Podcasts about The New England Journal of Medicine

This week, we explore a new standard of care for high-risk HER2-positive early breast cancer, long-acting therapy for people with HIV facing adherence challenges, a first-in-class trial of a p53 reactivator, and tecovirimat for mpox. We review group B streptococcal disease and a revealing case of prosthetic joint infection. Perspectives examine the role of folate therapy, Medicare drug-price negotiation, AI in medical education, and incidental findings.

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-473 Overview: Join us as we review long-term outcomes from a recently published trial on prostate-specific antigen (PSA) testing and prostate cancer mortality. Learn how updated evidence informs shared decision-making and balances early detection with potential harms. Equip yourself to guide patients through nuanced discussions on PSA testing's limitations, mortality data, and meaningful clinical impact. Episode resource links: N Engl J Med 2025;393:1669-80. DOI: 10.1056/NEJMoa2503223 Recommendation: Prostate Cancer: Screening | United States Preventive Services Taskforce Guest: Robert A. Baldor MD, FAAFP Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  The views expressed in this podcast are those of Dr. Domino and his guests and do not necessarily reflect the views of Pri-Med.

In this special edition on Obesity as a Chronic Disease our host, Dr. Neil Skolnik will discuss the root causes of obesity, the hormonal changes and metabolic adaptation that occurs when a person has obesity, and the implications of understanding obesity as a chronic disease for clinical practice. This special episode is supported by an independent educational grant from Lilly. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health Donna Ryan, M.D, Professor Emeritus at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. Past President of both the Obesity Society and the World Obesity Federation Susan Kuchera, M.D, Associate Clinical Professor of Family and Community Medicine in the Sidney Kimmel Medical College of Thomas Jefferson University, Program Director of the Jefferson Health Abington Family Medicine Residency Program. Selected references: Changes in Energy Expenditure Resulting from Altered Body Weight. N Engl J Med 1995;332:621-628 Long-Term Persistence of Hormonal Adaptations to Weight Loss. N Engl J Med 2011;365:1597-1604

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-473 Overview: Join us as we review long-term outcomes from a recently published trial on prostate-specific antigen (PSA) testing and prostate cancer mortality. Learn how updated evidence informs shared decision-making and balances early detection with potential harms. Equip yourself to guide patients through nuanced discussions on PSA testing's limitations, mortality data, and meaningful clinical impact. Episode resource links: N Engl J Med 2025;393:1669-80. DOI: 10.1056/NEJMoa2503223 Recommendation: Prostate Cancer: Screening | United States Preventive Services Taskforce Guest: Robert A. Baldor MD, FAAFP Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  The views expressed in this podcast are those of Dr. Domino and his guests and do not necessarily reflect the views of Pri-Med.

Sarah Poland, MD, lead author of a recently published article in the journal ONCOLOGY titled Advances in Immunotherapy for Breast Cancer, highlighted key findings from her review in a conversation with CancerNetwork®.1 Throughout the discussion, she spoke about: Shifting Perspectives on Immunogenicity: Historically, breast cancer was considered a “cold,” poorly immunogenic tumor due to low tumor mutational burden (TMB) and few tumor-infiltrating lymphocytes (TILs). Poland highlighted how clinical research has shifted this perspective, particularly through the study of triple-negative breast cancer (TNBC), which often exhibits higher PD-L1 expression and immune infiltration.Key Clinical Milestones: The review highlighted foundational data that established immunotherapy as a standard of care: Early-Stage TNBC: The phase 3 KEYNOTE-522 trial (NCT03036488) established pembrolizumab (Keytruda) plus chemotherapy as a standard neoadjuvant treatment for stage II to III TNBC.2 Metastatic TNBC: The phase 3 KEYNOTE-355 trial (NCT02819518) demonstrated the benefit of pembrolizumab in PD-L1–positive metastatic disease.3 Managing Toxicity and Rechallenge: Poland addressed the feasibility of pembrolizumab rechallenge after an immune-related adverse effect (irAE), emphasizing that while possible, it requires a highly individualized approach based on the severity and timing of the initial toxicity.The Future Landscape: Beyond PD-1/PD-L1 inhibitors, the discussion covered emerging technologies that are poised to redefine treatment: Antibody-Drug Conjugates (ADCs): Exploration of novel combinations of ADCs with immunotherapy. Emerging Modalities: The potential role of bispecific antibodies and vaccine trials utilizing tumor antigens. Subtype Expansion: Emerging evidence supporting the efficacy of immunotherapy in hormone receptor–positive and HER2-positive subtypes, moving beyond the traditional focus on TNBC. Unmet Educational Needs: Poland emphasized the importance of resources that connect providers and patients, particularly in translating complex trial data into clinical practice and addressing patient concerns regarding the newest therapies and trials.Poland is from the Department of Medicine in the Section of Hematology/Oncology at The University of Chicago.References1.        Poland S, de Oliveira Andrade M, Nanda R. Advances in immunotherapy for breast cancer. Oncology (Williston Park). 2026;40(1):8-15. doi:10.46883/2026.259210612.        Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa19105493.        Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809

This week, we highlight major advances in multiple myeloma, gene therapy for cystinosis, and experimental treatments for myotonic dystrophy. We review long-term outcomes of aortic-valve replacement, strategies for secondary stroke prevention, and a revealing diagnostic case of eosinophilic disease in an older adult. A Sounding Board explores FDA approval standards. Perspectives delve into tobacco cessation, influenza evolution, and the uncertainty patients and clinicians share when facing life-altering diagnoses.

Sonja Rasmussen is a professor in the Department of Genetic Medicine at Johns Hopkins School of Medicine. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S.A. Rasmussen and D.B. Jernigan. Antigenic Drift and Antivaccine Shift in the 2025–2026 Influenza Season. N Engl J Med 2026;394:732-735.

Rheumatoid Arthritis explained, including pathophysiology and typical signs and symptoms (extra articular too!). We also look at rheumatoid arthritis diagnosis (with rheumatoid factor / Anti CCP) and medications such as DMARDsPDFs available here: https://rhesusmedicine.com/pages/rheumatologyConsider subscribing on YouTube (if you found any of the info useful!): https://www.youtube.com/channel/UCRks8wB6vgz0E7buP0L_5RQ?sub_confirmation=1Patreon: https://www.patreon.com/rhesusmedicineBuy Us A Coffee!: https://www.buymeacoffee.com/rhesusmedicineTimestamps:0:00 What is Rheumatoid Arthritis?0:23 Rheumatoid Arthritis Pathophysiology 2:58 Rheumatoid Arthritis Symptoms5:16 Rheumatoid Arthritis Diagnosis 7:02 Rheumatoid Arthritis Treatment LINK TO SOCIAL MEDIA: https://www.instagram.com/rhesusmedicine/ReferencesMSD Manual Professional Edition (2025) Rheumatoid arthritis. MSD Manual Professional Edition. Available at: https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/joint-disorders/rheumatoid-arthritisBMJ Best Practice (2025) Rheumatoid arthritis – Symptoms, diagnosis and treatment. BMJ Best Practice. Available at: https://bestpractice.bmj.com/topics/en-gb/105Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR. Kelly and Firestein's Textbook of Rheumatology. 11th ed. Elsevier; 2021.McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205–2219.Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023–2038.Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 10th ed. Elsevier; 2021.Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Elsevier; 2020.Please remember this podcast and all content from Rhesus Medicine is meant for educational purposes only and should not be used as a guide to diagnose or to treat. Please consult a healthcare professional for medical advice. 

Dr Remle Crowe returns to the podcast to discuss three new papers with Dr Jarvis: Two papers on epinephrine in cardiact arrest (including one on trauma!) and one on pulse oximetry in hypoxemic patients with darker skin. We might nerd out a bit on methodology, tacos, and have a few book recommendations.Citations: Martin DS, Doidge JC, Gould D, et al.: The impact of skin tone on performance of pulse oximeters used by NHS England COVID Oximetry @home scheme: measurement and diagnostic accuracy study. BMJ. 2026;January 14;392Witt CE, Shatz DV, Robinson BRH, et al.: Epinephrine in Prehospital Traumatic Cardiac Arrest—Life Saving or False Hope? Prehospital Emergency Care. 2026;January 2;30(1):153–61.Lilien EJ, Ashburn NP, George TS, et al.: Single Dose Epinephrine Protocol Is Associated With Improved Survival of Older Adults With Out‐Of‐Hospital Cardiac Arrest. Academic Emergency Medicine. 2025Perez CP: Invisible Women: Data Bias in a World Designed for Men. New York, NY, Abrams Press, 2019.O'Neil C: Weapons of Math Destruction: How Big Data Increases Inequality and Threatens Democracy. New York, NY, Crown Publishing Group, 2017. • 6. Perkins GD, Ji C, Deakin CD, et al.: A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018;August 23;379(8):711–21.

