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// ─── THEME ────────────────────────────────────────────────────────────────────
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// ─── HELPER FUNCTIONS ─────────────────────────────────────────────────────────

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// ─── SLIDE 1: TITLE ──────────────────────────────────────────────────────────
let s1 = pres.addSlide();
titleSlide(s1,
  "Hypertensive Disorders in Pregnancy",
  "Focus on Pre-eclampsia: From Pathogenesis to Management"
);

// ─── SLIDE 2: OVERVIEW / AGENDA ──────────────────────────────────────────────
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const agendaItems = [
  "1.  Classification & Definitions",
  "2.  Epidemiology & Risk Factors",
  "3.  Etiopathogenesis",
  "4.  Prediction of Pre-eclampsia",
  "5.  Prevention Strategies",
  "6.  Clinical Features",
  "7.  Investigations",
  "8.  Management – Antihypertensive Drugs",
  "9.  Management – Delivery & Complications",
  "10. HELLP Syndrome & Eclampsia",
];
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// ─── SLIDE 3: SECTION 1 DIVIDER – CLASSIFICATION ─────────────────────────────
let s3 = pres.addSlide();
sectionDivider(s3, "Classification & Definitions of Hypertensive Disorders in Pregnancy", "1", "10");

// ─── SLIDE 4: CLASSIFICATION TABLE ───────────────────────────────────────────
let s4 = pres.addSlide();
tableSlide(s4,
  "Classification of Hypertensive Disorders in Pregnancy",
  ["Disorder", "Definition", "Onset"],
  [
    ["Gestational\nHypertension", "New HTN (≥140/90 mmHg) after 20 weeks\nNo maternal organ dysfunction\nResolves by 12 weeks postpartum", "≥20 weeks"],
    ["Pre-eclampsia", "New HTN after 20 weeks + maternal organ\ndysfunction OR uteroplacental dysfunction\n(proteinuria not essential if other criteria present)", "≥20 weeks"],
    ["Eclampsia", "Seizures in woman with pre-eclampsia\n(may occur without prior HTN)", "Any time"],
    ["Chronic\nHypertension", "BP ≥140/90 mmHg pre-pregnancy or\nbefore 20 weeks; persists >12 weeks\npostpartum", "<20 weeks\nor pre-existing"],
    ["Superimposed\nPre-eclampsia", "New organ dysfunction after 20 weeks in\na woman with chronic hypertension", "≥20 weeks"],
    ["White-coat\nHypertension", "Office BP ≥140/90; Home BP <135/85\n~8% risk of pre-eclampsia (double baseline)", "Any time"],
  ],
  { accent: C.navy }
);

// ─── SLIDE 5: DEFINITIONS – PRE-ECLAMPSIA ────────────────────────────────────
let s5 = pres.addSlide();
contentSlide(s5, "Pre-eclampsia: Diagnostic Criteria (ISSHP 2018 / ACOG)", [
  "Essential: New hypertension after 20 weeks – SBP ≥140 mmHg OR DBP ≥90 mmHg on two occasions",
  "PLUS at least one of the following additional criteria:",
  { sub: "Proteinuria: uPCR >30 mg/mmol (≥0.3 mg/mg), or >300 mg/24 hr, or dipstick ≥2+" },
  { sub: "Renal: Serum creatinine >1.0–1.1 mg/dL or doubling of baseline creatinine" },
  { sub: "Hematologic: Platelets <150 × 10⁹/L, hemolysis, or DIC" },
  { sub: "Hepatic: AST/ALT >40 U/L (twice normal); RUQ/epigastric pain" },
  { sub: "Neurological: Seizures (eclampsia), persistent headache, visual disturbances" },
  { sub: "Uteroplacental: FGR, abnormal umbilical artery Doppler, stillbirth" },
  "Proteinuria alone is NOT required if other organ dysfunction exists",
  "Severe features: SBP ≥160 mmHg or DBP ≥110 mmHg, severe headache, visual changes, pulmonary oedema, platelets <100 × 10⁹/L",
], { accent: C.teal });

