Question: A 44-year-old homeless man presents to the emergency department after being stabbed multiple times in the abdomen. The patient is intoxicated and is unable to offer further history. His temperature is 97.5°F (36.4°C), blood pressure is 92/52 mmHg, pulse is 145/min, respirations are 33/min, and oxygen saturation is 90% on room air. He is intubated to protect his airway, given 2 units of packed red blood cells, and sent to the operating room for an exploratory laparotomy. The patient is subsequently admitted to the intensive care unit. He is extubated the next day and appears well. His vitals are within normal limits. Physical exam reveals sparse hair that is falling out throughout the patient’s body. He has a rash by the corners of his mouth. The patient has multiple loose bowel movements and on day 6 the patient’s surgical wound does not appear to be healing. It is held together only by the sutures with minimal underlying healing. Which of the following is most likely deficient in this patient?

Answer: Zinc

Explanation:
This homeless patient who likely has poor nutritional status presents with angular cheilitis, sparse hair that is falling out, diarrhea, and poor wound healing, all of which are suggestive of zinc deficiency.

Zinc is involved in many physiologic processes and is an important mineral to include in the diet. Zinc deficiency is common in patients with poor nutritional status such as the homeless, individuals living in developing nations without access to food, and patients with eating disorders. Many malabsorptive conditions can cause zinc deficiency including steatorrhea and chronic pancreatitis. Zinc deficiency presents with impaired wound healing and impaired immune function. Other symptoms suggestive of zinc deficiency include xerosis, alopecia, stomatitis, oral ulceration, angular cheilitis, impaired vision (night blindness), impaired smell/taste, diarrhea, and anorexia. The treatment of zinc deficiency involves zinc supplementation and workup for any other nutritional deficiencies.

Nagata etc al. study the incidence of zinc deficiency among younger patients with anorexia nervosa. The authors find that men and women are both equally likely to have zinc deficiency when admitted. The authors recommend screening all patients with eating disorders for zinc deficiency.

Incorrect Answers:
Answer A: Riboflavin deficiency may present with angular cheilitis, stomatitis, and a non-specific rash. The treatment involves supplementing or consuming foods with riboflavin; however, it is rare in the developed world to be riboflavin deficient (due to fortified foods) and would not cause such significant wound healing issues as in this patient.

Answer B: Thiamine deficiency is common in alcoholics and can cause Wernicke-Korsakoff syndrome, which presents with ataxia, nystagmus, and ophthalmoplegia in addition to amnesia. The treatment involves the administration of high-dose thiamine.

Answer C: Vitamin C deficiency causes scurvy, which presents with easy fractures, bleeding gums or loose teeth, delayed wound healing, and perifollicular hemorrhages. It is common in the homeless and alcoholics. Treatment involves vitamin C replacement or a diet rich in fruits and vegetables.

Answer D: Vitamin D deficiency is common in the homeless, alcoholics, or those who suffer from steatorrhea (such as chronic pancreatitis or Crohn disease). It presents with weak, soft bones (osteomalacia/osteoporosis), and hypocalcemia which may present with paresthesias and tetany. Treatment involves replacement of vitamin D.

Bullet Summary:
Zinc deficiency presents with poor wound healing, hair loss, infertility, diarrhea, anorexia, and impaired immune function.


Question: A 51-year-old man presents to his primary care provider for intermittent shaking of his hands. For the last several years he has noticed this "shaking" when he brushes his teeth and prepares a cup of coffee in the morning. The shaking then gradually improves over the course of the day. His medical history is otherwise notable for hypertension and hyperlipidemia. His only home medication is pravastatin. The patient smokes half a pack per day of cigarettes and drinks 2-3 beers throughout the day. His family history is significant for Parkinson disease in his father. On physical exam, his temperature is 98.6°F (37.0°C), blood pressure is 159/84, pulse is 74/min, and respirations are 12/min. He has a high-frequency bilateral hand tremor elicited on finger-to-nose testing. His neurological exam is otherwise unremarkable. Which of the following medications should this patient be started on?

Answer: Propranolol

Explanation:
This patient presents with a high frequency bilateral action tremor, which suggests a diagnosis of benign essential tremor. In light of his concomitant hypertension, the patient should be started on propranolol.

Benign essential tremor usually presents as a bilateral tremor of the hands that is observed during fine motor movements. Patients present with worsening tremors with posturing and with voluntary movement and improve with alcohol and rest. First-line treatment includes propranolol and primidone, with propranolol being preferred for patients with hypertension or vascular risk factors. Refractory cases can be treated with deep brain stimulation which is often a last-line intervention.

Shanker reviewed the diagnosis and treatment of patients with essential tremors. She discusses how this disease presents with an action tremor that lasts for at least 3 years. She recommends treatment with propranolol or primidone.

Incorrect Answers:
Answer A: Alprazolam is sometimes used as second-line therapy for essential tremor refractory to propranolol and primidone but would not be used as initial therapy in this patient. Benzodiazepines can be used in patients with panic disorders.

Answer B: Primidone is a barbiturate that is another first-line treatment for essential tremor. For this patient, propranolol would be preferred to also treat this patient’s underlying hypertension. Primidone can be used in patients without other underlying comorbidities.

Answer D: Topiramate is an antiepileptic that may be used as a second-line treatment option for essential tremor. It would not be used as initial drug therapy. Topiramate can be used in the treatment of patients with partial seizures that present with motor symptoms.

Answer E: Trihexyphenidyl is an anticholinergic medication that is used to treat early Parkinson disease in which tremor is the predominant symptom. Despite this patient’s family history of Parkinson disease, the tremor in Parkinson disease usually presents as an asymmetric, “pill-rolling” resting tremor rather than an action tremor.

Bullet Summary:
Propranolol is the first-line treatment for benign essential tremor in patients with concomitant hypertension.


Question: A 1-hour-old newborn boy is evaluated in the delivery room. He was born at 37 weeks gestation to a 39-year-old G3P3 mother. The mother initially labored at home with a midwife but was transferred to the hospital for failure to progress. The infant was eventually delivered via Caesarean section. The mother declined all prenatal screening tests during this pregnancy. His temperature is 98.6°F (37°C), blood pressure is 63/41 mmHg, pulse is 133/min, and respirations are 39/min. His Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. His weight is 3.0 kg (6.6 lb), and his height and his head circumference are in the 30th and 40th percentiles, respectively. On physical exam, he is found to have a 3 cm full-thickness defect in the abdominal wall to the right of the umbilicus with evisceration of a loop of the bowel. The abdominal defect is immediately covered in sterile saline dressings and an orogastric tube and 2 peripheral intravenous lines are placed. This condition is most likely associated with which of the following additional findings?

Answer: A normal cardiac exam

Explanation:
This patient presents with a full-thickness defect in the abdominal wall lateral to the umbilicus with evisceration of the bowel, which suggests a diagnosis of gastroschisis. Gastroschisis is not associated with any cardiac defects.

Gastroschisis and omphalocele are the most common abdominal wall defects found in infants and there are important differences between them. Whereas the eviscerated bowel in gastroschisis is not covered by a membrane, the exposed bowel in the omphalocele is covered by a membranous sac. The abdominal wall defect in gastroschisis is located lateral to the umbilicus, whereas in omphalocele the defect is midline. The distinction is also important for management, as omphalocele is commonly associated with other extraintestinal defects whereas fewer than 10% of cases of gastroschisis are associated with an extraintestinal abnormality. Treatment is with surgical correction of the abdominal wall defect.

Skarsgard reviews the evidence regarding the diagnosis and treatment of gastroschisis. He discusses how this is one of the most common birth defects managed in the ICU setting. He recommends urgent surgical correction.

Incorrect Answers:
Answer B: A bicuspid aortic valve occurs in many cases of Turner syndrome. This disease presents with a webbed neck, short stature, low hairline, broad (“shield”) chest, bicuspid aortic valve, horseshoe kidney, and streak ovaries. Treatment is supportive with surgical fixation of cardiac defects and hormone supplementation with growth hormone.

Answer C: Endocardial cushion defects are most commonly found in trisomy 21 (Down syndrome). Over a third of individuals with trisomy 21 have a complete atrioventricular septal defect, and another third have isolated ventricular septal defects. Infants with Down syndrome commonly present with the upslanting palpebral fissures, flat nasal bridge, transverse palmar crease, and hypotonia. Treatment is with supportive care of these deformities such as surgical correction of cardiac defects.

Answer D: Tetralogy of Fallot is most often associated with trisomy 21 (Down syndrome) and 22q11 deletion syndromes. Infants with Down syndrome commonly present with upslanting palpebral fissures, flat nasal bridge, transverse palmar crease, and hypotonia. Treatment is with supportive care of these deformities such as surgical correction of cardiac defects.

Answer E: Ventricular septal defects occur in several genetic syndromes, including trisomy 21 (Down syndrome) and trisomy 13 (Patau syndrome). Infants with trisomy 13 commonly present with cleft lip or palate, polydactyly, and severe intellectual disability. This disease is not compatible with survival past 1 year of age so treatment can involve termination of pregnancy or supportive care.

Bullet Summary:
Gastroschisis presents with an abdominal wall defect with evisceration of the bowel that is lateral to the umbilicus and is not usually associated with other birth defects.


Question: A 6-month-old boy is brought to the pediatrician by his parents for a routine visit. His parents report that he is feeding and stooling well and they have just started experimenting with solid foods. His parents are concerned because a few weeks ago he started rolling from back to front in addition to front to back, but he now struggles when placed on his back. The patient was noted to be developmentally appropriate for his age at his last visit 2 months ago. On physical exam, the patient seems well-nourished and has no dysmorphic features. His temperature is 98.6°F (37°C), blood pressure is 77/49 mmHg, pulse is 112/min, and respirations are 24/min. In the examination room, he is able to roll from front to back but cannot roll from back to front. He is not able to sit without support and makes no attempt at bouncing when supported in a standing position. The patient’s abdomen is non-tender and soft without hepatosplenomegaly. His patellar reflexes are 4+ bilaterally. He is found to have the ocular finding seen in Figure A. Accumulation of which of the following would most likely be found in this patient’s cells?

Answer: GM2-ganglioside

Explanation:
This 6-month-old boy who presents with developmental regression, a “cherry-red” macula, and hyperreflexia most likely has a diagnosis of Tay-Sachs disease. Tay-Sachs disease is caused by a deficiency of beta-hexosaminidase A that results in the accumulation of GM2-ganglioside.

