const {
  Document, Packer, Paragraph, TextRun, Table, TableRow, TableCell,
  Header, Footer, AlignmentType, HeadingLevel, BorderStyle, WidthType,
  ShadingType, VerticalAlign, PageNumber, PageBreak, ImageRun,
  TableOfContents, UnderlineType, LineRuleType
} = require('docx');
const fs = require('fs');
const https = require('https');
const http = require('http');
const path = require('path');

// ─────────────────────────────────────────────────────────────────────
// Helper: download an image from URL → Buffer
// ─────────────────────────────────────────────────────────────────────
function downloadImage(url) {
  return new Promise((resolve, reject) => {
    const proto = url.startsWith('https') ? https : http;
    proto.get(url, (res) => {
      const chunks = [];
      res.on('data', (chunk) => chunks.push(chunk));
      res.on('end', () => resolve(Buffer.concat(chunks)));
      res.on('error', reject);
    }).on('error', reject);
  });
}

// ─────────────────────────────────────────────────────────────────────
// Style helpers
// ─────────────────────────────────────────────────────────────────────
const FONT = "Times New Roman";
const FONT_SIZE = 24; // 12pt in half-points
const FONT_SIZE_LARGE = 28; // 14pt
const FONT_SIZE_TITLE = 36; // 18pt
const LINE_SPACING = { before: 0, after: 120, line: 480, lineRule: LineRuleType.AUTO }; // ~double
const SINGLE_SPACE = { before: 0, after: 120, line: 240, lineRule: LineRuleType.AUTO };

function body(text, opts = {}) {
  return new Paragraph({
    children: [new TextRun({ text, font: FONT, size: FONT_SIZE, ...opts })],
    spacing: LINE_SPACING,
    alignment: AlignmentType.JUSTIFIED,
  });
}

function bodyRuns(runs, opts = {}) {
  return new Paragraph({
    children: runs,
    spacing: LINE_SPACING,
    alignment: AlignmentType.JUSTIFIED,
    ...opts
  });
}

function heading1(text) {
  return new Paragraph({
    text,
    heading: HeadingLevel.HEADING_1,
    spacing: { before: 480, after: 240 },
    alignment: AlignmentType.LEFT,
  });
}

function heading2(text) {
  return new Paragraph({
    text,
    heading: HeadingLevel.HEADING_2,
    spacing: { before: 360, after: 160 },
  });
}

function heading3(text) {
  return new Paragraph({
    text,
    heading: HeadingLevel.HEADING_3,
    spacing: { before: 240, after: 120 },
  });
}

function pageBreak() {
  return new Paragraph({ children: [new PageBreak()] });
}

function blank() {
  return new Paragraph({ text: '', spacing: SINGLE_SPACE });
}

function centered(text, opts = {}) {
  return new Paragraph({
    children: [new TextRun({ text, font: FONT, size: opts.size || FONT_SIZE, bold: opts.bold, ...opts })],
    alignment: AlignmentType.CENTER,
    spacing: opts.spacing || SINGLE_SPACE,
  });
}

function bold(text, size) {
  return new TextRun({ text, font: FONT, size: size || FONT_SIZE, bold: true });
}
function normal(text, size) {
  return new TextRun({ text, font: FONT, size: size || FONT_SIZE });
}
function italic(text, size) {
  return new TextRun({ text, font: FONT, size: size || FONT_SIZE, italics: true });
}
function superscript(text) {
  return new TextRun({ text, font: FONT, size: 18, superScript: true });
}

// ─────────────────────────────────────────────────────────────────────
// Table helpers
// ─────────────────────────────────────────────────────────────────────
function cell(text, shaded = false, bold_text = false) {
  return new TableCell({
    children: [new Paragraph({
      children: [new TextRun({ text, font: FONT, size: FONT_SIZE, bold: bold_text })],
      spacing: SINGLE_SPACE,
      alignment: AlignmentType.CENTER,
    })],
    shading: shaded ? { fill: "D9E1F2", type: ShadingType.CLEAR, color: "auto" } : undefined,
    verticalAlign: VerticalAlign.CENTER,
    margins: { top: 80, bottom: 80, left: 120, right: 120 },
  });
}

function tableCaption(text, num) {
  return new Paragraph({
    children: [
      new TextRun({ text: `Table ${num}: `, font: FONT, size: FONT_SIZE, bold: true }),
      new TextRun({ text, font: FONT, size: FONT_SIZE, italics: true }),
    ],
    spacing: { before: 100, after: 200 },
    alignment: AlignmentType.CENTER,
  });
}

function figCaption(text, num) {
  return new Paragraph({
    children: [
      new TextRun({ text: `Figure ${num}: `, font: FONT, size: FONT_SIZE, bold: true }),
      new TextRun({ text, font: FONT, size: FONT_SIZE, italics: true }),
    ],
    spacing: { before: 100, after: 200 },
    alignment: AlignmentType.CENTER,
  });
}

// ─────────────────────────────────────────────────────────────────────
// Build alvarado score table
// ─────────────────────────────────────────────────────────────────────
function alvaradoTable() {
  const rows = [
    ["SYMPTOMS", "", true],
    ["Migration of pain to right iliac fossa", "1", false],
    ["Anorexia", "1", false],
    ["Nausea / Vomiting", "1", false],
    ["SIGNS", "", true],
    ["Tenderness in right lower quadrant", "2", false],
    ["Rebound tenderness", "1", false],
    ["Elevated temperature (>37.3°C)", "1", false],
    ["LABORATORY", "", true],
    ["Leukocytosis (WBC >10,000/mm³)", "2", false],
    ["Left shift (neutrophilia)", "1", false],
    ["TOTAL", "10", true],
  ];
  return new Table({
    width: { size: 100, type: WidthType.PERCENTAGE },
    rows: rows.map((r, i) =>
      new TableRow({
        children: [
          cell(r[0], r[2], r[2]),
          cell(r[1], r[2], r[2]),
        ],
      })
    ),
    borders: {
      top: { style: BorderStyle.SINGLE, size: 8 },
      bottom: { style: BorderStyle.SINGLE, size: 8 },
      left: { style: BorderStyle.SINGLE, size: 8 },
      right: { style: BorderStyle.SINGLE, size: 8 },
      insideH: { style: BorderStyle.SINGLE, size: 4 },
      insideV: { style: BorderStyle.SINGLE, size: 4 },
    },
  });
}

