Heme
A 27-year-old woman is evaluated for spontaneous bruising. She reports a history of heavy menses since menarche, requiring treatment for iron deficiency anemia. Her mother and maternal uncle also have a history of bleeding. She takes no medications.
On physical examination, vital signs are normal. She has ecchymoses on her extremities, but her skin texture and joint mobility are normal. The remainder of the examination is unremarkable.
Laboratory studies:
Activated partial thromboplastin time: 37 s
Hemoglobin: 11.5 g/dL (115 g/L)
Leukocyte count: 8000/μL (8 × 109/L)
Mean corpuscular volume: 78 fL
Platelet count: 140,000/μL (140 × 109/L)
Prothrombin time: 13 s
Factor VIII: 40%
The platelet function testing result is abnormal.
Which of the following is the most likely diagnosis?
A. Ehlers-Danlos syndrome
B. Hemophilia A carrier
C. Immune thrombocytopenic purpura
D. von Willebrand disease
Answer: D
Diagnose von Willebrand disease.
Key Points
The most likely cause of this patient's bruising and menorrhagia is von Willebrand disease (vWD) (Option D). vWD, the most common hereditary bleeding disorder, is caused by deficiency or ineffectiveness of von Willebrand factor (vWF). vWF promotes platelet adhesion and functions as a protective carrier protein for factor VIII, so a mild secondary decrease in factor VIII level occurs in patients with vWD. vWF deficiency leads to mucocutaneous bleeding that mimics thrombocytopenia. Menorrhagia and bleeding after minor procedures such as dental extraction or tonsillectomy are common manifestations. As in typical cases of vWD, this patient was young at the onset of bleeding symptoms and has a family history of bleeding. vWD is an autosomal-dominant disease and can affect men and women, so her family history is also consistent with this diagnosis. Although the activated partial thromboplastin time may be prolonged or normal, an abnormal platelet function testing result would suggest vWD, making this a useful initial evaluation tool. The diagnosis is confirmed by finding a reduction in von Willebrand antigen (quantitative analysis) and reduced vWF ristocetin cofactor activity (a measurement of the functional affect).
Ehlers-Danlos syndrome (EDS) describes a group of rare genetic disorders affecting connective tissue and characterized by one of several features, including skin hyper-elasticity, skin fragility, and joint hypermobility, all of which are absent in this patient. Bruising can be a common symptom of EDS; however, EDS would not explain the mucocutaneous bleeding pattern or the laboratory abnormalities in this patient (Option A).
Although a factor VIII level of 40% can be seen in carriers of hemophilia A, the patient's family history is inconsistent with this diagnosis (Option B). Hemophilia A has an X-linked recessive pattern of inheritance, with men being affected and women remaining asymptomatic carriers. Platelet function testing would be normal in patients with hemophilia A.
Immune thrombocytopenic purpura is associated with a low platelet count but not a qualitative platelet abnormality (Option C). The platelet count is normal.
A 37-year-old woman is evaluated in the emergency department for fever 1 week after her second cycle of chemotherapy for breast cancer. She has no focal symptoms, is otherwise healthy, and takes no medications. The patient lives with her partner 20 minutes from the hospital.
On physical examination, temperature is 38.3 °C (101 °F); other vital signs are normal. She appears well. There is a healed right mastectomy incision, and the left chest port is in place without erythema or tenderness.
Laboratory studies show a leukocyte count of 1,600/µL (1.6 × 10 9/L) with an absolute neutrophil count of 600/μL (0.6 × 109/L), hemoglobin level of 11.1 g/dL (111 g/L), and platelet count 167,000/µL (167 × 10 9/L). Urinalysis and basic metabolic panel are normal. Blood cultures are obtained.
Chest radiograph is normal.
Which of the following is the most appropriate treatment for this patient?
A. Begin cefepime; admit the patient
B. Begin cefepime and gentamicin; admit the patient
C. Begin ciprofloxacin and amoxicillin/clavulanic acid; discharge the patient home
D. Discharge the patient home with close follow-up
Answer: C
Treat low-risk neutropenic fever in an outpatient.
Key Points
The most appropriate treatment is to begin ciprofloxacin and amoxicillin/clavulanic acid and discharge the patient home (Option C). Selected patients with fever and neutropenia can be managed as outpatients. If the patient is compliant, uncomplicated, hemodynamically stable, does not have significant comorbidities, has no known increased risk to be harboring resistant organisms, and has an anticipated short duration of neutropenia, outpatient management is an option. Published criteria for risk stratification for outpatient management include the Multinational Association for Supportive Care in Cancer index, Talcott's rules, or Clinical Index of Stable Febrile Neutropenia. Published criteria for outpatient management include (1) residence ≤1 hour or ≤30 miles (48 km) from the clinic or hospital, (2) patient's primary care physician or oncologist agrees to outpatient management, (3) ability to comply with logistic requirements, including frequent clinic visits, (4) family member or caregiver at home 24 hours/day, (5) access to a telephone and transportation 24 hours/day, and (6) no history of noncompliance with treatment protocols. Patients should have frequent follow-up by phone or in the office to reassess their status.
Cefepime (Option A) is an antipseudomonal β-lactam that is often used as empiric parenteral therapy for febrile neutropenia in hospitalized patients. However, studies have demonstrated that there is a similar level of safety and efficacy with oral versus intravenous regimens as initial empiric therapy for the treatment of low-risk febrile neutropenia.
Clinical studies have also demonstrated that there is no better survival or therapeutic success but rather an increased risk of toxicity from adding an aminoglycoside to a broad-spectrum β-lactam, such as cefepime (Option B), in the treatment of febrile neutropenia.
Given the patient's neutropenia and documented fever, observation without antibiotics (Option D) would not be appropriate, as patients with fever and neutropenia can become quite ill rather quickly without antibiotics.
A 28-year-old woman is evaluated for a 2-month history of left-sided neck and shoulder pain and paresthesia in her left arm from her fingers to her shoulder. Her symptoms worsen with overhead arm activity. She takes no medications.
On physical examination, she has full range of motion in her left neck, shoulder, elbow, and wrist. Muscle bulk, tone, and strength in the upper extremities are normal bilaterally. Neurologic examination reveals normal reflexes and sensation in the upper extremities bilaterally. Upper extremity pulses are full and equal. There is no cyanosis, swelling, or edema.
Which of the following is the most likely diagnosis?
A. Arterial thoracic outlet syndrome
B. Cervical radiculopathy
C. Neurogenic thoracic outlet syndrome
D. Venous thoracic outlet syndrome
C. Diagnose neurogenic thoracic outlet syndrome
This patient probably has neurogenic thoracic outlet syndrome (nTOS) (Option C). nTOS is caused by compression of the nerve roots of the brachial plexus in the interscalene triangle of the neck (bordered by the anterior and middle scalene muscles and the first rib). Young, thin, active women with repetitive overhead stress to an upper extremity are most likely to experience nTOS, which typically presents with nonradicular and anatomically widespread symptoms (numbness, paresthesia, and pain) affecting the arm, neck, and shoulder. Atrophic weakness of hand and arm muscles can occur but is typically a late manifestation. Neck rotation, head tilting, arm abduction, and arm external rotation may provoke symptoms in some patients. Electrodiagnostic studies are frequently normal, and imaging may reveal an anomalous cervical rib, which predisposes to this condition. First-line therapy for nTOS includes physical therapy focusing on improving posture and strengthening the shoulder girdle muscles.
Arterial TOS (aTOS) (Option A) is caused by subclavian artery compression, with or without thrombosis; it usually occurs in the presence of an anomalous cervical rib. Symptoms include arm or hand pain (which may be exertional), weakness, paresthesia, coolness, and pallor. Some patients may have blood pressure discrepancies between the arms or diminished pulses in the affected extremity. On occasion, a bruit may be auscultated over the ipsilateral subclavian artery. This patient has no evidence of the arterial insufficiency that is characteristic of aTOS.
Cervical radiculopathy (Option B) often presents with constant neck and shoulder pain in a radicular distribution. The pain is aggravated by the position of the neck. The wide anatomic distribution and nonradicular nature of this patient's symptoms make cervical nerve root compression less likely.
Venous TOS (vTOS) (Option D) is caused by compression of the subclavian vein within the costoclavicular junction where it passes anterior to the anterior scalene muscle. vTOS is characterized by substantial upper extremity swelling as well as pain in the upper extremity, chest, and shoulder. Cyanosis may be present. vTOS is most common in young, active men and often affects the dominant upper extremity. The absence of swelling or cyanosis and the presence of paresthesia make vTOS unlikely in this patient.
