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This week, we share advances in treatment for EGFR-mutated lung cancer, a brain-penetrant enzyme therapy for a rare pediatric disorder, and dual targeting of extramedullary myeloma. We review cardiogenic shock, work through a challenging diagnostic puzzle in a young woman with recurrent illness, and explore Perspectives on corporatized care, vaccine policy, AI in medicine, and where clinicians carry grief.
Today, Dave Furfaro, Luke Hedrick, and Robert Wharton discuss the PREDMETH trial published in The New England Journal of Medicine in 2025. This was a non-inferiority trial comparing prednisone to methotrexate for upfront therapy in treatment-naive sarcoidosis patients. Listen in for a break down of the trial, analysis, and clinically applicable pearls. Article and Reference Todays’ episode discusses the PREDMETH trial published in NEJM in 2025. Kahlmann V, Janssen Bonás M, Moor CC, Grutters JC, Mostard RLM, van Rijswijk HNAJ, van der Maten J, Marges ER, Moonen LAA, Overbeek MJ, Koopman B, Loth DW, Nossent EJ, Wagenaar M, Kramer H, Wielders PLML, Bonta PI, Walen S, Bogaarts BAHA, Kerstens R, Overgaauw M, Veltkamp M, Wijsenbeek MS; PREDMETH Collaborators. First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate. N Engl J Med. 2025 Jul 17;393(3):231-242. doi: 10.1056/NEJMoa2501443. Epub 2025 May 18. PMID: 40387020. https://www.nejm.org/doi/full/10.1056/NEJMoa2501443 Meet Our Hosts Luke Hedrick is an Associate Editor at Pulm PEEPs and runs the Rapid Fire Journal Club Series. He is a senior PCCM fellow at Emory, and will be starting as a pulmonary attending at Duke University next year. Robert Wharton is a recurring guest on Pulm PEEPs as a part of our Rapid Fire Journal Club Series. He completed his internal medicine residency at Mt. Sinai in New York City, and is currently a first year pulmonary and critical care fellow at Johns Hopkins. Key Learning Points Clinical context Prednisone remains the traditional first-line treatment for pulmonary sarcoidosis when treatment is indicated, with evidence for short-term improvements in symptoms, radiographic findings, and pulmonary function—but with substantial, familiar steroid toxicities (weight gain, insomnia, HTN/DM, infection risk, etc.). Despite widespread use, glucocorticoids haven't been robustly tested head-to-head against many alternatives as initial therapy, and evidence for preventing long-term decline (especially in severe disease) is limited. Immunosuppressants (like methotrexate) are often used as steroid-sparing agents, but guideline recommendations are generally conditional/low-quality evidence, and practice varies. Why PREDMETH matters It addresses a real-world question: Can methotrexate be an initial alternative to prednisone in pulmonary sarcoidosis, rather than being reserved only for steroid-sparing later? It also probes a common clinical belief: MTX has slower onset than prednisone (often assumed, not well-proven). Trial design (what to know) Open-label, randomized, noninferiority trial across 17 hospitals in the Netherlands. Included patients with pulmonary sarcoidosis who had a clear pulmonary indication to start systemic therapy (moderate/severe symptoms plus objective risk features like reduced FVC/DLCO or documented decline, plus parenchymal abnormalities). Excluded: non–treatment-naïve patients and those whose primary indication was extrapulmonary disease. Treat-to-tolerability with escalation: both drugs started low and were slowly increased; switch/add-on allowed for inadequate efficacy or unacceptable side effects. Primary endpoint: change in FVC (with the usual caveat that FVC is “objective-ish,” but effort-dependent and not always patient-centered). Noninferiority margin: 5% FVC, justified as within biologic/measurement variation and “not clinically relevant.” Outcomes assessed at weeks 4, 16, 24; powered for ~110 patients to detect the NI margin. Patient population (who this applies to) Mostly middle-aged (~40s) with mild-to-moderate physiologic impairment on average (FVC ~77% predicted; DLCO ~70% predicted). Netherlands-based cohort with limited Black representation (~7%), which matters for generalizability. Would have been helpful to know more about comorbidities (e.g., diabetes), which can strongly influence prednisone risk. Main findings (what happened) Methotrexate was noninferior to prednisone at week 24 for FVC: Between-group difference in least-squares mean change at week 24: −1.17 percentage points (favoring prednisone) with CI −4.27 to +1.93, staying within the 5% NI margin. Timing mattered: Prednisone showed earlier benefit (notably by week 4) in FVC and across quality-of-life measures. By week 24, those early differences largely washed out—possibly because MTX “catches up,” and/or because crossover increased over time. In their reporting, MTX didn't meet noninferiority for FVC until week 24, supporting the practical message that prednisone works faster. Crossover and analysis nuance (important for interpretation) Crossover was fairly high, which complicates noninferiority interpretation: MTX arm: some switched to prednisone for adverse events and others had prednisone added for disease progression/persistent symptoms. Prednisone arm: some had MTX added. In noninferiority trials, heavy crossover can bias intention-to-treat analyses toward finding “no difference” (making noninferiority easier to claim). Per-protocol analyses avoid some of that but introduce other biases. They reported both. Safety signals (what to remember clinically) Adverse events were very common in both arms (almost everyone), mostly mild. Side-effect patterns fit expectations: Prednisone: more insomnia (and classic steroid issues). MTX: more headache/cough/rash, and notably liver enzyme elevations (about 1 in 4), with a small number discontinuing. Serious adverse events were rare; numbers were too small to confidently separate “signal vs noise,” but overall known risk profiles apply. Limitations (why you shouldn't over-read it) Open-label design, and FVC—while objective-ish—is still effort-dependent and can be influenced by expectation/behavior. Small trial, limiting subgroup conclusions (e.g., severity strata, different phenotypes). Generalizability issues (Netherlands demographics; US populations have higher rates of obesity/metabolic syndrome, which may tilt the steroid risk-benefit equation). Crossover reduces precision and interpretability of between-group differences over time. Practice implications (the “so what”) For many patients with pulmonary sarcoidosis needing systemic therapy, MTX is a reasonable initial alternative to prednisone when thinking long-term tolerability and steroid avoidance. Prednisone likely provides faster symptom/QoL relief in the first weeks—so it may be preferable when rapid improvement is important. The trial strengthens the case for a patient-centered discussion: short-term relief vs side-effect tradeoffs, and the possibility of early combination therapy in more severe cases (suggested, not proven).
