Jeopardy Board Review

Cardiology

100

A 48-year-old woman is evaluated during a new-patient visit. She reports no symptoms. She is fairly sedentary but is trying to become more active by joining the local health club. She has noticed that she is “out of shape” but can cycle on a stationary bike with moderate intensity to the end of her 30-minute workout. Medical history is otherwise unremarkable. She takes no medications.

On physical examination, vital signs are normal. The estimated central venous pressure is 6 cm H2O. The apical impulse is not palpable. Cardiac examination reveals a grade 2/6 midsystolic murmur localized to the left sternal border without radiation. The murmur does not change with respiration or handgrip but does diminish in intensity with standing. The S2 is physiologically split. There are no clicks. The lungs are clear to auscultation. Peripheral pulses are normal in volume and contour. No edema is present.

Which of the following is the most appropriate management?

A Cardiac magnetic resonance imaging

B Transesophageal echocardiography

C Transthoracic echocardiography

D Routine clinical follow-up without imaging

Answer & Critique Correct Answer: D

Educational Objective: Diagnose a benign heart murmur.

Key Point

Short, soft systolic murmurs (grade <3) that are well localized to the left sternal border and are not associated with symptoms often do not require further investigation.

The most appropriate management is routine clinical follow-up without imaging. Cardiac murmurs result from increased blood flow across a normal orifice (such as with anemia, thyrotoxicosis, pregnancy, or atrial septal defect), turbulent flow through a narrowed orifice (such as with aortic stenosis or mitral stenosis), or regurgitant flow through an incompetent valve (such as with aortic regurgitation or mitral regurgitation). Timing in the cardiac cycle, chest wall location, radiation, intensity, configuration, duration, and pitch all assist in the differential diagnosis.

Not all systolic murmurs are pathologic. Asymptomatic patients with short, soft systolic murmurs (grade <3) well localized to the left sternal border and associated with normal heart sounds do not usually require further investigation. Benign murmurs typically decrease in intensity with standing. The presence of any diastolic or continuous murmur, cardiac symptoms (chest pain, dyspnea, syncope), or abnormalities on examination (clicks, abnormal S2, abnormal pulses) requires evaluation by echocardiography.

Various interventions may alter the intensity of murmurs. The murmur of hypertrophic cardiomyopathy may increase with standing or Valsalva maneuver; both maneuvers decrease venous return, which decreases left ventricular chamber size and increases the degree of obstruction. The click and murmur of mitral valve prolapse may move earlier in systole and increase in intensity as left ventricular volume decreases (standing or Valsalva maneuver). Aortic outflow murmurs increase in intensity in the beat following a premature ventricular contraction due to increased left ventricular volume. Murmurs of mitral regurgitation, ventricular septal defect, and aortic regurgitation increase with handgrip because of increased cardiac output and peripheral resistance. Right-sided heart murmurs may increase during inspiration due to increased venous return.

Characteristics of the S2 may assist in determining the diagnosis or the severity of a valvular lesion. A fixed split of S2 (present during inspiration and expiration instead of only inspiration) results from a delay in right ventricular emptying and is strongly associated with atrial septal defect. A paradoxical split of S2 (present during expiration) indicates a delay in left ventricular emptying, such as with severe aortic stenosis. Presence of a physiologic split (present during inspiration) is helpful for excluding severe aortic stenosis.

Because this patient likely has a benign systolic heart murmur and is asymptomatic, imaging with echocardiography or cardiac magnetic resonance imaging is not necessary.

200

A 65-year-old woman is evaluated during a routine examination. She was diagnosed with a cardiac murmur in early adulthood. She is active, healthy, and without symptoms. She takes no medications.

On physical examination, vital signs are normal. A grade 3/6 holosystolic murmur preceded by multiple clicks is present at the apex. Physical findings are otherwise unremarkable.

An echocardiogram demonstrates a left ventricular ejection fraction of 50%. The left ventricle is moderately dilated with an end-systolic dimension of 42 mm. Myxomatous degeneration of the mitral valve is present with severe regurgitation due to posterior leaflet prolapse.

Which of the following is the most appropriate next step in management?

A Serial clinical and echocardiographic evaluations

B Surgical mitral valve repair

C Surgical mitral valve replacement

D Transcatheter mitral valve repair

Answer & CritiqueCorrect Answer: B

Educational Objective: Treat degenerative mitral regurgitation with surgical mitral valve repair.

Key Point

Mitral valve repair is strongly recommended for chronic severe primary mitral regurgitation in symptomatic patients with left ventricular ejection fraction greater than 30%, asymptomatic patients with left ventricular dysfunction, and patients undergoing another cardiac surgical procedure.

The most appropriate next step in management is surgical mitral valve repair. Myxomatous degeneration of the mitral valve is common, affecting 1% to 2% of the general population. In 10% of patients, the valvular lesion can progress, become life threatening, and require surgery. The only definitive therapy for severe mitral regurgitation is mitral valve surgery. Options are mitral valve repair, mitral valve replacement with preservation of part or all of the mitral apparatus, and mitral valve replacement with removal of the mitral apparatus. Mitral valve repair is generally preferred to valve replacement because it is associated with improved survival in retrospective studies. Mitral valve repair is strongly recommended for chronic severe primary mitral regurgitation in (1) symptomatic patients with left ventricular ejection fraction greater than 30%, (2) asymptomatic patients with left ventricular dysfunction (left ventricular ejection fraction of 30%-60% and/or left ventricular end-systolic diameter ≥40 mm), and (3) patients undergoing another cardiac surgical procedure. Additionally, mitral valve repair is reasonable in asymptomatic patients with chronic severe primary mitral regurgitation who have new-onset atrial fibrillation or pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg). Notably, a left ventricular ejection fraction of 60% or less is used in defining left ventricular systolic dysfunction in mitral regurgitation because ventricular emptying into the left atrium contributes to the relatively lower afterload conditions and higher ejection fraction despite impaired left ventricular performance.

Serial evaluations every 6 to 12 months are recommended for patients with severe mitral regurgitation who do not have indications for surgery. This patient meets the criteria for surgery; therefore, serial evaluations would not be appropriate at this time.

Many patients who could benefit from mitral valve repair are denied surgery because of high surgical risk, advanced age, or comorbid conditions. A catheter-based device can improve mitral valve function by delivering a clip percutaneously to approximate the valve leaflet edges and improve leaflet coaptation at the origin of the mitral regurgitation jet. The device is approved for patients with significant symptomatic degenerative mitral regurgitation for whom mitral valve surgery poses a prohibitive risk. This patient is healthy and does not have comorbid conditions that would significantly increase surgical risk; therefore, transcatheter repair is not indicated.

300

A 64-year-old man is evaluated in the office 7 days after discharge from the hospital for non–ST-elevation myocardial infarction. He was treated with percutaneous coronary intervention using a radial artery approach. Right femoral artery access was initially attempted, but the catheter guidewire could not be passed. During the procedure, an abdominal aortogram was obtained (shown). He has not had any symptoms of claudication. Medical history is significant for hyperlipidemia. He is a current smoker with a 40-pack-year history. Medications are low-dose aspirin, ticagrelor, metoprolol, and atorvastatin.

On physical examination, vital signs are stable. The right femoral pulse is faint, and a bruit is heard over the right femoral artery. No foot or toe ulceration is noted.

In addition to aggressive risk factor modification, which of the following is the most appropriate management?

A Cilostazol

B Cardiac rehabilitation

C Endovascular iliac stenting

D Vorapaxar

Answer & Critique Correct Answer: B

Educational Objective: Treat asymptomatic lower extremity peripheral artery disease.

Key Point

Asymptomatic lower extremity peripheral artery disease is managed with aggressive risk factor modification; cilostazol and surgical intervention do not affect progression of disease or prevent acute limb ischemia.

In this patient with asymptomatic peripheral artery disease (PAD) and acute coronary syndrome treated with percutaneous coronary intervention, the most appropriate next step in management is cardiac rehabilitation. Cardiac rehabilitation is indicated in all patients after hospitalization for acute coronary syndrome and percutaneous coronary intervention. In some patients, exercise can provoke symptoms of intermittent claudication; however, the presence of PAD is not a contraindication to cardiac rehabilitation.

Cilostazol, a phosphodiesterase inhibitor with antiplatelet and vasodilatory properties, is not indicated in patients without claudication, such as this one. There is no evidence that cilostazol prevents progression of disease or improves outcomes in asymptomatic patients with PAD.

This patient's iliac artery stenosis could be treated safely and effectively with an endovascular approach; however, endovascular treatment of PAD is not recommended in asymptomatic patients. There is no empiric evidence that endovascular intervention prevents disease progression to intermittent claudication or critical limb ischemia.

Vorapaxar inhibits thrombin-induced and thrombin receptor agonist peptide–induced platelet aggregation. Vorapaxar reversibly inhibits protease-activated receptor-1, although its long half-life makes it effectively irreversible. It does not appear to affect coagulation parameters, nor does it inhibit platelet aggregation due to adenosine diphosphate, collagen, or thromboxane mimetic activities. Vorapaxar has been shown to reduce hospitalizations for acute limb ischemia in patients with symptomatic PAD, an effect that was mostly driven by patients who experienced lower extremity bypass graft thrombosis. When added to standard antiplatelet therapy, vorapaxar was also associated with a significant increase in major bleeding. In this patient with asymptomatic PAD, the benefits of adding vorapaxar to standard therapy are uncertain.