Key Point
A 74-year-old woman is evaluated during a follow-up visit for hypertension and slowly progressive chronic kidney disease. She reports that she feels well and has no symptoms. Medications are atenolol, cholecalciferol, hydralazine, nifedipine, simvastatin, and sodium bicarbonate.
On physical examination, blood pressure is 130/70 mm Hg; other vital signs are normal. The remainder of the examination is unremarkable.
Laboratory studies show an estimated glomerular filtration rate of 28 mL/min/1.73 m2.
Which of the following is the most appropriate management?
A. Arteriovenous fistula placement evaluation
B. Dialysis initiation
C. Kidney transplant evaluation
D. Renal replacement therapy education
Answer: D
Prepare a patient for end-stage kidney disease by providing renal replacement therapy education.
Key Point
This most appropriate management is renal replacement therapy (RRT) education (Option D). This patient with slowly progressive chronic kidney disease (CKD) is at borderline stage G3/G4. When estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2, the patient should be referred for RRT education. It is appropriate to begin the education process for the patient to learn about RRT options, including in-center and home hemodialysis, peritoneal dialysis, kidney transplantation, and non-dialytic medical management, to make an informed decision in the future. An RRT education session empowers the patient to make decisions regarding venous access or preemptive kidney transplant to ensure a controlled initiation of RRT. It also helps prevents the risk for initiating dialysis emergently. Patients who receive preparatory RRT education before they are diagnosed with end-stage kidney disease are more likely to select a home modality for RRT, be listed for a kidney transplant, or receive a preemptive kidney transplant and may have a mortality benefit compared with patients who do not receive similar education.
Evaluation for arteriovenous fistula (AVF) placement (Option A) is indicated after the patient has learned about RRT options and chooses to receive hemodialysis in the future. After this decision, the patient is referred for arm-access evaluation. Patients with suitable anatomy should have AVF placement well in advance of anticipated ESKD to allow adequate maturation of the vein to allow robust blood flow needed for hemodialysis.
For patients amenable to dialysis (Option B), studies demonstrate no benefit in starting it in asymptomatic patients or at a specific eGFR cutoff compared with watchful waiting and initiating dialysis for symptoms or metabolic abnormalities that are refractory to medical treatment.
Patients should be referred to a kidney transplant center for evaluation (Option C) when the eGFR is 15 to 29 mL/min/1.73 m2. Early referral is important because preemptive kidney transplants (transplants before needing dialysis) are associated with improved clinical outcomes compared with receiving a transplant after starting dialysis. Early referral also allows adequate time to identify suitable living donors; if no living donor is available, early listing is essential to begin the waiting process for a deceased-donor kidney. Referral for evaluation will be appropriate if this patient selects this mode of RRT following RRT education.
A 48-year-old man is evaluated for recurrent pericarditis. Six months ago, he had acute pericarditis treated with ibuprofen and colchicine. His symptoms resolved completely within 3 weeks of initiation of therapy. Evaluations for an infectious cause and connective tissue disease were negative. The patient's symptoms recurred after ibuprofen was tapered over 1 month with continuation of colchicine. Ibuprofen was re-initiated at a high dose with resolution of symptoms and tapered over a 2-month period. His current symptoms began 24 hours ago. Currently, his only medication is colchicine.
On physical examination, temperature is 38.0 °C (100.4 °F); other vital signs are normal. Pulsus paradoxus of 10 mm Hg is present. There is no jugular venous distention. The lungs are clear to auscultation. A friction rub is heard at the left sternal border and apex.
ECG shows normal sinus rhythm with widespread ST-segment elevation of 0.5 to 1.0 mm. Echocardiogram shows a small circumferential pericardial effusion (diastolic echo-free space, 3 mm) without evidence of tamponade.
Which of the following is the most appropriate treatment?
A. Anakinra
B. Colchicine and intravenous immune globulin
C. Ibuprofen
D. Ibuprofen, colchicine, and prednisone
Answer: D
Treat recurrent pericarditis.
Key Point
The most appropriate treatment is triple therapy with an NSAID, such as ibuprofen; colchicine; and a glucocorticoid, such as prednisone (Option D). This patient meets the definition of recurrent idiopathic pericarditis, having a documented first episode of acute pericarditis followed by a recurrent episode after a symptom-free interval of 4 to 6 weeks. This patient had a favorable response to initial treatment with an NSAID and colchicine, followed by recurrent symptoms after tapering standard therapy on two different occasions. Recurrence occurs in 15% to 30% of pericarditis cases, and the recurrence rate is higher when initial therapy does not include colchicine. In patients initially treated only with NSAIDs, it would be reasonable to use the combination of NSAIDs and colchicine to treat a recurrence. In patients initially treated with both colchicine and NSAIDs, the addition of a low to moderate dose of prednisone is reasonable to achieve better control of symptoms. When patients re-present with pain but without other evidence of pericarditis, cardiac CT or MRI and measurement of C-reactive protein level may inform the decision of whether to add glucocorticoids. Infectious diseases, including tuberculosis, must be excluded before starting a glucocorticoid. Glucocorticoids are not recommended as first-line therapy for acute pericarditis.
The interleukin-1 receptor antagonist anakinra (Option A) has shown benefit in small trials for treatment of colchicine-resistant, glucocorticoid-dependent recurrent pericarditis, but it is not, at present, FDA approved for this use. Consideration should be given to initiating rilonacept, an FDA-approved interleukin-1 trap that demonstrated early and sustained relief of signs and symptoms of inflammation and significant reduction in the risk for recurrent pericarditis.
Intravenous immune globulin (Option B) has been used with some success to treat pericarditis that recurs despite combination therapy including prednisone. For this patient, glucocorticoid treatment should precede consideration of intravenous immune globulin.
Ibuprofen monotherapy without colchicine (Option C) may be considered to treat an initial episode of acute pericarditis, but it is unlikely to be effective in patients with recurrent pericarditis.
A 48-year-old woman is evaluated for easy bruising. She has no history of gingival bleeding, menorrhagia, or bleeding following procedures. Medical history is notable only for systemic lupus erythematosus. Medications are prednisone, hydroxychloroquine, and NSAIDs as needed.
On physical examination, vital signs and examination findings are normal.
Laboratory studies show an activated partial thromboplastin time of 38 seconds, platelet count of 190,000/μL (190 × 109/L), and prothrombin time of 12.5 seconds.
Which of the following is the most appropriate diagnostic test?
A. Factor VIII inhibitor titer
B. Factor XI level
C. Factor XII level
D. Mixing study
Answer: D
Evaluate a patient with a prolonged activated partial thromboplastin time.
Key Point
Evaluation of a prolonged activated partial thromboplastin time (aPTT) begins with a mixing study in which equal parts of a patient's plasma and control plasma are combined; the aPTT assay is performed immediately following the mix and again following an incubation period (Option D). The immediate mixing study will not correct in the presence of most factor inhibitors. Some inhibitors, specifically factor VIII inhibitor, will correct immediately but will not correct after incubation. Therefore, mixing study results should always be reported immediately and after incubation. The result of the mixing study for this patient will help to determine the general cause of the prolonged aPTT (factor deficiency versus inhibitor) and to guide the subsequent, more specific evaluation. Because this patient has an autoimmune disorder, a lupus anticoagulant might explain the prolonged aPTT without evident bleeding; it is characterized by a prolonged aPTT that fails to correct when mixed with control plasma. Patients with a lupus anticoagulant may be asymptomatic; however, approximately 30% of patients with a lupus anticoagulant may develop arterial and/or venous thrombosis.
Factor VIII inhibitors can arise in the setting of hemophilia A, following exposure to factor VIII replacement therapy, or can develop spontaneously in the setting of autoimmune disease, malignancy, pregnancy, and certain medications. Weak, low-titer inhibitors may not cause spontaneous bleeding. The presence of a factor VIII inhibitor is suspected when a mixing study demonstrates immediate correction of the prolonged aPTT after mixing but subsequent prolongation of the aPTT following incubation. Evaluation of factor VIII levels and inhibitor titers would be prompted only if this sequence of events is demonstrated on the mixing study (Option A).
Factor XI deficiency can result in a bleeding diathesis because factor XI is activated by thrombin. A mixing study in a patient with factor XI deficiency would result in complete correction of the prolonged aPTT that is sustained after incubation. Factor XII activity is reflected in the aPTT but is not of clinical importance in hemostasis. Factor XII deficiency is a rare autosomal-recessive condition in which homozygous patients have a markedly prolonged aPTT but no history of excessive bleeding or hemorrhage. In a patient with factor XII deficiency, the mixing study would completely correct the aPTT. These results would prompt measurement of specific factor levels (Options B, C).
A 27-year-old woman is evaluated following a recently confirmed diagnosis of early-stage nodular sclerosing Hodgkin lymphoma. She has had no fevers, night sweats, or weight loss. Medical history is unremarkable, and she takes no medications.
