Ryan O'Keefe

MD/MBA @PennMedicine @Wharton | Hospitalist | Creator @pointofcaremed | Follow for clinical threads and pearls

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Creutzfeld-Jakob Disease (CJD)

Brain MRI with DWI is the most critical initial imaging modality for suspected CJD, with cortical ribboning being a highly suggestive finding.

The modern gold-standard CSF test to diagnose CJD is the Real-Time Quaking-Induced Conversion (RT-QuIC) assay, which has high sensitivity and specificity for detecting the pathogenic prion protein. Older, less specific markers include elevated 14-3-3 and Tau proteins.

Definitive diagnosis is via brain biopsy or autopsy showing spongiform degeneration, neuronal loss, and gliosis.

The presence of a normal gait in a patient with significant dementia is a key localizing feature, pointing away from subcortical/limbic diseases (such as Lewy Body Dementia, Vascular Dementia, NPH) and more towards a primary cortical process like Alzheimer's or CJD.

True "reversibility" of a chronic dementia that has evolved over months is exceptionally rare and is primarily a feature of pressure-mediated processes such as NPH and subdural hematomas.

Source: CPS - April 2, 2026 VMR with Rabih & Fahed - forgetfulness & confusion

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

IDA Causing a Prothrombotic State

Severe iron deficiency anemia is an underrecognized prothrombotic state that can contribute to thrombosis through mechanisms like reactive thrombocytosis and endothelial dysfunction.

Source: CPS - April 1, 2026 VMR with Maddy & Zakariyya G - headache

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

IDA Causing a Prothrombotic State

Severe iron deficiency anemia is an underrecognized prothrombotic state that can contribute to thrombosis through mechanisms like reactive thrombocytosis and endothelial dysfunction.

Source: CPS - April 1, 2026 VMR with Maddy & Zakariyya G - headache

[Ryan O'Keefe @ROKeefeMD]

@EvanDownUnder Interesting. The most recent patient I cared for with this a few months ago was mostly having progressive subacute headache without any focal deficits.

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Dural Venous Sinus Thrombosis

Dural Venous Sinus Thrombosis, also known as Cerebral Venous Sinus Thrombosis, is the occlusion of cerebral venous sinuses or cortical veins by a thrombus.

It is an uncommon cause of stroke that tends to affect younger women. Though clinical presentations vary, headache is the most common symptom. Headaches can be acute and severe ("thunderclap"), subacute, or chronic.

Other presentations include focal neurological deficits, seizures, and signs of increased ICP. A key feature is that a normal neurological exam can be present despite a severe headache, which may delay diagnosis.

Source: CPS - April 1, 2026 VMR with Maddy & Zakariyya G - headache

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Pyogenic Liver Abscess

A pyogenic liver abscess is a pus-filled cavity within the liver caused by bacterial infection.

The most common etiology of pyogenic liver abscess is ascending infection from the biliary tract. Thus, imaging for biliary obstruction (via choledocholithiasis, malignancy, stricture) is crucial.

Patients can present acutely with fever, chills, and RUQ pain. It can also present more insidiously, especially in older adults with non-specific symptoms like malaise, anorexia, and weight loss.

Blood cultures are positive in only about 50% of cases.

Successful management requires source control (abscess drainage and/or biliary decompression via ERCP) and a prolonged course of antibiotics (typically 4-6 weeks).

Source: NEJM - Case 12-2026 An 86-Year-Old Woman With Anorexia, Weight Loss, And Liver Lesions

[Dereck Paul, MD @dereckwpaul]

At leading AI companies, software agents are using AI to write 90% of their code. The same thing will happen in medicine, where doctors will use AI to complete 90% of clinical work. In some cases, the AI-Native doctor is already here.

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Narcolepsy

Narcolepsy type 1 is a chronic central nervous system disorder of hypersomnolence caused by a loss of orexin (hypocretin)-producing neurons in the lateral hypothalamus, thought to be due to an autoimmune process.

Cataplexy is the pathognomonic feature - it is the sudden, brief loss of voluntary muscle tone triggered by strong emotions, typically positive ones like laughter or surprise.

The symptoms of narcolepsy are frequently misattributed to psychiatric conditions like depression, ADHD, or laziness, leading to an average diagnostic delay of 8-10 years.

The underlying pathophysiology is a loss of orexin-producing neurons, which disrupts the stability of wakefulness and allows for the inappropriate intrusion of REM sleep phenomena (atonia, dreams) into wakefulness.

Source - NEJM Case 11-2026 A 24-Year-Old Man With Depression, Anhedonia, And Fatigue

[Ryan O'Keefe @ROKeefeMD]

Q: How do you hide $100 from a hospitalist?

A: Put it under a dressing just changed by wound care!

Seriously though, this CPS case of a septic patient who ended up having a toothpick stuck in their leg with lymphedema was wild and a reminder of how valuable it can be to do a thorough exam when unclear about source control!

A few pearls:

- In a patient with sepsis who fails to improve or worsens despite appropriate antibiotics, aggressively search for an undrained abscess or an uncontrolled source, such as a retained foreign body or infected hardware.

- Organic foreign bodies like wood are radiolucent and will be missed on X-Ray and often on CT. Ultrasound is the preferred initial imaging modality for suspected superficial foreign bodies.

- Organic materials like wood are notoriously challenging as they are porous, harbor bacteria, and can incite a significant inflammatory response, often leading to abscess formation.

- Streptococcus constellatus, a member of the Strep anginosus group, is notorious for its propensity to form abscesses. Finding it growing in a BCx should prompt an aggressive search for a purulent collection.

Source: CPS - April 24, 2026 VMR with Youssef & Mengyu - weakness and hypotension

[Ryan O'Keefe @ROKeefeMD]

Fun Fact: The name strep "agalactiae" (Group B Strep) translates from Latin to "without milk," as the bacteria was first identified as a cause of mastitis and led to reduced milk production in dairy cows.

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Aseptic (Viral) Meningitis Presentations

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

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Scurvy and Extensive Bruising

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

[Ryan O'Keefe @ROKeefeMD]

Learn more clinical pearls from the Point of Care Medicine Substack!

https://t.co/ZmHneqb8do

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Anti-MuSK Myasthenia Gravis

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