python3 -c " import pdfplumber text = [] with pdfplumber.open('/tmp/workspace/attachments/07988e43-2765-49c5-a378-763590f6789f/PIIS1542356524011364.pdf') as pdf: print(f'Pages: {len(pdf.pages)}') for i, page in enumerate(pdf.pages): t = page.extract_text() if t: text.append(f'=== PAGE {i+1} ===\n{t}') full = '\n'.join(text) with open('/tmp/workspace/paper_text.txt', 'w') as f: f.write(full) print('Done. Characters:', len(full)) "

mkdir -p /tmp/workspace/hemochromatosis-pptx && python3 << 'PYEOF' from pptx import Presentation from pptx.util import Inches, Pt, Emu from pptx.dml.color import RGBColor from pptx.enum.text import PP_ALIGN, MSO_ANCHOR from pptx.oxml.ns import qn from lxml import etree from io import BytesIO prs = Presentation() prs.slide_width = Inches(13.333) prs.slide_height = Inches(7.5) blank = prs.slide_layouts[6] # ─── Color palette ─── DARK_BLUE = RGBColor(0x0D, 0x2B, 0x55) # deep navy MID_BLUE = RGBColor(0x14, 0x5A, 0x8A) # header accent ACCENT_GOLD = RGBColor(0xC8, 0x96, 0x20) # gold accent LIGHT_BG = RGBColor(0xF0, 0xF5, 0xFA) # slide background WHITE = RGBColor(0xFF, 0xFF, 0xFF) BODY_GRAY = RGBColor(0x33, 0x33, 0x33) LIGHT_LINE = RGBColor(0xCC, 0xDD, 0xEE) LIGHT_GOLD = RGBColor(0xFF, 0xF3, 0xCC) SECTION_TEAL= RGBColor(0x0A, 0x7A, 0x7A) def set_bg(slide, color): bg = slide.background fill = bg.fill fill.solid() fill.fore_color.rgb = color def add_rect(slide, left, top, width, height, fill_color, border_color=None): shape = slide.shapes.add_shape(1, Inches(left), Inches(top), Inches(width), Inches(height)) shape.fill.solid() shape.fill.fore_color.rgb = fill_color if border_color: shape.line.color.rgb = border_color shape.line.width = Pt(1) else: shape.line.fill.background() return shape def add_text(slide, text, left, top, width, height, font_size, bold=False, color=None, align=PP_ALIGN.LEFT, italic=False, wrap=True): if color is None: color = BODY_GRAY tb = slide.shapes.add_textbox(Inches(left), Inches(top), Inches(width), Inches(height)) tf = tb.text_frame tf.word_wrap = wrap tf.margin_left = Pt(4) tf.margin_right = Pt(4) tf.margin_top = Pt(2) tf.margin_bottom = Pt(2) p = tf.paragraphs[0] p.alignment = align run = p.add_run() run.text = text run.font.size = Pt(font_size) run.font.bold = bold run.font.italic = italic run.font.color.rgb = color run.font.name = "Calibri" return tb def add_multiline(slide, items, left, top, width, height, font_size, color=None, bold=False, bullet=True, line_spacing=1.15): if color is None: color = BODY_GRAY tb = slide.shapes.add_textbox(Inches(left), Inches(top), Inches(width), Inches(height)) tf = tb.text_frame tf.word_wrap = True tf.margin_left = Pt(4) tf.margin_right = Pt(4) tf.margin_top = Pt(2) tf.margin_bottom = Pt(2) from pptx.util import Pt as PPt from pptx.oxml.ns import qn from lxml import etree for i, item in enumerate(items): p = tf.paragraphs[0] if i == 0 else tf.add_paragraph() if bullet: p.level = 0 run = p.add_run() prefix = "• " if bullet else "" run.text = prefix + item run.font.size = Pt(font_size) run.font.bold = bold run.font.color.rgb = color run.font.name = "Calibri" return tb def header_bar(slide, title, subtitle=None): add_rect(slide, 0, 0, 13.333, 1.2, DARK_BLUE) add_rect(slide, 0, 1.2, 13.333, 0.08, ACCENT_GOLD) add_text(slide, title, 0.3, 0.1, 12.7, 0.85, font_size=28, bold=True, color=WHITE, align=PP_ALIGN.LEFT) if subtitle: add_text(slide, subtitle, 0.3, 0.82, 12.7, 0.42, font_size=14, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.LEFT) def section_divider(slide, section_title): set_bg(slide, DARK_BLUE) add_rect(slide, 0, 2.8, 13.333, 0.1, ACCENT_GOLD) add_text(slide, section_title, 0.5, 2.2, 12.3, 1.5, font_size=40, bold=True, color=WHITE, align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 1 — Title slide # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, DARK_BLUE) add_rect(slide, 0, 0, 13.333, 7.5, DARK_BLUE) add_rect(slide, 0, 2.5, 13.333, 0.12, ACCENT_GOLD) add_rect(slide, 0, 4.8, 13.333, 0.08, RGBColor(0x14, 0x5A, 0x8A)) add_text(slide, "Diagnosis and Treatment of", 0.5, 0.8, 12.3, 0.9, font_size=28, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) add_text(slide, "HEMOCHROMATOSIS", 0.5, 1.5, 12.3, 1.1, font_size=52, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_text(slide, "A Narrative Review — Adams PC & Ryan JD", 0.5, 2.7, 12.3, 0.6, font_size=18, color=ACCENT_GOLD, align=PP_ALIGN.CENTER) add_text(slide, "Clinical Gastroenterology and Hepatology 2025; 23:1477–1485", 0.5, 3.3, 12.3, 0.5, font_size=14, color=RGBColor(0x99, 0xBB, 0xCC), align=PP_ALIGN.CENTER, italic=True) add_text(slide, "Hepatology Seminar Presentation", 0.5, 5.1, 12.3, 0.5, font_size=16, color=RGBColor(0x88, 0xAA, 0xCC), align=PP_ALIGN.CENTER) add_text(slide, "Western University, Canada | Beaumont Hospital, Dublin, Ireland", 0.5, 5.6, 12.3, 0.5, font_size=13, color=RGBColor(0x77, 0x99, 0xBB), align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 2 — Overview / Outline # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Presentation Outline") sections = [ "1. Background & Epidemiology", "2. Pathophysiology — Hepcidin & Iron Regulation", "3. Diagnosis: Biochemical & Genetic Testing", "4. Diagnosis: Liver Fibrosis Assessment", "5. Diagnosis: Extra-hepatic Manifestations", "6. Population Screening & Family Cascade Testing", "7. Treatment — Phlebotomy", "8. Emerging Therapies (Mini-hepcidin, CRISPR)", "9. Summary & Key Messages", ] for i, s in enumerate(sections): col = 0 if i < 5 else 6.8 row = 1.5 + (i % 5) * 0.95 add_rect(slide, col + 0.2, row, 5.9, 0.75, WHITE, MID_BLUE) add_text(slide, s, col + 0.35, row + 0.1, 5.6, 0.55, font_size=14, color=DARK_BLUE, bold=(i == 0)) # ═══════════════════════════════════════════════════════════════ # SLIDE 3 — Section divider: Background & Epidemiology # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) section_divider(slide, "Background & Epidemiology") add_text(slide, "The most common genetic disease in persons of European ancestry", 0.5, 3.2, 12.3, 0.8, font_size=20, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 4 — Background # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Background", "Ancient disease — HFE variants found in 4,000-year-old human fossils (NW Europe)") add_multiline(slide, [ "Originally proposed as a survival advantage: enhanced iron absorption in iron-deficient environments", "C282Y variant (845G→A) in the HFE gene is the predominant pathogenic variant", "Excess iron absorption leads to progressive organ damage:", ], 0.4, 1.45, 12.5, 1.5, font_size=17, color=DARK_BLUE) # sub-items add_multiline(slide, [ "Liver fibrosis → Cirrhosis → Hepatocellular carcinoma (HCC)", "Arthritis (metacarpophalangeal joints)", "Cardiomyopathy / arrhythmia", "Diabetes mellitus", "Hypogonadism", ], 0.8, 2.85, 12.0, 2.2, font_size=15.5, color=MID_BLUE) add_rect(slide, 0.4, 5.25, 12.5, 0.85, LIGHT_GOLD, ACCENT_GOLD) add_text(slide, "Key Point: Early identification and treatment prevents virtually all serious complications", 0.55, 5.3, 12.1, 0.75, font_size=15.5, bold=True, color=RGBColor(0x7A, 0x50, 0x00)) # ═══════════════════════════════════════════════════════════════ # SLIDE 5 — Epidemiology # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Epidemiology of HFE Hemochromatosis") stats = [ ("1 in 227", "North American patients\nof European ancestry\n(HEIRS Study)"), ("1 in 156", "Northern England\n(UK Biobank)"), ("1 in 100", "Ireland — highest\nprevalence worldwide"), ("1 in 5\nmales", "Develop morbidity\nassociated with HC\n(UK Biobank)"), ("1 in 10\nmales", "Develop severe liver\ndisease if untreated"), ] for i, (num, label) in enumerate(stats): x = 0.4 + i * 2.55 add_rect(slide, x, 1.45, 2.3, 2.4, DARK_BLUE) add_rect(slide, x, 3.85, 2.3, 1.5, WHITE, MID_BLUE) add_text(slide, num, x + 0.05, 1.65, 2.2, 1.5, font_size=24, bold=True, color=ACCENT_GOLD, align=PP_ALIGN.CENTER) add_text(slide, label, x + 0.05, 3.9, 2.2, 1.35, font_size=12.5, color=DARK_BLUE, align=PP_ALIGN.CENTER) add_text(slide, "Clinical penetrance is NOT absolute — 1 in 10 females also develop morbidity", 0.4, 5.55, 12.5, 0.7, font_size=15, italic=True, color=MID_BLUE) # ═══════════════════════════════════════════════════════════════ # SLIDE 6 — Pathophysiology # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Pathophysiology — Hepcidin & Iron Regulation") add_text(slide, "Central Mechanism: Hepcidin Deficiency", 0.4, 1.4, 12.5, 0.6, font_size=20, bold=True, color=DARK_BLUE) steps = [ ("Normal", "Hepcidin (liver hormone) regulates intestinal iron absorption\nby degrading ferroportin on enterocytes"), ("In HFE-HC", "Mutant HFE protein → Impaired hepcidin upregulation\n→ Constitutively low hepcidin"), ("Result", "Unregulated iron absorption via ferroportin\n→ Progressive systemic iron accumulation"), ("Outcome", "Iron deposits in liver, heart, pancreas, joints, gonads\n→ Oxidative stress & fibrosis"), ] for i, (label, text) in enumerate(steps): y = 2.1 + i * 1.1 add_rect(slide, 0.4, y, 2.0, 0.85, MID_BLUE) add_text(slide, label, 0.45, y + 0.12, 1.9, 0.6, font_size=15, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_rect(slide, 2.4, y, 10.5, 0.85, WHITE, LIGHT_LINE) add_text(slide, text, 2.55, y + 0.06, 10.2, 0.75, font_size=14.5, color=BODY_GRAY) if i < 3: add_text(slide, "↓", 1.25, y + 0.85, 0.5, 0.3, font_size=14, bold=True, color=ACCENT_GOLD, align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 7 — Section: Diagnosis # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) section_divider(slide, "Diagnosis") add_text(slide, "Biochemical testing • Genetic testing • Liver fibrosis assessment • Extra-hepatic manifestations", 0.5, 3.3, 12.3, 0.8, font_size=18, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 8 — Biochemical Diagnosis # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Biochemical Diagnosis — Serum Iron Studies") # Table header cols = ["Test", "Description / Threshold", "Clinical Use"] widths = [2.8, 6.2, 3.8] xs = [0.3, 3.1, 9.3] y0 = 1.5 add_rect(slide, 0.3, y0, 12.7, 0.55, DARK_BLUE) for j, (c, w, x) in enumerate(zip(cols, widths, xs)): add_text(slide, c, x + 0.08, y0 + 0.07, w - 0.16, 0.42, font_size=13.5, bold=True, color=WHITE) rows = [ ("Transferrin Saturation (TS)", "Fasting TS ≥45% used as screening threshold; poor reproducibility", "Initial screen — not diagnostic alone"), ("Serum Ferritin", ">300 µg/L (men) / >200 µg/L (women) → elevated\nKey: >1000 µg/L predicts advanced fibrosis", "Best non-invasive marker of iron burden; guides # phlebotomies"), ("HFE Genetic Test\n(C282Y)", "C282Y homozygosity is the diagnostic genetic test of choice;\nH63D compound heterozygote rarely causes disease", "Confirms diagnosis; drives family cascade testing"), ("MRI Liver (R2/R2*)", "Quantifies liver iron concentration (LIC) non-invasively;\nIron appears dark on T2-weighted sequences", "Avoids liver biopsy in most cases; tracks treatment response"), ("Liver Biopsy", "Gold standard for fibrosis staging; now reserved for\nferritin >1000 or transaminase elevation", "Reserved for uncertain diagnosis