ITE Internal Medicine In-Training Exam — Questions and Answers

Question 1: A 49-year-old man with newly diagnosed hepatocellular carcinoma (HCC) has a single lesion measuring 3.8 cm in a cirrhotic liver (Child-Pugh A, ECOG 0). No vascular invasion or extrahepatic spread is seen on imaging. He is placed on the transplant waitlist (Milan criteria met). While awaiting transplant, locoregional therapy is being considered. Which statement best reflects current evidence regarding bridging therapy?

Thermal ablation (RFA/MWA) should not be used for lesions >3 cm because complete ablation is uniformly unachievable
Stereotactic body radiation therapy (SBRT) is contraindicated as bridging for HCC in cirrhosis due to high rates of radiation-induced liver disease
Transarterial chemoembolization (TACE) is the preferred bridging modality and has been shown in randomized trials to improve post-transplant survival compared to no treatment
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)

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 2: 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?

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

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 3: 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?

Combination oral ambrisentan plus tadalafil (Correct answer)
IV epoprostenol infusion
Oral bosentan plus inhaled iloprost
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 4: 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?

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

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 5: A 67-year-old woman is intubated for hypoxemic respiratory failure. On assist-control volume-targeted ventilation: TV 420 mL (6 mL/kg IBW), RR 24, PEEP 12, FiO2 0.7. P/F ratio is 96 (severe ARDS). Peak pressure is 38 cmH2O, plateau pressure is 34 cmH2O. She is paralyzed with cisatracurium. An esophageal balloon is placed: end-expiratory esophageal pressure is +18 cmH2O. What does the transpulmonary plateau pressure calculation reveal, and what is the appropriate ventilator adjustment?

Transpulmonary plateau = 34 cmH2O; plateau pressure is safe and no adjustment is indicated
Transpulmonary plateau = 16 cmH2O; current driving pressure is acceptable, no change needed
Transpulmonary plateau = 16 cmH2O; current plateau is safe, increase PEEP to titrate by transpulmonary PEEP (Correct answer)
Transpulmonary plateau = 52 cmH2O; decrease tidal volume to 4 mL/kg IBW

Correct answer: Transpulmonary plateau = 16 cmH2O; current plateau is safe, increase PEEP to titrate by transpulmonary PEEP

Transpulmonary pressure (PL) = airway pressure − esophageal pressure (as a surrogate for pleural pressure). Transpulmonary plateau = 34 (plateau) − 18 (esophageal pressure) = 16 cmH2O, which is within the safe range (<25 cmH2O). This means the elevated plateau pressure (34 cmH2O, above the conventional 30 cmH2O threshold) is explained by a high chest wall elastance (e.g., obesity, abdominal hypertension, pleural effusions), not by dangerous overdistension of the lungs. The appropriate action is to use transpulmonary PEEP titration — titrate PEEP to achieve a positive end-expiratory transpulmonary pressure (PEEP − esophageal EEP > 0) to maintain alveolar recruitment, rather than reflexively lowering PEEP because of the high airway plateau. The transpulmonary plateau of 16 cmH2O does NOT indicate a need to reduce TV further, as lung stress is already safe.

Question 6: 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?

Allogeneic stem cell transplant
Phlebotomy to reduce hematocrit plus low-dose aspirin (Correct answer)
Hydroxyurea cytoreduction alone
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 7: 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?

Pioglitazone
Alogliptin
Empagliflozin or liraglutide (Correct answer)
Sitagliptin

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

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

Correct answer: Tumor lysis syndrome

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

Question 9: A 61-year-old lung transplant recipient (18 months post-transplant) on tacrolimus, mycophenolate, and prednisone presents with subacute sinusitis and new right-sided proptosis. CT shows opacification of the right ethmoid and sphenoid sinuses with bony erosion into the right orbital apex. Biopsy of sinus tissue reveals broad, aseptate hyphae with right-angle branching. Serum galactomannan is negative; beta-D-glucan is negative. What is the SINGLE most important initial management step beyond antifungal therapy?

Addition of adjunctive hyperbaric oxygen therapy
Emergent surgical debridement of necrotic tissue (Correct answer)
Reduction of immunosuppression, particularly mycophenolate
Initiation of granulocyte colony-stimulating factor (G-CSF) to restore neutrophil function

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 10: 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?

Starting IV epoprostenol while weaning oral therapies
IV diuresis with furosemide 40 mg
Inhaled nitric oxide at 20 ppm
Aggressive IV fluid resuscitation with 2L normal saline (Correct answer)

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 11: 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?

Supplemental oxygen via nasal cannula at night
Continuous positive airway pressure (CPAP) (Correct answer)
Uvulopalatopharyngoplasty (UPPP)
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 12: A 35-year-old African American woman presents with bilateral hilar lymphadenopathy, erythema nodosum, and polyarthritis. Serum ACE is elevated. Bronchoscopy with BAL shows lymphocytosis with CD4:CD8 ratio of 5:1. What is the MOST likely diagnosis?

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

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 13: 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?

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

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

SGLT2 inhibitors directly inhibit beta-cell insulin secretion, causing absolute insulin deficiency
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
Empagliflozin competes with ketone bodies for renal tubular reabsorption, falsely elevating serum ketone measurements

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 15: 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?

Impending respiratory failure requiring preparation for intubation (Correct answer)
Successful bronchodilation reducing dynamic hyperinflation
Adequate compensation for metabolic acidosis
Hyperventilation-induced hypocapnia returning to baseline

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 16: 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?

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

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 17: A 55-year-old man with known HCM and LVOT obstruction (peak gradient 65 mmHg at rest) develops severe mitral regurgitation on surveillance echo. TEE shows systolic anterior motion (SAM) of the anterior mitral leaflet and elongated leaflets with no intrinsic leaflet pathology. He is on maximally tolerated disopyramide and metoprolol. Which statement best guides the approach to his MR?

Refer for septal reduction therapy (surgical myectomy preferred); the MR will likely resolve after relieving obstruction (Correct answer)
Refer for isolated mitral valve repair, as the MR is independent of the LVOT obstruction
Add an ACE inhibitor to reduce afterload and decrease MR severity
Perform percutaneous mitral valve repair (MitraClip) to treat the MR while deferring septal therapy

Correct answer: Refer for septal reduction therapy (surgical myectomy preferred); the MR will likely resolve after relieving obstruction

In HCM, the majority of MR results directly from SAM-septal contact causing mitral leaflet malcoaptation — it is a secondary, flow-dependent phenomenon rather than intrinsic valve disease. After successful septal reduction (myectomy or alcohol septal ablation), LVOT gradient relief eliminates the forward drag that causes SAM, and MR resolves or improves significantly in >90% of cases. Surgical myectomy is preferred over alcohol septal ablation because it allows simultaneous direct inspection and repair of elongated leaflets if intrinsic pathology is found. Isolated valve repair would not address the root cause. ACE inhibitors are relatively contraindicated in obstructive HCM as afterload reduction can worsen obstruction. MitraClip would not address the underlying mechanism.

Question 18: 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
Continue both at reduced doses
Discontinue both metformin and linagliptin
Discontinue metformin; continue linagliptin (Correct answer)

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 19: 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?

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

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 20: 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?

Osimertinib 80 mg daily (Correct answer)
Erlotinib 150 mg daily
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 21: 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) and amoxicillin for 10 days
A proton pump inhibitor (PPI), metronidazole, and amoxicillin for 14 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 22: A 38-year-old male with no prior lung disease is found to have bilateral apical bullae. He is a tall, thin male. Which genetic condition should be considered?

Marfan syndrome (Correct answer)
Alpha-1 antitrypsin deficiency
Birt-Hogg-Dubé syndrome
Cystic fibrosis

Correct answer: Marfan syndrome

Marfan syndrome is associated with apical bullae and spontaneous pneumothorax in tall, thin individuals due to connective tissue abnormalities affecting the lung.

Question 23: A 34-year-old woman presents with hypertension, hypokalemia, and suppressed plasma renin activity. Aldosterone-to-renin ratio is markedly elevated. CT abdomen shows bilateral adrenal hyperplasia. Adrenal vein sampling reveals a lateralization ratio of 1.8 (left:right). Which is the most appropriate next step?

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

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 24: A 55-year-old woman with metastatic non-small cell lung adenocarcinoma harboring an EGFR exon 20 insertion mutation has progressed on first-line platinum-based chemotherapy. Her oncologist considers targeted therapy. Which agent is specifically FDA-approved for EGFR exon 20 insertion mutations in NSCLC after platinum-based chemotherapy?

Afatinib
Osimertinib
Erlotinib
Amivantamab-vmjw (Correct answer)

Correct answer: Amivantamab-vmjw

EGFR exon 20 insertions are distinct from the classic sensitizing mutations (exon 19 deletions, L858R) and confer primary resistance to first-, second-, and third-generation EGFR TKIs (erlotinib, afatinib, osimertinib). Amivantamab-vmjw, a bispecific EGFR-MET antibody, received FDA approval specifically for EGFR exon 20 insertion NSCLC after platinum-based chemotherapy based on the CHRYSALIS trial. Mobocertinib (now withdrawn) was another option but is no longer available. Osimertinib is approved for exon 19 del/L858R (first-line) and T790M (after first-gen TKI), not exon 20 insertions.

Question 25: 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?

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

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 26: 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?

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

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 27: 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?

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)
Resect the pNET first to reduce the risk of Zollinger-Ellison syndrome
Address both simultaneously with a single operative session to minimize anesthetic risk

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 28: 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?

Microscopic polyangiitis (MPA)
Granulomatosis with polyangiitis (GPA)
Goodpasture syndrome (anti-GBM disease)
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 29: 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 induces ectopic PTH production
Lithium raises the calcium set-point for PTH suppression (Correct answer)
Lithium-induced autonomous parathyroid adenoma
Lithium causes vitamin D toxicity

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

Her histology confirms AIH type 1; azathioprine can serve dual purpose as immunosuppression for both IBD and AIH after steroid induction
Azathioprine is the most likely causative agent and should be stopped; liver biopsy alone cannot distinguish drug-induced liver injury from AIH
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

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 31: 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?

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

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 32: A 48-year-old man is found to have an LDL of 310 mg/dL despite high-intensity statin therapy. Genetic testing confirms heterozygous familial hypercholesterolemia. What is the most appropriate add-on therapy?

Ezetimibe plus a PCSK9 inhibitor (Correct answer)
Niacin 2g daily
Omega-3 fatty acids 4g daily
Cholestyramine 8g twice daily

Correct answer: Ezetimibe plus a PCSK9 inhibitor

Ezetimibe plus a PCSK9 inhibitor (evolocumab or alirocumab) provides additive LDL lowering and is recommended for FH patients not at goal on maximally tolerated statins.

Question 33: A 74-year-old woman with a mechanical mitral valve on warfarin requires elective knee replacement surgery. What is the appropriate perioperative anticoagulation strategy?

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

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 34: 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
Phenytoin
Lamotrigine (Correct answer)

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 35: 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
Babesiosis
Rocky Mountain Spotted Fever
Anaplasmosis (Anaplasma phagocytophilum) (Correct answer)

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 36: 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)
Aqueous crystalline penicillin G IV for 10-14 days (neurosyphilis coverage)
Benzathine penicillin G 2.4 million units IM once (primary syphilis) (Correct answer)
Doxycycline 100 mg orally twice daily for 28 days (late latent alternative)

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

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

Question 37: A 72-year-old man with chronic severe aortic regurgitation has serial echocardiograms over 4 years. Current echo shows: LVEF 52%, LV end-systolic diameter (LVESD) 49 mm, LV end-diastolic diameter (LVEDD) 72 mm. He is asymptomatic and his exercise tolerance is excellent. What is the most appropriate next step?

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

Correct answer: Refer for aortic valve replacement surgery now

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

Question 38: 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
Micafungin IV
Liposomal amphotericin B plus flucytosine (Correct answer)
Fluconazole 400mg daily

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 39: 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?

