Questioning Medicine

CME-- Discharge Questions Answered in 2025

Lin Z, et al. Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency. Science 2026 Feb 5; 391:eadz4075. DOI: 10.1126/science.adz4075. Premature ovarian insufficiency is usually one of those diagnoses that shuts the door on fertility: ovarian function is lost before age 40, mature follicles are scarce to nonexistent, and we have no reliable way to turn things back on. In most textbooks, that's the end of the story. A group in Hong Kong is now asking a different question: what if the problem isn't just the follicles, but the neighborhood they live in? In aged mice, they found that the ovarian stroma becomes fibrotic and stiff, and that this mechanical stiffness itself seems to suppress follicle maturation. Loosen up the stroma, and previously dormant follicles begin to wake up. To turn that concept into something clinically relevant, the team screened nearly 1,300 drugs that are already approved for other human uses, looking for agents that could activate follicles in mice. Ten made the cut. One of them, finerenone-an oral nonsteroidal mineralocorticoid receptor antagonist better known to nephrologists and cardiologists-also reduced collagen production in the ovarian stroma, effectively softening the tissue environment. That observation led to a small, first-in-human trial. Fourteen women with POI-associated infertility received finerenone 20 mg twice weekly, with monthly ultrasound monitoring. Over 3 to 7 months, follicular development was seen in all participants, and eight produced mature oocytes. IVF was attempted when possible, and early embryos were obtained in three women; longer-term follow-up and pregnancy outcomes are still pending. It's a fascinating mechanobiology story: instead of stimulating the follicle directly with gonadotropins or growth factors, the intervention targets the physical properties of the follicular niche. But there are important caveats. The study is tiny, uncontrolled, and POI is not an absolute guarantee of infertility-spontaneous ovulation and pregnancy do occasionally occur. Without a control group and without live-birth data, we cannot know yet how much of this signal represents true drug effect versus background noise. For now, finerenone should stay firmly in the realm of clinical trials when it comes to fertility. But conceptually, this work opens a new front: treating infertility not just as an endocrine or genetic problem, but as a disease of tissue mechanics. If future studies confirm these findings, we may be looking at the beginnings of a paradigm shift in how we think about "irreversible" ovarian failure-and a new source of hope for patients who today are told their options are exhausted.

Stavropoulou E, et al. Reassessing the 2023 International Society for Cardiovascular Infectious Diseases Duke clinical criteria for infective endocarditis: Impact of excluding fever and updating diagnostic definitions. Clin Infect Dis 2025 Dec 31; [e-pub]. DOI: 10.1093/cid/ciaf737.  Big takeaways About 35% of patients truly had IE. Fever showed up in 80% of patients both with and without IE, so it did not help distinguish them. Dropping fever from the criteria actually made them better:   Sensitivity improved: 77% (no-fever) vs 74% (standard). Specificity improved a lot: 80% vs 49%. "Possible IE" shrank from 39% to 17%, meaning fewer gray-zone cases. Only 0.4% of patients without IE were incorrectly labeled as having IE.  Both are widely used and both can work for regular (non-crusted) scabies. The SCRATCH trial: who won?In the SCRATCH trial from France, researchers treated about 1000 people in 300 households with confirmed scabies. Each household was randomized to: Whole-body 5% permethrin cream on days 0 and 10, orOral ivermectin (weight-based) on days 0 and 10.They then checked who was cured at day 28. Here's what they found:Household cure ratesPermethrin: 88% curedIvermectin: 72% curedTranslation: For every 6 households treated with permethrin instead of ivermectin, one extra household was fully cured (NNT  6). Index (main) patient cure ratesPermethrin: 92%Ivermectin: 77%That's one extra person cured for about every 7 treated with permethrin instead of ivermectin (NNT  7). Side effectSkin irritation-type reactions: 14% with permethrin vs 10% with ivermectin.So permethrin wins on cure, with a small trade-off in local skin reactions. 

