ITE Internal Medicine In-Training Exam — Questions and Answers

Question 1: A 26-year-old woman with type 1 diabetes presents with recurrent DKA episodes despite good outpatient compliance. She has celiac antibodies positive on screening. How does undiagnosed celiac disease contribute to DKA in type 1 diabetes?

Celiac increases glucagon secretion
Malabsorption leads to unpredictable glucose-insulin matching (Correct answer)
Celiac disease causes insulin resistance
Celiac destroys beta cells directly

Correct answer: Malabsorption leads to unpredictable glucose-insulin matching

Celiac disease-related malabsorption causes erratic carbohydrate absorption, making glucose-insulin matching unpredictable and precipitating hypoglycemia or hyperglycemia and DKA.

Question 2: 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 gentamicin for 6 weeks
Vancomycin plus gentamicin for 6 weeks
Linezolid monotherapy for 8 weeks given prosthetic valve involvement
Ampicillin plus ceftriaxone for 6 weeks (Correct answer)

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 3: A 44-year-old woman presents with a 3-week history of pleuritic chest pain, facial rash worsened by sun, and joint pain. ANA is 1:640. Which antibody is most specific for systemic lupus erythematosus?

Anti-Scl-70 antibody
Anti-SSA (Ro) antibody
Anti-dsDNA antibody (Correct answer)
Anti-CCP antibody

Correct answer: Anti-dsDNA antibody

Anti-dsDNA antibodies are highly specific for SLE (>95%) and correlate with disease activity and lupus nephritis.

Question 4: 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?

CRH stimulation test
High-dose (250 mcg) ACTH (cosyntropin) stimulation test (Correct answer)
24-hour urine free cortisol measurement
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 5: A 29-year-old woman presents with weakness, hyperpigmentation, salt craving, and orthostatic hypotension. Labs show Na 128 mEq/L, K 5.8 mEq/L, and glucose 62 mg/dL. ACTH stimulation test shows a peak cortisol of 10 mcg/dL at 60 minutes. What is the most likely diagnosis?

Primary adrenal insufficiency (Addison's disease) (Correct answer)
Congenital adrenal hyperplasia (non-classic)
Secondary adrenal insufficiency
Cushing syndrome

Correct answer: Primary adrenal insufficiency (Addison's disease)

Primary adrenal insufficiency (Addison's disease) is characterized by loss of both cortisol and aldosterone, causing hyponatremia, hyperkalemia, hyperpigmentation (elevated ACTH), and a blunted cortisol response to ACTH stimulation.

Question 6: 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?

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

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 7: 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?

Band ligation (Correct answer)
Coagulation therapy
Sclerotherapy
Hemostatic clips

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 8: A 63-year-old man with Stage IV NSCLC (adenocarcinoma) is found to have an EGFR exon 19 deletion on molecular testing. He has good performance status and no brain metastases. Which first-line treatment provides the longest progression-free survival?

Erlotinib 150 mg daily
Osimertinib 80 mg daily (Correct answer)
Carboplatin/pemetrexed plus pembrolizumab
Gefitinib 250 mg daily

Correct answer: Osimertinib 80 mg daily

Osimertinib (3rd generation EGFR TKI) demonstrated superior PFS and OS over 1st generation TKIs in the FLAURA trial and is the preferred first-line agent for EGFR-mutated NSCLC.

Question 9: 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?

Cholestyramine
Rifampin
Obeticholic acid (Correct answer)
Bezafibrate

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 10: 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 left heart disease (Group 2) (Correct answer)
Pulmonary hypertension due to lung disease (Group 3)
Idiopathic pulmonary arterial hypertension

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 11: 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
Initiate a 2–4 week steroid trial and reassess imaging to exclude IgG4-related disease (Correct answer)
Check serum IgG subclass panel and repeat IgG4 in 4 weeks
Order EUS-FNA of the pancreatic mass to confirm pancreatic adenocarcinoma

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 12: 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:

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

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 13: 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?

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

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

Insulin
Sulfonylureas
Metformin (Correct answer)
DPP-4 inhibitors

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 15: Which of the following is the first-line treatment for primary hypertension?

ACE inhibitors (Correct answer)
Beta-blockers
Calcium channel blockers
Loop diuretics

Correct answer: ACE inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are generally considered first-line treatment for primary hypertension, especially in patients with co-existing conditions like diabetes or chronic kidney disease. They work by blocking the production of angiotensin II, leading to vasodilation and reduced blood pressure. Current guidelines often recommend ACE inhibitors or ARBs as initial therapy.

Question 16: A 55-year-old man with known bicuspid aortic valve and aortic stenosis (valve area 0.7 cm², mean gradient 48 mmHg) is asymptomatic. Echo shows ascending aorta diameter of 4.6 cm. He is an avid marathon runner and asks about continued competitive running. Which statement BEST represents current guidelines?

He may continue low-intensity exercise but should avoid competitive sports due to aortic diameter alone
He may continue marathon running given his asymptomatic status; reassess in 1 year
He should undergo aortic valve replacement now given severe AS regardless of symptoms
He should avoid competitive sports; surveillance imaging every 6 months; refer for surgery given combined AS severity and aortic dilation (Correct answer)

Correct answer: He should avoid competitive sports; surveillance imaging every 6 months; refer for surgery given combined AS severity and aortic dilation

Per ACC/AHA guidelines, patients with bicuspid aortic valve and aortic dilation ≥4.5 cm (or ≥4.0 cm with rapid growth or family history of dissection) should avoid competitive sports due to aortic dissection risk. Combined with severe AS (AVA 0.7 cm², mean gradient 48 mmHg), the threshold for surgical intervention is lowered — current guidelines (2021 ACC/AHA Valvular Heart Disease) allow consideration of AVR in asymptomatic severe AS when undergoing other cardiac surgery (e.g., aortic repair), or with very low surgical risk and falling EF or high gradient. With ascending aorta ≥4.5 cm in bicuspid AV disease, surgical repair at the time of AVR is indicated. Referral for surgery is appropriate here on combined indications. Unrestricted marathon running is dangerous given aortic dimensions.

Question 17: 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)
Pulmonary hypertension due to ILD alone; PAH-specific therapy offers no benefit
Combined pre- and post-capillary PH; phosphodiesterase-5 inhibitors are contraindicated
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 18: 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 300mg daily for 9 months
Isoniazid plus rifapentine weekly for 12 weeks (3HP) (Correct answer)
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 19: A 61-year-old woman presents with acute chest pain. ECG shows ST depression in V1-V4 and ST elevation in aVR. Troponin is rapidly rising. She is hemodynamically stable. Emergent coronary angiography shows 90% stenosis of the left main coronary artery with TIMI-2 flow and 70% mid-LAD lesion. Her SYNTAX score is 38. Which revascularization strategy is MOST appropriate?

Emergency CABG with left internal mammary artery to LAD and saphenous vein graft to circumflex (Correct answer)
Medical management with GPIIb/IIIa inhibitor and reassess in 48 hours
PCI of left main with FFR-guided assessment of LAD lesion
PCI of left main only; defer LAD based on hemodynamic stability

Correct answer: Emergency CABG with left internal mammary artery to LAD and saphenous vein graft to circumflex

A SYNTAX score ≥33 in the setting of left main disease identifies patients who derive significantly greater survival benefit from CABG versus PCI (SYNTAX trial, NOBLE trial, EXCEL trial long-term data). With a score of 38 and a two-vessel disease pattern (left main + LAD), CABG with LIMA-to-LAD provides a proven long-term survival advantage and lower rates of repeat revascularization. PCI of left main in complex disease (SYNTAX ≥33) is associated with higher MACCE rates. In a hemodynamically stable patient, emergent CABG is feasible and preferred. Deferring the LAD or using medical management alone with rising troponin and high-grade left main disease is inappropriate. FFR assessment should not delay definitive revascularization in this acute high-risk presentation.

Question 20: A 28-year-old man presents with genital ulcers and painful inguinal lymphadenopathy (buboes). He recently returned from a trip to Africa. The ulcers are soft and painful. What is the most likely diagnosis and treatment?

Genital herpes; acyclovir 400mg TID
Chancroid; azithromycin 1g single dose (Correct answer)
LGV; doxycycline 100mg BID x 21 days
Syphilis; benzathine penicillin G IM

Correct answer: Chancroid; azithromycin 1g single dose

Chancroid (Haemophilus ducreyi) presents with painful soft ulcers and suppurative buboes; azithromycin 1g PO single dose is one of the recommended treatments.

Question 21: A 55-year-old man has low serum testosterone (180 ng/dL), LH 0.8 mIU/mL (low), and FSH 1.0 mIU/mL (low). MRI pituitary is normal. He takes opioids chronically for back pain. What is the diagnosis?

Primary hypogonadism
Opioid-induced hypogonadotropic hypogonadism (Correct answer)
Idiopathic hypogonadotropic hypogonadism
Klinefelter syndrome

Correct answer: Opioid-induced hypogonadotropic hypogonadism

Chronic opioid use suppresses GnRH pulsatility, reducing LH and FSH secretion and resulting in secondary (hypogonadotropic) hypogonadism with low testosterone.

Question 22: A 45-year-old woman with stage IIIA Hodgkin lymphoma achieves complete remission after ABVD chemotherapy. A PET scan performed after cycle 2 shows a Deauville score of 3. What is the most appropriate management?

Add rituximab to the remaining ABVD cycles
Escalate to BEACOPPescalated immediately
Consolidate with autologous stem cell transplant
Continue standard ABVD for the planned total course (Correct answer)

Correct answer: Continue standard ABVD for the planned total course

A Deauville score of 3 on interim PET (after 2 cycles of ABVD) is considered a negative scan per the Lugano criteria and indicates an adequate early response. Current evidence (RATHL trial) supports continuing standard ABVD without escalation for interim PET-negative patients with classic Hodgkin lymphoma. Escalation to BEACOPPescalated is reserved for PET-positive patients (Deauville 4–5). ASCT is for relapsed/refractory disease. Rituximab is not active in Hodgkin lymphoma (which is CD20-negative on Reed-Sternberg cells).

Question 23: A 65-year-old immunocompetent man presents with fever, altered mental status, and CSF pleocytosis with lymphocyte predominance, elevated protein, and normal glucose. HSV-1 encephalitis is suspected. What test confirms the diagnosis?

Brain biopsy for Cowdry type A inclusions
Serum HSV IgM antibodies
CSF culture for HSV
CSF HSV PCR (Correct answer)

Correct answer: CSF HSV PCR

CSF HSV PCR is the diagnostic test of choice for HSV encephalitis, with sensitivity >95% and specificity >99%, replacing brain biopsy as the gold standard.

Question 24: 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)
Starting IV epoprostenol while weaning oral therapies
Inhaled nitric oxide at 20 ppm
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 25: 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?

Continue metformin at reduced dose and add a GLP-1 receptor agonist
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

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 26: 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?

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

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 27: A 45-year-old with type 2 diabetes and a history of alcohol use disorder is found unresponsive. Labs: glucose 310 mg/dL, pH 7.24, bicarbonate 14 mEq/L, Na 138, Cl 96, anion gap 28. Serum lactate 1.1 mmol/L. Serum ethanol is undetectable. Urine is positive for ketones. Osmol gap is 22 mOsm/kg (normal <10). Which diagnosis best explains all findings?

Concurrent DKA and toxic alcohol ingestion (methanol or ethylene glycol) contributing to elevated osmol gap and anion gap (Correct answer)
Uremic acidosis with coincidental hyperglycemia from stress response and false-positive urine ketones
DKA alone — the osmol gap elevation is a spurious result from hyperglycemia causing pseudohyponatremia
Alcoholic ketoacidosis with stress hyperglycemia, as ethanol is cleared but its metabolic effects persist

Correct answer: Concurrent DKA and toxic alcohol ingestion (methanol or ethylene glycol) contributing to elevated osmol gap and anion gap

The combination of an elevated anion gap metabolic acidosis AND an elevated osmol gap strongly suggests toxic alcohol co-ingestion (methanol or ethylene glycol) in addition to DKA. DKA alone does not explain the osmol gap of 22 (normal <10). Toxic alcohols are metabolized to organic acids that close the osmol gap as they accumulate (early ingestion = high osmol gap/low anion gap; late ingestion = low osmol gap/high anion gap) — a mixed picture suggests intermediate timing. Undetectable serum ethanol does not exclude toxic alcohols. Emergent fomepizole, nephrology consultation, and ophthalmology evaluation (for methanol) are indicated while managing the DKA simultaneously. This is a life-threatening dual diagnosis that requires high clinical suspicion.

Question 28: 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?

Pulmonary Langerhans cell histiocytosis
Lymphangioleiomyomatosis (LAM) (Correct answer)
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 29: 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 600 mL, PEEP of 5 cm H₂O, and permissive hypercapnia is strictly avoided
Tidal volume of 300 mL, PEEP of 15 cm H₂O, and respiratory rate of 35 breaths/min
Tidal volume of 750 mL, PEEP of 5 cm H₂O, and plateau pressure < 40 cm H₂O
Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O (Correct answer)

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 30: 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?

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

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 31: 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?

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

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 32: 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 33: 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?

SGLT2 inhibitor
Insulin glargine
Pioglitazone
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 34: 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?

Perform surgical lung biopsy to distinguish UIP from NSIP pattern before initiating any treatment
Start high-dose methylprednisolone 1 mg/kg/day, given the BAL lymphocytosis suggesting an inflammatory, steroid-responsive process
Start nintedanib given the rapid FVC decline, recognizing it slows progression in SSc-ILD regardless of inflammatory activity (Correct answer)
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 35: A 50-year-old man with type 2 diabetes and a recent MI (6 weeks ago) has HbA1c 8.5%. He is on metformin and a sulfonylurea. Which agent should be added given his cardiovascular history?

Empagliflozin or liraglutide (Correct answer)
Alogliptin
Sitagliptin
Pioglitazone

Correct answer: Empagliflozin or liraglutide

SGLT-2 inhibitors (empagliflozin, dapagliflozin) and GLP-1 agonists (liraglutide, semaglutide) have demonstrated cardiovascular mortality reduction in patients with established ASCVD and are preferred add-on agents.

