    bl(st, [
        "<b>Meningocele:</b> sac containing only CSF and dura protruding through skull base defect",
        "<b>Meningoencephalocele:</b> sac containing dura + brain tissue (encephalocele)",
        "Both arise from constant CSF pressure over a weakened skull base region",
        "Clinical significance: do NOT biopsy a pulsatile nasal mass - could be encephalocele!",
        "Diagnosis: MR cisternography shows meningocele best (soft tissue detail)",
    ], S); sp(st, 2)

    vq(st, "Q3. What is intrathecal fluorescein and how is it used in CSF rhinorrhoea?", S)
    bl(st, [
        "Fluorescent dye injected intrathecally (into CSF space) to identify site of CSF leak intraoperatively",
        "Preparation: 0.1 mL of 10% IV fluorescein in 10 mL patient's own CSF; "
          "infuse slowly over 30 min intrathecally before surgery",
        "Intraoperatively: endoscopy identifies green fluorescent CSF at defect site",
        "After repair: absence of fluorescein confirms adequate closure",
        "Dose-dependent risk: grand mal seizures, death (with high doses). "
          "Low dose (50 mg or less) is safe (Keerl et al., 420 cases)",
        "NOT FDA-approved; requires informed consent",
    ], S); sp(st, 2)

    vq(st, "Q4. What are the causes of spontaneous CSF rhinorrhoea?", S)
    bl(st, [
        "Idiopathic intracranial hypertension (BIH / pseudotumour cerebri) - "
          "raised ICP erodes skull base",
        "Empty sella syndrome (with raised ICP)",
        "Meningocele / meningoencephalocele through skull base defect",
        "Long lateral lamella of cribriform plate (Keros Type 3) - "
          "thin at junction with roof of ethmoid, prone to spontaneous leak",
        "Arachnoid granulations herniating into sinuses (temporal bone tegmen especially)",
    ], S); sp(st, 2)

    vq(st, "Q5. What is the surgical approach of choice for CSF rhinorrhoea repair?", S)
    bl(st, [
        "Endoscopic Endonasal Approach (EEA) - gold standard since early 1990s",
        "Advantages: no facial incision, minimal morbidity, excellent visualisation, "
          "day surgery or short stay, success rate 80-95%",
        "Steps: FESS to expose defect -> confirm with intrathecal fluorescein -> "
          "denude mucosa around defect -> multilayer graft closure -> fibrin glue -> nasal pack",
        "Grafts: free mucosal graft / fat / fascia lata / biosynthetic dural substitute",
        "Multilayer (underlay + overlay) technique: superior results to single-layer repair",
        "Lumbar drain 3-5 days post-op helps healing",
        "Transcranial route reserved for: large defects, meningoencephalocele, "
          "failed EEA, tumour-associated leak",
    ], S); sp(st, 2)

    vq(st, "Q6. What is a CSF gusher at stapedectomy? How is it managed?", S)
    bl(st, [
        "Profuse CSF rush from middle ear on opening oval window during stapedectomy",
        "Mechanism: abnormal connection between subarachnoid space and perilymph "
          "(through dilated cochlear aqueduct or internal auditory meatus)",
        "Causes: X-linked stapes gusher (POU3F4 gene mutation on X chromosome), "
          "Mondini deformity (inner ear malformation), enlarged cochlear aqueduct",
        "<b>Management:</b> Do NOT pack tightly (risk of tension pneumocephalus). "
          "Seal with fat graft + temporalis fascia. Lumbar drain to reduce ICP. "
          "Consider abandoning the procedure.",
        "Pre-op imaging (CT inner ear) mandatory to detect Mondini deformity before stapedectomy",
    ], S); sp(st, 2)

    vq(st, "Q7. What is Keros classification and its relevance in CSF rhinorrhoea?", S)
    bl(st, [
        "Keros classification describes depth of olfactory fossa (lateral lamella of cribriform plate):",
    ], S)
    bl(st, [
        "Type 1: depth 1-3 mm (low risk - lateral lamella short and sturdy)",
        "Type 2: depth 4-7 mm (moderate risk)",
        "Type 3: depth 8-16 mm (HIGH RISK - long lateral lamella, very thin, "
          "prone to spontaneous CSF leak and FESS injury)",
    ], S, sub=True)
    bl(st, [
        "Relevant in FESS: surgeon must be aware of Keros type on pre-op CT "
          "to avoid inadvertent skull base perforation",
    ], S); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Cummings ORL 7e Ch.48 | Scott-Brown's OHN&S 8e Vol 1 & 2 | "
        "Costanzo Physiology 7e | KJ Lee Essential ORL 11e | "
        "Keerl et al. (intrathecal fluorescein, 420 cases)",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/CSF_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="CSF - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Streptococcal Pharyngitis - ENT PG Exam Notes (5-6 pages, bullet-point style)
# Palette 16: Dark teal-green / deep maroon / warm ochre-gold

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 16: Dark teal-green (#0A4035) / deep maroon (#6B0020) / warm ochre-gold (#7A5200)
C_H1_BG  = colors.HexColor("#0A4035")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#6B0020")
C_H2_BG  = colors.HexColor("#FFF0F3")
C_H3_FG  = colors.HexColor("#7A5200")
C_H3_BG  = colors.HexColor("#FFF8E6")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#0A4035")
C_ALT    = colors.HexColor("#E6F5F0")
C_PEARL  = colors.HexColor("#E6F5F0")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#0A4035")
C_VQ_BG  = colors.HexColor("#FFF8E6")
C_VQ_FG  = colors.HexColor("#7A5200")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("STREPTOCOCCAL PHARYNGITIS - ENT PG EXAM NOTES", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Cummings ORL 7e (Ch.201), Scott-Brown's OHN&S 8e, "
        "KJ Lee Essential ORL 11e, Dhingra ENT 8e",
        S["sub"]))
    rule(st); sp(st, 2)

    # 1. DEFINITION & AETIOLOGY
    h1(st, "1.  DEFINITION & AETIOLOGY", S)
    bl(st, [
        "<b>Definition:</b> Acute inflammation of the pharynx and/or tonsils caused by "
          "Group A beta-haemolytic Streptococcus (GABHS) - "
          "<i>Streptococcus pyogenes</i>",
        "<b>Organism:</b> Gram-positive cocci in chains; Lancefield Group A; "
          "beta-haemolysis on blood agar",
        "<b>Virulence factors:</b> M-protein (antiphagocytic; key target for antibodies); "
          "streptolysin O and S; streptokinase; hyaluronidase; erythrogenic toxin (causes scarlet fever rash)",
        "<b>Epidemiology:</b> Most common bacterial cause of acute pharyngitis. "
          "Accounts for 15-30% of all sore throat visits in children, 5-15% in adults",
        "<b>Peak age:</b> 5-15 years (school-age children). Rare under 3 years. "
          "15 million outpatient visits per year (USA) for pharyngitis (Cummings ORL 7e)",
        "<b>Transmission:</b> Droplet spread; direct contact. Outbreaks in "
          "schools, military barracks, institutions",
        "<b>Seasonality:</b> Late autumn and winter (temperate climates)",
    ], S)
    sp(st, 4)

    # 2. PATHOPHYSIOLOGY
    h1(st, "2.  PATHOPHYSIOLOGY", S)
    bl(st, [
        "GABHS adheres to pharyngeal epithelium via M-protein and fibronectin-binding proteins",
        "Invades superficial mucosal epithelium -> acute inflammatory response "
          "(oedema, vascular congestion, polymorphonuclear infiltration, exudate formation)",
        "<b>Toxin-mediated effects:</b>",
    ], S)
    bl(st, [
        "Streptolysin O -> lyses RBCs, WBCs, platelets; stimulates anti-streptolysin O (ASO) antibody",
        "Erythrogenic toxin -> rash of scarlet fever (superantigen T-cell activation)",
        "Streptokinase -> dissolves fibrin; enhances tissue invasion",
    ], S, sub=True)
    bl(st, [
        "<b>Immune-mediated complications (post-streptococcal):</b> molecular mimicry between "
          "streptococcal M-protein epitopes and cardiac tissue (Type II hypersensitivity) -> "
          "Acute Rheumatic Fever (ARF); also post-streptococcal glomerulonephritis (PSGN)",
        "GABHS is the ONLY pharyngeal organism whose eradication with antibiotics "
          "definitively prevents ARF",
    ], S)
    pearl(st,
        "KEY PEARL: Treating GABHS pharyngitis with a full 10-day course of penicillin "
        "PREVENTS Acute Rheumatic Fever (ARF) - the most important reason to use antibiotics. "
        "However, antibiotics do NOT prevent post-streptococcal glomerulonephritis (PSGN). "
        "(Cummings ORL 7e)", S)
    sp(st, 4)

    # 3. CLINICAL FEATURES
    h1(st, "3.  CLINICAL FEATURES", S)
    h2(st, "Symptoms", S)
    bl(st, [
        "Sudden (rapid) onset severe sore throat",
        "Odynophagia (pain on swallowing) and dysphagia",
        "High fever (38.5-40 deg C) with rigors",
        "Headache, malaise, myalgia",
        "Otalgia (referred pain via glossopharyngeal nerve)",
        "Nausea, vomiting, abdominal pain (especially children)",
        "<b>ABSENCE of:</b> cough, rhinorrhoea, hoarseness, oral ulcers - "
          "these features point to VIRAL pharyngitis",
    ], S)
    h2(st, "Signs", S)
    bl(st, [
        "Oropharyngeal erythema (diffuse, including soft palate)",
        "Tonsillar enlargement with <b>exudate</b> (creamy-white patches on tonsils)",
        "<b>Palatal petechiae</b> (haemorrhagic spots on soft palate) - "
          "highly specific for GABHS",
        "<b>Uvular oedema</b> (swollen uvula - 'pointing' uvula may indicate peritonsillar abscess)",
        "<b>Tender anterior cervical lymphadenopathy</b> (jugulodigastric / tonsillar nodes)",
        "<b>Scarlatiniform rash</b> (if Scarlet Fever): fine erythematous sandpaper-like rash "
          "starting neck/chest -> trunk/extremities within 24h; fades in 7 days",
        "<b>Strawberry tongue</b> (in Scarlet Fever): enlarged red papillae, initially with "
          "white coating then 'red strawberry' appearance by day 4-5",
    ], S)
    sp(st, 4)

    # 4. DIAGNOSIS
    h1(st, "4.  DIAGNOSIS", S)
    h2(st, "Centor Score / McIsaac Score (Clinical Prediction)", S)
    bl(st, [
        "Used to estimate probability of GABHS and guide testing/treatment",
        "<b>Centor criteria (1 point each):</b>",
    ], S)
    bl(st, [
        "Tonsillar exudate",
        "Tender anterior cervical lymphadenopathy",
        "Fever (history or measured > 38 deg C)",
        "Absence of cough",
        "<b>McIsaac modification:</b> adds Age factor: +1 if 3-14 years; 0 if 15-44 years; "
          "-1 if 45 years or older",
    ], S, sub=True)
    bl(st, [
        "Score 0-1: Very low probability (~2-6%) GABHS; no testing or antibiotics needed",
        "Score 2-3: Moderate probability; test with rapid antigen test; treat if positive",
        "Score 4-5: High probability (>50%); treat empirically OR test first",
    ], S)
    h2(st, "Laboratory Tests", S)
    bl(st, [
        "<b>Throat swab culture (Gold Standard):</b> swab tonsillar surface and posterior pharynx; "
          "culture on blood agar; 24-48 hours result. Sensitivity 90-95%, Specificity ~99%",
        "<b>Rapid Antigen Detection Test (RADT) / Rapid Strep Test:</b> "
          "detects Group A carbohydrate antigen. Results in 5-10 minutes. "
          "Specificity ~98%; Sensitivity 70-90%. "
          "Negative RADT + high clinical suspicion -> confirm with throat culture",
        "<b>ASO titre (Anti-Streptolysin O):</b> rises 2-4 weeks after infection. "
          "Useful for retrospective confirmation, not acute diagnosis. "
          "Normal < 200 IU/mL in adults; elevated in rheumatic fever workup",
        "<b>Anti-DNase B:</b> more sensitive than ASO for skin infections and PSGN; "
          "useful when ASO normal but GAS infection suspected",
        "<b>FBC:</b> leucocytosis with neutrophilia (neutrophil predominance in bacterial pharyngitis "
          "vs lymphocytosis in viral / EBV)",
        "<b>Monospot test:</b> if EBV/infectious mononucleosis (IM) suspected - "
          "palatal petechiae + exudate + splenomegaly + lymphocytosis + atypical lymphocytes",
    ], S)
    caut(st,
        "NEVER give AMOXICILLIN or AMPICILLIN if EBV/infectious mononucleosis (IM) is suspected "
        "- causes widespread maculopapular rash in 80-100% of EBV patients. "
        "Use a non-aminopenicillin antibiotic if bacterial co-infection treatment needed.", S)
    sp(st, 4)

    # 5. TREATMENT
    h1(st, "5.  TREATMENT", S)
    h2(st, "Antibiotic Therapy", S)
    dose(st,
        "FIRST LINE: Phenoxymethylpenicillin (Penicillin V) orally x 10 days "
        "OR Amoxicillin 500 mg TDS orally x 10 days. "
        "10-day course mandatory to eradicate GABHS and prevent ARF. "
        "Single IM Benzathine Penicillin G (1.2 MU) = alternative if compliance concern.", S)
    bl(st, [
        "<b>Why 10 days?</b> Shorter courses are associated with higher relapse rates "
          "and failure to prevent ARF",
        "<b>Penicillin failure rate:</b> 7-37%. Causes: beta-lactamase-producing co-bacteria "
          "in tonsil protecting GABHS, poor tissue penetration, resistance",
        "<b>Penicillin allergy (non-anaphylactic):</b> First-generation cephalosporin "
          "(Cephalexin 500 mg TDS x 10 days)",
        "<b>Penicillin anaphylaxis / allergy:</b> Clindamycin 300 mg TDS x 10 days "
          "OR Clarithromycin 250 mg BD x 10 days "
          "OR Azithromycin 500 mg OD x 5 days",
        "<b>Penicillin failure or recurrence:</b> Amoxicillin-clavulanic acid "
          "(Augmentin) or Clindamycin - preferred (Cummings ORL 7e)",
        "<b>Macrolide resistance:</b> emerging due to hypervariable region of GAS M-protein gene; "
          "check local sensitivities",
        "Antibiotics reduce fever by 24h, sore throat by 16h; reduce contagiousness "
          "within 24h of starting treatment",
    ], S)
    h2(st, "Symptomatic / Supportive", S)
    bl(st, [
        "Paracetamol (Acetaminophen) or Ibuprofen for fever and pain",
        "Adequate hydration, soft diet, rest",
        "Salt water gargles (adjunct only)",
        "<b>Avoid Aspirin</b> (especially children - risk of Reye's syndrome)",
        "<b>Steroids:</b> NOT routinely indicated. "
          "Single dose Dexamethasone 10 mg IV/IM may be used for severe dysphagia / "
          "pain relief in adults (supported by evidence); reduces symptom severity but "
          "not duration significantly",
    ], S)
    sp(st, 4)

    # 6. COMPLICATIONS
    h1(st, "6.  COMPLICATIONS", S)
    h2(st, "Suppurative Complications (direct spread / local)", S)
    bl(st, [
        "<b>Peritonsillar Abscess (Quinsy):</b> most common suppurative complication. "
          "Pus collects between tonsillar capsule and superior constrictor muscle. "
          "Trismus, hot-potato voice, uvular deviation to opposite side, "
          "bulging of soft palate. Tx: needle aspiration / I&D + antibiotics + "
          "tonsillectomy (interval or hot)",
        "<b>Parapharyngeal abscess:</b> spread to parapharyngeal space. "
          "Neck swelling, torticollis, medial displacement of lateral pharyngeal wall. "
          "CT neck + IV antibiotics + surgical drainage",
        "<b>Retropharyngeal abscess:</b> typically in children < 6 years "
          "(retropharyngeal nodes regress after age 6). Neck extension, stridor, "
          "dysphagia. CT + drainage",
        "<b>Otitis media:</b> ascending Eustachian tube infection",
        "<b>Sinusitis:</b> ascending infection to paranasal sinuses",
        "<b>Mastoiditis / meningitis / brain abscess</b> (rare, serious)",
        "<b>Lemierre's syndrome:</b> Fusobacterium necrophorum thrombophlebitis of "
          "internal jugular vein after pharyngitis. Septic emboli to lungs. "
          "Requires anticoagulation + prolonged antibiotics",
    ], S)
    h2(st, "Non-Suppurative (Immune-Mediated) Complications", S)
    bl(st, [
        "<b>Acute Rheumatic Fever (ARF):</b> 2-4 weeks after GABHS pharyngitis "
          "(NOT after skin infection). Jones criteria: 2 major or 1 major + 2 minor "
          "criteria + evidence of preceding GABHS infection. "
          "Major criteria: carditis, polyarthritis, Sydenham's chorea, erythema marginatum, "
          "subcutaneous nodules. PREVENTED by 10-day penicillin course",
        "<b>Rheumatic Heart Disease (RHD):</b> mitral valve most commonly affected. "
          "Result of recurrent ARF. Secondary prophylaxis (monthly Benzathine Penicillin) "
          "prevents recurrence",
        "<b>Post-Streptococcal Glomerulonephritis (PSGN):</b> 1-3 weeks after GABHS "
          "pharyngitis (or skin infection). Immune complex deposition in glomeruli. "
          "NOT prevented by antibiotics",
        "<b>PANDAS</b> (Paediatric Autoimmune Neuropsychiatric Disorders Associated with "
          "Streptococcal infections): OCD, tics, behavioural changes in children "
          "temporally linked to GABHS",
        "<b>PFAPA syndrome</b> (Periodic Fever, Aphthous stomatitis, Pharyngitis, "
          "Adenitis): periodic febrile episodes every 4-8 weeks in children under 5; "
          "self-limiting; tonsillectomy curative",
    ], S)
    caut(st,
        "ARF vs PSGN: ANTIBIOTICS PREVENT ARF but do NOT prevent PSGN. "
        "ARF occurs only after pharyngeal GABHS (not skin). "
        "PSGN can follow pharyngeal OR skin GABHS infection. "
        "This is a FAVOURITE EXAM DISTINCTION.", S)
    sp(st, 4)