Episode 212: Managing HFpEFHyo Mun and Jordan Redden (medical students) explain how to manage HFpEF with medications and touch some basics about nonpharmacologic treatments. Dr. Arreaza asks insightful questions to guide the discussion. Written by Hyo Mun, MSIV, American University of the Caribbean; and Jordan Redden, MSIV, Ross University School of Medicine. Comments by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Treatment of HFpEFArreaza: Mike, if you had to name the one therapy everyone with HFpEF should be on, what is it?Mike: That's easy! SGLT-2 inhibitors. This is the one slam-dunk we have in HFpEF. Empagliflozin (Jardiance) or dapagliflozin (Farxiga) should be started in essentially every patient with HFpEF, and it doesn't matter if they have diabetes or not.Jordan: And that's worth repeating, because people still think of these as “diabetes drugs.” They're not anymore. In HFpEF, SGLT-2 inhibitors reduce heart-failure hospitalizations, improve symptoms, improve quality of life, and even reduce cardiovascular death.Dr. Arreaza: They're also simple. Empagliflozin 10 mg daily or dapagliflozin 10 mg daily. No titration, no drama. The effectiveness of these meds was established around 2019 with DAPA-HF and later with DELIVER. These were trials thatdemonstrated that dapagliflozin reduces worsening heart failure and cardiovascular events across the full spectrum of heart failure, from reduced to preserved ejection fraction, independent of diabetes status.Mike: And the number needed to treat is about 28 to prevent one heart-failure hospitalization. That's excellent for a disease where we historically had almost nothing that worked.Jordan: They're also safe in chronic kidney disease down to an eGFR of about 25, which makes them even more useful in this population.Dr. Arreaza: Alright. We got SGLT-2 inhibitor, what's next?Mike: Volume management. Loop diuretics are still the backbone of symptom control in HFpEF. If the patient is volume overloaded, you diurese, and you diurese aggressively.Jordan: The goal is euvolemia. Dry weight, no edema, no orthopnea, no waking up gasping for air. A lot of these patients end up needing chronic oral loop diuretics to stay there.Dr. Arreaza: Something to remember: HFpEF patients don't tolerate congestion well, and being “a little wet” is not benign. Let's move into RAAS inhibition. Where do ARBs and ACE inhibitors fit in?Mike: Between ARBs and ACE inhibitors, ARBs are the winners in HFpEF. They actually reduce heart failure hospitalizations—drugs like candesartan, losartan, valsartan. ACE inhibitors? Not so much. They showed minimal benefit in older HFpEF patients, which is why we go with ARBs instead.Jordan: But a lot of clinicians get nervous about ACE inhibitors and ARBs because of kidney function, so it's worth talking through how these drugs actually work in the kidney.Dr. Arreaza: Yes, misunderstanding may lead to unnecessary drug discontinuation.Jordan: Under normal conditions, the afferent arteriole brings blood into the glomerulus, and the efferent arteriole is constricted by angiotensin II. That constriction keeps pressure high in the glomerulus and maintains filtration.Mike: Here's what happens with an ACE inhibitor: you block angiotensin II, the efferent arteriole relaxes, glomerular pressure drops, and GFR dips slightly. Creatinine bumps up a little, and that scares people, but that's actually the whole point—that's how you get kidney protection long-term.Jordan: High intraglomerular pressure causes hyperfiltration injury and scarring over time. Lowering that pressure protects the kidney long-term. The short-term GFR drop is the price you pay for long-term benefits.Dr. Arreaza: So let's talk about CKD, because this is where people panic.Mike: Right. ACE inhibitors and ARBs are not contraindicated in chronic kidney disease. In fact, they're recommended even in advanced stages. They reduce progression to kidney failure by about a third.Jordan: The key is how you use them. Start low. Check creatinine and potassium one to two weeks after starting, then periodically. A creatinine rise up to 30% from baseline is acceptable. That's not kidney injury, that's physiology.Dr. Arreaza: And what about potassium creeping up?Mike: You adjust the dose or add a potassium binder. You don't just automatically stop the drug.Dr. Arreaza: Now there is one absolute contraindication everyone needs to know about! (board exam test)Jordan: Bilateral renal artery stenosis. This is the big one. In these patients, the kidneys are completely dependent on angiotensin II–mediated efferent constriction to maintain GFR. Take that away, and GFR collapses.Mike: Creatinine can jump dramatically within days. If you see a creatinine rise of 20% or more shortly after starting an ACE inhibitor, you should be thinking about bilateral renal artery stenosis and stopping the drug immediately.Dr. Arreaza: After revascularization, though, many patients can tolerate ACE inhibitors again, so this isn't always permanent. What about cardiorenal syndrome? That's where things get uncomfortable.Mike: It is uncomfortable, but cardiorenal syndrome isn't a contraindication. These patients have severe heart failure and kidney disease, and their mortality is actually higher than patients with heart failure alone.Jordan: ACE inhibitors still reduce mortality and slow kidney disease progression in this group. Studies show that stopping ACE inhibitors during acute heart-failure admissions increases in-hospital mortality three- to four-fold.Dr. Arreaza: So we are cautious, but we don't avoid it.Mike: Exactly. Start low, titrate slowly, monitor labs closely, accept up to a 30% creatinine rise. You only stop if kidney function keeps worsening, or potassium gets dangerously high.Dr. Arreaza: Alright. Let's move on. What about mineralocorticoid receptor antagonists… MRA?Jordan: Spironolactone or eplerenone might reduce hospitalizations in HFpEF, but the data is mixed. This is more of a “select patients” situation.Mike: And you have to watch potassium and kidney function carefully, especially if they're already on an ACE inhibitor or ARB.Dr. Arreaza: What about sacubitril-valsartan, also known as Entresto®?Mike: Entresto may help patients with mildly reduced EF roughly in the 45 to 57% range. It's not first-line for HFpEF, but in select patients, it's reasonable.Dr. Arreaza: Now let's clarify one of the biggest sources of confusion: beta blockers.Jordan: Beta blockers are not a treatment for HFpEF itself. They're only indicated if the patient has another reason to be on them, like coronary disease or atrial fibrillation.Mike: And timing really matters here. You absolutely do not start beta blockers during acute decompensated heart failure. Their negative inotropic effects can make things worse when patients are volume overloaded.Jordan: But, and this is critical, you also don't stop them if the patient is already taking one. Abrupt withdrawal causes a sympathetic surge and dramatically increases mortality.Dr. Arreaza: If a patient is admitted on a beta blocker, what do we do?Mike: Continue it at the same dose or reduce it slightly if they're really unstable. Once they're euvolemic and stable, you can carefully titrate up.Jordan: And watch for chronotropic incompetence. HFpEF patients often rely on heart-rate response to exercise, and beta blockers can worsen exercise intolerance.Dr. Arreaza: Beyond medications, HFpEF is really about treating comorbidities. Aerobic activity can be an initial strategy to improve exercise intolerance and has evidence of improving aerobic function and quality of life. Sodium restriction: improves symptoms, does not decrease risk of death or hospitalizations.Mike: Hypertension control is huge. For diabetes, the SGLT-2 inhibitors will perform double duty. For obesity, weight loss improves symptoms, and GLP-1 agonists like semaglutide are absolute gamechangers.Jordan: Don't forget sleep apnea, atrial fibrillation, and lifestyle. Exercise improves the quality of life, even if it doesn't change hard outcomes. Lifestyle is the main treatment. Dr. Arreaza: And when should you refer to cardiology?Mike: You should refer when the diagnosis isn't clear; symptoms are not responding to treatment, difficult volume management, end-organ dysfunction, or if you are concerned about advanced heart failure.Dr. Arreaza: So, it has been a great discussion. What is the takeaway?Mike: HFpEF treatment isn't about one magic drug -- it's about volume control, SGLT2 inhibitors, smart use of RAAS blockade, and aggressive management of comorbidities.Jordan: And it's understanding the physiology, so you don't withhold life-saving therapies out of fear.Dr. Arreaza: Well said. If you found this helpful, share it with a friend or colleague and rate us wherever you listen. This is Dr. Arreaza, signing off.Jordan/Mike: Thanks! Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Barzin A, Barnhouse KK, Kane SF. Heart Failure With Preserved Ejection Fraction. Am Fam Physician. 2025;112(4):435-440.Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. Circulation. 2022;145(18):e895-e1032.Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2023;81(18):1835-1878.Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461.Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098.Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392.Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction. Lancet. 2003;362(9386):777-781.Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381(17):1609-1620.Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084.Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590.Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from COVID-19. JAMA Cardiol. 2020;5(11):1265-1273.Basso C, Leone O, Rizzo S, et al. Pathological features of COVID-19-associated myocardial injury. Eur Heart J. 2020;41(39):3827-3835.Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615.Badve SV, Roberts MA, Hawley CM, et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in adults with estimated GFR less than 60 mL/min per 1.73 m². Ann Intern Med. 2024;177(8):953-963.Navis G, Faber HJ, de Zeeuw D, de Jong PE. ACE inhibitors and the kidney: a risk-benefit assessment. Drug Saf. 1996;15(3):200-211.Textor SC, Novick AC, Tarazi RC, et al. Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease. Ann Intern Med. 1985;102(3):308-314.Hackam DG, Spence JD, Garg AX, Textor SC. Role of renin-angiotensin system blockade in atherosclerotic renal artery stenosis and renovascular hypertension. Hypertension. 2007;50(6):998-1003.Ronco C, Haapio M, House AA, et al. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52(19):1527-1539.Prins KW, Neill JM, Tyler JO, et al. Effects of beta-blocker withdrawal in acute decompensated heart failure. JACC Heart Fail. 2015;3(8):647-653.Jondeau G, Neuder Y, Eicher JC, et al. B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode. Eur Heart J. 2009;30(18):2186-2192.Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.

In part one of this two-part series, Dr. Tesha Monteith and Dr. Andrew Hershey summarize findings from the SPACE trial evaluating fremanezumab in adolescents and children with migraine. Show citation: Hershey AD, Szperka CL, Barbanti P, et al. Fremanezumab in Children and Adolescents with Episodic Migraine. N Engl J Med. 2026;394(3):243-252. doi:10.1056/NEJMoa2504546  Show transcript:  Dr. Tesha Monteith: Hi, this is Tesha Monteith with the Neurology Minute. I'm here with Andrew Hershey, Professor of Pediatrics and Director of the Division of Neurology at Cincinnati Children's and the Children's Headache Center. We're here talking about his new paper published in the New England Journal of Medicine, Fremanezumab in Children and Adolescents with Episodic Migraine. Andrew, thank you for being on our Neurology Minutes. Dr. Andrew Hershey: Thank you for inviting me. Dr. Tesha Monteith: Can you summarize the findings of the space trial investigating Fremanezumab for adolescents and children with migraine? Dr. Andrew Hershey: This is one of the four monoclonal antibodies against CGRP, or it's this receptor that had been proven effective for adults. And it's the first one, the formazepam, that's been able to report its effectiveness in children and adolescents with less than 15 headache days per month. This study looked at over 200 children adolescents that were in a double-blinded randomized placebo controlled study. And reached its primary, as well as its secondary endpoint of a reduction compared to placebo. And the number of attacks of migraine per month, as well as a greater than 50% reduction in the number of headache attacks per month, with minimal to no side effects, the most notable side effect being injection site erythema. Dr. Tesha Monteith: Great. Thank you so much for providing that update. Do check out the full podcast for more details about his paper and the treatment of migraine in children and adolescents. This is Tesha Monteith. Thank you for listening to the Neurology Minute.  

In this episode of the progesterone series, Dr. Brendan McCarthy — Chief Medical Officer of Protea Medical Center in Tempe, Arizona — explores the often misunderstood relationship between progesterone, estrogen, and breast health. For decades, women have been taught to fear their breasts and fear hormones. While awareness matters, fear is disempowering — and it has left many women confused about what's actually happening in their bodies. In this episode, we discuss: Why breast tissue is dynamic, not static How estrogen stimulates growth and progesterone restores balance The role of progesterone in breast tissue maturation and architecture Why dense or fibrocystic breasts often reflect unopposed estrogen How restoring ovulation and progesterone can reduce breast pain and density in some women The difference between natural progesterone vs synthetic progestins Where the fear around progesterone and breast cancer really came from Progesterone is not something to fear — it is a hormone of organization, balance, and maturation. Understanding how it works allows women to approach breast health with clarity instead of anxiety.

This week includes studies on promising new therapies for IgA nephropathy, evolving antithrombotic strategies after coronary stenting, and the inciting antigen in rare vaccine-related clotting syndromes. We review the urgent challenge of mucormycosis and follow the case of a young woman with headaches and hypertension. We discuss human-subjects research. Perspectives examine rural health, data interoperability, drug labels in the courts, and a pediatrician's dilemma.

Carmel Shacharis an assistant clinical professor of law and faculty director of the Health Law and Policy Clinic at Harvard Law School. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. H. Howard and C. Shachar. The Rural Health Transformation Program — An Avenue for Promoting Administrative Policies. N Engl J Med 2026;394:625-627.

In this special series on Oral GLP-1 Receptor Agonists, Dr. Neil Skolnik will discuss the first of the GLP-1 RAs to receive FDA approval, Semaglutide.  This special episode is sponsored with support from Novo Nordisk. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health W. Timothy Garvey, MD.,  Butterworth Professor and University Professor of Medicine in the Department of Nutrition Sciences at the University of Alabama at Birmingham. Selected references: Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Knop, Filip K et al. The Lancet, Volume 402, Issue 10403, 705 – 719 Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. Wharton Sean et al. N Engl J Med 2025;393:1077-1087 Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Lincoff, A Michael, et al.  N Engl J Med 2023;389:2221-2232  

Abdominal organ procurement is a high-stakes operation that blends anatomy, speed, and coordinated teamwork. In this Behind the Knife episode, the UNMC transplant team walks through the practical “how-to” of deceased donor abdominal recovery—covering OR roles and logistics, key anatomic maneuvers, cannulation/flush troubleshooting, and the workflow differences that matter most between donation after brain death (DBD) and donation after circulatory death (DCD).HostsMadeline Cloonan, MD PhD – General Surgery Resident, University of Nebraska Medical Center (@maddie_cloonan) Evelyn Waugh, MD – Transplant Surgery Fellow, University of Nebraska Medical Center Jacqueline Dauch, MD – Abdominal Transplant Surgeon, University of Nebraska Medical Center Alex Maskin, MD – Kidney & Pancreas Transplant Surgeon, University of Nebraska Medical CenterLearning Objectives Compare DBD vs DCD donor workflow and define total vs functional warm ischemia.  Identify key OR roles and the ethical/legal separation of death declaration from procurement teams.  Outline the core steps of abdominal procurement, including exposure, cannulation, cross-clamp, and organ removal sequence.  Apply a practical troubleshooting approach when flush flow is inadequate References  Englesbe MJ, Mulholland MW. Operative Techniques in Transplantation Surgery. Philadelphia, PA: Wolters Kluwer; 2018. Tullius SG, Rabb H. Improving the supply and quality of deceased-donor organs for transplantation. N Engl J Med. 2018;378(20):1924–1933. doi:10.1056/NEJMra1708700. https://pubmed.ncbi.nlm.nih.gov/29768153/ Croome KP, Barbas AS, Whitson B, et al. American Society of Transplant Surgeons recommendations on best practices in donation after circulatory death organ procurement. Am J Transplant. 2023;23(2):171–179. doi:10.1016/j.ajt.2022.10.009. https://pubmed.ncbi.nlm.nih.gov/36695685/ Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  If you liked this episode, check out our recent episodes here: https://behindtheknife.org/listenBehind the Knife Premium:General Surgery Oral Board Review Course: https://behindtheknife.org/premium/general-surgery-oral-board-reviewTrauma Surgery Video Atlas: https://behindtheknife.org/premium/trauma-surgery-video-atlasDominate Surgery: A High-Yield Guide to Your Surgery Clerkship: https://behindtheknife.org/premium/dominate-surgery-a-high-yield-guide-to-your-surgery-clerkshipDominate Surgery for APPs: A High-Yield Guide to Your Surgery Rotation: https://behindtheknife.org/premium/dominate-surgery-for-apps-a-high-yield-guide-to-your-surgery-rotationVascular Surgery Oral Board Review Course: https://behindtheknife.org/premium/vascular-surgery-oral-board-audio-reviewColorectal Surgery Oral Board Review Course: https://behindtheknife.org/premium/colorectal-surgery-oral-board-audio-reviewSurgical Oncology Oral Board Review Course: https://behindtheknife.org/premium/surgical-oncology-oral-board-audio-reviewCardiothoracic Oral Board Review Course: https://behindtheknife.org/premium/cardiothoracic-surgery-oral-board-audio-reviewDownload our App:Apple App Store: https://apps.apple.com/us/app/behind-the-knife/id1672420049Android/Google Play: https://play.google.com/store/apps/details?id=com.btk.app&hl=en_US