or cirrhosis staging"), ] for i, row in enumerate(rows): bg = WHITE if i % 2 == 0 else RGBColor(0xE8, 0xF2, 0xFA) y = y0 + 0.55 + i * 0.95 add_rect(slide, 0.3, y, 12.7, 0.93, bg, LIGHT_LINE) for j, (cell, w, x) in enumerate(zip(row, widths, xs)): add_text(slide, cell, x + 0.08, y + 0.04, w - 0.16, 0.86, font_size=12, color=DARK_BLUE if j == 0 else BODY_GRAY, bold=(j == 0)) # ═══════════════════════════════════════════════════════════════ # SLIDE 9 — Diagnostic Algorithm # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Diagnostic Algorithm for HFE Hemochromatosis") boxes = [ (4.5, 1.4, 4.3, 0.75, "Elevated Transferrin Saturation (≥45%)\nor Elevated Serum Ferritin", DARK_BLUE, WHITE), (4.5, 2.5, 4.3, 0.75, "HFE Genetic Testing\n(C282Y + H63D)", MID_BLUE, WHITE), (0.5, 3.9, 3.5, 0.75, "C282Y Homozygote\n→ Confirmed HC", SECTION_TEAL, WHITE), (4.5, 3.9, 4.3, 0.75, "C282Y / H63D Compound\nHet → low iron burden", RGBColor(0x8B, 0x4F, 0x00), WHITE), (9.0, 3.9, 3.8, 0.75, "Other variants or\nnegative → reconsider", RGBColor(0x66, 0x33, 0x00), WHITE), (0.5, 5.2, 3.5, 0.75, "Assess serum ferritin,\nliver fibrosis, organs", DARK_BLUE, WHITE), ] for (x, y, w, h, txt, bg, fg) in boxes: add_rect(slide, x, y, w, h, bg) add_text(slide, txt, x + 0.1, y + 0.06, w - 0.2, h - 0.12, 12.5, color=fg, align=PP_ALIGN.CENTER) # arrows arrows = [ (6.65, 2.15, 6.65, 2.5), (4.5, 2.87, 2.25, 3.9), (6.65, 3.25, 6.65, 3.9), (8.8, 2.87, 10.9, 3.9), (2.25, 4.65, 2.25, 5.2), ] for (x1, y1, x2, y2) in arrows: from pptx.util import Inches as I line = slide.shapes.add_connector(1, I(x1), I(y1), I(x2), I(y2)) line.line.color.rgb = ACCENT_GOLD line.line.width = Pt(2) add_text(slide, "↑ Note: Diagnosis has shifted from phenotyping (low reproducibility) → genotyping (simple, reliable)", 0.3, 6.5, 12.7, 0.7, font_size=13.5, italic=True, color=MID_BLUE) # ═══════════════════════════════════════════════════════════════ # SLIDE 10 — Serum Ferritin: Key Thresholds # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Serum Ferritin — The Most Important Clinical Marker") thresholds = [ ("<300 µg/L (men)\n<200 µg/L (women)", "Normal range", WHITE, DARK_BLUE), ("300–1000 µg/L", "Elevated — confirm genotype;\ncheck for secondary causes;\nmonitor and consider phlebotomy", RGBColor(0xFFF3CC), RGBColor(0x7A, 0x50, 0x00)), (">1000 µg/L", "High risk — 1 in 5 have\nadvanced liver fibrosis (F3/F4);\nurgent phlebotomy indicated", RGBColor(0xFF, 0xE0, 0xE0), RGBColor(0x8B, 0x00, 0x00)), ] for i, (val, meaning, bg, fg) in enumerate(thresholds): x = 0.5 + i * 4.2 add_rect(slide, x, 1.5, 3.9, 1.2, DARK_BLUE) add_text(slide, val, x + 0.1, 1.55, 3.7, 1.1, font_size=20, bold=True, color=ACCENT_GOLD, align=PP_ALIGN.CENTER) add_rect(slide, x, 2.7, 3.9, 1.8, bg, MID_BLUE) add_text(slide, meaning, x + 0.15, 2.75, 3.6, 1.7, font_size=14, color=fg, align=PP_ALIGN.CENTER) add_text(slide, "Additional uses of serum ferritin:", 0.5, 4.7, 12.5, 0.5, font_size=16, bold=True, color=DARK_BLUE) add_multiline(slide, [ "Best non-invasive estimate of total body iron stores", "Guides expected number of phlebotomies required for de-ironing", "Indicator of liver disease risk", "Target for maintenance therapy: ferritin <50 µg/L (complete de-ironing) or <300 µg/L (ongoing maintenance)", ], 0.5, 5.25, 12.5, 2.0, font_size=14, color=DARK_BLUE) # ═══════════════════════════════════════════════════════════════ # SLIDE 11 — Liver Fibrosis Assessment # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Liver Fibrosis Assessment in Hemochromatosis") add_text(slide, "All C282Y homozygotes should be screened for liver fibrosis — approx. 20% of adult males will be affected", 0.4, 1.35, 12.5, 0.55, font_size=14.5, italic=True, color=MID_BLUE) tools = [ ("Abdominal Ultrasound", "Baseline for all; assess steatosis, cirrhosis, portal hypertension, HCC screening"), ("APRI Score", ">0.44 → good detection of advanced fibrosis (AUROC 0.86–0.88)\n<0.37 → NPV 88.6% for advanced fibrosis"), ("FIB-4 Score", ">1.1 → good detection of advanced fibrosis\n<0.73 → NPV 92% for advanced fibrosis"), ("Transient Elastography\n(FibroScan)", "Liver stiffness <6.4 kPa → high NPV for ruling out advanced fibrosis\nCaution: poor correlation with APRI/FIB-4 in some HC studies"), ("MRI R2/R2* (LiverMultiScan)", "Non-invasive; simultaneous iron quantification (LIC) and fibrosis staging\nCorrelates with liver biopsy; emerging preferred modality"), ("Liver Biopsy", "Gold standard for staging; reserved for ferritin >1000 µg/L AND elevated transaminases\nOr when non-invasive tests are discordant"), ] for i, (tool, desc) in enumerate(tools): col = 0 if i < 3 else 6.7 row = 2.1 + (i % 3) * 1.55 add_rect(slide, col + 0.2, row, 2.5, 1.35, MID_BLUE) add_text(slide, tool, col + 0.3, row + 0.2, 2.3, 0.95, font_size=12.5, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_rect(slide, col + 2.7, row, 3.8, 1.35, WHITE, LIGHT_LINE) add_text(slide, desc, col + 2.85, row + 0.08, 3.6, 1.2, font_size=12, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 12 — Extra-hepatic Manifestations # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Extra-hepatic Manifestations of Hemochromatosis") organs = [ ("Musculoskeletal", [ "Arthritis most common extra-hepatic complaint", "27.9% males require joint replacement vs. 17.1% controls (UK Biobank)", "Metacarpophalangeal (MCP) joints — classic 2nd/3rd MCP arthropathy", "Baseline DEXA scan for osteoporosis in C282Y homozygotes >40 yrs", ]), ("Cardiovascular", [ "<3% C282Y homozygotes develop clinically significant