// ─── SLIDE 6: SECTION 2 DIVIDER – EPIDEMIOLOGY ───────────────────────────────
let s6 = pres.addSlide();
sectionDivider(s6, "Epidemiology & Risk Factors", "2", "10");

// ─── SLIDE 7: EPIDEMIOLOGY ────────────────────────────────────────────────────
let s7 = pres.addSlide();
twoColSlide(s7,
  "Epidemiology of Hypertensive Disorders",
  {
    header: "Global Burden",
    items: [
      "Hypertension complicates 10–12% of all pregnancies",
      "Pre-eclampsia: 4.6% of pregnancies globally",
      "Eclampsia: 1.4% of pregnancies globally (range 0.02–2.9%)",
      "LMIC: PE/eclampsia accounts for ~30% of maternal deaths",
      "Mortality 200× higher in LMICs than high-income countries",
      "Recurrence risk: 15–65% depending on gestational age at index episode",
    ]
  },
  {
    header: "High-Risk Groups",
    items: [
      "Nulliparous women (higher risk vs. multiparous)",
      "Black, Asian, Hispanic, Indigenous populations",
      "Advancing maternal age (>40 years)",
      "Previous preeclampsia (highest risk)",
      "Multiple gestation",
      "IVF/ART pregnancies",
      "Obesity (BMI >30), diabetes, CKD",
    ]
  },
  { accent: C.navy }
);

// ─── SLIDE 8: RISK FACTORS ────────────────────────────────────────────────────
let s8 = pres.addSlide();
twoColSlide(s8,
  "Risk Factors for Pre-eclampsia",
  {
    header: "Maternal / Obstetric Factors",
    items: [
      "Nulliparity",
      "Multiple-gestation pregnancy",
      "Previous pre-eclampsia (esp. <34 weeks)",
      "Molar pregnancy, Trisomy 13, hydrops",
      "Prior IUGR or placental abruption",
      "Gestational diabetes",
      "ART / IVF conception",
      "Interpregnancy interval >7 years",
    ]
  },
  {
    header: "Comorbidities & Paternal Factors",
    items: [
      "Chronic hypertension",
      "Pre-gestational diabetes mellitus",
      "Chronic kidney disease",
      "Antiphospholipid syndrome (APS)",
      "Systemic lupus erythematosus",
      "Thrombophilia",
      "PCOS",
      "New partner / ICSI conception",
      "Father born from PE-affected pregnancy",
    ]
  },
  { accent: C.teal }
);

// ─── SLIDE 9: SECTION 3 DIVIDER – ETIOPATHOGENESIS ───────────────────────────
let s9 = pres.addSlide();
sectionDivider(s9, "Etiopathogenesis of Pre-eclampsia", "3", "10");

// ─── SLIDE 10: TWO-STAGE MODEL ────────────────────────────────────────────────
let s10 = pres.addSlide();
contentSlide(s10, "Two-Stage Model of Pre-eclampsia Pathogenesis", [
  "STAGE 1 – Placental (asymptomatic, before 20 weeks):",
  { sub: "Inadequate cytotrophoblast invasion of spiral arteries" },
  { sub: "Failure of spiral artery remodeling → vessels remain narrow, high-resistance" },
  { sub: "Uteroplacental ischaemia → hypoxic placental environment" },
  { sub: "Hypoxia-inducible factor 1α (HIF-1α) elevated in placenta" },
  { sub: "Activated placenta releases anti-angiogenic factors into maternal circulation" },
  "STAGE 2 – Maternal systemic (symptomatic, clinical PE):",
  { sub: "Circulating sFlt-1 (soluble fms-like tyrosine kinase-1) rises → binds VEGF & PlGF" },
  { sub: "PlGF (placental growth factor) falls → endothelial dysfunction" },
  { sub: "Widespread maternal endothelial damage → hypertension, proteinuria, organ dysfunction" },
  { sub: "Neurological, renal, hepatic, haematological involvement" },
  "Key concept: Placental ischaemia triggers systemic maternal endothelial injury",
], { accent: C.teal });

