Rapid-Fire Pearls From Clinical Cases (March 2026)

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from March 2026.

This is a rare paraneoplastic syndrome characterized by severe hypoglycemia caused by a tumor that is not of pancreatic islet cell origin. It is most commonly associated with large mesenchymal tumors (solitary fibrous tumors, leiomyosarcomas) or epithelial tumors (HCC).

The underlying mechanism of the hypoglycemia is the tumor's secretion of a high-molecular-weight form of insulin-like growth factor II ("big IGF-II"). This molecule binds to and activates insulin receptors, leading to increased glucose uptake by peripheral tissues and suppression of hepatic glucose production, mimicking the effects of excess insulin.

You will see low or undetectable insulin, C-peptide, and proinsulin levels. Ketone production is also suppressed due to the insulin-like effect of IGF-II.

Surgical resection of the tumor is curative and results in immediate normalization of the glucose level.

Source: NEJM - Case 9-2026 A 12-Year-Old Girl With Altered Mental Status And Hypoglycemia

The classic triad of meningitis (fever, nuchal rigidity, altered mental status) is often absent in elderly or immunocompromised hosts, requiring a high index of suspicion.

In patients with meningitis 2/2 strep pneumo, BCx are often positive and inflammatory markers like procalcitonin are usually elevated.

Empiric treatment for suspected bacterial meningitis must include coverage for drug-resistant strep pneumo (vancomycin plus a third-generation cephalosporin like ceftriaxone), as resistance can lead to clinical failure with monotherapy.

The benefit of adjunctive dexamethasone in bacterial meningitis is greatest when given just before or with the first dose of antibiotics; its utility is diminished in delayed presentations.

Source: March 4, 2026 VMR with Steph & Zaven - altered mental status & fever

Bleeding on a renally-cleared anticoagulant (like apixaban) can create a vicious cycle: hemorrhage causes pre-renal AKI, which impairs drug clearance, leading to supratherapeutic anticoagulation and worsening hemorrhage.

Source: March 5, 2026 VMR with Rabih & Mohammed - acute epistaxis

Progressive, asymmetric weakness with preserved sensation should always raise concern for a motor neuron disease like ALS.

Electrodiagnostics (EMG/NCS) are the cornerstone of diagnosis. NCS should show normal sensory nerve function. EMG confirms widespread lower motor nerve (LMN) damage, revealing evidence of active denervation (fibrillations, positive sharp waves) and chronic reinnervation (large, polyphasic motor unit potentials) in multiple body regions, often demonstrating subclinical involvement.

The Progressive Muscular Atrophy (PMA) subtype of ALS presents with predominantly lower motor neuron signs, making it a key mimic of myopathy or neuropathy and a frequent diagnostic challenge.

In the setting of profound weakness, reflexes will be diminished or absent regardless of etiology; therefore, hyporeflexia loses its specific localizing value for neuropathy versus advanced myopathy.

The "split-hand" sign (preferential atrophy of the thenar/first dorsal interosseous muscles) and its "split-leg" analogue are specific physical signs of ALS.

A low serum creatinine is a powerful indicator of significant muscle atrophy and should not be dismissed as simply "good renal function" in a patient with weakness.

MRI of the brain and spine is crucial to exclude structural mimics like spinal cord compression or myelopathy, but is typically unremarkable in ALS itself.

A muscle biopsy may be performed to exclude myositis; in ALS it shows features of neurogenic atrophy (grouped fiber atrophy), not primary inflammation or necrosis.

Source: March 6, 2026 VMR with Rabih & Rahul - progressive lower extremity weakness

Hypotension is a measurement, whereas shock is a clinical syndrome of end-organ hypoperfusion. The primary goal is to determine if hypotension is causing shock by assessing vital organs, primarily the brain (mental status) and kidneys (urine output).

The central venous pressure (CVP) is the most important diagnostic branch point.

Low CVP points to hypovolemic or distributive shock.

