Cardiovascular disease (CVD) is the leading cause of death globally, accounting for ~17.9M deaths/year. In the US, ~6.2M adults have heart failure (HF), with lifetime risk ~20% at age 40. Coronary artery disease (CAD) affects ~20M Americans; hypertension (HTN) affects ~47% of US adults. Atrial fibrillation (Afib) prevalence rises sharply with age (0.1% in <55 → >9% in ≥80). Valvular disease is present in ~2.5% of the population, predominantly aortic stenosis (AS) in the elderly and mitral regurgitation (MR). Venous thromboembolism (VTE) incidence is 1–2 per 1,000 person-years.

HFrEF involves progressive LV systolic dysfunction driven by neurohormonal activation — RAAS, sympathetic surges, and maladaptive cardiac remodeling (fibrosis, dilation). HFpEF is dominated by diastolic dysfunction, LV stiffness, and systemic inflammation (linked to obesity, HTN, diabetes). CAD results from atherosclerotic plaque rupture/erosion causing acute thrombosis; STEMI is transmural (occlusive), NSTEMI is subendocardial. HTN increases afterload, promoting LV hypertrophy. Afib arises from ectopic foci (pulmonary veins) with re-entrant circuits sustained by atrial remodeling. Aortic dissection starts with an intimal tear in the ascending aorta (Type A) or descending (Type B), propagating through the media. VTE: Virchow triad (stasis, hypercoagulability, endothelial injury).

HF: dyspnea on exertion, orthopnea, PND, peripheral edema, JVD, S3 gallop. CAD: stable angina (retrosternal pressure, exertion-relieved) vs ACS (prolonged pain, diaphoresis, dyspnea). STEMI: ST-elevation + troponin rise. NSTEMI: troponin + without ST-elevation. Afib: palpitations, irregularly irregular pulse, fatigue, dyspnea; can be asymptomatic. AS: classic triad — angina, syncope, HF (poor prognosis once symptomatic). MR: holosystolic murmur at apex radiating to axilla. Pericarditis: sharp pleuritic pain, worse supine, relieved leaning forward. Aortic dissection: sudden severe tearing chest pain radiating to back, pulse deficit, syncope. PAD: claudication, rest pain, non-healing ulcers.

ECG: ischemia, LVH, Afib, pericarditis (diffuse PR depression + concave STE). Troponin (hs-cTn) for ACS. BNP/NT-proBNP for HF (exclusion <100 pg/mL). Echocardiography: LVEF, diastolic function, valve gradients (AS: mean gradient >40 mmHg, area <1.0 cm²). Coronary angiography with FFR (<0.80 = ischemic). CT coronary calcium score. CTPA for PE. ABI (<0.9 = PAD). Holter for paroxysmal Afib. CHA„DS„-VASc for stroke risk. HAS-BLED for bleed risk.

HFrEF GDMT: quadruple therapy — ARNI (sacubitril/valsartan) or ACEi/ARB + beta-blocker (bisoprolol, carvedilol) + MRA (spironolactone) + SGLT2i (dapagliflozin). HFpEF: SGLT2i first-line; manage HTN, diuresis. STEMI: emergent PCI (<90 min) or fibrinolysis. NSTEMI: risk-stratify (GRACE) → early invasive vs conservative. DAPT (ASA + ticagrelor/prasugrel) 12 months. HTN: target <130/80; thiazide, CCB, ACEi/ARB first-line. Afib: rate/rhythm control. Anticoagulate if CHA„DS„-VASc ≥2 (DOACs preferred). AS: SAVR or TAVR for severe symptomatic. Pericarditis: NSAIDs + colchicine. Aortic dissection: Type A → emergent surgery; Type B → medical (HR <60, SBP 100–120). PAD: exercise, antiplatelet, statin, revascularization. VTE: DOACs 3–6 months.

COPD is the 3rd leading cause of death worldwide (~3.2M deaths/year). Asthma affects ~262M people globally. Pneumonia: CAP incidence ~5–11/1000 adults; HAP ~2–5/1000 hospitalizations. ILD: IPF ~3–9/100,000; sarcoidosis ~10–20/100,000. PE accounts for ~100,000 US deaths annually. OSA affects ~25% of adults (substantially underdiagnosed). Pleural effusion: transudate vs exudate determined by Light’s criteria.

COPD: chronic inflammation (neutrophils, macrophages, CD8+ T-cells) from smoke → emphysema (alveolar destruction, loss of elastic recoil) + chronic bronchitis (mucus gland hyperplasia, airway narrowing). Asthma: Th2-driven eosinophilic inflammation, IgE-mediated mast cell degranulation, bronchial hyperresponsiveness, reversible obstruction. Pneumonia: microbial lung parenchyma invasion — CAP (Strep pneumo most common), HAP (MRSA, Pseudomonas). IPF: aberrant wound healing → fibroblast foci → honeycombing (UIP pattern). PE: thrombus (usually from DVT) occludes pulmonary artery → increased dead space, RV pressure overload.

COPD: chronic cough, sputum, dyspnea, wheezing, prolonged expiration, barrel chest. Asthma: episodic wheezing, cough, chest tightness, nocturnal worsening. Pneumonia: fever, productive cough, pleuritic pain, crackles, egophony. IPF: insidious dry cough, exertional dyspnea, Velcro crackles, clubbing. PE: acute dyspnea, pleuritic pain, hemoptysis, tachycardia, hypoxia; massive PE → hypotension, syncope, RV strain. OSA: loud snoring, witnessed apneas, excessive daytime sleepiness, obesity. Pleural effusion: diminished breath sounds, dullness, decreased tactile fremitus.

PFTs: FEV1/FVC <0.70 confirms COPD (GOLD 1–4 by FEV1). Methacholine challenge for asthma. CXR for pneumonia, ILD, effusion. CT chest for detailed evaluation. PE: PERC rule → if +, D-dimer → if +, CTPA (gold standard). V/Q if contrast contraindicated. ABG: hypoxemia, hypercapnia; A-a gradient widened in PE. Polysomnography for OSA (AHI ≥5 + symptoms). Thoracentesis: Light’s criteria (LDH, protein).

COPD: smoking cessation (#1). GOLD 2025: LAMA/LABA for group B/D; ICS if eosinophils ≥300. Pulmonary rehab, O„ if PaO&bdq; ≤55. Exacerbations: bronchodilators, steroids, abx. Asthma: GINA step 1–5 — as-needed ICS-formoterol (mild); ICS/LABA + LAMA (severe); biologics (mepolizumab, benralizumab) for T2-high. CAP: CURB-65. Empiric: macrolide (outpatient) or beta-lactam + macrolide (inpatient). HAP: antipseudomonal beta-lactam + MRSA coverage. IPF: antifibrotics (pirfenidone, nintedanib) slow progression. PE: DOACs first-line; thrombolysis for massive PE. OSA: CPAP first-line, weight loss. Pleural effusion: treat cause; therapeutic thoracentesis if dyspneic.

GERD affects 18–28% of North Americans. PUD prevalence ~5–10%; H. pylori in 70–90% of duodenal and 50–70% of gastric ulcers. IBD: UC ~10–20/100,000, Crohn’s ~5–15/100,000. IBS affects 10–15% globally (Rome IV). Hep B infects ~257M chronically; Hep C ~58M. Cirrhosis causes 1.3M deaths/year. NAFLD affects ~25% globally — now leading cause of liver transplant in many regions. Pancreatitis incidence ~30–50/100,000. Celiac disease ~1% prevalence, significant underdiagnosis.