we look at CODE LVO and what does being frail even mean?????vaccines may not help baby and antibiotics still don't help viral illness

CME song --Check the Lytes

CME - sodium, potassium, calcium

 10.1016/j.jaip.2025.07.005.40675327All of the videos were found to be useful or very useful, 99% were of moderate or high reliability, and 99% had moderate to excellent educational quality  Prostate-specific antigen levels among participants receiving annual testing. JAMA Oncol 2025 Nov; 11:1341 10.1001/jamaoncol.2025.3386.40965920PSA levels at or above 4.0 ng/mL fell below that threshold on the next annual test 30% of the time. 10.1016/S2665-9913(25)00250-4.During 10 years of follow-up, patients in the PKA and TKA groups did not differ significantly in pain, function, or quality of lifehttps://www.nejm.org/doi/full/10.1056/NEJMoa2508026?query=TOCAmong patients who underwent CABG for an acute coronary syndrome, ticagrelor plus aspirin did not result in a lower incidence of death, myocardial infarction, stroke, https://www.nejm.org/doi/full/10.1056/NEJMoa2509907?query=TOCIn this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalization for influenza or pneumonia than a standard dose among older adults.  https://www.nejm.org/doi/full/10.1056/NEJMoa2509834?query=TOCAmong community-dwelling adults 65 to 79 years of age, there appeared to be fewer hospitalizations for influenza or pneumonia with high-dose inactivated influenza vaccine than with the standard dose but the NNT is like 1500! https://pmc.ncbi.nlm.nih.gov/articles/PMC12594118/Afib should not be screened even if the authors say yes https://pubmed.ncbi.nlm.nih.gov/40997143/defines the US cost-effectiveness threshold as $120 000 per quality-adjusted life year gained,  https://pubmed.ncbi.nlm.nih.gov/40481660/In CKD, electronic letter nudges for patients or primary care practices did not differ from no letters for prescriptions of guideline-recommended RASis or SGLT2is at 6 months.  https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673625015922?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673625015922%3Fshowall%3Dtrue&referrer=https:%2F%2Fclinician.nejm.org%2Fβ-blocker therapy on clinical outcomes in patients with myocardial infarction and mildly reduced (40–49%)  https://www.nejm.org/doi/10.1056/NEJMoa2512686#ap2&uccLastUpdatedDate=2025-12-12%2005%3A34%3A29.658%20%2B0000&rememberMe=falseIn this meta-analysis including individual-patient data from five randomized trials, beta-blocker therapy did not reduce the incidence of death from any cause, myocardial infarction, or heart failure in patients with an LVEF of at least 50% after myocardial infarction without other indications for beta-blockers.

Wolfe R, Broder JC, Zhou Z, et al. Aspirin, cardiovascular events, and major bleeding in older adults: extended follow-up of the ASPREE trial. Eur Heart J. 12 Aug 2025. [Epub ahead of print]. https://pubmed.ncbi.nlm.nih.gov/40796244/ Donocan LE et al. Closed-loop insulin delivery in type 1 diabetes in pregnancy: The CIRCUIT randomized clinical trial. JAMA 2025 Oct 24; [e-pub]. (https://doi.org/10.1001/jama.2025.19578) https://jamanetwork.com/journals/jama/fullarticle/2822766 https://onlinelibrary.wiley.com/doi/full/10.1002/art.24894?msockid=3f10fb6c3d086e4c32e2ede23c9e6fbc https://pubmed.ncbi.nlm.nih.gov/41118187/ https://pubmed.ncbi.nlm.nih.gov/41115754/  https://pubmed.ncbi.nlm.nih.gov/41138956/ 

Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction - https://www.nejm.org/doi/full/10.1056/NEJMoa2504735?query=WB  McGuire DK et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med 2025 Mar 29; [e-pub]. (https://doi.org/10.1056/NEJMoa2501006) Interactive Virtual Presence to Remotely Assist Parents With Car Seat Installation https://pubmed.ncbi.nlm.nih.gov/41077424/  Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis  https://pubmed.ncbi.nlm.nih.gov/41115437/ 

https://pubmed.ncbi.nlm.nih.gov/40767818/This is a great example for students and residents to look and see that the abstract does not always match what the paper actually says