Hypovolemic shock is caused by a "hole" in the cardiovascular system leading to intravascular volume loss (via hemorrhage, GI losses, severe dehydration). Management is volume repletion and controlling the source of loss. In hypovolemic shock with no obvious source of bleeding, remember the hidden spaces: the retroperitoneum, thigh, and GI tract.

Distributive shock is a hunt for a "substance" causing vasodilation. Think sepsis, anaphylaxis, drugs, or a critical hormone deficiency like cortisol.

High CVP indicates an "arrest of flow" problem (cardiogenic or obstructive).

"Arrest of Flow" (cardiogenic/obstructive) is uniquely morbid because it reduces organ perfusion from two sides: low arterial inflow and high venous outflow pressure.

The difference between obstructive and cardiogenic shock is myocardial health.

Obstructive shock features a healthy pump facing a mechanical block and may transiently benefit from fluids. Examples include massive pulmonary embolism, cardiac tamponade, tension pneumothorax, dynamic LV outflow tract obstruction. Management involves temporizing with fluids to help the healthy heart push against the obstruction while urgently addressing the mechanical cause via needle decompression, pericardial synthesis, or thrombolysis/thrombectomy.

Cardiogenic shock is primary pump failure where fluids are more likely detrimental. It can be caused by myocardial infarction or end-stage cardiomyopathy. It’s often a slower progressive process. Management involves inotropes, vasopressors, and mechanical circulatory support, as well as addressing the cause of cardiac dysfunction.

Source: Academy w/ Rabih - Hypotension - March 8, 2026

In patients with new VP shunt presenting with fever or altered mental status, shunt-associated meningitis should be a primary consideration even with any typical presentation.

Classic meningeal signs, like nuchal rigidity, are frequently absent in device-related CNS infections. In such cases, fever and confusion might be the only clues.

Abdominal pain can be a red herring in VP Schott infections, representing irritation or infection of the distal catheter tip rather than a primary intra-abdominal process.

Source: March 9, 2026 Mainstream Mondays VMR with Maddy & Zakariyya G - 3 days of weakness and RUQ pain

The physical exam triad of an elevated JVP, a left parasternal heave, and a loud P2 is highly suggestive of severe pulmonary hypertension and significant RV strain.

A left parasternal heave is a palpable, sustained lifting of the chest wall along the left sternal border (the patient’s left).

A loud P2 (pulmonic component of the second heart sound, S2) is an accentuated sound from the pulmonary valve closing (“slamming shut”) at the end of ventricular systole, and is heard best at the upper left sternal border.

D-shaped left ventricular septum on echocardiography is a classic sign of severe RV pressure overload.

Acute RV failure can trigger a vicious "spiral of death" where hypoxemia and acidosis worsen pulmonary vascular resistance, which further strains the RV, decreases cardiac output, and perpetuates the cycle.

Breaking the RV “death spiral” involves supporting systemic blood pressure which helps perfuse the RV, optimizing preload (often with diuretics), and reducing RV afterload with pulmonary vasodilators such as inhaled nitric oxide or IV prostacyclines. Of course, treating any inciting cause (PE, infection) is also critical.

Intubation is extremely high-risk in patients with acute RV failure, as positive pressure ventilation and sedative agents can precipitate hemodynamic collapse by reducing preload and increasing afterload.

Source: March 11, 2026 VMR with Sharmin & Kirtan - SOB and fever and 1 day of chest pain

Chronic lithium toxicity is a state of lithium accumulation that occurs in patients on long-term therapy, typically precipitated by a decrease in renal clearance.

Common medications that reduce lithium clearance and precipitate toxicity include NSAIDs, ACE/ARBs, and thiazides.

Unlike acute overdose which presents with prominent GI symptoms, chronic toxicity manifests primarily with neurologic dysfunction.

Common presentations include ataxia, dysarthria (slurred speech), tremor, confusion, and encephalopathy, which can progress to seizures and coma.

An elevated serum lithium level confirms the diagnosis, though the absolute level correlates poorly with the severity of chronic neurologic symptoms.

Lithium can also independently cause a neutrophilic leukocytosis, which can confound the clinical picture when an infection is also present.