// ─── SLIDE 11: MOLECULAR MECHANISMS ──────────────────────────────────────────
let s11 = pres.addSlide();
contentSlide(s11, "Molecular & Immunological Mechanisms", [
  "Anti-angiogenic factors:",
  { sub: "sFlt-1 (sVEGFR-1): sequesters free VEGF and PlGF, preventing endothelial repair" },
  { sub: "Endoglin (sEng): inhibits TGF-β1, impairs NO signalling → vasoconstriction" },
  "Pro-angiogenic deficiency:",
  { sub: "PlGF reduced weeks before clinical onset → key screening biomarker" },
  { sub: "VEGF reduction → impaired glomerular endothelial function → proteinuria" },
  "Immunological tolerance failure:",
  { sub: "Inadequate maternal immune tolerance to paternal antigens" },
  { sub: "NK cell and regulatory T-cell dysfunction at decidua" },
  "Oxidative stress:",
  { sub: "Ischaemia-reperfusion injury of placenta → reactive oxygen species" },
  { sub: "Lipid peroxidation, NF-κB activation → pro-inflammatory cytokines (IL-6, TNF-α)" },
  "Genetic predisposition: polymorphisms in sFlt-1, HLA, AGT, eNOS genes",
], { accent: C.navy });

// ─── SLIDE 12: SPIRAL ARTERY REMODELING ──────────────────────────────────────
let s12 = pres.addSlide();
twoColSlide(s12,
  "Normal vs Defective Spiral Artery Remodeling",
  {
    header: "Normal Pregnancy",
    items: [
      "Extravillous cytotrophoblasts (EVTs) invade decidua and myometrium",
      "EVTs replace smooth muscle & elastin of spiral arteries",
      "Arteries transform into wide, low-resistance conduits",
      "High blood flow at low velocity and pulsatility to placenta",
      "Adequate O₂ and nutrient exchange to fetus",
    ]
  },
  {
    header: "Pre-eclampsia",
    items: [
      "Shallow trophoblast invasion (superficial decidual layer only)",
      "Spiral arteries remain narrow, muscular, high-resistance",
      "Uteroplacental ischaemia and oxidative stress",
      "Ischaemic placenta releases sFlt-1, sEng into circulation",
      "Systemic endothelial dysfunction → HTN, proteinuria, organ damage",
    ]
  },
  { accent: C.teal }
);

// ─── SLIDE 13: SECTION 4 DIVIDER – PREDICTION ────────────────────────────────
let s13 = pres.addSlide();
sectionDivider(s13, "Prediction of Pre-eclampsia", "4", "10");

// ─── SLIDE 14: PREDICTION – FIRST TRIMESTER SCREENING ────────────────────────
let s14 = pres.addSlide();
contentSlide(s14, "First-Trimester Combined Screening (11–13+6 weeks)", [
  "FMF (Fetal Medicine Foundation) Combined Algorithm – best validated model:",
  { sub: "Uterine artery pulsatility index (UtA-PI) – reflects incomplete remodeling" },
  { sub: "Mean arterial pressure (MAP) – maternal vascular tone" },
  { sub: "Serum PAPP-A (pregnancy-associated plasma protein-A) – reduced in PE" },
  { sub: "Serum PlGF (placental growth factor) – reduced in early PE" },
  { sub: "Maternal history & demographics (BMI, ethnicity, obstetric history)" },
  "Detection rates (at 10% FPR):",
  { sub: "Preterm PE (<37 wks): ~75–85% detection with combined algorithm" },
  { sub: "Term PE: ~40–50% detection" },
  "Second-trimester biomarkers: PlGF <100 pg/mL at 19–23 weeks strongly predictive",
  "Third-trimester: sFlt-1/PlGF ratio >38 rules in PE (sensitivity ~80%, specificity ~78%)",
  "sFlt-1/PlGF ratio <38 has high negative predictive value (NPV ~99%) for ruling out PE within 1 week",
], { accent: C.teal });