    # 7. TONSILLECTOMY INDICATIONS (Paradise/AAO criteria)
    h1(st, "7.  INDICATIONS FOR TONSILLECTOMY IN RECURRENT STREP TONSILLITIS", S)
    h2(st, "Paradise Criteria (AAO-HNS Guidelines)", S)
    bl(st, [
        "Minimum 7 episodes in the preceding year, OR",
        "Minimum 5 episodes per year in each of the preceding 2 years, OR",
        "Minimum 3 episodes per year in each of the preceding 3 years",
        "<b>PLUS</b> each episode must include at least ONE of:",
    ], S)
    bl(st, [
        "Temperature > 38.3 deg C",
        "Cervical lymphadenopathy (node > 2 cm or tender)",
        "Tonsillar exudate",
        "Positive GABHS culture or rapid strep test",
    ], S, sub=True)
    bl(st, [
        "Children with LESS severe disease: unlikely to benefit from tonsillectomy "
          "(Cummings ORL 7e)",
        "Additional indications: peritonsillar abscess (interval tonsillectomy), "
          "PFAPA syndrome, obstructive sleep apnoea with tonsillar hypertrophy",
        "Post-tonsillectomy haemorrhage risk increases in patients operated for "
          "recurrent tonsillitis vs obstructive disease",
    ], S)
    sp(st, 4)

    # 8. DIFFERENTIAL DIAGNOSIS TABLE
    h1(st, "8.  DIFFERENTIAL DIAGNOSIS OF PHARYNGITIS (Comparison)", S)
    data = [
        ["Feature",         "GABHS",                "Viral (incl. EBV)",    "Diphtheria"],
        ["Onset",           "Rapid",                "Gradual",              "Rapid"],
        ["Age",             "Peak 5-15 years",      "Any age",              "Unimmunized any age"],
        ["Fever",           "High (> 38.5 deg C)",  "None / low-grade",     "High"],
        ["Cough",           "ABSENT (key feature)", "Present (rhinorrhoea,\nhoarseness)", "Absent"],
        ["Exudate",         "White/creamy on tonsils","None or white (EBV)", "Greyish membrane\nextending to uvula"],
        ["Membrane",        "None",                 "None (EBV: white\ntonsil coat)", "GREY THICK membrane;\nbleeds on removal"],
        ["Petechiae",       "Palatal petechiae",    "Palatal petechiae (EBV)","None"],
        ["Lymph nodes",     "Tender anterior\ncervical",  "Generalised\n(EBV: posterior chain too)", "Bull-neck oedema"],
        ["Splenomegaly",    "No",                   "Yes (EBV)",            "No"],
        ["Rash",            "Scarlatiniform (if\nScarlet Fever)", "None (EBV: rash if\namoxicillin given)", "None"],
        ["Key test",        "Throat culture /\nRADT; ASO titre", "Monospot; EBV antibody\ntiters; lymphocytosis", "Culture; Elek toxin test"],
        ["Treatment",       "Penicillin 10 days",   "Supportive; NO\namoxicillin for EBV", "Antitoxin + penicillin\n+ diphtheria booster"],
    ]
    st.append(tbl(data, [W*0.18, W*0.275, W*0.275, W*0.27], S))
    sp(st, 4)

    # 9. VIVA Q&A
    h1(st, "9.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. Why is a full 10-day course of penicillin necessary for GABHS pharyngitis?", S)
    bl(st, [
        "To completely eradicate GABHS from the pharynx - shorter courses have higher relapse rates",
        "CRITICAL: 10-day eradication prevents Acute Rheumatic Fever (ARF) - the most "
          "serious sequela of GABHS pharyngitis",
        "Does NOT prevent PSGN (glomerulonephritis) - that is NOT antibiotic-preventable",
        "Phenoxymethylpenicillin (Pen V) or Amoxicillin x 10 days = first-line",
        "Single IM Benzathine Penicillin G = option for compliance issues",
    ], S); sp(st, 2)

    vq(st, "Q2. What is Centor Score and how is it used?", S)
    bl(st, [
        "Clinical prediction score to estimate probability of GABHS pharyngitis",
        "4 criteria (1 point each): Exudate, Tender anterior LN, Fever, Absence of cough",
        "McIsaac adds age: +1 if 3-14 years; -1 if 45+ years",
        "Score 0-1: viral likely, no test/antibiotics; Score 2-3: test first (RADT); "
          "Score 4-5: treat empirically",
        "Purpose: avoid antibiotics for viral pharyngitis while identifying true GABHS cases",
    ], S); sp(st, 2)

    vq(st, "Q3. How does GABHS cause Acute Rheumatic Fever?", S)
    bl(st, [
        "Molecular mimicry: streptococcal M-protein shares epitopes with cardiac myosin, "
          "sarcolemmal membrane proteins, and valvular endothelium",
        "Antibodies against M-protein cross-react with cardiac tissue -> Type II "
          "hypersensitivity -> myocarditis, endocarditis (Aschoff bodies), pericarditis",
        "ONLY pharyngeal GABHS causes ARF (not skin strep) - reason: higher M-protein "
          "expression / immune response at pharyngeal site",
        "Diagnosed by revised Jones criteria (2015 WHO): 2 major or 1 major + 2 minor + "
          "evidence of recent GABHS",
        "Prevention: complete eradication with 10-day penicillin course",
    ], S); sp(st, 2)

    vq(st, "Q4. What is Scarlet Fever and how is it managed?", S)
    bl(st, [
        "Variant of GABHS pharyngitis caused by strains producing erythrogenic toxin "
          "(pyrogenic exotoxins A, B, C) - superantigen-mediated T-cell activation",
        "Rash: fine erythematous sandpaper-like rash; starts neck/chest -> descends; "
          "within 24h of onset; fades in 7-10 days with desquamation",
        "Pastia's lines: rash accentuation in skin folds (antecubital, inguinal)",
        "Tongue: White strawberry tongue (Day 1-3) -> Red strawberry tongue (Day 4-5)",
        "Circumoral pallor (pallor around mouth with flushed cheeks)",
        "Management: Same as GABHS pharyngitis - penicillin x 10 days",
    ], S); sp(st, 2)

    vq(st, "Q5. What are the differences between ARF and PSGN as complications of GABHS?", S)
    data2 = [
        ["Feature",       "Acute Rheumatic Fever (ARF)",     "Post-streptococcal GN (PSGN)"],
        ["Latent period", "2-4 weeks after pharyngitis",      "1-3 weeks after pharyngitis;\n3-6 weeks after skin infection"],
        ["Site of GABHS", "ONLY pharynx (not skin)",          "Pharynx OR skin (pyoderma)"],
        ["Mechanism",     "Molecular mimicry / Type II "
                          "hypersensitivity (anti-M protein)",  "Immune complex deposition "
                                                               "(Type III) in glomeruli"],
        ["Prevented by\nantibiotics?", "YES - 10-day penicillin prevents ARF", "NO - antibiotics do not "
                                                                             "prevent PSGN"],
        ["Recurrence",    "Common; secondary prophylaxis "
                          "required (Benzathine Pen monthly)", "Rare recurrence"],
        ["Diagnosis",     "Jones criteria + ASO titre rise",  "Haematuria, oedema, "
                                                               "hypertension; low C3; "
                                                               "anti-DNase B"},
    ]
    st.append(tbl(data2, [W*0.22, W*0.39, W*0.39], S)); sp(st, 2)

    vq(st, "Q6. What is PFAPA and how is it treated?", S)
    bl(st, [
        "Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis",
        "Children typically under 5 years; episodes every 4-8 weeks like clockwork",
        "Pharyngitis WITHOUT positive GABHS culture (not strep infection - but associated)",
        "Each episode resolves spontaneously in 3-6 days",
        "Single dose of corticosteroid (prednisolone 1-2 mg/kg) aborts episode rapidly",
        "Definitive treatment: TONSILLECTOMY - curative in most cases",
    ], S); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Cummings ORL 7e Ch.201 | Scott-Brown's OHN&S 8e | "
        "KJ Lee Essential ORL 11e | Dhingra ENT 8e | "
        "AAO-HNS Tonsillectomy Guidelines | WHO Jones Criteria 2015",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Strep_Pharyngitis_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Streptococcal Pharyngitis - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_strep_pharyngitis.py'

#!/usr/bin/env python3
# Verrucous Carcinoma - ENT PG Exam Notes (5-6 pages, bullet-point style)
# Palette 17: Dark mahogany-brown / steel-blue / deep olive-green

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 17: Dark mahogany (#5C1A00) / steel-blue (#1A3A5C) / deep olive-green (#3A4A00)
C_H1_BG  = colors.HexColor("#5C1A00")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#1A3A5C")
C_H2_BG  = colors.HexColor("#EAF0FA")
C_H3_FG  = colors.HexColor("#3A4A00")
C_H3_BG  = colors.HexColor("#F0F5E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#5C1A00")
C_ALT    = colors.HexColor("#FFF5F0")
C_PEARL  = colors.HexColor("#FFF5F0")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#5C1A00")
C_VQ_BG  = colors.HexColor("#EAF0FA")
C_VQ_FG  = colors.HexColor("#1A3A5C")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("VERRUCOUS CARCINOMA - ENT PG EXAM NOTES", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Cummings ORL 7e, Scott-Brown's OHN&S 8e, Andrews' Diseases of the Skin, "
        "Dhingra ENT 8e, KJ Lee Essential ORL 11e",
        S["sub"]))
    rule(st); sp(st, 2)

    # 1. DEFINITION & HISTORICAL NOTE
    h1(st, "1.  DEFINITION & HISTORICAL NOTE", S)
    bl(st, [
        "<b>Verrucous Carcinoma (VC)</b> = a distinct, rare, low-grade, well-differentiated "
          "variant of squamous cell carcinoma (SCC) characterised by an "
          "exophytic, warty (verrucous) growth pattern with <b>pushing margins</b> "
          "(not infiltrating), minimal cytological atypia, and locally destructive behaviour",
        "First described by <b>Lauren V. Ackermann in 1948</b> - hence also called "
          "<b>'Ackermann's Tumour'</b>",
        "Classified as a <b>low-grade malignancy</b> with excellent prognosis when "
          "treated adequately",
        "<b>Key biological characteristics:</b>",
    ], S)
    bl(st, [
        "Locally invasive and destructive (can erode bone and cartilage)",
        "DOES NOT metastasize in its pure form",
        "Hybrid VC (mixed with conventional SCC) = CAN metastasize",
        "Tends to recur after incomplete excision",
    ], S, sub=True)
    pearl(st,
        "MEMORY AID: Verrucous = Wart-like. Ackermann's Tumour = locally aggressive, "
        "does NOT metastasize, does NOT respond well to radiotherapy. "
        "Surgery is the treatment of choice. (Cummings ORL 7e)", S)
    sp(st, 4)

    # 2. CLASSIFICATION / TYPES
    h1(st, "2.  CLASSIFICATION - THREE MAJOR SUBTYPES", S)
    bl(st, [
        "Verrucous carcinoma is clinically classified into three main subtypes based on site:",
    ], S)
    num(st, "1", "Oral Florid Papillomatosis",
        "VC of the oral mucosa. The most common ENT/head-and-neck site. "
        "Associated with tobacco (chewing and smoking), areca nut (betel quid), "
        "oral submucous fibrosis, and HPV. "
        "Sites within oral cavity: buccal mucosa (most common), gingiva, tongue, lip, alveolar ridge.", S)
    num(st, "2", "Epithelioma Cuniculatum (Carcinoma Cuniculatum)",
        "VC of the plantar surface of the foot. "
        "Multiple sinuses opening on the surface resembling 'rabbit burrows' (cuniculatum = rabbit in Latin). "
        "Large exophytic mass; can erode underlying bone. "
        "Associated with pressure, chronic trauma, HPV-6/11.", S)
    num(st, "3", "Giant Condyloma of Buschke-Lowenstein (Buschke-Lowenstein Tumour)",
        "VC of the anogenital region (penis, vulva, perineum, anus). "
        "Strongly associated with HPV-6 and HPV-11 (low-risk types). "
        "Giant exophytic lesion resembling condyloma acuminatum but with locally destructive behaviour. "
        "May be difficult to distinguish from benign condyloma without deep biopsy.", S)
    bl(st, [
        "<b>In the ENT/Head and Neck context:</b> two ENT sites are important:",
    ], S)
    bl(st, [
        "<b>Oral cavity (oral florid papillomatosis)</b> - most common head and neck site",
        "<b>Larynx</b> - second most common site in the head and neck; "
          "most VC of the larynx occurs on the <b>true vocal cords</b> (Cummings ORL 7e)",
    ], S, sub=True)
    sp(st, 4)

    # 3. EPIDEMIOLOGY & AETIOLOGY
    h1(st, "3.  EPIDEMIOLOGY & AETIOLOGY / RISK FACTORS", S)
    h2(st, "Epidemiology", S)
    bl(st, [
        "Rare tumour - accounts for 1-10% of all oral cavity malignancies",
        "Predominantly affects <b>middle-aged to elderly men</b> (5th-7th decade)",
        "M:F ratio approximately 3:1 for oral VC",
        "More common in South and Southeast Asia (tobacco chewing habits)",
    ], S)
    h2(st, "Risk Factors / Aetiology", S)
    bl(st, [
        "<b>Tobacco - most important risk factor for oral VC:</b>",
    ], S)
    bl(st, [
        "Chewing tobacco / betel quid / areca nut (most strongly associated)",
        "Smoking (cigarettes, bidi, hookah)",
        "Reverse smoking (smoking with lit end inside mouth - common in Andhra Pradesh/India)",
    ], S, sub=True)
    bl(st, [
        "<b>HPV (Human Papillomavirus):</b> role is controversial in oral and laryngeal VC",
    ], S)
    bl(st, [
        "HPV DNA detected in variable proportion of VC patients",
        "Low-risk HPV types: HPV-6, HPV-11 (especially genital VC / Buschke-Lowenstein)",
        "High-risk HPV types: HPV-16, HPV-18 (in some oral cases)",
        "HOWEVER: several studies show HPV is NOT etiopathogenetically associated with "
          "head and neck VC - mere presence of HPV DNA does not confirm causation (Cummings ORL 7e)",
    ], S, sub=True)
    bl(st, [
        "<b>Chronic irritation / trauma</b> (poorly fitting dentures, chronic mucosal trauma)",
        "<b>Oral submucous fibrosis (OSMF):</b> pre-malignant condition associated with "
          "areca nut chewing; can progress to VC or conventional SCC",
        "<b>Chronic inflammation / scarring:</b> VC can arise in scars, "
          "amputation stumps, fistulae of osteomyelitis, chronic venous ulcers",
        "<b>Poor oral hygiene and nutrition (contributory)</b>",
        "UV light is NOT a significant risk factor (unlike conventional cutaneous SCC)",
    ], S)
    sp(st, 4)

    # 4. PATHOLOGY
    h1(st, "4.  PATHOLOGY", S)
    h2(st, "Gross / Macroscopic Features", S)
    bl(st, [
        "Large, exophytic, warty (papillomatous/verrucous) surface - 'cauliflower-like' appearance",
        "White or grey surface with thick keratinised projections",
        "Broad-based, sessile, firm mass; may be huge (especially Buschke-Lowenstein tumour)",
        "Base of lesion appears to push into surrounding tissues rather than invade irregularly",
        "Cut section: irregular endophytic extensions, multiple crevices like rabbit burrows (cuniculatum)",
        "Underlying bone/cartilage may be eroded by mass effect",
    ], S)
    h2(st, "Microscopic / Histological Features (KEY)", S)
    bl(st, [
        "<b>Thickened papillary projections</b> with marked surface keratinisation "
          "(hyperkeratosis and parakeratosis)",
        "<b>Bulbous rete ridges / invaginations</b> of well-differentiated squamous epithelium "
          "pushing downward into stroma (pushing margin = NOT spiky infiltrative margin)",
        "<b>Well-differentiated squamous epithelium</b> - cells are large, "
          "pale/eosinophilic (apple-pink glassy cytoplasm), abundant keratin",
        "<b>MINIMAL CYTOLOGICAL ATYPIA</b> - this is the key histological feature "
          "distinguishing VC from conventional SCC",
        "<b>Thin fibrovascular cores</b> within papillary fronds",
        "<b>Marked peritumoral chronic inflammatory infiltrate</b> at the base",
        "<b>Pushing (not infiltrating) deep margin</b> - smooth tumour-stroma interface, "
          "NOT the irregular spiky infiltrating margin of conventional SCC",
        "NO lymphovascular invasion in pure VC; no perineural invasion",
    ], S)
    caut(st,
        "IMPORTANT: Superficial biopsies of VC frequently appear BENIGN and miss the diagnosis. "
        "Deep incisional biopsy from the BASE of the lesion is mandatory. "
        "Patients may require MULTIPLE biopsies before diagnosis is established. "
        "(Cummings ORL 7e, Andrews' Diseases of the Skin)", S)
    h2(st, "Hybrid Verrucous Carcinoma", S)
    bl(st, [
        "Mixed tumour: foci of conventional SCC within a VC",
        "Behaves like conventional SCC - CAN metastasize to cervical nodes",
        "Must be treated like conventional SCC (including neck dissection if nodes involved)",
        "Previously, some cases of irradiated VC that appeared to 'transform anaplastically' "
          "were likely hybrid tumours misdiagnosed as pure VC (Cummings ORL 7e)",
    ], S)
    sp(st, 4)

    # 5. CLINICAL FEATURES
    h1(st, "5.  CLINICAL FEATURES", S)
    h2(st, "Oral Verrucous Carcinoma (Oral Florid Papillomatosis)", S)
    bl(st, [
        "<b>Site:</b> Buccal mucosa most common, followed by gingiva/alveolar ridge, "
          "hard palate, tongue, floor of mouth",
        "Presents as a white, warty, exophytic, cauliflower-like or papillomatous growth",
        "May begin as a white patch (leukoplakia) or erythroleukoplakia that becomes "
          "progressively exophytic and warty",
        "Slow growing over months to years - patient may underestimate its significance",
        "History of tobacco chewing, betel quid use, bidi smoking",
        "Pain and odynophagia are late features (early lesions often painless)",
        "Loosening of teeth / fixity to underlying bone when alveolar ridge involved",
        "Trismus if masseter/pterygoid muscles involved (late)",
    ], S)
    h2(st, "Laryngeal Verrucous Carcinoma", S)
    bl(st, [
        "<b>Site:</b> True vocal cords (most common laryngeal site)",
        "Presents as progressive hoarseness - the earliest and main symptom",
        "White warty exophytic mass on cord(s) on laryngoscopy",
        "May mimic laryngeal papillomatosis (RRP) clinically",
        "Dysphagia and stridor are late features (subglottic extension)",
        "Cervical lymphadenopathy: reactive (peritumoral inflammation) > metastatic "
          "(pure VC does not metastasize)",
    ], S)
    sp(st, 4)

