ITE Internal Medicine In-Training Exam — Questions and Answers

Question 1: 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)
Avoiding all sedation and analgesia to promote rapid extubation
Maintaining deep sedation (RASS -4 to -5) to ensure patient comfort and prevent ventilator recall
Administering continuous high-dose benzodiazepines without a daily awakening trial

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

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

Question 2: A 45-year-old woman with butterfly-shaped facial erythema sparing the nasolabial folds, discoid lesions on the scalp, and photosensitivity is found to have oral ulcers and positive ANA. Which of the following skin findings would be MOST characteristic of her underlying diagnosis?

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

Correct answer: Malar rash sparing the nasolabial folds

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

Question 3: A 40-year-old man presents for a routine health evaluation. He is asymptomatic but reports that his father was diagnosed with colon cancer at age 48. He has no other personal or family history of cancer. According to current U.S. Preventive Services Task Force (USPSTF) and ACG guidelines, what is the most appropriate recommendation for colorectal cancer screening for this patient?

Begin screening now with a stool-based test (FIT).
Begin screening with colonoscopy at age 50.
No screening is necessary until he develops symptoms.
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 4: A 30-year-old woman with recurrent UTIs asks about post-coital prophylaxis. She has 3 UTIs per year, all temporally related to sexual intercourse. Which regimen is appropriate?

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

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

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

Question 5: 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)
Tumor size alone (>2 cm)
Tumor location in the small bowel rather than stomach
CD117 positivity

Correct answer: Combination of tumor size and mitotic rate

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

Question 6: 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?

Restrictive pattern due to asbestosis (Correct answer)
Normal spirometry with isolated DLCO reduction from pulmonary vascular disease
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 7: 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
Legionella pneumophila; azithromycin or fluoroquinolone (Correct answer)
Staphylococcus aureus; vancomycin
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 8: A 30-year-old woman presents with dysuria and urinary frequency. Urine culture grows >100,000 CFU/mL of E. coli sensitive to all agents. She is 10 weeks pregnant. What is the appropriate antibiotic?

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

Correct answer: Nitrofurantoin 100mg BID x 5 days

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

Question 9: 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 10: A 35-year-old woman presents with a 3-month history of symmetric, painful swelling of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, morning stiffness lasting 2 hours, and fatigue. Labs show RF positive, anti-CCP positive, ESR 68. Which of the following is the most appropriate initial disease-modifying therapy?

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

Correct answer: Methotrexate

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

Question 11: 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?

24-hour sedation holiday before attempting extubation
Repeat ABG to confirm PaO2 >80 mmHg
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 12: 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?

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

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 13: 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?

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

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 14: 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
Mucor/Rhizopus species (Correct answer)
Fusarium solani
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 15: A 44-year-old man is found to have a 2.5 cm hepatic lesion on ultrasound done for elevated liver enzymes. He has no cirrhosis and no known liver disease. MRI shows a well-demarcated lesion with arterial phase hyperenhancement, peripheral nodular enhancement, and progressive centripetal fill-in on delayed phases. The most likely diagnosis and appropriate next step are:

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

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 16: 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?

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

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

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

Question 17: A 55-year-old man with newly diagnosed type 2 diabetes has an HbA1c of 7.8%, BMI 36 kg/m², no cardiovascular disease, and normal renal function. What is the most appropriate pharmacotherapy beyond lifestyle modification?

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

Correct answer: Metformin + GLP-1 receptor agonist

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

Question 18: A 60-year-old man with known CAD is prescribed ranolazine for refractory angina. Which mechanism of action explains its antianginal effect?

Inhibition of L-type calcium channels reducing heart rate
Nitric oxide-mediated coronary vasodilation
Beta-1 receptor blockade reducing inotropy
Inhibition of late sodium current reducing myocardial oxygen demand (Correct answer)

Correct answer: Inhibition of late sodium current reducing myocardial oxygen demand

Ranolazine inhibits the late inward sodium current (I_Na late), which reduces intracellular calcium overload and myocardial oxygen demand without significantly affecting heart rate or blood pressure.

Question 19: A 38-year-old woman with Graves' disease has been on methimazole 10 mg daily for 18 months. Her free T4 and TSH are now normal. She is eager to pursue definitive therapy. She is 10 weeks pregnant. Her TRAb titer is 4.2 IU/L (reference < 1.75). Which statement best guides clinical decision-making regarding fetal and neonatal thyroid risk?

Methimazole should be switched to propylthiouracil for the remainder of the pregnancy to eliminate teratogenic risk
Elevated maternal TRAb at > 3× upper limit of normal in the third trimester predicts fetal/neonatal hyperthyroidism and warrants fetal surveillance with Doppler thyroid vascularity and fetal heart rate monitoring (Correct answer)
TRAb does not cross the placenta in the first trimester, so current titer has no fetal implications until after 20 weeks
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 20: A 35-year-old woman on oral contraceptives develops sudden-onset pleuritic chest pain and dyspnea. CT angiography confirms pulmonary embolism. Which anticoagulant is preferred for long-term treatment?

Dabigatran following 5-10 days of parenteral anticoagulation
Rivaroxaban or apixaban (DOAC) (Correct answer)
Aspirin 325mg daily
Warfarin with INR target 2-3

Correct answer: Rivaroxaban or apixaban (DOAC)

DOACs (rivaroxaban or apixaban) are first-line for PE treatment in non-pregnant patients without antiphospholipid syndrome, offering convenience with non-inferior efficacy.

Question 21: 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
Ethambutol daily for 12 months
Isoniazid daily for 9 months

Correct answer: Isoniazid and rifapentine once weekly for 3 months

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

Question 22: A 55-year-old woman with obesity and type 2 diabetes has AST 78 and ALT 92. Ultrasound shows echogenic liver. Which histologic finding distinguishes NASH from simple steatosis?

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

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

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

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

Question 24: 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?

7 days
42 days
28 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 25: 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
Bismuth quadruple therapy (Correct answer)
Repeat the same triple therapy regimen
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 26: 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?

Add high-flow nasal cannula at 40 L/min in combination with BiPAP
Initiate invasive mechanical ventilation with volume-control mode (Correct answer)
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 27: A 28-year-old woman with Graves' disease is in her first trimester of pregnancy. Which antithyroid drug is preferred during this period?

Radioactive iodine
Potassium iodide
Methimazole
Propylthiouracil (PTU) (Correct answer)

Correct answer: Propylthiouracil (PTU)

PTU is preferred in the first trimester because methimazole is associated with embryopathy (aplasia cutis, choanal atresia) during organogenesis.

Question 28: A 61-year-old man with a history of neck irradiation for Hodgkin lymphoma 25 years ago is found to have a 2.2 cm thyroid nodule on incidental imaging. Fine-needle aspiration returns Bethesda Category III (atypia of undetermined significance). Repeat FNA after 3 months again returns Bethesda III. Molecular testing shows a TERT promoter mutation without RAS or BRAF mutations. What is the most appropriate next step?

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

Correct answer: Surgical resection

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

Question 29: 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)
Bile acid synthesis inhibition
Inhibition of TNF-alpha synthesis
Immunosuppression of autoreactive T cells

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 30: 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?

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

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 31: A 38-year-old woman with recurrent kidney stones has 24-hour urine showing calcium oxalate supersaturation, hypercalciuria (320 mg/day), normal serum calcium, low urine citrate, and normal urine uric acid. What is the first-line treatment?

Potassium citrate alone
Hydrochlorothiazide plus potassium citrate (Correct answer)
Allopurinol
Dietary calcium restriction

Correct answer: Hydrochlorothiazide plus potassium citrate

Idiopathic hypercalciuria with calcium oxalate nephrolithiasis is treated with thiazides to reduce urinary calcium plus potassium citrate to increase urinary citrate and correct hypokalemia.

Question 32: A 28-year-old man with severe hemophilia A (factor VIII activity <1%) presents with rapidly expanding knee hemarthrosis after a fall. What is the first-line treatment?

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

Correct answer: Factor VIII concentrate replacement therapy

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

Question 33: A patient recovering from DKA develops worsening headache, confusion, and pupillary changes 6 hours into treatment. What is the most likely diagnosis?

Hypoglycemia from insulin overdose
Cerebral edema (Correct answer)
Septic encephalopathy
Hypokalemia-induced arrhythmia

Correct answer: Cerebral edema

Cerebral edema is a life-threatening complication of DKA treatment, most common in children, caused by rapid fluid shifts and osmotic changes during correction.

Question 34: A 29-year-old woman presents with recurrent episodes of severe epigastric pain, nausea, and elevated lipase (peak 1,800 U/L) over the past 2 years. She has no gallstones, drinks no alcohol, takes no medications, and has normal triglycerides. Genetic testing reveals a heterozygous SPINK1 N34S variant and a heterozygous CFTR F508del variant. MRCP is normal. What is the pathophysiologic basis for her recurrent pancreatitis?

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

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 35: A 70-year-old woman presents with proximal muscle weakness, difficulty rising from a chair, bilateral shoulder and hip girdle aching, an ESR of 95 mm/hr, and a CRP of 4.2 mg/dL. She has no muscle enzyme elevation and normal EMG. What is the most likely diagnosis?

Polymyalgia rheumatica (PMR) (Correct answer)
Fibromyalgia
Hypothyroid myopathy
Polymyositis

Correct answer: Polymyalgia rheumatica (PMR)

PMR presents in patients >50 with bilateral proximal girdle stiffness/aching, markedly elevated inflammatory markers, but normal CK and EMG — distinguishing it from inflammatory myopathy. Polymyositis has elevated CK and abnormal EMG. Fibromyalgia does not cause elevated ESR. Hypothyroid myopathy may elevate CK and TSH would be abnormal.

Question 36: A 58-year-old man with chronic hypersensitivity pneumonitis is evaluated for lung transplant candidacy. His PFTs show FVC 48% predicted, DLCO 32% predicted. He is started on antifibrotic therapy. Six months later, his FVC has declined by 12% absolute. Which finding on high-resolution CT would MOST strongly suggest accelerated progression requiring urgent transplant re-evaluation?

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

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

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

Question 37: A 61-year-old man with alcohol-related cirrhosis (Child-Pugh B) and a history of variceal bleeding is on nadolol. He develops refractory ascites requiring large-volume paracentesis every 2 weeks despite maximal diuretic therapy. Creatinine is 1.0 mg/dL, sodium is 128 mEq/L. He is listed for liver transplant. What is the most appropriate next intervention?

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

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 38: 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 39: 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 NKCC2 in the thick ascending limb of Henle
Inactivating mutation in NCC in the distal convoluted tubule (Correct answer)
Inactivating mutation in ROMK causing neonatal salt wasting then hypokalemia

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 40: 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 41: 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)
Lymphoma with pulmonary involvement
Berylliosis
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 42: What is the most common precipitating factor for DKA in patients with established type 1 diabetes?

Insulin omission (Correct answer)
New onset diabetes
Infection or illness
Myocardial infarction

Correct answer: Insulin omission

Insulin omission (non-adherence) is the most common precipitating cause of DKA in patients with known type 1 diabetes.

Question 43: A 52-year-old woman is admitted to the ICU with septic shock from urosepsis. On day 3, she is improving, with vasopressors being weaned. Labs show Na 131 mEq/L (was 139 mEq/L on admission). She is euvolemic on exam. Urine sodium is 48 mEq/L, urine osmolality 520 mOsm/kg, serum osmolality 272 mOsm/kg. She received 3 L of D5W over 24 hours and is on empiric vancomycin and piperacillin-tazobactam. Which mechanism MOST contributes to her hyponatremia?

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

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

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

Question 44: 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:

Transsphenoidal surgery
External beam radiation
Bromocriptine or cabergoline (Correct answer)
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 45: 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?