400

A 72-year-old woman is evaluated during a routine office visit. She has a 3-year history of heart failure with preserved ejection fraction and a long history of hypertension. She has exertional dyspnea with walking around the house, almost nightly paroxysmal nocturnal dyspnea, and peripheral edema. Cardiac catheterization performed 2 years ago revealed normal coronary arteries. Medications are hydrochlorothiazide and diltiazem.

On physical examination, the patient is afebrile, blood pressure is 136/82 mm Hg, pulse rate is 48/min, and respiration rate is 18/min. There is jugular venous distention. An S4 is present. Pulmonary examination reveals no wheezes or crackles. Peripheral edema is noted.

Laboratory studies are significant for a serum creatinine  level of 1.2 mg/dL (106.1 µmol/L) and a serum sodium  level of 139 mEq/L (139 mmol/L).

Which of the following is the most appropriate management?

A Add ivabradine.

B Add valsartan.

C Discontinue hydrochlorothiazide and diltiazem and start furosemide.

D Refer for pacemaker placement.

Answer & CritiqueCorrect Answer: C

Educational Objective: Treat heart failure with preserved ejection fraction.

Key Point:

The cornerstone of treatment for patients with heart failure with preserved ejection fraction is diuretic therapy to maintain euvolemia.

The most appropriate management is to discontinue hydrochlorothiazide and diltiazem and start furosemide. This elderly woman with heart failure with preserved ejection fraction (HFpEF) has signs and symptoms of volume overload in the setting of bradycardia. The cornerstone of treatment for patients with HFpEF is diuretic therapy to maintain euvolemia. Antihypertensive agents should also be used to maintain normal blood pressure in the setting of hypertension. Despite treatment with hydrochlorothiazide, this patient has evidence of volume overload, and she should be switched to furosemide for more efficacious diuresis. This patient is also taking diltiazem, which may be causing her bradycardia, and this agent should be discontinued. If the patient's heart rate fails to improve, she should be referred for pacemaker placement.

Ivabradine is a sinus node modulator that reduces heart failure–associated hospitalizations in select heart failure patients; however, it is indicated as therapy only in patients with a reduced left ventricular ejection fraction and heart rate higher than 70/min while receiving β-blocker therapy.

Although ACE inhibitors, angiotensin receptor blockers (such as valsartan), β-blockers, and aldosterone antagonists have been studied for the treatment of HFpEF, no drugs have been shown to reduce morbidity or mortality in these patients. Most recently, in the TOPCAT trial, there was no difference in the primary combined endpoint of death, aborted cardiac arrest, or heart failure hospitalization with spironolactone compared with placebo; however, spironolactone was associated with a reduction in heart failure hospitalizations. Notably, a retrospective analysis showed that spironolactone reduced the incidence of cardiovascular death and heart failure hospitalization in patients in the Americas compared with those in Eastern Europe, likely because of different patient demographic characteristics across regions.

Pacemaker placement would be indicated only for symptomatic bradycardia in the absence of a reversible cause; the response to diltiazem discontinuation should be assessed before pacemaker placement is considered in this patient.

500

A 68-year-old man is evaluated for a 2-month history of exertional dyspnea. Medical history is significant for diabetes mellitus, hypertension, and hyperlipidemia. Medications are lisinopril, hydrochlorothiazide, metformin, and atorvastatin.

On physical examination, vital signs are normal. Oxygen saturation is 99% breathing ambient air. Cardiopulmonary examination shows a regular rhythm and a paradoxically split S2. There is no peripheral edema.

An electrocardiogram is shown.

Which of the following is the most appropriate diagnostic test to perform next?

A  Adenosine single-photon emission CT

B Coronary artery calcium scoring

C Exercise single-photon emission CT

D Exercise electrocardiography

Correct Answer: A

Educational Objective: Evaluate for coronary artery disease in a patient with left bundle branch block on a baseline electrocardiogram.

Key Point

In patients with left bundle branch block, the preferred diagnostic test for coronary artery disease is a vasodilator stress test because myocardial perfusion imaging with exercise or dobutamine stress may result in a false-positive perfusion defect in the basilar septum.

Adenosine single-photon emission CT is the most appropriate next diagnostic test. This patient with several cardiovascular risk factors has exertional dyspnea, which may be an angina equivalent, and he should undergo stress testing to evaluate for coronary artery disease (CAD). Because his electrocardiogram (ECG) shows left bundle branch block, ST-segment changes with exercise cannot be used to evaluate for the presence of obstructive CAD. He must undergo stress testing with additional imaging, such as nuclear perfusion imaging or stress echocardiography. Exercise is typically the preferred mode of stress because of the additional functional information it provides. However, in the case of left bundle branch block, myocardial perfusion imaging with exercise or dobutamine stress may result in a false-positive perfusion defect in the basilar septum, and these stressors should be avoided. Instead, vasodilator stress testing should be used. Vasodilators, such as dipyridamole, regadenoson, and adenosine, produce hyperemia and a flow disparity between myocardium supplied by unobstructed vessels and myocardium supplied by the stenotic vessel (due to the inability of the distal vasculature to dilate).

Coronary artery calcium scoring, which quantifies the amount of calcium in the walls of the coronary arteries, would document the presence of atherosclerotic disease in this symptomatic patient with risk factors, but it would not determine whether there is obstructive CAD. Although the absence of any coronary artery calcification has been shown to have a high specificity for the absence of obstructive CAD, trials evaluating coronary artery calcium scoring have typically focused on primary prevention in asymptomatic patients.

ECG Criteria for LBBB.

• QRS duration ≥ 120ms
• Dominant S wave in V1 and V2
• Broad monophasic R wave in lateral leads (I, aVL, V5-6)
• Absence of Q waves in lateral leads
• Prolonged R wave peak time > 60ms in leads V5-6

ID

100

A 25-year-old woman is hospitalized with a 4-day history of fever and cough productive of brown sputum. She is at 14 weeks' gestation with her first pregnancy. Medical history is significant for mild persistent asthma. Medications are an albuterol inhaler, beclomethasone inhaler, and a prenatal vitamin.

On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is normal, pulse rate is 122/min, and respiration rate is 24/min. Oxygen saturation  is 94% breathing ambient air. Crackles are heard at the left lung base on pulmonary auscultation.

Chest radiograph shows a left lower lobe infiltrate.

Which of the following is the most likely cause of pneumonia in this patient?

A Escherichia coli

B Klebsiella pneumonia

C Listeria monocytogenes

D Staphylococcus aureus

E Streptococcus pneumoniae

Answer & CritiqueCorrect Answer: E

Educational Objective: Evaluate community-acquired pneumonia in a pregnant patient.

Key Point:

The microbiology of community-acquired pneumonia in pregnancy is similar to that seen in the general population; among patients requiring hospitalization, the most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms, including Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumonia.

Streptococcus pneumoniae is the most likely cause of this patient's community-acquired pneumonia (CAP). Pneumonia is the most common cause of fatal nonobstetric infection in pregnancy. The microbiology of CAP in pregnancy is similar to that seen in the general population. Among patients requiring hospitalization, the most common pathogens are S. pneumoniae, Haemophilus influenzae, and atypical organisms, including Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Empiric treatment of pregnant patients is similar to that in nonpregnant adults, although quinolones and tetracyclines are relatively contraindicated because of the potential for teratogenic effects. In addition to these common bacterial causes of CAP, pregnant women are at increased risk for serious viral pneumonia from influenza virus and varicella-zoster virus, so it is recommended that pregnant women receive seasonal influenza vaccination.

Gram-negative bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter species, Escherichia coli, and Enterobacter species, are rarely implicated in CAP, including among pregnant women hospitalized for pneumonia. Most patients with CAP caused by gram-negative bacteria have a predisposing risk factor, such as bronchiectasis, cystic fibrosis, or COPD, and develop severe pneumonia necessitating admission and care in the ICU.

Pregnancy causes a decrease in T-cell function, and pregnant women are at increased risk for severe Listeria infections, including meningitis and sepsis. However, Listeria rarely causes pulmonary infection and would be an unlikely cause of infection in this patient.

Staphylococcus aureus is an increasingly recognized cause of CAP, with risk factors including antecedent viral infection or injection drug use. Maternal S. aureus infection can occur perinatally, related to delivery, surgery, or indwelling lines, but remains a rare cause of CAP in the prenatal period.

200

A 55-year-old man is evaluated in the hospital for antibiotic management of a diabetic foot ulcer. He was hospitalized 3 days ago for debridement of a draining great toe ulcer. A radiograph of the left foot showed osteomyelitis of the great toe. Empiric piperacillin-tazobactam was started after debridement of the ulcer, and a bone biopsy was obtained intraoperatively. Medical history is significant for diabetes mellitus with nephropathy. Medications are metformin, insulin glargine, and piperacillin-tazobactam. Today the patient is clinically improved.

On physical examination, vital signs are normal. A large, deep plantar ulcer penetrates to the bone of the left great toe with minimal surrounding erythema and no evidence of necrotic tissue.

The bone culture grows Pseudomonas aeruginosa (sensitive to piperacillin-tazobactam, ceftazidime, ciprofloxacin, aztreonam, and tobramycin) and Bacteroides fragilis.

Which of the following is the most appropriate management?