// Sensitivity/specificity comparison table
function sensitivityTable() {
  const header = ["Study (Year)", "n", "Cut-off", "Sensitivity (%)", "Specificity (%)", "PPV (%)", "NPV (%)", "AUC"];
  const data = [
    ["Ohle et al. (2011)", "42 studies", "≤4 (rule out)", "99", "—", "—", "—", "—"],
    ["Ohle et al. (2011)", "42 studies", "≥7 (rule in)", "—", "81", "—", "—", "—"],
    ["Frountzas et al. (2018)", "2161", "Pooled", "69", "77", "—", "—", "0.79"],
    ["Bai et al. (2023) [children]", "2579", "Pooled", "76", "71", "—", "—", "0.81"],
    ["Awan et al. (2024)", "2235", "Pooled", "67", "74", "—", "—", "0.74"],
    ["Gebreselassie et al. (2023)", "235", "≥5", "99.1", "55.6", "98.2", "62.5", "—"],
    ["Aleem Khalid et al. (2024)", "230", "≥7 (MAS+CRP)", "91.2", "88.5", "91.8", "64.5", "—"],
    ["PMC study (2024)", "171", "≥6", "94.62", "87.80", "96.09", "83.72", "0.985"],
  ];
  return new Table({
    width: { size: 100, type: WidthType.PERCENTAGE },
    rows: [
      new TableRow({
        children: header.map(h => cell(h, true, true)),
        tableHeader: true,
      }),
      ...data.map(row =>
        new TableRow({ children: row.map(d => cell(d, false, false)) })
      ),
    ],
    borders: {
      top: { style: BorderStyle.SINGLE, size: 8 },
      bottom: { style: BorderStyle.SINGLE, size: 8 },
      left: { style: BorderStyle.SINGLE, size: 8 },
      right: { style: BorderStyle.SINGLE, size: 8 },
      insideH: { style: BorderStyle.SINGLE, size: 4 },
      insideV: { style: BorderStyle.SINGLE, size: 4 },
    },
  });
}

// Comparison with other scores table
function comparisonTable() {
  const header = ["Scoring System", "Components", "Max Score", "Sensitivity", "Specificity", "AUC", "Advantage"];
  const data = [
    ["Alvarado (MANTRELS)", "Symptoms, signs, labs", "10", "69–99%", "55–88%", "0.74–0.98", "Simple, widely validated"],
    ["Modified Alvarado (MANTREL)", "Symptoms, signs, labs (no left shift)", "9", "72–97%", "60–85%", "0.80–0.95", "No differential required"],
    ["RIPASA", "Clinical + demographics", "17.5", "94%", "55%", "0.94", "More sensitive, esp. Asians"],
    ["AIR Score", "Labs + symptoms + signs", "12", "88–97%", "80–89%", "0.90", "Severity stratification"],
    ["Pediatric Appendicitis Score (PAS)", "Pediatric-specific criteria", "10", "85–90%", "65–80%", "0.87", "Designed for children"],
    ["Adult Appendicitis Score (AAS)", "Clinical + labs", "23", "89%", "40%", "0.88", "Best for safe discharge"],
  ];
  return new Table({
    width: { size: 100, type: WidthType.PERCENTAGE },
    rows: [
      new TableRow({
        children: header.map(h => cell(h, true, true)),
        tableHeader: true,
      }),
      ...data.map(row =>
        new TableRow({ children: row.map(d => cell(d, false, false)) })
      ),
    ],
    borders: {
      top: { style: BorderStyle.SINGLE, size: 8 },
      bottom: { style: BorderStyle.SINGLE, size: 8 },
      left: { style: BorderStyle.SINGLE, size: 8 },
      right: { style: BorderStyle.SINGLE, size: 8 },
      insideH: { style: BorderStyle.SINGLE, size: 4 },
      insideV: { style: BorderStyle.SINGLE, size: 4 },
    },
  });
}

// ─────────────────────────────────────────────────────────────────────
// MAIN
// ─────────────────────────────────────────────────────────────────────
async function main() {
  console.log("Downloading ultrasound image...");
  let usImageBuffer = null;
  try {
    usImageBuffer = await downloadImage("https://cdn.orris.care/cdss_images/3e341fa9c6e8ae9f39fdb1089287035d8822fd59e1fca936835e40ba06173424.png");
    console.log("Image downloaded:", usImageBuffer.length, "bytes");
  } catch (e) {
    console.warn("Image download failed:", e.message);
  }

  const children = [];

  // ─── TITLE PAGE ──────────────────────────────────────────────────
  children.push(blank(), blank(), blank());
  children.push(centered("REVIEW OF LITERATURE", { size: FONT_SIZE_TITLE, bold: true, spacing: SINGLE_SPACE }));
  children.push(blank());
  children.push(centered("Accuracy of the Alvarado Score in the", { size: FONT_SIZE_LARGE, bold: true, spacing: SINGLE_SPACE }));
  children.push(centered("Diagnosis of Acute Appendicitis", { size: FONT_SIZE_LARGE, bold: true, spacing: SINGLE_SPACE }));
  children.push(blank(), blank());
  children.push(centered("A Thesis Submitted in Partial Fulfillment of the Requirements", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(centered("for the Degree of Master of Surgery (MS General Surgery)", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(blank(), blank());
  children.push(centered("Submitted by:", { size: FONT_SIZE, bold: true, spacing: SINGLE_SPACE }));
  children.push(centered("[Candidate Name]", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(centered("Roll No.: [XXXX]", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(blank());
  children.push(centered("Supervisor:", { size: FONT_SIZE, bold: true, spacing: SINGLE_SPACE }));
  children.push(centered("[Supervisor Name], MBBS, FCPS", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(centered("[Department of General Surgery]", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(blank(), blank());
  children.push(centered("[University / Institution Name]", { size: FONT_SIZE, bold: true, spacing: SINGLE_SPACE }));
  children.push(centered("Academic Year 2024–2026", { size: FONT_SIZE, spacing: SINGLE_SPACE }));
  children.push(pageBreak());

  // ─── TABLE OF CONTENTS (manual) ─────────────────────────────────
  children.push(heading1("TABLE OF CONTENTS"));
  const tocItems = [
    ["1. Introduction", "3"],
    ["2. Epidemiology of Acute Appendicitis", "5"],
    ["3. Anatomy and Pathophysiology", "7"],
    ["4. Clinical Features and Diagnosis", "9"],
    ["5. The Alvarado Scoring System", "12"],
    ["6. Diagnostic Accuracy of the Alvarado Score", "15"],
    ["   6.1 Sensitivity and Specificity", "15"],
    ["   6.2 Cut-off Points and Risk Stratification", "17"],
    ["   6.3 Gender-specific Performance", "18"],
    ["   6.4 Pediatric Populations", "19"],
    ["   6.5 Low-income and Developing Countries", "20"],
    ["7. Comparison with Other Scoring Systems", "21"],
    ["8. Role of Imaging and Biomarkers", "22"],
    ["9. Limitations of the Alvarado Score", "23"],
    ["10. Conclusion of Review", "24"],
    ["Bibliography", "25"],
  ];
  tocItems.forEach(([title, page]) => {
    children.push(new Paragraph({
      children: [
        new TextRun({ text: title, font: FONT, size: FONT_SIZE }),
        new TextRun({ text: "  ....  " + page, font: FONT, size: FONT_SIZE }),
      ],
      spacing: { before: 60, after: 60 },
    }));
  });
  children.push(pageBreak());