Early enteral nutrition via nasojejunal tube within 24-48 hours (Correct answer)
Bowel rest until pain resolves
Parenteral nutrition within 24 hours
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 40: 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 will decrease as hyperthyroidism resolves (Correct answer)
INR will increase as hyperthyroidism resolves
Methimazole directly inhibits warfarin metabolism
INR is unaffected by thyroid status

Correct answer: INR will decrease as hyperthyroidism resolves

Hyperthyroidism accelerates clotting factor catabolism, increasing INR; as thyroid function normalizes with treatment, clotting factor turnover slows and INR decreases, requiring warfarin dose adjustment upward.

Question 41: 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?

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

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 42: 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?

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

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 43: 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?

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

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 44: 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)
Surgical embolectomy
Systemic thrombolysis with IV alteplase
Catheter-directed thrombolysis

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 45: A 38-year-old woman presents with a blistering rash. On examination, flaccid bullae arise on normal-appearing skin, rupture easily leaving erosions, and the Nikolsky sign is positive (lateral pressure causes skin to shear). Direct immunofluorescence shows intercellular IgG deposition in a 'fishnet' pattern in the epidermis. What is the diagnosis?

Dermatitis herpetiformis
Linear IgA bullous dermatosis
Pemphigus vulgaris (Correct answer)
Bullous pemphigoid

Correct answer: Pemphigus vulgaris

Pemphigus vulgaris is an autoimmune blistering disease characterized by flaccid bullae, positive Nikolsky sign, mucosal involvement, and intercellular IgG deposition (anti-desmoglein antibodies) in a fishnet/reticular pattern on DIF. Bullous pemphigoid has tense bullae, negative Nikolsky, and linear IgG at the dermal-epidermal junction. Dermatitis herpetiformis shows IgA deposits in papillary dermis.

Question 46: A 40-year-old woman with SLE develops worsening hypertension and proteinuria of 3.5 g/day. Serum creatinine rises from 0.9 to 1.8 mg/dL over 3 months. The next best step is:

Start cyclophosphamide empirically
Repeat urinalysis in 6 months
Kidney biopsy (Correct answer)
Increase hydroxychloroquine dose

Correct answer: Kidney biopsy

Kidney biopsy is needed to classify lupus nephritis histologically, which guides immunosuppressive therapy selection.

Question 47: 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
Initiate rituximab, as anti-Scl-70 positivity with BAL lymphocytosis defines a rituximab-responsive phenotype
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)

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 48: 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?

Cefotaxime 2g IV q8h (Correct answer)
Amoxicillin-clavulanate PO
Vancomycin plus piperacillin-tazobactam
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 49: 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 50: A 29-year-old woman with type 1 diabetes presents with severe DKA: arterial pH 6.86, HCO₃ 3 mEq/L, serum potassium 2.8 mEq/L, glucose 540 mg/dL. IV fluids and aggressive potassium replacement are initiated. Which approach to bicarbonate administration is most consistent with current evidence-based guidelines?

Bicarbonate should be reserved for patients with concurrent hyperkalemia, where it can serve dual purposes
Bicarbonate must be given immediately via rapid infusion to reverse the metabolic acidosis before starting insulin
Bicarbonate is absolutely contraindicated in DKA regardless of pH, as it worsens CSF acidosis through CO₂ accumulation across the blood-brain barrier
Bicarbonate may be considered given pH < 6.9, but should be withheld until potassium is repleted to ≥ 3.5 mEq/L, as correction of acidosis will drive potassium intracellularly and risk life-threatening hypokalemia (Correct answer)

Correct answer: Bicarbonate may be considered given pH < 6.9, but should be withheld until potassium is repleted to ≥ 3.5 mEq/L, as correction of acidosis will drive potassium intracellularly and risk life-threatening hypokalemia

ADA guidelines acknowledge that bicarbonate may be considered for adults with pH < 6.9, but it must never be given before potassium is safely above 3.5 mEq/L. As acidosis resolves (whether from insulin or bicarbonate), H⁺ moves out of cells and K⁺ moves back in — with a potassium of 2.8, this shift could precipitate fatal arrhythmias. Insulin therapy should also be withheld until K⁺ ≥ 3.5 mEq/L for the same reason. Rapid bicarbonate infusion is always contraindicated (risk of paradoxical CNS acidosis, osmotic shift). The absolute contraindication framing in choice C is too extreme — guidelines do allow consideration at pH < 6.9.

Question 51: 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?

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

Correct answer: Hepatorenal syndrome

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

Question 52: A 28-year-old with type 1 DM presents with DKA. Blood glucose is 420 mg/dL and beta-hydroxybutyrate is elevated. After 8 hours of treatment, glucose is 180 mg/dL but pH remains 7.15 and anion gap is still elevated. What is the most appropriate next step?

Stop insulin and reassess in 2 hours
Administer sodium bicarbonate
Add dextrose to IV fluids and continue insulin (Correct answer)
Increase insulin infusion rate

Correct answer: Add dextrose to IV fluids and continue insulin

When glucose falls below 200-250 mg/dL before anion gap closes, dextrose should be added to IV fluids to allow continuation of insulin until ketoacidosis resolves.

Question 53: 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?

Initiate invasive mechanical ventilation with volume-control mode (Correct answer)
Add high-flow nasal cannula at 40 L/min in combination with BiPAP
Increase BiPAP IPAP to 20 cmH2O and reassess in 2 hours
Administer IV doxapram as a respiratory stimulant to avoid intubation

Correct answer: Initiate invasive mechanical ventilation with volume-control mode

This patient has failed a trial of noninvasive ventilation (NIV) — defined by worsening ABG, declining mental status, and inability to cooperate — after an adequate trial period (≥1–2 hours). NIV failure mandates prompt transition to invasive mechanical ventilation to prevent respiratory arrest. Increasing BiPAP settings is unlikely to help when the patient is already deteriorating on NIV. Combining HFNC with BiPAP is not a validated rescue strategy and would delay definitive airway management. Doxapram is rarely used in modern practice, not recommended in guidelines for COPD exacerbation, and is not appropriate when mental status is declining.

Question 54: 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 can be downstaged with locoregional therapy and listed if within Milan criteria for ≥6 months (Correct answer)
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 exceeds Milan criteria and should be referred for systemic therapy only

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

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

Question 55: A 75-year-old woman on lithium for bipolar disorder for 30 years presents with nephrogenic diabetes insipidus, CKD stage 4 (eGFR 22), and small echogenic kidneys on ultrasound. What renal pathology is most characteristic of chronic lithium nephrotoxicity?

Chronic interstitial fibrosis with microcystic tubular changes (Correct answer)
Focal segmental glomerulosclerosis
Mesangial proliferative glomerulonephritis
Membranous nephropathy

Correct answer: Chronic interstitial fibrosis with microcystic tubular changes

Chronic lithium nephrotoxicity causes characteristic cortical and medullary microcysts from distal tubular injury, accompanied by interstitial fibrosis and tubular atrophy.

Question 56: A 50-year-old woman with systemic lupus erythematosus presents with dyspnea, elevated JVP, and an echocardiogram showing a thickened pericardium with respiratory variation in mitral inflow >25%. What is the diagnosis?

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

Correct answer: Constrictive pericarditis

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

Question 57: 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
Humoral hypercalcemia of malignancy via PTHrP (Correct answer)
Local osteolytic metastases releasing calcium
Adrenal insufficiency from metastases

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 58: A 70-year-old man with ischemic cardiomyopathy (EF 25%) has a fasting blood glucose of 115 mg/dL. Which antidiabetic agent has demonstrated cardiovascular mortality benefit in patients with heart failure with reduced EF?

Liraglutide (GLP-1 agonist)
Metformin
Empagliflozin (SGLT2 inhibitor) (Correct answer)
Sitagliptin (DPP-4 inhibitor)

Correct answer: Empagliflozin (SGLT2 inhibitor)

SGLT2 inhibitors like empagliflozin and dapagliflozin reduce cardiovascular death and heart failure hospitalizations in HFrEF, even in patients without diabetes.

Question 59: A 45-year-old female immigrant from Southeast Asia presents with progressive exertional dyspnea. She has a history of rheumatic fever in childhood. On exam, she has an opening snap and a low-pitched diastolic rumble at the apex. She is found to be in atrial fibrillation with a rapid ventricular response. Echocardiography confirms severe rheumatic mitral stenosis (valve area 0.9 cm²). Which of the following medications is contraindicated for anticoagulation in this patient?

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

Correct answer: Dabigatran.

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

Question 60: 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?

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

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 61: 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?

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

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 62: A patient with HHS is treated with IV fluids. After 4 liters of 0.9% NaCl, glucose is 600 mg/dL and osmolality is 340. What is the next most appropriate fluid?

Switch to 0.45% NaCl (Correct answer)
Switch to D5 0.45% NaCl
Switch to D5W
Continue 0.9% NaCl

Correct answer: Switch to 0.45% NaCl

After initial volume resuscitation with isotonic saline, 0.45% NaCl (hypotonic) is used to replace free water deficit and gradually correct hyperosmolality in HHS.

Question 63: 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?

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

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 64: 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 65: 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?

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

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 66: 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
Pituitary radiation
Bromocriptine or cabergoline (Correct answer)

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 67: A 45-year-old woman presents with progressive fatigue, splenomegaly, and a WBC of 185,000/µL with a left shift. BCR-ABL1 is detected by FISH. She is started on imatinib 400 mg daily. After 3 months, her BCR-ABL1 transcript level by quantitative PCR is 15% (IS). After 6 months, it is 12% (IS). According to ELN 2022 guidelines, what is the most appropriate next step?

Perform ABL kinase domain mutation analysis and switch to a second-generation TKI (Correct answer)
Continue imatinib and reassess at 12 months
Add hydroxyurea to imatinib for cytoreduction
Switch to dasatinib or nilotinib due to treatment failure

Correct answer: Perform ABL kinase domain mutation analysis and switch to a second-generation TKI

ELN 2022 guidelines define BCR-ABL1 >10% (IS) at 6 months as treatment failure (not just warning). At 6 months, the target is BCR-ABL1 ≤10% (IS) — achieving major molecular response milestone. This patient at 12% at 6 months has failed the 6-month milestone. The appropriate next step is ABL kinase domain mutation testing to guide TKI selection, followed by switching to a second-generation TKI (dasatinib, nilotinib, or bosutinib). Simply continuing imatinib without change is inadequate for a failure response.

Question 68: A 62-year-old woman with polycythemia vera (JAK2 V617F positive) controlled on hydroxyurea presents with a 3-month history of increasing spleen size, constitutional symptoms, and worsening anemia requiring transfusions (hemoglobin 7.8 g/dL). Bone marrow biopsy shows >20% blasts. Cytogenetics reveal del(17p) and complex karyotype. What is the most appropriate diagnosis and management strategy?

Hydroxyurea-induced myelodysplasia; stop hydroxyurea and transition to anagrelide
Post-PV myelofibrosis progressing to accelerated phase; start ruxolitinib and defer transplant evaluation
Myelofibrosis with myeloid metaplasia; initiate fedratinib as second-line JAK inhibitor therapy
Blast-phase transformation of PV (secondary AML); consider venetoclax + azacitidine and evaluate for allogeneic SCT (Correct answer)

Correct answer: Blast-phase transformation of PV (secondary AML); consider venetoclax + azacitidine and evaluate for allogeneic SCT

Blast phase (blast crisis) of polycythemia vera — defined as ≥20% blasts in bone marrow or peripheral blood — represents transformation to secondary AML, a recognized complication of MPN. This is distinct from post-PV myelofibrosis or accelerated phase (10–19% blasts). The complex karyotype including del(17p) (TP53 locus) confers very high-risk cytogenetics. Standard AML induction has poor outcomes; venetoclax + azacitidine (HMA/ven) is increasingly used for TP53-mutated or complex-karyotype secondary AML in older/unfit patients, with allo-HSCT in CR1 as the only potentially curative option. Ruxolitinib addresses myelofibrosis symptoms but is not appropriate for blast-phase disease. The blast count of >20% definitively excludes the MF accelerated phase designation.