In this episode of "PICU Doc on Call," Drs. Pradip Kamat and Rahul Damania dive into a pediatric ICU case involving a 4-year-old girl who presents with severe anemia and bleeding, ultimately diagnosed with von Willebrand disease (VWD). They chat about the causes and different types of VWD, walk through the key clinical features, and break down how to diagnose and manage this condition. Drs. Kamat and Damania highlight the important roles of desmopressin and factor concentrates in treatment. Throughout the episode, they stress the need to recognize VWD in kids who have mucosal bleeding and offer practical tips for intensivists on lab evaluation and treatment strategies for this common inherited bleeding disorder.Show Nighlights: Clinical case discussion of a 4-year-old girl with severe anemia and bleeding symptomsDiagnosis of von Willebrand disease (VWD) and its significance in pediatric critical careEtiology and pathogenesis of von Willebrand diseaseClassification of von Willebrand disease into types (Type 1, Type 2 with subtypes, Type 3)Clinical manifestations and symptoms associated with VWDDiagnostic approach for identifying von Willebrand disease, including laboratory testsManagement strategies for VWD, including desmopressin and von Willebrand factor concentratesRole of adjunctive therapies such as antifibrinolytics and hormonal treatmentsImportance of multidisciplinary collaboration in managing complex bleeding disordersOverview of the pathophysiology of von Willebrand factor and its role in hemostasisReferences:Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter ***.Reference 1: Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med. 2016 Nov 24;375(21):2067-2080.Reference 2: Ng C, Motto DG, Di Paola J. Diagnostic approach to von Willebrand disease. Blood. 2015 Mar 26;125(13):2029-37.Platton S, Baker P, Bowyer A, et al. Guideline for laboratory diagnosis and monitoring of von Willebrand disease: A joint guideline from the United Kingdom Haemophilia Centre Doctors' Organisation and the British Society for Hematology. Br J Haematol 2024 May;204(5):1714-1731.Mohinani A, Patel S, Tan V, Kartika T, Olson S, DeLoughery TG, Shatzel J. Desmopressin as a hemostatic and blood-sparing agent in bleeding disorders. Eur J Haematol. 2023 May;110(5):470-479. doi: 10.1111/ejh.13930. Epub 2023 Feb 12. PMID: 36656570; PMCID: PMC10073345.

Episode 211: Understanding HFpEF.  Hyo Mun and Jordan Redden (medical students) explain the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and how it differentiates from HFrEF. Dr. Arreaza asks insightful questions and summarizes some key elements of HFpEF. Written by Hyo Mun, MS4, American University of the Caribbean; and Jordan Redden, MS4, Ross University School of Medicine. Comments and edits by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.What is EF? Just imagine, the heart is a pump, blood gets into the heart through the veins, the ventricles fill up and then squeeze the blood out. So, the percent of blood that is pumped out is the EF. Let's start at the beginning. What is HFpEF?Mike: HFpEF stands for heart failure with preserved ejection fraction. Basically, these patients squeeze normally—their ejection fraction is 50% or higher—but here's the thing: the heart can't relax and fill the way it should. The muscle gets stiff, almost like a thick leather boot that just won't stretch. And because the ventricle can't fill properly, pressure starts backing up into the lungs and the rest of the body. That's when patients start experiencing shortness of breath, leg swelling, fatigue—all those classic symptoms.Dr. Arreaza: And this is where people get fooled by the ejection fraction.Mike: Exactly. The ejectionfraction tells you total left ventricular emptying, not just forward flow.Jordan: The classic example is severe mitral regurgitation. You can eject 60% of your blood volume and still be in cardiogenic shock because most of that blood is leaking backward into the left atrium instead of going into the aorta. So, you get pulmonary edema, hypotension, fatigue, all with a “normal” EF. Which is honestly terrifying if you're over-relying on echo reports without thinking clinically.Dr. Arreaza: And in HFpEF, functional mitral regurgitation often shows up later in the disease. It's not usually the primary cause; it's more of a marker of advanced disease. Moderate to severe MR in HFpEF independently predicts worse outcomes, including a higher risk of mortality or heart failure hospitalization. So, let's contrast this with HFrEF. How are these two different?Mike: HFrEF—heart failure with reduced ejection fraction—is a pumping problem. The heart muscle is weak and can't contracteffectively. Ejection fraction drops below 40%, and this is your classic systolic dysfunction.Jordan: HFpEF, on the other hand, is diastolic dysfunction. The heart muscle is thick, fibrotic, and noncompliant. It squeezes fine, but it just doesn't relax, even though the EF looks reassuring on paper.Mike: I like to explain it this way: HFrEF is a weak heart that can't squeeze. HFpEF is a stiff heart that can't relax. Totally different problems.Dr. Arreaza: And then there's the gray zone: heart failure with mildly reduced EF, or HFmrEF. That's an EF between 41 and 49% with evidence of elevated filling pressures. It really shares the features of both worlds. So, what actually causes HFpEF versus HFrEF?Jordan: HFpEF is basically what happens when all the problems of modern living catch up with you. You've got chronic hypertension, obesity, diabetes, metabolic syndrome, aging, systemic inflammation—all of these things slowly remodel the heart over years. The muscle gets thick and stiff, and eventually the ventricle just loses its ability to relax. So, HFpEF is really a disease of metabolic dysfunction and chronic stress in the heart. Mike: HFrEF is more about direct injury. Think about myocardial infarctions, ischemic cardiomyopathy, viral myocarditis, alcohol toxicity, chemotherapy like doxorubicin, genetic cardiomyopathies, or chronic uncontrolled tachycardia. These insults actually damage or kill heart muscle cells, leading to a dilated, weak ventricle that can't pump effectively.Dr. Arreaza: So the short version: HFpEF is caused by chronic metabolic and hypertensive stress, while HFrEF is caused mainly by myocardial damage. A question we get a lot: does HFpEF eventually turn into HFrEF? What do you guys think?Mike: In most cases, no. HFpEF patients usually stay HFpEF throughout their disease course. They don't just “burn out” and turn into HFrEF.Jordan: They're generally separate disease entities with different pathophysiology. A patient with HFpEF can develop HFrEF if they have a big myocardial infarction or ongoing ischemia that damages the muscle, but that's not the natural progression.Mike: Interestingly though, the opposite can happen. Some HFrEF patients actually improve their ejection fraction with good medical therapy—that's called HF with improved EF—and it's a great sign that treatment is working.Dr. Arreaza: Another question. How do HFpEF and HFrEF compare to restrictive cardiomyopathy and constrictive pericarditis?Jordan: Clinically, they can all look very similar: dyspnea, edema, fatigue, but the underlying mechanisms are completely different.Mike: In HFpEF, the myocardium itself is stiff from hypertrophy and fibrosis. The problem is intrinsic to the heart muscle, and EF stays preserved. Echoshows diastolic dysfunction with elevated filling pressures.Jordan: In HFrEF, the myocardium is weak. The ventricle is often dilated and contracts poorly, with a reduced EF.Mike: Restrictive cardiomyopathy is different. Here, the myocardium gets infiltrated by abnormal stuff—amyloid, iron, sarcoid—and that makes it extremely stiff. It can look like HFpEF on the surface, but it's usually more severe. On Echo You'll see biatrial enlargement, small ventricles, and preserved EF. And importantly, it's a pathologic diagnosis, so you need advanced imaging or biopsy to confirm it.Jordan: Constrictive pericarditis is another mimic, but here the myocardium is usually normal. The problem is that the pericardium is thickened, calcified, and rigid. This will physically prevent the heart from being filled. Imaging shows pericardial thickening, septal bounce, and respiratory variation in flow, and cath shows equalization of diastolic pressures, which is the hallmark of constrictive pericarditis.Dr. Arreaza: So the takeaway is: HFpEF is a clinical syndrome driven by common metabolic and hypertensive causes, while restrictive and constrictive diseases are specific pathologic entities. If “HFpEF” is unusually severe or not responding to treatment, you need to think beyond HFpEF. Which type of heart failure is more common right now?Mike: Good question, the answer is: HFpEF. It now accounts for up to 60% of all heart failure cases, and it's still rising.Dr. Arreaza: Why is that?Jordan: Because people are living longer, gaining weight, and developing more metabolic syndrome. HFpEF thrives in older, or people with obesity, hypertension, or diabetes: basically, the modern American population. At the same time, better treatment of acute MIs means fewer people are developing HFrEF from massive heart attacks.Mike: HFpEF is the heart failure epidemic of the 21st century. It's honestly the cardiology equivalent of type 2 diabetes.Dr. Arreaza: Let's talk aboutCOVID-19. (2025 and still talking about it) Does it actually increase heart failure risk?Mike: Yes, absolutely. COVID increases both acute and long-term heart failure risk.Jordan: During acute infection, COVID can cause myocarditis, trigger massive inflammation, and precipitate acute decompensated heart failure, especially in patients with pre-existing disease. It also causes microthrombi, which can injure the myocardium.Mike: And after infection, even mild cases are linked to a significantly higher risk of developing new heart failure within the following year. Both HFpEF and HFrEF rates go up.Dr. Arreaza: I remember seeing this in 2021, we had a patient with acute COVID and HFrEF, her EF was about 10%, I lost contact with the patient and at the end I don't know what happened to her. What's the pathophysiology of COVID and heart failure?Mike: COVID causes direct viral injury through ACE2 receptors, triggers massive inflammation that damages the endothelium and heart muscle, leads to microvascular clotting and fibrosis—all mechanisms that promote HFpEF.Jordan: Add autonomic dysfunction, persistent low-grade inflammation, and worsening metabolic syndrome, and you've got a perfect storm for heart failure.Dr. Arreaza: Bottom line: COVID is a cardiovascular disease as much as a respiratory one. If someone had COVID and now has unexplained dyspnea or fatigue, think about heart failure. Get an echo, get a BNP, start treatment. Last big question: why did we have so many therapies for HFrEF but essentially none for HFpEF for years?Mike: HFrEF is mechanistically straightforward. You've got a weak heart with excessive neurohormonal activation going on — so you block RAAS, block the sympathetic system, drop the afterload. The drugs make sense.Jordan: HFpEF is messy. It's not one disease. It's stiffness, fibrosis, inflammation, microvascular dysfunction, metabolic disease, atrial fibrillation, all overlapping. One drug can't fix all of that.Mike: And some drugs that worked beautifully in HFrEF actually made HFpEF worse. Take Beta blockers, for example.  They slow heart rate, which is a problem because HFpEF patients rely on heart rate to maintain their cardiac output.Jordan: The breakthrough came with SGLT-2 inhibitors: diabetes drugs that unexpectedly addressed multiple HFpEF mechanisms at once: volume, metabolism, inflammation, and myocardial energetics.Dr. Arreaza: The miracle drug for HFpEF! Alright, let's wrap up.Mike: Bottom line: HFpEF is common, complex, and dangerous: even if the EF looks “normal.”Jordan: And if you're relying on ejection fraction alone, HFpEF will humble you every time.Dr. Arreaza: If you liked this episode, share it with a friend or a colleague and rate us wherever you listen. This is Dr. Arreaza, signing off.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Barzin A, Barnhouse KK, Kane SF. Heart Failure With Preserved Ejection Fraction. Am Fam Physician. 2025;112(4):435-440.Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. Circulation. 2022;145(18):e895-e1032.Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2023;81(18):1835-1878.Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461.Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098.Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392.Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction. Lancet. 2003;362(9386):777-781.Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381(17):1609-1620.Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084.Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590.Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from COVID-19. JAMA Cardiol. 2020;5(11):1265-1273.Basso C, Leone O, Rizzo S, et al. Pathological features of COVID-19-associated myocardial injury. Eur Heart J. 2020;41(39):3827-3835.Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615.Badve SV, Roberts MA, Hawley CM, et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in adults with estimated GFR less than 60 mL/min per 1.73 m². Ann Intern Med. 2024;177(8):953-963.Navis G, Faber HJ, de Zeeuw D, de Jong PE. ACE inhibitors and the kidney: a risk-benefit assessment. Drug Saf. 1996;15(3):200-211.Textor SC, Novick AC, Tarazi RC, et al. Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease. Ann Intern Med. 1985;102(3):308-314.Hackam DG, Spence JD, Garg AX, Textor SC. Role of renin-angiotensin system blockade in atherosclerotic renal artery stenosis and renovascular hypertension. Hypertension. 2007;50(6):998-1003.Ronco C, Haapio M, House AA, et al. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52(19):1527-1539.Prins KW, Neill JM, Tyler JO, et al. Effects of beta-blocker withdrawal in acute decompensated heart failure. JACC Heart Fail. 2015;3(8):647-653.Jondeau G, Neuder Y, Eicher JC, et al. B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode. Eur Heart J. 2009;30(18):2186-2192.Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/. 