cardiac iron overload", "Dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmias", "Young patients (<30 yrs) or juvenile hemochromatosis at higher risk", "Baseline ECG + echocardiogram if symptoms present", ]), ("Endocrine", [ "Diabetes: iron deposits in pancreatic beta cells (bronze diabetes)", "Baseline HbA1c + fasting glucose in all C282Y homozygotes", "Hypogonadism: iron deposits in pituitary — low testosterone in men", "Osteoporosis: excess liver disease, hypogonadism, or direct iron effect", ]), ] for i, (organ, points) in enumerate(organs): x = 0.3 + i * 4.35 add_rect(slide, x, 1.5, 4.15, 0.6, DARK_BLUE) add_text(slide, organ, x + 0.1, 1.55, 3.95, 0.5, font_size=16, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_rect(slide, x, 2.1, 4.15, 4.1, WHITE, MID_BLUE) for j, pt in enumerate(points): add_text(slide, "• " + pt, x + 0.2, 2.18 + j * 0.95, 3.8, 0.88, font_size=12.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 13 — When to suspect in clinical practice # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "When to Suspect Hemochromatosis — Clinical Red Flags") add_text(slide, "Consider hemochromatosis in any patient of Northern European descent with:", 0.4, 1.42, 12.5, 0.55, font_size=16, bold=True, color=DARK_BLUE) flags = [ ("Liver", "Unexplained elevated liver enzymes\nNAFLD with disproportionate fibrosis\nCirrhosis with no clear aetiology\nHCC (especially non-cirrhotic)"), ("Metabolic", "Type 2 diabetes with no obvious risk factors\nHypogonadism in young/middle-aged men\nFatigue, lethargy — unexplained"), ("Musculoskeletal", "Early-onset arthritis especially MCP joints\nProgressive joint replacement needs\nOsteoporosis in young individuals"), ("Family History", "First-degree relative with confirmed HFE HC\nFamily history of early cirrhosis or HCC\nIrish, Celtic, or Northern European ancestry"), ] for i, (category, text) in enumerate(flags): col = 0.4 if i < 2 else 6.8 row = 2.15 + (i % 2) * 2.25 add_rect(slide, col, row, 6.0, 0.5, MID_BLUE) add_text(slide, category, col + 0.2, row + 0.06, 5.7, 0.4, font_size=14, bold=True, color=WHITE) add_rect(slide, col, row + 0.5, 6.0, 1.6, WHITE, LIGHT_LINE) add_text(slide, text, col + 0.2, row + 0.55, 5.7, 1.48, font_size=13, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 14 — Genetic Testing & Variants # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "HFE Genetic Variants — What Clinicians Need to Know") variants = [ ("C282Y Homozygote\n(C282Y/C282Y)", "845G→A substitution in exon 4\nMost significant variant — accounts for\n~85–90% of HFE-HC in Northern Europeans\nGold standard for diagnosis", "HIGH", "Confirmed hereditary hemochromatosis"), ("Compound Heterozygote\n(C282Y/H63D)", "One copy each of C282Y + H63D variants\nMinor increase in serum iron; rarely\ncauses significant iron overload without\nother risk factors (alcohol, NAFLD)", "LOW–MODERATE", "Mild biochemical elevation; rarely causes end-organ disease"), ("H63D Homozygote\n(H63D/H63D)", "Two copies of H63D variant\nVery mild effect on iron studies;\nnot considered pathogenic alone\nin most clinical guidelines", "VERY LOW", "Not considered clinically significant HFE-HC"), ] for i, (name, genetics, risk, clinical) in enumerate(variants): y = 1.55 + i * 1.75 add_rect(slide, 0.3, y, 3.8, 1.55, DARK_BLUE) add_text(slide, name, 0.4, y + 0.15, 3.6, 1.3, font_size=13.5, bold=True, color=WHITE, align=PP_ALIGN.CENTER) risk_color = RGBColor(0xC8, 0x20, 0x20) if risk == "HIGH" else (RGBColor(0xC8, 0x96, 0x20) if "MODERATE" in risk else RGBColor(0x11, 0x77, 0x33)) add_rect(slide, 4.1, y, 2.5, 1.55, WHITE, risk_color) add_text(slide, "Risk Level", 4.2, y + 0.08, 2.3, 0.45, 11, bold=True, color=risk_color) add_text(slide, risk, 4.2, y + 0.5, 2.3, 0.8, 14, bold=True, color=risk_color, align=PP_ALIGN.CENTER) add_rect(slide, 6.6, y, 6.4, 1.55, RGBColor(0xF5, 0xF8, 0xFF), LIGHT_LINE) add_text(slide, genetics + "\n\n→ " + clinical, 6.75, y + 0.08, 6.1, 1.38, 12, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 15 — Section: Screening # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) section_divider(slide, "Population Screening &\nFamily Cascade Testing") add_text(slide, "Who to screen • When to screen • How to screen", 0.5, 3.55, 12.3, 0.8, font_size=18, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 16 — Population Screening # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Population Screening for Hemochromatosis") add_text(slide, "Current evidence supports targeted, not universal, population screening", 0.4, 1.42, 12.5, 0.55, font_size=15, italic=True, color=MID_BLUE) col1 = [ "Large blood donor screening studies (Europe, North America) consistently find ~1 in 200 donors to be C282Y homozygotes", "Irish neonatal screening study: C282Y prevalence 1 in 100 (highest globally)", "UK Biobank: 1 in 5 male C282Y homozygotes develop morbidity — changing perception from 'benign' to clinically significant", "HEIRS Study (100,000 participants): largest prospective screening study; defined prevalence across racial/ethnic groups", "Genetic testing is simple, cheap, and reliable — one-time lifelong test", ] col2 = [ "Arguments FOR population screening: High prevalence in at-risk groups; treatable with low-cost intervention; prevention of end-organ damage possible", "Arguments AGAINST: Incomplete penetrance; limited evidence from RCTs; risk of discrimination/insurance issues", "Current recommendation: Targeted screening of persons of Northern European ancestry with elevated iron indices", "Cost-effectiveness analyses favour genotype-based screening over phenotype-based in high-prevalence populations", ] add_text(slide, "Evidence Base", 0.4, 2.1, 6.2, 0.48, font_size=15, bold=True, color=DARK_BLUE) add_multiline(slide, col1, 0.4, 2.58, 6.2, 3.8, font_size=12.5, color=BODY_GRAY) add_text(slide, "Screening Debate", 6.8, 2.1, 6.1, 0.48, font_size=15, bold=True, color=DARK_BLUE) add_multiline(slide, col2, 6.8, 2.58, 6.1, 3.8, font_size=12.