Veno-venous ECMO as a bridge to lung transplantation (Correct answer)
Cyclosporine A added to corticosteroids
High-dose methylprednisolone 1g IV daily for 3 days
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 46: A patient with a bioprosthetic aortic valve develops structural valve deterioration (SVD) 12 years postoperatively and is now symptomatic. She is a moderate surgical risk (STS 4%). What is the preferred intervention?

Balloon valvuloplasty of the bioprosthesis
Medical management
Valve-in-valve TAVR (Correct answer)
Redo surgical AVR

Correct answer: Valve-in-valve TAVR

Valve-in-valve TAVR within a failed bioprosthesis is preferred over redo surgery for patients with moderate-to-high surgical risk and appropriate bioprosthesis anatomy.

Question 47: A 71-year-old man with stage G4 CKD (eGFR 18 mL/min/1.73m²) presents for pre-dialysis planning. He is found to have a serum bicarbonate of 16 mEq/L. Serum potassium is 5.1 mEq/L. A urine anion gap (UAG) is calculated to be +12 mEq/L. Which of the following statements about his acid-base status and management is MOST accurate?

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

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

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

Question 48: A 52-year-old man undergoes selective inferior petrosal sinus sampling (IPSS) for suspected Cushing's disease. Basal central-to-peripheral ACTH ratio is 1.8. After CRH stimulation, the ratio rises to 2.4 on the right side and 1.6 on the left. MRI of the pituitary is unremarkable. What is the most appropriate next step in management?

Diagnose ectopic ACTH syndrome and proceed with CT chest/abdomen/pelvis
Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary (Correct answer)
Repeat IPSS with simultaneous bilateral sampling under strict catheter position verification
Order repeat 24-hour urine free cortisol and late-night salivary cortisol to confirm hypercortisolism

Correct answer: Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary

An IPSS central-to-peripheral ACTH ratio ≥ 2 basal or ≥ 3 post-CRH confirms pituitary-source Cushing's disease with ~95% sensitivity and specificity. Here the post-CRH ratio is 2.4 on the right (≥ 2 is sufficient for lateralization when ≥ 3 threshold is not reached, though many centers use ≥ 1.4 lateralization ratio). Since pituitary source is confirmed (post-CRH ratio 2.4 > 2.0) and lateralization favors the right, right-sided hemipituitary exploration is appropriate even with a negative MRI — approximately 40–60% of corticotroph adenomas are MRI-occult. Ectopic ACTH is excluded by the central-to-peripheral gradient. Repeating biochemical confirmation is unnecessary after IPSS confirmation. Repeating IPSS is not indicated when the procedure was technically successful.

Question 49: A patient with DKA has a corrected sodium of 148 mEq/L. How is corrected sodium calculated in hyperglycemia?

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

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

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

Question 50: Which of the following is the first-line treatment for primary hypertension?

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

Correct answer: ACE inhibitors

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

Question 51: 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?

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

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

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

Question 52: 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?

HLA-DQ2 and HLA-DQ8 genetic testing
Anti-Saccharomyces cerevisiae antibodies (ASCA)
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 53: A 72-year-old man with a 3-year history of multiple myeloma (IgG kappa, on lenalidomide maintenance) develops slowly progressive renal failure over 6 months, now at GFR 19 mL/min/1.73m². Urinalysis shows no hematuria, no casts, and trace proteinuria on dipstick. 24-hour urine protein is 4.2 g, but urine protein electrophoresis reveals the protein is 92% Bence-Jones protein (free kappa light chains) with minimal albumin. Renal biopsy shows Congo red–negative amorphous eosinophilic material filling tubular lumens with giant cell reaction. Which condition is most likely?

Light chain deposition disease (LCDD)
Light chain cast nephropathy (myeloma kidney) (Correct answer)
AL amyloidosis with renal involvement
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID)

Correct answer: Light chain cast nephropathy (myeloma kidney)

Light chain cast nephropathy (myeloma kidney) is characterized by intratubular precipitation of monoclonal free light chains with uromodulin (Tamm-Horsfall protein), forming obstructing casts with a surrounding giant cell inflammatory reaction. On biopsy, casts appear amorphous and eosinophilic, and are Congo red–negative (distinguishing from amyloid). The trace dipstick proteinuria with large 24-hour protein confirms the protein is primarily light chains (not detected by albumin-based dipstick). AL amyloidosis is Congo red–positive and typically shows glomerular involvement with nephrotic-range albumin. LCDD shows linear light chain deposits along tubular and glomerular basement membranes (PAS-positive nodular glomerulosclerosis), not intraluminal casts. PGNMID presents with glomerulonephritis and would show intraglomerular deposits on immunofluorescence.

Question 54: 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?

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

Correct answer: Piperacillin-tazobactam

In high-risk febrile neutropenia, empiric monotherapy with an anti-pseudomonal beta-lactam is the standard of care. Piperacillin-tazobactam, cefepime, meropenem, or imipenem-cilastatin are all appropriate first-line choices. Ceftriaxone lacks reliable Pseudomonas aeruginosa coverage. Vancomycin is not recommended for routine initial empiric therapy unless specific indications are present, such as suspected catheter-related infection, pneumonia, hemodynamic instability, or known MRSA colonization. Metronidazole would only be added if an anaerobic source, like an intra-abdominal infection, is suspected.

Question 55: A 28-year-old man presents with genital ulcers and painful inguinal lymphadenopathy (buboes). He recently returned from a trip to Africa. The ulcers are soft and painful. What is the most likely diagnosis and treatment?

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

Correct answer: Chancroid; azithromycin 1g single dose

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

Question 56: A 22-year-old African American man with known sickle cell disease presents with severe bilateral leg bone pain, fever of 38.4°C, and WBC 12,500/μL. His Hgb is 6.9 g/dL compared to a baseline of 7.1 g/dL. What is the most likely diagnosis?

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

Correct answer: Vaso-occlusive (pain) crisis

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

Question 57: Which of the following patients with severe aortic stenosis requires concurrent coronary artery bypass grafting (CABG) at the time of surgical AVR?

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

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

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

Question 58: 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 59: 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?

12 hours per day
15 hours per day (Correct answer)
8 hours per day
24 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 60: A 55-year-old woman with recently diagnosed hypersensitivity pneumonitis (HP) is found to have a pet cockatiel at home. After antigen avoidance, symptoms persist and DLCO is 52% predicted. Which finding on surgical lung biopsy would indicate chronic fibrotic HP rather than subacute HP?

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

Correct answer: Peribronchiolar fibrosis with architectural distortion and honeycombing

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

Question 61: 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
Lansoprazole (Correct answer)
Sertraline
Olmesartan

Correct answer: Lansoprazole

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

Question 62: A 48-year-old male with scleroderma presents with hemoptysis and renal failure. Urinalysis shows RBC casts. ANCA is negative. Chest CT shows bilateral ground-glass opacities. Anti-GBM antibody is positive. What is the diagnosis?

Microscopic polyangiitis
Diffuse alveolar hemorrhage from scleroderma
Goodpasture syndrome (Correct answer)
Granulomatosis with polyangiitis

Correct answer: Goodpasture syndrome

Anti-GBM antibody positivity with pulmonary hemorrhage and rapidly progressive glomerulonephritis (RBC casts) is diagnostic of Goodpasture syndrome.

Question 63: 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?

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

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 64: 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)
Artemisinin partial resistance emergence and treatment failure
Immune reconstitution inflammatory syndrome (IRIS)
Artesunate-induced QTc prolongation and arrhythmia

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 65: 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?

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

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

Add adjunctive caspofungin for possible co-infection
Switch to IV pentamidine and add corticosteroids
Initiate mechanical ventilation before continuing PCP therapy
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 67: A 66-year-old woman is started on amiodarone for persistent atrial fibrillation. Six months later she presents with dyspnea and is found to have bilateral pleural effusions and a diffuse interstitial infiltrate on CT chest. PFTs show a restrictive pattern with DLCO 52% predicted. Bronchoscopy with BAL shows foamy macrophages. Which of the following is the most appropriate next step?

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

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

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

Question 68: 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?

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

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

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

Question 69: A 58-year-old man with alcoholic cirrhosis develops confusion and asterixis. Ammonia level is elevated. Which treatment is most appropriate?

Zinc supplementation
Lactulose (Correct answer)
Rifaximin
Neomycin

Correct answer: Lactulose

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

Question 70: 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
Adrenalectomy
Salivary cortisol testing
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 71: 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 72: A 58-year-old man with systemic sclerosis presents with progressive dyspnea over 6 months. PFTs show FVC 62%, DLCO 38%, FEV1/FVC 0.82. Right heart catheterization reveals mPAP 28 mmHg, PCWP 12 mmHg, PVR 3.2 WU. Chest HRCT shows no significant ILD. Which of the following best characterizes his pulmonary hemodynamic profile?

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

Correct answer: Borderline mPAP not meeting criteria for pulmonary hypertension

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

Question 73: A 63-year-old woman presents with progressive proximal muscle weakness over 4 months, difficulty climbing stairs, and dysphagia. CK is 4,200 U/L. ANA is positive 1:320. Anti-Jo-1 antibody is negative. Anti-MDA5 antibody is strongly positive. Chest CT shows bilateral ground-glass opacities and reticulation in both lower lobes. Muscle biopsy shows perifascicular atrophy with MHC-I upregulation. Which of the following is most accurate regarding her prognosis and management?

Perifascicular atrophy confirms polymyositis; initiate high-dose prednisone alone
Anti-MDA5 is associated with low ILD risk; lung findings likely represent an independent process
This pattern suggests amyopathic dermatomyositis with high risk of rapidly progressive ILD; aggressive immunosuppression is warranted (Correct answer)
Anti-MDA5 positivity predicts an excellent prognosis; treat with hydroxychloroquine monotherapy

Correct answer: This pattern suggests amyopathic dermatomyositis with high risk of rapidly progressive ILD; aggressive immunosuppression is warranted

Anti-MDA5 (anti-melanoma differentiation-associated gene 5) antibody is associated with clinically amyopathic dermatomyositis (CADM) or dermatomyositis with relatively mild myositis but a very high risk of rapidly progressive interstitial lung disease (RP-ILD), which carries a mortality rate of 30–50% even with treatment. Perifascicular atrophy with MHC-I upregulation is the histologic signature of dermatomyositis (not polymyositis). This patient's presentation — ground-glass opacities + reticulation + anti-MDA5 — requires aggressive combination immunosuppression (high-dose corticosteroids + calcineurin inhibitor such as tacrolimus + possibly rituximab or cyclophosphamide). Hydroxychloroquine monotherapy is wholly inadequate. Anti-Jo-1 is associated with antisynthetase syndrome; anti-MDA5 carries a distinct and more dire pulmonary phenotype.

Question 74: 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
Cabergoline (Correct answer)
Stereotactic radiosurgery

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

Placement of a nasogastric tube for gastric decompression
Administration of prophylactic broad-spectrum antibiotics
Immediate ERCP to assess for biliary obstruction
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 76: 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?

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

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

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

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

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

Question 78: 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
Micafungin for a minimum of 14 days after last positive blood culture (Correct answer)
Amphotericin B liposomal formulation to avoid echinocandin resistance
High-dose fluconazole (800 mg/day) given stable clinical status

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

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

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

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

Question 80: 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?

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

Correct answer: Voriconazole 6mg/kg IV q12h x 2 doses, then 4mg/kg q12h

Voriconazole is the preferred first-line treatment for invasive pulmonary aspergillosis based on superior efficacy demonstrated in landmark clinical trials.

Question 81: 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 requires pre-transplant eradication with IV antibiotics before listing
It is a relative contraindication requiring additional workup
It is not a contraindication to transplantation
It is an absolute contraindication at most transplant centers (Correct answer)

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

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

Question 82: A 68-year-old man with atrial fibrillation and hypertension presents 90 minutes after sudden onset right-sided weakness and aphasia. CT head is negative for hemorrhage. His INR is 1.1 (not on anticoagulation). What is the most appropriate immediate intervention?