// ─── SLIDE 15: SECTION 5 DIVIDER – PREVENTION ────────────────────────────────
let s15 = pres.addSlide();
sectionDivider(s15, "Prevention of Pre-eclampsia", "5", "10");

// ─── SLIDE 16: PREVENTION ─────────────────────────────────────────────────────
let s16 = pres.addSlide();
twoColSlide(s16,
  "Prevention Strategies for Pre-eclampsia",
  {
    header: "Pharmacological",
    items: [
      "Low-dose aspirin (LDA): 75–150 mg/day from ≤16 weeks",
      { sub: "Indicated in high-risk women (previous PE, CKD, APS, diabetes, multiple gestation)" },
      { sub: "Reduces preterm PE by ~62%, term PE by ~14% (ASPRE trial)" },
      { sub: "Best if initiated at 11–14 weeks based on FMF screening" },
      "Calcium supplementation: 1.5–2 g/day elemental calcium",
      { sub: "Recommended where dietary intake is <600 mg/day" },
      { sub: "WHO recommendation for low-calcium intake populations" },
      { sub: "Reduces PE risk by ~55% (Cochrane meta-analysis)" },
      "Pravastatin / metformin: under investigation, not yet standard of care",
    ]
  },
  {
    header: "Non-pharmacological",
    items: [
      "Pre-conception weight loss in obese women",
      "Optimal management of pre-existing conditions (DM, HTN, CKD, APS)",
      "Folic acid supplementation (5 mg/day in high-risk)",
      "Regular antihypertensive therapy in chronic HTN",
      "Smoking cessation (paradoxically protective but not recommended!)",
      "Adequate rest; avoid excessive physical exertion",
      "Close antenatal surveillance in high-risk women",
    ]
  },
  { accent: C.green }
);

// ─── SLIDE 17: SECTION 6 DIVIDER – CLINICAL FEATURES ─────────────────────────
let s17 = pres.addSlide();
sectionDivider(s17, "Clinical Features of Pre-eclampsia", "6", "10");

// ─── SLIDE 18: CLINICAL FEATURES ─────────────────────────────────────────────
let s18 = pres.addSlide();
twoColSlide(s18,
  "Clinical Features of Pre-eclampsia",
  {
    header: "Symptoms",
    items: [
      "Often asymptomatic early (BP monitoring essential)",
      "Severe headache (frontal, occipital) – cerebral oedema/vasospasm",
      "Visual disturbances: blurred vision, photopsia, scotomata",
      "Epigastric or RUQ pain – hepatic capsule distension, liver oedema",
      "Nausea and vomiting",
      "Sudden rapid oedema – face, hands, feet",
      "Reduced fetal movements (uteroplacental insufficiency)",
      "Seizures (eclampsia) – may be first presentation",
    ]
  },
  {
    header: "Signs",
    items: [
      "BP ≥140/90 mmHg (severe: ≥160/110 mmHg)",
      "Oedema: pitting oedema of hands, face, legs",
      "Weight gain >0.5 kg/week (non-dependent oedema)",
      "Proteinuria on dipstick (≥2+)",
      "Hyperreflexia, clonus (neurological involvement)",
      "Fundoscopy: arteriolar narrowing, papilloedema",
      "Jaundice (severe hepatic involvement)",
      "Oliguria (<500 mL/24 hr) – severe renal impairment",
      "FGR, oligohydramnios on ultrasound",
    ]
  },
  { accent: C.red }
);

// ─── SLIDE 19: SECTION 7 DIVIDER – INVESTIGATIONS ────────────────────────────
let s19 = pres.addSlide();
sectionDivider(s19, "Investigations", "7", "10");