Vít Schlesinger je zakladatel česko-dánského produktového studia Blackfish, ale taky stratég, horal a sportovec. Mluvili jsme o tom, v čem je Blackfish jiné než agentury. Proč dnes mají tolik klientů ze Skandinávie a proč nechce od klientů brief? Jak studio zvládlo krizi, kdy přišlo o řadu zaměstnanců a klientů? Pojďte si pro trochu jinou byznysovou inspiraci – smooth is fast! Partnery podcastu jsou: SmartEmailing – Profesionální nástroj pro váš e-mail marketing. Czech On-line Expo – Největší akce v českém digitálu a e-commerce: Veletrh. Konference. Festival.
In this episode, we breakdown the new article and research looking at ketamine and etomidate for intubation. Dr. Mell breaks down the article and what it really means for emergency medicine and airway management. We have this article..."So What" with Dr. Howie Mell
This week, we look at ctDNA-guided immunotherapy for bladder cancer, cardiovascular outcomes with tirzepatide, and evidence that one HPV vaccine dose may be enough. We explore high-dose rifampin for tuberculous meningitis, review measles amid rising outbreaks, and follow a challenging case of gastrointestinal bleeding. Essays examine how clinicians navigate post-Dobbs care, tobacco harm among people with mental illness, congenital syphilis, and sustaining medical research.
Anne Zink is a lecturer and senior fellow at the Yale School of Public Health. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A.B. Zink, N.C. McCann, and R.P. Walensky. From Crisis to Action — Policy Pathways to Reverse the Rise in Congenital Syphilis. N Engl J Med 2025;393:2388-2391.
Listener discretion is advised. References: Casey, J., Seitz, K., et al. (2025). Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. NEJM. Available: https://www.nejm.org/doi/full/10.1056/NEJMoa2511420?query=featured_home Farkas. (Dec 10, 2025). PulmCrit: Hot take on RSI trial of ketamine vs etomidate. Available: https://emcrit.org/pulmcrit/rsitrial/ Srivatsa S, Chawla M, Hernandez M, et al. Helicopter transport of trauma patients continues to be overutilized: a call for universal transport criterion. Am Surg. Published online September 13, 2025:31348251378910. doi:10.1177/00031348251378910.
