ITE Internal Medicine In-Training Exam — Questions and Answers

Question 1: A 34-year-old woman presents with hypertension, hypokalemia, and suppressed plasma renin activity. Aldosterone-to-renin ratio is markedly elevated. CT abdomen shows bilateral adrenal hyperplasia. Adrenal vein sampling reveals a lateralization ratio of 1.8 (left:right). Which is the most appropriate next step?

Start mineralocorticoid receptor antagonist therapy and avoid surgery
Proceed with left adrenalectomy based on lateralization ratio
Repeat adrenal vein sampling with cosyntropin stimulation (Correct answer)
Order 11-deoxycortisol levels to evaluate for 11β-hydroxylase deficiency

Correct answer: Repeat adrenal vein sampling with cosyntropin stimulation

A lateralization ratio <2.0 without cosyntropin stimulation is indeterminate. Current Endocrine Society guidelines recommend adrenal vein sampling with cosyntropin (ACTH) stimulation to maximize cortisol secretion, correct for dilution, and improve selectivity index reliability. A selectivity index ≥3:1 post-stimulation confirms successful cannulation. Surgery should only be considered with a clear lateralization ratio ≥4:1 on stimulated sampling. Without confirming lateralization, proceeding to unilateral adrenalectomy risks persistent hypertension and unnecessary surgery.

Question 2: A 45-year-old woman with type 2 diabetes on an SGLT-2 inhibitor presents with nausea, vomiting, and fatigue. Labs: glucose 195 mg/dL, pH 7.21, bicarbonate 13 mEq/L, anion gap 22 mEq/L, beta-hydroxybutyrate 4.8 mmol/L. Urine dipstick shows 3+ ketones. Which statement best explains her presentation?

The dipstick overestimates ketosis because SGLT-2 inhibitors cause false-positive nitroprusside reactions
She likely has HHS superimposed on mild DKA, as glucose below 250 mg/dL excludes true DKA
SGLT-2 inhibitors can cause euglycemic DKA by increasing glucagon-to-insulin ratio and promoting ketogenesis independent of hyperglycemia (Correct answer)
Her DKA is caused by SGLT-2 inhibitor-induced lactic acidosis masquerading as ketoacidosis

Correct answer: SGLT-2 inhibitors can cause euglycemic DKA by increasing glucagon-to-insulin ratio and promoting ketogenesis independent of hyperglycemia

SGLT-2 inhibitors can precipitate euglycemic DKA — a dangerous and underrecognized condition where DKA occurs despite near-normal glucose levels. The mechanism involves SGLT-2 inhibitor-mediated glucosuria (lowering glucose threshold), increased glucagon secretion relative to insulin, volume contraction, and a caloric-restriction state, all of which promote lipolysis and ketogenesis. Glucose levels may be <200 mg/dL, misleading providers into excluding DKA. The classic criterion of glucose >250 mg/dL does NOT apply in this setting. Euglycemic DKA from SGLT-2 inhibitors is a known FDA warning.

Question 3: A 44-year-old woman presents with recurrent episodes of abdominal pain, nausea, and watery diarrhea for 3 years. Colonoscopy shows normal mucosa; random colonic biopsies reveal a subepithelial collagen band measuring 18 µm with surface epithelial damage and mixed inflammatory infiltrate in the lamina propria. Stool cultures and Clostridioides difficile testing are negative. Which medication, if recently started, is the most common pharmacologic cause of this finding?

Sertraline
Metformin
Lansoprazole (Correct answer)
Olmesartan

Correct answer: Lansoprazole

Collagenous colitis (collagen band >10 µm) is strongly associated with proton pump inhibitor use, particularly lansoprazole (and to a lesser extent omeprazole and other PPIs), as well as NSAIDs, SSRIs, and ranitidine. Among PPIs, lansoprazole has the highest association with collagenous colitis, with an odds ratio significantly elevated in multiple case-control studies. Olmesartan is classically associated with olmesartan-induced enteropathy (sprue-like) affecting the small bowel, not collagenous colitis. Metformin and sertraline have weaker associations. The collagen band of 18 µm confirms collagenous colitis.

Question 4: A patient with stage 5 CKD presents to the emergency department with altered mental status. Which of the following findings represents the most urgent indication to initiate hemodialysis?

Blood urea nitrogen (BUN) of 120 mg/dL
Refractory peripheral edema
Uremic pericarditis with a friction rub (Correct answer)
Serum creatinine of 9.0 mg/dL

Correct answer: Uremic pericarditis with a friction rub

While elevated BUN and creatinine, and fluid overload are indications for dialysis, the most urgent, life-threatening indications are remembered by the mnemonic AEIOU (Acidosis, Electrolytes, Intoxication, Overload, Uremia). Uremic pericarditis is a life-threatening complication of uremia that can lead to pericardial effusion and tamponade. It is an absolute and urgent indication for initiating hemodialysis.

Question 5: A 65-year-old patient is mechanically ventilated in the ICU for pneumonia. The clinical team is discussing the sedation strategy. Which of the following approaches has been associated with improved clinical outcomes, including shorter duration of mechanical ventilation and ICU length of stay?

Administering continuous high-dose benzodiazepines without a daily awakening trial
Avoiding all sedation and analgesia to promote rapid extubation
Maintaining deep sedation (RASS -4 to -5) to ensure patient comfort and prevent ventilator recall
Using daily sedation interruptions combined with a protocol targeting light sedation (RASS 0 to -2) (Correct answer)

Correct answer: Using daily sedation interruptions combined with a protocol targeting light sedation (RASS 0 to -2)

Maintaining a light level of sedation (e.g., Richmond Agitation-Sedation Scale [RASS] 0 to -2) in critically ill, mechanically ventilated patients is associated with better outcomes. Studies have shown that strategies combining daily interruptions of sedative infusions ('sedation vacations') with protocols that target light sedation lead to a shorter duration of mechanical ventilation, reduced ICU length of stay, and decreased incidence of delirium without increasing psychological stress. Deep sedation is associated with adverse outcomes, while avoiding all sedation may not be feasible or safe for all patients.

Question 6: A 40-year-old woman presents with two episodes of unilateral optic neuritis over 2 years plus a history of transient bilateral leg weakness that resolved completely. MRI of the brain and spine shows periventricular white matter lesions disseminated in space and time. CSF shows oligoclonal bands. What is the most likely diagnosis?

CNS vasculitis
Acute disseminated encephalomyelitis (ADEM)
Relapsing-remitting multiple sclerosis (RRMS) (Correct answer)
Neuromyelitis optica spectrum disorder (NMOSD)

Correct answer: Relapsing-remitting multiple sclerosis (RRMS)

The presentation of relapsing neurological episodes with lesions disseminated in space and time, periventricular MRI lesions, and CSF oligoclonal bands satisfies McDonald criteria for RRMS. NMOSD typically involves longitudinally extensive spinal cord lesions and AQP4-IgG positivity. CNS vasculitis and ADEM are typically monophasic or have distinct features.

Question 7: A patient with rheumatic mitral stenosis is started on anticoagulation for a new LAA thrombus. After 3 months of therapeutic anticoagulation, repeat TEE shows persistent thrombus. What is the next step?

Perform immediate surgical mitral valve replacement
Proceed with PMBC with careful technique
Aspirate thrombus percutaneously under fluoroscopic guidance
Continue anticoagulation for another 3 months and repeat TEE (Correct answer)

Correct answer: Continue anticoagulation for another 3 months and repeat TEE

If LAA thrombus persists after 3 months of therapeutic anticoagulation, extending anticoagulation for another 3 months is reasonable before reassessing suitability for PMBC.

Question 8: A 22-year-old African American man with known sickle cell disease presents with severe bilateral leg bone pain, fever of 38.4°C, and WBC 12,500/μL. His Hgb is 6.9 g/dL compared to a baseline of 7.1 g/dL. What is the most likely diagnosis?

Vaso-occlusive (pain) crisis (Correct answer)
Aplastic crisis
Acute chest syndrome
Splenic sequestration crisis

Correct answer: Vaso-occlusive (pain) crisis

Severe bone pain with near-baseline hemoglobin and no respiratory symptoms is characteristic of a vaso-occlusive pain crisis.

Question 9: During rounds in the medical ICU, you review a patient's ventilator waveforms. The flow-time scalar shows flow not returning to zero before the next breath is delivered, and the pressure-time scalar shows an initial negative deflection at the start of each breath followed by a rapid pressure rise. The patient is on volume-assist control. Which of the following best explains these findings and their clinical consequence?

Reverse triggering: ventilator-initiated breaths entraining diaphragmatic contractions, increasing VILI risk
Patient-ventilator dyssynchrony from flow starvation causing breath stacking and dynamic hyperinflation
Auto-PEEP from intrinsic PEEP causing ineffective triggering and increased work of breathing (Correct answer)
Double-triggering due to neural inspiratory time exceeding set ventilator inspiratory time

Correct answer: Auto-PEEP from intrinsic PEEP causing ineffective triggering and increased work of breathing

The flow-time waveform showing flow not returning to zero indicates gas trapping (auto-PEEP). The negative pressure deflection at breath onset reflects the patient's effort needed to overcome auto-PEEP before the ventilator triggers, dramatically increasing work of breathing. This is distinct from reverse triggering (which occurs in deeply sedated patients without spontaneous respiratory drive) and flow starvation (which causes a 'scooped' pressure waveform, not a negative deflection). Double-triggering produces two pressure spikes in rapid succession. Auto-PEEP must be measured with an expiratory hold maneuver and addressed by reducing respiratory rate, increasing expiratory time, or adjusting PEEP settings.

Question 10: A 45-year-old woman with butterfly-shaped facial erythema sparing the nasolabial folds, discoid lesions on the scalp, and photosensitivity is found to have oral ulcers and positive ANA. Which of the following skin findings would be MOST characteristic of her underlying diagnosis?

Malar rash sparing the nasolabial folds (Correct answer)
Violaceous papules over the knuckles (Gottron's papules)
Target lesions on the palms and soles
Psoriasiform plaques on extensor surfaces

Correct answer: Malar rash sparing the nasolabial folds

The malar (butterfly) rash of SLE characteristically spares the nasolabial folds, distinguishing it from rosacea. Psoriasiform plaques are seen in psoriasis. Gottron's papules are pathognomonic for dermatomyositis. Target lesions suggest erythema multiforme.

Question 11: A 60-year-old man with COPD is hospitalized with healthcare-associated pneumonia. He has no prior antibiotic exposure. What empiric coverage is most appropriate?

Levofloxacin monotherapy
Piperacillin-tazobactam plus vancomycin (Correct answer)
Ceftriaxone plus azithromycin
Azithromycin monotherapy

Correct answer: Piperacillin-tazobactam plus vancomycin

Healthcare-associated pneumonia requires broad-spectrum coverage for MRSA and Pseudomonas, making piperacillin-tazobactam plus vancomycin the appropriate empiric regimen.

Question 12: A 58-year-old man with hypertension and type 2 diabetes presents with exertional dyspnea. Echocardiography shows an EF of 58%, grade II diastolic dysfunction, E/e' ratio of 16, and left atrial volume index of 42 mL/m². He is started on an SGLT2 inhibitor. Which mechanism BEST explains its cardiovascular benefit in heart failure with preserved ejection fraction (HFpEF)?

Direct inhibition of the renin-angiotensin-aldosterone system at the tubular level
Upregulation of myocardial beta-adrenergic receptor density improving lusitropy
Competitive inhibition of sodium-calcium exchanger reducing intracellular calcium overload
Reduction of preload via osmotic diuresis and natriuresis, reducing myocardial wall stress (Correct answer)

Correct answer: Reduction of preload via osmotic diuresis and natriuresis, reducing myocardial wall stress

SGLT2 inhibitors reduce hospitalizations and cardiovascular death in HFpEF (EMPEROR-Preserved trial with empagliflozin; DELIVER trial with dapagliflozin). The primary hemodynamic mechanism is osmotic diuresis and natriuresis, which reduces intravascular volume, lowers ventricular filling pressures (preload), and decreases myocardial wall stress — a critical pathophysiologic driver in HFpEF. They do not directly inhibit RAAS, upregulate beta receptors, or act as NCX inhibitors.

Question 13: A 34-year-old woman with a history of lithium therapy for bipolar disorder presents with polyuria, polydipsia, and a serum sodium of 148 mEq/L. Her urine osmolality after 8 hours of water deprivation is 185 mOsm/kg. After administration of desmopressin (DDAVP), urine osmolality rises to 210 mOsm/kg. Which pathophysiologic mechanism best explains this blunted response to exogenous ADH?

Destruction of posterior pituitary magnocellular neurons by lithium nephrotoxicity
Upregulation of cyclooxygenase-2 leading to prostaglandin-mediated vasoconstriction of vasa recta
Downregulation of aquaporin-2 channels in the collecting duct due to impaired cAMP-mediated signaling (Correct answer)
Competitive inhibition of ADH at V2 receptors in the renal medulla

Correct answer: Downregulation of aquaporin-2 channels in the collecting duct due to impaired cAMP-mediated signaling

Lithium causes nephrogenic diabetes insipidus by entering principal cells via ENaC channels and inhibiting adenylyl cyclase, reducing cAMP generation downstream of the V2 receptor. This impairs PKA-mediated phosphorylation and insertion of aquaporin-2 (AQP2) water channels into the apical membrane. The post-DDAVP rise in urine osmolality from 185 to 210 mOsm/kg (< 50% increase) confirms nephrogenic DI — partial response occurs because some residual AQP2 expression remains. Lithium does not destroy pituitary neurons, does not competitively antagonize V2 receptors, and COX-2 upregulation is not the primary mechanism of concentrating defect.

Question 14: A 45-year-old woman presents with jaundice, pruritus, and elevated alkaline phosphatase. AMA is positive. What is the most likely diagnosis?

Primary sclerosing cholangitis
Autoimmune hepatitis
Choledocholithiasis
Primary biliary cholangitis (Correct answer)

Correct answer: Primary biliary cholangitis

Anti-mitochondrial antibody (AMA) positivity with cholestatic pattern strongly suggests primary biliary cholangitis, a chronic autoimmune bile duct disease predominantly affecting middle-aged women.

Question 15: A 29-year-old man with known cystic fibrosis (CF) has FEV1 that has declined to 25% predicted despite maximal inhaled therapy. He is listed for lung transplantation. His most recent sputum grows Burkholderia cepacia complex. How does this organism affect transplant candidacy?

It is an absolute contraindication at most transplant centers (Correct answer)
It is not a contraindication to transplantation
It is a relative contraindication requiring additional workup
It requires pre-transplant eradication with IV antibiotics before listing

Correct answer: It is an absolute contraindication at most transplant centers

Burkholderia cepacia complex (especially genomovar III/cenocepacia) is considered an absolute contraindication to lung transplantation at most centers due to dramatically increased post-transplant mortality.

Question 16: Which of the following correctly describes the mortality difference between DKA and HHS?

DKA has higher mortality than HHS
HHS has higher mortality than DKA (Correct answer)
Mortality is equal between DKA and HHS
DKA is fatal in >50% of cases in modern ICUs

Correct answer: HHS has higher mortality than DKA

HHS carries higher mortality (~15%) compared to DKA (~1-5%), largely because it affects older patients with more comorbidities and often presents later.

Question 17: A 66-year-old man with hypertension is started on chlorthalidone. Two weeks later he reports muscle cramps. Labs: Na 138 mEq/L, K 3.0 mEq/L, Cl 94 mEq/L, HCO3 29 mEq/L, urine Cl 60 mEq/L. What acid-base disorder is present?

Respiratory alkalosis with renal compensation
Mixed metabolic alkalosis and respiratory alkalosis
Metabolic alkalosis with appropriate respiratory compensation (Correct answer)
Metabolic acidosis with respiratory compensation

Correct answer: Metabolic alkalosis with appropriate respiratory compensation

Thiazide diuretics cause metabolic alkalosis via volume contraction, increased aldosterone, and direct H+ and K+ loss in the collecting duct.

Question 18: A 55-year-old woman presents with sudden onset severe headache described as 'the worst headache of my life.' CT head is negative. What is the next best step?

Lumbar puncture (Correct answer)
MRI brain with gadolinium
Repeat CT in 6 hours
Discharge with analgesics

Correct answer: Lumbar puncture

Lumbar puncture is required after a negative CT to detect xanthochromia, which indicates subarachnoid hemorrhage not visible on CT.

Question 19: A 55-year-old man presents with serum creatinine of 3.2 mg/dL, hemoglobin of 8.8 g/dL, and ferritin of 210 ng/mL with transferrin saturation of 18%. He is on erythropoiesis-stimulating agents. What is the most appropriate next step for his anemia management?

Administer IV iron (Correct answer)
Increase ESA dose
Add vitamin B12 supplementation
Transfuse packed red blood cells

Correct answer: Administer IV iron

Functional iron deficiency (low TSAT despite adequate ferritin) in CKD patients on ESA therapy should be corrected with IV iron to optimize erythropoiesis.

Question 20: A 58-year-old man with HIV (CD4 count 45 cells/µL) on antiretroviral therapy presents with 3 weeks of progressive dyspnea, fever, and bilateral infiltrates. BAL reveals Pneumocystis jirovecii. He is started on TMP-SMX but worsens on day 3 with PaO2 of 58 mmHg on room air. Which adjunctive intervention is most appropriate at this point?

Add adjunctive caspofungin for possible co-infection
Switch to IV pentamidine and add corticosteroids
Add corticosteroids (prednisone 40 mg twice daily) (Correct answer)
Initiate mechanical ventilation before continuing PCP therapy

Correct answer: Add corticosteroids (prednisone 40 mg twice daily)

Adjunctive corticosteroids are indicated in PCP pneumonia when PaO2 < 70 mmHg on room air or A-a gradient > 35 mmHg, and are most beneficial when started within 72 hours of anti-PCP therapy. Prednisone 40 mg BID for 5 days, then tapered, reduces inflammation-driven respiratory failure and mortality. Switching to pentamidine is reserved for TMP-SMX failure after an adequate trial (≥5-7 days), not on day 3. Caspofungin has no role here, and mechanical ventilation is not the priority before optimizing medical management.

Question 21: A 28-year-old man has recurrent episodes of jaundice after fasting and during illness. All liver enzymes are normal except indirect bilirubin of 3.5 mg/dL. What is the most likely diagnosis?

Gilbert syndrome (Correct answer)
Crigler-Najjar syndrome type I
Dubin-Johnson syndrome
Rotor syndrome

Correct answer: Gilbert syndrome

Gilbert syndrome presents with isolated unconjugated hyperbilirubinemia triggered by fasting, stress, or illness, with otherwise normal liver function and benign prognosis.

Question 22: A 50-year-old woman with rheumatoid arthritis on methotrexate presents with new onset dyspnea and bilateral ground-glass opacities on CT chest. BAL shows eosinophilia. Lung biopsy reveals organizing pneumonia pattern. Which statement about this drug-induced lung injury is TRUE?

The organizing pneumonia pattern from methotrexate typically responds to corticosteroids (Correct answer)
Methotrexate must be permanently discontinued and can never be restarted
High-dose cyclophosphamide is the treatment of choice
Methotrexate-induced lung disease carries a >50% mortality rate

Correct answer: The organizing pneumonia pattern from methotrexate typically responds to corticosteroids

Methotrexate-induced organizing pneumonia typically responds well to discontinuation of methotrexate and systemic corticosteroids, with most patients recovering fully.

Question 23: A 34-year-old male with a history of alcohol abuse presents to the emergency department with severe, constant epigastric pain radiating to the back, nausea, and vomiting for the past 12 hours. His serum lipase is 2500 U/L. Vital signs are stable, and there are no signs of organ failure. According to the 2024 ACG guidelines, which of the following is the most critical initial management step?

Moderately aggressive intravenous fluid resuscitation with Lactated Ringer's solution (Correct answer)
Immediate ERCP to assess for biliary obstruction
Administration of prophylactic broad-spectrum antibiotics
Placement of a nasogastric tube for gastric decompression

Correct answer: Moderately aggressive intravenous fluid resuscitation with Lactated Ringer's solution

The cornerstone of initial management for acute pancreatitis is fluid resuscitation to support intravascular volume and maintain end-organ perfusion. The 2024 ACG guidelines suggest moderately aggressive, goal-directed fluid resuscitation. Lactated Ringer's solution is preferred over normal saline as it has been associated with a reduced systemic inflammatory response. Prophylactic antibiotics are not recommended in the absence of infected necrosis, and ERCP is only indicated if there is evidence of acute cholangitis.

Question 24: A 35-year-old woman presents with amenorrhea, galactorrhea, and headaches. MRI shows a 16 mm pituitary lesion. Prolactin is 2800 ng/mL. Visual field testing is normal. What is the first-line treatment?

Transsphenoidal surgery
Pituitary radiation
Bromocriptine or cabergoline (Correct answer)
Octreotide

Correct answer: Bromocriptine or cabergoline

Dopamine agonists (cabergoline preferred over bromocriptine) are first-line for macroprolactinomas, effectively reducing tumor size and normalizing prolactin in most patients.

Question 25: A 44-year-old woman is referred for evaluation of refractory ascites. She has no history of liver disease, alcohol use, or malignancy. Paracentesis reveals: total protein 4.2 g/dL, LDH 320 U/L, glucose 78 mg/dL, SAAG 0.8 g/dL, cytology negative. Right heart catheterization shows: PCWP 28 mmHg, right atrial pressure 24 mmHg, pulmonary artery pressure 42/20 mmHg. What is the most likely diagnosis?

Budd-Chiari syndrome
Hepatic sinusoidal obstruction syndrome
Constrictive pericarditis (Correct answer)
Tuberculous peritonitis

Correct answer: Constrictive pericarditis

The key findings are a low SAAG (<1.1 g/dL), exudative ascites (high protein), and right heart catheterization demonstrating elevated right atrial pressure equal to PCWP — a hallmark of constrictive pericarditis (equalization of diastolic pressures). Constrictive pericarditis causes elevated venous pressures that transude protein-rich fluid into the peritoneum, but because there is no portal hypertension, SAAG is low. Budd-Chiari syndrome produces high-SAAG ascites (>1.1) from hepatic venous obstruction. Sinusoidal obstruction syndrome also causes high-SAAG ascites and typically follows bone marrow transplant or hepatotoxin exposure. Tuberculous peritonitis produces exudative, low-SAAG ascites but would not explain the cardiac catheterization findings.

Question 26: A 34-year-old woman with type 1 diabetes presents with DKA (pH 7.18, glucose 320 mg/dL, anion gap 24). She is started on an insulin drip and IV fluids. Six hours later, her glucose has normalized to 180 mg/dL, but her anion gap remains elevated at 20 and bicarbonate is 14 mEq/L. Which of the following is the most appropriate next step?

Increase the insulin drip rate to accelerate anion gap closure
Discontinue the insulin drip and transition to subcutaneous insulin
Continue the insulin drip and add dextrose to the IV fluids (Correct answer)
Administer sodium bicarbonate to correct the persistent acidosis

Correct answer: Continue the insulin drip and add dextrose to the IV fluids

DKA resolution is defined by anion gap normalization (<12), not glucose normalization. When glucose reaches ~200 mg/dL before the anion gap closes, dextrose must be added to IV fluids to allow the insulin drip to continue. Discontinuing insulin prematurely allows continued ketogenesis. Bicarbonate is not indicated at pH >7.0 in DKA, and increasing the insulin rate without glucose supplementation risks hypoglycemia without meaningfully accelerating ketone clearance.

Question 27: Which drug interaction is most clinically significant in a patient taking warfarin who is newly prescribed amiodarone?

Amiodarone displaces warfarin from albumin only
Amiodarone decreases warfarin absorption
Amiodarone increases renal warfarin clearance
Amiodarone inhibits CYP2C9, increasing warfarin effect (Correct answer)

Correct answer: Amiodarone inhibits CYP2C9, increasing warfarin effect

Amiodarone inhibits CYP2C9 (and CYP3A4), significantly reducing warfarin metabolism and increasing anticoagulant effect, requiring close INR monitoring and dose reduction.

Question 28: A 62-year-old man presents with episodic headaches, palpitations, and diaphoresis. Blood pressure is 185/110 mmHg during an episode. 24-hour urine metanephrines are elevated. What is the most appropriate initial treatment before surgery?

ACE inhibitor alone
Calcium channel blocker alone
Beta-blocker alone
Alpha-blocker (phenoxybenzamine) followed by beta-blocker (Correct answer)

Correct answer: Alpha-blocker (phenoxybenzamine) followed by beta-blocker

Alpha-blockade must be established before beta-blockade in pheochromocytoma to prevent paradoxical hypertension from unopposed alpha stimulation.

Question 29: A 40-year-old man returns from a trip to sub-Saharan Africa with fever, chills, and headache starting 10 days after return. Peripheral blood smear shows ring forms in >5% of RBCs with multiple rings per cell. What is the treatment?

Quinine plus doxycycline
Chloroquine 600mg base then 300mg at 6h, 24h, 48h
IV artesunate (Correct answer)
Atovaquone-proguanil plus doxycycline

Correct answer: IV artesunate

Severe falciparum malaria (parasitemia >5%) requires IV artesunate, which is now available in the US and superior to IV quinine for severe disease.

Question 30: Which laboratory finding would most strongly suggest HHS rather than DKA in a hyperglycemic patient?

Serum glucose > 600 mg/dL
Absence of significant ketonemia with pH > 7.3 (Correct answer)
Serum osmolality > 320 mOsm/kg
Blood urea nitrogen > 30 mg/dL

Correct answer: Absence of significant ketonemia with pH > 7.3

The hallmark distinguishing feature of HHS from DKA is the absence of significant ketoacidosis (pH > 7.3, bicarbonate > 18 mEq/L, minimal ketonemia).

Question 31: A 58-year-old man with chronic hypersensitivity pneumonitis is evaluated for lung transplant candidacy. His PFTs show FVC 48% predicted, DLCO 32% predicted. He is started on antifibrotic therapy. Six months later, his FVC has declined by 12% absolute. Which finding on high-resolution CT would MOST strongly suggest accelerated progression requiring urgent transplant re-evaluation?

Bilateral ground-glass opacities superimposed on fibrotic background (Correct answer)
Enlarged mediastinal lymph nodes measuring 1.2 cm short axis
New basilar honeycombing with traction bronchiectasis
New mosaic attenuation with air trapping on expiratory views

Correct answer: Bilateral ground-glass opacities superimposed on fibrotic background

Bilateral ground-glass opacities superimposed on a fibrotic background in a patient with chronic hypersensitivity pneumonitis represent an acute exacerbation (AE-HP), which carries a mortality exceeding 50% and constitutes a medical emergency requiring urgent re-evaluation for transplant listing. AE-HP is analogous to acute exacerbations of IPF and is distinct from progressive fibrosis. New honeycombing represents chronic progression but not acute decompensation. Mosaic attenuation with air trapping is a feature of HP itself (small airways involvement) and is not an acute finding. Mediastinal lymphadenopathy is a nonspecific finding in HP and does not signal urgent deterioration.

Question 32: A 52-year-old woman is admitted to the ICU with septic shock from urosepsis. On day 3, she is improving, with vasopressors being weaned. Labs show Na 131 mEq/L (was 139 mEq/L on admission). She is euvolemic on exam. Urine sodium is 48 mEq/L, urine osmolality 520 mOsm/kg, serum osmolality 272 mOsm/kg. She received 3 L of D5W over 24 hours and is on empiric vancomycin and piperacillin-tazobactam. Which mechanism MOST contributes to her hyponatremia?

Hypotonic fluid administration compounded by non-osmotic ADH release from hemodynamic recovery (Correct answer)
Reset osmostat syndrome from malnutrition and critical illness
SIADH from pain and stress response causing inappropriate ADH secretion
Cerebral salt wasting triggered by hemodynamic instability

Correct answer: Hypotonic fluid administration compounded by non-osmotic ADH release from hemodynamic recovery

This patient received 3 L of D5W (a hypotonic fluid) in the context of improving septic shock. As hemodynamic instability resolves, the baroreceptor-mediated non-osmotic ADH stimulus diminishes, but transitioning to hypotonic fluids during a phase when ADH levels are still relatively elevated causes iatrogenic hyponatremia. This is a classically under-recognized ICU scenario. While SIADH from stress exists, the history points to a primarily iatrogenic hypotonic fluid contribution. Reset osmostat maintains serum Na at a new lower set point without ongoing natriuresis. Cerebral salt wasting requires a CNS insult and presents with hypovolemia and urinary sodium loss, not euvolemia.

Question 33: A 48-year-old woman is found to have a 1.8 cm thyroid nodule incidentally on a carotid ultrasound. Her TSH level is normal. A dedicated thyroid ultrasound is performed and describes the nodule as solid, markedly hypoechoic, with a taller-than-wide shape and microcalcifications. Based on these high-risk features, which of the following is the most appropriate next step in management?

Reassurance and repeat ultrasound in 12 months
Fine-needle aspiration (FNA) biopsy (Correct answer)
Measurement of serum thyroglobulin
Trial of levothyroxine suppression therapy

Correct answer: Fine-needle aspiration (FNA) biopsy

According to the American Thyroid Association (ATA) and ACR TI-RADS guidelines, a nodule >1 cm with high-suspicion sonographic features warrants a fine-needle aspiration (FNA) biopsy. The features described (solid, markedly hypoechoic, taller-than-wide, microcalcifications) place this nodule in the highest risk category for malignancy (TI-RADS 5). Reassurance would be inappropriate. Levothyroxine suppression is not recommended for the management of thyroid nodules. Serum thyroglobulin is primarily used as a tumor marker for surveillance after thyroidectomy, not for the initial diagnosis of a nodule.

Question 34: A 52-year-old woman with systemic lupus erythematosus on mycophenolate mofetil and prednisone 20 mg/day develops progressive dyspnea and dry cough over 3 weeks. CT chest shows bilateral ground-glass opacities in a perihilar distribution. Bronchoalveolar lavage fluid reveals silver-stain-positive cysts and trophozoites. She was NOT on Pneumocystis jirovecii pneumonia (PJP) prophylaxis. Her LDH is 520 U/L (ULN 250), PaO2 on room air is 58 mmHg, and A-a gradient is 48 mmHg. Which adjunctive therapy is MOST indicated alongside TMP-SMX?

Adjunctive corticosteroids are contraindicated in immunosuppressed patients with PJP
Inhaled pentamidine to augment anti-Pneumocystis coverage
Methylprednisolone 1 g IV daily for 3 days (pulse therapy) for underlying SLE flare
Prednisone 40 mg PO twice daily for 5 days, then taper over 21 days (Correct answer)

Correct answer: Prednisone 40 mg PO twice daily for 5 days, then taper over 21 days

Adjunctive corticosteroids are indicated in moderate-to-severe PJP (defined as PaO2 <70 mmHg on room air or A-a gradient >35 mmHg), as they reduce inflammation-mediated hypoxemia and decrease mortality. The standard regimen is prednisone 40 mg PO twice daily for days 1–5, 40 mg daily for days 6–10, then 20 mg daily for days 11–21. Pulse methylprednisolone (1 g/day) is for SLE nephritis or other autoimmune crises — not PJP. The misconception that corticosteroids are contraindicated in immunosuppressed patients is incorrect; the benefit is well-established in HIV and non-HIV PJP. Inhaled pentamidine has no adjunctive role in established PJP.

Question 35: A 55-year-old man with diabetes presents with right lower extremity cellulitis and fever. He was treated with cephalexin for 5 days without improvement. What additional coverage should be empirically added?

TMP-SMX or doxycycline (MRSA coverage) (Correct answer)
Clindamycin alone
Metronidazole
Piperacillin-tazobactam

Correct answer: TMP-SMX or doxycycline (MRSA coverage)

Failure to improve on beta-lactam therapy for cellulitis should prompt consideration of MRSA, and empiric MRSA coverage with TMP-SMX or doxycycline should be added.

Question 36: A 72-year-old man with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two prior lines of therapy achieves complete remission following CAR-T cell therapy (axicabtagene ciloleucel). Three weeks post-infusion, he develops fever (39.2°C), hypotension requiring vasopressors, and neurological symptoms including confusion and seizures. Ferritin is 42,000 ng/mL. What is the most appropriate immediate management?

Tocilizumab plus dexamethasone, with anakinra considered for refractory disease (Correct answer)
Rituximab infusion to deplete residual CAR-T cells
High-dose methylprednisolone alone for immune effector cell-associated neurotoxicity syndrome (ICANS)
Tocilizumab alone targeting IL-6 receptor for cytokine release syndrome (CRS)

Correct answer: Tocilizumab plus dexamethasone, with anakinra considered for refractory disease

This patient has concurrent severe CRS (Grade 3–4: hypotension requiring vasopressors) and severe ICANS (Grade 3–4: seizures, confusion). Per ASTCT consensus guidelines, severe CRS requires tocilizumab; however, tocilizumab has limited CNS penetrance and may worsen ICANS by shifting cytokines centrally. For concurrent severe CRS and ICANS, the standard approach is tocilizumab (for CRS) PLUS dexamethasone (for ICANS, given its CNS penetrance). Anakinra (IL-1 blockade) is considered for steroid-refractory cases. Tocilizumab alone is insufficient when ICANS is severe. Rituximab would deplete CAR-T cells and eliminate any therapeutic benefit.

Question 37: A 51-year-old woman with scleroderma presents to the emergency department with sudden-onset severe headache and blood pressure of 218/126 mmHg. Her creatinine has risen from 0.9 to 3.1 mg/dL over the past week. Peripheral blood smear shows schistocytes; platelet count is 58,000/μL; LDH is elevated; ADAMTS13 activity is 62% (normal >67%). Urinalysis shows 2+ protein and RBC casts. She is currently on glucocorticoids (prednisone 30 mg/day) started 2 weeks ago for inflammatory arthritis. Which is the most critical immediate intervention?

Begin hemodialysis emergently to manage uremic complications
Administer eculizumab for atypical hemolytic uremic syndrome
Start captopril (short-acting ACE inhibitor) urgently and taper glucocorticoids (Correct answer)
Initiate therapeutic plasma exchange for thrombotic thrombocytopenic purpura

Correct answer: Start captopril (short-acting ACE inhibitor) urgently and taper glucocorticoids

This presentation is scleroderma renal crisis (SRC), a hypertensive emergency driven by RAAS-mediated renal ischemia and intimal hyperplasia in small renal arteries. Glucocorticoid use (particularly doses >15 mg prednisone/day) is the strongest known precipitant of SRC. The microangiopathic hemolytic anemia (MAHA) and thrombocytopenia are secondary to severe hypertension-induced endothelial injury, not primary TTP (ADAMTS13 activity >10% excludes TTP). The cornerstone of SRC management is aggressive, prompt ACE inhibitor therapy — captopril is preferred for its short duration of action and titratability. ACE inhibitors have been shown to improve renal outcomes even if dialysis is required acutely. Glucocorticoids must be tapered as quickly as the inflammatory indication allows. Plasma exchange and eculizumab are not indicated here; emergent dialysis addresses uremia but does not treat the underlying vasospastic mechanism.

Question 38: A 45-year-old returning traveler from sub-Saharan Africa presents with fever, myalgia, and headache 5 days after return. Blood smear shows 14% parasitemia with P. falciparum. He is alert but tachycardic and his creatinine is 2.1 mg/dL (baseline 0.9). IV artesunate is initiated. Forty-eight hours later, parasitemia has fallen to 0.3%, he is afebrile and clinically improved. Which complication should be MOST carefully monitored for over the next 2–6 weeks?

Artesunate-induced QTc prolongation and arrhythmia
Artemisinin partial resistance emergence and treatment failure
Post-artesunate delayed hemolysis (PADH) (Correct answer)
Immune reconstitution inflammatory syndrome (IRIS)

Correct answer: Post-artesunate delayed hemolysis (PADH)

Post-artesunate delayed hemolysis (PADH) is an increasingly recognized complication occurring 1–6 weeks after IV artesunate treatment, particularly in patients with initial high parasitemia (>5%). The mechanism involves clearance of pRBCs followed by delayed destruction of the 'once-infected' RBCs that were transiently spared. Patients may develop significant anemia requiring transfusion despite apparent clinical cure. QTc prolongation (choice B) is associated with quinine/quinidine, not artesunate. IRIS (choice C) does not apply here. Artemisinin resistance (choice D) is a concern in Southeast Asia, not the primary monitoring concern in the immediate post-treatment period.

Question 39: A 48-year-old man with no cardiac history presents with syncope preceded by dizziness while standing. On exam, systolic BP drops from 140 to 95 mmHg after 3 minutes of standing. Heart rate does not compensate appropriately. The most likely diagnosis is:

Hypovolemia
Vasovagal syncope
Autonomic dysfunction (orthostatic hypotension) (Correct answer)
Cardiac arrhythmia

Correct answer: Autonomic dysfunction (orthostatic hypotension)

Orthostatic hypotension with inadequate heart rate response suggests autonomic neuropathy; common causes include diabetes, Parkinson's disease, and certain medications.