Efficacy and safety of Baxdrostat in uncontrolled and resistant hypertension compared to placebo in phase three when there are MRA available that are cheap and availableA randomised trial of physical therapy for meniscal tear and knee pain discovers that home exercises are just as good as inperson physical therapya Pragmatic trial of glucocorticoids for community acquired pneumonia that I don't think you can trust

gabapentin may increase COPD exacerbationsBenzo for ETOH might be long gone..guess what is going to replace itAnticoagulation after ablation.... what do you do with it?BBlocker in those with cirrhosis and varices

Clinicians should refer patients for liver transplant evaluation after any decompensation event—such as ascites or variceal bleeding—regardless of MELD score. After a first decompensation, 5-year mortality is 20–30%; after a second, it rises to 80–90%. Refractory ascites carries a 50% 1-year mortality, and overt hepatic encephalopathy has a 25–40% 1-year mortality. After an initial variceal bleed, the 1-year rebleeding risk is 60% without prophylaxis. There are no strict BMI or age cutoffs, and frailty has minimal effect on post-transplant outcomes. Substance use, including alcohol, is not a contraindication to referral—current guidelines no longer require a 6-month abstinence period. CitationsKing LY et al. Guidance for timely referral to liver transplantation. Clin Gastroenterol Hepatol 2025 Aug 5; [e-pub]. (https://doi.org/10.1016/j.cgh.2025.07.032)

Study Summary: Emergent Carotid Stenting in Acute Stroke ThrombectomyA multicenter registry study in Catalonia (2017–2023) evaluated outcomes in 578 patients with acute ischemic stroke and tandem lesions (large-vessel occlusion plus extracranial carotid stenosis). Patients were divided into two groups: those who received emergent carotid artery stenting (E-CAS) and those who did not (non-CAS).Key Findings: Favorable outcomes (modified Rankin Scale 0–2) were more common in the E-CAS group at: 90 days: 46% vs. 37% 1 year: Odds ratio 1.35 Recanalization rates were higher with E-CAS: 92% vs. 73% No significant differences in: Hemorrhagic transformation at 36 hours (though a trend toward higher rates with E-CAS) 1-year mortality Conclusion:Emergent carotid stenting during thrombectomy may improve functional outcomes and recanalization without significantly increasing bleeding or mortality. However, as this was not a randomized trial, results should be interpreted cautiously. Further randomized studies are needed.  Ezcurra-Díaz G et al. Emergent carotid artery stenting in patients with acute ischemic stroke with tandem lesions: One-year follow-up results from the SECURIS study. Neurology 2025 Oct 7; 105:e214067.    Gabapentinoids for Postoperative Pain: No Benefit FoundStudy Overview: A large randomized, placebo-controlled trial in the U.K. (GAP study) evaluated the effectiveness of gabapentin for postoperative pain in 1,200 patients undergoing various cardiac, thoracic, and abdominal surgeries.Intervention: Gabapentin group: 600 mg pre-op, then 300 mg twice daily for 2 days post-op Control group: Placebo Key Findings: Slight pain reduction at 1 hour post-op (4.0 vs. 3.5 on 11-point scale) No difference in pain at later time points No differences in: Opioid use Serious adverse events Length of hospital stay Commentary: Despite widespread off-label use, this large, well-designed trial found no meaningful benefit of gabapentin for postoperative pain. While short-term use appeared safe, prolonged use may pose risks (e.g., sedation, falls, respiratory depression). Clinicians are advised to reconsider routine perioperative use of gabapentinoids.  Baos S et al. Gabapentin for pain management after major surgery: A placebo-controlled, double-blinded, randomized clinical trial (the GAP study). Anesthesiology 2025 Oct; 143:851.