  // ─── 1. INTRODUCTION ─────────────────────────────────────────────
  children.push(heading1("1. INTRODUCTION"));

  children.push(body(
    "Acute appendicitis is the most common abdominal surgical emergency encountered worldwide, and its timely and accurate diagnosis remains one of the most challenging problems in emergency medicine and general surgery. The condition has been recognized clinically since the late 19th century, and despite enormous advances in diagnostic technology, it continues to pose significant diagnostic uncertainty owing to its variable and often atypical clinical presentations."
  ));
  children.push(body(
    "The appendix is a narrow, finger-like tubular structure arising from the cecum at the confluence of the three taeniae coli. Acute appendicitis results from obstruction of the appendiceal lumen, leading to progressive bacterial overgrowth, mucosal ischemia, and, if left untreated, perforation with life-threatening peritonitis. The lifetime risk of developing acute appendicitis is approximately 8.6% in males and 6.7% in females in Western nations, and may be as high as 16–17% in some Asian populations. Globally, over 300,000 appendectomies are performed annually in the United States alone."
  ));
  children.push(body(
    "The diagnosis of acute appendicitis is primarily clinical, based on a thorough history and physical examination supplemented by laboratory and radiological investigations. However, clinical diagnosis alone carries a negative appendectomy rate of 15–25%, with higher rates in women of reproductive age (up to 40%) and elderly patients. Delayed diagnosis, conversely, increases the risk of perforation, with rates as high as 20–30% in patients presenting late or in atypical fashion. Both extremes — unnecessary surgery and delayed diagnosis — lead to significant morbidity and healthcare resource utilization."
  ));
  children.push(body(
    "To bridge this diagnostic gap, numerous clinical scoring systems have been developed over the past four decades. Among them, the Alvarado score, first published by Dr. Alfredo Alvarado in 1986 in the Annals of Emergency Medicine, is the most widely studied and adopted tool in clinical practice globally. The score integrates symptoms, signs, and laboratory data into a numerical index that stratifies patients into low, moderate, and high probability groups for acute appendicitis."
  ));
  children.push(body(
    "Despite its widespread use, the diagnostic accuracy of the Alvarado score has been the subject of extensive investigation. Results vary widely across populations, age groups, genders, and healthcare settings. Several systematic reviews and meta-analyses have addressed this variability, revealing that while the score performs well as a rule-out tool at lower cut-off values, its ability to confirm the diagnosis at higher cut-off points is inconsistent — particularly in women and children."
  ));
  children.push(body(
    "This review of literature critically evaluates the published evidence on the accuracy of the Alvarado score in diagnosing acute appendicitis. It encompasses the epidemiology of the condition, the anatomy and pathophysiology of appendicitis, clinical diagnostic approaches, the development and scoring methodology of the Alvarado system, and its performance characteristics across diverse populations. Comparative data with other contemporary scoring systems — including the RIPASA score, the Appendicitis Inflammatory Response (AIR) score, the Pediatric Appendicitis Score (PAS), and the Adult Appendicitis Score (AAS) — are also reviewed. The goal is to provide a comprehensive, evidence-based foundation for the thesis and contextualize the local study within the global literature."
  ));
  children.push(pageBreak());

  // ─── 2. EPIDEMIOLOGY ─────────────────────────────────────────────
  children.push(heading1("2. EPIDEMIOLOGY OF ACUTE APPENDICITIS"));
  children.push(body(
    "Acute appendicitis is the most common acute surgical condition of the abdomen across all age groups worldwide. In the United States, it accounts for approximately 5% of all emergency department visits in patients under 65 years of age and 30% of all acute surgical abdominal emergencies in patients under 50 years of age. The overall incidence in North America is estimated at 82 to 110 cases per 100,000 population per year, translating to over 318,000 hospital admissions annually (Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 12th ed.)."
  ));
  children.push(body(
    "The peak incidence occurs in the second and third decades of life, with the highest rates seen among adolescents and young adults aged 10 to 30 years. However, appendicitis can affect patients of any age, and atypical presentations are particularly common in the very young (under 5 years) and the elderly (over 65 years). In pediatric patients younger than 5 years, the perforation rate approaches 70–80% due to diagnostic delay and the inability of young children to communicate localizing symptoms effectively. In the elderly, the perforation rate is similarly elevated due to blunted inflammatory response and the presence of confounding comorbidities."
  ));
  children.push(body(
    "There is a recognized male predominance in the overall lifetime risk of appendicitis. Males have an 8.6% lifetime risk compared to 6.7% in females, although females are disproportionately affected by diagnostic uncertainty due to the overlap of appendicitis with gynecological pathology. Studies from Asia, including South Asia and Southeast Asia, report incidence rates nearly double those seen in Western populations, though this is partially attributed to differences in dietary fiber intake, hygiene standards, and reporting practices."
  ));
  children.push(body(
    "The negative appendectomy rate — the proportion of patients undergoing appendectomy who are found to have a histologically normal appendix — has historically ranged from 15% to 25%. With the widespread adoption of computed tomography (CT) scanning in diagnostic workup, this rate has been reduced to approximately 5% in many developed centers. However, in resource-limited settings and developing countries, the negative appendectomy rate remains significantly higher, highlighting the continued clinical importance of accurate, low-cost diagnostic tools such as the Alvarado score."
  ));
  children.push(body(
    "Complications of acute appendicitis, including perforation, peritonitis, and appendiceal abscess, occur in approximately 17–20% of all cases and contribute substantially to morbidity, prolonged hospital stay, and healthcare costs. The economic burden of acute appendicitis is considerable, and reducing both missed diagnoses and unnecessary operations is a major healthcare priority globally."
  ));
  children.push(pageBreak());