Question 40: A 28-year-old woman presents with fever, rash on palms and soles, and headache after camping in North Carolina in May. Peripheral smear shows no parasites but thrombocytopenia and hyponatremia are present. What is the treatment?

Azithromycin 500mg daily
Doxycycline 100mg BID (Correct answer)
Ciprofloxacin 500mg BID
Chloramphenicol 500mg QID

Correct answer: Doxycycline 100mg BID

Rocky Mountain Spotted Fever (Rickettsia rickettsii) is treated empirically with doxycycline 100mg BID, which should not be delayed awaiting confirmatory testing.

Question 41: A 71-year-old woman is admitted with confusion, fatigue, and hypercalcemia (calcium 13.8 mg/dL). PTH is suppressed at 4 pg/mL. PTHrP is undetectable. 1,25-dihydroxyvitamin D (calcitriol) is markedly elevated at 210 pg/mL (normal 18–72). 25-hydroxyvitamin D is normal. ACE level is mildly elevated. CT chest reveals bilateral hilar lymphadenopathy and pulmonary nodules. Which is the most likely cause of her hypercalcemia?

Primary hyperparathyroidism with parathyroid carcinoma
Occult malignancy producing ectopic PTH
Granulomatous disease with autonomous 1α-hydroxylase activity (Correct answer)
Vitamin D toxicity from supplement overconsumption

Correct answer: Granulomatous disease with autonomous 1α-hydroxylase activity

The pattern of suppressed PTH, undetectable PTHrP, and markedly elevated 1,25-dihydroxyvitamin D with normal 25-hydroxyvitamin D is classic for granulomatous disease (most likely sarcoidosis here, supported by hilar lymphadenopathy and elevated ACE). Activated macrophages within granulomas express 1α-hydroxylase, which converts 25-OH vitamin D to the active 1,25-OH form without the normal feedback inhibition from PTH or calcium. Vitamin D toxicity raises 25-OH vitamin D, not 1,25-OH (except in granulomatous disease). PTHrP-mediated hypercalcemia (humoral hypercalcemia of malignancy) would show elevated PTHrP, not elevated calcitriol. Primary hyperparathyroidism would show elevated or inappropriately normal PTH.

Question 42: A 58-year-old man with IPF is admitted with acute respiratory failure requiring mechanical ventilation after a 2-week history of worsening dyspnea without identifiable trigger. BAL shows no infection. Despite lung-protective ventilation, he deteriorates. Which of the following has demonstrated a mortality benefit in acute exacerbation of IPF?

High-dose methylprednisolone 1g IV daily for 3 days
Rituximab plus plasma exchange
Cyclosporine A added to corticosteroids
Veno-venous ECMO as a bridge to lung transplantation (Correct answer)

Correct answer: Veno-venous ECMO as a bridge to lung transplantation

Acute exacerbations of IPF carry an extremely poor prognosis with in-hospital mortality exceeding 50-80%. No pharmacological intervention (steroids, rituximab, cyclosporine) has shown consistent mortality benefit in randomized trials. VV-ECMO as a bridge to lung transplantation is the only strategy with evidence of survival benefit in carefully selected patients who are transplant-eligible. High-dose steroids are commonly used but lack RCT evidence of benefit and carry significant harm risk.

Question 43: A 40-year-old woman has chronic diarrhea, flushing, and wheezing. Urinary 5-HIAA is markedly elevated. Which imaging study is most appropriate to localize the primary tumor?

MRI liver
CT abdomen with contrast
Octreotide scan (somatostatin receptor scintigraphy) (Correct answer)
PET scan with FDG

Correct answer: Octreotide scan (somatostatin receptor scintigraphy)

Somatostatin receptor scintigraphy (octreotide scan or Ga-68 DOTATATE PET/CT) is the preferred functional imaging modality to localize carcinoid tumors expressing somatostatin receptors.

Question 44: A 61-year-old man with alcohol-related cirrhosis (Child-Pugh B) and a history of variceal bleeding is on nadolol. He develops refractory ascites requiring large-volume paracentesis every 2 weeks despite maximal diuretic therapy. Creatinine is 1.0 mg/dL, sodium is 128 mEq/L. He is listed for liver transplant. What is the most appropriate next intervention?

Add midodrine and octreotide to improve renal perfusion
Initiate terlipressin for hyponatremia
Place a transjugular intrahepatic portosystemic shunt (TIPS) (Correct answer)
Switch from nadolol to carvedilol for better portal pressure reduction

Correct answer: Place a transjugular intrahepatic portosystemic shunt (TIPS)

TIPS is the most appropriate intervention for refractory ascites in a transplant candidate with preserved renal function (creatinine 1.0) and Child-Pugh B (not C, where benefit is less clear). TIPS reduces portal hypertension, eliminates or dramatically reduces the need for paracentesis, and can bridge patients to transplant. Midodrine/octreotide is used for hepatorenal syndrome, not refractory ascites. Terlipressin targets HRS-AKI, not hyponatremia per se. Carvedilol switch does not address the mechanical ascites problem. Contraindications to TIPS (hepatic encephalopathy, cardiac dysfunction) are not present here.

Question 45: A 49-year-old woman with scleroderma-associated interstitial lung disease (ILD) develops progressive dyspnea over 3 months. HRCT shows new bilateral ground-glass opacities predominantly in the upper and mid-lung zones overlying a background of subpleural reticulation with honeycombing at the bases. PFTs show a rapid decline: FVC dropped from 72% to 54% predicted over 6 months. Anti-topoisomerase I (Scl-70) antibody is strongly positive. Bronchoscopic BAL shows 38% lymphocytes. Which of the following management decisions is BEST supported by current evidence?

Start nintedanib given the rapid FVC decline, recognizing it slows progression in SSc-ILD regardless of inflammatory activity (Correct answer)
Start high-dose methylprednisolone 1 mg/kg/day, given the BAL lymphocytosis suggesting an inflammatory, steroid-responsive process
Perform surgical lung biopsy to distinguish UIP from NSIP pattern before initiating any treatment
Initiate rituximab, as anti-Scl-70 positivity with BAL lymphocytosis defines a rituximab-responsive phenotype

Correct answer: Start nintedanib given the rapid FVC decline, recognizing it slows progression in SSc-ILD regardless of inflammatory activity

Nintedanib is FDA-approved for SSc-ILD based on the SENSCIS trial, which demonstrated a significant reduction in FVC decline rate regardless of background immunosuppression. This patient has an alarming 18% absolute FVC decline in 6 months (severe progression), which is a clear indication to escalate therapy with an antifibrotic. High-dose corticosteroids in SSc-ILD carry substantial risks (including scleroderma renal crisis) and are not supported by evidence as a first-line or high-dose therapy — mycophenolate or low-dose prednisone are the immunosuppressive backbone. BAL lymphocytosis in the setting of SSc is a nonspecific finding and does not reliably predict steroid responsiveness. While rituximab has emerging evidence in SSc-ILD, it is not defined by anti-Scl-70 positivity specifically, and there is no validated biomarker-based indication. Surgical biopsy is high-risk and not needed when HRCT + clinical context are diagnostic of SSc-ILD, especially with active progression requiring urgent treatment.

Question 46: A 19-year-old with new-onset type 1 diabetes is admitted for DKA. After 10 hours of appropriate insulin infusion and IV fluids, his anion gap normalizes but his bicarbonate remains at 16 mEq/L. Arterial pH is 7.32. He has received 5 L of 0.9% normal saline. What is the most likely explanation for his persistent acidosis?

Inadequate insulin dosing with persistent ketogenesis despite normalized anion gap
Renal tubular acidosis precipitated by the episode of DKA
Hyperchloremic non-anion-gap metabolic acidosis from large-volume normal saline resuscitation (Correct answer)
Occult lactic acidosis from tissue hypoperfusion during the DKA episode

Correct answer: Hyperchloremic non-anion-gap metabolic acidosis from large-volume normal saline resuscitation

Large-volume resuscitation with 0.9% normal saline (chloride content 154 mEq/L) causes dilutional hyperchloremia, which produces a non-anion-gap (hyperchloremic) metabolic acidosis. As DKA resolves, ketoanions are metabolized and the anion gap closes, but the bicarbonate remains low because of the superimposed hyperchloremic acidosis from saline. This is a well-recognized phenomenon and does not represent treatment failure. Clinicians must distinguish between persistent ketoacidosis (rising or non-closing anion gap) and this benign iatrogenic acidosis (closed anion gap, elevated chloride). Using balanced crystalloids (e.g., lactated Ringer's or PlasmaLyte) reduces but does not eliminate this effect.

Question 47: A 58-year-old man with type 2 diabetes, CKD stage 3b (eGFR 32 mL/min/1.73m²), and HFrEF (EF 35%) presents for medication reconciliation. His current regimen includes metformin, lisinopril, carvedilol, and furosemide. His HbA1c is 8.9%. Which adjustment is MOST appropriate?

Discontinue metformin and initiate empagliflozin 10 mg daily (Correct answer)
Continue metformin and add sitagliptin with dose adjustment for CKD
Discontinue metformin and initiate insulin glargine
Continue metformin at reduced dose and add a GLP-1 receptor agonist

Correct answer: Discontinue metformin and initiate empagliflozin 10 mg daily

Metformin is contraindicated when eGFR falls below 30 mL/min/1.73m² and should be used with caution below 45. With eGFR of 32, it should be discontinued. Empagliflozin (an SGLT2 inhibitor) has robust evidence for cardiovascular and renal benefit in HFrEF patients with T2DM, reducing hospitalizations and mortality. While its glucose-lowering efficacy diminishes at lower eGFRs, its cardiorenal benefits persist down to eGFR ≥20. GLP-1 agonists lack dedicated HFrEF outcome data comparable to SGLT2i, and sitagliptin requires dose reduction but does not provide cardiorenal protective benefits. Insulin glargine is reasonable but does not address the cardiorenal risk reduction opportunity.

Question 48: A 40-year-old man presents for a routine health evaluation. He is asymptomatic but reports that his father was diagnosed with colon cancer at age 48. He has no other personal or family history of cancer. According to current U.S. Preventive Services Task Force (USPSTF) and ACG guidelines, what is the most appropriate recommendation for colorectal cancer screening for this patient?

Begin screening now with a stool-based test (FIT).
Begin screening now with colonoscopy. (Correct answer)
Begin screening with colonoscopy at age 50.
No screening is necessary until he develops symptoms.

Correct answer: Begin screening now with colonoscopy.

For individuals with a first-degree relative diagnosed with colorectal cancer before the age of 60, screening guidelines recommend initiating colonoscopy at age 40, or 10 years younger than the age at which the relative was diagnosed, whichever comes first. In this case, 10 years before his father's diagnosis at age 48 would be age 38. Since the patient is now 40, he should begin screening with colonoscopy immediately.

Question 49: A 35-year-old man with a dog bite to his hand 8 hours ago presents for evaluation. He is up to date on tetanus and the wound has been thoroughly irrigated. What organism most commonly causes infection in dog bites?

Pasteurella multocida (Correct answer)
Staphylococcus aureus
Eikenella corrodens
Capnocytophaga canimorsus

Correct answer: Pasteurella multocida

Pasteurella multocida is the most common pathogen isolated from dog and cat bite wounds, typically causing rapid-onset cellulitis within 24 hours.

Question 50: A 68-year-old with GOLD stage IV COPD presents with acute hypercapnic respiratory failure. Initial ABG on 28% FiO2: pH 7.24, PaCO2 78 mmHg, PaO2 52 mmHg. NIV is initiated with appropriate settings. Reassessment at 90 minutes shows pH 7.26, PaCO2 74 mmHg. The patient remains alert with GCS 14. Which factor, present at initial evaluation, is the STRONGEST independent predictor of subsequent NIV failure requiring intubation?

Presence of concurrent pneumonia as the precipitating trigger
Failure of pH to improve to ≥7.30 within the first 60–120 minutes of NIV (Correct answer)
Initial PaCO2 greater than 75 mmHg
APACHE II score greater than 17 on presentation

Correct answer: Failure of pH to improve to ≥7.30 within the first 60–120 minutes of NIV

Multiple prospective studies identify failure of pH to improve within 1–2 hours of NIV as the single strongest predictor of NIV failure in acute hypercapnic COPD exacerbation. This patient's pH improved only from 7.24 to 7.26 at 90 minutes — a minimal response that portends intubation. Initial PaCO2 level alone does not independently predict failure; many patients with very high PaCO2 respond well. While a low GCS (particularly <8–11) is a contraindication to NIV, this patient has a GCS of 14. Pneumonia as a trigger carries a worse prognosis but is not the strongest independent predictor of NIV failure per se. The early pH trajectory is the key decision-making signal.

Question 51: A 50-year-old male smoker presents with a 30-pack-year history. Screening for lung cancer with low-dose CT is recommended for which age range and smoking history per USPSTF guidelines?

Ages 55-80 with ≥30 pack-year history, currently smoking or quit within 10 years
Ages 50-80 with ≥20 pack-year history, currently smoking or quit within 15 years (Correct answer)
Ages 45-75 with ≥25 pack-year history
Ages 40-70 with ≥10 pack-year history

Correct answer: Ages 50-80 with ≥20 pack-year history, currently smoking or quit within 15 years

The 2021 USPSTF guidelines recommend annual low-dose CT screening for adults ages 50-80 with ≥20 pack-year history who currently smoke or quit within 15 years.

Question 52: A 34-year-old woman with SLE on hydroxychloroquine and low-dose prednisone develops fever, rigors, and altered mental status 10 days after a camping trip in Missouri. Blood smear shows intraerythrocytic ring forms with occasional multiple rings per cell and 'Maltese cross' (tetrad) forms. Parasitemia is 6%. Which of the following is the MOST appropriate treatment?

Quinine plus doxycycline for 7 days
Chloroquine 1g followed by 500 mg at 6, 24, and 48 hours
Atovaquone plus azithromycin for 7–10 days (Correct answer)
Atovaquone-proguanil for 3 days

Correct answer: Atovaquone plus azithromycin for 7–10 days

Maltese cross (tetrad) forms are pathognomonic for Babesia microti, not Plasmodium. This patient has babesiosis, which is endemic in the upper Midwest and Northeast. The treatment of choice is atovaquone plus azithromycin for 7–10 days (or up to 6 weeks in severe/immunocompromised cases). Exchange transfusion should be considered when parasitemia exceeds 10%, in cases of severe hemolysis, or end-organ compromise. Chloroquine (choice C) treats only chloroquine-sensitive Plasmodium. Quinine plus doxycycline (choice B) is an alternative for babesiosis but is second-line due to toxicity. Atovaquone-proguanil (choice D) is for malaria prophylaxis/treatment, not babesiosis.

Question 53: Phentolamine is administered before surgical resection of a pheochromocytoma. What is its primary purpose?

Lower perioperative cortisol levels
Reduce catecholamine synthesis
Prevent tachyarrhythmias during induction
Block alpha-adrenergic receptors to prevent hypertensive crisis (Correct answer)

Correct answer: Block alpha-adrenergic receptors to prevent hypertensive crisis

Alpha-blockade with phentolamine (or phenoxybenzamine) is essential to prevent severe hypertension from catecholamine release during tumor manipulation.

Question 54: A 70-year-old man undergoes hip arthroplasty and develops fever and wound drainage at day 14. Joint aspiration grows MRSA. What is the antibiotic of choice for MRSA prosthetic joint infection?

Daptomycin 6mg/kg IV daily
Cefazolin 2g IV q8h
Linezolid 600mg BID
Vancomycin IV dosed to trough 15-20 mcg/mL (Correct answer)

Correct answer: Vancomycin IV dosed to trough 15-20 mcg/mL

Vancomycin IV remains the standard of care for MRSA prosthetic joint infections, typically combined with rifampin for biofilm penetration in device-associated infections.

Question 55: A 62-year-old patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). Ascitic fluid PMN count is 350 cells/µL. What is the empiric antibiotic of choice?

Metronidazole plus ciprofloxacin
Vancomycin plus piperacillin-tazobactam
Cefotaxime 2g IV q8h (Correct answer)
Amoxicillin-clavulanate PO

Correct answer: Cefotaxime 2g IV q8h

Cefotaxime (or ceftriaxone) is the empiric antibiotic of choice for SBP, providing excellent gram-negative coverage without nephrotoxicity in an already vulnerable population.

Question 56: A 61-year-old man with a history of neck irradiation for Hodgkin lymphoma 25 years ago is found to have a 2.2 cm thyroid nodule on incidental imaging. Fine-needle aspiration returns Bethesda Category III (atypia of undetermined significance). Repeat FNA after 3 months again returns Bethesda III. Molecular testing shows a TERT promoter mutation without RAS or BRAF mutations. What is the most appropriate next step?

Radioactive iodine ablation
Repeat FNA a third time in 6 months
Surgical resection (Correct answer)
Active surveillance with repeat ultrasound in 12 months

Correct answer: Surgical resection

TERT promoter mutations are associated with aggressive thyroid malignancy, dedifferentiation, and increased risk of recurrence and mortality — even when found in isolation. In the context of a persistently Bethesda III nodule with TERT promoter mutation, plus a history of prior therapeutic neck irradiation (a major risk factor for thyroid malignancy), surgical resection is the appropriate next step. Current ATA guidelines support surgery for Bethesda III nodules with high-risk molecular markers. Active surveillance or repeat FNA would be inappropriate given the combined risk profile. RAI is not used for initial management of indeterminate nodules.

Question 57: A 34-year-old woman with lupus nephritis (class IV) is maintained on mycophenolate mofetil and hydroxychloroquine. She presents with a creatinine rise from 0.9 to 2.1 mg/dL over 6 weeks, new proteinuria of 3.8 g/day, and a urine sediment showing RBC casts. Repeat renal biopsy shows class IV-S (A/C) disease with 40% tubular atrophy and interstitial fibrosis. Which of the following is the most appropriate next step?

Increase mycophenolate mofetil dose to 3 g/day and add pulse methylprednisolone
Add belimumab to the existing mycophenolate regimen
Initiate voclosporin in addition to mycophenolate and low-dose corticosteroids (Correct answer)
Switch to IV cyclophosphamide (NIH protocol) and high-dose corticosteroids

Correct answer: Initiate voclosporin in addition to mycophenolate and low-dose corticosteroids

Voclosporin (a next-generation calcineurin inhibitor) combined with mycophenolate mofetil and low-dose corticosteroids is now FDA-approved for active lupus nephritis and has shown superior complete renal response rates in the AURORA trial. This patient has active disease (RBC casts, rising creatinine, heavy proteinuria) despite maintenance MMF, justifying escalation. The significant chronic damage (40% tubular atrophy/interstitial fibrosis) on biopsy argues against aggressive cyclophosphamide, which would not reverse established fibrosis and carries greater toxicity. Belimumab is approved as add-on therapy but has less evidence for acute flare with active sediment.

Question 58: A 58-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) presents with worsening dyspnea and near-syncope. Echo shows a resting LVOT gradient of 65 mmHg. He is on maximal doses of metoprolol. Which of the following interventions is MOST appropriate as the next step?

Start amlodipine for afterload reduction
Begin low-dose dobutamine infusion
Initiate digoxin to improve contractility
Add disopyramide to his current regimen (Correct answer)

Correct answer: Add disopyramide to his current regimen

Disopyramide is a class IA antiarrhythmic with potent negative inotropic properties that reduces dynamic LVOT obstruction in HOCM. It is guideline-recommended as an add-on to beta-blockers when symptoms persist. Digoxin increases contractility and worsens obstruction. Amlodipine causes vasodilation and reflex tachycardia, exacerbating the gradient. Dobutamine dramatically worsens LVOT obstruction and is contraindicated.

Question 59: A 30-year-old woman is diagnosed with moderate-to-severe ulcerative colitis affecting the left side of her colon. She has failed to respond to a 4-week course of high-dose oral and rectal 5-aminosalicylic acid (5-ASA) agents. Which of the following medication classes is an appropriate next step to induce remission?

Long-term broad-spectrum antibiotics
Cholestyramine
Loperamide
Oral corticosteroids (Correct answer)

Correct answer: Oral corticosteroids

For patients with moderate-to-severe ulcerative colitis who do not respond to first-line 5-ASA therapy, systemic corticosteroids (e.g., oral prednisone) are the next step to induce remission. Biologic agents like TNF-alpha inhibitors (e.g., infliximab) or other advanced therapies are options for corticosteroid-refractory or dependent disease, or as first-line therapy in severe cases, but a course of corticosteroids is a standard intermediate step. Loperamide is for symptomatic control and should be used with caution, while antibiotics and cholestyramine are not standard induction therapies for UC.

Question 60: A 35-year-old female presents to the emergency department with pleuritic chest pain and shortness of breath that began yesterday. She has no significant past medical history but reports using oral contraceptive pills. Her vital signs are: heart rate 95 bpm, blood pressure 120/80 mmHg, respiratory rate 18, and oxygen saturation 98% on room air. There is no unilateral leg swelling. The physician has a low clinical suspicion for pulmonary embolism (PE). Which of the following would allow the physician to use the Pulmonary Embolism Rule-out Criteria (PERC) to safely exclude PE without further testing?

A negative D-dimer test
A normal chest X-ray
A Wells score of 1.5
The patient meeting all eight PERC criteria (Correct answer)

Correct answer: The patient meeting all eight PERC criteria

The PERC rule is a clinical decision tool used to rule out pulmonary embolism in patients deemed low-risk by clinical gestalt (pre-test probability <15%). If a patient meets all eight of the PERC criteria (age <50, HR <100 bpm, SaO2 >94%, no unilateral leg swelling, no hemoptysis, no recent trauma/surgery, no prior PE/DVT, no exogenous estrogen use), the likelihood of PE is extremely low, and no further diagnostic workup (like a D-dimer) is needed. This patient does not meet the criteria due to estrogen use.

Question 61: A 50-year-old man who received bilateral lung transplantation for COPD 5 years ago presents with 7 months of progressive exertional dyspnea. His best post-transplant FEV1 was 2.8 L. Current spirometry: FEV1 1.72 L (61% of baseline), FEV1/FVC 0.52. HRCT shows expiratory air trapping and subtle bronchiectasis. Bronchoscopy reveals grossly normal airways. BAL is negative for bacteria, fungi, and viruses. Transbronchial biopsies show no acute rejection and no lymphocytic bronchiolitis. Which statement regarding diagnosis and treatment is most accurate?

This is BOS grade 2; first-line therapy includes azithromycin and optimization of immunosuppression (Correct answer)
Biopsy showing fibrous obliteration of small airways is required before BOS can be diagnosed
Extracorporeal photopheresis (ECP) should be initiated immediately as it is first-line for this BOS grade
Normal-appearing airways at bronchoscopy excludes bronchiolitis obliterans syndrome

Correct answer: This is BOS grade 2; first-line therapy includes azithromycin and optimization of immunosuppression

Bronchiolitis obliterans syndrome (BOS) is defined and graded clinically by sustained FEV1 decline from the post-transplant baseline, after excluding other causes: BOS grade 1 = 66–80%, grade 2 = 51–65%, grade 3 = ≤50%. This patient's FEV1 is 61% of his personal best, placing him in BOS grade 2. BOS is a CLINICAL diagnosis — transbronchial biopsy has poor sensitivity for the patchy small-airway fibrosis and is NOT required. Normal-appearing central airways are expected, as BOS affects small bronchioles beyond bronchoscopic visualization. First-line management includes azithromycin (anti-inflammatory/immunomodulatory), optimization of calcineurin inhibitor levels, and adding or switching mycophenolate. Extracorporeal photopheresis is a second- or third-line salvage option for progressive BOS refractory to standard therapy.

Question 62: A 45-year-old man with a history of dyspepsia undergoes an upper endoscopy which reveals a 1.5 cm duodenal ulcer. A biopsy is positive for Helicobacter pylori. The patient has no known drug allergies. The local clarithromycin resistance rate is known to be over 20%. Which of the following is the most appropriate first-line eradication therapy?

A proton pump inhibitor (PPI), metronidazole, and amoxicillin for 14 days
A proton pump inhibitor (PPI), bismuth subsalicylate, metronidazole, and tetracycline for 14 days (Correct answer)
A proton pump inhibitor (PPI) and amoxicillin for 10 days
A proton pump inhibitor (PPI), clarithromycin, and amoxicillin for 14 days

Correct answer: A proton pump inhibitor (PPI), bismuth subsalicylate, metronidazole, and tetracycline for 14 days

In regions where the clarithromycin resistance rate is high (>15-20%), standard clarithromycin-based triple therapy is no longer recommended as first-line treatment due to low eradication rates. The American College of Gastroenterology (ACG) guidelines recommend bismuth quadruple therapy (a PPI, bismuth, metronidazole, and tetracycline) for 14 days as a preferred first-line option in this scenario.

Question 63: A 29-year-old nurse undergoes routine employee health screening and is found to have a positive tuberculin skin test (15 mm induration). She is asymptomatic and her chest X-ray is negative for active disease. According to current CDC guidelines, which of the following is a preferred short-course regimen for treating latent tuberculosis infection (LTBI)?

Isoniazid daily for 9 months
Ethambutol daily for 12 months
Levofloxacin daily for 6 months
Isoniazid and rifapentine once weekly for 3 months (Correct answer)

Correct answer: Isoniazid and rifapentine once weekly for 3 months

The CDC preferentially recommends short-course, rifamycin-based regimens for the treatment of LTBI due to higher completion rates and similar efficacy compared to the older 9-month isoniazid regimen. The preferred regimens include once-weekly isoniazid plus rifapentine for 3 months (3HP), daily rifampin for 4 months (4R), or daily isoniazid plus rifampin for 3 months (3HR). While 9 months of daily isoniazid is still an acceptable alternative, it is no longer the sole preferred regimen. Ethambutol and levofloxacin are not first-line agents for treating LTBI.

Question 64: A 44-year-old woman presents with episodic epigastric pain, diarrhea, and multiple duodenal ulcers despite PPI therapy. Fasting gastrin level is 1200 pg/mL (normal <100). What is the most appropriate next diagnostic step?

Secretin stimulation test (Correct answer)
H. pylori testing
CT scan of the abdomen
Repeat endoscopy

Correct answer: Secretin stimulation test

The secretin stimulation test is the gold standard for diagnosing Zollinger-Ellison syndrome; paradoxical rise in gastrin >200 pg/mL after secretin injection confirms gastrinoma.

Question 65: A 62-year-old man with decompensated alcoholic cirrhosis undergoes a diagnostic paracentesis for new-onset ascites. His medical history is negative for prior spontaneous bacterial peritonitis (SBP). The ascitic fluid analysis reveals a total protein of 1.1 g/dL, a serum-ascites albumin gradient (SAAG) of 1.8 g/dL, and an absolute neutrophil count (ANC) of 80 cells/mm³. His serum creatinine is 1.4 mg/dL and total bilirubin is 3.5 mg/dL. According to current AASLD guidelines, which of the following is the most appropriate next step regarding SBP prophylaxis?

No prophylaxis is needed as he has never had an episode of SBP.
Initiate prophylaxis only if the ascitic fluid culture becomes positive.
Administer a one-time dose of intravenous ceftriaxone and discharge.
Initiate long-term prophylaxis with a daily oral fluoroquinolone or trimethoprim-sulfamethoxazole. (Correct answer)

Correct answer: Initiate long-term prophylaxis with a daily oral fluoroquinolone or trimethoprim-sulfamethoxazole.

Primary prophylaxis for SBP is indicated in patients with cirrhosis and ascites if the ascitic fluid protein is <1.5 g/dL along with evidence of advanced liver failure (e.g., Child-Pugh score ≥9 and bilirubin ≥3 mg/dL) or renal dysfunction (creatinine ≥1.2 mg/dL). This patient meets the criteria with an ascitic fluid protein of 1.1 g/dL, creatinine of 1.4 mg/dL, and bilirubin of 3.5 mg/dL. Lifelong daily oral prophylaxis, typically with ciprofloxacin or trimethoprim-sulfamethoxazole, is the standard of care.

Question 66: A 34-year-old woman returns from a 2-week safari in sub-Saharan Africa. She presents with cyclic fevers every 72 hours, splenomegaly, and thrombocytopenia. Peripheral smear shows large ring forms and occasional banana-shaped gametocytes. Parasite density is 6% of RBCs infected. Which management strategy is most appropriate?

IV quinidine gluconate plus doxycycline with cardiac monitoring
IV artesunate with close monitoring for post-artesunate delayed hemolysis (Correct answer)
Oral chloroquine given the 72-hour fever cycle suggesting P. malariae
Oral atovaquone-proguanil as outpatient therapy

Correct answer: IV artesunate with close monitoring for post-artesunate delayed hemolysis

The 72-hour fever cycle plus banana-shaped gametocytes indicates Plasmodium falciparum (the 72-hour cycle reflects schizogony timing, not tertian malaria; gametocytes are pathognomonic for P. falciparum). With >5% parasitemia, this meets criteria for severe malaria requiring IV artesunate, now the preferred first-line treatment over quinidine gluconate in the US (CDC emergency protocol). Post-artesunate delayed hemolysis (PADH) occurs weeks later in high-burden patients and requires monitoring. Quinidine gluconate is no longer readily available and carries significant cardiac toxicity risk. Oral therapy is inappropriate for severe/high-density malaria.

Question 67: A 42-year-old individual with HIV is found to have a CD4+ T-cell count of 85 cells/µL and is seropositive for Toxoplasma gondii. According to the CDC and NIH guidelines, which of the following prophylactic medications is indicated?

Valganciclovir
Azithromycin
Trimethoprim-sulfamethoxazole (Correct answer)
Itraconazole

Correct answer: Trimethoprim-sulfamethoxazole

Trimethoprim-sulfamethoxazole is indicated for primary prophylaxis against both *Pneumocystis jirovecii* pneumonia (PJP) and toxoplasmosis in this patient. Prophylaxis for PJP should be initiated when the CD4 count is <200 cells/µL, and prophylaxis for toxoplasmosis should be initiated in seropositive patients when the CD4 count is <100 cells/µL. Trimethoprim-sulfamethoxazole is the preferred agent for both conditions. Azithromycin is used for *Mycobacterium avium* complex (MAC) prophylaxis when the CD4 count is <50 cells/µL. Valganciclovir and Itraconazole are not indicated for primary prophylaxis in this scenario.

Question 68: A 58-year-old with severe mitral stenosis develops atrial fibrillation. Her resting ventricular rate is 110 bpm. Which is the most appropriate initial rate control agent?

Metoprolol or diltiazem (Correct answer)
Digoxin alone
Flecainide
Amiodarone

Correct answer: Metoprolol or diltiazem

Beta-blockers (metoprolol) or non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are preferred for ventricular rate control in AF with mitral stenosis.

Question 69: A 66-year-old woman is started on amiodarone for persistent atrial fibrillation. Six months later she presents with dyspnea and is found to have bilateral pleural effusions and a diffuse interstitial infiltrate on CT chest. PFTs show a restrictive pattern with DLCO 52% predicted. Bronchoscopy with BAL shows foamy macrophages. Which of the following is the most appropriate next step?

Continue amiodarone and add high-dose prednisone 60 mg daily
Discontinue amiodarone, switch to an alternative antiarrhythmic, and initiate corticosteroids (Correct answer)
Discontinue amiodarone only; corticosteroids are not indicated for amiodarone pulmonary toxicity
Reduce amiodarone dose to 100 mg daily and repeat PFTs in 3 months

Correct answer: Discontinue amiodarone, switch to an alternative antiarrhythmic, and initiate corticosteroids

Amiodarone pulmonary toxicity (APT) is a life-threatening complication occurring in 1-5% of patients. The combination of new restrictive physiology, reduced DLCO, bilateral infiltrates, and foamy macrophages on BAL (pathognomonic phospholipidosis from drug accumulation) confirms the diagnosis. Management requires: (1) discontinuation of amiodarone — dose reduction is insufficient as the drug's half-life is 40-55 days and tissue accumulation persists; (2) initiation of corticosteroids (prednisone 40-60 mg/day) because inflammation-mediated injury responds to steroids and untreated APT has >10% mortality; (3) substitution with an alternative rhythm control agent (e.g., dofetilide, dronedarone, or rate control strategy). Continuing amiodarone even with steroids allows ongoing pulmonary injury. Corticosteroids ARE indicated given the severity of presentation.

Question 70: A 72-year-old woman sustains a hip fracture after a fall from standing height. A subsequent DEXA scan reveals a T-score of -2.8 at the femoral neck. She has no contraindications to oral medications and her renal function is normal. Which of the following is the most appropriate initial long-term pharmacologic therapy?

Teriparatide
Oral alendronate (Correct answer)
Denosumab
Raloxifene

Correct answer: Oral alendronate

This patient has established, severe osteoporosis, defined by the presence of a fragility fracture. According to major clinical guidelines (AACE/ACE), oral bisphosphonates such as alendronate are the recommended first-line therapy for most postmenopausal women with osteoporosis. They are effective at reducing both vertebral and hip fractures, are cost-effective, and have an extensive safety record. Denosumab is also a first-line option but is often used in those who cannot tolerate oral bisphosphonates. Teriparatide, an anabolic agent, is typically reserved for very high-risk patients or those who fail bisphosphonate therapy. Raloxifene is less potent and is not proven to reduce the risk of hip fractures.

Question 71: A 38-year-old woman presents with pleuritic chest pain, dyspnea, and hemoptysis 2 weeks after a total knee replacement. CT pulmonary angiography confirms bilateral pulmonary emboli without RV dysfunction. She has no contraindications to anticoagulation. What is the MOST appropriate treatment?

Catheter-directed thrombolysis
Systemic thrombolysis with IV alteplase
Anticoagulation with rivaroxaban or apixaban (Correct answer)
Surgical embolectomy

Correct answer: Anticoagulation with rivaroxaban or apixaban

Submassive PE without hemodynamic compromise or severe RV dysfunction is treated with anticoagulation alone; DOACs (rivaroxaban or apixaban) are preferred for low-risk PE.

Question 72: A 42-year-old woman presents with several months of progressive fatigue, weight loss, nausea, and orthostatic dizziness. On examination, her blood pressure is 90/60 mmHg, and she has hyperpigmentation of her palmar creases. Laboratory studies reveal hyponatremia and hyperkalemia. A baseline 8 AM serum cortisol level is 2.8 µg/dL (low). Which of the following tests is the most appropriate next step to confirm the diagnosis of primary adrenal insufficiency?

24-hour urine free cortisol measurement
High-dose (250 mcg) ACTH (cosyntropin) stimulation test (Correct answer)
CRH stimulation test
Metyrapone test

Correct answer: High-dose (250 mcg) ACTH (cosyntropin) stimulation test

The clinical presentation and initial laboratory findings are highly suggestive of primary adrenal insufficiency (Addison's disease). The standard and most definitive diagnostic test is the high-dose (250 mcg) ACTH stimulation test. A failure of serum cortisol to rise to an adequate level (typically >18-20 µg/dL) after cosyntropin administration confirms the diagnosis. A 24-hour urine free cortisol is used to screen for cortisol excess (Cushing's syndrome). The CRH stimulation test is used to differentiate between secondary (pituitary) and tertiary (hypothalamic) adrenal insufficiency. The metyrapone test is rarely used.

Question 73: A 28-year-old woman presents with a 6-month history of amenorrhea, galactorrhea, and a serum prolactin of 340 ng/mL. MRI reveals a 14 mm pituitary macroadenoma. She is started on cabergoline 0.5 mg twice weekly. After 6 months of therapy, her prolactin normalizes and repeat MRI shows > 50% tumor reduction. She asks about discontinuing therapy to attempt pregnancy. Which statement best characterizes the risk of tumor growth during pregnancy if cabergoline is stopped?

Risk is approximately 50% because dopamine agonist withdrawal universally causes rebound hyperprolactinemia exceeding baseline levels
Risk of symptomatic tumor enlargement during pregnancy is approximately 20–30% for macroadenomas not surgically treated prior to conception (Correct answer)
Risk is eliminated because prolactin normalization on cabergoline indicates a microadenoma misclassified by MRI resolution
Risk of symptomatic tumor enlargement is < 5% because physiologic estrogen suppresses corticotroph proliferation during pregnancy

Correct answer: Risk of symptomatic tumor enlargement during pregnancy is approximately 20–30% for macroadenomas not surgically treated prior to conception

For prolactinomas, the risk of clinically significant tumor enlargement during pregnancy depends on adenoma size and prior treatment. Macroadenomas (≥ 10 mm) that have not been surgically debulked carry a ~20–30% risk of symptomatic growth during pregnancy when dopamine agonists are discontinued, due to estrogen-driven lactotroph proliferation. This compares to < 3% for microadenomas. The 50% reduction in tumor size on cabergoline is favorable but does not eliminate risk for a macroadenoma. Estrogen does not suppress corticotrophs (it stimulates lactotrophs). Tumor reduction on dopamine agonist therapy does not reclassify a macroadenoma. Rebound hyperprolactinemia upon withdrawal does not universally exceed baseline and is not the primary mechanism of tumor growth risk.

