Ryan O'Keefe

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

[Alex Lupi @AlexLupiMed]

1/8 @ChatGPT Dots just replaced my main @openclaw use case for personal knowledge management as a physician in training.

https://t.co/C6JUFGI7gD is an Open Source framework & includes setup instructions for yourself with Dots + @obsdmd's headless CLI.

Thread below 🧵

[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):

Working Up An Insidious Autoimmune Disease

Otherwise young, healthy patients can have significant multi-system disease and yet still be completely asymptomatic, especially if this chronic or insidious process involves organs with high reserves, such as the lungs, liver, or bone marrow.

If a patient presents with unexplained pancytopenia and signs of systemic inflammation, such as an elevated total protein, systemic autoimmune diseases like lupus should remain high on the differential.

Unexpectedly high, elevated LFTs in an otherwise asymptomatic patient should have a CK sent to assess for a potential myositis.

AST is especially abundant in muscle.

A positive syphilis test discovered during the workup of a likely underlying autoimmune disease should be taken with a grain of salt, given the potential for false positives caused by anti-phospholipid antibodies.

When patients present with complex multi-system signs and symptoms, a detailed physical exam can reveal subtle clues like nail fold capillary changes or periungual erythema.

However, it’s important to avoid anchoring on some incidental findings given individual elements of the exam can be red herrings and so you need to take in the totality of the patient’s presentation.

Source: CPS - June 13, 2026 Clinical Reasoning Expeditions VMR with Jeffrey & Ramaswamy - 36 yo M w/no complaints

[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):

Parasitic Liver Lesions

A presumed pyogenic liver abscess that ultimately has negative cultures and does not seem to respond to antibiotics should make you think about potential fungal or parasitic causes, as well as non-infectious mimics.

If a patient has notable eosinophilia, this can change the differential for a hepatic lesion and point toward a parasitic etiology, such as Fasciola, echinococcus, or visceral larva migrans.

Migratory hepatic lesions seen on repeat imaging can be a clue for the acute phase of fascioliasis.

The lesions change location based on the fluke’s journey through the liver parenchyma as it causes destruction.

Although parasitic serologies can be useful, they can also cause a lot of confusion since positive results can indicate prior exposures and not an active infection.

There’s also a lot of cross-reactivity among different helminths that can cause even more confusion.

Even in cases where it’s not entirely certain what the final diagnosis is, if a patient who did not respond to broad-spectrum antibiotics has a dramatic response to a specific therapy (such as triclabendazole for fascioliasis), this can be all you need to help confirm the diagnosis.

Source: CPS - June 12, 2026 VMR with Rabih & Reza - 58/F With Persistent RUQ Pain And Intermittent Fever

[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):

Primary Ciliary Dyskinesia (PCD)

A lifelong history of wet coughs with repeat sinus and ear infections should make you think about defects in mucociliary clearance, like PCD or cystic fibrosis.

The combination of bronchiectasis, chronic sinusitis, and male infertility caused by azoospermia is typical of PCD.

Nearly all males with PCD have immotile sperm because of the structural similarity between cilia and sperm flagella.

Low nasal nitric oxide can help distinguish PCD from other causes of bronchiectasis.

This is because functional cilia are a major source of nitric oxide in the upper airways.

The location of bronchiectasis can help differentiate between PCD and cystic fibrosis.

Patients with PCD will typically have middle and lower lobe disease, whereas those with cystic fibrosis will show an upper lobe predominance.

Situs inversus is present in only about 50% of patients with PCD.

Source: CPS - June 11, 2026 VMR with Rabih & Youssef - Cough

[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):

Alcoholic Cardiomyopathy

Alcoholic cardiomyopathy is a non-ischemic, dilated cardiomyopathy that is caused by chronic, heavy alcohol use.

It is a diagnosis of exclusion after other common causes have been ruled out.

The pathophysiology involves direct toxic effects of alcohol and its metabolites on cardiomyocytes.

This leads to impaired contractility and ventricular dilation.

Labs, such as an elevated GGT and a transaminitis with AST > ALT, can be clues to alcohol being the cause in a patient with a new diagnosis of heart failure.

Echo will classically show four-chamber dilation with global hypokinesis.

Complete abstinence from alcohol can sometimes lead to complete recovery of cardiac function.

Patients are otherwise treated with standard GDMT.

Source: CPS - June 8, 2026 Mainstream Mondays VMR with Youssef & Magnus - palpitations and B/L lower limb edema

[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):

Grave’s Disease

Although Grave’s classically presents with a hypermetabolic state, including weight loss, heat intolerance, tremor, anxiety, or palpitations, it can also present with a wide and sometimes confusing constellation of signs.

This can make the diagnosis challenging when the clinical picture is murky.

While weight loss is classically associated with Graves, paradoxical weight gain can be seen if a profoundly increased appetite (hyperphagia) outpaces a heightened metabolic rate.