GERD: transient LES relaxations, hypotensive LES, hiatal hernia → acid/pepsin exposure. PUD: H. pylori (urease-producing) or NSAIDs (COX-1 inhibition, reduced prostaglandins) → mucosal erosion. Crohn’s: transmural inflammation, skip lesions, fistulas, granulomas, Th1/Th17. UC: continuous mucosal inflammation from rectum proximally. IBS: altered gut-brain axis, visceral hypersensitivity, dysmotility. Hep B: HBV DNA integration → chronic hepatitis → cirrhosis/HCC. NAFLD: insulin resistance, lipotoxicity → steatosis → NASH → fibrosis. Pancreatitis: premature trypsinogen activation → autodigestion. Celiac: HLA-DQ2/DQ8 T-cell response to gliadin → villous atrophy.

GERD: heartburn, regurgitation, dysphagia, cough. PUD: epigastric pain — duodenal (relieved by food) vs gastric (worse with food). Crohn’s: RLQ pain, diarrhea, weight loss, perianal fistulas. UC: bloody diarrhea, tenesmus, urgency. IBS: chronic abdominal pain related to defecation, altered stool (Rome IV ≥1 day/week). Acute hepatitis: jaundice, RUQ pain, nausea, transaminitis. Cirrhosis: ascites, spider angiomas, caput medusae, encephalopathy, varices. NAFLD: usually asymptomatic; hepatomegaly, elevated ALT/AST (<2× ULN). Pancreatitis: epigastric pain radiating to back, N/V, elevated lipase. Celiac: diarrhea, bloating, weight loss, iron-deficiency anemia, dermatitis herpetiformis. GI bleed: hematemesis/melena (upper) vs hematochezia (lower).

GERD/PUD: EGD with biopsy. H. pylori: stool antigen, urea breath test, or biopsy urease. IBD: colonoscopy + ileoscopy with biopsies; CT/MR enterography for Crohn’s. IBS: Rome IV clinical diagnosis (exclude alarm features: bleeding, weight loss, age >50, FHx). Viral hepatitis: serology (HBsAg, anti-HBc, HBsAb; anti-HCV, HCV RNA). Cirrhosis: transient elastography (FibroScan), labs (albumin ↓, INR ↑, platelets ↓), MELD-Na. NAFLD: US shows steatosis; FibroScan for fibrosis. Pancreatitis: lipase >3× ULN + typical pain. Celiac: TTG-IgA + total IgA; EGD/biopsy confirms. GI bleed: EGD first (upper), colonoscopy (lower), CT angio if massive.

GERD: lifestyle (elevate head, avoid triggers), PPIs. PUD: H. pylori eradication — triple therapy (PPI + amoxicillin + clarithromycin) 14 days; quadruple if resistance. Crohn’s: mesalamine → steroids → immunomodulators (azathioprine) → anti-TNF (infliximab). UC: mesalamine first-line; steroids for flares; anti-TNF or JAKi for refractory. IBS: fiber, antispasmodics, low-FODMAP, rifaximin for IBS-D. Hep B: tenofovir or entecavir. Hep C: pangenotypic DAAs (sofosbuvir/velpatasvir) 12 weeks. Cirrhosis: diuretics for ascites, beta-blockers for variceal prophylaxis, lactulose/rifaximin for encephalopathy. NAFLD/NASH: weight loss ≥7%; vitamin E (non-diabetic, biopsy-proven NASH). Pancreatitis: aggressive IVF, NPO, pain control. Celiac: strict gluten-free diet lifelong. GI bleed: resuscitate, PPI drip, restrictive transfusion (Hb <7), endoscopic therapy (clips, banding for varices).

AKI occurs in ~15% of hospitalized patients, 50% in ICU. CKD affects ~15% of US adults (37M); ~2.5M have ESRD. Glomerulonephritis accounts for ~10% of ESRD. Electrolyte disorders are among the most common lab abnormalities. Acid-base disturbances are universal in critical illness. Global CKD burden rising, driven by diabetes and hypertension.

AKI: pre-renal (hypoperfusion → RAAS activation), intrinsic (ATN from ischemia/nephrotoxins, AIN from drugs), post-renal (obstruction → increased intratubular pressure). CKD: progressive nephron loss → hyperfiltration → glomerulosclerosis → declining eGFR. Nephrotic: podocyte injury (MCD, FSGS, membranous). Nephritic: immune complex deposition (post-strep, lupus, IgA, RPGN). Electrolytes: Na via water balance (ADH); K via shifts (insulin, catecholamines) and total body; Ca via PTH, vitamin D. Acid-base: Henderson-Hasselbalch; respiratory (CO&bdq;) vs metabolic (HCO³−).

AKI: oliguria, fluid overload, uremia, hyperkalemia, metabolic acidosis. CKD: fatigue, edema, pruritus, nocturia, metallic taste, neuropathy. Nephrotic: periorbital/peripheral edema, frothy urine. Nephritic: hematuria (cola-colored), HTN, edema, RBC casts. Hypernatremia: thirst, confusion, seizures. Hyponatremia: headache, confusion, seizures (if acute/severe). Hypokalemia: weakness, cramps, U-waves, arrhythmias. Hyperkalemia: peaked T, weakness, cardiac arrest. Hypercalcemia: stones, bones, groans, psychic moans. Metabolic acidosis: Kussmaul respirations, fatigue.

AKI: BUN/Cr >20 (pre-renal), FeNa <1% (pre-renal) / >2% (ATN), urine microscopy (muddy brown casts = ATN; RBC casts = GN; WBC casts = AIN). Renal US to r/o obstruction. CKD: eGFR (CKD-EPI), urine ACR, staging (G1–5, A1–3). GN serology: C3/C4, ANA, ANCA, anti-GBM, dsDNA, SPEP. Renal biopsy for definitive diagnosis. Electrolytes: serum + urine levels, osmolality. Acid-base: ABG + BMP → anion gap (AG = Na − Cl − HCO³), delta ratio (ΔAG/ΔHCO³), Winter’s formula (PaCO&bdq; = 1.5 × [HCO³] + 8 ± 2).

AKI: IVF (pre-renal), hold nephrotoxins, relieve obstruction. RRT indications: “AEIOU” — Acidosis (pH <7.15), Electrolytes (K >6.5), Ingestion, Overload (pulmonary edema), Uremia (pericarditis, encephalopathy). CKD: BP target <130/80; ACEi/ARB for proteinuria; SGLT2i if eGFR >25. Dietary: low Na, restrict K/PO´/protein. Anemia: iron, ESAs. MBD: phosphate binders (sevelamer), vitamin D. GN: nephrotic → RAAS blockade, diuretics, steroids (MCD); nephritic → immunosuppression (steroids + cyclophosphamide for RPGN). Hyponatremia: correct ≤8 mEq/L/24h to avoid ODS; 3% NaCl if seizures. Hyperkalemia: Ca gluconate (cardiac) + insulin/glucose + albuterol + loop diuretic/resins. Metabolic acidosis: treat underlying; NaHCO³ if pH <7.1.

Diabetes affects ~537M adults globally (IDF 2021); T2DM 90–95%. DKA ~100,000 hospitalizations/year US. Hypothyroidism ~5%, hyperthyroidism ~1.2%. Adrenal insufficiency ~150–300/million. Cushing ~0.2–5/million/year. PCOS 6–12% of reproductive-age women. Dyslipidemia ~40% of US adults. Osteoporosis ~10M Americans over 50.

T1DM: autoimmune β-cell destruction (islet cell antibodies, GAD-65) → absolute insulin deficiency → ketogenesis. T2DM: insulin resistance + progressive β-cell dysfunction. DKA: insulin deficiency → lipolysis → ketone bodies → AG metabolic acidosis. HHS: hyperglycemia >600 mg/dL, hyperosmolality, minimal ketosis. Hypothyroidism (Hashimoto’s): autoimmune thyroid destruction. Hyperthyroidism (Graves’): TSI stimulates TSH receptor. Cushing: ACTH-dependent (pituitary 70%) vs ACTH-independent (adrenal). Hyperaldosteronism: renin-independent aldosterone excess. Ca metabolism: PTH ↑ Ca²± (bone resorption, renal reabsorption, vitamin D activation).