Tay-Sachs disease is a genetic disorder caused by an autosomal recessive deficiency of the beta-hexosaminidase A enzyme. This disease presents in infants aged 2-6 months with progressive neurodegeneration, hypotonia, feeding difficulties, and a “cherry red” spot on the macula. Tay-Sachs disease shares many features with Niemann-Pick disease; however, Niemann-Pick disease presents with the additional findings of hepatosplenomegaly and hyporeflexia whereas Tay-Sachs presents with hyperreflexia without hepatosplenomegaly. Both diseases are more common in the Ashkenazi Jewish population. There is no curative treatment for this disease so treatment is generally supportive.

Solovyeva et al. review the evidence regarding the diagnosis and treatment of Tay-Sachs disease. They discuss how this disease normally presents with muscle weakness, ataxia, speech, and mental disorders. They recommend considering novel treatments such as substrate reduction therapy.

Figure/Illustration A is a fundoscopic exam demonstrating a “cherry-red” spot on the macula (blue circle). This finding is seen in both Tay-Sachs disease and Niemann-Pick disease.

Incorrect Answers:
Answer A: Cerebroside sulfate accumulates in metachromic leukodystrophy, which is caused by an autosomal recessive deficiency in arylsufatase A. This disease presents with optic atrophy and seizures in childhood. Patients will later develop dementia, psychiatric disease, and neuropathy. There is no cure so treatment is supportive.

Answer B: Galactocerebroside accumulates in Krabbe disease, which is caused by an autosomal recessive deficiency in galactocerebrosidase. Krabbe disease presents in early infancy with developmental regression, hypotonia, and areflexia. Treatment is supportive with musculoskeletal bracing as needed.

Answer C: Glucocerebroside accumulates in Gaucher disease, which is caused by an autosomal recessive deficiency in glucocerebrosidase. Gaucher disease presents with pancytopenia and hepatosplenomegaly. “Gaucher cells,” or lipid-laden macrophages resembling crumpled tissue paper, can be seen on histology. Treatment is with enzyme replacement therapy.

Answer E: Sphingomyelin accumulates in Niemann-Pick disease, an autosomal recessive sphingolipidosis caused by a deficiency in sphingomyelinase. Niemann-Pick disease presents with many of the same features as Tay-Sachs disease but has additional findings of hyporeflexia and hepatosplenomegaly.

Bullet Summary:
Tay-Sachs disease is caused by a deficiency of beta-hexosaminidase A resulting in the accumulation of GM2-ganglioside.


Question: A 25-year-old man presents to his primary care provider for a routine appointment. He feels well and has no complaints. His medical and surgical history is significant for the reconstruction of a torn anterior cruciate ligament in his right knee. His family history is significant for a mother with “thyroid problems” and a father with coronary artery disease. The patient is an information technology specialist at a local company. He is sexually active with men. His temperature is 98.6°F (37.0°C), blood pressure is 124/82 mmHg, pulse is 71/min, and respirations are 12/min. On physical exam, the patient is tall and slender with a BMI of 21 kg/m2. A single nodule can be palpated on the patient’s thyroid. He has palpable cervical lymphadenopathy. On cardiac exam, he has a normal S1/S2 with no murmurs, rubs, or gallops, and his lungs are clear bilaterally. His abdomen is soft and non-tender without hepatosplenomegaly. A physical exam of the perioral region can be seen in Figure A. Which of the following additional findings is most likely to be found in this patient?

Answer: Elevated plasma metanephrines

Explanation:
This patient presents with tall stature, mucosal neuromas of the lips and tongue, an isolated thyroid nodule, and a family history of thyroid disease, which suggests a diagnosis of multiple endocrine neoplasia type 2 (MEN2B). MEN2B is also associated with pheochromocytomas, which cause elevated plasma metanephrines.

MEN2B is caused by a gain-of-function mutation in the RET proto-oncogene and presents with medullary carcinoma of the thyroid, pheochromocytoma, Marfanoid habitus, and mucosal neuromas. Medullary thyroid carcinoma (MTC) occurs in almost all patients with MEN2B and is often metastatic at the time of diagnosis. Patients should be screened for pheochromocytoma using plasma fractionated metanephrines at the time of diagnosis of MTC. Intestinal neuromas may also lead to intestinal manifestations such as chronic constipation and megacolon. Treatment is with surgical excision of malignant lesions and active screening for future development of tumors.

Castinetti et al. review the evidence regarding the diagnosis and treatment of MEN2B. They discuss how often the first presentation of this disease involves the diagnosis of medullary thyroid carcinoma. They recommend developing techniques for earlier diagnosis of this disease in order to allow for better survival.

Figure/Illustration A is a clinical photograph demonstrating mucosal neuromas, which are painless nodules on the lips or tongue (red circles). These findings are characteristically seen in multiple endocrine neoplasia type 2B.

Incorrect Answers:
Answer B: An elevated serum calcium level would suggest parathyroid hyperplasia, which is a feature of both type 1 and type 2A multiple endocrine neoplasia. Rather than hypercalcemia, this patient is likely to have an elevated serum calcitonin level due to his medullary thyroid carcinoma.

Answer C: An elevated serum prolactin level would suggest the presence of a prolactinoma, which is a pituitary tumor that may be seen in type 1 multiple endocrine neoplasia (MEN1). Other findings in this disorder include parathyroid and pancreatic tumors. Treatment is with surgical excision of malignant lesions.

Answer D: Fasting hypoglycemia would suggest the presence of an insulinoma, which is a less common pancreatic tumor that may be seen in MEN1. Other findings in this disorder include parathyroid and pancreatic tumors. Patients with an insulinoma require surgical excision in order to allow for proper glucose homeostasis.

Answer E: A positive fecal occult blood test would raise suspicion for colorectal cancer, which is a feature of Peutz-Jeghers syndrome (PJS). The extraintestinal manifestations of PJS include mucocutaneous pigmented macules on the lips and perioral region. Treatment is with screening for colorectal cancer and surgical excision of malignant lesions.

Bullet Summary:
Multiple endocrine neoplasia type 2B presents with medullary thyroid carcinoma, pheochromocytoma, Marfanoid habitus, and mucosal neuromas.


Question: A 29-year-old woman comes to the emergency department complaining of painful genital ulcers that have been present for 4 days as well as low-grade fever and malaise. She denies any recent travel, new sexual partners, or antibiotic use. Physical examination reveals multiple clustered vesicles and shallow ulcers in the vulvar region. A Tzanck smear shows multinucleated giant cells. Which of the following medications is most appropriate for treating her condition?

Answer: Acyclovir

Explanation:
The patient's painful genital ulcers coupled with the presence of multinucleated giant cells on a Tzanck smear are indicative of a herpes simplex virus type 2 (HSV-2) infection. Acyclovir is the treatment of choice.

Herpes infections can present with painful genital ulcers and low-grade fever. The Tzanck smear showing multinucleated giant cells further confirms the diagnosis though the diagnosis is typically made on clinical grounds and treated empirically. Acyclovir is the drug of choice for treating HSV-2 as it inhibits viral DNA polymerase, preventing the virus from replicating. The drug can reduce the duration and severity of symptoms but does not eradicate the virus entirely.

Groves (2016) emphasizes that genital herpes, caused by the herpes simplex virus (HSV), affects over 400 million people worldwide. The infection is lifelong, with vesicular outbreaks in genital areas that can ulcerate. While HSV-1 and HSV-2 are both culprits, the latter increases the risk of HIV acquisition. The polymerase chain reaction assay is the recommended diagnostic method. Nucleoside analogues are effective treatments, and pregnant women with the condition are advised antiviral prophylaxis from the 36th week until delivery to prevent neonatal complications.

Incorrect Answers:
Answer B: Amoxicillin is an antibiotic ineffective against viral infections like HSV-2. It is commonly used for bacterial infections such as streptococcal pharyngitis.

Answer C: Fluconazole is an antifungal agent is used for treating fungal infections like Candida which may cause esophagitis or vaginitis.

Answer D: Metronidazole is used primarily for anaerobic bacterial and protozoal infections.

Answer E: Trimethoprim-sulfamethoxazole is used for bacterial infections like urinary tract infections and also offers MRSA coverage.

Bullet Summary:
Acyclovir is the drug of choice for treating herpes simplex virus infections.


Question: A 32-year-old G1P0 woman at 12 weeks gestation presents to her obstetrician for a follow-up appointment. She first presented 4 weeks ago with bilateral hand tremors. At that time, she was found to have a thyroid-stimulating hormone (TSH) concentration <0.01 mU/L and an elevated free T4. She was started on propranolol and propylthiouracil. The dosage of both medications has been titrated to the maximum dose. She reports mild improvement in her symptoms but continues to experience sweating and palpitations. She has a past medical history of polycystic ovary syndrome. Her family history is notable for hypothyroidism in her mother. She does not smoke cigarettes, stopped drinking alcohol prior to pregnancy, and does not use drugs. Her temperature is 97.6°F (36.4°C), blood pressure is 113/70 mmHg, pulse is 126/min, and respirations are 18/min. On physical exam, she appears anxious, mildly diaphoretic and has a non-tender prominence on her neck which is shown in Figure A. Which of the following is the most appropriate next step in management?

Answer: Thyroidectomy in the 2nd trimester

Explanation:
This patient who initially presented with tremors, a suppressed TSH, and elevated T4 has Graves disease which was appropriately treated with propranolol and propylthiouracil. However, she has persistent symptoms (diaphoresis, palpitations, tachycardia, nontender goiter) despite maximum doses of these medications, which should then be treated with surgical thyroidectomy which can be performed safely in the 2nd trimester of pregnancy.

Graves disease is caused by TSH receptor antibodies that activate the TSH receptor to synthesize thyroid hormone, leading to hyperthyroidism with suppressed TSH levels. The initial treatment for Graves disease is symptom control with a beta-blocker (e.g., propranolol) and inhibition of thyroid hormone synthesis with a thionamide (e.g., propylthiouracil or methimazole). In the 1st trimester of pregnancy, propylthiouracil is preferred to methimazole. In the 2nd and 3rd trimesters, methimazole is the preferred thionamide. The treatment of choice in pregnancy for Graves disease that is refractory to propranolol and a thionamide is thyroidectomy, which can safely be performed in the 2nd trimester. This is reserved only for more severe cases refractory to medical treatment. In nonpregnant patients, radioiodine ablation is the preferred treatment for refractory Graves disease but is contraindicated during pregnancy due to the risk of ablating the fetal thyroid.

Davies et al. reviewed the pathogenesis, diagnosis, and treatment of Graves disease. They found that Graves disease is caused by autoantibodies to the TSH receptor, resulting in overactive thyroid hormone secretion. They recommend that Graves's disease be treated with antithyroid drugs, radioiodine ablation, or surgery depending on clinical characteristics.