On physical examination, vital signs are normal. There is a healing surgical scar over the mid left neck. A 3- × 2-cm left supraclavicular lymph node is palpable. There is no other adenopathy and no hepatosplenomegaly.
Complete blood count is normal. Erythrocyte sedimentation rate is 22 mm/h.
CT and PET scans detect left cervical and supraclavicular adenopathy as well as an anterior mediastinal mass measuring 5 × 4 cm. No infradiaphragmatic disease is noted.
Which of the following is the most appropriate management?
A. Checkpoint inhibitor immunotherapy
B. Combination chemotherapy followed by autologous hematopoietic stem cell transplantation
C. Combination chemotherapy followed by radiation therapy
D. Radiation therapy alone
Answer: C
Treat early-stage Hodgkin lymphoma.
Key Points
For this patient with early-stage Hodgkin lymphoma, the most appropriate treatment options would be combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine followed by radiation therapy (Option C). Unfavorable prognostic factors for early-stage Hodgkin lymphoma include the presence of a large mediastinal mass, an elevated sedimentation rate, involvement of multiple nodal sites, extranodal involvement, age 50 years and older, or massive splenic disease. The combination of chemotherapy and irradiation is associated with a high rate of cure in early-stage disease, even with adverse prognostic features. Using both modalities in combination has allowed for high cure rates while using shorter courses of chemotherapy (two to four cycles) and lower cumulative doses of radiation given to smaller fields, thus minimizing the potential for long-term toxicities. Chemotherapy alone could also be an appropriate option for this patient, avoiding irradiation entirely, if she has a complete metabolic response by interim PET/CT after two to three cycles of treatment (risk-adapted therapy). Avoiding radiation therapy may be associated with a slightly higher risk of relapse but avoids the risk of late radiation therapy–induced toxicities.
Treatment with checkpoint inhibitors such as nivolumab and pembrolizumab (Option A) may be considered for patients experiencing a second or later relapse and those who relapse after autologous hematopoietic stem cell transplantation. Combination chemotherapy and irradiation, or in some instances, chemotherapy alone is the preferred first-line therapy and is associated with nearly a 75% cure rate.
Chemotherapy with ifosfamide, carboplatin, and etoposide followed by autologous hematopoietic stem cell transplantation (Option B) is an option for patients with relapsed, refractory Hodgkin lymphoma, but this is a salvage approach and is not used as first-line treatment.
Although radiation therapy alone (Option D) can be curative for early-stage classical Hodgkin lymphoma, the cure rate is higher with the addition of chemotherapy. Furthermore, older studies using radiation therapy alone, with larger fields and higher doses, were associated with an increased risk of late second malignancies as well as organ (cardiac, pulmonary, thyroid) dysfunction. Thus, essentially all patients with early-stage Hodgkin lymphoma currently receive chemotherapy as part of their treatment.
A 62-year-old woman is evaluated for a change in her abdominal and pelvic pain symptoms. The patient has been followed for 3 years for medically unexplained symptoms. Her typical symptoms have included chronic pelvic pain of unknown cause and migrating upper abdominal pain. An extensive evaluation, including endoscopy, advanced imaging, and laboratory evaluation, has been negative. Her symptoms have been stable for the past 2 years until recently. Her new abdominal symptom is central boring pain that has been present for 6 weeks and is associated with anorexia, diarrhea, and a 2-kg (4.4-lb) weight loss. She is currently taking no medications.
On physical examination, vital signs are normal. The mid-abdomen is tender to deep palpation.
Which of the following is the most appropriate initial management?
A. CT of the abdomen and pelvis
B. Depression screening
C. Exploration of psychosocial stressors
D. Nortriptyline
Answer: A
Evaluate new symptoms in a patient with medically unexplained symptoms.
Key Point
The most appropriate management is CT of the abdomen and pelvis (Option A). This patient's chronic gastrointestinal symptoms have changed significantly. Further evaluation with imaging is warranted. In patients with medically unexplained symptoms (MUS), each presenting symptom merits a relevant history and physical examination. In most cases, previous records should be reviewed before the evaluation is repeated or extended unless the patient's condition has significantly changed. If new symptoms arise or symptoms change, clinicians should respond empathically and perform an appropriately thorough investigation. This patient has new symptoms after a period of relative stability. The new symptoms are associated with a significant “red flag” of weight loss and should not be dismissed. Advanced imaging is a reasonable starting point in the evaluation of this patient.
Patients with MUS often have mental health comorbidities, including a high prevalence of depression and anxiety. Screening for these disorders (Option B) is helpful because appropriate treatment often improves patient symptoms and function. However, onset of new abdominal pain after a period of stability associated with abdominal tenderness to palpation and weight loss signals the possibility of a condition other than depression, and additional investigation is required.
A tenet of a healing therapeutic relationship is that the physician helps the patient explore the relationship between psychological stressors and symptoms (Option C), particularly symptoms that appear to be functional (i.e., without a clear understanding of the medical basis for the symptoms). This patient's new symptom is probably not functional given the history and physical findings, and a direct approach at finding an underlying cause is of highest priority.
Nortriptyline (Option D) is often prescribed for patients with chronic pain syndromes, including fibromyalgia, nonulcer dyspepsia, and irritable bowel syndrome. However, this patient will benefit from a careful evaluation of the new pain before symptom-directed therapy is prescribed.
A 43-year-old man is evaluated during a routine follow-up visit for end-stage kidney disease due to IgA nephropathy. He received a living-donor related kidney transplant 5 years ago. He is asymptomatic. Medical history is also significant for hypertension. Medications are prednisone, mycophenolate mofetil, tacrolimus, lisinopril, metoprolol, and atorvastatin.
All physical examination findings, including vital signs, are normal.
Laboratory studies show a serum creatinine level of 0.8 mg/dL (70.7 µmol/L) and a fasting blood glucose level of 99 mg/dL (5.5 mmol/L).
Which of the following is the most appropriate screening test at this time?
A. Colonoscopy
B. Low-dose chest CT
C. Oral glucose tolerance test
D. Skin examination
Answer: D
Screen for skin cancer in a kidney transplant recipient.
Key Points
The most appropriate screening test to perform next is a skin examination (Option D). This patient, who is at increased risk for multiple types of skin cancer, should be referred to a dermatologist or a clinician with special expertise for annual screening; screening frequency is increased for patients who have a history of skin cancer. Kidney transplant recipients are at increased risk for various complications due to their original underlying end-stage kidney disease and the use of chronic immunosuppressive medications, which may be related to risks for altered immune surveillance or idiosyncratic medication side effects. Kidney transplant recipients are at increased risk for several other malignancies, including renal cell carcinoma, colon cancer, lung cancer, thyroid cancer, anogenital cancers, and posttransplant lymphoproliferative disease. These patients are also at increased risk for cardiovascular disease, and those treated with glucocorticoids, calcineurin inhibitors, and mTOR inhibitors are at increased risk for new-onset diabetes after transplant (NODAT).
The U.S. Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer in asymptomatic adults aged 45 to 75 years. The USPSTF supports using the test that is most likely to result in completion of screening. Options include colonoscopy (Option A), flexible sigmoidoscopy, CT colonography, stool-based testing, and combination of stool-based testing and flexible sigmoidoscopy. This patient should be screened for colon cancer beginning at 45 years of age.
A low-dose chest CT (Option B) to screen for lung cancer is not indicated. Although patients on immunosuppressive medications are at increased risk for various cancers, screening for non-skin cancers should follow guidelines for the general population. The criteria for screening include those who are aged 55 to 74-80 years (guidelines differ on ages to discontinue screening), have at least a 30-pack-year smoking history, and are current smokers or have quit within the last 15 years.
Kidney transplant recipients are at risk for NODAT. Posttransplant fasting glucose and symptoms should be monitored. Fasting glucose is monitored more frequently in the first year after transplant and then annually in the absence of symptoms to suggest hyperglycemia. The diagnosis of NODAT is made based on the same criteria as that for the general population. An oral glucose tolerance test (Option C) is not indicated for this patient with a normal fasting blood glucose.
An 84-year-old man is evaluated before hospital discharge following an exacerbation of heart failure. He has an implantable cardioverter-defibrillator. Medications are lisinopril, furosemide, carvedilol, and spironolactone. During hospitalization, the patient received intravenous furosemide at a dosage twice that of his home oral dosage.
On physical examination, vital signs are normal. BMI is 28. Central venous pressure is not elevated. There is no S3, and there are no pulmonary crackles.
Serum creatinine level has returned to the baseline level, and electrolytes are normal.