T1DM: polyuria, polydipsia, weight loss, DKA. T2DM: often asymptomatic; polyuria, fatigue, blurred vision, recurrent infections. DKA: N/V, abdominal pain, Kussmaul, fruity odor, AMS. HHS: profound dehydration, AMS, seizures. Hypothyroidism: fatigue, weight gain, cold intolerance, constipation, dry skin, bradycardia, delayed reflexes. Hyperthyroidism: weight loss, heat intolerance, tachycardia, tremor, lid lag, exophthalmos. Cushing: central obesity, moon face, purple striae, easy bruising, proximal myopathy. Addison: hyperpigmentation, orthostatic hypotension, hyponatremia, hyperkalemia. Hypercalcemia: nephrolithiasis, bone pain, constipation, short QT. Hypocalcemia: perioral numbness, Chvostek/Trousseau, prolonged QT, tetany. PCOS: oligomenorrhea, hirsutism, acne, infertility.

Diabetes: FBG ≥126, HbA1c ≥6.5%, OGTT 2h ≥200, or random ≥200 + sx. DKA: glucose >250, pH <7.3, HCO³ <15, β-OHB ≥3, + AG. HHS: glucose >600, osm >320, no ketones. Thyroid: TSH (screening). Graves: TSI + RAIU (diffuse increased). Thyroid nodules: US + FNA (Bethesda). Adrenal: ACTH stim test (cosyntropin) for insufficiency; midnight salivary cortisol + DST for Cushing; ARR for aldosteronism. Ca: corrected Ca = measured + 0.8(4 − alb). PTH: low in non-PTH hypercalcemia; high in primary hyperpara. Osteoporosis: DXA T-score ≤−2.5. PCOS: Rotterdam criteria (2 of 3: oligo-anovulation, hyperandrogenism, PCO morphology). Dyslipidemia: fasting lipid panel + ASCVD risk estimator.

T1DM: basal-bolus insulin (MDI/pump), carb counting. DKA/HHS: IVF (0.9% NS), insulin (0.1 U/kg bolus + drip), K+ repletion if <5.3, dextrose when glucose <250. T2DM: metformin first-line; add SGLT2i or GLP-1 RA if ASCVD/HF/CKD. Hypothyroidism: levothyroxine (1.6 μg/kg/day); TSH goal 0.5–2.5. Hyperthyroidism: methimazole, β-blockers, RAI or surgery. Adrenal insufficiency: HC 15–25 mg/day + fludrocortisone (if primary). Cushing: transsphenoidal surgery (pituitary); adrenalectomy (adrenal source). Conn: spironolactone/eplerenone. Hyperparathyroidism: parathyroidectomy if symptomatic or meets criteria. Osteoporosis: bisphosphonates first-line; denosumab, teriparatide for high risk. PCOS: OCPs (hirsutism), metformin (metabolic), letrozole (ovulation). Dyslipidemia: statins; ezetimibe/PCSK9i if refractory.

RA affects 0.5–1.0% globally (2–3:1 F:M). SLE ~20–150/100,000 (9:1 F:M). Gout ~4% US adults. AS ~0.1–1.4%, HLA-B27 associated. PsA ~0.3–1%, in ~30% of psoriasis. Vasculitides are rare: GPA ~10/million. Scleroderma ~50–300/million. Sjogren ~0.1–1.0% (9:1 F:M). Osteoporosis ~200M women worldwide.

RA: autoimmune synovitis (Th17, TNF-α, IL-6, ACPA/RF) → pannus → cartilage/bone erosion. SLE: loss of tolerance → anti-nuclear antibodies (ANA, dsDNA, Smith) → immune complex deposition → multi-organ damage. Gout: MSU crystals activate NLRP3 inflammasome → IL-1β → neutrophil influx. Pseudogout: CPPD crystals. AS: HLA-B27 misfolding → IL-23/IL-17 axis → enthesitis, sacroiliitis, syndesmophytes. ANCA vasculitis: necrotizing small-vessel inflammation (GPA, MPA, EGPA). Scleroderma: endothelial dysfunction (Raynaud’s) + fibroblast activation (fibrosis). Osteoporosis: imbalance of osteoblast vs osteoclast activity.

RA: symmetric small-joint polyarthritis (MCP, PIP, wrists, MTP), morning stiffness ≥30 min, ulnar deviation, swan-neck/Boutonniere deformities, nodules. SLE: malar rash, DLE, oral ulcers, serositis, arthritis, lupus nephritis, hematologic, CNS. Gout: acute monoarthritis (1st MTP = podagra), red/hot/swollen/excruciating; tophi in chronic. AS: <40 y/o chronic low back pain (improves with exercise), loss of lordosis, Schober +, uveitis. PsA: DIP, dactylitis, enthesitis, nail pitting. GPA: triad — respiratory granulomas + GN + vasculitis; c-ANCA (PR3+) in 90%. Scleroderma: CREST + ILD + PAH + renal crisis. Sjogren: xerophthalmia + xerostomia + parotid enlargement + lymphoma risk. Osteoporosis: asymptomatic until fragility fracture (hip, wrist, vertebral).

RA: RF, anti-CCP (>95% specificity), ESR/CRP, X-ray (erosions, joint space narrowing). ACR/EULAR 2010 criteria. SLE: ANA (screening, >99% sensitive), anti-dsDNA, anti-Smith, anti-Ro/La, low C3/C4. 2019 EULAR/ACR criteria (≥10). Gout: synovial fluid polarized microscopy (negatively birefringent MSU crystals), serum urate >6.8. AS: MRI SI joints (sacroiliitis), HLA-B27. Vasculitis: ANCA (c-ANCA/PR3 for GPA, p-ANCA/MPO for MPA), tissue biopsy (gold). Scleroderma: ANA (nucleolar), anti-Scl-70 (diffuse), anti-centromere (limited/CREST), PFTs, echo PAH. Sjogren: Schirmer test, salivary gland biopsy (focus score), anti-Ro/SSA. Osteoporosis: DXA + FRAX.

RA: early DMARD — MTX + folic acid first-line. Add TNFi (adalimumab) or IL-6i (tocilizumab) or JAKi (tofacitinib) if inadequate response. SLE: HCQ for all (reduces flares, improves survival). Mycophenolate or cyclophosphamide for lupus nephritis III/IV. Belimumab for non-renal. Gout: acute — NSAIDs, colchicine, steroids. Chronic — allopurinol first-line, goal urate <6 (<5 if tophi). AS: NSAIDs, anti-TNF, IL-17i (secukinumab). PsA: TNFi, IL-17i, IL-23i, PDE4i (apremilast). Vasculitis: high-dose steroids + rituximab/cyclophosphamide. Scleroderma: MMF for ILD, ERA/PDE5i for PAH, ACEi for renal crisis. Sjogren: artificial tears, pilocarpine, HCQ. Osteoporosis: bisphosphonates (alendronate), denosumab, teriparatide, romosozumab; Ca 1200 mg + vit D 800 IU/day.

Sepsis: ~49M cases/yr globally, 11M deaths (~20% of all deaths worldwide). The #1 cause of death in hospitals. Respiratory tract infections: pneumonia (5th leading cause of death globally), TB (~10M new cases/yr, 1.5M deaths). HIV: ~39M living with HIV globally, ~1.3M new infections/yr. Antimicrobial resistance (AMR): ~1.3M direct deaths/yr; could reach 10M/yr by 2050 without action. Endocarditis: incidence ~15/100,000/yr, increasing; ~30% associated with prosthetic valves/device. Osteomyelitis: 1-3% of orthopedic surgeries complicated by infection; chronic osteomyelitis in 20% of acute if untreated.