    # 6. DIAGNOSIS
    h1(st, "6.  DIAGNOSIS", S)
    bl(st, [
        "<b>Clinical examination:</b> site, size, surface character, mobility, "
          "fixity, trismus, neck nodes",
        "<b>Deep incisional biopsy (mandatory):</b> from BASE of lesion, not just surface. "
          "Multiple biopsies may be needed. Surface-only biopsy gives false-negative result",
        "<b>Histopathology</b> (as described above): hallmarks are pushing margin, "
          "well-differentiated epithelium, minimal atypia",
        "<b>Orthopantomogram (OPG):</b> mandible/maxilla involvement; bone erosion",
        "<b>CECT (CT with contrast) face and neck:</b> extent of primary, "
          "bone destruction, neck nodal status",
        "<b>MRI:</b> better soft tissue delineation; perineural spread; "
          "deep muscle involvement; skull base",
        "<b>Chest X-ray / CT chest:</b> distant metastasis (rare in pure VC)",
        "<b>HPV testing</b> (p16 immunohistochemistry): not routinely needed for VC "
          "management but may be performed for academic/research purposes",
    ], S)
    sp(st, 4)

    # 7. TREATMENT
    h1(st, "7.  TREATMENT", S)
    h2(st, "Surgery (Treatment of Choice)", S)
    bl(st, [
        "<b>Conservative surgical excision with adequate margins</b> = gold standard treatment",
        "Wide local excision with 1-1.5 cm clear margins",
        "<b>Oral VC:</b> transoral excision for small lesions; "
          "mandibulotomy / lip split approach for larger lesions; "
          "composite resection (jaw + soft tissue) if bone involved",
        "<b>Laryngeal VC:</b> endoscopic CO2 laser excision for small cord lesions; "
          "partial laryngectomy (cordectomy, vertical partial laryngectomy) for larger lesions; "
          "total laryngectomy only if no other option (preferred to be avoided)",
        "<b>Neck dissection: NOT indicated</b> for pure VC (does not metastasize). "
          "Enlarged nodes = reactive lymphadenopathy. "
          "Neck dissection ONLY if metastases proven (fine needle aspiration / biopsy) "
          "OR if hybrid VC identified",
        "Surgical salvage after recurrence is UNIVERSALLY SUCCESSFUL in VC (Cummings ORL 7e)",
        "Mohs micrographic surgery: option for cutaneous VC (carcinoma cuniculatum) "
          "to achieve complete margin control",
        "5-year survival with surgery: approaches 90% for pure VC (excellent prognosis)",
    ], S)
    h2(st, "Radiotherapy - Controversial and Relatively Contraindicated", S)
    caut(st,
        "RADIOTHERAPY IS RELATIVELY CONTRAINDICATED in pure Verrucous Carcinoma. "
        "VC is LESS RADIOSENSITIVE than conventional SCC. "
        "Higher risk of residual/recurrent disease with RT than surgery. "
        "Most importantly: RT may induce ANAPLASTIC TRANSFORMATION of VC into "
        "a more aggressive, metastasising tumour. "
        "(Cummings ORL 7e; Andrews' Diseases of the Skin; Berek & Novak's Gynecology)", S)
    bl(st, [
        "RT is indicated ONLY when:",
    ], S)
    bl(st, [
        "Extensive lesion where surgery = total laryngectomy (RT as organ-preservation attempt)",
        "Patient unfit for surgery (poor surgical risk)",
        "Recurrence not amenable to further surgery",
        "Palliative intent",
    ], S, sub=True)
    bl(st, [
        "Note: Some authors now believe anaplastic transformation after RT was due to "
          "HYBRID VC cases misdiagnosed as pure VC - true risk may be lower (Cummings ORL 7e)",
    ], S)
    h2(st, "Chemotherapy", S)
    bl(st, [
        "Role limited; used for recurrent/unresectable cases or as adjunct",
        "Agents used (with variable success): Bleomycin, 5-Fluorouracil (5-FU), "
          "Cisplatin, Methotrexate",
        "Intralesional/systemic Interferon alfa (IFN-alfa): used in some series",
        "Topical Imiquimod and CO2 laser: options for cutaneous VC",
        "Photodynamic therapy (PDT): experimental option for cutaneous VC",
    ], S)
    sp(st, 4)

    # 8. COMPARISON TABLE
    h1(st, "8.  VERRUCOUS CARCINOMA vs CONVENTIONAL SCC  (Comparison)", S)
    data = [
        ["Feature",              "Verrucous Carcinoma (VC)",           "Conventional SCC"],
        ["Differentiation",      "Well-differentiated throughout",      "Variable (well to poorly diff.)"],
        ["Growth pattern",       "Exophytic, warty, pushing margin",    "Exophytic AND/OR endophytic,\ninfiltrating margin"],
        ["Cytological atypia",   "MINIMAL / absent",                    "Moderate to marked"],
        ["Metastasis",           "DOES NOT metastasize (pure form)",    "Common - lymph node,\ndistant spread"],
        ["Local invasion",       "YES - locally destructive;\ncan erode bone", "YES - aggressive local invasion"],
        ["Lymph node",           "Reactive enlargement only\n(peritumoral inflammation)", "True metastatic nodes common"],
        ["Prognosis",            "EXCELLENT - 5-year survival ~90%",    "Depends on stage/grade"],
        ["Radiotherapy",         "LESS radiosensitive; AVOID -\nrisk of anaplastic transformation", "Standard modality;\nradiosensitive"],
        ["Neck dissection",      "NOT indicated (pure VC)",             "Indicated based on N-stage"],
        ["Surgery",              "Conservative excision preferred;\nsurgical salvage always possible", "Wide excision + reconstruction;\nneck dissection"],
        ["HPV role",             "Controversial; variable association", "HPV-16/18 in oropharyngeal SCC\n(well-established)"],
        ["Biopsy challenge",     "Deep biopsy MANDATORY;\nsuperficial biopsy = false negative", "Surface biopsy usually adequate"],
    ]
    st.append(tbl(data, [W*0.26, W*0.37, W*0.37], S))
    sp(st, 4)

    # 9. VIVA Q&A
    h1(st, "9.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. What is Verrucous Carcinoma? Who first described it?", S)
    bl(st, [
        "VC = rare, low-grade, well-differentiated variant of SCC with exophytic warty growth "
          "and pushing (non-infiltrating) margins",
        "First described by <b>Lauren V. Ackermann in 1948</b> - known as Ackermann's Tumour",
        "Key features: minimal cytological atypia, no metastasis (pure form), "
          "locally destructive, excellent prognosis",
        "Three subtypes: Oral florid papillomatosis / Epithelioma cuniculatum / "
          "Buschke-Lowenstein tumour",
    ], S); sp(st, 2)

    vq(st, "Q2. Why is superficial biopsy inadequate in Verrucous Carcinoma?", S)
    bl(st, [
        "The surface of VC shows only well-differentiated epithelium with minimal atypia - "
          "which appears BENIGN histologically",
        "The diagnostic pushing margin and bulbous rete ridge pattern are only visible "
          "at the BASE of the tumour",
        "A superficial biopsy misses the deep architectural features needed for diagnosis",
        "Multiple deep incisional biopsies from the BASE are essential",
        "This is why patients are often diagnosed only after multiple biopsies",
    ], S); sp(st, 2)

    vq(st, "Q3. Why is radiotherapy avoided in Verrucous Carcinoma?", S)
    bl(st, [
        "VC is LESS radiosensitive than conventional SCC (higher failure/recurrence rate with RT)",
        "Major concern: RT may induce ANAPLASTIC TRANSFORMATION of VC "
          "into a highly aggressive, metastasising tumour",
        "Some studies show corrected 5-year survival of 94% with surgery alone vs "
          "42% with surgery + radiation (though radiation group had more advanced disease)",
        "Current consensus: RT reserved only for extensive unresectable VC or unfit patients",
        "Note: cases of 'anaplastic transformation' post-RT may have been misdiagnosed "
          "HYBRID VC (with SCC foci) rather than true pure VC",
    ], S); sp(st, 2)

    vq(st, "Q4. What is Hybrid Verrucous Carcinoma and how does it differ from pure VC?", S)
    bl(st, [
        "Hybrid VC = contains foci of CONVENTIONAL SCC within an otherwise typical VC",
        "Unlike pure VC, hybrid VC CAN metastasize to cervical lymph nodes",
        "Must be treated as conventional SCC - wider excision + neck dissection if nodes involved",
        "All VC specimens must be thoroughly sampled histologically to exclude hybrid form",
        "Hybrid VC likely accounts for some reported cases of 'metastatic VC' and "
          "'VC with anaplastic transformation after RT'",
    ], S); sp(st, 2)

    vq(st, "Q5. What is the role of HPV in Verrucous Carcinoma?", S)
    bl(st, [
        "HPV role is CONTROVERSIAL in oral and laryngeal VC",
        "Low-risk HPV types (HPV-6, HPV-11) are associated with genital VC "
          "(Buschke-Lowenstein tumour)",
        "Some series detect HPV DNA in oral/laryngeal VC; others show no association",
        "Multiple studies demonstrate HPV is NOT etiopathogenetically associated "
          "with head and neck VC (Cummings ORL 7e)",
        "Presence of HPV DNA alone does not confirm causation - may be incidental finding",
        "Contrast with oropharyngeal SCC: HPV-16/18 is well-established causally there",
    ], S); sp(st, 2)

    vq(st, "Q6. What are the histological differences between VC and conventional SCC?", S)
    bl(st, [
        "VC: Minimal cytological atypia; pushing smooth margin; bulbous rete ridges; "
          "well-differentiated throughout; abundant keratin; apple-pink glassy cytoplasm; "
          "no lymphovascular invasion",
        "Conventional SCC: Moderate to marked cytological atypia; "
          "irregular infiltrating margin; nuclear pleomorphism, hyperchromasia; "
          "abnormal mitoses; variable differentiation; perineural and lymphovascular invasion",
        "Peritumoral inflammation is MARKED in VC (reactive - NOT metastatic)",
        "VC: thin fibrovascular cores within papillary fronds (unlike condyloma which has "
          "central connective tissue cores)",
    ], S); sp(st, 2)

    vq(st, "Q7. What are the common ENT sites and key management points for VC?", S)
    bl(st, [
        "Head and neck sites: Oral cavity (most common - buccal mucosa) "
          "and Larynx (second most common - true vocal cords)",
        "Management principles:",
    ], S)
    bl(st, [
        "Surgery = treatment of choice (conservative excision with clear margins)",
        "No neck dissection for pure VC (does not metastasize)",
        "Avoid radiotherapy (less radiosensitive; anaplastic transformation risk)",
        "Surgical salvage of recurrence is always successful",
        "Hybrid VC (with SCC foci) = treat as conventional SCC",
        "5-year survival approaches 90% with adequate surgery",
    ], S, sub=True); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Cummings ORL 7e Ch.105 | Andrews' Diseases of the Skin 13e | "
        "Dermatology 2-Vol Set 5e (Bolognoa) | Scott-Brown's OHN&S 8e | "
        "Dhingra ENT 8e | KJ Lee Essential ORL 11e | "
        "Ackermann LV (1948) - original description",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/VerrucousCarcinoma_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Verrucous Carcinoma - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Le Fort Fractures - ENT PG Exam Notes (5-6 pages, bullet-point style)
# Palette 18: Deep cobalt-blue / dark crimson / warm sienna-gold

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 18: Deep cobalt-blue (#0A2A6B) / dark crimson (#7A0030) / warm sienna-gold (#7A4A00)
C_H1_BG  = colors.HexColor("#0A2A6B")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#7A0030")
C_H2_BG  = colors.HexColor("#FFF0F5")
C_H3_FG  = colors.HexColor("#7A4A00")
C_H3_BG  = colors.HexColor("#FFF8E6")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#0A2A6B")
C_ALT    = colors.HexColor("#EAF0FF")
C_PEARL  = colors.HexColor("#EAF0FF")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#0A2A6B")
C_VQ_BG  = colors.HexColor("#FFF8E6")
C_VQ_FG  = colors.HexColor("#7A4A00")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    # TITLE
    st.append(Paragraph("LE FORT FRACTURES - ENT PG EXAM NOTES", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e Vol 1 (Ch.107), KJ Lee Essential ORL 11e, "
        "Cummings ORL 7e, Tintinalli Emergency Medicine, Dhingra ENT 8e",
        S["sub"]))
    rule(st); sp(st, 2)

    # 1. INTRODUCTION
    h1(st, "1.  INTRODUCTION", S)
    bl(st, [
        "<b>Le Fort fractures</b> = a classification of midfacial (maxillary) fractures "
          "describing patterns of bone separation at three levels of the midface",
        "First described by <b>Rene Le Fort (1901)</b>, a French surgeon, "
          "based on cadaveric experiments applying blunt force trauma to the midface",
        "All three Le Fort fracture levels share one common feature: "
          "<b>involvement of the pterygoid plates</b> of the sphenoid bone",
        "The midface bone is generally very thin and offers little resistance to "
          "anterior and lateral forces (Scott-Brown's OHN&S 8e)",
        "<b>Common causes:</b> road traffic accidents (RTA / MVA), assault, "
          "falls, sports injuries; high-energy mechanisms required",
        "Incidence of midfacial fractures in MVAs has declined due to vehicle restraint systems",
        "Pure Le Fort fractures are uncommon in high-energy injuries; "
          "most involve MIXED patterns (Le Fort I + II, Le Fort II + III, "
          "+ zygomatic + nasoethmoidal components)",
    ], S)
    pearl(st,
        "KEY PEARL: ALL Le Fort fractures involve the PTERYGOID PLATES of the sphenoid. "
        "This is the one anatomical constant across all three Le Fort levels. "
        "(Scott-Brown's OHN&S 8e)", S)
    sp(st, 4)

    # 2. ANATOMY - BUTTRESSES
    h1(st, "2.  RELEVANT ANATOMY - FACIAL BUTTRESSES", S)
    bl(st, [
        "The facial skeleton is not a uniform mass - it has thickened areas of bone "
          "called <b>BUTTRESSES</b> that provide structural support and resistance to forces",
        "Between buttresses, bone is thin and fragile (antral walls, orbital floor, nasal bones)",
        "<b>Vertical buttresses (bear masticatory loads vertically):</b>",
    ], S)
    bl(st, [
        "Nasomaxillary buttress: along piriform aperture up to frontal bone",
        "Zygomaticomaxillary buttress: from zygomatic body to zygomaticofrontal suture",
        "Pterygomaxillary buttress: pterygoid plates to posterior maxilla",
    ], S, sub=True)
    bl(st, [
        "<b>Horizontal buttresses (connect vertical buttresses transversely):</b>",
    ], S)
    bl(st, [
        "Frontal bar (supraorbital rim)",
        "Infraorbital rim",
        "Zygomatic arch",
        "Maxillary alveolus / hard palate",
    ], S, sub=True)
    bl(st, [
        "Fracture lines in Le Fort injuries follow the WEAKEST zones between buttresses",
        "Buttresses are the key sites for ORIF (open reduction internal fixation) "
          "during surgical repair - they provide adequate bone stock for plate and screw fixation",
    ], S)
    sp(st, 4)

    # 3. LE FORT CLASSIFICATION - DETAILED
    h1(st, "3.  LE FORT CLASSIFICATION - FRACTURE LINES IN DETAIL", S)

    h2(st, "Le Fort I - Horizontal / Guerin Fracture / 'Floating Palate'", S)
    bl(st, [
        "<b>Also called:</b> Guerin fracture, Transverse maxillary fracture, Low-level fracture",
        "<b>Level:</b> Horizontal fracture running ABOVE the floor of the nasal cavity "
          "(just above the apices of the upper teeth)",
        "<b>Fracture line passes through:</b>",
    ], S)
    bl(st, [
        "Anterior wall of maxillary sinuses",
        "Inferior third of the nasal septum",
        "Lower parts of BOTH medial and lateral pterygoid plates",
        "Lateral walls of maxillary sinuses (just above floor level)",
    ], S, sub=True)
    bl(st, [
        "<b>Segment mobilised:</b> ONLY the hard palate + maxillary alveolus + "
          "upper teeth (like a 'floating plate' or 'loose upper denture')",
        "<b>Mobility test:</b> grasp upper teeth / hard palate between thumb and index finger; "
          "rock gently -> only HARD PALATE MOVES; nose and orbits remain fixed",
        "<b>Clinical features specific to Le Fort I:</b> malocclusion, "
          "pain on biting, trismus, mobile upper teeth, "
          "epistaxis, intraoral bruising (buccal sulcus haematoma)",
    ], S)
    sp(st, 3)

    h2(st, "Le Fort II - Pyramidal Fracture / 'Floating Maxilla'", S)
    bl(st, [
        "<b>Also called:</b> Pyramidal fracture, Subzygomatic fracture",
        "<b>Shape:</b> Pyramid-shaped fragment with apex at nasofrontal suture "
          "and base at the maxillary alveolus",
        "<b>Fracture line passes through:</b>",
    ], S)
    bl(st, [
        "Nasofrontal suture (junction of nasal bones and frontal bone)",
        "Medial orbital walls (through lacrimal bone to medial orbital floor)",
        "Infraorbital rim (just medial to or through infraorbital foramen) "
          "-> infraorbital nerve involvement -> infraorbital anaesthesia",
        "Zygomaticomaxillary suture (NOT through the zygoma itself)",
        "Posterior wall of maxillary sinuses",
        "Pterygoid plates (both medial and lateral)",
    ], S, sub=True)
    bl(st, [
        "<b>Segment mobilised:</b> central maxilla + hard palate + nasal complex "
          "(nose moves with the palate, but eyes do NOT move)",
        "<b>Mobility test:</b> grasp nose and hard palate together -> "
          "NOSE + PALATE move together as one unit; eyes remain fixed",
        "<b>Clinical features specific to Le Fort II:</b> "
          "infraorbital nerve anaesthesia (cheek, upper lip, nose), "
          "CSF rhinorrhoea (nasofrontal fracture may breach dura), "
          "epistaxis, bilateral peri-orbital bruising, "
          "dish-face deformity (retruded midface), open-bite malocclusion, "
          "nasal bridge depression, step deformity at infraorbital rim",
        "Infraorbital nerve damaged by fracture involvement at infraorbital foramen "
          "(Scott-Brown's OHN&S 8e)",
    ], S)
    sp(st, 3)

    h2(st, "Le Fort III - Craniofacial Disjunction / 'Floating Face'", S)
    bl(st, [
        "<b>Also called:</b> Craniofacial dysjunction / disjunction, "
          "Total facial fracture, High-level fracture",
        "<b>Definition:</b> Complete separation of the ENTIRE FACIAL SKELETON "
          "from the cranial base - 'face floating from skull'",
        "<b>Fracture line passes through:</b>",
    ], S)
    bl(st, [
        "Nasofrontal suture (same as Le Fort II)",
        "Medial orbital wall -> superior orbital fissure",
        "Orbital floor -> lateral orbital wall",
        "Greater wing of sphenoid",
        "Zygomaticofrontal suture (ZF suture) - KEY: ZF suture involvement "
          "distinguishes Le Fort III from Le Fort II",
        "Zygomatic arch fracture (always broken in Le Fort III)",
        "Across entire orbit floor and medial wall",
        "Pterygomaxillary fissure and sphenopalatine foramen",
        "Runs inferior to the optic foramen (optic nerve usually spared unless separate injury)",
        "Both pterygoid plates bilaterally",
    ], S, sub=True)
    bl(st, [
        "<b>Segment mobilised:</b> ENTIRE face including orbits, zygoma, nose, "
          "maxilla - 'face floats off skull'. Only skull base remains fixed",
        "<b>Mobility test:</b> grasp entire face (hard palate + nose + "
          "zygomatic regions simultaneously) -> ENTIRE FACE moves including EYES "
          "(globes held in position only by optic nerves)",
        "<b>Clinical features specific to Le Fort III:</b> "
          "lengthening of face ('dish-face'), massive peri-orbital bruising "
          "('panda eyes' / 'raccoon eyes'), severe CSF rhinorrhoea, "
          "bilateral subconjunctival haemorrhage, ophthalmoplegia, "
          "massive haemorrhage (from sphenopalatine and anterior ethmoidal arteries), "
          "airway compromise",
        "<b>Pure Le Fort III is rare</b> - usually a mixture of Le Fort II + "
          "zygomatic fractures + other facial fractures (KJ Lee Essential ORL 11e)",
    ], S)
    sp(st, 4)