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 17 — Family Cascade Testing # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Family Cascade Testing — Recommended Approach") add_text(slide, "All first-degree relatives of a confirmed C282Y homozygote should be offered testing", 0.4, 1.42, 12.5, 0.55, font_size=16, bold=True, color=DARK_BLUE) steps2 = [ ("Step 1", "Proband confirmed as C282Y homozygote"), ("Step 2", "Test the proband's partner/spouse for C282Y carrier status"), ("Step 3", "If partner is C282Y negative → children cannot be C282Y homozygotes → testing NOT needed"), ("Step 4", "If partner is C282Y positive → test children for C282Y homozygosity"), ("Step 5", "Siblings of proband: autosomal recessive → 25% risk; test all adult siblings"), ("Step 6", "Cascade to extended family as appropriate; target adults only (testing not recommended in children)"), ] for i, (step, desc) in enumerate(steps2): y = 2.1 + i * 0.82 add_rect(slide, 0.4, y, 1.6, 0.72, MID_BLUE) add_text(slide, step, 0.45, y + 0.12, 1.5, 0.5, font_size=14, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_rect(slide, 2.0, y, 11.0, 0.72, WHITE if i % 2 == 0 else RGBColor(0xE8, 0xF2, 0xFA), LIGHT_LINE) add_text(slide, desc, 2.15, y + 0.1, 10.7, 0.54, font_size=13.5, color=BODY_GRAY) add_rect(slide, 0.4, 7.0, 12.5, 0.3, LIGHT_GOLD, ACCENT_GOLD) add_text(slide, "Non-adult children: screening NOT recommended — defer to adulthood", 0.55, 7.02, 12.1, 0.26, font_size=12, bold=True, color=RGBColor(0x7A, 0x50, 0x00)) # ═══════════════════════════════════════════════════════════════ # SLIDE 18 — Section: Treatment # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) section_divider(slide, "Treatment of Hemochromatosis") add_text(slide, "Phlebotomy • Emerging therapies • Lifestyle", 0.5, 3.5, 12.3, 0.8, font_size=18, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 19 — Phlebotomy: Overview # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Phlebotomy — The Cornerstone of Treatment") add_text(slide, '"Treatment of hemochromatosis by phlebotomy has stood the test of time and is a very safe and cost-effective treatment"', 0.5, 1.42, 12.3, 0.75, font_size=15, italic=True, color=MID_BLUE, align=PP_ALIGN.CENTER) cards = [ ("Mechanism", "Each 500 mL phlebotomy removes ~200–250 mg of iron\nElicits compensatory erythropoiesis mobilising iron from storage"), ("Induction Phase", "Weekly phlebotomy until iron depleted\nTarget: ferritin <50 µg/L\nNumber of sessions guided by initial ferritin level"), ("Maintenance Phase", "Phlebotomy every 3–4 months (lifelong)\nTarget: ferritin <300 µg/L (some guidelines: <50 µg/L)\nMinimum 3× per year — one per season"), ("Benefits", "Reduces liver stiffness and fibrosis progression\nReduces risk: diabetes, cirrhosis, liver cancer, death\nSurvival equivalent to general population if treated early"), ("Side Effects", "Well tolerated; fatigue in some patients\nContraindicated in severe anaemia\nErythrocytapheresis available for intolerant patients"), ("Urgency", "Urgent phlebotomy: ferritin >1000 µg/L, symptomatic,\nor evidence of end-organ damage"), ] for i, (title, body) in enumerate(cards): col = 0.3 + (i % 3) * 4.35 row = 2.3 + (i // 3) * 2.15 add_rect(slide, col, row, 4.05, 0.5, DARK_BLUE) add_text(slide, title, col + 0.1, row + 0.07, 3.85, 0.38, 13, bold=True, color=WHITE) add_rect(slide, col, row + 0.5, 4.05, 1.5, WHITE, MID_BLUE) add_text(slide, body, col + 0.12, row + 0.58, 3.82, 1.35, 12.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 20 — Phlebotomy: Practical Guide # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Practical Management Guide for Phlebotomy") add_text(slide, "Monitoring during treatment", 0.4, 1.42, 12.5, 0.5, font_size=17, bold=True, color=DARK_BLUE) monitor = [ "FBC before each phlebotomy — withhold if Hb <12 g/dL (women) or <13 g/dL (men)", "Serum ferritin every 3 months during induction; annually during maintenance", "Liver function tests (ALT/AST) every 6–12 months", "HbA1c annually in those with diabetes or insulin resistance", "Abdominal ultrasound every 6 months in confirmed cirrhosis (HCC surveillance)", "AFP: serial measurement in cirrhotic patients as part of HCC surveillance", ] add_multiline(slide, monitor, 0.4, 1.95, 12.5, 3.0, font_size=14, color=DARK_BLUE) add_text(slide, "Expected outcomes with adequate treatment", 0.4, 5.05, 12.5, 0.5, font_size=17, bold=True, color=DARK_BLUE) outcomes = [ "Non-cirrhotic patients treated early: normal life expectancy", "Liver fibrosis: regression possible; liver biopsy improvement documented", "Diabetes: may partially improve; established cirrhosis or severe neuropathy may not reverse", "Arthropathy: usually does not improve with treatment — symptomatic management required", ] add_multiline(slide, outcomes, 0.4, 5.6, 12.5, 1.75, font_size=14, color=MID_BLUE) # ═══════════════════════════════════════════════════════════════ # SLIDE 21 — Evidence for Treatment Benefits # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Evidence for Treatment Benefits of Phlebotomy") add_text(slide, "Key