Figure A demonstrates goiter, a common finding in Graves disease that reflects thyroid growth in response to activation by TSH receptor antibodies.

Incorrect Answers:
Answer A: Continuing routine prenatal care does not address the symptoms of the patient's hyperthyroidism. Poorly-controlled hyperthyroidism can lead to spontaneous abortion, premature labor, low birth weight, heart failure, and preeclampsia in pregnant individuals. Therefore, Graves disease should be treated in pregnant individuals.

Answer B: Methimazole is a thionamide that is an alternative to propylthiouracil in nonpregnant individuals. It is more potent than propylthiouracil. Methimazole is contraindicated during the 1st trimester of pregnancy due to its teratogenic effects on the fetus during organogenesis.

Answer C: Oral iodinated contrast agents inhibit the peripheral conversion of T4 to T3 and may be used in thyroid storm in nonpregnant patients outside of the United States. Patients with thyroid storm present with tachycardia, arrhythmias, heart failure, and hyperpyrexia.

Answer D: Radioiodine ablation is the preferred definitive treatment for Graves disease in nonpregnant individuals. It is contraindicated in pregnancy as fetal thyroid tissue has developed by 10-12 weeks of gestation and may be ablated alongside the maternal tissue.

Bullet Summary:
Initial treatment of Graves disease in pregnancy is propranolol and propylthiouracil, whereas severe symptoms that are refractory to medical management should be treated with thyroidectomy.


Question: A 54-year-old man presents to the clinic with 4 weeks of persistently worsening back pain. The pain is localized to 1 spot in his lower back and is worse with physical activity. His medical history is pertinent for intravenous drug use. He has no past surgical history. His temperature is 36.8°C (98.2°F), blood pressure is 118/90 mmHg, pulse is 92/min, respirations are 13/min, and oxygen saturation is 99% on room air. On physical exam, he has midline back tenderness to palpation at L2-L3. Laboratory workup reveals an erythrocyte sedimentation rate of 112 mm/h and C-reactive protein of 10 mg/dL. Which of the following is the most likely diagnosis?

Answer: Osteomyelitis

Explanation:
This patient with a history of intravenous drug use who presents with worsening focal back pain and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) most likely has vertebral osteomyelitis.

Vertebral osteomyelitis typically occurs via three routes: hematogenous spread from a distant site (the most common mechanism), direct inoculation from spinal surgery or trauma, or contiguous spread from adjacent soft tissue infection. Patients usually present with back or neck pain, with or without fever, and the most common clinical finding is local tenderness to percussion over the involved posterior spinous process. Risk factors include injection drug use, degenerative spine disease, prior spinal surgery, infective endocarditis, diabetes mellitus, corticosteroid therapy, and other immunocompromised states. Vital signs may be normal, and laboratory evaluation commonly reveals an elevated white blood cell count, ESR, and CRP. An MRI of the spine is the most appropriate diagnostic test. In stable patients, antimicrobial therapy should be withheld until a microbiological diagnosis is confirmed; once the diagnosis is confirmed, pathogen-directed therapy should then be administered.

Beronius et al. conducted a retrospective study on vertebral osteomyelitis in pursuit of diagnostic criteria to simplify the diagnosis and classification of vertebral osteomyelitis. The authors found that elevated ESR and CRP are found in most patients with vertebral osteomyelitis. The authors recommend clinicians have a high index of suspicion for vertebral osteomyelitis in order to avoid delayed diagnosis.

Incorrect Answers:
Answer A: Ankylosing spondylitis is an inflammatory arthritis of the spine and is often associated with one or more articular or periarticular extraspinal features, including synovitis, dactylitis, and enthesitis. Patients typically present with chronic back pain and loss of mobility before the age of 45.

Answer B: Degenerative spine disease involves osteoarthritis of the spine and is associated with increasing age, presenting commonly as sharp or chronic pain in the neck or back. It typically does not result in radiculopathy, defined as irritation or injury of a nerve root, causing pain, weakness, numbness, or tingling in specific distributions depending on the location of the affected nerve root. Though it is certainly on the differential for this patient, his elevated ESR and CRP make osteomyelitis a more likely diagnosis.

Answer C: Herniated disc can cause a variety of symptoms depending on the position and size of the herniation. If the herniated disk impinges on a nerve, patients may have radiculopathy.

Answer D: Metastatic tumor is typically suspected in patients with back pain in the setting of a known malignancy. The most common primary cancers that metastasize to bone include breast, prostate, thyroid, lung, and renal cancer.

Bullet Summary:
Vertebral osteomyelitis typically presents as focal back pain, with or without fever, with an elevated erythrocyte sedimentation rate and C-reactive protein.


Question: A 55-year-old woman presents to the primary care clinic for her annual visit. She has no complaints and is asymptomatic. She has a history of hypertension, hyperlipidemia, and diabetes. Her medications are lisinopril, amlodipine, atorvastatin, and metformin. There is no family history of malignancy. She is a non-smoker and drinks 3-4 standard drinks per week. Her temperature is 98.2°F (36.8°C), blood pressure is 142/84 mmHg, pulse is 82/min, and respirations are 16/min. On physical exam, a solid, immobile neck mass is palpated inferior to the cricoid cartilage to the left of midline. An ultrasound is obtained and shows a 1.2 cm hypoechoic mass with microcalcifications. Serum thyroid-stimulating hormone (TSH) concentration is 7.2 µU/mL. Which of the following is the most appropriate next step in management?

Answer: Fine needle aspiration

Explanation:
This patient’s presentation with an asymptomatic thyroid nodule with suspicious ultrasound features (≥ 1 cm hypoechoic mass with microcalcifications) and elevated TSH is concerning for thyroid malignancy. The most appropriate next step in management is a fine needle aspiration (FNA).

The first step in the diagnostic work-up of a thyroid nodule, which can be found incidentally in asymptomatic individuals or in the presence of obstructive or vocal symptoms, includes an ultrasound and measurement of serum TSH levels. If TSH is normal or elevated, this suggests a hypofunctioning (“cold”) nodule, which increases the risk of cancer. These nodules should undergo FNA if suspicious sonographic findings are present. Suspicious sonographic findings include irregular margins, microcalcifications, taller-than-wide shape, and rim calcifications in nodules ≥ 1 cm in diameter. If TSH is low, then thyroid scintigraphy (radioiodine scan) should be performed to confirm whether the nodule is hyperfunctioning (“hot”). Hyperfunctioning nodules are rarely cancerous, so these patients can often avoid FNA. Hyperfunctioning nodules such as toxic adenomas which cause overt hyperthyroid symptoms may warrant further treatment with radioiodine, surgery, or anti-thyroid medications.

Durante et al. review the epidemiology and diagnostic approach to thyroid nodules. The authors find that nodules with suspicious sonographic patterns such as solid composition, hypoechogenicity, irregular margins, and microcalcifications should undergo cytological evaluation. The authors recommend molecular testing only in cases in which cytology is indeterminate.

Incorrect Answers:
Answer B: Propylthiouracil is a thionamide that inhibits thyroid peroxidase, thus preventing thyroid hormone synthesis. It can be used for the symptomatic control of hyperthyroidism in toxic adenomas prior to definitive surgical resection. It is not indicated for the treatment of a hypofunctioning nodule.

Answer C: Radioiodine ablation can be used in the treatment of a toxic adenoma, which would take up the radioactive iodine. It is not indicated for the treatment of a hypofunctioning nodule, which would not exhibit radioiodine uptake.

Answer D: Surgical removal of the mass is a treatment option for a malignant thyroid nodule. Although a hypofunctioning nodule is more likely to be malignant, an FNA should be performed first to confirm the diagnosis.

Answer E: Thyroid scintigraphy is used for thyroid nodules with low TSH, which increases the probability of a hyperfunctioning nodule. Confirmation of a hyperfunctioning nodule can help prevent further invasive diagnostic work-up because hyperfunctioning nodules are unlikely to be malignant. Thyroid scintigraphy would not be appropriate in this patient with an elevated TSH.

Bullet Summary:
The next step in management for a thyroid nodule with suspicious sonographic features and an elevated TSH is fine needle aspiration.


Question: A 45-year-old man with a past medical history of obesity presents with a concern about his sexual performance. He has a history of depression which is well managed with fluoxetine. He states that since starting the medication, his sexual drive has increased, yet he is unable to achieve orgasm. As a result, he refuses to take the medication anymore. He has a past medical history of diabetes and notes that his home blood glucose readings have been higher lately. His temperature is 98.3°F (36.8°C), blood pressure is 127/82 mmHg, pulse is 88/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam reveals an obese man in no acute distress with a normal affect and non-focal neurologic exam. The physician agrees to change the patient’s antidepressant. Which of the following is the most appropriate treatment for this patient?

Answer: Bupropion

Explanation:
This patient is presenting with anorgasmia in the setting of treatment with a selective serotonin reuptake inhibitor (SSRI). Given his obesity, worsening home blood glucose levels, and desire for improved sexual performance, bupropion is an appropriate medication.

Bupropion is an antidepressant that is not used first-line except in certain circumstances. Situations where bupropion is an appropriate agent for the management of depression include smoking cessation as it decreases smoking cravings. Bupropion is also weight neutral and is preferred in obese patients, patients who are gaining weight on other medications, and patients with poorly-managed diabetes. Finally, it does not have any sexual side effects in contrast to SSRIs. However, bupropion lowers the seizure threshold and should be avoided in patients at higher risk for seizures. Bupropion is sometimes given with other antidepressants for patients with persistent or refractory symptoms.

Patel et al. review bupropion. They note the effectiveness of bupropion in managing depression and note that it can be given with other agents. They recommend its use, in particular, for smoking cessation or patients who need a more weight-neutral treatment.

Incorrect Answers:
Answer B: Electroconvulsive therapy is a highly effective therapy for depression; however, it is generally used in cases of severe suicidality, malnutrition due to food refusal secondary to depressive disorder, or last line when other medications have failed. This patient is primarily experiencing sexual side-effects and has gained weight, making bupropion a more viable initial alternative.

Answer C: Escitalopram is merely a different SSRI that will lead to similar side effects. Thus, it would not be appropriate. Changing SSRIs is appropriate if the first SSRI does not work after an appropriate trial period of at least 4 weeks in the management of depression. Other changes when an SSRI fails to control symptoms include increasing the dose.

Answer D: Mirtazapine is an antidepressant that increases appetite and leads to weight gain and would further worsen this patient’s obesity. It is preferred in conditions such as anorexia nervosa given weight gain is preferable in this population.

Answer E: Phenelzine is a monoamine oxidase inhibitor and is usually used third-line (or later) in the management of depression given side-effects such as hypertensive crisis and the long washout period and interactions with other medications. Bupropion is a safer initial alternative.