    # 4. COMBINED CLINICAL FEATURES TABLE
    h1(st, "4.  LE FORT FRACTURES - COMPARISON TABLE", S)
    data = [
        ["Feature",              "Le Fort I",                    "Le Fort II",                  "Le Fort III"],
        ["Also called",          "Guerin fracture;\nFloating palate",
                                                                  "Pyramidal fracture;\nFloating maxilla",
                                                                                                  "Craniofacial\ndysjunction;\nFloating face"],
        ["Fracture level",       "LOWEST - above\nnasal floor",  "MID - pyramid-\nshaped",      "HIGHEST - separates\nentire face from skull"],
        ["What moves",           "ONLY hard palate\n+ teeth",    "Nose + hard\npalate (not eyes)", "ENTIRE face\nincl. orbits + eyes"],
        ["Pterygoid plates",     "Lower part involved",           "Full involvement",             "Full involvement"],
        ["ZF suture",            "NOT involved",                  "NOT involved",                 "INVOLVED (key)"],
        ["Zygomatic arch",       "Intact",                        "Intact",                       "BROKEN"],
        ["Infraorbital nerve",   "Not involved",                  "Often damaged ->\nanaesthesia cheek/lip", "May be involved"],
        ["CSF leak",             "Absent",                        "May occur\n(nasofrontal Fx)", "COMMON\n(nasofrontal + orbital Fx)"],
        ["Ocular signs",         "None",                          "None",                         "Diplopia, enophthalmos,\nophthalmoplegia"],
        ["Malocclusion",         "Open bite;\nupper teeth mobile", "Open bite",                   "Severe open bite"],
        ["Facial deformity",     "Minimal (elongated\nface if impacted)", "Dish-face;\nsunken nose", "Severe dish-face;\nface lengthening"],
        ["CSF rhinorrhoea",      "No",                            "Possible",                     "Yes - common"],
        ["Haemorrhage",          "Moderate",                      "Moderate-severe",              "SEVERE (sphenopal.\nartery, ethmoidal a.)"],
        ["Le Fort's description","Horizontal",                    "Pyramid",                      "Craniofacial\ndisjunction"],
    ]
    st.append(tbl(data, [W*0.23, W*0.255, W*0.255, W*0.26], S))
    sp(st, 4)

    # 5. CLINICAL ASSESSMENT
    h1(st, "5.  CLINICAL ASSESSMENT & INVESTIGATION", S)
    h2(st, "History & Mechanism", S)
    bl(st, [
        "High-energy blunt force to face: RTA, dashboard injury, assault, fall from height",
        "Symptoms: facial pain, swelling, malocclusion, visual disturbance, nasal bleeding, "
          "difficulty breathing/swallowing",
        "Always assess for associated injuries: head injury (GCS), cervical spine injury "
          "(assume until cleared), chest/abdominal trauma",
    ], S)
    h2(st, "Primary Survey - ABCDE (Airway Priority)", S)
    caut(st,
        "AIRWAY is the IMMEDIATE PRIORITY in Le Fort II and III fractures. "
        "Posterior impaction of the maxilla + massive haemorrhage can cause "
        "rapid airway obstruction. Secure airway FIRST before all else. "
        "If nasotracheal intubation attempted in Le Fort II/III - risk of intracranial "
        "tube passage through cribriform plate (CSF leak = relative contraindication). "
        "Orotracheal intubation preferred; surgical airway (tracheostomy) if necessary.", S)
    bl(st, [
        "<b>Airway:</b> blood/clots in pharynx, posterior impaction of maxilla, "
          "unstable fragments. Manually retract maxilla forward if impacted (finger behind soft palate)",
        "<b>Bleeding control:</b> anterior-posterior nasal packing (Epistat balloon); "
          "oral packing for hard palate fractures. "
          "Torrential bleeding from sphenopalatine artery -> "
          "angiographic embolisation if packing fails",
        "<b>CSF leak:</b> check for 'halo sign' on white gauze; "
          "do NOT pack tightly if CSF leak confirmed",
        "<b>Eyes:</b> assess visual acuity, extra-ocular movements, "
          "enophthalmos, diplopia (orbital floor fracture), pupillary reaction",
        "<b>Neurological:</b> GCS; associated TBI is common",
    ], S)
    h2(st, "Examination of Midfacial Fracture", S)
    bl(st, [
        "Inspection: facial asymmetry, lengthening, peri-orbital bruising "
          "(panda eyes), subconjunctival haemorrhage, epistaxis, CSF rhinorrhoea",
        "<b>Mobility test (DEFINITIVE CLINICAL TEST):</b>",
    ], S)
    bl(st, [
        "One hand stabilises forehead; other hand grasps hard palate / maxillary teeth",
        "Rock the midface gently: observe which structures move",
        "Le Fort I -> only hard palate + teeth move",
        "Le Fort II -> nose + hard palate move together",
        "Le Fort III -> entire face (including eyes/orbits) moves",
    ], S, sub=True)
    bl(st, [
        "Palpation: step deformity at infraorbital rim (Le Fort II), "
          "ZF suture tenderness (Le Fort III), buccal sulcus haematoma",
        "Dental occlusion: open bite deformity common in all Le Fort fractures",
        "Infraorbital nerve sensation: hypoaesthesia of cheek/upper lip (Le Fort II)",
    ], S)
    h2(st, "Investigations", S)
    bl(st, [
        "<b>CT Face - Gold Standard:</b> thin-slice axial + coronal + 3D reconstructions. "
          "Defines fracture lines, degree of comminution, orbital involvement, "
          "skull base involvement, optic canal",
        "<b>Plain X-rays (OM views - Waters' view, PA, lateral):</b> initial screening "
          "but inadequate for definitive assessment; largely replaced by CT",
        "<b>MRI:</b> for optic nerve injury, intracranial extension, dural tear",
        "<b>FBC, coagulation screen, group and crossmatch:</b> "
          "haemorrhage is significant in Le Fort II/III",
        "<b>CT head:</b> associated intracranial injury",
        "<b>Beta-2 transferrin (nasal fluid):</b> confirm CSF rhinorrhoea",
    ], S)
    sp(st, 4)

    # 6. MANAGEMENT
    h1(st, "6.  MANAGEMENT", S)
    h2(st, "Emergency / Immediate", S)
    bl(st, [
        "Secure airway (orotracheal intubation preferred; "
          "tracheostomy if necessary in massive facial disruption)",
        "Control haemorrhage: anterior-posterior nasal packing; "
          "epistat balloon; oral packing for palatal fractures; "
          "angiographic embolisation as last resort",
        "IV access, fluid resuscitation, blood transfusion",
        "Manual disimpaction of posteriorly impacted maxilla: "
          "index and middle finger placed BEHIND soft palate, pull forward",
        "Nasogastric tube ONLY after ensuring no CSF rhinorrhoea "
          "(risk of intracranial insertion if cribriform plate fractured)",
        "IV antibiotics (broad-spectrum) for open fractures, CSF leak",
        "Ophthalmology review if visual disturbance or orbital involvement",
    ], S)
    h2(st, "Definitive Surgical Repair (ORIF)", S)
    bl(st, [
        "<b>Timing:</b> within 5-7 days once patient stabilised and swelling allows "
          "adequate assessment. Delay >2-3 weeks -> fibrous union -> harder reduction",
        "<b>Principle:</b> restore dental occlusion first, then reduce and fix fractures "
          "from inferior to superior (bottom-up) for Le Fort I and II; "
          "coronal approach for Le Fort III",
        "<b>Maxillomandibular Fixation (MMF) / Intermaxillary Fixation (IMF):</b>",
    ], S)
    bl(st, [
        "Erich Arch Bars: stainless steel bars wired to upper and lower teeth; "
          "hooks attach rubber bands -> establishes correct occlusion",
        "Ernst Ligatures, Ivy Loops: direct tooth-to-tooth wiring",
        "Bone screws with hooks (modern technique): screwed directly into maxilla/mandible",
    ], S, sub=True)
    bl(st, [
        "<b>Open Reduction Internal Fixation (ORIF) with titanium miniplates:</b> "
          "1.5-2.0 mm plates; at least 2-3 screws each side of fracture",
        "<b>Le Fort I repair:</b> intraoral approach (gingivobuccal sulcus incision); "
          "fixation at piriform rim and zygomaticomaxillary buttresses bilaterally",
        "<b>Le Fort II repair:</b> intraoral + lower eyelid / transconjunctival incision; "
          "fixation at infraorbital rim, nasofrontal junction, "
          "zygomaticomaxillary buttresses; orbital floor reconstruction if needed",
        "<b>Le Fort III repair:</b> CORONAL (bicoronal) incision + "
          "lower eyelid + intraoral incisions; "
          "fixation at frontozygomatic suture, zygomatic arch, "
          "nasofrontal junction, orbital walls; NOE (naso-orbito-ethmoid) repair if needed. "
          "Most complex; requires multiple surgical exposures (KJ Lee Essential ORL 11e)",
        "<b>Rowe Disimpaction Forceps:</b> used to disengage impacted maxilla "
          "when digital reduction is insufficient before rigid fixation",
        "MMF usually removed once rigid fixation applied; "
          "surgeon may leave in place for 2-4 weeks if fixation precarious",
    ], S)
    sp(st, 4)

    # 7. COMPLICATIONS
    h1(st, "7.  COMPLICATIONS", S)
    h2(st, "Immediate", S)
    bl(st, [
        "Airway obstruction (posterior impaction + haemorrhage)",
        "Massive haemorrhage (from sphenopalatine, descending palatine, "
          "anterior ethmoidal, and internal maxillary arteries)",
        "Aspiration (blood, teeth, bone fragments)",
        "CSF leak + meningitis (Le Fort II and III)",
        "Optic nerve injury / blindness (Le Fort III with orbital apex involvement)",
        "Associated TBI (intracranial haemorrhage, contusion)",
    ], S)
    h2(st, "Delayed / Late", S)
    bl(st, [
        "Malocclusion: open bite, crossbite if inadequate reduction",
        "Facial deformity: midface retrusion, enophthalmos, telecanthus",
        "Infraorbital nerve hypoaesthesia (Le Fort II - may be permanent)",
        "Diplopia (entrapped orbital fat or inferior rectus in orbital floor fracture)",
        "Anosmia (olfactory nerve disruption)",
        "Post-traumatic sinusitis / mucocoele",
        "Osteomyelitis (especially in compound/contaminated fractures)",
        "Non-union / malunion (if fixation inadequate or delayed treatment)",
        "Epiphora (dacryocystic injury -> lacrimal obstruction in Le Fort II)",
        "Persistent CSF rhinorrhoea -> meningitis",
    ], S)
    sp(st, 4)

    # 8. VIVA Q&A
    h1(st, "8.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. What is the ONE anatomical structure involved in ALL three Le Fort fractures?", S)
    bl(st, [
        "The <b>PTERYGOID PLATES</b> of the sphenoid bone",
        "Both medial and lateral pterygoid plates are fractured in Le Fort I, II, and III",
        "This is because all Le Fort fractures extend posteriorly to the pterygomaxillary junction",
        "Clinical relevance: posterior haemorrhage from pterygoid plexus is common in all levels",
    ], S); sp(st, 2)

    vq(st, "Q2. How do you clinically distinguish Le Fort I, II, and III at bedside?", S)
    bl(st, [
        "<b>Mobility test:</b> one hand stabilises forehead; other grasps hard palate and rocks",
        "Le Fort I: ONLY hard palate + upper teeth move (nose stays fixed) - 'loose denture'",
        "Le Fort II: NOSE + HARD PALATE move together (eyes/orbits stay fixed) - 'floating maxilla'",
        "Le Fort III: ENTIRE FACE moves including orbits/eyes - 'floating face / craniofacial disjunction'",
        "KEY DISTINCTION Le Fort II vs III: in Le Fort III, "
          "the zygomatic arch is fractured and ZF suture is involved -> "
          "orbits move with the face",
    ], S); sp(st, 2)

    vq(st, "Q3. Why is nasotracheal intubation relatively contraindicated in Le Fort II/III?", S)
    bl(st, [
        "Le Fort II and III fractures frequently fracture the CRIBRIFORM PLATE "
          "(nasofrontal component of these fractures)",
        "A fractured cribriform plate creates a direct communication between the "
          "nasal cavity and the anterior cranial fossa",
        "Nasotracheal tube may pass INTRACRANIALLY through the fractured cribriform plate "
          "instead of into the trachea -> catastrophic complication",
        "OROTRACHEAL intubation is preferred",
        "If oral route impossible -> surgical airway (cricothyrotomy or tracheostomy)",
    ], S); sp(st, 2)

    vq(st, "Q4. What is the significance of the facial buttresses in Le Fort fracture repair?", S)
    bl(st, [
        "Buttresses are thickened bony pillars providing structural support to the midface",
        "Fractures follow the WEAK zones between buttresses",
        "Buttresses provide adequate BONE STOCK for plate and screw fixation in ORIF",
        "Key vertical buttresses for fixation: nasomaxillary, zygomaticomaxillary, "
          "pterygomaxillary",
        "Key horizontal buttresses: infraorbital rim, frontal bar, zygomatic arch, "
          "maxillary alveolus",
        "Strategy: restore each buttress with miniplates (1.5-2.0 mm) "
          "to reconstruct 3D facial skeleton",
    ], S); sp(st, 2)

    vq(st, "Q5. What is the Le Fort IV fracture?", S)
    bl(st, [
        "Not part of the original Le Fort (1901) classification",
        "Le Fort IV = Le Fort III pattern + FRONTAL BONE fracture "
          "(involvement of the anterior cranial fossa)",
        "Represents the most severe midfacial disruption with intracranial extension",
        "Associated with significant TBI, CSF leak, dural tear",
        "Requires combined neurosurgical + maxillofacial approach",
        "(Described in Tintinalli Emergency Medicine; not universally used in all classifications)",
    ], S); sp(st, 2)

    vq(st, "Q6. What is craniofacial disjunction and how is it managed?", S)
    bl(st, [
        "Craniofacial disjunction = Le Fort III fracture = "
          "complete separation of entire face from skull base",
        "<b>Emergency:</b> "
          "Airway (oral intubation / tracheostomy); "
          "haemorrhage control (nasal packing, angioembolisation); "
          "manual forward traction on face to relieve posterior impaction",
        "<b>Definitive (ORIF):</b> Bicoronal flap + transconjunctival + "
          "intraoral approach; "
          "fixation at frontozygomatic suture, zygomatic arches, "
          "nasofrontal junction with titanium plates; "
          "orbital floor and medial wall reconstruction; "
          "MMF for correct occlusion",
        "<b>Complications:</b> anosmia, telecanthus, enophthalmos, "
          "persistent CSF rhinorrhoea, facial elongation if under-reduced",
    ], S); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Scott-Brown's OHN&S 8e Vol 1 Ch.107 | KJ Lee Essential ORL 11e | "
        "Cummings ORL 7e Ch.20 | Tintinalli Emergency Medicine 9e | "
        "Dhingra ENT 8e | Le Fort R (1901) - original cadaveric study",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/LeFort_Fractures_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Le Fort Fractures - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

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Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_le_fort.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/ptc-notes/generate_le_fort.py'

#!/usr/bin/env python3
# Facial Nerve Palsy Following Head Injury - ENT PG Exam Notes (5-6 pages)
# Palette 19: Dark teal-slate (#0C3D4A) / deep plum-red (#6B0A3A) / amber-olive (#5C4A00)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

# Palette 19
C_H1_BG  = colors.HexColor("#0C3D4A")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#6B0A3A")
C_H2_BG  = colors.HexColor("#FFF0F5")
C_H3_FG  = colors.HexColor("#5C4A00")
C_H3_BG  = colors.HexColor("#FFF8E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#0C3D4A")
C_ALT    = colors.HexColor("#E6F3F7")
C_PEARL  = colors.HexColor("#E6F3F7")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#0C3D4A")
C_VQ_BG  = colors.HexColor("#FFF8E0")
C_VQ_FG  = colors.HexColor("#5C4A00")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("FACIAL NERVE PALSY FOLLOWING HEAD INJURY", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e Vol 2 (Ch.112), Cummings ORL 7e, "
        "KJ Lee Essential ORL 11e, Dhingra ENT 8e, Fisch & Mattox Microsurgery",
        S["sub"]))
    rule(st); sp(st, 2)