In this special series on Automated Insulin Delivery our host, Dr. Neil Skolnik will discuss with the benefits of Automated Insulin Delivery for people with Type 2 Diabetes with two master clinicians, one an diabetes specialist, the other a primary care doctor. This special episode is supported by an independent educational grant from Insulet. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health Davida Kruger, MSN, APN-BC,BC-ADM,  Henry Ford Health, Detroit, Michigan. Past Chair of the American Diabetes Associations Research Foundation, Past president, Health Care and Education of the American Diabetes Association. Susan Kuchera, M.D. - Program Director of the Jefferson Health Abington Family Medicine Residency Program, Clinical Associate Professor of Family and Community Medicine in the Sidney Kimmel Medical College of Thomas Jefferson University Selected references: Automated Insulin Delivery in Adults With Type 2 Diabetes A Nonrandomized Clinical Trial. JAMA Network Open. 2025;8(2):e2459348. A Randomized Trial of Automated Insulin Delivery in Type 2 Diabetes.  N Engl J Med 2025;392:1801-12 Automated Insulin Pump in Type 2 Diabetes – Editorial - N Engl J Med 2025;392:1862-1863

This week, we look at new evidence on oral cholesterol-lowering therapy, the evolving role of beta-blockers after myocardial infarction, and advances in breast and prostate cancer treatment. We review the inherited risk of coronary disease. We also work through a revealing diagnostic case in a young woman and reflect on science under pressure, corporatized insurance, the reach of FDA law, and what it means to live with life-sustaining technology.

Leemore Dafny is a professor of business administration at Harvard Business School and a professor of public policy at the Harvard Kennedy School. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. L. Dafny. Health Insurance after Corporatization — What Next? N Engl J Med 2026;394:521-523.

🧭 REBEL Rundown 🗝️ Key Points 💉 Hydrocortisone Saves Lives:The 2023 Cape Cod Trial (NEJM) showed a clear mortality benefit and reduced need for intubation in severe CAP patients treated with hydrocortisone.📊 Guidelines Are Catching Up:The SCCM (2024) and ERS now recommend steroids for severe CAP, while ATS/IDSA updates are still pending.🔥 Redefining “Severe”:Patients requiring high FiO₂ (>50%), noninvasive or mechanical ventilation, or PSI >130 meet criteria for steroid therapy — even outside the ICU.🍬 Main Risk = Hyperglycemia:Elevated glucose was the most consistent adverse effect, but rates of GI bleed and secondary infection were not increased.🧭 Early, Targeted Use Matters:Start hydrocortisone within 24 hours of identifying severity — especially in patients with high CRP (>150) or strong inflammatory response. Click here for Direct Download of the Podcast. 📝 Introduction Corticosteroids have long sparked debate in the treatment of bacterial pneumonia — once viewed with skepticism, now increasingly supported by high-quality evidence. In this episode, Dr. Alex Chapa joins the REBEL Core Cast team to explore how the 2023 Cape Cod Trial (NEJM) reshaped practice and guideline recommendations for severe community-acquired pneumonia (CAP). 📖 Historical Context & Long-Standing Skepticism For decades, the use of steroids in pneumonia was controversial.Early Use: Steroids entered practice in the 1940s and 50s for autoimmune inflammation, but there was immediate hesitation regarding secondary superinfections.Mixed Data: From the 1980s to the 2000s, small studies emerged on severe pneumonia and ARDS, but the data was inconsistent. Different trials used varying definitions of “severe” pneumonia and different C-reactive protein (CRP) cutoffs, making the data “spread” and easy to “cherry pick” to support or deny a benefit.Past Guidelines: This uncertainty was reflected in official guidelines:2007 (ATS/IDSA): The American Thoracic Society and the Infectious Diseases Society of America did not address the topic due to insufficient data.2019 (ATS/IDSA): Pre-COVID, the guidelines recommended against using corticosteroids in severe CAP. They acknowledged no benefit for non-severe pneumonia, but the data for severe pneumonia was considered too weak to endorse.Pre-Trial Consensus: Prior to 2023, the consensus was to avoid steroids in non-severe pneumonia, while severe pneumonia remained a “gray area” with no treatment showing a clear mortality difference. 📜 The Landmark Cape Cod Trial (NEJM 2023) The Cape Cod trial, published in the New England Journal of Medicine in 2023, reignited the discussion by providing robust, positive data.Trial Design: Phase 3, multi-center, double-blind, randomized, controlled trial.Intervention: 800 patients randomized to two groups, Hydrocortisone as a continuous infusion (200mg/day) versus a placebo infusion.Taper: On day 4, clinicians would decide whether to continue the infusion or begin a taper based on clinical response.Population: Patients with severe CAP, defined by meeting at least one of the following criteria:Pneumonia Severity Index (PSI) > 130.O2 by FiO2 ratio < 300.Need for mechanical or non-invasive ventilation (with PEEP ≥ 5).Need for high FiO2 (>50%) via non-rebreather or heated high flow.Primary Outcomes: Death for any cause 6.2% (hydrocortisone) vs 11.9% (placebo)Secondary outcomes:Death from any cause at 90 days 9.3% (hydrocortisone) vs 14.7% (placebo)Endotracheal intubation 18% (hydrocortisone) vs 29% (placebo)Hospital-acquired infections 9.8% (hydrocortisone) vs 11.1% (placebo)Gastrointestinal bleeding 2.3% (hydrocortisone) vs 3.3% (placebo)Vasopressor initiation by day 28 15.3% (hydrocortisone) vs 25.0% (placebo)Key Findings: The trial demonstrated superiority for hydrocortisone 📋 Updated Guidelines & Current Practice The Cape Cod trial, along with subsequent meta-analyses, has begun to change official recommendations.Society of Critical Care Medicine (SCCM): In 2024, an SCCM expert panel, reviewing the Cape Cod trial and 18 others, strongly recommended corticosteroids for severe CAP. They concluded that steroids reduce mortality and the need for mechanical ventilation.Meta-Analysis (Smit et al.): A 2024 meta-analysis in Lancet Respiratory confirmed the 30-day mortality benefit.European Respiratory Society (ERS): The ERS has issued a recommendation to use steroids for severe pneumonia but still urges caution regarding side effects.ATS/IDSA: As of the podcast recording, the ATS/IDSA had not yet updated their 2019 guidelines. 🛠️ Practical Application for Clinicians Defining “Severe” CAP: The key is to identify patients who qualify as “severe”. This can be done using:Scoring Tools: The PSI is the best validated tool for mortality but is cumbersome. Simpler tools like CURB-65 or SMART-COP are practical and acceptable for defining severity. 2023 meta-analysis from by Zaki et al showed both work well, but CURB-65 has better mortality prediction early on.Cape Cod Criteria: Any patient meeting the trial’s inclusion criteria (e.g., high-flow O2, non-invasive ventilation) qualifies, regardless of location (ED, floor, or ICU).Biomarkers: While not required, a CRP level was used in many studies. A CRP > 150 (Cape Cod) or > 204 (Smit meta-analysis) strongly indicates severe inflammation that would benefit from steroids.Clinical Judgment: A patient who looks “sick,” has “soft” blood pressure, or has dense infiltrates and high oxygen needs (e.g., >50% FiO2 on high flow) is a candidate.Adverse Effects:Hyperglycemia: This was the most significant risk identified, with rates between 6-12%. This is a primary concern, especially in patient populations with high BMI.GI Bleed & Secondary Infection: Fears of these side effects, which contributed to historical skepticism, were not borne out in the Cape Cod trial. The data does not support being overly concerned.Other Side Effects: Mood changes, delirium, insomnia, and agitation in the elderly are known side effects of steroids that were not specifically addressed in the trial but remain clinical concerns. 🔄 Clinical Pathway for Steroids in Severe CAP Unanswered Questions & Future Research Possible remaining questions:Biomarkers: Can we find a more precise CRP level to distinguish moderate from severe disease? Could other markers like ferritin or IL-6 be used? Dosing & Tapering: How much immunomodulation is needed, and when is it truly safe to taper?Gender Differences: Early data suggests females may respond better to steroids and experience fewer side effects. The question of female patients with severe CAP require less corticosteroids needs further exploration. 👉 Clinical Bottom Line The current literature, spearheaded by the Cape Cod trial, now supports the use of corticosteroids in severe community-acquired pneumonia. The best evidence currently points to hydrocortisone, started early (within 24 hours) after severity is identified using a validated tool. While hyperglycemia is a risk, the previous fears of GI bleeding and secondary infections were not substantiated in recent, rigorous trials. 📚 References Chapa-Rodriguez A, Abou-Elmagd T, O’Rear C, Narechania S. Do patients with severe community-acquired bacterial pneumonia benefit from systemic corticosteroids?. Cleve Clin J Med. 2025;92(10):600-604. PMID: 41033846Dequin PF, Meziani F, Quenot JP, et al. Hydrocortisone in Severe Community-Acquired Pneumonia. N Engl J Med. 2023;388(21):1931-1941. PMID: 36942789Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med. 2024;52(5):e219-e233. PMID: 38240492 Post Peer Reviewed By: Marco Propersi, DO (Twitter/X: @Marco_propersi), and Mark Ramzy, DO (X: @MRamzyDO) 👤 Show Notes Alex Chapa, MD PGY 5 Pulmonary Critical Care Fellow Cape Fear Valley Medical Center Fayetteville NC 🔎 Your Deep-Dive Starts Here REBEL Core Cast 149: Review of Corticosteroids in Community-Acquired Pneumonia Corticosteroids have long sparked debate in the treatment of bacterial ... Thoracic and Respiratory Read More The post REBEL Core Cast 149: Review of Corticosteroids in Community-Acquired Pneumonia appeared first on REBEL EM - Emergency Medicine Blog.

With Felix Lindberg, Karolinska Institutet & Södersjukhuset Hospital, Stockholm – Sweden and Marianna Fontana, National Amyloidosis Center, University College London, London – UK. In this episode, Felix Lindberg and Marianna Fontana discuss the evolving landscape in the treatment of cardiac amyloidosis. After exploring the pathophysiology of cardiac AL and ATTR amyloidosis and recent years' insights about the epidemiology of these conditions, they focus on the transformation that has occurred in the therapeutic options for cardiac ATTR amyloidosis. The conversation addresses the key mechanistic differences and trial data on stabilizers and silencers, how to approach patient selection for these therapies, as well as emerging therapies including anti-amyloid antibodies. The discussion also highlights the importance of early diagnosis and key red flags that should elicit suspicion of cardiac amyloidosis. Suggested reading: Vutisiran in patients with transthyretin amyloidosis with cardiomyopathy. Fontana M, et al. N Engl J Med. 2025. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. Maurer M, et al. N Engl J Med. 2018. Efficacy and safety of acoramidis in tranthyretin amyloid cardiomyopathy. Gillmore JD, et al. N Engl J Med. 2024. CRISPR-Cas9 gene editing with nexiguran ziclumeran for ATTR cardiomyopathy. Fontana M, et al. N Engl J Med. 2024. Conventional heart failure therapy in cardiac ATTR amyloidosis. Ioannou A, et al. Eur Heart J. 2023. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Gillmore JD, et al. Circulation. 2016. Current landscape of therapies for transthyretin amyloid cardiomyopathy. Griffin JM, et al. JACC Heart Fail. 2025. Transthyretin amyloid cardiomyopathy: from cause to novel treatments. Fontana M, et al. Eur Heart J. 2026. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Garcia-Pavia P, et al. Eur Heart J. 2021. This 2026 HFA Cardio Talk podcast series is supported by Bayer in the form of unrestricted financial support. The discussion has not been influenced in any way by its sponsor.

This week, we explore new therapies to reduce pancreatitis risk in severe hypertriglyceridemia, advances in breast cancer treatment, and long-term results of gene therapy for hemophilia B. We discuss vision-threatening vascular emergencies, the mental health effects of firearm injury on families, and care for peripheral artery disease. We also follow a revealing diagnostic case in an older woman with respiratory failure. Perspectives reflect on hypertension control, immunization access, chronic disease policy, and on the inherited risk of disease.

Robert Kocher is an adjunct professor at the Stanford University School of Medicine, a nonresident senior scholar at the University of Southern California Schaeffer Institute, and a partner at Venrock. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S.P. Kishore and R. Kocher. The Hypertension Control Paradox — Why Is America Stuck? N Engl J Med 2026;394:417-420.