A Add tobramycin to piperacillin-tazobactam

B Switch piperacillin-tazobactam to aztreonam

C Switch piperacillin-tazobactam to ceftazidime

D Switch piperacillin-tazobactam to oral ciprofloxacin and metronidazole

Answer & CritiqueCorrect Answer: D

Educational Objective: Manage conversion of intravenous antimicrobial therapy to oral antimicrobial therapy.

Key Point

Intravenous-to-oral antibiotic switching should be considered in patients who have an intact and functioning gastrointestinal tract, whose clinical status is improving, and who are not being treated for an infection for which parenteral therapy is preferred.

This patient's therapy should be switched from intravenous piperacillin-tazobactam to oral ciprofloxacin and metronidazole. He has a diabetic foot ulcer and osteomyelitis of the left great toe caused by Pseudomonas aeruginosa and Bacteroides fragilis. Ciprofloxacin and metronidazole have excellent bioavailability and will penetrate bone adequately with oral administration. Continuing intravenous therapy offers no advantage for this patient, and intravenous therapy has risks that include developing a venous catheter–associated bloodstream infection. Intravenous-to-oral antibiotic switching should be considered in patients who have an intact and functioning gastrointestinal tract, whose clinical status is improving, and who are not being treated for an infection for which parenteral therapy is preferred (for example, endocarditis or meningitis). Common infectious scenarios for which a switch from intravenous to oral therapy should be considered include community-acquired pneumonia, bacterial peritonitis, pyelonephritis, septic arthritis, and skin and soft tissue infections. When switching from a parenteral to an oral antibiotic agent, the bioavailability of the oral antibiotics must be considered.

A second antipseudomonal agent is not required for this patient's osteomyelitis. He also has kidney disease, which should discourage use of an aminoglycoside. Therefore, adding tobramycin while continuing intravenous antibiotic therapy would not be the best management for this patient who can de-escalate to oral therapy.

Although aztreonam and ceftazidime have good antipseudomonal activity, neither agent has any anaerobic activity to cover B. fragilis.

300

A 26-year-old man is hospitalized for a 3-month history of fever, night sweats, and weakness. Medical history is notable for kidney transplantation 5 years ago. Medications are prednisone and mycophenolate.

On physical examination, temperature is 38.1 °C (100.5 °F), blood pressure is 135/62 mm Hg, pulse rate is 68/min, and respiration rate is 20/min. The sclerae are pale. Cervical, supraclavicular, and axillary lymphadenopathy are noted. Abdominal examination reveals hepatosplenomegaly.

Laboratory studies:

Hemoglobin 8.4 mg/dL (84 g/L)

Leukocyte count 2300/µL (2.3 × 109/L)

Platelet count 98,000/µL (98 × 109/L)

Creatinine  (stable) 1.1 mg/dL (97.2 µmol/L)

Which of the following is the most likely cause of his symptoms?

A Cytomegalovirus

B Epstein-Barr virus

C Herpes simplex virus type 1

D Polyoma BK virus

Answer & CritiqueCorrect Answer: B

Educational Objective: Diagnose Epstein-Barr virus infection in a kidney transplant recipient.

Key Point:

Post-transplant lymphoproliferative disorder caused by Epstein-Barr virus can present several years after transplantation with fever, pancytopenia, generalized lymphadenopathy, and hepatosplenomegaly.

This patient's symptoms are most likely caused by infection with Epstein-Barr virus (EBV). He most likely has posttransplant lymphoproliferative disorder (PTLD). His clinical presentation of fever, pancytopenia, generalized lymphadenopathy, and hepatosplenomegaly is consistent with this diagnosis, considering his kidney transplantation and immunosuppressive therapy. PTLD risk is higher in patients with a history of pre-existing EBV infection treated with lymphocyte-depleting agents and in those receiving sirolimus and tacrolimus compared with those receiving mycophenolate and cyclosporine. PTLD can range from a benign monoclonal gammopathy to a malignant lymphoma. PTLD should be considered in any patient presenting with fever and lymphadenopathy or an extranodal mass; treatment includes reduction of immunosuppression and rituximab or other chemotherapy.

Although numerous viral infections can complicate transplantation, cytomegalovirus is the most significant. The risk for reactivation is related to serologic status of the donor and recipient and is most likely in seronegative recipients from a seropositive donor; it is unlikely when donor and recipient are both negative. Like EBV, cytomegalovirus can reactivate and cause pancytopenia, hepatitis, pneumonitis, esophagitis, colitis, or adrenalitis in solid-organ transplant recipients. Cytomegalovirus reactivation is also associated with organ rejection, secondary infection, and an increased risk for graft loss and death. However, cytomegalovirus does not cause generalized lymphadenopathy or hepatosplenomegaly. Cytomegalovirus-seropositive transplant recipients or cytomegalovirus-negative recipients with positive donors should receive prophylactic valganciclovir or undergo routine monitoring for cytomegalovirus viremia.

Herpes simplex virus can also reactivate in the setting of immunosuppressive therapy, but it would be more likely to present with oral or genital ulcers.

Polyoma BK virus reactivation occurs in approximately 5% of kidney transplant recipients and can cause kidney allograft dysfunction or loss. It can present with a gradual, asymptomatic increase in the serum creatinine level with tubulointerstitial nephritis or, less commonly, with ureteral stenosis. Patients may have polyoma BK virus on polymerase chain reaction of the urine or serum or may have polyoma BK virus inclusion-bearing epithelial cells called “decoy cells.”

The treatment is to reduce immunosuppression. This patient's stable serum creatinine level argues against this diagnosis.

400

A 47-year-old woman is evaluated in the hospital for pyelonephritis not responding to antibiotic therapy. Five days ago she was evaluated in an urgent care center for abdominal and back pain, nausea, fever, and dysuria. She was started on oral ciprofloxacin for a urinary tract infection (UTI). Symptoms did not respond to this treatment, and two days ago, she was hospitalized. Acute pyelonephritis was diagnosed, and she was treated with intravenous fluids, vancomycin, and cefepime. Since hospitalization, her clinical condition has deteriorated, with continued fever and worsening flank pain. She also has stage 2 chronic kidney disease, recurrent UTIs, and a 6-year history of poorly controlled type 2 diabetes mellitus. Medications are amoxicillin, metformin, and insulin glargine.

On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is 130/60 mm Hg, pulse rate is 106/min, and respiration rate is 22/min. Abdominal examination reveals diminished bowel sounds, bilateral costovertebral angle tenderness, and suprapubic pain. Other examination findings are unremarkable.

Laboratory studies:

Hemoglobin 

11 g/dL (110 g/L)

Leukocyte count 

21,000/µL (21 × 109/L) with 91% neutrophils and 9% lymphocytes

Platelet count 

167,000/µL (167 × 109/L)

Creatinine 

1.8 mg/mL (159 µmol/L)

Urinalysis

10 erythrocytes/hpf, leukocytes too numerous to count, many yeast forms, trace protein, and 4+ glucose.

Urine culture results show 10,000 colony-forming units of Candida glabrata. Blood culture results are negative.

A CT scan of the abdomen with contrast shows bilateral perinephric stranding, no masses, and no renal abscesses.

Which of the following is the most likely diagnosis?

A Acute diverticulitis

B Antibiotic-resistant bacterial pyelonephritis

C Candida pyelonephritis

D Renal infarction

Answer & CritiqueCorrect Answer: C

Educational Objective: Diagnose invasive candidiasis.

Key Point

In patients with invasive candidiasis, therapy with an oral azole (if the Candida species is susceptible) or amphotericin B should be initiated immediately; the total duration of therapy should be 10 to 14 days.

This patient has Candida pyelonephritis, a form of invasive candidiasis. She has several risk factors for candidiasis, such as recently taking broad-spectrum antibiotics, uncontrolled diabetes mellitus, and a history of recurrent urinary tract infections. These risk factors, in combination with the findings of yeast, leukocytes, and erythrocytes in the urine, is classic for this infection. Although the urine culture only grew 10,000 colony-forming units of Candida glabrata, the colony count may not correlate with active infection in Candida infections of the urinary tract. Thus, antifungal therapy with amphotericin B should be initiated immediately. After identification of the species, the antifungal agent may be de-escalated to an oral azole if the Candida species is susceptible to azoles. The total duration should be 10 to 14 days of antifungal therapy.

Acute diverticulitis may present with the same manifestations this patient had. However, the bilateral flank pain and the lack of abdominal pain make diverticulitis less likely. In addition, the urinalysis results showing leukocytes too numerous to count and the classic CT scan finding of perinephric stranding point to a kidney infection.

Antibiotic-resistant bacterial pyelonephritis is a possibility and could explain her progressive symptoms despite appropriate antibiotic therapy for pyelonephritis. However, this diagnosis is excluded by the patient's urine culture, which showed only Candida species.

Patients with acute kidney infarction typically present with acute flank pain or generalized abdominal pain, often associated with nausea and vomiting and, less commonly, with fever; hematuria is present in one-third of patients. Over half of kidney infarctions are cardioembolic, and atrial fibrillation is commonly found in patients with this diagnosis. A contrast-enhanced CT scan will show a wedge-shaped perfusion defect. This patient's normal abdominal contrast-enhanced CT scan and urinalysis argue against kidney infarction.