Question 36: Which of the following features most strongly differentiates papillary thyroid carcinoma from follicular thyroid carcinoma on fine needle aspiration?

Nuclear grooves, pseudoinclusions, and Orphan Annie eye nuclei (Correct answer)
Colloid abundance
Hurthle cell metaplasia
Psammoma bodies in follicular architecture

Correct answer: Nuclear grooves, pseudoinclusions, and Orphan Annie eye nuclei

Papillary thyroid carcinoma is diagnosed by characteristic nuclear features: grooves, pseudo-inclusions, and pale (Orphan Annie eye) nuclei on cytology.

Question 37: 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
Primary biliary cholangitis (Correct answer)
Autoimmune hepatitis
Choledocholithiasis

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 38: 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?

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

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 39: A 58-year-old man with newly diagnosed acute promyelocytic leukemia (APL) is started on ATRA and arsenic trioxide. On day 4, he develops fever to 39.2°C, weight gain of 3 kg, and new bilateral pulmonary infiltrates. His WBC has risen from 2,000 to 18,000/µL. Which of the following is the most appropriate next step?

Initiate broad-spectrum antibiotics and hold ATRA pending cultures
Add dexamethasone 10 mg IV twice daily and continue ATRA (Correct answer)
Discontinue ATRA immediately and start idarubicin
Perform bronchoscopy with BAL before any treatment changes

Correct answer: Add dexamethasone 10 mg IV twice daily and continue ATRA

This presentation is classic differentiation syndrome (formerly retinoic acid syndrome), which occurs in APL patients receiving ATRA or arsenic trioxide due to rapid differentiation and cytokine release from maturing promyelocytes. Management is high-dose corticosteroids (dexamethasone 10 mg IV BID) while continuing ATRA unless severe respiratory compromise requires temporary interruption. Discontinuing ATRA outright without steroids is incorrect; the syndrome is not infectious in origin, making antibiotics alone insufficient; and delaying treatment for bronchoscopy would be dangerous.

Question 40: 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?

Glipizide
Pioglitazone
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 41: 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?

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

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 42: Which of the following best describes the mechanism of action of ursodeoxycholic acid (UDCA) in primary biliary cholangitis?

Bile acid synthesis inhibition
Inhibition of TNF-alpha synthesis
Immunosuppression of autoreactive T cells
Displacement of toxic bile acids and hepatoprotection (Correct answer)

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 43: A 68-year-old female with severe chronic aortic regurgitation and an LVEF of 35% is symptomatic with dyspnea on exertion despite being on optimal medical therapy for heart failure, including a beta-blocker and diuretic. Her blood pressure is 145/70 mmHg. Which medication class, if added, would be most beneficial for afterload reduction in this patient?

Digoxin.
Hydralazine.
Non-dihydropyridine calcium channel blockers.
Angiotensin-converting enzyme (ACE) inhibitors. (Correct answer)

Correct answer: Angiotensin-converting enzyme (ACE) inhibitors.

In patients with symptomatic severe chronic aortic regurgitation who are not surgical candidates, or in those with LV systolic dysfunction, afterload reduction is a key component of medical management. ACE inhibitors or Angiotensin Receptor Blockers (ARBs) are preferred agents for this purpose, as they reduce systemic vascular resistance, decrease the regurgitant volume, and improve forward cardiac output. While hydralazine also reduces afterload, ACE inhibitors have more established benefits in heart failure with reduced ejection fraction. Non-dihydropyridine calcium channel blockers can have negative inotropic effects and are generally avoided. Digoxin may be used for rate control or symptoms but does not primarily address afterload.

Question 44: 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)
Initiating vasopressor therapy with norepinephrine
Measuring serum lactate level
Administering a 30 mL/kg crystalloid fluid bolus

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 45: Which of the following is the most common cause of sudden cardiac death in athletes under 35 years of age in the United States?

Arrhythmogenic right ventricular cardiomyopathy
Hypertrophic cardiomyopathy (Correct answer)
Long QT syndrome
Anomalous coronary artery origin

Correct answer: Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is the most common cause of sudden cardiac death in young US athletes, typically from ventricular arrhythmias during intense exertion.

Question 46: A 72-year-old man with low-flow, low-gradient severe aortic stenosis (AVA 0.7 cm², mean gradient 28 mmHg, LVEF 30%) undergoes dobutamine stress echocardiography. At peak dobutamine dose, AVA increases to 0.9 cm² and mean gradient rises to 35 mmHg. What is the most accurate interpretation?

Pseudo-severe aortic stenosis — the valve is not truly severe (Correct answer)
Indeterminate — cardiac catheterization with Gorlin formula required
True severe aortic stenosis with contractile reserve — proceed with AVR
True severe aortic stenosis without contractile reserve — medical management only

Correct answer: Pseudo-severe aortic stenosis — the valve is not truly severe

In low-flow, low-gradient AS, dobutamine stress echo differentiates true severe from pseudo-severe stenosis. When the AVA increases to >1.0 cm² with dobutamine, this indicates pseudo-severe stenosis — the low resting AVA is due to incomplete leaflet opening from low forward flow, not fixed severe stenosis. Here the AVA increased to 0.9 cm², which approaches but does not reach 1.0 cm²; however, the pattern of AVA increase with gradient increase (not a proportionally greater gradient increase) supports pseudo-severe AS. True severe AS with contractile reserve shows a fixed AVA (<1.0 cm²) despite increasing flow with a significant gradient rise.

Question 47: A 68-year-old former shipyard worker presents with progressive dyspnea and pleural plaques on chest CT. Pulmonary function testing shows FVC 68%, FEV1 70%, FEV1/FVC 0.82, DLCO 55% predicted. What type of pattern is present and what is the MOST likely diagnosis?

Mixed pattern due to mesothelioma
Normal spirometry with isolated DLCO reduction from pulmonary vascular disease
Obstructive pattern due to asbestos-related COPD
Restrictive pattern due to asbestosis (Correct answer)

Correct answer: Restrictive pattern due to asbestosis

A reduced FVC with preserved FEV1/FVC ratio (restrictive pattern) combined with reduced DLCO and occupational asbestos exposure indicates asbestosis (interstitial fibrosis from asbestos).

Question 48: 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?

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

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 49: 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
Initiate invasive mechanical ventilation with volume-control mode (Correct answer)
Administer IV doxapram as a respiratory stimulant to avoid intubation
Add high-flow nasal cannula at 40 L/min in combination with BiPAP

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 50: 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?

Ustekinumab
Infliximab (Correct answer)
Natalizumab
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 51: 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?

Empagliflozin competes with ketone bodies for renal tubular reabsorption, falsely elevating serum ketone measurements
SGLT2 inhibition increases renal glucose excretion, lowering plasma glucose while glucagon-mediated ketogenesis is simultaneously upregulated (Correct answer)
SGLT2 inhibition causes volume depletion, triggering stress-hormone-mediated lipolysis independently of insulin levels
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 52: Which of the following is the most common cause of acute pancreatitis in the United States?

Hypertriglyceridemia
Alcohol
Medications
Gallstones (Correct answer)

Correct answer: Gallstones

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

Question 53: Which of the following best explains the mechanism of anion gap metabolic acidosis in DKA?

Loss of bicarbonate through the kidneys
Lactic acid accumulation from tissue hypoperfusion
Hyperchloremia from normal saline administration
Accumulation of beta-hydroxybutyrate and acetoacetate (Correct answer)

Correct answer: Accumulation of beta-hydroxybutyrate and acetoacetate

DKA causes anion gap acidosis due to accumulation of ketoacids (beta-hydroxybutyrate and acetoacetate) from unregulated fatty acid oxidation.

Question 54: 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?

Continue with as-needed short-acting beta-agonist (SABA) only
Prescribe a daily long-acting beta-agonist (LABA) inhaler
Prescribe a daily low-dose inhaled corticosteroid (ICS) and continue SABA as needed
Prescribe as-needed low-dose inhaled corticosteroid (ICS)-formoterol (Correct answer)

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 55: 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?

Phlebotomy to reduce platelet count
Cytoreductive therapy with hydroxyurea plus aspirin
Anagrelide as monotherapy
Low-dose aspirin alone (Correct answer)

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 56: 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?

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

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 57: A 52-year-old woman presents with sudden-onset 'thunderclap' headache that she describes as the worst headache of her life, reaching peak intensity in seconds. CT head is negative. What is the next most appropriate diagnostic step?

Lumbar puncture for xanthochromia and RBC count (Correct answer)
MRI brain with gadolinium
Empiric sumatriptan and reassurance
CT angiography of the head deferred to outpatient

Correct answer: Lumbar puncture for xanthochromia and RBC count

A thunderclap headache with normal CT requires lumbar puncture to rule out subarachnoid hemorrhage (SAH), which can be CT-negative in up to 2–5% of cases in the first 6–12 hours but positive for xanthochromia on LP. MRI is less sensitive than LP for early SAH. Delaying CTA or treating empirically without LP risks missing a potentially fatal condition.

Question 58: 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
Early enteral nutrition via nasojejunal tube within 24-48 hours (Correct answer)
Bowel rest until pain resolves
Oral clear liquids when amylase normalizes

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 59: A patient on amiodarone develops fatigue, weight gain, and bradycardia. TSH is 42 mIU/L and free T4 is 0.4 ng/dL. What is the most appropriate management?

Obtain thyroid ultrasound and defer treatment
Administer Lugol's iodine
Start levothyroxine replacement (Correct answer)
Discontinue amiodarone only

Correct answer: Start levothyroxine replacement

Amiodarone-induced hypothyroidism requires levothyroxine replacement; amiodarone discontinuation is often not feasible due to underlying cardiac disease.

Question 60: 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?

Add hydroxyurea to achieve hematocrit <45% (Correct answer)
Begin therapeutic anticoagulation with warfarin alone
Switch aspirin to clopidogrel for superior platelet inhibition
Initiate ruxolitinib as first-line cytoreductive therapy

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

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

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 62: A 62-year-old female presents to the emergency department with an acute onset of shortness of breath. Her medical history is significant for hypertension. On examination, her blood pressure is 155/95 mmHg, heart rate is 105 bpm, and respiratory rate is 24 breaths/min. She has bilateral crackles on lung auscultation and 2+ pitting edema in her lower extremities. A B-type natriuretic peptide (BNP) level is markedly elevated. Transthoracic echocardiogram reveals a left ventricular ejection fraction of 35%. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure, which of the following medication classes should be initiated in this patient, in addition to a diuretic, once she is hemodynamically stable?

A beta-blocker
An angiotensin receptor-neprilysin inhibitor (ARNI)
All of the above (Correct answer)
An SGLT2 inhibitor

Correct answer: All of the above

The 2022 AHA/ACC/HFSA Heart Failure Guideline recommends quadruple therapy for heart failure with reduced ejection fraction (HFrEF). This includes an ARNI (or ACE inhibitor/ARB), an evidence-based beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter-2 (SGLT2) inhibitor. These four classes of medications are the cornerstone of guideline-directed medical therapy (GDMT) and should be initiated as tolerated to improve symptoms and reduce mortality.

Question 63: 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)
0.45% NaCl (hypotonic saline)
0.9% NaCl (isotonic saline) (Correct answer)
Lactated Ringer's solution

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 64: 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
Baseline CSF cryptococcal antigen titer
Adequacy of serial therapeutic lumbar punctures to control intracranial pressure (Correct answer)
Time to CSF culture sterilization

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 65: A 40-year-old HIV-positive man (CD4 40) on antiretrovirals develops vision loss. Fundoscopic exam shows yellow-white perivascular exudates with hemorrhage ('pizza pie' appearance). What is the diagnosis and treatment?

CMV retinitis; IV ganciclovir or oral valganciclovir (Correct answer)
Ocular histoplasmosis; itraconazole
Cryptococcal chorioretinitis; fluconazole
Toxoplasma retinitis; pyrimethamine plus sulfadiazine

Correct answer: CMV retinitis; IV ganciclovir or oral valganciclovir

CMV retinitis in advanced AIDS presents with the classic 'pizza pie' fundoscopic appearance and is treated with valganciclovir 900mg BID for induction followed by maintenance therapy.

Question 66: A 47-year-old woman with type 1 diabetes is 8 hours into treatment for DKA. Her admission phosphate was 2.6 mg/dL. Repeat labs now show phosphate 1.1 mg/dL, potassium 3.7 mEq/L, glucose 220 mg/dL. She is asymptomatic with no respiratory distress, normal cardiac rhythm, and no signs of hemolysis. Which statement most accurately describes the role of phosphate replacement in her management?

Routine phosphate replacement is standard of care in DKA and should be initiated for any phosphate below 2.0 mg/dL based on multiple RCTs demonstrating improved outcomes
Routine phosphate replacement has not demonstrated clinical benefit in RCTs; replacement may be considered for severe hypophosphatemia (< 1.0–1.5 mg/dL) complicated by cardiac dysfunction, respiratory muscle weakness, or hemolytic anemia (Correct answer)
Phosphate replacement is contraindicated in DKA because IV phosphate salts invariably cause symptomatic hypocalcemia
Hypophosphatemia in DKA is entirely driven by osmotic diuresis and corrects spontaneously with IV fluids, eliminating any need for supplementation

Correct answer: Routine phosphate replacement has not demonstrated clinical benefit in RCTs; replacement may be considered for severe hypophosphatemia (< 1.0–1.5 mg/dL) complicated by cardiac dysfunction, respiratory muscle weakness, or hemolytic anemia

Phosphate levels fall during DKA treatment as insulin drives phosphate intracellularly. However, randomized controlled trials have consistently failed to show that routine phosphate replacement improves clinical outcomes. The ADA therefore does not recommend routine replacement. The exception is severe hypophosphatemia (generally < 1.0–1.5 mg/dL) in the presence of specific complications where it becomes clinically relevant: cardiac dysfunction (phosphate-dependent myocardial contractility), respiratory muscle weakness (risk of ventilatory failure), or hemolytic anemia. At 1.1 mg/dL without symptoms or organ dysfunction, this patient is borderline but does not yet meet the threshold for mandatory replacement. Hypocalcemia is a real concern with phosphate infusion but is not an absolute contraindication.