On this week’s episode, we’re continuing our Guidelines Series exploring the 2022 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension. If you missed our first episode in the series, give it a listen to hear about the most recent recommendations regarding Pulmonary Hypertension definitions, screening, and diagnostics. Today, we’re talking about the next steps after diagnosis. Specifically, we’ll be discussing risk stratification, establishing treatment goals, and metrics for re-evaluation. We’ll additionally introduce the mainstays of pharmacologic therapy for Pulmonary Hypertension. Meet Our Co-Hosts Rupali Sood  grew up in Las Vegas, Nevada and made her way over to Baltimore for medical school at Johns Hopkins. She then completed her internal medicine residency training at Massachusetts General Hospital before returning back to Johns Hopkins, where she is currently a pulmonary and critical care medicine fellow. Rupali’s interests include interstitial lung disease, particularly as related to oncologic drugs, and bedside medical education. Tom Di Vitantonio  is originally from New Jersey and attended medical school at Rutgers, New Jersey Medical School in Newark. He then completed his internal medicine residency at Weill Cornell, where he also served as a chief resident. He currently is a pulmonary and critical care medicine fellow at Johns Hopkins, and he’s passionate about caring for critically ill patients, how we approach the management of pulmonary embolism, and also about medical education of trainees to help them be more confident and patient centered. Key Learning Points 1) Episode Roadmap How to set treatment goals, assess symptom burden, and risk-stratify patients with suspected/confirmed pulmonary arterial hypertension (PAH). What tools to use to re-evaluate patients on treatment Intro to major PAH medication classes and how they map to pathways. 2) Case-based diagnostic reasoning Patient: 37-year-old woman with exertional dyspnea, mild edema, abnormal echo, telangiectasias + epistaxis → raises suspicion for HHT (hereditary hemorrhagic telangiectasia) and/or early connective tissue disease. Key reasoning move: start broad (Groups 2–5) and narrow using history/exam/testing. In a young patient without obvious left heart or lung disease, think more about Group 1 PAH (idiopathic/heritable/associated). HHT teaching point: HHT can cause PH in more than one way: More common: high-output PH from AVMs (often hepatic/pulmonary) Rare (1–2% mentioned): true PAH phenotype (vascular remodeling; associated with ALK1 in some patients), behaving like Group 1 PAH. 3) Functional class assessment WHO Functional Class: Class I: no symptoms with ordinary activity, only with exertion Class II: symptoms with ordinary activity Class III: symptoms with less-than-ordinary activity (can't do usual chores/shopping without dyspnea) Class IV: symptoms at rest Practical bedside tip they give: Ask if the patient can walk at their own pace or keep up with a similar-age peer/partner. If not, think Class II (or worse). 4) Risk stratification at diagnosis: why, how, and which tools Big principle: treatment choices are driven by risk, and the goal is to move patients to low-risk quickly. ESC/ERS approach at diagnosis (as described): Use a 3-strata model predicting 1-year mortality: Low: 20% ESC/ERS risk assessment variables (10 domains discussed): Clinical progression, signs of right heart failure, syncope WHO FC Biomarkers (NT-proBNP) Exercise capacity (6MWD) Hemodynamics Imaging (echo; sometimes cardiac MRI) CPET (peak VO₂; VE/VCO₂ slope) They note: even if you don't have everything, the calculator can still be useful with ≥3 variables. REVEAL 2.0: Builds on similar core variables but adds further patient context (demographics, renal function, BP, DLCO, etc.) Case result: both tools put her in intermediate risk (ESC/ERS ~1.6; REVEAL 2.0 score 8), underscoring that mild symptoms can still equal meaningful mortality risk. 5) Treatment goals and follow-up philosophy What they explicitly prioritize: Help patients feel better, live longer, and stay out of the hospital Use risk tools to communicate prognosis and to track improvement Reassess frequently (they mention ~every 3 months early on) until low risk is achieved “Time-to-low-risk” is an important treatment goal Also emphasized: The diagnosis is psychologically heavy; patients need clear counseling, reassurance about the plan, and connection to support groups. 6) Medication classes for the treatment of PAH Nitric oxide–cGMP pathway PDE5 inhibitors: sildenafil, tadalafil Soluble guanylate cyclase stimulator: riociguat Important safety point: don't combine PDE5 inhibitors with riociguat (risk of significant hypotension/hemodynamic effects) Endothelin receptor antagonists (ERAs) “-sentan” drugs: bosentan (less used due to side effects/interactions), ambrisentan, macitentan Teratogenicity emphasized Hepatotoxicity that requires LFT monitoring Can cause fluid retention and peripheral edema Prostacyclin pathway Prostacyclin analogs/agonists: Epoprostenol (potent; short half-life; IV administration) Treprostinil (IV/SubQ/oral/inhaled options) Selexipag (oral prostacyclin receptor agonist) 7) Sotatercept (post-guidelines) They note sotatercept wasn't in 2022 ESC/ERS but is now “a game changer” in practice: Mechanism: ligand trap affecting TGF-β signaling / remodeling biology Positioned as potentially more disease-modifying than pure vasodilators Still evolving: where to place it earlier vs later in regimens is an active question in the field 8) How risk category maps to initial treatment intensity General approach they outline: High risk at diagnosis: parenteral prostacyclin (IV/SubQ) strongly favored, often aggressive early Intermediate risk: at least dual oral therapy (typically PDE5i + ERA); escalate if not achieving low risk Low risk: at least one oral agent; many still use dual oral depending on etiology/trajectory For the case: intermediate-risk → start dual oral therapy (they mention tadalafil + ambrisentan as a typical choice), reassess in ~3 months; add a third agent (e.g., selexipag/prostacyclin pathway) if not low risk.  References and Further Reading Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. Erratum in: Eur Heart J. 2023 Apr 17;44(15):1312. doi: 10.1093/eurheartj/ehad005. PMID: 36017548. Condon DF, Nickel NP, Anderson R, Mirza S, de Jesus Perez VA. The 6th World Symposium on Pulmonary Hypertension: what’s old is new. F1000Res. 2019 Jun 19;8:F1000 Faculty Rev-888. doi: 10.12688/f1000research.18811.1. PMID: 31249672; PMCID: PMC6584967. Maron BA. Revised Definition of Pulmonary Hypertension and Approach to Management: A Clinical Primer. J Am Heart Assoc. 2023 Apr 18;12(8):e029024. doi: 10.1161/JAHA.122.029024. Epub 2023 Apr 7. PMID: 37026538; PMCID: PMC10227272. Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grünig E, Kopeć G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6. PMID: 36877098. Ruopp NF, Cockrill BA. Diagnosis and Treatment of Pulmonary Arterial Hypertension: A Review. JAMA. 2022 Apr 12;327(14):1379-1391. doi: 10.1001/jama.2022.4402. Erratum in: JAMA. 2022 Sep 6;328(9):892. doi: 10.1001/jama.2022.13696. PMID: 35412560.

In this episode, we explore evolving evidence on anticoagulation after atrial fibrillation ablation, long-term outcomes with immunotherapy for melanoma, and promising new treatments for hepatitis D and triple-negative breast cancer. We review advances in physiologic pacing for heart failure and work through a challenging case involving fever, rash, and neurologic symptoms. An article considers fairness for late-career physicians, and Perspectives discuss misconceptions about autism, access to contraception, and the financial pressures shaping health care.

Tara Eicher is a postdoctoral research fellow in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. T. Eicher, J. Quackenbush, and A. Ne'eman. Challenging Claims of an Autism Epidemic — Misconceptions and a Path Forward. N Engl J Med 2026;394:313-315.

This week, we explore new evidence on managing asymptomatic carotid stenosis, restoring vision in advanced macular degeneration, and preventing migraine in children. We discuss innovative cellular therapy for autoimmune disease, review sudden cardiac arrest in athletes, and describe a case of severe systemic infection with vision loss. Perspectives examine global tobacco risks, the future of telehealth payment, Medicare coverage of new technologies, and the things physicians carry.

Tara Sklar is the faculty director of the Health Law and Policy Program at the University of Arizona James E. Rogers College of Law and associate director of telehealth law and policy at the University of Arizona College of Medicine–Tucson Arizona Telemedicine Program. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. T. Sklar and B. Richman. Financing Telehealth — Moving Beyond Payment Parity. N Engl J Med 2026;394:211-213.

Luke Hedrick, Dave Furfaro, and recurrent RFJC guest Robert Wharton are joined again today by Nicole Ng to discuss the FIBRONEER-IPF trial investigating Nerandomilast in patients with IPF. This trial was published in NEJM in 2025 and looked at Neradomilast vs placebo for treating patients with IPF, on or off background anti-fibrotic therapy. This agents is now FDA approved for pulmonary fibrosis, and understanding the trial results is essential for any pulmonary physician treating patients with IPF or progressive pulmonary fibrosis. Article and Reference Today’s episode discusses the FIBRONEER-IPF trial published in NEJM in 2025. Richeldi L, Azuma A, Cottin V, Kreuter M, Maher TM, Martinez FJ, Oldham JM, Valenzuela C, Clerisme-Beaty E, Gordat M, Wachtlin D, Liu Y, Schlecker C, Stowasser S, Zoz DF, Wijsenbeek MS; FIBRONEER-IPF Trial Investigators. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025 Jun 12;392(22):2193-2202. doi: 10.1056/NEJMoa2414108. Epub 2025 May 18. PMID: 40387033. https://www.nejm.org/doi/abs/10.1056/NEJMoa2414108 Meet Our Guests 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 pulmonary and critical care fellow at Johns Hopkins. Dr. Nicole Ng is an Assistant Profess of Medicine at Mount Sinai Hospital, and is the Associate Director of the Interstitial Lung Disease Program for the Mount Sinai National Jewish Health Respiratory Institute. Infographic Key Learning Points Why this trial mattered IPF therapies remain limited: nintedanib and pirfenidone slow (but do not stop) decline and often cause GI side effects. Nerandomilast is a newer agent (a preferential PDE4B inhibitor) with antifibrotic + immunomodulatory effects. Phase 2 data (NEJM 2022) looked very promising (suggesting near-“halt” of FVC decline), so this phase 3 trial was a big test of that signal. Trial design essentials Industry-sponsored, randomized, double-blind, placebo-controlled, large multinational study (332 sites, 36 countries). Population: IPF diagnosed via guideline-aligned criteria with central imaging review and multidisciplinary diagnostic confirmation. Intervention: nerandomilast 18 mg BID, 9 mg BID, or placebo; stratified by background antifibrotic use. Primary endpoint: change in FVC at 52 weeks, analyzed with a mixed model for repeated measures. Key secondary endpoint: time to first acute exacerbation, respiratory hospitalization, or death (composite). Who was enrolled Typical IPF trial demographics: ~80% male, mean age ~70, many former smokers. Many were already on background therapy (~45% nintedanib, ~30–33% pirfenidone). Notable exclusions included significant liver disease, advanced CKD, recent major cardiovascular events, and psychiatric risk (suicidality/severe depression), reflecting class concerns seen with other PDE4 inhibitors. Efficacy: what the primary endpoint showed Nerandomilast produced a statistically significant but modest reduction in annual FVC decline vs placebo (roughly 60–70 mL difference). Importantly, it did not halt FVC decline the way the phase 2 data suggested; patients still progressed. Important nuance: interaction with pirfenidone Patients on pirfenidone had ~50% lower nerandomilast trough levels. Clinically: 9 mg BID looked ineffective with pirfenidone, so 18 mg BID is needed if used together. In those not on background therapy or on nintedanib, 9 mg and 18 mg looked similar—suggesting the apparent “dose-response” might be partly driven by the pirfenidone drug interaction Secondary and patient-centered outcomes were neutral No demonstrated benefit in the composite outcome (exacerbation/resp hospitalization/death) or its components. Quality of life measures were neutral and declined in all groups, emphasizing that slowing FVC alone may not translate into felt improvement without a disease-reversing therapy. The discussants noted this may reflect limited power/duration for these outcomes and mentioned signals from other datasets/pooling that might suggest mortality benefit—but in this specific trial, the key secondary endpoint was not positive. Safety and tolerability Diarrhea was the main adverse event: Higher overall with the 18 mg dose, and highest when combined with nintedanib (up to ~62%). Mostly mild/manageable; discontinuation due to diarrhea was relatively uncommon (but higher in those on nintedanib). Reassuringly, there was no signal for increased depression/suicidality/vasculitis despite psychiatric exclusions and theoretical class risk. How to interpret “modest FVC benefit” clinically The group framed nerandomilast as another tool that adds incremental slowing of progression. They emphasized that comparing absolute FVC differences across trials (ASCEND/INPULSIS vs this trial) is tricky because populations and “natural history” in placebo arms have changed over time (earlier diagnosis, improved supportive care, etc.). They highlighted channeling bias: patients already on antifibrotics may be sicker (longer disease duration, lower PFTs, more oxygen), complicating subgroup comparisons. Practical takeaways for real-world use All three antifibrotics are “fair game”; choice should be shared decision-making based on goals, tolerability, dosing preferences, and logistics. Reasons they favored nerandomilast in practice: No routine lab monitoring (major convenience advantage vs traditional antifibrotics). Generally better GI tolerability than nintedanib. BID dosing (vs pirfenidone TID). Approach to combination therapy: They generally favor add-on rather than immediate combination to reduce confusion about side effects—while acknowledging it may slow reaching “maximal therapy.” Dosing guidance emphasized: Start 18 mg BID for IPF, especially if combined with pirfenidone (since dose reduction may make it ineffective). 9 mg BID may be considered if dose reduction is needed and the patient is not on pirfenidone (e.g., monotherapy or with nintedanib).