Management involves holding Lithium, providing aggressive IV hydration to enhance renal clearance and treating the underlying cause of AKI.

Source: March 13, 2026 VMR with Rabih & Anmolpreet - dysuria, cloudy urine, and urinary incontinence

Lisinopril is a known but rare cause of pancreatitis, with a proposed mechanism involving an idiosyncratic reaction or angioedema of the pancreatic duct.

Drug-induced acute pancreatitis is a diagnosis of exclusion, often suspected when there is a close temporal relationship between starting a medication and the onset of symptoms.

Biliary sludge seen on ultrasound, while not a definitive obstructing stone, can still be a risk factor for pancreatitis and should be considered in the differential diagnosis.

Source: CPS - March 16, 2026 Mainstream Mondays VMR with Youssef & Magnus - acute abdominal pain

Haptoglobin can be falsely normal during active hemolysis if significant systemic inflammation is also present, as haptoglobin is an acute phase reactant.

For example, this may be seen with autoimmune hemolytic anemia in the setting of lupus.

Autoimmune hemolytic anemia (AIHA) can be the first manifestation of SLE, sometimes preceding the full systemic diagnosis by months or years.

Source: CPS - March 17, 2026 VMR with Ravi & Mengyu - fatigue, joint pains, and 1 month of rash

The combination of significant cardiomyopathy (especially with fibrosis) and skeletal myopathy should strongly raise suspicion for a genetic cause (Danon disease, laminopathies) over an autoimmune process.

Muscle and cardiac MRI patterns are critical for diagnosis; fatty infiltration without edema suggests a chronic dystrophic or metabolic process, not acute inflammation.

A detailed family history is crucial even in elderly patients; a pattern of sudden death in young male relatives is a powerful clue for an X-linked cardiodegenerative disorders.

In X-linked dominant disorders, female carriers often have a later onset and milder phenotype than affected males due to random X-inactivation (lyonization).

Source: CPS - March 20, 2026 VMR with Rabih & CPS Team - lower extremity weakness

Bladder diverticula are outpouchings of the bladder mucosa through the muscularis propria (bladder wall).

While some are congenital, most are acquired due to chronically elevated intravesical pressure, typically from bladder outlet obstruction (benign prostatic hyperplasia, urethral stricture). This high pressure forces the mucosa to herniate through weaker points in the bladder wall.

Many diverticula are asymptomatic. When symptoms occur, they can include recurrent UTIs (due to urine stasis), incomplete emptying, or gross hematuria.

Bleeding arises from fragile, superficial blood vessels lining the thin diverticular wall, which can rupture spontaneously or from chronic irritation.

The clinical presentation of painless gross hematuria can mimic that of bladder cancer, which must always be ruled out.

Painless gross hematuria, especially with clots, strongly suggests a lower urinary tract source (bladder, prostate) rather than a glomerular origin.

Cystoscopy is the gold standard for diagnosis and management. It allows for direct visualization of the diverticular openings, evaluation of the entire bladder lining to exclude malignancy, evacuation of clots, and potential cauterization of bleeding vessels.

Source: CPS - Mainstream Mondays VMR with Youssef & Sawsan - hematuria

Renal osteodystrophy is a complex bone disease that occurs in patients with CKD.

Its pathogenesis is driven by disturbances in mineral metabolism.

Failing kidneys are unable to excrete phosphate, leading to hyperphosphatemia, and cannot synthesize active vitamin D (calcitriol), which causes hypocalcemia.

These two abnormalities provide a powerful, chronic stimulus for the parathyroid glands to secrete parathyroid hormone (PTH), leading to secondary hyperparathyroidism.

Common presentations range from asymptomatic bone changes to bone pain, muscle weakness, and pathological fractures.

X-rays can reveal a spectrum of findings, including subperiosteal bone resorption, osteopenia, and cystic bone lesions known as osteitis fibrosa cystica or "brown tumors." These are collections of osteoclasts, giant cells, and fibrous tissue that appear as osteolytic lesions and represent a severe manifestation of hyperparathyroidism.

