Ryan O'Keefe

Daily Pearl(s): Obstructive Urosepsis in a Horseshoe Kidney Obstructive urosepsis is a life-threatening emergency in which a UTI is complicated by a blockage that prevents clearance of infected urine, raising collecting-system pressure and driving bacterial translocation into the bloodstream. A horseshoe kidney's fused lower poles create unusual ureteral courses and insertion angles that promote urinary stasis, predisposing to stones and obstruction. In patients with unusual urinary anatomy, infection may present atypically without GU symptoms; a horseshoe kidney can refer pain to the mid-abdomen or epigastric regions and mimic pancreatitis. The degree of hydronephrosis does not always correlate with severity of infection, so do not be falsely reassured by mild to moderate dilation. Management requires prompt broad-spectrum antibiotics plus urgent urinary decompression (percutaneous nephrostomy or ureteral stenting) to achieve source control. Source: Atypical Epigastric Pain Reveals Obstructive Urosepsis in a Horseshoe Kidney (Annals of IM)

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Daily Pearl(s): IgG4-Related Disease (IgG4-RD) IgG4-RD is a systemic immune-mediated fibroinflammatory condition; classic sites are the pancreas, salivary or lacrimal glands, and retroperitoneum, but essentially any organ can be involved. Consider IgG4-RD in the differential for cryptogenic stroke, especially with multifocal or atypical large-vessel vasculopathy in patients lacking traditional atherosclerotic risk factors. In patients with vascular stenosis that progresses despite standard antiplatelet or anticoagulant therapy, consider an underlying inflammatory vasculitis. A serum IgG4 >135 mg/dL is consistent with the diagnosis but is neither fully sensitive nor specific, so an elevated level is a clue rather than proof. Diagnosis requires biopsy, since other inflammatory and malignant conditions can raise IgG4 levels; histology shows a lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis with an IgG4:IgG ratio >40%. PET is especially useful for identifying biopsy sites, with salivary glands and superficial lymph nodes being accessible and high-yield. Glucocorticoids are first-line and often produce rapid responses, with rituximab or MMF for maintenance or steroid-refractory disease; immunosuppression can not only halt progression but also reverse stenosis. Source: Progressive Internal Carotid Artery Occlusion in IgG4-Related Disease (Annals of IM)

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Daily Pearl(s): Multiple Endocrine Neoplasia Type 1 (MEN1) MEN1 (Wermer's syndrome) is an autosomal dominant disorder from mutations in the MEN1 tumor suppressor gene, marked by tumors of the "three Ps": parathyroid, pituitary, and pancreas or duodenum. Primary hyperparathyroidism is the most common (>90%) and earliest manifestation, often presenting with hypercalcemia or its sequelae like nephrolithiasis, bone pain, constipation, or fatigue. Vague systemic symptoms like fatigue or constipation alongside an endocrine abnormality such as irregular menses should raise suspicion; the addition of kidney stones raises it further given likely underlying hypercalcemia. Chronic hypercalcemia can mimic IBS, particularly the constipation-predominant type, so check a calcium level before formally diagnosing IBS. Patients with recurrent kidney stones should always have a BMP checked to rule out metabolic causes like hypercalcemia. In patients diagnosed with endocrine tumors at a young age, a detailed family history can be critical, as it may change surgical planning for hyperparathyroidism (asymmetric four-gland hyperplasia versus a single resectable adenoma). A full endocrine screen for suspected MEN1 includes prolactin, gastrin, IGF-1, insulin, and glucose, but the final diagnosis is confirmed with genetic testing. Source: May 7, 2026 VMR with Rabih & Sarah B - painful urination and hematuria (CPS)

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Daily Pearl(s): Pheochromocytoma Pheochromocytoma is another “great mimicker”; catecholamine excess can produce a wide range of symptoms, including diverse arrhythmias and paroxysmal hypertension. The textbook triad is episodic headache, diaphoresis, and tachycardia, but presentation is highly variable and most patients have sustained or intermittent, difficult-to-control hypertension. Though uncommon, life-threatening ventricular arrhythmias such as polymorphic VT are possible. Screen with plasma-free metanephrines or 24-hour urinary fractionated metanephrines, both of which are highly sensitive, then localize with CT or MRI of the abdomen and pelvis. Preoperative alpha-adrenergic blockade (phenoxybenzamine or doxazosin) is required before surgery, and beta-blockers are added only after adequate alpha blockade. Initiating beta-blockade before alpha-blockade in a pheochromocytoma can precipitate a hypertensive crisis. Complete surgical resection is often curative. Source: Polymorphic Ventricular Tachycardia, Sarcoidosis, and the Unmasking of a Pheochromocytoma (Annals of Internal Medicine)