In this special series on Automated Insulin Delivery our host, Dr. Neil Skolnik will discuss with the benefits of Automated Insulin Delivery for people with Type 2 Diabetes. This special episode is supported by an independent educational grant from Insulet. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health Davida Kruger, MSN, APN-BC,BC-ADM,  Henry Ford Health, Detroit, Michigan. Past Chair of the American Diabetes Associations Research Foundation, Past president, Health Care and Education of the American Diabetes Association. Ashlyn Smith, MMS, PA-C, DFAAPA, LSC, Distinguished Fellow of the American Academy of PAs, Certified Diabetes Prevention Program Lifestyle Coach, Founder of ELM Endocrinology & Lifestyle Medicine, PLLC., Past President of the American Society of Endocrine Physician Assistants, Adjunct faculty at Midwestern University, Selected references: Automated Insulin Delivery in Adults With Type 2 Diabetes A Nonrandomized Clinical Trial. JAMA Network Open. 2025;8(2):e2459348. A Randomized Trial of Automated Insulin Delivery in Type 2 Diabetes.  N Engl J Med 2025;392:1801-12 Automated Insulin Pump in Type 2 Diabetes – Editorial - N Engl J Med 2025;392:1862-1863

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-467 Overview: Join us as we discuss recent changes to newborn hepatitis B vaccination recommendations and review the risks, benefits, and rationale for immunizing this patient population. Come away with confidence to navigate new guidance, thoughtfully address parental concerns, and provide evidence-based care that promotes both infant and public health. Episode resource links: N Engl J Med 2019;380:2041-2050  DOI: 10.1056/NEJMra181047 Clin Infect Dis. 2021 Nov 2;73(9):e3317-e3323. doi: 10.1093/cid/ciaa898.  Guest: Robert A. Baldor MD, FAAFP   Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-467 Overview: Join us as we discuss recent changes to newborn hepatitis B vaccination recommendations and review the risks, benefits, and rationale for immunizing this patient population. Come away with confidence to navigate new guidance, thoughtfully address parental concerns, and provide evidence-based care that promotes both infant and public health. Episode resource links: N Engl J Med 2019;380:2041-2050  DOI: 10.1056/NEJMra181047 Clin Infect Dis. 2021 Nov 2;73(9):e3317-e3323. doi: 10.1093/cid/ciaa898.  Guest: Robert A. Baldor MD, FAAFP   Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  

This week, we explore new options in cardiovascular prevention, fish-oil supplementation in dialysis patients, RSV vaccination, and cutting-edge cellular therapy for leukemia. We discuss advances in lung cancer treatment, approaches to functional dyspepsia, and a complex case of severe infection after travel. Perspectives examine access to and cost of weight-loss drugs, the promise and risks of AI in clinical care, and what it means to care for others while carrying personal loss.

Rachel Sachs is a professor of law at Washington University in St. Louis. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S.B. Dusetzina and R.E. Sachs. Insurance Coverage and Pricing of Weight-Loss Drugs in the United States. N Engl J Med 2026;394:105-107. S. Gondi, A.S. Kesselheim, and B.N. Rome. Generic Liraglutide — Overlooked but Not Forgotten. N Engl J Med. DOI: 10.1056/NEJMp2515668.

Peripheral artery disease has been called the ‘silent circulatory crisis'—affecting millions, limiting mobility, and quietly raising the risk of heart attack, stroke, and limb loss. For decades, treatment focused on walking programs, aspirin, and sometimes a stent or bypass. But today, the landscape is changing. From PCSK9 inhibitors that drive cholesterol to record lows, to GLP-1 agonists like semaglutide improving walking distance, to novel antithrombotic strategies that balance bleeding and clotting—PAD care is entering a new era. In this episode, we'll explore the breakthroughs, the evidence behind them, and what they mean for patients who just want to keep moving forward." Hosted by the University of Michigan Department of Vascular Surgery: - Robert Beaulieu, Program Director - Frank Davis, Assistant Professor of Surgery - Luciano Delbono, PGY-5 House Officer - Andrew Huang, PGY-4 House Officer - Carolyn Judge, PGY-2 House Officer Learning objectives:  1.  Describe the current evidence-based recommendations for multifactorial medical management of peripheral artery disease (PAD), including lipid, glycemic, and antithrombotic strategies per 2024 SVS/AHA guidelines.  2. Interpret the clinical implications of the FOURIER trial regarding the role of PCSK9 inhibition in reducing cardiovascular events in patients with atherosclerotic disease, including PAD.  3.  Evaluate the emerging role of GLP-1 receptor agonists, such as semaglutide, in improving walking performance and quality of life among patients with diabetic PAD based on findings from the STRIDE trial. Sponsor URL: https://www.goremedical.com/ References:  H. L. Gornik et al., “2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease,” JACC, vol. 83, no. 24, pp. 2497–2604, June 2024, doi: 10.1016/j.jacc.2024.02.013. L. Mazzolai et al., “2024 ESC Guidelines for the management of peripheral arterial and aortic diseases: Developed by the task force on the management of peripheral arterial and aortic diseases of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), and the European Society of Vascular Medicine (ESVM),” Eur Heart J, vol. 45, no. 36, pp. 3538–3700, Sept. 2024, doi: 10.1093/eurheartj/ehae179. https://pubmed.ncbi.nlm.nih.gov/40169145/ M. S. Sabatine et al., “Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease,” N Engl J Med, vol. 376, no. 18, pp. 1713–1722, May 2017, doi: 10.1056/NEJMoa1615664. https://pubmed.ncbi.nlm.nih.gov/28304224/ M. P. Bonaca et al., “Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial,” Lancet, vol. 405, no. 10489, pp. 1580–1593, May 2025, doi: 10.1016/S0140-6736(25)00509-4. https://pubmed.ncbi.nlm.nih.gov/40169145/ N. E. Hubbard, D. Lim, and K. L. Erickson, “Beef tallow increases the potency of conjugated linoleic acid in the reduction of mouse mammary tumor metastasis,” J Nutr, vol. 136, no. 1, pp. 88–93, Jan. 2006, doi: 10.1093/jn/136.1.88. https://pubmed.ncbi.nlm.nih.gov/16365064/ Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more.   If you liked this episode, check out our recent episodes here: https://behindtheknife.org/listen Behind the Knife Premium: General Surgery Oral Board Review Course: https://behindtheknife.org/premium/general-surgery-oral-board-review Trauma Surgery Video Atlas: https://behindtheknife.org/premium/trauma-surgery-video-atlas Dominate Surgery: A High-Yield Guide to Your Surgery Clerkship: https://behindtheknife.org/premium/dominate-surgery-a-high-yield-guide-to-your-surgery-clerkship Dominate Surgery for APPs: A High-Yield Guide to Your Surgery Rotation: https://behindtheknife.org/premium/dominate-surgery-for-apps-a-high-yield-guide-to-your-surgery-rotation Vascular Surgery Oral Board Review Course: https://behindtheknife.org/premium/vascular-surgery-oral-board-audio-review Colorectal Surgery Oral Board Review Course: https://behindtheknife.org/premium/colorectal-surgery-oral-board-audio-review Surgical Oncology Oral Board Review Course: https://behindtheknife.org/premium/surgical-oncology-oral-board-audio-review Cardiothoracic Oral Board Review Course: https://behindtheknife.org/premium/cardiothoracic-surgery-oral-board-audio-review Download our App: Apple App Store: https://apps.apple.com/us/app/behind-the-knife/id1672420049 Android/Google Play: https://play.google.com/store/apps/details?id=com.btk.app&hl=en_US

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.

Ambar La Forgia is an assistant professor in the Management of Organizations group at the University of California, Berkeley Haas School of Business. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A. La Forgia. From Patients to Consumers — The Corporatization of Ambulatory Care. N Engl J Med 2026;394:1-3.

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-465 Overview: Many patients with coronary artery disease take aspirin, but how should clinicians navigate management when an anticoagulant is also needed? In this episode, we review indications for therapy, explore evidence on dual use, and discuss how to counsel patients on balancing cardiovascular benefits with the risks of combination therapy. Episode resource links: Lemesle G, Didier R, Steg PG, et al. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. N Engl J Med. Published online August 31, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2507532 Guest: Alan M. Ehrlich, MD, FAAFP   Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-465 Overview: Many patients with coronary artery disease take aspirin, but how should clinicians navigate management when an anticoagulant is also needed? In this episode, we review indications for therapy, explore evidence on dual use, and discuss how to counsel patients on balancing cardiovascular benefits with the risks of combination therapy. Episode resource links: Lemesle G, Didier R, Steg PG, et al. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. N Engl J Med. Published online August 31, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2507532 Guest: Alan M. Ehrlich, MD, FAAFP   Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  

CardioNerds (Dr. Colin Blumenthal, Dr. Kelly Arps, and Dr. Natalie Marrero) discuss anti-arrhythmic drugs in the management of atrial fibrillation and atrial flutter with electrophysiologist Dr. Andrew Epstein. We discuss two major classes of anti-arrhythmic drugs, class IC and class III, as well as digoxin. Dr. Epstein explains their mechanisms of action, indications and specific patient populations in which they would be particularly helpful, efficacy, adverse side effects, contraindications, and key drug-drug interactions. We also elaborate on defining clinical trials and their clinical implications. Given the large burden of atrial fibrillation and atrial flutter in our patient population and the high prevalence of anti-arrhythmic drug use, this episode is sure to be applicable to many practicing physicians and trainees. Audio editing by CardioNerds academy intern, Grace Qiu.  Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Atrial Fibrillation PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls Anti-arrhythmic drugs should not be thought of as an alternative to ablation but, instead, should be considered an adjunct to catheter ablation.   Class IC anti-arrhythmic drugs, flecainide and propafenone, are highly efficacious for acute cardioversion and a great option for patients with infrequent episodes of AF who do not have a history of ischemic heart disease.    Class III anti-arrhythmic drugs like ibutilide, sotalol, and dofetilide, are highly effective for acute conversion; however, they require hospitalization for close monitoring during initiation and dose titration given the risk of prolonged QT.   Amiodarone should not be used as a first line agent given its toxicities, prolonged half-life, large volume of distribution, and drug-drug interactions.   Dr. Epstein notes that, “All drugs are poisons with a few beneficial side effects,” when highlighting the many adverse side effects of anti-arrhythmic drugs, particularly amiodarone, and the importance of balancing their benefit in rhythm control with their side effect profile.   Notes Notes: Notes drafted by Dr. Natalie Marrero. What are the Class IC anti-arrhythmic drugs and what indications exist for their use?   Class IC anti-arrhythmic drugs are anti-arrhythmic drugs that work by blocking sodium channels and, thereby, prolonging depolarizing.   Class IC anti-arrhythmic drugs include flecainide and propafenone.   Class IC anti-arrhythmic drugs are good agents to use in patients that have infrequent episodes of AF and do not want daily dosing as these agents can be used by patients when they feel palpitations and desire acute conversion back to sinus rhythm (“pill in the pocket” approach).    What are the adverse consequences and/or contraindications to using a class IC agent?  Class IC anti-arrhythmic agents are contraindicated in patients with a history of ischemic heart disease based on increased mortality associated with their use in these patients in the CAST trial.   Given the results of the CAST trial, providers should screen annually for ischemia via a functional stress test in patients on these drugs at risk for coronary disease.   These drugs can increase 1:1 conduction of atrial flutter and, therefore, require concomitant use of a beta blocker.   These agents are generally well-tolerated without any organ toxicities; however, they can precipitate heart failure in patients with cardiomyopathies, cause sinus node depression, and unmask genetic arrythmias such as a Brugada pattern.   What are the class III agents and what are indications for their use?   Class III agents are drugs that block the potassium channel, prolonging the QT, and include Ibutilide, Sotalol, and Dofetilide.    Class III agents can be considered in patients with or without a history of ischemic heart disease that desire effective acute chemical cardioversion and are willing to go to the hospital for close monitoring during dose initiation and titration.   Other specific circumstances in which one can use these agents, specifically Ibutilide, are in patients with recurrent atrial fibrillation and Wolf Parkinson White (due to slowed conduction via the accessory pathway).  What are the adverse consequences and/or contraindications to using a class III agent?  Ibutilide, Sotalol, and Dofetilide prolong the QT and increase the risk of torsade de pointes, which is why they require ECG monitoring in-patient during drug initiation and dose titration.    These agents are generally well-tolerated.   Sotalol should be avoided or used cautiously in patients with left ventricular dysfunction, while dofetilide can be used and has dose-response beneficial effects in patients with left ventricular dysfunction.   Both sotalol and dofetilide are renally cleared with specific creatinine clearance cutoffs (CrCl < 20 for dofetilide and CrCl