clinical evidence supporting phlebotomy in HFE-HC:", 0.4, 1.42, 12.5, 0.55, font_size=16, bold=True, color=DARK_BLUE) evidence = [ ("Liver Fibrosis", "Phlebotomy associated with reduced liver fibrosis scores and reversal in pre-cirrhotic patients (multiple cohort studies; Adams et al)"), ("Liver Cancer Risk", "Untreated C282Y homozygotes: significantly elevated HCC risk; treated early — risk approaches general population"), ("Cirrhosis Prevention", "Diagnosis and treatment before cirrhosis develops: survival equivalent to age-matched population"), ("Diabetes", "HbA1c improvement documented in newly diagnosed DM patients undergoing phlebotomy; established beta-cell failure may not recover"), ("Quality of Life", "Reduction in fatigue, lethargy, and mood disturbance after iron depletion (observational studies)"), ("Cost-effectiveness", "Phlebotomy is among the most cost-effective interventions in chronic disease management — avoids expensive sequelae"), ("Mortality", "Cirrhotic HC patients: increased mortality, particularly HCC and liver failure; emphasises need for early diagnosis"), ] for i, (cat, text) in enumerate(evidence): y = 2.05 + i * 0.72 bg = WHITE if i % 2 == 0 else RGBColor(0xE8, 0xF2, 0xFA) add_rect(slide, 0.4, y, 12.5, 0.68, bg, LIGHT_LINE) add_text(slide, cat + ":", 0.55, y + 0.1, 2.3, 0.5, 13, bold=True, color=DARK_BLUE) add_text(slide, text, 2.85, y + 0.1, 9.9, 0.5, 12.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 22 — Lifestyle & Dietary Advice # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Lifestyle Modifications in Hemochromatosis") add_multiline(slide, [ "Alcohol: avoid or minimise — synergistic hepatotoxicity; potentiates liver fibrosis progression", "Vitamin C: avoid high-dose supplements (>500 mg/day) — enhances non-haem iron absorption; promotes free radical generation from iron", "Raw shellfish: avoid — Vibrio vulnificus infection is disproportionately lethal in iron-overloaded patients", "Red meat: moderate reduction may marginally reduce haem iron load, but not a substitute for phlebotomy", "Tea (especially English tea): polyphenols inhibit non-haem iron absorption — can be beneficial", "Iron-fortified foods: iron supplementation in food was common in 1950s; some evidence reduction of iron fortification in Scandinavia had minor population health effects", "Coffee: emerging data on hepatoprotective effects in iron overload; moderate consumption is safe", "Proton pump inhibitors (PPIs): reduce gastric acid → modestly reduce iron absorption; not sufficient alone to manage HC", ], 0.4, 1.45, 12.5, 5.5, font_size=14, color=DARK_BLUE) # ═══════════════════════════════════════════════════════════════ # SLIDE 23 — Section: Emerging Therapies # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) section_divider(slide, "Emerging Therapies") add_text(slide, "Mini-hepcidin • Gene editing (CRISPR) • Erythrocytapheresis", 0.5, 3.5, 12.3, 0.8, font_size=18, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) # ═══════════════════════════════════════════════════════════════ # SLIDE 24 — Emerging Therapies: Mini-Hepcidin & CRISPR # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Emerging Therapies — On the Horizon") therapies = [ ("Synthetic Mini-Hepcidin\n(Parenteral)", [ "Rationale: directly replace deficient hepcidin → block ferroportin → reduce intestinal iron absorption", "Animal model data: effective at reducing intestinal absorption but does NOT mobilise hepatic iron stores", "Proposed strategy: initial de-ironing with phlebotomy, then maintenance with periodic hepcidin injections", "Potential benefit: reduce frequency of maintenance phlebotomy sessions", "Challenges: must demonstrate superiority or non-inferiority to phlebotomy; cost; injection burden", "Status: Phase I/II trials underway — not yet approved for clinical use", ], MID_BLUE), ("CRISPR Gene Editing", [ "Concept: correct the C282Y mutation in HFE gene → restore normal hepcidin regulation", "Early animal model data: proof-of-concept correction achieved in mice", "Challenge: liver-targeted somatic gene editing required; off-target effects; long-term safety unknown", "Liver is amenable to AAV-based delivery — relevant advantage over other tissues", "Timeline: still in pre-clinical / early clinical research phase", "Must ultimately be compared against phlebotomy — the benchmark treatment", ], SECTION_TEAL), ("Erythrocytapheresis", [ "Selective removal of red blood cells via apheresis — removes more iron per session than standard phlebotomy", "Advantage: fewer sessions needed; better tolerated in some patients (less haemodynamic change)", "Indicated when phlebotomy is poorly tolerated (e.g., cardiovascular disease, difficulty with venous access)", "Not routinely available in all centres; higher cost", "May be combined with phlebotomy in severe juvenile hemochromatosis with cardiac dysfunction", ], DARK_BLUE), ] for i, (name, points, color) in enumerate(therapies): x = 0.3 + i * 4.35 add_rect(slide, x, 1.5, 4.1, 0.7, color) add_text(slide, name, x + 0.1, 1.55, 3.9, 0.6, font_size=13, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_rect(slide, x, 2.2, 4.1, 4.8, WHITE, LIGHT_LINE) for j, pt in enumerate(points): add_text(slide, "• " + pt, x + 0.15, 2.28 + j * 0.75, 3.8, 0.68, font_size=11.