Question 69: A 58-year-old man presents with exertional chest pain. Stress testing shows 2mm ST depression in leads V4-V6 at 5 METs. What is the most appropriate next step?

Refer for coronary angiography (Correct answer)
Increase beta-blocker dosage and repeat stress test
Perform cardiac MRI stress perfusion imaging
Start long-acting nitrates and retest in 3 months

Correct answer: Refer for coronary angiography

High-risk stress test findings (≥2mm ST depression, low exercise capacity <5 METs) warrant prompt coronary angiography for definitive evaluation.

Question 70: A 45-year-old woman develops acute respiratory distress syndrome (ARDS) after septic shock. P/F ratio is 95. Which ventilator strategy has the strongest mortality benefit?

High PEEP strategy with FiO2 titration only
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)
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 71: A 72-year-old woman presents with acute onset of bright red blood per rectum, crampy left lower quadrant pain, and tenesmus without systemic symptoms. CT shows segmental colonic wall thickening at the splenic flexure. What is the most likely diagnosis?

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

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 72: 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
Hydroxychloroquine
Sirolimus (rapamycin) (Correct answer)
Doxycycline

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 73: A 35-year-old competitive athlete collapses during a basketball game. Resuscitation is successful. ECG shows deep T-wave inversions in V1–V4 and left axis deviation. His father died suddenly at age 40. What is the most likely diagnosis?

Coronary artery vasospasm
Long QT syndrome
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) (Correct answer)

Correct answer: Arrhythmogenic right ventricular cardiomyopathy (ARVC)

ARVC characteristically presents with T-wave inversions in right precordial leads, ventricular arrhythmias triggered by exercise, and a family history of sudden death.

Question 74: 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?

Juxtaglomerular cell tumor (reninoma) (Correct answer)
Primary hyperaldosteronism (Conn syndrome)
Adrenocortical carcinoma
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 75: 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?

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

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 76: 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?

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

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

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

Question 77: A 50-year-old man with known esophageal varices presents with hematemesis. He is hemodynamically stable after resuscitation. What is the most appropriate endoscopic treatment?

Hemostatic clips
Coagulation therapy
Sclerotherapy
Band ligation (Correct answer)

Correct answer: Band ligation

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

Question 78: 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 is not a contraindication to transplantation
It requires pre-transplant eradication with IV antibiotics before listing
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 79: 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
Eosinophilic infiltrates with mucous plugging
Diffuse alveolar damage with hyaline membranes
Peribronchiolar fibrosis with architectural distortion and honeycombing (Correct answer)

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

Continue cabergoline throughout pregnancy to prevent tumor regrowth
Stop cabergoline once pregnancy is confirmed, as tumor enlargement risk is low with microadenoma (Correct answer)
Switch to bromocriptine before conception since it has a longer safety record in pregnancy
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 81: 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 82: A 65-year-old female is diagnosed with severe, symptomatic, degenerative mitral regurgitation (MR) and is referred for surgical evaluation. Her LVEF is 65% and left ventricular end-systolic dimension (LVESD) is 38 mm. Which of the following is the preferred surgical approach?

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

Correct answer: Mitral valve repair.

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

Question 83: 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 84: 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?

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

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

<70 mg/dL (Correct answer)
<130 mg/dL
<50 mg/dL
<100 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 86: A 74-year-old man with poorly controlled type 2 diabetes is brought in confused and lethargic. Labs: Na 148 mEq/L, glucose 978 mg/dL, BUN 66 mg/dL, creatinine 2.2 mg/dL, HCO₃ 22 mEq/L, pH 7.38. Measured serum osmolality is 374 mOsm/kg. Which value most accurately reflects the tonicity responsible for his neurological symptoms?

Measured serum osmolality of 374 mOsm/kg, because it captures all solutes including urea
Corrected serum sodium of 163 mEq/L, because it accounts for the dilutional effect of hyperglycemia
Osmol gap (measured minus calculated) of approximately 5 mOsm/kg, which signals the severity of the hyperosmolar state
Effective osmolality of approximately 350 mOsm/kg, calculated as 2[Na] + glucose/18, because urea is an ineffective osmole that freely crosses cell membranes (Correct answer)

Correct answer: Effective osmolality of approximately 350 mOsm/kg, calculated as 2[Na] + glucose/18, because urea is an ineffective osmole that freely crosses cell membranes

Effective (or tonicity) osmolality = 2[Na] + glucose (mg/dL)/18. In this patient: 2(148) + 978/18 ≈ 296 + 54 = 350 mOsm/kg. Urea is excluded because it is an ineffective osmole — it crosses cell membranes freely and does not generate an osmotic gradient across cells. Including urea in the osmolality falsely inflates the value without contributing to tonicity. The neurological manifestations of HHS correlate with effective osmolality; the diagnostic threshold is ≥ 320 mOsm/kg. A corrected sodium helps adjust for hyperglycemia but does not directly yield an osmolality value.

Question 87: A 55-year-old woman with IgA nephropathy has a urine protein-to-creatinine ratio of 1.8 g/g and eGFR of 52 mL/min/1.73m². Which additional therapy beyond RAS blockade has demonstrated benefit in slowing CKD progression in this condition?

Sparsentan (Correct answer)
Hydroxychloroquine
Rituximab
Mycophenolate mofetil

Correct answer: Sparsentan

Sparsentan, a dual endothelin-angiotensin receptor antagonist, has demonstrated significant proteinuria reduction and renal protective effects in IgA nephropathy.

Question 88: 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)
Daptomycin monotherapy for 6 weeks
Ampicillin plus gentamicin for 4–6 weeks
Vancomycin plus gentamicin 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 89: 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 combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) (Correct answer)
A short-acting beta-agonist (SABA) as needed with no maintenance therapy
A combination of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA)
A long-acting muscarinic antagonist (LAMA) monotherapy

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 90: 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?

Risk of thyroid storm
Exogenous subclinical hyperthyroidism accelerates bone loss (Correct answer)
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 91: 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?

Gluten-free diet (Correct answer)
Prednisone
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 92: 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?

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

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 93: 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:

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

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

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

Question 94: Which anticoagulation regimen is recommended for a patient with a bileaflet mechanical aortic valve prosthesis with no additional risk factors?

Warfarin with INR target 2.0-3.0 (Correct answer)
Aspirin 325 mg daily alone
Dabigatran 150 mg twice daily
Warfarin with INR target 2.5-3.5

Correct answer: Warfarin with INR target 2.0-3.0

For a bileaflet mechanical AVR with no additional thromboembolic risk factors, warfarin with INR target 2.0-3.0 is recommended; higher targets are needed for additional risk factors.

Question 95: 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 96: A 50-year-old woman with rheumatoid arthritis on methotrexate presents with new onset dyspnea and bilateral ground-glass opacities on CT chest. BAL shows eosinophilia. Lung biopsy reveals organizing pneumonia pattern. Which statement about this drug-induced lung injury is TRUE?

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

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 97: 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?

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

Correct answer: Constrictive pericarditis

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

Question 98: A 55-year-old female ex-smoker with COPD (FEV1 45% predicted) has had 3 exacerbations in the past year requiring hospitalization. Her current regimen is LAMA + LABA. What additional therapy has shown mortality benefit in this patient?

Roflumilast
Pulmonary rehabilitation
Azithromycin prophylaxis
Inhaled corticosteroid (ICS) (Correct answer)

Correct answer: Inhaled corticosteroid (ICS)

Adding ICS to LAMA+LABA (triple therapy) reduces exacerbations and has shown mortality benefit in COPD patients with frequent exacerbations, particularly those with elevated eosinophils.

Question 99: A 45-year-old woman presents with jaundice, pruritus, and elevated alkaline phosphatase. AMA is positive. What is the most likely diagnosis?

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

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 100: 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, 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?

Perform bronchoscopy with BAL to rule out infection before treating
Discontinue ATRA immediately and initiate idarubicin
Start hydroxyurea to control leukocytosis
Add dexamethasone 10 mg IV twice daily and continue ATRA (Correct answer)

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

This presentation is classic for differentiation syndrome (formerly ATRA syndrome), occurring in ~25% of APL patients treated with ATRA or arsenic trioxide. It is characterized by fever, weight gain, pulmonary infiltrates, and rising WBC. The correct management is to add high-dose dexamethasone (10 mg IV BID) while continuing ATRA — discontinuation is reserved only for severe cases with renal failure or respiratory failure requiring mechanical ventilation. Early steroid intervention is life-saving and ATRA should not be stopped empirically.

Question 101: An ICU patient develops ventilator-associated pneumonia (VAP) on day 8. Endotracheal cultures grow Pseudomonas aeruginosa. Which antibiotic combination should be used empirically given concern for multidrug-resistant (MDR) Pseudomonas?

Meropenem plus ceftolozane-tazobactam
Piperacillin-tazobactam monotherapy
Ceftazidime-avibactam plus colistin
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 102: 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
Ivermectin 200mcg/kg daily x 2 days (Correct answer)
Mebendazole 500mg single dose
Albendazole 400mg BID x 7 days

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 103: 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
High-flow nasal cannula at 40 L/min
Immediate endotracheal intubation
Non-invasive positive pressure ventilation (NIPPV) (Correct answer)

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 104: 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
Metformin 2000 mg twice daily (Correct answer)
Sitagliptin
Empagliflozin

Correct answer: Metformin 2000 mg twice daily

Metformin is contraindicated when eGFR falls below 30, but at eGFR 52 it can be continued at current dose; however, doubling to 2000 mg twice daily (4000 mg/day) exceeds the maximum recommended dose of 2550 mg/day and is not indicated.

Question 105: 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)
Vedolizumab
Natalizumab

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

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

Correct answer: Lumbar puncture

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

Question 107: 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?

Baseline CSF cryptococcal antigen titer
Adequacy of serial therapeutic lumbar punctures to control intracranial pressure (Correct answer)
CD4 count at time of diagnosis
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 108: A 58-year-old man with alcoholic cirrhosis develops confusion and asterixis. Ammonia level is elevated. Which treatment is most appropriate?

Lactulose (Correct answer)
Rifaximin
Zinc supplementation
Neomycin

Correct answer: Lactulose

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

Question 109: A 26-year-old normotensive woman presents with recurrent muscle cramps and fatigue. Labs: K+ 2.8 mEq/L, HCO3- 31 mEq/L, Mg2+ 1.2 mg/dL (low), spot urine Ca/Cr ratio 0.04 (hypocalciuria). She takes no medications. Urine chloride and potassium are inappropriately elevated. Which molecular defect best explains this constellation of findings?

Gain-of-function mutation in CaSR causing hypercalciuria and hypomagnesemia
Inactivating mutation in ROMK causing neonatal salt wasting then hypokalemia
Inactivating mutation in NCC in the distal convoluted tubule (Correct answer)
Inactivating mutation in NKCC2 in the thick ascending limb of Henle

Correct answer: Inactivating mutation in NCC in the distal convoluted tubule

This is Gitelman syndrome, caused by loss-of-function mutations in SLC12A3 encoding NCC (the thiazide-sensitive Na-Cl cotransporter) in the distal convoluted tubule. The DCT is responsible for Mg reabsorption via TRPM6 channels and calcium reabsorption — NCC dysfunction causes hypomagnesemia and hypocalciuria (the same effect as chronic thiazide use). Bartter syndrome (types 1/2/3 affecting NKCC2, ROMK, or CLCNKB in the TAL) causes hypercalciuria, not hypocalciuria. The triad of hypokalemic metabolic alkalosis + hypomagnesemia + hypocalciuria is pathognomonic for Gitelman.

Question 110: 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 111: A 40-year-old woman presents with two episodes of unilateral optic neuritis over 2 years plus a history of transient bilateral leg weakness that resolved completely. MRI of the brain and spine shows periventricular white matter lesions disseminated in space and time. CSF shows oligoclonal bands. What is the most likely diagnosis?