In this episode of the Evolving Wellness Podcast, I delve into the complexities of vitamin D and melatonin, particularly during the winter months. I discuss the natural decline of vitamin D levels in winter, the critical role of melatonin, and how modern lifestyles disrupt these hormonal balances. The conversation covers the impact of stress, alcohol, and blue light on health, the importance of circadian rhythms, and the potential benefits and drawbacks of vitamin D supplementation. Links: Become a substack subscriber & get early access to podcasts + free courses - https://open.substack.com/pub/sarahkleinerwellness/p/uvbred-light-protocol?r=5eztl9&utm_campaign=post&utm_medium=web&showWelcomeOnShare=trueHoliday Sale - https://www.sarahkleinerwellness.com/SKW-holidayFree Webinar - https://www.sarahkleinerwellness.com/mycircadianapp-free-webinarTimestamps:00:00 Introduction to Vitamin D and Melatonin02:47 Understanding Seasonal Changes in Vitamin D Levels06:13 The Role of Melatonin in Winter Health09:00 Impact of Modern Lifestyle on Vitamin D and Melatonin11:51 The Effects of Stress and Alcohol on Hormonal Balance15:08 Circadian Rhythms and Their Importance17:51 The Dangers of Blue Light and Sleep Disruption21:07 Winter Infections and Their Impact on Vitamin D23:59 Pros and Cons of Vitamin D Supplementation27:13 Understanding Individual Variability in Vitamin D Metabolism29:52 Short-Term Vitamin D Supplementation: When Is It Appropriate?33:14 The Importance of Comprehensive Testing and Monitoring36:01 Conclusion and Future DirectionsReferences & further reading:Article: You've been warned about sunlight but not about supplements - http://sarahkleinerwellness.com/blog/you-ve-been-warned-about-sunlight-but-not-supplementsArticle - Can vitamin D supplements lower your melatonin? https://sarahkleinerwellness.substack.com/p/can-vitamin-d-supplements-lower-yourManson et al. VITAL primary outcomes. N Engl J Med. 2019. PMID: 30415629Sanders et al. Annual high-dose D ↑ falls/fractures. JAMA. 2010. PMID: 20157135Bischoff-Ferrari et al. Monthly high-dose D ↑ falls. JAMA Intern Med. 2016. PMID: 26747333Jackson et al. WHI Ca+D ↑ kidney stones. N Engl J Med. 2006. PMID: 16481635Slominski et al. Melatonin, mitochondria & skin photobiology. Cell Mol Life Sci. 2020.Hamblin MR. Anti-inflammatory photobiomodulation. AIMS Biophys. 2017.Deng et al. Magnesium, vitamin D status & mortality (NHANES). BMC Med. 2013.Holick et al. Translocation of cutaneous vitamin D₃. Endocrinology. 1994.This video is not medical advice & as a supporter to you and your health journey - I encourage you to monitor your labs and work with a professional!________________________________________Get all my free guides and product recommendations to get started on your journey!https://www.sarahkleinerwellness.com/all-free-resourcesCheck out all my courses to understand how to improve your mitochondrial health & experience long lasting health! (Use code PODCAST to save 10%) - https://www.sarahkleinerwellness.com/coursesSign up for my newsletter to get special offers in the future! -https://sarahkleinerwellness.kit.com/profile?_gl=1*1gs7n29*_gcl_aw*R0NMLjE3NjQwOTIxNjcuQ2owS0NRaUF4SlhKQmhEX0FSSXNBSF9KR2poSEZxTTl0blpDSEl4SjYyRHdpa1FuNGc3QXplVll4NVktSFhmSFZZamEwVDAtcU92YXlfQWFBbHp0RUFMd193Y0I.*_gcl_au*MTgwMTYwMTMxMi4xNzYzMzIwODkyLjYyODE4ODI3NC4xNzY1NTA5NjM3LjE3NjU1MDk2MzY.Free Guide to Building your perfect quantum day (start here) -https://www.sarahkleinerwellness.com/opt-in-9d5f6918-77a8-40d7-bedf-93ca2ec8387fMy free product guide with all product recommendations and discount codes:https://www.canva.com/design/DAF7mlgZpJI/xVyE4tiQFEWJmh_Xwx8Kbw/view?utm_content=DAF7mlgZpJI&utm_campaign=designshare&utm_medium=link2&utm_source=uniquelinks&utlId=h0782b52987

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).

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.

Osteomyelitis in children is common enough to miss and serious enough to matter. In this episode of PEM Currents, we review a practical, evidence-based approach to pediatric acute hematogenous osteomyelitis, focusing on diagnostic strategy, imaging decisions including FAST MRI, and modern antibiotic management. Topics include age-based microbiology, empiric and pathogen-directed antibiotic selection with dosing, criteria for early transition to oral therapy, and indications for orthopedic and infectious diseases consultation. Special considerations such as MRSA, Kingella kingae, daycare clustering, and shortened treatment durations are discussed with an emphasis on safe, high-value care. Learning Objectives After listening to this episode, learners will be able to: Identify the key clinical, laboratory, and imaging findings that support the diagnosis of acute hematogenous osteomyelitis in children, including indications for FAST MRI and contrast-enhanced MRI. Select and dose appropriate empiric and pathogen-directed antibiotic regimens for pediatric osteomyelitis based on patient age, illness severity, and local MRSA prevalence, and determine when early transition to oral therapy is appropriate. Determine when consultation with orthopedics and infectious diseases is indicated, and recognize clinical features that warrant prolonged therapy or more conservative management. References Woods CR, Bradley JS, Chatterjee A, et al. Clinical practice guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 guideline on diagnosis and management of acute hematogenous osteomyelitis in pediatrics. J Pediatric Infect Dis Soc. 2021;10(8):801-844. doi:10.1093/jpids/piab027 Woods CR, Bradley JS, Chatterjee A, et al. Clinical practice guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2023 guideline on diagnosis and management of acute bacterial arthritis in pediatrics. J Pediatric Infect Dis Soc. 2024;13(1):1-59. doi:10.1093/jpids/piad089 Stephan AM, Platt S, Levine DA, et al. A novel risk score to guide the evaluation of acute hematogenous osteomyelitis in children. Pediatrics. 2024;153(1):e2023063153. doi:10.1542/peds.2023-063153 Alhinai Z, Elahi M, Park S, et al. Prediction of adverse outcomes in pediatric acute hematogenous osteomyelitis. Clin Infect Dis. 2020;71(9):e454-e464. doi:10.1093/cid/ciaa211 Burns JD, Upasani VV, Bastrom TP, et al. Age and C-reactive protein associated with improved tissue pathogen identification in children with blood culture-negative osteomyelitis: results from the CORTICES multicenter database. J Pediatr Orthop. 2023;43(8):e603-e607. doi:10.1097/BPO.0000000000002448 Peltola H, Pääkkönen M. Acute osteomyelitis in children. N Engl J Med. 2014;370(4):352-360. doi:10.1056/NEJMra1213956 Transcript This transcript was provided via use of the Descript AI application Welcome to PEM Currents, the Pediatric Emergency Medicine Podcast. As always, I'm your host, Brad Sobolewski, and today we're covering osteomyelitis in children. We're going to talk about diagnosis and imaging, and then spend most of our time where practice variation still exists: antibiotic selection, dosing, duration, and the evidence supporting early transition to oral therapy. We'll also talk about when to involve orthopedics, infectious diseases, and whether daycare outbreaks of osteomyelitis are actually a thing. So what do I mean by pediatric osteomyelitis? In children, osteomyelitis is most commonly acute hematogenous osteomyelitis. That means bacteria seed the bone via the bloodstream. The metaphysis of long bones is particularly vulnerable due to vascular anatomy that favors bacterial deposition. Age matters. In neonates, transphyseal vessels allow infection to cross into joints, increasing the risk of concomitant septic arthritis. In older children, those vessels involute, and infection tends to remain metaphyseal and confined to bone rather than spreading into the joint. For children three months of age and older, empiric therapy must primarily cover Staphylococcus aureus, which remains the dominant pathogen. Other common organisms include group A streptococcus and Streptococcus pneumoniae. In children six to 36 months of age, especially those in daycare, Kingella kingae is an important and often underrecognized pathogen. Kingella infections are typically milder, may present with lower inflammatory markers, and frequently yield negative routine cultures. Kingella is usually susceptible to beta-lactams like cefazolin, but is consistently resistant to vancomycin and often resistant to clindamycin and antistaphylococcal penicillins. This has direct implications for empiric antibiotic selection. Common clinical features of osteomyelitis include fever, localized bone pain, refusal to bear weight, and pain with movement of an adjacent joint. Fever may be absent early, particularly with less virulent organisms like Kingella. A normal white blood cell count does not exclude osteomyelitis. Only about one-third of children present with leukocytosis. CRP and ESR are generally more useful, particularly CRP for monitoring response to therapy. No single CRP cutoff reliably diagnoses or excludes osteomyelitis in children. While CRP is elevated in most cases of acute hematogenous osteomyelitis, the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America note that high-quality data defining diagnostic thresholds are limited. A CRP above 20 milligrams per liter is commonly used to support clinical suspicion, with pooled sensitivity estimates around 80 to 85 percent, but no definitive value mandates the diagnosis. Lower values do not exclude disease, particularly in young children, as CRP is normal in up to 40 percent of Kingella kingae infections. CRP values tend to be higher in Staphylococcus aureus infections, especially MRSA, and higher levels are associated with complications such as abscess, bacteremia, and thrombosis, though specific cutoffs are not absolute. In summary, CRP is most useful for monitoring treatment response. It typically peaks two to four days after therapy initiation and declines rapidly with effective treatment, with a 50 percent reduction within four days seen in the majority of uncomplicated cases. Blood cultures should be obtained in all children with suspected osteomyelitis, ideally before starting antibiotics when feasible. In children, blood cultures alone can sometimes identify the pathogen. Plain radiographs are still recommended early, not because they're sensitive for acute osteomyelitis, but because they help exclude fracture, malignancy, or foreign body and establish a baseline. MRI with and without contrast is the preferred advanced imaging modality. MRI confirms the diagnosis, defines the extent of disease, and identifies complications such as subperiosteal abscess, physeal involvement, and concomitant septic arthritis. MRI findings can also guide the need for surgical consultation. Many pediatric centers now use FAST MRI protocols for suspected osteomyelitis, particularly from the emergency department. FAST MRI uses a limited sequence set, typically fluid-sensitive sequences like STIR or T2 with fat suppression, without contrast. These studies significantly reduce scan time, often avoid the need for sedation, and retain high sensitivity for bone marrow edema and soft tissue inflammation. FAST MRI is particularly useful when the clinical question is binary: is there osteomyelitis or not? It's most appropriate in stable children without high concern for abscess, multifocal disease, or surgical complications. If FAST MRI is positive, a full contrast-enhanced MRI may still be needed to delineate abscesses, growth plate involvement, or adjacent septic arthritis. If FAST MRI is negative but clinical suspicion remains high, further imaging may still be necessary. The Pediatric Infectious Diseases Society and the Infectious Diseases Society of America recommend empiric antibiotic selection based on regional MRSA prevalence, patient age, and illness severity, with definitive therapy guided by culture results and susceptibilities. Empiric therapy should never be delayed in an ill-appearing or septic child. In well-appearing, stable children, antibiotics may be briefly delayed to obtain imaging or tissue sampling, but this requires close inpatient observation. For children three months and older with non–life-threatening disease, empiric therapy hinges on local MRSA rates. In regions with low community-acquired MRSA prevalence, generally under 10 percent, reasonable empiric options include cefazolin, oxacillin, or nafcillin. When MRSA prevalence exceeds 10 to 20 percent, empiric therapy should include an MRSA-active agent. Clindamycin is appropriate when local resistance rates are low, while vancomycin is preferred when clindamycin resistance is common or the child has had significant healthcare exposure. For children with severe disease or sepsis, vancomycin is generally preferred regardless of local MRSA prevalence. Some experts recommend combining vancomycin with oxacillin or nafcillin to ensure optimal coverage for MSSA, group A streptococcus, and MRSA. In toxin-mediated or high-inoculum infections, the addition of clindamycin may be beneficial due to protein synthesis inhibition. Typical IV dosing includes cefazolin 100 to 150 milligrams per kilogram per day divided every eight hours; oxacillin or nafcillin 150 to 200 milligrams per kilogram per day divided every six hours; clindamycin 30 to 40 milligrams per kilogram per day divided every six to eight hours; and vancomycin 15 milligrams per kilogram every six hours for serious infections, with appropriate monitoring. Ceftaroline or daptomycin may be considered in select MRSA cases when first-line agents are unsuitable. For methicillin-susceptible Staphylococcus aureus, first-generation cephalosporins or antistaphylococcal penicillins remain the preferred parenteral agents. For oral therapy, high-dose cephalexin, 75 to 100 milligrams per kilogram per day divided every six hours, is preferred. Clindamycin is an alternative when beta-lactams cannot be used. For clindamycin-susceptible MRSA, clindamycin is the preferred IV and oral agent due to excellent bioavailability and bone penetration, and it avoids the renal toxicity associated with vancomycin. For clindamycin-resistant MRSA, vancomycin or ceftaroline are preferred IV agents. Oral options are limited, and linezolid is generally the preferred oral agent when transition is possible. Daptomycin may be used parenterally in children older than one year without pulmonary involvement, typically with infectious diseases and pharmacy input. Beta-lactams remain the drugs of choice for Kingella kingae, Streptococcus pyogenes, and Streptococcus pneumoniae. Vancomycin has no activity against Kingella, and clindamycin is often ineffective. For Salmonella osteomyelitis, typically seen in children with sickle cell disease, third-generation cephalosporins or fluoroquinolones are used. In underimmunized children under four years, consider Haemophilus influenzae type b, with therapy guided by beta-lactamase production. Doxycycline has not been prospectively studied in pediatric acute hematogenous osteomyelitis. There are theoretical concerns about reduced activity in infected bone and risks related to prolonged therapy. While short courses are safe for certain infections, the longer durations required for osteomyelitis increase the risk of adverse effects. Doxycycline should be considered only when no other active oral option is available, typically in older children, and with infectious diseases consultation. It is not appropriate for routine treatment. Many hospitals automatically consult orthopedics when children are admitted with osteomyelitis, and this is appropriate. Early orthopedic consultation should be viewed as team-based care, not failure of medical management. Consult orthopedics when MRI shows abscess or extensive disease, there is concern for septic arthritis, the child fails to improve within 48 to 72 hours, imaging suggests devitalized bone or growth plate involvement, there is a pathologic fracture, the patient is a neonate, or diagnostic bone sampling or operative drainage is being considered. Routine surgical debridement is not required for uncomplicated cases. Infectious diseases consultation is also often automatic and supported by guidelines. ID is particularly valuable for antibiotic selection, dosing, IV-to-oral transition, duration decisions, bacteremia management, adverse reactions, and salvage regimens. Even in straightforward cases, ID involvement often facilitates shorter IV courses and earlier oral transition. Osteomyelitis is generally not contagious, and clustering is uncommon for Staphylococcus aureus. Kingella kingae is the key exception. It colonizes the oropharynx of young children and spreads via close contact. Clusters of invasive Kingelladisease have been documented in daycare settings. Suspicion should be higher in children six to 36 months from the same daycare, with recent viral illness, mild systemic symptoms, refusal to bear weight, modest CRP elevation, and negative routine cultures unless PCR testing is used. Public health intervention is not typically required, but awareness is critical. There is no minimum required duration of IV therapy for uncomplicated acute hematogenous osteomyelitis. Transition to oral therapy should be based on clinical improvement plus CRP decline. Many children meet criteria within two to six days. Oral antibiotics must be dosed higher than standard outpatient regimens to ensure adequate bone penetration. Common regimens include high-dose cephalexin, clindamycin, or linezolid in select cases. The oral agent should mirror the IV agent that produced clinical improvement. Total duration is typically three to four weeks, and in many cases 15 to 20 days is sufficient. MRSA infections or complicated cases usually require four to six weeks. Early oral transition yields outcomes comparable to prolonged IV therapy with fewer complications. Most treatment-related complications occur during parenteral therapy, largely due to catheter-related issues. Take-home points: osteomyelitis in children is a clinical diagnosis supported by labs and MRI. Empiric antibiotics should be guided by age, illness severity, and local MRSA prevalence. Early transition to high-dose oral therapy is safe and effective when clinical response and CRP support it. Orthopedics and infectious diseases consultation improve care and reduce variation. FAST MRI is changing how we diagnose osteomyelitis. Daycare clustering is uncommon except with Kingella kingae. That's all for this episode. If there are other topics you'd like us to cover, let me know. If you have the time, leave a review on your favorite podcast platform. It helps more people find the show and learn from it. For PEM Currents, this has been Brad Sobolewski. See you next time.    