  // ─── 3. ANATOMY AND PATHOPHYSIOLOGY ──────────────────────────────
  children.push(heading1("3. ANATOMY AND PATHOPHYSIOLOGY"));
  children.push(heading2("3.1 Anatomy of the Appendix"));
  children.push(body(
    "The vermiform appendix is a narrow, tubular, blind-ended diverticulum arising from the posteromedial aspect of the cecum, at the convergence of the three taeniae coli. In adults, the appendix measures between 2 and 20 cm in length, with a mean of approximately 9 cm. Its external diameter is 3–8 mm in the non-inflamed state. The appendix contains lymphoid tissue in its submucosa (referred to as gut-associated lymphoid tissue, GALT), which is particularly abundant in childhood and adolescence — a factor thought to contribute to the peak incidence of appendicitis in these age groups."
  ));
  children.push(body(
    "The position of the appendix is variable. The most common position is retrocecal (65–70%), which may alter the clinical presentation by causing back or flank pain rather than classic right lower quadrant (RLQ) pain. Other positions include pelvic (30%), subcecal, preileal, and paracolic. These anatomical variations account for the wide spectrum of atypical presentations seen in clinical practice and contribute to diagnostic uncertainty."
  ));
  children.push(body(
    "The blood supply to the appendix is provided by the appendicular artery, a branch of the ileocolic artery. This is an end-artery, meaning there is no collateral circulation. Once thrombosis of the appendicular vessels occurs in advanced appendicitis, gangrene and subsequent perforation develop rapidly."
  ));
  children.push(heading2("3.2 Pathophysiology of Acute Appendicitis"));
  children.push(body(
    "The fundamental event initiating acute appendicitis is obstruction of the appendiceal lumen. In approximately 60% of cases, this is caused by a fecalith (calcified fecal material). Other causes include lymphoid hyperplasia (particularly common in children in response to viral infections), inspissated mucus, foreign bodies, parasites, and, rarely, carcinoid tumors or adenocarcinoma."
  ));
  children.push(body(
    "Obstruction leads to continued secretion of mucus by the appendiceal mucosa, with progressive accumulation of intraluminal pressure. As the pressure rises, venous outflow is compromised, resulting in vascular congestion and mucosal ischemia. Bacterial overgrowth follows rapidly, with translocation of intestinal flora through the devitalized mucosa. The resulting local inflammation stimulates visceral afferent nerve fibers (T10 dermatome), which are perceived as vague periumbilical pain — the early hallmark of appendicitis."
  ));
  children.push(body(
    "As inflammation progresses and involves the parietal peritoneum overlying the appendix, somatic nerve fibers are activated, producing the characteristic shift of pain to the right lower quadrant. This migration of pain — from periumbilical to right iliac fossa — is one of the most diagnostically reliable symptoms and accounts for one point in the Alvarado scoring system."
  ));
  children.push(body(
    "Untreated, the process culminates in transmural necrosis and perforation, typically within 24–72 hours of symptom onset in adults. Perforation may be contained by the omentum and adjacent bowel loops (forming an appendiceal mass or phlegmon) or may lead to diffuse peritonitis. The systemic response includes fever, leukocytosis with neutrophilia, and elevation of acute-phase reactants such as C-reactive protein (CRP)."
  ));
  children.push(pageBreak());

  // ─── 4. CLINICAL FEATURES AND DIAGNOSIS ──────────────────────────
  children.push(heading1("4. CLINICAL FEATURES AND DIAGNOSIS"));
  children.push(heading2("4.1 History and Symptoms"));
  children.push(body(
    "The classic presentation of acute appendicitis begins with prodromal symptoms of anorexia, nausea, and vague periumbilical or central abdominal pain. Within 6 to 8 hours, the pain typically migrates to the right lower quadrant (McBurney's point), coinciding with the onset of localized peritoneal irritation. Low-grade fever (37.5–38.5°C) and mild leukocytosis are typically present in uncomplicated appendicitis. A higher temperature and markedly elevated white blood cell count suggest perforation or abscess formation."
  ));
  children.push(body(
    "Anorexia is reported in approximately 68–90% of patients with appendicitis and was emphasized by Alvarado in the original description of his scoring system. Nausea and vomiting occur in 50–75% of cases, usually following the onset of pain rather than preceding it — a feature that helps differentiate appendicitis from gastroenteritis, where vomiting typically precedes pain. However, the classic triad of migration of pain, anorexia, and nausea is present in only 50–60% of patients, and atypical presentations are far more frequent than commonly assumed."
  ));
  children.push(heading2("4.2 Physical Examination Signs"));
  children.push(body(
    "Tenderness at McBurney's point (one-third of the distance from the anterior superior iliac spine to the umbilicus along a line between them) remains the single most reliable physical finding in acute appendicitis. Guarding and rebound tenderness reflect parietal peritoneal involvement and are associated with moderate-to-severe disease. Several classical clinical signs have been described:"
  ));
  children.push(new Paragraph({
    children: [new TextRun({ text: "• Rovsing's Sign: ", font: FONT, size: FONT_SIZE, bold: true }), normal("Right lower quadrant pain elicited by palpation of the left lower quadrant (cross-pressure sign).")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [new TextRun({ text: "• Psoas Sign: ", font: FONT, size: FONT_SIZE, bold: true }), normal("Pain in the right lower quadrant on extension of the right hip, indicating inflammation adjacent to the psoas muscle (retrocecal appendicitis).")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [new TextRun({ text: "• Obturator Sign: ", font: FONT, size: FONT_SIZE, bold: true }), normal("Pain on internal rotation of the flexed right hip, suggesting a pelvic appendix.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [new TextRun({ text: "• Dunphy's Sign: ", font: FONT, size: FONT_SIZE, bold: true }), normal("Increased pain on coughing, indicating peritoneal inflammation.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(body(
    "It must be noted, as emphasized by the Sabiston Textbook of Surgery, that these signs are indicators of localized peritonitis rather than diagnostically specific for appendicitis. Their presence adds to clinical suspicion but cannot confirm the diagnosis in isolation."
  ));
  children.push(heading2("4.3 Laboratory Investigations"));
  children.push(body(
    "Leukocytosis with a predominance of neutrophils is the most frequently cited laboratory abnormality in acute appendicitis, present in approximately 80–90% of histologically confirmed cases. A white blood cell (WBC) count greater than 10,000/mm³ is used as one of the components of the Alvarado score. However, a normal WBC count is found in approximately 10% of proven cases and must not be used in isolation to exclude the diagnosis."
  ));
  children.push(body(
    "A 'left shift' — referring to an increase in the proportion of immature neutrophil precursors (band forms) in the differential count — is another feature incorporated into the original Alvarado score, reflecting the degree of bacterial stimulation of the bone marrow. This component is often omitted in the Modified Alvarado Score (MANTREL) due to the requirement for a manual differential count, which is not always readily available."
  ));
  children.push(body(
    "C-reactive protein (CRP), while not part of the original Alvarado score, has been extensively studied as an adjunct marker. CRP levels are typically elevated in appendicitis but lack sufficient specificity to diagnose the condition in isolation. Combined with the Alvarado score or Modified Alvarado Score, CRP has been shown to significantly improve diagnostic accuracy. Aleem Khalid et al. (2024) demonstrated that the combination of Modified Alvarado Score with CRP achieved a sensitivity of 91.2% and specificity of 88.5%, superior to either measure alone."
  ));
  children.push(heading2("4.4 Imaging Investigations"));
  children.push(body(
    "Ultrasound (US) of the abdomen has been used for the diagnosis of appendicitis since the 1980s. The inflamed appendix appears as a dilated, non-compressible, aperistaltic tubular structure with a diameter greater than 6 mm (Fig. 1). The sensitivity of ultrasonography ranges from 71% to 94%, and specificity from 81% to 98%, but performance is highly operator-dependent. Ultrasound is the preferred first-line imaging modality in pediatric patients and pregnant women due to the absence of ionizing radiation."
  ));