Heparin drip with target aPTT 60–80 seconds
Aspirin 325 mg orally immediately
IV alteplase (tPA) if no contraindications (Correct answer)
Emergency carotid endarterectomy

Correct answer: IV alteplase (tPA) if no contraindications

IV tPA within 4.5 hours of ischemic stroke symptom onset is the standard of care when contraindications are absent. Aspirin is appropriate but is secondary to thrombolysis in the acute window. Carotid endarterectomy is for symptomatic carotid stenosis, not acute treatment. IV heparin is not recommended in acute ischemic stroke.

Question 83: 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?

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

Transarterial chemoembolization (TACE) is the preferred bridging modality and has been shown in randomized trials to improve post-transplant survival compared to no treatment
Stereotactic body radiation therapy (SBRT) is contraindicated as bridging for HCC in cirrhosis due to high rates of radiation-induced liver disease
Thermal ablation (RFA/MWA) should not be used for lesions >3 cm because complete ablation is uniformly unachievable
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 85: 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 causes vitamin D toxicity
Lithium-induced autonomous parathyroid adenoma
Lithium raises the calcium set-point for PTH suppression (Correct answer)

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 86: 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
Choledocholithiasis
Primary sclerosing cholangitis (Correct answer)
IgG4-related cholangiopathy

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 87: According to the 2021 IDSA and SHEA focused update, which of the following is the preferred first-line agent for an initial episode of non-severe Clostridioides difficile infection?

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

Correct answer: Oral Fidaxomicin

The 2021 IDSA/SHEA guidelines conditionally recommend oral fidaxomicin as the preferred agent over oral vancomycin for an initial episode of C. difficile infection (CDI). This preference is based on evidence showing fidaxomicin has a lower rate of CDI recurrence compared to vancomycin. Oral metronidazole is no longer recommended as a first-line agent for even mild-to-moderate disease. Fecal microbiota transplantation is reserved for patients with multiple recurrent episodes.

Question 88: 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?

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

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 89: Which finding on urinalysis is LEAST reliable for diagnosing DKA?

Urine pH low
Urine glucose strongly positive
Urine specific gravity elevated
Urine ketones (nitroprusside reaction) strongly positive (Correct answer)

Correct answer: Urine ketones (nitroprusside reaction) strongly positive

The urine nitroprusside reaction detects acetoacetate but not beta-hydroxybutyrate (the predominant ketone in DKA), so it can underestimate ketosis, especially early in treatment.

Question 90: A 45-year-old man is found to have isolated severe aortic regurgitation on echocardiography. He is completely asymptomatic with an LV end-systolic diameter of 48 mm and EF of 58%. He exercises vigorously without limitation. What is the most appropriate management?

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

Correct answer: Referral for aortic valve replacement

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

Question 91: What is the most common cause of community-acquired pneumonia in adults?

Streptococcus pneumoniae (Correct answer)
Haemophilus influenzae
Staphylococcus aureus
Mycoplasma pneumoniae

Correct answer: Streptococcus pneumoniae

Streptococcus pneumoniae is the most common bacterial cause of community-acquired pneumonia (CAP) in adults. This bacterium is responsible for a significant proportion of pneumonia cases, often leading to typical symptoms like fever, cough, and pleuritic chest pain. Vaccination against S. pneumoniae is available and recommended for certain populations.

Question 92: A 55-year-old male with newly diagnosed small cell lung cancer has disease confined to the right hemithorax and ipsilateral mediastinal nodes that can be encompassed in a radiation field. What is the classification and treatment approach?

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

Correct answer: Limited-stage SCLC — concurrent chemoradiation

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

Question 93: Which medication is contraindicated in a patient with acute heart failure?

Diuretics
ACE inhibitors
Beta-blockers (Correct answer)
Nitrates

Correct answer: Beta-blockers

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

Question 94: What is the first-line treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD)?

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

Correct answer: Systemic corticosteroids and antibiotics

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

Question 95: 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?

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

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 96: A 66-year-old male with a history of COPD presents to the emergency department with increased dyspnea, cough, and sputum production. He has a history of two exacerbations in the past year. His blood eosinophil count is 350 cells/µL. According to the 2024 GOLD report, which of the following is the most appropriate initial pharmacologic management for this patient's chronic condition?

A long-acting muscarinic antagonist (LAMA) monotherapy
A combination of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA)
A combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) (Correct answer)
A short-acting beta-agonist (SABA) as needed with no maintenance therapy

Correct answer: A combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA)

According to the 2024 GOLD guidelines, for a patient with a history of frequent exacerbations (≥2 in the past year) and a blood eosinophil count ≥300 cells/µL, initial therapy with a triple combination of ICS/LABA/LAMA is recommended. This approach targets bronchoconstriction with the dual bronchodilators (LABA/LAMA) and airway inflammation with the ICS, which is particularly beneficial in patients with eosinophilic features.

Question 97: 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 98: A 58-year-old man with type 2 diabetes presents with a foot ulcer that probes to bone. The most appropriate next diagnostic step is:

Plain X-ray of the foot
MRI of the foot (Correct answer)
Bone scan with technetium-99m
CT scan of the foot

Correct answer: MRI of the foot

MRI is the gold standard for diagnosing osteomyelitis as it has the highest sensitivity and specificity for bone marrow involvement.

Question 99: 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 therapy for at least 14 days
Antibiotic treatment until the C-reactive protein level normalizes

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

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

Correct answer: Continue standard ABVD for the planned total course

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

Question 101: A 34-year-old woman with systemic lupus erythematosus presents with nephrotic-range proteinuria (4.8 g/day), serum creatinine 1.9 mg/dL, and complement levels showing low C3 and C4. Kidney biopsy reveals mesangial and subendothelial immune deposits with 'wire-loop' lesions on light microscopy and no tubuloreticular inclusions on electron microscopy. Which ISN/RPS class of lupus nephritis is this, and what is the most appropriate induction therapy?

Class IV diffuse proliferative; high-dose mycophenolate mofetil plus glucocorticoids (Correct answer)
Class V membranous; tacrolimus monotherapy
Class II mesangial; hydroxychloroquine plus ACE inhibitor only
Class III focal proliferative; azathioprine plus low-dose prednisone

Correct answer: Class IV diffuse proliferative; high-dose mycophenolate mofetil plus glucocorticoids

Wire-loop lesions on light microscopy reflect large subendothelial deposits and are hallmark of Class IV (diffuse proliferative) lupus nephritis — the most severe and most common form requiring aggressive induction. Tubuloreticular inclusions are often seen in lupus but their absence does not exclude it. Induction with high-dose mycophenolate mofetil (2–3 g/day) plus corticosteroids is now preferred over cyclophosphamide in most patients, per current KDIGO and ACR guidelines, with equivalent efficacy and a better tolerability profile, especially for preservation of fertility.

Question 102: 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)
Flexible sigmoidoscopy
CT colonography

Correct answer: Colonoscopy

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

Question 103: A 60-year-old man with cirrhosis presents with acute upper GI bleeding. Endoscopy reveals esophageal varices with active oozing. In addition to endoscopic band ligation, which medication should be started immediately?

Proton pump inhibitor (pantoprazole)
Vasopressin
Propranolol
Octreotide (Correct answer)

Correct answer: Octreotide

Octreotide (somatostatin analogue) reduces portal pressure by causing splanchnic vasoconstriction and is given alongside endoscopic therapy for variceal bleeding.

Question 104: 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 is unaffected by thyroid status
Methimazole directly inhibits warfarin metabolism
INR will increase as hyperthyroidism resolves

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

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

Correct answer: Atypical carcinoid tumor

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

Question 106: 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?

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

Correct answer: Lung volume reduction surgery (LVRS)

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

Question 107: A patient with known coronary artery disease develops hypotension and pulmonary edema 3 days after an anterior MI. Echo shows a new VSD. What is the definitive treatment?

Percutaneous VSD closure as first-line therapy
Intra-aortic balloon pump as definitive therapy
Intravenous furosemide and vasopressors
Emergency surgical repair of the VSD (Correct answer)

Correct answer: Emergency surgical repair of the VSD

Post-MI VSD with cardiogenic shock carries very high mortality and requires emergency surgical repair, often with mechanical circulatory support as a bridge.

Question 108: 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 109: 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?

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

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

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

Correct answer: Amiodarone inhibits CYP2C9, increasing warfarin effect

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

Question 111: A 45-year-old asymptomatic man is found to have severe aortic regurgitation on routine echocardiography. LVEF is 58%, LV end-systolic dimension is 48 mm, and LV end-diastolic dimension is 72 mm. He exercises regularly without symptoms. What is the most appropriate next step?

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

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

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

Question 112: A patient in the ICU on mechanical ventilation has the following ABG: pH 7.50, PaCO2 30 mmHg, PaO2 95 mmHg, HCO3 23 mEq/L. Current settings: TV 500 mL, RR 18, PEEP 5, FiO2 0.40. What is the MOST appropriate ventilator adjustment?

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

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 113: 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?

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

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 114: 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?

3 years (Correct answer)
1 year
10 years
5 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 115: A 65-year-old man with chronic hepatitis C cirrhosis presents with confusion, asterixis, and ammonia level of 120 μmol/L. Which treatment reduces ammonia production in the gut?

Neomycin as first-line
Lactulose (Correct answer)
Sodium benzoate
Rifaximin alone as initial therapy

Correct answer: Lactulose

Lactulose is first-line for hepatic encephalopathy; it acidifies colonic contents, trapping ammonia as ammonium and promoting its excretion.

Question 116: 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
Suppressed TSH causes pituitary enlargement
Risk of Afib from subclinical hyperthyroidism
Exogenous subclinical hyperthyroidism accelerates bone loss (Correct answer)

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

Destruction of posterior pituitary magnocellular neurons by lithium nephrotoxicity
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

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

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

Correct answer: Add amiodarone for secondary prevention of VT recurrence

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

Question 119: 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
CT abdomen with contrast
MRI liver
Octreotide scan (somatostatin receptor scintigraphy) (Correct answer)

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 120: 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?

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

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

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

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

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

Question 122: 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?

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

Correct answer: Anaplasmosis (Anaplasma phagocytophilum)

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

Question 123: A patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). After treatment, which prophylactic antibiotic is recommended to prevent recurrence?

Metronidazole
Cephalexin
Amoxicillin-clavulanate
Norfloxacin (Correct answer)

Correct answer: Norfloxacin

Norfloxacin (or trimethoprim-sulfamethoxazole as an alternative) is recommended for long-term secondary prophylaxis after a first episode of SBP to reduce recurrence risk.

Question 124: A 45-year-old woman with known HIV on antiretroviral therapy presents with confusion, fever, and neck stiffness. CD4 count is 80 cells/μL. CSF shows lymphocytic pleocytosis and positive India ink stain. The treatment of choice is:

Fluconazole alone
Voriconazole
Liposomal amphotericin B plus flucytosine (Correct answer)
Caspofungin

Correct answer: Liposomal amphotericin B plus flucytosine

Cryptococcal meningitis induction therapy requires liposomal amphotericin B plus flucytosine for 2 weeks, followed by fluconazole consolidation.

Question 125: 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?

Jaw osteonecrosis upon stopping
Rebound hypercalcemia
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 126: 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 = 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
Transpulmonary plateau = 34 cmH2O; plateau pressure is safe and no adjustment is indicated

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 127: Which of the following is an established indication for intervention in a patient with asymptomatic severe primary mitral regurgitation?

Left ventricular ejection fraction (LVEF) of 65%.
Left ventricular end-systolic dimension (LVESD) of 38 mm.
Pulmonary artery systolic pressure (PASP) at rest of 55 mmHg. (Correct answer)
Age greater than 75 years.

Correct answer: Pulmonary artery systolic pressure (PASP) at rest of 55 mmHg.