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

Correct answer: Relapsing-remitting multiple sclerosis (RRMS)

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

Question 112: Which of the following best describes the mechanism of action of ursodeoxycholic acid (UDCA) in primary biliary cholangitis?

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

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 113: A 22-year-old man presents with a palpable neck mass, marfanoid habitus, multiple mucosal neuromas on the lips and tongue, and episodic hypertension. His mother died of thyroid cancer and a suspected cardiac event. Genetic testing confirms a RET proto-oncogene mutation. Compared to a patient with MEN2A, which of the following manifestations is most likely ABSENT in this patient?

RET codon mutation
Pheochromocytoma
Medullary thyroid carcinoma
Primary hyperparathyroidism (Correct answer)

Correct answer: Primary hyperparathyroidism

MEN2B (RET codon 918 mutation) comprises medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, marfanoid habitus, and intestinal ganglioneuromatosis — but does NOT include primary hyperparathyroidism. MEN2A (codons 634, 609, etc.) includes MTC + pheochromocytoma + primary hyperparathyroidism. Both syndromes carry RET mutations. MEN2B has the most aggressive MTC phenotype and prophylactic thyroidectomy is recommended in the first 6 months of life.

Question 114: A 38-year-old woman is found to have a 2.8 cm hepatic adenoma on imaging done for right upper quadrant pain. She takes oral contraceptive pills (OCPs). Biopsy demonstrates β-catenin mutation subtype. She desires future pregnancy. What is the most appropriate management?

Arterial embolization followed by MRI surveillance
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
Immediate surgical resection given β-catenin mutation subtype (Correct answer)

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 115: 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
Systemic thrombolysis with alteplase 100 mg IV over 2 hours after reversing INR
Catheter-directed therapy (mechanical thrombectomy or pharmacomechanical CDT) (Correct answer)
Surgical embolectomy via sternotomy

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

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

Question 116: A 45-year-old man presents with acute oliguric kidney injury, hemoptysis, and pANCA positivity. Kidney biopsy shows pauci-immune crescentic glomerulonephritis. What is the most appropriate induction therapy?

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

Correct answer: High-dose glucocorticoids plus cyclophosphamide or rituximab

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

Question 117: 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 118: 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?

Azithromycin
Trimethoprim-sulfamethoxazole (Correct answer)
Itraconazole
Valganciclovir

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 119: A 45-year-old woman presents with palpitations, tremor, and a painless diffuse goiter. TSH is 0.01 mIU/L, free T4 is 3.2 ng/dL. TSH receptor antibodies are positive. She wants the most definitive long-term cure. What is the best option?

Methimazole for 12–18 months
Total thyroidectomy (Correct answer)
Beta-blocker monotherapy
Radioactive iodine ablation

Correct answer: Total thyroidectomy

Total thyroidectomy provides the most immediate and definitive cure for Graves' disease and is preferred when the patient desires rapid, definitive resolution; RAI is effective but slower and may worsen ophthalmopathy.

Question 120: 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?

Alcoholic ketoacidosis with stress hyperglycemia, as ethanol is cleared but its metabolic effects persist
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
Concurrent DKA and toxic alcohol ingestion (methanol or ethylene glycol) contributing to elevated osmol gap and anion gap (Correct answer)

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 121: 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?

Endoscopic dilation should be avoided due to high risk of esophageal perforation exceeding 10%
Elimination diet (six-food elimination) is contraindicated in adults with confirmed eosinophilic esophagitis
Topical swallowed fluticasone or budesonide is first-line pharmacologic therapy after PPI failure (Correct answer)
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 122: 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)
Cryptococcal chorioretinitis; fluconazole
Toxoplasma retinitis; pyrimethamine plus sulfadiazine
Ocular histoplasmosis; itraconazole

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 123: 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?

Metformin
Olmesartan
Lansoprazole (Correct answer)
Sertraline

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 124: 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?

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

Correct answer: IV artesunate

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

Question 125: A patient with DKA has a measured osmolal gap of 22 mOsm/kg (normal <10). Which additional intoxication must be considered?

Acetaminophen toxicity
Salicylate toxicity
Ethylene glycol or methanol poisoning (Correct answer)
Isoniazid toxicity

Correct answer: Ethylene glycol or methanol poisoning

An elevated osmolal gap in the context of metabolic acidosis should prompt evaluation for toxic alcohol ingestion (ethylene glycol, methanol, isopropanol).

Question 126: 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?

Ceftriaxone plus ampicillin
Vancomycin, ceftriaxone, and ampicillin (Correct answer)
Vancomycin plus ceftriaxone
Meropenem monotherapy

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 127: 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?

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

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

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 129: 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?

Atovaquone-proguanil for 3 days
Atovaquone plus azithromycin for 7–10 days (Correct answer)
Chloroquine 1g followed by 500 mg at 6, 24, and 48 hours
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 130: A patient with Cushing's disease undergoes transsphenoidal surgery. Post-operatively, serum cortisol is 2 mcg/dL. What does this indicate?

Recurrence of hypercortisolism
Adrenal insufficiency requiring glucocorticoid replacement (Correct answer)
Surgical failure requiring repeat surgery
Normal post-operative finding requiring no treatment

Correct answer: Adrenal insufficiency requiring glucocorticoid replacement

Very low post-operative cortisol indicates successful tumor removal but requires exogenous glucocorticoid replacement until the HPA axis recovers.

Question 131: 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?

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

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 132: 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?

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

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 133: 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
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)
Methimazole should be switched to propylthiouracil for the remainder of the pregnancy to eliminate teratogenic risk
Neonatal Graves' disease risk is determined by maternal free T4 level at delivery, not by TRAb titer

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 134: 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?

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

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 135: 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?

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

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 136: 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?

Decrease respiratory rate to correct respiratory alkalosis (Correct answer)
Increase PEEP to improve oxygenation
Decrease FiO2 to 0.21
Increase tidal volume to increase minute ventilation

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 137: 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?

Rest
Electrolyte monitoring
Fluid replacement
Antibiotics (Correct answer)

Correct answer: Antibiotics

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

Question 138: 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?

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

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 139: 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
Reduce cabergoline dose and add bromocriptine
Discontinue cabergoline and initiate bromocriptine (Correct answer)

Correct answer: Discontinue cabergoline and initiate bromocriptine

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

Question 140: A patient with end-stage renal disease on peritoneal dialysis develops cloudy peritoneal effluent. Peritoneal fluid cell count shows 350 WBC/µL with 85% neutrophils. What is the most likely organism?

Pseudomonas aeruginosa
Staphylococcus aureus
Staphylococcus epidermidis (Correct answer)
Candida albicans

Correct answer: Staphylococcus epidermidis

Coagulase-negative staphylococci (S. epidermidis) are the most common cause of peritoneal dialysis-associated peritonitis, typically from touch contamination.

Question 141: 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?

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

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 142: 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?

Empagliflozin (Correct answer)
Pioglitazone
Glipizide
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 143: A 50-year-old male with a right pleural effusion undergoes thoracentesis. Analysis shows: protein 4.2 g/dL (serum 7.0), LDH 280 U/L (serum 180), glucose 40 mg/dL, pH 7.15. What is the most likely etiology?

Parapneumonic effusion/empyema (Correct answer)
Congestive heart failure
Pulmonary embolism
Hepatic hydrothorax

Correct answer: Parapneumonic effusion/empyema

The exudative effusion (meets Light's criteria) with low glucose, low pH, and high LDH is characteristic of a complicated parapneumonic effusion or empyema requiring chest tube drainage.

Question 144: 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?

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

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 145: A 68-year-old woman with hypertrophic obstructive cardiomyopathy (HOCM) and a resting LVOT gradient of 55 mmHg presents with NYHA class III dyspnea despite maximally tolerated metoprolol and disopyramide. She has a septal thickness of 22 mm and no coronary artery disease. Echocardiography reveals a suitable septal perforator anatomy. Which intervention is preferred?

Alcohol septal ablation (Correct answer)
Mavacamten initiation
ICD implantation
Septal myectomy

Correct answer: Alcohol septal ablation

Both surgical septal myectomy and alcohol septal ablation (ASA) are guideline-endorsed for drug-refractory HOCM with severe obstruction. Myectomy is generally preferred in younger patients or those with complex anatomy requiring concurrent repair. ASA is preferred in older patients or those with significant comorbidities who are high surgical risk, and when septal perforator anatomy is suitable. This 68-year-old patient with suitable anatomy and no need for concomitant surgery is an appropriate ASA candidate. ICD addresses sudden death risk but does not relieve obstruction. Mavacamten is a newer option but is reserved for patients before considering invasive septal reduction.

Question 146: 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?

Reassure and recheck calcium in 6 months
Refer for parathyroidectomy (Correct answer)
Start bisphosphonate therapy alone
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 147: A 72-year-old man with type 2 diabetes presents with altered mental status, serum glucose 1,140 mg/dL, plasma osmolality 382 mOsm/kg, pH 7.36, bicarbonate 22 mEq/L, and a small anion gap of 13. He is started on aggressive IV normal saline. Six hours later, his glucose has fallen to 600 mg/dL but his sodium has risen from 128 to 148 mEq/L. What is the most appropriate next step?

Administer a bolus of 3% NaCl to prevent cerebral edema from overly rapid osmolality correction
Add dextrose to the IV fluids immediately to prevent further osmolality reduction
Switch IV fluid to 0.45% NaCl to provide free water and reduce the corrected sodium (Correct answer)
Continue normal saline at the same rate because hypernatremia in HHS is expected and self-correcting

Correct answer: Switch IV fluid to 0.45% NaCl to provide free water and reduce the corrected sodium

In HHS, the initial fluid of choice is isotonic saline to restore intravascular volume, but once hemodynamic stability is achieved and the corrected sodium is rising (or already elevated), switching to 0.45% NaCl provides free water to correct the hyperosmolar state. Corrected sodium = measured Na + 1.6 × [(glucose − 100)/100]; a rising sodium during resuscitation signals that the free water deficit is not being adequately corrected. Overly rapid correction risks cerebral edema (though less common in adults than children), while under-correction perpetuates neurological impairment. Continuing isotonic saline in a patient with rising hypernatremia worsens the free water deficit.

Question 148: 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?

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

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

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

Question 149: 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?

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

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 150: 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)
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
Initiate veno-venous ECMO for refractory hypoxemia

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

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

Correct answer: Oral corticosteroids

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

Question 152: 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?

Pituitary radiation
Pegvisomant monotherapy
Somatostatin receptor ligand (octreotide LAR or lanreotide) (Correct answer)
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 153: A 55-year-old man who recently started allopurinol presents with widespread erythema, skin sloughing affecting >30% of body surface area, mucosal involvement, and fever. Skin biopsy shows full-thickness epidermal necrosis. What is this condition?

Pemphigus vulgaris
Toxic epidermal necrolysis (TEN) (Correct answer)
Staphylococcal scalded skin syndrome (SSSS)
Stevens-Johnson syndrome (SJS)

Correct answer: Toxic epidermal necrolysis (TEN)

TEN is defined by epidermal detachment affecting >30% BSA with full-thickness epidermal necrosis on biopsy, commonly drug-induced (allopurinol, sulfonamides, anticonvulsants). SJS involves <10% BSA detachment. SSSS affects mainly children and involves superficial epidermal cleavage from staph exotoxin. Pemphigus vulgaris presents with flaccid blisters from autoantibodies, not drug-induced.

Question 154: A 50-year-old male presents with progressive dyspnea, hypoxemia, and bilateral infiltrates 5 days after starting amiodarone. HRCT shows bilateral ground-glass opacities with consolidation in a peripheral distribution. What is the pathological pattern most likely seen on lung biopsy?

Diffuse alveolar damage (DAD)
Organizing pneumonia (OP) (Correct answer)
Lymphoid interstitial pneumonia (LIP)
Usual interstitial pneumonia (UIP)

Correct answer: Organizing pneumonia (OP)

Amiodarone pulmonary toxicity most commonly manifests as organizing pneumonia (OP) pattern, though it can also cause phospholipidosis and UIP; peripheral consolidation on CT is the OP hallmark.