Echocardiogram from this hospitalization shows ejection fraction of 25% with left ventricular end-diastolic dimension of 72 mm.
Which of the following is most likely to prevent early hospital readmission in this patient?
A. Echocardiography in 3 months
B. Follow-up office visit in 30 days
C. Follow-up telephone call in 2 days
D. Decrease in furosemide to original home dosage
Answer: C
Prevent heart failure readmission with early follow-up.
Key Point
A telephone call within 2 to 3 days (Option C) is recommended to prevent this patient's early readmission to the hospital. The 2019 American College of Cardiology expert consensus decision pathway for patients hospitalized with heart failure notes that up to 25% of patients are readmitted with heart failure within 30 days of the index hospitalization. Two key elements are associated with a successful transition from hospital to home: a follow-up phone call within 2 to 3 days of discharge and an office visit within 7 to 14 days of hospital discharge. The purpose of the follow-up phone call is to address signs of congestion, provide education and review adherence to the medication regimen, and confirm follow-up appointments and adequate transportation. The expert consensus decision pathway recommends a standardized approach to the follow-up telephone call, including use of a checklist to help organize the call.
For patients with an initial diagnosis of heart failure, it is appropriate to repeat echocardiography in 3 months (Option A) to assess the effect of medical therapy on ejection fraction and need for an implantable cardioverter-defibrillator (ICD). Echocardiography was performed in this patient in the hospital, and for a patient with known low ejection fraction and an ICD, there is no reason for echocardiography so soon unless there is a clinical change.
The first postdischarge appointment focuses on changes in clinical status, patient education, medication review and adjustment of dosages, and identification and correction of issues that might lead to worsening of heart failure and readmission. The recommended timing of the first follow-up visit is within 7 to 10 days of hospital discharge; 30 days (Option B) is too late.
Inadequate diuretic dosage is a common cause of heart failure readmissions. This patient required an increased furosemide dosage to achieve adequate diuresis. This suggests that the previous home diuretic dosage was inadequate, and an increase of at least double that dosage should be considered. Restarting the previous home dosage (Option D) might be considered for a patient who did not adhere to the medication regimen before hospitalization.
A 61-year-old woman with recent SARS-CoV-2 exposure is hospitalized for hypoxemic respiratory failure; she is also diagnosed with thrombocytopenia. Medical history is otherwise unremarkable, and she takes no medications.
On physical examination, temperature is 38.7 °C (101.7 °F), blood pressure is 105/80 mm Hg, pulse rate is 114/min, and respiration rate is 28/min. Oxygen saturation is 89% breathing ambient air. Cardiopulmonary examination reveals bibasilar crackles. She has no petechiae or ecchymoses.
Laboratory studies show a hemoglobin level of 10.6 g/dL (106 g/L), leukocyte count of 11,200/μL (11.2 × 109/L), and platelet count of 23,000/μL (23 × 109/L).
Ground-glass opacities consistent with SARS-CoV-2 are seen on a chest radiograph, and a SARS-CoV-2 test is positive.
The patient is given supplemental oxygen by nasal cannula, and treatment for severe SARS-CoV-2 is initiated.
Which of the following is the first test to perform in evaluating the patient's thrombocytopenia?
A. ADAMTS13
B. Antiplatelet antibodies
C. Direct antiglobulin test
D. Peripheral blood smear
Answer: D
Confirm thrombocytopenia with a peripheral blood smear.
Key Points
A peripheral blood smear (PBS) should be obtained (Option D). This patient has severe thrombocytopenia in the absence of petechiae, ecchymoses, or other bleeding manifestations. The first step in the evaluation of any patient with thrombocytopenia is to review the PBS and confirm the platelet count. Pseudothrombocytopenia occurs when a patient has antibodies to ethylenediaminetetraacetic acid (EDTA), causing platelets to clump together in vitro. In patients with platelet clumping on the PBS, an accurate count can be obtained from blood drawn in citrate or heparin instead of EDTA. Inaccurate platelet counts may also occur if the platelets are exceptionally large (complete blood count machine may count them as erythrocytes) or if erythrocyte fragments (schistocytes) are counted by the machine as if they were platelets (leading to a higher than actual platelet count).
Patients with thrombotic thrombocytopenic purpura (TTP) present with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The presence of MAHA is evidenced by elevated lactate dehydrogenase (LDH) and decreased haptoglobin levels, schistocytes on PBS, and a negative direct antiglobulin test result. If the PBS confirms thrombocytopenia and is positive for schistocytes, and if additional tests confirm the presence of erythrocyte destruction, an ADAMTS13 level less than 10% would support the diagnosis of TTP (Option A). If the PBS demonstrates clumping, repeating the platelet count from blood drawn in citrate or heparin is the next step.
Immune thrombocytopenic purpura (ITP) is a clinical diagnosis made by exclusion of other causes for thrombocytopenia, but even in patients with confirmed thrombocytopenia, antiplatelet antibodies are not helpful diagnostically because they are neither sensitive nor specific in the diagnosis of ITP (Option B). This patient does not have confirmed thrombocytopenia, and any additional testing to evaluate causes of thrombocytopenia are premature until the PBS is examined.
In a patient with anemia and thrombocytopenia, a direct antiglobulin test would be useful in evaluating for possible Evans syndrome (autoimmune hemolytic anemia and ITP) (Option C). However, before this diagnosis is entertained, thrombocytopenia must first be verified. A PBS may also support the diagnosis of autoimmune hemolytic anemia by the presence of spherocytes. If hemolysis is a consideration, supporting evidence for erythrocyte destruction should be obtained, including a reticulocyte count to evaluate for reticulocytosis, serum LDH, free hemoglobin level, and a urinalysis for hemoglobinuria. If erythrocyte destruction is confirmed, a direct antiglobulin test should be obtained.
A 66-year-old man is evaluated for increased confusion and lethargy over the past 2 days, as well as nausea and vomiting. He has also had diffuse bone pain that began 6 weeks ago and has worsened over the past month. His medical history is otherwise unremarkable, and he takes no medications.
On physical examination, temperature is 36.4 °C (97.6 °F), blood pressure is 110/60 mm Hg, pulse rate is 110/min, and respiration rate is 16/min. He is somnolent but can be aroused. Mucous membranes are dry, and he has decreased skin turgor. Cardiopulmonary examination is normal.
Results of laboratory studies show an albumin level of 3.8 g/dL (38 g/L), calcium level of 14.8 mg/dL (3.7 mmol/L), and creatinine level of 2.5 mg/dL (221 µmol/L).
Which of the following is the most appropriate initial management?
A. Denosumab
B. Intravenous isotonic saline and calcitonin
C. Intravenous isotonic saline and furosemide
D. Zoledronic acid
Answer: B
Treat hypercalcemia of malignancy.
Key Points
This patient has hypercalcemia, likely due to malignancy, and should be treated urgently with intravenous isotonic saline and calcitonin (Option B). Hypercalcemia of malignancy occurs in 20% to 30% of patients with advanced cancer. It is most frequent in patients with myeloma and cancer of the lung, breast, kidney, head, and neck. Patients with severe or symptomatic hypercalcemia should receive isotonic saline volume expansion, which will increase renal perfusion and urine calcium excretion. The administration of isotonic saline at an initial rate of 200 to 300 mL/hour that is then adjusted to maintain the urine output at 100 to 150 mL/hour is a reasonable goal. Calcitonin increases kidney excretion of calcium and decreases bone resorption; it can decrease calcium within several hours in responsive patients. Tachyphylaxis to calcitonin may appear after 24 to 48 hours, so therapy is usually discontinued after this time period. This patient has an elevated serum creatinine level, which is a common complication of hypercalcemia, and intravenous isotonic saline may improve renal function as well.
Denosumab (Option A), a receptor activator of nuclear factor κB ligand inhibitor, is very effective in reducing serum calcium levels, but its effect is slower than isotonic saline and calcitonin, and it would not be the first treatment used in this situation. It has typically been reserved for patients who do not respond to bisphosphonate therapy, although some expert guidelines now recommend it over bisphosphonates. Denosumab can be used when bisphosphonate therapy is contraindicated, such as in patients with kidney failure. Patients receiving denosumab should be monitored for the subsequent development of hypocalcemia.
Furosemide (Option C), a loop diuretic, is not recommended unless kidney failure or heart failure is present, in which case volume expansion should precede the administration of furosemide to avoid hypotension and further kidney injury.
Bisphosphonates (Option D) are effective medications for correcting hypercalcemia of malignancy and are frequently used as a key part of management. However, their maximum effect occurs in 2 to 4 days, so they are usually given in conjunction with intravenous isotonic saline. Bisphosphonates are contraindicated in the setting of kidney failure.