Sepsis-3: life-threatening organ dysfunction due to dysregulated host response to infection. qSOFA: altered mental status, RR ≥22, SBP ≤100 (2/3 = high risk). Lactate ≥2 mmol/L + need for vasopressors to maintain MAP ≥65 → septic shock. Pathophysiology: pathogen PAMPs → TLR activation → pro-inflammatory cytokine storm (TNF-α, IL-1, IL-6) + anti-inflammatory response (immunoparalysis) → endothelial injury, microvascular thrombosis, mitochondrial dysfunction, multi-organ failure. Treatment: 1-hr bundle: blood cultures (2 sets), lactate, broad-spectrum ABx (within 1h), 30 mL/kg crystalloid if hypotension/lactate ≥4, vasopressors (norepinephrine first-line) if MAP <65 after fluids. Corticosteroids: if refractory shock despite adequate fluids + high-dose vasopressors. Source control within 6-12h. EGDT not superior to usual care (ARISE, ProCESS, ProMISe).

CAP: S. pneumoniae (~40%), H. influenzae, M. pneumoniae, C. pneumoniae, Legionella, viruses (COVID, influenza, RSV). CURB-65 (confusion, BUN >20, RR ≥30, BP <90/60, age ≥65) → severity. Treatment: outpt (no comorbidities): amoxicillin or doxycycline or macrolide. Outpt (comorbidities): amoxicillin-clavulanate + macrolide or respiratory FQ. Inpt (non-ICU): beta-lactam + macrolide. ICU: beta-lactam + macrolide or FQ. HAP/VAP: consider MDR pathogens (MRSA, Pseudomonas, ESBL). Duration: 5d (CAP), 7d (HAP/VAP) if responding. HCAP no longer a distinct category. Pneumococcal vaccine: PCV15/PCV20 + PPSV23.

Modified Duke Criteria (definite: 2 major OR 1 major + 3 minor OR 5 minor). Major: (1) positive blood cultures (typical organism from 2 sets, persistently positive, or Coxiella serology); (2) endocardial involvement (vegetation, abscess, new partial dehiscence of prosthetic valve). Minor: predisposition, fever, vascular phenomena, immunologic phenomena, microbiologic evidence. Native valve: S. aureus (most common), viridans group strep, Enterococcus, HACEK. Prosthetic valve: early (<1yr, coag-neg staph); late (>1yr, similar to native). IV drug use: S. aureus (especially tricuspid). Treatment: empiric vancomycin + ceftriaxone (native), vancomycin + cefepime + gentamicin (prosthetic). S. aureus: 6wk nafcillin/cefazolin (MSSA) or vancomycin/daptomycin (MRSA). Strep: 4wk PCN or ceftriaxone. Enterococcus: 6wk ampicillin + ceftriaxone (E. faecalis) or vancomycin + gentamicin. Indications for surgery: heart failure, uncontrolled infection (abscess, persistent bacteremia), prevention of embolism (large mobile vegetation >10mm after embolus, >15mm with high embolic risk).

Acute: hematogenous (pyogenic bacteria → metaphysis in children, vertebral in adults). Vertebral: S. aureus (most common), gram-neg rods (elderly, IVDU), TB (Pott disease). Diabetic foot: polymicrobial (S. aureus, Strep, anaerobes, Enterobacteriaceae, Pseudomonas). Diagnosis: ESR/CRP elevated; X-ray shows periosteal reaction/lytic lesions after 2-3wk; MRI (best sensitivity ~90%, specificity ~80%); biopsy + culture gold standard. Treatment: acute hematogenous: 4-6wk IV ABx (nafcillin/cefazolin for MSSA, vancomycin for MRSA). Vertebral: 6-12wk IV then oral if responding. Diabetic foot: based on bone culture; typically 6wk. Debridement required for: abscess, necrotic bone, hardware, chronic. Chronic: requires surgical debridement + 6-12wk ABx + dead space management.

Pulmonary TB: cough >3wk, hemoptysis, night sweats, fever, weight loss. CXR: apical infiltrates, cavities. Primary: Ghon focus + lymphadenopathy (Ghon complex). Reactivation: apical cavitary disease. Diagnosis: AFB smear + NAAT (GeneXpert) + culture (Lowenstein-Jensen, liquid broth). IGRA (Quantiferon) or PPD for latent TB. Treatment (drug-sensitive): 2-month intensive: RIPE (rifampin, INH, pyrazinamide, ethambutol) daily; then 4-month continuation: RI. Miliary TB: diffuse small nodules, treat 9-12mo → steroids for TB meningitis. MDR-TB: resistance to R + I; requires 18-24mo BPaL (bedaquiline, pretomanid, linezolid) or longer individualized regimen. LTBI: 4R (4mo rifampin) or 3HP (3mo weekly INH + rifapentine) or 9H. BCG: reduces miliary/meningeal TB in children.

Transmission: blood/sexual/perinatal. Natural history: acute HIV (mononucleosis-like 2-6wk) → asymptomatic latency (~8-10yr) → AIDS (CD4 <200 with opportunistic infections). Diagnosis: 4th-gen Ag/Ab combo (p24 + HIV1/2 Ab), confirmed by HIV-1 RNA or Western blot. Initial labs: CD4, viral load, HIV genotype (integrase + RT + protease), HLA-B*5701, tropism, HBsAg, HCV Ab, G6PD, TB screen, STI panel. ART: INSTI-based (DTG/RAV/ELV/cBIC) + 2 NRTIs (TAF/FTC or ABC/3TC). Start ART regardless of CD4. U=U (undetectable = untransmittable). PrEP: TAF/FTC (Descovy) daily (MSM) or TDF/FTC (Truvada) daily (all). PEP: RAL/DTG + TDF/FTC within 72h for 28d. OI prophylaxis: CD4 <200 → TMP-SMX (PCP); CD4 <100 → azithromycin (MAC); CD4 <50 → CMV monitoring. Immune reconstitution inflammatory syndrome (IRIS): paradoxical worsening after ART initiation → treat OI first, continue ART.

Meningitis: bacterial (S. pneumoniae, N. meningitidis, H. influenzae, L. monocytogenes, GBS, E. coli), viral (enterovirus, HSV, VZV, West Nile), fungal (cryptococcus). Empiric ABx: vancomycin + ceftriaxone + ampicillin (elderly/immunocompromised). Dexamethasone before/with ABx (pneumococcal). Encephalitis: HSV (temporal lobe, acyclovir), VZV, West Nile. Brain abscess: streptococci (viridans, anginosus), S. aureus, anaerobes, Enterobacteriaceae. Treatment: empiric ceftriaxone + metronidazole + vancomycin. N. meningitidis: droplet precautions, rifampin/ceftriaxone/cipro prophylaxis for contacts. Cryptococcal meningitis (HIV): L-AmB + flucytosine then fluconazole.

UTI: uncomplicated vs complicated → TMP-SMX or nitrofurantoin (uncomplicated); FQ or carbapenem (complicated, ESBL). Pyelonephritis: FQ or ceftriaxone 14d. C. difficile: mild-moderate → vancomycin 125mg PO QID 10d or fidaxomicin 200mg BID 10d; severe/fulminant → vancomycin PO + IV metronidazole. Cellulitis: beta-hemolytic strep + S. aureus; treat cephalexin or clindamycin. Necrotizing fasciitis: polymicrobial or GAS, urgent surgical debridement + broad spectrum ABx. Catheter-related BSI: remove line, treat 7-14d, S. aureus/Tx candida → TEE to rule out endocarditis.

