Ryan O'Keefe
@rokeefemd.bsky.social
MD/MBA PennMedicine/Wharton | Hospitalist | Onc, Pall Care, MedEd | Creator Point of Care Medicine | Clinical threads and pearls
Daily Pearl:
Platypnea-Orthodeoxia Syndrome (POS) should be suspected in any patient with hypoxemia that worsens in the upright position and improves when lying down, the clinical opposite of orthopnea.
Platypnea-Orthodeoxia Syndrome (POS) should be suspected in any patient with hypoxemia that worsens in the upright position and improves when lying down, the clinical opposite of orthopnea.
January 29, 2026 at 10:00 PM
Daily Pearl:
Platypnea-Orthodeoxia Syndrome (POS) should be suspected in any patient with hypoxemia that worsens in the upright position and improves when lying down, the clinical opposite of orthopnea.
Platypnea-Orthodeoxia Syndrome (POS) should be suspected in any patient with hypoxemia that worsens in the upright position and improves when lying down, the clinical opposite of orthopnea.
Daily Pearl:
Acute urinary retention is a critical red flag for central neurological processes, specifically in myelopathy or cauda equina syndrome.
This is especially true when there is associated bilateral limb weakness.
Source: CPS - November 14, 2025 VMR with Reza & Rabih
Acute urinary retention is a critical red flag for central neurological processes, specifically in myelopathy or cauda equina syndrome.
This is especially true when there is associated bilateral limb weakness.
Source: CPS - November 14, 2025 VMR with Reza & Rabih
January 28, 2026 at 10:00 PM
Daily Pearl:
Acute urinary retention is a critical red flag for central neurological processes, specifically in myelopathy or cauda equina syndrome.
This is especially true when there is associated bilateral limb weakness.
Source: CPS - November 14, 2025 VMR with Reza & Rabih
Acute urinary retention is a critical red flag for central neurological processes, specifically in myelopathy or cauda equina syndrome.
This is especially true when there is associated bilateral limb weakness.
Source: CPS - November 14, 2025 VMR with Reza & Rabih
Daily Pearl:
Bacillary Angiomatosis is a vascular proliferative disease caused by gram-negative bacilli, primarily Bartonella henselae or Bartonella quintana.
It almost exclusively affects immunocompromised individuals, most classically patients with advanced HIV and a CD4 count below 100.
Bacillary Angiomatosis is a vascular proliferative disease caused by gram-negative bacilli, primarily Bartonella henselae or Bartonella quintana.
It almost exclusively affects immunocompromised individuals, most classically patients with advanced HIV and a CD4 count below 100.
January 27, 2026 at 10:00 PM
Daily Pearl:
Bacillary Angiomatosis is a vascular proliferative disease caused by gram-negative bacilli, primarily Bartonella henselae or Bartonella quintana.
It almost exclusively affects immunocompromised individuals, most classically patients with advanced HIV and a CD4 count below 100.
Bacillary Angiomatosis is a vascular proliferative disease caused by gram-negative bacilli, primarily Bartonella henselae or Bartonella quintana.
It almost exclusively affects immunocompromised individuals, most classically patients with advanced HIV and a CD4 count below 100.
Daily Pearl:
Systemic lupus erythematosus (SLE) has a highly variable presentation ranging from mild mucocutaneous and joint disease to life-threatening organ failure.
Lupus nephritis is a major cause of morbidity and mortality.
Systemic lupus erythematosus (SLE) has a highly variable presentation ranging from mild mucocutaneous and joint disease to life-threatening organ failure.
Lupus nephritis is a major cause of morbidity and mortality.
January 26, 2026 at 10:00 PM
Daily Pearl:
Systemic lupus erythematosus (SLE) has a highly variable presentation ranging from mild mucocutaneous and joint disease to life-threatening organ failure.
Lupus nephritis is a major cause of morbidity and mortality.
Systemic lupus erythematosus (SLE) has a highly variable presentation ranging from mild mucocutaneous and joint disease to life-threatening organ failure.
Lupus nephritis is a major cause of morbidity and mortality.
Daily Pearl:
Myocardial infarction in young adults (typically defined as <45 years old) is often missed due to atypical presentations and a low index of suspicion.
Myocardial infarction in young adults (typically defined as <45 years old) is often missed due to atypical presentations and a low index of suspicion.