Question 155: 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:

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

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 156: 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?

Chest X-ray to confirm diagnosis
Bronchoscopy to assess for mucus plugging
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 157: 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?

9 months total
6 months total (Correct answer)
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 158: What is the most common cause of acquired mitral stenosis in adults in the United States?

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

Correct answer: Rheumatic heart disease

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

Question 159: 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
Low ACTH stimulation test response
Positive 21-hydroxylase antibodies

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 160: A 44-year-old never-smoker is found to have a 22 mm solid pulmonary nodule on CT performed after a motor vehicle accident. PET scan shows SUV max of 2.8 in the nodule. Bronchoscopy with BAL and transbronchial biopsy is non-diagnostic. CT-guided biopsy reveals scattered atypical lymphoid cells. Flow cytometry on the biopsy sample is pending. Which feature would MOST strongly argue against primary pulmonary MALT lymphoma and instead favor a reactive process?

Low-grade SUV on PET scan with indolent clinical course
Presence of lymphoepithelial lesions on histology
Polyclonal kappa and lambda light chain expression on flow cytometry (Correct answer)
Monoclonal B-cell population with CD20+/CD5-/CD10- immunophenotype

Correct answer: Polyclonal kappa and lambda light chain expression on flow cytometry

Primary pulmonary MALT lymphoma (extranodal marginal zone lymphoma) is characterized by a monoclonal B-cell proliferation, typically CD20+/CD5-/CD10-, with lymphoepithelial lesions on histology. A low PET SUV is characteristic of low-grade MALT lymphoma and does not distinguish it from reactive disease. Polyclonal kappa and lambda light chain expression on flow cytometry is the hallmark of a reactive (non-neoplastic) lymphoid proliferation, as malignant B-cell clones demonstrate light chain restriction (monoclonality). This finding would most strongly argue against lymphoma.

Question 161: A patient with MEN1 syndrome is found to have a gastrinoma. Which finding would be expected?

Hypocalcemia and low PTH
Low VIP levels with watery diarrhea
Elevated fasting serum gastrin with acid hypersecretion (Correct answer)
Suppressed insulin levels with hypoglycemia

Correct answer: Elevated fasting serum gastrin with acid hypersecretion

Gastrinomas cause Zollinger-Ellison syndrome, characterized by elevated fasting gastrin (>1000 pg/mL) and recurrent peptic ulcers from gastric acid hypersecretion.

Question 162: A 72-year-old woman undergoes right heart catheterization. Results: RA 8 mmHg, RV 42/10 mmHg, PA 42/22 mmHg (mean 30 mmHg), PCWP 18 mmHg, cardiac output 4.2 L/min. What is the pulmonary vascular resistance (PVR) and the correct classification of her pulmonary hypertension?

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

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 163: 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
Emergent surgery
Colonoscopy
Percutaneous drainage plus antibiotics (Correct answer)

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 164: 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?

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

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 165: 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?

Administration of prophylactic broad-spectrum antibiotics
Immediate ERCP to assess for biliary obstruction
Placement of a nasogastric tube for gastric decompression
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 166: A mechanically ventilated patient with ARDS (P/F ratio 90) is being managed with prone positioning and neuromuscular blockade. After 18 hours prone, the nurse notes plateau pressure has risen from 28 to 38 cmH2O with no change in PEEP or tidal volume. SpO2 is 84%. The MOST likely cause requiring immediate intervention is:

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

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 167: 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
Finerenone (Correct answer)
Pioglitazone

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 168: A 24-year-old female with a known history of intermittent asthma presents to the urgent care clinic with complaints of wheezing and shortness of breath for the past two days. She uses her albuterol inhaler 4-5 times a day with partial relief. She has no daily controller medication. According to the 2024 GINA guidelines, which of the following is the most appropriate long-term management plan to initiate?

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

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

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

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

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

Question 170: A 32-year-old woman with antiphospholipid syndrome (APS) and history of DVT is pregnant. How should her anticoagulation be managed during pregnancy?

Low molecular weight heparin (LMWH) throughout pregnancy (Correct answer)
No anticoagulation needed during pregnancy
Warfarin throughout pregnancy
Aspirin alone

Correct answer: Low molecular weight heparin (LMWH) throughout pregnancy

LMWH is the anticoagulant of choice in pregnancy as warfarin crosses the placenta and is teratogenic, particularly in the first trimester.

Question 171: A 66-year-old man with known COPD presents with worsening dyspnea and increased sputum production. Spirometry shows FEV1/FVC of 0.58 and FEV1 55% predicted. His current regimen is a LABA alone. The next best step is:

Add a LAMA (tiotropium) (Correct answer)
Start inhaled corticosteroids alone
Start systemic corticosteroids long-term
Add theophylline

Correct answer: Add a LAMA (tiotropium)

GOLD guidelines recommend combining LABA and LAMA for symptomatic COPD patients inadequately controlled on monotherapy to reduce exacerbations.

Question 172: 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 173: Which test is the most appropriate initial diagnostic tool for suspected pulmonary embolism?

D-dimer test (Correct answer)
CT pulmonary angiography
Chest X-ray
Ventilation-perfusion scan

Correct answer: D-dimer test

The D-dimer test is the most appropriate initial diagnostic tool for suspected pulmonary embolism (PE) in patients with a low or intermediate pre-test probability. A negative D-dimer test can effectively rule out PE, avoiding the need for more invasive imaging. However, a positive D-dimer requires further investigation.

Question 174: A patient with DKA has a serum phosphate of 1.1 mg/dL. Which complication is most closely associated with severe hypophosphatemia in DKA?

Acute kidney injury
Cardiac arrhythmias
Seizures
Respiratory muscle weakness and hemolytic anemia (Correct answer)

Correct answer: Respiratory muscle weakness and hemolytic anemia

Severe hypophosphatemia in DKA can cause respiratory muscle weakness, hemolysis, and rhabdomyolysis, though routine phosphate replacement is not recommended.

Question 175: A patient with IPF is being considered for antifibrotic therapy. Which of the following has been shown to slow decline in FVC in IPF?

N-acetylcysteine
Nintedanib (Correct answer)
Prednisone
Azathioprine

Correct answer: Nintedanib

Nintedanib (and pirfenidone) are approved antifibrotic agents that reduce the rate of FVC decline in IPF; corticosteroids and NAC have shown no benefit or harm.

Question 176: 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?

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

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 177: 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)
Discontinue metformin and initiate insulin glargine
Continue metformin and add sitagliptin with dose adjustment for CKD

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 178: A 28-year-old man presents with episodic severe headaches, diaphoresis, and palpitations. BP is 210/115 mmHg during an episode. 24-hour urine metanephrines are markedly elevated. Prior to surgical resection, which medication should be initiated FIRST?

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

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 179: 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
Azathioprine 150 mg/day
Nintedanib 150 mg twice daily (Correct answer)

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

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

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 181: 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 182: A 35-year-old woman with no prior pulmonary history presents with recurrent hemoptysis and is found to have bilateral ground-glass opacities on HRCT. Urinalysis shows 3+ hematuria with red cell casts. Serum creatinine is 2.4 mg/dL (baseline unknown). Anti-GBM antibody is positive. ANCA is also positive (PR3-ANCA). She is initiated on plasmapheresis and immunosuppression. Which of the following statements about her dual-positive serology is MOST accurate?

Dual-positive patients have a higher risk of relapse than single anti-GBM positive patients and may require prolonged immunosuppression beyond anti-GBM clearance (Correct answer)
Dual positivity is exceedingly rare and most likely represents a laboratory error; repeat testing before proceeding with treatment
The anti-GBM antibody is the dominant pathogenic driver; ANCA positivity does not affect prognosis or treatment
Patients with dual anti-GBM/ANCA positivity typically follow the clinical course of ANCA vasculitis, with lower rates of ESRD than anti-GBM disease alone

Correct answer: Dual-positive patients have a higher risk of relapse than single anti-GBM positive patients and may require prolonged immunosuppression beyond anti-GBM clearance

Dual anti-GBM/ANCA positivity occurs in approximately 30% of anti-GBM disease cases and carries a distinct clinical phenotype. These patients tend to have the severe, acute presentation of anti-GBM disease (rapidly progressive GN, pulmonary hemorrhage) but also the relapsing course of ANCA vasculitis. Unlike isolated anti-GBM disease (which rarely relapses once antibody clears), dual-positive patients have a higher relapse risk driven by the ANCA component and may need prolonged immunosuppression. ESRD rates are similar to or worse than anti-GBM alone, not better. This is not a laboratory artifact — the association is well-established.

Question 183: A 65-year-old strict vegetarian presents with fatigue, paresthesias in hands and feet, and glossitis. Labs show Hgb 9.2 g/dL, MCV 112 fL, and hypersegmented neutrophils on smear. Which lab finding would best confirm the diagnosis?

Low serum vitamin B12 level (Correct answer)
Positive direct Coombs test
Elevated serum ferritin
Low serum folate level

Correct answer: Low serum vitamin B12 level

Macrocytic anemia with neurological symptoms in a long-term strict vegetarian strongly suggests B12 deficiency, confirmed by low serum B12.

Question 184: 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?

VIPoma syndrome (Verner-Morrison)
Glucagonoma syndrome
Insulinoma-associated hypoglycemia
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 185: A 22-year-old college student presents with fever, pharyngitis, cervical lymphadenopathy, and splenomegaly. Heterophile antibody test is positive. Which complication requires activity restriction?

Airway obstruction
Splenic rupture risk (Correct answer)
Hepatitis
Thrombocytopenia

Correct answer: Splenic rupture risk

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

Question 186: 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?

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

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 187: 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?

Methylprednisolone 1 g IV daily for 3 days (pulse therapy) for underlying SLE flare
Prednisone 40 mg PO twice daily for 5 days, then taper over 21 days (Correct answer)
Adjunctive corticosteroids are contraindicated in immunosuppressed patients with PJP
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 188: A 67-year-old renal transplant recipient on tacrolimus develops culture-confirmed Candida glabrata fungemia. He is hemodynamically stable with no ophthalmologic involvement. Susceptibility testing shows elevated MIC to fluconazole (MIC 16 µg/mL). Which is the most appropriate definitive antifungal strategy?

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

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 189: A 47-year-old woman is diagnosed with cryptogenic organizing pneumonia (COP) confirmed by transbronchial biopsy. She is started on prednisone 1 mg/kg/day. At 10 weeks, CT shows near-complete resolution, and steroids are tapered and discontinued by week 14. At week 20, she returns with dyspnea, fever, and new bilateral peripheral consolidations on CT. Which management approach is most appropriate?

Restart prednisone at 1 mg/kg/day and plan a gradual taper over 12 months (Correct answer)
Initiate broad-spectrum antibiotics and repeat bronchoscopy to exclude superimposed infection
Perform surgical lung biopsy to exclude progression to fibrotic nonspecific interstitial pneumonia
Initiate cyclophosphamide for steroid-refractory organizing pneumonia

Correct answer: Restart prednisone at 1 mg/kg/day and plan a gradual taper over 12 months

COP has a relapse rate of up to 50–58% after steroid discontinuation, especially when steroids are tapered too quickly or the course is too short (<6 months). This patient's presentation — symptom recurrence after taper cessation with the same radiographic pattern — is classic relapse, not steroid-refractory disease. The correct approach is to restart prednisone at the full therapeutic dose (1 mg/kg/day) and then taper very slowly over 6–12 months to prevent re-relapse. Cyclophosphamide is reserved for truly refractory cases after multiple failed steroid courses. Surgical biopsy is not warranted when clinical and radiographic features are diagnostic of relapse. Antibiotics alone would be inappropriate without evidence of bacterial superinfection.

Question 190: When calculating the anion gap in a patient with Diabetic Ketoacidosis (DKA) and a glucose of 800 mg/dL, which sodium value should be used?