500

A 42-year-old man is evaluated in the hospital for increased pain and drainage from a previously healed surgical wound over the left fibula. He underwent open reduction and internal fixation of a fracture 4 weeks ago. The patient has undergone incision and surgical debridement of the wound. A bone culture revealed methicillin-sensitive Staphylococcus aureus. Medical history is otherwise noncontributory, and his only medication is ibuprofen for pain.

On physical examination, vital signs are normal. A surgical wound over the left lateral leg is well approximated with no erythema or drainage.

A plain radiograph before debridement shows nonunion of the fracture with screws and K-wires in place.

Which of the following is the most appropriate treatment?

A Cefazolin 

B Cefazolin and rifampin

C Ceftaroline

D Vancomycin and rifampin

Answer & CritiqueCorrect Answer: B

Educational Objective: Treat osteomyelitis associated with orthopedic hardware.

Key Point

Rifampin should be used in combination with another antistaphylococcal agent when managing Staphylococcus aureus osteomyelitis in the setting of orthopedic hardware if the hardware cannot be removed.

Cefazolin and rifampin are appropriate therapy for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis associated with orthopedic hardware. Identification of the causative pathogen, administration of adequate antimicrobials for a prolonged duration, surgical debridement (if warranted), and removal of orthopedic prosthetic devices (if feasible) influence the success of osteomyelitis treatment. Optimal management of this patient's infection includes hardware removal; however, this is not possible because the fracture has not yet healed. Hardware-associated infections caused by S. aureus are difficult to eradicate because of the biofilm that forms on the hardware. First-line treatment of MSSA osteomyelitis consists of a β-lactam agent such as cefazolin; a randomized controlled trial and systematic review of the literature have demonstrated that if infected hardware cannot be removed, the addition of rifampin increases the chances of therapeutic success compared with an antistaphylococcal agent alone.

Although cefazolin has activity against MSSA as well as good bone penetration, it would not be an appropriate therapeutic option for the treatment of hardware-associated osteomyelitis without the addition of rifampin.

Ceftaroline has coverage for MSSA, methicillin-resistant S. aureus, and Enterobacteriaceae, but it is unnecessarily broad coverage for the treatment of this patient's MSSA infection.

Vancomycin, a bacteriostatic agent, is less effective than β-lactam agents for the treatment of MSSA and is typically restricted to patients with drug intolerance or allergy.

GI

100

A 29-year-old woman is evaluated during a new-patient appointment. She was diagnosed with hepatitis B virus (HBV) infection 10 years ago; her mother had HBV infection, and it was presumed that the patient acquired the infection at birth. She reports feeling well. Her medical history is otherwise unremarkable and she takes no medication.

On physical examination, vital signs are normal, as is the remainder of the examination.

Laboratory studies are positive for hepatitis B surface antigen and positive for hepatitis B e antigen. The serum HBV DNA level is 20,000,000 IU/mL. Alanine aminotransferase and aspartate aminotransferase levels are within normal limits.

Which of the following is the most appropriate next step in management?

A Entecavir

B Hepatic ultrasonography

C Pegylated interferon

D Repeat liver chemistry tests in 6 months

E Tenofovir

Answer & CritiqueCorrect Answer: D

Educational Objective: Manage the immune-tolerant phase of hepatitis B viral infection.

Key Point

Patients with hepatitis B infection in the immune-tolerant phase require serial monitoring of aminotransferase levels.

Repeat liver chemistry testing in 6 months is the most appropriate next step in the management of this patient. The patient has hepatitis B virus (HBV) infection in the immune-tolerant phase, which can be determined by the likely vertical transmission and the patient's young age, positive hepatitis B e antigen (HBeAg), high viral load, and normal aminotransferase levels. Therefore, the patient only requires serial monitoring of aminotransferase levels. There are four typical phases of HBV infection: (1) immune tolerant, (2) immune active, (3) immune control (inactive), and (4) reactivation. Not all patients go through each phase. Patients with infection in the immune-tolerant phase do not have significant hepatic inflammation and have no fibrosis, and, therefore, do not require treatment. However, infection can progress to the immune-active, HBeAg-positive phase, in which hepatic inflammation, elevated aminotransferase levels, and fibrosis develop, underscoring the need for surveillance of aminotransferase levels.

Patients with HBV infection in the immune-active, HBeAg-positive and reactivation, HBeAg-negative phases require treatment if the alanine aminotransferase level is elevated. Antiviral therapy is also required for patients who present with acute liver failure, all patients with cirrhosis, and patients undergoing treatment with certain immunosuppressive or chemotherapy regimens. None of these scenarios apply to this patient, so she does not require antiviral treatment such as tenofovir, entecavir, or pegylated interferon.

Patients with HBV infection are at increased risk for hepatocellular carcinoma, even in the absence of cirrhosis. Patients from Southeast Asia should undergo hepatocellular carcinoma surveillance with ultrasonography starting at age 40 years for men and at age 50 years for women, and patients from sub-Saharan Africa should begin at age 20 years. Other indications include persistent inflammatory activity (defined as an elevated alanine aminotransferase level and HBV DNA levels greater than 10,000 IU/mL for at least a few years) and a family history of hepatocellular carcinoma. The preferred surveillance strategy is liver ultrasonography with or without α-fetoprotein measurement. This patient is not yet old enough to warrant hepatocellular carcinoma surveillance, so hepatic ultrasonography is not indicated.

200

A 48-year-old woman is evaluated for shortness of breath of 6 weeks' duration. She has cirrhosis due to primary biliary cholangitis.

On physical examination, vital signs are normal. Spider nevi are present on the skin. The cardiopulmonary examination is normal. There is no edema. When the patient is supine, oxygen saturation  is 98% breathing ambient air, but oxygen saturation  drops to 92% with standing.

A radiograph of the chest is normal.

Which of the following is the most appropriate diagnostic test?

A Bronchoscopy

B CT angiography

C Echocardiography with agitated saline

D Pulmonary function testing

Answer & CritiqueCorrect Answer: C

Educational Objective: Diagnose hepatopulmonary syndrome.

Key Point

The diagnosis of hepatopulmonary syndrome is made by demonstrating an arterial oxygen tension less than 80 mm Hg (10.7 kPa) breathing ambient air, or an alveolar-arterial gradient of 15 mm Hg (2 kPa) or greater, along with evidence of intrapulmonary shunting on echocardiography with agitated saline or macroaggregated albumin study.

Echocardiography with agitated saline is the most appropriate next test for this patient. Hepatopulmonary syndrome is a complication of cirrhosis caused by dilation of the pulmonary vasculature in the setting of advanced liver disease and portal hypertension. A high alveolar-arterial oxygen gradient results from functional shunting. Patients with hepatopulmonary syndrome usually have a preexisting diagnosis of liver disease and present with shortness of breath. Dilation of pulmonary vasculature occurs at the base of the lungs, so hypoxemia is most noted when patients are upright or sitting, when shunting is maximal. Classic features are platypnea (worsening shortness of breath in the upright position) and orthodeoxia (worsening arterial oxygen saturation in the upright position). Pulse oximetry is often used to screen for changes in the arterial oxygen saturation level with changes of position. The diagnosis is made by demonstrating an arterial oxygen tension less than 80 mm Hg (10.7 kPa) breathing ambient air, or an alveolar-arterial gradient of 15 mm Hg (2 kPa) or greater, along with evidence of intrapulmonary shunting on echocardiography with agitated saline or macroaggregated albumin study. The detection of intrapulmonary shunting of blood is best confirmed by echocardiography with agitated saline (also known as a bubble study), during which 

bubbles are identified in the left side of the heart after 5 beats, demonstrating that the shunting of blood is not intracardiac. Clinically significant hepatopulmonary syndrome is treated with supplemental oxygen and liver transplantation. Hepatopulmonary syndrome is a progressive condition that is ultimately fatal without liver transplantation.

Bronchoscopy is of no value in the diagnosis of platypnea or shunting disorders. It is potentially useful in the diagnosis of a pulmonary infiltrate or relief of an airway obstruction.

CT angiography can demonstrate the presence of large vascular shunts in the lungs but is rarely required to establish the diagnosis of hepatopulmonary syndrome. An additional benefit of CT angiography is its ability to show pulmonary emboli. In this patient, the presence of orthopnea is not consistent with pulmonary embolism. Transthoracic echocardiography with agitated saline is the gold standard for detecting pulmonary vascular dilatation and diagnosing hepatopulmonary syndrome.

Pulmonary function testing is useful for evaluating the presence of obstructive lung disease as well as restrictive lung disease. The normal pulmonary examination and normal chest radiography suggest that neither restrictive nor obstructive lung disease is contributing to this patient's presentation.

300

A 26-year-old woman with Crohn disease is evaluated for a 2-week history of worsening abdominal pain in the right lower quadrant. She reports passage of one to two formed and nonbloody stools per day with no changes in bowel habits. The patient has required three courses of prednisone for disease flares over the past year. Her only medication is azathioprine.

On physical examination, temperature is 37.7 °C (99.9 °F) and pulse rate is 115/min; other vital signs are normal. Abdominal examination shows fullness and tenderness in the right lower quadrant with no distinct mass. The remainder of the examination is unremarkable.

Laboratory studies show a hemoglobin  level of 10.5 g/dL (105 g/L) and a C-reactive protein  level of 32 mg/dL (320 mg/L). Leukocyte count and liver chemistry tests are normal.