January 25, 2026 at 10:00 PM
Daily Pearl:
Myocardial infarction in young adults (typically defined as <45 years old) is often missed due to atypical presentations and a low index of suspicion.
Myocardial infarction in young adults (typically defined as <45 years old) is often missed due to atypical presentations and a low index of suspicion.
Daily Pearl:
Anemia requiring transfusion signifies hematologic failure, making non-specific causes like anemia of chronic disease less likely and mandating an urgent workup for a primary bone marrow process or significant blood loss.
Anemia requiring transfusion signifies hematologic failure, making non-specific causes like anemia of chronic disease less likely and mandating an urgent workup for a primary bone marrow process or significant blood loss.
January 24, 2026 at 10:00 PM
Daily Pearl:
Anemia requiring transfusion signifies hematologic failure, making non-specific causes like anemia of chronic disease less likely and mandating an urgent workup for a primary bone marrow process or significant blood loss.
Anemia requiring transfusion signifies hematologic failure, making non-specific causes like anemia of chronic disease less likely and mandating an urgent workup for a primary bone marrow process or significant blood loss.
Daily Pearl:
An asymptomatic patient with a critically low glucose level should trigger consideration of pseudohypoglycemia.
Finger sticks should be avoided on arms that have an AV fistula for dialysis.
An asymptomatic patient with a critically low glucose level should trigger consideration of pseudohypoglycemia.
Finger sticks should be avoided on arms that have an AV fistula for dialysis.
January 23, 2026 at 10:00 PM
Daily Pearl:
An asymptomatic patient with a critically low glucose level should trigger consideration of pseudohypoglycemia.
Finger sticks should be avoided on arms that have an AV fistula for dialysis.
An asymptomatic patient with a critically low glucose level should trigger consideration of pseudohypoglycemia.
Finger sticks should be avoided on arms that have an AV fistula for dialysis.
Daily Pearl:
The phenomenon of pseudo-bradycardia in atrial fibrillation is the presence of a lower peripheral pulse rate than the apical or EKG rate.
It is a subtle sign of poor perfusion and impending hemodynamic compromise.
The phenomenon of pseudo-bradycardia in atrial fibrillation is the presence of a lower peripheral pulse rate than the apical or EKG rate.
It is a subtle sign of poor perfusion and impending hemodynamic compromise.
January 22, 2026 at 10:00 PM
Daily Pearl:
The phenomenon of pseudo-bradycardia in atrial fibrillation is the presence of a lower peripheral pulse rate than the apical or EKG rate.
It is a subtle sign of poor perfusion and impending hemodynamic compromise.
The phenomenon of pseudo-bradycardia in atrial fibrillation is the presence of a lower peripheral pulse rate than the apical or EKG rate.
It is a subtle sign of poor perfusion and impending hemodynamic compromise.
Daily Pearl:
The development of proteinuria in an active sediment can be the first localizing sign of a systemic vasculitis like microscopic polyangiitis (MPA).
MPA can lead to rapidly progressive glomerulonephritis.
The development of proteinuria in an active sediment can be the first localizing sign of a systemic vasculitis like microscopic polyangiitis (MPA).
MPA can lead to rapidly progressive glomerulonephritis.
January 21, 2026 at 10:00 PM
Daily Pearl:
The development of proteinuria in an active sediment can be the first localizing sign of a systemic vasculitis like microscopic polyangiitis (MPA).
MPA can lead to rapidly progressive glomerulonephritis.
The development of proteinuria in an active sediment can be the first localizing sign of a systemic vasculitis like microscopic polyangiitis (MPA).
MPA can lead to rapidly progressive glomerulonephritis.
Daily Pearl:
A hyperdynamic “flow murmur” can indicate high output heart failure.
This state means that despite an increase in cardiac output, the patient is experiencing tissue hypoperfusion.
A hyperdynamic “flow murmur” can indicate high output heart failure.
This state means that despite an increase in cardiac output, the patient is experiencing tissue hypoperfusion.
January 20, 2026 at 10:00 PM
Daily Pearl:
A hyperdynamic “flow murmur” can indicate high output heart failure.
This state means that despite an increase in cardiac output, the patient is experiencing tissue hypoperfusion.
A hyperdynamic “flow murmur” can indicate high output heart failure.
This state means that despite an increase in cardiac output, the patient is experiencing tissue hypoperfusion.