Right drug, right dose, right duration, right indication. De-escalate based on cultures. Shorten duration: CAP 5d, HAP 7d, UTI 3-5d (uncomplicated), pyelo 7d (if responding). Avoid FQ for uncomplicated infections unless no alternative. Use procalcitonin to guide ABx discontinuation in respiratory infections (PCT <0.25 → stop). Stewardship reduces C. diff, AMR, costs, length of stay.

Allergic diseases affect ~30% of the global population. Asthma: ~300M people worldwide; 5-10% severe (uncontrolled despite high-dose ICS/LABA). Allergic rhinitis: ~15-30% prevalence; costs ~$5B/yr in lost productivity and treatment. Food allergy: 6-8% children, 3-4% adults; 150-200 deaths/yr from anaphylaxis in US. Drug allergy: 10-15% of hospitalized patients report a drug allergy; most common = beta-lactams (10% of patients) but >90% of these tolerate PCN on testing. Primary immunodeficiencies (PIDs): prevalence ~1:1,200 live births; CVID most common symptomatic PID (1:25,000). Anaphylaxis: lifetime risk ~0.5-2%; fatality rate ~0.3-0.7/100,000 cases.

Definition: severe, life-threatening, generalized or systemic hypersensitivity reaction with rapid onset. Diagnostic criteria (NIAID/FASE): acute onset (min-hr) with involvement of skin/mucosa AND at least one of: respiratory compromise, reduced BP, end-organ dysfunction. Or: 2+ of: skin/mucosa, respiratory, BP, GI. Or: known allergen + hypotension alone. Triggers: food (peanut, tree nut, shellfish, egg, milk), medications (ABx, NSAIDs, biologics), insect venom (Hymenoptera), latex, exercise-induced, idiopathic. Pathophysiology: mast cell/basophil degranulation → histamine, tryptase, PAF, leukotrienes → vasodilation, bronchospasm, edema, urticaria, hypotension. Treatment: IM epinephrine (1:1000, 0.01 mg/kg, max 0.3-0.5 mg) anterolateral thigh, repeat q5-15min. No death from anaphylaxis is ascribable to epinephrine; death is due to delayed epinephrine. Adjuncts: H1/H2 blockers, steroids, albuterol. Observation: 4-6h (biphasic reaction in ~5%). Discharge: auto-injector, action plan, allergy referral. Indications for ICU: severe biphasic, need for epinephrine drip, severe airway compromise.

Variable airway obstruction due to chronic airway inflammation + bronchial hyperresponsiveness. Phenotypes: allergic (early-onset, IgE, eosinophilic, Th2-high), non-allergic (late-onset, neutrophilic, Th2-low), eosinophilic (adult-onset, severe, high FeNO/eos), exercise-induced (bronchoconstriction during exertion). Diagnosis: spirometry with bronchodilator (FEV1/FVC <0.70 + ≥12% ≥200mL improvement). Alternative: bronchial challenge (methacholine) if suspicion persists. Exhaled NO (FeNO) >50 ppb = eosinophilic inflammation. Treatment (GINA): Step 1: as-needed low-dose ICS-formoterol. Step 2: low-dose ICS-formoterol maintenance + reliever (MART). Step 3: medium-dose ICS-formoterol MART. Step 4: high-dose ICS-formoterol MART + add-on (LAMA, LTRA, theophylline). Step 5: add-on biologic (anti-IgE omalizumab, anti-IL5 mepolizumab/benralizumab/reslizumab, anti-IL4R dupilumab, anti-TSLP tezepelumab) + oral corticosteroids (lowest dose possible). Severe asthma: ≥50% of exacerbations prevented with biologics. Non-pharmacologic: allergen avoidance, smoking cessation, influenza/COVID/SARS2 vaccine, PAP for OSA, exercise, weight loss.

Seasonal vs perennial. Symptoms: sneezing, rhinorrhea, nasal congestion, itchy nose/eyes/palate, postnasal drip. Diagnosis: clinical + skin prick (prick/puncture) + sigE (ImmunoCAP). Treatment: intranasal corticosteroids (INCS) first-line (fluticasone, mometasone, triamcinolone). Intranasal antihistamines (azelastine, olopatadine). Oral antihistamines: 2nd gen (cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine). Montelukast: add-on for nocturnal symptoms (but boxed warning for neuropsychiatric events). Allergen immunotherapy (AIT): SCIT or SLIT, for moderate-severe uncontrolled with medications. Other: saline irrigation, allergen avoidance.

Type I (immediate, IgE-mediated): urticaria, angioedema, anaphylaxis within 1-6h. Type II (cytotoxic): hemolytic anemia, thrombocytopenia (e.g., PCN, cephalosporins, methyldopa). Type III (immune complex): serum sickness, DRESS, vasculitis. Type IV (delayed, T-cell-mediated): MPE, SJS/TEN, AGEP, DRESS. Penicillin allergy: 10% report, >90% tolerate; no cross-reactivity with cephalosporins except 1st gen (1-2% cross). If severe IgE-mediated (anaphylaxis, angioedema) → skin testing (PPL + MDM, then full-dose challenge if negative). If negative → de-label. Cephalosporin cross-reactivity: <2% (1st gen), <1% (2nd/3rd/4th). Sulfonamide allergy: cross-reactivity between sulfa antibiotics AND non-antibiotic sulfonamides is minimal. DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): 2-8wk after drug (allopurinol, anticonvulsants, sulfa, dapsone, minocycline); fever + rash + eosinophilia + organ involvement (liver, kidney, lung, heart). Treatment: stop drug, steroids, supportive care. SJS/TEN: <10% BSA (SJS) vs >30% (TEN); → stop all drugs, ICU burn unit, IVIG/cyclosporine, supportive wound care. SCORTEN predicts mortality.

IgE-mediated food allergy: most common triggers = peanut, tree nut, shellfish, fish, egg, milk, soy, wheat, sesame, finned fish. Diagnosis: sIgE + skin testing, oral food challenge (gold standard). Treatment: strict avoidance; auto-injector for all IgE-mediated food allergy (especially if prior anaphylaxis). OIT (oral immunotherapy) available for peanut (Palforzia) after skin testing. Chronic urticaria: spontaneous (CSU, autoimmune, >6wk) vs inducible (physical). First-line: 2nd gen H1 (up to 4x dose). Second-line: add H2, montelukast. Third-line: omalizumab (anti-IgE, ~70% complete response). Fourth-line: cyclosporine. Angioedema: histaminergic (urticaria + angioedema = treat with H1/H2/steroids) vs bradykinin-mediated (HAE: C1-inhibitor deficiency, ACEi-induced). HAE: no urticaria, no pruritus, often GI + laryngeal; treat with C1-INH replacement (Berinert, Cinryze), ecallantide (kallikrein inhibitor), icatibant (bradykinin B2 antagonist). ACEi-AE: stop ACEi; consider ARB (safe to switch).

CVID (Common Variable Immunodeficiency): onset 20-40yr, low IgG + IgA +/- IgM, impaired antibody response, recurrent sinopulmonary infections, autoimmune manifestations (ITP, AIHA, IBD), lymphoproliferation (lymphoma risk 30-50x). Treatment: IVIG/SCIG replacement q3-4wk. Bruton agammaglobulinemia (XLA): onset <2yr, absent B cells, all Ig low, recurrent bacterial/enteroviral infections; IVIG + avoid live vaccines. Severe combined immunodeficiency (SCID): onset <6mo, T cell absent/low, severe infections; emergency: hematopoietic stem cell transplant (HSCT). Chronic granulomatous disease (CGD): NADPH oxidase defect, recurrent catalase+ infections (S. aureus, Serratia, Burkholderia, Nocardia, Aspergillus), granuloma formation; prophylaxis TMP-SMX + itraconazole + IFN-γ; definitive: HSCT. Hyper-IgM syndrome: CD40L defect → normal/high IgM, low IgG/A/E, Pneumocystis + Cryptosporidium + neutropenia; IVIG + HSCT. Wiskott-Aldrich syndrome: X-linked, eczema + thrombocytopenia (small platelets) + recurrent infections + autoimmune + lymphoma; HSCT curative. Ataxia-telangiectasia: ATM mutation → cerebellar ataxia + telangiectasias + IgA/IgE deficiency + radiosensitivity + lymphoma risk; avoid radiation. DiGeorge (22q11.2 deletion): thymic aplasia → low T cells, hypocalcemia, conotruncal heart defects; if complete: thymus transplant or HSCT.