CT enterography shows asymmetric mural thickening and mucosal inflammation of a long segment of distal ileum without luminal narrowing.

Which of the following is the most appropriate treatment?

A Budesonide

B Infliximab

C Mesalamine

D Prednisone

Answer & CritiqueCorrect Answer: B

Educational Objective: Treat ileal Crohn disease.

Key Point

Anti–tumor necrosis factor agents such as infliximab are effective in inducing and maintaining remission in moderate to severe Crohn disease.

Infliximab is the most appropriate treatment for this patient. This patient has moderate to severe ileal Crohn disease that has required multiple courses of tapering prednisone for flares of disease over the last year, despite treatment with the immunomodulator azathioprine. Infliximab is an anti–tumor necrosis factor (TNF)-α antagonist effective in inducing and maintaining remission in moderate to severe Crohn disease. Other FDA-approved anti-TNF agents include adalimumab and certolizumab pegol. Evidence indicates that efficacy is better when an anti-TNF agent is used together with an immunomodulator. In addition, the risk for developing antibodies against the anti-TNF agent is lower with combination therapy. Patients whose disease does not respond to one anti-TNF agent are often switched to a second or third anti-TNF agent. Fibrostenosing Crohn disease in the absence of ongoing mucosal inflammation is unlikely to respond to any anti-TNF agent. Patients with no response to or intolerance of anti-TNF agents should be treated with either surgery or a leukocyte trafficking blocker (natalizumab or vedolizumab).

Budesonide is a potent glucocorticoid with high first-pass metabolism in the liver, which limits systemic side effects related to conventional glucocorticoids. Budesonide can be an effective therapy for treating mild flares of ileal Crohn disease, but it is unlikely to induce remission in more severe Crohn disease and cannot be used to maintain remission.

Mesalamine agents are mainly used to treat ulcerative colitis of mild to moderate severity. Mesalamine may have efficacy in treating mild to moderate Crohn colitis, but it is not efficacious in treating small-bowel Crohn disease.

Reinitiating prednisone may induce remission of the patient's current disease flare, but it would not be helpful for maintenance of remission. Because this patient has required three separate tapering doses of glucocorticoids over the last year, she requires a medication such as infliximab that can both induce remission and maintain Crohn disease in remission.

400

A 28-year-old woman is evaluated at 28 weeks' gestation. This is her first pregnancy. She has chronic hepatitis B virus (HBV) infection acquired through vertical transmission. The patient reports feeling well. Her only medication is a prenatal vitamin.

On physical examination, vital signs are normal. The uterus is enlarged, consistent with 28-week intrauterine gestation. No stigmata of chronic liver disease are noted.

Laboratory studies are positive for hepatitis B surface antigen and hepatitis B e antigen. The HBV DNA level is 300,000 IU/mL. The results of other studies, including alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels, are within normal limits.

Which of the following is the most appropriate next step in management?

A Cesarean delivery at term

B HBV DNA measurement in 3 months

C Pegylated interferon

D Tenofovir

Answer & CritiqueCorrect Answer: D

Educational Objective: Prevent vertical transmission of hepatitis B viral infection.

Key Point

Pregnant women who have hepatitis B virus DNA levels greater than 200,000 IU/mL at 24 to 28 weeks' gestation should be treated with tenofovir to prevent vertical transmission during delivery.

Tenofovir is the most appropriate next step in management of this patient, with the goal of preventing vertical transmission of hepatitis B virus (HBV) infection from mother to child during the course of delivery. Guidelines recommend treatment with lamivudine, telbivudine, or tenofovir for the prevention of vertical transmission in pregnant women who have HBV DNA levels greater than 200,000 IU/mL at 24 to 28 weeks' gestation. There are no head-to-head data comparing these regimens, but tenofovir is preferred over telbivudine and lamivudine due to lower rates of resistance. Tenofovir and telbivudine are the only FDA pregnancy category B agents. Lamivudine and other oral drugs used to treat HBV are category C agents, though there are reasonable data on the safety of lamivudine use in pregnancy in the HIV population. Only a few patients will become hepatitis B surface antigen–negative with treatment; therefore, cure of HBV infection is an unrealistic goal for most chronically infected patients.

There are no data suggesting that cesarean delivery is effective at preventing vertical transmission of HBV. All babies born to mothers with chronic HBV infection should receive active HBV vaccination and passive immunization (HBV immune globulin). The risk for developing chronic HBV infection is high (90%) in newborns who acquire HBV.

Because the patient's HBV DNA level is high enough (>200,000 IU/mL) to warrant treatment to prevent vertical transmission of HBV, measuring her HBV DNA level again in 3 months would not be appropriate without first instituting treatment.

Pegylated interferon is not considered safe in pregnancy and, therefore, would be an inappropriate choice for this patient. Pegylated interferon can be used to treat HBV infection in patients with high alanine aminotransferase levels, low HBV DNA levels, and without cirrhosis. Candidates for interferon have a desire for finite therapy, do not have cirrhosis, are not pregnant, and do not have significant psychiatric disease, cardiac disease, seizure disorder, cytopenia, or autoimmune disease.

500

A 55-year-old man is evaluated for ascites. He recently went to the emergency department, where paracentesis was performed. He was then discharged for outpatient follow-up. He has a history of cirrhosis due to nonalcoholic steatohepatitis and also has hypertension. Endoscopy 3 months earlier showed small varices without stigmata, making prophylaxis for esophageal variceal bleeding unnecessary. His only medication is lisinopril.

On physical examination, vital signs are normal; BMI is 28. Abdominal examination shows abdominal distention without tenderness.

Laboratory studies of the ascitic fluid show a leukocyte count of 80/µL with 20% neutrophils and protein level of 1.6 g/dL (16 g/L). Serum studies show a creatinine  level of 1.3 mg/dL (114.9 µmol/L) and sodium  level of 134 mEq/L (134 mmol/L).

An abdominal ultrasound from the emergency department shows changes consistent with cirrhosis. The portal vein and hepatic veins are patent with normal flow direction. A moderate amount of free-flowing ascites is seen.

In addition to initiating a sodium-restricted diet, which of the following is the most appropriate next step in management?

A Discontinue lisinopril

B Initiate free-water restriction

C Initiate propranolol

D Insert an indwelling drain into the peritoneal cavity

Answer & CritiqueCorrect Answer: A

Educational Objective: Treat ascites caused by portal hypertension.

Key Point

Medications that decrease kidney perfusion, including NSAIDs, ACE inhibitors, and angiotensin receptor blockers, should be discontinued in patients with ascites.

Discontinuing lisinopril is the most appropriate next step in the management of this patient with ascites. Blood pressure falls with worsening cirrhosis, resulting in reduced renal blood flow and glomerular filtration. A compensatory upregulation of the renin-angiotensin system results in increased levels of vasoconstrictors, including vasopressin, angiotensin, and aldosterone, which support systemic blood pressure and kidney function. ACE inhibitors and angiotensin receptor blockers impair the compensatory response to cirrhosis-related hypotension and thereby impair the ability to excrete excess sodium and water and may also affect survival. Medications that decrease kidney perfusion, including NSAIDs, ACE inhibitors such as lisinopril, and angiotensin receptor blockers, should be discontinued because their use often worsens ascites due to portal hypertension. The mainstay of therapy of ascites is to initiate dietary changes, restricting sodium intake to less than 2000 mg (87 mEq) daily. If sodium restriction does not result in significant improvement of ascites, the initiation of diuretic therapy with spironolactone with or without furosemide can be effective in increasing urinary sodium excretion.

Free-water restriction can be useful for the management of dilutional hyponatremia that is sometimes seen in patients with advanced liver dysfunction. This patient has a normal serum sodium concentration, so free-water restriction is not indicated.

Propranolol and other nonselective β-blockers are often used prophylactically for the prevention of variceal hemorrhage, but they do not have a role in the management of ascites. Furthermore, in some patients with ascites that is refractory to medical management, β-blockers may worsen clinical outcomes, including survival.

Indwelling drains for ascites have been used for patients with malignant ascites, but in the setting of portal hypertensive ascites, such as seen in this patient, indwelling drains are associated with a high risk for infection and their use is contraindicated.

Pulm

100

A 46-year-old man is evaluated for 6 months of exertional dyspnea, fatigue, and ankle edema. Recently he experienced near-syncope walking up two flights of stairs. He has no other medical problems and takes no medications.

On physical examination, blood pressure is 106/70 mm Hg, pulse rate is 94/min, and respiration rate is 18/min. Oxygen saturation  is 90% breathing ambient air. On cardiac examination, a prominent jugular venous a wave is present along with widened splitting of S2. Lung examination is unremarkable.

A transthoracic echocardiogram demonstrates a normal size left ventricle with ejection fraction of 65% and right ventricular enlargement. The estimated pulmonary artery systolic pressure is 58 mm Hg. Spirometry, lung volumes, and ventilation-perfusion scan are unremarkable; DLCO is 42% of predicted. CT angiogram of the chest is negative for pulmonary embolism and interstitial lung disease. Right heart catheterization demonstrates a mean pulmonary arterial pressure of 36 mm Hg, with no change with inhaled nitric oxide. Pulmonary capillary wedge pressure  is normal.

Which of the following is the most appropriate treatment?

A Bosentan

B Diltiazem 

C Metoprolol

D Pirfenidone

Answer & CritiqueCorrect Answer: A

Educational Objective: Treat pulmonary arterial hypertension.