Daily Pearl:
The yield of blood cultures in uncomplicated cellulitis is low, typically less than 5%, and thus they are not routinely recommended.
The yield of blood cultures in uncomplicated cellulitis is low, typically less than 5%, and thus they are not routinely recommended.
January 19, 2026 at 10:00 PM
Daily Pearl:
The yield of blood cultures in uncomplicated cellulitis is low, typically less than 5%, and thus they are not routinely recommended.
The yield of blood cultures in uncomplicated cellulitis is low, typically less than 5%, and thus they are not routinely recommended.
Daily Pearl:
Atrial fibrillation is rarely the sole cause of complete loss of cardiac output.
The loss of the atrial kick can contribute to a 15% to 25% reduction in cardiac output, which can cause hypotension in a vulnerable patient but is unlikely to be the cause of a PEA arrest.
Atrial fibrillation is rarely the sole cause of complete loss of cardiac output.
The loss of the atrial kick can contribute to a 15% to 25% reduction in cardiac output, which can cause hypotension in a vulnerable patient but is unlikely to be the cause of a PEA arrest.
January 18, 2026 at 10:00 PM
Daily Pearl:
Atrial fibrillation is rarely the sole cause of complete loss of cardiac output.
The loss of the atrial kick can contribute to a 15% to 25% reduction in cardiac output, which can cause hypotension in a vulnerable patient but is unlikely to be the cause of a PEA arrest.
Atrial fibrillation is rarely the sole cause of complete loss of cardiac output.
The loss of the atrial kick can contribute to a 15% to 25% reduction in cardiac output, which can cause hypotension in a vulnerable patient but is unlikely to be the cause of a PEA arrest.
Daily Pearl:
Sarcoidosis affects the lungs and intrathoracic lymph nodes in over 90% of cases.
However, any organ can be affected.
Hepatic involvement is common in 50-65% of patients but is often asymptomatic.
Sarcoidosis affects the lungs and intrathoracic lymph nodes in over 90% of cases.
However, any organ can be affected.
Hepatic involvement is common in 50-65% of patients but is often asymptomatic.
January 17, 2026 at 10:00 PM
Daily Pearl:
Sarcoidosis affects the lungs and intrathoracic lymph nodes in over 90% of cases.
However, any organ can be affected.
Hepatic involvement is common in 50-65% of patients but is often asymptomatic.
Sarcoidosis affects the lungs and intrathoracic lymph nodes in over 90% of cases.
However, any organ can be affected.
Hepatic involvement is common in 50-65% of patients but is often asymptomatic.
Daily Pearl:
Subacute “AMS” tied to personality changes should prompt head imaging, namely for a local process like a primary CNS malignancy or metastatic disease in the frontal lobes.
Source: CPS - Episode 431: The Clinical Unknown Series with Anmolpreet Kaur
Subacute “AMS” tied to personality changes should prompt head imaging, namely for a local process like a primary CNS malignancy or metastatic disease in the frontal lobes.
Source: CPS - Episode 431: The Clinical Unknown Series with Anmolpreet Kaur
January 16, 2026 at 10:00 PM
Daily Pearl:
Subacute “AMS” tied to personality changes should prompt head imaging, namely for a local process like a primary CNS malignancy or metastatic disease in the frontal lobes.
Source: CPS - Episode 431: The Clinical Unknown Series with Anmolpreet Kaur
Subacute “AMS” tied to personality changes should prompt head imaging, namely for a local process like a primary CNS malignancy or metastatic disease in the frontal lobes.
Source: CPS - Episode 431: The Clinical Unknown Series with Anmolpreet Kaur
Daily Pearl:
Severe hypomagnesemia can independently cause both hypokalemia (by affecting the ROMK channel in the kidneys) and hypocalcemia (by inducing PTH resistance).
Long-term PPI use can lead to profound hypomagnesemia.
Source: CPS - Episode 431: The Clinical Unknown Series
Severe hypomagnesemia can independently cause both hypokalemia (by affecting the ROMK channel in the kidneys) and hypocalcemia (by inducing PTH resistance).
Long-term PPI use can lead to profound hypomagnesemia.
Source: CPS - Episode 431: The Clinical Unknown Series
January 15, 2026 at 10:00 PM
Daily Pearl:
Severe hypomagnesemia can independently cause both hypokalemia (by affecting the ROMK channel in the kidneys) and hypocalcemia (by inducing PTH resistance).