For asymptomatic patients with severe primary mitral regurgitation and preserved LV function (LVEF >60% and LVESD <40 mm), surgery is indicated if new-onset atrial fibrillation or pulmonary hypertension (pulmonary artery systolic pressure >50 mmHg at rest) develops. An LVEF of 65% and LVESD of 38 mm are within the normal range and would not trigger intervention on their own. Advanced age is a factor in risk assessment but not a primary indication for surgery.

Question 128: Which of the following is a common first-line treatment for stable angina?

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

Correct answer: Aspirin and nitrates

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

Question 129: 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?

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

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 130: 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
Cisplatin-induced nephrotoxicity
Tumor lysis syndrome (Correct answer)

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 131: 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)
Hyperventilation-induced hypocapnia returning to baseline
Successful bronchodilation reducing dynamic hyperinflation
Adequate compensation for metabolic acidosis

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 132: 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?

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

Correct answer: Fidaxomicin 200mg BID x 10 days

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

Question 133: 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?

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

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 134: A 68-year-old woman with extensive-stage small cell lung cancer presents with serum sodium of 116 mEq/L, serum osmolality of 250 mOsm/kg, urine osmolality of 620 mOsm/kg, and urine sodium of 50 mEq/L. She appears euvolemic. What is the most likely cause?

Cerebral salt wasting
Primary adrenal insufficiency
Syndrome of inappropriate ADH secretion (SIADH) (Correct answer)
Hypervolemic hyponatremia from nephrotic syndrome

Correct answer: Syndrome of inappropriate ADH secretion (SIADH)

Small cell lung cancer commonly secretes ADH ectopically, causing SIADH with euvolemic hyponatremia and inappropriately concentrated urine with elevated urine sodium.

Question 135: A 34-year-old woman with SLE on hydroxychloroquine and low-dose prednisone develops fever, rigors, and altered mental status 10 days after a camping trip in Missouri. Blood smear shows intraerythrocytic ring forms with occasional multiple rings per cell and 'Maltese cross' (tetrad) forms. Parasitemia is 6%. Which of the following is the MOST appropriate treatment?

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

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 136: 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:

Clindamycin plus primaquine
Atovaquone
Dapsone
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 137: 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?

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

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 138: A 68-year-old woman with severe aortic stenosis (AVA 0.7 cm², mean gradient 52 mmHg) and an EF of 30% is evaluated for valve replacement. After dobutamine stress echocardiography, her AVA increases to 0.85 cm² and mean gradient increases to 48 mmHg. Which of the following best characterizes her condition and guides management?

True severe AS with contractile reserve — proceed with AVR given symptomatic low-flow, low-gradient physiology (Correct answer)
True severe AS without contractile reserve — valve replacement is contraindicated
Moderate AS with cardiomyopathy — defer intervention and optimize heart failure therapy
Pseudo-severe AS — medical optimization is preferred over valve replacement

Correct answer: True severe AS with contractile reserve — proceed with AVR given symptomatic low-flow, low-gradient physiology

This patient has low-flow, low-gradient severe AS with reduced EF. On dobutamine stress echo, the AVA remains <1.0 cm² (0.85 cm²) while the gradient increases, confirming TRUE severe AS with contractile reserve (EF augmentation). This distinguishes it from pseudo-severe AS, where AVA normalizes (>1.0 cm²) as gradient rises. Patients with true severe AS and contractile reserve have acceptable surgical risk and benefit from AVR (or TAVR). Those without contractile reserve (EF does not improve with dobutamine) carry higher procedural risk but may still benefit from TAVR on a case-by-case basis.

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

Correct answer: Discontinue cabergoline and initiate bromocriptine

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

Question 140: A 47-year-old previously healthy man is admitted with 4 days of fever, myalgias, and progressive hypoxemia. CXR shows bilateral interstitial infiltrates. BAL reveals: negative bacterial cultures, negative Legionella/Pneumococcal urinary antigens, negative respiratory viral panel (influenza, RSV, parainfluenza, adenovirus), negative PCP DFA. CD4 count is 620 cells/µL. Serum β-D-glucan is 478 pg/mL (normal <60). BAL galactomannan index is 0.6 (normal <0.5). He has no known immunosuppression. The most likely diagnosis is:

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

Correct answer: Invasive pulmonary aspergillosis

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

Question 141: 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?

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

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 142: 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?

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

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 143: 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 >25 mmHg with elevated cardiac output
Mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units (Correct answer)

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

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

Question 144: 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 folate level
Low serum vitamin B12 level (Correct answer)
Elevated serum ferritin
Positive direct Coombs test

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 145: A 29-year-old woman presents with 5 days of fever, sore throat, and cervical lymphadenopathy. Monospot test is negative. EBV VCA IgM is positive. Three weeks later she develops high fevers, ferritin 42,000 ng/mL, splenomegaly, cytopenia (neutrophils 0.8 × 10⁹/L, platelets 68 × 10⁹/L), elevated triglycerides, and fibrinogen 150 mg/dL. Bone marrow biopsy shows hemophagocytosis. Which finding would MOST strongly indicate that this is EBV-driven hemophagocytic lymphohistiocytosis (HLH) versus secondary HLH from another trigger?

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

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 146: 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?

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

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

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

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 148: 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?

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

Correct answer: Cefotaxime 2g IV q8h

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

Question 149: 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?

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

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

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

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 151: 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?

Place a rigid bronchoscope and apply endobronchial tamponade to the right upper lobe
Advance the ETT into the left mainstem bronchus to isolate and protect the non-bleeding lung (Correct answer)
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 152: 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?

Time to CSF culture sterilization
Adequacy of serial therapeutic lumbar punctures to control intracranial pressure (Correct answer)
Baseline CSF cryptococcal antigen titer
CD4 count at time of diagnosis

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 153: 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
Prerenal azotemia
Hepatorenal syndrome (Correct answer)
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 154: A 65-year-old immunocompetent man presents with fever, altered mental status, and CSF pleocytosis with lymphocyte predominance, elevated protein, and normal glucose. HSV-1 encephalitis is suspected. What test confirms the diagnosis?

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

Correct answer: CSF HSV PCR

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

Question 155: A 62-year-old man presents with a 3-week history of grouped vesicles on an erythematous base in a dermatomal distribution along the left T5–T6 dermatome, with significant burning pain. He is immunocompetent. Which of the following is the most appropriate management?

Valacyclovir 1000 mg three times daily for 7 days, started within 72 hours of rash onset (Correct answer)
No treatment needed; self-limiting in immunocompetent patients
Acyclovir cream applied topically to lesions
Prednisone 60 mg daily for 2 weeks without antiviral therapy

Correct answer: Valacyclovir 1000 mg three times daily for 7 days, started within 72 hours of rash onset

Oral valacyclovir (or famciclovir) is first-line for herpes zoster in adults, particularly to reduce duration, severity, and risk of postherpetic neuralgia. It must be started within 72 hours of rash onset for maximum benefit. Topical acyclovir is inadequate. Steroids alone without antivirals are not recommended. Treatment is always recommended in adults due to postherpetic neuralgia risk.

Question 156: 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)
Repeat endoscopy
CT scan of the abdomen

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 157: 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 158: A 49-year-old woman with scleroderma-associated interstitial lung disease (ILD) develops progressive dyspnea over 3 months. HRCT shows new bilateral ground-glass opacities predominantly in the upper and mid-lung zones overlying a background of subpleural reticulation with honeycombing at the bases. PFTs show a rapid decline: FVC dropped from 72% to 54% predicted over 6 months. Anti-topoisomerase I (Scl-70) antibody is strongly positive. Bronchoscopic BAL shows 38% lymphocytes. Which of the following management decisions is BEST supported by current evidence?

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

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 159: 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?

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

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 160: 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?

Pre-capillary PAH meeting WHO/ESC criteria; initiate dual oral combination therapy
Pulmonary hypertension due to ILD alone; PAH-specific therapy offers no benefit
Combined pre- and post-capillary PH; phosphodiesterase-5 inhibitors are contraindicated
Borderline pre-capillary PH; exercise RHC needed before initiating PAH therapy (Correct answer)

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 161: 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?

Surgical resection with anatomic lobectomy (Correct answer)
Concurrent chemoradiation
Stereotactic body radiation therapy (SBRT)
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 162: A 34-year-old woman with type 1 diabetes presents with recurrent hypoglycemia despite decreasing her insulin doses. She reports fatigue, salt cravings, and a 10-pound weight loss over 3 months. Morning cortisol is 3.2 mcg/dL. Which finding would most strongly support autoimmune polyglandular syndrome type 2 (APS-2) rather than isolated primary adrenal insufficiency?

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

Correct answer: Elevated TSH with low free T4

APS-2 (Schmidt syndrome) is defined by the co-occurrence of primary adrenal insufficiency with autoimmune thyroid disease (Hashimoto's or Graves') and/or type 1 diabetes. An elevated TSH with low free T4 (primary hypothyroidism) in a patient with type 1 diabetes and adrenal insufficiency confirms APS-2. Positive 21-hydroxylase antibodies confirm autoimmune etiology of the adrenal insufficiency but are present in isolated Addison's as well. Hyperkalemia/hyponatremia and low ACTH stimulation response are features of primary adrenal insufficiency regardless of whether it is isolated or part of APS-2.

Question 163: A 28-year-old woman is referred for evaluation of amenorrhea and galactorrhea. Serum prolactin is 340 ng/mL. MRI shows a 9 mm pituitary lesion. She desires pregnancy in the next year. She is started on cabergoline 0.5 mg twice weekly. After 6 months, prolactin normalizes and the lesion shrinks to 4 mm. She now asks about stopping cabergoline prior to conception. What is the most appropriate recommendation?

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

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

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

Question 164: 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)
CT chest/abdomen/pelvis with contrast
¹²³I-MIBG scintigraphy
⁶⁸Ga-DOTATATE PET/CT

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 165: A 61-year-old woman with longstanding rheumatoid arthritis presents with progressive dyspnea. Echo shows a mean mitral valve gradient of 8 mmHg, valve area of 1.3 cm², and pulmonary artery systolic pressure (PASP) of 62 mmHg. She is NYHA Class III. Mitral valve morphology is heavily calcified and subvalvular apparatus is fused. What is the preferred intervention?

Mitral valve replacement (MVR) (Correct answer)
Percutaneous balloon mitral valvuloplasty (PBMV)
Continued medical management with diuretics
Transcatheter mitral valve replacement (TMVR)

Correct answer: Mitral valve replacement (MVR)

PBMV is the preferred intervention for symptomatic mitral stenosis with favorable valve morphology (pliable, non-calcified, minimal subvalvular disease — Wilkins score ≤8). This patient has heavily calcified valves with fused subvalvular apparatus, making PBMV high-risk for MR and unlikely to succeed. MVR is the guideline-recommended intervention for symptomatic severe MS with unfavorable anatomy. TMVR for native mitral stenosis remains investigational. Diuretics alone are insufficient for NYHA Class III symptoms with hemodynamically significant MS.

Question 166: A 29-year-old woman with Crohn's disease on azathioprine and adalimumab presents with 3 weeks of right upper quadrant pain. Labs show ALT 340 U/L, AST 290 U/L, ALP 188 U/L, total bilirubin 2.1 mg/dL. She is ANA positive (1:160), anti-smooth muscle antibody negative, serum IgG 2,100 mg/dL (ULN 1,700). Liver biopsy shows interface hepatitis with lymphoplasmacytic infiltrate, rosette formation, and emperipolesis. Which statement about her diagnosis and management is most accurate?

This represents adalimumab-induced drug hepatotoxicity and the biologic should be stopped immediately
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)

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

Hepatitis
Airway obstruction
Splenic rupture risk (Correct answer)
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 168: 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?

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

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 169: A 62-year-old man with type 2 diabetes and CKD stage 3b (eGFR 38) is on maximally tolerated ACEI. His most recent urine albumin-to-creatinine ratio is 420 mg/g. Which agent should be added to further reduce cardiorenal risk?