Question 74: A 28-year-old man with severe hemophilia A (factor VIII activity <1%) presents with rapidly expanding knee hemarthrosis after a fall. What is the first-line treatment?

Fresh frozen plasma infusion
Cryoprecipitate infusion
Desmopressin (DDAVP)
Factor VIII concentrate replacement therapy (Correct answer)

Correct answer: Factor VIII concentrate replacement therapy

Hemophilia A is treated with specific factor VIII concentrate replacement, which is preferred over non-specific blood products for efficacy and safety.

Question 75: A 70-year-old nursing home resident with type 2 DM is found unresponsive. Labs show glucose 1,350 mg/dL, Na 152, osmolality 385 mOsm/kg, pH 7.35, bicarbonate 22. What is the diagnosis?

Hyperosmolar hyperglycemic state (HHS) (Correct answer)
Mixed DKA and HHS
Lactic acidosis
Severe DKA with hyperosmolality

Correct answer: Hyperosmolar hyperglycemic state (HHS)

HHS is characterized by extreme hyperglycemia (>600 mg/dL), hyperosmolality (>320 mOsm/kg), and absent or minimal ketoacidosis (pH >7.3, bicarb >18).

Question 76: A mechanically ventilated patient with ARDS (P/F ratio 88) on volume-control ventilation develops sudden worsening hypoxemia and decreased lung compliance. Trachea is midline, breath sounds are equal bilaterally, and the chest X-ray shows new bilateral opacities that were not present 6 hours ago. Plateau pressure has increased from 28 to 36 cmH2O. Which of the following is the most likely cause?

Ventilator-associated pneumonia
Right mainstem intubation
Worsening ARDS with disease progression (Correct answer)
Auto-PEEP with dynamic hyperinflation

Correct answer: Worsening ARDS with disease progression

The scenario describes sudden deterioration with new bilateral opacities, increased plateau pressure, and preserved symmetric breath sounds — this constellation is most consistent with worsening ARDS (disease progression). Right mainstem intubation would cause unilateral changes (decreased breath sounds on left, unilateral opacity) and tracheal deviation. Auto-PEEP causes increased peak pressures but plateau pressure elevation suggests decreased compliance, and dynamic hyperinflation would be associated with obstructive physiology and would not produce new bilateral opacities. VAP typically develops over 48+ hours with gradual changes and fever/leukocytosis, not acute bilateral deterioration within 6 hours without systemic signs, making it less likely to be the acute precipitant here.

Question 77: A 45-year-old man with hepatitis B (HBsAg positive, HBeAg positive, HBV DNA 8 log IU/mL, ALT 180) has liver biopsy showing moderate inflammation and bridging fibrosis. Which treatment is most appropriate?

Lamivudine
Tenofovir disoproxil fumarate (Correct answer)
Interferon-alpha monotherapy
Monitor without treatment

Correct answer: Tenofovir disoproxil fumarate

Tenofovir (TDF or TAF) is the preferred first-line treatment for chronic hepatitis B with significant disease activity and fibrosis due to its potency, high barrier to resistance, and safety profile.

Question 78: A 45-year-old man with known bicuspid aortic valve and moderate aortic regurgitation has an aortic root diameter of 4.8 cm and ascending aorta of 4.3 cm. He is asymptomatic with EF of 62% and LVESD of 42 mm. Which is the most appropriate management?

Initiate beta-blocker therapy to slow aortic root dilation and defer surgery
Refer for surgery now given aortic root ≥4.5 cm in a bicuspid aortic valve patient with additional risk modifier (Correct answer)
Refer for surgery only when EF drops below 55% or LVESD exceeds 50 mm
Observation with annual imaging; surgery threshold in BAV patients is aortic diameter ≥5.0 cm

Correct answer: Refer for surgery now given aortic root ≥4.5 cm in a bicuspid aortic valve patient with additional risk modifier

In bicuspid aortic valve (BAV) disease, the threshold for prophylactic aortic surgery is lower than in tricuspid valves. Current AHA/ACC guidelines recommend surgery at ≥5.5 cm for tricuspid valves but ≥5.0 cm for BAV. However, surgery is reasonable at ≥4.5 cm in BAV patients who have an additional risk modifier — such as a family history of aortic dissection, a rapid growth rate (>0.5 cm/year), or planned cardiac surgery for another indication. At 4.8 cm root with BAV, the threshold is met if any risk modifier exists; this patient warrants surgical referral evaluation. Beta-blockers alone do not change the aortopathy trajectory sufficiently to defer needed intervention.

Question 79: A 45-year-old female immigrant from Southeast Asia presents with progressive exertional dyspnea. She has a history of rheumatic fever in childhood. On exam, she has an opening snap and a low-pitched diastolic rumble at the apex. She is found to be in atrial fibrillation with a rapid ventricular response. Echocardiography confirms severe rheumatic mitral stenosis (valve area 0.9 cm²). Which of the following medications is contraindicated for anticoagulation in this patient?

Enoxaparin.
Heparin.
Dabigatran. (Correct answer)
Warfarin.

Correct answer: Dabigatran.

In patients with atrial fibrillation and moderate-to-severe rheumatic mitral stenosis, anticoagulation with a vitamin K antagonist (VKA) like warfarin is recommended. Non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, are not recommended and are considered contraindicated in this specific patient population due to a lack of evidence and potential for harm. Heparin and enoxaparin can be used for bridging or acute anticoagulation.

Question 80: A 25-year-old woman has elevated transaminases, Kayser-Fleischer rings, and neuropsychiatric symptoms. Serum ceruloplasmin is low. Which test best confirms the diagnosis of Wilson's disease?

Liver biopsy with quantitative copper (Correct answer)
24-hour urine copper
Genetic testing for ATP7B mutation
Serum copper level

Correct answer: Liver biopsy with quantitative copper

Liver biopsy with quantitative hepatic copper content >250 mcg/g dry weight is the gold standard for confirming Wilson's disease when clinical criteria are equivocal.

Question 81: A 38-year-old man with multiple endocrine neoplasia type 1 (MEN1) undergoes surveillance imaging and is found to have a 1.8 cm non-functioning pancreatic neuroendocrine tumor (pNET). His serum calcium is 11.4 mg/dL, PTH is 142 pg/mL, and gastrin is normal. He is otherwise asymptomatic. In MEN1, what is the correct sequence of surgical management when both hyperparathyroidism and a pNET require surgery?

Resect the pNET first to reduce the risk of Zollinger-Ellison syndrome
Address both simultaneously with a single operative session to minimize anesthetic risk
The pNET should be treated with somatostatin analogues first to shrink it before surgical planning
Perform parathyroidectomy first, as hypercalcemia stimulates gastrin and may unmask latent gastrinoma (Correct answer)

Correct answer: Perform parathyroidectomy first, as hypercalcemia stimulates gastrin and may unmask latent gastrinoma

In MEN1 patients with concurrent hyperparathyroidism and pNETs, parathyroidectomy should be performed first. Hypercalcemia potentiates gastrin secretion and exacerbates acid hypersecretion in gastrinoma (Zollinger-Ellison syndrome), making hypercalcemia correction essential before pancreatic surgery. Normalization of calcium can unmask true gastrin levels and improve control of ZES. The recommended operation for MEN1-related hyperparathyroidism is subtotal (3.5-gland) parathyroidectomy or total parathyroidectomy with autotransplantation. Performing pancreatic surgery first does not address the hormonal milieu driving gastric acid secretion and may complicate postoperative management.

Question 82: A 62-year-old woman with known pulmonary arterial hypertension presents with worsening dyspnea and right heart failure. Echocardiogram shows RV dilation and septal bowing. Which hemodynamic finding on right heart catheterization confirms WHO Group 1 PAH?

Systolic PAP >50 mmHg with normal PVR
Mean PAP >25 mmHg with elevated cardiac output
Mean PAP >20 mmHg with PCWP >15 mmHg
Mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units (Correct answer)

Correct answer: Mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units

Updated 2022 ESC/ERS guidelines define PAH (Group 1) as mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units on right heart catheterization.

Question 83: A mechanically ventilated patient with ARDS (P/F ratio 90) is being managed with prone positioning and neuromuscular blockade. After 18 hours prone, the nurse notes plateau pressure has risen from 28 to 38 cmH2O with no change in PEEP or tidal volume. SpO2 is 84%. The MOST likely cause requiring immediate intervention is:

Auto-PEEP from secretion plugging in the dependent airways
Ventilator-induced pneumothorax
Abdominal compartment syndrome causing increased chest wall elastance (Correct answer)
Selective right mainstem intubation due to ETT migration

Correct answer: Abdominal compartment syndrome causing increased chest wall elastance

Prone positioning increases intra-abdominal pressure and can unmask or worsen abdominal compartment syndrome (ACS), which raises chest wall (not lung) elastance, causing a rise in plateau pressure. In prone patients, ACS is a critical and often overlooked cause of acute plateau pressure rise. ETT migration is possible but would cause asymmetric breath sounds. Pneumothorax would cause sudden desaturation often with hemodynamic compromise. Secretion plugging would more likely raise peak airway pressure without proportionally raising plateau pressure.

Question 84: An ICU patient develops ventilator-associated pneumonia (VAP) on day 8. Endotracheal cultures grow Pseudomonas aeruginosa. Which antibiotic combination should be used empirically given concern for multidrug-resistant (MDR) Pseudomonas?

Meropenem plus ceftolozane-tazobactam
Piperacillin-tazobactam monotherapy
Cefepime plus tobramycin (Correct answer)
Ceftazidime-avibactam plus colistin

Correct answer: Cefepime plus tobramycin

For MDR Pseudomonas VAP, combination therapy with an antipseudomonal beta-lactam plus an aminoglycoside (e.g., cefepime plus tobramycin) is recommended pending susceptibilities.

Question 85: A patient with HHS has a serum osmolality of 345 mOsm/kg and blood glucose of 1100 mg/dL. Which IV fluid is most appropriate for initial resuscitation?

D5W (5% dextrose in water)
Lactated Ringer's solution
0.45% NaCl (hypotonic saline)
0.9% NaCl (isotonic saline) (Correct answer)

Correct answer: 0.9% NaCl (isotonic saline)

Isotonic normal saline (0.9% NaCl) is used first in HHS to restore circulating volume before transitioning to hypotonic fluids for free water replacement.

Question 86: Which class of medications should be AVOIDED in patients with severe aortic stenosis presenting with systemic hypertension?

Nitrates and systemic vasodilators (Correct answer)
Dihydropyridine calcium channel blockers
Low-dose beta-blockers
ACE inhibitors

Correct answer: Nitrates and systemic vasodilators

Potent vasodilators (nitrates, phosphodiesterase inhibitors, alpha-blockers) are dangerous in severe AS because fixed obstruction prevents cardiac output from increasing to compensate for the drop in SVR, causing severe hypotension.

Question 87: A 45-year-old man with HIV (CD4 50 cells/µL) presents with fever, headache, and neck stiffness. CSF shows elevated protein, low glucose, and India ink positive organisms. What is the first-line treatment?

Liposomal amphotericin B plus flucytosine (Correct answer)
Fluconazole 400mg daily
Micafungin IV
Voriconazole IV

Correct answer: Liposomal amphotericin B plus flucytosine

Cryptococcal meningitis in HIV patients is treated with induction therapy using liposomal amphotericin B plus flucytosine for 2 weeks, followed by fluconazole consolidation.

Question 88: A 55-year-old man with alcohol-associated hepatitis (AH) has a Maddrey Discriminant Function (MDF) of 48 and a Model for End-Stage Liver Disease (MELD) score of 26. He is started on prednisolone 40 mg daily. On day 7, his Lille score is calculated at 0.48. What is the most appropriate next step in management?

Discontinue prednisolone and transition to pentoxifylline
Continue prednisolone for a full 28-day course
Discontinue prednisolone and refer for early liver transplant evaluation at experienced center (Correct answer)
Add N-acetylcysteine to ongoing prednisolone therapy for synergistic benefit

Correct answer: Discontinue prednisolone and refer for early liver transplant evaluation at experienced center

The Lille score predicts corticosteroid response at day 7. A Lille score ≥0.45 indicates steroid non-response (predicts ~75% 6-month mortality). In non-responders, continuing prednisolone confers no survival benefit and increases infection risk — it should be stopped. Pentoxifylline has not been shown to rescue steroid non-responders and is no longer recommended as salvage. N-acetylcysteine as adjunct (ATTIR trial data) showed no 6-month mortality benefit. Early liver transplantation (LT) for severe AH without a 6-month abstinence period is performed at select experienced centers, and landmark trials (Mathurin et al., ACCELERATE-AH) demonstrate improved survival in carefully selected patients with first-episode severe AH and strong psychosocial support.

Question 89: A 35-year-old person who injects drugs presents with a fever of 38.8°C (101.8°F) and a new holosystolic murmur. Blood cultures are drawn, and an echocardiogram is ordered. According to the modified Duke criteria, which of the following findings constitutes a major criterion for the diagnosis of infective endocarditis?

Presence of Janeway lesions
Echocardiogram showing an oscillating intracardiac mass on a valve (Correct answer)
Positive blood culture for *Staphylococcus epidermidis* from a single sample
Fever >38.0°C

Correct answer: Echocardiogram showing an oscillating intracardiac mass on a valve

The modified Duke criteria classify findings into major and minor categories. The major criteria include: (1) positive blood cultures typical for infective endocarditis and (2) evidence of endocardial involvement. Evidence of endocardial involvement on an echocardiogram includes an oscillating intracardiac mass (vegetation), abscess, or new partial dehiscence of a prosthetic valve. Fever, vascular phenomena (like Janeway lesions), and immunologic phenomena are all minor criteria. A single positive blood culture with a common skin contaminant like *S. epidermidis* does not meet the major criterion for blood cultures.

Question 90: A 58-year-old man with COPD presents with acute hypercapnic respiratory failure. ABG shows pH 7.28, PaCO2 72 mmHg, PaO2 58 mmHg on room air. Which intervention is MOST appropriate as first-line therapy?

Immediate endotracheal intubation
Non-invasive positive pressure ventilation (NIPPV) (Correct answer)
Heliox administration
High-flow nasal cannula at 40 L/min

Correct answer: Non-invasive positive pressure ventilation (NIPPV)

NIPPV (BiPAP) is the first-line intervention for acute hypercapnic respiratory failure in COPD, reducing intubation rates, mortality, and hospital length of stay.

Question 91: A 38-year-old man undergoes capsule endoscopy for obscure gastrointestinal bleeding. The study identifies a solitary 1.2 cm subepithelial lesion in the mid-jejunum with a central umbilication. Histology reveals spindle cells positive for CD117 (c-KIT) and DOG1, with a mitotic rate of 8 per 50 HPF. What feature most critically determines the malignant potential classification of this tumor?

Tumor size alone (>2 cm)
Tumor location in the small bowel rather than stomach
Combination of tumor size and mitotic rate (Correct answer)
CD117 positivity

Correct answer: Combination of tumor size and mitotic rate

Gastrointestinal stromal tumors (GISTs) are risk-stratified using BOTH tumor size AND mitotic rate (per 50 HPF), along with tumor site, per the Modified NIH Consensus Criteria and AFIP criteria. This jejunal GIST at 1.2 cm with 8 mitoses/50 HPF falls into a high-risk category because of the elevated mitotic rate despite small size. Location (small bowel vs. gastric) also modifies risk but does not replace the size+mitotic rate combination. CD117 positivity confirms diagnosis but does not classify malignant potential. Size alone is insufficient.

Question 92: A 34-year-old female is diagnosed with hypertension, with blood pressures consistently around 160/105 mmHg despite therapy with two antihypertensive agents. She has no family history of hypertension. On physical examination, a faint bruit is audible in the right upper abdominal quadrant. Which of the following is the most appropriate next step to investigate the likely cause of her secondary hypertension?

Overnight dexamethasone suppression test
Plasma aldosterone-to-renin ratio
24-hour urine collection for metanephrines
Renal artery duplex ultrasound (Correct answer)

Correct answer: Renal artery duplex ultrasound

The patient's demographic (young female), resistant hypertension, and the presence of an abdominal bruit are highly suggestive of renal artery stenosis due to fibromuscular dysplasia (FMD). A renal artery duplex ultrasound is an excellent non-invasive initial test to screen for this condition. The other options are used to investigate other causes of secondary hypertension: pheochromocytoma (metanephrines), Cushing's syndrome (dexamethasone suppression), and primary aldosteronism (aldosterone-renin ratio), which are less likely given the specific clinical clue of an abdominal bruit.

Question 93: A 58-year-old man with systemic sclerosis presents with progressive dyspnea over 6 months. PFTs show FVC 62%, DLCO 38%, FEV1/FVC 0.82. Right heart catheterization reveals mPAP 28 mmHg, PCWP 12 mmHg, PVR 3.2 WU. Chest HRCT shows no significant ILD. Which of the following best characterizes his pulmonary hemodynamic profile?

Borderline mPAP not meeting criteria for pulmonary hypertension (Correct answer)
Pre-capillary pulmonary hypertension consistent with Group 1 PAH
Combined pre- and post-capillary pulmonary hypertension
Post-capillary pulmonary hypertension due to left heart disease

Correct answer: Borderline mPAP not meeting criteria for pulmonary hypertension

Per the updated 2022 ESC/ERS guidelines, the threshold for pulmonary hypertension was lowered to mPAP >20 mmHg (from >25 mmHg). However, to classify as Group 1 PAH, the criteria require mPAP >20 mmHg AND PCWP ≤15 mmHg AND PVR ≥2 WU. While this patient meets mPAP >20 and PCWP ≤15, his PVR of 3.2 WU does meet criteria — but critically, his mPAP of 28 mmHg IS above 20 mmHg. Re-evaluating: mPAP 28 > 20, PCWP 12 ≤ 15, PVR 3.2 ≥ 2 WU — this IS pre-capillary PH meeting Group 1 PAH criteria under 2022 guidelines. However, note that the 'borderline' category (mPAP 21–24 mmHg) is a distinct entity requiring exercise testing. At mPAP 28, this patient meets full pre-capillary PAH criteria in the setting of systemic sclerosis (SSc-PAH, Group 1). The correct answer is A — pre-capillary PH consistent with Group 1 PAH, given mPAP >20, PCWP ≤15, and PVR ≥2 WU with an underlying connective tissue disease.

Question 94: A 72-year-old man with chronic severe aortic regurgitation has serial echocardiograms over 4 years. Current echo shows: LVEF 52%, LV end-systolic diameter (LVESD) 49 mm, LV end-diastolic diameter (LVEDD) 72 mm. He is asymptomatic and his exercise tolerance is excellent. What is the most appropriate next step?

Start an ACE inhibitor to delay surgery
Perform exercise stress echocardiography to unmask symptoms
Refer for aortic valve replacement surgery now (Correct answer)
Continue surveillance echocardiography in 6–12 months

Correct answer: Refer for aortic valve replacement surgery now

Per current ACC/AHA guidelines, AVR is indicated (Class I) for asymptomatic severe AR when LVESD ≥50 mm OR LVEDD >65 mm OR LVEF <55%. This patient's LVESD is 49 mm (borderline) but LVEDD is 72 mm, which exceeds the 65 mm threshold — meeting an independent surgical indication regardless of symptoms or EF. Waiting risks irreversible LV dysfunction. ACE inhibitors do not delay surgical timing in asymptomatic patients meeting size criteria. Exercise stress echo has no guideline-supported role in this scenario when structural thresholds are already met.

Question 95: A mechanically ventilated patient with ARDS has refractory hypoxemia (P/F ratio 65) despite optimized ventilator settings and prone positioning for 18 hours. Which rescue therapy should be considered next?

Venovenous extracorporeal membrane oxygenation (VV-ECMO) (Correct answer)
Partial liquid ventilation with perfluorocarbon
High-frequency oscillatory ventilation (HFOV)
Inhaled nitric oxide

Correct answer: Venovenous extracorporeal membrane oxygenation (VV-ECMO)

VV-ECMO is the rescue therapy for severe refractory ARDS when conventional strategies including prone positioning have failed, as supported by the CESAR and EOLIA trials.

Question 96: A 67-year-old man with stage 3b CKD (GFR 34), type 2 diabetes, and hypertension presents with resistant hypertension despite maximum-dose lisinopril, amlodipine, and chlorthalidone. His aldosterone-to-renin ratio (ARR) is 42 ng/dL per ng/mL/hr (>30 is positive screen). Adrenal CT shows bilateral adrenal hyperplasia. His serum potassium is 3.2 mEq/L. Which intervention is most appropriate before planning adrenal vein sampling (AVS)?

Proceed directly to bilateral adrenalectomy given bilateral CT findings
Start spironolactone 25 mg daily and reassess ARR in 6 weeks
Add low-dose dexamethasone suppression to distinguish glucocorticoid-remediable aldosteronism
Replace potassium to ≥3.5 mEq/L, discontinue interfering medications, and then perform AVS (Correct answer)

Correct answer: Replace potassium to ≥3.5 mEq/L, discontinue interfering medications, and then perform AVS

AVS is the definitive test to distinguish unilateral from bilateral primary aldosteronism (PA) and guides surgical versus medical management. However, hypokalemia itself suppresses aldosterone secretion and can produce false-negative AVS results; potassium must be repleted to ≥3.5 mEq/L before AVS. Additionally, interfering medications (mineralocorticoid receptor antagonists, beta-blockers, ACE inhibitors) must be discontinued or substituted with non-interfering agents (alpha-blockers, verapamil) before the test. Bilateral CT findings do not reliably distinguish bilateral hyperplasia from bilateral macro-adenomas or contralateral micro-adenomas — CT misclassifies lateralization in ~25% of cases. Bilateral adrenalectomy would be inappropriate without AVS confirmation of true bilateral disease. Glucocorticoid-remediable aldosteronism (GRA/FH-I) is suspected when PA begins before age 20 or has strong family history; it is not a first-line consideration here.

Question 97: What is the goal LDL cholesterol level for a high-risk patient with cardiovascular disease?

<50 mg/dL
<100 mg/dL
<130 mg/dL
<70 mg/dL (Correct answer)

Correct answer: <70 mg/dL

For high-risk patients with established cardiovascular disease, the goal LDL cholesterol level is typically less than 70 mg/dL. Aggressive lowering of LDL cholesterol in this population has been shown to significantly reduce the risk of recurrent cardiovascular events. In some very high-risk cases, even lower targets may be considered.

Question 98: A 48-year-old male smoker with hyperlipidemia and hypertension has a resting ECG showing Q waves in leads II, III, and aVF. He has no chest pain history. What is the most likely explanation?

Left ventricular hypertrophy
Wolff-Parkinson-White syndrome
Prior inferior myocardial infarction (Correct answer)
Normal variant in these leads

Correct answer: Prior inferior myocardial infarction

Pathological Q waves in the inferior leads (II, III, aVF) in the setting of multiple cardiovascular risk factors most likely represent a prior silent inferior MI.

Question 99: A 58-year-old man with alcoholic cirrhosis develops confusion and asterixis. Ammonia level is elevated. Which treatment is most appropriate?

Neomycin
Zinc supplementation
Rifaximin
Lactulose (Correct answer)

Correct answer: Lactulose

Lactulose is first-line therapy for hepatic encephalopathy, reducing ammonia absorption by acidifying colonic contents and promoting excretion.

Question 100: A 6-month-old boy has had recurrent pneumonia caused by Pneumocystis jirovecii, oral candidiasis, and failure to thrive since birth. On examination, no lymph nodes are palpable. CBC shows lymphopenia. Which immunodeficiency is most likely?

DiGeorge syndrome
Common variable immunodeficiency (CVID)
Severe combined immunodeficiency (SCID) (Correct answer)
X-linked agammaglobulinemia (XLA)

Correct answer: Severe combined immunodeficiency (SCID)

SCID presents in infancy with both T and B cell deficiency, causing susceptibility to bacterial, viral, and opportunistic infections (including PCP and Candida). XLA presents later after maternal antibody wanes and predominantly affects B cells, causing bacterial infections. CVID presents in young adults. DiGeorge involves T cell deficiency from thymic aplasia but B cells are intact.

Question 101: A 45-year-old man with bilateral renal artery stenosis (confirmed on CTA) and resistant hypertension undergoes revascularization. Post-procedure, his creatinine rises sharply from 1.4 to 3.1 mg/dL over 48 hours. His blood pressure has improved to 130/82 mmHg on the same medications. Urinalysis shows no casts, no eosinophils. Which mechanism most likely explains the acute creatinine rise in this clinical context?

Loss of post-stenotic angiotensin II–mediated efferent arteriolar tone causing a precipitous drop in intraglomerular pressure in the previously hyperperfused kidneys (Correct answer)
Contrast-induced acute tubular necrosis from the angiographic contrast used during revascularization
Reperfusion injury with reactive oxygen species causing tubular cell necrosis bilaterally
Cholesterol crystal embolization to the renal microvasculature during catheter manipulation

Correct answer: Loss of post-stenotic angiotensin II–mediated efferent arteriolar tone causing a precipitous drop in intraglomerular pressure in the previously hyperperfused kidneys

In chronic bilateral renal artery stenosis, the kidneys adapt to reduced perfusion pressure by upregulating angiotensin II, which preferentially constricts the efferent arteriole to maintain glomerular filtration pressure. After successful revascularization, perfusion pressure is restored, but the kidneys lose that angiotensin II–driven efferent constriction. The result is a paradoxical acute decline in GFR — sometimes called 'renal artery stenosis revascularization-associated AKI' — due to normalization of perfusion pressure in a system that had been relying on efferent tone to filter. This is distinct from contrast nephropathy (which typically peaks at 48–72 hours and is associated with ATN on biopsy) and cholesterol embolization (which causes eosinophiluria, livedo reticularis, and slow progressive renal failure, not acute post-procedure rise in a hypertension-improving patient).

Question 102: A 61-year-old woman with resistant hypertension (BP 158/96 mmHg on ACEI, amlodipine, and chlorthalidone) has plasma aldosterone-to-renin ratio of 35 (ng/dL)/(ng/mL/h). CT adrenals are normal. What is the next step?

Adrenal vein sampling (Correct answer)
24-hour urine aldosterone collection
Begin spironolactone empirically
Add doxazosin for suspected pheochromocytoma

Correct answer: Adrenal vein sampling

An elevated ARR with biochemically confirmed primary hyperaldosteronism requires adrenal vein sampling to distinguish unilateral adenoma (surgical) from bilateral hyperplasia (medical).

Question 103: A 70-year-old man presents with dysphagia to solids progressively worsening over 3 months with a 15-pound weight loss. What is the most appropriate initial evaluation?

CT chest/abdomen
Barium swallow
Esophageal manometry
Upper endoscopy (Correct answer)

Correct answer: Upper endoscopy

Upper endoscopy (EGD) is the preferred initial test for progressive dysphagia with alarm features because it allows direct visualization and biopsy to evaluate for malignancy.

Question 104: A 45-year-old man with type 2 diabetes, hypertension, and CKD stage G3b A3 (eGFR 38 mL/min, urine ACR 920 mg/g) is on maximum-dose lisinopril 40 mg daily. His BP is 138/88 mmHg and HbA1c is 7.1%. He asks about adding a second agent for kidney protection. Which combination provides the STRONGEST evidence for additive cardiorenal protection in this specific scenario?

Add spironolactone for aldosterone escape
Add losartan (dual RAS blockade)
Add irbesartan to target tighter proteinuria reduction
Add finerenone (Correct answer)

Correct answer: Add finerenone

Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, demonstrated significant reductions in both the composite kidney endpoint (40% eGFR decline, ESKD, renal death) and cardiovascular events in the FIDELIO-DKD and FIGARO-DKD trials when added to maximum-tolerated RAS blockade in patients with diabetic kidney disease and significant albuminuria. Its selectivity for the MR results in less hyperkalemia and gynecomastia than spironolactone. Dual RAS blockade (ACEi + ARB) is contraindicated given the ONTARGET trial showing increased AKI, hyperkalemia, and hypotension without cardiovascular benefit. Spironolactone has no dedicated outcome trial data in DKD at scale and carries higher hyperkalemia risk at eGFR <45.

Question 105: A 52-year-old woman presents with acute-onset chest pain that began while arguing with a family member. ECG shows diffuse ST elevation with deep T-wave inversions in precordial leads. Troponin-I peaks at 1.8 ng/mL. Emergent coronary angiography reveals no obstructive coronary artery disease. Left ventriculography demonstrates apical ballooning with basal hyperkinesis. Cardiac MRI shows myocardial edema but no late gadolinium enhancement. What is the most feared in-hospital complication of her condition?

Massive pulmonary embolism from apical thrombus embolization
Complete heart block requiring temporary pacing
Ventricular free-wall rupture
Dynamic left ventricular outflow tract obstruction with cardiogenic shock (Correct answer)

Correct answer: Dynamic left ventricular outflow tract obstruction with cardiogenic shock

This is Takotsubo (stress) cardiomyopathy, characterized by apical ballooning, emotional/physical trigger, no obstructive CAD, and absent late gadolinium enhancement. The most feared acute hemodynamic complication is dynamic LVOT obstruction, occurring in up to 10–20% of cases. Basal hypercontractility combined with reduced cavity size from catecholamine surge creates a Venturi effect, causing systolic anterior motion (SAM) of the mitral valve and obstruction. This can precipitate cardiogenic shock — paradoxically worsened by inotropes or volume depletion. Free-wall rupture and complete heart block are far more characteristic of STEMI. Apical thrombus can form but massive PE from it acutely is rare.

Question 106: A 60-year-old man undergoes right heart catheterization. Results: RA pressure 18 mmHg, RV 55/20 mmHg, PA 55/28 mmHg (mean 38), PCWP 24 mmHg, cardiac output 3.8 L/min. What is the MOST likely diagnosis?

Chronic thromboembolic pulmonary hypertension (CTEPH)
Pulmonary hypertension due to lung disease (Group 3)
Idiopathic pulmonary arterial hypertension
Pulmonary hypertension due to left heart disease (Group 2) (Correct answer)

Correct answer: Pulmonary hypertension due to left heart disease (Group 2)

Elevated PCWP (>15 mmHg) with elevated mean PAP indicates post-capillary (Group 2) pulmonary hypertension due to left heart disease, not pre-capillary PAH.

Question 107: A 25-year-old man presents with a painless penile ulcer with indurated borders and bilateral inguinal lymphadenopathy. Dark-field microscopy confirms the diagnosis. What is the treatment of choice?

Doxycycline 100mg BID x 14 days
Ceftriaxone 250mg IM single dose
Benzathine penicillin G 2.4 million units IM single dose (Correct answer)
Azithromycin 1g PO single dose

Correct answer: Benzathine penicillin G 2.4 million units IM single dose

Primary syphilis is treated with benzathine penicillin G 2.4 million units IM as a single dose, which is curative for early syphilis.

Question 108: A 58-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) presents with worsening dyspnea and presyncope. Echo shows LVOT gradient of 70 mmHg at rest. He is on metoprolol succinate 200 mg daily. Which intervention is MOST appropriate if symptoms persist despite optimal medical therapy and he is found to have a single dominant septal perforator supplying the hypertrophied septum?

Alcohol septal ablation (Correct answer)
Addition of disopyramide
Dual-chamber pacing with short AV delay
Surgical myectomy

Correct answer: Alcohol septal ablation

Alcohol septal ablation (ASA) is preferred when anatomy is suitable — specifically, when a dominant septal perforator clearly supplies the target area of hypertrophy, as confirmed by myocardial contrast echocardiography. Surgical myectomy is generally preferred for younger patients and those with complex anatomy, but ASA is anatomically ideal here. Dual-chamber pacing is no longer recommended as primary therapy (insufficient gradient reduction). Disopyramide can augment medical therapy but is not the answer when catheter-based intervention is anatomically optimal and medical therapy has already been maximized.

Question 109: A 38-year-old man with relapsed/refractory classical Hodgkin lymphoma progresses after brentuximab vedotin and pembrolizumab. He undergoes salvage chemotherapy with GDP (gemcitabine, dexamethasone, cisplatin) and achieves a partial response. PET-CT shows Deauville score 4 in a single mediastinal node. He proceeds to autologous SCT with BEAM conditioning. Which of the following post-transplant strategies is most strongly supported by randomized evidence to improve PFS in this setting?

Maintenance brentuximab vedotin for up to 2 years (Correct answer)
Observation alone with PET surveillance every 3 months
Consolidative involved-field radiation to the residual Deauville 4 node
Maintenance pembrolizumab to exploit post-transplant immune reconstitution

Correct answer: Maintenance brentuximab vedotin for up to 2 years

The AETHERA trial (NEJM 2015) was a landmark phase III RCT demonstrating that brentuximab vedotin (BV) maintenance for up to 2 years post-ASCT significantly improved PFS (42.9 vs 24.1 months, HR 0.57) in high-risk cHL patients, including those with primary refractory disease, relapse within 12 months, or extranodal disease. This led to FDA approval of BV in this post-ASCT maintenance setting. Pembrolizumab post-ASCT is under investigation but lacks mature phase III randomized evidence. Consolidative RT to a single Deauville 4 node is sometimes used but is not supported by the same level of RCT evidence as BV maintenance.

Question 110: A 55-year-old patient develops fever and diarrhea 4 days after starting clindamycin for a skin infection. Stool testing is positive for C. difficile toxin. She has her first episode. What is the preferred treatment?

Fidaxomicin 200mg BID x 10 days (Correct answer)
Oral vancomycin 125mg QID x 10 days
Rifaximin 400mg TID x 10 days
Metronidazole 500mg TID x 10 days

Correct answer: Fidaxomicin 200mg BID x 10 days

Current IDSA guidelines recommend fidaxomicin as preferred first-line therapy for initial C. difficile infection due to lower recurrence rates compared to vancomycin.

Question 111: A 38-year-old woman with Crohn's disease on azathioprine and infliximab develops right lower quadrant pain, fever, and a palpable mass. CT imaging shows a phlegmon involving the terminal ileum with an adjacent 4 cm abscess. She has no peritonitis. The optimal initial management is:

CT-guided percutaneous drainage plus antibiotics, with infliximab held (Correct answer)
Increase infliximab dose to induce remission and resolve the abscess
Colonoscopy with balloon dilation of any associated stricture
Emergent surgical resection of the terminal ileum

Correct answer: CT-guided percutaneous drainage plus antibiotics, with infliximab held

In Crohn's disease complicated by an intra-abdominal abscess, the standard of care is source control first — percutaneous drainage (if technically feasible) plus broad-spectrum antibiotics — before any escalation of immunosuppression. Anti-TNF agents (infliximab) are contraindicated in the setting of undrained abscess because immunosuppression worsens septic outcomes. Emergent surgery is reserved for peritonitis, failure of drainage, or inaccessible abscesses. Colonoscopy and stricture dilation are not appropriate in the acute septic phase.

Question 112: A medical ICU patient with septic shock from gram-negative bacteremia has been on norepinephrine 0.35 mcg/kg/min and vasopressin 0.03 units/min for 18 hours. MAP is 62 mmHg. Bedside echocardiography reveals: EF 15%, severely dilated left ventricle, TAPSE 12 mm, dilated RV with septal flattening in systole. CVP is 22 mmHg. ScvO2 is 58%. Lactate is 6.2 mmol/L trending upward. Which hemodynamic intervention is MOST appropriate at this time?

Add epinephrine infusion and prepare for intra-aortic balloon pump (Correct answer)
Administer 1L crystalloid bolus to optimize preload before adding inotropes
Add phenylephrine to increase SVR and improve coronary perfusion pressure
Begin dobutamine infusion at 5 mcg/kg/min

Correct answer: Add epinephrine infusion and prepare for intra-aortic balloon pump

This patient has septic cardiomyopathy with biventricular failure (EF 15%, TAPSE 12 mm, RV dilation with septal D-sign in systole), refractory shock (MAP 62 on dual vasopressors), and worsening end-organ perfusion (rising lactate, low ScvO2). The CVP of 22 mmHg indicates the patient is already volume overloaded, making fluid administration contraindicated and potentially harmful. Dobutamine alone may worsen hypotension through vasodilation in an already vasoplegic state. Phenylephrine (pure alpha agonist) would increase afterload against a failing LV and RV, worsening cardiac output. Epinephrine provides inotropic support (beta-1) while maintaining vasoconstriction (alpha), and in biventricular failure refractory to norepinephrine + vasopressin, it is the preferred next agent. IABP should be prepared given the severity of LV failure and refractory shock — it reduces LV afterload and augments diastolic coronary perfusion, providing a bridge to recovery or escalation.