In this week's podcast, we sit down with Drs. Sarguni Singh, Christian Furman, and Lynn Flint, three authors of the recent Journal of the American Geriatrics Society article, "Rehab and Death: Improving End-of-Life Care for Medicare Skilled Nursing Facility Beneficiaries." The authors dive into the challenges facing seriously ill older adults discharged to Skilled Nursing Facilities (SNFs), where fragmented care transitions, misaligned Medicare policies, and inadequate access to palliative care often result in burdensome hospitalizations and goal-discordant care. The discussion highlights key barriers in Medicare's SNF and hospice benefits, including the inability to access concurrent hospice and SNF care, and explores solutions to improve care. Among the recommendations is leveraging Medicare's Patient Driven Payment Model (PDPM) to reimburse SNFs for providing palliative care, commissioning a Government Accountability Office (GAO) report on SNF utilization at the end of life, and piloting a model that allows time-limited concurrent hospice and rehabilitation care. Also, check out these two resources if you want a deeper dive: Our past podcast we did, now nearly 6 years ago, on the original NEJM paper, Rehabbed to Death. Joan Carpenter's article titled "Forced to Choose: When Medicare Policy Disrupts End-of-Life Care" in the Journal of Aging & Social Policy
Send us a textSummary: Microplastics are showing up in our water, food, air—and in human tissues. In this episode, I unpack what the best studies actually show (and don't), why risk is plausible but not proven, and the realistic steps you can take today without panic. In this episode, I cover:What microplastics are and why they're everywhere—from packaging and clothing to tire dust—and why production is still projected to rise ~70% by 2040 (OECD). OECD+2OECD+2The signal that caught my attention: patients with microplastics in carotid artery plaque had a markedly higher 3-year risk of heart attack, stroke, or death (NEJM). Association, not proof—but concerning. The Guardian+3New England Journal of Medicine+3PubMed+3What's turning up in the brain: autopsy work suggests rising microplastic loads in brain tissue, though causality remains unknown (Nature Medicine coverage). Nature+2Nature+2Everyday exposure: a liter of bottled water can contain ~240,000 plastic particles—mostly nanoplastics—using newer detection methods (NIH Research Matters). TIME+3National Institutes of Health (NIH)+3NCBI+3Indoor vs. outdoor air: estimates suggest we inhale tens of thousands of microplastic particles daily, with higher indoor concentrations (PLOS One). PLOS+1My takeaways for you (progress, not perfection):Respect the signal without catastrophizing. Human data are early, but cardiovascular and neurologic signals merit attention. New England Journal of Medicine+1Make the easy swaps: store food in glass, don't microwave plastic, favor loose-leaf tea over plastic-based tea bags, and replace plastic cutting boards with wood or glass. (These trim exposure; they don't eliminate it.) Air matters: consider a HEPA purifier for main living/sleeping areas and vacuum regularly; natural-fiber clothing sheds fewer synthetic particles. Water choices: where safe, use tap water with a quality home filter and a reusable (non-plastic) bottle—especially given the nanoplastic findings in some bottled waters. National Institutes of Health (NIH)Listener corner: You asked for more quick-hit myth busters (yes, we'll do “Does chicken soup speed recovery?”), and thanks for the reminder to wear a
Send us a textCoffee and heart rhythm don't have to be enemies. We dig into a new randomized trial across the US, Canada, and Australia suggesting that caffeinated coffee may lower the risk of recurrent atrial fibrillation compared with abstaining, then connect the dots with real-world monitoring, ablation strategy, and day-to-day choices that influence heart health.We start by grounding AFib in plain terms: what it is, why so many people never feel it, and how stroke risk rises when the atria stop driving a steady beat. From there, we step into the electrophysiology lab to explain why trouble often starts near the pulmonary veins and how clinicians map and ablate rogue electrical tissue. Along the way, we highlight the role of wearables like Apple Watch in catching silent arrhythmias and guiding decisions, a shift that is rapidly improving detection and management outside the clinic.Then we unpack the DECAF trial's headline: coffee drinkers showed meaningfully lower recurrence of AFib or flutter over six months versus those who abstained. We explore possible reasons, from caffeine's adenosine receptor antagonism and calcium signaling effects to the antioxidant and mitochondrial support offered by coffee's polyphenols. We also compare with NEJM data in the general population showing no significant increase in ectopy, putting fears into perspective. Finally, we get practical: dosing and timing to protect sleep, what brewing methods change, how dairy proteins can blunt polyphenol absorption, and when unfiltered versus filtered makes sense if you're balancing lipids and antioxidants.If you enjoy coffee and live with AFib, these insights can help you personalize your cup without losing sight of the fundamentals: anticoagulation when indicated, smart rate or rhythm control, and balanced training that avoids chronic overload. If this conversation helps you think differently about caffeine, subscribe, share with someone who cares about heart health, and leave a review so others can find it.For powerpoint slide deck, video recording and reference open-source articles go to: www.thehealthedgepodcast.com
This week, we look at new studies on high-dose influenza vaccines for older adults, antiplatelet therapy after coronary surgery, and HER2-targeted immunotherapy for advanced bladder cancer. We review complex regional pain syndrome and a pediatric case of fever and rash. We also explore FDA innovation and safety, aspirin's role in metastasis prevention, the meaning of “the good doctor,” smallpox in the Revolution, and how AI may reshape medical science.
The ACIP voted to replace universal newborn hepatitis B vaccination with shared clinical decision-making for infants of mothers who test negative, a move strongly criticized by major medical and public health groups who warn it could reverse decades of progress in preventing pediatric hepatitis B. A large NEJM trial found that a single dose of HPV vaccine provides protection equivalent to two doses over five years, supporting simplified global vaccination strategies. Real-world evidence from nearly 5,000 patients shows dapagliflozin and empagliflozin deliver similar safety and effectiveness across all forms of heart failure.
Reshma Ramachandran is an assistant professor of medicine at the Yale School of Medicine. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. J.D. Wallach, J.S. Ross, and R. Ramachandran. Enhancing FDA Drug-Safety Surveillance — Beyond Releasing Daily Adverse-Event Data. N Engl J Med 2025;393:2284-2286.
Geodetické zaměření ukázalo, že obchodníci neoprávněně zabírají stovky metrů veřejného prostranství. Nejméně dvě desítky míst by tak měli trhovci vyklidit. Dostali na to čas do konce letošního roku.