Spironolactone
Finerenone (Correct answer)
Hydralazine
Amlodipine

Correct answer: Finerenone

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has demonstrated reduction in CKD progression and cardiovascular events in diabetic CKD when added to RAS blockade.

Question 170: A 44-year-old woman is referred for evaluation of refractory ascites. She has no history of liver disease, alcohol use, or malignancy. Paracentesis reveals: total protein 4.2 g/dL, LDH 320 U/L, glucose 78 mg/dL, SAAG 0.8 g/dL, cytology negative. Right heart catheterization shows: PCWP 28 mmHg, right atrial pressure 24 mmHg, pulmonary artery pressure 42/20 mmHg. What is the most likely diagnosis?

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

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 171: A 25-year-old man is found to have bilateral adrenal masses and hypertension. Urine metanephrines are markedly elevated. Before surgical planning, which additional workup is mandatory?

Thyroid function tests
Serum aldosterone-to-renin ratio
Serum calcitonin and RET proto-oncogene mutation testing (Correct answer)
24-hour urine cortisol

Correct answer: Serum calcitonin and RET proto-oncogene mutation testing

Bilateral pheochromocytoma raises concern for MEN2 or VHL; serum calcitonin screens for medullary thyroid cancer and RET mutation testing identifies MEN2.

Question 172: A 45-year-old HIV-positive man (CD4 180, not on ART) is diagnosed with PCP pneumonia. His PaO2 on room air is 58 mmHg. In addition to TMP-SMX, what adjunctive therapy should be started?

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

Correct answer: Systemic corticosteroids (prednisone 40mg BID)

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

Question 173: 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
Thoracoscopy with decortication
Chest tube drainage plus IV antibiotics (Correct answer)
Intrapleural tPA plus DNase

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 174: 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?

Serum copper level
24-hour urine copper
Liver biopsy with quantitative copper (Correct answer)
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 175: 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)
Toxoplasma retinitis; pyrimethamine plus sulfadiazine
Cryptococcal chorioretinitis; fluconazole
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 176: A 42-year-old individual with HIV is found to have a CD4+ T-cell count of 85 cells/µL and is seropositive for Toxoplasma gondii. According to the CDC and NIH guidelines, which of the following prophylactic medications is indicated?

Itraconazole
Trimethoprim-sulfamethoxazole (Correct answer)
Valganciclovir
Azithromycin

Correct answer: Trimethoprim-sulfamethoxazole

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

Question 177: A 72-year-old man undergoes TAVR for severe calcific aortic stenosis. Post-procedure TEE shows a small, eccentric paravalvular leak (PVL) graded as mild-to-moderate. His 30-day echocardiogram shows the PVL is unchanged. He remains mildly symptomatic with dyspnea on exertion. Which statement about his prognosis and management is most accurate?

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

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

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

Question 178: 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
Azithromycin 1g PO single dose
Benzathine penicillin G 2.4 million units IM single dose (Correct answer)
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 179: A 67-year-old man with a prior STEMI (2 years ago) is found to have an EF of 30%. He is on maximally tolerated guideline-directed medical therapy including sacubitril-valsartan, carvedilol, eplerenone, and dapagliflozin. His current NYHA class is II, HR is 72 bpm in sinus rhythm, BP is 108/66 mmHg. He has a LBBB with QRS duration of 158 ms. Which intervention has the strongest mortality benefit at this stage?

Addition of ivabradine to further reduce heart rate
Implantable cardioverter-defibrillator (ICD) without resynchronization
Cardiac resynchronization therapy with defibrillator (CRT-D) implantation (Correct answer)
Referral for cardiac transplant evaluation given NYHA class II despite GDMT

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

This patient meets optimal CRT-D criteria: EF ≤35%, LBBB morphology with QRS ≥150 ms, NYHA class II on GDMT, and sinus rhythm. CRT-D reduces all-cause mortality by ~36% in this population (MADIT-CRT, REVERSE trials) and provides superior benefit over ICD alone due to the reverse remodeling effect of resynchronization, which can meaningfully improve EF. Ivabradine is indicated when HR ≥70 bpm on maximally tolerated beta-blocker in sinus rhythm — his HR of 72 is borderline and the QRS abnormality is the dominant remediable finding. ICD alone would not address dyssynchrony. Transplant is premature for NYHA class II.

Question 180: A 45-year-old woman is found to have a serum calcium of 11.4 mg/dL and PTH of 88 pg/mL (normal 15–65). She is asymptomatic. Bone density shows T-score of −2.0 at lumbar spine. Which is the best next step?

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

Correct answer: Refer for parathyroidectomy

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

Question 181: 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
Malabsorption leads to unpredictable glucose-insulin matching (Correct answer)
Celiac increases glucagon secretion
Celiac disease causes insulin resistance

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 182: 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?

Osimertinib
Amivantamab-vmjw (Correct answer)
Afatinib
Erlotinib

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 183: 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
Prolactinoma
Primary hypothyroidism (Hashimoto's) (Correct answer)
Primary hyperparathyroidism

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

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

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

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

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 186: 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?

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

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 187: 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?

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

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

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

Question 188: A 40-year-old man is admitted to the ICU with septic shock from pneumonia. After 6 hours of resuscitation with 4 L of crystalloid, he remains hypotensive with MAP 58 mmHg. He is on norepinephrine 0.18 mcg/kg/min. Point-of-care echo shows hyperdynamic LV function with IVC collapsibility >50%. What intervention is MOST appropriate?

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

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 189: A 45-year-old man with recurrent sinopulmonary infections since age 25 is found to have serum IgG of 280 mg/dL (normal 700–1600), IgA of 15 mg/dL, and IgM of 40 mg/dL. He has normal T cell counts but markedly reduced B cell numbers. What is the most appropriate long-term management?

Intravenous immunoglobulin (IVIG) replacement therapy (Correct answer)
Prophylactic trimethoprim-sulfamethoxazole
Bone marrow transplantation
Subcutaneous interferon-gamma injections

Correct answer: Intravenous immunoglobulin (IVIG) replacement therapy

Common variable immunodeficiency (CVID) is characterized by low IgG, IgA, and IgM with normal T cells and recurrent bacterial infections in adults. The mainstay of treatment is IVIG (or SCIG) replacement to prevent infections. TMP-SMX prophylaxis is used for PCP in T cell deficiencies, not antibody deficiencies. BMT is reserved for SCID. Interferon-gamma is used for chronic granulomatous disease.

Question 190: A 24-year-old man presents with painless cervical lymphadenopathy, fever, drenching night sweats, and 12-lb weight loss over 2 months. Lymph node biopsy reveals large binucleated cells with prominent 'owl-eye' nucleoli. What is the most likely diagnosis?

Hodgkin lymphoma (Correct answer)
EBV infectious mononucleosis
Non-Hodgkin lymphoma
Sarcoidosis

Correct answer: Hodgkin lymphoma

Reed-Sternberg cells (large binucleated cells with prominent 'owl-eye' nucleoli) on biopsy are pathognomonic for Hodgkin lymphoma.

Question 191: An elderly patient on long-term lithium therapy presents with polyuria and polydipsia. Urine osmolality remains low after water restriction but does not improve after DDAVP. What is the mechanism?

Lithium causes central DI by damaging the posterior pituitary
Lithium blocks aquaporin-2 insertion in collecting ducts causing nephrogenic DI (Correct answer)
Lithium stimulates excessive ADH secretion
Lithium increases renal glucose reabsorption

Correct answer: Lithium blocks aquaporin-2 insertion in collecting ducts causing nephrogenic DI

Lithium causes nephrogenic DI by inhibiting the response of collecting duct principal cells to ADH, impairing aquaporin-2 trafficking.

Question 192: A 45-year-old male traveler develops profuse watery diarrhea, nausea, and vomiting 2 days after returning from India. Stool cultures show Vibrio cholerae. What is the primary treatment priority?

Doxycycline 300mg single dose
IV fluid resuscitation with Ringer's lactate (Correct answer)
Azithromycin 1g single dose
Ciprofloxacin 1g 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 193: An 80-year-old man with severe AS is deemed high surgical risk (STS score 8%). He has no contraindications to TAVR. What is the recommended approach?

Medical management with diuretics
Balloon aortic valvuloplasty alone
Surgical AVR despite high risk
Transcatheter aortic valve replacement (TAVR) (Correct answer)

Correct answer: Transcatheter aortic valve replacement (TAVR)

TAVR is recommended for symptomatic severe AS in patients at high or prohibitive surgical risk (STS ≥8% or institutional agreement on high risk).

Question 194: 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
Repeat adrenal vein sampling with cosyntropin stimulation (Correct answer)
Proceed with left adrenalectomy based on lateralization ratio

Correct answer: Repeat adrenal vein sampling with cosyntropin stimulation

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

Question 195: 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
Azithromycin prophylaxis
Pulmonary rehabilitation
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 196: A 52-year-old man with type 2 diabetes on metformin and a GLP-1 receptor agonist presents with an HbA1c of 8.9%. He has an eGFR of 28 mL/min/1.73m² and urine albumin-to-creatinine ratio of 420 mg/g. He has no history of bladder cancer or recurrent UTIs. Which agent is most appropriate to add for cardiorenal protection?

Pioglitazone
Insulin glargine
Finerenone (Correct answer)
SGLT2 inhibitor

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

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

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

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

Question 198: A 72-year-old man with CKD stage 3 and a porcine aortic valve replacement (6 years ago) is diagnosed with Enterococcus faecalis endocarditis (blood cultures, 4/4 bottles positive). MIC of ampicillin is 0.25 µg/mL; gentamicin MIC is 500 µg/mL (high-level aminoglycoside resistance, HLAR); no beta-lactamase detected. What is the MOST appropriate antibiotic regimen?

Daptomycin monotherapy for 6 weeks
Ampicillin plus ceftriaxone for 6 weeks (Correct answer)
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 199: A 44-year-old woman presents with recurrent syncope and palpitations. Holter monitoring captures a polymorphic ventricular tachycardia triggered exclusively by catecholamine surges (emotion, exercise). She has a structurally normal heart, normal QTc (440 ms), and a family history of sudden death in young relatives. Genetic testing is most likely to reveal a mutation in which gene?

RYR2 (Correct answer)
KCNH2
KCNQ1
SCN5A

Correct answer: RYR2

This clinical picture — catecholamine-triggered bidirectional or polymorphic VT, structurally normal heart, normal QTc, and family history of sudden death — is classic for catecholaminergic polymorphic ventricular tachycardia (CPVT). The most common causative mutation is in RYR2, encoding the cardiac ryanodine receptor (type 2), which regulates sarcoplasmic reticulum calcium release. Abnormal 'leaky' RYR2 during adrenergic stimulation causes spontaneous calcium sparks and delayed afterdepolarizations triggering VT. KCNQ1 and KCNH2 mutations cause Long QT syndrome types 1 and 2; SCN5A mutations cause LQTS type 3 or Brugada syndrome.

Question 200: A 35-year-old woman presents with amenorrhea, galactorrhea, and headaches. MRI shows a 16 mm pituitary lesion. Prolactin is 2800 ng/mL. Visual field testing is normal. What is the first-line treatment?

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

Correct answer: Bromocriptine or cabergoline

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

Question 201: A 58-year-old multiple myeloma patient on day +8 after autologous stem cell transplant develops fever of 39.2°C with ANC of 150 cells/μL and no identifiable infection source. What is the most appropriate immediate management?

Oral ciprofloxacin with close outpatient monitoring
Empiric antifungal therapy alone
G-CSF (filgrastim) administration only
Broad-spectrum IV antibiotics with anti-Pseudomonal coverage (e.g., piperacillin-tazobactam) (Correct answer)

Correct answer: Broad-spectrum IV antibiotics with anti-Pseudomonal coverage (e.g., piperacillin-tazobactam)

Febrile neutropenia requires prompt initiation of broad-spectrum intravenous antibiotics covering gram-negative organisms including Pseudomonas to prevent septic mortality.