Question 113: A 45-year-old HIV-positive man (CD4 180, not on ART) is diagnosed with PCP pneumonia. His PaO2 on room air is 58 mmHg. In addition to TMP-SMX, what adjunctive therapy should be started?

Systemic corticosteroids (prednisone 40mg BID) (Correct answer)
G-CSF support
Inhaled pentamidine
Adjunctive atovaquone

Correct answer: Systemic corticosteroids (prednisone 40mg BID)

Adjunctive corticosteroids are indicated for PCP when PaO2 < 70 mmHg or A-a gradient > 35 mmHg, as they reduce mortality by preventing inflammatory deterioration.

Question 114: A 28-year-old with type 1 diabetes is admitted in DKA (pH 6.98, bicarbonate 6 mEq/L, glucose 480 mg/dL, potassium 5.8 mEq/L). The team initiates IV fluids. When should insulin infusion be started?

Immediately, as insulin is the cornerstone of DKA treatment and delays worsen outcomes
Only after bicarbonate infusion has raised pH above 7.1 to prevent insulin resistance from severe acidosis
After IV potassium supplementation has been given and serum potassium is confirmed ≥3.5 mEq/L (Correct answer)
After serum potassium exceeds 5.0 mEq/L, since current hyperkalemia provides a safety buffer

Correct answer: After IV potassium supplementation has been given and serum potassium is confirmed ≥3.5 mEq/L

Although this patient is hyperkalemic (5.8 mEq/L), this is a falsely reassuring value — insulin drives potassium intracellularly, and the total body potassium in DKA is always depleted despite the apparent serum excess. The ADA protocol mandates holding insulin if K⁺ <3.5 mEq/L until potassium is repleted (risk of life-threatening hypokalemia and arrhythmia). With K⁺ ≥3.5 mEq/L, insulin can be started. This patient at 5.8 mEq/L should begin IV fluids and potassium monitoring; once K⁺ is confirmed ≥3.5 mEq/L (which it already is here), insulin infusion begins — but the key principle is never start insulin in hypokalemia. Bicarbonate is generally not indicated in DKA (except pH <6.9), and it does not need to precede insulin.

Question 115: A 72-year-old female is brought to the emergency department from a nursing home with a fever of 39.1°C (102.4°F), a respiratory rate of 28 breaths/min, and confusion. Her blood pressure is 85/50 mmHg despite receiving a 1L bolus of normal saline. A chest X-ray confirms a right lower lobe pneumonia. According to the Surviving Sepsis Campaign guidelines, which of the following interventions is the highest priority within the first hour of recognition?

Obtaining blood cultures and administering broad-spectrum antibiotics (Correct answer)
Administering a 30 mL/kg crystalloid fluid bolus
Measuring serum lactate level
Initiating vasopressor therapy with norepinephrine

Correct answer: Obtaining blood cultures and administering broad-spectrum antibiotics

The Surviving Sepsis Campaign guidelines emphasize the immediate initiation of treatment in patients with sepsis and septic shock. The 'Hour-1 Bundle' includes several critical actions. While fluid resuscitation (30 mL/kg crystalloid for hypotension) and measuring lactate are essential, the highest priority is to obtain blood cultures *before* administering broad-spectrum antibiotics, with the goal of starting antibiotics within the first hour of recognition. Delayed antibiotic administration is associated with increased mortality.

Question 116: Which medication is contraindicated in a patient with acute heart failure?

ACE inhibitors
Diuretics
Beta-blockers (Correct answer)
Nitrates

Correct answer: Beta-blockers

Beta-blockers are generally contraindicated in the acute phase of decompensated heart failure. While beneficial in stable chronic heart failure, their negative inotropic effects can worsen cardiac output and precipitate cardiogenic shock in acutely unwell patients. They should typically be withheld or carefully titrated once the patient is stable.

Question 117: A 65-year-old man with cirrhosis and ascites develops acute kidney injury. Creatinine rises from 1.0 to 2.6 mg/dL over 48 hours despite albumin infusion and diuretic discontinuation. Urine sodium is <10 mEq/L. What is the most likely diagnosis?

Prerenal azotemia
Hepatorenal syndrome (Correct answer)
Contrast nephropathy
Acute tubular necrosis

Correct answer: Hepatorenal syndrome

Hepatorenal syndrome (HRS) is characterized by functional renal failure in cirrhotic patients with very low urine sodium (<10), absence of improvement with volume expansion, and no intrinsic renal disease.

Question 118: A 67-year-old man with COPD (on tiotropium and salmeterol/fluticasone) is admitted for an acute exacerbation. On hospital day 3, he develops new-onset AF with RVR (HR 138 bpm), BP 102/68 mmHg, and SpO2 88% on 4L NC. He has no prior history of AF and no structural heart disease by recent echo. Which rhythm-control strategy is MOST appropriate at this time?

Synchronized electrical cardioversion immediately
IV metoprolol 5 mg for rate control followed by rhythm assessment
IV amiodarone infusion (Correct answer)
Oral flecainide 300 mg as a pill-in-the-pocket strategy

Correct answer: IV amiodarone infusion

In a COPD exacerbation complicated by new AF with hemodynamic compromise (hypotension and hypoxia), amiodarone is the preferred agent. Beta-blockers (including metoprolol) are relatively contraindicated in acute COPD exacerbations due to risk of bronchospasm, particularly with significant airflow obstruction. Flecainide (a class IC agent) is contraindicated in patients with structural or ischemic heart disease and is not appropriate for acute inpatient management of this complexity. Electrical cardioversion, while appropriate for hemodynamic instability, should be preceded by attempts at pharmacological rate/rhythm control when the patient is not in immediate hemodynamic collapse (BP 102, not in shock). Amiodarone has both rate-control and rhythm-conversion properties, lacks significant bronchoconstriction risk, and is guideline-recommended for AF cardioversion in critically ill patients.

Question 119: A patient with type 1 diabetes develops recurrent hypoglycemia without adrenergic warning symptoms. This condition is best described as:

Brittle diabetes
Dawn phenomenon
Somogyi phenomenon
Hypoglycemia-associated autonomic failure (Correct answer)

Correct answer: Hypoglycemia-associated autonomic failure

Hypoglycemia-associated autonomic failure (HAAF) results from prior hypoglycemic episodes blunting counter-regulatory and symptomatic responses.

Question 120: A 30-year-old woman presents with a pruritic, well-demarcated, silvery-scaled plaques on the elbows, knees, and scalp. She also reports nail pitting. Which of the following systemic associations should be screened for in this patient?

Hashimoto's thyroiditis
Primary biliary cholangitis
Celiac disease
Psoriatic arthritis (Correct answer)

Correct answer: Psoriatic arthritis

Psoriasis is strongly associated with psoriatic arthritis, which occurs in approximately 20–30% of psoriasis patients. Internists should screen for joint symptoms, enthesitis, and dactylitis. While psoriasis has some immune associations, psoriatic arthritis is the most clinically relevant and directly linked systemic comorbidity to screen for.

Question 121: A 38-year-old man presents with fatigue, easy bruising, and gingival bleeding for 3 weeks. CBC shows WBC 68,000/μL with 85% blasts, Hgb 7.8 g/dL, and platelets 18,000/μL. Bone marrow confirms AML. Which induction chemotherapy regimen is standard?

Rituximab monotherapy
CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
Imatinib plus hydroxyurea
Cytarabine for 7 days plus daunorubicin for 3 days ('7+3') (Correct answer)

Correct answer: Cytarabine for 7 days plus daunorubicin for 3 days ('7+3')

The '7+3' regimen — 7 days of continuous infusion cytarabine plus 3 days of an anthracycline — is the standard induction for AML.

Question 122: A patient with severe acute pancreatitis is being managed in the ICU. CT shows 40% pancreatic necrosis without infection. When should nutritional support be initiated?

Parenteral nutrition within 24 hours
Oral clear liquids when amylase normalizes
Bowel rest until pain resolves
Early enteral nutrition via nasojejunal tube within 24-48 hours (Correct answer)

Correct answer: Early enteral nutrition via nasojejunal tube within 24-48 hours

Early enteral nutrition via nasojejunal (or nasogastric) tube within 24-48 hours is preferred in severe pancreatitis to maintain gut barrier function and reduce infectious complications compared to TPN.

Question 123: Which of the following is the most common cause of acute pancreatitis in the United States?

Medications
Hypertriglyceridemia
Gallstones (Correct answer)
Alcohol

Correct answer: Gallstones

Gallstones (biliary pancreatitis) account for approximately 40% of acute pancreatitis cases in the US, making it the most common etiology.

Question 124: A 28-year-old man with type 1 diabetes and a history of alcohol use presents with DKA. Initial labs: glucose 210 mg/dL, pH 7.22, anion gap 26 mEq/L, beta-hydroxybutyrate elevated, phosphate 0.9 mg/dL. He is started on insulin and fluids. Which complication is he at highest risk for as treatment progresses?

Lactic acidosis from metformin accumulation
Hyperkalemia refractory to insulin therapy
Hyperosmolar coma from overly rapid glucose correction
Respiratory muscle weakness due to rebound hypophosphatemia (Correct answer)

Correct answer: Respiratory muscle weakness due to rebound hypophosphatemia

This patient already has severe hypophosphatemia (0.9 mg/dL) at presentation, which is exacerbated by insulin therapy — insulin drives phosphate intracellularly along with glucose and potassium. Profound hypophosphatemia (<1.0 mg/dL) can cause diaphragmatic weakness and respiratory failure, hemolytic anemia, and rhabdomyolysis. Phosphate replacement is warranted when levels fall below 1.0 mg/dL, especially in patients with baseline deficiency or who are at risk (e.g., alcohol users). Metformin-associated lactic acidosis would require metformin use, which is typically avoided in type 1 diabetes.

Question 125: A 55-year-old woman with class II obesity presents for cardiovascular risk assessment. Her 10-year ASCVD risk is 8%. LDL is 125 mg/dL. What is the most appropriate initial intervention?

Start high-intensity statin immediately
Lifestyle modification with shared decision-making about statin therapy (Correct answer)
Refer to cardiology before any therapy
Start fibrate therapy for triglycerides

Correct answer: Lifestyle modification with shared decision-making about statin therapy

A 10-year ASCVD risk of 7.5–10% is considered borderline; guidelines recommend shared decision-making about statin initiation after lifestyle modification counseling.

Question 126: Which lipoprotein pattern is most associated with premature atherosclerotic cardiovascular disease?

Elevated LDL-C with small dense LDL particles (Correct answer)
Elevated Lp(a) alone with normal LDL
Elevated HDL with low LDL
Isolated hypertriglyceridemia >150 mg/dL

Correct answer: Elevated LDL-C with small dense LDL particles

Small dense LDL particles are more atherogenic because they penetrate the endothelium more easily and are more susceptible to oxidation, driving plaque formation.

Question 127: A 67-year-old man with Stage IIIA non-small cell lung cancer (NSCLC) and ECOG performance status 1 has a PD-L1 expression of 85%. He has no driver mutations (EGFR/ALK negative). Which treatment approach is MOST appropriate?

Pembrolizumab monotherapy
EGFR-targeted therapy with osimertinib
Cisplatin/pemetrexed chemotherapy alone
Concurrent chemoradiation followed by durvalumab (Correct answer)

Correct answer: Concurrent chemoradiation followed by durvalumab

For unresectable Stage III NSCLC, concurrent chemoradiation followed by consolidation durvalumab (PACIFIC trial) is the standard of care regardless of PD-L1 expression.

Question 128: A 55-year-old with severe aortic stenosis and LVEF 25% (low-flow, low-gradient AS) has a mean gradient of 28 mmHg and AVA 0.75 cm². Dobutamine stress echo shows mean gradient increases to 52 mmHg and AVA remains 0.75 cm². What does this indicate?

Low-gradient AS due to measurement error
True severe AS with contractile reserve—AVR is likely beneficial (Correct answer)
Absence of contractile reserve—AVR is contraindicated
Pseudo-severe AS—aortic valve is not truly stenotic

Correct answer: True severe AS with contractile reserve—AVR is likely beneficial

An increase in mean gradient >40 mmHg with stable low AVA on dobutamine stress echo confirms true severe AS with contractile reserve, indicating likely benefit from AVR despite low LVEF.

Question 129: A 61-year-old woman with a 25 pack-year smoking history (quit 8 years ago) undergoes low-dose CT lung cancer screening. The scan reveals a 7 mm pure ground-glass nodule (GGN) in the right upper lobe. No solid component is identified. Which of the following management strategies is most consistent with current Lung-RADS and Fleischner Society guidelines for this finding?

CT follow-up at 3 and 5 years; if stable, no further follow-up needed
PET-CT scan to evaluate metabolic activity, as GGNs >6 mm have significant malignant potential
Surgical resection given size >6 mm in a high-risk patient (former smoker)
CT follow-up at 6 months to assess for interval growth or development of a solid component (Correct answer)

Correct answer: CT follow-up at 6 months to assess for interval growth or development of a solid component

Per Fleischner Society 2017 guidelines for incidental pulmonary nodules and Lung-RADS 2022 for screening-detected nodules, a pure ground-glass nodule (GGN) of 7 mm in a screening patient (high-risk by definition) is categorized as Lung-RADS 3 (probable benign) and warrants 6-month CT follow-up. The rationale: pure GGNs grow slowly and represent adenocarcinoma spectrum lesions (AIS, MIA, or invasive adenocarcinoma). PET-CT (answer B) is inappropriate — pure GGNs are typically FDG-negative even when malignant due to their indolent metabolic activity, making PET non-diagnostic. Answer C (3 and 5 year follow-up) is appropriate for GGNs <6 mm in low-risk patients per Fleischner (or for GGNs ≥6 mm in low-risk patients per some protocols), but in a screening context with a 7 mm GGN, 6-month follow-up per Lung-RADS takes precedence. Answer D (surgical resection) is not indicated without evidence of growth or solid component development — pure GGNs have a protracted natural history and immediate resection would represent overtreatment.

Question 130: A 55-year-old man with idiopathic pulmonary fibrosis (IPF) has FVC 65% predicted and DLCO 48% predicted. Honeycombing is present on HRCT. Which medication has been shown to slow FVC decline in IPF?

Nintedanib 150 mg twice daily (Correct answer)
Azathioprine 150 mg/day
Prednisone 60 mg/day
N-acetylcysteine 600 mg three times daily

Correct answer: Nintedanib 150 mg twice daily

Nintedanib (and pirfenidone) are the only FDA-approved antifibrotic agents that slow FVC decline in IPF; corticosteroids and azathioprine increase mortality in IPF.

Question 131: A 38-year-old woman with systemic lupus erythematosus (SLE) presents with progressive exertional dyspnea. Right heart catheterization shows: mPAP 38 mmHg, PCWP 10 mmHg, PVR 5.2 Wood units, cardiac output 4.1 L/min. ANA is positive; anti-dsDNA and anti-cardiolipin antibodies are elevated. She has no interstitial lung disease on HRCT. She is started on disease-modifying therapy for SLE. Which additional management is MOST appropriate for her pulmonary hypertension?

Combination upfront therapy with an endothelin receptor antagonist plus a PDE-5 inhibitor (Correct answer)
High-dose calcium channel blocker therapy given positive vasoreactivity is expected in CTD-PAH
Initiation of chronic anticoagulation with warfarin targeting INR 2.5–3.5 as primary PAH therapy
Long-term systemic corticosteroids at immunosuppressive doses as the primary pulmonary vasodilator

Correct answer: Combination upfront therapy with an endothelin receptor antagonist plus a PDE-5 inhibitor

This patient has WHO Group 1 pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH, specifically SLE). Her hemodynamics confirm pre-capillary PH (PCWP ≤15 mmHg, elevated PVR >3 WU). Upfront combination therapy (ERA + PDE-5i, e.g., ambrisentan + tadalafil, proven in AMBITION trial) is the standard of care for intermediate-to-high risk PAH, which this patient meets given her hemodynamic profile. Anticoagulation in PAH-CTD (unlike idiopathic PAH) has not shown benefit and may increase bleeding risk, especially with anti-cardiolipin antibodies unless antiphospholipid syndrome with thrombosis exists. CCB therapy requires acute vasoreactivity testing (rare in CTD-PAH, <1% respond). Corticosteroids treat the SLE but are not vasodilators.

Question 132: A 32-year-old woman presents with a 9-month history of amenorrhea and milky breast discharge. Her serum prolactin level is 150 ng/mL (normal <25 ng/mL). An MRI of the pituitary reveals a 7 mm microadenoma. Visual field testing is normal. What is the most appropriate initial treatment for this condition?

Stereotactic radiosurgery
Transsphenoidal surgery
Cabergoline (Correct answer)
Observation with serial MRIs

Correct answer: Cabergoline

The patient has a symptomatic prolactin-secreting microadenoma (prolactinoma). The first-line treatment for virtually all prolactinomas, regardless of size, is medical therapy with a dopamine agonist. Cabergoline is generally preferred over bromocriptine due to its higher efficacy and better side-effect profile. Dopamine agonists are highly effective at normalizing prolactin levels, restoring gonadal function (and thus menses), and shrinking the tumor. Surgery is considered second-line for patients who are intolerant of or resistant to medical therapy. Observation is not appropriate for a symptomatic patient. Radiation is a third-line option for aggressive or refractory tumors.

Question 133: A 45-year-old woman develops acute respiratory distress syndrome (ARDS) after septic shock. P/F ratio is 95. Which ventilator strategy has the strongest mortality benefit?

High PEEP strategy with FiO2 titration only
Pressure-controlled ventilation targeting RR <12 breaths/min
Low tidal volume ventilation at 6 mL/kg IBW with plateau pressure <30 cmH2O (Correct answer)
High tidal volume ventilation at 10 mL/kg IBW

Correct answer: Low tidal volume ventilation at 6 mL/kg IBW with plateau pressure <30 cmH2O

The ARDSNet trial demonstrated that low tidal volume ventilation (6 mL/kg IBW) with plateau pressure <30 cmH2O reduces mortality by 22% compared to higher tidal volumes.

Question 134: A 35-year-old woman with diarrhea, bloating, and weight loss has anti-tissue transglutaminase IgA antibodies. Duodenal biopsy shows villous atrophy and crypt hyperplasia. What is the first-line treatment?

Prednisone
Gluten-free diet (Correct answer)
Azathioprine
Mesalamine

Correct answer: Gluten-free diet

Celiac disease is treated with strict adherence to a gluten-free diet, which leads to mucosal healing and resolution of symptoms in the majority of patients.

Question 135: A 47-year-old previously healthy man is admitted with 4 days of fever, myalgias, and progressive hypoxemia. CXR shows bilateral interstitial infiltrates. BAL reveals: negative bacterial cultures, negative Legionella/Pneumococcal urinary antigens, negative respiratory viral panel (influenza, RSV, parainfluenza, adenovirus), negative PCP DFA. CD4 count is 620 cells/µL. Serum β-D-glucan is 478 pg/mL (normal <60). BAL galactomannan index is 0.6 (normal <0.5). He has no known immunosuppression. The most likely diagnosis is:

Disseminated histoplasmosis
Invasive pulmonary aspergillosis (Correct answer)
Pneumocystis jirovecii pneumonia with false-negative DFA
Cryptogenic organizing pneumonia

Correct answer: Invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA) best explains this presentation. While classic IPA occurs in neutropenic hosts, it is well-recognized in non-classically immunocompromised patients, including those with viral pneumonias, ICU patients, and those with occult immune defects. The BAL galactomannan index ≥0.5 is highly specific for IPA in BAL (sensitivity ~70%, specificity ~90%). The elevated β-D-glucan (>80 pg/mL is significant; 478 is markedly elevated) further supports a fungal etiology. PCP DFA false negatives occur but would be unusual with a β-D-glucan this markedly elevated without PCP; moreover, the CD4 count of 620 makes PCP unlikely. Histoplasmosis would typically require urine/serum Histoplasma antigen and does not elevate galactomannan. COP is non-infectious and would not elevate these fungal biomarkers.

Question 136: A 44-year-old nonsmoking woman presents with progressive dyspnea and diffuse cystic lung disease on CT. She also has recurrent pneumothoraces and chylothorax. Serum VEGF-D is markedly elevated. What is the MOST likely diagnosis?

Lymphangioleiomyomatosis (LAM) (Correct answer)
Pulmonary Langerhans cell histiocytosis
Birt-Hogg-Dubé syndrome
Pulmonary emphysema

Correct answer: Lymphangioleiomyomatosis (LAM)

LAM presents in women of childbearing age with diffuse thin-walled cysts, chylothorax, recurrent pneumothorax, and markedly elevated serum VEGF-D (>800 pg/mL is diagnostic).

Question 137: When transitioning from IV insulin to subcutaneous insulin at the end of DKA treatment, what is the most important timing consideration?

Give subcutaneous long-acting insulin 2 hours before stopping IV insulin (Correct answer)
Stop IV insulin immediately when anion gap closes
Wait until the patient is eating a full meal before any subcutaneous dose
Overlap subcutaneous and IV insulin for 30 minutes only

Correct answer: Give subcutaneous long-acting insulin 2 hours before stopping IV insulin

Long-acting subcutaneous insulin should be administered at least 2 hours before stopping IV insulin to prevent recurrence of ketoacidosis due to insulin gap.

Question 138: A 35-year-old woman with Graves' disease and exophthalmos presents with palpitations and heat intolerance. TSH is suppressed and free T4 is markedly elevated. She desires rapid control of symptoms. Which agent provides the fastest symptomatic relief?

Propranolol (beta-blocker) (Correct answer)
Methimazole
Radioactive iodine
Thyroidectomy

Correct answer: Propranolol (beta-blocker)

Beta-blockers rapidly control adrenergic symptoms (palpitations, tremor, anxiety) of hyperthyroidism within hours, while antithyroid drugs take weeks to reduce hormone levels.

Question 139: A 49-year-old man with newly diagnosed hepatocellular carcinoma (HCC) has a single lesion measuring 3.8 cm in a cirrhotic liver (Child-Pugh A, ECOG 0). No vascular invasion or extrahepatic spread is seen on imaging. He is placed on the transplant waitlist (Milan criteria met). While awaiting transplant, locoregional therapy is being considered. Which statement best reflects current evidence regarding bridging therapy?

Thermal ablation (RFA/MWA) should not be used for lesions >3 cm because complete ablation is uniformly unachievable
Stereotactic body radiation therapy (SBRT) is contraindicated as bridging for HCC in cirrhosis due to high rates of radiation-induced liver disease
Bridging therapy is recommended to reduce dropout risk from waitlist progression, though no randomized trial has proven a post-transplant survival benefit over no bridging (Correct answer)
Transarterial chemoembolization (TACE) is the preferred bridging modality and has been shown in randomized trials to improve post-transplant survival compared to no treatment

Correct answer: Bridging therapy is recommended to reduce dropout risk from waitlist progression, though no randomized trial has proven a post-transplant survival benefit over no bridging

Bridging locoregional therapy (TACE, ablation, SBRT, Y-90) for HCC while awaiting transplant is widely recommended to prevent waitlist dropout due to tumor progression beyond Milan criteria. However, no randomized controlled trial has demonstrated a statistically significant improvement in post-transplant recurrence-free or overall survival compared to observation alone — the benefit is in reducing dropout, not necessarily improving post-transplant outcomes. SBRT is an accepted bridging modality in cirrhosis when technically appropriate. RFA/MWA can achieve complete ablation for lesions 3–5 cm, particularly with microwave technology, though rates are lower than for <3 cm lesions.

Question 140: A 58-year-old man with hypertension presents with sudden-onset tearing chest pain radiating to the back. BP is 180/100 in the right arm and 150/85 in the left arm. Which imaging study is most appropriate?

CT angiography of the chest (Correct answer)
Transthoracic echocardiogram
Coronary angiography
Ventilation-perfusion scan

Correct answer: CT angiography of the chest

CT angiography is the gold standard for diagnosing aortic dissection, which is suggested by the tearing pain and blood pressure differential between arms.

Question 141: What is the first-line treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD)?

Inhaled corticosteroids and beta-blockers
Antihistamines and nasal decongestants
Systemic corticosteroids and antibiotics (Correct answer)
Bronchodilators and leukotriene antagonists

Correct answer: Systemic corticosteroids and antibiotics

The first-line treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD) typically involves systemic corticosteroids and antibiotics. Corticosteroids reduce airway inflammation, while antibiotics are often prescribed to cover potential bacterial infections, which frequently trigger exacerbations. Bronchodilators are also crucial for symptom relief.

Question 142: Which of the following is an absolute contraindication to percutaneous mitral balloon commissurotomy (PMBC)?

Left atrial thrombus (Correct answer)
Mild mitral regurgitation (MR grade 1+)
Atrial fibrillation
Mild aortic regurgitation

Correct answer: Left atrial thrombus

Left atrial thrombus is an absolute contraindication to PMBC because balloon inflation risks thrombus embolization and stroke.

Question 143: A patient with long-standing Crohn's disease develops right lower quadrant pain and fever. CT shows a 4 cm fluid collection adjacent to the terminal ileum. What is the best next step?

IV antibiotics alone
Percutaneous drainage plus antibiotics (Correct answer)
Colonoscopy
Emergent surgery

Correct answer: Percutaneous drainage plus antibiotics

A walled-off abscess in Crohn's disease is best managed with percutaneous drainage plus antibiotics, avoiding emergent surgery and allowing inflammation to subside before elective resection if needed.

Question 144: A 30-year-old presents with crampy abdominal pain, bloody diarrhea, and fever after eating at a barbecue. Stool culture grows Shiga toxin-producing E. coli O157:H7. Which treatment should be avoided?

Electrolyte monitoring
Rest
Fluid replacement
Antibiotics (Correct answer)

Correct answer: Antibiotics

Antibiotics are contraindicated in STEC O157:H7 infection because they may increase Shiga toxin release, raising the risk of hemolytic uremic syndrome (HUS).

Question 145: A 52-year-old woman with primary biliary cholangitis (PBC) on ursodeoxycholic acid presents with pruritus, fatigue, and an alkaline phosphatase that remains 3× the upper limit of normal after 12 months of therapy. LFTs show ALT 55 U/L, bilirubin 1.1 mg/dL. Which second-line agent is most appropriate to add?

Fibrate (bezafibrate)
Obeticholic acid (Correct answer)
Rifampin
Cholestyramine

Correct answer: Obeticholic acid

Obeticholic acid (OCA), a farnesoid X receptor agonist, is FDA-approved as second-line therapy for PBC in patients with inadequate response to UDCA, defined as alkaline phosphatase ≥1.67× ULN and/or elevated bilirubin after 12 months. Cholestyramine and rifampin target pruritus symptomatically but do not alter disease progression. Fibrates (bezafibrate/fenofibrate) are used off-label in some European guidelines but are not FDA-approved for PBC. OCA is the guideline-endorsed add-on in this scenario.

Question 146: A 62-year-old woman is evaluated for recurrent bilateral pleural effusions. Thoracentesis reveals: protein 2.1 g/dL (serum 7.0 g/dL), LDH 88 U/L (serum LDH 210 U/L), glucose 88 mg/dL, pH 7.42, WBC 240 cells/µL (85% lymphocytes), triglycerides 210 mg/dL. Which of the following is the most likely diagnosis?

Chylothorax (Correct answer)
Lymphoma-associated exudative effusion
Hepatic hydrothorax
Yellow nail syndrome

Correct answer: Chylothorax

A pleural fluid triglyceride level >110 mg/dL is diagnostic of chylothorax, regardless of other parameters. This is the pathognomonic finding here. Hepatic hydrothorax is a transudate (low protein, low LDH by Light's criteria) not an exudate, and triglycerides would not be elevated. Lymphoma can cause exudative lymphocytic effusions but would not elevate triglycerides unless there is associated chylothorax from thoracic duct obstruction — in that case the etiology is still chylothorax. Yellow nail syndrome causes exudative effusions with lymphocytosis but does not cause elevated triglycerides. The triglyceride level of 210 mg/dL is the discriminating finding that makes chylothorax the definitive diagnosis.

Question 147: A 65-year-old man with a mechanical aortic valve develops fever, positive blood cultures for viridans streptococcus, and a new perivalvular abscess on TEE. What does the abscess finding indicate?

Outpatient antibiotic therapy is sufficient
Cardiac surgery consultation is required (Correct answer)
Repeat TEE in 2 weeks is the next step
Empiric switch to vancomycin is required

Correct answer: Cardiac surgery consultation is required

Perivalvular abscess is a class I indication for urgent cardiac surgery in prosthetic valve endocarditis, as medical therapy alone is insufficient.

Question 148: A 72-year-old woman has a resting heart rate of 38 bpm and ECG showing P waves with no relationship to QRS complexes, which are narrow at 60 bpm. She is asymptomatic. What is the most appropriate treatment?

Observation with Holter monitoring
Permanent pacemaker implantation (Correct answer)
Temporary transvenous pacing only
IV atropine immediately

Correct answer: Permanent pacemaker implantation

Complete (third-degree) AV block with an escape rhythm, even if asymptomatic, carries risk of syncope and sudden death and is a Class I indication for permanent pacemaker.

Question 149: A patient is found to have H. pylori infection on urea breath test after completing a PPI plus clarithromycin-based triple therapy. What is the best next step?

Repeat the same triple therapy regimen
Endoscopy with biopsy culture
Bismuth quadruple therapy (Correct answer)
Metronidazole monotherapy

Correct answer: Bismuth quadruple therapy

After failure of clarithromycin-based triple therapy, bismuth quadruple therapy (PPI + bismuth + tetracycline + metronidazole) is recommended as salvage treatment.

Question 150: A 61-year-old man with compensated cirrhosis (Child-Pugh A) due to NASH is found to have a 2.2 cm arterially enhancing hepatic lesion with washout on portal venous phase on contrast-enhanced MRI. He undergoes curative-intent resection. Three months post-resection, surveillance MRI shows a new 1.8 cm lesion in the contralateral lobe with identical enhancement pattern. Which statement regarding his candidacy for liver transplantation is most accurate?

Recurrence post-resection is an absolute contraindication to liver transplantation
He meets UCSF criteria and may be listed after demonstrating 6 months of stable disease
He can be downstaged with locoregional therapy and listed if within Milan criteria for ≥6 months (Correct answer)
He exceeds Milan criteria and should be referred for systemic therapy only

Correct answer: He can be downstaged with locoregional therapy and listed if within Milan criteria for ≥6 months

Post-resection HCC recurrence does NOT absolutely preclude transplantation. UNOS/OPTN policy supports downstaging of HCC outside Milan criteria using locoregional therapies (TACE, ablation, TARE). If the tumor burden is reduced to within Milan criteria (single lesion ≤5 cm, or up to 3 lesions each ≤3 cm) and maintained for ≥6 months with AFP response, patients can be listed. The new 1.8 cm lesion alone is within Milan and the prior resected lesion is no longer present — this patient may be evaluated for transplant after downstaging and disease stability confirmation. UCSF criteria (single ≤6.5 cm or ≤3 lesions with largest ≤4.5 cm and total ≤8 cm) are used by some centers but UNOS policy is based on Milan.

Question 151: A 50-year-old woman with systemic lupus erythematosus presents with dyspnea, elevated JVP, and an echocardiogram showing a thickened pericardium with respiratory variation in mitral inflow >25%. What is the diagnosis?

Constrictive pericarditis (Correct answer)
Pulmonary arterial hypertension
Dilated cardiomyopathy
Restrictive cardiomyopathy

Correct answer: Constrictive pericarditis

Constrictive pericarditis presents with elevated JVP, Kussmaul's sign, and exaggerated respiratory variation in Doppler inflow velocities, and is a known complication of SLE.

Question 152: A 44-year-old woman is found to have a serum calcium of 11.8 mg/dL on routine labs. PTH is 78 pg/mL (normal 15–65), PTHrP is undetectable, 25-OH vitamin D is 18 ng/mL, and 24-hour urine calcium is 95 mg/day (normal >200 mg/day for diagnosis of PHPT). Urine calcium-to-creatinine clearance ratio is 0.008. She is asymptomatic. What is the MOST likely diagnosis and appropriate next step?

Secondary hyperparathyroidism due to vitamin D deficiency; replete vitamin D
Familial hypocalciuric hypercalcemia; no treatment required, reassure and screen family members (Correct answer)
Primary hyperparathyroidism; refer for parathyroidectomy
Primary hyperparathyroidism; manage conservatively with bisphosphonates

Correct answer: Familial hypocalciuric hypercalcemia; no treatment required, reassure and screen family members

Familial hypocalciuric hypercalcemia (FHH) is characterized by mildly elevated calcium, inappropriately normal or elevated PTH, and — critically — low urine calcium excretion. The calcium-to-creatinine clearance ratio (CCCR) below 0.01 (especially <0.01) strongly favors FHH over primary hyperparathyroidism (PHPT), where the CCCR is typically >0.02. FHH results from an inactivating mutation in the calcium-sensing receptor (CaSR), causing the kidney and parathyroid to 'sense' a higher calcium setpoint. Surgery is not indicated and will not resolve the hypercalcemia. Bisphosphonates and vitamin D repletion are not appropriate for FHH. Genetic testing (CaSR mutation) can confirm the diagnosis.

Question 153: A 65-year-old man with bicuspid aortic valve has severe AR with LVEF 55% and LVESD 52 mm but no symptoms. What is the most appropriate management?

Surgical aortic valve replacement (Correct answer)
Percutaneous aortic valve replacement
Reassure and follow up in 2 years
Start beta-blocker therapy

Correct answer: Surgical aortic valve replacement

In severe AR, surgery is indicated when LVESD ≥50 mm (Class IIa) or ≥55 mm (Class I) even in asymptomatic patients to prevent irreversible LV dysfunction.

Question 154: A 45-year-old man is found to have WBC 90,000/μL with predominantly mature neutrophils and myelocytes, low leukocyte alkaline phosphatase score, and splenomegaly. BCR-ABL fusion gene is detected on PCR. What is the first-line treatment?

Imatinib (a BCR-ABL tyrosine kinase inhibitor) (Correct answer)
Allogeneic stem cell transplant upfront
Cytarabine and daunorubicin induction chemotherapy
Hydroxyurea alone

Correct answer: Imatinib (a BCR-ABL tyrosine kinase inhibitor)

CML driven by the BCR-ABL fusion (Philadelphia chromosome) is treated with BCR-ABL tyrosine kinase inhibitors such as imatinib as first-line therapy.

Question 155: A 65-year-old female is diagnosed with severe, symptomatic, degenerative mitral regurgitation (MR) and is referred for surgical evaluation. Her LVEF is 65% and left ventricular end-systolic dimension (LVESD) is 38 mm. Which of the following is the preferred surgical approach?

Mitral valve repair. (Correct answer)
Mitral valve replacement with a mechanical valve.
Mitral valve replacement with a bioprosthetic valve.
Transcatheter edge-to-edge repair (TEER).

Correct answer: Mitral valve repair.

For patients with severe primary mitral regurgitation who are symptomatic and have preserved left ventricular function, mitral valve repair is the preferred surgical technique over replacement when it is feasible and likely to be durable. Repair is associated with lower operative mortality, better preservation of postoperative LV function, and improved long-term survival compared to mitral valve replacement. Mechanical and bioprosthetic replacements are typically reserved for cases where repair is not possible. TEER is generally considered for patients who are at high or prohibitive surgical risk.

Question 156: A 39-year-old woman presents with progressive weight gain, hypertension, and new-onset diabetes. Laboratory evaluation confirms hypercortisolism (elevated UFC 3x ULN, failed 1 mg overnight DST). Morning plasma ACTH is 52 pg/mL (normal 7–63 pg/mL). MRI of the pituitary with gadolinium at a tertiary center shows no discrete lesion. What is the most appropriate next diagnostic step to localize the source of ACTH?

CT chest and abdomen to evaluate for ectopic ACTH-secreting tumor
CRH stimulation test with peripheral ACTH measurement
High-dose 8 mg overnight dexamethasone suppression test
Bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation (Correct answer)

Correct answer: Bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation

In ACTH-dependent Cushing's syndrome with a negative pituitary MRI, BIPSS is the gold standard for distinguishing Cushing's disease (pituitary source) from ectopic ACTH secretion. Up to 40–50% of pituitary corticotroph microadenomas are missed on MRI. BIPSS measures ACTH in the inferior petrosal sinuses (draining the pituitary) versus a peripheral vein; a central-to-peripheral gradient ≥2.0 at baseline or ≥3.0 after CRH stimulation localizes to the pituitary with >95% sensitivity and specificity. High-dose DST and CRH stimulation testing have insufficient discriminatory power when MRI is non-diagnostic.