This week, we look at new trials on glucocorticoids for pneumonia in Africa, shunting for normal-pressure hydrocephalus, and pegcetacoplan for two rare kidney diseases. We review updated vaccine evidence for Covid-19, RSV, and influenza, and present a case of respiratory decline and muscle weakness. Perspectives explore health care incentives, U.S. global health strategy, and bringing AI-enabled care to rural America.
Robert Huckman is a professor of business administration at Harvard Business School and a research associate at the National Bureau of Economic Research. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. D.M. Cutler and R.S. Huckman. Has Corporatization Met Its Match? The Challenge of Making Money by Keeping People Healthy. N Engl J Med 2025;393:2177-2180.
Ženy XYZ #22: Feministický podcast, ve kterém Silvie Lauder, Markéta Plíhalová a Clara Zanga řeší důležitá aktuální témata.Nový Gender Equality Index je venku. Mapuje, jak je na tom s nerovnostmi mezi pohlavími Evropská unie a jednotlivé členské státy. Například v kategorii zastoupení žen ve vrcholné politice jsou rozdíly obrovské. Jaké nové ukazatele výzkumníci a výzkumnice prozkoumali? Jak se liší náhled na genderové stereotypy mezi mladými muži a ženami - a co to může přinést? A jak v žebříčku dopadli Češi a Češky? Ve 22. díle feministického podcastu Ženy XYZ o tom diskutovaly redaktorky Respektu Silvie Lauder a Markéta Plíhalová.
Thrilled to see a major step forward in dengue prevention!
This week, we look at new studies on early aspirin discontinuation after myocardial infarction, an antiviral pill for dengue prevention, and CRISPR-based gene editing for lipid disorders. We review bedside clinical teaching and present a complex case of seizures and visual disturbances. Perspectives explore antidepressant safety in pregnancy, restoring trust in public health, academic medical centers' venture investments, and a young physician's wrinkled white coat.
Nishant Uppal is an instructor in medicine at Massachusetts General Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. N. Uppal and Z. Song. Venture Capital Investments by U.S. Academic Medical Centers. N Engl J Med 2025;393:2077-2080.
Delighted to share a concise update on the latest NEJM review of Long QT Syndrome
This week, we look at new research on potassium optimization in patients with defibrillators, reducing antihypertensive therapy in nursing homes, an mRNA influenza vaccine, and belzutifan for rare neuroendocrine tumors. We review long QT syndrome and present a case of abnormal behavior and seizures in a young man. We also explore perspectives on primary care reform, tobacco cessation in HIV and tuberculosis care, corporate control in health care, and the simple power of compassion with ice cream.
Jane Zhu is an associate professor of medicine in the Division of General Internal Medicine at Oregon Health and Science University. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. J.M. Zhu and H. Rooke-Ley. Regulating Corporate Control in Health Care — Oregon's Attempt to Revive the CPOM Doctrine. N Engl J Med 2025;393:1972-1974.
Send us a textBe honest—have you ever rescued a French fry from the floor? In this bite-size myth episode, I test the famous “5-second rule.” I walk through what actually transfers to your food (fast), when that matters, and why a little microbial exposure isn't always the villain—while drawing a hard line for high-risk settings and situations.Key Topics & TakeawaysThe verdict meter: The 5-second rule is false—bacteria can transfer in
In this episode, we look at new trials on deferring arterial catheterization in shock, beta-blocker use after myocardial infarction, and a treatment for triple-negative breast cancer. We review acromegaly. A case describes a man with dyspnea, edema, and pacemaker lead displacement. We explore perspectives on the burdens of primary care, the erosion of harm reduction, child health policy, and the meaning of hospice.
Joshua Barocas is an associate professor of medicine at the University of Colorado Anschutz Medical Campus. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. J.A. Barocas. The Erosion of Harm Reduction. N Engl J Med 2025;393:1865-1867. B.A. Barsky, A. Caplan-Bricker, and C. Robertson. Religious Liberty as a Shield for Public Health — The Case of Overdose-Prevention Centers. N Engl J Med 2025;393:1867-1869.