Biologic immunogenicity: monoclonal antibodies can induce anti-drug antibodies (ADA) → loss of response (neutralizing ADA) or hypersensitivity (infusion reactions). Premedicate with antihistamines + steroids for infusion reactions. Mastocytosis: clonal mast cell accumulation (often KIT D816V), mediator release → flushing, tachycardia, hypotension, GI; triggers: NSAIDs, opioids, alcohol, heat, physical stimuli; treatment: H1/H2, cromolyn, omalizumab, cladribine (advanced). Hereditary angioedema (HAE): C1-INH deficiency (Type I, 85%) or dysfunction (Type II, 15%), autosomal dominant. Positive family hx, recurrent angioedema without urticaria, often laryngeal edema (50% lifetime risk of fatal asphyxiation). Treatment of attack: C1-INH, ecallantide, icatibant. Prophylaxis: androgens (danazol, stanozolol), tranexamic acid (mild), C1-INH q3-4d (severe), lanadelumab (monoclonal anti-kallikrein, q2-4wk). COVID-19: vaccine reactions (anaphylaxis <1:100K doses; delayed urticaria 1-2%) are manageable and not contraindication to 2nd dose (see guidelines).

Anemia ~1.9B globally (iron deficiency #1). SCD ~100K Americans, ~20M globally. Thalassemia: α-thal (Asia/Africa), β-thal (Mediterranean). VWD ~1% (most common inherited bleeding disorder). Hemophilia A ~1/5000 males. DIC common in sepsis/trauma/malignancy. TTP ~4/million. Leukemia: AML ~20K/yr, CLL most common adult, CML ~8K, ALL ~6K. Lymphoma: HL ~8.5K, NHL ~77K/yr. Myeloma ~35K/yr. MDS ~10–15K/yr US.

Microcytic anemia: Fe deficiency (low ferritin, low Fe, high TIBC), thalassemia (microcytosis out of proportion), ACD (high ferritin, low Fe, low TIBC). Macrocytic: B12 def (demyelination + anemia), folate def (anemia only), MDS, alcohol. Hemolytic: intrinsic (spherocytosis, G6PD, SCD) vs extrinsic (AIHA, MAHA). SCD: HbS polymerizes → sickling → vaso-occlusion → hemolysis → organ damage. Thalassemia: ↓ globin chain → ineffective erythropoiesis + iron overload. VWD: quantitative/qualitative VWF deficiency. Hemophilia A/B: X-linked FVIII/FIX deficiency. DIC: systemic coagulation activation → microthrombi + factor consumption. TTP: ADAMTS13 deficiency → uncleaved VWF multimers → microthrombi. HUS: Shiga toxin → endothelial damage. Leukemia: clonal proliferation with maturation arrest (AML = Auer rods; CML = BCR-ABL; CLL = CD5+; ALL = lymphoblasts). Lymphoma: HL = Reed-Sternberg (CD15+, CD30+); NHL = heterogeneous (DLBCL, FL, MALT). Myeloma: clonal plasma cells → M-protein → lytic lesions, hyperCa, renal failure, anemia.

Anemia: fatigue, pallor, DOE, palpitations, glossitis (Fe/B12), koilonychia (Fe). SCD: acute pain crises, acute chest syndrome, aplastic crisis (parvovirus B19), autosplenectomy, stroke. Thalassemia major: severe anemia, failure to thrive, skeletal deformities, hepatosplenomegaly, iron overload. VWD: easy bruising, epistaxis, menorrhagia, prolonged surgical bleeding. Hemophilia: hemarthroses, deep hematomas, muscle bleeds. DIC: concurrent bleeding and thrombosis. TTP: MAHA + thrombocytopenia + fever + neuro sx + renal (pentad). HUS: MAHA + thrombocytopenia + AKI (post-diarrheal). Leukemia: cytopenias (fatigue, infection, bleeding), fever, bone pain, lymphadenopathy, gum hypertrophy (AML M4/M5). CML: incidental WBC elevation, splenomegaly. Lymphoma: painless LAD, B-symptoms (fever, night sweats, weight loss). Myeloma: CRAB — hyperCalcemia, Renal failure, Anemia, Bone lesions. MDS: cytopenias with hypercellular marrow.

CBC + indices (MCV, MCH, RDW), reticulocyte count. Fe studies, B12, folate. Hemolysis: LDH ↑, haptoglobin ↓, bili ↑, DAT (Coombs). Smear: schistocytes (TTP/HUS, DIC), spherocytes (AIHA), sickle cells, target cells, tear drops (myelofibrosis). Hb electrophoresis for SCD/thal. VWD: VWF Ag, ristocetin cofactor, FVIII, multimers. Hemophilia: FVIII/FIX activity, prolonged PTT (corrects). DIC: platelets ↓, PT/PTT ↑, D-dimer ↑, fibrinogen ↓. TTP: ADAMTS13 <10%. BMB: essential for leukemia, myeloma, MDS. Cytogenetics: BCR-ABL (CML), FLT3/NPM1 (AML). SPEP + immunofixation + free light chains (myeloma). Skeletal survey: lytic lesions.

Fe deficiency: oral ferrous sulfate (reticulocytosis day 7–10, Hb +1 g/dL q2–3wk). IV Fe if intolerant. B12: IM/SC 1000 μg monthly. SCD: HU first-line (↓ crises); L-glutamine, crizanlizumab, voxelotor. Transfusion for acute chest syndrome/stroke. Penicillin ppx + vaccines. β-thal major: regular transfusions + chelation (deferasirox). VWD: DDAVP (type 1); VWF concentrates (type 2/3). Hemophilia A: FVIII concentrates; emicizumab for ppx (with/without inhibitors). DIC: treat cause; platelets if bleeding, cryo if fibrinogen <100, FFP if INR ↑. TTP: PLEX + steroids + rituximab; avoid platelets. AML: 7+3 induction + consolidation; targeted (FLT3i, IDHi, venetoclax + HMA). CML: TKI (imatinib, dasatinib, nilotinib). CLL: watchful waiting (early); ibrutinib, venetoclax. ALL: multi-agent chemo + CAR-T for refractory. HL: ABVD ×2–4 + RT. NHL: R-CHOP (DLBCL), R-bendamustine (FL). Myeloma: VRd (bortezomib, lenalidomide, dex) + daratumumab; auto SCT. MDS: supportive; lenalidomide (del5q); HMA (azacitidine); transplant for eligible.

Cancer is the 2nd leading cause of death globally (~10M deaths/yr). Lung cancer is the leading cancer killer (1.8M deaths/yr). NSCLC 85%, SCLC 15%. Breast cancer is the most common cancer in women (~2.3M cases/yr). CRC is 3rd most common (~1.9M cases/yr). Prostate cancer is 2nd most common in men (~1.4M cases/yr). Effective screening (USPSTF) reduces mortality for breast, cervical, colorectal, and lung cancers.