// ─── SLIDE 20: INVESTIGATIONS ─────────────────────────────────────────────────
let s20 = pres.addSlide();
tableSlide(s20,
  "Investigations in Pre-eclampsia",
  ["System", "Test", "Finding / Significance"],
  [
    ["Renal", "Urine PCR / dipstick; 24hr protein; serum creatinine", "Proteinuria ≥0.3 g/24hr; Cr rise >90 µmol/L"],
    ["Haematological", "FBC, blood film, coagulation", "Thrombocytopenia <150×10⁹/L; microangiopathic haemolysis; prolonged PT/APTT in DIC"],
    ["Hepatic", "LFTs (AST, ALT, LDH, bilirubin)", "AST/ALT >40 U/L; elevated LDH (HELLP); bilirubin↑"],
    ["Metabolic", "Serum uric acid, urea", "Hyperuricaemia (>360 µmol/L); urea rises with severe AKI"],
    ["Cardiovascular", "Blood pressure profile; ECG", "Persistent ≥140/90; severe ≥160/110"],
    ["Biomarkers", "PlGF, sFlt-1/PlGF ratio", "PlGF <100 pg/mL; sFlt-1/PlGF ratio >38 = PE confirmed"],
    ["Imaging", "Uterine / umbilical artery Doppler; fetal biometry", "Absent/reversed EDF in umbilical artery; FGR <10th centile"],
    ["Neurological", "CT / MRI brain if seizures/altered consciousness", "PRES (posterior reversible encephalopathy syndrome), haemorrhage"],
  ],
  { accent: C.teal }
);

// ─── SLIDE 21: SECTION 8 DIVIDER – MANAGEMENT ────────────────────────────────
let s21 = pres.addSlide();
sectionDivider(s21, "Management of Pre-eclampsia", "8", "10");

// ─── SLIDE 22: ANTIHYPERTENSIVE MANAGEMENT ────────────────────────────────────
let s22 = pres.addSlide();
tableSlide(s22,
  "Antihypertensive Drug Management in Pregnancy",
  ["Drug", "Route", "Use in Pregnancy", "Notes"],
  [
    ["Labetalol", "Oral/IV", "First-line (oral & IV)", "α+β blocker; preserves uteroplacental flow; avoid in asthma"],
    ["Nifedipine (LA)", "Oral", "First-line (oral)", "Once-daily slow release; may cause headache/oedema"],
    ["Methyldopa", "Oral", "First-line (oral)", "Most safety data; sedation; short half-life; 3–4×/day"],
    ["Hydralazine", "IV", "Acute severe HTN", "2nd line IV; risk maternal hypotension + abruption"],
    ["Nicardipine", "IV infusion", "Acute severe HTN", "Extensive tocolytic safety data; effective"],
    ["Magnesium sulfate", "IV/IM", "Seizure prophylaxis\n+ treatment of eclampsia", "Loading 4g IV over 20min; maintenance 1g/hr; target Mg 2–3.5 mmol/L; antidote: calcium gluconate"],
    ["ACE inhibitors\nARBs", "Oral", "CONTRAINDICATED", "Fetotoxic; oligohydramnios, renal dysgenesis, IUGR, skull defects"],
    ["Atenolol", "Oral", "Avoid", "Associated with IUGR"],
    ["Nitroprusside", "IV", "Avoid if possible", "Risk of fetal cyanide toxicity if >4 hours use"],
  ],
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// ─── SLIDE 23: GENERAL MANAGEMENT & DELIVERY ──────────────────────────────────
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  "General Management Principles & Timing of Delivery",
  {
    header: "Antenatal Management",
    items: [
      "Hospitalization for severe features or rapidly worsening disease",
      "Treat acute severe HTN within 30–60 minutes (SBP ≥160 or DBP ≥110)",
      "Target BP: 130–150 / 80–100 mmHg",
      "Fluid balance: restrict IV fluids to 80 mL/hr; avoid overload (risk: pulmonary oedema)",
      "Corticosteroids (betamethasone 12 mg IM × 2 doses) if <34 weeks for fetal lung maturity",
      "Magnesium sulfate for seizure prophylaxis in severe PE",
      "Fetal monitoring: CTG, biophysical profile, Doppler",
      "Thromboprophylaxis: LMWH if prolonged immobility",
    ]
  },
  {
    header: "Timing of Delivery",
    items: [
      "Definitive treatment = delivery of placenta",
      "<34 weeks + severe PE: steroids → delivery within 24–48 hrs",
      "34–37 weeks: individualise; consider delivery",
      "≥37 weeks: deliver promptly",
      "Route: vaginal delivery preferred if cervix favourable",
      "LSCS for obstetric indications or deteriorating condition",
      "Postpartum: HTN may worsen in first 3–5 days; continue antihypertensives",
      "Screen at 6 weeks postpartum; long-term CV risk counselling",
    ]
  },
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);