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Daily Pearl(s): Bartonella quintana Endocarditis Bartonella is a leading cause of culture-negative endocarditis. Bartonella quintana is a slow-growing gram-negative rod transmitted by the human body louse and historically associated with “trench fever”; risk factors include homelessness, alcohol use, and crowded living conditions. The presentation is often subacute and may lack overt fever, so stay alert for immune-mediated complications such as glomerulonephritis or a vasculitic rash. Do not rule out endocarditis based on negative blood cultures alone when the clinical picture is suggestive; the diagnosis of Bartonella endocarditis relies on serology. A high IgG titer (>1:800) plus a positive IgM is consistent with the diagnosis. A low C3 with a normal C4 is a clue to an underlying infection-related glomerulonephritis. Treatment is prolonged: doxycycline for at least six weeks, often combined with gentamicin for the first two weeks, and valve replacement is frequently required. Source: Glomerulonephritis Caused by Bartonella quintana Endocarditis (Annals of Internal Medicine)

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Daily Pearl(s): Tumefactive Multiple Sclerosis (MS) Tumefactive MS is a great mimicker of CNS malignancy and infection. It is defined by large, tumor-like demyelinating lesions greater than 2 cm and can be the initial presentation of MS. The differential for ring-enhancing brain lesions is broad, and tumefactive MS should always be considered. The “open-ring” sign on contrast-enhanced MRI is a specific clue for demyelinating disease; abscesses show a complete uniform ring and high-grade gliomas a thick irregular ring. The absence of central restricted diffusion within a ring-enhancing lesion makes a pyogenic abscess much less likely. CSF-restricted oligoclonal bands or an elevated free light chain index supports an MS diagnosis. Treatment is high-dose IV corticosteroids for the acute attack, with plasma exchange as second-line, followed by long-term disease-modifying therapy. While MS is typically a disease of young adults, late-onset MS (after age 50) can occur and may present with an aggressive, tumefactive subtype. Source: Case 15-2026: A 64-Year-Old Woman With Fatigue, Memory Changes, and Falls (NEJM)

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Daily Pearl(s): Random B12 pearls B12 deficiency leads to megaloblastic hematopoiesis with an MCV over 100 and hypersegmented neutrophils. Many patients present without this because of concurrent iron deficiency or CKD. In severe B12 deficiency, expect reticulocytosis within 3 to 5 days of treatment, hemoglobin normalization within 1 to 2 months, and neurologic recovery over months. If you don’t see reticulocytosis when you expect it, think iron deficiency. B12 deficiency causes glossitis and angular cheilitis from impaired epithelial cell turnover.

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Daily Pearl(s): What should you think if B12 levels are actually high? An unexplained, persistent elevation above 1000 pg/mL should raise suspicion for myeloproliferative neoplasms like CML, solid tumors of the liver, lung, or GI tract, and liver disease including cirrhosis and hepatitis. The mechanism is overproduction of transport proteins or decreased hepatic clearance.

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Daily Pearl(s): How do you dose B12 replacement? Oral is 1,000 to 2,000 mcg cyanocobalamin daily, which serves as both load and maintenance when the cause persists. IM cyanocobalamin is 1,000 mcg daily or every other day for 1 to 2 weeks, then 1,000 mcg weekly for 4 to 8 weeks, then 1,000 mcg monthly for life if the cause is irreversible.

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Daily Pearl(s): What should be done if a patient is incidentally diagnosed with B12 deficiency? Ask if the patient is a strict vegan. Then evaluate for pernicious anemia, which should be thought of as the end-stage of an autoimmune atrophic gastritis that destroys parietal cells. Worth identifying for the B12 risk, and also because it is a risk factor for gastric cancer. Test for anti-intrinsic factor antibodies. They are 95% specific but only 50 to 70% sensitive, so a negative test does not rule out disease. Anti-parietal cell antibodies are 80% sensitive and less specific.