Bullet Summary:
Patients with depression who experience sexual side effects or weight gain on SSRIs may be switched to bupropion.


Question: A 69-year-old patient presents to the emergency department with shortness of breath and substernal pain. The patient has a medical history of obesity, anxiety, and constipation. He is currently not taking any medications and has not filled his prescriptions for over 1 year. An ECG is obtained and is seen in Figure A. The patient is managed appropriately and is discharged on atorvastatin, metoprolol, aspirin, clopidogrel, and sodium docusate. The patient visits his primary care physician 4 weeks later and claims to be doing better. He has been taking his medications and resting. At this visit, his temperature is 99.5°F (37.5°C), blood pressure is 130/87 mmHg, pulse is 80/min, respirations are 11/min, and oxygen saturation is 96% on room air. The patient states he feels better since the incident. Which of the following is the most appropriate next step in management?

Continue current medications and schedule follow up

Answer: Add lisinopril

Explanation:
This patient is presenting after a myocardial infarction for a follow-up appointment. The most appropriate next step in management is to start an angiotensin-converting enzyme (ACE) inhibitor such as lisinopril.

When a patient experiences a myocardial infarction, there are certain medications that the patient should be started on that lower mortality. These medications include beta-blockers, aspirin, statins, other antiplatelet agents (clopidogrel), and ACE inhibitors. ACE inhibitors can reduce mortality after myocardial infarction by reducing afterload, allowing the damaged myocardium to maintain its ejection fraction. These medications also inhibit ventricular remodeling in this disease. ACE inhibitors most prominently reduce mortality if a patient's ejection fraction is reduced. Of note, ACE inhibitors also reduce mortality in diabetes by decreasing hyperfiltration damage to the glomeruli.

Jering et al. hypothesized that using an angiotensin receptor neprilysin inhibitor would improve mortality in patients who have sustained a myocardial infarction. They discuss how an ACE inhibitor is the standard of care in patients currently. They recommend performing a randomized controlled trial comparing these treatment modalities.

Figure/Illustration A demonstrates an ECG with ST elevation (red circles) in leads II, III, and AVF. These ST elevations are indicative of a STEMI.

Incorrect Answers:
Answer A: Hydrochlorothiazide can be used to manage this patient's blood pressure; however, this drug does not lower mortality like an ACE inhibitor. In the setting of patients with myocardial infarctions, inhibition of detrimental ventricular remodeling is key for lowering mortality.

Answer C: Nifedipine is a calcium channel blocker that can be used to reduce blood pressure; however, it does not reduce mortality in patients who have experienced an MI. Calcium channel blockers tend to have few side effects and can be safely started in most patients.

Answer D: Continuing current medications and scheduling a follow-up appointment misses the opportunity for the patient to be started on a mortality-lowering ACE inhibitor. In patients who are amenable to starting a new medication, an ACE inhibitor should be administered to all patients who have sustained an MI.

Answer E: Switching to carvedilol would be unnecessary and not likely to benefit this patient as much as adding an ACE inhibitor. Metoprolol is the preferred beta blocker in patients who have sustained an MI. In the absence of idiosyncratic side effects, there is no indication to use another beta blocker.

Bullet Summary:
Patients who have experienced a myocardial infarction should be discharged on mortality-lowering drugs such as aspirin, beta-blockers, anti-platelet agents, and ACE inhibitors.


Question: A 67-year-old man presents to the emergency department with shortness of breath. His dyspnea began 1 hour ago while he was sitting in a chair watching television. He also endorses lightheadedness and fatigue but denies chest pain. Two weeks ago, he had a mitral valve repair for mitral insufficiency secondary to myxomatous degeneration. His medical history is otherwise significant for hypertension and diabetes mellitus, for which he takes metformin and lisinopril. His temperature is 98.8°F (37.1°C), blood pressure is 85/54 mmHg, pulse is 48/min, and respirations are 22/min. On physical exam, he appears to be in moderate distress. He has normal cardiac sounds with an irregular rhythm. His lungs are clear to auscultation bilaterally, and his electrocardiogram can be seen in Figure A. The patient is given an initial dose of atropine but this has no effect. Which of the following is the most appropriate next step in management?

Answer: Transvenous pacing

Explanation:
This patient who presents with lightheadedness has an ECG consistent with a Mobitz type 2 2nd-degree heart block. Because the patient is symptomatic from his dysrhythmia and it did not respond to atropine, the most appropriate next step is transvenous pacing.

Mobitz type 2 2nd-degree heart block can be distinguished from Mobitz type 1 (Wenckebach) by the length of the PR interval. Whereas the PR interval in Mobitz type 1 becomes progressively longer with each beat, the PR intervals in Mobitz type 2 are consistent in length and the QRS complexes drop suddenly. While Mobitz type 1 heart block is usually caused by atrioventricular (AV) node dysfunction, Mobitz type 2 is caused by dysfunction below the AV node in the His-Purkinje system. Patients with either type of heart block can present with lightheadedness or syncope. Since this pattern has a risk of progressing into 3rd-degree heart block, hemodynamic compromise, and asystole, Mobitz type 2 heart block is an indication for placement of a permanent pacemaker. Unstable patients who do not respond to atropine and/or other medical management should undergo transcutaneous or transvenous pacing.

Clark and Prystowsky present the pathophysiology of heart block. They discuss how dysfunction at the infranodal level leads to type 2 2nd-degree heart block. They recommend pacing in symptomatic patients.

Figure/Illustration A is an ECG that is characterized by consistent PR intervals (red lines) and sudden drops in the QRS complex. This pattern is classically seen with a Mobitz type 2 2nd-degree heart block.

Incorrect Answers:
Answer A: Adenosine can be used to terminate supraventricular tachycardia. These patients will present with tachycardia rather than bradycardia and will experience palpitations in addition to lightheadedness. The rhythm is rapid and regular with a narrow QRS complex.

Answer C: Cardioversion can be used to convert atrial flutter, atrial fibrillation, stable monomorphic ventricular tachycardia, or recalcitrant supraventricular tachycardia (non-responsive to adenosine or vagal maneuvers) to sinus rhythm, but it is not used for 2nd-degree heart block.

Answer B: Atropine can improve Mobitz type 1 2nd-degree heart block but tends not to be effective in Mobitz type 2 heart block in a stable patient. Atropine might be an appropriate treatment in symptomatic 3rd-degree heart block or Mobitz type 2 heart block; however, if it fails to improve a patient's symptoms, pacing is the most appropriate next step.

Answer D: Procainamide is a class 1A antiarrhythmic medication used to treat Wolff-Parkinson-White syndrome. This would present with an upgoing delta wave that occurs prior to the QRS complex. This medication does not play a role in the management of 2nd-degree heart block.

Bullet Summary:
Hemodynamically unstable patients with Mobitz type 2 2nd-degree heart block should be managed with transvenous pacing followed by a permanent pacemaker.


Question: A 3-day-old boy is evaluated in the hospital nursery for the delayed passage of meconium. The patient is breastfed, has been feeding well every 2 hours, and is urinating over 8 times per day. He was born at 35 weeks gestation to a 27-year-old G4P4 mother. The patient is of Ashkenazi Jewish descent and the patient’s parents refused all prenatal genetic testing. The pregnancy was uncomplicated until the patient’s mother had a spontaneous rupture of membranes at 35 weeks of gestation. The patient’s 3 older siblings are all healthy. The patient’s temperature is 98.2°F (36.8°C), blood pressure is 48/32 mmHg, pulse is 164/min, and respirations are 48/min. On physical exam, he appears to be in moderate distress. He has no dysmorphic features, and his abdomen is distended and non-tender. Bowel sounds are absent. Which of the following is the most appropriate next step in management?

Answer: Abdominal radiograph

Explanation:
Delayed passage of meconium should be evaluated with an abdominal radiograph to rule out bowel perforation. Patients with a perforation require emergency surgery.

All neonates should pass meconium in the first 48 hours of life. Patients that fail do to so should be evaluated with an abdominal radiograph to exclude the possibility of bowel perforation. If free air is seen on the abdominal radiograph, patients should be taken for emergent surgery to repair the perforation. If bowel perforation is ruled out, a workup should be done to determine the etiology of the delayed passage, which would most likely include a contrast enema to differentiate between meconium ileus and Hirschsprung disease. Treatment is with meconium removal or excision of the defective segment respectively.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Incorrect Answers:
Answer A: An abdominal radiograph would be faster than an abdominal CT to rule out an indication for emergency surgery. The use of CT should also be restricted in the pediatric population due to the radiation exposure involved. Adult patients with unclear radiographic findings can be further assessed using a contrast CT scan.

Answer C: Contrast enema is the test of choice to differentiate meconium ileus from Hirschsprung disease, but the most important first step is to rule out bowel perforation. Patients who do not have perforation can then undergo this test to determine the etiology of failure to pass meconium.

Answer D: Sweat testing would aid in the diagnosis of cystic fibrosis, particularly in this patient who has had no prenatal screening. The first step in management should be an abdominal radiograph to rule out bowel perforation. Cystic fibrosis can be treated with pancreatic enzyme replacement and pulmonary therapy.

Answer E: Upper gastrointestinal series is used to make the diagnosis of intestinal malrotation, which more commonly presents with bilious vomiting secondary to midgut volvulus rather than the delayed passage of meconium. Treatment is with surgical derotation.

Bullet Summary:
Neonates who fail to pass meconium in the first 48 hours of life should be urgently evaluated with an abdominal radiograph to rule out bowel perforation.


Question: A 25-year-old man presents to his primary care physician with anxiety and fatigue. During this past week, he has been unable to properly study and prepare for final exams because he is exhausted. He has been going to bed early but is unable to get a good night’s sleep. He admits to occasional cocaine and marijuana use. Otherwise, the patient has no significant medical history and is not taking any medications. His temperature is 98.6°F (37°C), blood pressure is 115/71 mmHg, pulse is 72/min, and respirations are 12/min. On physical exam, the patient is a tired and anxious appearing young man. His neurological exam is within normal limits. The patient states that he fears he will fail his courses if he does not come up with a solution. Which of the following is the most appropriate initial step in management?

Answer: Sleep hygiene education

Explanation:
This patient is presenting with trouble sleeping without a known organic cause, for which the most appropriate initial step in management is to discuss sleep hygiene with the patient.