Question 67: A 40-year-old man is admitted to the ICU with septic shock from pneumonia. After 6 hours of resuscitation with 4 L of crystalloid, he remains hypotensive with MAP 58 mmHg. He is on norepinephrine 0.18 mcg/kg/min. Point-of-care echo shows hyperdynamic LV function with IVC collapsibility >50%. What intervention is MOST appropriate?

Begin hydrocortisone 200 mg/day for refractory septic shock
Administer an additional 2 L of IV fluid bolus (Correct answer)
Add vasopressin 0.03 units/min to norepinephrine
Start dobutamine for cardiogenic shock

Correct answer: Administer an additional 2 L of IV fluid bolus

IVC collapsibility >50% indicates volume responsiveness; additional fluid resuscitation is appropriate when dynamic indices suggest ongoing hypovolemia in distributive shock.

Question 68: 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?

Liposomal amphotericin B 3mg/kg/day
Micafungin 150mg IV daily
Fluconazole 400mg IV daily
Voriconazole 6mg/kg IV q12h x 2 doses, then 4mg/kg q12h (Correct answer)

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 69: 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?

TRAb does not cross the placenta in the first trimester, so current titer has no fetal implications until after 20 weeks
Neonatal Graves' disease risk is determined by maternal free T4 level at delivery, not by TRAb titer
Methimazole should be switched to propylthiouracil for the remainder of the pregnancy to eliminate teratogenic risk
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)

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 70: A 44-year-old woman has a TSH of 0.02 mIU/L and free T4 of 2.8 ng/dL. She takes levothyroxine 150 mcg/day for hypothyroidism. She is asymptomatic. DEXA shows T-score −2.1 at lumbar spine. What is the most important reason to adjust her levothyroxine?

Exogenous subclinical hyperthyroidism accelerates bone loss (Correct answer)
Risk of thyroid storm
Risk of Afib from subclinical hyperthyroidism
Suppressed TSH causes pituitary enlargement

Correct answer: Exogenous subclinical hyperthyroidism accelerates bone loss

Exogenous subclinical hyperthyroidism (suppressed TSH) accelerates bone turnover and exacerbates osteoporosis, making dose reduction important in this patient with already reduced bone density.

Question 71: 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?

Staphylococcus aureus
Eikenella corrodens
Pasteurella multocida (Correct answer)
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 72: 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?

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

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 73: 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?

Temporary transvenous pacing only
Permanent pacemaker implantation (Correct answer)
Observation with Holter monitoring
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 74: 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)?

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

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 75: A 38-year-old woman presents with hypertension, hypokalemia, and metabolic alkalosis. Plasma aldosterone-to-renin ratio is markedly elevated. CT abdomen shows a 1.8 cm right adrenal adenoma. What is the definitive treatment?

Fludrocortisone suppression test and observation
Laparoscopic right adrenalectomy (Correct answer)
Lifelong spironolactone therapy
Bilateral adrenalectomy

Correct answer: Laparoscopic right adrenalectomy

A unilateral aldosterone-producing adenoma confirmed by adrenal vein sampling is best treated with laparoscopic unilateral adrenalectomy, which is curative in most cases.

Question 76: 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?

Meropenem plus vancomycin plus dexamethasone (Correct answer)
Aztreonam plus vancomycin plus dexamethasone
Chloramphenicol plus rifampin plus dexamethasone
Trimethoprim-sulfamethoxazole plus vancomycin plus dexamethasone

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 77: 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. She undergoes adrenal vein sampling (AVS), which demonstrates a lateralization ratio of 1.8 (right:left). Which of the following is the most appropriate next step?

Order 11C-metomidate PET scan to identify unilateral adenoma
Treat with mineralocorticoid receptor antagonist (spironolactone) rather than surgery (Correct answer)
Repeat AVS with cosyntropin stimulation to improve accuracy
Proceed with right adrenalectomy based on lateralization ratio

Correct answer: Treat with mineralocorticoid receptor antagonist (spironolactone) rather than surgery

A lateralization ratio of ≥4:1 (or ≥3:1 with cosyntropin stimulation) is generally required to confirm unilateral disease and proceed with adrenalectomy. A ratio of 1.8 is non-lateralizing, indicating bilateral hyperplasia rather than a unilateral adenoma. In bilateral adrenal hyperplasia causing primary aldosteronism, the treatment of choice is medical management with a mineralocorticoid receptor antagonist such as spironolactone or eplerenone, not surgery. Proceeding with adrenalectomy based on an inadequate lateralization ratio would likely result in surgical failure without biochemical cure.

Question 78: A 40-year-old woman with myelodysplastic syndrome has a del(5q) as the sole cytogenetic abnormality, transfusion-dependent anemia, and platelet count of 450,000/μL. Which agent is specifically indicated?

Erythropoiesis-stimulating agents
Lenalidomide (Correct answer)
Decitabine
Azacitidine

Correct answer: Lenalidomide

Lenalidomide is specifically approved for transfusion-dependent MDS with isolated del(5q) and produces high rates of transfusion independence.

Question 79: 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
Chloramphenicol 500mg QID
Ciprofloxacin 500mg BID
Doxycycline 100mg BID (Correct answer)

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 80: A 22-year-old woman presents with her second unprovoked tonic-clonic seizure. MRI brain is normal. EEG shows 3 Hz spike-and-wave discharges. She is of childbearing age. Which antiepileptic drug is MOST appropriate as initial monotherapy?

Valproate
Carbamazepine
Lamotrigine (Correct answer)
Phenytoin

Correct answer: Lamotrigine

Lamotrigine is appropriate for generalized epilepsy (consistent with 3 Hz spike-wave = absence/generalized epilepsy) and carries a lower teratogenic risk compared to valproate, making it preferable for women of childbearing potential. Valproate is highly effective but is a known teratogen (neural tube defects). Phenytoin and carbamazepine can worsen absence seizures.

Question 81: A 55-year-old man with newly diagnosed type 2 diabetes has an A1C of 8.2%, eGFR of 55 mL/min, and established cardiovascular disease. Which medication has the greatest cardiovascular mortality benefit?

Empagliflozin (SGLT-2 inhibitor) (Correct answer)
Pioglitazone (thiazolidinedione)
Sitagliptin (DPP-4 inhibitor)
Glipizide (sulfonylurea)

Correct answer: Empagliflozin (SGLT-2 inhibitor)

SGLT-2 inhibitors like empagliflozin have demonstrated cardiovascular mortality reduction in patients with established CVD in landmark trials (EMPA-REG).

Question 82: 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?

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

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 83: A 29-year-old woman with obesity (BMI 41) and no other comorbidities presents with excessive daytime sleepiness, morning headaches, and bilateral papilledema on fundoscopic exam. Polysomnography shows AHI 52 events/hour, mean SaO2 88%, with prolonged periods of hypoventilation. Arterial blood gas while awake shows pH 7.37, PaCO2 52 mmHg, PaO2 62 mmHg, HCO3 30 mEq/L. Serum bicarbonate elevation is consistent with chronic compensation. Which diagnostic criterion BEST supports a diagnosis of Obesity Hypoventilation Syndrome (OHS) rather than OSA with nocturnal hypoventilation alone?

BMI greater than 35 kg/m² with Epworth Sleepiness Scale score above 10
Nocturnal SaO2 nadir below 85% on polysomnography
AHI greater than 30 events/hour on polysomnography
Awake daytime hypercapnia (PaCO2 ≥45 mmHg) in the absence of other causes of hypoventilation (Correct answer)

Correct answer: Awake daytime hypercapnia (PaCO2 ≥45 mmHg) in the absence of other causes of hypoventilation

The cardinal diagnostic criterion for Obesity Hypoventilation Syndrome (OHS) is awake daytime hypercapnia (PaCO2 ≥45 mmHg) in an obese patient (BMI ≥30) after excluding other causes of hypoventilation (e.g., COPD, neuromuscular disease, chest wall deformity, hypothyroidism). This patient's awake PaCO2 of 52 mmHg with elevated bicarbonate confirms chronic daytime CO2 retention. OSA alone — even with severe nocturnal desaturation — does not cause daytime hypercapnia in the absence of impaired ventilatory control. The AHI, nocturnal SaO2 nadir, BMI threshold, and ESS score are not diagnostic of OHS; they suggest OSA but cannot distinguish it from OHS without the daytime gas exchange criterion.

Question 84: 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?

Immediate surgical resection given β-catenin mutation subtype (Correct answer)
Arterial embolization followed by MRI surveillance
Discontinue OCPs and repeat MRI in 6 months; proceed to resection regardless of size change
Discontinue OCPs and repeat MRI in 6 months; resect only if adenoma grows >5 cm

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 85: 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?

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

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 86: 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?

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

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 87: 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?

Anti-TNF biologic therapy
A nonsteroidal anti-inflammatory drug (NSAID) at full therapeutic dose (Correct answer)
Methotrexate 15 mg weekly
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 88: A 71-year-old man with stage G4 CKD (eGFR 18 mL/min/1.73m²) presents for pre-dialysis planning. He is found to have a serum bicarbonate of 16 mEq/L. Serum potassium is 5.1 mEq/L. A urine anion gap (UAG) is calculated to be +12 mEq/L. Which of the following statements about his acid-base status and management is MOST accurate?

A positive UAG confirms distal (type 1) renal tubular acidosis (dRTA) as the cause; treatment is potassium citrate to avoid the sodium load
A positive UAG in this context indicates a gastrointestinal source of bicarbonate loss; colonoscopy should be performed to rule out villous adenoma
A positive UAG in CKD-associated metabolic acidosis reflects impaired ammoniagenesis rather than distal tubular proton secretion failure, and oral sodium bicarbonate supplementation slows CKD progression per randomized trial data (Correct answer)
UAG is unreliable in CKD; serum bicarbonate alone determines the acid-base diagnosis, and treatment with dialysis initiation is preferred over alkali therapy

Correct answer: A positive UAG in CKD-associated metabolic acidosis reflects impaired ammoniagenesis rather than distal tubular proton secretion failure, and oral sodium bicarbonate supplementation slows CKD progression per randomized trial data

In advanced CKD, metabolic acidosis is primarily due to reduced ammoniagenesis — the kidneys cannot produce enough NH₃/NH₄⁺ to buffer and excrete the daily acid load. A positive UAG (Na⁺ + K⁺ – Cl⁻ > 0 in urine) indicates low urinary ammonium, consistent with impaired ammoniagenesis rather than a GI bicarbonate loss (which would produce a negative UAG due to high ammonium). This is distinct from dRTA, which also gives a positive UAG but involves a proton pump defect in the collecting duct, not global ammoniagenesis failure. The Kidney Diseases: Improving Global Outcomes (KDIGO) guidelines and the BASE trial (and other RCTs) support oral sodium bicarbonate supplementation to target serum bicarbonate ≥22 mEq/L, with evidence that alkali therapy reduces the rate of eGFR decline.

Question 89: A 66-year-old woman with atrial fibrillation and a CHA₂DS₂-VASc score of 4 is started on apixaban. She asks about dietary restrictions. What is the most accurate counseling?

Avoid all green leafy vegetables as with warfarin
No significant dietary restrictions required (Correct answer)
Avoid grapefruit but monitor INR monthly
Limit vitamin K intake to <90 mcg/day

Correct answer: No significant dietary restrictions required

Unlike warfarin, apixaban (a direct oral anticoagulant) does not require dietary vitamin K restriction or routine INR monitoring.

Question 90: A 22-year-old college student presents with fever, pharyngitis, cervical lymphadenopathy, and splenomegaly. Heterophile antibody test is positive. Which complication requires activity restriction?

Thrombocytopenia
Airway obstruction
Splenic rupture risk (Correct answer)
Hepatitis

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 91: 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?

Heliox administration
Immediate endotracheal intubation
Non-invasive positive pressure ventilation (NIPPV) (Correct answer)
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 92: A 44-year-old woman has recurrent syncopal episodes during emotional stress. ECG shows a prolonged QTc of 520ms. She is started on nadolol. Which additional measure is most important for preventing sudden death?

Potassium supplementation to maintain K+ >4.5 mEq/L
Avoidance of all QT-prolonging medications (Correct answer)
Implantable cardioverter-defibrillator placement
Left cardiac sympathetic denervation

Correct answer: Avoidance of all QT-prolonging medications

Avoidance of QT-prolonging drugs (antiarrhythmics, antibiotics, antiemetics, antipsychotics) is critical in congenital long QT syndrome to prevent torsades de pointes.

Question 93: 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?

Trimethoprim-sulfamethoxazole DS BID x 7 days
Ciprofloxacin 500mg BID x 3 days
Nitrofurantoin 100mg BID x 5 days (Correct answer)
Doxycycline 100mg BID x 7 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 94: 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?

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

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 95: 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?

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

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

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 97: A 28-year-old with HIV (CD4 count 45 cells/µL) presents with fever, dry cough, and progressive dyspnea over 3 weeks. LDH is markedly elevated. CXR shows bilateral interstitial infiltrates. What is the first-line treatment?

Fluconazole
Trimethoprim-sulfamethoxazole + prednisone (Correct answer)
Ganciclovir
Azithromycin + ethambutol

Correct answer: Trimethoprim-sulfamethoxazole + prednisone

PCP pneumonia in HIV patients with moderate-to-severe disease (PaO2 <70 mmHg or A-a gradient >35) is treated with TMP-SMX plus adjunctive corticosteroids.

Question 98: A 25-year-old male with cystic fibrosis has FEV1 that has declined from 65% to 42% over 2 years despite optimal inhaled therapy. He has the F508del/F508del genotype. Which CFTR modulator regimen is most appropriate?

Ataluren
Ivacaftor alone
Lumacaftor-ivacaftor
Elexacaftor-tezacaftor-ivacaftor (Trikafta) (Correct answer)

Correct answer: Elexacaftor-tezacaftor-ivacaftor (Trikafta)

Elexacaftor-tezacaftor-ivacaftor (Trikafta) is approved for F508del homozygous patients age ≥2 and produces the greatest improvement in lung function of any available CFTR modulator combination.