This massive meta-analysis of 484 randomized, double-blind, placebo-controlled trials (104,176 participants) quantified the blood pressure–lowering effects of major antihypertensive drug classes and their combinations. It introduces a new intensity-based classification system and an online calculator to predict BP-lowering efficacy based on drug, dose, and baseline BP.Study Design: 484 trials, 104,176 participants 5 major drug classes: ACE inhibitors, ARBs, β-blockers, calcium channel blockers (CCBs), and diuretics Focus: Placebo-corrected reduction in systolic BP (SBP) Mean baseline BP: 154/100 mm Hg Mean follow-up: 8.6 weeks Key Findings Monotherapy (Standard Dose): Average SBP reduction: 8.7 mm Hg By class: ACE inhibitors: 6.8 mm Hg ARBs: 8.5 mm Hg β-blockers: 8.9 mm Hg CCBs: 9.5 mm Hg Thiazide diuretics: 10.8 mm Hg Dose Doubling:Adds ~1.5 mm Hg SBP reduction (except β-blockers, which add only ~0.5 mm Hg) Dual Therapy (Standard Dose of Each): Average SBP reduction: 14.9 mm Hg Dose doubling adds ~2.5 mm Hg more Triple Therapy: SBP reduction: Up to 22.5 mm Hg (quadruple therapy even higher in one trial)

Practice Pearls: “Skip Leg Day” (Sometimes)For PAD patients who can’t tolerate leg workouts, upper body aerobic training is a strong, evidence-backed alternative. It’s not just a workaround—it’s a workout. CitationAhiskali GN, Demirel A, Yamikan H, Kutukcu EC. The Effects of Upper Extremity and Lower Extremity Aerobic Exercise Training in Patients with Peripheral Arterial Disease: A Systematic Review. J Vasc Surg. 2025. doi: 10.1016/j.jvs.2025.07.060

GLP1 drugs work but they likely need lifestyle modificationsNo convincing evidence GLP1 cause thyroid cancer in humans BUT contraindication if family history existStopping therapy usually results in weight gainInsurance coverage for weight loss is limited and variable  Semaglutide for type 2 diabetes max dose is 2.0 mg weekly Semaglutide for weight loss has a goal dose of 2.4 mg weekly Diagnose steatotic liver disease with imaging and 1 metabolic risk factor (or biopsy) After diagnosis check FIB-4: Low risk, continue to monitor with FIB-4 every 2-3yrs  Intermediate risk, order VCTE and consider referral if >F1  High risk order a VCTE and referral (20% end with SLD) 2 FDA approved medications for liver fibrosis are not cheap, expect insurance push back

OMED COPD CME

All of these articles have been talked about on questioning medicine social media on tik tok and instagram but here is an update of my recent reading

Buelt, Andrew | 2:13 PM (1 hour ago) |  | to mehttps://jamanetwork.com/journals/jama/fullarticle/2833338 Conclusions and Relevance  These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.    Lee S et al. Live zoster vaccination and cardiovascular outcomes: A nationwide, South Korean study. Eur Heart J 2025 May 5; [e-pub]. (https://doi.org/10.1093/eurheartj/ehaf230) In a new South Korean study, researchers evaluated nearly 1.3 million people (age ≥50) who were entered into a nationwide database. In an analysis adjusted for numerous confounders and with an average follow-up of 6 years, people who received a VZV vaccine had significantly lower risk (by ≈25%) for overall adverse cardiovascular events, heart failure, cerebrovascular disorders, ischemic heart disease, thrombotic disorders, and arrhythmias.  https://pubmed.ncbi.nlm.nih.gov/40658956/ Conclusion: Findings indicate that VNPs were more effective than NRT for smoking cessation in this population. Given the challenges for cessation among these socially disadvantaged populations, VNPs present a promising treatment option for this priority group.   https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0326804   We did not find that haloperidol was arrhythmogenic or increased mortality in these largely short-duration trials. Further research to clarify actual clinical outcomes related to QTPmeds is important to inform safe prescribing practices.