In any patient that presents with a chief complaint of fatigue, it is always best to assess how they are sleeping. After a physical exam is performed in order to rule out signs or symptoms of a severe organic cause (neurologic deficits), the most appropriate initial step in management is to discuss sleep hygiene with the patient. Sleep hygiene includes discussing the patient’s exposure to light (eliminate exposure to blue light at night), altering diet (no large meals or caffeine before bed), and behavioral modification (only using the bed for sleep). Once a trial of proper sleep hygiene has been tried, then it would be appropriate to potentially move on to other interventions including pharmacological interventions.

Horne presents evidence regarding the best sleep hygiene practices. He discusses how exercise and avoidance of caffeine near bedtime is beneficial to helping with insomnia. He recommends using these interventions prior to pharmacologic treatment.

Incorrect Answers:
Answer A: Alprazolam is a benzodiazepine that could be used to help with this patient’s anxiety and could help them sleep. However, benzodiazepines are potent drugs with addictive properties and would not be used as first-line treatment for insomnia. Lifestyle modifications should be tried first to determine if these will be effective in helping the patient sleep.

Answer B: Melatonin is a supplement that is often used to improve sleep quality. Starting the patient on a supplement is plausible as an initial step in management, but it would not take precedence over educating the patient regarding sleep hygiene. These interventions often are very effective and have no side effects.

Answer C: Polysomnography could be the most appropriate initial step in management if an organic cause for this patient’s sleep problems (such as obstructive sleep apnea) is suspected. There is nothing suggesting an organic cause for this patient’s sleep issues and it is highly likely that a college-age student near finals period would benefit from a discussion on sleep hygiene prior to an expensive diagnostic test such as polysomnography.

Answer E: Zolpidem is a muscle relaxant and hypnotic with a similar mechanism of action to a benzodiazepine. Zolpidem has the potential to be addicting and would not be tried prior to sleep hygiene interventions. Some patients who are refractory to other interventions may benefit from the use of Zolpidem.

Bullet Summary:
Any patient that presents with fatigue and trouble sleeping without a clear organic cause should first be counseled in sleep hygiene habits prior to any other interventions or diagnostic tests.


Question: A 67-year-old man presents to the emergency room reporting sudden-onset abdominal and back pain that began 3 hours ago. He was eating dinner when he started feeling severe pain in his abdomen that made him lose his appetite. He denies any diarrhea or hematochezia and says the pain is not affected by movement. He has a history of hypertension, hyperlipidemia, and depression. He currently takes amlodipine and atorvastatin and is compliant with his medications. He has a 45-pack-year smoking history, but he does not drink alcohol or use any illicit drugs. His temperature is 98.6°F (37°C), his blood pressure is 110/64 mmHg, pulse is 97/min, and respirations are 15/min. Physical exam is notable for diffuse abdominal tenderness without rigidity or guarding. During evaluation, the patient becomes diaphoretic and pale and reports that he feels fatigued. Repeat blood pressure is 87/50 and pulse is 127. Intravenous fluid boluses are administered. Which of the following is the most likely diagnosis?

Answer: Ruptured abdominal aortic aneurysm

Explanation:
This patient who presents with sudden-onset abdominal pain, hemodynamic instability (symptomatic hypotension with tachycardia), and significant history of hypertension and smoking most likely has a ruptured abdominal aortic aneurysm (AAA).

Abdominal aortic aneurysms are dilations in the vessel wall that can predispose to rupture. Risk factors for AAA include advanced age (> 60 years), smoking history, male sex, and history of atherosclerosis. AAA can be asymptomatic or mildly symptomatic until it markedly expands or ruptures, leading to abdominal pain, back pain, or flank pain. The evaluation of suspected AAA depends on the hemodynamic stability of the patient and prior knowledge (or lack thereof) of the existence of an AAA. A hemodynamically unstable patient with a known history of AAA should be assumed to have a ruptured AAA and undergo surgical intervention without further workup (though bedside ultrasound can support the diagnosis). In an unstable patient without a known history, a bedside ultrasound to confirm the diagnosis should precede surgical intervention. In a hemodynamically stable patient with or without a known AAA history, an abdominal CTA is appropriate.

Sakalihasan et al. present a review of the presentation and treatment of abdominal aortic aneurysms. They discuss how patients are often asymptomatic until catastrophic rupture occurs. They recommend immediate surgical repair of the aneurysm during ruptures to prevent death.

Incorrect Answers
Answer A: Acute pancreatitis also presents with abdominal pain and can present with hemodynamic instability in severe cases of hemorrhagic conversion of pancreatitis. This is a rare entity and is less likely in this patient. Treatment is immediate transcatheter arterial embolization for unstable patients with hemorrhagic pancreatitis.

Answer B: Aortic dissection has similar risk factors to AAA (history of hypertension, advanced age) and also presents with acute onset back pain. Dissection normally occurs in the setting of hypertension. This diagnosis is possible but less likely in this man with a history of smoking.

Answer C: Ischemic colitis can also present with abdominal pain in a patient with risk factors for atherosclerotic disease. It is associated with hematochezia and diarrhea and is unlikely to cause the level of hypotension in this patient. Treatment is with restoration of blood flow to the ischemic bowel segment or resection if this is not possible. Management is usually centered on medical optimization.

Answer D: Perforated viscus is a surgical emergency that can also present acutely with hemodynamic instability and severe abdominal pain. However, signs of peritoneal irritation are usually present (guarding, rigidity). Treatment is with immediate surgical exploration and repair or resection.

Bullet Summary:
Patients with new-onset back and abdominal pain and a positive smoking history that progresses to hemodynamic instability should be suspected of having a ruptured abdominal aortic aneurysm.


Question: A 15-month-old boy presents with his mother for his well-child exam. His mother is concerned about his vision, as she noticed him squinting while watching television. The patient was born at 39 weeks of gestation via spontaneous vaginal delivery. He is up to date with routine vaccinations. He is able to walk alone, speak 3 words, and scribble with a crayon. His temperature is 98.6°F (37.0°C), blood pressure is 80/55 mmHg, pulse is 105/min, and respirations are 25/min. On exam, his pupils are round and reactive to light. A photograph of his eyes is shown in Figure A. When focusing on the pediatrician's penlight, the patient's left eye wanders. However, when the right eye is covered, the left eye refocuses on the light. The rest of his neurological exam, including extraocular movements, is within normal limits. Which of the following is the most appropriate next step in management for this patient?

Answer: Patch the right eye

Explanation:
This patient, with a history that suggests decreased visual acuity, a positive cover test (refixation of the misaligned eye upon covering the appropriately aligned eye), and an asymmetric corneal light reflex in Figure A, is presenting with strabismus. Of the answer choices, only patching the sound eye (right eye) is an appropriate treatment.

Strabismus occurs when a patient's eyes are not aligned properly. It often presents in children with one or both eyes turning inward, outward, upward, or downward. Patients will often tilt their heads or squint their eyes to correct this misalignment. Without proper treatment, there is a significant risk of developing amblyopia. Amblyopia is a developmental disorder in the visual cortex caused by abnormal visual stimuli. Untreated strabismus is the most common cause of amblyopia; it is secondary to visual loss from the deviated eye. The treatment of choice is wearing an eye patch over the appropriately tracking eye (sound eye), thereby encouraging the use of the deviated eye and preventing vision loss in this eye. Other treatments include surgical correction of strabismus, pharmacological penalization of the sound eye with atropine, and dichoptic movies and video games.

Gopal et al. discuss the pathophysiology, prevention, and therapy for amblyopia as it relates to strabismus. The authors find that the earlier clinically refractive error and strabismus are detected and treated, the greater the likelihood of preventing amblyopia. The authors recommend treating amblyopia with the correction of refractive errors, patching, and pharmacologic treatments.

Figure/Illustration A shows displacement of the light reflex from the center of the pupil in this patient's right eye, as indicated by the black arrow. This is known as an asymmetric corneal light reflex and is seen in strabismus.

Incorrect Answers:
Answer A: Brain MRI is part of the initial workup for retinoblastoma. Retinoblastoma typically presents in early childhood with visual loss, leukocoria, and an abnormal red reflex, which this patient does not have.

Answer B: Head CT in a pediatric patient could be used to rule out hemorrhage following blunt head trauma. This patient has not experienced head trauma and has no symptoms of traumatic brain injury (abnormal neurologic exam, loss of consciousness seizures). CT scans are not preferred in pediatric patients to avoid radiation exposure.

Answer C: Patching the left eye (the inappropriately tracking eye) would not treat this patient's strabismus and would likely increase his risk for amblyopia due to further decreasing his visual stimuli in this eye.

Answer E: The Bielschowsky head tilt test is used to help diagnose trochlear nerve (CN IV) palsy. Patients with a unilateral trochlear nerve and subsequent superior oblique palsy experience double vision when tilting their head to one side, which is improved by tilting the head towards the shoulder on the unaffected side. A trochlear nerve palsy typically presents with difficulty looking down and a head tilt away from the side of the lesion, unlike this patient who appears to have a visual acuity deficit.

Bullet Summary:
Patching the appropriately aligned eye is the treatment of choice for strabismus to prevent progression to amblyopia.


Question: A 14-day-old girl is brought to the emergency department for diarrhea. Her mother reports that the patient began having “explosive” diarrhea 6 hours ago. The patient has little interest in feeding since leaving the hospital after her birth and has not yet regained her birth weight. Her immediate postnatal period was otherwise significant for 2 episodes of bilious vomiting that resolved with the temporary use of a nasogastric tube and expulsion of stool during a digital rectal exam. The patient passed meconium on the 3rd day of life. Her temperature is 101.8°F (38.8°C), blood pressure is 58/37 mmHg, pulse is 148/min, and respirations are 38/min. On physical exam, the patient appears to be in moderate distress. She has no dysmorphic features and she has a normal S1/S2 without any murmurs, rubs, or gallops. Her abdomen is firm and distended. A digital rectal exam reveals a tight anal sphincter and precipitates a release of gas and liquid stool. Her abdominal radiograph can be seen in Figure A. Which of the following is the most accurate test to diagnose this patient’s condition?

Answer: Rectal suction biopsy

Explanation:
This neonatal patient presents with bilious vomiting, failure to thrive, colonic distension on an abdominal radiograph, and new fever and tachycardia, which suggests a diagnosis of Hirschsprung disease complicated by enterocolitis. A rectal suction biopsy is the most accurate test to diagnose Hirschsprung disease.

Hirschsprung disease presents in the neonatal period with bilious vomiting, failure to pass meconium in the first 48 hours of life, failure to thrive, and temporary relief of the intestinal obstruction by digital rectal exam. The most severe neonatal complication of Hirschsprung disease is Hirschsprung-associated enterocolitis, which presents in the first few weeks to months of life with explosive diarrhea, fever, and abdominal pain/distension. The most appropriate first step to diagnose Hirschsprung disease is a contrast enema, which may visualize a “transition zone” where the caliber of the intestine switches from the dilated proximal colon to the narrowed aganglionic segment. The most accurate test is a rectal suction biopsy, which will show a lack of ganglion cells. Surgical removal of the aganglionic portion of the colon is preferred management.