Key Point

Before administering advance therapy for patients with pulmonary arterial hypertension (PAH), particularly idiopathic PAH, vasoreactivity testing directs agent selection by identifying those who may respond to calcium channel blockers.

The most appropriate treatment is bosentan. This patient has pulmonary hypertension most consistent with Group 1 (pulmonary arterial hypertension [PAH]), based upon the right heart catheterization demonstrating high pulmonary arterial pressures in the absence of left-sided heart failure, lung disease, and venous thromboembolic disease. Before administering advanced therapy for patients with PAH, vasoreactivity testing with nitric oxide is performed to identify those who may respond to calcium channel blockers (CCBs). CCBs are desirable therapy because they are less expensive and have fewer side effects than other forms of advanced therapy. Failure to achieve a favorable hemodynamic response with nitric oxide predicts unresponsiveness to CCBs and the need for other advanced therapy. The endothelin receptor antagonist bosentan is one of many oral pulmonary vasoactive drugs that is indicated in PAH in patients with negative vasoreactivity testing, such as this patient, some of which have been shown to increase exercise capacity and improve echocardiographic parameters.

CCBs such as diltiazem may be used in the setting of PAH when a response to a vasodilator such as nitric oxide is demonstrated during right heart catheterization. When a response is not found, CCBs are not indicated.

β-Blockers such as metoprolol do not have a proved role specific to PAH, though they might be used as an adjunct agent for supraventricular tachyarrhythmias that are common in this population.

Pirfenidone is an antifibrotic agent indicated for the treatment of idiopathic pulmonary fibrosis. Pulmonary hypertension is frequently observed in patients with idiopathic pulmonary fibrosis, but pirfenidone would not be indicated for a patient with PAH without idiopathic pulmonary fibrosis.

200

A 62-year-old woman is evaluated in the emergency department for worsening dyspnea on exertion during the last 2 weeks. She has a history of severe COPD and an FEV1  of 45% of predicted. She has a cough productive of yellow sputum and wheezing during the same time period. She has a 20-pack-year history of smoking but quit 10 years ago. Her albuterol inhaler and nebulizer have provided temporary relief at home. Current medications are umeclidinium/vilanterol, mometasone, and albuterol.

On physical examination, temperature is normal, blood pressure is 132/64 mm Hg, pulse rate is 110/min, and respiration rate is 30/min. Oxygen saturation is 90% on 6 L/min of oxygen by nasal cannula. Cardiopulmonary examination reveals tachycardia, tachypnea with accessory muscle use, and decreased breath sounds throughout with a prolonged expiratory phase and end expiratory wheezes. She has no jugular venous distention or edema.

Laboratory studies reveal an arterial PCO2 of 46 mm Hg (6.11 kPa). Complete blood count, serum electrolytes , and blood glucose  are normal.

A chest radiograph shows hyperinflated lungs with flattening of the diaphragms but no infiltrate.

Which of the following is the most appropriate next additional test?

A CT pulmonary angiogram

B Electrocardiogram

C Sputum culture

D Sputum Gram stain

Answer & CritiqueCorrect Answer: B

Educational Objective: Evaluate an acute exacerbation of COPD.

Key Point

The first steps in managing a patient with a presumed COPD exacerbation are to confirm the diagnosis and to evaluate other causes of the acute presentation.

An electrocardiogram should be obtained for this patient to evaluate other causes of her acute presentation, such as acute myocardial infarction, arrhythmia, and atrial fibrillation. The first steps in managing a patient with a presumed COPD exacerbation are to confirm the diagnosis. Studies helpful in the evaluation may include pulse oximetry to assess oxygenation or guide oxygen therapy; a chest radiograph to rule out an alternative diagnosis; a complete blood count to identify the presence of polycythemia, anemia, or leukocytosis; arterial blood gas studies; a biochemical panel to assess for electrolyte and glycemic abnormalities; and an electrocardiogram to evaluate tachycardia (as in this patient) and for other possible cardiac comorbidity. This patient has already had a chest radiograph and appropriate laboratory studies but an electrocardiogram is also indicated.

Patients with pulmonary embolism (PE) can present with symptoms similar to a COPD exacerbation. Because of this, pretest probability models such as the Wells criteria have been developed and validated to assist in clinical decision making. Patients who have a low pretest probability for PE using the Wells criteria, such as this patient, and who meet all Pulmonary Embolism Rule-Out Criteria do not need further testing to rule out PE. Physicians should obtain a D-dimer assay in patients with intermediate pretest probability for PE or for those with a low pretest probability for PE who do not meet all Pulmonary Embolism Rule-Out Criteria. In these patients, imaging studies should not be used for initial evaluation.

A sputum culture or Gram stain is not routinely used to assess COPD exacerbations as it rarely changes management. For patients with a confirmed COPD exacerbation with cough, increased sputum, and dyspnea, antibiotics are usually initiated regardless of the results of the sputum Gram stain or culture.

300

A 71-year-old man is evaluated during a follow-up visit for sleep-related breathing pauses observed by the hospital staff when he was admitted for implantation of a cardioverter-defibrillator for ischemic cardiomyopathy (left ventricular ejection fraction  of 30%). He has recently experienced dyspnea, a few episodes of which have awakened him from sleep. He has no insomnia or daytime sleepiness. He has dyslipidemia, stable coronary artery disease, and hypertension. Current medications are aspirin, atorvastatin, valsartan, metoprolol, and nitroglycerin as needed.

On physical examination, vital signs are normal. Oxygen saturation  is 93% breathing ambient air. BMI is 23. Lung examination reveals bibasilar crackles, faint end-expiratory wheezing, neck vein distention, and 1+ ankle edema.

Polysomnography demonstrates central sleep apnea with a Cheyne-Stokes breathing pattern.

Which of the following is the most appropriate treatment of the patient's central sleep apnea?

A Adaptive servo-ventilation

B Auto-adjusting positive airway pressure

C Furosemide

D Supplemental oxygen

Answer & CritiqueCorrect Answer: C

Educational Objective: Treat heart failure in a patient with a Cheyne-Stokes breathing pattern.

Key Point

Initial treatment of central sleep apnea should target modifiable risk factors; medical optimization of heart failure has been shown to improve central sleep apnea and Cheyne-Stokes breathing and should precede other therapies for sleep apnea.

Diuresis with furosemide is the most appropriate treatment option. This patient has central sleep apnea with Cheyne-Stokes breathing in the setting of decompensated heart failure, a state of ventilatory instability. Cheyne-Stokes breathing is an abnormal respiratory pattern characterized by cyclic crescendo-decrescendo respiratory effort during sleep (and sometimes during wakefulness), in the absence of upper airway obstruction. Apnea accompanying the decrescendo effort defines central sleep apnea. The degree of central sleep apnea tends to correlate with left ventricular dysfunction. This patient has evidence on examination of volume overload (crackles and wheezing on lung exam, jugular venous distention, peripheral edema). Optimizing medical management of heart failure and improving fluid balance should precede other therapies for sleep apnea.

Adaptive servo-ventilation is a form of positive airway pressure therapy initially designed as a treatment of Cheyne-Stokes breathing. However, a large multicenter trial unexpectedly showed increased mortality in a subset of patients with systolic heart failure (left ventricular ejection fraction less than 45%) and central sleep apnea treated with adaptive servo-ventilation.

Auto-adjusting positive airway pressure is not an initial treatment for central sleep apnea. It is used to treat obstructive sleep apnea, where proprietary algorithms deliver varying pressure sufficient to prevent upper airway closure.

Supplemental oxygen is sometimes used in advanced heart failure where impaired gas exchange results in hypoxemia. This patient has preserved oxyhemoglobin saturation. Small trials have studied the use of nocturnal supplemental oxygen in the setting of central sleep apnea, with variable results. Such treatment would be premature before optimization of fluid status.

400

A 72-year-old woman is evaluated in the hospital for a pneumothorax. The patient has severe, oxygen-dependent COPD complicated by several exacerbations. She was hospitalized 72 hours ago with abrupt onset of chest pain and dyspnea. Chest radiography confirmed the presence of a large left-sided pneumothorax and a thoracostomy tube was placed. She had 90% expansion of the lung following thoracostomy.

On physical examination, the patient is frail appearing but comfortable. Vital signs are normal. Oxygen saturation  is 96% breathing 3 L/min of oxygen through nasal cannula. Pulmonary examination reveals diminished but present breath sounds bilaterally. A left thoracostomy tube is in place.

Chest radiograph demonstrates resolution of pneumothorax with a thoracostomy tube in place.

Which of the following is the most appropriate management?

A Clamp thoracostomy tube

B Place thoracostomy tube to high suction

C Pleurodesis

D Remove thoracostomy tube

Answer & CritiqueCorrect Answer: C

Educational Objective: Treat secondary spontaneous pneumothorax with chemical pleurodesis.

Key Point

Recurrence prevention with pleurodesis is recommended after the first occurrence of secondary spontaneous pneumothorax.