The measured serum sodium value. (Correct answer)
The sodium value corrected for hyperglycemia.
The sodium value after 1 liter of fluid resuscitation.
An average of the measured and corrected sodium values.

Correct answer: The measured serum sodium value.

The anion gap is calculated using the formula: Na+ – (Cl- + HCO3-). For the purpose of assessing the degree of acidosis and monitoring its resolution in DKA, the measured (uncorrected) serum sodium should be used. Using the corrected sodium, which is adjusted for the dilutional effect of hyperglycemia, would falsely elevate the anion gap and overestimate the severity of the acidosis. The corrected sodium is useful for assessing the patient's true hydration status and free water deficit.

Question 191: 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?

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

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

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

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

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

Question 193: A 34-year-old woman with type 1 diabetes on an SGLT2 inhibitor presents with nausea, vomiting, and malaise. Blood glucose is 198 mg/dL, pH 7.18, bicarbonate 9 mEq/L, anion gap 24, serum ketones strongly positive, and urine ketones 4+. Which of the following best explains this presentation?

The patient has concurrent starvation ketosis superimposed on mild hyperglycemia from insulin deficiency
SGLT2 inhibitors cause a type B lactic acidosis that mimics DKA on laboratory testing
SGLT2 inhibitors promote renal glucose excretion, lowering blood glucose while allowing ketogenesis to continue, resulting in euglycemic DKA (Correct answer)
SGLT2 inhibitors impair glucagon suppression, leading to paradoxical hyperglucagonemia and ketosis without hyperglycemia

Correct answer: SGLT2 inhibitors promote renal glucose excretion, lowering blood glucose while allowing ketogenesis to continue, resulting in euglycemic DKA

SGLT2 inhibitors cause euglycemic DKA by promoting urinary glucose excretion (lowering serum glucose) while simultaneously increasing glucagon secretion and free fatty acid oxidation, driving ketogenesis. The result is significant ketoacidosis with only mildly elevated or even normal glucose — a dangerous presentation that can be missed if providers anchor on the glucose level. Standard DKA criteria require glucose >250 mg/dL, so euglycemic DKA is often underdiagnosed. Recognition requires a low threshold for checking ketones/pH in SGLT2i users who appear ill regardless of glucose.

Question 194: 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 destroys beta cells directly
Celiac disease causes insulin resistance
Celiac increases glucagon secretion
Malabsorption leads to unpredictable glucose-insulin matching (Correct answer)

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 195: A 38-year-old male returns from a camping trip in the Ohio River Valley with fever, night sweats, and a hilar mass on CXR. Serum LDH is mildly elevated. Urine Histoplasma antigen is positive. What is the most appropriate treatment?

Amphotericin B liposomal formulation
Fluconazole
Itraconazole for 12 weeks (Correct answer)
Observation — self-limited illness

Correct answer: Itraconazole for 12 weeks

Mild-to-moderate pulmonary histoplasmosis with symptoms >4 weeks (chronic or subacute) is treated with itraconazole for 6–12 weeks; amphotericin B is reserved for severe or disseminated disease.

Question 196: A 28-year-old woman presents with a 6-month history of amenorrhea, galactorrhea, and a serum prolactin of 340 ng/mL. MRI reveals a 14 mm pituitary macroadenoma. She is started on cabergoline 0.5 mg twice weekly. After 6 months of therapy, her prolactin normalizes and repeat MRI shows > 50% tumor reduction. She asks about discontinuing therapy to attempt pregnancy. Which statement best characterizes the risk of tumor growth during pregnancy if cabergoline is stopped?

Risk is eliminated because prolactin normalization on cabergoline indicates a microadenoma misclassified by MRI resolution
Risk of symptomatic tumor enlargement is < 5% because physiologic estrogen suppresses corticotroph proliferation during pregnancy
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

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 197: 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
Crigler-Najjar syndrome type I
Dubin-Johnson syndrome
Gilbert syndrome (Correct answer)

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 198: A 50-year-old man with type 2 diabetes has an HbA1c of 9.2% despite maximum metformin. He has established atherosclerotic cardiovascular disease. Which agent should be added next according to current guidelines?

Sulfonylurea
DPP-4 inhibitor
Thiazolidinedione
GLP-1 receptor agonist with proven CV benefit (Correct answer)

Correct answer: GLP-1 receptor agonist with proven CV benefit

ADA guidelines prioritize GLP-1 receptor agonists with proven cardiovascular benefit (liraglutide, semaglutide) or SGLT-2 inhibitors in patients with established ASCVD.

Question 199: A 30-year-old woman presents with a pruritic, well-demarcated, silvery-scaled plaques on the elbows, knees, and scalp. She also reports nail pitting. Which of the following systemic associations should be screened for in this patient?

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

Correct answer: Psoriatic arthritis

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

Question 200: 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?

Repeat MRI in 3 months
Liver biopsy
Alpha-fetoprotein measurement only
Proceed with treatment per LI-RADS 5 criteria (Correct answer)

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 201: 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?

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

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 202: 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 sarcoidosis
Organic dust toxic syndrome (ODTS)
Acute hypersensitivity pneumonitis (Farmer's lung) (Correct answer)

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

Hypertriglyceridemia
Gallstones (Correct answer)
Alcohol
Medications

Correct answer: Gallstones

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

Question 204: 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
Secretin stimulation test (Correct answer)
CT scan of the abdomen
Repeat endoscopy

Correct answer: Secretin stimulation test

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

Question 205: 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
Fidaxomicin 200mg BID x 10 days (Correct answer)
Oral vancomycin 125mg QID x 10 days

Correct answer: Fidaxomicin 200mg BID x 10 days

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

Question 206: A 55-year-old man with type 2 diabetes and chronic kidney disease (eGFR 28 mL/min) has a recent STEMI with residual EF of 35%. He is initiated on guideline-directed medical therapy. Which agent from the following list provides BOTH cardiovascular mortality reduction AND slowing of CKD progression in this patient population, independent of glycemic control?

Pioglitazone (thiazolidinedione)
Empagliflozin (SGLT2 inhibitor) (Correct answer)
Exenatide (GLP-1 receptor agonist)
Sitagliptin (DPP-4 inhibitor)

Correct answer: Empagliflozin (SGLT2 inhibitor)

SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) have demonstrated cardiovascular mortality reduction in patients with HFrEF (EMPEROR-Reduced, DAPA-HF) and nephroprotective effects (EMPA-KIDNEY, CREDENCE) independent of glucose lowering. They are now guideline-recommended in HFrEF with or without diabetes. Sitagliptin showed neutral CV effects (TECOS) with no renal benefit. GLP-1 agonists reduce MACE but lack robust HF and CKD benefit in this specific population. Pioglitazone causes fluid retention and worsens HF — it is contraindicated in this setting.

Question 207: A 58-year-old male is admitted to the ICU with sepsis and develops acute respiratory distress syndrome (ARDS). He is intubated and placed on mechanical ventilation. His height is 178 cm (5'10") and his ideal body weight is 75 kg. According to the ARDSNet protocol and current clinical practice guidelines, which of the following represents the most appropriate initial ventilator settings?

Tidal volume of 300 mL, PEEP of 15 cm H₂O, and respiratory rate of 35 breaths/min
Tidal volume of 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)
Tidal volume of 600 mL, PEEP of 5 cm H₂O, and permissive hypercapnia is strictly avoided

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 208: 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
Intrapleural tPA plus DNase
Chest tube drainage plus IV antibiotics (Correct answer)
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 209: Which scoring system is used to prioritize liver transplant allocation in the United States?

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

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

Bronchial artery embolization
Position patient with left side down and consult interventional radiology (Correct answer)
Emergent left pneumonectomy
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 211: According to the 2021 IDSA and SHEA focused update, which of the following is the preferred first-line agent for an initial episode of non-severe Clostridioides difficile infection?

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

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 212: 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 213: 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?

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

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 214: Which echocardiographic parameter is most useful for determining surgical timing in asymptomatic chronic severe mitral regurgitation?

Pulmonary artery systolic pressure alone
Left atrial size
Left ventricular end-systolic diameter (LVESD) (Correct answer)
Left ventricular end-diastolic diameter

Correct answer: Left ventricular end-systolic diameter (LVESD)

LVESD ≥40-45 mm in severe chronic MR is the key echocardiographic threshold that prompts surgical intervention even in asymptomatic patients.

Question 215: 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?

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

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 216: 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?

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

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 217: 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)
Ceftriaxone plus azithromycin
Levofloxacin monotherapy
Azithromycin monotherapy

Correct answer: Piperacillin-tazobactam plus vancomycin

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

Question 218: A 45-year-old woman presents with episodic hypertension, diaphoresis, and palpitations. 24-hour urine shows elevated normetanephrine but normal metanephrine. Plasma normetanephrine is 3.2× the upper limit of normal. MRI adrenals are unremarkable. What is the next most appropriate imaging study?

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

Correct answer: ¹⁸F-FDOPA PET/CT

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

Question 219: Which class of medications should be AVOIDED in patients with severe aortic stenosis presenting with systemic hypertension?

Low-dose beta-blockers
Dihydropyridine calcium channel blockers
ACE inhibitors
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 220: 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)
Secondary adrenal insufficiency
Cushing syndrome
Congenital adrenal hyperplasia (non-classic)

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 221: 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 222: 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?

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

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 223: 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?

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

Correct answer: Worsening ARDS with disease progression

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

Question 224: A 72-year-old woman sustains a hip fracture after a fall from standing height. A subsequent DEXA scan reveals a T-score of -2.8 at the femoral neck. She has no contraindications to oral medications and her renal function is normal. Which of the following is the most appropriate initial long-term pharmacologic therapy?

Teriparatide
Oral alendronate (Correct answer)
Denosumab
Raloxifene

Correct answer: Oral alendronate

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

Question 225: 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
Pasteurella multocida (Correct answer)
Capnocytophaga canimorsus
Eikenella corrodens

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 226: A 35-year-old man develops angioedema of the lip and tongue 2 weeks after starting lisinopril for hypertension. He has no urticaria and no prior allergic history. Which mechanism best explains this reaction?

Bradykinin accumulation due to ACE inhibition (Correct answer)
Complement-mediated C1 esterase inhibitor deficiency
Direct histamine release from lisinopril
IgE-mediated mast cell degranulation

Correct answer: Bradykinin accumulation due to ACE inhibition

ACE inhibitor-induced angioedema is bradykinin-mediated, not IgE or histamine-mediated. ACE normally degrades bradykinin; inhibition leads to bradykinin accumulation causing vascular leakage. This explains why it does not respond to antihistamines or steroids. Hereditary angioedema involves C1 esterase inhibitor deficiency but is not drug-induced. Direct histamine release is not the mechanism for lisinopril.

Question 227: A 29-year-old woman with Marfan syndrome is found to have an aortic root diameter of 4.8 cm. She wishes to become pregnant. What counseling is most appropriate?

Prophylactic aortic root repair is recommended before pregnancy given high dissection risk at this diameter (Correct answer)
Beta-blockers should be discontinued in favor of calcium channel blockers during pregnancy
Elective cesarean delivery eliminates the risk of aortic dissection
Pregnancy is safe if aortic root is <5.0 cm; proceed without intervention

Correct answer: Prophylactic aortic root repair is recommended before pregnancy given high dissection risk at this diameter

In Marfan syndrome, prophylactic aortic root repair is recommended before pregnancy when the aortic root is ≥4.5 cm, given the substantial risk of dissection during pregnancy and delivery.

Question 228: 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?

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

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

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

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 230: A 44-year-old woman is evaluated for recurrent hemoptysis. CT chest shows bilateral hilar lymphadenopathy and a 1.2 cm endobronchial lesion in the right lower lobe bronchus. Bronchoscopy reveals a smooth, yellowish submucosal lesion. Biopsy shows nests of uniform cells with round nuclei, rare mitoses, and positive staining for chromogranin A, synaptophysin, and TTF-1. Which of the following is most accurate regarding her diagnosis?