The ARRIVE Trial and the Term Breech Trial reshaped modern birth practices in ways researchers never intended. From skyrocketing inductions to the loss of vaginal breech training, these studies reveal how even “gold-standard” science can miss the human side of birth.Clara invites you to take a mindful pause: to look beyond the data, question how evidence gets translated into policy, get curious about how the research was designed, and remember that true evidence-based care must center the individual—not just the research.You'll Learn:What the ARRIVE Trial and the Term Breech Trial actually found (and what they didn't)How these studies shifted policy, practice, and training worldwideWhy over-reliance on “evidence” can erase skills, intuition, and personal choiceHow to bring mindfulness into your decision-making about induction, breech birth, or any medical recommendationWhy traditional and holistic birth practices still matter—even if they've never been studiedMindful Reflection“Mindfulness isn't about ignoring evidence—it's about pausing long enough to ask, ‘Does this research apply to me, in my body, in this context?' True evidence-based care is a dialogue between research, clinician experience, and your own wisdom.”Resources MentionedDownload Clara's Free Birth Plan Template, used at over 5,000 births.Ready for an evidence based birth class? Check out A Path to A Powerful BirthThe Birth Advocacy Toolkit is a great option for expectant parents who have already taken a class but want to make sure their preferences are heard and want evidence based information to help make their decisions. Evidence Based Birth: Evidence on the ARRIVE Trial and Elective Induction at 39 WeeksEvidence Based Birth: Evidence on Breech BirthGrobman WA, et al. Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. NEJM, 2018.Evidence Based Birth: “Evidence on the ARRIVE Trial and Elective Induction at 39 Weeks.”Nethery E, et al. Obstet Gynecol, 2023. Post-ARRIVE induction impact study.Hannah ME, et al. Planned Cesarean vs Planned Vaginal Birth for Breech. Lancet, 2000.Kotaska A. BMJ, 2004. “Inappropriateness of RCTs for complex intrapartum phenomena.”Goffinet F, et al. PREMODA Study. Am J Obstet Gynecol, 2006.RCOG Green-top Guideline No. 20b (2017).ACOG Committee Opinion No. 745 (2018).SOGC No. 384 (2019).Get 20% off your first monthly subscription with NEEDED Vitamins
Rethinking "default lines" in the ICU
In this episode, we discuss long-term outcomes after chest-wall irradiation for breast cancer, new treatments for psoriasis and obesity, and early results on a vaccine for Lassa fever. We review opioid deprescribing and a clinical case describes spiraling into a distant past. Perspectives examine the corporatization of health care, the health effects of new energy legislation, and Medicaid cuts affecting U.S. children.
Yashaswini Singh is an assistant professor of health services, policy, and practice at Brown University. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. Y. Singh. The Antitrust Antidote to Hospital and Nursing Home Corporatization — Promises and Pitfalls. N Engl J Med 2025;393:1761-1764.
Right on the heels of the release of the 2025 AHA guidelines, including one on preferentially using IVs over IOs, comes two RCTs in the same edition of NEJM that compare intial attempts with IVs to IOs in out of hospital cardiac arrest. Dr Jarvis discusses these two papers while answer a listeners question, and tries to put this, and early epinephrine, into context. And he might throw in some commentary about the AHA's recommendations on mCPR and Heads Up CPR.Citations:1. Couper K, Ji C, Deakin CD, et al. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2025;392(4):336-348. doi:10.1056/NEJMoa24077802. Vallentin MF, Granfeldt A, Klitgaard TL, et al. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. N Engl J Med. 2025;392(4):349-360. doi:10.1056/NEJMoa2407616
Here's a polished podcast blurb suitable for LinkedIn, BlueSky, or Apple Podcasts listings — written in the JIMD Podcast tone and style: ⸻ It's one of the most talked-about breakthroughs of 2025, a first-in-human demonstration of in vivo gene editing to treat an inherited metabolic disease. In this episode, Kiran Musunuru and Rebecca Ahrens-Nicklas are joined by Julien Baruteau to unpack what this means for the field. They explore the science behind gene editing, the importance of ethical design, and the emotional weight of stopping therapy once enzyme function is restored. The conversation bridges the NEJM landmark paper (Musunuru et al., 2025) and the accompanying JIMD editorial (Rahman & Baruteau, 2025), reflecting on what this moment tells us about the future of metabolic medicine and how ready we are for it. First in Human Gene Editing for an Inherited Metabolic Disease Shamima Rahman, Julien Baruteau https://doi.org/10.1002/jimd.70056 Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease Kiran Musunuru, et al https://www.nejm.org/doi/10.1056/NEJMoa2504747