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 25 — Management Summary Table # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Diagnosis & Treatment Summary — Key Tables") add_text(slide, "Table 2: Evolution of Diagnostic Tests", 0.4, 1.42, 6.2, 0.5, font_size=15, bold=True, color=DARK_BLUE) add_text(slide, "Table 3: Treatments Compared to Phlebotomy", 6.8, 1.42, 6.1, 0.5, font_size=15, bold=True, color=DARK_BLUE) diag_rows = [ ("Serum Ferritin", "Non-specific; elevated by inflammation", "→ Still best clinical iron marker"), ("Transferrin Sat", "Unreliable reproducibility", "→ Useful initial screen only"), ("Liver Biopsy", "Invasive; gold standard for fibrosis", "→ Now reserved for selected cases"), ("HFE Genetic Test", "Simple, reliable, once-only test", "→ Now diagnostic test of choice"), ("MRI Liver", "Advanced non-invasive LIC + fibrosis", "→ Replaces biopsy in most cases"), ("Elastography", "Non-invasive fibrosis assessment", "→ Good NPV for ruling out F3/F4"), ] for i, (test, limitation, update) in enumerate(diag_rows): y = 2.0 + i * 0.78 bg = WHITE if i % 2 == 0 else RGBColor(0xE8, 0xF2, 0xFA) add_rect(slide, 0.4, y, 6.1, 0.72, bg, LIGHT_LINE) add_text(slide, test, 0.55, y + 0.1, 1.8, 0.54, 12, bold=True, color=DARK_BLUE) add_text(slide, limitation, 2.35, y + 0.1, 2.2, 0.54, 11, color=RGBColor(0x88, 0x22, 0x22)) add_text(slide, update, 4.55, y + 0.1, 1.8, 0.54, 11, color=SECTION_TEAL) tx_rows = [ ("Phlebotomy", "Established", "Excellent", "Low", "✓ Standard of care"), ("Mini-Hepcidin", "Phase I/II", "TBD", "Medium", "Promising — maintenance only"), ("CRISPR", "Pre-clinical", "TBD", "TBD", "Potential cure — decades away"), ("Erythrocytapheresis", "Established", "High", "High", "Specialised centres; intolerant patients"), ("Dietary modification", "Established", "Low", "Low", "Adjunct only — never monotherapy"), ("Liver Transplant", "Established (cirrhosis)", "Variable", "High", "End-stage disease; corrects defect"), ] tx_heads = ["Treatment", "Status", "Efficacy", "Cost", "Role"] tx_widths = [2.5, 1.5, 1.2, 1.1, 2.5] tx_xs = [6.8, 9.3, 10.8, 12.0, 13.1] # last col goes off — adjust tx_xs2 = [6.8, 9.05, 10.35, 11.4, 12.25] tw2 = [2.1, 1.15, 0.9, 0.75, 1.0] add_rect(slide, 6.8, 2.0, 6.1, 0.5, DARK_BLUE) for j, (h, w, x) in enumerate(zip(tx_heads, tw2, tx_xs2)): add_text(slide, h, x + 0.05, 2.05, w - 0.1, 0.4, 11, bold=True, color=WHITE) for i, row in enumerate(tx_rows): y = 2.5 + i * 0.72 bg = WHITE if i % 2 == 0 else RGBColor(0xE8, 0xF2, 0xFA) add_rect(slide, 6.8, y, 6.1, 0.68, bg, LIGHT_LINE) for j, (cell, w, x) in enumerate(zip(row, tw2, tx_xs2)): add_text(slide, cell, x + 0.05, y + 0.1, w - 0.1, 0.5, 10.5, color=DARK_BLUE if j == 0 else BODY_GRAY, bold=(j == 0)) # ═══════════════════════════════════════════════════════════════ # SLIDE 26 — Special Populations # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Special Populations & Clinical Scenarios") pops = [ ("Juvenile Hemochromatosis\n(Non-HFE)", [ "Caused by HJV or HAMP gene mutations", "Presents in 2nd–3rd decade — severe cardiac and endocrine involvement", "Cardiac dysfunction may require urgent erythrocytapheresis + phlebotomy", "Rapid diagnosis and treatment essential — fatal without treatment", ]), ("Pregnancy", [ "Physiological iron demand often masks diagnosis during pregnancy", "Ferritin can be transiently low — may delay diagnosis", "Phlebotomy safe in pregnancy if clinically necessary", "Counsel re: autosomal recessive inheritance to partner", ]), ("Cirrhotic Hemochromatosis", [ "Significantly elevated HCC risk — 6-month ultrasound + AFP surveillance mandatory", "Phlebotomy still beneficial: improves portal pressure, reduces inflammation", "Liver transplantation corrects the underlying metabolic defect", "Transplant outcomes similar to other aetiologies if iron overload not the only organ affected", ]), ("Blood Donation", [ "Phlebotomy blood from HC patients: used for therapeutic transfusion in some countries", "Varies by national blood service policy — check local guidelines", "Allows patients to participate actively in managing their condition", "Reduces logistical burden and cost where acceptable", ]), ] for i, (title, pts) in enumerate(pops): col = 0.3 if i % 2 == 0 else 6.85 row = 1.5 if i < 2 else 4.05 add_rect(slide, col, row, 6.2, 0.55, DARK_BLUE) add_text(slide, title, col + 0.1, row + 0.06, 6.0, 0.44, 13, bold=True, color=WHITE) add_rect(slide, col, row + 0.55, 6.2, 2.3, WHITE, MID_BLUE) for j, pt in enumerate(pts): add_text(slide, "• " + pt, col + 0.2, row + 0.62 + j * 0.54, 5.85, 0.5, 12.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 27 — Unresolved Questions / Future Directions # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Unresolved Questions & Future Directions") qs = [ ("Population Screening", "Should universal genetic screening be implemented for C282Y in Northern European populations? Cost-effectiveness data are favourable but RCT evidence lacking."), ("Optimal Ferritin Target", "Ferritin <50 µg/L (full de-ironing) vs. <300 µg/L for maintenance — which target maximises outcomes with minimum therapy burden?"), ("Penetrance Prediction", "Can we predict which C282Y homozygotes will develop clinical disease? Polygenic risk scores, modifier genes, and environmental factors are under study."), ("Hepcidin Therapy", "Can hepcidin injections replace or reduce maintenance phlebotomy? Combination trials (phlebotomy induction + hepcidin maintenance) are ongoing."), ("CRISPR Gene Editing", "Will somatic gene editing achieve durable correction of HFE mutation? Long-term safety and delivery challenges remain significant."), ("Non-HFE HC", "Optimal management algorithms for HJV, TFR2, SLC40A1, and HAMP mutations — rare but clinically severe; more data