The most appropriate management of this patient with severe COPD and secondary pneumothorax is pleurodesis. Pneumothorax (air in the pleural space) can occur spontaneously, as a result of trauma, or iatrogenically. Spontaneous pneumothorax is further characterized as a primary spontaneous pneumothorax (PSP) in a person without underlying lung disease or a secondary spontaneous pneumothorax (SSP) in a person with underlying lung disease. Patients presenting with SSP are at higher risk for persistent air leak, further expansion of the pneumothorax, or pneumothorax recurrence due to their underlying lung disease. Intervention to prevent recurrence includes both chemical and mechanical pleurodesis, which is recommended in all patients with SSP and after the second occurrence of a PSP. In patients with SSP the cause of persistent air leak following pneumothorax is usually subpleural bullae or cysts. Additional interventions are required to close the leak. For patients who are surgical candidates, video-assisted thoracoscopic surgery (VATS) is recommended to locate and staple or resect blebs followed by mechanical pleurodesis. Patients who cannot tolerate surgery are treated with blood patch or chemical pleurodesis. These procedures are designed to seal the leak and prevent recurrence of pneumothorax. A blood patch is performed by injecting a quantity of the patient's blood into the thoracostomy tube. Chemical pleurodesis is performed by instilling tetracycline or one of its derivatives or specialized talc powder through the thoracostomy tube. Success rate for chemical pleurodesis ranges from 60% to 90% but it is not as effective as mechanical pleurodesis using VATS.

Clamping or removing the thoracostomy tube would not be appropriate because the patient has a secondary spontaneous pneumothorax and the likelihood of recurrence is high.

Placing the thoracostomy tube to high suction would not be appropriate because high levels of suction can increase the risk for reexpansion and pulmonary edema; in addition, the pneumothorax has resolved so no additional suction is needed.

500

A 36-year-old woman is evaluated for dry cough and progressive dyspnea that limits her ability to exercise. She initially presented 8 weeks ago with cough, fever, sputum production, and dyspnea. A chest radiograph at that time revealed left-lower-lobe opacities; she was diagnosed with pneumonia and treated with azithromycin but had little improvement in her symptoms. Her fever and sputum production have resolved. She is a nonsmoker.

On physical examination, vital signs are normal. Lungs are clear to auscultation.

Repeat chest radiograph reveals patchy opacities bilaterally and several nodular densities that are peripherally predominant in different locations than previous radiographs. High-resolution CT scan of the chest shows extensive ground-glass changes bilaterally with several areas of nodular consolidation that are peripherally predominant and along bronchovascular bundles.

Which of the following is the most likely diagnosis?

A Acute HIV infection

B Community-acquired pneumonia

C Cryptogenic organizing pneumonia

D Idiopathic pulmonary fibrosis

Answer & CritiqueCorrect Answer: C

Educational Objective: Diagnose cryptogenic organizing pneumonia.

Key Point

A typical presentation of cryptogenic organizing pneumonia includes cough, fever, and malaise for 6 to 8 weeks that does not respond to antibiotics; patchy opacities on chest radiograph; and ground-glass opacities on CT scan that are peripherally distributed; glucocorticoids are first-line therapy.

The most likely diagnosis is cryptogenic organizing pneumonia. This patient has a subacute history of progressive dyspnea and persistent cough after an initial history consistent with community-acquired pneumonia. Despite treatment with appropriate antibiotic therapy, she now has clear evidence of new opacities that are located in different areas, are peripherally predominant, and coalesce along broncho-vascular bundles. These findings are consistent with a diagnosis of organizing pneumonia, which involves proliferation of granulation tissue within alveolar ducts, alveolar spaces, and surrounding areas of chronic inflammation. There are many known causes of this pattern, including acute infections and autoimmune disorders like rheumatoid arthritis. The term cryptogenic organizing pneumonia is reserved for individuals who have this pattern but do not have a clear associated cause. Patients with cryptogenic organizing pneumonia will typically present with a 6-to-8-week history of symptoms that mimic community-acquired pneumonia. Typically, an initial empiric treatment of infection is given but fails; subsequently, noninfectious causes are considered. This patient has a subacute illness that began with viral symptoms, persistent and progressive cough and dyspnea that are not responsive to past antibiotics, and radiographic findings typical of cryptogenic organizing pneumonia. Patients with cryptogenic organizing pneumonia respond well to glucocorticoids. Glucocorticoids are slowly tapered during the subsequent 6 months.

Acute HIV is unlikely in this patient who initially presented with symptoms of community-acquired pneumonia and whose fever has resolved. Although acute HIV symptoms are not specific, the most common presentation includes persistence of symptoms including fever.

Recurrent community-acquired pneumonia is also unlikely in this patient who was appropriately treated with azithromycin and whose symptoms have partially improved with resolution of the fever and sputum production.

Idiopathic pulmonary fibrosis (IPF) is a disease that affects older patients (the mean age of presentation is in the mid- to late 60s) and presents with chronic (longer than 6 months) symptoms of dry cough and shortness of breath. This patient's presentation is not consistent with these criteria, making a diagnosis of IPF unlikely.

IM

100

A 35-year-old woman is evaluated after laboratory test results showed an elevated LDL cholesterol level during routine screening. Family history is remarkable for myocardial infarction in her father at age 45 years. She takes no medications.

On physical examination, vital signs are normal. BMI is 30. The remainder of the examination is unremarkable.

Laboratory studies:

Alanine aminotransferase 30 U/L

Thyroid-stimulating hormone Normal

Total cholesterol 294 mg/dL (7.61 mmol/L)

LDL cholesterol 195 mg/dL (5.05 mmol/L)

HDL cholesterol 55 mg/dL (1.42 mmol/L)

Triglycerides  220 mg/dL (2.49 mmol/L)

The patient is instructed in therapeutic lifestyle changes to lower her risk for atherosclerotic cardiovascular disease (ASCVD).

According to the American Heart Association/American College of Cardiology cholesterol treatment guideline, which of the following is the most appropriate additional treatment for primary prevention of ASCVD in this patient?

A Evolocumab

B High-intensity rosuvastatin

C Moderate-intensity atorvastatin

D No additional treatment is necessary

Answer & CritiqueCorrect Answer: B

Educational Objective: Treat a patient with an LDL cholesterol level higher than 190 mg/dL (4.92 mmol/L).

Key Point

The American Heart Association and American College of Cardiology recommend that patients aged 20 years or older with an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher should receive high-intensity statin therapy for primary prevention of atherosclerotic cardiovascular disease.

The most appropriate treatment for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in this patient is high-intensity statin therapy with rosuvastatin or atorvastatin. According to the 2018 American Heart Association (AHA)/American College of Cardiology (ACC) Guideline on the Management of Blood Cholesterol, patients aged 20 years or older with severe LDL cholesterol elevation (≥190 mg/dL [4.92 mmol/L]) should receive the maximum tolerated statin therapy for primary prevention of ASCVD, regardless of 10-year risk for ASCVD. High-intensity statin therapy is recommended unless there are contraindications to its use. Sexually active women of childbearing age who are receiving statin therapy should be counseled to use a reliable form of contraception. Women who plan to become pregnant should stop taking statins 1 to 2 months before pregnancy is attempted. Those who become pregnant while on therapy should discontinue statins as soon as the pregnancy is discovered. It is reasonable to intensify statin therapy as tolerated to achieve an LDL cholesterol reduction of at least 50%. In contrast to the AHA/ACC recommendation, the U.S. Preventive Services Task Force recommends initiating low- to moderate-intensity statin therapy in adults aged 40 to 75 years without a history of ASCVD who have one or more traditional ASCVD risk factors (dyslipidemia, diabetes mellitus, hypertension, or smoking) and a calculated 10-year ASCVD event risk of 10% or higher. Similarly, the U.S. Department of Veterans Affairs/U.S. Department of Defense cholesterol guideline recommends moderate-intensity statin therapy for patients with a 10-year ASCVD risk of 12% or more, an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher, or diabetes.

In the absence of familial hypercholesterolemia or severe hypercholesterolemia despite maximally tolerated cholesterol-lowering therapy with a statin and ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, are not indicated in the primary prevention of ASCVD. Cost, treatment burden (injections), and absence of long-term safety data argue against their use in primary prevention. Such treatment might be considered if LDL cholesterol cannot be sufficiently reduced in the highest-risk patients.

In patients with an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher, initial treatment with a moderate-intensity statin is less preferred according to the AHA/ACC guidelines; however, if the patient is unable to tolerate high-intensity therapy, down-titration to moderate-intensity therapy could be considered, especially if adequate LDL cholesterol reduction can be achieved.

An evaluation for secondary causes of hyperlipidemia is also indicated in patients with an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher. The most common secondary causes are obesity, hypothyroidism, biliary obstruction, and nephrotic syndrome. Medications can also increase LDL cholesterol level, and some of the most commonly implicated drugs include cyclosporine, HIV medications (such as protease inhibitors), glucocorticoids, and amiodarone. If a secondary cause is not identified, LDL cholesterol level elevation is considered primary, and family members should undergo screening because severe hypercholesterolemia is often genetically determined, as may be the case with this patient who has a first-degree relative with premature ASCVD.

200

A 36-year-old woman is evaluated for posterior neck pain and stiffness that began 1 week ago while she was doing sit-ups. The pain is worse with movement of the head. She has limited range of motion of the neck in all directions. The pain does not radiate down her arms, and she has not had arm weakness, parethesias, or other neurologic symptoms. She reports no systemic symptoms. The pain is lessened with ibuprofen.

On physical examination, vital signs are normal. On palpation, tenderness of the cervical paraspinal muscles is noted. There is no cervical spine tenderness. Symptoms are not reproduced when the examiner bends the patient's head to either side while also extending the neck and applying a downward axial load (Spurling test). Neurologic examination is normal.

