Ryan O'Keefe

Daily Pearl(s): Ketoacidosis and NAGMA Ketoacidosis, commonly seen in conditions like diabetic ketoacidosis (DKA) and alcoholic ketoacidosis, classically presents as a high anion gap metabolic acidosis due to the accumulation of unmeasured ketone anions (beta-hydroxybutyrate, acetoacetate). However, in rare instances where renal function is preserved, the kidneys can compensate. This occurs via enhanced excretion of the negatively charged ketone bodies in the urine. To maintain electroneutrality, the renal tubules increase the reabsorption of chloride, leading to a hyperchloremic metabolic acidosis, which manifests as a NAGMA. Thus, you should always check a serum beta-hydroxybutyrate level, regardless of the calculated anion gap. Source: CPS - RLR Case Challenge #163

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Gabapentin Toxicity Gabapentin toxicity can cause significant central nervous system and respiratory depression, particularly in vulnerable populations. This syndrome is classically associated with drug accumulation in the setting of acute or chronic kidney disease but can also occur in patients with underlying respiratory compromise, such as COPD, obesity hypoventilation syndrome, or severe restrictive chest wall disease. The combination of hypoactive encephalopathy (somnolence) and myoclonus should raise immediate suspicion for a toxic-metabolic cause, with medication toxicity being a primary consideration. Source: CPS - RLR Case Challenge #161

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Abdominal inflammation is often visualized on a CT scan by the presence of fat stranding. However, in patients with very little intra-abdominal adipose tissue, there often isn’t enough fat to become inflamed and signal the problem. This can create a false negative CT scan in cachectic patients. Source: CPS - RLR Case Challenge #160

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Alcohol-related Neuropathy Alcohol-related neuropathy results from a dual mechanism - the direct neurotoxic effects of alcohol and its metabolites on peripheral nerves, and secondary nutritional deficiencies, most notably of thiamine (Vitamin B1) but also folate, B6, and B12. The classic presentation is a distal, symmetric, painful, sensory-predominant polyneuropathy that follows a length-dependent (”stocking-glove”) pattern. Patients typically complain of burning, tingling, and numbness in the feet, which gradually ascends. Motor symptoms like weakness and muscle atrophy appear later in the disease course. Labs may show macrocytosis with a high MCV, an AST to ALT ratio >2, elevated GGT, deficiency is in folate, magnesium, and thiamine. Specific biomarkers like phosphatidylethanol (PEth) are highly sensitive and specific for recent (2-4 weeks) heavy alcohol consumption. EMG is the key diagnostic test to characterize the neuropathy which classically shows a length-dependent, sensory greater than motor, axonal polyneuropathy. Source: CPS - Episode 435 Neurology Vmr Weakness And Numbness

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): The diagnosis of sarcoidosis is one of exclusion; the presence of non-caseating granulomas on biopsy is necessary but requires a thorough workup to rule out infectious and malignant mimics before confirming the diagnosis. In cases of suspected infiltrative disease with organomegaly and systemic symptoms, imaging (CT/PET) is critical to identify biopsy targets, but the principle “the tissue is the issue” holds true, as a definitive diagnosis almost always requires pathology. Source: CPS - Episode 432 Spaced Learning Series Subacute Inflammation

Papa's Pod is finally coming back! This is a hematology podcast with a focus on clinical care (not just data) and what you actually have to know to care for patients! I plan to do one episode a week (first will be CART in myeloma) and open to requests! podcasts.apple.com/us/podcast/pap…

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Reactive Arthritis The triad of arthritis, urethritis/pelvic symptoms, and a preceding infection is classic for reactive arthritis, which is the form of spondyloarthropathy. Although this is typically triggered by gastrointestinal (salmonella, campylobacter) and genitourinary infections (chlamydia), COVID is an increasingly recognized trigger. Enthesitis is the pathologic hallmark of spondyloarthropathies. Pain at tendon/ligament insertions (plantar fasciitis, epicondylitis) is a diagnostic clue. MRI findings showing insertional tendinopathy can provide crucial evidence for enthesitis when an exam is nonspecific. Spondyloarthropathies are often sero-negative, thus the diagnosis can and should be made on clinical grounds, even when there’s normal inflammatory markers and a negative HLA-B27. Source: CPS - December 30, 2025 Rheumatology VMR with Greg Kirschen & Jeffrey Shen - Altered Mental Status

@ASanchez_PS @Mark_Heslin @MadellenaC @AdamRodmanMD hell of a lineup!

Conference invite for my Diagnostic Excellence friends! ✨ You will recognize some faces ... @Mark_Heslin @MadellenaC @AdamRodmanMD #DxEx

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Dengue Fever The triad of fever, thrombocytopenia, and leukopenia in a patient with a relevant travel history or residence in an endemic area is suggestive for dengue fever. Dengue is a mosquito-borne viral illness caused by the dengue virus and is endemic in tropical and subtropical regions. The clinical course typically follows three phases. The febrile phase lasts for 2-7 days and is marked by high fever, severe myalgias (“breakbone fever”), retro-orbital pain, headaches, often a rash. The critical phase lasts for 24-48 hours and begins around the time of defervescence. It’s characterized by increased capillary permeability, which leads to plasma leakage. The presence of warning signs such as abdominal pain, persistent vomiting, mucosal bleeding, and clinical fluid accumulation with ascites and/or pleural effusions can signal risk for severe dengue resulting in shock, severe bleeding, or organ failure. Management is largely supportive. NSAIDs should generally be avoided due to the risk of hemorrhage and the setting of thrombocytopenia. Bicytopenias and transaminitis can mimic many conditions, including other viral infections (EBV, CMV, or HIV), tick-borne illnesses, and even hematologic malignancies. Source: CPS - December 30, 2025 - VMR with Ravi & Anmolpreet - Abrupt Rash

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Bronchial anthracofibrosis (black pigmented airways) is most commonly caused by biomass fuel exposure, but it can also be an unusual manifestation of endobronchial tuberculosis. The differential for a hyperpigmented endobronchial lesion includes anthracofibrosis, metastatic melanoma, old hemorrhage, and carcinoid tumors, necessitating biopsy for definitive diagnosis. Source: CPS - December 25, 2025 - VMR with Kuchal & Rabih - Hemoptysis & Fever

Learn more clinical pearls from the Point of Care Medicine Substack! open.substack.com/pub/rokeefemd/…

Daily Pearl(s): Scrub Typhus Reactive arthritis is most commonly associated with GU (chlamydia) and GI (salmonella, shigella) infections, but rare infectious triggers like Orientia tsutsugamush must be considered in the right context. This organism more commonly causes Scrub typhus, an acute febrile illness transmitted by the bite of chiggers (larval mites). It is endemic in parts of Asia, Australia, and the Pacific Islands. The classic presentation includes fever, headache, myalgia, and often a characteristic eschar at the bite site, followed by a maculopapular rash. Doxycycline is the drug of choice and typically leads to rapid defervescence and clinical improvement within 48 hours. Source: CPS - December 24, 2025 - VMR with Kirtan and Youssef - Difficulty Walking & Hip Pain