You've read about how this groundbreaking trial on ketamine vs etomidate for RSI "Changes Everything!" on the socials. Or perhaps "it's horribly biased and unnecessary... we're already knew all this!". Why? Well.. social media. Listen in as Dr Jarvis discusses not just this trial, but what the evidence landscape was before it was released. Why was it done, how was it done, what does it show, and how can we integrate it into our practice?Citations:1. Casey JD, Seitz KP, Driver BE, et al. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med. Published online December 9, 2025.2. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374(9686):293-300. 3. Matchett G, Gasanova I, Riccio CA, et al. Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med. 2022;48(1):78-91. 4. Koroki T, Kotani Y, Yaguchi T, et al. Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis. Crit Care. 2024;28(1):48. 5. Yeh RW, Valsdottir LR, Yeh MW, et al. Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial. BMJ. 2018;363:k5094. doi:10.1136/bmj.k5094

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.

In this solo episode, Darin reframes one of the most misunderstood forces in life — stress. Instead of seeing it as the enemy, he explores how stress is actually a messenger, guiding you back to alignment, safety, and awareness. Through science, spirituality, and lived experience, Darin breaks down how stress shows us where we're trying to control, where we're disconnected, and where our nervous system is calling for attention. He unpacks the layers of modern stress — from trauma and environment to community and purpose — and offers practical, embodied tools to restore calm, clarity, and resilience.     What You'll Learn 00:00:00 – Welcome to Super Life: Solutions for a Healthier Life and Better World 00:00:32 – Sponsor Spotlight: TheraSauna - Natural Healing Technologies (15% off with code Darrandai) 00:02:10 – The Super Life Podcast: Finding Contentment, Happiness, and Purpose 00:02:51 – Today's Topic: Stress - Reframing Stress as an Ally and Dashboard Light 00:04:54 – The "No Choice" Universe: Reconnecting to Infinite Possibilities 00:05:16 – The Reality of Stress: Statistics and the Impact of Chronic Stress 00:06:21 – Stress is Layered: Beyond a Single Cause, Addressing Chronic Stress 00:08:29 – Solutions for a Super Life: Safety over Calm and the Vagal Response 00:09:38 – The Inner Dialogue Layer: Trauma, Unconsciousness, and Spiritual Bypassing 00:11:47 – The Social Field Layer: Relationships, Community, and Finding Your Way Home 00:14:20 – Sponsor Spotlight: Bite Toothpaste - Sustainable, Non-Toxic Tabs (20% off with code Darin20) 00:16:35 – Creating Your Own Vision: Setting Boundaries with Media and Social Algorithms 00:17:29 – Finding Your Purpose: From Raising Children to Healing Injuries 00:18:35 – Environmental and Existential Stress Layers: Clutter, Noise, and Service 00:19:26 – Stress Load and Resiliency: Why Small Triggers Cause Blow-Ups 00:20:02 – Understanding the Dashboard Light: Acknowledging Unwillingness 00:20:35 – Safety as the Signal: Body Relaxation and Providing Inner Security 00:23:44 – Reframing Trauma: Was it the Protector You Needed at the Time? 00:25:00 – Releasing Trauma: Techniques, The Healing Code, and Waking the Tiger 00:26:06 – Finishing the Survival Response: Shaking, Crying, Screaming, and Stretching 00:26:38 – Stress as a Multiplier: Impact on Immune System, Heart, and Aging 00:28:10 – Stress Slows Repair: Inflammation, Cardiovascular Risk, and Cellular Aging 00:29:48 – The Integrative Approach: Changing Your Environments to Support Anti-Stress 00:30:07 – Actionable Stress Solutions: Circadian Rhythm, Nature, and Noise Reduction 00:30:44 – Actionable Stress Solutions: Gratitude, Conscious Breath, and Movement 00:31:32 – Energy Drains to Eliminate: Conflict, Clutter, Scrolling, and Late Caffeine 00:32:17 – Connecting to Greater Purpose: The Super Life Patreon Platform 00:32:54 – Morning/Night Questions: Letting Go, Creating, and Contributing 00:33:17 – Final Toolkit: Slow Breathing, Movement, Nature, Sauna, and Sleep 00:34:25 – The Invitation: Digging into all Layers of a Super Life on Patreon   Thank You to Our Sponsors Therasage: Go to www.therasage.com and use code DARIN at checkout for 15% off Bite Toothpaste: Go to trybite.com/DARIN20 or use code DARIN20 for 20% off your first order. Find More from Darin Olien: Instagram: @darinolien Podcast: SuperLife Podcast Website: superlife.com Book: Fatal Conveniences   Key Takeaway "Stress isn't your enemy — it's your compass. Every wave of tension points you back to what's asking for care, attention, and love. When you stop fighting stress and start listening to it, you don't just survive — you evolve."       Bibliography (selected, peer-reviewed) Sources: Gallup Global Emotions (2024); Gallup U.S. polling (2024); APA Stress in America (2023); Natarajan et al., Lancet Digital Health (2020); Orini et al., UK Biobank (2023); Martinez et al. (2022); Leiden University (2025). Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. N Engl J Med.1991;325(9):606–612. New England Journal of Medicine Cohen S, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci USA. 2012;109(16):5995–5999. PNAS Kiecolt-Glaser JK, et al. Slowing of wound healing by psychological stress. Lancet. 1995;346(8984):1194–1196. The Lancet Kiecolt-Glaser JK, et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing.Arch Gen Psychiatry. 2005;62(12):1377–1384. JAMA Network Tawakol A, et al. Relation between resting amygdalar activity and cardiovascular events. Lancet.2017;389(10071):834–845. The Lancet Epel ES, et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA.2004;101(49):17312–17315. PNAS McEwen BS, Stellar E. Stress and the individual: mechanisms leading to disease. Arch Intern Med.1993;153(18):2093–2101. PubMed McEwen BS, Wingfield JC. Allostasis and allostatic load. Ann N Y Acad Sci. 1998;840:33–44. PubMed Felitti VJ, et al. Relationship of childhood abuse and household dysfunction to many leading causes of death in adults (ACE Study). Am J Prev Med. 1998;14(4):245–258. AJP Mon Online Edmondson D, et al. PTSD and cardiovascular disease. Ann Behav Med. 2017;51(3):316–327. PMC Afari N, et al. Psychological trauma and functional somatic syndromes: a systematic review and meta-analysis.Psychosom Med. 2014;76(1):2–11. PMC Goyal M, et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA Intern Med. 2014;174(3):357–368. PMC Qiu Q, et al. Forest therapy: effects on blood pressure and salivary cortisol—a meta-analysis. Int J Environ Res Public Health. 2022;20(1):458. PMC Laukkanen T, et al. Sauna bathing and reduced fatal CVD and all-cause mortality. JAMA Intern Med.2015;175(4):542–548. JAMA Network Zureigat H, et al. Physical activity lowers CVD risk by reducing stress-related neural activity. J Am Coll Cardiol.2024;83(16):1532–1546. PMC Holt-Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: a meta-analytic review. PLoS Med.2010;7(7):e1000316. PMC Chen Y-R, Hung K-W. EMDR for PTSD: meta-analysis of RCTs. PLoS One. 2014;9(8):e103676. PLOS Hoppen TH, et al. Network/pairwise meta-analysis of PTSD psychotherapies—TF-CBT highest efficacy overall.Psychol Med. 2023;53(14):6360–6374. PubMed van der Kolk BA, et al. Yoga as an adjunctive treatment for PTSD: RCT. J Clin Psychiatry. 2014;75(6):e559–e565. PubMed Kelly U, et al. Trauma-center trauma-sensitive yoga vs CPT in women veterans: RCT. JAMA Netw Open.2023;6(11):e2342214. JAMA Network Bentley TGK, et al. Breathing practices for stress and anxiety reduction: components that matter. Behav Sci (Basel). 2023;13(9):756.