needed."), ] for i, (q, a) in enumerate(qs): y = 1.5 + i * 0.98 add_rect(slide, 0.4, y, 3.8, 0.88, MID_BLUE) add_text(slide, q, 0.5, y + 0.12, 3.6, 0.65, 13, bold=True, color=WHITE) add_rect(slide, 4.2, y, 9.0, 0.88, WHITE, LIGHT_LINE) add_text(slide, a, 4.35, y + 0.08, 8.75, 0.74, 12.5, color=BODY_GRAY) # ═══════════════════════════════════════════════════════════════ # SLIDE 28 — Key Messages # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, DARK_BLUE) add_rect(slide, 0, 0, 13.333, 0.08, ACCENT_GOLD) add_rect(slide, 0, 1.1, 13.333, 0.08, ACCENT_GOLD) add_text(slide, "Key Take-Home Messages", 0.5, 0.12, 12.3, 0.88, font_size=30, bold=True, color=WHITE, align=PP_ALIGN.CENTER) messages = [ ("1", "Hemochromatosis is common — 1 in 227 North Americans and 1 in 100 Irish individuals carry the C282Y homozygous genotype."), ("2", "Clinical penetrance is significant: 1 in 5 males will develop morbidity; 1 in 10 will develop severe liver disease without treatment."), ("3", "C282Y genetic testing is the diagnostic test of choice — replacing unreliable phenotypic tests."), ("4", "Serum ferritin >1000 µg/L is the threshold demanding urgent action — 1 in 5 will have advanced fibrosis."), ("5", "Phlebotomy is safe, cheap, and effective — it has stood the test of time and prevents virtually all complications if initiated early."), ("6", "Family cascade testing is essential — all first-degree relatives should be offered C282Y testing."), ("7", "Emerging therapies (hepcidin, CRISPR) are promising but must ultimately be tested against phlebotomy."), ] for i, (num, msg) in enumerate(messages): y = 1.25 + i * 0.87 add_rect(slide, 0.3, y, 0.75, 0.72, ACCENT_GOLD) add_text(slide, num, 0.32, y + 0.1, 0.71, 0.52, 22, bold=True, color=DARK_BLUE, align=PP_ALIGN.CENTER) add_text(slide, msg, 1.15, y + 0.1, 12.0, 0.62, 14, color=WHITE) # ═══════════════════════════════════════════════════════════════ # SLIDE 29 — References # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, LIGHT_BG) header_bar(slide, "Key References") refs = [ "1. Adams PC, Jeffrey G, Ryan J. Haemochromatosis. Lancet 2023; 401:1811–1821.", "2. Adams PC, Reboussin DM, Barton JC, et al (HEIRS). Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005; 352:1769–1778.", "3. Pilling LC, Tamosauskaite J, Jones G, et al. Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. BMJ 2019; 364:k5222.", "4. Lucas MR, Atkins JL, Pilling LC, et al. HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank. BMJ Open 2024.", "5. Allen KJ, Gurrin LC, Constantine CC, et al. Iron-overload–related disease in HFE hereditary hemochromatosis. N Engl J Med 2008; 358:221–230.", "6. Legros L, et al. Noninvasive assessment of liver fibrosis in C282Y homozygous hemochromatosis. Hepatology 2022.", "7. Zoller H, et al. European Association for the Study of the Liver: EASL Clinical Practice Guidelines for HFE Haemochromatosis. J Hepatol 2022; 77:479–502.", "8. Adams PC, Ryan JD. Diagnosis and Treatment of Hemochromatosis. Clin Gastroenterol Hepatol 2025; 23:1477–1485. [Source paper for this presentation]", ] for i, ref in enumerate(refs): y = 1.5 + i * 0.68 bg = WHITE if i % 2 == 0 else RGBColor(0xE8, 0xF2, 0xFA) add_rect(slide, 0.4, y, 12.5, 0.62, bg, LIGHT_LINE) bold = (i == 7) add_text(slide, ref, 0.55, y + 0.07, 12.1, 0.5, 12, color=DARK_BLUE if bold else BODY_GRAY, bold=bold) # ═══════════════════════════════════════════════════════════════ # SLIDE 30 — Closing / Thank You # ═══════════════════════════════════════════════════════════════ slide = prs.slides.add_slide(blank) set_bg(slide, DARK_BLUE) add_rect(slide, 0, 2.8, 13.333, 0.1, ACCENT_GOLD) add_text(slide, "Thank You", 0.5, 0.6, 12.3, 1.5, font_size=52, bold=True, color=WHITE, align=PP_ALIGN.CENTER) add_text(slide, "Diagnosis and Treatment of Hemochromatosis", 0.5, 2.1, 12.3, 0.7, font_size=22, color=RGBColor(0xBB, 0xCC, 0xDD), align=PP_ALIGN.CENTER) add_text(slide, "Adams PC & Ryan JD — Clinical Gastroenterology and Hepatology 2025; 23:1477–1485", 0.5, 2.95, 12.3, 0.65, font_size=15, italic=True, color=ACCENT_GOLD, align=PP_ALIGN.CENTER) add_text(slide, "Questions & Discussion", 0.5, 3.8, 12.3, 0.65, font_size=24, color=WHITE, align=PP_ALIGN.CENTER) add_text(slide, "Western University, London, Canada | Beaumont Hospital, Dublin, Ireland", 0.5, 4.7, 12.3, 0.5, font_size=14, color=RGBColor(0x88, 0xAA, 0xCC), align=PP_ALIGN.CENTER) add_text(slide, "Open access article — CC BY 4.0 — https://doi.org/10.1016/j.cgh.2024.10.041", 0.5, 5.35, 12.3, 0.5, font_size=12, color=RGBColor(0x77, 0x99, 0xBB), align=PP_ALIGN.CENTER, italic=True) # Save out_path = "/tmp/workspace/hemochromatosis-pptx/Hemochromatosis_Hepatology_Seminar.pptx" buf = BytesIO() prs.save(buf) with open(out_path, "wb") as f: f.write(buf.getvalue()) print(f"Saved: {out_path}") print(f"Slides: {len(prs.slides)}") PYEOF

python3 -c " # Find the problematic lines import re code = open('/dev/stdin').read() " << 'EOF' # Let me check - the issue is RGBColor(0x7A, 0x50, 0x00) usage in slide 10 text add # Looking at 'color=RGBColor(0x7A, 0x50, 0x00)' -- that should be fine # Actually checking line 310 -- could be in the section where LIGHT_GOLD is passed # The issue: RGBColor(0xCC, 0xDD, 0xEE) -- that's 3 args, should be fine # Let me check the actual error more carefully -- line 310 in the script echo "Checking line numbers" EOF python3 -c " with open('/dev/stdin') as f: pass print('done') "

~/hemochromatosis-pptx/build_pptx.py

cd /tmp/workspace/hemochromatosis-pptx && python3 build_pptx.py