Lung: NSCLC subtypes — adenocarcinoma (most common, peripheral, non-smokers), squamous (central, cavitating), large cell. SCLC (neuroendocrine, rapid, paraneoplastic). Driver mutations: EGFR, ALK, ROS1, KRAS, BRAF, MET, RET, NTRK. Breast: HR+ (ER/PR+), HER2+, triple-negative. BRCA1/BRCA2 → familial. CRC: adenoma-carcinoma sequence (APC → KRAS → TP53) vs MSI (Lynch). Prostate: androgen-dependent growth; Gleason grading (3+4, 4+3, etc.). Paraneoplastic: SCLC (SIADH, LEMS), squamous (hypercalcemia/PTHrP).

Lung: cough, hemoptysis, dyspnea, chest pain, hoarseness (recurrent laryngeal), Horner (Pancoast), SVCS, post-obstructive pneumonia. Breast: painless mass, axillary LAD, peau d’orange, nipple retraction, bloody discharge. CRC: change in bowel habits, hematochezia, weight loss, IDA (right colon). Prostate: often asymptomatic; urinary obstruction, hematuria, bone pain (mets). Palliative: pain, nausea, dyspnea, constipation, fatigue, depression, existential distress.

Lung: CT chest + PET-CT. Tissue via bronchoscopy/EBUS/CT-guided. Molecular: EGFR, ALK, ROS1, PD-L1, NGS. Breast: mammogram + US + core biopsy. ER/PR/HER2/ki-67. CRC: colonoscopy + biopsy; CT CAP; MSI/MMR testing. Prostate: PSA (shared decision); MRI before biopsy; Gleason scoring; PSMA-PET for mets. General: TNM staging determines treatment. ECOG performance status critical.

NSCLC: I–III → surgery ± chemo. III unresectable → chemoradiation + durvalumab. IV → targeted if driver (osimertinib for EGFR, alectinib for ALK, entrectinib for NTRK). IO (pembrolizumab) if PD-L1 ≥50% or + chemo. SCLC: etoposide + platinum + atezolizumab/durvalumab; PCI for limited-stage. Breast: lumpectomy + SLNB + RT vs mastectomy. Adjuvant: endocrine (tamoxifen/AI) if HR+; trastuzumab if HER2+; neoadjuvant chemo for TN/HER2+. CRC: surgical resection; FOLFOX/CAPOX for stage III/high-risk II. Stage IV: FOLFOX/FOLFIRI + bevacizumab or anti-EGFR (RAS wt, left). IO for MSI-H. Prostate: active surveillance (low risk); prostatectomy or RT (intermediate/high). ADT for advanced; abiraterone/enzalutamide for CRPC; docetaxel, radium-223. Palliative: WHO ladder (acetaminophen → NSAIDs → weak → strong opioids). Nausea: ondansetron, metoclopramide, dexamethasone, olanzapine. Bowel regimen with opioids.

Stroke is the #1 cause of disability globally. ~795K strokes/yr US (87% ischemic, 10% ICH, 3% SAH). Epilepsy ~50M worldwide. Dementia ~55M globally (Alzheimer’s 60–80%). Parkinson’s ~1% over age 60. Migraine ~12% of adults. MS ~2.8M globally. GBS ~0.5–2/100K/yr. MG ~20–40/100,000.

Ischemic stroke: thrombotic (large/small vessel), embolic (cardioembolic, cryptogenic). Hemorrhagic: hypertensive (basal ganglia, thalamus), amyloid angiopathy (lobar), aneurysm (SAH), AVM. Seizures: abnormal synchronous neuronal discharge (focal vs generalized). Alzheimer’s: amyloid plaques (Aβ42) + neurofibrillary tangles (tau). Parkinson’s: substantia nigra dopamine neuron loss → Lewy bodies (α-synuclein). Migraine: CSD → trigeminovascular activation → CGRP release. MS: CNS demyelination (T-cell mediated). GBS: molecular mimicry → anti-ganglioside antibodies → peripheral demyelination/axonal. MG: AChR antibodies (80–90%) → impaired neuromuscular transmission.

Stroke: sudden focal deficit (FAST). NIHSS score. Anterior: hemiparesis, hemisensory, aphasia (dominant), neglect (non-dominant). Posterior: vertigo, diplopia, ataxia, visual field cuts. Seizures: focal aware → focal impaired → generalized tonic-clonic → absence; post-ictal confusion. Alzheimer’s: insidious short-term memory loss → progressive cognitive decline. Parkinson’s: TRAP — Tremor (resting, pill-rolling), Rigidity (cogwheel), Akinesia/bradykinesia, Postural instability (asymmetric onset). Migraine: unilateral throbbing 4–72h, N/V, photo/phonophobia ± aura. Cluster: severe orbital pain + autonomic features (lacrimation, rhinorrhea, miosis). Tension: bilateral band-like tightness. MS: relapsing-remitting (optic neuritis, transverse myelitis, sensory/motor). GBS: ascending symmetric flaccid paralysis, areflexia; Miller-Fisher (opthalmoplegia, ataxia, areflexia, anti-GQ1b). MG: fluctuating weakness — ptosis, diplopia, dysphagia, proximal limbs; improves with rest, worsens with use. Myasthenic crisis.

Stroke: non-contrast CT (r/o hemorrhage), CTA (LVO), MRI DWI (acute infarct). NIHSS, Carotid Dopplers, ECHO, telemetry. TIA: ABCD² score. Seizures: EEG (interictal epileptiform), MRI brain, labs (Na, glucose, Ca, Mg). Dementia: MoCA (<26 abnormal), MRI, labs (B12, TSH, RPR, HIV), CSF Aβ/tau. Parkinson’s: clinical; DaTscan if uncertain. Headache: SNNOOP10 red flags → CT/MR, LP, ESR. MS: MRI (demyelinating lesions, Dawson fingers), CSF (oligoclonal bands, elevated IgG), evoked potentials. GBS: LP (cytoalbuminologic dissociation), EMG/NCS (demyelinating). MG: AChR antibodies (80%), RNS (decremental), SFEMG (most sensitive), chest CT for thymoma.

Acute ischemic stroke: IV tPA within 4.5h (r/o hemorrhage, strict criteria). Mechanical thrombectomy for LVO within 6–24h (perfusion imaging). Stroke unit. DAPT 21d for minor stroke/TIA. Secondary ppx: antiplatelet + high-intensity statin + BP control ± anticoagulation. ICH: BP <140, reverse anticoagulation (PCC, idarucizumab, andexanet). Seizures: lamotrigine, levetiracetam (broad). Focal: carbamazepine, oxcarbazepine. Generalized: valproate, lamotrigine, levetiracetam. Status: lorazepam → fosphenytoin/valproate/levetiracetam → anesthetics. Alzheimer’s: donepezil, rivastigmine (mild-moderate); memantine (moderate-severe). Parkinson’s: carbidopa/levodopa (most effective), DA agonists, MAO-Bi, DBS. Migraine acute: triptans, NSAIDs, gepants, ditans. Prevention: β-blockers, topiramate, amitriptyline, CGRP mAbs (erenumab). Cluster: O&bdq; 12–15 L/min, sumatriptan SC; verapamil for prevention. MS: relapse → IV methylprednisolone. DMT: IFN, GA, fingolimod, dimethyl fumarate, natalizumab, ocrelizumab. GBS: IVIG or PLEX; ICU monitoring (FVC, NIF). MG: pyridostigmine + steroids/azathioprine/MMF. Thymectomy if thymoma or generalized AChR+ MG. Myasthenic crisis → IVIG/PLEX + ICU.

Older adults (>65) are the fastest-growing population (1.5B by 2050). Frailty ~10–15% of community-dwelling older adults. Polypharmacy (≥5 meds) in 40%; potentially inappropriate medications in 25–50% (Beers Criteria). Falls: ~30% of older adults fall each year; 10% serious injury. Delirium ~30% of hospitalized older adults (50% ICU). Pressure injuries ~2.5M/yr US ($9–11B cost). Elder abuse ~10% (often unrecognized).