A 28-year-old woman is evaluated in the emergency department for an episode of syncope. Before the syncopal event, she was standing motionless in a warm environment for several minutes, and then she felt warm, dizzy, and nauseated. She lost consciousness for less than 30 seconds. She experienced no trauma during the event and had no confusion afterward. She has previously experienced presyncope at work while standing for long periods of time but had never lost consciousness. She has no medical problems and takes no medications.
On physical examination, vital signs and the remainder of the examination are normal.
An ECG is normal.
Which of the following is the most appropriate treatment?
A. Avoidance of triggers
B. Fludrocortisone
C. Midodrine
D. Propranolol
Answer: A
Treat vasovagal syncope.
Key Points
The most appropriate treatment is education about avoidance of triggers (Option A). This patient probably has vasovagal syncope, which is provoked by noxious stimuli, fear, stress, or heat overexposure and is preceded by a prodrome of warmth, dizziness, and nausea. In cases of vasovagal (reflex) syncope, explaining the diagnosis to the patient is strongly recommended, along with targeted education about avoiding triggers (e.g., prolonged standing, warm environments) and how to cope with noxious events (e.g., blood draws). In addition, physical counterpressure measures, such as squatting and leg crossing, and increased fluid and salt intake can decrease the risk for recurrence of the syncopal event in selected patients.
Fludrocortisone (Option B) has mineralocorticoid activity that increases blood volume through sodium and water retention. Hypertension and hypokalemia are expected adverse effects. Fludrocortisone might be considered for patients with vasovagal syncope not responding to avoidance of triggers and physical counterpressure measures. Studies show a 31% non–statistically significant reduction in recurrent syncope in patients with frequent vasovagal syncope after 2 weeks of therapy. Fludrocortisone is not indicated in this patient who has yet to try more effective means of syncope prevention that are associated with fewer side effects.
Midodrine (Option C) is metabolized to a peripherally active α-agonist that may counter the reduction of sympathetic neural outflow and resultant venous pooling associated with vasovagal syncopal. A meta-analysis suggests that midodrine can reduce recurrent vasovagal syncopal episodes by 43%. However, this patient has yet to try less expensive, and presumably safer, nonpharmacologic options.
Trials of β-blockers for the prevention of vasovagal syncope have, for the most part, been negative. However, some studies have documented benefit with β-blocker therapy in patients aged 42 years or older. It is unlikely that this young patient needs or will respond to β-blocker therapy, such as propranolol (Option D).
A 53-year-old woman is evaluated for an increase in her serum creatinine level. History is significant for long-standing hypertension treated with lisinopril. She reports no changes to her medication regimen during the past year.
On physical examination, blood pressure is 145/92 mm Hg, and pulse rate is 84/min; other vital signs are normal. The remainder of the examination is unremarkable.
Laboratory studies:
Creatinine
1.2 mg/dL (106.1 µmol/L); 6 months ago: 0.7 mg/dL (61.9 µmol/L)
Estimated glomerular filtration rate
>52 mL/min/1.73 m2
Urinalysis
Specific gravity 1.014; pH 5.7; no blood; trace protein
Urine albumin-creatinine ratio
290 mg/g
Ultrasound reveals normal-sized kidneys with increased echogenicity; no hydronephrosis or abnormalities of the collecting system are seen.
Which of the following is the most appropriate management?
A. Obtain kidney biopsy
B. Obtain random urine protein-creatinine ratio
C. Recheck serum creatinine in 3 months
D. Substitute hydrochlorothiazide for lisinopril
Answer: A
Evaluate progressive kidney disease.
Key Point
The most appropriate management is kidney biopsy (Option A) for this patient with a significant decline in kidney function. In addition, this patient has unexplained moderately increased albuminuria and an increase in echogenicity on kidney ultrasound, suggesting a chronic condition. Clinical and laboratory features are often insufficient for definitive diagnosis of kidney disease. Therefore, kidney biopsy may be essential for diagnosis and management. Indications include glomerular hematuria, severely increased albuminuria, acute or chronic kidney disease of unclear cause, and kidney transplant dysfunction or monitoring. In this case, the patient has an elevated serum creatinine level with albuminuria and possible chronic kidney disease without a clear cause. Although further urine and serologic testing will be performed to guide diagnosis, a kidney biopsy will provide definitive diagnosis.
The patient has moderately increased albuminuria (albumin-creatinine ratio of 30-300 mg/g). The urine protein-creatinine ratio will be greater than the urine albumin-creatinine ratio due to the presence of nonalbumin protein and therefore will be in the pathologic range. Therefore, random urine protein-creatinine ratio (Option B) will not add new information in this case.
Because the patient has a significant loss of kidney function, a reassessment of serum creatinine in 3 months (Option C) would not be appropriate and would result in potentially harmful delay in the diagnosis of a treatable disease.
Discontinuation of lisinopril for hydrochlorothiazide (Option D) is not indicated. Due to preferential dilation of the efferent arteriole, the ACE inhibitor lisinopril may reduce glomerular filtration rate and increase serum creatinine; however, this change in serum creatinine will occur within days of drug initiation and then will stabilize. In this case, the serum creatinine increased without a change in dose, suggesting that lisinopril is not the cause of the rising serum creatinine and will not be resolved by discontinuing the drug. In addition, treatment with lisinopril cannot account for the presence of albuminuria.
A 45-year-old woman is evaluated for occasional palpitations. She also has hypertension. Medications are chlorthalidone and diltiazem.
On physical examination, vital signs are normal. Cardiac examination reveals an irregular rhythm. There is a midsystolic click and late systolic murmur at the apex, radiating to the back. There are no signs of heart failure.
An ECG shows atrial fibrillation, with a ventricular rate of 80/min.
A transthoracic echocardiogram shows severe posteriorly directed mitral regurgitation, with a left ventricular ejection fraction of 55% and left ventricular end-systolic dimension of 60 mm. There is severe anterior mitral valve prolapse; hemodynamic measurements indicate severe mitral regurgitation.
Which of the following is the most appropriate next step in management?
A. Cardiac magnetic resonance imaging
B. Surgical mitral valve repair
C. Transcatheter mitral valve repair
D. Transesophageal echocardiography
Answer: B
Treat primary (degenerative) severe mitral regurgitation with surgical mitral valve repair.
Key Points
The most appropriate next step in management is surgical mitral valve repair (Option B). This patient's echocardiogram is consistent with severe mitral regurgitation, defined as an effective regurgitant orifice area of 0.4 cm2 or greater, a regurgitant volume of 60 mL or greater, or a vena contracta of 0.7 cm or greater. The mitral regurgitation is primary (degenerative), as indicated by the patient's midsystolic click and late mitral regurgitation (both seen in mitral valve prolapse) and the demonstration of anterior prolapse by echocardiography. Although the presence of symptoms resulting from severe mitral regurgitation (such as shortness of breath and volume overload) is an indication for intervention, class 1 indications for intervention in asymptomatic patients include a left ventricular (LV) ejection fraction of 60% or less and/or an LV end-systolic dimension of 40 mm or greater. Surgical mitral valve repair is first-line therapy for patients with primary severe mitral regurgitation meeting indications for intervention.
In most cases, transthoracic echocardiography (TTE) provides the data needed for adequate cardiac evaluation of the patient with mitral regurgitation. However, in cases in which TTE image quality is poor, cardiac magnetic resonance (CMR) imaging (Option A) may be of value in mitral regurgitation evaluation. This patient does not have an indication for CMR imaging.
In severely symptomatic patients (New York Heart Association class III or IV) with primary severe mitral regurgitation and high or prohibitive surgical risk, transcatheter mitral valve repair (transcatheter edge-to-edge repair [TEER]) (Option C) is reasonable if mitral valve anatomy is favorable for the repair procedure and the patient's life expectancy is at least 1 year. This patient meets no indication for TEER.
Transesophageal echocardiography (Option D) may be pursued when TTE is insufficient to determine either the exact severity or the mechanism of mitral regurgitation (primary versus secondary); this patient's TTE was sufficient to identify the nature and severity of the mitral regurgitation.
A 38-year-old woman is evaluated 1 week before elective cholecystectomy. Medical history is significant for hemoglobin SS sickle cell disease with approximately one or two vaso-occlusive pain events annually, which are managed in the outpatient setting. Medications are folic acid and oxycodone as needed during pain events.
Laboratory studies show a hemoglobin level of 7.9 g/dL (79 g/L).
Which of the following is the most appropriate perioperative management?
A. Postoperative simple transfusion; target hemoglobin 10 g/dL (100 g/L)
B. Preoperative hydroxyurea
C. Preoperative exchange transfusion; target hemoglobin S less than 30%
D. Preoperative simple transfusion; target hemoglobin 10 g/dL (100 g/L)
Answer: D
Manage sickle cell anemia perioperatively.