Question 202: 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:

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

Correct answer: Abdominal compartment syndrome causing increased chest wall elastance

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

Question 203: A 63-year-old man with Stage IV NSCLC (adenocarcinoma) is found to have an EGFR exon 19 deletion on molecular testing. He has good performance status and no brain metastases. Which first-line treatment provides the longest progression-free survival?

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

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

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

Correct answer: Hyperosmolar hyperglycemic state (HHS)

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

Question 205: 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?

Klinefelter syndrome
Idiopathic hypogonadotropic hypogonadism
Opioid-induced hypogonadotropic hypogonadism (Correct answer)
Primary 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 206: A patient with rheumatic mitral stenosis is started on anticoagulation for a new LAA thrombus. After 3 months of therapeutic anticoagulation, repeat TEE shows persistent thrombus. What is the next step?

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

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

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

Question 207: 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?

Weekly serum cryptococcal antigen titers
Renal function and electrolytes for amphotericin B nephrotoxicity
Daily CBC to monitor flucytosine-induced bone marrow suppression
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 208: A 66-year-old man with hypertension is started on chlorthalidone. Two weeks later he reports muscle cramps. Labs: Na 138 mEq/L, K 3.0 mEq/L, Cl 94 mEq/L, HCO3 29 mEq/L, urine Cl 60 mEq/L. What acid-base disorder is present?

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

Correct answer: Metabolic alkalosis with appropriate respiratory compensation

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

Question 209: 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?

Transarterial chemoembolization (TACE)
Radiofrequency ablation (RFA)
Liver transplantation within Milan criteria (Correct answer)
Stereotactic body radiation therapy (SBRT)

Correct answer: Liver transplantation within Milan criteria

For a patient with cirrhosis and a single HCC ≤2 cm (well within Milan criteria: single lesion ≤5 cm or ≤3 lesions each ≤3 cm), liver transplantation provides the only curative treatment for both the HCC and the underlying cirrhosis, offering the best long-term survival and lowest recurrence rates (~10–15% at 5 years vs. ~50–70% after ablation). With a MELD-Na of 12 and Child-Pugh A status, this patient is an excellent transplant candidate. RFA achieves excellent local control for small HCC but does not address the cirrhotic liver field defect, leading to high intrahepatic recurrence. TACE is palliative for intermediate-stage HCC and is not the preferred modality for early-stage resectable/transplantable disease.

Question 210: 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)
Doxycycline 100 mg orally twice daily for 28 days (late latent alternative)
Benzathine penicillin G 2.4 million units IM once (primary syphilis) (Correct answer)
Aqueous crystalline penicillin G IV for 10-14 days (neurosyphilis coverage)

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

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

Question 211: A 32-year-old pregnant woman (20 weeks) is diagnosed with Graves' disease. TSH is suppressed, free T4 is 3.4 ng/dL. Which antithyroid drug is preferred during the second trimester?

Radioactive iodine (RAI)
Propylthiouracil (PTU)
Beta-blocker monotherapy
Methimazole (Correct answer)

Correct answer: Methimazole

Methimazole is preferred after the first trimester; PTU is preferred in the first trimester due to methimazole's teratogenicity risk early in pregnancy, and RAI is absolutely contraindicated in pregnancy.

Question 212: 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
Barium swallow
Upper endoscopy (Correct answer)

Correct answer: Upper endoscopy

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

Question 213: A patient with IPF is being considered for antifibrotic therapy. Which of the following has been shown to slow decline in FVC in IPF?

Azathioprine
Prednisone
N-acetylcysteine
Nintedanib (Correct answer)

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 214: 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
Vedolizumab
Natalizumab
Infliximab (Correct answer)

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 215: 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)
Oral clear liquids when amylase normalizes
Bowel rest until pain resolves
Parenteral nutrition within 24 hours

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 216: 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)
Clindamycin alone
Metronidazole

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 217: 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)
Cholestyramine
Fibrate (bezafibrate)
Rifampin

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

Prescribe a daily low-dose inhaled corticosteroid (ICS) and continue SABA as needed
Prescribe as-needed low-dose inhaled corticosteroid (ICS)-formoterol (Correct answer)
Continue with as-needed short-acting beta-agonist (SABA) only
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 219: 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?

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

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 220: A 40-year-old woman from Southeast Asia presents with fever, night sweats, weight loss, and a productive cough for 3 months. AFB smear is positive. She starts RIPE therapy. After 2 months, cultures show full susceptibility. What is the total treatment duration?

6 months total (Correct answer)
4 months total
9 months total
12 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 221: 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?

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

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 222: Which finding on thyroid ultrasound carries the HIGHEST risk of malignancy?

Hypoechoic nodule with microcalcifications and irregular margins (Correct answer)
Purely cystic nodule >4 cm
Spongiform nodule
Hyperechoic nodule with comet-tail artifact

Correct answer: Hypoechoic nodule with microcalcifications and irregular margins

Hypoechoic nodules with microcalcifications and irregular margins carry the highest malignancy risk and warrant FNA biopsy.

Question 223: What is the most common cause of community-acquired pneumonia (CAP) in adults?

Streptococcus pneumoniae (Correct answer)
Haemophilus influenzae
Mycoplasma pneumoniae
Legionella pneumophila

Correct answer: Streptococcus pneumoniae

Streptococcus pneumoniae is consistently identified as the most common bacterial cause of community-acquired pneumonia (CAP) in adults. This pathogen is responsible for a significant portion of pneumonia cases, often presenting with classic symptoms like fever, cough, and pleuritic chest pain. Vaccination against S. pneumoniae is an important preventive measure.

Question 224: A 52-year-old man undergoes surgical resection of a 3 cm pancreatic neuroendocrine tumor. Post-operatively, he develops persistent hypoglycemia with glucose nadir of 38 mg/dL during a 72-hour fast. Insulin level is 18 µU/mL, C-peptide is 4.2 ng/mL, and proinsulin is 22 pmol/L (normal <5). Urine sulfonylurea screen is negative. Which additional test would most definitively differentiate nesidioblastosis from occult insulinoma recurrence?

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

Correct answer: Selective arterial calcium stimulation with hepatic venous sampling

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

Question 225: 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?

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

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 226: 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)
Catheter-directed thrombolysis
Systemic thrombolysis with IV alteplase
Surgical embolectomy

Correct answer: Anticoagulation with rivaroxaban or apixaban

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

Question 227: A 60-year-old with known achalasia undergoes esophageal manometry showing aperistalsis and incomplete lower esophageal sphincter relaxation. Which treatment has the lowest risk of GERD as a complication?

Heller myotomy with fundoplication (Correct answer)
Botulinum toxin injection
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 228: A 50-year-old man with known esophageal varices presents with hematemesis. He is hemodynamically stable after resuscitation. What is the most appropriate endoscopic treatment?

Hemostatic clips
Sclerotherapy
Band ligation (Correct answer)
Coagulation therapy

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 229: 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?

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

Correct answer: Staphylococcus epidermidis

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

Question 230: 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?

Sitagliptin
Glipizide
Metformin 2000 mg twice daily (Correct answer)
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 231: 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?

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

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

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

Question 232: 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
Echinocandin plus itraconazole
Fluconazole 400mg daily x 12 months
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 233: A mechanically ventilated patient with ARDS (P/F ratio 88) on volume-control ventilation develops sudden worsening hypoxemia and decreased lung compliance. Trachea is midline, breath sounds are equal bilaterally, and the chest X-ray shows new bilateral opacities that were not present 6 hours ago. Plateau pressure has increased from 28 to 36 cmH2O. Which of the following is the most likely cause?

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

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 234: 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 refer for early liver transplant evaluation at experienced center (Correct answer)
Continue prednisolone for a full 28-day course
Discontinue prednisolone and transition to pentoxifylline

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

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

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 236: A 72-year-old man with peripheral artery disease and claudication at 1 block has an ABI of 0.55. He already walks regularly. What is the next best step in management?

Emergent vascular surgery referral for limb salvage
Aortofemoral bypass surgery
Aspirin 81mg plus clopidogrel 75mg
Cilostazol 100mg twice daily (Correct answer)

Correct answer: Cilostazol 100mg twice daily

Cilostazol, a phosphodiesterase-3 inhibitor, improves claudication symptoms and walking distance and is indicated for symptomatic PAD when exercise alone is insufficient.

Question 237: A 28-year-old with type 1 diabetes is admitted in DKA (pH 6.98, bicarbonate 6 mEq/L, glucose 480 mg/dL, potassium 5.8 mEq/L). The team initiates IV fluids. When should insulin infusion be started?

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

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

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

Question 238: An 80-year-old woman with severe symptomatic aortic stenosis is deemed high surgical risk. Which factor most strongly favors TAVR over surgical AVR?

Presence of moderate aortic regurgitation
Predicted operative mortality >8% using STS score (Correct answer)
Bicuspid aortic valve anatomy
Severe peripheral vascular disease limiting transfemoral access

Correct answer: Predicted operative mortality >8% using STS score

High surgical risk (STS mortality score ≥8%) is the primary indication favoring TAVR, which has demonstrated non-inferior or superior outcomes in this population.

Question 239: A 38-year-old man with multiple endocrine neoplasia type 1 (MEN1) undergoes surveillance imaging and is found to have a 1.8 cm non-functioning pancreatic neuroendocrine tumor (pNET). His serum calcium is 11.4 mg/dL, PTH is 142 pg/mL, and gastrin is normal. He is otherwise asymptomatic. In MEN1, what is the correct sequence of surgical management when both hyperparathyroidism and a pNET require surgery?

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

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

Denosumab
Raloxifene
Teriparatide
Oral alendronate (Correct answer)

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 241: 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?

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

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

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

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 243: 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 244: A 45-year-old man with a history of dyspepsia undergoes an upper endoscopy which reveals a 1.5 cm duodenal ulcer. A biopsy is positive for Helicobacter pylori. The patient has no known drug allergies. The local clarithromycin resistance rate is known to be over 20%. Which of the following is the most appropriate first-line eradication therapy?

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

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

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

Question 245: A 52-year-old man with cirrhosis presents with fever, altered mental status, and nuchal rigidity. CSF shows: WBC 1,800 cells/µL (95% PMNs), glucose 28 mg/dL (serum glucose 110 mg/dL), protein 380 mg/dL. Blood and CSF cultures are pending. He has a severe penicillin allergy (anaphylaxis). Which empiric antibiotic regimen is most appropriate?

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

Correct answer: Meropenem plus vancomycin plus dexamethasone

This presentation is consistent with bacterial meningitis requiring empiric coverage for S. pneumoniae, N. meningitidis, and in a cirrhotic patient (immunocompromised), Listeria monocytogenes. Standard therapy (ceftriaxone + vancomycin + ampicillin) cannot be used given anaphylaxis to penicillin. Meropenem is the preferred carbapenem alternative — it has excellent CNS penetration and covers all three pathogens including Listeria (unlike aztreonam, which has no gram-positive or Listeria coverage). Vancomycin covers penicillin-resistant pneumococcus. Dexamethasone should be given with or before the first antibiotic dose. Aztreonam lacks gram-positive coverage entirely. Chloramphenicol has poor activity against Listeria and significant toxicity. TMP-SMX does not cover pneumococcus adequately in this acute setting.

Question 246: 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?