Which of the following is the most likely diagnosis?

A Cervical myelopathy

B Cervical radiculopathy

C Cervical sprain

D Whiplash-associated neck pain

Answer & CritiqueCorrect Answer: C

Educational Objective: Diagnose cervical sprain.

Key Point

Pain associated with cervical sprain is usually an aching sensation that is isolated to the neck but can radiate to the posterior head or shoulders; physical examination usually shows decreased range of motion, tenderness to palpation, and reproduction of the pain with flexion or extension, but no neurologic findings.

This patient most likely has a cervical sprain (nonspecific or axial neck pain), which is the most common cause of neck pain. The pain associated with cervical sprain is usually an aching sensation that is isolated to the neck, but it can radiate to the posterior head or shoulders. The pain does not typically radiate into the arms. Cervical sprain symptoms can be precipitated by an unaccustomed activity or overuse. Physical examination of the neck usually shows decreased range of motion, tenderness to palpation, and reproduction of the pain with flexion or extension. The condition is also notable for the absence of abnormal neurologic findings.

Cervical myelopathy (compression of the cervical spinal cord) can also cause neck pain. Common clinical manifestations include progressive worsening of symptoms, difficulty with fine object manipulation and manual dexterity, and gait abnormalities. This patient's symptoms are not consistent with cervical myelopathy.

Cervical radiculopathy is caused by disk herniation or bony degeneration causing compression of adjacent nerve roots; it is characterized by neck pain associated with radiating arm pain and paresthesias that follow a dermatomal distribution. On examination, affected patients frequently have reproduction of their pain with the Spurling test (examiner bends the patient's head to the affected side while extending the neck and applying a downward pressure on the top of the head). Symptoms can be improved by holding the patient's hand on the affected side above the patient's head 

(shoulder abduction test). This patient's presentation is not consistent with cervical radiculopathy.

Whiplash-associated neck pain is a poorly understood entity that refers to cervical sprain that develops in the setting of trauma, such as a car accident, which produces an abrupt flexion/extension movement of the cervical spine. Typical symptoms include persistent severe pain, spasm, loss of range of motion in the neck, and occipital headache. Because this patient's neck pain did not result from direct abrupt flexion/extension trauma, it would be incorrect to classify it as whiplash-associated neck pain.

300

An 84-year-old woman in hospice care is evaluated for “death rattle” that is disturbing to family members. She is in the active phases of dying, and her family is distressed by her noisy respiratory secretions; they are worried that she is choking. Medications are haloperidol, hydromorphone, lactulose, and acetaminophen.

On physical examination, respiration rate is 12/min. She is not responsive but does not appear uncomfortable. Extremities are cool. There are oropharyngeal secretions that produce a rattling and gurgling sound with inspiration.

Which of the following is the most appropriate initial management?

A Atropine ophthalmic drops given sublingually

B Glycopyrronium

C Scopolamine patch

D Suctioning by catheter 

E Symptom explanation and reassurance

Answer & Critique Correct Answer: E

Educational Objective: Manage audible oropharyngeal secretions in a patient at the end of life.

Key Point

Audible posterior oropharyngeal secretions (“death rattle”) are common at the end of life and are best managed with family education and reassurance.

This patient has audible posterior oropharyngeal secretions, which are most appropriately managed with family education and reassurance. Although several studies suggest that respiratory distress is not typically associated with these secretions, caregivers are often concerned by what is commonly referred to as the “death rattle.” The first steps in management include caregiver education and anticipatory guidance. Additionally, repositioning often allows secretions to drain without pharmacologic intervention. Mouth hygiene with a sponge swab may also be helpful.

Current literature does not support the routine use of antimuscarinic drugs in the treatment of death rattle. A 2014 literature review acknowledged that death rattle leads to distress in both relatives and professional caregivers; however, its impact on patients is unclear, and medical therapy is unproven. Studies involving atropine, glycopyrronium, scopolamine, hyoscine butylbromide, and/or octreotide were reviewed, and only one study used a placebo group. There is currently no evidence that the use of any antimuscarinic drug is superior to no treatment. In addition, the use of anticholinergic agents in patients who are awake can lead to undesirable symptoms, such as dry mouth and urinary retention.

Suctioning by catheter should be avoided in managing end-of-life secretions unless the secretions are causing the patient obvious respiratory distress or cough. Suction catheters can cause local trauma.

400

A 77-year-old woman is seen for a preoperative medical evaluation before resection of the sigmoid colon for recurrent diverticulitis scheduled 5 days from now. She has nonvalvular atrial fibrillation and is receiving long-term warfarin, without a history of bleeding complications. She has no history of stroke, transient ischemic attack, or intracardiac thrombus. History is also significant for hypertension. Medications are warfarin, chlorthalidone, and metoprolol.

The physical examination, including vital signs, is normal.

The INR measurement is 2.3. Calculated CHADS2 score is 2, and CHA2DS2-VASc score is 4.

In addition to withholding warfarin before surgery, which of the following is the most appropriate management of this patient's perioperative anticoagulation?

A Begin aspirin, 81 mg/d

B Begin enoxaparin when the INR drops below 2.0

C Begin unfractionated heparin when the INR drops below 2.0

D No additional interventions

Answer & CritiqueCorrect Answer: D

Educational Objective: Manage perioperative anticoagulation in a patient receiving warfarin.

Key Point

In patients on warfarin who are undergoing surgery, bridging anticoagulation is typically reserved for patients at highest risk for thromboembolism.

The most appropriate management of this patient's preoperative anticoagulation is to withhold warfarin without bridging anticoagulation. Anticoagulant therapy increases the risk for perioperative hemorrhage and should be discontinued in most patients before surgery. Bridging anticoagulation is the administration of therapeutic doses of short-acting parenteral therapy, usually heparin, when anticoagulant therapy is being withheld during the perioperative period in patients with elevated thrombotic risk. This patient is undergoing a procedure associated with elevated bleeding risk, and she has no history of stroke, transient ischemic attack (TIA), or intracardiac thrombus. Therefore, the risks of bridging anticoagulation outweigh the thrombotic risk, and the warfarin should be withheld without bridging anticoagulation.

There is no role for aspirin in bridging anticoagulation. In patients with normal kidney function who require bridging anticoagulation, low-molecular-weight heparin is the agent of choice.

In 2019, the American Heart Association/American College of Cardiology/Heart Rhythm Society updated their 2014 guideline on the management of atrial fibrillation. For patients with atrial fibrillation without a mechanical heart valve, the updated guideline recommends that decisions about bridging therapy should balance the risk for stroke with the risk for bleeding. Bridging is typically reserved for patients at highest risk for thromboembolism. The 2018 American College of Chest Physicians guideline on antithrombotic therapy for atrial fibrillation recommends forgoing bridging in patients with atrial fibrillation on warfarin who do not have a mechanical valve and are otherwise not at high risk for thromboembolism. This patient has no additional risk factors for thromboembolism other than chronic atrial fibrillation, and perioperative bridging is not required.

500

A hospital system's initial analysis of costs related to prolonged hospital stays revealed that surgical wound infections account for a large proportion of costs. Assessment of the surgical data for the hospital showed that the postoperative wound infection rate is 19%.

Which of the following is the most appropriate tool to assist in reducing postoperative wound sepsis at this institution?

A Clinical audit

B Control chart

C Lean model

D Model for Improvement

Answer & CritiqueCorrect Answer: D

Educational Objective: Identify an appropriate quality improvement model to reduce postoperative wound infection.

Key Point

The Model for Improvement relies on identifying a goal to be accomplished with a change, determining how the results of a change will be measured, and deciding on the changes that will bring about an improvement.

The most appropriate tool to assist in reducing postoperative wound sepsis at this institution is the Model for Improvement. The Model for Improvement focuses on achieving specific and measurable results in a specified population. This model relies on identifying a goal to be accomplished with a change, determining how the results of a change will be measured, and deciding on the changes that will bring about an improvement. These changes are tested and implemented using the Plan-Do-Study-Act (PDSA) cycle. PDSA cycles are rapid tests of improvement, and additional PDSA cycles are completed until the desired results are achieved. A medical center, for example, may set the specific goal of decreasing central line–associated bloodstream infections and use the PDSA cycle to rapidly implement and assess the impact of changes, such as using a central line bundle.

A clinical audit involves measuring current practices against desirable outcomes, which are usually guideline based. Feedback is often provided at the individual level. The audit can identify deviations from desired care (for example, surgical infection rate) but does not establish a goal, an intervention, or a metric to gauge the success of the intervention for the purposes of systematically improving care.

A control chart is a commonly used quality improvement tool. Control charts graphically display variation in a process over time and can help determine whether variation is related to a predictable or unpredictable cause. Control charts can additionally be used to determine whether an intervention has had a positive change. This tool could be useful in measuring change but does not involve goal setting or selecting and implementing an intervention, which are required elements in quality improvement models.

The Lean model focuses on closely examining a system's processes and eliminating non−value-added activities, or waste, within that system. By using a tool called value stream mapping that graphically displays the steps of a process (and the time required for each step) from beginning to end, inefficient areas (waste) in a process can be identified and addressed. The Lean model would not be particularly helpful in identifying causes of surgical site infection, selecting and implementing an intervention, and measuring the outcome.