A subtle high-frequency tremor is another classic sign of hyperthyroidism.

It represents an “exaggerated physiologic tremor.”

A positive ANA and RF can be seen in autoimmune thyroid disease and does not mean the patient also has concomitant lupus or RA.

Source: CPS - June 6, 2026 Clinical Reasoning Expeditions VMR with Jeffrey & Rahul - Painful Red Right Eye

[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):

Iliopsoas Hematoma with Compressive Lumbar Plexopathy

An iliopsoas hematoma is a retroperitoneal bleed into the iliopsoas muscle compartment.

These bleeds most commonly happen as a complication of anticoagulation, trauma, or coagulopathy.

The retroperitoneal space is large enough to contain a considerable amount of blood and thus can be a hidden etiology of an otherwise unexplained acute hemoglobin drop.

The expanding hematoma can compress the lumbar plexus and lead to a specific pattern of weak hip flexion, weak knee extension, sensory loss over the anterior thigh, and an absent patellar reflex.

The specific constellation of symptoms localizes to the L2-L4 distribution of the lumbar plexus.

A key physical exam finding can be the patient’s posture.

Patients will often hold the affected hip in flexion and external rotation since this position will minimize tension on the iliopsoas muscle and can alleviate pressure placed on the plexus.

Asymmetric lower extremity edema may also be present due to venous obstruction from the hematoma’s mass effect.

A CT non-contrast is the fastest and most effective way to confirm the diagnosis.

Source: CPS - June 5, 2026 VMR with Rabih & Vale - Lower Extremity Weakness + 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):

Cryptococcal Meningitis

The typical CSF profile for meningitis includes low glucose and high protein.

Cryptococcal meningitis will usually show a lymphocytic pleocytosis.

However, in significant overwhelming infections, there may be a neutrophilic pleocytosis instead, which may create confusion.

The diagnosis of any opportunistic infection, such as cryptococcal meningitis, should prompt a workup for immunodeficiency, especially HIV.

The opening pressure is often severely elevated and is the cause of major morbidity, including headaches and vision loss.

Management is emergent and involves treating the infection and controlling the elevated pressure.

Induction therapy is with IV amphotericin and oral flucytosine.

Managing elevated intracranial pressure often requires serial therapeutic LPs.

ART for HIV is typically delayed for at least 2-4 weeks in order to prevent immune reconstitution inflammatory syndrome (IRIS).

Source: CPS - June 4, 2026 VMR with Rabih & Kevin - Altered Mental Status

[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):

Burning Mouth Syndrome

Burning Mouth Syndrome is a chronic pain disorder in which the patient experiences a burning, scalding, or tingling sensation in their mouth.

There are no identifiable oral lesions or abnormal lab findings.

It’s considered a form of neuropathic pain.

It is often idiopathic, but it can be caused by other conditions.

Burning Mouth Syndrome has paradoxical improvement of oral pain while eating or drinking.

This is likely due to sensory distraction.

It most commonly affects the tongue but can also involve the lips, gums, and palate.

Patients may experience altered taste or dry mouth.

Long-term use of metformin or PPIs can cause B12 malabsorption, which itself can present with oral symptoms.

Thus, B12 deficiency should be ruled out as potential etiology.

Management can include topical clonazepam, TCAs like amitriptyline, or gabapentinoids.

Source: CPS - June 1, 2026 Mainstream Mondays VMR with Youssef & Seeme - 1 Month History Of Mouth Sores

[Ryan O'Keefe @ROKeefeMD]

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

https://t.co/u8tq9tLwf8

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Causes of Dark Urine

Isolated dark urine without systemic symptoms can be from a local GU problem (painless hematuria), or the presence of a benign molecule such as an exogenous drug (like rifampin) or endogenous bilirubin.

Bilirubin > 10-12 in an otherwise well patient suggests extrahepatic biliary obstruction.

Intrinsic liver disease that is severe enough to cause such high bilirubin almost certainly would also cause some sort of profound systemic illness, such as encephalopathy or coagulopathy.

Source: CPS - May 31, 2026 - Academy VMR w/ Rabih & Team - Dark urine with a Dark Dx

[Ryan O'Keefe @ROKeefeMD]

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

https://t.co/u8tq9tLwf8

[Ryan O'Keefe @ROKeefeMD]

Daily Pearl(s):

Differentiating Between Causes of Dyspnea

At its core, dyspnea is a neurological sensation.

It can be triggered by deficits in oxygenation, ventilation, or perfusion.

Patients with dyspnea that have a normal exam, EKG, and basic labs might have a “hidden” structural cause, like PE or diaphragmatic issues.

They may also have a central or neurogenic cause, such as anxiety, metabolic acidosis, or deconditioning.

A walk test can help differentiate between these.

True structural limitations like those seen in PE should lead to overtly reduced exercise capacity.

Source: CPS - May 31, 2026 - Academy VMR w/ Rabih & Team - Dissecting Dyspnea