Typical carcinoid: 5-year survival >90%, somatostatin receptor scintigraphy preferred for staging
Atypical carcinoid: defined by 2–10 mitoses/2mm² or necrosis, higher nodal metastasis rate than typical carcinoid (Correct answer)
Large cell neuroendocrine carcinoma: TTF-1 positivity distinguishes it from atypical carcinoid
Small cell lung cancer: neuroendocrine marker positivity confirms SCLC regardless of mitotic rate

Correct answer: Atypical carcinoid: defined by 2–10 mitoses/2mm² or necrosis, higher nodal metastasis rate than typical carcinoid

The biopsy findings — rare mitoses, chromogranin/synaptophysin positivity, TTF-1 positivity — are consistent with a pulmonary carcinoid tumor. The distinction between typical and atypical carcinoid is critical: typical carcinoid has <2 mitoses/2mm² and no necrosis; atypical carcinoid has 2–10 mitoses/2mm² OR foci of necrosis. 'Rare mitoses' suggests typical carcinoid in this case, but the question tests knowledge of atypical carcinoid criteria. Answer B accurately defines atypical carcinoid (2–10 mitoses/2mm² or necrosis) and correctly notes its higher rate of lymph node metastasis compared to typical carcinoid (~30–70% vs <15%). Answer A is largely correct for typical carcinoid but Ga-68 DOTATATE PET-CT is now preferred over somatostatin receptor scintigraphy. Answer C is wrong — SCLC has >10 mitoses/2mm² and extensive necrosis. Answer D is wrong — TTF-1 does not distinguish these entities. B is the most accurate standalone statement.

Question 231: A 58-year-old man with type 2 diabetes, CKD stage G3b (eGFR 32 mL/min/1.73m²), and blood pressure 152/94 mmHg on lisinopril 40 mg/day and amlodipine 10 mg/day presents with persistent hyperkalemia (K⁺ 5.8 mEq/L). His urine albumin-to-creatinine ratio (UACR) is 820 mg/g. Which of the following represents the most evidence-based next pharmacologic intervention?

Switch lisinopril to sacubitril/valsartan
Add spironolactone 25 mg daily
Add patiromer and uptitrate lisinopril to 80 mg daily
Add finerenone 10 mg daily (Correct answer)

Correct answer: Add finerenone 10 mg daily

Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, has demonstrated cardiorenal protection in T2D with CKD in the FIDELIO-DKD and FIGARO-DKD trials, reducing the risk of kidney failure progression and cardiovascular events. Unlike spironolactone, finerenone has a lower risk of severe hyperkalemia due to its pharmacokinetic profile and was studied specifically in CKD patients with albuminuria. In patients with eGFR ≥25 and K⁺ ≤5.0 mEq/L, finerenone 10 mg (or 20 mg if eGFR ≥60) is initiated. However, the current K⁺ is 5.8 — clinically, potassium should first be managed. That said, among the answer choices, finerenone is the approved agent with the strongest evidence base for this phenotype. Spironolactone lacks large RCT data in CKD with hyperkalemia and worsens it more than finerenone.

Question 232: 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.
Initiate prophylaxis only if the ascitic fluid culture becomes positive.
No prophylaxis is needed as he has never had an episode of SBP.

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 233: A 72-year-old male with COPD and FEV1 30% predicted is evaluated for lung volume reduction surgery (LVRS). Which finding would make him an IDEAL candidate for LVRS?

FEV1 <20% predicted with homogeneous disease
Alpha-1 antitrypsin deficiency with lower-lobe predominant emphysema
Homogeneous emphysema on CT with DLCO <20%
Upper-lobe predominant emphysema with low exercise capacity (Correct answer)

Correct answer: Upper-lobe predominant emphysema with low exercise capacity

The NETT trial showed survival benefit for LVRS in patients with upper-lobe predominant emphysema and low exercise capacity; homogeneous disease with FEV1/DLCO <20% showed excess mortality.

Question 234: A 45-year-old woman with type 2 diabetes on an SGLT-2 inhibitor presents with nausea, vomiting, and fatigue. Labs: glucose 195 mg/dL, pH 7.21, bicarbonate 13 mEq/L, anion gap 22 mEq/L, beta-hydroxybutyrate 4.8 mmol/L. Urine dipstick shows 3+ ketones. Which statement best explains her presentation?

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

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

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

Question 235: 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
CT chest/abdomen
Upper endoscopy (Correct answer)
Barium swallow

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 236: A 55-year-old man with STEMI is treated with primary PCI. Two days later he develops new hypotension, elevated JVP, and a new holosystolic murmur at the left lower sternal border. What is the most likely diagnosis?

Ventricular septal defect (VSD) (Correct answer)
Acute mitral regurgitation due to papillary muscle rupture
Free wall rupture with tamponade
Dressler syndrome

Correct answer: Ventricular septal defect (VSD)

Post-MI VSD typically occurs 2–5 days after infarction, presenting with a new harsh holosystolic murmur, right heart failure signs, and hemodynamic compromise.

Question 237: 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?

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

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 238: 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?

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

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 239: 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)
Bile duct proliferation
Portal fibrosis only
Macrovesicular fat deposits

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

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

Correct answer: Internal hernia with small bowel obstruction

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

Question 241: 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 highly specific for follicular thyroid carcinoma and supports proceeding directly to total thyroidectomy (Correct answer)
It predicts radioiodine resistance but does not differentiate benign from malignant follicular lesions
It is diagnostic of papillary thyroid carcinoma and mandates central neck dissection
It confirms benign adenoma and lobectomy can be avoided entirely

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 242: 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)
Klinefelter syndrome
Idiopathic hypogonadotropic hypogonadism

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 243: A 61-year-old woman with a 6-cm right adrenal mass found incidentally on CT for renal colic. She has well-controlled hypertension on amlodipine. Biochemical workup: 1-mg overnight DST cortisol 4.2 µg/dL, plasma metanephrines normal, aldosterone/renin ratio normal, DHEA-S low-normal. Her ACTH is 8 pg/mL (low-normal). Repeat DST with 8 mg dexamethasone shows cortisol 3.8 µg/dL. What is the most appropriate next management step?

Perform adrenal vein sampling to confirm lateralization before recommending adrenalectomy
Adrenalectomy is indicated because the 6-cm size and autonomous cortisol secretion together meet criteria for surgical resection (Correct answer)
Initiate metyrapone therapy to reduce cortisol and reassess blood pressure control before deciding on surgery
Repeat imaging in 6 months; the biochemical profile does not meet criteria for autonomous cortisol secretion

Correct answer: Adrenalectomy is indicated because the 6-cm size and autonomous cortisol secretion together meet criteria for surgical resection

This lesion meets two independent indications for adrenalectomy: (1) size ≥ 4 cm, which raises concern for adrenocortical carcinoma (ACC risk increases substantially above 4 cm, and ACC is the primary size-based surgical indication for adrenal incidentalomas); and (2) autonomous cortisol secretion (ACS), confirmed by post-1-mg DST cortisol > 1.8 µg/dL — here 4.2 µg/dL with a suppressed ACTH of 8 pg/mL. The high-dose 8-mg DST is used for Cushing's disease (pituitary origin), not adrenal lesions; failure to suppress on high-dose DST in an adrenal source is expected and does not add diagnostic value. Medical therapy is not a definitive treatment for ACS with a resectable lesion, and adrenal vein sampling is used for primary aldosteronism lateralization, not cortisol-producing adenomas.

Question 244: 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?

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
Elevated EBV DNA in peripheral blood by PCR with markedly elevated sNK cell activity

Correct answer: Homozygous PRF1 (perforin) mutation on genetic testing

While EBV is a common trigger of secondary HLH, the discovery of a homozygous PRF1 (perforin-1) mutation definitively identifies primary/familial HLH (FHL2), which typically presents in early adulthood triggered by viral infections (especially EBV). This distinction is critical: primary HLH requires hematopoietic stem cell transplantation as definitive therapy, while secondary HLH may remit with immunosuppression and treatment of the trigger. Elevated EBV PCR (choice A) confirms viral trigger but doesn't distinguish primary from secondary. Ferritin >50,000 (choice B) increases HLH specificity but doesn't differentiate primary vs. secondary. CD8+ infiltration (choice D) is a histologic feature seen in both.

Question 245: A patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). After treatment, which prophylactic antibiotic is recommended to prevent recurrence?

Cephalexin
Norfloxacin (Correct answer)
Metronidazole
Amoxicillin-clavulanate

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 246: A 45-year-old woman is evaluated for amenorrhea and galactorrhea. MRI shows a 6 mm pituitary microadenoma. Prolactin level is 210 ng/mL. She is started on cabergoline. After 12 months, her prolactin normalizes and repeat MRI shows tumor resolution. She desires to discontinue cabergoline. Which of the following factors is most strongly associated with sustained remission after dopamine agonist withdrawal?

Normalization of prolactin for at least 2 years and radiological tumor disappearance (Correct answer)
Female sex and microadenoma size < 5 mm
Absence of cabergoline side effects during treatment
Prolactin nadir below 5 ng/mL during therapy

Correct answer: Normalization of prolactin for at least 2 years and radiological tumor disappearance

The Endocrine Society guidelines recommend that dopamine agonist withdrawal may be attempted after at least 2 years of therapy if prolactin has normalized and the tumor is no longer visible on MRI. Studies show that radiological disappearance of the adenoma and sustained normoprolactinemia for ≥2 years are the strongest predictors of durable remission after withdrawal. Approximately 21–31% of patients achieve lasting remission after cabergoline discontinuation under these criteria. The prolactin nadir during therapy and patient sex are not validated predictors of remission. The absence of side effects is clinically useful but not predictive of remission.

Question 247: 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?

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

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 248: 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
Patient-ventilator dyssynchrony from flow starvation causing breath stacking and dynamic hyperinflation
Auto-PEEP from intrinsic PEEP causing ineffective triggering and increased work of breathing (Correct answer)
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 249: A 35-year-old woman with mitral valve prolapse presents with palpitations. Echo shows classic MVP with bileaflet prolapse and mild MR. Her resting ECG shows no pre-excitation. What is the most appropriate management?

Mitral valve repair
Implantable cardioverter-defibrillator
Reassurance and follow-up with periodic echocardiography (Correct answer)
Prophylactic antiarrhythmic therapy

Correct answer: Reassurance and follow-up with periodic echocardiography

Most patients with MVP and palpitations without high-risk features (severe MR, LV dysfunction, complex ventricular ectopy, T-wave changes in inferolateral leads) require only reassurance and surveillance.

Question 250: 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)
Transarterial chemoembolization (TACE)
Liver transplantation within Milan criteria (Correct answer)

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 251: 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?

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

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 252: A 32-year-old woman presents with galactorrhea, amenorrhea, and a prolactin level of 210 ng/mL. MRI shows a 12 mm pituitary lesion. First-line treatment is:

Bromocriptine or cabergoline (Correct answer)
Transsphenoidal surgery
External beam radiation
Observation with repeat MRI in 6 months

Correct answer: Bromocriptine or cabergoline

Dopamine agonists (cabergoline preferred) are first-line treatment for prolactinomas regardless of size.

Question 253: A 58-year-old male with acute myeloid leukemia is undergoing induction chemotherapy. He develops a fever of 39.2°C (102.6°F) and his absolute neutrophil count is 150 cells/mm³. He is hemodynamically stable with no clear source of infection on initial examination. According to IDSA guidelines, which of the following is the most appropriate initial empiric antibiotic regimen?

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

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 254: 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?

Yellow nail syndrome
Lymphoma-associated exudative effusion
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 255: A 50-year-old immunocompromised patient presents with fever, pleuritic chest pain, and a pulmonary nodule with halo sign on CT. Galactomannan antigen returns elevated. What is the most appropriate initial antifungal?

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

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 256: 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 257: A 38-year-old woman is evaluated for osteoporosis with a T-score of -2.9 at the lumbar spine. She has no fractures. Labs reveal calcium 10.9 mg/dL, phosphorus 2.0 mg/dL, PTH 88 pg/mL (normal 15–65), and 24-hour urine calcium of 95 mg/24h (low). Vitamin D is normal. Genetic testing shows a heterozygous inactivating mutation in CaSR (calcium-sensing receptor). Which management is most appropriate?