Question 99: Which criterion must be met before transitioning a DKA patient from IV to subcutaneous insulin?

pH > 7.30 only
Blood glucose < 200 mg/dL
Urine ketones negative
Anion gap closure AND ability to eat (Correct answer)

Correct answer: Anion gap closure AND ability to eat

DKA resolution requires anion gap closure, pH >7.3, and bicarbonate >18; the patient must also be able to tolerate oral intake before transitioning to subcutaneous insulin.

Question 100: 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?

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

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 101: A 35-year-old woman presents with a 3-month history of symmetric, painful swelling of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, morning stiffness lasting 2 hours, and fatigue. Labs show RF positive, anti-CCP positive, ESR 68. Which of the following is the most appropriate initial disease-modifying therapy?

Prednisone 40 mg daily
Methotrexate (Correct answer)
Naproxen 500 mg twice daily
Hydroxychloroquine monotherapy

Correct answer: Methotrexate

Methotrexate is the anchor DMARD for rheumatoid arthritis and is first-line per ACR guidelines. Prednisone addresses symptoms but is not a DMARD. NSAIDs provide symptom relief without disease modification. Hydroxychloroquine alone is insufficient for seropositive RA with active synovitis.

Question 102: 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
Tuberculous peritonitis
Constrictive pericarditis (Correct answer)

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 103: 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?

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

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 104: 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?

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

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 105: 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?

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

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 106: A 60-year-old male with long-standing GERD and Barrett's esophagus develops a dry cough and progressive dyspnea. HRCT shows basal-predominant reticulation with traction bronchiectasis and honeycombing. The BAL shows 6% lymphocytes. What is the most likely diagnosis?

Cryptogenic organizing pneumonia
Hypersensitivity pneumonitis
Idiopathic pulmonary fibrosis (IPF) (Correct answer)
NSIP associated with GERD

Correct answer: Idiopathic pulmonary fibrosis (IPF)

The HRCT pattern of bibasilar honeycombing with traction bronchiectasis represents UIP pattern, most consistent with IPF, even in the context of GERD; low BAL lymphocytes also favor IPF over HP.

Question 107: A 45-year-old female farmer presents with acute dyspnea, fever, and bilateral infiltrates 4-6 hours after entering a hay storage barn. Precipitating antibodies to Thermophilic actinomycetes are positive. What is the diagnosis?

Allergic bronchopulmonary aspergillosis (ABPA)
Acute hypersensitivity pneumonitis (Farmer's lung) (Correct answer)
Acute sarcoidosis
Organic dust toxic syndrome (ODTS)

Correct answer: Acute hypersensitivity pneumonitis (Farmer's lung)

Farmer's lung is a classic form of acute hypersensitivity pneumonitis caused by inhalation of thermophilic actinomycetes from moldy hay, occurring 4–8 hours after exposure.

Question 108: 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?

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

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 109: 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?

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

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 110: A 72-year-old male with a history of hypertension presents for a routine evaluation. He denies chest pain, dyspnea, or syncope. On physical exam, you note a grade 3/6 late-peaking systolic ejection murmur at the right upper sternal border that radiates to the carotids. An echocardiogram reveals a calcified aortic valve with a peak velocity of 4.5 m/s, a mean gradient of 50 mm Hg, and an aortic valve area of 0.8 cm². His left ventricular ejection fraction (LVEF) is 65%. Which of the following is the most appropriate next step in management?

Perform an exercise stress test to confirm asymptomatic status. (Correct answer)
Begin afterload reduction with an ACE inhibitor.
Initiate medical therapy with a beta-blocker and schedule a follow-up in one year.
Refer for surgical aortic valve replacement (SAVR).

Correct answer: Perform an exercise stress test to confirm asymptomatic status.

According to the 2020 ACC/AHA guidelines, for asymptomatic patients with severe aortic stenosis, exercise testing is reasonable to confirm the absence of symptoms and to assess hemodynamic response. The development of symptoms during exercise would be an indication for intervention. Medical therapy with beta-blockers or ACE inhibitors has not been proven to alter the natural history of aortic stenosis and is not the primary treatment. While the patient has severe aortic stenosis based on echocardiographic criteria, intervention is primarily indicated for symptomatic patients or those with LV dysfunction. Therefore, confirming his asymptomatic status with objective testing is the most appropriate next step before considering valve replacement.

Question 111: 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?

Anticoagulation with rivaroxaban or apixaban (Correct answer)
Systemic thrombolysis with IV alteplase
Catheter-directed thrombolysis
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 112: A 55-year-old man with newly diagnosed type 2 diabetes has an HbA1c of 7.8%, BMI 36 kg/m², no cardiovascular disease, and normal renal function. What is the most appropriate pharmacotherapy beyond lifestyle modification?

Sulfonylurea alone
Metformin alone
Metformin + GLP-1 receptor agonist (Correct answer)
Insulin glargine

Correct answer: Metformin + GLP-1 receptor agonist

Current ADA guidelines favor early combination therapy in patients with HbA1c >1.5–2% above goal; adding a GLP-1 agonist to metformin also promotes weight loss, which is beneficial in this obese patient.

Question 113: 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
Hyperventilation-induced hypocapnia returning to baseline
Adequate compensation for metabolic acidosis
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 114: 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?

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

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 115: 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)
Azithromycin prophylaxis 250 mg daily
Inhaled triple therapy (LABA/LAMA/ICS)
Bronchoscopic lung volume reduction with endobronchial valves

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 116: A patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). After treatment, which prophylactic antibiotic is recommended to prevent recurrence?

Norfloxacin (Correct answer)
Metronidazole
Amoxicillin-clavulanate
Cephalexin

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 117: 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?

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

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 118: 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?

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

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 119: A 44-year-old female never-smoker develops cough and hemoptysis. Bronchoscopy reveals a polypoid endobronchial lesion in the right lower lobe. Biopsy shows carcinoid features with 3 mitoses/10 HPF and focal necrosis. What is the diagnosis?

Large cell neuroendocrine carcinoma
Typical carcinoid tumor
Small cell lung carcinoma
Atypical carcinoid tumor (Correct answer)

Correct answer: Atypical carcinoid tumor

Atypical carcinoid is defined by 2–10 mitoses/10 HPF and/or foci of necrosis, distinguishing it from typical carcinoid (<2 mitoses/10 HPF, no necrosis); both differ from high-grade neuroendocrine tumors.

Question 120: 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)
Weekly serum cryptococcal antigen titers
Renal function and electrolytes for amphotericin B nephrotoxicity
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 121: 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?

Aspergillus fumigatus
Candida albicans
Mucor/Rhizopus species (Correct answer)
Fusarium solani

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 122: A patient with DKA has a corrected sodium of 148 mEq/L. How is corrected sodium calculated in hyperglycemia?

Add 2.4 mEq/L for every 100 mg/dL glucose above 100
Subtract 1.6 mEq/L for every 100 mg/dL glucose above 100
No correction needed; measure directly
Add 1.6 mEq/L for every 100 mg/dL glucose above 100 (Correct answer)

Correct answer: Add 1.6 mEq/L for every 100 mg/dL glucose above 100

Corrected sodium is calculated by adding 1.6 mEq/L (or 2.4 mEq/L per some guidelines) for every 100 mg/dL glucose above 100 to account for osmotic dilution.

Question 123: A 62-year-old man with known acromegaly has a post-surgical IGF-1 still 2.5× the upper limit of normal. MRI shows no residual tumor. What is the most appropriate next step in management?

Somatostatin receptor ligand (octreotide LAR or lanreotide) (Correct answer)
Pegvisomant monotherapy
Pituitary radiation
Repeat surgery

Correct answer: Somatostatin receptor ligand (octreotide LAR or lanreotide)

When post-surgical IGF-1 remains elevated without visible residual tumor, somatostatin receptor ligands are first-line medical therapy; pegvisomant is reserved for those not responding to or intolerant of somatostatin analogues.

Question 124: 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 >20 mmHg with PCWP >15 mmHg
Mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units (Correct answer)
Mean PAP >25 mmHg with elevated cardiac output

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 125: A 55-year-old male with newly diagnosed small cell lung cancer has disease confined to the right hemithorax and ipsilateral mediastinal nodes that can be encompassed in a radiation field. What is the classification and treatment approach?

Limited-stage SCLC — surgery followed by chemotherapy
Extensive-stage SCLC — chemotherapy alone
Extensive-stage SCLC — chemo + immunotherapy
Limited-stage SCLC — concurrent chemoradiation (Correct answer)

Correct answer: Limited-stage SCLC — concurrent chemoradiation

Limited-stage SCLC (confined to one hemithorax within a tolerable radiation field) is treated with concurrent platinum-based chemotherapy and thoracic radiation, with prophylactic cranial irradiation if response is achieved.

Question 126: 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?

Choledocholithiasis
IgG4-related cholangiopathy
Primary biliary cholangitis
Primary sclerosing cholangitis (Correct answer)

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 127: 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 tidal volume to increase minute ventilation
Decrease FiO2 to 0.21
Increase PEEP to improve oxygenation
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 128: 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?

Denosumab
Raloxifene
Oral alendronate (Correct answer)
Teriparatide

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 129: 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?

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

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 130: A 65-year-old man with metastatic lung cancer develops calcium of 13.5 mg/dL, low PTH, low 1,25-dihydroxyvitamin D, and elevated PTHrP. Which mechanism best explains his hypercalcemia?

Ectopic 1-alpha hydroxylase activity
Adrenal insufficiency from metastases
Humoral hypercalcemia of malignancy via PTHrP (Correct answer)
Local osteolytic metastases releasing calcium

Correct answer: Humoral hypercalcemia of malignancy via PTHrP

Elevated PTHrP with suppressed PTH and low 1,25-(OH)2D is the hallmark of humoral hypercalcemia of malignancy, the most common cause of cancer-related hypercalcemia.

Question 131: 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?

Itraconazole
Valganciclovir
Trimethoprim-sulfamethoxazole (Correct answer)
Azithromycin

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 132: A patient receiving cisplatin-based chemotherapy develops a serum creatinine rise from 0.9 to 2.1 mg/dL. Urinalysis shows granular casts and low urine sodium. What is the mechanism of nephrotoxicity?

Prerenal azotemia from vomiting
Interstitial nephritis from hypersensitivity
Direct proximal tubular cell injury (Correct answer)
Obstructive uropathy from uric acid crystals

Correct answer: Direct proximal tubular cell injury

Cisplatin causes direct proximal tubular injury through accumulation of platinum-DNA adducts, leading to tubular necrosis.

Question 133: 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 short-acting beta-agonist (SABA) as needed with no maintenance therapy
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)

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 134: 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?

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

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 135: 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 atovaquone-proguanil as outpatient therapy
Oral chloroquine given the 72-hour fever cycle suggesting P. malariae

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 136: 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
Bismuth quadruple therapy (Correct answer)
Endoscopy with biopsy culture
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 137: 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?

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

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 138: 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?

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

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 139: 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 = 52 cmH2O; decrease tidal volume to 4 mL/kg IBW
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)

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 140: 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:

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

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 141: 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?

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)
Aqueous crystalline penicillin G IV for 10-14 days (neurosyphilis coverage)

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 142: 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?

Elevated EBV DNA in peripheral blood by PCR with markedly elevated sNK cell activity
Ferritin level greater than 50,000 ng/mL
Homozygous PRF1 (perforin) mutation on genetic testing (Correct answer)
Bone marrow biopsy showing CD8+ T-cell infiltration with hemophagocytosis

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 143: 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?

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

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 144: 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
Azithromycin 1g single dose
Ciprofloxacin 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 145: A 58-year-old man with a history of medullary thyroid carcinoma (MTC) treated with total thyroidectomy 10 years ago presents with rising calcitonin levels (current: 850 pg/mL). Neck ultrasound, CT chest/abdomen, and bone scan are all negative. Which of the following is the most appropriate next step in evaluation?

Start vandetanib therapy
Empiric external beam radiation therapy to the neck
Order 68Ga-DOTATATE PET/CT scan
Perform selective venous catheterization with calcitonin sampling to localize occult disease (Correct answer)

Correct answer: Perform selective venous catheterization with calcitonin sampling to localize occult disease

In biochemically persistent or recurrent MTC with negative conventional imaging, selective venous catheterization with calcitonin gradient sampling is the next step to localize occult metastatic disease (typically hepatic micrometastases or lymph nodes). This technique can identify a hepatic or regional gradient pointing toward a specific site of disease. 68Ga-DOTATATE PET is used for somatostatin receptor-positive tumors (e.g., carcinoid, paraganglioma) and has limited utility in MTC. Vandetanib is reserved for progressive, symptomatic, or unresectable/metastatic MTC — not indicated without confirmed active disease. Empiric radiation is inappropriate without a defined target.

Question 146: Which class of medications should be AVOIDED in patients with severe aortic stenosis presenting with systemic hypertension?

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

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 147: 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?

EGFR-targeted therapy with osimertinib
Cisplatin/pemetrexed chemotherapy alone
Pembrolizumab monotherapy
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 148: A 25-year-old man presents with bilateral testicular germ cell tumor markers showing elevated AFP and beta-hCG. Staging CT shows retroperitoneal lymph nodes up to 3 cm but no visceral metastases. What is the first-line treatment?

Orchiectomy followed by BEP chemotherapy (Correct answer)
BEP chemotherapy without surgery
Orchiectomy and retroperitoneal lymph node dissection only
Orchiectomy followed by radiation alone

Correct answer: Orchiectomy followed by BEP chemotherapy

For intermediate or high-risk nonseminomatous GCT with elevated markers and lymph node involvement, orchiectomy followed by BEP (bleomycin, etoposide, cisplatin) is standard.

Question 149: 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?

Inhaled pentamidine
Systemic corticosteroids (prednisone 40mg BID) (Correct answer)
G-CSF support
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 150: 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
Repeat TEE in 2 weeks is the next step
Empiric switch to vancomycin is required
Cardiac surgery consultation is required (Correct answer)

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 151: Which finding on echocardiography is most consistent with severe mitral stenosis?