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

Correct answer: Emergent surgical debridement of necrotic tissue

This presentation is classic for invasive mucormycosis (Mucorales — broad aseptate hyphae with wide-angle branching, contrasting with Aspergillus which has septate hyphae with acute-angle branching). The negative galactomannan and beta-D-glucan are consistent since Mucorales do not produce these biomarkers. While reduction of immunosuppression is important, the SINGLE most critical initial step in rhino-orbital-cerebral mucormycosis is aggressive surgical debridement of all necrotic tissue — this is a surgical emergency that determines survival. Antifungal therapy (liposomal amphotericin B) without surgery has very high mortality. Hyperbaric oxygen (choice C) is adjunctive and unproven. G-CSF (choice D) is useful in neutropenic mucormycosis, not transplant-associated disease.

Question 247: Which scoring system is used to prioritize liver transplant allocation in the United States?

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

Correct answer: MELD score

The MELD (Model for End-stage Liver Disease) score, based on bilirubin, INR, and creatinine, is used by UNOS to prioritize patients for liver transplant allocation.

Question 248: A 52-year-old woman with primary biliary cholangitis (PBC) on ursodeoxycholic acid presents with worsening pruritus, fatigue, and a rising alkaline phosphatase despite 12 months of therapy. Her ALP remains >1.67× the upper limit of normal. Which second-line agent has demonstrated reduction in ALP and improved transplant-free survival in this setting?

Obeticholic acid (Correct answer)
Rifampin
Cholestyramine
Bezafibrate

Correct answer: Obeticholic acid

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

Question 249: 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?

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

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

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

Question 250: What is the recommended diagnostic test for a patient presenting with acute chest pain and suspected myocardial infarction?

Exercise stress test
Electrocardiogram (ECG) (Correct answer)
Echocardiogram
Chest X-ray

Correct answer: Electrocardiogram (ECG)

An Electrocardiogram (ECG) is the recommended initial diagnostic test for a patient with acute chest pain and suspected myocardial infarction. It provides crucial information about the heart's electrical activity, allowing for the rapid identification of ST-segment elevation myocardial infarction (STEMI) or other ischemic changes. This immediate assessment guides urgent treatment decisions.

Question 251: 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?

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

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 252: A 40-year-old woman presents with hypertension, hypokalemia, and suppressed plasma renin activity. Aldosterone-to-renin ratio is markedly elevated. What is the next best diagnostic step?

Start spironolactone empirically
Proceed directly to adrenal vein sampling
Confirm with oral sodium loading or fludrocortisone suppression test (Correct answer)
Obtain urine catecholamines

Correct answer: Confirm with oral sodium loading or fludrocortisone suppression test

An elevated aldosterone-to-renin ratio is a screening test; confirmatory testing (salt loading or fludrocortisone suppression) is required before adrenal imaging or vein sampling.

Question 253: A 28-year-old man presents with episodic severe headaches, diaphoresis, and palpitations. BP is 210/115 mmHg during an episode. 24-hour urine metanephrines are markedly elevated. Prior to surgical resection, which medication should be initiated FIRST?

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

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 254: 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. Water deprivation test shows urine osmolality of 180 mOsm/kg after 8 hours, rising to 195 mOsm/kg after exogenous desmopressin (DDAVP). Which mechanism best explains her condition?

Lithium-induced downregulation of aquaporin-2 channels in the collecting duct, causing nephrogenic diabetes insipidus refractory to ADH (Correct answer)
Lithium-induced hyperparathyroidism elevating calcium and impairing urinary concentrating ability
Primary polydipsia with suppressed ADH causing a partial central diabetes insipidus picture
Suppressed ADH secretion from the posterior pituitary due to lithium toxicity causing central diabetes insipidus

Correct answer: Lithium-induced downregulation of aquaporin-2 channels in the collecting duct, causing nephrogenic diabetes insipidus refractory to ADH

Lithium is the classic cause of nephrogenic diabetes insipidus (NDI). It enters principal cells via ENaC and accumulates intracellularly, blocking adenylyl cyclase activation downstream of the V2 receptor and causing degradation of aquaporin-2 water channels. In NDI, urine osmolality fails to rise appropriately after both water deprivation AND exogenous DDAVP (< 50% increase), distinguishing it from central DI (which responds to DDAVP with > 50% rise) and primary polydipsia (which typically concentrates urine partially during deprivation).

Question 255: A 44-year-old woman is found to have a serum calcium of 11.6 mg/dL on routine labs. PTH is 78 pg/mL (normal 15–65). 24-hour urine calcium is 95 mg/24h (reference > 200 mg for hypercalcemia). Her calcium-to-creatinine clearance ratio (CCCR) is 0.008. She has no symptoms and her DEXA scan shows Z-score of −1.0 at the lumbar spine. Her sister was recently diagnosed with the same condition. What is the most appropriate management?

Initiate cinacalcet to normalize serum calcium and reduce fracture risk
Obtain sestamibi scan and neck ultrasound to localize a parathyroid adenoma prior to surgery
Reassure and monitor without intervention; refer for genetic testing for CaSR or AP2S1 mutation (Correct answer)
Refer for parathyroidectomy given symptomatic primary hyperparathyroidism meeting surgical criteria

Correct answer: Reassure and monitor without intervention; refer for genetic testing for CaSR or AP2S1 mutation

This presentation is classic for Familial Hypocalciuric Hypercalcemia (FHH), an autosomal dominant condition caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) gene, or less commonly AP2S1 or GNA11. Key features: mild-moderate hypercalcemia, inappropriately normal-to-elevated PTH, markedly low 24-hour urine calcium (< 100 mg/day), and CCCR < 0.01 (the diagnostic threshold). Family history of similar calcium levels strongly supports FHH. FHH is benign — parathyroidectomy does not normalize calcium and is not indicated. Cinacalcet may lower calcium temporarily but is not standard of care for FHH. Genetic testing confirms the diagnosis and prevents unnecessary surgical intervention. DEXA Z-score of −1.0 does not meet criteria for parathyroidectomy even if primary hyperparathyroidism were confirmed.

Question 256: 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?

Sitagliptin
Pioglitazone
Glipizide
Empagliflozin (Correct answer)

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 257: 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 258: A 45-year-old man with hepatitis B (HBsAg positive, HBeAg positive, HBV DNA 8 log IU/mL, ALT 180) has liver biopsy showing moderate inflammation and bridging fibrosis. Which treatment is most appropriate?

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

Correct answer: Tenofovir disoproxil fumarate

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

Question 259: A 44-year-old woman with a prosthetic mitral valve (implanted 8 months ago) presents with 6 weeks of low-grade fever and fatigue. Blood cultures grow Enterococcus faecalis susceptible to ampicillin (MIC 2 µg/mL) and gentamicin (MIC 128 µg/mL via high-level aminoglycoside resistance screen). Echocardiogram confirms vegetation on the prosthetic valve without abscess. Which treatment regimen is preferred?

Ampicillin plus ceftriaxone for 6 weeks (Correct answer)
Vancomycin plus gentamicin for 6 weeks
Ampicillin 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 260: Which of the following is the most common cause of acute pancreatitis in the United States?

Gallstones (Correct answer)
Medications
Hypertriglyceridemia
Alcohol

Correct answer: Gallstones

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

Question 261: Which HbA1c target is most appropriate for a 78-year-old patient with type 2 diabetes, multiple comorbidities, and limited life expectancy?

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

Correct answer: <8.0%

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

Question 262: A 68-year-old woman with IgG kappa multiple myeloma on maintenance lenalidomide after autologous stem cell transplantation develops new-onset dyspnea and bilateral lower extremity edema 18 months post-transplant. Echocardiogram reveals a thickened interventricular septum (14 mm), diastolic dysfunction, and a 'sparkling' appearance. Serum protein electrophoresis shows no M-spike. What is the most likely diagnosis and appropriate next step?

Myeloma relapse with cardiac plasmacytoma; obtain PET-CT and restart induction therapy
Hypertensive heart disease; optimize antihypertensive therapy and continue lenalidomide
AL amyloidosis from plasma cell dyscrasia; perform fat pad biopsy and bone marrow biopsy with Congo red staining (Correct answer)
Lenalidomide-induced cardiomyopathy; discontinue lenalidomide and start beta-blocker therapy

Correct answer: AL amyloidosis from plasma cell dyscrasia; perform fat pad biopsy and bone marrow biopsy with Congo red staining

The clinical picture — diastolic dysfunction, thickened interventricular septum with 'sparkling' or 'granular' echocardiographic appearance, and bilateral edema in the context of a plasma cell dyscrasia — is classic for cardiac AL amyloidosis. The absence of an M-spike does not exclude AL amyloidosis, as the paraprotein may be below detection threshold, particularly after SCT. Fat pad biopsy (sensitivity ~70–80%) and bone marrow biopsy with Congo red staining are the preferred initial diagnostic steps. Lenalidomide-induced cardiotoxicity is not a recognized entity. Cardiac plasmacytoma would appear as a mass lesion, not diffuse thickening with diastolic dysfunction.

Question 263: 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?

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

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

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

Question 264: A 70-year-old man on mechanical ventilation develops sudden hemodynamic instability with decreased breath sounds on the left, tracheal deviation to the right, and rising peak airway pressures. What is the immediate management?

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

Correct answer: Needle decompression of the left hemithorax

Tension pneumothorax is a clinical diagnosis requiring immediate needle decompression at the 2nd intercostal space midclavicular line before imaging.

Question 265: 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 600 mL, PEEP of 5 cm H₂O, and permissive hypercapnia is strictly avoided
Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O (Correct answer)

Correct answer: Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O

The cornerstone of mechanical ventilation in ARDS is a lung-protective strategy to minimize ventilator-induced lung injury. This involves using a low tidal volume, typically 4-8 mL/kg of ideal body weight. For this 75 kg patient, 450 mL (6 mL/kg) is an appropriate initial tidal volume. Additionally, maintaining a plateau pressure (the pressure in the alveoli at the end of inspiration) below 30 cm H₂O is crucial to prevent barotrauma. An adequate level of PEEP (Positive End-Expiratory Pressure) is also used to prevent alveolar collapse and improve oxygenation. A PEEP of 10 cm H₂O is a reasonable starting point in moderate-to-severe ARDS.

Question 266: A 45-year-old man with a history of neck irradiation for Hodgkin lymphoma at age 20 is found to have a 1.2 cm thyroid nodule. Fine-needle aspiration returns Bethesda IV (follicular neoplasm). Molecular testing shows a PAX8-PPARγ rearrangement. Which statement most accurately characterizes the significance of this molecular finding?

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

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

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

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

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

Question 268: A 62-year-old woman has bilateral painless cervical and axillary lymphadenopathy. Flow cytometry of a lymph node biopsy shows CD5+, CD19+, CD20+ (dim), CD23+ cells with kappa light chain restriction. What is the most likely diagnosis?

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

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

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

Question 269: 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?

Cardiac surgery consultation is required (Correct answer)
Empiric switch to vancomycin is required
Repeat TEE in 2 weeks is the next step
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 270: 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?

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

Correct answer: Cefepime plus tobramycin

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

Question 271: A medical ICU patient with septic shock from gram-negative bacteremia has been on norepinephrine 0.35 mcg/kg/min and vasopressin 0.03 units/min for 18 hours. MAP is 62 mmHg. Bedside echocardiography reveals: EF 15%, severely dilated left ventricle, TAPSE 12 mm, dilated RV with septal flattening in systole. CVP is 22 mmHg. ScvO2 is 58%. Lactate is 6.2 mmol/L trending upward. Which hemodynamic intervention is MOST appropriate at this time?

Add phenylephrine to increase SVR and improve coronary perfusion pressure
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)

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

Oral quinine sulfate plus doxycycline for 7 days
IV artesunate followed by oral artemisinin-based combination therapy upon tolerating PO (Correct answer)
Oral atovaquone-proguanil
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 273: A 72-year-old woman presents with acute onset of bright red blood per rectum, crampy left lower quadrant pain, and tenesmus without systemic symptoms. CT shows segmental colonic wall thickening at the splenic flexure. What is the most likely diagnosis?

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

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 274: 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?