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

Correct answer: Parathyroidectomy is contraindicated; treat osteoporosis with bisphosphonates

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

Question 258: A 61-year-old woman with resistant hypertension (BP 158/96 mmHg on ACEI, amlodipine, and chlorthalidone) has plasma aldosterone-to-renin ratio of 35 (ng/dL)/(ng/mL/h). CT adrenals are normal. What is the next step?

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

Correct answer: Adrenal vein sampling

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

Question 259: A 30-year-old man presents with polyuria, polydipsia, and a serum sodium of 148 mEq/L. Urine osmolality is 110 mOsm/kg after water deprivation, rising to 680 mOsm/kg after desmopressin (DDAVP). What is the diagnosis?

Syndrome of inappropriate ADH
Nephrogenic diabetes insipidus
Central (neurogenic) diabetes insipidus (Correct answer)
Primary polydipsia

Correct answer: Central (neurogenic) diabetes insipidus

A markedly concentrated urine response to exogenous DDAVP after failure to concentrate with water deprivation indicates central diabetes insipidus, where ADH is deficient but the kidney can respond normally.

Question 260: A 68-year-old man on hemodialysis develops bacteremia with MSSA. TEE shows no vegetation. What is the recommended duration of antibiotic therapy for uncomplicated MSSA bacteremia?

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

Correct answer: 14 days

Uncomplicated S. aureus bacteremia (no endocarditis, no metastatic focus, clinical improvement by 72h) requires 14 days of IV anti-staphylococcal therapy.

Question 261: 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?

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

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 262: 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?

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

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 263: 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-Saccharomyces cerevisiae antibodies (ASCA)
HLA-DQ2 and HLA-DQ8 genetic testing
Anti-gliadin IgG antibody
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 264: A 54-year-old man with BMI 47 kg/m² is evaluated for hypersomnia and morning headaches. ABG on room air: pH 7.37, PaCO2 54 mmHg, PaO2 57 mmHg, HCO3 30 mEq/L. Polysomnography shows AHI of 41/hr with prolonged hypopneas and oxygen nadir of 69%. Serum TSH and spirometry are normal. Which treatment strategy has the strongest evidence for reducing mortality compared to CPAP alone in this patient's condition?

Bilevel positive airway pressure with a spontaneous-timed backup rate (BPAP-ST) (Correct answer)
Supplemental nocturnal oxygen at 2–3 L/min via nasal cannula
High-flow nasal cannula therapy at 30 L/min with FiO2 0.40
Adaptive servo-ventilation (ASV) targeting residual respiratory events

Correct answer: Bilevel positive airway pressure with a spontaneous-timed backup rate (BPAP-ST)

This patient has obesity hypoventilation syndrome (OHS) — defined by BMI ≥30 kg/m², awake hypercapnia (PaCO2 ≥45 mmHg), and exclusion of other causes. OHS involves both upper-airway obstruction and impaired central ventilatory drive, so CPAP alone often fails to correct hypoventilation. BPAP-ST provides dual-pressure support plus a mandatory backup rate to treat hypoventilation directly, and trials (including the PICKWICK study) demonstrate superior PaCO2 correction and survival benefit over oxygen or CPAP. ASV is contraindicated in heart failure with EF ≤45% (SERVE-HF trial) and is not indicated for OHS-related hypoventilation. Supplemental oxygen alone can worsen hypercapnia by removing the hypoxic drive.

Question 265: 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?

Start dobutamine for cardiogenic shock
Administer an additional 2 L of IV fluid bolus (Correct answer)
Add vasopressin 0.03 units/min to norepinephrine
Begin hydrocortisone 200 mg/day for refractory septic 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 266: A 58-year-old woman with rheumatoid arthritis on methotrexate and prednisone presents with fever, productive cough, and bilateral infiltrates. LDH is elevated. BAL shows Pneumocystis jirovecii. The drug of choice is:

Atovaquone
Dapsone
Clindamycin plus primaquine
Trimethoprim-sulfamethoxazole (TMP-SMX) (Correct answer)

Correct answer: Trimethoprim-sulfamethoxazole (TMP-SMX)

TMP-SMX is the treatment of choice for PCP pneumonia; adjunctive steroids are added when PaO₂ <70 mmHg or A-a gradient >35 mmHg.

Question 267: 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?

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

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

Isoniazid and rifapentine once weekly for 3 months (Correct answer)
Levofloxacin daily for 6 months
Isoniazid daily for 9 months
Ethambutol daily for 12 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 269: 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 antibiotics targeting Staphylococcus aureus (Correct answer)
Increase prednisone dose and reassess in 48 hours
Add empiric vancomycin and piperacillin-tazobactam and repeat BAL
Chest tube drainage and add empiric antifungal therapy

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

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

Question 270: A 67-year-old male with right lower lobe lung adenocarcinoma is found to have an EGFR exon 19 deletion. What is the preferred first-line systemic therapy?

Carboplatin + paclitaxel
Pembrolizumab
Osimertinib (Correct answer)
Crizotinib

Correct answer: Osimertinib

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the preferred first-line treatment for EGFR-mutant metastatic NSCLC based on the FLAURA trial.

Question 271: A 32-year-old healthy woman has incidental platelet count of 26,000/μL on routine CBC. She has no bleeding symptoms, is on no medications, and has normal-appearing platelets on peripheral smear. What is the most likely diagnosis?

Thrombotic thrombocytopenic purpura (TTP)
Heparin-induced thrombocytopenia (HIT)
Immune thrombocytopenic purpura (ITP) (Correct answer)
Disseminated intravascular coagulation (DIC)

Correct answer: Immune thrombocytopenic purpura (ITP)

Isolated thrombocytopenia with normal platelet morphology and no medications or systemic illness in a healthy young person is most consistent with ITP.

Question 272: An insulinoma is suspected in a patient with fasting hypoglycemia. Which laboratory finding pattern is diagnostic?

High insulin, high C-peptide, high proinsulin, negative sulfonylurea screen (Correct answer)
High insulin, high C-peptide, positive sulfonylurea screen
Low insulin, low C-peptide, low proinsulin
High insulin, low C-peptide, negative sulfonylurea screen

Correct answer: High insulin, high C-peptide, high proinsulin, negative sulfonylurea screen

Insulinoma produces endogenous insulin with elevated C-peptide and proinsulin; exogenous insulin use causes low C-peptide, and sulfonylurea abuse is excluded by drug screen.

Question 273: 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
Salivary cortisol testing
Adrenalectomy
Repeat imaging in 6–12 months and reassay hormones annually (Correct answer)

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 274: 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?

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

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 275: 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?

Doxycycline 100mg BID x 7 days
Ciprofloxacin 500mg BID x 3 days
Nitrofurantoin 100mg BID x 5 days (Correct answer)
Trimethoprim-sulfamethoxazole DS 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 276: A 52-year-old man undergoes selective inferior petrosal sinus sampling (IPSS) for suspected Cushing's disease. Basal central-to-peripheral ACTH ratio is 1.8. After CRH stimulation, the ratio rises to 2.4 on the right side and 1.6 on the left. MRI of the pituitary is unremarkable. What is the most appropriate next step in management?

Diagnose ectopic ACTH syndrome and proceed with CT chest/abdomen/pelvis
Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary (Correct answer)
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

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 277: 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?

Perform endoscopic ultrasound-guided fine needle aspiration of the stricture
Start ursodeoxycholic acid at 28–30 mg/kg/day and repeat MRCP in 3 months
Repeat brush cytology with fluorescence in situ hybridization (FISH) (Correct answer)
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 278: 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
Ampicillin plus ceftriaxone for 6 weeks (Correct answer)
Vancomycin plus gentamicin for 6 weeks
Linezolid monotherapy for 8 weeks given prosthetic valve involvement

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

Rifampin 600mg daily for 4 months
Isoniazid plus rifapentine weekly for 12 weeks (3HP) (Correct answer)
Isoniazid 300mg daily for 6 months
Isoniazid 300mg daily for 9 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 280: A 67-year-old man with stage 3b CKD (GFR 34), type 2 diabetes, and hypertension presents with resistant hypertension despite maximum-dose lisinopril, amlodipine, and chlorthalidone. His aldosterone-to-renin ratio (ARR) is 42 ng/dL per ng/mL/hr (>30 is positive screen). Adrenal CT shows bilateral adrenal hyperplasia. His serum potassium is 3.2 mEq/L. Which intervention is most appropriate before planning adrenal vein sampling (AVS)?

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

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

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

Question 281: 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)
Non-islet cell tumor hypoglycemia
Exogenous insulin administration
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 282: 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?

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

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

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

Correct answer: Add disopyramide to his current regimen

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

Question 284: 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?

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

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

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 286: 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?

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

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 287: 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?

Aztreonam plus vancomycin plus dexamethasone
Trimethoprim-sulfamethoxazole plus vancomycin plus dexamethasone
Meropenem plus vancomycin plus dexamethasone (Correct answer)
Chloramphenicol plus rifampin 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 288: 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
CSF culture for HSV
CSF HSV PCR (Correct answer)
Serum HSV IgM antibodies

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 289: 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?

Ciprofloxacin 500mg BID
Azithromycin 500mg daily
Chloramphenicol 500mg QID
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 290: 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?

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

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 291: A 78-year-old woman with osteoporosis takes alendronate. After 5 years of therapy, a DXA scan shows T-score of -2.4. She denies new fractures. What is the most appropriate next step?

Switch to teriparatide
Drug holiday (discontinue bisphosphonate for 1-2 years) (Correct answer)
Continue alendronate indefinitely
Add denosumab to alendronate

Correct answer: Drug holiday (discontinue bisphosphonate for 1-2 years)

A drug holiday after 5 years of bisphosphonate therapy is recommended for low-risk patients as the drug remains in bone and continues to work.

Question 292: 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 293: A 32-year-old woman has recurrent episodes of angioedema without urticaria, triggered by stress and minor trauma, with no identifiable allergen. Her C4 level is consistently low. C1 esterase inhibitor (C1-INH) level and function are markedly reduced. Family history reveals her father had similar episodes. What is the most likely diagnosis?

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

Correct answer: Hereditary angioedema (HAE) type I

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

Question 294: A 62-year-old woman with heart failure with reduced ejection fraction (HFrEF, EF 30%) is on optimal medical therapy. QRS duration is 155ms with LBBB morphology. Which intervention improves mortality?

Cardiac resynchronization therapy with defibrillator (CRT-D) (Correct answer)
Implantable cardioverter-defibrillator alone
Surgical ventricular reconstruction
Cardiac contractility modulation device

Correct answer: Cardiac resynchronization therapy with defibrillator (CRT-D)

CRT-D is indicated in HFrEF patients with LBBB and QRS ≥150ms on GDMT, reducing mortality and hospitalization by resynchronizing ventricular contraction.

Question 295: 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
Colonoscopy (Correct answer)
CT colonography
Flexible sigmoidoscopy

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 296: 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?

Rifampin
Bezafibrate
Obeticholic acid (Correct answer)
Cholestyramine

Correct answer: Obeticholic acid

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

Question 297: A 70-year-old man undergoes hip arthroplasty and develops fever and wound drainage at day 14. Joint aspiration grows MRSA. What is the antibiotic of choice for MRSA prosthetic joint infection?

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

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

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

Question 298: 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:

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

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

Hashimoto's thyroiditis
Toxic multinodular goiter
Graves' disease (Correct answer)
Subacute 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 300: 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 glipizide; initiate a GLP-1 receptor agonist with demonstrated nephroprotective outcomes data
Continue current regimen; add empagliflozin 10 mg daily given its EMPA-REG outcomes benefit
Discontinue metformin and linagliptin; initiate an SGLT2 inhibitor titrated to the lowest approved dose for kidney protection (Correct answer)
Discontinue metformin; add finerenone to the existing regimen

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

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

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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