  if (usImageBuffer) {
    children.push(new Paragraph({
      children: [new ImageRun({
        data: usImageBuffer,
        transformation: { width: 400, height: 220 },
      })],
      alignment: AlignmentType.CENTER,
      spacing: { before: 200, after: 100 },
    }));
    children.push(figCaption(
      "Right lower quadrant ultrasound in a 10-year-old boy with acute abdominal pain showing a dilated fluid-filled tubular structure with increased vascularity (A) and an echogenic focus consistent with an appendicolith (B), consistent with acute appendicitis. (Source: Current Surgical Therapy, 14th ed.)",
      "1"
    ));
  }

  children.push(body(
    "Computed tomography (CT) of the abdomen and pelvis with intravenous contrast has become the gold standard imaging investigation for acute appendicitis in adults in resource-rich settings. An appendiceal diameter greater than 10 mm, peri-appendiceal fat stranding, failure of contrast to fill the appendix lumen, and the presence of a fecalith are diagnostic CT features. The sensitivity of CT ranges from 91% to 99% and specificity from 90% to 99%, and its widespread use has reduced the negative appendectomy rate to approximately 5%. However, concerns about radiation exposure, cost, and availability in developing countries limit its universal application."
  ));
  children.push(body(
    "Magnetic resonance imaging (MRI) is increasingly employed in pregnant patients and children in whom radiation avoidance is paramount. MRI offers sensitivity and specificity approaching those of CT without ionizing radiation, though its availability, cost, and longer acquisition time remain limiting factors."
  ));
  children.push(pageBreak());

  // ─── 5. THE ALVARADO SCORING SYSTEM ──────────────────────────────
  children.push(heading1("5. THE ALVARADO SCORING SYSTEM"));
  children.push(heading2("5.1 Historical Background and Development"));
  children.push(body(
    "The Alvarado score was first described by Dr. Alfredo Alvarado in a landmark 1986 paper published in the Annals of Emergency Medicine, titled 'A Practical Score for the Early Diagnosis of Acute Appendicitis' (PMID: 3963537). The score was developed through a prospective study of 305 patients presenting to a single center with suspected appendicitis. Alvarado observed that a combination of clinical and laboratory features — specifically, migration of pain, anorexia, nausea/vomiting, tenderness in the right lower quadrant, rebound tenderness, elevated temperature, leukocytosis, and left shift of the WBC differential — provided reliable risk stratification."
  ));
  children.push(body(
    "The mnemonic MANTRELS was originally used to remember the score's components: Migration of pain, Anorexia, Nausea/vomiting, Tenderness in RLQ, Rebound tenderness, Elevated temperature, Leukocytosis, and left Shift. The score garnered rapid adoption due to its simplicity, cost-effectiveness, and the fact that it required no specialized investigations beyond a standard complete blood count."
  ));
  children.push(heading2("5.2 Components and Scoring Criteria"));
  children.push(body("The Alvarado score is composed of eight variables totaling 10 points, as presented in Table 1:"));
  children.push(blank());
  children.push(alvaradoTable());
  children.push(tableCaption("The Alvarado Score (MANTRELS) for Early Diagnosis of Acute Appendicitis (Alvarado, 1986; Sleisenger & Fordtran, 12th ed.)", "1"));

  children.push(heading2("5.3 Interpretation and Risk Stratification"));
  children.push(body(
    "In the original study, Alvarado proposed the following clinical interpretation of the total score:"
  ));
  children.push(new Paragraph({
    children: [bold("Score 1–4: "), normal("Low probability of appendicitis — observation and discharge with close follow-up may be appropriate.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("Score 5–6: "), normal("Possible appendicitis — surgical consultation warranted; imaging recommended to clarify diagnosis.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("Score 7–8: "), normal("Probable appendicitis — strong indication for surgical intervention with or without confirmatory imaging.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("Score 9–10: "), normal("Definite appendicitis — immediate appendectomy indicated without further imaging delay.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(body(
    "Subsequent studies have refined these cut-off thresholds. The most widely accepted clinical practice, supported by the systematic review of Ohle et al. (2011), is to use a cut-off of ≤4 as a 'rule out' criterion — with a pooled sensitivity of 99% overall — and a cut-off of ≥7 as a 'rule in' criterion, though specificity at this threshold is only 81% overall. Medscape and MDCalc clinical decision tools currently recommend CT scan for scores of 4–6 and direct surgical consultation for scores ≥7."
  ));
  children.push(heading2("5.4 The Modified Alvarado Score (MANTREL)"));
  children.push(body(
    "The Modified Alvarado Score (MAS), also known as MANTREL, was introduced to simplify application by removing the 'left shift' component, reducing the maximum score from 10 to 9. This modification was proposed because a full differential blood count is not always available in resource-limited emergency settings. The MAS assigns the same 9-point total to the remaining eight variables. Although the MAS sacrifices some granularity, studies have demonstrated comparable performance to the original Alvarado score in most clinical settings. Meta-analyses of pediatric data (Bai et al., 2023) found that the Modified Alvarado Score achieved a pooled sensitivity of 87% (vs 76% for the original), though with lower specificity (47%)."
  ));
  children.push(pageBreak());