    # 1. INTRODUCTION
    h1(st, "1.  INTRODUCTION", S)
    bl(st, [
        "Facial nerve palsy following head injury = one of the most distressing complications "
          "of temporal bone / skull base trauma",
        "Incidence: facial nerve paralysis occurs in approximately "
          "<b>7% of longitudinal</b> and <b>40-50% of transverse</b> temporal bone fractures",
        "The facial nerve is the <b>most commonly injured cranial nerve</b> in temporal bone trauma",
        "Management is deferred until the patient is <b>medically and neurologically stable</b>, "
          "as most cases involve life-threatening associated injuries (Scott-Brown's OHN&S 8e)",
        "Two critical questions at presentation:",
    ], S)
    bl(st, [
        "<b>IMMEDIATE or DELAYED onset?</b> - determines prognosis and urgency of surgery",
        "<b>COMPLETE or INCOMPLETE palsy?</b> - determines need for investigation and timing",
    ], S, sub=True)
    pearl(st,
        "IMMEDIATE complete palsy = nerve transection / severe injury = urgent surgical exploration. "
        "DELAYED onset palsy = neuropraxia / perineural oedema = conservative management first; "
        "excellent spontaneous recovery expected. "
        "(Cummings ORL 7e; KJ Lee Essential ORL 11e)", S)
    sp(st, 4)

    # 2. ANATOMY - RELEVANT
    h1(st, "2.  RELEVANT ANATOMY OF THE FACIAL NERVE", S)
    bl(st, [
        "Facial nerve (CN VII) exits brainstem at cerebellopontine angle (CPA), "
          "enters internal auditory canal (IAC) -> travels through temporal bone in "
          "the facial nerve canal (Fallopian canal)",
        "<b>Three segments within temporal bone:</b>",
    ], S)
    bl(st, [
        "<b>Labyrinthine segment</b> (3-5 mm): from IAC fundus to geniculate ganglion. "
          "Narrowest part of Fallopian canal (0.68 mm). "
          "MOST VULNERABLE segment in temporal bone trauma. "
          "No perineural epineurium here = least able to tolerate oedema/compression",
        "<b>Tympanic (horizontal) segment</b> (11 mm): from geniculate ganglion "
          "to pyramidal eminence. Runs along medial wall of middle ear just below "
          "horizontal semicircular canal. Dehiscent (thin bone / no bone) in "
          "approximately 55% of normal temporal bones = vulnerable",
        "<b>Mastoid (vertical) segment</b> (13 mm): from pyramidal eminence "
          "to stylomastoid foramen. Gives off branch to stapedius muscle and "
          "chorda tympani (taste, submandibular/sublingual salivation)",
    ], S, sub=True)
    bl(st, [
        "Extratemporal: after stylomastoid foramen -> pes anserinus -> "
          "five branches: Temporal, Zygomatic, Buccal, Marginal mandibular, Cervical "
          "(TZBMC - To Zanzibar By Motor Car)",
        "<b>Geniculate ganglion</b>: first genu; gives off Greater Superficial Petrosal Nerve (GSPN) "
          "for lacrimal gland, and connects to Nerve to Stapedius. "
          "Most common site of injury in temporal bone fractures",
    ], S)
    sp(st, 4)

    # 3. TEMPORAL BONE FRACTURES
    h1(st, "3.  TEMPORAL BONE FRACTURES AND FACIAL NERVE INJURY", S)
    h2(st, "Classification of Temporal Bone Fractures", S)
    bl(st, [
        "<b>Traditional classification (by fracture line orientation):</b>",
    ], S)
    bl(st, [
        "<b>Longitudinal fracture (80%):</b> parallel to long axis of petrous bone. "
          "Caused by lateral temporal blow (e.g. temple). "
          "Fracture runs through squamous temporal bone -> EAC -> middle ear -> "
          "anterior to cochlea -> foramen lacerum / foramen ovale. "
          "Facial nerve palsy in ~7% (usually neuropraxia at geniculate ganglion). "
          "CHL (ossicular disruption), haemotympanum, TM tear common. "
          "Cochlea usually spared; SNHL uncommon",
        "<b>Transverse fracture (20%):</b> perpendicular to long axis of petrous bone. "
          "Caused by frontal or occipital blow (front/back of head). "
          "Fracture crosses petrous pyramid -> through cochlea, labyrinth, IAC -> "
          "foramen magnum. Facial nerve palsy in 40-50% (often complete). "
          "Severe SNHL / dead ear; vertigo; haemotympanum without TM tear. "
          "Higher severity injuries",
    ], S, sub=True)
    bl(st, [
        "<b>Modern classification (by cochlear involvement):</b>",
    ], S)
    bl(st, [
        "<b>Otic capsule-sparing fracture</b>: more common; equivalent to longitudinal. "
          "Facial palsy in ~6%; generally better prognosis",
        "<b>Otic capsule-violating fracture</b>: less common; equivalent to transverse. "
          "Facial palsy in ~30%; significantly worse outcomes; dead ear; "
          "higher rate of complete nerve damage",
    ], S, sub=True)
    h2(st, "Sites of Facial Nerve Injury in Temporal Bone Fractures", S)
    bl(st, [
        "<b>Geniculate ganglion (most common):</b> "
          "site most commonly injured in temporal bone fractures, "
          "especially longitudinal fractures. "
          "Nerve is tethered here and vulnerable to shearing forces",
        "<b>Perigeniculate region / labyrinthine segment:</b> most narrow segment; "
          "least tolerance to oedema; pressure injury common",
        "Tympanic segment: vulnerable in longitudinal fractures "
          "(fracture line passes medial to middle ear)",
        "Mastoid segment: may be injured in through-and-through injuries",
        "Extratemporal: knife wounds, penetrating face trauma",
    ], S)
    h2(st, "Mechanisms of Facial Nerve Injury", S)
    bl(st, [
        "<b>Neuropraxia (Sunderland Grade I):</b> conduction block, no axon disruption; "
          "best prognosis; complete recovery expected",
        "<b>Axonotmesis (Sunderland Grade II-IV):</b> axon disruption but endoneurium intact; "
          "Wallerian degeneration of distal nerve occurs; recovery possible but slower; "
          "may have some synkinesis",
        "<b>Neurotmesis (Sunderland Grade V):</b> complete nerve transection; "
          "no spontaneous recovery; requires surgical repair",
        "<b>Compression / perineural oedema:</b> nerve intact but compressed "
          "within bony canal by haematoma or oedema -> delayed palsy; "
          "good prognosis with decompression or spontaneous resolution",
        "<b>Bony spicule</b> penetrating nerve: direct mechanical injury",
    ], S)
    sp(st, 4)

    # 4. CLINICAL ASSESSMENT
    h1(st, "4.  CLINICAL ASSESSMENT", S)
    h2(st, "History", S)
    bl(st, [
        "Mechanism of head injury: RTA, fall, assault, gunshot, blast",
        "<b>ONSET OF PALSY - most critical question:</b>",
    ], S)
    bl(st, [
        "<b>Immediate onset</b> (at time of injury): "
          "nerve is transected, compressed by bony fragment, or severely disrupted. "
          "Poor spontaneous prognosis. Warrants urgent investigation and likely surgery",
        "<b>Delayed onset</b> (hours to days after injury): "
          "perineural oedema developing in the narrow Fallopian canal. "
          "Excellent prognosis - spontaneous recovery in 90-95%",
    ], S, sub=True)
    bl(st, [
        "Associated symptoms: hearing loss (CHL vs SNHL), tinnitus, vertigo, "
          "otorrhoea, CSF otorrhoea, otalgia, blood from ear",
        "History of loss of consciousness, GCS at scene",
    ], S)
    h2(st, "Physical Examination", S)
    bl(st, [
        "<b>Facial nerve grading - House-Brackmann Scale:</b>",
    ], S)
    bl(st, [
        "Grade I: Normal function",
        "Grade II: Mild dysfunction - slight weakness on close inspection; "
          "eye closes completely with effort",
        "Grade III: Moderate dysfunction - obvious weakness; "
          "eye closes completely with effort",
        "Grade IV: Moderately severe - obvious disfiguring weakness; "
          "eye does NOT close completely",
        "Grade V: Severe - barely perceptible movement",
        "Grade VI: Total paralysis - no movement",
    ], S, sub=True)
    bl(st, [
        "<b>Topographic assessment</b> (to localise lesion level in facial nerve):",
    ], S)
    bl(st, [
        "Lacrimation test (Schirmer test): GSPN function. "
          "Reduced lacrimation -> lesion above geniculate ganglion (proximal to GSPN origin)",
        "Stapedial reflex (audiometry): Nerve to stapedius. "
          "Absent reflex -> lesion above stapedius nerve origin (in tympanic segment or proximal)",
        "Taste testing (electrogustometry / sugar/salt anterior 2/3 tongue): chorda tympani. "
          "Absent taste -> lesion above chorda tympani origin (above lower mastoid segment)",
        "If all three abnormal -> lesion at or proximal to geniculate ganglion "
          "(perigeniculate or labyrinthine region)",
    ], S, sub=True)
    bl(st, [
        "Ear: haemotympanum, TM perforation, CSF otorrhoea, Battle's sign "
          "(mastoid ecchymosis - retroauricular bruising; appears 24-48h after injury)",
        "Audiometry: CHL (ossicular disruption in longitudinal Fx), SNHL (transverse Fx)",
        "Nystagmus, Romberg test (vestibular injury)",
    ], S)
    sp(st, 4)

    # 5. INVESTIGATIONS
    h1(st, "5.  INVESTIGATIONS", S)
    h2(st, "Imaging", S)
    bl(st, [
        "<b>HRCT temporal bone (Gold Standard):</b> 0.5-1 mm axial and coronal slices. "
          "Shows fracture line, involvement of Fallopian canal, cochlear/labyrinthine involvement, "
          "ossicular disruption, otic capsule status, intracranial air. "
          "Guides surgical approach",
        "<b>MRI with contrast:</b> identifies nerve enhancement (perineural inflammation), "
          "haematoma compressing nerve, intracranial pathology (epidural haematoma, "
          "cerebral contusion)",
    ], S)
    h2(st, "Electrophysiological Tests - KEY for Management Decisions", S)
    bl(st, [
        "<b>Electroneuronography (ENoG) / Evoked EMG:</b>",
    ], S)
    bl(st, [
        "Compares amplitude of compound muscle action potential (CMAP) of affected "
          "vs unaffected side",
        "Reflects percentage of viable (non-degenerated) axons remaining",
        "Best performed 3-14 days after injury (Wallerian degeneration takes 72h to develop)",
        "<b>> 90% degeneration</b> (< 10% of normal amplitude) within 14 days = "
          "indication for surgical decompression",
        "ENoG > 90% degeneration + no voluntary motor units on EMG = worst prognosis = surgery",
        "Most sensitive objective test for prognosis in traumatic facial palsy",
    ], S, sub=True)
    bl(st, [
        "<b>Electromyography (EMG):</b>",
    ], S)
    bl(st, [
        "Assesses voluntary motor unit potentials in facial muscles",
        "Fibrillation potentials = denervation (Wallerian degeneration occurred)",
        "Polyphasic potentials = reinnervation (recovery occurring)",
        "EMG is positive after 14-21 days (earlier testing unreliable)",
        "Used alongside ENoG: if fibrillation without voluntary units -> surgery",
        "Polyphasic units (even if few) = some axons recovering -> continue conservative",
    ], S, sub=True)
    bl(st, [
        "<b>Nerve Excitability Test (NET) and Maximal Stimulation Test (MST):</b> "
          "older bedside tests; less objective; largely replaced by ENoG",
        "<b>BERA/ABR:</b> assess cochlear function (auditory brainstem response); "
          "important for surgical planning",
        "Audiometry: pure tone + impedance audiometry",
    ], S)
    sp(st, 4)

    # 6. MANAGEMENT
    h1(st, "6.  MANAGEMENT", S)
    h2(st, "General / Initial", S)
    bl(st, [
        "Stabilise patient: ATLS principles; head injury, cervical spine, "
          "haemorrhage management take priority",
        "Facial nerve management deferred until medically and neurologically stable "
          "(Scott-Brown's OHN&S 8e)",
        "<b>Eye care:</b> IMMEDIATE and ongoing - corneal exposure due to lagophthalmos "
          "threatens vision. Lubricating eye drops hourly, eye ointment at night, "
          "moisture chamber, taping eyelid closed at night. "
          "Ophthalmology review if corneal ulcer develops",
    ], S)
    h2(st, "Conservative Management (Delayed / Incomplete Palsy)", S)
    bl(st, [
        "For <b>delayed-onset palsy</b> and all <b>incomplete (partial) palsies</b>: "
          "conservative management first",
        "<b>High-dose corticosteroids:</b> Prednisolone 1 mg/kg/day x 10-14 days "
          "(then taper) - reduces perineural oedema in Fallopian canal. "
          "Best started within 72 hours of injury",
        "Serial clinical examination with House-Brackmann grading",
        "Serial ENoG at 3 days, 7 days, 14 days",
        "Physiotherapy: facial exercises to maintain muscle tone",
        "<b>Expected outcome:</b> 90-95% of delayed-onset palsies recover completely "
          "or near-completely without surgery",
    ], S)
    dose(st,
        "Steroids: Prednisolone 1 mg/kg/day (max 60 mg) for 10-14 days, "
        "then taper over 5-7 days. "
        "Start within 72 hours of palsy onset for maximum benefit. "
        "Cover with proton-pump inhibitor.", S)
    h2(st, "Surgical Management - Facial Nerve Decompression", S)
    h3(st, "Indications for Surgery", S)
    bl(st, [
        "<b>Immediate complete palsy</b> confirmed at time of injury "
          "(nerve transected / bony fragment penetrating nerve)",
        "<b>ENoG > 90% degeneration</b> (< 10% remaining amplitude) "
          "within <b>14 days</b> of onset, AND no voluntary motor units on EMG",
        "No spontaneous recovery after 3-6 months of conservative management",
        "HRCT shows bony spicule impaling the nerve, or haematoma compressing nerve "
          "in Fallopian canal",
    ], S)
    h3(st, "Timing of Surgery", S)
    bl(st, [
        "<b>Immediate palsy:</b> explore as early as possible (within 2-3 weeks ideally) "
          "once patient medically stable",
        "<b>ENoG-guided:</b> when ENoG threshold reached (>90% degeneration within 14 days)",
        "Delay beyond 3-4 weeks -> fibrous tissue in nerve canal -> "
          "harder dissection; worse outcomes",
        "Delay beyond 12 months -> irreversible muscle atrophy (motor end-plates lost)",
    ], S)
    h3(st, "Surgical Approaches", S)
    bl(st, [
        "<b>Transmastoid approach:</b> accesses tympanic and mastoid segments. "
          "Most commonly used approach for traumatic facial nerve decompression. "
          "Preserves hearing",
        "<b>Middle cranial fossa (MCF) approach:</b> accesses labyrinthine segment "
          "and geniculate ganglion (most common injury site). "
          "Requires neurosurgical/otological expertise. Preserves hearing",
        "<b>Translabyrinthine approach:</b> best access to entire intratemporal "
          "facial nerve; used when hearing already absent (transverse Fx with dead ear)",
        "Most complete decompression: MCF + transmastoid combined approach "
          "(accesses entire intratemporal course)",
    ], S)
    h3(st, "Surgical Technique", S)
    bl(st, [
        "Decompress nerve by removing bone of Fallopian canal "
          "(at least 180 degrees circumference, ideally 270 degrees)",
        "Do NOT open the epineurium routinely (risk of damage to fascicles)",
        "If nerve is transected: end-to-end anastomosis (if < 1 cm gap) "
          "OR cable graft using sural nerve / greater auricular nerve "
          "(if gap > 1 cm)",
        "If irreversible nerve damage with no proximal stump: "
          "hypoglossal-facial anastomosis (XII-VII), masseteric branch reinnervation, "
          "gracilis free muscle transfer",
    ], S)
    sp(st, 4)

    # 7. COMPARISON TABLE
    h1(st, "7.  LONGITUDINAL vs TRANSVERSE TEMPORAL BONE FRACTURE (Comparison)", S)
    data = [
        ["Feature",              "Longitudinal Fracture",               "Transverse Fracture"],
        ["Frequency",            "80% of temporal bone Fx",             "20% of temporal bone Fx"],
        ["Force direction",      "Lateral temporal blow",               "Frontal or occipital blow"],
        ["Fracture line",        "Parallel to petrous pyramid;\nthrough EAC, middle ear, "
                                  "anterior to cochlea",                 "Perpendicular to petrous;\nthrough cochlea, labyrinth, IAC"],
        ["Facial nerve palsy",   "~7% (usually neuropraxia;\ngeniculate ganglion)", "40-50% (often complete;\nmore severe)"],
        ["Hearing loss",         "CHL - ossicular disruption\n(incudostapedial most common)", "Severe SNHL / dead ear\n(cochlear/labyrinthine Fx)"],
        ["TM",                   "Often torn / perforated;\nblood from ear",  "Intact; haemotympanum only"],
        ["Cochlea/Labyrinth",    "Spared (otic capsule\nsparing)",      "Violated (otic capsule\nviolating)"],
        ["Vertigo",              "Mild / transient\n(concussion of labyrinth)", "Severe, protracted\n(labyrinthine destruction)"],
        ["Battle's sign",        "May be present",                       "May be present"],
        ["CSF otorrhoea",        "Less common",                          "More common\n(tegmen or dural breach)"],
        ["Prognosis FN",         "Excellent (neuropraxia;\nspontaneous recovery)", "Guarded (axonotmesis /\nneurotmesis more common)"],
    ]
    st.append(tbl(data, [W*0.22, W*0.39, W*0.39], S))
    sp(st, 4)