Key Points
Preoperative simple transfusion should be performed, targeting a hemoglobin level of 10 g/dL (100 g/L) (Option D). Sickle cell disease (SCD) carries an increased risk of perioperative complications with surgeries other than low-risk procedures (e.g., skin biopsy). This increased risk is particularly true in those with hemoglobin SS or hemoglobin Sβ° disease. Evidence-based care for patients with hemoglobin SS disease undergoing surgeries other than low-risk procedures is to provide simple erythrocyte transfusion. This recommendation is based on results from a clinical trial in which patients were randomized either to no transfusion or to simple transfusion to achieve a hemoglobin level of 10 g/dL (100 g/L) preoperatively. A significant increase in serious adverse events was seen in those who did not receive transfusion. Patients who received transfusion also had a lower incidence of developing acute chest syndrome. No data are available on outcomes using postoperative transfusion (Option A).
Hydroxyurea reduces vaso-occlusive events in SCD, with some data demonstrating improved survival with long-term use. Its efficacy appears to be partially related to increasing hemoglobin F production and decreasing the relative concentration of hemoglobin S. It should be considered for use in adults who have significant clinical manifestations, including three or more painful vaso-occlusive events per year. However, hydroxyurea use has not been studied specifically for the perioperative setting (Option B). Benefits are typically seen with chronic use, and it is unlikely to have a positive effect for this patient having a surgery in 1 week.
A more aggressive approach using exchange transfusion to reduce the hemoglobin S to less than 30% is no more effective at reducing adverse outcomes with surgery than preoperative simple transfusion, including no difference in rates of acute chest syndrome (Option C). Additionally, fewer transfusion-related complications are experienced in those who receive simple transfusion.
A 55-year-old woman is admitted to the hospital for chemotherapy following a diagnosis of Burkitt lymphoma. She is considered to be at high risk for tumor lysis syndrome.
On physical examination, blood pressure is 110/60 mm Hg and pulse rate is 110/min; the remainder of her vital signs are normal. The patient has large, palpable, bilateral cervical, supraclavicular, and axillary lymphadenopathy. Cardiopulmonary examination is normal.
CT imaging of the chest, abdomen, and pelvis at the time of diagnosis revealed bulky mediastinal and periaortic lymphadenopathy.
Intravenous isotonic saline is administered at 200 mL/hour.
Which of the following is the most appropriate additional preventive therapy?
A. Acetazolamide
B. Allopurinol
C. Furosemide
D. Rasburicase
Answer: D
Prevent tumor lysis syndrome.
Key Points
This patient should receive rasburicase (Option D) to prevent tumor lysis syndrome (TLS). TLS occurs when tumor cells release their contents into the bloodstream, either spontaneously or as a result of treatment, leading to hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte abnormalities can lead to acute kidney injury, cardiac arrhythmias, seizures, and death. The risk of TLS can be categorized based on the volume of cancer mass present, the cell-lysis potential of the cancer, and patient characteristics of preexisting kidney failure, dehydration, acidosis, hypotension, or nephrotoxin exposure. TLS is seen most often in patients with highly proliferative hematologic malignancies, such as acute leukemia and high-grade lymphomas, such as Burkitt lymphoma, but can develop in other cancers. Patients at intermediate risk for TLS can be managed with monitoring of laboratory values, hydration, and allopurinol, and those at high risk, such as this patient, should receive vigorous intravenous hydration and rasburicase, a urate oxidase enzyme that metabolizes urate to allantoin, before receiving chemotherapy. Rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency, and allopurinol should be used instead.
Acetazolamide (Option A) or bicarbonate is not recommended in the prevention of TLS because urine alkalization will increase the risk of hyperphosphatemia and the precipitation of calcium phosphate crystals.
Allopurinol (Option B) may be used to prevent TLS in patients at intermediate risk. Allopurinol is not the first-line agent for prophylaxis in patients at high risk for TLS because it does not work as quickly or consistently as rasburicase. Allopurinol prevents the formation of serum urate through xanthine oxidase inhibition but does not reduce existing serum urate levels by metabolizing urate to a more soluble metabolic end product as does rasburicase.
Furosemide (Option C) might be considered in some patients to increase urine flow, particularly in those who become volume overloaded with aggressive intravenous volume expansion. This patient displays some evidence of hypovolemia with low blood pressure and tachycardia, however, and furosemide is contraindicated.
A 68-year-old woman is evaluated in the hospital for agitated delirium. She has metastatic non–small cell lung cancer. She was admitted to the hospital 5 days ago with acute hypoxic respiratory failure, and she opted for a comfort-directed care strategy. She is currently receiving oxygen through nasal cannula and parenteral opioids for dyspnea and bone pain. She became agitated 2 days ago, and after a thorough search excluded reversible causes, she was treated with intravenous haloperidol. Response to haloperidol was initially positive but is now waning. Her only other medication is morphine.
On physical examination, pulse rate is 121/min, respiration rate is 26/min, and oxygen saturation is 93% breathing 3 L/min oxygen by nasal cannula. The patient is not oriented or responding appropriately to questions. She is agitated and is attempting to climb out of bed.
Which of the following is the most appropriate next step in management?
A. Add parenteral lorazepam
B. Change haloperidol to olanzapine
C. Stop haloperidol
D. Stop morphine
Answer: A
Treat delirium at the end of life.
Key Point
The most appropriate next step in management is to add parenteral lorazepam (Option A) to the patient's current medications. Delirium is an acute-onset disorder associated with fluctuation in mental status. It may manifest as either inattention and agitation or hypoactivity. Terminally ill patients often experience delirium, and in elderly patients with cancer, delirium is associated with increased morbidity. Regardless of the presentation of delirium, diagnosis and treatment are indicated to ensure patient safety and to provide comfort to both patient and family. Potentially reversible causes of delirium, such as noise, medication side effects, pain, bladder distention, constipation, and dehydration, should be addressed. There is very little evidence supporting the use of antipsychotics, such as haloperidol, in the treatment of delirium, but they are commonly prescribed. Benzodiazepines are typically avoided for patients at the end of life, primarily because of greater incidence of paradoxical reactions, including worsened delirium. However, recent evidence from clinical trials show a potential benefit with the addition of lorazepam to haloperidol for agitated delirium in hospitalized patients at the end of life. In this case, the patient initially had a positive response to parenteral haloperidol, but it is now ineffective. Given that the goal of therapy is the patient's comfort, a trial of lorazepam and haloperidol would be reasonable at this time.
There is no evidence to suggest that second-generation antipsychotics, such as olanzapine, (Option B) are more effective than haloperidol in the management of patients with agitated delirium.
Stopping haloperidol (Option C) should not be considered until a trial of haloperidol and lorazepam can be evaluated as a treatment for this patient's agitated delirium.
This patient was started on opioids to manage pain from bony metastatic lung cancer as well as dyspnea refractory to medical management, two indications for which opioids are considered first-line therapy. In a patient receiving comfort-directed care, pain management with morphine should not be discontinued (Option D).
Bibliography
A 28-year-old man is evaluated for hematuria that he noted on awakening and a 3-day history of fever, runny nose, and cough. One year ago, he had an episode of gross hematuria after running a half marathon. Evaluation at that time resulted in a biopsy diagnosis of IgA nephropathy. He has no other medical problems and takes no medications.
On physical examination, temperature is 37.9 °C (100.2 °F), and blood pressure is 110/70 mm Hg; other vital signs are normal. The nasal mucosa is edematous, with serous discharge. Examination of the oropharynx reveals erythema without exudate. There is no lymphadenopathy. Lungs are clear to auscultation. The remainder of the examination is unremarkable.
Laboratory studies show a serum creatinine level of 0.9 mg/dL (79.6 µmol/L); urinalysis shows 3+ blood, trace protein, too numerous to count erythrocytes, and no casts. Streptococcal rapid antigen test is negative.
Which of the following is the most appropriate management?
A. Amoxicillin
B. CT of the abdomen and pelvis
C. Prednisone
D. Clinical observation
Answer: D
Manage gross hematuria in IgA nephropathy.
Key Points
The most appropriate management is clinical observation (Option D). This patient can be reassured that the gross hematuria is related to his underlying IgA nephropathy and will resolve spontaneously. Recurrent gross hematuria, in which the hematuria occurs in the setting of an upper respiratory infection (synpharyngitic hematuria) or after heavy exertion, is a common manifestation of IgA nephropathy in younger patients; it usually portends a benign clinical course with recurrent episodes of gross hematuria without progression to chronic kidney disease. Other predictors of a benign prognosis include a normal serum creatinine concentration and blood pressure as well as minimal proteinuria.