Question 157: A 72-year-old woman undergoes right heart catheterization. Results: RA 8 mmHg, RV 42/10 mmHg, PA 42/22 mmHg (mean 30 mmHg), PCWP 18 mmHg, cardiac output 4.2 L/min. What is the pulmonary vascular resistance (PVR) and the correct classification of her pulmonary hypertension?

PVR ≈ 1.4 Wood units; normal pulmonary hemodynamics
PVR ≈ 2.9 Wood units; isolated post-capillary pulmonary hypertension
PVR ≈ 5.7 Wood units; pre-capillary pulmonary hypertension
PVR ≈ 2.9 Wood units; combined pre- and post-capillary pulmonary hypertension (Correct answer)

Correct answer: PVR ≈ 2.9 Wood units; combined pre- and post-capillary pulmonary hypertension

PVR = (mean PA pressure − PCWP) / CO = (30 − 18) / 4.2 ≈ 2.86 Wood units. A PVR ≥ 3 Wood units defines a pre-capillary component. Her PCWP of 18 mmHg (>15 mmHg) indicates post-capillary hypertension (elevated left-sided filling pressures). However, the diastolic pressure gradient (DPG = diastolic PA pressure − PCWP = 22 − 18 = 4 mmHg; <7 mmHg) and a PVR just below 3 WU place her at the borderline. By updated ESC/ERS 2022 criteria, PH with mPAP >20 mmHg, PCWP >15 mmHg, and PVR ≥2 WU classifies as combined pre- and post-capillary PH (CpcPH), reflecting intrinsic pulmonary vascular remodeling on top of left heart disease.

Question 158: Which of the following patients with severe aortic stenosis requires concurrent coronary artery bypass grafting (CABG) at the time of surgical AVR?

Patient with coronary stenosis of 70% in the LAD (Correct answer)
Patient with coronary stenosis of 30% in RCA
Patient with prior PCI with drug-eluting stent 2 months ago
Patient with coronary calcium score of 300

Correct answer: Patient with coronary stenosis of 70% in the LAD

Concomitant CABG is recommended for significant CAD (≥70% stenosis in major coronary arteries) at the time of AVR to reduce perioperative MI risk.

Question 159: A 29-year-old woman with Crohn's disease on azathioprine and adalimumab presents with 3 weeks of right upper quadrant pain. Labs show ALT 340 U/L, AST 290 U/L, ALP 188 U/L, total bilirubin 2.1 mg/dL. She is ANA positive (1:160), anti-smooth muscle antibody negative, serum IgG 2,100 mg/dL (ULN 1,700). Liver biopsy shows interface hepatitis with lymphoplasmacytic infiltrate, rosette formation, and emperipolesis. Which statement about her diagnosis and management is most accurate?

Her histology confirms AIH type 1; azathioprine can serve dual purpose as immunosuppression for both IBD and AIH after steroid induction
This is de novo autoimmune hepatitis (AIH) associated with TNF-α inhibitor therapy; steroids should be initiated and adalimumab discontinued (Correct answer)
Azathioprine is the most likely causative agent and should be stopped; liver biopsy alone cannot distinguish drug-induced liver injury from AIH
This represents adalimumab-induced drug hepatotoxicity and the biologic should be stopped immediately

Correct answer: This is de novo autoimmune hepatitis (AIH) associated with TNF-α inhibitor therapy; steroids should be initiated and adalimumab discontinued

De novo autoimmune hepatitis (AIH) is a well-documented immune-mediated adverse effect of TNF-α inhibitors (adalimumab, infliximab, etanercept). It presents with AIH histology (interface hepatitis, rosettes, emperipolesis), positive ANA, elevated IgG, and often ASMA negative — mimicking classic AIH type 1. Management requires discontinuation of the offending TNF inhibitor AND initiation of corticosteroids (prednisone ± azathioprine). Simply stopping the drug without immunosuppression often leads to incomplete resolution. Azathioprine can cause hepatotoxicity (nodular regenerative hyperplasia, peliosis hepatis) but not this histologic pattern. While azathioprine can treat AIH, the TNF inhibitor must be stopped given its likely causative role, and an alternative biologic for IBD (e.g., vedolizumab or ustekinumab) should be considered.

Question 160: A 72-year-old man with CKD stage 3 and a porcine aortic valve replacement (6 years ago) is diagnosed with Enterococcus faecalis endocarditis (blood cultures, 4/4 bottles positive). MIC of ampicillin is 0.25 µg/mL; gentamicin MIC is 500 µg/mL (high-level aminoglycoside resistance, HLAR); no beta-lactamase detected. What is the MOST appropriate antibiotic regimen?

Daptomycin monotherapy for 6 weeks
Vancomycin plus gentamicin for 6 weeks
Ampicillin plus gentamicin for 4–6 weeks
Ampicillin plus ceftriaxone for 6 weeks (Correct answer)

Correct answer: Ampicillin plus ceftriaxone for 6 weeks

This is a pivotal nuance: the organism has high-level aminoglycoside resistance (HLAR, defined as gentamicin MIC ≥500 µg/mL), which abolishes the synergistic bactericidal effect of ampicillin-aminoglycoside. In HLAR enterococcal endocarditis, the recommended regimen is ampicillin plus ceftriaxone (double beta-lactam therapy), which achieves synergy via saturation of different penicillin-binding proteins. This is particularly important in patients with CKD where aminoglycosides pose nephrotoxicity risk. Vancomycin (choice C) is inappropriate because the organism is ampicillin-susceptible. Daptomycin monotherapy (choice D) is not guideline-endorsed as sole therapy for endocarditis.

Question 161: A 72-year-old woman presents with acute onset of bright red blood per rectum, crampy left lower quadrant pain, and tenesmus without systemic symptoms. CT shows segmental colonic wall thickening at the splenic flexure. What is the most likely diagnosis?

Ulcerative colitis flare
Diverticular hemorrhage
Ischemic colitis (Correct answer)
Colorectal cancer

Correct answer: Ischemic colitis

Ischemic colitis classically affects watershed areas like the splenic flexure in older patients and presents with acute crampy pain and bloody diarrhea; segmental distribution on CT is characteristic.

Question 162: A 29-year-old woman presents with recurrent episodes of severe epigastric pain, nausea, and elevated lipase (peak 1,800 U/L) over the past 2 years. She has no gallstones, drinks no alcohol, takes no medications, and has normal triglycerides. Genetic testing reveals a heterozygous SPINK1 N34S variant and a heterozygous CFTR F508del variant. MRCP is normal. What is the pathophysiologic basis for her recurrent pancreatitis?

CFTR mutations alone cause ductal obstruction sufficient to trigger recurrent acute pancreatitis
Compound heterozygosity creates a threshold effect that overwhelms pancreatic trypsin inhibitor capacity (Correct answer)
SPINK1 mutations directly activate trypsinogen, triggering autodigestion
The CFTR F508del variant causes exocrine pancreatic insufficiency that secondarily activates inflammatory cascades

Correct answer: Compound heterozygosity creates a threshold effect that overwhelms pancreatic trypsin inhibitor capacity

SPINK1 encodes the pancreatic secretory trypsin inhibitor (PSTI), which serves as a fail-safe by inhibiting prematurely activated trypsin. The N34S variant reduces PSTI inhibitory capacity but alone is insufficient to cause disease (present in ~2% of the general population). CFTR mutations impair ductal bicarbonate secretion and fluid flow, increasing pancreatic juice viscosity and acinar cell stress. The combination (compound heterozygosity) creates a threshold effect: each variant independently provides a modest susceptibility, but together they overwhelm compensatory mechanisms — a 'two-hit' model. SPINK1 does not directly activate trypsinogen; it inhibits trypsin. CFTR mutations alone rarely cause recurrent acute pancreatitis without additional modifiers. F508del does cause exocrine insufficiency in cystic fibrosis, but this is not the mechanism driving acute pancreatitis.

Question 163: A 55-year-old man has serum calcium of 11.4 mg/dL, PTH of 95 pg/mL (normal 15–65), and normal renal function. Urine calcium-to-creatinine clearance ratio is 0.005. What is the most likely diagnosis?

Familial hypocalciuric hypercalcemia (Correct answer)
Malignancy-associated hypercalcemia
Vitamin D toxicity
Primary hyperparathyroidism

Correct answer: Familial hypocalciuric hypercalcemia

A urine calcium-to-creatinine clearance ratio <0.01 with hypercalcemia and elevated PTH indicates familial hypocalciuric hypercalcemia (FHH), not primary hyperparathyroidism.

Question 164: A 45-year-old woman with longstanding Raynaud's phenomenon develops progressive skin tightening extending above the elbows, dysphagia, and pulmonary hypertension. Which antibody is MOST closely associated with this presentation?

Anti-dsDNA
Anti-centromere antibody
Anti-topoisomerase I (Anti-Scl-70) (Correct answer)
Anti-U1 RNP

Correct answer: Anti-topoisomerase I (Anti-Scl-70)

Anti-Scl-70 (anti-topoisomerase I) is associated with diffuse cutaneous systemic sclerosis, which involves skin thickening proximal to the elbows and carries a higher risk of interstitial lung disease and pulmonary hypertension. Anti-centromere is associated with limited cutaneous SSc (CREST). Anti-U1 RNP is associated with mixed connective tissue disease. Anti-dsDNA is specific for SLE.

Question 165: A 58-year-old male with a bicuspid aortic valve is found to have severe chronic aortic regurgitation (AR) on a routine echocardiogram. He is completely asymptomatic. His LVEF is 52% and his LV end-diastolic dimension is 72 mm. Blood pressure is 130/50 mmHg. According to the most recent guidelines, which of the following is the strongest indication for aortic valve replacement in this patient?

The left ventricular ejection fraction. (Correct answer)
The presence of a bicuspid aortic valve.
The severe degree of regurgitation.
The wide pulse pressure.

Correct answer: The left ventricular ejection fraction.

The 2020 ACC/AHA guidelines lowered the threshold for intervention in asymptomatic severe aortic regurgitation. Aortic valve replacement is recommended for asymptomatic patients with severe AR if the LVEF is 55% or less. This patient's LVEF is 52%, which is a clear indication for surgery to prevent irreversible left ventricular dysfunction. While the bicuspid valve is the etiology and the wide pulse pressure is a physical finding, the LVEF is the key parameter guiding the timing of intervention in this asymptomatic patient.

Question 166: A 45-year-old man presents with acute oliguric kidney injury, hemoptysis, and pANCA positivity. Kidney biopsy shows pauci-immune crescentic glomerulonephritis. What is the most appropriate induction therapy?

High-dose glucocorticoids plus cyclophosphamide or rituximab (Correct answer)
Plasmapheresis alone
Rituximab alone
Mycophenolate mofetil plus prednisone

Correct answer: High-dose glucocorticoids plus cyclophosphamide or rituximab

ANCA-associated vasculitis with rapidly progressive GN requires induction with high-dose glucocorticoids combined with either cyclophosphamide or rituximab.

Question 167: A 55-year-old man with no prior GI history has a positive fecal immunochemical test (FIT). What is the most appropriate next step?

Flexible sigmoidoscopy
Repeat FIT in 1 year
CT colonography
Colonoscopy (Correct answer)

Correct answer: Colonoscopy

A positive FIT requires diagnostic colonoscopy to evaluate for colorectal cancer or adenomatous polyps; no alternative testing is appropriate after a positive non-invasive screen.

Question 168: A 72-year-old man with systolic heart failure (EF 30%) and LBBB (QRS 158 ms) undergoes CRT-D implantation. Six months later, he remains persistently symptomatic and repeat echo shows EF 32%. Device interrogation confirms >98% biventricular pacing. Which of the following is the most likely explanation for non-response?

True electrical non-responder due to extensive scar burden (Correct answer)
Suboptimal AV delay programming
Lead dislodgement causing loss of left ventricular capture
Inadequate rate control causing tachycardia-mediated cardiomyopathy

Correct answer: True electrical non-responder due to extensive scar burden

Approximately 30% of patients who receive CRT are non-responders. When biventricular pacing is confirmed at >98% and AV/VV intervals are optimized, persistent non-response most often reflects extensive myocardial fibrosis or scar burden (commonly from prior MI) that prevents mechanical resynchronization despite electrical correction. Lead dislodgement would reduce pacing percentages. AV delay optimization is a consideration but is less likely when pacing percentages are adequate. Tachycardia-mediated cardiomyopathy would require uncontrolled rapid rates, which are not suggested here.

Question 169: A 27-year-old previously healthy man is referred for evaluation of recurrent gross hematuria that occurs 1–2 days after upper respiratory infections. Urinalysis shows 3+ blood and 2+ protein. Serum creatinine is 1.3 mg/dL. C3, C4, ANA, ANCA, and anti-GBM antibodies are all normal. Kidney biopsy shows IgA-dominant mesangial deposits with Oxford MEST-C score M1E1S0T0C0. Which of the following best predicts his long-term renal prognosis, and what does current evidence suggest regarding treatment?

S score (segmental sclerosis) is the strongest predictor of GFR decline; if UACR >1 g/g despite maximum RAS blockade, targeted-release budesonide (Tarpeyo) reduces proteinuria and slows progression (Correct answer)
E score (endocapillary proliferation) alone determines prognosis; tonsillectomy has Level I evidence for reducing recurrences globally
M score (mesangial hypercellularity) is the strongest Oxford predictor; cyclophosphamide plus corticosteroids are first-line regardless of proteinuria level
T score (tubular atrophy) is the dominant predictor; fish oil (omega-3) has strong RCT evidence supporting its use as primary immunosuppression

Correct answer: S score (segmental sclerosis) is the strongest predictor of GFR decline; if UACR >1 g/g despite maximum RAS blockade, targeted-release budesonide (Tarpeyo) reduces proteinuria and slows progression

In the Oxford MEST-C classification, the T score (tubular atrophy/interstitial fibrosis) is classically the strongest predictor of long-term GFR decline and ESKD risk, but among the answer choices, S (segmental sclerosis) and T together are the dominant MEST variables. The Oxford Validation study confirmed T and S as independent predictors. Regarding treatment, targeted-release budesonide (Nefecon/Tarpeyo) was FDA-approved in 2021 based on the NefIgArd trial, showing significant reduction in proteinuria and 24-week eGFR preservation in patients with persistent proteinuria ≥1 g/day on maximized RAS blockade. Cyclophosphamide is not standard first-line; tonsillectomy has weak evidence outside Japan; fish oil trials (STOP-IgAN, etc.) have not shown benefit as primary therapy.

Question 170: A 72-year-old man undergoes TAVR for severe calcific aortic stenosis. Post-procedure TEE shows a small, eccentric paravalvular leak (PVL) graded as mild-to-moderate. His 30-day echocardiogram shows the PVL is unchanged. He remains mildly symptomatic with dyspnea on exertion. Which statement about his prognosis and management is most accurate?

Mild-to-moderate PVL after TAVR is associated with increased mortality and warrants consideration of repeat intervention if symptoms persist (Correct answer)
Mild PVL is a benign finding after TAVR and requires no further follow-up beyond standard annual echo
PVL after TAVR always resolves within 6 months as the valve fully expands into the annulus
Medical management with diuretics and ACE inhibitors eliminates the excess mortality risk associated with PVL

Correct answer: Mild-to-moderate PVL after TAVR is associated with increased mortality and warrants consideration of repeat intervention if symptoms persist

Even mild-to-moderate paravalvular leak (PVL) after TAVR is independently associated with increased short- and long-term mortality — a finding replicated across multiple large registries including PARTNER and CoreValve trials. Unlike surgical AVR PVL, transcatheter PVL may partially reduce with valve expansion, but moderate or greater PVL rarely resolves fully. Symptomatic patients with ≥mild-moderate PVL should be evaluated for re-dilation (post-dilatation), valve-in-valve TAVR, or surgical correction. Medical optimization alone does not abolish the mortality risk conferred by significant residual PVL.

Question 171: A 52-year-old woman with primary biliary cholangitis (PBC) on ursodeoxycholic acid presents with worsening pruritus, fatigue, and a rising alkaline phosphatase despite 12 months of therapy. Her ALP remains >1.67× the upper limit of normal. Which second-line agent has demonstrated reduction in ALP and improved transplant-free survival in this setting?

Obeticholic acid (Correct answer)
Rifampin
Bezafibrate
Cholestyramine

Correct answer: Obeticholic acid

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, is FDA-approved as second-line therapy in PBC for patients with inadequate response to UDCA. In the POISE trial, OCA significantly reduced ALP and total bilirubin, and long-term data suggest improved transplant-free survival. Cholestyramine treats pruritus but does not alter disease progression. Rifampin is used off-label for pruritus only. Bezafibrate (a PPAR agonist) shows promise and is approved in some countries but is not FDA-approved for this indication.

Question 172: What is the first-line treatment for type 2 diabetes mellitus?

Insulin
Sulfonylureas
DPP-4 inhibitors
Metformin (Correct answer)

Correct answer: Metformin

Metformin is the recommended first-line treatment for most patients with type 2 diabetes mellitus, alongside lifestyle modifications. It works by decreasing hepatic glucose production and improving insulin sensitivity in peripheral tissues. Metformin is effective, generally well-tolerated, and has a favorable safety profile.

Question 173: A 55-year-old man with a St. Jude mechanical mitral valve prosthesis on warfarin (INR target 2.5–3.5) requires elective cholecystectomy. His current INR is 3.1. What is the most appropriate perioperative anticoagulation strategy?

Bridge with low-molecular-weight heparin after stopping warfarin 5 days preoperatively
Stop warfarin 5 days preoperatively with no bridging; restart immediately postoperatively
Bridge with unfractionated heparin infusion after stopping warfarin 5 days preoperatively (Correct answer)
Continue warfarin with no interruption if INR is within therapeutic range

Correct answer: Bridge with unfractionated heparin infusion after stopping warfarin 5 days preoperatively

Mechanical mitral valve prostheses carry a high thromboembolic risk (Class I indication for bridging per ACC/AHA). Unlike mechanical aortic valves in low-risk patients, mechanical mitral valves require bridging anticoagulation when warfarin must be interrupted. The preferred bridging agent is intravenous unfractionated heparin (UFH) in the inpatient setting, particularly for high-risk valves, because UFH can be rapidly reversed with protamine and has more predictable pharmacokinetics in the perioperative period. LMWH is an alternative but is less preferred for mechanical mitral valves given limited data and inability to rapidly reverse. Continuing full anticoagulation through surgery increases bleeding risk and is inappropriate for most elective surgeries.

Question 174: A 70-year-old man with osteoporosis has a T-score of −3.1 at the hip. He has been on alendronate for 7 years. He now reports right thigh pain and X-ray shows cortical thickening of the subtrochanteric femur. What is the best next step?

Switch to denosumab
Discontinue bisphosphonate and consider teriparatide (Correct answer)
Continue alendronate and add calcium/vitamin D
Refer for prophylactic hip nailing

Correct answer: Discontinue bisphosphonate and consider teriparatide

Atypical femoral fractures are a recognized complication of prolonged bisphosphonate use; the drug should be discontinued and anabolic therapy with teriparatide may promote healing.

Question 175: A 28-year-old woman develops urticaria, angioedema, bronchospasm, and hypotension within 15 minutes of receiving amoxicillin. Which of the following is the MOST critical immediate intervention?

Methylprednisolone 125 mg IV
Epinephrine 0.3–0.5 mg IM into the anterolateral thigh (Correct answer)
Albuterol inhaler for bronchospasm
Diphenhydramine 50 mg IV

Correct answer: Epinephrine 0.3–0.5 mg IM into the anterolateral thigh

Epinephrine IM is the drug of choice for anaphylaxis and must be given immediately — it is the only agent that addresses the life-threatening cardiovascular and respiratory components. Antihistamines and corticosteroids are adjuncts and are never substitutes for epinephrine. Albuterol addresses bronchospasm but not the systemic reaction. Delay in epinephrine administration is the leading cause of anaphylaxis fatality.

Question 176: A 72-year-old woman is admitted with confusion and fatigue. Labs: Na 118 mEq/L, K 3.8 mEq/L, BUN 8 mg/dL, creatinine 0.7 mg/dL, serum osmolality 248 mOsm/kg, urine osmolality 520 mOsm/kg, urine Na 68 mEq/L. She takes escitalopram and hydrochlorothiazide. Thyroid and cortisol are normal. She has no edema and appears euvolemic. Which feature would MOST reliably distinguish SIADH from the cerebral salt-wasting syndrome (CSWS) as the etiology?

Urine osmolality greater than serum osmolality
Serum uric acid level less than 4 mg/dL
Urine sodium concentration greater than 40 mEq/L
Clinical assessment of extracellular fluid (ECF) volume status (Correct answer)

Correct answer: Clinical assessment of extracellular fluid (ECF) volume status

The definitive distinguishing feature between SIADH and CSWS is extracellular fluid (ECF) volume status: SIADH is characterized by normal-to-expanded ECF (euvolemic or mildly hypervolemic), whereas CSWS is a salt-wasting nephropathy leading to true hypovolemia with volume depletion. Both conditions share elevated urine sodium (>40 mEq/L), urine osmolality > serum osmolality, and even low serum uric acid (both cause fractional uric acid excretion >12%). In CSWS, fluid restriction (SIADH treatment) worsens the condition, while volume and sodium replacement is correct. In practice, CVP measurement or careful clinical volume assessment (orthostatic BP, skin turgor, mucous membranes, weight trend) is the key differentiator. This distinction is critical because CSWS commonly occurs after subarachnoid hemorrhage.

Question 177: During management of a patient with massive hemoptysis (>600 mL/24 hrs) due to a right-sided cavitary lesion, the patient is intubated with a standard ETT and placed in the lateral decubitus position. After initial bronchoscopy confirms bleeding from the right upper lobe, the patient becomes hypoxic (SpO2 72%) and hemodynamic status deteriorates. Which of the following interventions is most immediately appropriate to stabilize oxygenation?

Insert a bronchial blocker into the right mainstem bronchus via the current ETT
Initiate veno-venous ECMO for refractory hypoxemia
Advance the ETT into the left mainstem bronchus to isolate and protect the non-bleeding lung (Correct answer)
Place a rigid bronchoscope and apply endobronchial tamponade to the right upper lobe

Correct answer: Advance the ETT into the left mainstem bronchus to isolate and protect the non-bleeding lung

In the acute setting of massive hemoptysis with hemodynamic compromise and severe hypoxemia, the most immediately life-saving maneuver is isolation of the non-bleeding (left) lung by advancing the ETT into the left mainstem bronchus. This prevents aspiration of blood into the good lung and allows oxygenation to continue from the unaffected side. A bronchial blocker (option D) is also a valid approach but requires bronchoscopic guidance and takes more time to position correctly — advancing the ETT into the left mainstem can be done rapidly and blindly in extremis. Rigid bronchoscopy with tamponade is an excellent definitive intervention but requires additional setup time and personnel. VV-ECMO is not appropriate as the first-line emergency maneuver when simpler airway maneuvers can rapidly restore oxygenation.

Question 178: A 58-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) presents with worsening exertional syncope. Echo shows a resting LVOT gradient of 55 mmHg. He is already on metoprolol 200 mg/day. Which of the following interventions is MOST appropriate at this stage?

Add disopyramide to his current regimen (Correct answer)
Initiate digoxin to improve cardiac output
Add a low-dose loop diuretic to reduce preload
Start verapamil and discontinue metoprolol

Correct answer: Add disopyramide to his current regimen

Disopyramide is a class IA antiarrhythmic with strong negative inotropic properties that reduces LVOT obstruction in HOCM. When a maximally tolerated beta-blocker fails to adequately control symptoms or LVOT gradient, adding disopyramide is the preferred pharmacologic escalation before considering invasive therapies (septal myectomy or alcohol septal ablation). Verapamil is an alternative to beta-blockers but should not be combined with them due to risk of heart block and hypotension. Digoxin is contraindicated in HOCM as it increases inotropy, worsening obstruction. Diuretics reduce preload and can dangerously worsen obstruction in HOCM.

Question 179: A 52-year-old man with diabetes presents with serum creatinine rising from 1.0 to 1.8 mg/dL after starting lisinopril. Renal artery duplex shows elevated resistive indices bilaterally with post-stenotic turbulence. What should be done?

Discontinue lisinopril and pursue further imaging to assess for bilateral renal artery stenosis (Correct answer)
Add amlodipine and continue lisinopril
Discontinue lisinopril and arrange renal artery stenting urgently
Continue lisinopril at reduced dose and recheck creatinine in 2 weeks

Correct answer: Discontinue lisinopril and pursue further imaging to assess for bilateral renal artery stenosis

A >30% rise in creatinine after ACE inhibitor initiation suggests bilateral renal artery stenosis or stenosis in a solitary kidney; ACE inhibitor should be stopped and vascular imaging pursued.

Question 180: A 58-year-old man with HIV (CD4 count 45 cells/µL, viral load 120,000 copies/mL) presents with 3 weeks of progressive headache and altered mentation. CSF analysis shows: opening pressure 28 cmH₂O, WBC 8 cells/µL (lymphocytes), glucose 42 mg/dL (serum 90 mg/dL), protein 65 mg/dL, India ink positive. Cryptococcal antigen titer is 1:2048. After starting liposomal amphotericin B plus flucytosine, what is the MOST critical monitoring parameter during the first two weeks of induction therapy?

Serial CSF opening pressures via therapeutic lumbar punctures (Correct answer)
Renal function and electrolytes for amphotericin B nephrotoxicity
Weekly serum cryptococcal antigen titers
Daily CBC to monitor flucytosine-induced bone marrow suppression

Correct answer: Serial CSF opening pressures via therapeutic lumbar punctures

Elevated intracranial pressure (ICP) is the leading cause of early morbidity and mortality in cryptococcal meningitis. The IDSA guidelines mandate serial therapeutic lumbar punctures to maintain opening pressure below 20 cmH₂O; failure to manage ICP aggressively causes blindness, herniation, and death. While amphotericin B nephrotoxicity (choice D) is important and monitored, and flucytosine-related myelosuppression (choice C) is relevant, neither is the 'most critical' determinant of early outcome. Serum CrAg titers (choice B) are not useful for short-term monitoring.

Question 181: A 29-year-old man with no significant medical history presents with a 2-day history of fever (39.2°C), sore throat, and diffuse maculopapular rash involving the palms and soles. He has painless, shallow oral ulcers and painless bilateral inguinal lymphadenopathy. RPR is reactive at 1:128; FTA-ABS is positive. He reports unprotected receptive anal intercourse 6 weeks ago with a new male partner. He denies HIV-risk factors but HIV-1/2 antigen/antibody combination assay returns positive. HIV-1 RNA PCR returns at 1,200,000 copies/mL with CD4 count pending. What is the MOST appropriate next step?

Treat syphilis with benzathine penicillin G 2.4 million units IM × 3 doses (weekly) and defer ART for 2 weeks
Treat syphilis with benzathine penicillin G 2.4 million units IM × 1 dose and initiate ART immediately (Correct answer)
Initiate ART immediately and defer syphilis treatment pending neurosyphilis evaluation
Perform LP to rule out neurosyphilis before initiating any treatment

Correct answer: Treat syphilis with benzathine penicillin G 2.4 million units IM × 1 dose and initiate ART immediately

This presentation is classic for secondary syphilis (palmoplantar rash, mucous patches, lymphadenopathy) occurring during acute HIV infection (high viral load, acute retroviral syndrome symptoms overlap). Secondary syphilis without neurologic symptoms is treated with benzathine penicillin G 2.4 million units IM as a single dose — not 3 doses (which is reserved for latent syphilis >1 year duration or unknown duration). LP for neurosyphilis is not required unless neurologic or ocular symptoms are present. Current guidelines (DHHS, IDSA) strongly recommend immediate ART initiation regardless of CD4 count, including during acute HIV infection, due to benefits in reducing reservoir establishment, transmission, and inflammation. Deferring ART is not indicated.

Question 182: Which of the following is the most appropriate insulin regimen for mild DKA (pH 7.25-7.30, patient alert and tolerating oral intake)?

Subcutaneous rapid-acting insulin only (Correct answer)
IV insulin infusion at 0.1 units/kg/hr
No insulin; treat with IV fluids alone
Subcutaneous basal-bolus insulin regimen

Correct answer: Subcutaneous rapid-acting insulin only

Mild DKA in a patient able to eat can be managed with subcutaneous rapid-acting insulin alone rather than IV infusion, per ADA guidelines.

Question 183: A 22-year-old college student presents with fever, pharyngitis, cervical lymphadenopathy, and splenomegaly. Heterophile antibody test is positive. Which complication requires activity restriction?

Airway obstruction
Splenic rupture risk (Correct answer)
Hepatitis
Thrombocytopenia

Correct answer: Splenic rupture risk

Splenic rupture is a rare but life-threatening complication of infectious mononucleosis; patients should avoid contact sports and strenuous activity for at least 3-4 weeks.

Question 184: A 28-year-old woman is referred for evaluation of amenorrhea and galactorrhea. Serum prolactin is 340 ng/mL. MRI shows a 9 mm pituitary lesion. She desires pregnancy in the next year. She is started on cabergoline 0.5 mg twice weekly. After 6 months, prolactin normalizes and the lesion shrinks to 4 mm. She now asks about stopping cabergoline prior to conception. What is the most appropriate recommendation?

Continue cabergoline throughout pregnancy to prevent tumor regrowth
Obtain visual field testing monthly during pregnancy regardless of lesion size
Stop cabergoline once pregnancy is confirmed, as tumor enlargement risk is low with microadenoma (Correct answer)
Switch to bromocriptine before conception since it has a longer safety record in pregnancy

Correct answer: Stop cabergoline once pregnancy is confirmed, as tumor enlargement risk is low with microadenoma

For prolactinoma microadenomas (<10 mm), the risk of clinically significant tumor enlargement during pregnancy is very low (~2-3%). The standard approach is to discontinue dopamine agonist therapy once pregnancy is confirmed, as cabergoline's safety data in first-trimester exposure is reassuring but not as extensive as bromocriptine. Importantly, cabergoline should be stopped — not continued — during pregnancy in microadenoma patients. Monthly visual fields are unnecessary for microadenomas; surveillance is reserved for macroadenomas. Switching to bromocriptine before conception is a valid historical approach but is not mandatory — cabergoline is acceptable and has sufficient safety data in early pregnancy.

Question 185: A 67-year-old renal transplant recipient on tacrolimus develops culture-confirmed Candida glabrata fungemia. He is hemodynamically stable with no ophthalmologic involvement. Susceptibility testing shows elevated MIC to fluconazole (MIC 16 µg/mL). Which is the most appropriate definitive antifungal strategy?

Voriconazole due to its superior bioavailability over echinocandins
Amphotericin B liposomal formulation to avoid echinocandin resistance
High-dose fluconazole (800 mg/day) given stable clinical status
Micafungin for a minimum of 14 days after last positive blood culture (Correct answer)

Correct answer: Micafungin for a minimum of 14 days after last positive blood culture

Candida glabrata (now reclassified as Nakaseomyces glabrata) frequently demonstrates reduced fluconazole susceptibility, with MIC ≥8 µg/mL classified as dose-dependent susceptible or resistant. Echinocandins (micafungin, anidulafungin, caspofungin) are first-line for C. glabrata candidemia per IDSA guidelines. Duration is at minimum 14 days from the first negative blood culture in non-neutropenic patients. Fluconazole at high dose is inappropriate for an MIC of 16 µg/mL (resistant by EUCAST criteria). Voriconazole is not preferred for Candida candidemia and has significant interactions with tacrolimus. Amphotericin B carries nephrotoxicity risk especially in a transplant patient and is reserved for refractory cases.

Question 186: A 61-year-old man with type 2 diabetes and an eGFR of 28 mL/min/1.73m² presents for medication review. His HbA1c is 8.9%. Current medications include metformin 1000 mg BID, glipizide 10 mg BID, and linagliptin 5 mg daily. His blood pressure is 148/92 mmHg and urine albumin-to-creatinine ratio is 620 mg/g. Which change to his diabetes regimen has the strongest evidence for reducing risk of kidney disease progression at this stage?

Continue current regimen; add empagliflozin 10 mg daily given its EMPA-REG outcomes benefit
Discontinue metformin and glipizide; initiate a GLP-1 receptor agonist with demonstrated nephroprotective outcomes data
Discontinue metformin and linagliptin; initiate an SGLT2 inhibitor titrated to the lowest approved dose for kidney protection (Correct answer)
Discontinue metformin; add finerenone to the existing regimen

Correct answer: Discontinue metformin and linagliptin; initiate an SGLT2 inhibitor titrated to the lowest approved dose for kidney protection

At eGFR 28, metformin is contraindicated (hold at eGFR < 30) due to lactic acidosis risk. SGLT2 inhibitors — specifically canagliflozin (CREDENCE, eGFR ≥ 20) and dapagliflozin (DAPA-CKD, eGFR ≥ 25) — have robust RCT evidence for reducing CKD progression, cardiovascular events, and ESKD in patients with diabetic kidney disease and elevated albuminuria, and can be used at reduced eGFR (down to ~20–25) primarily for kidney protection even when glycemic effect is minimal. Linagliptin should be discontinued if an SGLT2 inhibitor is added to avoid therapeutic overlap without additive organ-protection benefit. GLP-1 RAs (semaglutide — FLOW trial) show nephroprotection but do not replace SGLT2 inhibitors at this eGFR. Finerenone requires concurrent RAAS blockade and is added to — not a replacement for — SGLT2 inhibitor therapy. Empagliflozin at eGFR 28 with urine ACR > 200 is appropriate per EMPA-KIDNEY trial data (eGFR 20–45 enrolled), making option C more complete and mechanistically accurate.

Question 187: A 28-year-old woman presents with amenorrhea, galactorrhea, and a serum prolactin of 340 ng/mL. MRI reveals a 1.8 cm pituitary macroadenoma. She is started on cabergoline 0.5 mg twice weekly. After 6 months, prolactin normalizes and the tumor shrinks 60%, but she reports new-onset compulsive gambling and hypersexuality. What is the most appropriate next step?

Reduce cabergoline dose and add bromocriptine
Refer for transsphenoidal surgery immediately
Add an SSRI and continue cabergoline at the same dose
Discontinue cabergoline and initiate bromocriptine (Correct answer)

Correct answer: Discontinue cabergoline and initiate bromocriptine

Impulse control disorders (ICDs) — including pathological gambling, hypersexuality, binge eating, and compulsive shopping — are a recognized class effect of dopamine agonists, particularly cabergoline, due to stimulation of mesolimbic D3/D4 receptors. When ICDs develop, cabergoline should be discontinued. Bromocriptine has a lower affinity for extrastriatal dopamine receptors and a substantially lower risk of ICD and is the preferred alternative. Simply reducing cabergoline may not eliminate the risk and may compromise tumor control. Surgery is indicated for dopamine agonist resistance or intolerance, not as the first step when an alternative agonist is available. Adding an SSRI does not address the dopaminergic mechanism driving the ICD.

Question 188: A 32-year-old man presents with low back pain and stiffness for 8 months, worse in the morning and improving with exercise, not rest. He is HLA-B27 positive. Sacroiliac joint MRI shows bone marrow edema. Which of the following is the most appropriate initial therapy?

Methotrexate 15 mg weekly
Anti-TNF biologic therapy
A nonsteroidal anti-inflammatory drug (NSAID) at full therapeutic dose (Correct answer)
Systemic corticosteroids

Correct answer: A nonsteroidal anti-inflammatory drug (NSAID) at full therapeutic dose

NSAIDs at full doses are first-line therapy for axial spondyloarthritis (ankylosing spondylitis) per ASAS and ACR guidelines. Methotrexate is not effective for axial disease. Anti-TNF biologics are indicated only after failure of at least two NSAIDs. Systemic corticosteroids are not recommended for axial disease.

Question 189: A 52-year-old man with type 2 diabetes on metformin and a GLP-1 receptor agonist presents with an HbA1c of 8.9%. He has an eGFR of 28 mL/min/1.73m² and urine albumin-to-creatinine ratio of 420 mg/g. He has no history of bladder cancer or recurrent UTIs. Which agent is most appropriate to add for cardiorenal protection?

Pioglitazone
Insulin glargine
SGLT2 inhibitor
Finerenone (Correct answer)

Correct answer: Finerenone

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has demonstrated cardiorenal protection in CKD with type 2 diabetes (FIDELIO-DKD and FIGARO-DKD trials) and is approved for use down to eGFR ≥25 mL/min/1.73m². SGLT2 inhibitors are generally not recommended when eGFR <30 mL/min/1.73m² for glycemic benefit, though some (empagliflozin, dapagliflozin) have cardiorenal indications down to eGFR ≥20-25 for CKD protection — however, at eGFR 28 with significant albuminuria on a GLP-1 agonist already, finerenone provides additive benefit and is the guideline-preferred addition in this scenario. Pioglitazone carries fluid retention risk at this CKD stage.