    # 8. VIVA Q&A
    h1(st, "8.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. Why is immediate vs delayed onset of palsy so important in traumatic facial palsy?", S)
    bl(st, [
        "<b>Immediate (at time of injury):</b> nerve is transected, severely compressed "
          "by bony fragment, or crushed. No spontaneous recovery possible. "
          "Requires urgent investigation and likely surgical decompression/repair",
        "<b>Delayed (hours to days post-injury):</b> "
          "mechanism = progressive perineural oedema in narrow Fallopian canal. "
          "Nerve is structurally intact (neuropraxia). "
          "90-95% recover spontaneously or with steroids. "
          "Conservative management first",
        "This distinction is the single most important clinical decision-making step "
          "in traumatic facial palsy management",
    ], S); sp(st, 2)

    vq(st, "Q2. What is ENoG and what are the surgical thresholds?", S)
    bl(st, [
        "ENoG = Electroneuronography. Measures compound muscle action potential "
          "(CMAP) amplitude of affected side vs normal side as percentage",
        "Reflects percentage of viable (non-Wallerian-degenerated) axons remaining",
        "Best performed 3-14 days after injury (Wallerian degeneration = 72h to develop)",
        "<b>Surgical threshold: > 90% degeneration</b> (< 10% amplitude remaining) "
          "within 14 days + NO voluntary motor units on EMG",
        "Below this threshold: conservative management; "
          "above = surgical decompression indicated",
        "Polyphasic EMG units = reinnervation occurring = continue conservative",
    ], S); sp(st, 2)

    vq(st, "Q3. What is the most common site of facial nerve injury in temporal bone fractures?", S)
    bl(st, [
        "<b>Geniculate ganglion / perigeniculate region</b> = most commonly injured site",
        "Reasons:",
    ], S)
    bl(st, [
        "Nerve is tethered / angulated at geniculate ganglion (first genu)",
        "GSPN pulls the nerve anteriorly during trauma (traction injury)",
        "Labyrinthine segment immediately proximal is the narrowest part of Fallopian canal "
          "(no tolerance for oedema)",
        "Most temporal bone fracture lines pass close to or through the geniculate fossa",
    ], S, sub=True); sp(st, 2)

    vq(st, "Q4. How do you perform topographic localisation of the lesion in traumatic facial palsy?", S)
    bl(st, [
        "Test each branch in a proximal-to-distal fashion:",
    ], S)
    bl(st, [
        "Schirmer test (lacrimation): tests GSPN -> reduced tears = lesion above geniculate ganglion",
        "Stapedial reflex (impedance audiometry): absent = lesion above nerve to stapedius "
          "(proximal to pyramidal eminence / tympanic segment)",
        "Electrogustometry (anterior 2/3 tongue taste): tests chorda tympani -> "
          "absent taste = lesion above chorda tympani (lower mastoid segment or proximal)",
        "All three abnormal -> lesion at geniculate ganglion or labyrinthine segment",
    ], S, sub=True)
    bl(st, [
        "Note: topographic tests are unreliable in acute trauma (oedema affects results). "
          "HRCT and ENoG are more reliable for acute management decisions",
    ], S); sp(st, 2)

    vq(st, "Q5. What is the surgical approach of choice for decompression in traumatic facial palsy?", S)
    bl(st, [
        "Depends on site of injury and hearing status:",
    ], S)
    bl(st, [
        "<b>Labyrinthine segment / geniculate ganglion:</b> "
          "Middle Cranial Fossa (MCF) approach - preserves hearing",
        "<b>Tympanic + mastoid segments:</b> "
          "Transmastoid approach - preserves hearing",
        "<b>Complete intratemporal decompression:</b> "
          "MCF + transmastoid combined approach",
        "<b>Hearing already lost (transverse Fx with dead ear):</b> "
          "Translabyrinthine approach - best access, no hearing to preserve",
    ], S, sub=True)
    bl(st, [
        "Decompress 180-270 degrees of Fallopian canal circumference; "
          "do NOT open epineurium routinely",
        "If transection: end-to-end if < 1 cm gap; "
          "cable graft (sural / greater auricular nerve) if > 1 cm gap",
    ], S); sp(st, 2)

    vq(st, "Q6. What is Battle's sign and what does it indicate?", S)
    bl(st, [
        "Battle's sign = <b>retroauricular / mastoid ecchymosis</b> "
          "(bruising behind the ear, overlying the mastoid process)",
        "Appears <b>24-48 hours after head injury</b> (delayed bruising as blood tracks "
          "through mastoid air cells to skin)",
        "Indicates <b>temporal bone fracture</b> (specifically posterior temporal / "
          "mastoid involvement)",
        "Named after Dr. William Henry Battle (1855-1936)",
        "Clinical significance: always examine the mastoid region in head injury patients. "
          "Battle's sign should trigger HRCT temporal bone. "
          "Associated with CSF otorrhoea, haemotympanum, and facial nerve injury risk",
    ], S); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Scott-Brown's OHN&S 8e Vol 2 Ch.112 | Cummings ORL 7e | "
        "KJ Lee Essential ORL 11e | Dhingra ENT 8e | "
        "Fisch U & Mattox D: Microsurgery of the Skull Base | "
        "Sunderland Nerve Classification",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/FacialNervePalsy_HeadInjury_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Facial Nerve Palsy Following Head Injury - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Gentamicin - ENT PG Exam Notes (5-6 pages, bullet-point style)
# Palette 20: Dark indigo-navy (#1A1A4A) / deep rose-red (#8B0035) / warm bronze (#6B4A00)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

C_H1_BG  = colors.HexColor("#1A1A4A")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#8B0035")
C_H2_BG  = colors.HexColor("#FFF0F5")
C_H3_FG  = colors.HexColor("#6B4A00")
C_H3_BG  = colors.HexColor("#FFF8E0")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#1A1A4A")
C_ALT    = colors.HexColor("#EEEEFF")
C_PEARL  = colors.HexColor("#EEEEFF")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#1A1A4A")
C_VQ_BG  = colors.HexColor("#FFF8E0")
C_VQ_FG  = colors.HexColor("#6B4A00")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("GENTAMICIN - ENT PG EXAM NOTES", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Shambaugh Surgery of the Ear, Cummings ORL 7e, KJ Lee Essential ORL 11e, "
        "Dhingra ENT 8e, Harrison's Internal Medicine 22e, BNF / Standard Pharmacology",
        S["sub"]))
    rule(st); sp(st, 2)

    # 1. OVERVIEW
    h1(st, "1.  OVERVIEW & CLASSIFICATION", S)
    bl(st, [
        "<b>Gentamicin</b> = an <b>aminoglycoside antibiotic</b> of major importance in ENT "
          "for two distinct roles: (1) systemic antibiotic for gram-negative infections, "
          "(2) intratympanic (IT) vestibular ablation agent for Meniere's disease",
        "<b>Class:</b> Aminoglycoside antibacterial; naturally derived from "
          "<i>Micromonospora purpurea</i> (note: 'mycin' suffix = from Streptomyces; "
          "'micin' suffix = from Micromonospora)",
        "<b>Other aminoglycosides:</b> Streptomycin, Tobramycin, Amikacin, Neomycin, "
          "Netilmicin, Kanamycin. Gentamicin = most widely used systemic aminoglycoside",
        "<b>Molecular basis:</b> polycationic (positively charged at physiological pH); "
          "amino sugars linked to an aminocyclitol ring",
    ], S)
    sp(st, 4)

    # 2. PHARMACOLOGY
    h1(st, "2.  PHARMACOLOGY", S)
    h2(st, "Mechanism of Action", S)
    bl(st, [
        "<b>Target:</b> 30S ribosomal subunit of bacteria",
        "<b>Mechanism:</b> Binds to 16S rRNA of the 30S subunit -> "
          "causes misreading of mRNA codons -> incorporation of wrong amino acids "
          "-> formation of non-functional / toxic proteins -> "
          "bacterial cell death (BACTERICIDAL)",
        "Additionally: disrupts bacterial cell membrane integrity "
          "(abnormal proteins insert into membrane -> increased permeability -> "
          "further aminoglycoside uptake = 'self-promoting uptake')",
        "Requires AEROBIC conditions (energy-dependent uptake via electron transport chain). "
          "Therefore, INACTIVE against strict anaerobes",
        "<b>Concentration-dependent killing</b> (NOT time-dependent): "
          "maximum effect at high peak concentrations. "
          "Justifies once-daily dosing (higher peak, same total dose)",
        "Exhibits a significant <b>Post-Antibiotic Effect (PAE)</b>: "
          "bacterial suppression persists even after drug concentration falls below MIC",
    ], S)
    h2(st, "Spectrum of Activity", S)
    bl(st, [
        "<b>Primarily gram-negative aerobic bacilli:</b>",
    ], S)
    bl(st, [
        "<i>Pseudomonas aeruginosa</i> (very important in ENT - malignant otitis externa)",
        "<i>Escherichia coli, Klebsiella, Proteus, Enterobacter, Serratia</i>",
        "<i>Acinetobacter</i>",
    ], S, sub=True)
    bl(st, [
        "<b>Gram-positive synergy (with beta-lactams):</b> "
          "Gentamicin + penicillin/ampicillin = SYNERGISTIC against "
          "<i>Enterococcus</i> and <i>Streptococcus viridans</i> (endocarditis)",
        "<b>Inactive against:</b> Streptococcus pneumoniae, most anaerobes, "
          "MRSA (alone), fungi, viruses",
        "In ENT: key use in <b>malignant otitis externa</b> "
          "(Pseudomonas) and severe gram-negative head and neck infections",
    ], S)
    h2(st, "Pharmacokinetics", S)
    bl(st, [
        "<b>Absorption:</b> NOT absorbed orally (ionised, hydrophilic). "
          "Given IM or IV. Topical forms for ear drops",
        "<b>Distribution:</b> Vd = 0.25 L/kg (extracellular fluid mainly). "
          "Does NOT cross blood-brain barrier well (CSF levels low). "
          "Does NOT enter cells well. "
          "DOES concentrate in renal cortex and inner ear (cochlear and vestibular endolymph)",
        "<b>Protein binding:</b> very low (< 10%)",
        "<b>Elimination:</b> excreted unchanged by glomerular filtration. "
          "Half-life 2-3 hours (normal renal function); "
          "prolonged markedly in renal impairment",
        "<b>Does NOT cross blood-brain barrier:</b> not used for meningitis alone",
        "<b>Crosses placenta:</b> ototoxicity risk to foetus",
    ], S)
    sp(st, 4)

    # 3. SYSTEMIC USE IN ENT
    h1(st, "3.  SYSTEMIC USE IN ENT", S)
    h2(st, "Indications in ENT", S)
    bl(st, [
        "<b>Malignant (Necrotising) Otitis Externa:</b> most important ENT indication. "
          "Caused by <i>Pseudomonas aeruginosa</i> in diabetics / immunocompromised. "
          "IV anti-pseudomonal antibiotics: ciprofloxacin preferred; "
          "gentamicin may be used as part of combination regimen for severe cases",
        "<b>Severe gram-negative head and neck infections:</b> "
          "deep neck space infections, parapharyngeal abscess with gram-negative organisms",
        "<b>Gentamicin ear drops (topical):</b> "
          "used for chronic otitis media with gram-negative organisms "
          "(Pseudomonas, Proteus) in patients with non-intact tympanic membrane. "
          "NOTE: risk of ototoxicity with drops in perforated TM is debated - "
          "use with caution",
    ], S)
    h2(st, "Dosing (Systemic)", S)
    dose(st,
        "Standard dosing: 3-5 mg/kg/day IV/IM in DIVIDED doses (TDS) - older regimen. "
        "Once-daily dosing (ODD / Extended Interval Dosing): 5-7 mg/kg IV once daily - "
        "preferred for most patients (better peak:MIC ratio; less nephrotoxicity). "
        "Adjust for renal function: reduce dose or extend interval. "
        "Therapeutic Drug Monitoring (TDM): MANDATORY.", S)
    h2(st, "Therapeutic Drug Monitoring (TDM)", S)
    bl(st, [
        "<b>Peak level</b> (drawn 30-60 min after IV infusion): "
          "target 5-10 mcg/mL (TDS dosing) for efficacy",
        "<b>Trough level</b> (drawn just before next dose): "
          "target < 2 mcg/mL (TDS dosing). "
          "Elevated trough = drug accumulating -> risk of nephrotoxicity and ototoxicity",
        "<b>Once-daily dosing:</b> use Hartford Nomogram / AUC monitoring; "
          "trough should be UNDETECTABLE before next dose",
        "Monitor: serum creatinine, urea, urine output, audiometry (if prolonged use)",
    ], S)
    sp(st, 4)

    # 4. OTOTOXICITY - MAJOR SECTION
    h1(st, "4.  OTOTOXICITY OF GENTAMICIN", S)
    h2(st, "Overview", S)
    bl(st, [
        "Ototoxicity = toxic damage to the inner ear (cochlea and/or vestibular system) "
          "from drug exposure",
        "Gentamicin is <b>predominantly VESTIBULOTOXIC</b> "
          "(cf. amikacin, neomycin = predominantly cochleotoxic)",
        "<b>Incidence:</b> cochlear toxicity 2-25%; vestibular toxicity up to 30% "
          "with prolonged courses",
        "Ototoxicity may be <b>irreversible</b> - hair cells in inner ear do NOT regenerate "
          "in mammals (unlike in fish and birds)",
    ], S)
    h2(st, "Mechanism of Ototoxicity", S)
    bl(st, [
        "<b>Uptake:</b> Gentamicin enters hair cells via mechanoelectrical transduction "
          "channels (MET channels / TRPA1) and endocytosis. "
          "It accumulates in hair cell cytoplasm and lysosomes",
        "<b>Reactive Oxygen Species (ROS) generation:</b> "
          "Gentamicin forms iron-gentamicin chelate complexes -> "
          "produces free radicals (ROS) via Fenton reaction. "
          "ROS cause lipid peroxidation of hair cell membranes -> oxidative stress -> "
          "apoptosis (programmed cell death) of hair cells",
        "<b>Mitochondrial damage:</b> ROS damage mitochondrial DNA and function. "
          "Mitochondrial A1555G mutation (12S rRNA) dramatically increases susceptibility "
          "(Shambaugh Surgery of the Ear): aminoglycoside binds mutant rRNA -> "
          "mimics normal rRNA binding site -> prevents mitochondrial protein translation "
          "-> hair cell death at lower drug concentrations",
        "<b>Site of cochlear damage:</b> outer hair cells (OHC) in the BASAL TURN of the cochlea "
          "are destroyed FIRST (basal turn = high-frequency region). "
          "Therefore, high-frequency SNHL appears first (4-8 kHz). "
          "Progresses from base toward apex with increasing dose/duration",
        "<b>Site of vestibular damage:</b> type I hair cells of the cristae ampullaris "
          "and maculae are selectively destroyed. "
          "Gentamicin preferentially damages the dark cells of the vestibular labyrinth",
    ], S)
    pearl(st,
        "SELECTIVE VESTIBULOTOXICITY: Gentamicin selectively accumulates in VESTIBULAR "
        "hair cells (not cochlear) because vestibular dark cells have a specific uptake "
        "mechanism for aminoglycosides. This property is EXPLOITED therapeutically "
        "in intratympanic gentamicin for Meniere's disease. "
        "(Cummings ORL 7e; KJ Lee Essential ORL 11e)", S)
    h2(st, "Risk Factors for Ototoxicity", S)
    bl(st, [
        "High cumulative dose and prolonged duration of treatment",
        "High trough drug levels (drug accumulation - most important risk factor)",
        "Renal impairment (drug accumulates -> elevated sustained levels)",
        "Concurrent use of other ototoxic drugs: loop diuretics (frusemide, ethacrynic acid), "
          "cisplatin, vancomycin, quinine, salicylates",
        "Pre-existing sensorineural hearing loss",
        "<b>Mitochondrial A1555G mutation (mt-rRNA 12S mutation):</b> "
          "hypersensitivity to aminoglycoside ototoxicity even at low doses; "
          "maternally inherited; screening recommended before aminoglycoside use "
          "(Shambaugh Surgery of the Ear)",
        "Age extremes (neonates and elderly), fever, dehydration",
        "Bacteraemia (increased entry to inner ear vasculature)",
    ], S)
    caut(st,
        "FRUSEMIDE + GENTAMICIN = HIGH-RISK COMBINATION. "
        "Loop diuretics increase permeability of stria vascularis blood-labyrinth barrier, "
        "causing dramatically increased gentamicin entry into endolymph -> "
        "irreversible severe SNHL. Avoid combination if possible; "
        "if unavoidable, maximise interval between doses.", S)
    h2(st, "Clinical Features of Ototoxicity", S)
    bl(st, [
        "<b>Cochlear toxicity:</b> "
          "high-frequency SNHL (initially 4-8 kHz; often not noticed by patient). "
          "Bilateral, symmetric. Tinnitus may precede hearing loss. "
          "Progresses to conversational frequencies with continued exposure",
        "<b>Vestibular toxicity:</b> "
          "oscillopsia (visual blurring with head movement), "
          "unsteady gait / ataxia, bilateral vestibulopathy, "
          "Dandy's syndrome (difficulty walking in dark / on uneven surfaces), "
          "positive Romberg test",
        "<b>SILENT ototoxicity:</b> hearing loss in high frequencies is subclinical initially; "
          "often not detected until significant damage has occurred. "
          "Hence audiometric monitoring is MANDATORY during systemic use",
    ], S)
    h2(st, "Monitoring for Ototoxicity", S)
    bl(st, [
        "Pre-treatment baseline audiogram",
        "Serial audiograms during prolonged treatment (every 7-14 days or per protocol)",
        "Vestibular function tests: head thrust test, dynamic visual acuity",
        "Trough drug levels: keep < 2 mcg/mL (TDS dosing)",
        "Renal function: creatinine, eGFR, urine output monitoring",
    ], S)
    sp(st, 4)