Amoxicillin (Option A) would be indicated to treat streptococcal pharyngitis. However, this diagnosis is unlikely in the presence of cough, the absence of pharyngeal exudate and cervical lymphadenopathy, and a negative rapid antigen test.
CT of the abdomen and pelvis (Option B) is an appropriate screening test for unexplained gross hematuria, which may be due to the presence of a stone or mass in the kidney or bladder. However, this patient has a known diagnosis of IgA nephropathy and a classic presentation of synpharyngitic hematuria; the gross hematuria is well explained, and imaging is not required.
Glucocorticoid therapy, such as with prednisone (Option C), is unnecessary in a mild form of nonprogressive IgA nephropathy. The use of immunosuppression in progressive IgA nephropathy remains controversial: The STOP-IgAN study showed no benefit of glucocorticoid therapy in slowing the decline of kidney function, and the TESTING study was terminated early due to significantly increased risk for adverse events in patients treated with glucocorticoids. Therefore, glucocorticoid therapy is reserved for severe forms of IgA nephropathy deemed high risk for rapid progression to end-stage kidney disease.
A 21-year-old woman is evaluated in the hospital following cardiac arrest that occurred during a collegiate cross-country race. She received cardiopulmonary resuscitation at the scene and has recovered while at the hospital. She has no pertinent personal medical history. The patient takes no medications.
On physical examination, vital signs are normal. The remainder of the examination is unremarkable.
Laboratory studies are within normal limits.
Echocardiogram shows normal left ventricular function and right ventricular dilation and dysfunction. Results from cardiac catheterization are normal.
Metoprolol is initiated.
Which of the following is the most appropriate additional management before discharge?
A. Amiodarone
B. Genetic testing
C. Implantable cardioverter-defibrillator
D. Lisinopril
Answer: C
Provide secondary prevention of sudden cardiac death using an implantable cardioverter-defibrillator.
Key Point
The most appropriate additional management before discharge is implantable cardioverter-defibrillator (ICD) placement (Option C) in this athlete who presented with rescued sudden cardiac death. Patients with sustained ventricular arrhythmias (>30 seconds) or cardiac arrest without a reversible cause have a class 1 recommendation for secondary prevention with ICD placement. Despite her normal left ventricular function, an ICD is warranted before discharge, barring a clear, acute contraindication (e.g., active bacteremia). ICDs are indicated and effective in the setting of secondary prevention of sudden cardiac death, even if the cause is not confirmed (unless it is very clear that the cause is acutely reversible and correctable). However, her presentation is not unusual for arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited “wear-and-tear” disorder that primarily affects the right ventricle but may be seen in the left. Ventricular arrhythmias are often the initial presentation, and some are very dramatic (as in this case); they are also very likely to recur. Cardiac magnetic resonance imaging would be helpful to assess myocardial infiltration, ideally before ICD placement. A major facet of her treatment will be exertional limitation, often a major challenge for patients who are athletes.
Amiodarone (Option A) is a multichannel antiarrhythmic agent that may be necessary in patients with ARVC and refractory ventricular arrhythmias. However, this patient has yet to have a trial of exertional limitation and/or a β-blocker (e.g., metoprolol), and she is quite young to commit to amiodarone as first-line therapy. Furthermore, amiodarone is not nearly as effective as is an ICD in preventing sudden cardiac death.
Genetic testing (Option B) may be helpful to understand this patient's disease risk and severity, and results may have implications for her future children and other family members. However, genetic testing is not required for diagnosis or ICD placement, and it should not be undertaken without prior genetic counseling. Therefore, it is not necessary before discharge, as it is unlikely to affect immediate decision making regarding ICD placement.
Lisinopril (Option D) may be helpful for patients with new left ventricular dysfunction and has been recommended in patients with ARVC with right ventricular dysfunction; however, it has no current role in this patient. Furthermore, it is not as imperative before discharge as is an ICD.
A 28-year-old woman is seen to establish care. Medical history is significant for acute lymphoblastic leukemia diagnosed and treated at age 5 years; she has been leukemia free since completion of therapy that included anthracycline and high-dose glucocorticoids. Bone mineral density measurement following treatment was normal. An echocardiogram performed 1 year ago was normal. She reports regular menses. She has no medical problems and takes no medications. She is not sexually active and does not smoke cigarettes, use recreational drugs, or drink alcohol. She exercises 150 minutes per week.
The physical examination is unremarkable. BMI is 28. Cervical cancer screening is performed.
Complete blood count is normal.
Which of the following is the most appropriate additional survivorship assessment to perform next?
A. Bone marrow biopsy
B. Estrogen and progesterone levels
C. Exercise stress test
D. Lipids and fasting glucose
E. Whole genome sequencing
Answer: D
Screen for dyslipidemia and diabetes mellitus in survivors of pediatric leukemia.
Key Points
Screening for diabetes and dyslipidemia should be performed (Option D). Survivors of pediatric leukemia (typically acute lymphoblastic leukemia, ALL) are at increased risk of developing metabolic syndrome as a result of exposure to cancer chemotherapy. The primary care physician should also request a treatment summary to fully ascertain the risk of cardiovascular disease, metabolic syndrome, and secondary malignancies for this patient. Studies have shown that adult survivors of childhood ALL are more likely to have features of metabolic syndrome, including high BMI, truncal obesity, dyslipidemia, insulin resistance, and hypertension compared with age-matched controls. Therefore, regular screening for dyslipidemia, diabetes, and hypertension is recommended. Those in remission for 20 years or more are not at risk of ALL recurrence. High-dose glucocorticoids, typical of ALL regimens, pose a risk for osteopenia. A normal bone mineral density measurement at the time of entry into long-term care does not need to be repeated until age 65 years unless other risk factors for osteoporosis develop. Patients should be counseled about lifestyle risk factors, age-based screening, and early reporting of persistent symptoms.
Although adult ALL survivors are at risk of therapy-related acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), this risk does not usually extend beyond 15 years. This patient has a normal complete blood count, so bone marrow examination and whole genome sequencing for AML or MDS are not indicated (Options A, E).
Leukemia therapy in childhood does not usually compromise ovarian function. This patient has regular menses, which further confirms normal ovarian function. Checking estrogen and progesterone levels would not be helpful (Option B).
Exposure to anthracycline during therapy for childhood ALL can lead to heart failure in adulthood. However, exercise stress testing is not the appropriate test to evaluate cardiac function (Option C). Echocardiography to screen for left ventricular dysfunction should be performed at intervals of 3 to 5 years, particularly if anthracycline exposure was high or if chest irradiation was used. In addition, female survivors have a higher risk of myocardial dysfunction during pregnancy.
A 77-year-old woman undergoes follow-up evaluation for recently diagnosed stage I adenocarcinoma of the lung. Medical history is notable for very severe COPD that limits her ability to dress unaided. Her medications are an inhaled corticosteroid, salmeterol, tiotropium, roflumilast, and an albuterol inhaler as needed.
On physical examination, respiration rate is 25/min; other vital signs are normal. Oxygen saturation is 91% breathing 3 L/min of oxygen by nasal cannula. BMI is 20, and she is thin with significant muscle wasting. She has a prolonged expiratory phase of respiration and decreased breath sounds bilaterally.
Surgical and pulmonary consults concur that the patient is too chronically disabled to safely undergo elective thoracic surgery.
Which of the following is the most appropriate treatment?
A. Combination platinum-based chemotherapy
B. Combined chemotherapy and radiation therapy
C. Immunotherapy
D. Stereotactic radiation therapy
Answer: D
Treat stage I non–small lung cancer with stereotactic radiation therapy.
Key Points
The most appropriate treatment for this patient's stage I non–small cell lung cancer is stereotactic radiation therapy (Option D). Surgery is the standard treatment for stage I and some stage II non–small cell lung cancers, and in patients treated with surgery, 5-year survival is about 60% to 70%. However, not all patients are surgical candidates. Before undergoing surgery, it is critical to perform a medical evaluation to ensure that surgery would not be associated with undue risk. That was done in this case, and it was determined that this patient was not a surgical candidate. Multiple studies have shown that stereotactic radiation therapy is an effective treatment for this patient population, with demonstrated excellent rates of local control, particularly in patients with stage I cancers. This patient, who is not fit for surgery, is a good candidate for such treatment.
Combination platinum-based chemotherapy (Option A) is another accepted treatment for patients with metastatic non–small cell lung cancer. However, it is not an accepted treatment for early-stage disease. Although treatment with stereotactic radiation therapy can be curative, treatment with combination chemotherapy would not be curative and is not indicated for this patient.