A markedly elevated alkaline phosphatase without significant liver enzyme elevation strongly suggests a bone origin, indicating a state of high bone turnover.

Source: CPS - March 23, 2026 VMR with Alec & Austin - bilateral hip pain for 3 hours

Pulmonary Hydatid Disease is a zoonotic parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus.

Humans are accidental hosts, typically infected by ingesting eggs from the feces of definitive hosts (dogs) that have been in contact with intermediate hosts (sheep). An occupation as a farmer with exposure to both animals can be a critical clue for a zoonotic infection like Echinococcosis.

The combination of a chronic pulmonary process, eosinophilia, and imaging of a complex cystic lesion should strongly raise suspicion for a parasitic etiology.

While the liver is the most common organ affected by hydatid disease, the lungs are the second most common site, and isolated pulmonary disease can occur without hepatic involvement.

Rupture of a pulmonary hydatid cyst into the pleural space is a well-described cause of secondary spontaneous pneumothorax, often presenting as a hydropneumothorax with an air-fluid level.

Recognizing classic radiologic signs on CT, such as the "water lily sign," is virtually pathognomonic for a ruptured hydatid cyst.

Source: CPS - VMR with Ravi & Kirtan - chest pain & SOB for 3 months

Anti-MuSK Myasthenia Gravis is a rare and often severe autoimmune subtype of MG where antibodies target Muscle-Specific Kinase, a protein essential for organizing acetylcholine receptors at the neuromuscular junction.

This differs from the more common form caused by anti-AChR antibodies. The clinical presentation of MuSK-MG is often distinct, with a predilection for severe bulbar (dysphagia, dysarthria), facial, and respiratory muscle weakness, which can lead to rapid decompensation.

Neck weakness is also common, while significant limb weakness may be less prominent than in AChR-positive MG.

The history of fatigable weakness - symptoms that worsen with activity and progress throughout the day- is the cardinal clue for a neuromuscular junction disorder.

EMG with repetitive nerve stimulation is a critical diagnostic workhorse, providing objective evidence of neuromuscular junction fatigability, especially when serology is negative or ambiguous.

Source: CPS - March 26, 2026 VMR with Rabih & Saketh - progressive weakness

Scurvy is a disease caused by a severe deficiency of vitamin C (ascorbic acid), an essential cofactor for collagen synthesis.

The resulting defective collagen leads to capillary fragility, poor wound healing, and abnormal bone formation.

Classic presentations include cutaneous findings like perifollicular hemorrhages (which may initially be obscured by extensive bruising), "corkscrew" hairs, and ecchymoses, which can become confluent and mimic vasculitis.

Other key features are gingivitis with bleeding gums, poor dentition, and severe myalgias or bone pain from hemarthrosis or subperiosteal hemorrhage.

These findings can be even worse when there’s a coexisting coagulopathy.

Severe pain accompanying cutaneous purpura is atypical for simple bruising and should raise suspicion for bleeding into deeper structures, such as the subperiosteal hemorrhage classic for scurvy.

Management is straightforward with oral vitamin C replacement, leading to a rapid reversal of symptoms. Bleeding often ceases within 24-48 hours, and skin and bone pain improve within weeks.

Source: CPS - March 27, 2026 VMR with Rabih & Reza - rash and bilateral leg pain

Enteroviruses (Coxsackievirus, Echovirus) are the most common cause of aseptic (viral) meningitis.

The classic presentation includes fever, headache, photophobia, and nuchal rigidity.

However, enteroviruses can also invade the spinal cord (myelitis), leading to more complex neurological syndromes.

This can manifest as an acute flaccid paralysis similar to poliomyelitis, by affecting the anterior horn cells (lower motor neurons), or as a more complex myelopathy involving other spinal tracts, resulting in a mixed picture of upper and lower motor neuron signs

The hallmark of typical enteroviral meningitis is a lymphocytic pleocytosis with normal glucose and normal or mildly elevated protein in the CSF. However, the CSF can be deceptively normal early in the infection.

Source: CPS - March 31, 2026 VMR with John & Maddy - acute ascending weakness