The FiltrateJoel Topf @kidneyboy.bsky.socialSwapnil Hiremath@hswapnil.medsky.socialAC @medpeedskidneys.bsky.socialSpecial GuestMike Walsh Associate Professor in the Departments of Medicine and Health Research Methods, Evidence, and Impact, McMaster University as well as a Scientist at the Population Health Research Institute and a nephrologist at St. Joseph's Healthcare Hamilton where he is the Chair of the Clinical Nephrology Research Group. Editing and Show Notes bySophia AmbrusoThe Kidney Connection written and performed by Tim YauShow NotesALCHEMIST (NephJC Shorts, Rossignol et al Lancet 2025)AC is in her 83rd year of med-peds fellowship.Joel's monologue brings us all down.Prophylactic ICD therapy doesn't improve sudden cardiac death or all-cause mortality in HD patients in the ICD2 trial (Jukema JW et al. Circulation 2019)Initiation with statins do not impact MACE endpoints or atherosclerotic events (4D AURORA trial Fellstrom BC et al. NEJM 2009 & SHARP trial Baigent C et al. Lancet 2011)Mike tries to liven up the mood by mentioning positive outcomes with iron therapy in heart failure with the PIVOTAL trial (Macdougall IC et al. NEJM 2018)TOPHAT trial revealed treatment with spironolactone in HFpEF did not affect MACE outcomes. (Pitt B et al. NEJM 2014)NephTrials ‘Run-in periods in clinical trials: What can we ACHIEVE?'SPIN D trial - spironolactone dose finding trial in ESRD (Charytan DM et al. Kidney Int 2018)Mike shares the human experience of the trial after being instructed to end the trial prematurely and being told they have “answered their question”Study in Japan - spironolactone predominantly benefits male over females (cannot find this)Male vs female benefit not observed in ACHIEVE despite Mike's initial hypothesisSwap compares and contrasts ACHIEVE, ALCHEMIST & Meta-analysis (Pyne L et al. Lancet 2025)Mike discusses how nonadherence to spironolactone impacted the intention to treat outcomes in the trial.What is a high risk of bias for dummies?Mike, Swap & Joel ponder future nsMRA or ASI trials hemodialysis?Tubular secretionsSwap is probably stalking Martha Wells by now, has moved on from Witch King, now onto Queen Demon on Good ReadsAC is adding to her brood, 2 dogs (Snickers & Harper), 1 childDungeon Crawler Call - a science fantasy book series by Matt Dinniman (on goodreads), which he lovingly referred to as complete nerd trash.Joel is binging on the series Task on HBO max, featuring Mark Ruffalo as FBI agent.NephJC is having its annual fundraiser (get your tickets here) at ASN. Providing a party shuttle that is leaving every 30 minutes from the conference center. As always, it will feature a live podcast recording covering the ASN late breaking, high impact clinical trials.Swap describes the high impact model at ASN this year - go big or go home.
This week, we look at new findings from the European prostate cancer screening study, advances in lung cancer therapy, physical therapy for meniscal tear, and a promising vaccine for Salmonella Paratyphi A. We review noninvasive liver fibrosis assessment and a complex clinical case, and explore perspectives on concierge care, kidney disease equity, WIC enrollment, community health, FDA regulation, and standing with colleagues in Gaza.
Autism isn't new, but our understanding of it has changed dramatically. It's now recognized as a broad neurodevelopmental spectrum that shapes how millions of people perceive, process, and interact with the world. In this episode, we explore what autism is AND isn't, from its earliest signs in infancy to its deep genetic roots, and why misinformation about it continues to spread. We speak with three remarkable experts leading the field in early detection, genetics, and public education: DR. AMI KLIN, PhD, Director of the Marcus Autism Center at Emory University and a pioneer in early autism research, whose work shows autism can be identified in babies as young as two months old. DR. JOSEPH BUXBAUM, PhD, Director of the Seaver Autism Center at Mount Sinai and a global leader in autism genetics, uncovering hundreds of genes linked to the condition. DR. ANDREA LOVE, immunologist, microbiologist, and founder of ImmunoLogic, known for her clear, evidence-based communication about vaccines, immunity, and autism myths. Together, we discuss: • What autism really is, and how the definitions have evolved • How it develops in infancy (and why early diagnosis can be so critical) • The powerful genetic evidence behind autism • The persistence of vaccine myths, and how misinformation spreads • How technology like eye-tracking can detect autism early • The rise of “profound autism” and what it means for families • The future of genetics-based treatments and therapy Whether you're autistic yourself, a parent navigating a new diagnosis, or simply seeking understanding, we're thrilled to share this extensive, in-depth episode with you. This is... Your Brain On Autism. SUPPORTED BY: the 2026 NEURO World Retreat. A 5-day journey through science, nature, and community, on the California coastline: https://www.neuroworldretreat.com/ ‘Your Brain On' is hosted by neurologists, scientists, and public health advocates Ayesha and Dean Sherzai. ‘Your Brain On... Autism' • SEASON 6 • EPISODE 1 LINKS Dr. Ami Klin at Emory University: https://ctsn.emory.edu/faculty/klin-ami.html Dr. Ami Klin at Marcus Autism Center: https://www.marcus.org/about-marcus-autism-center/meet-our-leadership/ami-klin Dr. Joseph Buxbaum at Mount Sinai: https://profiles.icahn.mssm.edu/joseph-d-buxbaum