Question 190: A 65-year-old asymptomatic woman is found to have a serum calcium of 11.4 mg/dL (normal range 8.6-10.3 mg/dL) on routine labs. A repeat level confirms hypercalcemia. Subsequent workup reveals an elevated intact PTH of 110 pg/mL (normal 15-65 pg/mL) and a 24-hour urine calcium of 350 mg. Her eGFR is 75 mL/min, and a DEXA scan shows a T-score of -1.8 at the lumbar spine. According to the guidelines from the International Workshop on Asymptomatic Primary Hyperparathyroidism, which of the following is a clear indication for parathyroidectomy in this patient?

Serum calcium level >1.0 mg/dL above the upper limit of normal (Correct answer)
DEXA scan T-score of -1.8
Age of 65 years
24-hour urine calcium of 350 mg/day

Correct answer: Serum calcium level >1.0 mg/dL above the upper limit of normal

The patient has asymptomatic primary hyperparathyroidism. The current guidelines for recommending parathyroidectomy include several criteria. One major criterion is a serum calcium level 1.0 mg/dL or more above the upper limit of the normal range. In this case, the upper limit is 10.3 mg/dL, so a level ≥11.3 mg/dL is an indication for surgery. Her level of 11.4 mg/dL meets this criterion. The other options are incorrect: the age criterion is for patients <50 years old, the bone density criterion is a T-score of ≤ -2.5 (osteoporosis), and the hypercalciuria criterion is typically >400 mg/day.

Question 191: A 38-year-old woman is evaluated for osteoporosis with a T-score of -2.9 at the lumbar spine. She has no fractures. Labs reveal calcium 10.9 mg/dL, phosphorus 2.0 mg/dL, PTH 88 pg/mL (normal 15–65), and 24-hour urine calcium of 95 mg/24h (low). Vitamin D is normal. Genetic testing shows a heterozygous inactivating mutation in CaSR (calcium-sensing receptor). Which management is most appropriate?

Begin cinacalcet to normalize serum calcium and suppress PTH
Parathyroidectomy is contraindicated; treat osteoporosis with bisphosphonates (Correct answer)
Obtain a sestamibi scan and proceed with selective adenoma resection
Refer for parathyroidectomy as standard primary hyperparathyroidism guidelines apply

Correct answer: Parathyroidectomy is contraindicated; treat osteoporosis with bisphosphonates

This patient has Familial Hypocalciuric Hypercalcemia (FHH) due to a heterozygous loss-of-function CaSR mutation. The hallmark is hypercalcemia with inappropriately normal/elevated PTH and markedly low urine calcium excretion (typically <100 mg/24h, calcium-to-creatinine clearance ratio <0.01). Parathyroidectomy does NOT cure FHH — the set-point abnormality is in peripheral tissues (kidney, parathyroid), not a discrete adenoma. Surgery leaves patients hypercalcemic and risks permanent hypoparathyroidism. Cinacalcet may modestly lower calcium in FHH but is not routinely indicated except in the rare homozygous neonatal form. Sestamibi would be misleading, as there is no adenoma. Treating the complication (osteoporosis with bisphosphonates) without curative surgery is appropriate management.

Question 192: Which of the following is a common first-line treatment for stable angina?

ACE inhibitors and diuretics
Calcium channel blockers and statins
Aspirin and nitrates (Correct answer)
Beta-blockers and anticoagulants

Correct answer: Aspirin and nitrates

Aspirin and nitrates are common first-line treatments for stable angina. Aspirin helps prevent clot formation and reduces the risk of myocardial infarction, while nitrates provide rapid relief of anginal symptoms by causing vasodilation and reducing myocardial oxygen demand. This combination addresses both symptom management and cardiovascular event prevention.

Question 193: A 67-year-old man on warfarin (INR 2.4) for atrial fibrillation develops a massive pulmonary embolism with hemodynamic instability. He had a hemorrhagic stroke 8 weeks ago. Which management strategy is most appropriate?

Systemic thrombolysis with alteplase 100 mg IV over 2 hours after reversing INR
Catheter-directed therapy (mechanical thrombectomy or pharmacomechanical CDT) (Correct answer)
Anticoagulation dose escalation with unfractionated heparin and vasopressors
Surgical embolectomy via sternotomy

Correct answer: Catheter-directed therapy (mechanical thrombectomy or pharmacomechanical CDT)

Systemic thrombolysis is an absolute contraindication within 3 months of hemorrhagic stroke. Anticoagulation alone with UFH is insufficient for a massive PE with hemodynamic instability. Surgical embolectomy is appropriate but requires cardiothoracic surgery availability and carries high operative risk. Catheter-directed therapy (CDT) — including aspiration thrombectomy — offers a middle ground: it achieves rapid thrombus debulking with much lower thrombolytic drug doses (or no thrombolytics at all in mechanical CDT), making it the preferred advanced reperfusion strategy when systemic thrombolysis is contraindicated.

Question 194: A 45-year-old woman with breast cancer develops a platelet count of 12,000/μL and microangiopathic hemolytic anemia 3 weeks after starting gemcitabine. ADAMTS13 activity is normal. What is the diagnosis?

Drug-induced TTP (Correct answer)
Immune thrombocytopenic purpura
Heparin-induced thrombocytopenia
Disseminated intravascular coagulation

Correct answer: Drug-induced TTP

Gemcitabine is a well-known cause of drug-induced thrombotic microangiopathy (TTP-like syndrome) with normal ADAMTS13, distinguishing it from idiopathic TTP.

Question 195: A 78-year-old man is admitted to the hospital with radiographically confirmed community-acquired pneumonia (CAP). He is clinically stable with normal vital signs, mental status, and oral intake. According to the most recent American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines, which of the following is an appropriate duration of antibiotic therapy for this patient?

A course of 3-5 days, provided he has achieved clinical stability (Correct answer)
A fixed 10-day course of antibiotics
Antibiotic treatment until the C-reactive protein level normalizes
Antibiotic therapy for at least 14 days

Correct answer: A course of 3-5 days, provided he has achieved clinical stability

Recent updates to the ATS/IDSA guidelines for community-acquired pneumonia recommend a shorter duration of antibiotic therapy for patients who are clinically stable. For both outpatients and inpatients with non-severe CAP who achieve clinical stability (resolution of vital sign abnormalities, ability to eat, normal mentation), a course of antibiotics as short as 3-5 days is now conditionally recommended. This is a shift from previous recommendations of longer, fixed-duration courses and aims to reduce antibiotic exposure and resistance.

Question 196: A 57-year-old woman undergoes upper endoscopy for dysphagia. Biopsies from the mid-esophagus show ≥15 eosinophils per high-power field, with no response to an 8-week course of twice-daily proton pump inhibitor therapy. She has no peripheral eosinophilia. Which statement about her subsequent management is most accurate?

Topical swallowed fluticasone or budesonide is first-line pharmacologic therapy after PPI failure (Correct answer)
Endoscopic dilation should be avoided due to high risk of esophageal perforation exceeding 10%
Elimination diet (six-food elimination) is contraindicated in adults with confirmed eosinophilic esophagitis
Systemic prednisone is required because topical steroids do not penetrate the esophageal mucosa adequately

Correct answer: Topical swallowed fluticasone or budesonide is first-line pharmacologic therapy after PPI failure

After failure of PPI therapy (which itself can treat PPI-responsive esophageal eosinophilia and is required to confirm the EoE diagnosis), topical swallowed corticosteroids — fluticasone propionate (swallowed from an MDI) or budesonide oral suspension — are first-line pharmacologic treatment for eosinophilic esophagitis (EoE). Systemic steroids are not routinely used due to side effects. Six-food elimination diet (milk, wheat, egg, soy, nuts, seafood) is a validated non-pharmacologic option in adults. Endoscopic dilation is safe and effective for fibrostenotic EoE; perforation risk is low (<1%), not >10%.

Question 197: A 45-year-old woman is found to have an incidental serum calcium of 10.9 mg/dL on routine labs, confirmed on repeat fasting testing. PTH is 68 pg/mL (normal 15–65 pg/mL). Her 24-hour urine calcium is 92 mg/day. Her brother has similar asymptomatic hypercalcemia. Urine creatinine is 1.2 g/day and serum creatinine is 0.9 mg/dL. Which finding most reliably differentiates her condition from primary hyperparathyroidism and argues against parathyroidectomy?

Absence of nephrolithiasis or osteoporosis
Calcium-to-creatinine clearance ratio less than 0.01 (Correct answer)
Serum calcium below 11.0 mg/dL
Mildly elevated PTH in the setting of hypercalcemia

Correct answer: Calcium-to-creatinine clearance ratio less than 0.01

A calcium-to-creatinine clearance ratio (CaCCR) < 0.01 is the hallmark of familial hypocalciuric hypercalcemia (FHH), caused by a loss-of-function mutation in the calcium-sensing receptor (CaSR). The mutated CaSR causes the kidney to avidly reabsorb calcium, producing low urinary calcium despite hypercalcemia. In primary hyperparathyroidism, CaCCR is typically > 0.02. The positive family history and low urine calcium in this case are classic for FHH. Surgery is not indicated because the condition is benign and PTX will not correct it.

Question 198: A 52-year-old woman with massive hemoptysis (>600 mL in 24 hours) from a left lower lobe cavitary lesion is hemodynamically stable. What is the MOST appropriate immediate management?

Bronchial artery embolization
Rigid bronchoscopy with Fogarty balloon tamponade
Position patient with left side down and consult interventional radiology (Correct answer)
Emergent left pneumonectomy

Correct answer: Position patient with left side down and consult interventional radiology

In massive hemoptysis, positioning the bleeding lung in the dependent (down) position protects the unaffected lung and is the immediate stabilizing maneuver before definitive treatment.

Question 199: A 67-year-old man with type 2 diabetes and CKD (eGFR 28 mL/min/1.73m²) undergoes elective knee arthroplasty. On post-operative day 5, he develops fever to 38.9°C and knee pain. Arthrocentesis yields 85,000 WBCs/µL (95% PMNs), glucose 20 mg/dL (serum 110 mg/dL), and cultures grow oxacillin-susceptible Staphylococcus aureus. TEE is negative for endocarditis. What is the MINIMUM recommended duration of IV antibiotic therapy before considering oral step-down?

4–6 weeks of IV therapy without oral step-down option for prosthetic joint infections (Correct answer)
2 weeks, with oral step-down permissible after clinical improvement and bacteremia clearance
2 weeks IV followed by chronic oral suppressive therapy
6 weeks regardless of clinical response

Correct answer: 4–6 weeks of IV therapy without oral step-down option for prosthetic joint infections

Prosthetic joint infections (PJI) due to Staphylococcus aureus require prolonged IV antibiotic therapy. Per IDSA guidelines for PJI managed with debridement and implant retention (DAIR), the recommended regimen is 2–6 weeks of IV therapy followed by oral rifampin-based combination therapy (e.g., rifampin plus a fluoroquinolone) for 3–6 months. However, for retained hardware with S. aureus PJI, oral step-down to rifampin + ciprofloxacin after initial IV therapy is guideline-supported. The critical distinction here is that the question asks about minimum IV duration before step-down — which is 2 weeks IV (not 4–6 weeks of exclusive IV). Option B is a common misconception. IDSA supports oral rifampin-based step-down after initial IV induction.

Question 200: A 44-year-old man is found to have a 2.5 cm hepatic lesion on ultrasound done for elevated liver enzymes. He has no cirrhosis and no known liver disease. MRI shows a well-demarcated lesion with arterial phase hyperenhancement, peripheral nodular enhancement, and progressive centripetal fill-in on delayed phases. The most likely diagnosis and appropriate next step are:

Hepatic hemangioma — reassurance and no further workup needed (Correct answer)
Cholangiocarcinoma — ERCP with brushings
Focal nodular hyperplasia — confirmatory hepatobiliary contrast MRI phase assessment
Hepatocellular carcinoma — proceed to thermal ablation

Correct answer: Hepatic hemangioma — reassurance and no further workup needed

The described MRI pattern — peripheral nodular arterial enhancement with progressive centripetal fill-in ('light bulb' sign on T2, scalloped margins) — is pathognomonic for a hepatic cavernous hemangioma. In a non-cirrhotic patient without risk factors, this classic pattern on MRI is sufficient for diagnosis; no biopsy or further invasive workup is needed. HCC would show washout appearance in a cirrhotic liver. FNH shows a central scar and homogeneous arterial blush. Cholangiocarcinoma would show different ductal features.

Question 201: A patient with Burkitt lymphoma develops oliguria, creatinine rising to 3.1 mg/dL, potassium of 6.8 mEq/L, phosphorus of 8.2 mg/dL, calcium of 7.1 mg/dL, and uric acid of 14 mg/dL 24 hours after starting chemotherapy. What is the most likely complication?

Septic acute tubular necrosis
Tumor lysis syndrome (Correct answer)
Cisplatin-induced nephrotoxicity
Contrast-induced nephropathy

Correct answer: Tumor lysis syndrome

Tumor lysis syndrome occurs when massive tumor cell death releases intracellular contents, causing hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia with acute kidney injury.

Question 202: A 62-year-old male with a 10-year history of type 2 diabetes mellitus and a prior myocardial infarction has an HbA1c of 7.8% on metformin monotherapy. His eGFR is 65 mL/min/1.73m². According to the most recent American Diabetes Association (ADA) guidelines, which of the following medications would be the most appropriate addition to his regimen?

Pioglitazone
Glipizide
Empagliflozin (Correct answer)
Sitagliptin

Correct answer: Empagliflozin

For patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD), guidelines strongly recommend adding an agent with proven cardiovascular benefit. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated a significant reduction in major adverse cardiovascular events, cardiovascular mortality, and hospitalization for heart failure in this patient population. Glipizide (a sulfonylurea) increases insulin secretion but carries a risk of hypoglycemia and is cardiovascular neutral. Sitagliptin (a DPP-4 inhibitor) is also weight and cardiovascular neutral. Pioglitazone (a thiazolidinedione) can cause weight gain and fluid retention, and should be used with caution in patients at risk for heart failure.

Question 203: A 55-year-old man with type 2 diabetes on metformin, empagliflozin, and insulin glargine presents with nausea, vomiting, and abdominal pain. Glucose is 198 mg/dL, bicarbonate 11 mEq/L, pH 7.19, anion gap 24, beta-hydroxybutyrate 4.8 mmol/L, and urine ketones 3+. Which factor most directly explains why euglycemic diabetic ketoacidosis (euDKA) occurs with SGLT2 inhibitors?

SGLT2 inhibition causes volume depletion, triggering stress-hormone-mediated lipolysis independently of insulin levels
SGLT2 inhibition increases renal glucose excretion, lowering plasma glucose while glucagon-mediated ketogenesis is simultaneously upregulated (Correct answer)
Empagliflozin competes with ketone bodies for renal tubular reabsorption, falsely elevating serum ketone measurements
SGLT2 inhibitors directly inhibit beta-cell insulin secretion, causing absolute insulin deficiency

Correct answer: SGLT2 inhibition increases renal glucose excretion, lowering plasma glucose while glucagon-mediated ketogenesis is simultaneously upregulated

SGLT2 inhibitors cause euDKA through a two-pronged mechanism: (1) they increase urinary glucose excretion, which lowers plasma glucose and reduces the insulin-to-glucagon ratio (lower glucose → less insulin secretion → relative glucagon excess); (2) SGLT2 inhibitors directly increase glucagon secretion via an alpha-cell mechanism, driving ketogenesis from free fatty acids. The result is ketoacidosis without significant hyperglycemia. SGLT2 inhibitors do not directly inhibit beta-cell insulin secretion. They do not interfere with ketone measurement assays. While volume depletion and stress hormones can contribute, the primary mechanism is the glucose-lowering effect uncoupling the usual signal that suppresses ketogenesis, combined with direct glucagonotropic effects.

Question 204: A 61-year-old man with a 20-year history of well-controlled Crohn's disease on azathioprine presents with painless jaundice, pruritus, and a 12 kg weight loss over 4 months. CT scan shows a 3.5 cm hypodense mass in the pancreatic head and dilated intrahepatic ducts. CA 19-9 is 9 U/mL (normal). Serum IgG4 is 620 mg/dL (normal <140). What is the most critical next step before proceeding to Whipple resection?

Proceed to surgery; IgG4 elevation in the context of mass lesion is likely spurious
Check serum IgG subclass panel and repeat IgG4 in 4 weeks
Order EUS-FNA of the pancreatic mass to confirm pancreatic adenocarcinoma
Initiate a 2–4 week steroid trial and reassess imaging to exclude IgG4-related disease (Correct answer)

Correct answer: Initiate a 2–4 week steroid trial and reassess imaging to exclude IgG4-related disease

A markedly elevated IgG4 (>2× upper limit of normal, here ~4.4× ULN) in the context of obstructive jaundice and a pancreatic mass raises serious concern for type 1 autoimmune pancreatitis (AIP), which can mimic pancreatic adenocarcinoma on imaging. AIP is dramatically steroid-responsive; a short empirical steroid trial (prednisone 40 mg/day for 2–4 weeks) with repeat imaging is an established diagnostic maneuver recommended by international consensus (HISORt criteria). If the mass resolves or significantly decreases, AIP is confirmed and surgery is avoided. Proceeding directly to Whipple risks unnecessary major surgery for a benign, treatable condition. EUS-FNA has poor sensitivity for AIP and may not be conclusive.

Question 205: A 45-year-old man with a history of neck irradiation for Hodgkin lymphoma at age 20 is found to have a 1.2 cm thyroid nodule. Fine-needle aspiration returns Bethesda IV (follicular neoplasm). Molecular testing shows a PAX8-PPARγ rearrangement. Which statement most accurately characterizes the significance of this molecular finding?

It confirms benign adenoma and lobectomy can be avoided entirely
It is highly specific for follicular thyroid carcinoma and supports proceeding directly to total thyroidectomy (Correct answer)
It predicts radioiodine resistance but does not differentiate benign from malignant follicular lesions
It is diagnostic of papillary thyroid carcinoma and mandates central neck dissection

Correct answer: It is highly specific for follicular thyroid carcinoma and supports proceeding directly to total thyroidectomy

PAX8-PPARγ rearrangement is found in approximately 30–40% of follicular thyroid carcinomas (FTC) and only rarely in follicular adenomas. Unlike BRAF V600E (which is diagnostic of malignancy in PTC), PAX8-PPARγ is not 100% specific but significantly increases the probability of malignancy in a Bethesda IV nodule, typically guiding surgeons toward total thyroidectomy rather than diagnostic lobectomy alone. It is not a feature of PTC and does not mandate central neck dissection, which is reserved for PTC with high-risk features. The presence of this rearrangement does not confirm benignity. While some FTCs show radioiodine resistance, this is not the primary clinical implication of PAX8-PPARγ — the malignancy risk stratification is.

Question 206: A 25-year-old woman with type 1 diabetes uses an insulin pump. She is found unconscious by her roommate. Glucometer reads 28 mg/dL. IV access cannot be obtained. What is the immediate treatment?

Dextrose 50% sublingual
Glucagon 1 mg intramuscularly (Correct answer)
Oral glucose gel under the tongue
Halt the insulin pump only

Correct answer: Glucagon 1 mg intramuscularly

Glucagon IM (or subcutaneously) is the appropriate treatment for severe hypoglycemia when IV access is unavailable and the patient cannot safely take oral glucose.

Question 207: A 50-year-old woman with morbid obesity develops sudden-onset severe abdominal pain after bariatric surgery 3 years ago. CT shows dilated small bowel loops with mesenteric swirling. What is the most likely diagnosis?

Internal hernia with small bowel obstruction (Correct answer)
Adhesive bowel obstruction
Marginal ulcer
Dumping syndrome

Correct answer: Internal hernia with small bowel obstruction

Internal hernia through mesenteric defects created during Roux-en-Y gastric bypass is a well-recognized complication presenting with small bowel obstruction and the CT finding of 'mesenteric swirl.'

Question 208: A 62-year-old woman presents with a blood pressure of 210/118 mmHg, encephalopathy, and serum creatinine of 3.8 mg/dL (baseline unknown). Peripheral blood smear shows schistocytes, LDH 890 U/L, haptoglobin undetectable, and platelets 68,000/µL. The direct Coombs test is negative. Pregnancy test is negative. She has no prior history of hypertension. Plasma ADAMTS13 activity returns at 72% (normal >67%). Which diagnosis and treatment is most appropriate?

Atypical hemolytic uremic syndrome (aHUS); complement blockade with eculizumab
HELLP syndrome; magnesium sulfate and emergent delivery planning
Thrombotic thrombocytopenic purpura (TTP); emergent plasma exchange plus corticosteroids
Malignant hypertension causing secondary thrombotic microangiopathy (TMA); urgent blood pressure control with IV labetalol or nicardipine without plasma exchange (Correct answer)

Correct answer: Malignant hypertension causing secondary thrombotic microangiopathy (TMA); urgent blood pressure control with IV labetalol or nicardipine without plasma exchange

This is the classic mimicry trap: severe hypertension (especially malignant hypertension) can cause endothelial injury, secondary TMA with microangiopathic hemolytic anemia, thrombocytopenia, and AKI — a picture that resembles TTP or aHUS. The key differentiator is ADAMTS13 activity: TTP classically shows ADAMTS13 <10%. Here, ADAMTS13 is 72% (normal), effectively ruling out TTP. The clinical context of extreme blood pressure as the presenting finding, without a prior history, favors hypertension-induced TMA. The correct treatment is urgent antihypertensive therapy; plasma exchange is not indicated in hypertension-induced TMA, and eculizumab should be reserved for confirmed aHUS after excluding malignant HTN as the cause. HELLP is excluded by negative pregnancy test.

Question 209: A 65-year-old man with type 2 diabetes presents with burning pain, numbness, and tingling in both feet in a 'stocking' distribution. Nerve conduction studies show reduced amplitude and slowed conduction velocity in distal sensory nerves bilaterally. Which of the following is MOST appropriate for neuropathic pain control?

Gabapentin plus opioids as first-line combination
Duloxetine or pregabalin (Correct answer)
Celecoxib 200 mg twice daily
Amitriptyline 150 mg at bedtime

Correct answer: Duloxetine or pregabalin

Duloxetine and pregabalin are FDA-approved first-line agents for diabetic peripheral neuropathic pain with strong evidence and favorable risk profiles. Opioids are not first-line. High-dose amitriptyline (150 mg) carries significant anticholinergic and cardiac risk; low doses may be used but are not first-line. NSAIDs do not address neuropathic pain mechanisms.

Question 210: A 52-year-old man with primary sclerosing cholangitis (PSC) and ulcerative colitis presents with a 6-week history of progressive jaundice, weight loss, and a dominant biliary stricture on MRCP. CA 19-9 is 450 U/mL. Brush cytology of the stricture is negative for malignancy. What is the most appropriate next step in management?

Repeat brush cytology with fluorescence in situ hybridization (FISH) (Correct answer)
Perform endoscopic ultrasound-guided fine needle aspiration of the stricture
Proceed directly to orthotopic liver transplantation evaluation
Start ursodeoxycholic acid at 28–30 mg/kg/day and repeat MRCP in 3 months

Correct answer: Repeat brush cytology with fluorescence in situ hybridization (FISH)

In PSC with a dominant stricture, a single negative brush cytology does not exclude cholangiocarcinoma (CCA). FISH detects chromosomal polysomy and has significantly higher sensitivity (~40–60%) than routine cytology alone (~20%) for CCA in PSC. FISH is the recommended adjunct when cytology is negative but clinical suspicion remains high. High-dose UDCA is not recommended (and may be harmful in PSC). EUS-FNA is technically difficult for proximal bile duct strictures and carries seeding risk. OLT evaluation is premature without confirmed CCA diagnosis via established Mayo criteria.

Question 211: A 35-year-old woman is found to have latent tuberculosis infection (LTBI) with a positive IGRA. She has no active TB symptoms. She is not pregnant and has no liver disease. What is the preferred LTBI treatment regimen?

Rifampin 600mg daily for 4 months
Isoniazid plus rifapentine weekly for 12 weeks (3HP) (Correct answer)
Isoniazid 300mg daily for 9 months
Isoniazid 300mg daily for 6 months

Correct answer: Isoniazid plus rifapentine weekly for 12 weeks (3HP)

The 3HP regimen (weekly isoniazid plus rifapentine for 12 weeks) is preferred for LTBI due to superior completion rates compared to 9-month isoniazid monotherapy.

Question 212: Which of the following is the preferred initial fluid for a patient presenting with DKA and hemodynamic instability (BP 80/50)?

Lactated Ringer's solution at 500 mL/hr
Colloid (albumin) infusion
0.45% NaCl at 250 mL/hr
0.9% NaCl at 1 L/hr bolus (Correct answer)

Correct answer: 0.9% NaCl at 1 L/hr bolus

Isotonic 0.9% NaCl is the initial fluid of choice for volume resuscitation in DKA, particularly in hemodynamically unstable patients.

Question 213: A 44-year-old woman with HIV (CD4 count 38 cells/µL, not on ART) presents with 3 weeks of progressive dyspnea and nonproductive cough. CXR shows bilateral perihilar infiltrates. BAL silver stain is positive for Pneumocystis jirovecii. She is started on TMP-SMX and prednisone. On day 5, she develops worsening hypoxemia with new unilateral consolidation and pleural effusion. Pleural fluid analysis: pH 7.18, glucose 28 mg/dL, LDH 2,400 U/L, protein 5.1 g/dL, 85% neutrophils. The MOST appropriate next step is:

Increase prednisone dose and reassess in 48 hours
Chest tube drainage and add antibiotics targeting Staphylococcus aureus (Correct answer)
Add empiric vancomycin and piperacillin-tazobactam and repeat BAL
Chest tube drainage and add empiric antifungal therapy

Correct answer: Chest tube drainage and add antibiotics targeting Staphylococcus aureus

This pleural fluid has pH <7.20, glucose <40 mg/dL, and LDH >1,000 U/L — criteria for a complicated parapneumonic effusion or frank empyema requiring chest tube drainage. The clinical context (severely immunocompromised HIV patient on PCP treatment with worsening on day 5) raises concern for a secondary bacterial superinfection. Staphylococcus aureus (including MRSA) is a particularly important pathogen in this context because PCP itself predisposes to pneumatocele formation and subsequent Staph superinfection. Vancomycin (targeting MRSA) plus a beta-lactam broad-spectrum agent is appropriate, but the pleural fluid characteristics mandate drainage first, making option C (drainage + Staph-directed coverage) more precisely correct. Increasing steroids alone would be inappropriate given an infected pleural space. Adding antifungal therapy without drainage does not address the empyema.

Question 214: A 50-year-old man with known esophageal varices presents with hematemesis. He is hemodynamically stable after resuscitation. What is the most appropriate endoscopic treatment?

Hemostatic clips
Sclerotherapy
Coagulation therapy
Band ligation (Correct answer)

Correct answer: Band ligation

Endoscopic variceal band ligation (EVL) is the preferred endoscopic treatment for acute esophageal variceal bleeding due to its superior efficacy and lower complication rate compared to sclerotherapy.

Question 215: A 72-year-old woman with chronic heart failure with reduced ejection fraction (HFrEF, EF 30%) on optimal medical therapy develops symptomatic bradycardia (HR 42 bpm) requiring dose reduction of her carvedilol. Her NT-proBNP is markedly elevated. Which of the following best explains the mortality benefit of ivabradine in this clinical context?

It provides additional beta-adrenergic blockade synergistic with carvedilol
It decreases preload through venodilation
It reduces heart rate via I(f) current inhibition without negative inotropy (Correct answer)
It improves diastolic filling by prolonging the QT interval

Correct answer: It reduces heart rate via I(f) current inhibition without negative inotropy

Ivabradine selectively inhibits the funny current (I(f)) in the sinoatrial node, reducing heart rate without affecting myocardial contractility or vascular tone — a critical distinction in HFrEF where negative inotropy is harmful. This allows heart rate reduction when beta-blocker titration is limited by bradycardia or hypotension. It does not block beta receptors, does not cause venodilation, and does not prolong QT.

Question 216: A 72-year-old man presents with a 1-year history of resting tremor of the right hand, reduced arm swing while walking, a shuffling gait, and difficulty initiating movement. Cognitive function is intact. Which of the following is the most appropriate initial pharmacologic treatment?

Haloperidol
Memantine
Trihexyphenidyl
Carbidopa-levodopa (Correct answer)

Correct answer: Carbidopa-levodopa

Carbidopa-levodopa is the most effective symptomatic treatment for Parkinson's disease and is appropriate for an elderly patient with significant motor disability. Haloperidol is a dopamine antagonist that worsens parkinsonism. Trihexyphenidyl (anticholinergic) may be used for tremor but is poorly tolerated in the elderly due to cognitive side effects. Memantine is used for dementia, not Parkinson's motor symptoms.

Question 217: A 45-year-old woman is found to have a serum calcium of 11.4 mg/dL and PTH of 88 pg/mL (normal 15–65). She is asymptomatic. Bone density shows T-score of −2.0 at lumbar spine. Which is the best next step?

Start cinacalcet
Refer for parathyroidectomy (Correct answer)
Start bisphosphonate therapy alone
Reassure and recheck calcium in 6 months

Correct answer: Refer for parathyroidectomy

Asymptomatic primary hyperparathyroidism with a T-score ≤ −2.5 or other surgical criteria warrants parathyroidectomy, which is curative.

Question 218: A 44-year-old woman with a prosthetic mitral valve (implanted 8 months ago) presents with 6 weeks of low-grade fever and fatigue. Blood cultures grow Enterococcus faecalis susceptible to ampicillin (MIC 2 µg/mL) and gentamicin (MIC 128 µg/mL via high-level aminoglycoside resistance screen). Echocardiogram confirms vegetation on the prosthetic valve without abscess. Which treatment regimen is preferred?

Ampicillin plus ceftriaxone for 6 weeks (Correct answer)
Ampicillin plus gentamicin for 6 weeks
Linezolid monotherapy for 8 weeks given prosthetic valve involvement
Vancomycin plus gentamicin for 6 weeks

Correct answer: Ampicillin plus ceftriaxone for 6 weeks

High-level aminoglycoside resistance (HLAR) — defined as gentamicin MIC ≥500 µg/mL by high-level screen — eliminates synergistic benefit of ampicillin-gentamicin, the traditional combination for enterococcal endocarditis. A MIC of 128 µg/mL via screen indicates HLAR. The IDSA guidelines now recommend ampicillin plus ceftriaxone as an equivalent alternative with superior safety profile (no nephrotoxicity/ototoxicity), particularly for E. faecalis with HLAR — based on the GAMES cohort and subsequent validation. This regimen works through distinct PBP binding and is effective regardless of aminoglycoside resistance. Vancomycin plus gentamicin is inferior and still faces the HLAR issue. Linezolid lacks bactericidal activity and is not guideline-supported for enterococcal endocarditis.

Question 219: A 75-year-old man with COPD (FEV1 38% predicted) and hypoxemia at rest (PaO2 55 mmHg) has been started on long-term oxygen therapy. What is the minimum daily duration of supplemental oxygen recommended to improve survival?

24 hours per day
8 hours per day
12 hours per day
15 hours per day (Correct answer)

Correct answer: 15 hours per day

The NOTT trial established that continuous oxygen (>15 hours/day) improves survival in COPD with severe resting hypoxemia, with the greatest benefit at 24 hours.

Question 220: A 30-year-old woman presents with dysuria and urinary frequency. Urine culture grows >100,000 CFU/mL of E. coli sensitive to all agents. She is 10 weeks pregnant. What is the appropriate antibiotic?

Nitrofurantoin 100mg BID x 5 days (Correct answer)
Doxycycline 100mg BID x 7 days
Trimethoprim-sulfamethoxazole DS BID x 7 days
Ciprofloxacin 500mg BID x 3 days

Correct answer: Nitrofurantoin 100mg BID x 5 days

Nitrofurantoin is safe in the second trimester and is first-line for uncomplicated UTI in pregnancy; TMP-SMX and fluoroquinolones are avoided due to fetal risks.

Question 221: A 45-year-old male traveler develops profuse watery diarrhea, nausea, and vomiting 2 days after returning from India. Stool cultures show Vibrio cholerae. What is the primary treatment priority?

Doxycycline 300mg single dose
Ciprofloxacin 1g single dose
Azithromycin 1g single dose
IV fluid resuscitation with Ringer's lactate (Correct answer)

Correct answer: IV fluid resuscitation with Ringer's lactate

Aggressive fluid and electrolyte replacement is the cornerstone of cholera treatment, as severe dehydration causes most deaths; antibiotics are adjunctive.

Question 222: A 62-year-old woman has bilateral painless cervical and axillary lymphadenopathy. Flow cytometry of a lymph node biopsy shows CD5+, CD19+, CD20+ (dim), CD23+ cells with kappa light chain restriction. What is the most likely diagnosis?

Follicular lymphoma
Diffuse large B-cell lymphoma
Chronic lymphocytic leukemia / Small lymphocytic lymphoma (CLL/SLL) (Correct answer)
Mantle cell lymphoma

Correct answer: Chronic lymphocytic leukemia / Small lymphocytic lymphoma (CLL/SLL)

The CD5+, CD19+, CD20 (dim), CD23+ immunophenotype is characteristic of CLL/SLL, distinguishing it from other B-cell lymphomas.

Question 223: A patient with community-acquired pneumonia has a CURB-65 score of 3. What is the most appropriate disposition?

Emergency department observation only
Discharge with follow-up in 24 hours
Hospital admission, consider ICU (Correct answer)
Outpatient treatment with oral antibiotics

Correct answer: Hospital admission, consider ICU

A CURB-65 score of 3 indicates severe pneumonia with significant 30-day mortality risk, warranting hospital admission and possible ICU-level care.

Question 224: A 55-year-old woman with recently diagnosed hypersensitivity pneumonitis (HP) is found to have a pet cockatiel at home. After antigen avoidance, symptoms persist and DLCO is 52% predicted. Which finding on surgical lung biopsy would indicate chronic fibrotic HP rather than subacute HP?

Eosinophilic infiltrates with mucous plugging
Diffuse alveolar damage with hyaline membranes
Peribronchiolar fibrosis with architectural distortion and honeycombing (Correct answer)
Non-caseating granulomas with giant cells

Correct answer: Peribronchiolar fibrosis with architectural distortion and honeycombing

Chronic fibrotic HP is characterized by peribronchiolar fibrosis, bronchiolocentricity, and architectural distortion (including honeycombing), distinguishing it from subacute HP which shows granulomas without fibrosis.

Question 225: What is the most common cause of acquired mitral stenosis in adults in the United States?

Infective endocarditis
Congenital mitral stenosis
Calcific mitral annular stenosis in the elderly
Rheumatic heart disease (Correct answer)

Correct answer: Rheumatic heart disease

Rheumatic heart disease remains the most common cause of mitral stenosis worldwide and in the US, though calcific annular MS is increasing in the elderly population.

Question 226: A 52-year-old man undergoes surgical resection of a 3 cm pancreatic neuroendocrine tumor. Post-operatively, he develops persistent hypoglycemia with glucose nadir of 38 mg/dL during a 72-hour fast. Insulin level is 18 µU/mL, C-peptide is 4.2 ng/mL, and proinsulin is 22 pmol/L (normal <5). Urine sulfonylurea screen is negative. Which additional test would most definitively differentiate nesidioblastosis from occult insulinoma recurrence?

Repeat endoscopic ultrasound of the pancreatic remnant
68Ga-DOTATATE PET/CT scan
Glucagon stimulation test with C-peptide measurement
Selective arterial calcium stimulation with hepatic venous sampling (Correct answer)

Correct answer: Selective arterial calcium stimulation with hepatic venous sampling

Selective arterial calcium stimulation with hepatic venous sampling (ASVS) is the gold standard for localizing focal insulin hypersecretion. In nesidioblastosis (diffuse beta-cell hyperplasia), calcium stimulation causes a diffuse, non-localizing insulin response from multiple arterial territories. In a focal insulinoma, a stepwise dominant response is seen from the specific artery supplying that region. 68Ga-DOTATATE is ideal for somatostatin receptor-positive NETs but insulinomas often have low SSTR2 expression. Endoscopic ultrasound may miss small recurrences. Glucagon stimulation tests cannot differentiate focal from diffuse disease.

Question 227: A 62-year-old man undergoes colonoscopy showing a 1.5 cm sessile serrated lesion in the ascending colon. When should surveillance colonoscopy be performed?