Combined chemotherapy and radiation therapy (Option B) are used commonly for the treatment of stage III non–small cell lung cancer and is an accepted treatment for this group of patients. However, it has not been shown to be of benefit in patients with stage I or stage II disease and is not indicated for treatment of this patient.
Immunotherapy (Option C) plays an increasingly important role in the treatment of non–small cell lung cancer. It works by reversing inhibition of the cellular immune response caused by cancers. Although it has a role in the treatment of some patients with metastatic non–small cell lung cancer, it is not a standard treatment for patients with nonmetastatic disease.
A 62-year-old woman is evaluated for slowly progressive swelling of the right posterior elbow of 3 days' duration. She works as a gardener. The patient has no chronic medical conditions. She takes no medications.
On physical examination, vital signs are normal. The posterior aspect of the right elbow is swollen and slightly tender to palpation. No warmth, drainage, or other skin changes are noted. Range of motion of the right elbow is normal. There are no other joint abnormalities.
Which of the following is the most appropriate management?
A. Bursa aspiration
B. Glucocorticoid injection
C. Joint aspiration
D. Rest, ice, and protection
E. Surgical drainage
Answer: D
Treat noninfectious olecranon bursitis.
Key Points
The most appropriate management is rest, ice, and protection (elbow pads) (Option D). This patient has olecranon bursitis, manifesting as an accumulation of fluid in the olecranon bursa. Common causes include trauma, intensive physical labor, infection (septic bursitis), crystal deposition (uric acid, calcium phosphate), and inflammation from rheumatologic disorders. In this patient without symptoms of infection (no erythema, warmth, or significant pain) or rheumatologic disease, bursitis was probably induced by repetitive stress due to gardening. Supportive care with joint rest, ice, elbow protection, and as-needed NSAID therapy provides the best clinical outcome for aseptic, mechanical olecranon bursitis.
In some patients with evidence of olecranon bursitis, needle aspiration of the bursa (Option A) for fluid Gram stain, examination for crystals, and culture is indicated if the bursitis is associated with pain, erythema, and warmth. Infected superficial bursae, such as the olecranon and prepatellar, can lead to sepsis if not recognized and treated with needle drainage and antibiotics. In these cases, contiguous skin infection is commonly present. This patient has no evidence of concomitant skin infection or local signs of inflammation, and bursa aspiration is not indicated.
Glucocorticoid injection (Option B) should be avoided in patients with aseptic olecranon bursitis. In a systematic review, patients with aseptic bursitis treated with glucocorticoid injection had increased complications, including skin atrophy, without improved outcomes.
Joint aspiration (Option C) with Gram stain, microscopy for crystals, and culture should be performed when joint infection is suspected. Involvement of the joint is suggested by pain with elbow extension. In patients with fluid within the elbow joint, full extension decreases the volume of the joint capsule, thus distending the inflamed joint capsule and causing pain. This patient was able to extend the elbow joint without pain, ruling out joint infection and the need for joint aspiration.
Nonsurgical management of olecranon bursitis is significantly more effective than surgical management (Option E), leading to higher rates of clinical resolution. In addition, surgical incision and drainage is associated with higher rates of complications, persistent drainage, and bursal infections. Surgery may be necessary for infectious or refractory bursitis. In some cases of chronic olecranon bursitis, arthroscopic bursectomy is required.
A 23-year-old woman is evaluated during a follow-up visit for focal segmental glomerulosclerosis that was diagnosed 3 weeks ago. The edema in her lower extremities has not improved on her current regimen of prednisone, losartan, atorvastatin, and maximal doses of oral furosemide.
On physical examination, vital signs are normal. The patient weighs 72 kg (158.7 lb). There is 3-mm pitting edema of the lower extremities through the mid-thigh, equal on both sides. The remainder of the examination is unremarkable.
Laboratory studies:
Albumin
2.0 g/dL (20 g/L)
Total cholesterol
303 mg/dL (7.8 mmol/L)
Creatinine
0.6 mg/dL (53 µmol/L)
Urine protein-creatinine ratio
9150 mg/g
CT of the chest is normal.
Which of the following is the most appropriate management?
A. Add metolazone
B. Administer furosemide by continuous intravenous infusion
C. Administer furosemide by intravenous bolus
D. Discontinue prednisone; add cyclosporine
E. Hemodialysis with ultrafiltration
Answer: A
Manage edema associated with the nephrotic syndrome.
Key Point
The most appropriate management is to add metolazone (Option A). This patient with the nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) has refractory edema despite therapy with maximal doses of oral furosemide and therefore needs additional diuretic therapy. Addition of a second diuretic that works distal to the loop of Henle, such as a thiazide diuretic and/or a potassium-sparing diuretic, is the appropriate next step in management. In patients taking high-dose loop diuretics, increased delivery of salt and water to the distal portions of the nephron can lead to hypertrophy of these segments and overabsorption of sodium, undermining the effects of the loop diuretic.
Factors that warrant admission for intravenous (IV) diuretics include lack of response after addition of a thiazide and/or potassium-sparing diuretic to a loop diuretic; acute respiratory symptoms secondary to pulmonary edema; or significant ascites that raise concern for gut edema and malabsorption of oral diuretics. These factors are not present in this patient. A number of randomized clinical trials have evaluated the efficacy of a continuous IV infusion of loop diuretics compared with IV bolus therapy (Options B, C). Findings indicated that continuous IV infusion is associated with less ototoxicity than bolus injections of loop diuretics, but clear evidence of its diuretic superiority is lacking, at the minimum in heart failure patients.
This patient's significant edema alongside persistent nephrotic-range proteinuria and hypoalbuminemia does not warrant discontinuation of prednisone (first-line therapy for FSGS) for the addition of cyclosporine (second-line therapy for FSGS) (Option D), as the patient has received glucocorticoid therapy for only 3 weeks. In adults with FSGS, therapeutic response can take up to 12 to 16 weeks. Therefore, it would be premature to consider this patient refractory to glucocorticoid therapy.
Hemodialysis with ultrafiltration (Option E) for edema is reserved for patients with anasarca, significant kidney dysfunction, and an inability to diurese on maximal doses of IV diuretics.
A 56-year-old man is hospitalized for an ST-elevation myocardial infarction. He is treated with percutaneous coronary intervention and is now asymptomatic. Medical history is significant for hypertension and paroxysmal atrial fibrillation. Outpatient medications are flecainide, rivaroxaban, metoprolol, and lisinopril.
A predischarge ECG shows sinus rhythm (heart rate, 58/min), a QRS complex duration of 124 ms, and a right bundle branch block pattern. An echocardiogram reveals a mildly reduced left ventricular ejection fraction with an inferior wall motion abnormality.
Which of the following is the most appropriate management?
A. Ambulatory ECG monitoring
B. Discontinue flecainide
C. Discontinue metoprolol
D. Exercise stress testing
Answer: B
Discontinue flecainide in a patient with ischemic heart disease.
Key Point
The most appropriate management is to discontinue flecainide (Option B). This patient has ischemic heart disease and previously diagnosed paroxysmal atrial fibrillation (AF). Amiodarone, dofetilide, flecainide, propafenone, sotalol, and dronedarone may be used to maintain sinus rhythm in patients with AF. Antiarrhythmic drug selection is guided by the patient's comorbid conditions and safety considerations. Flecainide is a class IC antiarrhythmic agent and, along with propafenone, is absolutely contraindicated in patients with ischemic heart disease, given the increased risk for ventricular arrhythmias in this population. This patient also has evidence of left ventricular (LV) dysfunction on a post–myocardial infarction echocardiogram, which may be due to infarcted (as opposed to stunned) myocardium and may lead to increased long-term risk for ventricular arrhythmias. Furthermore, his ECG shows widening of the QRS interval, which may reflect adverse effects of flecainide. This drug, therefore, is not safe in this patient; it should be discontinued and not restarted.
Although ambulatory ECG monitoring (Option A) at discharge may be helpful to assess AF burden, rates, and symptoms, it should not be used to guide flecainide therapy in this patient, given his contraindications, which ambulatory ECG monitoring will not address.
There is no reason to stop metoprolol (Option C). This patient's heart rate is only mildly bradycardic, does not appear to be causing adverse effects, and is unlikely to be affecting his right bundle branch block. Aggressive β-blockade is warranted, given his recent myocardial infarction, coronary artery disease, and LV dysfunction. Furthermore, he will likely need metoprolol for rate control, if or when he reverts to AF.
In the revascularized patient with stable or absent ischemic symptoms, there is no role for predischarge stress testing (Option D). Although exercise stress testing is sometimes used to assess the QRS duration during exercise in patients treated with class IC antiarrhythmic drugs, it will not change management in this patient. This patient already has QRS prolongation at rest and an absolute contraindication to flecainide because of his coronary artery disease.