Pressure half-time of 90 ms
Mitral valve area of 1.0 cm² (Correct answer)
Mitral valve area of 1.8 cm²
Mean transmitral gradient of 3 mmHg

Correct answer: Mitral valve area of 1.0 cm²

Severe mitral stenosis is defined by an MVA ≤1.5 cm², with very severe disease defined as MVA ≤1.0 cm².

Question 152: 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?

42 days
14 days (Correct answer)
7 days
28 days

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 153: A 74-year-old woman with a mechanical mitral valve on warfarin requires elective knee replacement surgery. What is the appropriate perioperative anticoagulation strategy?

Switch to rivaroxaban perioperatively for ease of management
Stop warfarin 5 days before surgery with UFH bridging; restart warfarin post-op (Correct answer)
Stop warfarin without bridging as risk of thrombosis is low
Continue warfarin at half-dose throughout the perioperative period

Correct answer: Stop warfarin 5 days before surgery with UFH bridging; restart warfarin post-op

Mechanical mitral valves carry high thromboembolic risk, requiring bridging with unfractionated or low-molecular-weight heparin when warfarin is held perioperatively.

Question 154: 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?

Elimination diet (six-food elimination) is contraindicated in adults with confirmed eosinophilic esophagitis
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%
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 155: A 45-year-old patient from the Ohio River Valley presents with fever, weight loss, and mediastinal lymphadenopathy. BAL reveals intracellular yeast within macrophages. What is the treatment for severe disseminated histoplasmosis?

Liposomal amphotericin B followed by itraconazole (Correct answer)
Echinocandin plus itraconazole
Fluconazole 400mg daily x 12 months
Voriconazole 200mg BID

Correct answer: Liposomal amphotericin B followed by itraconazole

Severe or disseminated histoplasmosis is treated with liposomal amphotericin B for induction (1-2 weeks) followed by step-down to itraconazole for 12 months.

Question 156: 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
Atovaquone-proguanil plus doxycycline
IV artesunate (Correct answer)

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 157: 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
Prednisone 40 mg PO twice daily for 5 days, then taper over 21 days (Correct answer)
Methylprednisolone 1 g IV daily for 3 days (pulse therapy) for underlying SLE flare
Inhaled pentamidine to augment anti-Pneumocystis coverage

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

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 159: 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?

Fluid replacement
Electrolyte monitoring
Rest
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 160: 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?

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

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

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 162: 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?

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

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 163: Which scoring system is used to prioritize liver transplant allocation in the United States?

Child-Pugh score
King's College Criteria
MELD score (Correct answer)
APACHE II

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 164: 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?

Single-dose TMP-SMX SS taken within 2 hours of intercourse (Correct answer)
Daily TMP-SMX DS continuously for 6 months
Cranberry extract 500mg daily
Nitrofurantoin 100mg nightly for 12 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 165: 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:

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

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 166: A 17-year-old girl with obesity, short stature, and shortened 4th and 5th metacarpals has labs showing Ca2+ 7.1 mg/dL, PO4 6.3 mg/dL, PTH 310 pg/mL, and TSH 9.1 mIU/L with normal free T4. Exogenous PTH infusion fails to raise urinary cAMP or phosphate excretion. Her father has the same body habitus but has normal calcium, PTH, and TSH. A GNAS mutation is found in the family. Which mechanism explains why the father is phenotypically similar but metabolically normal?

Penetrance of GNAS mutations is age-dependent and his phenotype will emerge after age 40
The father carries an X-linked recessive allele that requires hemizygosity for full expression
Tissue-specific maternal imprinting of GNAS means only the maternally inherited allele is expressed in kidney and pituitary (Correct answer)
The father has a somatic mosaic mutation with low variant allele frequency

Correct answer: Tissue-specific maternal imprinting of GNAS means only the maternally inherited allele is expressed in kidney and pituitary

Pseudohypoparathyroidism type 1a (PHP1a) requires a maternally inherited GNAS mutation because Gsα is expressed only from the maternal allele in the kidney, pituitary, and other key tissues due to genomic imprinting. The father carries the same GNAS mutation and has Albright's hereditary osteodystrophy (AHO) phenotype — short stature, brachydactyly, subcutaneous ossifications — but because the paternal GNAS allele is silenced in hormone-responsive tissues, he has no PTH or TSH resistance. This paternal inheritance pattern is called pseudopseudohypoparathyroidism (PPHP).

Question 167: Which physical examination finding is most specific for cardiac tamponade?

Pulsus paradoxus >10 mmHg (Correct answer)
Pericardial friction rub
Elevated JVP with Kussmaul's sign
Distant heart sounds

Correct answer: Pulsus paradoxus >10 mmHg

Pulsus paradoxus (>10 mmHg drop in systolic BP during inspiration) is the most specific physical finding for cardiac tamponade.

Question 168: 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) and amoxicillin for 10 days
A proton pump inhibitor (PPI), clarithromycin, and amoxicillin for 14 days
A proton pump inhibitor (PPI), bismuth subsalicylate, metronidazole, and tetracycline for 14 days (Correct answer)

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 169: 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?

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

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 170: A 58-year-old woman on long-term lithium therapy presents with fatigue and a calcium of 10.8 mg/dL. PTH is 72 pg/mL (high-normal). What is the most likely mechanism of her hypercalcemia?

Lithium causes vitamin D toxicity
Lithium induces ectopic PTH production
Lithium raises the calcium set-point for PTH suppression (Correct answer)
Lithium-induced autonomous parathyroid adenoma

Correct answer: Lithium raises the calcium set-point for PTH suppression

Lithium elevates the calcium threshold for PTH suppression (shifts the set-point), resulting in inappropriately elevated PTH and mild hypercalcemia; this is usually reversible upon lithium discontinuation.

Question 171: A 54-year-old male smoker presents with facial plethora and headaches. Labs show Hgb 19.6 g/dL, Hct 62%, normal O2 saturation, and JAK2 V617F mutation. Splenomegaly is present. What is the most appropriate initial treatment?

Phlebotomy to reduce hematocrit plus low-dose aspirin (Correct answer)
Hydroxyurea cytoreduction alone
Allogeneic stem cell transplant
Erythropoietin supplementation

Correct answer: Phlebotomy to reduce hematocrit plus low-dose aspirin

Polycythemia vera is initially managed with phlebotomy to reduce hematocrit below 45% and low-dose aspirin to prevent thrombosis.

Question 172: A 25-year-old male presents with gross hematuria and mild bilateral flank pain that began 2 days after the onset of an upper respiratory infection. His blood pressure is 150/95 mmHg. Urinalysis reveals numerous red blood cells, red blood cell casts, and 2+ proteinuria. What is the most likely diagnosis?

IgA nephropathy (Correct answer)
Membranous nephropathy
Minimal change disease
Post-streptococcal glomerulonephritis

Correct answer: IgA nephropathy

The presentation of gross hematuria occurring concurrently with or just a few days after an upper respiratory tract infection (synpharyngitic hematuria) is the classic presentation for IgA nephropathy. Post-streptococcal glomerulonephritis typically has a longer latent period of 1-3 weeks after the infection. Minimal change disease and membranous nephropathy are causes of nephrotic syndrome and typically present with heavy proteinuria and edema, not a nephritic picture with prominent hematuria and RBC casts.

Question 173: A 22-year-old woman with Turner syndrome (45,X) presents for routine evaluation. Which endocrine complication is she at highest risk for?

Cushing syndrome
Primary hypothyroidism (Hashimoto's) (Correct answer)
Primary hyperparathyroidism
Prolactinoma

Correct answer: Primary hypothyroidism (Hashimoto's)

Women with Turner syndrome have a significantly increased prevalence of autoimmune thyroid disease, particularly Hashimoto's thyroiditis and primary hypothyroidism.

Question 174: 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
Renal artery duplex ultrasound (Correct answer)
24-hour urine collection for metanephrines
Plasma aldosterone-to-renin ratio

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 175: A 67-year-old man undergoes coronary angiography and is found to have a 50% left main stenosis. FFR measurement yields 0.79. What is the most appropriate management?

PCI of the left main lesion (Correct answer)
Urgent CABG given left main disease
Medical therapy alone, as FFR >0.80 is non-ischemic
Repeat angiography in 6 months

Correct answer: PCI of the left main lesion

An FFR of 0.79 (≤0.80) indicates hemodynamically significant ischemia; left main disease with positive FFR warrants revascularization, with CABG preferred over PCI for left main.

Question 176: A 45-year-old asymptomatic man is found to have severe aortic regurgitation on routine echocardiography. LVEF is 58%, LV end-systolic dimension is 48 mm, and LV end-diastolic dimension is 72 mm. He exercises regularly without symptoms. What is the most appropriate next step?

Serial echocardiography every 6–12 months with continued observation
Exercise stress testing to unmask symptoms before deciding on surgery
Aortic valve replacement now based on LV end-diastolic dimension
Aortic valve replacement based on LV end-systolic dimension threshold (Correct answer)

Correct answer: Aortic valve replacement based on LV end-systolic dimension threshold

According to ACC/AHA guidelines, aortic valve replacement is indicated in asymptomatic severe AR when LVEF falls below 55% OR when LV end-systolic dimension (LVESD) exceeds 50 mm (Class I). This patient's LVESD is 48 mm — just below the threshold — and LVEF is 58%. However, a LVESD of 50 mm is the cutoff; at 48 mm, surgery is not yet mandated. Importantly, LVESD ≥50 mm is the key threshold, not LVEDD. The LVEDD of 72 mm alone is not a Class I surgical indication (threshold would be >65 mm as a lower-evidence indicator). Close follow-up every 6–12 months is appropriate here.

Question 177: 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?

INR is unaffected by thyroid status
INR will decrease as hyperthyroidism resolves (Correct answer)
INR will increase as hyperthyroidism resolves
Methimazole directly inhibits warfarin metabolism

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 178: 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?

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

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 179: A 52-year-old man with a mechanical aortic valve (on-X bileaflet) and no other risk factors (no AF, no prior thromboembolism, no LV dysfunction) has been maintained on warfarin with a target INR of 2.0-3.0. His last 12 INR values over 18 months have been 100% in range. Based on updated evidence, what change to his anticoagulation regimen should be considered?

Lower INR target to 1.5-2.0 combined with aspirin 100 mg daily, based on the PROACT Xa trial data (Correct answer)
Add aspirin 81 mg to his current warfarin regimen to reduce thromboembolic risk
Switch to rivaroxaban 20 mg daily to reduce bleeding risk
No change; INR target 2.0-3.0 remains standard of care for all mechanical aortic valves

Correct answer: Lower INR target to 1.5-2.0 combined with aspirin 100 mg daily, based on the PROACT Xa trial data

The PROACT Xa trial (2023) specifically evaluated the On-X bileaflet mechanical aortic valve — an FDA-approved trial demonstrating non-inferiority of INR 1.5-2.0 plus aspirin 100 mg versus standard INR 2.0-3.0 in low-risk patients (no AF, no prior TE, preserved EF, no additional risk factors). On-X valves have superior hemodynamic and flow characteristics (nearly central flow, reduced thrombogenicity) compared to older mechanical valves. The FDA approved a labeling change for On-X AVR specifically. This is the ONLY mechanical valve with approved lower INR targeting. DOACs (rivaroxaban, apixaban) are contraindicated in ALL mechanical valves (RE-ALIGN trial showed excess thrombosis and bleeding). Adding aspirin to an already optimally anticoagulated patient increases bleeding without benefit in this low-risk scenario.

Question 180: What is the first-line treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD)?

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

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 181: 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?

Lobular inflammation and hepatocyte ballooning (Correct answer)
Macrovesicular fat deposits
Bile duct proliferation
Portal fibrosis only

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 182: 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?

Uvulopalatopharyngoplasty (UPPP)
Continuous positive airway pressure (CPAP) (Correct answer)
Supplemental oxygen via nasal cannula at night
Bilevel positive airway pressure (BiPAP)

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 183: 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?

Initiation of granulocyte colony-stimulating factor (G-CSF) to restore neutrophil function
Addition of adjunctive hyperbaric oxygen therapy
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 184: 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)
Stereotactic body radiation therapy (SBRT)
Liver transplantation within Milan criteria (Correct answer)
Transarterial chemoembolization (TACE)

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 185: 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?

Benzathine penicillin G 2.4 million units IM single dose (Correct answer)
Ceftriaxone 250mg IM single dose
Doxycycline 100mg BID x 14 days
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 186: 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:

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

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 187: 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?

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

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 188: 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 189: A 55-year-old man is being weaned from mechanical ventilation after 10 days for ARDS. He passes a spontaneous breathing trial (SBT) using PSV 5/PEEP 5 for 30 minutes with stable vitals and adequate oxygenation. What is the NEXT most important assessment before extubation?

Assessment of airway patency, cough strength, and secretion management (Correct answer)
Repeat ABG to confirm PaO2 >80 mmHg
24-hour sedation holiday before attempting extubation
Echocardiogram to rule out cardiac dysfunction

Correct answer: Assessment of airway patency, cough strength, and secretion management

After a successful SBT, the primary determinant of extubation success is the ability to protect and maintain the airway, including adequate cough strength and secretion clearance.

Question 190: 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?

Adhesive bowel obstruction
Internal hernia with small bowel obstruction (Correct answer)
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 191: A 32-year-old woman with no prior medical history presents with fever, myalgias, and rash one week after tick removal in New England. CBC shows leukopenia and thrombocytopenia. What is the most likely diagnosis?

Lyme disease
Anaplasmosis (Anaplasma phagocytophilum) (Correct answer)
Rocky Mountain Spotted Fever
Babesiosis

Correct answer: Anaplasmosis (Anaplasma phagocytophilum)

Anaplasmosis (formerly HME/HGA) presents with fever, leukopenia, thrombocytopenia, and elevated transaminases after Ixodes tick bite in the Northeast; treated with doxycycline.