Frailty: multi-system decline — sarcopenia, neuroendocrine dysregulation (↓ IGF-1, ↑ cortisol), immune dysfunction (↑ IL-6, CRP). Phenotype: weight loss, exhaustion, weakness, slow gait, low activity. Polypharmacy: altered PK (↓ renal/hepatic clearance, ↓ Vd, ↓ albumin) + altered PD (↑ sensitivity to CNS drugs, anticholinergics) → ↑ ADEs, drug interactions, prescribing cascade. Falls: multifactorial — age-related changes + environment + medications (especially psychotropics, antihypertensives). Delirium: acute brain dysfunction — neurotransmitter imbalance (↓ ACh, ↑ DA, ↑ 5-HT) + neuroinflammation. Dementia pathology discussed above. Pressure injuries: unrelieved pressure → ischemia → necrosis. Elder abuse: risk factors — caregiver stress, dependency, social isolation, cognitive impairment.

Frailty: Fried phenotype ≥3 of 5 — unintentional weight loss ≥10 lb/yr, exhaustion, weak grip, slow gait (>5s/15ft), low activity. Polypharmacy: ADEs (falls, hypotension, bleeding, delirium), drug interactions, prescribing cascade. Falls: assess cause, gait, balance, orthostatics, vision, medications. Delirium: acute, fluctuating, inattention, disorganized thinking, AMS (hyperactive vs hypoactive = missed). Delirium vs dementia: acute vs chronic, fluctuating vs stable, reversible vs progressive. Dementia: chronic progressive cognitive decline. Pressure injuries: Stage I (non-blanchable) → II (partial) → III (full, visible fat) → IV (bone/muscle) → Unstageable (eschar). Common sites: sacrum, heels, trochanters. Elder abuse: physical (bruises, fractures), emotional, financial, neglect (poor hygiene, untreated conditions, malnutrition).

Geriatric assessment: medical, functional (ADLs/IADLs), cognitive (MoCA), mobility (TUG), nutrition (MNA), vision/hearing, social, advance care planning. Polypharmacy: medication reconciliation (brown bag), Beers Criteria, STOPP/START. Delirium: CAM — acute + fluctuating + inattention + disorganized thinking or AMS. Workup: CBC, BMP, glucose, Ca, Mg, TSH, B12, UA, tox, cultures, ABG, EEG. Falls: postural BP, vision, neuro exam, TUG (>12s = high risk), ECG, medication review. Pressure injury: NPUAP staging; labs (albumin, wound culture if infected). Elder abuse: screen (EASI), mandatory reporting, imaging for occult fractures, social work/APS.

Frailty: resistance + aerobic exercise, protein ≥1.2 g/kg/d, vitamin D 800 IU + Ca 1200, deprescribe. Polypharmacy: systematic deprescribing — taper benzodiazepines, PPIs, anticholinergics, antihistamines, avoid tight glycemic control. BP target: individualize (SBP <150 usually). Falls: multifactorial — exercise, medication adjustment (reduce psychotropics), vision, environment, vitamin D, assistive devices, hip protectors. Delirium: identify + treat cause. Non-pharmacologic: reorientation, family, sleep, early mobility, sensory aids. Pharmacologic (only if severe agitation): low-dose haloperidol 0.25–1 mg or quetiapine 12.5–25 mg. Avoid benzodiazepines (except withdrawal). Dementia: cholinesterase inhibitors + memantine; non-pharmacologic for BPSD first. Pressure injuries: prevention — reposition q2h, pressure-redistributing surfaces, moisture management, nutrition. Treatment — debridement, dressings, offloading; Stage III/IV → flap closure. Elder abuse: mandatory reporting, safety plan, legal interventions, caregiver support/respite, placement if needed.

Preventive medicine reduces cancer mortality by 30–50% for screened cancers. Only ~50% of eligible US adults receive recommended preventive services. CVD + cancer = ~50% of all deaths (both modifiable). Vaccine-preventable diseases still cause ~50K adult deaths/yr US. ~40% of US adults have obesity (BMI ≥30). Tobacco is the #1 preventable cause of death (480K/yr). Genetic screening identifies 5–10% with hereditary cancer syndromes.

Primary: prevent before disease (vaccines, lifestyle, chemoprevention). Secondary: early detection of asymptomatic disease (screening). Tertiary: prevent progression/complications of established disease. Health behaviors shaped by social determinants. The 5Ms guide geriatric prevention: Mobility, Mind, Medications, Multicomplexity, Matters Most. Vaccines work through humoral/cell-mediated immunity; herd immunity at 80–95% coverage. Genetic screening identifies heritable mutations for targeted prevention.

Breast: biennial mammography 50–74 (shared decision 40–49). Cervical: Pap q3y 21–65; HPV co-test q5y 30–65. CRC: FIT q1y or colonoscopy q10y 45–75. Lung: LDCT 50–80, ≥20 pk-yr, current/quit ≤15 yr. Prostate: shared decision 55–69. Osteoporosis: DXA women ≥65. AAA: one-time US men 65–75 ever smoked. T2DM: screen 35–70 with overweight/obesity. HTN: screen at any age. Lipids: men ≥35, women ≥45 with risk. HIV: screen 15–65 (once; annually if high risk). Hep C: one-time 18–79. Syphilis: at-risk. Depression: all adults (PHQ-9). Anxiety: adults <65. Unhealthy drug use: 18+. IPV: reproductive-age women. Tobacco: ask, advise, refer. Unhealthy alcohol: screen + brief intervention. Obesity: screen + refer (BMI ≥30). Aspirin primary ppx: age 40–59 with 10-yr ASCVD ≥10%, low bleed risk.

Influenza: annually (≥6mo; high-dose/adjuvanted for ≥65). Tdap: one dose then Td/Tdap q10y; Tdap each pregnancy 27–36wk. HPV: 2-dose at 11–12 (catch-up through 26; shared decision 27–45). Pneumococcal: PCV15/PCV20 + PPSV23 (if PCV15) for ≥65 or high-risk. Zoster: RZV 2-dose at ≥50. COVID-19: annual updated 2025–26 vaccine (≥6mo; ≥65: 2 doses/season). RSV: one dose for ≥75 or ≥60 with chronic conditions. HepA: at-risk. HepB: all ≥19 (catch-up). MMR: 1 dose if no immunity (born ≥1957). Varicella: 2 doses if no immunity (born ≥1980). Meningococcal ACWY: if asplenia, complement deficiency, MSM, HIV, college. MenB: shared decision 16–23. Travel vaccines: per destination.

Tobacco: 5 As (Ask, Advise, Assess, Assist, Arrange). Varenicline most effective pharmacotherapy. Diet: Mediterranean (Level A for CVD prevention) — fruits, veg, whole grains, fish, olive oil, nuts. Activity: 150 min/wk moderate or 75 vigorous + 2d strength. Weight: intensive behavioral interventions; GLP-1 RA (semaglutide, tirzepatide) if BMI ≥30 or ≥27 + comorbidity; bariatric surgery if BMI ≥40 or ≥35 + comorbidity. Alcohol: ≤2/d men, ≤1/d women. Sleep: 7–9h. Sun: SPF 30+ broad-spectrum. Genetic: BRCA → enhanced screening, RRSO 35–40 (BRCA1) or 40–45 (BRCA2), PARPi for treatment. Lynch → colonoscopy q1–2y starting 20–25, prophylactic hysterectomy. FH → high-intensity statin + ezetimibe + PCSK9i; cascade screening. Hemochromatosis → HFE (C282Y) → phlebotomy. FAP → APC mutation → prophylactic colectomy. Always genetic counseling before/after testing.