Kessman reviews the evidence regarding the diagnosis and treatment of Hirschsprung disease. She discusses how the diagnosis can be made using a rectal suction biopsy. She recommends monitoring patients closely for enterocolitis for years after surgical treatment.

Figure/Illustration A is an abdominal radiograph demonstrating diffuse proximal colonic distension (red circle) with a paucity of air in the rectosigmoid. This finding suggests a diagnosis of Hirschsprung disease.

Incorrect Answers:
Answer A: A contrast enema is both a diagnostic and therapeutic intervention for intussusception. It may also be used in the workup of bilious emesis to help differentiate between Hirschsprung disease and meconium ileus, but it is not the most accurate test.

Answer B: Genetic testing would be used to diagnose cystic fibrosis, which is associated with meconium ileus. Although meconium ileus presents with delayed passage of meconium (> 48 hours of life), meconium ileus is not relieved by a digital rectal exam. Treatment is with irrigation and removal of the meconium.

Answer C: Intraoperative cholangiogram is the gold standard for diagnosing biliary atresia. Biliary atresia presents with jaundice, pale stools or dark urine, and hepatomegaly over the first week to 2 months of life. Treatment is with urgent surgical intervention to prevent liver failure.

Answer E: Upper gastrointestinal series is used to diagnose intestinal malrotation, as the ligament of Treitz can be visualized on the right side of the abdomen. Malrotation may present with bilious vomiting if the malrotation has been complicated by midgut volvulus, but it would not be relieved by digital disimpaction. Treatment is with surgical derotation of the volvulus.

Bullet Summary:
The most accurate test to diagnose Hirschsprung disease is a rectal suction biopsy to demonstrate the absence of ganglion cells.


Question: A 37-year-old woman presents to her physician for mood changes and recent falls over the course of 3 months. She feels more irritable with her husband and children and does not find pleasure in creating art anymore. Over the last 2 weeks, she has been sleeping approximately 5 hours a night and had a fall while walking in her home with the lights off. She denies any head trauma or loss of consciousness associated with the fall. She has a medical history of generalized anxiety disorder and hypothyroidism for which she takes escitalopram and levothyroxine. She had a Roux-en-Y gastric bypass 5 years ago. She has been in a monogamous relationship with her husband for the last 15 years and uses a copper intrauterine device. Physical examination is notable for a depressed affect. Pupils are equal, round, and reactive to light and accommodation. She has 4/5 strength in the bilateral lower extremities and brisk patellar reflexes. Which of the following is most likely the cause of this patient's symptoms?

Answer: Reduced functional parietal cell count

Explanation:
This patient's mood changes and findings concerning for subacute combined degeneration (fall in the dark, impaired proprioception, weakness, and brisk patellar reflexes), and history of Roux-en-Y gastric bypass surgery are concerning for vitamin B12 deficiency. Roux-en-y gastric bypass reduces parietal cell count, leading to reduced intrinsic factor secretion, which is needed for vitamin B12 absorption.

Roux-en-Y gastric bypass is a laparoscopic bariatric procedure that creates a small gastric pouch from the stomach with a gastrojejunal and jejunojejunal anastomosis. This causes small volumes of food to be consumed and decreases nutrient absorption. The small gastric pouch contains very few parietal cells, which decreases hydrochloric acid and intrinsic factor secretion. The reduced intrinsic factor secretion impairs the protection of vitamin B12 against HCl and reduces absorption in the ileum. Vitamin B12 deficiency can lead to neuropsychiatric changes (depressed mood, irritability, and insomnia) and subacute combined degeneration (weakness, sensory ataxia, peripheral neuropathy, and upper motor neuron signs). Patients who undergo Roux-en-Y gastric bypass must be given high doses of vitamin B12 (often intramuscularly) in order to prevent deficiency.

Alexandrou et al. review long-term micronutrient deficiencies after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). The authors find that vitamin B12 deficiency was significantly higher in patients with RYGB compared with sleeve gastrectomy. The authors recommend adherence to supplemental iron and vitamin intake in all patients who undergo bariatric surgery.

Incorrect Answers:
Answer A: Poor iron absorption is a well-known complication of Roux-en-Y gastric bypass surgery due to bypass of the duodenum and proximal jejunum. Poor iron absorption leads to microcytic anemia from iron deficiency and presents with generalized fatigue and conjunctival pallor. Iron deficiency anemia would not present with brisk reflexes and impaired proprioception.

Answer B: Prior Treponema pallidum exposure can result in tabes dorsalis, a neurological complication of syphilis, and is seen in patients with a history of multiple sexual partners who do not use barrier protection. The spirochete leads to disease in the posterior columns (vibration and proprioception sensation). Patients present with sensory ataxia (similar to subacute combined degeneration), lancinating pain (in the limbs, back, or face), and an Argyll-Robertson pupil (impaired pupillary constriction to light but intact pupillary constriction to accommodation).

Answer C: Reduced central nervous system dopamine and serotonin are seen in patients with major depressive disorder which does not cause sensory ataxia with brisk reflexes.

Answer E: Subtherapeutic levothyroxine dose would result in hypothyroidism, which can present with depressed mood, cold intolerance, bradycardia, and delayed relaxation of deep tendon reflexes. Roux-en-Y is an effective means of losing weight, and as the body mass decreases with weight loss, the required dose of levothyroxine is decreased. It would not present with the abnormal neurologic findings seen in this patient.

Bullet Summary:
Roux-en-Y bariatric surgery increases the risk of vitamin B12 deficiency via reduction of food intake, decreased functional parietal cell count, and reduced absorption of vitamin B12 (which may cause subacute combined degeneration).


Question: A 23-year-old man presents to the emergency department after he was rescued while hiking in Alaska. The patient was found on a mountain trail non-responsive. His temperature is 91°F (32.8°C), blood pressure is 103/61 mmHg, pulse is 60/min, respirations are 11/min, and oxygen saturation is 97% on room air. The patient is placed under a warm air circulator, and his extremities are bathed in warm water. An ECG is performed as seen in Figure A. Dark bullae are noted on the patient's extremities. His mental status rapidly improves with warming. Laboratory studies are ordered and are pending. Which of the following is most likely to be found in this patient?

Answer: Hypocalcemia

Explanation:
This patient is presenting after being found outside with hypothermia and frostbite (dark bullae noted on the extremities in the setting of being out in the cold). Frostbite can lead to rhabdomyolysis, which may cause hyperkalemia (causing ECG changes including peaked T waves and QRS widening as seen in this patient) and hypocalcemia (the most common electrolyte finding in frostbite).

Frostbite occurs when there is an extensive freezing injury to tissues and can cause benign swelling, erythema, and pain, all the way to insensate extremities with necrosis and permanent dysfunction. More severe forms of frostbite can cause rhabdomyolysis or breakdown of the muscles. Breakdown of the muscle cells leads to leakage of the intracellular contents. Common electrolyte derangements include hyperkalemia and hypophosphatemia. Hypocalcemia is the most common electrolyte derangement in rhabdomyolysis. It occurs due to the deposition of calcium in the necrotic muscle cells and the sequestration of calcium in the exposed sarcoplasmic reticulum. Note that hypocalcemia requires no treatment unless it is causing symptoms or ECG changes (such as QT prolongation). The management of rhabdomyolysis is centered on fluid administration to protect the kidney from myoglobin which is released from damaged muscles and is nephrotoxic.

Zimmerman and Shen review rhabdomyolysis. They note that rhabdomyolysis can be commonly associated with myoglobinuria, hyperkalemia, hypocalcemia, and hyperphosphatemia. They suggest that an elevated creatine kinase level is indicated to support the diagnosis.

Figure/Illustration A is an ECG demonstrating peaked T waves (blue arrows) which are associated with hyperkalemia.

Incorrect Answers:
Answer A: Elevated troponin may be seen in rhabdomyolysis. This is a non-cardiac cause of an elevated troponin; however, this is less common than hypocalcemia in rhabdomyolysis and is neither sensitive nor specific.

Answer C: Hypomagnesemia is not a common electrolyte disturbance seen in rhabdomyolysis; however, hypomagnesemia may cause hypocalcemia (from impaired PTH release) and hypokalemia (from renal wasting of potassium). Note that this mechanism is separate from rhabdomyolysis.

Answer D: Hypophosphatemia is common in refeeding syndrome and malnourished patients (such as those with alcohol use disorder) and presents with diffuse muscle weakness. Rather, hyperphosphatemia would be seen in rhabdomyolysis as it is released from damaged muscle cells.

Answer E: Red blood cells on urine microscopy would be seen in a nephritic syndrome in addition to red blood cell casts. Note that the urine dipstick will be positive for red blood cells in rhabdomyolysis due to cross-reactivity with myoglobin; however, there are minimal/no red blood cells actually present.

Bullet Summary:
Frostbite can result in rhabdomyolysis which commonly causes hyperkalemia, hyperphosphatemia, and hypocalcemia (the most common derangement).


Question: An 8-year-old boy is brought to the emergency department by his parents for evaluation. He has had headache and fever for the last 2 days, and this morning he was confused and had difficulty answering questions. He also developed a rash this morning. He recently returned from summer camp. He has no significant medical history and takes no medications. His temperature is 104°F (40°C), pulse is 120/min, blood pressure is 105/60 mmHg, and respirations are 22/min. On exam, flexion of the neck causes flexion of the hips and knees. Fundoscopic exam reveals no papilledema. Examination of the patient's rash is shown in Figure A. Which of the following is the most appropriate next step in management?

Lumbar puncture, ceftriaxone, vancomycin, and methylprednisolone

Vancomycin, ceftriaxone, and dexamethasone

Answer: Lumbar puncture, ceftriaxone, vancomycin, and methylprednisolone

Explanation:
This patient with fever, headache, signs of meningeal irritation, and a purpuric rash likely has bacterial meningitis. The most appropriate initial step in management is a lumbar puncture as well as ceftriaxone, vancomycin, and methylprednisolone.

Meningitis classically presents with fever, neck stiffness or headache, and altered mental status. Specific physical exam findings that can suggest the diagnosis include meningeal signs such as a positive Kernig sign (inability to extend the knee while the hip is flexed) and Brudzinski sign (flexion of the neck results in flexion of lower extremities). Common causative agents include Streptococcus pneumoniae and Neisseria meningitidis. The latter of which is associated with the purpuric rash seen in this patient. The best initial step in management is a lumbar puncture followed promptly by IV broad spectrum antibiotics. Once the diagnosis/infectious agent is confirmed, the antibiotic agents can be refined. Other early steps in management include early blood cultures and fluid resuscitation. Steroids should be given in the setting of suspected Waterhouse-Friderichsen syndrome and concern for adrenal failure.