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

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

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

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

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

Question 276: 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
Antibiotics (Correct answer)
Fluid replacement
Electrolyte monitoring

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

6 weeks regardless of clinical response
4–6 weeks of IV therapy without oral step-down option for prosthetic joint infections (Correct answer)
2 weeks IV followed by chronic oral suppressive therapy
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 278: A 30-year-old pregnant woman at 32 weeks develops BP of 158/102 mmHg, 3+ proteinuria, and a platelet count of 82,000/µL with elevated LDH. What is the most appropriate next step?

Emergent delivery after maternal stabilization (Correct answer)
IV magnesium only and recheck labs in 24 hours
IV labetalol and expectant management until 37 weeks
Oral nifedipine and close outpatient monitoring

Correct answer: Emergent delivery after maternal stabilization

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) at ≥32 weeks warrants delivery after maternal stabilization with magnesium and antihypertensives.

Question 279: A 58-year-old woman with rheumatic mitral stenosis presents with progressive dyspnea. Echocardiography shows a mitral valve area of 1.3 cm², mean gradient of 7 mmHg, and a Wilkins score of 6. She has mild mitral regurgitation and no left atrial thrombus on TEE. Which intervention is most appropriate?

Medical management with beta-blockers and anticoagulation
Percutaneous mitral balloon commissurotomy (PMBC) (Correct answer)
Mitral valve replacement with mechanical prosthesis
Mitral valve repair via open commissurotomy

Correct answer: Percutaneous mitral balloon commissurotomy (PMBC)

PMBC is indicated for symptomatic severe mitral stenosis (MVA ≤1.5 cm²) when valve morphology is favorable (Wilkins score ≤8), there is no significant MR (mild is acceptable), and no left atrial thrombus. This patient meets all criteria. A Wilkins score of 6 indicates excellent valve pliability, with expected good procedural outcomes. Surgical options are reserved for patients with unfavorable anatomy (Wilkins >8), significant MR (≥moderate), or left atrial thrombus.

Question 280: 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?

Order EUS-FNA of the pancreatic mass to confirm pancreatic adenocarcinoma
Check serum IgG subclass panel and repeat IgG4 in 4 weeks
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 281: A 71-year-old man with severe aortic stenosis (AVA 0.7 cm², mean gradient 52 mmHg) and EF of 25% is evaluated for intervention. Despite optimizing heart failure therapy, his EF remains 25%. Dobutamine stress echocardiography shows a rise in mean gradient to 68 mmHg with valve area increasing to only 0.82 cm², and contractile reserve (EF increases to 35%) is demonstrated. What does this response MOST accurately indicate?

Pseudo-severe AS: the true AVA is not hemodynamically significant and medical therapy should continue
Moderate AS with reduced EF from a separate cardiomyopathy: delay valve intervention
True severe AS with contractile reserve: the patient is higher risk but likely to benefit from AVR/TAVR (Correct answer)
Low-flow, low-gradient AS without contractile reserve: palliative care is the preferred approach

Correct answer: True severe AS with contractile reserve: the patient is higher risk but likely to benefit from AVR/TAVR

In low-flow, low-gradient severe AS (EF <50%, mean gradient <40 mmHg), dobutamine stress echo distinguishes true severe AS from pseudo-severe AS and identifies contractile reserve. Here, the gradient rises (≥40 mmHg under stress) and valve area remains <1.0 cm² (0.82 cm²) — confirming true severe AS. Contractile reserve (EF improvement ≥10 percentage points) is demonstrated. This combination predicts a favorable surgical/TAVR outcome with ~70% chance of EF improvement post-intervention. In pseudo-severe AS, the valve area would normalize to ≥1.0 cm² at higher flows. Lack of contractile reserve (no EF rise) confers high operative risk but intervention may still be considered.

Question 282: A 38-year-old man with type 1 diabetes is recovering from DKA. After 10 hours of insulin infusion, his glucose is 198 mg/dL, anion gap is 10 mEq/L, bicarbonate is 19 mEq/L, and he is eating a meal. The team decides to transition to subcutaneous insulin. He has never been on insulin before. Which transition strategy is most appropriate?

Give subcutaneous rapid-acting insulin only and stop the infusion 30 minutes later once absorption begins
Discontinue the infusion immediately upon administration of the first subcutaneous dose to prevent insulin stacking and hypoglycemia
Administer subcutaneous basal insulin and maintain the insulin infusion concurrently for a minimum of 2 hours before discontinuing the drip (Correct answer)
Wait until the bicarbonate normalizes to > 22 mEq/L and glucose falls below 140 mg/dL before attempting any transition

Correct answer: Administer subcutaneous basal insulin and maintain the insulin infusion concurrently for a minimum of 2 hours before discontinuing the drip

IV regular insulin has an extremely short half-life (approximately 4–5 minutes). Abrupt discontinuation without adequate subcutaneous overlap results in rapid loss of insulin action, quickly leading to DKA recurrence — a preventable and dangerous complication. The correct strategy is to give subcutaneous basal insulin and continue the IV infusion for at least 2 hours (some protocols recommend longer) to allow subcutaneous absorption to reach therapeutic levels before the drip is stopped. The transition criteria used here (anion gap closure, tolerating PO intake) are appropriate; it is the overlap step that is critical and frequently missed. Basal insulin is chosen because this patient has no prior regimen to resume.

Question 283: Which diagnostic test is most appropriate for a patient presenting with chest pain and suspected acute coronary syndrome (ACS)?

High-sensitivity troponin test (Correct answer)
Coronary angiography
CT coronary angiography
Stress echocardiography

Correct answer: High-sensitivity troponin test

The high-sensitivity troponin test is the most appropriate initial diagnostic tool for a patient with chest pain and suspected acute coronary syndrome (ACS). Troponin is a cardiac biomarker released into the bloodstream when heart muscle is damaged. High-sensitivity assays allow for earlier detection of myocardial injury, aiding in rapid diagnosis and risk stratification.

Question 284: A 70-year-old man on warfarin for atrial fibrillation presents with an INR of 8.5 and active bleeding from a GI source. The most appropriate immediate treatment is:

Fresh frozen plasma alone
4-factor prothrombin complex concentrate (PCC) plus vitamin K IV (Correct answer)
Vitamin K IV alone
Withhold warfarin and observe

Correct answer: 4-factor prothrombin complex concentrate (PCC) plus vitamin K IV

4-factor PCC provides rapid reversal of warfarin anticoagulation and is preferred over FFP for life-threatening bleeding due to faster administration and smaller volume.

Question 285: 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 286: 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?

IV artesunate (Correct answer)
Chloroquine 600mg base then 300mg at 6h, 24h, 48h
Atovaquone-proguanil plus doxycycline
Quinine 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 287: 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?

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

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 288: 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
Nintedanib 150 mg twice daily (Correct answer)
Prednisone 60 mg/day
Azathioprine 150 mg/day

Correct answer: Nintedanib 150 mg twice daily

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

Question 289: 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
Increase infliximab dose to induce remission and resolve the abscess
CT-guided percutaneous drainage plus antibiotics, with infliximab held (Correct answer)
Colonoscopy with balloon dilation of any associated stricture

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 290: A 48-year-old woman with obesity (BMI 38) presents with daytime somnolence, morning headaches, and an AHI of 42 events/hour with SpO2 nadir of 78% on polysomnography. What is the MOST appropriate first-line treatment?

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

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 291: A patient with chronic hyponatremia is treated with hypertonic saline. Sodium corrects rapidly from 112 to 132 mEq/L over 24 hours. What is the most feared complication?

Central DI
Hypertensive emergency
Cerebral edema
Osmotic demyelination syndrome (Correct answer)

Correct answer: Osmotic demyelination syndrome

Overly rapid correction of chronic hyponatremia (>10–12 mEq/L/24h) causes osmotic demyelination syndrome (central pontine myelinolysis).

Question 292: A 28-year-old woman presents with a 6-month history of amenorrhea, galactorrhea, and a serum prolactin of 340 ng/mL. MRI reveals a 14 mm pituitary macroadenoma. She is started on cabergoline 0.5 mg twice weekly. After 6 months of therapy, her prolactin normalizes and repeat MRI shows > 50% tumor reduction. She asks about discontinuing therapy to attempt pregnancy. Which statement best characterizes the risk of tumor growth during pregnancy if cabergoline is stopped?

Risk is approximately 50% because dopamine agonist withdrawal universally causes rebound hyperprolactinemia exceeding baseline levels
Risk 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)

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 293: 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?

Sitagliptin
Alogliptin
Pioglitazone
Empagliflozin or liraglutide (Correct answer)

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

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

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 295: A 38-year-old man presents with fever, new murmur, and positive blood cultures for Streptococcus viridans. Echocardiography shows a 12mm vegetation on the mitral valve. Which finding would prompt urgent surgical consultation?

Positive blood cultures persisting for 48 hours
Vegetation size >10mm alone
Heart failure due to severe mitral regurgitation (Correct answer)
ESR greater than 100 mm/hr

Correct answer: Heart failure due to severe mitral regurgitation

Heart failure secondary to valve dysfunction from endocarditis is the most common indication for urgent surgery, as it significantly increases mortality without intervention.

Question 296: A 57-year-old man undergoes colonoscopy for a positive stool occult blood test. A 2 cm polyp is removed; pathology shows T2N0M0 invasive adenocarcinoma of the colon. What is the most appropriate next step?

Systemic chemotherapy without surgery
Surgical resection of the involved colon segment (Correct answer)
Surveillance colonoscopy in 1 year only
Radiation therapy alone

Correct answer: Surgical resection of the involved colon segment

T2 colon cancer has invaded the muscularis propria and requires surgical resection; polypectomy alone is inadequate for disease that extends beyond the submucosa (T1).

Question 297: 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 298: A 58-year-old woman with systemic sclerosis presents with progressive dyspnea over 6 months. PFTs show FVC 62%, DLCO 38% predicted, FEV1/FVC ratio 0.82. Right heart catheterization reveals mPAP 28 mmHg, PCWP 10 mmHg, PVR 3.2 Wood units. Six-minute walk distance is 310 meters. Which of the following best describes her hemodynamic classification and the most appropriate next step?

Pre-capillary pulmonary hypertension (Group 3); optimize treatment of underlying ILD before adding PAH-specific therapy (Correct answer)
Post-capillary pulmonary hypertension; initiate diuresis and treat diastolic dysfunction
Pre-capillary pulmonary hypertension (Group 1); initiate combination ambrisentan + tadalafil therapy
Borderline pulmonary hypertension; repeat RHC in 12 months without pharmacotherapy

Correct answer: Pre-capillary pulmonary hypertension (Group 3); optimize treatment of underlying ILD before adding PAH-specific therapy

This patient has SSc-associated ILD with PH. Per updated 2022 ESC/ERS guidelines, mPAP 28 mmHg with PVR ≥2 Wood units qualifies as pre-capillary PH. However, in the context of significant ILD (FVC <70% and markedly reduced DLCO), she fits Group 3 PH (due to lung disease), not Group 1 PAH. The priority is optimizing ILD treatment (e.g., nintedanib or mycophenolate) before layering PAH-specific vasodilators, which can worsen ventilation-perfusion mismatch in ILD-dominant disease. Initiating Group 1 PAH combination therapy without addressing ILD could be harmful.

Question 299: A 34-year-old woman with systemic sclerosis presents with 6 months of progressive dyspnea. PFTs show TLC 62% predicted, DLCO 38% predicted, FVC/FEV1 ratio 0.82. Right heart catheterization reveals mPAP 42 mmHg, PCWP 9 mmHg, PVR 6.8 Wood units, and cardiac output 4.1 L/min. She is WHO functional class III. Which of the following is the most appropriate initial therapy?

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

Correct answer: Combination oral ambrisentan plus tadalafil

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

Question 300: A 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; resect only if adenoma grows >5 cm
Discontinue OCPs and repeat MRI in 6 months; proceed to resection regardless of size change
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.

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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