5 years
1 year
10 years
3 years (Correct answer)

Correct answer: 3 years

Sessile serrated lesions ≥10 mm or with dysplasia warrant 3-year surveillance colonoscopy per current ACG guidelines due to their malignant potential.

Question 228: A 60-year-old with known achalasia undergoes esophageal manometry showing aperistalsis and incomplete lower esophageal sphincter relaxation. Which treatment has the lowest risk of GERD as a complication?

Heller myotomy with fundoplication (Correct answer)
Pneumatic dilation
Botulinum toxin injection
Per-oral endoscopic myotomy (POEM)

Correct answer: Heller myotomy with fundoplication

Heller myotomy combined with partial fundoplication (Dor or Toupet) reduces post-procedural GERD compared to myotomy alone or POEM, which disrupts the anti-reflux barrier without fundoplication.

Question 229: A 45-year-old woman presents with episodic hypertension, diaphoresis, and palpitations. 24-hour urine shows elevated normetanephrine but normal metanephrine. Plasma normetanephrine is 3.2× the upper limit of normal. MRI adrenals are unremarkable. What is the next most appropriate imaging study?

¹⁸F-FDOPA PET/CT (Correct answer)
⁶⁸Ga-DOTATATE PET/CT
¹²³I-MIBG scintigraphy
CT chest/abdomen/pelvis with contrast

Correct answer: ¹⁸F-FDOPA PET/CT

This presentation is consistent with a paraganglioma (extra-adrenal pheochromocytoma), given the predominant normetanephrine elevation and negative adrenal MRI. ¹⁸F-FDOPA PET/CT has the highest sensitivity for detecting head-and-neck and thoracic paragangliomas, and is the preferred functional imaging for biochemically confirmed pheochromocytoma/paraganglioma when conventional imaging is negative. ¹²³I-MIBG has lower sensitivity (~80%) and is less useful for head-and-neck paragangliomas. ⁶⁸Ga-DOTATATE is preferred for metastatic or SDHB-related paragangliomas. CT is less sensitive than functional imaging for occult lesions.

Question 230: A 38-year-old with Crohn's disease on azathioprine develops a perianal fistula that fails to close with antibiotics. What biologic therapy is FDA-approved for fistulizing Crohn's disease?

Natalizumab
Ustekinumab
Infliximab (Correct answer)
Vedolizumab

Correct answer: Infliximab

Infliximab is the only biologic with FDA approval specifically for fistulizing Crohn's disease, demonstrated in the landmark ACCENT II trial to induce and maintain fistula closure.

Question 231: A 34-year-old woman with systemic sclerosis presents with 6 months of progressive dyspnea. PFTs show TLC 62% predicted, DLCO 38% predicted, FVC/FEV1 ratio 0.82. Right heart catheterization reveals mPAP 42 mmHg, PCWP 9 mmHg, PVR 6.8 Wood units, and cardiac output 4.1 L/min. She is WHO functional class III. Which of the following is the most appropriate initial therapy?

Oral bosentan plus inhaled iloprost
IV epoprostenol infusion
Combination oral ambrisentan plus tadalafil (Correct answer)
Oral sildenafil monotherapy

Correct answer: Combination oral ambrisentan plus tadalafil

This patient has Group 1 pulmonary arterial hypertension (PAH) associated with systemic sclerosis, WHO FC III. The AMBITION trial demonstrated that upfront combination therapy with an ERA (ambrisentan) plus a PDE5 inhibitor (tadalafil) reduced the risk of clinical failure events by 50% compared to monotherapy in treatment-naive patients. Current guidelines (ESC/ERS 2022, ACC/AHA 2022) recommend upfront oral combination therapy as preferred initial strategy for FC II–III PAH. IV epoprostenol is preferred for FC IV or rapidly deteriorating patients. Bosentan is preferred over ambrisentan in scleroderma-associated PAH with ILD due to liver safety concerns, but the ambrisentan/tadalafil combination has the strongest evidence for initial combination therapy.

Question 232: A 34-year-old woman returning from a 3-week trip to sub-Saharan Africa presents with 5 days of fever, rigors, myalgias, and headache. Thick and thin blood smears show Plasmodium falciparum with 6% parasitemia. She is alert, oriented, and tolerating oral intake. Serum creatinine is 1.1 mg/dL, bilirubin 2.8 mg/dL, blood glucose 88 mg/dL. Which treatment is most appropriate?

IV quinidine gluconate plus doxycycline with telemetry monitoring
Oral quinine sulfate plus doxycycline for 7 days
Oral atovaquone-proguanil
IV artesunate followed by oral artemisinin-based combination therapy upon tolerating PO (Correct answer)

Correct answer: IV artesunate followed by oral artemisinin-based combination therapy upon tolerating PO

Parasitemia ≥5% in Plasmodium falciparum infection meets the CDC definition of severe malaria regardless of the absence of classic organ failure criteria, mandating IV artesunate as first-line therapy. IV artesunate is now the preferred agent over IV quinidine (which is no longer commercially available in the US) due to superior efficacy and safety. After clinical improvement and ability to tolerate oral medications, transition to a full course of oral ACT (e.g., artemether-lumefantrine) is required to complete treatment. Oral-only regimens are insufficient for parasitemia at this level.

Question 233: A 32-year-old woman has recurrent episodes of angioedema without urticaria, triggered by stress and minor trauma, with no identifiable allergen. Her C4 level is consistently low. C1 esterase inhibitor (C1-INH) level and function are markedly reduced. Family history reveals her father had similar episodes. What is the most likely diagnosis?

Hereditary angioedema (HAE) type I (Correct answer)
Idiopathic histaminergic angioedema
Acquired angioedema from C1-INH deficiency
ACE inhibitor-induced angioedema

Correct answer: Hereditary angioedema (HAE) type I

HAE type I is caused by autosomal dominant deficiency of C1 esterase inhibitor (low levels and function), leading to bradykinin-mediated angioedema without urticaria. Attacks are triggered by stress/trauma. Low C4 is a reliable screening marker. ACE inhibitor angioedema occurs in patients on that drug. Acquired HAE is associated with lymphoproliferative disease and presents in older patients without family history.

Question 234: A 30-year-old woman with recurrent UTIs asks about post-coital prophylaxis. She has 3 UTIs per year, all temporally related to sexual intercourse. Which regimen is appropriate?

Cranberry extract 500mg daily
Single-dose TMP-SMX SS taken within 2 hours of intercourse (Correct answer)
Nitrofurantoin 100mg nightly for 12 months
Daily TMP-SMX DS continuously for 6 months

Correct answer: Single-dose TMP-SMX SS taken within 2 hours of intercourse

Post-coital single-dose TMP-SMX or nitrofurantoin is effective prophylaxis for women whose UTIs are clearly linked to sexual activity.

Question 235: A 29-year-old MSM presents with painful genital ulcers, tender inguinal lymphadenopathy, and a reactive RPR 1:64 with confirmatory TPPA. He reports a prior syphilis infection treated 3 years ago with benzathine penicillin G, with documented fourfold RPR decline to 1:4. His current neurological exam is normal, and LP is deferred. Which treatment is most appropriate?

Aqueous crystalline penicillin G IV for 10-14 days (neurosyphilis coverage)
Benzathine penicillin G 2.4 million units IM weekly for 3 doses (late latent protocol)
Benzathine penicillin G 2.4 million units IM once (primary syphilis) (Correct answer)
Doxycycline 100 mg orally twice daily for 28 days (late latent alternative)

Correct answer: Benzathine penicillin G 2.4 million units IM once (primary syphilis)

This patient has secondary syphilis (painful ulcer at primary site plus lymphadenopathy plus RPR 1:64 representing a fourfold or greater rise from documented nadir of 1:4). Secondary syphilis represents early syphilis (<1 year duration) and is treated with a single dose of benzathine penicillin G 2.4 million units IM — not the 3-dose regimen, which is reserved for late latent or latent syphilis of unknown duration. The 1:64 titer compared to a documented nadir of 1:4 (fourfold rise = 1:16 → 1:64) confirms reinfection rather than treatment failure. With a normal neurological exam and no ocular symptoms, LP is not required. IV penicillin is reserved for confirmed neurosyphilis.

Question 236: A 44-year-old man with alcoholic cirrhosis (Child-Pugh C) presents with worsening abdominal distension and fever. Diagnostic paracentesis reveals PMN count of 320 cells/µL. He is initiated on cefotaxime. Blood cultures return with Escherichia coli susceptible to all agents tested. On hospital day 3, his creatinine rises from 0.9 to 2.7 mg/dL despite IV fluid hydration. Which intervention has the strongest evidence for preventing this complication at the TIME OF SBP DIAGNOSIS?

Terlipressin 1 mg IV every 4 hours initiated when creatinine exceeds 1.5 mg/dL
Albumin 1.5 g/kg IV on day 1 and 1 g/kg on day 3 of antibiotic therapy (Correct answer)
Norepinephrine infusion titrated to MAP ≥65 mmHg to maintain renal perfusion
Midodrine plus octreotide plus albumin (triple therapy) beginning at diagnosis

Correct answer: Albumin 1.5 g/kg IV on day 1 and 1 g/kg on day 3 of antibiotic therapy

Spontaneous bacterial peritonitis (SBP) triggers systemic inflammation that precipitates hepatorenal syndrome (HRS) in susceptible cirrhotics. The landmark Sort et al. trial (NEJM 1999) demonstrated that albumin infusion at 1.5 g/kg on day 1 and 1 g/kg on day 3 of antibiotic initiation significantly reduced the incidence of HRS and improved 3-month survival compared to antibiotics alone. This is the standard of care per AASLD and EASL guidelines and is initiated AT THE TIME OF DIAGNOSIS, not after creatinine rises. Terlipressin is used for established HRS-AKI. Midodrine/octreotide/albumin is used for HRS management, not SBP prophylaxis. Norepinephrine is a vasopressor without evidence in this preventive role.

Question 237: A 65-year-old man with severe COPD (FEV1/FVC 0.52, FEV1 32% predicted) has symptoms despite maximal bronchodilator therapy. CT shows heterogeneous emphysema predominantly in the upper lobes with low exercise capacity. Which intervention has demonstrated mortality benefit in this population?

Lung volume reduction surgery (LVRS) (Correct answer)
Bronchoscopic lung volume reduction with endobronchial valves
Inhaled triple therapy (LABA/LAMA/ICS)
Azithromycin prophylaxis 250 mg daily

Correct answer: Lung volume reduction surgery (LVRS)

The NETT trial demonstrated that LVRS reduces mortality and improves exercise capacity in COPD patients with upper-lobe predominant emphysema and low baseline exercise capacity.

Question 238: A 72-year-old woman with a history of breast cancer treated 8 years ago presents with back pain and a serum protein electrophoresis showing an M-spike of 1.1 g/dL (IgG kappa). Bone marrow biopsy shows 7% plasma cells. Serum free light chain ratio is 2.4 (normal). She has no lytic lesions, anemia, hypercalcemia, or renal insufficiency. What is the correct diagnosis and initial management?

MGUS; reassure and monitor annually
Multiple myeloma; initiate VRd (bortezomib, lenalidomide, dexamethasone)
Smoldering multiple myeloma; initiate lenalidomide to prevent progression
Smoldering multiple myeloma; observation with monitoring every 3–6 months (Correct answer)

Correct answer: Smoldering multiple myeloma; observation with monitoring every 3–6 months

This patient meets criteria for smoldering multiple myeloma (SMM): M-spike ≥1 g/dL (IgG), bone marrow plasma cells 10–59% or M-spike meeting threshold, but ABSENCE of CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions) or SLiM criteria. Note: 7% plasma cells technically falls below the 10% SMM threshold, making this a borderline case; however, the M-spike of 1.1 g/dL IgG satisfies SMM M-protein criterion per IMWG 2014. Standard care is observation. Lenalidomide was studied in QUIREDEX trial for high-risk SMM only, and is not standard of care. MGUS requires M-spike <3 g/dL AND <10% plasma cells AND no end-organ damage — the M-spike threshold alone can differentiate.

Question 239: A 72-year-old with severe symptomatic aortic regurgitation and LVEF of 45% declines surgery. Which medication is most appropriate to reduce afterload?

Nifedipine or ACE inhibitor (Correct answer)
Digoxin
Spironolactone
Metoprolol

Correct answer: Nifedipine or ACE inhibitor

Vasodilators (long-acting nifedipine, ACE inhibitors, or ARBs) reduce afterload and are indicated in symptomatic severe AR when surgery is not an option or as a bridge.

Question 240: A 55-year-old woman with hypertrophic obstructive cardiomyopathy (HOCM) and a resting LVOT gradient of 68 mmHg develops worsening exertional dyspnea despite maximally tolerated doses of metoprolol. Echocardiography reveals severe, posteriorly-directed mitral regurgitation due to systolic anterior motion (SAM) of the mitral valve. She has no significant septal perforator anatomy on coronary angiogram. Which intervention is most appropriate?

Addition of disopyramide to the beta-blocker regimen
MitraClip for primary correction of the SAM-related mitral regurgitation
Alcohol septal ablation targeting the first septal perforator
Surgical myectomy with concurrent mitral valve repair/replacement (Correct answer)

Correct answer: Surgical myectomy with concurrent mitral valve repair/replacement

In HOCM, SAM-related MR is secondary to the outflow tract obstruction — it is not a primary valve pathology. Correcting the obstruction (myectomy) typically eliminates SAM and the associated MR. This patient has failed maximal medical therapy and has no suitable septal perforator for alcohol ablation (a contraindication to ASA). Surgical septal myectomy is therefore the procedure of choice, and concurrent intraoperative assessment allows mitral valve repair/replacement if the MR does not resolve after myectomy. Disopyramide could be tried before surgery but is not appropriate as a next step when the patient has already failed maximally tolerated beta-blockade and has no suitable anatomy for ASA. MitraClip addresses the mitral valve without treating the underlying obstruction causing the SAM, making it inappropriate here.

Question 241: A 28-year-old man presents with episodic severe headaches, diaphoresis, and palpitations. BP is 210/115 mmHg during an episode. 24-hour urine metanephrines are markedly elevated. Prior to surgical resection, which medication should be initiated FIRST?

Alpha-blocker (phenoxybenzamine) (Correct answer)
ACE inhibitor (lisinopril)
Beta-blocker (propranolol)
Calcium channel blocker (amlodipine)

Correct answer: Alpha-blocker (phenoxybenzamine)

Alpha-blockade must be established before beta-blockade in pheochromocytoma to prevent unopposed alpha-adrenergic stimulation and hypertensive crisis.

Question 242: A 58-year-old man presents with symmetric leg swelling, ascites, and elevated JVP that increases with inspiration (Kussmaul's sign). Echo shows normal LV function with a thick bright pericardium. What hemodynamic pattern is expected on right heart catheterization?

Pulmonary artery systolic pressure >60 mmHg
Equalization of diastolic pressures across all chambers (Correct answer)
Low right atrial pressure with high PCWP
Elevated PCWP with low cardiac output only

Correct answer: Equalization of diastolic pressures across all chambers

Constrictive pericarditis produces equalization of diastolic pressures (right atrial, RV end-diastolic, PCWP all within 5 mmHg) due to the rigid pericardial shell.

Question 243: Which scoring system is used to prioritize liver transplant allocation in the United States?

APACHE II
MELD score (Correct answer)
Child-Pugh score
King's College Criteria

Correct answer: MELD score

The MELD (Model for End-stage Liver Disease) score, based on bilirubin, INR, and creatinine, is used by UNOS to prioritize patients for liver transplant allocation.

Question 244: A 62-year-old man with a history of IV drug use presents with fever, a new holosystolic murmur at the left sternal border, and blood cultures growing Staphylococcus aureus. Transthoracic echo shows a 1.2 cm tricuspid valve vegetation with severe tricuspid regurgitation and preserved RV function. He is started on appropriate antibiotics. On day 5 of therapy, he remains febrile with persistent bacteremia. What is the most important next step?

Refer immediately for surgical valve debridement or replacement
Perform TEE to evaluate for perivalvular extension or abscess (Correct answer)
Change antibiotic coverage to daptomycin for persistent MRSA bacteremia
Add rifampin to the antibiotic regimen for biofilm penetration

Correct answer: Perform TEE to evaluate for perivalvular extension or abscess

Persistent bacteremia (>5–7 days) in the setting of Staphylococcus aureus endocarditis despite appropriate antibiotics is a major red flag for complications including perivalvular abscess, intracardiac fistula, or extensive infection not visualized on TTE. TEE is indicated to evaluate for these complications because TTE has limited sensitivity for perivalvular extension, especially on the right side. TEE findings would then guide surgical decision-making. Rifampin may be added for prosthetic valve endocarditis or device-associated infections, but is not standard for native valve IE. Surgery is indicated but requires TEE assessment first to define the extent of disease and surgical targets.

Question 245: A 67-year-old woman is intubated for hypoxemic respiratory failure. On assist-control volume-targeted ventilation: TV 420 mL (6 mL/kg IBW), RR 24, PEEP 12, FiO2 0.7. P/F ratio is 96 (severe ARDS). Peak pressure is 38 cmH2O, plateau pressure is 34 cmH2O. She is paralyzed with cisatracurium. An esophageal balloon is placed: end-expiratory esophageal pressure is +18 cmH2O. What does the transpulmonary plateau pressure calculation reveal, and what is the appropriate ventilator adjustment?

Transpulmonary plateau = 34 cmH2O; plateau pressure is safe and no adjustment is indicated
Transpulmonary plateau = 16 cmH2O; current driving pressure is acceptable, no change needed
Transpulmonary plateau = 16 cmH2O; current plateau is safe, increase PEEP to titrate by transpulmonary PEEP (Correct answer)
Transpulmonary plateau = 52 cmH2O; decrease tidal volume to 4 mL/kg IBW

Correct answer: Transpulmonary plateau = 16 cmH2O; current plateau is safe, increase PEEP to titrate by transpulmonary PEEP

Transpulmonary pressure (PL) = airway pressure − esophageal pressure (as a surrogate for pleural pressure). Transpulmonary plateau = 34 (plateau) − 18 (esophageal pressure) = 16 cmH2O, which is within the safe range (<25 cmH2O). This means the elevated plateau pressure (34 cmH2O, above the conventional 30 cmH2O threshold) is explained by a high chest wall elastance (e.g., obesity, abdominal hypertension, pleural effusions), not by dangerous overdistension of the lungs. The appropriate action is to use transpulmonary PEEP titration — titrate PEEP to achieve a positive end-expiratory transpulmonary pressure (PEEP − esophageal EEP > 0) to maintain alveolar recruitment, rather than reflexively lowering PEEP because of the high airway plateau. The transpulmonary plateau of 16 cmH2O does NOT indicate a need to reduce TV further, as lung stress is already safe.

Question 246: A 66-year-old male with a history of COPD presents to the emergency department with increased dyspnea, cough, and sputum production. He has a history of two exacerbations in the past year. His blood eosinophil count is 350 cells/µL. According to the 2024 GOLD report, which of the following is the most appropriate initial pharmacologic management for this patient's chronic condition?

A long-acting muscarinic antagonist (LAMA) monotherapy
A combination of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA)
A combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) (Correct answer)
A short-acting beta-agonist (SABA) as needed with no maintenance therapy

Correct answer: A combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA)

According to the 2024 GOLD guidelines, for a patient with a history of frequent exacerbations (≥2 in the past year) and a blood eosinophil count ≥300 cells/µL, initial therapy with a triple combination of ICS/LABA/LAMA is recommended. This approach targets bronchoconstriction with the dual bronchodilators (LABA/LAMA) and airway inflammation with the ICS, which is particularly beneficial in patients with eosinophilic features.

Question 247: A 44-year-old woman with systemic sclerosis presents with progressive exertional dyspnea. PFTs show FVC 68% predicted, TLC 70% predicted, DLCO 38% predicted. Right heart catheterization reveals mPAP 29 mmHg, PAWP 10 mmHg, PVR 3.2 WU. Which of the following most accurately characterizes her hemodynamic profile and guides management?

Borderline pre-capillary PH; exercise RHC needed before initiating PAH therapy (Correct answer)
Combined pre- and post-capillary PH; phosphodiesterase-5 inhibitors are contraindicated
Pulmonary hypertension due to ILD alone; PAH-specific therapy offers no benefit
Pre-capillary PAH meeting WHO/ESC criteria; initiate dual oral combination therapy

Correct answer: Borderline pre-capillary PH; exercise RHC needed before initiating PAH therapy

Per 2022 ESC/ERS guidelines, PAH is defined by mPAP >20 mmHg, PAWP ≤15 mmHg, and PVR ≥2 WU at rest. This patient meets the mPAP and PAWP criteria but PVR is 3.2 WU (borderline). Crucially, her mPAP of 29 mmHg is below the old threshold of 25 mmHg but above the new 20 mmHg threshold — however, with borderline values, exercise RHC may unmask significant exercise-induced PH and better delineate whether PAH-specific therapy is warranted before committing to combination therapy. Immediate dual therapy initiation would be premature given the borderline hemodynamics.

Question 248: A 28-year-old woman presents with a one-year history of intermittent abdominal cramping, bloating, and chronic diarrhea. She reports unintentional weight loss of 10 lbs. Laboratory studies reveal a microcytic anemia with a hemoglobin of 10.5 g/dL. She is currently consuming a regular diet. According to the American College of Gastroenterology (ACG), which of the following is the most appropriate initial serologic test for celiac disease?

Anti-gliadin IgG antibody
Anti-Saccharomyces cerevisiae antibodies (ASCA)
HLA-DQ2 and HLA-DQ8 genetic testing
Tissue transglutaminase (tTG) IgA antibody plus total serum IgA (Correct answer)

Correct answer: Tissue transglutaminase (tTG) IgA antibody plus total serum IgA

The ACG guidelines recommend IgA anti-tissue transglutaminase (tTG-IgA) antibody as the preferred single test for the initial detection of celiac disease in adults. It is highly sensitive and specific. It is crucial to measure total serum IgA concurrently to rule out selective IgA deficiency, which is more common in patients with celiac disease and can cause a false-negative tTG-IgA result. If IgA deficiency is present, IgG-based tests (e.g., tTG-IgG) should be performed.

Question 249: A 30-year-old man presents with recurrent episodes of painless rectal bleeding and crampy abdominal pain. Colonoscopy shows continuous mucosal inflammation from the rectum to the splenic flexure. The most likely diagnosis is:

Ulcerative colitis (Correct answer)
Crohn's disease
Infectious colitis
Ischemic colitis

Correct answer: Ulcerative colitis

Ulcerative colitis characteristically begins in the rectum and extends proximally in a continuous pattern, unlike the skip lesions of Crohn's disease.

Question 250: A 50-year-old immunocompromised patient presents with fever, pleuritic chest pain, and a pulmonary nodule with halo sign on CT. Galactomannan antigen returns elevated. What is the most appropriate initial antifungal?

Fluconazole 400mg IV daily
Liposomal amphotericin B 3mg/kg/day
Voriconazole 6mg/kg IV q12h x 2 doses, then 4mg/kg q12h (Correct answer)
Micafungin 150mg IV daily

Correct answer: Voriconazole 6mg/kg IV q12h x 2 doses, then 4mg/kg q12h

Voriconazole is the preferred first-line treatment for invasive pulmonary aspergillosis based on superior efficacy demonstrated in landmark clinical trials.

Question 251: A 58-year-old male is admitted to the ICU with sepsis and develops acute respiratory distress syndrome (ARDS). He is intubated and placed on mechanical ventilation. His height is 178 cm (5'10") and his ideal body weight is 75 kg. According to the ARDSNet protocol and current clinical practice guidelines, which of the following represents the most appropriate initial ventilator settings?

Tidal volume of 300 mL, PEEP of 15 cm H₂O, and respiratory rate of 35 breaths/min
Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O (Correct answer)
Tidal volume of 600 mL, PEEP of 5 cm H₂O, and permissive hypercapnia is strictly avoided
Tidal volume of 750 mL, PEEP of 5 cm H₂O, and plateau pressure < 40 cm H₂O

Correct answer: Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O

The cornerstone of mechanical ventilation in ARDS is a lung-protective strategy to minimize ventilator-induced lung injury. This involves using a low tidal volume, typically 4-8 mL/kg of ideal body weight. For this 75 kg patient, 450 mL (6 mL/kg) is an appropriate initial tidal volume. Additionally, maintaining a plateau pressure (the pressure in the alveoli at the end of inspiration) below 30 cm H₂O is crucial to prevent barotrauma. An adequate level of PEEP (Positive End-Expiratory Pressure) is also used to prevent alveolar collapse and improve oxygenation. A PEEP of 10 cm H₂O is a reasonable starting point in moderate-to-severe ARDS.

Question 252: A 58-year-old woman with rheumatic mitral stenosis (MVA 1.1 cm², mean gradient 14 mmHg) has moderate mitral regurgitation, a Wilkins score of 9, and no left atrial thrombus on TEE. She develops atrial fibrillation with rapid ventricular response. Which is the most appropriate next step in valve management?

Defer valve intervention; rate-control AF and anticoagulate, then reassess in 3 months
Refer directly for surgical mitral valve replacement given the Wilkins score >8 (Correct answer)
Perform PMBC only after successful cardioversion and confirmed sinus rhythm for >4 weeks
Proceed with percutaneous mitral balloon commissurotomy (PMBC) because the MVA <1.5 cm² with new AF qualifies her

Correct answer: Refer directly for surgical mitral valve replacement given the Wilkins score >8

A Wilkins score >8 predicts suboptimal outcomes and higher restenosis rates after PMBC. Additionally, this patient has moderate mitral regurgitation — moderate MR (≥2+) is a relative contraindication to PMBC because balloon inflation may worsen regurgitation acutely. With both an unfavorable valve morphology (Wilkins 9) and coexisting moderate MR, surgical mitral valve repair or replacement is the preferred intervention. PMBC is most appropriate when Wilkins ≤8, MR is absent or trivial, and the valve anatomy is pliable. Deferring intervention is inappropriate given symptomatic hemodynamically significant MS.

Question 253: A 52-year-old man with cirrhosis presents with fever, altered mental status, and nuchal rigidity. CSF shows: WBC 1,800 cells/µL (95% PMNs), glucose 28 mg/dL (serum glucose 110 mg/dL), protein 380 mg/dL. Blood and CSF cultures are pending. He has a severe penicillin allergy (anaphylaxis). Which empiric antibiotic regimen is most appropriate?

Trimethoprim-sulfamethoxazole plus vancomycin plus dexamethasone
Aztreonam plus vancomycin plus dexamethasone
Chloramphenicol plus rifampin plus dexamethasone
Meropenem plus vancomycin plus dexamethasone (Correct answer)

Correct answer: Meropenem plus vancomycin plus dexamethasone

This presentation is consistent with bacterial meningitis requiring empiric coverage for S. pneumoniae, N. meningitidis, and in a cirrhotic patient (immunocompromised), Listeria monocytogenes. Standard therapy (ceftriaxone + vancomycin + ampicillin) cannot be used given anaphylaxis to penicillin. Meropenem is the preferred carbapenem alternative — it has excellent CNS penetration and covers all three pathogens including Listeria (unlike aztreonam, which has no gram-positive or Listeria coverage). Vancomycin covers penicillin-resistant pneumococcus. Dexamethasone should be given with or before the first antibiotic dose. Aztreonam lacks gram-positive coverage entirely. Chloramphenicol has poor activity against Listeria and significant toxicity. TMP-SMX does not cover pneumococcus adequately in this acute setting.

Question 254: A 52-year-old man with hepatitis C-related cirrhosis has a 2.5 cm liver lesion showing arterial enhancement and washout on multiphasic MRI. What is the most appropriate next step?

Proceed with treatment per LI-RADS 5 criteria (Correct answer)
Alpha-fetoprotein measurement only
Repeat MRI in 3 months
Liver biopsy

Correct answer: Proceed with treatment per LI-RADS 5 criteria

A LI-RADS 5 lesion (arterial hyperenhancement with washout and capsule in a cirrhotic patient) is diagnostic for hepatocellular carcinoma; biopsy is not required before treatment planning.

Question 255: A 60-year-old man with a history of atrial fibrillation on warfarin is started on methimazole for Graves' disease. After 6 weeks his TSH normalizes. Which lab change is most expected regarding his anticoagulation?

Methimazole directly inhibits warfarin metabolism
INR will decrease as hyperthyroidism resolves (Correct answer)
INR will increase as hyperthyroidism resolves
INR is unaffected by thyroid status

Correct answer: INR will decrease as hyperthyroidism resolves

Hyperthyroidism accelerates clotting factor catabolism, increasing INR; as thyroid function normalizes with treatment, clotting factor turnover slows and INR decreases, requiring warfarin dose adjustment upward.

Question 256: A 71-year-old man with known pulmonary arterial hypertension (WHO Group 1) on ambrisentan and tadalafil presents with acute decompensation. RHC reveals: RAP 18 mmHg, mPAP 62 mmHg, PCWP 8 mmHg, CO 2.1 L/min, PVR 25.7 Wood units. Exam shows cool extremities, JVD, RV gallop, and moderate ascites. Which of the following treatment strategies is MOST likely to cause acute clinical deterioration in this patient?

Aggressive IV fluid resuscitation with 2L normal saline (Correct answer)
Inhaled nitric oxide at 20 ppm
Starting IV epoprostenol while weaning oral therapies
IV diuresis with furosemide 40 mg

Correct answer: Aggressive IV fluid resuscitation with 2L normal saline

In acute decompensated pulmonary arterial hypertension with right ventricular failure, the RV is severely afterloaded (PVR 25.7 Wood units) and preload-dependent but has a very limited ability to handle additional volume. The RV in this setting operates on the flat or descending portion of its Starling curve. Aggressive IV fluid resuscitation will cause RV overdistension, which shifts the interventricular septum leftward via ventricular interdependence, compresses the LV, reduces LV filling and cardiac output, and precipitates hemodynamic collapse. Inhaled nitric oxide selectively reduces PVR and is a first-line rescue therapy. Gentle IV diuresis offloads the congested RV and is appropriate given RAP of 18 and clinical signs of RV failure. Transitioning to IV epoprostenol in decompensated PAH is an evidence-based escalation strategy that can be lifesaving. Fluids are contraindicated unless there is clear evidence of hypovolemia.

Question 257: A 29-year-old woman presents with 5 days of fever, sore throat, and cervical lymphadenopathy. Monospot test is negative. EBV VCA IgM is positive. Three weeks later she develops high fevers, ferritin 42,000 ng/mL, splenomegaly, cytopenia (neutrophils 0.8 × 10⁹/L, platelets 68 × 10⁹/L), elevated triglycerides, and fibrinogen 150 mg/dL. Bone marrow biopsy shows hemophagocytosis. Which finding would MOST strongly indicate that this is EBV-driven hemophagocytic lymphohistiocytosis (HLH) versus secondary HLH from another trigger?

Bone marrow biopsy showing CD8+ T-cell infiltration with hemophagocytosis
Homozygous PRF1 (perforin) mutation on genetic testing (Correct answer)
Ferritin level greater than 50,000 ng/mL
Elevated EBV DNA in peripheral blood by PCR with markedly elevated sNK cell activity

Correct answer: Homozygous PRF1 (perforin) mutation on genetic testing

While EBV is a common trigger of secondary HLH, the discovery of a homozygous PRF1 (perforin-1) mutation definitively identifies primary/familial HLH (FHL2), which typically presents in early adulthood triggered by viral infections (especially EBV). This distinction is critical: primary HLH requires hematopoietic stem cell transplantation as definitive therapy, while secondary HLH may remit with immunosuppression and treatment of the trigger. Elevated EBV PCR (choice A) confirms viral trigger but doesn't distinguish primary from secondary. Ferritin >50,000 (choice B) increases HLH specificity but doesn't differentiate primary vs. secondary. CD8+ infiltration (choice D) is a histologic feature seen in both.

Question 258: A 55-year-old with type 2 DM on an SGLT2 inhibitor presents with fatigue, nausea, and blood glucose of 210 mg/dL. pH is 7.20, bicarbonate 12, and urine ketones are large. What is this presentation called?

Starvation ketosis
Hyperosmolar hyperglycemic state
Euglycemic DKA (Correct answer)
Alcoholic ketoacidosis

Correct answer: Euglycemic DKA

Euglycemic DKA, associated with SGLT2 inhibitors, presents with ketoacidosis but relatively normal blood glucose due to glycosuria and altered glucagon/insulin ratio.

Question 259: A 48-year-old woman with obesity (BMI 38) presents with daytime somnolence, morning headaches, and an AHI of 42 events/hour with SpO2 nadir of 78% on polysomnography. What is the MOST appropriate first-line treatment?

Continuous positive airway pressure (CPAP) (Correct answer)
Uvulopalatopharyngoplasty (UPPP)
Bilevel positive airway pressure (BiPAP)
Supplemental oxygen via nasal cannula at night

Correct answer: Continuous positive airway pressure (CPAP)

CPAP is the first-line treatment for moderate-to-severe obstructive sleep apnea, effectively eliminating apneic events and improving symptoms.

Question 260: A 40-year-old woman from Southeast Asia presents with fever, night sweats, weight loss, and a productive cough for 3 months. AFB smear is positive. She starts RIPE therapy. After 2 months, cultures show full susceptibility. What is the total treatment duration?

6 months total (Correct answer)
9 months total
12 months total
4 months total

Correct answer: 6 months total

Drug-susceptible pulmonary tuberculosis is treated with 2 months of RIPE followed by 4 months of rifampin and isoniazid, for a total of 6 months.

Question 261: A 24-year-old female with a known history of intermittent asthma presents to the urgent care clinic with complaints of wheezing and shortness of breath for the past two days. She uses her albuterol inhaler 4-5 times a day with partial relief. She has no daily controller medication. According to the 2024 GINA guidelines, which of the following is the most appropriate long-term management plan to initiate?

Prescribe a daily long-acting beta-agonist (LABA) inhaler
Prescribe as-needed low-dose inhaled corticosteroid (ICS)-formoterol (Correct answer)
Prescribe a daily low-dose inhaled corticosteroid (ICS) and continue SABA as needed
Continue with as-needed short-acting beta-agonist (SABA) only

Correct answer: Prescribe as-needed low-dose inhaled corticosteroid (ICS)-formoterol

The 2024 Global Initiative for Asthma (GINA) guidelines strongly recommend against treatment with a short-acting beta-agonist (SABA) alone due to safety concerns. The preferred approach (Track 1) for patients with mild asthma (symptoms less than daily) is to use an as-needed low-dose inhaled corticosteroid (ICS)-formoterol combination inhaler. This strategy provides both rapid symptom relief from the formoterol and anti-inflammatory action from the ICS, reducing the risk of severe exacerbations compared to SABA-only treatment.

Question 262: A 35-year-old man with sickle cell disease presents with gradual onset renal insufficiency, isosthenuria, hematuria, and inability to concentrate urine. Urinalysis shows no casts. What is the most likely renal complication?

Sickle cell nephropathy with focal segmental glomerulosclerosis (Correct answer)
Renal cortical necrosis
Renal papillary necrosis
Membranoproliferative glomerulonephritis

Correct answer: Sickle cell nephropathy with focal segmental glomerulosclerosis

Sickle cell nephropathy progresses from early tubular defects (hyposthenuria) to FSGS-pattern glomerular disease from hyperfiltration in surviving nephrons.

Question 263: A 72-year-old man with a history of alcoholism is brought to the emergency department with a 24-hour history of high fever, severe headache, nuchal rigidity, and confusion. A lumbar puncture is planned but will be delayed for a CT scan of the head. Which of the following empiric antimicrobial regimens should be administered immediately?

Vancomycin, ceftriaxone, and ampicillin (Correct answer)
Ceftriaxone plus ampicillin
Meropenem monotherapy
Vancomycin plus ceftriaxone

Correct answer: Vancomycin, ceftriaxone, and ampicillin

For adults over the age of 50 with suspected bacterial meningitis, empiric therapy must cover the most common pathogens, including *Streptococcus pneumoniae*, *Neisseria meningitidis*, and *Listeria monocytogenes*. The combination of vancomycin (for resistant pneumococcus), a third-generation cephalosporin like ceftriaxone (for pneumococcus and meningococcus), and ampicillin (for *Listeria*) is the recommended regimen. Omitting ampicillin would leave the patient vulnerable to *Listeria*, which has increased incidence in older adults, pregnant women, and the immunocompromised.

Question 264: A 55-year-old man presents with fatigue and splenomegaly. Labs show WBC 85,000/μL with a predominance of mature granulocytes, hemoglobin 10 g/dL, platelets 600,000/μL, and Philadelphia chromosome positive. Which tyrosine kinase inhibitor is first-line therapy?