    # 5. INTRATYMPANIC GENTAMICIN
    h1(st, "5.  INTRATYMPANIC (IT) GENTAMICIN FOR MENIERE'S DISEASE", S)
    h2(st, "Rationale", S)
    bl(st, [
        "Meniere's disease = endolymphatic hydrops. Characterised by episodes of "
          "vertigo, fluctuating SNHL, tinnitus, and aural fullness",
        "In refractory Meniere's (failed dietary sodium restriction, betahistine, diuretics), "
          "ablation or reduction of vestibular function in the affected ear is required",
        "<b>Rationale:</b> gentamicin's selective vestibulotoxicity is EXPLOITED to "
          "chemically ablate the vestibular neuroepithelium of the affected ear",
        "Goal: destroy vestibular hair cells -> eliminate vestibular drive from affected ear "
          "-> brainstem ignores asymmetric input -> vertigo attacks cease",
        "<b>Advantage over surgical labyrinthectomy:</b> "
          "minimally invasive; preserves residual hearing in many patients; "
          "outpatient procedure",
    ], S)
    h2(st, "Patient Selection Criteria", S)
    bl(st, [
        "Definite or probable Meniere's disease (AAO-HNS criteria)",
        "Failed conservative therapy: "
          "low-salt diet (< 2g Na/day), betahistine, thiazide diuretics "
          "for at least 3-6 months",
        "Disabling vertigo attacks with significant functional impairment",
        "Unilateral disease (only ear) - bilateral Meniere's: greater caution",
        "Residual serviceable hearing in the ear: "
          "IT gentamicin preferred (over surgical ablation) when hearing to be preserved",
        "<b>Contraindication:</b> only-hearing ear (significant cochleotoxicity risk), "
          "known aminoglycoside hypersensitivity, pregnancy",
    ], S)
    h2(st, "Technique of Intratympanic Injection", S)
    bl(st, [
        "<b>Preparation:</b> Gentamicin 26.7 mg/mL (diluted from 40 mg/mL vial "
          "with sodium bicarbonate to achieve pH 6.4) - standard concentration used in most protocols",
        "<b>Procedure:</b> Patient supine with affected ear up; "
          "topical anaesthetic (EMLA cream or phenol) on TM; "
          "inject 0.3-0.5 mL through posteroinferior quadrant of TM using fine needle (25-27G); "
          "patient remains in same position for 20-30 minutes",
    ], S)
    h2(st, "Dosing Protocols", S)
    bl(st, [
        "<b>Low-dose / Titration protocol (Harker-Driscoll; 'symptom-guided'):</b>",
    ], S)
    bl(st, [
        "Single injection; reassess at 4-6 weeks",
        "Repeat injection only if vertigo continues",
        "Maximum 3-4 injections per course",
        "LOWER risk of hearing loss; slower onset of vestibular ablation",
        "Most commonly used UK and Australasian practice",
    ], S, sub=True)
    bl(st, [
        "<b>Fixed / High-dose protocol (Blakley protocol):</b>",
    ], S)
    bl(st, [
        "Weekly injections x 4 regardless of response",
        "More rapid and complete vestibular ablation",
        "HIGHER risk of significant hearing loss (up to 30%)",
        "Less favoured now due to hearing risk",
    ], S, sub=True)
    bl(st, [
        "<b>Daily / Continuous titration protocol:</b> daily injections until "
          "vestibular response (oscillopsia, imbalance) develops; "
          "high efficacy; high hearing loss risk",
    ], S)
    h2(st, "Outcomes", S)
    bl(st, [
        "Vertigo control: 70-90% of patients achieve complete or substantial "
          "relief of vertigo attacks",
        "Hearing preservation: low-dose protocol - approximately 15-20% risk of "
          "worsening hearing loss; high-dose protocol - up to 30% risk",
        "Cochlear safety improved with low-dose titration regimens",
        "May require repeat treatment if vertigo recurs",
    ], S)
    sp(st, 4)

    # 6. AMINOGLYCOSIDE COMPARISON
    h1(st, "6.  AMINOGLYCOSIDE COMPARISON - ENT RELEVANT", S)
    data = [
        ["Aminoglycoside",  "Primary Toxicity",     "ENT Relevance",               "Notes"],
        ["Gentamicin",      "VESTIBULOTOXIC\n(predominantly)", "IT injection - Meniere's;\nMalignant OE (Pseudomonas)", "Most important for ENT;\nselective vestibular damage"],
        ["Streptomycin",    "VESTIBULOTOXIC\n(predominantly)", "IT injection - Meniere's\n(older protocol)",           "First aminoglycoside;\nnow rarely used systemically"],
        ["Neomycin",        "COCHLEOTOXIC\n(very potent)",     "Topical ear drops -\nNEVER if TM perforated",         "Most ototoxic aminoglycoside;\nnot given systemically"],
        ["Amikacin",        "COCHLEOTOXIC",          "Resistant gram-negative\ninfections",                           "Used when gentamicin-\nresistant organisms"],
        ["Tobramycin",      "Cochleo + vestibulo",   "Pseudomonas infections;\npediatric cystic fibrosis",            "Similar to gentamicin;\ninhaled for CF"],
        ["Netilmicin",      "LEAST ototoxic\namino.", "Less ototoxic option\nfor prolonged use",                      "Lower incidence of\nototoxicity than gentamicin"],
        ["Kanamycin",       "Cochleotoxic",          "Used in DOTS regimen\nfor MDR-TB",                              "TB treatment; significant\nototoxicity risk"],
    ]
    st.append(tbl(data, [W*0.20, W*0.20, W*0.30, W*0.30], S))
    sp(st, 4)

    # 7. VIVA Q&A
    h1(st, "7.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. What is the mechanism of action of gentamicin?", S)
    bl(st, [
        "Binds to 16S rRNA of the 30S ribosomal subunit",
        "Causes misreading of mRNA codons -> aberrant/toxic proteins -> bactericidal effect",
        "Disrupts bacterial cell membrane -> further self-promoting drug uptake",
        "Requires oxygen (aerobic conditions) -> inactive against strict anaerobes",
        "Concentration-dependent killing + prolonged post-antibiotic effect (PAE)",
        "Justifies once-daily dosing regimen",
    ], S); sp(st, 2)

    vq(st, "Q2. Why is gentamicin predominantly vestibulotoxic rather than cochleotoxic?", S)
    bl(st, [
        "Gentamicin selectively accumulates in vestibular dark cells "
          "(specific transporter-mediated uptake)",
        "Destroys type I and type II vestibular hair cells of cristae ampullaris and maculae",
        "Lower concentrations are required to damage vestibular vs cochlear hair cells",
        "Contrast: neomycin / amikacin = predominantly cochleotoxic (cochlear uptake higher)",
        "This property is deliberately EXPLOITED in intratympanic gentamicin "
          "for Meniere's disease vestibular ablation",
    ], S); sp(st, 2)

    vq(st, "Q3. What is the mechanism of aminoglycoside ototoxicity at the cellular level?", S)
    bl(st, [
        "Gentamicin enters hair cells via MET channels and endocytosis",
        "Forms iron-gentamicin chelate complex -> generates reactive oxygen species (ROS) "
          "via Fenton reaction",
        "ROS cause lipid peroxidation of hair cell membranes and mitochondrial damage",
        "Triggers apoptosis (caspase cascade) of outer hair cells",
        "Basal turn OHC destroyed first (high-frequency) -> progresses apically",
        "Mitochondrial A1555G mutation (12S rRNA): mutant rRNA mimics aminoglycoside "
          "binding site on bacterial rRNA -> drug binds -> "
          "blocks mitochondrial protein synthesis -> hair cell death at very low doses. "
          "Maternally inherited (Shambaugh Surgery of the Ear)",
    ], S); sp(st, 2)

    vq(st, "Q4. What is the role of intratympanic gentamicin in Meniere's disease?", S)
    bl(st, [
        "Chemical vestibular ablation for refractory Meniere's disease "
          "(failed conservative Rx: salt restriction, betahistine, diuretics)",
        "Mechanism: selective vestibulotoxicity destroys vestibular hair cells of "
          "affected ear -> eliminates unilateral abnormal vestibular drive -> "
          "brainstem compensates -> vertigo attacks controlled",
        "Technique: 0.3-0.5 mL gentamicin 26.7 mg/mL injected through posteroinferior TM; "
          "ear up for 20-30 min post-injection",
        "Low-dose titration protocol preferred: single injection; repeat only if vertigo persists; "
          "max 3-4 injections; lower hearing risk (15-20%)",
        "Efficacy: 70-90% vertigo control",
        "Advantage over surgical ablation: minimally invasive, outpatient, "
          "preserves hearing in majority",
    ], S); sp(st, 2)

    vq(st, "Q5. What are the contraindications and precautions for gentamicin use?", S)
    bl(st, [
        "<b>Contraindications:</b> known aminoglycoside hypersensitivity; "
          "myasthenia gravis (neuromuscular blockade potentiation); "
          "pregnancy (foetal ototoxicity); only-hearing ear (IT gentamicin)",
        "<b>Major precautions:</b>",
    ], S)
    bl(st, [
        "Renal impairment: dose reduction mandatory; TDM essential",
        "Concurrent frusemide / ethacrynic acid: high risk of severe irreversible SNHL",
        "Concurrent cisplatin or vancomycin: additive ototoxicity",
        "Mitochondrial A1555G mutation carriers: extreme sensitivity - "
          "even small doses cause profound SNHL",
        "Elderly and neonates: impaired drug clearance",
        "Pre-existing SNHL or vestibular dysfunction",
        "Prolonged duration and high cumulative dose: monitor TDM and audiometry",
    ], S, sub=True); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Shambaugh Surgery of the Ear 6e | Cummings ORL 7e | "
        "KJ Lee Essential ORL 11e | Dhingra ENT 8e | Harrison's Internal Medicine 22e | "
        "BNF 2024 | AAO-HNS Meniere's Guidelines | "
        "Harker-Driscoll IT Gentamicin Protocol",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/Gentamicin_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Gentamicin - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()

#!/usr/bin/env python3
# Ludwig's Angina - ENT PG Exam Notes (5-6 pages, bullet-point style)
# Palette 21: Dark olive-charcoal (#2A3A1A) / deep burgundy-red (#7A0020) / teal-steel (#005C5C)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.enums import TA_CENTER
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

pt = 1
FONT_DIR = "/usr/share/fonts/truetype/liberation"
try:
    pdfmetrics.registerFont(TTFont("Lib",  f"{FONT_DIR}/LiberationSans-Regular.ttf"))
    pdfmetrics.registerFont(TTFont("LibB", f"{FONT_DIR}/LiberationSans-Bold.ttf"))
    pdfmetrics.registerFontFamily("Lib", normal="Lib", bold="LibB")
    NM, BD = "Lib", "LibB"
except Exception:
    NM, BD = "Helvetica", "Helvetica-Bold"

C_H1_BG  = colors.HexColor("#2A3A1A")
C_H1_FG  = colors.HexColor("#FFFFFF")
C_H2_FG  = colors.HexColor("#7A0020")
C_H2_BG  = colors.HexColor("#FFF0F3")
C_H3_FG  = colors.HexColor("#005C5C")
C_H3_BG  = colors.HexColor("#E6F5F5")
C_BODY   = colors.HexColor("#000000")
C_TH     = colors.HexColor("#2A3A1A")
C_ALT    = colors.HexColor("#EEF5EC")
C_PEARL  = colors.HexColor("#EEF5EC")
C_CAUT   = colors.HexColor("#B22222")
C_CAUT_BG= colors.HexColor("#FFF0F0")
C_DOSE   = colors.HexColor("#1A5C2A")
C_DOSE_BG= colors.HexColor("#EAF5EC")
C_RULE   = colors.HexColor("#2A3A1A")
C_VQ_BG  = colors.HexColor("#E6F5F5")
C_VQ_FG  = colors.HexColor("#005C5C")

M = 15*mm
WP, HP = A4
BS, BL, CL = 10.5, 16, 13

def styles():
    s = {}
    s["title"] = ParagraphStyle("title", fontName=BD, fontSize=14, leading=18,
        textColor=C_H1_FG, backColor=C_H1_BG, alignment=TA_CENTER,
        spaceAfter=2, borderPad=(7,9,7,9))
    s["sub"] = ParagraphStyle("sub", fontName=NM, fontSize=9, leading=12,
        textColor=colors.HexColor("#555555"), alignment=TA_CENTER, spaceAfter=3)
    s["h1"] = ParagraphStyle("h1", fontName=BD, fontSize=11.5, leading=15,
        textColor=C_H1_FG, backColor=C_H1_BG,
        spaceBefore=7, spaceAfter=4, leftIndent=4, borderPad=(4,5,4,5))
    s["h2"] = ParagraphStyle("h2", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H2_FG, backColor=C_H2_BG,
        spaceBefore=5, spaceAfter=3, leftIndent=3, borderPad=(3,4,3,4))
    s["h3"] = ParagraphStyle("h3", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_H3_FG, backColor=C_H3_BG,
        spaceBefore=4, spaceAfter=2, leftIndent=3, borderPad=(2,3,2,3))
    s["pt"] = ParagraphStyle("pt", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=16, firstLineIndent=-16, spaceAfter=3)
    s["bl"] = ParagraphStyle("bl", fontName=NM, fontSize=BS, leading=BL,
        textColor=C_BODY, leftIndent=14, firstLineIndent=-10, spaceAfter=2)
    s["sbl"] = ParagraphStyle("sbl", fontName=NM, fontSize=9.5, leading=13,
        textColor=C_BODY, leftIndent=26, firstLineIndent=-10, spaceAfter=2)
    s["pearl"] = ParagraphStyle("pearl", fontName=BD, fontSize=10, leading=14,
        textColor=C_BODY, backColor=C_PEARL,
        spaceAfter=3, spaceBefore=2, leftIndent=6, rightIndent=6, borderPad=(3,5,3,5))
    s["caut"] = ParagraphStyle("caut", fontName=BD, fontSize=10, leading=14,
        textColor=C_CAUT, backColor=C_CAUT_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["dose"] = ParagraphStyle("dose", fontName=BD, fontSize=10, leading=14,
        textColor=C_DOSE, backColor=C_DOSE_BG,
        spaceAfter=2, spaceBefore=2, leftIndent=6, borderPad=(2,4,2,4))
    s["cell"] = ParagraphStyle("cell", fontName=NM, fontSize=9.5, leading=CL, textColor=C_BODY)
    s["cellh"] = ParagraphStyle("cellh", fontName=BD, fontSize=9.5, leading=CL, textColor=colors.white)
    s["vq"] = ParagraphStyle("vq", fontName=BD, fontSize=10.5, leading=14,
        textColor=C_VQ_FG, backColor=C_VQ_BG,
        spaceAfter=1, spaceBefore=4, leftIndent=5, borderPad=(3,5,3,5))
    return s

def rule(st): st.append(HRFlowable(width="100%", thickness=0.6, color=C_RULE, spaceAfter=3, spaceBefore=2))
def sp(st, h=4): st.append(Spacer(1, h))
def h1(st,t,S): st.append(Paragraph(t, S["h1"]))
def h2(st,t,S): st.append(Paragraph(t, S["h2"]))
def h3(st,t,S): st.append(Paragraph(t, S["h3"]))
def bl(st, items, S, sub=False):
    k = "sbl" if sub else "bl"
    for i in items: st.append(Paragraph(f"• {i}", S[k]))
def pearl(st,t,S): st.append(Paragraph(f"★ {t}", S["pearl"]))
def caut(st,t,S):  st.append(Paragraph(f"⚠ {t}", S["caut"]))
def dose(st,t,S):  st.append(Paragraph(f"♥ {t}", S["dose"]))
def num(st, n, label, text, S):
    st.append(Paragraph(f"<b>{n}. {label}</b> - {text}", S["pt"]))
def vq(st, q, S): st.append(Paragraph(q, S["vq"]))

def tbl(data, cw, S):
    rows = [[Paragraph(c, S["cellh"] if ri==0 else S["cell"]) for c in row]
            for ri, row in enumerate(data)]
    t = Table(rows, colWidths=cw, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0), C_TH),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [colors.white, C_ALT]),
        ("BOX",           (0,0),(-1,-1), 0.6, C_RULE),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0),(-1,-1), 4),("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("FONTSIZE",      (0,0),(-1,-1), 9.5),
        ("LEADING",       (0,0),(-1,-1), CL),
    ]))
    return t


def build(st, S):
    W = WP - 2*M

    st.append(Paragraph("LUDWIG'S ANGINA - ENT PG EXAM NOTES", S["title"]))
    st.append(Paragraph(
        "10-Mark Exam Answer  |  KNRUHS ENT PG  |  "
        "Sources: Scott-Brown's OHN&S 8e Vol 2, Bailey & Love's Surgery 28e, "
        "Cummings ORL 7e, KJ Lee Essential ORL 11e, Tintinalli Emergency Medicine 9e",
        S["sub"]))
    rule(st); sp(st, 2)

    # 1. DEFINITION & HISTORY
    h1(st, "1.  DEFINITION & HISTORICAL NOTE", S)
    bl(st, [
        "<b>Ludwig's Angina</b> = a rapidly progressing, potentially life-threatening "
          "bilateral cellulitis of the floor of mouth, simultaneously involving "
          "the <b>sublingual, submandibular (submaxillary), and submental spaces</b>",
        "Named after German physician <b>Wilhelm Friedrich von Ludwig (1836)</b> who "
          "described the clinical entity: brawny submandibular swelling + "
          "inflammatory oedema of the floor of mouth + putrid halitosis",
        "<b>'Angina'</b> comes from Latin 'angere' = to strangle/choke - "
          "refers to the choking sensation and airway threat, NOT cardiac angina",
        "<b>KEY FEATURES that define Ludwig's Angina:</b>",
    ], S)
    bl(st, [
        "Bilateral involvement of submandibular space",
        "CELLULITIS (not abscess) - no pus in classic form; woody, brawny induration",
        "Spreads along fascial planes (NOT via lymphatics - lymphatics not involved)",
        "Involves sublingual space ABOVE mylohyoid AND submandibular space BELOW mylohyoid",
        "Rapidly progressive with high risk of airway compromise",
    ], S, sub=True)
    pearl(st,
        "CLASSIC DESCRIPTION: Brawny ('board-like'), non-pitting, non-fluctuant "
        "induration of the floor of mouth and submandibular region. "
        "NO fluctuance (cellulitis, not abscess) in the classic form. "
        "Tongue elevated and displaced posteriorly. "
        "(Bailey and Love's Surgery 28e; KJ Lee Essential ORL 11e)", S)
    sp(st, 4)

    # 2. ANATOMY
    h1(st, "2.  RELEVANT ANATOMY - SPACES INVOLVED", S)
    h2(st, "Submandibular Space", S)
    bl(st, [
        "Paired space below the floor of mouth, divided by the <b>mylohyoid muscle</b> into:",
    ], S)
    bl(st, [
        "<b>Sublingual space (above mylohyoid):</b> "
          "between tongue and mylohyoid. Contains sublingual glands, "
          "Wharton's duct, lingual nerve, hypoglossal nerve",
        "<b>Submylohyoid / Submaxillary space (below mylohyoid):</b> "
          "between mylohyoid and hyoid bone. Contains submandibular gland and lymph nodes",
    ], S, sub=True)
    bl(st, [
        "<b>Submental space:</b> midline, between chin and hyoid. "
          "Communicates with both submandibular spaces across midline",
        "Submandibular space extends from floor of mouth to muscular attachments "
          "at the hyoid bone (Tintinalli EM 9e)",
        "<b>Critical communications:</b> submandibular space communicates posteriorly with "
          "the parapharyngeal space -> retropharyngeal space -> danger space -> "
          "posterior mediastinum (route of descending necrotising mediastinitis)",
        "<b>Mylohyoid muscle:</b> divides the sublingual and submandibular spaces. "
          "Infection crosses this boundary via the posterior free edge of mylohyoid "
          "(no barrier posteriorly) or through the muscle itself",
    ], S)
    h2(st, "Why is Ludwig's Angina So Dangerous?", S)
    bl(st, [
        "Tongue elevation by sublingual space swelling -> posterior displacement "
          "of tongue -> obstructs oropharyngeal airway",
        "Floor of mouth oedema -> glossoptosis (tongue falls back) -> asphyxia",
        "Infection tracks posteriorly -> parapharyngeal -> retropharyngeal -> "
          "danger space -> MEDIASTINUM (descending necrotising mediastinitis = DNM) "
          "-> potentially fatal",
        "Laryngeal spread -> glottic oedema -> stridor and complete airway obstruction",
        "Late presentation + delayed airway management = death from asphyxia",
    ], S)
    sp(st, 4)