Dr. Andrea Love's website: https://www.immunologic.org/ Dr. Andrea Love on Instagram: https://www.instagram.com/dr.andrealove REFERENCES Autism Spectrum Disorder: A Review. JAMA, 2023. https://jamanetwork.com/journals/jama/article-abstract/2800182 Is There a Bias Towards Males in the Diagnosis of Autism? A Systematic Review and Meta-Analysis. https://link.springer.com/article/10.1007/s11065-023-09630-2 Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability. https://pubmed.ncbi.nlm.nih.gov/38592388/ Eye-Tracking–Based Measurement of Social Visual Engagement Compared With Expert Clinical Diagnosis of Autism. https://jamanetwork.com/journals/jama/fullarticle/2808996 Rare coding variation provides insight into the genetic architecture and phenotypic context of autism. https://www.nature.com/articles/s41588-022-01104-0 Rare coding variation illuminates the allelic architecture, risk genes, cellular expression patterns, and phenotypic context of autism. https://www.medrxiv.org/content/10.1101/2021.12.20.21267194v1 Andrew Wakefield and the fabricated history of the alleged vaccine-autism link. https://geneticliteracyproject.org/2024/04/29/andrew-wakefield-and-the-fabricated-history-of-the-alleged-vaccine-autism-link/ VACCINES & AUTISM 1. Major Cohort Studies Hviid et al., 2019 – Annals of Internal Medicine A nationwide study of 657,461 Danish children found no increased risk of autism in vaccinated children compared to unvaccinated peers — even among those with risk factors such as a sibling with autism. Ann Intern Med. 2019;170(8):513–520 Madsen et al., 2002 – New England Journal of Medicine In 537,303 Danish children, researchers found no difference in autism rates between vaccinated and unvaccinated groups, and no relationship with age, timing, or date of vaccination. NEJM. 2002;347:1477–1482 Jain et al., 2015 – Journal of the American Medical Association (JAMA) A U.S. cohort of 95,727 children — including those with siblings with autism — showed no link between MMR vaccination and autism risk, even in genetically predisposed children. JAMA. 2015;313(15):1534–1540 Madsen et al., 2003 – JAMA A study of 467,450 Danish children found no relationship between thimerosal-containing vaccines and autism. JAMA. 2003;290(13):1763–1766 DeStefano et al., 2022 – Vaccine A retrospective cohort of over 500,000 U.S. children with ASD found no increase in adverse events or worsening of autism-related symptoms following vaccination. Vaccine. 2022;40(16):2391–2398 2. Population-Level Epidemiologic Evidence Taylor et al., 1999 – The Lancet One of the earliest large epidemiological studies found autism prevalence was the same in vaccinated and unvaccinated children, and the age of onset was unrelated to the timing of MMR vaccination. Read: Lancet. 1999;353(9169):2026–2029 Institute of Medicine (U.S.) Immunization Safety Review, 2011 A global review of studies from the U.S., Denmark, Sweden, and the U.K. concluded there is no causal relationship between vaccination status and autism, and no plausible biological mechanism linking vaccines (including thimerosal) to ASD. Read: National Academies Press / PubMed 20669467 3. Systematic Reviews and Meta-Analyses Taylor et al., 2014 – Vaccine A comprehensive meta-analysis of 10 studies including over 1.2 million children found no association between vaccination and autism or ASD. Vaccine. 2014;32(29):3623–3629 Maglione et al., 2014 – Pediatrics Review of 67 high-quality studies covering the full U.S. immunization schedule concluded that vaccines are safe, adverse events are rare, and there is no link to autism, type 1 diabetes, or other chronic conditions. Pediatrics. 2014;134(2):325–337 Parker et al., 2004 – Pediatrics Systematic review of 10 primary studies examining thimerosal exposure found no relationship between vaccines and ASD. Authors noted that studies showing an association were methodologically flawed or biased, while robust studies consistently showed safety. Pediatrics. 2004;113(6):1904–1910 Offit & Hackett, 2003 – Clinical Infectious Diseases Review of immunology and epidemiology concluded that claims that vaccines “overwhelm” or “damage” the immune system are not biologically plausible based on how the immune system actually functions. Clin Infect Dis. 2003;46(9):1450–1456
In this episode, we look at new research on mucoactive therapy for bronchiectasis, aspirin use in anticoagulated patients with coronary disease, and sotatercept for early pulmonary arterial hypertension. We explore the genetics behind misdiagnosed common diseases and review uncertainty in medical training. We also share a case of woman with abdominal distention, edema, and pleural effusions and Perspectives on sickle cell disease, fetal personhood, and living with a genetic diagnosis.
Eberechi Nwogu-Onyemkpa is an assistant professor in the Division of Palliative Medicine at Washington University in St. Louis. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. E. Nwogu-Onyemkpa and Others. Involving Palliative Care to Improve Outcomes in Sickle Cell Disease. N Engl J Med 2025;393:1553-1556. E. Costa and Others. Thirty Years of Hydroxyurea for Sickle Cell Anemia — Scientific Progress, Global Health Gaps. N Engl J Med 2025;393:1556-1559.