// ─── SLIDE 24: HELLP SYNDROME & ECLAMPSIA ─────────────────────────────────────
let s24 = pres.addSlide();
twoColSlide(s24,
  "HELLP Syndrome & Eclampsia",
  {
    header: "HELLP Syndrome",
    items: [
      "H – Haemolysis (microangiopathic; LDH >600 U/L, schistocytes)",
      "EL – Elevated Liver enzymes (AST/ALT >70 U/L)",
      "LP – Low Platelets (<100 × 10⁹/L)",
      "Classif: Tennessee (complete/incomplete); Mississippi (Class I/II/III by platelets)",
      "Complications: hepatic rupture/haematoma, DIC, renal failure, abruption",
      "Management: MgSO₄, aggressive BP control, correct coagulopathy, urgent delivery",
      "Dexamethasone may transiently improve platelet count",
    ]
  },
  {
    header: "Eclampsia",
    items: [
      "Tonic-clonic seizures in woman with PE (or may be first presentation)",
      "Prevalence: ~0.3% of hypertensive pregnancies in high-income countries",
      "Immediate management: ABC, left lateral tilt, O₂",
      "Magnesium sulfate: 4 g IV over 5–10 min (loading dose)",
      "Maintenance: 1 g/hr IV infusion for 24 hrs after last fit",
      "Magnesium superior to diazepam/phenytoin for prevention of recurrent seizures",
      "Monitor: patellar reflexes, respiratory rate, urine output, Mg levels",
      "Antidote: calcium gluconate 10 mL of 10% solution IV",
    ]
  },
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);

// ─── SLIDE 25: SUMMARY & KEY MESSAGES ────────────────────────────────────────
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  "Pre-eclampsia: NEW HTN after 20 weeks + organ dysfunction – proteinuria NOT mandatory",
  "Two-stage model: defective trophoblast invasion → placental ischaemia → systemic endothelial injury",
  "sFlt-1↑ and PlGF↓ are the key angiogenic imbalance driving maternal disease",
  "First-trimester screening (UtA-PI + MAP + PAPP-A + PlGF) achieves ~80% detection of preterm PE",
  "Low-dose aspirin from ≤16 weeks reduces preterm PE by ~62% in high-risk women",
  "Calcium 1.5–2 g/day halves PE risk where dietary calcium is low",
  "Labetalol, nifedipine, methyldopa – first-line antihypertensives; ACEi/ARBs absolutely contraindicated",
  "Magnesium sulfate is the drug of choice for seizure prophylaxis and treatment of eclampsia",
  "Delivery is the ONLY cure – timing balances maternal safety vs fetal maturity",
  "Long-term: 4× increased lifetime CVD risk; screen and counsel at every postpartum visit",
];
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// ─── WRITE FILE ───────────────────────────────────────────────────────────────
const outPath = "/home/daytona/workspace/preeclampsia-ppt/Hypertensive_Disorders_Pregnancy_PE.pptx";
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