Question 192: 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
Order repeat 24-hour urine free cortisol and late-night salivary cortisol to confirm hypercortisolism
Repeat IPSS with simultaneous bilateral sampling under strict catheter position verification
Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary (Correct answer)

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 193: 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?

Fever >38.0°C
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

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 194: 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?

Esophageal manometry
Barium swallow
CT chest/abdomen
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 195: A 45-year-old alcoholic presents with vomiting, abdominal pain, glucose of 95 mg/dL, pH 7.22, and large serum ketones. Which diagnosis is most consistent?

DKA
HHS
Alcoholic ketoacidosis (Correct answer)
Lactic acidosis from metformin

Correct answer: Alcoholic ketoacidosis

Alcoholic ketoacidosis (AKA) presents with ketoacidosis, near-normal or low glucose, and a history of alcohol use and decreased oral intake.

Question 196: 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?

Oral quinine sulfate plus doxycycline for 7 days
IV quinidine gluconate plus doxycycline with telemetry monitoring
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 197: Which HbA1c target is most appropriate for a 78-year-old patient with type 2 diabetes, multiple comorbidities, and limited life expectancy?

<7.0%
<6.5%
<8.0% (Correct answer)
<9.0%

Correct answer: <8.0%

ADA guidelines recommend a less stringent HbA1c target of <8.0% for older patients with complex health status to minimize hypoglycemia risk without benefit.

Question 198: 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?

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

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 199: A 52-year-old man presents with increased hat and shoe size over 5 years, jaw prominence, and hyperhidrosis. Random GH is 12 ng/mL. What is the confirmatory test for acromegaly?

Insulin tolerance test (ITT)
IGF-1 level alone
24-hour urine GH
GH after oral glucose tolerance test (OGTT) (Correct answer)

Correct answer: GH after oral glucose tolerance test (OGTT)

In acromegaly, GH fails to suppress to <1 ng/mL after 75 g oral glucose load (OGTT); this is the gold-standard confirmatory test because random GH levels fluctuate.

Question 200: 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?

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

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 201: A 35-year-old man has hypertension, hypokalemia, and metabolic alkalosis. Plasma renin activity is markedly elevated, as is aldosterone. CT shows a 3 cm right renal artery mass. What is the most likely diagnosis?

Primary hyperaldosteronism (Conn syndrome)
Adrenocortical carcinoma
Juxtaglomerular cell tumor (reninoma) (Correct answer)
Pheochromocytoma

Correct answer: Juxtaglomerular cell tumor (reninoma)

A juxtaglomerular cell tumor (reninoma) secretes renin autonomously, causing secondary hyperaldosteronism with high renin; in primary hyperaldosteronism, renin would be suppressed.

Question 202: A 48-year-old man presents with massive pleural effusion. Thoracentesis reveals exudative fluid (LDH 380 U/L, protein 4.2 g/dL, pH 7.15, glucose 42 mg/dL). Gram stain is negative, but culture grows Streptococcus milleri. What is the MOST appropriate next management step?

IV antibiotics alone with repeat thoracentesis in 48 hours
Chest tube drainage plus IV antibiotics (Correct answer)
Intrapleural tPA plus DNase
Thoracoscopy with decortication

Correct answer: Chest tube drainage plus IV antibiotics

A complicated parapneumonic effusion with pH <7.20 and glucose <60 mg/dL with positive culture (empyema) requires chest tube drainage combined with IV antibiotics.

Question 203: 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 204: 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?

Transarterial chemoembolization (TACE) is the preferred bridging modality and has been shown in randomized trials to improve post-transplant survival compared to no treatment
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)
Thermal ablation (RFA/MWA) should not be used for lesions >3 cm because complete ablation is uniformly unachievable

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 205: A 29-year-old man is referred for evaluation of hematuria and proteinuria (1.2 g/day). He has a family history of end-stage renal disease in his maternal grandfather and sensorineural hearing loss diagnosed at age 12. Renal biopsy electron microscopy shows thinning and splitting of the glomerular basement membrane (GBM) with a characteristic 'basket-weave' pattern. Genetic testing confirms a heterozygous pathogenic variant in COL4A5. Which statement about his prognosis and management is MOST accurate?

Rituximab therapy targeting podocyte autoantibodies should be considered given the proteinuria level
As a heterozygous carrier of X-linked Alport syndrome, he is unlikely to progress to ESKD and requires only annual monitoring
His sensorineural hearing loss confirms autosomal recessive inheritance, requiring testing of both parents before estimating ESKD risk
ACE inhibitor therapy initiated before proteinuria exceeds 0.5 g/day has been shown to delay ESKD by approximately 13 years in retrospective studies (Correct answer)

Correct answer: ACE inhibitor therapy initiated before proteinuria exceeds 0.5 g/day has been shown to delay ESKD by approximately 13 years in retrospective studies

COL4A5 mutations cause X-linked Alport syndrome (XLAS). Males with XLAS are hemizygous and almost invariably progress to ESKD, typically by age 20-30 without treatment. Retrospective data from the European Alport Registry (Gross et al.) demonstrated that ACE inhibitor therapy started at the stage of microhematuria alone (before proteinuria develops) delayed ESKD by approximately 13 years compared to treatment started at the proteinuria stage, and by about 13 years compared to no treatment. This supports early nephroprotective intervention. Males with COL4A5 mutations are NOT mild carriers — that term applies to heterozygous females, who have variable expression. The basket-weave GBM is the EM hallmark of Alport syndrome regardless of inheritance pattern.

Question 206: Which finding is characteristic of obstructive lung disease on spirometry?

Normal FEV1 with reduced FVC
Increased total lung capacity
Decreased FEV1/FVC ratio (Correct answer)
Increased FEV1/FVC ratio

Correct answer: Decreased FEV1/FVC ratio

A decreased FEV1/FVC ratio is the characteristic finding of obstructive lung disease on spirometry. This indicates that the forced expiratory volume in one second (FEV1) is disproportionately reduced compared to the forced vital capacity (FVC), reflecting airflow limitation due to airway obstruction. This ratio is key for diagnosing conditions like COPD and asthma.

Question 207: A 40-year-old woman has an incidentally discovered 2.5 cm adrenal mass on CT for kidney stones. She has no hypertension or symptoms. Hormonal workup shows: normal aldosterone/renin ratio, normal 24-hour urine catecholamines, and 1 mg overnight dexamethasone suppression test shows cortisol of 3.8 mcg/dL. What is the next step?

PET scan to rule out malignancy
Repeat imaging in 6–12 months and reassay hormones annually (Correct answer)
Adrenalectomy
Salivary cortisol testing

Correct answer: Repeat imaging in 6–12 months and reassay hormones annually

An adrenal incidentaloma <4 cm that is hormonally inactive (cortisol suppresses to <5 mcg/dL on 1 mg DST) should be followed with repeat imaging at 6–12 months and annual hormonal reassessment per guidelines.

Question 208: 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
10 years
1 year
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 209: 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
Veno-venous ECMO as a bridge to lung transplantation (Correct answer)
Rituximab plus plasma exchange
Cyclosporine A added to corticosteroids

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 210: 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:

Invasive pulmonary aspergillosis (Correct answer)
Disseminated histoplasmosis
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 211: 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 212: 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?

Metronidazole plus Ciprofloxacin
Vancomycin plus Cefepime
Ceftriaxone
Piperacillin-tazobactam (Correct answer)

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 213: 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 214: A 63-year-old man with chronic lymphocytic leukemia (CLL) and del(17p) by FISH receives venetoclax plus obinutuzumab. After completing 12 months of fixed-duration therapy, he achieves MRD-undetectable remission. Six months later, he presents with rapidly enlarging lymph nodes, a LDH of 4× ULN, and a biopsy showing large B-cell lymphoma. This transformation is most accurately described as:

Richter transformation to diffuse large B-cell lymphoma (Correct answer)
Tumor lysis syndrome from residual CLL proliferation
Venetoclax-induced BCL-2 independent apoptosis failure
Secondary resistance via BTK C481S mutation

Correct answer: Richter transformation to diffuse large B-cell lymphoma

Richter transformation (RT) refers to the development of an aggressive lymphoma — most commonly DLBCL (~95% of RT cases) — in a patient with pre-existing CLL/SLL. It occurs in 2–10% of CLL patients and portends a very poor prognosis (median survival ~5–8 months). Key features include rapid lymph node enlargement, markedly elevated LDH, B symptoms, and histologic confirmation of large cell transformation. BTK C481S mutation causes ibrutinib resistance, not venetoclax resistance. Tumor lysis syndrome occurs during treatment initiation, not months post-therapy.

Question 215: 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?

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

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 216: 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?

Elevated TSH with low free T4 (Correct answer)
Hyperkalemia with hyponatremia
Positive 21-hydroxylase antibodies
Low ACTH stimulation test response

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 217: 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?

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

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 218: 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)
Start ursodeoxycholic acid at 28–30 mg/kg/day and repeat MRCP in 3 months
Perform endoscopic ultrasound-guided fine needle aspiration of the stricture
Proceed directly to orthotopic liver transplantation evaluation

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 219: A 35-year-old woman with systemic lupus erythematosus (SLE) presents with acute dyspnea and hemoptysis. Chest X-ray shows bilateral alveolar infiltrates. Bronchoscopy with BAL returns progressively bloodier returns from all lobes. ANA titer is 1:640. Anti-dsDNA is markedly elevated. Urinalysis shows RBC casts. What is the MOST likely diagnosis?

Granulomatosis with polyangiitis (GPA)
Goodpasture syndrome (anti-GBM disease)
Microscopic polyangiitis (MPA)
Diffuse alveolar hemorrhage (DAH) from SLE (Correct answer)

Correct answer: Diffuse alveolar hemorrhage (DAH) from SLE

Diffuse alveolar hemorrhage in the setting of active SLE (elevated anti-dsDNA, lupus nephritis with RBC casts) is most consistent with SLE-associated DAH, a life-threatening complication.

Question 220: 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?

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

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 221: A 70-year-old male with known COPD presents with increased sputum production, change in sputum color, and worsening dyspnea. He is managed outpatient with a short-acting bronchodilator. Which antibiotic is most appropriate for an uncomplicated AECOPD without risk factors for Pseudomonas?

Cefepime
Ciprofloxacin
Azithromycin or doxycycline (Correct answer)
Piperacillin-tazobactam

Correct answer: Azithromycin or doxycycline

Amoxicillin-clavulanate, macrolides (azithromycin), or doxycycline are appropriate for uncomplicated AECOPD; Pseudomonas coverage is only needed with risk factors (frequent exacerbations, prior isolation, bronchiectasis).

Question 222: 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 223: 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?

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

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 224: Which of the following is the most common cause of hyperthyroidism?

Toxic multinodular goiter
Subacute thyroiditis
Graves' disease (Correct answer)
Hashimoto's thyroiditis

Correct answer: Graves' disease

Graves' disease is the most common cause of hyperthyroidism, an autoimmune disorder where the body produces antibodies that stimulate the thyroid gland to produce excessive thyroid hormones. This leads to symptoms such as weight loss, heat intolerance, and palpitations. It is characterized by diffuse thyroid enlargement and often ophthalmopathy.

Question 225: 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?

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

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 226: 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?

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

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 227: 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)
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
High-dose calcium channel blocker therapy given positive vasoreactivity is expected in CTD-PAH

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 228: 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?

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

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

Correct answer: Refer for parathyroidectomy

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

Question 230: 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?

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

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 231: 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 232: A 58-year-old man with alcoholic cirrhosis develops confusion and asterixis. Ammonia level is elevated. Which treatment is most appropriate?

Rifaximin
Neomycin
Lactulose (Correct answer)
Zinc supplementation

Correct answer: Lactulose

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

Question 233: A 52-year-old woman with type 2 diabetes on empagliflozin, metformin, and lisinopril presents with 2 days of vomiting and decreased oral intake. She is tachypneic with Kussmaul breathing. Labs: glucose 181 mg/dL, Na 138, Cl 102, HCO₃ 9 mEq/L, pH 7.16, beta-hydroxybutyrate 4.4 mmol/L. Which mechanism best explains her ketoacidosis despite a near-normal glucose?

Ketosis-prone type 2 diabetes triggered by volume depletion, independent of SGLT2 inhibitor effects
Type 4 renal tubular acidosis precipitated by lisinopril in the setting of volume depletion
Relative insulin deficiency with glucagon excess driving ketogenesis, while SGLT2 inhibition promotes urinary glucose excretion and lowers the renal threshold for glycosuria (Correct answer)
Lactic acidosis from metformin accumulation in the setting of acute kidney injury

Correct answer: Relative insulin deficiency with glucagon excess driving ketogenesis, while SGLT2 inhibition promotes urinary glucose excretion and lowers the renal threshold for glycosuria

SGLT2 inhibitors can cause euglycemic DKA (euDKA) by increasing the glucagon-to-insulin ratio (promoting ketogenesis) while simultaneously lowering the renal threshold for glucose excretion. Blood glucose remains near-normal despite true DKA because glucosuria is markedly enhanced. Clinicians must maintain a high index of suspicion for euDKA in patients on SGLT2 inhibitors, especially during fasting, surgery, or intercurrent illness. Metformin-associated lactic acidosis is possible but would show an elevated lactate rather than elevated ketones. Type 4 RTA causes a non-anion gap hyperchloremic acidosis.

Question 234: 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 phenylephrine to increase SVR and improve coronary perfusion pressure
Administer 1L crystalloid bolus to optimize preload before adding inotropes
Begin dobutamine infusion at 5 mcg/kg/min
Add epinephrine infusion and prepare for intra-aortic balloon pump (Correct answer)

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 235: 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?

Chloroquine 1g followed by 500 mg at 6, 24, and 48 hours
Atovaquone-proguanil for 3 days
Atovaquone plus azithromycin for 7–10 days (Correct answer)
Quinine plus doxycycline for 7 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 236: 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?

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

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 237: 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?

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

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 238: A 68-year-old woman with osteoporosis and a T-score of −3.0 at the hip has been on denosumab for 3 years. She asks about stopping therapy. What is the most important risk to counsel her about?