Long-term PPI use can lead to profound hypomagnesemia.
Source: CPS - Episode 431: The Clinical Unknown Series
Severe hypomagnesemia can independently cause both hypokalemia (by affecting the ROMK channel in the kidneys) and hypocalcemia (by inducing PTH resistance).
Long-term PPI use can lead to profound hypomagnesemia.
Source: CPS - Episode 431: The Clinical Unknown Series
Daily Pearl:
An extremely high platelet count in the setting of infection should raise suspicion for “pus under pressure” - a walled-off, encapsulated infection like an abscess that the body is struggling to contain.
An extremely high platelet count in the setting of infection should raise suspicion for “pus under pressure” - a walled-off, encapsulated infection like an abscess that the body is struggling to contain.
January 14, 2026 at 10:00 PM
Daily Pearl:
An extremely high platelet count in the setting of infection should raise suspicion for “pus under pressure” - a walled-off, encapsulated infection like an abscess that the body is struggling to contain.
An extremely high platelet count in the setting of infection should raise suspicion for “pus under pressure” - a walled-off, encapsulated infection like an abscess that the body is struggling to contain.
Daily Pearl:
Behcet’s disease is a chronic, relapsing, multi-system inflammatory disorder of unknown etiology, characterized by a vasculitis that can affect both arteries and veins of all sizes.
The classic triad is recurrent oral ulcers, genital ulcers, and uveitis.
Behcet’s disease is a chronic, relapsing, multi-system inflammatory disorder of unknown etiology, characterized by a vasculitis that can affect both arteries and veins of all sizes.
The classic triad is recurrent oral ulcers, genital ulcers, and uveitis.
January 13, 2026 at 10:00 PM
Daily Pearl:
Behcet’s disease is a chronic, relapsing, multi-system inflammatory disorder of unknown etiology, characterized by a vasculitis that can affect both arteries and veins of all sizes.
The classic triad is recurrent oral ulcers, genital ulcers, and uveitis.
Behcet’s disease is a chronic, relapsing, multi-system inflammatory disorder of unknown etiology, characterized by a vasculitis that can affect both arteries and veins of all sizes.
The classic triad is recurrent oral ulcers, genital ulcers, and uveitis.
Best of Clinical Cases from October 2025!
IM and Hospital Medicine Recap
Check out the most recent Substack post published this AM!
My favorite lessons and pearls from the best clinical cases from @CPSolvers @Dx_Atypia @runthelistpod @NEJM
Zero fluff, high-yield.
Link below!
IM and Hospital Medicine Recap
Check out the most recent Substack post published this AM!
My favorite lessons and pearls from the best clinical cases from @CPSolvers @Dx_Atypia @runthelistpod @NEJM
Zero fluff, high-yield.
Link below!
January 13, 2026 at 5:00 PM
Best of Clinical Cases from October 2025!
IM and Hospital Medicine Recap
Check out the most recent Substack post published this AM!
My favorite lessons and pearls from the best clinical cases from @CPSolvers @Dx_Atypia @runthelistpod @NEJM
Zero fluff, high-yield.
Link below!
IM and Hospital Medicine Recap
Check out the most recent Substack post published this AM!
My favorite lessons and pearls from the best clinical cases from @CPSolvers @Dx_Atypia @runthelistpod @NEJM
Zero fluff, high-yield.
Link below!
Daily Pearl:
In aspiration PNA, elderly patients may present with atypical signs of infection, such as functional decline, confusion, or tachypnea, in the absence of fever due to immunosenescence.
In aspiration PNA, elderly patients may present with atypical signs of infection, such as functional decline, confusion, or tachypnea, in the absence of fever due to immunosenescence.
January 12, 2026 at 10:00 PM
Daily Pearl:
In aspiration PNA, elderly patients may present with atypical signs of infection, such as functional decline, confusion, or tachypnea, in the absence of fever due to immunosenescence.
In aspiration PNA, elderly patients may present with atypical signs of infection, such as functional decline, confusion, or tachypnea, in the absence of fever due to immunosenescence.
Daily Pearl:
Lithium is a major cause of thyroid dysfunction (hypothyroidism, goiter, and thyroiditis). The effects can persist after cessation.
Lithium is a major cause of thyroid dysfunction (hypothyroidism, goiter, and thyroiditis). The effects can persist after cessation.