  // ─── 6. DIAGNOSTIC ACCURACY ──────────────────────────────────────
  children.push(heading1("6. DIAGNOSTIC ACCURACY OF THE ALVARADO SCORE"));
  children.push(heading2("6.1 Sensitivity and Specificity — Evidence from Systematic Reviews"));
  children.push(body(
    "The most comprehensive and frequently cited analysis of the Alvarado score's diagnostic accuracy is the systematic review and meta-analysis by Ohle et al. (2011), published in BMC Medicine (PMID: 22204638). This Tier-1 evidence study included 42 validation studies and assessed the score's performance at two primary cut-off points: ≤4 (rule-out threshold) and ≥7 (rule-in threshold)."
  ));
  children.push(body(
    "Key findings from Ohle et al. (2011):"
  ));
  children.push(new Paragraph({
    children: [bold("Rule-out (cut-off ≤4): "), normal("Sensitivity was 99% overall (96% in men, 99% in women, 99% in children). This means that a score of 4 or below reliably excludes appendicitis in virtually all patients.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("Rule-in (cut-off ≥7): "), normal("Specificity was 81% overall but only 57% in men, 73% in women, and 76% in children — reflecting poor performance when using the score to confirm the diagnosis. The score over-predicted the probability of appendicitis in women across all risk strata and inconsistently in children.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(body(
    "A later meta-analysis by Frountzas et al. (2018), published in the International Journal of Surgery (PMID: 30017607), included 12 randomized studies and 2161 patients comparing the Alvarado and RIPASA scores. The pooled sensitivity of the Alvarado score was 69% (95% CI: 67–71%) and specificity 77% (95% CI: 74–80%), with an AUC of 0.7944. In contrast, the RIPASA score demonstrated higher sensitivity (94%) but lower specificity (55%)."
  ));
  children.push(body(
    "The 2024 meta-analysis by Awan et al. (PMID: 38789384), comparing the Alvarado and Tzanakis scores in 2235 patients across 14 studies, reported pooled Alvarado sensitivity of 67% (95% CI: 65–69%) and specificity of 74% (95% CI: 69–79%), with an AUC of 0.7389. This study concluded that the Tzanakis score is superior in sensitivity, diagnostic odds ratio, and AUC, while the Alvarado score is marginally better at excluding the diagnosis."
  ));
  children.push(body("Table 2 summarizes the diagnostic accuracy parameters from major published studies:"));
  children.push(blank());
  children.push(sensitivityTable());
  children.push(tableCaption("Summary of diagnostic accuracy parameters of the Alvarado Score across major published studies", "2"));
  children.push(blank());

  children.push(heading2("6.2 Cut-off Points and Clinical Decision-Making"));
  children.push(body(
    "The choice of cut-off point profoundly influences the clinical utility of the Alvarado score. At a cut-off of ≤4, the score functions as an excellent 'rule-out' tool with near-perfect sensitivity, supporting safe discharge or watchful observation without further workup. At a cut-off of ≥7, specificity ranges widely between studies (57–89%), and many authors recommend supplementary imaging (ultrasound or CT) before proceeding to surgery for intermediate scores (5–6)."
  ));
  children.push(body(
    "An important single-center study published in 2024 (PMC11236940) evaluated 171 patients suspected of appendicitis and found that at a cut-off of ≥6, the Alvarado score achieved a sensitivity of 94.62% and specificity of 87.80%, with an AUC of 0.985 (95% CI: 0.954–0.998). These results, while high, reflect the variability seen across institutions and patient populations. Notably, the combination of the Alvarado score with abdominal ultrasound in this study produced a negative appendectomy rate of only 5.1%, reinforcing the value of integrating the clinical score with imaging."
  ));
  children.push(body(
    "McKay and Shepherd's widely referenced protocol, endorsed on Medscape's clinical calculator, proposes: CT scan for scores 4–6; surgical consultation for scores ≥7; no further imaging needed for scores ≤3 given the very low pretest probability. This framework remains a practical and evidence-guided approach in emergency settings."
  ));

  children.push(heading2("6.3 Gender-specific Performance"));
  children.push(body(
    "One of the most consistent findings across validation studies is that the Alvarado score over-predicts the probability of appendicitis in females. Ohle et al. (2011) demonstrated that the score is well-calibrated in men across all risk strata, but over-predicts in women across all risk strata (low, intermediate, and high). This is attributable to the substantial overlap of appendicitis with gynecological conditions — including ovarian torsion, ruptured ovarian cysts, pelvic inflammatory disease, and ectopic pregnancy — which produce similar clinical and laboratory findings."
  ));
  children.push(body(
    "The negative appendectomy rate in women has historically been 2–3 times higher than in men. In women of reproductive age, the Alvarado score should be interpreted with caution, and pelvic ultrasound is strongly recommended for scores in the intermediate range (5–6). Gebreselassie et al. (2023) confirmed this pattern in an African cohort, reporting specificity of 80% in males versus only 25% in females at a cut-off of ≥5."
  ));

  children.push(heading2("6.4 Accuracy in Pediatric Populations"));
  children.push(body(
    "The application of the Alvarado score in the pediatric population has been extensively evaluated. The systematic review and meta-analysis by Bai et al. (2023), published in the Journal of Pediatric Surgery (PMID: 36966018), included 26 studies with 2579 pediatric cases. The combined sensitivity was 76.0% (95% CI: 74–78%) and specificity was 71.0% (95% CI: 68–74%), with a combined AUC of 0.81, indicating moderate diagnostic accuracy. The modified Alvarado score performed better in terms of sensitivity (87%, 95% CI: 85–88%) but worse in specificity (47%)."
  ));
  children.push(body(
    "The authors concluded that the Alvarado score is a useful auxiliary tool in the diagnosis of acute appendicitis in children but is insufficient as a standalone diagnostic criterion. They recommended that the score be combined with imaging or other biomarkers for optimal accuracy in this population. Tintinalli's Emergency Medicine also notes that in children, scoring systems including Alvarado and the Samuel (Pediatric Appendicitis) score require integration with clinical judgment, as their individual performance falls short of definitive diagnosis."
  ));
  children.push(body(
    "The Pediatric Appendicitis Score (PAS), developed by Samuel in 2002, was specifically designed for children and includes unique variables such as pain elicited by hopping and cough/percussion tenderness. In direct comparisons, the PAS has demonstrated superior specificity (65–80%) over the Alvarado score in pediatric settings while maintaining comparable sensitivity."
  ));

  children.push(heading2("6.5 Performance in Low-income and Developing Countries"));
  children.push(body(
    "Several studies have evaluated the Alvarado score in low-income and developing country settings where advanced imaging is often unavailable. Gebreselassie et al. (2023), in a prospective cross-sectional study of 235 Ethiopian adults (PMID: 37346382), reported an overall sensitivity of 99.1% and positive predictive value of 98.2% at a cut-off of ≥5. These high values suggest that the Alvarado score retains clinical utility in resource-constrained environments, particularly as a 'rule-in' tool."
  ));
  children.push(body(
    "Similar results have been reported from Pakistan, Nigeria, and other low-middle income countries, where the score has been validated as an effective triage tool that can safely guide the decision to perform appendectomy without necessitating CT scanning. These findings are especially relevant for the current thesis, which examines the score's utility in a [local] institutional setting."
  ));
  children.push(pageBreak());