Development of monoclonal gammopathy
Rapid bone loss and increased vertebral fracture risk upon discontinuation (Correct answer)
Rebound hypercalcemia
Jaw osteonecrosis upon stopping

Correct answer: Rapid bone loss and increased vertebral fracture risk upon discontinuation

Denosumab discontinuation causes a rebound increase in bone turnover markers and rapid bone loss, significantly increasing vertebral fracture risk; transition to a bisphosphonate is recommended before stopping.

Question 239: A 70-year-old woman on warfarin for atrial fibrillation presents with a supratherapeutic INR of 9.2 but no active bleeding. What is the most appropriate management?

Administer fresh frozen plasma
Hold warfarin only and recheck INR in 24 hours (Correct answer)
Give 4-factor PCC immediately
Hold warfarin and give IV vitamin K 10 mg

Correct answer: Hold warfarin only and recheck INR in 24 hours

For supratherapeutic INR without bleeding, holding warfarin and rechecking INR is appropriate; vitamin K is added for INR >10 or high bleeding risk.

Question 240: A 68-year-old man with non-ischemic dilated cardiomyopathy (EF 22%) is on optimal GDMT. He experiences an episode of sustained VT terminated by his ICD. Which medication change is most appropriate?

Increase digoxin dose to improve cardiac output
Discontinue beta-blocker to prevent proarrhythmic effects
Add amiodarone for secondary prevention of VT recurrence (Correct answer)
Switch from sacubitril/valsartan to ACE inhibitor alone

Correct answer: Add amiodarone for secondary prevention of VT recurrence

Amiodarone is the most effective antiarrhythmic for reducing ICD shocks in patients with structural heart disease and sustained VT, used as secondary prevention.

Question 241: A 55-year-old man with no prior GI history has a positive fecal immunochemical test (FIT). What is the most appropriate next step?

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

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 242: 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)
The CFTR F508del variant causes exocrine pancreatic insufficiency that secondarily activates inflammatory cascades
SPINK1 mutations directly activate trypsinogen, triggering autodigestion

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 243: 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?

High-dose methylprednisolone alone for immune effector cell-associated neurotoxicity syndrome (ICANS)
Rituximab infusion to deplete residual CAR-T cells
Tocilizumab plus dexamethasone, with anakinra considered for refractory disease (Correct answer)
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 244: A 30-year-old woman with lymphangioleiomyomatosis (LAM) has progressive dyspnea and FEV1/FVC of 0.62. Which treatment has been shown to stabilize lung function in LAM?

Progesterone therapy
Doxycycline
Hydroxychloroquine
Sirolimus (rapamycin) (Correct answer)

Correct answer: Sirolimus (rapamycin)

Sirolimus, an mTOR inhibitor, has been shown in clinical trials to stabilize FEV1, improve quality of life, and reduce chylous effusions in LAM.

Question 245: A 48-year-old woman with rheumatic mitral stenosis (MVA 1.2 cm²) develops symptomatic dyspnea. Echo shows pliable leaflets, no significant MR, and no left atrial thrombus. What is the preferred intervention?

Mitral valve replacement with bioprosthesis
Medical therapy with diuretics only
Open surgical commissurotomy
Percutaneous mitral balloon commissurotomy (PMBC) (Correct answer)

Correct answer: Percutaneous mitral balloon commissurotomy (PMBC)

PMBC is the procedure of choice for symptomatic moderate-severe MS with favorable valve morphology (pliable leaflets, minimal calcification, no significant MR, no LA thrombus).

Question 246: A 70-year-old nursing home resident develops fever, productive cough, and hypoxia. Urinary antigen is positive. She has sulfa allergy. CXR shows lobar consolidation. What is the most likely pathogen and first-line treatment?

Klebsiella pneumoniae; piperacillin-tazobactam
Legionella pneumophila; azithromycin or fluoroquinolone (Correct answer)
Staphylococcus aureus; vancomycin
Streptococcus pneumoniae; ceftriaxone

Correct answer: Legionella pneumophila; azithromycin or fluoroquinolone

Positive urinary antigen in pneumonia diagnoses Legionella; first-line treatment is a macrolide (azithromycin) or respiratory fluoroquinolone (levofloxacin).

Question 247: A 45-year-old man is found to have isolated severe aortic regurgitation on echocardiography. He is completely asymptomatic with an LV end-systolic diameter of 48 mm and EF of 58%. He exercises vigorously without limitation. What is the most appropriate management?

Referral for aortic valve replacement (Correct answer)
Continued surveillance with echo every 6–12 months
Repeat echo in 3–5 years given preserved EF
Start ACE inhibitor therapy to delay surgery

Correct answer: Referral for aortic valve replacement

Per 2021 ACC/AHA Valvular Heart Disease Guidelines, aortic valve replacement is indicated in asymptomatic severe AR when the LV end-systolic diameter (LVESD) reaches ≥50 mm (Class I) or when LVESD is 45–49 mm in patients undergoing cardiac surgery for another reason, OR when LVESD ≥45 mm with evidence of progressive LV enlargement. At 48 mm LVESD with preserved (but not normal) EF, this patient meets criteria for surgery referral under the ≥50 mm threshold approached — notably, guidelines also support surgery at LVESD index ≥25 mm/m². Surveillance alone is insufficient at this dilation level. ACE inhibitors do not have proven benefit in asymptomatic severe AR with preserved EF.

Question 248: 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 of symptomatic tumor enlargement during pregnancy is approximately 20–30% for macroadenomas not surgically treated prior to conception (Correct answer)
Risk is approximately 50% because dopamine agonist withdrawal universally causes rebound hyperprolactinemia exceeding baseline levels
Risk of symptomatic tumor enlargement is < 5% because physiologic estrogen suppresses corticotroph proliferation during pregnancy
Risk is eliminated because prolactin normalization on cabergoline indicates a microadenoma misclassified by MRI resolution

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 249: 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?

Surgical resection given size >6 mm in a high-risk patient (former smoker)
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
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 250: 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?

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

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 251: A 50-year-old woman on long-term prednisone for rheumatoid arthritis develops disseminated Strongyloides infection. What is the treatment?

Praziquantel 20mg/kg TID x 1 day
Albendazole 400mg BID x 7 days
Ivermectin 200mcg/kg daily x 2 days (Correct answer)
Mebendazole 500mg single dose

Correct answer: Ivermectin 200mcg/kg daily x 2 days

Ivermectin is the drug of choice for Strongyloides stercoralis; in disseminated disease, it is given daily until stool exams are negative for 2 consecutive weeks.

Question 252: A 38-year-old competitive cyclist presents with exertional chest discomfort and is found to have an anomalous origin of the left coronary artery from the right sinus of Valsalva (ALCAPA from right sinus) with an interarterial course. Cardiac MRI shows a perfusion defect in the LAD territory with stress. He is currently asymptomatic at rest. What is the most appropriate management?

Percutaneous coronary intervention with stenting of the anomalous segment
Surgical coronary reimplantation or unroofing procedure (Correct answer)
Annual surveillance with cardiac MRI and exercise stress testing
Restriction from competitive sports and medical management with beta-blockers

Correct answer: Surgical coronary reimplantation or unroofing procedure

Anomalous origin of a coronary artery from the opposite sinus (ACAOS) with an interarterial course carries a significant risk of sudden cardiac death, particularly during exertion, due to compression of the anomalous vessel between the aorta and pulmonary artery. When there is objective evidence of ischemia (as shown by perfusion defect on stress MRI), surgical correction — either reimplantation or unroofing of the intramural segment — is strongly indicated regardless of symptom status at rest. This is a Class I recommendation in current guidelines. Beta-blockers alone are insufficient. PCI is not appropriate for this anatomical variant. Annual surveillance without correction is inadequate given confirmed ischemia.

Question 253: Which murmur characteristic distinguishes hypertrophic obstructive cardiomyopathy (HOCM) from valvular aortic stenosis?

HOCM murmur increases with standing; AS murmur does not (Correct answer)
HOCM murmur is diastolic; AS is systolic
HOCM murmur radiates to the carotids; AS does not
HOCM murmur decreases with Valsalva; AS increases

Correct answer: HOCM murmur increases with standing; AS murmur does not

HOCM murmur increases with standing (decreased preload worsens obstruction) and Valsalva, whereas AS murmur decreases with maneuvers that reduce preload.

Question 254: 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?

Fecal Microbiota Transplantation
Oral Fidaxomicin (Correct answer)
Oral Metronidazole
Oral Vancomycin

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 255: 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?

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

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 256: A 63-year-old man with known coronary artery disease presents with chest pain. ECG shows new ST elevations in leads V1–V4. He is taken for emergent PCI. Angiography reveals a total occlusion of the proximal LAD. After successful recanalization, the patient develops progressive hypotension and hypoxia. Repeat echo shows new severe right ventricular dilation and paradoxical septal motion. Which mechanism BEST explains the hemodynamic compromise?

Reperfusion-induced pulmonary edema from sudden LV recovery
No-reflow phenomenon causing persistent anterior wall akinesis
Papillary muscle rupture causing acute mitral regurgitation
Ventricular interdependence causing LV underfilling from acute RV failure (Correct answer)

Correct answer: Ventricular interdependence causing LV underfilling from acute RV failure

The proximal LAD supplies the RV free wall via the right ventricular branches (especially the first diagonal and septal perforators). Acute proximal LAD occlusion can cause concomitant RV infarction. The dilated, failing RV shifts the interventricular septum leftward into the LV cavity (paradoxical septal motion), physically restricting LV filling — this is ventricular interdependence. The shared pericardial space means the dilated RV compresses LV diastolic volume, reducing preload and CO. Management requires volume loading to maintain RV preload, avoidance of vasodilators, and consideration of mechanical support. This is distinct from no-reflow (which causes persistent ST elevation but not the echo findings described), MR (which would show a flail leaflet), or pulmonary edema (which would cause LV dysfunction signs).

Question 257: 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?

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

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 258: 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?

Hypersensitivity pneumonitis
Lymphoma with pulmonary involvement
Berylliosis
Sarcoidosis (Correct answer)

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 259: A patient on warfarin for atrial fibrillation presents with INR of 8.4 but has no active bleeding. What is the most appropriate management?

Hold warfarin and administer IV vitamin K plus fresh frozen plasma
Continue warfarin and recheck INR in 24 hours
Administer 4-factor prothrombin complex concentrate (PCC)
Hold warfarin and administer oral vitamin K (Correct answer)

Correct answer: Hold warfarin and administer oral vitamin K

For supratherapeutic INR without active bleeding, holding warfarin and giving oral vitamin K to gradually lower the INR is the appropriate management.

Question 260: 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?

Splenic sequestration crisis
Vaso-occlusive (pain) crisis (Correct answer)
Acute chest syndrome
Aplastic 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 261: 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?

Lansoprazole (Correct answer)
Metformin
Sertraline
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 262: 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
Linezolid 600mg BID
Cefazolin 2g IV q8h
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 263: A 35-year-old woman with sickle cell disease presents with sudden onset severe chest pain, fever, new pulmonary infiltrates, and oxygen saturation of 88%. Which intervention is most critical?

Hydroxyurea initiation
Empiric antibiotics alone
IV morphine and observation
Exchange transfusion (Correct answer)

Correct answer: Exchange transfusion

Acute chest syndrome with hypoxia is life-threatening; exchange transfusion rapidly reduces HbS percentage and is the key intervention when oxygenation is compromised.

Question 264: A patient with HHS develops focal neurological deficits during treatment. What is the most likely etiology?

Hypoglycemia from insulin overdose
Thrombotic stroke due to hyperviscosity (Correct answer)
Cerebral edema from rapid osmolality correction
Hyponatremia from aggressive fluid replacement

Correct answer: Thrombotic stroke due to hyperviscosity

HHS is associated with a hypercoagulable, hyperviscous state that increases risk of arterial and venous thrombotic events, including ischemic stroke.

Question 265: 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?

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

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 266: A 25-year-old woman develops a diffuse maculopapular rash 10 days after starting ampicillin for mononucleosis. She denies prior penicillin allergy. What is the correct interpretation of this reaction?

This confirms true IgE-mediated penicillin allergy requiring permanent avoidance
She has delayed-type hypersensitivity (Type IV) to penicillin class antibiotics
This is a non-allergic ampicillin rash associated with EBV infection, not a true penicillin allergy (Correct answer)
She should receive immediate allergy testing to confirm cross-reactivity

Correct answer: This is a non-allergic ampicillin rash associated with EBV infection, not a true penicillin allergy

Ampicillin given during active EBV (mononucleosis) infection causes a nonallergic maculopapular rash in up to 80–100% of patients — this is not an IgE-mediated drug allergy. Mislabeling this as penicillin allergy leads to unnecessary avoidance of an important antibiotic class. The rash is immune-complex-mediated and specific to the EBV-ampicillin interaction.

Question 267: A 52-year-old man with type 2 diabetes on metformin and sitagliptin presents with recurrent hypoglycemia. He is not on sulfonylureas or insulin. Supervised 72-hour fast reproduces hypoglycemia at hour 18: glucose 41 mg/dL, insulin 22 µU/mL, C-peptide 4.8 ng/mL, proinsulin 22 pmol/L (elevated), beta-hydroxybutyrate 0.1 mmol/L (suppressed), and insulin secretagogue screen is negative. What is the most likely diagnosis?

Insulinoma (Correct answer)
Exogenous insulin administration
Non-islet cell tumor hypoglycemia
Insulin autoimmune syndrome (Hirata disease)

Correct answer: Insulinoma

The classic biochemical fingerprint of insulinoma is hypoglycemia with endogenously elevated insulin, C-peptide, and proinsulin, suppressed beta-hydroxybutyrate (indicating insulin-mediated inhibition of lipolysis), and a negative secretagogue screen. Exogenous insulin would suppress C-peptide and proinsulin. Insulin autoimmune syndrome (Hirata disease) is associated with extremely high total insulin levels (often >100 µU/mL) due to insulin-antibody complexes and is more common in Japanese patients or those exposed to thiol compounds; the free/total insulin ratio is key. Non-islet cell tumor hypoglycemia is mediated by IGF-2, causing suppressed insulin and C-peptide.