December 29, 2025 at 10:00 PM
Daily Pearl:
Lithium is a major cause of thyroid dysfunction (hypothyroidism, goiter, and thyroiditis). The effects can persist after cessation.
Lithium is a major cause of thyroid dysfunction (hypothyroidism, goiter, and thyroiditis). The effects can persist after cessation.
Daily Pearl:
Refractory or recurrent giardia is a red flag for a humoral immunodeficiency (such as CVID, IgA deficiency).
Patients with CVID have an increased lifetime risk of cancer, especially B-cell lymphoma and gastric cancer.
Refractory or recurrent giardia is a red flag for a humoral immunodeficiency (such as CVID, IgA deficiency).
Patients with CVID have an increased lifetime risk of cancer, especially B-cell lymphoma and gastric cancer.
December 28, 2025 at 10:00 PM
Daily Pearl:
Refractory or recurrent giardia is a red flag for a humoral immunodeficiency (such as CVID, IgA deficiency).
Patients with CVID have an increased lifetime risk of cancer, especially B-cell lymphoma and gastric cancer.
Refractory or recurrent giardia is a red flag for a humoral immunodeficiency (such as CVID, IgA deficiency).
Patients with CVID have an increased lifetime risk of cancer, especially B-cell lymphoma and gastric cancer.
Daily Pearl(s):
The triad of trismus ("lockjaw") , dysphagia, and reflex spasms in a patient with a potential wound is tetanus until proven otherwise.
The triad of trismus ("lockjaw") , dysphagia, and reflex spasms in a patient with a potential wound is tetanus until proven otherwise.
December 25, 2025 at 10:00 PM
Daily Pearl(s):
The triad of trismus ("lockjaw") , dysphagia, and reflex spasms in a patient with a potential wound is tetanus until proven otherwise.
The triad of trismus ("lockjaw") , dysphagia, and reflex spasms in a patient with a potential wound is tetanus until proven otherwise.
Daily Pearl:
Postpartum heart failure is not always peripartum cardiomyopathy. Also consider thyrotoxicosis, as pregnancy can trigger or unmask Graves disease.
Postpartum heart failure is not always peripartum cardiomyopathy. Also consider thyrotoxicosis, as pregnancy can trigger or unmask Graves disease.
December 24, 2025 at 10:00 PM
Daily Pearl:
Postpartum heart failure is not always peripartum cardiomyopathy. Also consider thyrotoxicosis, as pregnancy can trigger or unmask Graves disease.
Postpartum heart failure is not always peripartum cardiomyopathy. Also consider thyrotoxicosis, as pregnancy can trigger or unmask Graves disease.
Daily Pearl:
Disseminated histoplasmosis is a key (albeit rare) cause of bilateral adrenal destruction and Addison disease, particularly in endemic areas like the Mississippi River Valley.
Disseminated histoplasmosis is a key (albeit rare) cause of bilateral adrenal destruction and Addison disease, particularly in endemic areas like the Mississippi River Valley.
December 23, 2025 at 10:00 PM
Daily Pearl:
Disseminated histoplasmosis is a key (albeit rare) cause of bilateral adrenal destruction and Addison disease, particularly in endemic areas like the Mississippi River Valley.
Disseminated histoplasmosis is a key (albeit rare) cause of bilateral adrenal destruction and Addison disease, particularly in endemic areas like the Mississippi River Valley.
Daily Pearl:
The combination of hypertension and thrombocytosis in a patient with new ascites is a major red flag against a diagnosis of cirrhosis.
A low SAAG (<1.1 g/dL) reliably indicates a non-portal hypertensive cause of ascites.
The combination of hypertension and thrombocytosis in a patient with new ascites is a major red flag against a diagnosis of cirrhosis.
A low SAAG (<1.1 g/dL) reliably indicates a non-portal hypertensive cause of ascites.
December 22, 2025 at 10:00 PM
Daily Pearl:
The combination of hypertension and thrombocytosis in a patient with new ascites is a major red flag against a diagnosis of cirrhosis.
A low SAAG (<1.1 g/dL) reliably indicates a non-portal hypertensive cause of ascites.
The combination of hypertension and thrombocytosis in a patient with new ascites is a major red flag against a diagnosis of cirrhosis.
A low SAAG (<1.1 g/dL) reliably indicates a non-portal hypertensive cause of ascites.