  // ─── 7. COMPARISON WITH OTHER SCORING SYSTEMS ────────────────────
  children.push(heading1("7. COMPARISON WITH OTHER SCORING SYSTEMS"));
  children.push(body(
    "While the Alvarado score remains the most widely used clinical scoring tool for suspected appendicitis globally, several alternative and modified systems have been developed to address its limitations. Table 3 provides a comparative overview of the major scoring systems currently in use:"
  ));
  children.push(blank());
  children.push(comparisonTable());
  children.push(tableCaption("Comparison of major clinical scoring systems for the diagnosis of acute appendicitis", "3"));
  children.push(blank());

  children.push(heading2("7.1 RIPASA Score"));
  children.push(body(
    "The Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score was developed in Brunei in 2010 to improve diagnostic accuracy in Asian populations, where the Alvarado score had shown lower specificity. The RIPASA score includes 14 parameters, incorporating demographic factors (age, sex, nationality), symptoms, signs, and an optional urinalysis finding, with a maximum score of 17.5. Frountzas et al. (2018) demonstrated that RIPASA has a significantly higher pooled sensitivity of 94% compared to 69% for Alvarado, though at the cost of lower specificity (55% vs 77%). The RIPASA score may be particularly advantageous in populations with a lower baseline incidence of appendicitis."
  ));
  children.push(heading2("7.2 Appendicitis Inflammatory Response (AIR) Score"));
  children.push(body(
    "The AIR score, developed by Anderson et al. in 2008, incorporates inflammatory markers (WBC, CRP) with clinical findings and is weighted to assess disease severity. Unlike the Alvarado score, the AIR score stratifies patients into low-, intermediate-, and high-risk groups with treatment implications for each tier. The Sabiston Textbook of Surgery notes that the most recent international consensus guidelines for appendicitis management recommend the use of AIR or AAS over the Alvarado score, as the former are considered superior for both ruling in and ruling out the diagnosis. The area under the ROC curve for AIR has been reported at 0.90 in prospective cohort studies."
  ));
  children.push(heading2("7.3 Adult Appendicitis Score (AAS)"));
  children.push(body(
    "The Adult Appendicitis Score was developed in Finland in 2014 and encompasses up to 23 points, incorporating CRP, WBC with differential, body temperature, and clinical findings. A comparative study by Ghali et al. (2023, PMID: 37577253) of 1303 patients found that AAS is more accurate than the Alvarado score, particularly in selecting safe candidates for emergency department discharge. AAS also reduced the need for radiological imaging and the negative appendectomy rate more effectively than the Alvarado score."
  ));
  children.push(pageBreak());

  // ─── 8. ROLE OF IMAGING AND BIOMARKERS ───────────────────────────
  children.push(heading1("8. ROLE OF IMAGING AND BIOMARKERS IN CONJUNCTION WITH THE ALVARADO SCORE"));
  children.push(heading2("8.1 Imaging"));
  children.push(body(
    "A well-established clinical algorithm integrates the Alvarado score with selective imaging to optimize diagnostic accuracy. For patients with low Alvarado scores (≤4), imaging is generally not required given the very low pretest probability. For intermediate scores (5–6), ultrasound is recommended as the first-line imaging modality, particularly in women, children, and pregnant patients. If ultrasound is non-diagnostic, CT scanning provides definitive evaluation. For scores ≥7, direct surgical consultation is appropriate, with imaging reserved for diagnostic uncertainty or to facilitate a laparoscopic approach."
  ));
  children.push(body(
    "The combination of the Alvarado score with ultrasound has been shown in multiple studies to achieve negative appendectomy rates below 5% — comparable to CT-guided decision-making — while substantially reducing radiation exposure and healthcare costs. In centers with high-quality ultrasonography, this combination is increasingly adopted as the standard diagnostic pathway."
  ));
  children.push(heading2("8.2 Biomarkers"));
  children.push(body(
    "CRP has emerged as the most clinically useful biomarker adjunct to the Alvarado score. Elevated CRP (>10 mg/L) is seen in the majority of histologically confirmed appendicitis cases, and its combination with the Modified Alvarado Score (MAS) significantly enhances diagnostic accuracy. Aleem Khalid et al. (2024, PMID: 39677268) demonstrated that MAS combined with CRP achieved sensitivity of 91.2%, specificity of 88.5%, PPV of 91.8%, and NPV of 64.5% — making the combined approach particularly useful in resource-limited settings where CT is unavailable."
  ));
  children.push(body(
    "Procalcitonin and interleukin-6 have also been investigated as potential adjuncts but have not demonstrated consistent superiority over CRP. Among all biomarkers studied, none provides sufficient standalone specificity to confirm or exclude appendicitis, reinforcing the value of the multi-parameter approach embodied by clinical scoring systems."
  ));
  children.push(pageBreak());

  // ─── 9. LIMITATIONS ──────────────────────────────────────────────
  children.push(heading1("9. LIMITATIONS OF THE ALVARADO SCORE"));
  children.push(body(
    "Despite its widespread adoption and extensive validation, the Alvarado score carries several well-recognized limitations that clinicians must understand when interpreting its results:"
  ));
  children.push(new Paragraph({
    children: [bold("1. Reduced specificity at high cut-off: "), normal("The score's primary strength lies in its high sensitivity for rule-out at ≤4. At the rule-in cut-off of ≥7, specificity is only 57–81% depending on population and study design, limiting its utility for definitive surgical decision-making without imaging confirmation.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("2. Gender bias: "), normal("The score over-predicts appendicitis in females due to the overlapping clinical presentation of gynecological conditions. Its use without pelvic ultrasound in women of reproductive age may contribute to unnecessary appendectomies.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("3. Pediatric performance: "), normal("The score has only moderate accuracy in children (AUC 0.81), and both the Pediatric Appendicitis Score and modified versions outperform the original Alvarado score in this population.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("4. Elderly patients: "), normal("The Alvarado score performs poorly in elderly patients who often present atypically with blunted systemic responses (minimal leukocytosis, low-grade or absent fever), leading to low scores even in the presence of advanced disease including perforation.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("5. Subjectivity of clinical components: "), normal("The assessments of rebound tenderness, migration of pain, and anorexia may be subjective and observer-dependent, introducing inter-rater variability.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("6. Superseded by newer scoring systems: "), normal("Contemporary evidence, as acknowledged in the Sabiston Textbook and multiple consensus guidelines, recommends AIR and AAS over the Alvarado score for their superior overall diagnostic performance, particularly for severity stratification.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(new Paragraph({
    children: [bold("7. Limited utility for perforated appendicitis: "), normal("Studies have shown that the score may not reliably distinguish between simple and perforated appendicitis, limiting its role in severity assessment beyond initial triage.")],
    spacing: LINE_SPACING, alignment: AlignmentType.JUSTIFIED,
  }));
  children.push(pageBreak());