Linder et. al review meningococcal meningitis. They discuss the pathophysiology, clinical manifestations, and diagnosis. They describe the association of purpuric rash with meningococcal infection, and note that this is indicative of disseminated intravascular coagulation.

Figure A. demonstrates a purpuric rash over the lower extremities, which is classically associated with meningococcal meningitis. However, this can occur with meningitis or bacteremia from other infectious agents, as it is indicative of disseminated intravascular coagulation.

Incorrect Answers:
Answer A: Blood and urine cultures would be appropriate initial management for a fever of unknown origin and in this patient. Early antibiotics must be given as well to reduce mortality and improve outcomes.

Answer C: MRI brain would not be appropriate in this setting. While CNS imaging is sometimes indicated prior to lumbar puncture if signs of increased intracranial pressure such as papilledema are present, CT imaging is typically preferred. Time required to obtain MR imaging is prohibitive and would delay definitive care for this patient.

Answer D: Vancomycin and ceftriaxone are an appropriate initial antibiotic regimen for meningitis in children and adults. However, steroids are often added empirically. Lumbar puncture should be performed prior to administration of antibiotics (if possible) to avoid sterilization of the CSF.

Answer E: Vancomycin, ceftriaxone, and prednisone are an appropriate initial regimen for meningitis in adults. Steroids have been shown to reduce inflammation and prevent neurologic sequelae. However, lumbar puncture should be performed prior to administration of antibiotics if possible to avoid sterilization of the CSF. Also, IV steroids are preferred rather than oral in ill patients.

Bullet Summary:
The best initial step in management for meningitis is a lumbar puncture followed by broad-spectrum antibiotics and steroids.


Question: A 55-year-old man presents to the emergency department with chest pressure and diaphoresis. His symptoms started at work when he was lifting boxes. He states that he currently feels crushing pressure over his chest. He is given aspirin and an ECG is performed in triage, as seen in Figure A. His past medical history is notable for diabetes and obesity. He has smoked 1 pack of cigarettes per day for the past 30 years. His temperature is 97.9°F (36.6°C), blood pressure is 155/99 mmHg, pulse is 110/min, respirations are 22/min, and oxygen saturation is 98% on room air. Physical exam reveals an uncomfortable, diaphoretic man. His heart and breath sounds are unremarkable. A repeat ECG in the emergency department is performed, also seen in Figure A. The patient’s chest pain is worse when the ECG in the emergency department is taken, compared to the one taken in triage. He is given nitroglycerin, with minimal improvement in his symptoms. A troponin level is drawn. Which of the following is the most appropriate next step in management?

Answer: Repeat ECG in 10 minutes

Explanation:
This patient is presenting with a pattern of chest pain (pressure and diaphoresis) that is highly concerning for an acute myocardial infarction. This patient initially has ST depressions (in triage) followed by ST segment normalization and possibly hyperacute T waves which raises concern for an acute ST elevation myocardial infarction (STEMI) requiring frequent ECGs to determine if a STEMI evolves.

A STEMI presents with crushing substernal chest pain, diaphoresis, chest pressure, nausea, vomiting, and abdominal pain among many other possible presentations. When a patient presents with symptoms concerning for a STEMI, aspirin should be administered and an ECG should be performed. Early in a myocardial infarction, ST depressions with hyperacute T waves may be present. As the infarction evolves, the T waves may become more acute and the ST segment will begin to elevate. There may be a brief period of pseudonormalization where the ST segment appears to be normal. If the patient appears better, this can be reassuring. However, ongoing chest pain in the setting of these findings raises concern for pseudonormalization of the ST segment (an ST segment that is going to continue to rise). Nitroglycerin can be administered to see if the patient can become chest pain-free, and serial ECGs should be performed to determine if a STEMI is present. If symptoms resolve and the ECG is stable, this is reassuring and medical optimization and an elective catheterization may be performed. If the ECG evolves into a STEMI, then cardiac catheterization is indicated emergently.

Daga et al. discuss STEMI and its workup. They note the ECG manifestations, and the pathophysiology in addition to the appropriate workup of acute coronary syndrome. They recommend aspirin and catheterization in an acute STEMI.

Figure/Illustration A demonstrates an initial ECG with ST depression (blue arrows) followed by pseudonormalization of the ST segment (green arrows) and possibly hyperacute T waves (black arrows), which are concerning for ischemia.

Incorrect Answers:
Answer A: Cardiac catheterization may be required in this patient; however, if the patient’s chest pain improves or if the troponin is negative, it is unlikely he is having an acute myocardial infarction requiring immediate catheterization. Repeating the ECG will allow for triaging of the patient and will aid in determining if emergency cardiac catheterization is needed.

Answer B: Chest radiography is appropriate in the workup of chest pain as it can rule out diagnoses such as pneumothorax or may suggest diagnoses such as an aortic dissection (type A) if there is a widened mediastinum. In this patient, the ST segment changes and characteristic history make acute coronary syndrome a more likely diagnosis, and while a chest radiograph should be performed at some point, repeating the ECG is a more dire initial step in management.

Answer C: CK-MB level could be helpful in determining if a myocardial infarction has occurred as it elevates rapidly and also decreases fairly rapidly. This makes it useful when diagnosing a new myocardial infarction after a recent infarction as the troponin may still be elevated from the previous infarction. This patient has no history of recent myocardial infarction, and a repeat ECG is more dire to determine if this patient needs emergent intervention. Of note, the decision for emergent catheterization should not wait on cardiac biomarkers.

Answer D: Heparin should not be given empirically to patients in chest pain. It does not necessarily decrease mortality but does increase the risk of bleeding. It is often given to patients with an NSTEMI.

Bullet Summary:
Pseudonormalization occurs when an ST depression begins to elevate and appears normal in the setting of a myocardial infarction, requiring close monitoring and serial ECGs to ensure that a ST elevation myocardial infarction does not occur.


Question:
A 47-year-old woman presents to the clinic with 3 weeks of increased thirst and urination. She has a history of obesity, hypertension, and depression for which she takes losartan and sertraline. She has smoked 1 pack of cigarettes per day for 30 years. Her temperature is 99.5°F (37.5°C), blood pressure is 148/90 mmHg, pulse is 84/min, and respirations are 15/min. Physical exam is unremarkable, including no costovertebral or suprapubic tenderness to palpation. Laboratory studies are performed and show:

Serum:
Na+: 140 mEq/L
K+: 4.4 mEq/L
HCO3-: 21 mEq/L
Blood urea nitrogen (BUN): 38 mg/dL
Creatinine: 1.1 mg/dL
Glucose: 215 mg/dL

Which of the following is the most appropriate screening test for nephropathy in this patient?

Answer: Urine albumin-to-creatinine ratio

Explanation:
This patient with a history of obesity and hypertension presenting with polyuria and polydipsia in the setting of an elevated random blood glucose (> 200 mg/dL) likely has a new diagnosis of type 2 diabetes mellitus. The urine albumin-to-creatinine ratio is the most appropriate early test for diabetic nephropathy.

Early detection of diabetic nephropathy is key to management, as the complication eventually leads to overt kidney disease and renal failure. The diagnosis of diabetic nephropathy is based on > 30 mg/g of albuminuria for > 3 months. Patients with type 2 diabetes mellitus should be screened annually with a random urine albumin-to-creatinine ratio starting at diagnosis. Elevation of urine albumin warrants treatment with ACE inhibitors or angiotensin receptor blockers. Blood pressure control slows the progression of diabetic nephropathy. Patients with type 2 diabetes mellitus and diabetic nephropathy should be started on a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Patients with persistent albuminuria despite both ACE/ARB and SGLT2 inhibitor therapy should be started on the nonsteroidal selective mineralocorticoid receptor antagonist (MRA) finerenone.

Bakris et al. study the efficacy of finerenone, a nonsteroidal selective MRA, in the treatment of patients with albuminuria in patients with chronic kidney disease (CKD) and type 2 diabetes. The authors found in a randomized control trial that finerenone reduced the incidence of a composite outcome of kidney failure. The authors recommend the use of finerenone in patients with persistent albuminuria despite optimal medical therapy to prevent risks of CKD progression and cardiovascular events.

Incorrect Answers:
Answer A: Creatinine clearance changes over the time course of diabetic nephropathy and can be normal or elevated (due to glomerular hyperfiltration) in early diabetic nephropathy. Therefore, it is an unreliable test for early diabetic nephropathy compared to the more sensitive urine albumin-to-creatinine ratio.

Answer B: Hemoglobin A1c is a test that reflects the average blood glucose over the past 2 to 3 months. While this test provides information on a patient's glycemic control, it does not directly assess the presence or extent of diabetic nephropathy.

Answer C: Oral glucose tolerance test is the test of choice for diagnosing gestational diabetes. It does not play a role in the detection of diabetic nephropathy.

Answer E: Urine protein dipstick is a useful test to detect proteinuria. This test is insensitive to low levels of albumin. Therefore, it is considered an inferior test to urine albumin-to-creatinine ratio in the diagnosis of diabetic nephropathy.

Bullet Summary:
Urine albumin-to-creatinine ratio testing is the most sensitive test to detect moderately elevated levels of urinary albumin excretion, a known byproduct of diabetic nephropathy.


Question: A 60-year-old man presents to his primary care physician with weight gain. He states that ever since his wife died 4 months ago, he has been eating and sleeping more and no longer engages in any activities he once enjoyed such as hiking or fishing. He feels guilty for not spending more time with his wife before she died. He was recently fired for making several major bookkeeping mistakes at work as an accountant as he had trouble focusing. The patient is requesting oxycodone at this appointment as he states he has burning pain in his legs that feels worse now than it has in years past. The patient has a past medical history of obesity, poorly controlled diabetes, hypertension, and peripheral vascular disease. His temperature is 98.7°F (37.1°C), blood pressure is 129/82 mmHg, pulse is 83/min, respirations are 15/min, and oxygen saturation is 99% on room air. Physical exam reveals a stable gait and reduced sensation symmetrically over the lower extremities. He complains of electric pain when touching his lower extremities. His affect seems depressed. Which of the following is the most appropriate treatment for this patient?