Question 268: A 38-year-old woman is evaluated for episodic hypertension (BPs reaching 210/120 mmHg) associated with palpitations, diaphoresis, and headache, occurring 2–3 times per week and lasting 20–30 minutes. Between episodes her BP is 118/74 mmHg. 24-hour urine metanephrines: normetanephrine 3,200 mcg/24h (normal <900), metanephrine 1,800 mcg/24h (normal <400). MRI abdomen shows a 4.2 cm right adrenal mass. She undergoes preoperative preparation. Which of the following represents the CORRECT sequence and pharmacologic approach prior to surgery?

Beta-blockade first (propranolol) to control heart rate, then add alpha-blockade
Alpha-blockade first (phenoxybenzamine or doxazosin) for at least 7–14 days, then add beta-blockade only after adequate alpha-blockade is achieved (Correct answer)
Combined alpha- and beta-blockade started simultaneously on day 1
Calcium channel blockade with amlodipine as monotherapy, avoiding alpha- and beta-blockers

Correct answer: Alpha-blockade first (phenoxybenzamine or doxazosin) for at least 7–14 days, then add beta-blockade only after adequate alpha-blockade is achieved

Preoperative management of pheochromocytoma requires alpha-blockade FIRST, followed by beta-blockade only after adequate alpha-blockade is established (typically after 7–14 days). Initiating beta-blockade first or simultaneously without prior alpha-blockade can precipitate a hypertensive crisis: beta-2 blockade eliminates vasodilatory compensation while catecholamine-driven alpha-1 stimulation remains unopposed, causing severe vasoconstriction. Phenoxybenzamine (non-competitive, non-selective alpha-blocker) is the classic choice; selective alpha-1 blockers (doxazosin, prazosin) are also used. Beta-blockers are then added to control reflex tachycardia from alpha-blockade. Calcium channel blockers may be used as adjuncts but are not adequate monotherapy for operative preparation in high-output pheo.

Question 269: 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?

ACE inhibitor (lisinopril)
Beta-blocker (propranolol)
Calcium channel blocker (amlodipine)
Alpha-blocker (phenoxybenzamine) (Correct answer)

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 270: 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?

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
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

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 271: A 45-year-old woman presents to the clinic for a follow-up visit. Her blood pressure today is 148/92 mmHg. A reading last month was 145/90 mmHg. She has no other medical problems. According to the JNC 8 guidelines, what is the recommended initial treatment for her hypertension?

Losartan
Amlodipine
Lisinopril
Hydrochlorothiazide (Correct answer)

Correct answer: Hydrochlorothiazide

For the general non-black population, including those with diabetes, the JNC 8 guidelines recommend one of four classes of medications as initial therapy: a thiazide-type diuretic, a calcium channel blocker (CCB), an angiotensin-converting enzyme inhibitor (ACEI), or an angiotensin receptor blocker (ARB). All four options presented are considered acceptable first-line agents in this patient. However, thiazide diuretics have been a long-standing and well-supported choice.

Question 272: 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?

Initiate cinacalcet to normalize serum calcium and reduce fracture risk
Refer for parathyroidectomy given symptomatic primary hyperparathyroidism meeting surgical criteria
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)

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 273: A 72-year-old woman has a 2.4 cm solid pulmonary nodule discovered incidentally on CT. She has a 40 pack-year smoking history and stopped 5 years ago. PET scan shows SUV of 4.8 in the nodule. CT-guided biopsy shows adenocarcinoma. Staging workup reveals no metastatic disease. What is the preferred management for Stage IA NSCLC in a patient with FEV1 70% predicted?

Concurrent chemoradiation
Stereotactic body radiation therapy (SBRT)
Wedge resection due to borderline lung function
Surgical resection with anatomic lobectomy (Correct answer)

Correct answer: Surgical resection with anatomic lobectomy

Anatomic lobectomy is the standard of care for resectable Stage I NSCLC in operable patients; FEV1 70% predicted is sufficient for lobectomy, making surgery preferable to SBRT.

Question 274: 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
Competitive inhibition of sodium-calcium exchanger reducing intracellular calcium overload
Reduction of preload via osmotic diuresis and natriuresis, reducing myocardial wall stress (Correct answer)
Upregulation of myocardial beta-adrenergic receptor density improving lusitropy

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 275: A 44-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) and a total kidney volume (TKV) of 2,100 mL (height-adjusted TKV class 1C) is on tolvaptan 60/30 mg daily. She develops serum ALT 6× the upper limit of normal and mild jaundice. Her creatinine is stable. What is the most appropriate management?

Reduce tolvaptan to 45/15 mg daily and monitor LFTs weekly
Permanently discontinue tolvaptan and do not rechallenge (Correct answer)
Switch to somatostatin analogue (lanreotide) and continue monitoring
Hold tolvaptan, evaluate for alternative hepatic causes, and rechallenge at lower dose if LFTs normalize

Correct answer: Permanently discontinue tolvaptan and do not rechallenge

Tolvaptan carries an FDA black-box warning for serious and potentially fatal hepatotoxicity. Drug-induced liver injury from tolvaptan is an idiosyncratic reaction, and clinical guidelines recommend permanent discontinuation when ALT exceeds 3× ULN with symptoms or 8× ULN without symptoms. Jaundice with ALT 6× ULN clearly meets criteria for permanent discontinuation. Rechallenge is explicitly contraindicated. Dose reduction does not mitigate idiosyncratic hepatotoxicity. Lanreotide may slow cyst growth but lacks the TKV-slowing efficacy of tolvaptan and would not substitute its mechanism; moreover, the scenario calls for managing the hepatotoxicity.

Question 276: 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
Carbidopa-levodopa (Correct answer)
Trihexyphenidyl
Memantine

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 277: 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?

Continue prednisolone for a full 28-day course
Discontinue prednisolone and transition to pentoxifylline
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 278: A 48-year-old woman with type 2 diabetes on metformin and linagliptin develops worsening renal function (eGFR now 22 mL/min). Which medication adjustment is most appropriate?

Switch linagliptin to sitagliptin
Discontinue both metformin and linagliptin
Discontinue metformin; continue linagliptin (Correct answer)
Continue both at reduced doses

Correct answer: Discontinue metformin; continue linagliptin

Metformin is contraindicated when eGFR <30 mL/min; linagliptin, unlike other DPP-4 inhibitors, is primarily excreted via bile and requires no renal dose adjustment even in severe CKD.

Question 279: A 32-year-old nonsmoking female develops sudden onset pleuritic chest pain and dyspnea. CXR shows a 30% right-sided pneumothorax. She has no prior history. What is the most appropriate next step?

Needle aspiration (Correct answer)
Observation with 100% oxygen
Video-assisted thoracoscopic surgery (VATS)
Small-bore chest tube placement

Correct answer: Needle aspiration

For a first episode of primary spontaneous pneumothorax >20%, needle aspiration is the recommended first-line intervention per BTS guidelines.

Question 280: 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?

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

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 281: A 38-year-old man with MEN1 syndrome undergoes screening. He is found to have a fasting gastrin level of 890 pg/mL (normal <100) and multiple small duodenal ulcers. What syndrome is he most likely developing?

Glucagonoma syndrome
Insulinoma-associated hypoglycemia
VIPoma syndrome (Verner-Morrison)
Zollinger-Ellison syndrome (gastrinoma) (Correct answer)

Correct answer: Zollinger-Ellison syndrome (gastrinoma)

Markedly elevated gastrin causing refractory peptic ulcer disease is diagnostic of Zollinger-Ellison syndrome (gastrinoma), which occurs in 20–30% of MEN1 patients and is the most common functional pancreatic tumor in MEN1.

Question 282: A patient presents with hypercalcemia, low PTH, elevated PTHrP, and a lung mass. What is the mechanism of hypercalcemia?

Excessive calcitriol production by granulomas
Osteolytic metastases releasing calcium
Humoral hypercalcemia of malignancy via PTHrP (Correct answer)
Ectopic PTH secretion by the tumor

Correct answer: Humoral hypercalcemia of malignancy via PTHrP

PTHrP (PTH-related peptide) secreted by squamous cell carcinomas mimics PTH action, causing humoral hypercalcemia of malignancy with suppressed native PTH.

Question 283: 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?

H. pylori testing
CT scan of the abdomen
Secretin stimulation test (Correct answer)
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 284: 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 ≈ 2.9 Wood units; combined pre- and post-capillary pulmonary hypertension (Correct answer)
PVR ≈ 2.9 Wood units; isolated post-capillary pulmonary hypertension
PVR ≈ 5.7 Wood units; pre-capillary pulmonary hypertension
PVR ≈ 1.4 Wood units; normal pulmonary hemodynamics

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 285: A 55-year-old postmenopausal woman is found to have a T-score of -2.8 at the lumbar spine. She has no prior fractures. FRAX 10-year hip fracture probability is 4%. What is the most appropriate next step?

Start teriparatide given T-score below -2.5
Initiate bisphosphonate therapy immediately
Reassess with FRAX including bone mineral density and treat if major osteoporotic fracture risk ≥20% or hip ≥3% (Correct answer)
Repeat DEXA scan in 1 year

Correct answer: Reassess with FRAX including bone mineral density and treat if major osteoporotic fracture risk ≥20% or hip ≥3%

NOF/AACE guidelines recommend pharmacotherapy when 10-year major osteoporotic fracture risk ≥20% or hip fracture risk ≥3%, using FRAX with BMD integrated into the decision.

Question 286: 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)
Vancomycin plus ceftriaxone
Meropenem monotherapy
Ceftriaxone plus ampicillin

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 287: A 55-year-old man with type 2 diabetes in DKA (pH 7.10, K+ 5.8 mEq/L) is started on IV insulin. Thirty minutes later, his telemetry shows peaked T-waves and a widening QRS. A repeat potassium is 6.4 mEq/L. What is the most likely explanation and the most appropriate intervention?

Acidosis correction has been inadequate; administer calcium gluconate for cardiac membrane stabilization (Correct answer)
Insulin resistance is preventing potassium shift; double the insulin drip rate
Hyponatremia is masking true potassium toxicity; administer hypertonic saline
The patient has pseudohyperkalemia from hemolysis; repeat the specimen before treating

Correct answer: Acidosis correction has been inadequate; administer calcium gluconate for cardiac membrane stabilization

In severe acidosis, insulin-mediated potassium uptake is blunted, and the transcellular shift may be insufficient to prevent dangerous hyperkalemia early in treatment. When EKG changes of hyperkalemia (peaked T-waves, widened QRS) are present at K+ ≥6.5 or with EKG changes at any level, calcium gluconate is immediately indicated to stabilize the cardiac membrane — it does not lower potassium but protects against lethal arrhythmia while other measures work. Doubling insulin without addressing the cardiac emergency is dangerous. Pseudohyperkalemia would not typically cause EKG changes, and the clinical scenario does not suggest it.

Question 288: A 68-year-old male with a history of type 2 diabetes and heart failure is brought to the emergency department with altered mental status. His laboratory values are as follows: Glucose 950 mg/dL, Na+ 148 mEq/L, K+ 5.1 mEq/L, Cl- 105 mEq/L, HCO3- 20 mEq/L, BUN 88 mg/dL, Creatinine 2.5 mg/dL. Urine ketones are trace. Which of the following is the most critical initial step in management?

Administer an intravenous insulin bolus.
Administer intravenous potassium chloride.
Administer intravenous 0.9% normal saline. (Correct answer)
Administer 0.45% normal saline.

Correct answer: Administer intravenous 0.9% normal saline.

The patient's presentation with severe hyperglycemia, hyperosmolality (calculated osmolality >320 mOsm/kg), and minimal acidosis is consistent with Hyperosmolar Hyperglycemic State (HHS). The most critical initial step in managing HHS is aggressive fluid resuscitation to restore intravascular volume and improve tissue perfusion. Isotonic saline (0.9%) is the initial fluid of choice. Insulin administration should only begin after fluid resuscitation has been initiated, and potassium levels should be closely monitored as insulin will drive potassium into the cells.

Question 289: 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
Colonoscopy
Percutaneous drainage plus antibiotics (Correct answer)
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 290: A 70-year-old man with hypertension, CKD stage 3 (eGFR 42), and recent MI is found to have serum potassium of 5.9 mEq/L on lisinopril and spironolactone. What is the most appropriate management?

Switch to hydralazine and isosorbide dinitrate
Discontinue lisinopril and continue spironolactone
Discontinue spironolactone and continue lisinopril
Add patiromer and continue both medications (Correct answer)

Correct answer: Add patiromer and continue both medications

Patiromer (or sodium zirconium cyclosilicate) can lower serum potassium sufficiently to allow continuation of both cardiorenal protective agents in patients with hyperkalemia.

Question 291: Which screening test is recommended for colorectal cancer in adults aged 50–75 years?

CT colonography every 2 years
Capsule endoscopy
Fecal occult blood test (FOBT) annually (Correct answer)
Colonoscopy every 5 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 292: 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?

Bronchoscopy to assess for mucus plugging
Chest X-ray to confirm diagnosis
Needle decompression of the left hemithorax (Correct answer)
Increase PEEP to recruit atelectatic lung

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

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

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 294: 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?

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

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 295: 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?

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

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 296: 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?

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

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 297: A 48-year-old woman has fatigue, weight gain, constipation, and bradycardia. TSH is 48 mIU/L and free T4 is undetectable. She takes no medications. What is the most appropriate initial treatment?

Desiccated thyroid extract
Levothyroxine 1.6 mcg/kg/day
Levothyroxine 25 mcg/day with gradual titration (Correct answer)
Liothyronine (T3) alone

Correct answer: Levothyroxine 25 mcg/day with gradual titration

In severe hypothyroidism, especially in older adults or those with cardiac risk, levothyroxine should be started at a low dose (25–50 mcg/day) and titrated slowly to avoid precipitating cardiac ischemia or arrhythmia.

Question 298: 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 299: 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 300: 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?

Glipizide
Sitagliptin
Empagliflozin
Metformin 2000 mg twice daily (Correct answer)

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.

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%

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