  // ─── 10. CONCLUSION OF REVIEW ────────────────────────────────────
  children.push(heading1("10. CONCLUSION OF REVIEW"));
  children.push(body(
    "The Alvarado score, first introduced in 1986, has stood the test of time as a practical, low-cost, and widely applicable clinical tool for the early diagnosis of acute appendicitis. The global literature, encompassing over 175 published validation studies and multiple high-quality systematic reviews and meta-analyses, consistently demonstrates that the score is an excellent 'rule-out' diagnostic aid at a cut-off of ≤4, with near-perfect sensitivity across adult males, females, and children."
  ));
  children.push(body(
    "However, the evidence also highlights important limitations of the score in confirming the diagnosis at higher cut-off values. Its tendency to over-predict appendicitis in women and children, its moderate performance in elderly and atypical presentations, and its supersession by newer systems such as AIR and AAS in terms of overall diagnostic accuracy are recognized shortcomings. Contemporary guidelines increasingly recommend the Alvarado score as part of an integrated diagnostic pathway — supplemented by ultrasound or CT imaging for intermediate-risk patients — rather than as a standalone decision-making tool."
  ));
  children.push(body(
    "The growing body of evidence from low-income countries confirms that the Alvarado score retains significant clinical value in resource-constrained settings, where advanced imaging is not readily available. In such contexts, the score can guide triage, reduce unnecessary delays, and lower the negative appendectomy rate when applied within an evidence-based clinical framework."
  ));
  children.push(body(
    "This review of literature provides the theoretical and evidential foundation for the present thesis, which prospectively evaluates the accuracy of the Alvarado score in diagnosing acute appendicitis in [local institutional context]. The findings of this thesis will contribute to the existing body of literature and will help determine the optimal diagnostic strategy for acute appendicitis within the local healthcare setting."
  ));
  children.push(pageBreak());

  // ─── BIBLIOGRAPHY ─────────────────────────────────────────────────
  children.push(heading1("BIBLIOGRAPHY"));
  const refs = [
    ["1.", "Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med. 1986 May;15(5):557–64. PMID: 3963537."],
    ["2.", "Ohle R, O'Reilly F, O'Brien KK, Fahey T, Dimitrov BD. The Alvarado score for predicting acute appendicitis: a systematic review. BMC Med. 2011 Dec 28;9:139. doi: 10.1186/1741-7015-9-139. PMID: 22204638."],
    ["3.", "Bai S, Hu S, Zhang Y, Guo S, Zhu R, Zeng J. The Value of the Alvarado Score for the Diagnosis of Acute Appendicitis in Children: A Systematic Review and Meta-Analysis. J Pediatr Surg. 2023 Oct;58(10):1888–1897. doi: 10.1016/j.jpedsurg.2023.02.060. PMID: 36966018."],
    ["4.", "Awan AR, Khan ZU, Saleem H, Iqbal H, Ahmad W, Khan AR. A comparison of the accuracy of Tzanakis and Alvarado Score in the diagnosis of acute appendicitis: A systematic review and meta-analysis. Surgeon. 2024 Oct;22(5):e250–e258. doi: 10.1016/j.surge.2024.04.013. PMID: 38789384."],
    ["5.", "Frountzas M, Stergios K, Kopsini D, Schizas D, Kontzoglou K, Toutouzas K. Alvarado or RIPASA score for diagnosis of acute appendicitis? A meta-analysis of randomized trials. Int J Surg. 2018 Aug;56:307–314. doi: 10.1016/j.ijsu.2018.07.003. PMID: 30017607."],
    ["6.", "Gebreselassie H, Zeleke H, Ashebir D. Diagnosis of Acute Appendicitis: A Cross-sectional Study on Alvarado's Score from a Low Income Country. Open Access Emerg Med. 2023;15:207–214. doi: 10.2147/OAEM.S410119. PMID: 37346382."],
    ["7.", "Ghali MS, Hasan S, Al-Yahri O, et al. Adult appendicitis score versus Alvarado score: A comparative study in the diagnosis of acute appendicitis. Surg Open Sci. 2023 Aug;13:8–14. doi: 10.1016/j.sopen.2023.07.007. PMID: 37577253."],
    ["8.", "Aleem Khalid AU, Quarrell A, Chandran A, Javed T, Ahmad N. Diagnostic Accuracy of the Modified Alvarado Score and Serum C-reactive Protein in Acute Appendicitis. Cureus. 2024 Nov;16(11):e73664. doi: 10.7759/cureus.73664. PMID: 39677268."],
    ["9.", "Issaiy M, Zarei D, Saghazadeh A. Artificial Intelligence and Acute Appendicitis: A Systematic Review of Diagnostic and Prognostic Models. World J Emerg Surg. 2023 Dec 19;18(1):59. PMID: 38114983."],
    ["10.", "Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. 21st ed. Philadelphia: Elsevier; 2022."],
    ["11.", "Cameron JL, Cameron AM, eds. Current Surgical Therapy. 14th ed. Philadelphia: Elsevier; 2023."],
    ["12.", "Sleisenger MH, Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 11th ed. Philadelphia: Elsevier; 2021."],
    ["13.", "Tintinalli JE, Ma OJ, Yealy DM, et al., eds. Tintinalli's Emergency Medicine: A Comprehensive Study Guide. 9th ed. New York: McGraw-Hill; 2020."],
    ["14.", "Marx JA, Hockberger RS, Walls RM, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice. 9th ed. Philadelphia: Elsevier; 2023."],
    ["15.", "Gray's Anatomy for Students. 4th ed. Philadelphia: Elsevier; 2020."],
    ["16.", "Aydin S, Karavas E, Senbil DC. Imaging of acute appendicitis: Advances. World J Gastrointest Surg. 2022 Apr 27;14(4):272–284. PMID: 35664368."],
    ["17.", "Anderson RE. The natural history and traditional management of appendicitis revisited: spontaneous resolution and predominance of prehospital perforations imply that a correct diagnosis is more important than a prompt diagnosis. World J Surg. 2007;31(1):86–92."],
    ["18.", "Andersson M, Andersson RE. The appendicitis inflammatory response score: a tool for the diagnosis of acute appendicitis that outperforms the Alvarado score. World J Surg. 2008;32(8):1843–9."],
    ["19.", "Samuel M. Pediatric appendicitis score. J Pediatr Surg. 2002;37(6):877–881."],
    ["20.", "Swanson's Family Medicine Review: A Problem-Oriented Approach. 9th ed. Philadelphia: Elsevier; 2023."],
  ];

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  const outputPath = "/home/daytona/workspace/alvarado-review/Alvarado_Score_Review_of_Literature.docx";
  fs.writeFileSync(outputPath, buffer);
  console.log("Document written to:", outputPath, "(", buffer.length, "bytes)");
}

main().catch(console.error);

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/alvarado-review/build_doc.js'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/alvarado-review/build_doc.js'