Nilotinib
Dasatinib
Imatinib (Correct answer)
Ponatinib

Correct answer: Imatinib

Imatinib (Gleevec) was the first BCR-ABL tyrosine kinase inhibitor approved for CML and remains a standard first-line option alongside second-generation agents.

Question 265: A 57-year-old man with compensated cirrhosis (Child-Pugh A, MELD-Na 12) due to NASH is found on surveillance ultrasound to have a 1.8 cm arterially enhancing hepatic nodule with washout appearance on gadoxetate-enhanced MRI (LI-RADS 5). AFP is 18 ng/mL. He has no extrahepatic disease. Which treatment modality offers the best long-term survival benefit for this patient?

Radiofrequency ablation (RFA)
Liver transplantation within Milan criteria (Correct answer)
Transarterial chemoembolization (TACE)
Stereotactic body radiation therapy (SBRT)

Correct answer: Liver transplantation within Milan criteria

For a patient with cirrhosis and a single HCC ≤2 cm (well within Milan criteria: single lesion ≤5 cm or ≤3 lesions each ≤3 cm), liver transplantation provides the only curative treatment for both the HCC and the underlying cirrhosis, offering the best long-term survival and lowest recurrence rates (~10–15% at 5 years vs. ~50–70% after ablation). With a MELD-Na of 12 and Child-Pugh A status, this patient is an excellent transplant candidate. RFA achieves excellent local control for small HCC but does not address the cirrhotic liver field defect, leading to high intrahepatic recurrence. TACE is palliative for intermediate-stage HCC and is not the preferred modality for early-stage resectable/transplantable disease.

Question 266: A 68-year-old woman with extensive-stage small cell lung cancer presents with serum sodium of 116 mEq/L, serum osmolality of 250 mOsm/kg, urine osmolality of 620 mOsm/kg, and urine sodium of 50 mEq/L. She appears euvolemic. What is the most likely cause?

Hypervolemic hyponatremia from nephrotic syndrome
Cerebral salt wasting
Syndrome of inappropriate ADH secretion (SIADH) (Correct answer)
Primary adrenal insufficiency

Correct answer: Syndrome of inappropriate ADH secretion (SIADH)

Small cell lung cancer commonly secretes ADH ectopically, causing SIADH with euvolemic hyponatremia and inappropriately concentrated urine with elevated urine sodium.

Question 267: Which finding on ECG is most consistent with hyperkalemia in a patient with chronic kidney disease?

Prominent U waves
ST segment depression
Prolonged QT interval
Tall peaked T waves (Correct answer)

Correct answer: Tall peaked T waves

Hyperkalemia classically produces tall, narrow, peaked T waves as one of the earliest ECG manifestations.

Question 268: A 48-year-old woman with ulcerative colitis develops worsening right upper quadrant pain, jaundice, and pruritus. MRCP shows multifocal strictures and dilations of intrahepatic and extrahepatic bile ducts. What is the most likely diagnosis?

IgG4-related cholangiopathy
Choledocholithiasis
Primary sclerosing cholangitis (Correct answer)
Primary biliary cholangitis

Correct answer: Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is strongly associated with ulcerative colitis and presents with the characteristic 'beaded' appearance of multifocal biliary strictures on MRCP.

Question 269: A 55-year-old diabetic woman presents with right facial pain, black eschar on the palate, and periorbital edema. CT shows sinus involvement extending to the orbit. What is the likely pathogen?

Fusarium solani
Candida albicans
Aspergillus fumigatus
Mucor/Rhizopus species (Correct answer)

Correct answer: Mucor/Rhizopus species

Rhinocerebral mucormycosis caused by Mucorales (Mucor/Rhizopus) classically occurs in diabetic ketoacidosis, presenting with black necrotic eschar and rapid orbital/CNS spread.

Question 270: A 38-year-old woman is found to have a 2.8 cm hepatic adenoma on imaging done for right upper quadrant pain. She takes oral contraceptive pills (OCPs). Biopsy demonstrates β-catenin mutation subtype. She desires future pregnancy. What is the most appropriate management?

Arterial embolization followed by MRI surveillance
Immediate surgical resection given β-catenin mutation subtype (Correct answer)
Discontinue OCPs and repeat MRI in 6 months; resect only if adenoma grows >5 cm
Discontinue OCPs and repeat MRI in 6 months; proceed to resection regardless of size change

Correct answer: Immediate surgical resection given β-catenin mutation subtype

Hepatocellular adenomas with β-catenin activation mutations carry a significantly elevated risk of malignant transformation to hepatocellular carcinoma (estimated 10–fold higher than other subtypes). Current guidelines recommend resection for β-catenin–mutated adenomas regardless of size because of this malignant potential, particularly in a patient who desires future pregnancy (which increases rupture and growth risk). The standard size threshold of 5 cm applies to non-β-catenin subtypes. Embolization is reserved for hemorrhagic or symptomatic adenomas not amenable to resection.

Question 271: A 61-year-old woman with a 6-cm right adrenal mass found incidentally on CT for renal colic. She has well-controlled hypertension on amlodipine. Biochemical workup: 1-mg overnight DST cortisol 4.2 µg/dL, plasma metanephrines normal, aldosterone/renin ratio normal, DHEA-S low-normal. Her ACTH is 8 pg/mL (low-normal). Repeat DST with 8 mg dexamethasone shows cortisol 3.8 µg/dL. What is the most appropriate next management step?

Initiate metyrapone therapy to reduce cortisol and reassess blood pressure control before deciding on surgery
Perform adrenal vein sampling to confirm lateralization before recommending adrenalectomy
Repeat imaging in 6 months; the biochemical profile does not meet criteria for autonomous cortisol secretion
Adrenalectomy is indicated because the 6-cm size and autonomous cortisol secretion together meet criteria for surgical resection (Correct answer)

Correct answer: Adrenalectomy is indicated because the 6-cm size and autonomous cortisol secretion together meet criteria for surgical resection

This lesion meets two independent indications for adrenalectomy: (1) size ≥ 4 cm, which raises concern for adrenocortical carcinoma (ACC risk increases substantially above 4 cm, and ACC is the primary size-based surgical indication for adrenal incidentalomas); and (2) autonomous cortisol secretion (ACS), confirmed by post-1-mg DST cortisol > 1.8 µg/dL — here 4.2 µg/dL with a suppressed ACTH of 8 pg/mL. The high-dose 8-mg DST is used for Cushing's disease (pituitary origin), not adrenal lesions; failure to suppress on high-dose DST in an adrenal source is expected and does not add diagnostic value. Medical therapy is not a definitive treatment for ACS with a resectable lesion, and adrenal vein sampling is used for primary aldosteronism lateralization, not cortisol-producing adenomas.

Question 272: A 38-year-old woman with Graves' disease has been on methimazole 10 mg daily for 18 months. Her free T4 and TSH are now normal. She is eager to pursue definitive therapy. She is 10 weeks pregnant. Her TRAb titer is 4.2 IU/L (reference < 1.75). Which statement best guides clinical decision-making regarding fetal and neonatal thyroid risk?

Methimazole should be switched to propylthiouracil for the remainder of the pregnancy to eliminate teratogenic risk
Neonatal Graves' disease risk is determined by maternal free T4 level at delivery, not by TRAb titer
Elevated maternal TRAb at > 3× upper limit of normal in the third trimester predicts fetal/neonatal hyperthyroidism and warrants fetal surveillance with Doppler thyroid vascularity and fetal heart rate monitoring (Correct answer)
TRAb does not cross the placenta in the first trimester, so current titer has no fetal implications until after 20 weeks

Correct answer: Elevated maternal TRAb at > 3× upper limit of normal in the third trimester predicts fetal/neonatal hyperthyroidism and warrants fetal surveillance with Doppler thyroid vascularity and fetal heart rate monitoring

TRAb (TSH receptor antibodies) are IgG immunoglobulins that cross the placenta from the first trimester onward and can stimulate the fetal thyroid (which becomes responsive to TSH at ~20 weeks). Maternal TRAb > 3× ULN (here 4.2 vs ULN 1.75, ratio ~2.4 — borderline) in the second and especially third trimester identifies fetuses at risk for fetal and neonatal hyperthyroidism. Guidelines (ATA, ETA) recommend fetal surveillance (Doppler thyroid vascularity, fetal heart rate, growth) in women with elevated TRAb. TRAb does cross the placenta from the first trimester. Neonatal Graves' disease risk is primarily predicted by TRAb titer, not free T4. Regarding drug choice: PTU is preferred in the FIRST trimester (lower teratogenic risk), and methimazole is generally acceptable after 16 weeks — the instruction to switch PTU for the remainder of pregnancy is incorrect; PTU has its own risk profile (hepatotoxicity) and the switch timing guidance is the reverse of current recommendations.

Question 273: Which screening test is recommended for colorectal cancer in adults aged 50–75 years?

Fecal occult blood test (FOBT) annually (Correct answer)
Capsule endoscopy
Colonoscopy every 5 years
CT colonography every 2 years

Correct answer: Fecal occult blood test (FOBT) annually

The Fecal Occult Blood Test (FOBT) performed annually is a recommended screening test for colorectal cancer in adults aged 50-75 years. It detects microscopic amounts of blood in the stool, which can be an early sign of colorectal cancer or polyps. While colonoscopy is also a screening option, FOBT is a less invasive and more frequent initial screening method.

Question 274: A 44-year-old woman with SLE is admitted for pleuritic chest pain and dyspnea. D-dimer is elevated at 4.2 µg/mL. CT pulmonary angiography shows bilateral subsegmental pulmonary emboli. Her platelet count is 62,000/µL, aPTT is prolonged at 68 seconds (1:1 mixing study does NOT correct), and anti-β2-glycoprotein I IgG is markedly positive. Which anticoagulation strategy is most appropriate?

Apixaban 10 mg twice daily for 7 days then 5 mg twice daily
Warfarin with a target INR of 3.0–4.0, bridged with unfractionated heparin (Correct answer)
Warfarin with a target INR of 2.0–3.0, bridged with unfractionated heparin
Rivaroxaban 15 mg twice daily for 3 weeks then 20 mg daily

Correct answer: Warfarin with a target INR of 3.0–4.0, bridged with unfractionated heparin

This patient has antiphospholipid antibody syndrome (APS) confirmed by a positive anti-β2-glycoprotein I and a lupus anticoagulant (suggested by prolonged aPTT not correcting on mixing study). For high-risk APS (triple positivity or anti-β2GP1 positive with lupus anticoagulant), warfarin with a higher target INR of 3.0–4.0 is recommended over standard 2.0–3.0, particularly after arterial events or recurrent VTE. Direct oral anticoagulants (rivaroxaban, apixaban) are contraindicated in high-risk APS due to increased thrombotic recurrence rates demonstrated in the TRAPS trial. Bridging with UFH is necessary because warfarin's effect on APS monitoring (aPTT is unreliable) requires anti-Xa levels during the bridge phase.

Question 275: A 25-year-old woman is found to have BP of 170/100 mmHg on routine exam. Labs show hypokalemia, suppressed plasma renin activity, and elevated aldosterone. CT shows no adrenal mass. What is the best next diagnostic step?

24-hour urine metanephrines
Adrenal vein sampling (Correct answer)
Renal artery Doppler ultrasound
MRI of the pituitary

Correct answer: Adrenal vein sampling

Adrenal vein sampling is the gold standard for differentiating unilateral aldosterone-producing adenoma from bilateral adrenal hyperplasia when CT is non-diagnostic.

Question 276: A 58-year-old man with HIV (CD4 count 45 cells/µL, viral load 120,000 copies/mL) presents with 3 weeks of headache, fever, and confusion. CSF analysis reveals: opening pressure 320 mmHg, WBC 8 cells/µL (lymphocyte-predominant), glucose 45 mg/dL, protein 78 mg/dL, India ink positive. Cryptococcal antigen titer is 1:2048. After initiating liposomal amphotericin B plus flucytosine, what is the most critical determinant of 10-week mortality in this patient?

CD4 count at time of diagnosis
Adequacy of serial therapeutic lumbar punctures to control intracranial pressure (Correct answer)
Time to CSF culture sterilization
Baseline CSF cryptococcal antigen titer

Correct answer: Adequacy of serial therapeutic lumbar punctures to control intracranial pressure

In cryptococcal meningitis, elevated intracranial pressure (ICP) is the primary driver of early mortality. Serial therapeutic lumbar punctures (targeting opening pressure <200 mmHg) are the cornerstone of ICP management and have been shown in multiple studies — including the COAT trial — to be the most critical intervention affecting 10-week survival. While antifungal therapy addresses the underlying infection, uncontrolled ICP causes herniation and death before sterilization occurs. Baseline antigen titers and CD4 count are prognostic but not as actionable in the acute setting.

Question 277: A 67-year-old man is admitted with NSTEMI and undergoes PCI with drug-eluting stent (DES) to the LAD. He also has atrial fibrillation with CHA₂DS₂-VASc score of 4 and a history of GI bleed 8 months ago. What is the MOST evidence-based antithrombotic regimen at discharge?

Dual therapy: clopidogrel + rivaroxaban 15 mg daily for 12 months, then rivaroxaban alone
Triple therapy: aspirin + clopidogrel + rivaroxaban 20 mg daily for 6 months, then dual therapy
Dual therapy: clopidogrel + apixaban 5 mg BID for 1 month, then apixaban alone (Correct answer)
Dual therapy: aspirin + apixaban 5 mg BID for 12 months, then apixaban alone

Correct answer: Dual therapy: clopidogrel + apixaban 5 mg BID for 1 month, then apixaban alone

Current evidence (AUGUSTUS, ENTRUST-AF PCI trials) supports 'dual therapy' (P2Y12 inhibitor + DOAC, without aspirin) in patients with AF requiring OAC after PCI, as it reduces bleeding without significantly increasing ischemic events. The AUGUSTUS trial showed apixaban 5 mg BID + P2Y12 was superior to warfarin or aspirin-containing regimens for bleeding. Critically, given his recent GI bleed (8 months ago), minimizing bleeding risk by dropping aspirin early (after 1 month or at discharge) is appropriate. Rivaroxaban 15 mg (reduced dose for AF + PCI, as in ENTRUST) is an alternative, but apixaban-based dual therapy for 1 month transitioning to monotherapy is most aligned with current guidelines for high-bleed-risk patients. Triple therapy is no longer preferred given GI bleed history.

Question 278: A 58-year-old man with severe COPD (FEV1 28% predicted) is admitted for hypercapnic respiratory failure. After 2 hours of BiPAP, his ABG shows pH 7.29, PaCO2 72 mmHg, PaO2 68 mmHg on FiO2 0.40. His mental status is declining. Which of the following is the most appropriate next step in management?

Increase BiPAP IPAP to 20 cmH2O and reassess in 2 hours
Add high-flow nasal cannula at 40 L/min in combination with BiPAP
Initiate invasive mechanical ventilation with volume-control mode (Correct answer)
Administer IV doxapram as a respiratory stimulant to avoid intubation

Correct answer: Initiate invasive mechanical ventilation with volume-control mode

This patient has failed a trial of noninvasive ventilation (NIV) — defined by worsening ABG, declining mental status, and inability to cooperate — after an adequate trial period (≥1–2 hours). NIV failure mandates prompt transition to invasive mechanical ventilation to prevent respiratory arrest. Increasing BiPAP settings is unlikely to help when the patient is already deteriorating on NIV. Combining HFNC with BiPAP is not a validated rescue strategy and would delay definitive airway management. Doxapram is rarely used in modern practice, not recommended in guidelines for COPD exacerbation, and is not appropriate when mental status is declining.

Question 279: A 61-year-old lung transplant recipient (18 months post-transplant) on tacrolimus, mycophenolate, and prednisone presents with subacute sinusitis and new right-sided proptosis. CT shows opacification of the right ethmoid and sphenoid sinuses with bony erosion into the right orbital apex. Biopsy of sinus tissue reveals broad, aseptate hyphae with right-angle branching. Serum galactomannan is negative; beta-D-glucan is negative. What is the SINGLE most important initial management step beyond antifungal therapy?

Addition of adjunctive hyperbaric oxygen therapy
Initiation of granulocyte colony-stimulating factor (G-CSF) to restore neutrophil function
Reduction of immunosuppression, particularly mycophenolate
Emergent surgical debridement of necrotic tissue (Correct answer)

Correct answer: Emergent surgical debridement of necrotic tissue

This presentation is classic for invasive mucormycosis (Mucorales — broad aseptate hyphae with wide-angle branching, contrasting with Aspergillus which has septate hyphae with acute-angle branching). The negative galactomannan and beta-D-glucan are consistent since Mucorales do not produce these biomarkers. While reduction of immunosuppression is important, the SINGLE most critical initial step in rhino-orbital-cerebral mucormycosis is aggressive surgical debridement of all necrotic tissue — this is a surgical emergency that determines survival. Antifungal therapy (liposomal amphotericin B) without surgery has very high mortality. Hyperbaric oxygen (choice C) is adjunctive and unproven. G-CSF (choice D) is useful in neutropenic mucormycosis, not transplant-associated disease.

Question 280: A 35-year-old African American woman presents with bilateral hilar lymphadenopathy, erythema nodosum, and polyarthritis. Serum ACE is elevated. Bronchoscopy with BAL shows lymphocytosis with CD4:CD8 ratio of 5:1. What is the MOST likely diagnosis?

Sarcoidosis (Correct answer)
Hypersensitivity pneumonitis
Lymphoma with pulmonary involvement
Berylliosis

Correct answer: Sarcoidosis

Löfgren syndrome (bilateral hilar adenopathy, erythema nodosum, and arthritis) combined with elevated ACE and high BAL CD4:CD8 ratio is pathognomonic for sarcoidosis.

Question 281: A 34-year-old woman with type 1 diabetes presents with recurrent hypoglycemia despite decreasing her insulin doses. She reports fatigue, salt cravings, and a 10-pound weight loss over 3 months. Morning cortisol is 3.2 mcg/dL. Which finding would most strongly support autoimmune polyglandular syndrome type 2 (APS-2) rather than isolated primary adrenal insufficiency?

Positive 21-hydroxylase antibodies
Elevated TSH with low free T4 (Correct answer)
Low ACTH stimulation test response
Hyperkalemia with hyponatremia

Correct answer: Elevated TSH with low free T4

APS-2 (Schmidt syndrome) is defined by the co-occurrence of primary adrenal insufficiency with autoimmune thyroid disease (Hashimoto's or Graves') and/or type 1 diabetes. An elevated TSH with low free T4 (primary hypothyroidism) in a patient with type 1 diabetes and adrenal insufficiency confirms APS-2. Positive 21-hydroxylase antibodies confirm autoimmune etiology of the adrenal insufficiency but are present in isolated Addison's as well. Hyperkalemia/hyponatremia and low ACTH stimulation response are features of primary adrenal insufficiency regardless of whether it is isolated or part of APS-2.

Question 282: A 32-year-old woman presents to the ICU with status asthmaticus unresponsive to nebulized bronchodilators, systemic corticosteroids, and magnesium sulfate. She is becoming fatigued. ABG: pH 7.32, PaCO2 50 mmHg. What does the rising PaCO2 indicate in this context?

Successful bronchodilation reducing dynamic hyperinflation
Adequate compensation for metabolic acidosis
Hyperventilation-induced hypocapnia returning to baseline
Impending respiratory failure requiring preparation for intubation (Correct answer)

Correct answer: Impending respiratory failure requiring preparation for intubation

In an asthmatic who was initially hyperventilating (low PaCO2), normalization or rising PaCO2 indicates muscle fatigue and impending respiratory failure requiring intubation preparation.

Question 283: A 42-year-old woman is found to have a platelet count of 980,000/μL on routine CBC. She is asymptomatic with no prior thrombosis. Bone marrow biopsy confirms essential thrombocythemia with JAK2 V617F mutation. She has no cardiovascular risk factors. What is the appropriate management for this low-risk patient?

Low-dose aspirin alone (Correct answer)
Phlebotomy to reduce platelet count
Cytoreductive therapy with hydroxyurea plus aspirin
Anagrelide as monotherapy

Correct answer: Low-dose aspirin alone

Low-risk essential thrombocythemia (age <60, no prior thrombosis, no high-risk features) is managed with low-dose aspirin alone without cytoreduction.

Question 284: Which diagnostic test is most appropriate for a patient presenting with chest pain and suspected acute coronary syndrome (ACS)?

High-sensitivity troponin test (Correct answer)
Coronary angiography
CT coronary angiography
Stress echocardiography

Correct answer: High-sensitivity troponin test

The high-sensitivity troponin test is the most appropriate initial diagnostic tool for a patient with chest pain and suspected acute coronary syndrome (ACS). Troponin is a cardiac biomarker released into the bloodstream when heart muscle is damaged. High-sensitivity assays allow for earlier detection of myocardial injury, aiding in rapid diagnosis and risk stratification.

Question 285: Which of the following best describes the mechanism of action of ursodeoxycholic acid (UDCA) in primary biliary cholangitis?

Inhibition of TNF-alpha synthesis
Displacement of toxic bile acids and hepatoprotection (Correct answer)
Immunosuppression of autoreactive T cells
Bile acid synthesis inhibition

Correct answer: Displacement of toxic bile acids and hepatoprotection

UDCA works by replacing toxic hydrophobic bile acids, stimulating bile secretion, and providing cytoprotection to cholangiocytes, slowing disease progression in PBC.

Question 286: A 44-year-old woman is found to have a serum calcium of 11.6 mg/dL on routine labs. PTH is 78 pg/mL (normal 15–65). 24-hour urine calcium is 95 mg/24h (reference > 200 mg for hypercalcemia). Her calcium-to-creatinine clearance ratio (CCCR) is 0.008. She has no symptoms and her DEXA scan shows Z-score of −1.0 at the lumbar spine. Her sister was recently diagnosed with the same condition. What is the most appropriate management?

Obtain sestamibi scan and neck ultrasound to localize a parathyroid adenoma prior to surgery
Reassure and monitor without intervention; refer for genetic testing for CaSR or AP2S1 mutation (Correct answer)
Initiate cinacalcet to normalize serum calcium and reduce fracture risk
Refer for parathyroidectomy given symptomatic primary hyperparathyroidism meeting surgical criteria

Correct answer: Reassure and monitor without intervention; refer for genetic testing for CaSR or AP2S1 mutation

This presentation is classic for Familial Hypocalciuric Hypercalcemia (FHH), an autosomal dominant condition caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) gene, or less commonly AP2S1 or GNA11. Key features: mild-moderate hypercalcemia, inappropriately normal-to-elevated PTH, markedly low 24-hour urine calcium (< 100 mg/day), and CCCR < 0.01 (the diagnostic threshold). Family history of similar calcium levels strongly supports FHH. FHH is benign — parathyroidectomy does not normalize calcium and is not indicated. Cinacalcet may lower calcium temporarily but is not standard of care for FHH. Genetic testing confirms the diagnosis and prevents unnecessary surgical intervention. DEXA Z-score of −1.0 does not meet criteria for parathyroidectomy even if primary hyperparathyroidism were confirmed.

Question 287: A 68-year-old man on hemodialysis develops bacteremia with MSSA. TEE shows no vegetation. What is the recommended duration of antibiotic therapy for uncomplicated MSSA bacteremia?

28 days
42 days
7 days
14 days (Correct answer)

Correct answer: 14 days

Uncomplicated S. aureus bacteremia (no endocarditis, no metastatic focus, clinical improvement by 72h) requires 14 days of IV anti-staphylococcal therapy.

Question 288: A 45-year-old woman is found to have a JAK2 V617F-positive polycythemia vera. Her hematocrit is 52%, platelet count is 680,000/µL, and she has a prior history of splenic vein thrombosis. She is currently on phlebotomy and aspirin. Which of the following represents the most appropriate intensification of therapy?

Initiate ruxolitinib as first-line cytoreductive therapy
Add hydroxyurea to achieve hematocrit <45% (Correct answer)
Begin therapeutic anticoagulation with warfarin alone
Switch aspirin to clopidogrel for superior platelet inhibition

Correct answer: Add hydroxyurea to achieve hematocrit <45%

This patient is high-risk PV (age >60 OR prior thrombosis — she has both, being 45 with splenic vein thrombosis making her high-risk by thrombosis criterion). High-risk PV patients require cytoreductive therapy; hydroxyurea is first-line. The ECLAP and CYTO-PV trials demonstrated that maintaining hematocrit <45% significantly reduces thrombotic events. Ruxolitinib (a JAK1/2 inhibitor) is second-line for patients intolerant of or resistant to hydroxyurea, not first-line. Anticoagulation alone does not address the underlying erythrocytosis driving thrombotic risk.

Question 289: A 55-year-old man with type 2 diabetes and chronic kidney disease (eGFR 28 mL/min) has a recent STEMI with residual EF of 35%. He is initiated on guideline-directed medical therapy. Which agent from the following list provides BOTH cardiovascular mortality reduction AND slowing of CKD progression in this patient population, independent of glycemic control?

Sitagliptin (DPP-4 inhibitor)
Pioglitazone (thiazolidinedione)
Exenatide (GLP-1 receptor agonist)
Empagliflozin (SGLT2 inhibitor) (Correct answer)

Correct answer: Empagliflozin (SGLT2 inhibitor)

SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) have demonstrated cardiovascular mortality reduction in patients with HFrEF (EMPEROR-Reduced, DAPA-HF) and nephroprotective effects (EMPA-KIDNEY, CREDENCE) independent of glucose lowering. They are now guideline-recommended in HFrEF with or without diabetes. Sitagliptin showed neutral CV effects (TECOS) with no renal benefit. GLP-1 agonists reduce MACE but lack robust HF and CKD benefit in this specific population. Pioglitazone causes fluid retention and worsens HF — it is contraindicated in this setting.

Question 290: A 52-year-old woman with type 2 diabetes has an HbA1c of 9.2% on metformin 1000 mg twice daily. She has CKD stage 3a (eGFR 52 mL/min). Which medication is CONTRAINDICATED in this patient?

Empagliflozin
Metformin 2000 mg twice daily (Correct answer)
Sitagliptin
Glipizide

Correct answer: Metformin 2000 mg twice daily

Metformin is contraindicated when eGFR falls below 30, but at eGFR 52 it can be continued at current dose; however, doubling to 2000 mg twice daily (4000 mg/day) exceeds the maximum recommended dose of 2550 mg/day and is not indicated.

Question 291: A 58-year-old male with acute myeloid leukemia is undergoing induction chemotherapy. He develops a fever of 39.2°C (102.6°F) and his absolute neutrophil count is 150 cells/mm³. He is hemodynamically stable with no clear source of infection on initial examination. According to IDSA guidelines, which of the following is the most appropriate initial empiric antibiotic regimen?

Vancomycin plus Cefepime
Piperacillin-tazobactam (Correct answer)
Metronidazole plus Ciprofloxacin
Ceftriaxone

Correct answer: Piperacillin-tazobactam

In high-risk febrile neutropenia, empiric monotherapy with an anti-pseudomonal beta-lactam is the standard of care. Piperacillin-tazobactam, cefepime, meropenem, or imipenem-cilastatin are all appropriate first-line choices. Ceftriaxone lacks reliable Pseudomonas aeruginosa coverage. Vancomycin is not recommended for routine initial empiric therapy unless specific indications are present, such as suspected catheter-related infection, pneumonia, hemodynamic instability, or known MRSA colonization. Metronidazole would only be added if an anaerobic source, like an intra-abdominal infection, is suspected.

Question 292: A 67-year-old man with type 2 diabetes, stage 3b CKD (eGFR 38), and a recent MI (6 weeks ago) presents for medication reconciliation. His HbA1c is 8.9%. Current medications include metformin 500 mg BID, aspirin, atorvastatin, carvedilol, and lisinopril. Which adjustment to his diabetes regimen is most evidence-based?

Discontinue metformin; add dulaglutide 1.5 mg weekly for cardiovascular benefit
Discontinue metformin; initiate insulin glargine targeting HbA1c < 7.0%
Continue metformin; add semaglutide 0.5 mg weekly (Correct answer)
Continue metformin; add empagliflozin 10 mg daily

Correct answer: Continue metformin; add semaglutide 0.5 mg weekly

Metformin is acceptable at eGFR 38 (threshold for discontinuation is eGFR < 30). The patient needs an agent with proven cardiovascular benefit post-MI. GLP-1 receptor agonists (semaglutide, dulaglutide, liraglutide) have demonstrated MACE reduction in high-CV-risk patients and are safe in CKD stage 3b. SGLT2 inhibitors (empagliflozin) also carry CV and renal benefits, but their glycosuric efficacy diminishes significantly below eGFR 45 (particularly for glucose lowering), and empagliflozin's heart failure indication threshold is eGFR ≥ 20. At eGFR 38, semaglutide added to metformin provides superior glycemic control and CV benefit. Dulaglutide is also acceptable but discontinuing metformin without a clear contraindication is not indicated. Aggressive insulin targeting HbA1c < 7.0% post-MI carries hypoglycemia risk without proven MACE benefit.

Question 293: A 52-year-old man undergoes selective inferior petrosal sinus sampling (IPSS) for suspected Cushing's disease. Basal central-to-peripheral ACTH ratio is 1.8. After CRH stimulation, the ratio rises to 2.4 on the right side and 1.6 on the left. MRI of the pituitary is unremarkable. What is the most appropriate next step in management?

Diagnose ectopic ACTH syndrome and proceed with CT chest/abdomen/pelvis
Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary (Correct answer)
Repeat IPSS with simultaneous bilateral sampling under strict catheter position verification
Order repeat 24-hour urine free cortisol and late-night salivary cortisol to confirm hypercortisolism

Correct answer: Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary

An IPSS central-to-peripheral ACTH ratio ≥ 2 basal or ≥ 3 post-CRH confirms pituitary-source Cushing's disease with ~95% sensitivity and specificity. Here the post-CRH ratio is 2.4 on the right (≥ 2 is sufficient for lateralization when ≥ 3 threshold is not reached, though many centers use ≥ 1.4 lateralization ratio). Since pituitary source is confirmed (post-CRH ratio 2.4 > 2.0) and lateralization favors the right, right-sided hemipituitary exploration is appropriate even with a negative MRI — approximately 40–60% of corticotroph adenomas are MRI-occult. Ectopic ACTH is excluded by the central-to-peripheral gradient. Repeating biochemical confirmation is unnecessary after IPSS confirmation. Repeating IPSS is not indicated when the procedure was technically successful.

Question 294: A 55-year-old woman with obesity and type 2 diabetes has AST 78 and ALT 92. Ultrasound shows echogenic liver. Which histologic finding distinguishes NASH from simple steatosis?

Bile duct proliferation
Macrovesicular fat deposits
Portal fibrosis only
Lobular inflammation and hepatocyte ballooning (Correct answer)

Correct answer: Lobular inflammation and hepatocyte ballooning

NASH is distinguished from simple steatosis by the presence of lobular inflammation and hepatocyte ballooning injury, which drive fibrosis progression and risk of cirrhosis.

Question 295: A patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). After treatment, which prophylactic antibiotic is recommended to prevent recurrence?

Amoxicillin-clavulanate
Metronidazole
Cephalexin
Norfloxacin (Correct answer)

Correct answer: Norfloxacin

Norfloxacin (or trimethoprim-sulfamethoxazole as an alternative) is recommended for long-term secondary prophylaxis after a first episode of SBP to reduce recurrence risk.

Question 296: A patient in the ICU on mechanical ventilation has the following ABG: pH 7.50, PaCO2 30 mmHg, PaO2 95 mmHg, HCO3 23 mEq/L. Current settings: TV 500 mL, RR 18, PEEP 5, FiO2 0.40. What is the MOST appropriate ventilator adjustment?

Increase PEEP to improve oxygenation
Increase tidal volume to increase minute ventilation
Decrease FiO2 to 0.21
Decrease respiratory rate to correct respiratory alkalosis (Correct answer)

Correct answer: Decrease respiratory rate to correct respiratory alkalosis

The ABG shows respiratory alkalosis (low PaCO2, elevated pH) with adequate oxygenation; decreasing respiratory rate reduces minute ventilation and corrects hypocapnia.

Question 297: According to the 2021 IDSA and SHEA focused update, which of the following is the preferred first-line agent for an initial episode of non-severe Clostridioides difficile infection?

Oral Vancomycin
Oral Metronidazole
Fecal Microbiota Transplantation
Oral Fidaxomicin (Correct answer)

Correct answer: Oral Fidaxomicin

The 2021 IDSA/SHEA guidelines conditionally recommend oral fidaxomicin as the preferred agent over oral vancomycin for an initial episode of C. difficile infection (CDI). This preference is based on evidence showing fidaxomicin has a lower rate of CDI recurrence compared to vancomycin. Oral metronidazole is no longer recommended as a first-line agent for even mild-to-moderate disease. Fecal microbiota transplantation is reserved for patients with multiple recurrent episodes.

Question 298: A 70-year-old man on mechanical ventilation develops sudden hemodynamic instability with decreased breath sounds on the left, tracheal deviation to the right, and rising peak airway pressures. What is the immediate management?

Increase PEEP to recruit atelectatic lung
Needle decompression of the left hemithorax (Correct answer)
Chest X-ray to confirm diagnosis
Bronchoscopy to assess for mucus plugging

Correct answer: Needle decompression of the left hemithorax

Tension pneumothorax is a clinical diagnosis requiring immediate needle decompression at the 2nd intercostal space midclavicular line before imaging.

Question 299: A 63-year-old woman with known coronary artery disease presents with an acute inferior STEMI. Primary PCI is performed successfully to the right coronary artery. Post-procedure, she develops hypotension (BP 78/50) with clear lung fields, elevated JVP, and a new pansystolic murmur loudest at the left lower sternal border. ECG shows sinus bradycardia. What is the most likely diagnosis?

Ventricular septal rupture (Correct answer)
Right ventricular infarction with tricuspid regurgitation
Cardiac tamponade from free wall rupture
Acute mitral regurgitation due to papillary muscle rupture

Correct answer: Ventricular septal rupture

Post-MI ventricular septal rupture (VSR) classically presents 3–5 days after MI (though can be earlier) with sudden hemodynamic deterioration and a new harsh pansystolic murmur at the left lower sternal border, reflecting left-to-right shunting. Inferior MI commonly causes posterior VSR. Right ventricular infarction causes hypotension with clear lungs and elevated JVP but does not produce a new pansystolic murmur. Acute MR from papillary muscle rupture produces a murmur, but it is often apical/radiating to the axilla. Cardiac tamponade causes muffled heart sounds and pulsus paradoxus, not a new murmur.

Question 300: A 45-year-old woman with systemic lupus erythematosus presents with progressive exertional dyspnea. Echo shows preserved EF, impaired relaxation, and a pericardial effusion. Right heart catheterization demonstrates equalization of diastolic pressures across all four chambers (within 5 mmHg of each other). During inspiration, her systolic BP drops from 118 to 98 mmHg. Which hemodynamic finding would BEST distinguish constrictive pericarditis from cardiac tamponade in this patient?

Right atrial pressure waveform with prominent y-descent
Equalization of end-diastolic pressures on catheterization
Kussmaul sign on physical exam (Correct answer)
Presence of pulsus paradoxus > 10 mmHg

Correct answer: Kussmaul sign on physical exam

Kussmaul sign — a paradoxical rise (or failure to fall) in jugular venous pressure with inspiration — is classically associated with constrictive pericarditis, not tamponade. In tamponade, venous return increases with inspiration but the fixed pericardial volume prevents RV filling, so JVP falls normally or exaggerates. In constriction, the thickened pericardium prevents the RV from accommodating increased venous return, causing JVP to rise with inspiration. Pulsus paradoxus occurs in both conditions. A prominent y-descent is characteristic of constrictive pericarditis (rapid early ventricular filling then abrupt halt — 'square root sign'), while tamponade blunts the y-descent. Equalization of diastolic pressures occurs in both.

ITE Internal Medicine In-Training Exam

The ITE Internal Medicine In-Training Exam is an annual assessment for internal medicine residents covering cardiovascular disease, pulmonary and critical care, gastroenterology, infectious disease, and endocrinology to benchmark clinical knowledge.

300

Questions

360 min

Time Limit

60%

To Pass

Checking for saved progress...

Exam Rules

You can skip questions and return to them later
Flag questions for review before submitting
No feedback shown until you submit the entire exam
Unanswered questions count as wrong — answer everything
10 pretest questions are mixed in and don't affect your score
Timer auto-submits when time runs out
Your progress is auto-saved every 30 seconds

These practice questions were written with AI tools. They are not real exam questions. Exam facts are checked against the official sources listed below. Not reviewed by a subject-matter expert. Editorial policy

Sources & references

Exam facts on this page (fees, format, dates, passing scores) are checked against these official sources; the date is our last check. Editorial policy

acponline.org — Test delivery, eligibility, retake policy, time limit, fees, passing score, exam information · verified Nov 2026