Answer: Venlafaxine

Explanation:
This patient is presenting with sleep changes, interest loss, guilt, decrease in energy, and trouble concentrating for greater than 2 weeks concerning for major depressive disorder. In the setting of his diabetic neuropathy (lower extremity burning pain in the setting of poorly managed diabetes), a serotonin-norepinephrine reuptake inhibitor (SNRI) such as venlafaxine is the most appropriate initial treatment for this patient.

Major depressive disorder should always initially be managed with cognitive behavioral therapy and often medication. Typically, the first-line medication is a selective serotonin reuptake inhibitor (SSRI). However, SNRIs such as venlafaxine and duloxetine are viable first-line options. They are particularly preferred in patients with diabetic neuropathy as they treat both diabetic neuropathy and depression. SNRIs are also generally considered to be less sedating than SSRIs. For this reason, SNRIs are often a better initial drug in depression than SSRIs in diabetic patients with peripheral neuropathy.

Sansone and Sansone discuss SNRIs and their uses. They discuss how there are different efficacies and propensities of the different SNRIs. They recommend choosing an appropriate SNRI based on the patient's needs and comorbidities.

Incorrect Answers:
Answer A: Amitriptyline is a tricyclic antidepressant that can be used to treat depression in patients who also suffer from other neuropathic pain conditions or conditions such as fibromyalgia or irritable bowel syndrome. While it may also be used in diabetic neuropathy and depression, there is higher toxicity with this medication than SNRIs. For this reason, SNRIs are preferred. A TCA might be appropriate if the patient had already failed other first-line agents.

Answer B: Bupropion is a weight-neutral antidepressant that can be used in smoking cessation and patients who are trying to avoid the sexual side effects of SSRIs (anorgasmia). It would not address this patient's diabetic neuropathy, though it could be beneficial for his obesity.

Answer C: Escitalopram is an SSRI that could be used first-line for major depressive disorder. However, if a patient has a concomitant condition, it is better to choose a single agent that addresses both problems; thus, SNRIs are better first-line medications in this patient with diabetic neuropathy.

Answer D: Phenelzine is a monoamine oxidase inhibitor that can be used in atypical depression or as a third-line or later agent in the management of depression. This agent can cause a hypertensive crisis in the setting of tyramine consumption, has many medication interactions, and a long washout period. Thus, it is not usually a first or second-line agent. However, it is highly effective in patients who have failed other first-line agents and should still be used in appropriate candidates.

Bullet Summary:
SNRIs are appropriate first-line agents for major depressive disorder in patients with diabetic neuropathy.


Question: A 68-year-old woman presents to the emergency room with several days of frequent, nonbloody, watery stools. She recently completed a course of clindamycin 2 weeks ago for a tooth infection. Her medical history is notable for hypertension and hyperlipidemia for which she takes amlodipine and atorvastatin. She traveled recently and has no sick contacts. Her temperature is 37.0°C (98.6°F), blood pressure is 118/82 mmHg, pulse is 98/min, respirations are 14/min, and oxygen saturation is 98% on room air. On exam, her abdomen is soft, non-distended, and non-tender to palpation; however she has diffuse discomfort upon palpation of the abdomen with no rebound, rigidity, or guarding. Which of the following is most likely to confirm the diagnosis?

Answer: Stool toxin assay

Explanation:
This patient presenting with cramping abdominal pain and frequent watery diarrhea a few weeks after finishing a course of antibiotics most likely has Clostridioides difficile infection, for which the most appropriate confirmatory test is a stool toxin assay.

C. difficile infection should be suspected in patients with acute and clinically significant diarrhea with no obvious alternative explanation. It is associated with risk factors such as recent antibiotic use, hospitalization, and advanced age. Diagnosis is established via a positive enzyme immunoassay for C. difficile toxins and C. difficile glutamate dehydrogenase (GDH), or a positive nucleic acid amplification test (NAAT) for C. difficile toxins. The GDH enzyme immunoassay is highly sensitive for detecting C. difficile, but not specific for toxin-producing C. difficile, and thus the toxin enzyme immunoassay is submitted in conjunction. If the results of both are discordant, then NAAT is used to make the diagnosis. Treatment for C. difficile infection differs by disease severity and recurrence. Commonly used medications include fidaxomicin and oral vancomycin.

McDonald et al. review the guidelines for diagnosis and treatment of C. difficile and provide the algorithm for C. difficile testing as mentioned above. The authors also note that only liquid stool from patients with clinically significant and acute diarrhea should be submitted for testing. The authors recommend that formed stool from asymptomatic patients should not be tested because the presence of the C. difficile toxin gene does not distinguish between infection and asymptomatic carriage.

Incorrect Answers:
Answer A: Abdominal radiograph is an appropriate adjunctive diagnostic tool in patients with severe disease (e.g., severe abdominal pain and distension, fever, hypovolemia, lactic acidosis, marked leukocytosis) or fulminant colitis (marked by hypotension and ileus) to evaluate for toxic megacolon, bowel perforation, or other findings that warrant surgical intervention. In patients who are stable with low concern for severe disease or fulminant colitis, it would not be the preferred initial test for diagnosis nor would it be confirmatory.

Answer B: CT imaging of the abdomen and pelvis with oral and intravenous contrast is the preferred modality for detecting the presence of toxic megacolon, bowel perforation, or other findings that warrant surgical intervention in the setting of C. difficile colitis. Colonic dilatation of > 7 cm in diameter in the clinical setting of severe C. difficile infection is diagnostic. Other findings may include small bowel dilatation or scalloping of the bowel wall due to submucosal edema. While it would be reasonable to perform a CT scan in this patient, it would not confirm the diagnosis.

Answer C: Flexible sigmoidoscopy would be appropriate for cases in which an alternative diagnosis is suspected that requires direct visualization and/or biopsy of the bowel mucosa. It may also be helpful for patients with ileus or colitis in the absence of diarrhea as it allows for visualization of pseudomembranes on the inflamed mucosal surface, which are highly suggestive of C. difficile infection. In general, colonoscopy is a preferred and more accurate test.

Answer D: Rectal swab for selective anaerobic culture involves culture on a selective medium with toxin testing of isolated C. difficile. It is a highly sensitive test, but culture cannot distinguish toxin-producing strains from non-toxin-producing strains. A second test is required to detect toxin production by the cultured C. difficile strain (either enzyme immunoassay or nucleic acid amplification testing). Culture takes several days to finalize and as such, it is seldom used to establish a clinical diagnosis. It is most useful in patients with ileus and suspected C. difficile infection.

Bullet Summary:
The most appropriate confirmatory test for diagnosis of Clostridioides difficile infection is a stool toxin assay.


Question: A 21-year-old woman presents to her primary care physician due to a history of abdominal pain. She states that she has had recurrent bouts of mood swings, bloating, and abdominal pain that occur together approximately every 4 weeks. She states that when these symptoms occur, she gets into frequent arguments at work, is unable to concentrate, and sleeps longer than usual. Furthermore, she has episodes of extreme anxiety during these periods, leading her to take off time from work. She notes that these symptoms are causing distress in her interpersonal relationships as well. She has no past medical history and takes no medications. She experienced menarche at age 12 and has regular periods. Her temperature is 98.2°F (36.8°C), blood pressure is 100/70 mmHg, pulse is 75/min, and respirations are 12/min. Physical exam reveals a nontender abdomen. Pelvic exam reveals a closed cervix with no cervical motion or adnexal tenderness. Her cardiopulmonary and neurological exams are unremarkable. Which of the following is the most likely diagnosis?

Answer: Premenstrual dysophoric disorder

Explanation:
This patient with recurrent abdominal pain, bloating, and mood changes causing interpersonal difficulties related to the menstrual cycle likely has premenstrual dysphoric disorder. Premenstrual dysphoric disorder is a variant of premenstrual syndrome (PMS) characterized by prominent irritability and disruption of everyday life.

Premenstrual dysphoric disorder is a variant of PMS characterized by recurrent physical and behavioral symptoms that manifest during the luteal phase of the menstrual cycle and resolve with menstruation. The diagnosis is made by criteria outlined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). To make a diagnosis of premenstrual dysphoric disorder, symptoms such as marked affective lability or marked irritability or anger must be present along with signs such as decreased concentration, hypersomnia or insomnia, and decreased interest in usual activities. These symptoms must cause significant distress or interfere with work, school, or relationships and must present 1 week before the onset of menses and resolve the week following menses. The initial management of premenstrual dysphoric disorder involves a pregnancy test to rule out pregnancy and a menstrual diary to prospectively confirm symptoms and their relationship to the menstrual cycle for 2 consecutive cycles. Following confirmation of a diagnosis of premenstrual dysphoric disorder, treatment involves lifestyle changes, antidepressant/anxiolytic medications, or hormonal therapies such as oral contraceptive pills (OCPs).

Bhatia et al. discuss premenstrual dysphoric disorder. They note that premenstrual dysphoric disorder affects 2-10% of women of reproductive age. They note that serotonin dysregulation may be relevant to the etiology and treatment of premenstrual dysphoric disorder.

Incorrect Answers:
Answer A: Generalized anxiety disorder (GAD) is anxiety characterized by symptoms such as restlessness, fatigue, and irritability lasting > 6 months unrelated to any specific triggers. The topics of anxiety should be unrelated to one another. This patient's anxiety and symptoms are temporally related to her menstrual cycle, making premenstrual dysphoric disorder a more likely diagnosis.

Answer B: Major depressive disorder (MDD) is characterized by depressed mood and at least 5 of 9 "SIG E CAPS" symptoms for 2 weeks or longer. These symptoms include sleep disturbance, anhedonia, guilt, loss of energy, loss of concentration, appetite/weight changes, psychomotor retardation or agitation, and suicidal ideation. Though this patient exhibits some of these symptoms, premenstrual dysphoric disorder is a more likely diagnosis as she exhibits these symptoms temporally related to her menstrual cycle.

Answer C: Panic disorder is characterized by 4 or more panic attacks (sweating, palpitations, shaking, paresthesias) in a 4-week period or ≥ 1 panic attack followed by at least 1 month of fear of another panic attack. Though this patient experiences anxiety that leads her to avoid her work, she does not have any of the characteristic signs of a panic attack and therefore does not meet the criteria for diagnosis of panic disorder.

Answer E: PMS and premenstrual dysphoric disorder have overlap in their symptoms; however, premenstrual dysphoric disorder is characterized by symptoms that significantly affect daily functioning. This patient's symptoms have affected her work and relationships, making premenstrual dysphoric disorder a more likely diagnosis. Note that the workup and treatment is similar between these 2 conditions.

Bullet Summary:
Premenstrual dysphoric disorder (PMDD) is a variant of premenstrual syndrome (PMS) characterized by more severe physical and mood symptoms that affect daily functioning.