    # 3. AETIOLOGY & MICROBIOLOGY
    h1(st, "3.  AETIOLOGY & MICROBIOLOGY", S)
    h2(st, "Sources / Aetiology", S)
    bl(st, [
        "<b>Dental / odontogenic (most common - 75-90%):</b>",
    ], S)
    bl(st, [
        "Periapical abscess or infection of mandibular MOLAR teeth "
          "(especially 2nd and 3rd molars) - most common specific source",
        "The roots of the lower 2nd and 3rd molars lie BELOW the mylohyoid attachment -> "
          "infection enters the submandibular space directly",
        "Lower 1st molar roots lie ABOVE mylohyoid -> infection enters sublingual space first",
        "Pericoronitis around impacted lower wisdom teeth",
    ], S, sub=True)
    bl(st, [
        "<b>Non-odontogenic causes (minority):</b>",
    ], S)
    bl(st, [
        "Submandibular sialadenitis (stone / Wharton's duct calculus)",
        "Penetrating floor-of-mouth injuries / tongue piercings",
        "Frenuloplasty (described in adolescents)",
        "Parapharyngeal / peritonsillar abscess extending inferiorly",
        "Ludwig's angina without identifiable source (idiopathic - rare)",
        "Underlying oral cavity malignancy (always consider in adults)",
    ], S, sub=True)
    h2(st, "Microbiology", S)
    bl(st, [
        "<b>Polymicrobial</b> infection - mixed aerobic + anaerobic oral flora",
        "<b>Most common organisms:</b>",
    ], S)
    bl(st, [
        "<b>Streptococcus viridans group</b> (alpha-haemolytic streptococci) - "
          "most common aerobic organism",
        "<b>Staphylococcus species</b> (including MRSA in community-acquired cases)",
        "<b>Anaerobes (essential to cover):</b> Bacteroides, Peptostreptococcus, "
          "Fusobacterium, Prevotella, Porphyromonas",
        "Gram-negative rods: Klebsiella, E. coli (diabetic / immunocompromised patients)",
        "In diabetic / immunocompromised: more virulent / atypical organisms "
          "(Klebsiella, Pseudomonas, polymicrobial with resistant organisms)",
    ], S, sub=True)
    bl(st, [
        "<b>Predisposing conditions:</b> "
          "Diabetes mellitus (most important - altered immunity, "
          "impaired neutrophil function, poor wound healing), "
          "HIV / immunocompromised, malnutrition, IV drug abuse, "
          "poor dental hygiene, renal failure, malignancy",
    ], S)
    sp(st, 4)

    # 4. CLINICAL FEATURES
    h1(st, "4.  CLINICAL FEATURES", S)
    h2(st, "Symptoms", S)
    bl(st, [
        "Rapid onset of floor-of-mouth swelling / submandibular neck swelling",
        "Severe dental pain / toothache (preceding the swelling by hours to days)",
        "Trismus (difficulty opening mouth - spasm of pterygoid muscles)",
        "Dysphagia (pain and swelling limit swallowing)",
        "Odynophagia (painful swallowing)",
        "Drooling of saliva (cannot swallow)",
        "Fever, chills, rigors (systemic sepsis)",
        "Muffled / hot-potato voice (tongue and floor-of-mouth involvement)",
        "Stridor (late sign - impending airway obstruction - EMERGENCY)",
        "Dyspnoea / respiratory distress",
    ], S)
    h2(st, "Signs (Classic Triad)", S)
    bl(st, [
        "<b>1. BRAWNY, BOARD-LIKE, WOODY INDURATION:</b> "
          "bilateral non-pitting, non-fluctuant, non-tender-to-touch "
          "submandibular neck swelling. "
          "Hard ('board-like') texture - NOT soft or fluctuant like an abscess. "
          "Bilateral (crosses midline)",
        "<b>2. TONGUE ELEVATION + POSTERIOR DISPLACEMENT:</b> "
          "tongue pushed upward and backward by sublingual space oedema -> "
          "cannot close mouth; tongue may protrude",
        "<b>3. PUTRID HALITOSIS:</b> foul-smelling breath from mixed anaerobic infection",
    ], S)
    bl(st, [
        "Patient assumes 'sniffing position' (neck extended, leaning forward) "
          "to maximise airway diameter",
        "Floor of mouth: indurated, elevated, red, oedematous",
        "Trismus: limited mouth opening",
        "Submandibular + submental region: firm brawny swelling, "
          "skin tense and shiny, erythema",
        "'Bull-neck' appearance in advanced cases",
        "Signs of systemic sepsis: fever (38.5-40 deg C), tachycardia, hypotension (late)",
        "Stridor / use of accessory muscles of respiration = "
          "SEVERE airway compromise - IMMEDIATE action required",
    ], S)
    sp(st, 4)

    # 5. INVESTIGATIONS
    h1(st, "5.  INVESTIGATIONS", S)
    bl(st, [
        "<b>CECT Neck (Gold Standard imaging):</b> contrast-enhanced CT neck "
          "identifies extent of infection, space involvement, "
          "presence of pus / gas / abscess formation, "
          "airway compromise, vascular involvement. "
          "MOST USEFUL for surgical planning. "
          "However - do NOT delay airway management for CT",
        "<b>Dental panoramic tomograph (OPG):</b> identifies dental source "
          "(periapical abscess, periodontal disease, impacted wisdom tooth)",
        "<b>X-ray soft tissue neck / chest:</b> subcutaneous emphysema, "
          "mediastinal widening (descending mediastinitis)",
        "<b>FBC:</b> leucocytosis (elevated WBC with neutrophilia); "
          "elevated CRP and ESR",
        "<b>Blood cultures (x2):</b> before antibiotics; bacteraemia common",
        "<b>Pus culture + sensitivity:</b> from any incised / drained pus "
          "to guide antibiotic therapy",
        "<b>Blood glucose:</b> screen for undiagnosed/poorly controlled DM",
        "<b>Renal / liver function, coagulation screen:</b> baseline before surgery; "
          "sepsis-related organ dysfunction",
        "<b>Arterial blood gas:</b> if respiratory distress",
        "<b>Ultrasound neck:</b> can identify fluid collection; "
          "less useful than CT for deep spaces",
    ], S)
    sp(st, 4)

    # 6. MANAGEMENT
    h1(st, "6.  MANAGEMENT", S)
    caut(st,
        "AIRWAY IS THE IMMEDIATE PRIORITY - AIRWAY FIRST, EVERYTHING ELSE SECOND. "
        "Ludwig's angina is a SURGICAL AIRWAY EMERGENCY. "
        "Late intubation may be IMPOSSIBLE due to trismus, massive oedema, "
        "and distorted anatomy. Secure airway EARLY before swelling progresses. "
        "(KJ Lee Essential ORL 11e; Scott-Brown's OHN&S 8e)", S)
    h2(st, "Step 1: Airway Management", S)
    bl(st, [
        "<b>AWAKE FIBREOPTIC NASOPHARYNGOLARYNGOSCOPY (FOL):</b> "
          "assess degree of pharyngeal / supraglottic oedema and airway narrowing. "
          "Guides decision for intubation route",
        "<b>Awake Fibreoptic Intubation (AFOI) - technique of choice:</b> "
          "topical anaesthesia to airway; pass fibreoptic bronchoscope through nose "
          "-> visualise larynx -> railroad endotracheal tube over scope. "
          "Avoids muscle relaxants until airway secured. "
          "Preserves protective airway reflexes",
        "<b>Tracheostomy under local anaesthesia:</b> "
          "indicated when oral/nasal intubation impossible "
          "(severe trismus, massive oedema, distorted anatomy). "
          "Often required in advanced cases. "
          "A curved submental incision for drainage also allows tracheostomy "
          "through the same field",
        "<b>Awake surgical tracheostomy (under LA):</b> "
          "most reliable definitive airway in severe cases; "
          "sedation should be AVOIDED until airway secured "
          "(sedation -> apnoea -> impossible to mask-ventilate -> catastrophe)",
        "<b>Avoid rapid sequence induction (RSI) / muscle relaxants until airway secured</b>",
    ], S)
    h2(st, "Step 2: IV Antibiotics (Empiric, Broad-Spectrum)", S)
    dose(st,
        "FIRST LINE (mixed polymicrobial - aerobic + anaerobic coverage): "
        "Ampicillin-Sulbactam (Unasyn) 3g IV 6-hourly "
        "OR Co-amoxiclav (Augmentin) 1.2g IV 8-hourly. "
        "ADD Metronidazole 500mg IV 8-hourly if anaerobic cover inadequate. "
        "PENICILLIN ALLERGY: Clindamycin 600mg IV 6-hourly + Metronidazole. "
        "MRSA RISK: add Vancomycin or Linezolid. "
        "Diabetic / immunocompromised: add Piperacillin-Tazobactam (Tazocin) "
        "4.5g IV 8-hourly for gram-negative + Pseudomonas cover.", S)
    bl(st, [
        "Start IV antibiotics IMMEDIATELY - before imaging, before theatre if possible",
        "Total antibiotic duration: 7-14 days (IV until afebrile + clinical improvement "
          "x 48h, then oral step-down)",
        "Adjust based on culture + sensitivity results",
    ], S)
    h2(st, "Step 3: Surgical Drainage (When Indicated)", S)
    bl(st, [
        "<b>Indications for surgical drainage:</b>",
    ], S)
    bl(st, [
        "Failure to improve within 24-48 hours of IV antibiotics",
        "Evidence of pus / abscess formation on CT (gas, fluid loculation)",
        "Rapidly progressive infection with airway compromise",
        "Descending mediastinitis (urgent thoracic drainage)",
    ], S, sub=True)
    bl(st, [
        "<b>Surgical approach:</b>",
    ], S)
    bl(st, [
        "<b>Submental / submandibular incision (external approach):</b> "
          "most commonly used. Curved incision below chin (submental incision) "
          "extending into submandibular region bilaterally (2-3 cm below mandible). "
          "Allows access to both submandibular triangles and submental space",
        "Blunt dissection through platysma, anterior belly of digastric -> "
          "enter submandibular space -> break down loculations -> irrigate",
        "<b>Mylohyoid incision:</b> may be incised to decompress floor of mouth "
          "and enter sublingual space (Bailey and Love's 28e)",
        "Corrugated rubber drain / Penrose drain placed; wound lightly sutured "
          "(not tight closure - allows continued drainage)",
        "<b>Intraoral approach:</b> for sublingual space drainage if abscess "
          "is primarily above mylohyoid. Less favoured in severe cases",
        "<b>Combined intraoral + extraoral:</b> for comprehensive drainage of "
          "both sublingual AND submandibular compartments simultaneously",
        "Remove causative tooth (dental extraction) at same sitting or once "
          "acute phase resolved",
    ], S, sub=True)
    h2(st, "Step 4: Supportive Care", S)
    bl(st, [
        "ICU or HDU admission for monitoring airway, vital signs, urine output",
        "IV fluids, electrolyte correction",
        "Strict glycaemic control in diabetics (target glucose 6-10 mmol/L)",
        "Nutritional support: NG feeding if swallowing compromised",
        "Dexamethasone 8-12 mg IV: reduces oedema and inflammation (controversial "
          "but widely used in severe cases); do NOT use if suspicion of deep pus",
        "Pain management: IV analgesics; avoid NSAIDs (impair healing)",
        "Dental follow-up: extraction of causative tooth, dental rehabilitation",
    ], S)
    sp(st, 4)

    # 7. COMPLICATIONS
    h1(st, "7.  COMPLICATIONS", S)
    h2(st, "Immediate", S)
    bl(st, [
        "<b>Airway obstruction / asphyxia:</b> most feared immediate complication; "
          "cause of death if airway not secured",
        "<b>Aspiration of infected material:</b> during intubation attempts or spontaneously",
        "<b>Septic shock:</b> systemic sepsis from polymicrobial bacteraemia",
    ], S)
    h2(st, "Delayed / Spread of Infection", S)
    bl(st, [
        "<b>Descending Necrotising Mediastinitis (DNM):</b> "
          "most serious life-threatening complication. "
          "Infection tracks: submandibular -> parapharyngeal -> retropharyngeal -> "
          "danger space -> posterior mediastinum. "
          "Mortality 30-50%. Requires emergency thoracotomy / VATS drainage",
        "<b>Parapharyngeal abscess:</b> spread to lateral pharyngeal space",
        "<b>Retropharyngeal abscess:</b> posterior spread",
        "<b>Carotid artery erosion / pseudoaneurysm:</b> rare; from parapharyngeal spread",
        "<b>Internal jugular vein thrombophlebitis (Lemierre's syndrome):</b> "
          "septic thrombosis of IJV; septic pulmonary emboli; "
          "caused by Fusobacterium necrophorum",
        "<b>Jugular vein thrombosis:</b> from contiguous spread to parapharyngeal space",
        "<b>Osteomyelitis of mandible:</b> direct bone involvement",
        "<b>Cavernous sinus thrombosis:</b> via retrograde spread through valveless "
          "pterygoid venous plexus",
        "<b>Pericarditis / pleural empyema:</b> from mediastinal extension",
    ], S)
    bl(st, [
        "<b>Mortality:</b> in pre-antibiotic era ~50%. "
          "With modern treatment: 5-10%; higher in DM, delayed presentation, DNM",
    ], S)
    sp(st, 4)

    # 8. VIVA Q&A
    h1(st, "8.  VIVA QUESTIONS & ANSWERS", S)

    vq(st, "Q1. Define Ludwig's angina and state its classic clinical features.", S)
    bl(st, [
        "Rapidly progressing bilateral cellulitis of the floor of mouth involving "
          "submandibular, sublingual, and submental spaces simultaneously",
        "Named after Wilhelm Friedrich von Ludwig (1836)",
        "<b>Classic TRIAD:</b>",
    ], S)
    bl(st, [
        "BRAWNY, woody, board-like, non-fluctuant bilateral submandibular induration",
        "TONGUE ELEVATION + POSTERIOR DISPLACEMENT -> airway threat",
        "PUTRID HALITOSIS (mixed anaerobic infection)",
    ], S, sub=True)
    bl(st, [
        "Spreads via fascial planes (NOT lymphatics); rapid; bilateral",
        "CELLULITIS (not abscess) in classic form - no pus, no fluctuance",
    ], S); sp(st, 2)

    vq(st, "Q2. What is the most important first step in managing Ludwig's angina?", S)
    bl(st, [
        "<b>AIRWAY MANAGEMENT - first and foremost priority</b>",
        "Awake Fibreoptic Intubation (AFOI) = technique of choice: "
          "topical anaesthesia; fibreoptic bronchoscope via nose; railroad ETT",
        "Awake tracheostomy under local anaesthesia: indicated when intubation impossible "
          "(severe trismus, distorted anatomy, massive oedema)",
        "<b>NEVER give sedation / muscle relaxants BEFORE securing the airway</b> - "
          "apnoea + failed mask ventilation = lethal",
        "Only after airway secured: IV antibiotics, imaging, surgical drainage",
    ], S); sp(st, 2)

    vq(st, "Q3. What is the most common cause and what spaces are involved?", S)
    bl(st, [
        "Odontogenic source in 75-90% of cases",
        "Most common: periapical abscess of LOWER MOLAR TEETH "
          "(2nd/3rd molar roots lie below mylohyoid line -> directly into submandibular space)",
        "Spaces involved: sublingual (above mylohyoid) + "
          "submandibular/submaxillary (below mylohyoid) + submental (midline)",
        "All three spaces involved bilaterally = Ludwig's angina (by definition)",
    ], S); sp(st, 2)

    vq(st, "Q4. What is descending necrotising mediastinitis and how does it occur?", S)
    bl(st, [
        "Life-threatening spread of Ludwig's angina into the mediastinum via fascial planes",
        "<b>Route:</b> Submandibular space -> Parapharyngeal space -> "
          "Retropharyngeal space -> Danger space (between alar and prevertebral fascia) -> "
          "Posterior mediastinum",
        "Danger space extends from skull base to diaphragm = "
          "unobstructed route for rapid spread",
        "Presents with: chest pain, mediastinal widening on CXR, "
          "CT showing mediastinal gas/fluid",
        "<b>Management:</b> emergency thoracotomy or video-assisted thoracic surgery (VATS) + "
          "drainage + prolonged IV antibiotics. Mortality 30-50%",
    ], S); sp(st, 2)

    vq(st, "Q5. What antibiotics are used for Ludwig's angina?", S)
    bl(st, [
        "Polymicrobial infection requires BROAD-SPECTRUM cover of aerobes + anaerobes",
        "<b>First line:</b> Ampicillin-Sulbactam (Unasyn) 3g IV 6-hourly "
          "OR Co-amoxiclav 1.2g IV 8-hourly + Metronidazole 500mg IV 8-hourly",
        "<b>Penicillin allergy:</b> Clindamycin 600mg IV 6-hourly + Metronidazole",
        "<b>Diabetics / immunocompromised:</b> "
          "Piperacillin-Tazobactam 4.5g IV 8-hourly (covers Pseudomonas)",
        "<b>MRSA risk:</b> add Vancomycin 15-20 mg/kg IV 8-12 hourly",
        "Adjust after culture & sensitivity results; "
          "IV until afebrile x 48h then oral step-down; total 10-14 days",
    ], S); sp(st, 2)

    sp(st, 2)
    st.append(Paragraph(
        "Sources: Scott-Brown's OHN&S 8e Vol 2 Ch.37 | Bailey & Love's Surgery 28e Ch.52 | "
        "Cummings ORL 7e | KJ Lee Essential ORL 11e | Tintinalli Emergency Medicine 9e | "
        "Rosen's Emergency Medicine 9e",
        S["sub"]))


def main():
    out = "/home/daytona/workspace/ptc-notes/LudwigsAngina_ENT_PG_Exam.pdf"
    S = styles()
    story = []
    build(story, S)
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=M, rightMargin=M, topMargin=13*mm, bottomMargin=13*mm,
        title="Ludwig's Angina - ENT PG Exam Notes",
        author="Orris Medical AI", subject="KNRUHS ENT PG")
    doc.build(story)
    print(f"Done: {out}")

if __name__ == "__main__":
    main()