The FiltrateJoel Topf @kidneyboy.bsky.socialSwapnil Hiremath @hswapnil.medsky.socialNayan Arora captainchloride.bsky.socialSopia Ambruso @sophia-kidney.bsky.socialSpecial Guests Brendon Neuen @brendonneuen.bsky.social Associate Professor and Program Lead, Renal and Metabolic at The George Institute for Global Health. Nephrologist and Director of Kidney Trials at Royal North Shore Hospital.Neuen has had three prior appearances on Freely Filtered: EMPA Kidney, DUPLEX and Sparsentan in FSGS, FLOW and SemaglutideMuthiah Vaduganathan @mvaduganathan on X. Cardiologist at Brigham and Women's Hospital and Harvard Medical School. Assistant Professor of Medicine.Editing byJoel TopfThe Kidney Connection written and performed by Tim YauShow NotesDONATE to NephJC! Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes NEJM | NephJC SummaryFIDELIO Bakris et al, NEJM 2020 | NephJC Summary; subgroup throws doubt on efficacy of finerenone in patients on flozinsFIGARO Pitt et al, NEJM 2021; subgroups clearly shows finerenone works, flozins or notNEJM editorial (wrongly) saying do not use Flozins unless on RASi Don't use dual RAS blockade ONTARGET Yusuf et al, NEJM 2008; VA NEPHRON-D Fried et al NEJM 2013Why we cannot study finerenone in HFrEF (RALES Pitt et al NEJM 1999) Muthu is jealous of GFR slope and albuminuria surrogate endpoints and wants to borrow them for HFpEF (Inker et al EHJ 2025)Combination therapy and CV outcomes in hypertension (Wang et al JAMA Card 2024 on low dose combinations and BP; Egan et al Blood Pressure 2022 review of topic) CONFIRMATION HF trial registry entry (Finerenone and Empagliflozin in hospitalized patients with HF)23:20: Nayan and Swap miss a chance to say ‘de-flozination' to discuss stopping a flozin which would allow a patient to be included in the trial Finerenone is a CYP3A4 substrate (Heinig et al Clin Pharmacokinetics 2023); Useful list of CYP3A4 inducers and inhibitors Everyone should get an ABPM (Bugeja et al CMAJ 2022)EASiKIDNEY study design Albuminuria mediates CKD benefits with Finerenone (Agarwal et al Ann Intern Med 2023)GFR slope and Albuminuria and the FDA (Taylor et al eClin Med 2025) Dapagliflozin and Eplerenone combination crossover trial (Provenzano et al JASN 2022)Joel gets promoted! (PBFluids reflection) Bluesky NephJC Chat discussion on ‘renal remission' Withdrawal of Finerenone and worse outcomes from FINEARTS (Vaduganathan et al JACC 2025)Combination therapies Analysis from Brendan and Muthu (Neuen et al Circulation 2024)Do not use KFRE when GFR > 60 (KDIGO Practice Point 2.2.4: Note that risk prediction equations developed for use in people with CKD G3–G5, may not be valid for use in those with CKD G1–G2) Finerenone vs Spironolactone trial in Primary Aldosteronism (Hu et al Circulation 2025)FIND CKD trial design (Heerspink et al NDT 2025) FINE-ONE trial design (Heerspink et al Diab Res Practice 2023) Tubular SecretionsNayan keeping his chin up as Yankees lose and Mariners follow (MLB Playoffs)Sophia's adventures with Beekeeping (Royal Jelly?) Brendon loves listening to ‘Susan' by Raye Muthu is back into Taekwondo Swap is still reading Martha Wells (Witch King on GoodReads)Joel will be hiking the Laugavegur trail in Iceland
On March 7, 2025, we released an episode summarizing key aspects of a NEJM publication regarding male partner therapy for women with recurrent BV. Although that study had limitations, the results were very surprising. Now, on 10/16/25 (7 months later), the ACOG has a new Clinical Practice Update (CPU) on this very issue. In this episode we will briefly summarize that March 2025 NEJM publication and highlight the TWO updated clinical recommendations from the ACOG regarding male partner therapy for the prevention of BV in women. PLUS, we will briefly discuss why although male partner therapy should be considered, partner EPT is “not recommended” at this time by the ACOG. 1. ACOG CLINICAL PRACTICE UPDATE: Concurrent Sexual Partner Therapy to Prevent Bacterial Vaginosis Recurrence Obstetrics & Gynecology ():10.1097/AOG.0000000000006102, October 16, 2025. | DOI: 10.1097/AOG.00000000000061022. Chapa Clinical Pearls March 2025 Episode: https://open.spotify.com/episode/4sW9tTe9CdYVQsCRBjqQQP3. Vodstrcil LA, Plummer EL, Fairley CK, Hocking JS, Law MG, Petoumenos K, et al. Male-partner treatment to prevent recurrence of bacterial vaginosis. N Engl J Med 2025;392:947–57. doi: 10.1056/NEJMoa2405404STRONG COFFEE PROMO: 20% Off Strong Coffee Company https://strongcoffeecompany.com/discount/CHAPANOSPINOBG
In this episode, we look at new research in cervical cancer, lupus, gene therapy for immune deficiency, and malaria prevention in infants. We review hair loss in women, follow a case of tuberculosis in advanced HIV, and hear perspectives on vaccines, primary care, digital health, infection surveillance, AI in disaster response, Medicare policy, and bearing witness in conflict zones.
In this episode, Dr. Jonathan Chen joins the hosts to discuss his path from teenage programmer to Stanford physician-informatician and why machine learning has both thrilled and unnerved him. From his 2017 NEJM essay warning about “inflated expectations” to his latest studies showing GPT‑4 outperforming doctors on diagnostic tasks, Dr. Chen describes a discipline learning humility at machine speed. This conversation spans medical education, automation anxiety, magic, and why empathy—not memorization—may become the most valuable clinical skill. Transcript.