Podcasts about The New England Journal of Medicine

This week, we feature new research on acute respiratory failure, wheezing in childhood, lung cancer, and obesity. We review myeloproliferative neoplasms and follow a diagnostic case of a patient with myasthenia gravis who developed dyspnea and weakness. Perspectives explore medical marijuana research, AI in clinical care, sexual and gender minority health research, and the Perspectives Editor saying goodbye.

CardioNerds (Drs. Dr. Natalie Marrero, Dr. Ritika Tuli, and Dr. Rafael Toro Manotas) discuss multimodality imaging for risk stratification, evaluation, and management of chronic coronary artery disease with Dr. Panithaya Chareonthaitawee. Audio editing by CardioNerds intern Iman Razeghian. This episode was produced as part of the CardioNerds Academy curriculum by House Taussig under the guidance of House Chief, Dr. Natalie Marrero and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds. This discussion was planned in collaboration with the Mayo Clinic Cardiovascular Board Review Course. In this episode, we discuss the pathophysiology and risk stratification of chronic coronary artery disease (CAD), as well as the current landscape of non-invasive evaluation of this condition. CAD remains a leading cause of morbidity and mortality despite advances in pharmacological and non-pharmacological strategies for the prevention and treatment of atherosclerotic disease. The concept of chronic CAD has shifted from the traditional model of stable, obstructive, flow-limiting disease, toward the current understanding of a dynamic process that extends beyond obstructive epicardial lesions to include non-obstructive plaque, diffuse atherosclerosis, and microvascular disease. Similarly, the imaging modalities used to evaluate CAD have evolved, and clinicians now have an extensive menu of options, each with distinct advantages and limitations, that must be selected carefully to maximize diagnostic accuracy and optimize treatment guidance, while also considering resource availability, local expertise, and high-value care. By the end of the episode, listeners will understand the pathophysiology of chronic CAD, risk-stratify patients with suspected CAD, recognize the advantages and pitfalls of each non-invasive diagnostic modality, and select the most appropriate diagnostic tool for a given clinical scenario. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls: Chronic CAD is a complex process that extends beyond obstructive epicardial stenosis to include non-obstructive disease, dynamic plaque burden and ischemia, diffuse atherosclerosis, microvascular dysfunction, vasospasm, among others. When evaluating patients with suspected CAD, the diagnostic process should be guided by a specific and appropriate clinical question before ordering any tests. The current diagnostic tool arsenal is broadly divided into anatomic and functional imaging modalities. These are complementary, each with distinct properties and limitations, addressing different clinical questions and assessing different aspects of disease. Local availability and expertise, along with patient-specific considerations and contraindications, determine the choice of diagnostic modality. No single test is best for every patient. INOCA and coronary microvascular dysfunction represent a common and increasingly recognized entity that is diagnosable and treatable; initial evaluation includes non-invasive testing such as stress PET and stress CMR. References Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144(22):e368-e454. doi:10.1161/CIR.0000000000001029 https://pubmed.ncbi.nlm.nih.gov/34709879/ Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024;45(36):3415-3537. doi:10.1093/eurheartj/ehae177 https://pubmed.ncbi.nlm.nih.gov/39210710/ Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023;148(9):e9-e119. doi:10.1161/CIR.0000000000001168 https://pubmed.ncbi.nlm.nih.gov/37471501/ Edvardsen T, Asch FM, Davidson B, et al. Non-Invasive Imaging in Coronary Syndromes: Recommendations of The European Association of Cardiovascular Imaging and the American Society of Echocardiography, in Collaboration with The American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2022;35(4):329-354. doi:10.1016/j.echo.2021.12.012 https://pubmed.ncbi.nlm.nih.gov/35379446/ Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372(14):1291-1300. doi:10.1056/NEJMoa1415516 https://pubmed.ncbi.nlm.nih.gov/39210710/ Sharma A, Coles A, Sekaran NK, et al. Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease. J Am Coll Cardiol. 2019;73(8):893-902. doi:10.1016/j.jacc.2018.11.056 https://pubmed.ncbi.nlm.nih.gov/30819356/ SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018;379(10):924-933. doi:10.1056/NEJMoa1805971 https://pubmed.ncbi.nlm.nih.gov/30145934/ Li Z, Xu T, Wang Z, et al. Prognostic Significance of Computed Tomography-Derived Fractional Flow Reserve for Long-Term Outcomes in Individuals With Coronary Artery Disease. J Am Heart Assoc. 2025;14(2):e037988. doi:10.1161/JAHA.124.037988 https://pubmed.ncbi.nlm.nih.gov/39791423/ Bateman TM, Al-Mallah MH, et al. Clinical indications for positron emission tomography myocardial perfusion imaging and myocardial blood flow quantification: An American Society of Nuclear Cardiology position statement. J Nucl Cardiol. 2026;57:102619. doi:10.1016/j.nuclcard.2025.102619 https://pubmed.ncbi.nlm.nih.gov/41482140/ Taqueti VR, Di Carli MF. Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018;72(21):2625-2641. doi:10.1016/j.jacc.2018.09.042 https://pubmed.ncbi.nlm.nih.gov/30466521/ Taqueti VR, Hachamovitch R, Murthy VL, et al. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation. 2015;131(1):19-27. doi:10.1161/CIRCULATIONAHA.114.011939 https://pubmed.ncbi.nlm.nih.gov/25400060/ Mehta PK, Huang J, Levit RD, Malas W, Waheed N, Bairey Merz CN. Ischemia and no obstructive coronary arteries (INOCA): A narrative review. Atherosclerosis. 2022;363:8-21. doi:10.1016/j.atherosclerosis.2022.11.009 https://pubmed.ncbi.nlm.nih.gov/36423427/ Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. EuroIntervention. 2021;16(13):1049-1069. doi:10.4244/EIJY20M07_01 https://pubmed.ncbi.nlm.nih.gov/32624456/

CardioNerds (Dr. Apoorva Gangavelli, Dr. Cory Sejo, and Dr. Joseph Kassab), discuss tricuspid regurgitation evaluation and management with Dr. Sunil Mankad. This episode was produced as part of the CardioNerds Academy curriculum by House Einthoven under the guidance of House Chief, Dr. Apoorva Gangavelli and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds. This discussion was planned in collaboration with the Mayo Clinic Cardiovascular Board Review Course.  Audio editing by CardioNerds intern Emma Winakur. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Key Points: Tricuspid regurgitation is common and associated with increased mortality at every stage, regardless of etiology. Outcomes are worse with worsening severity, so accurate grading is critical. Etiology is critical to guide treatment decisions. Etiology includes primary vs secondary (atrial or ventricular) vs CIED-related TR. 3D echocardiography can be very helpful in determining TR etiology, especially in CIED-related TR. Diuresis with the goal of euvolemia is step one. Additionally, underlying contributory conditions (eg. pulmonary HTN, HFrEF, atrial fibrillation) should be addressed, if appropriate, and then TR severity reassessed. The choice between T-TEER and TTVR hinges on anatomy, RV function, pulmonary hypertension, and the ability to tolerate anticoagulation. T-TEER is generally first line in atrial functional TR with appropriate anatomy, in patients with poor RV function who cannot tolerate a sudden increase in RV afterload, or in patients who cannot tolerate the necessary anticoagulation with TTVR. TTVR is preferred with wide coaptation gaps and CIED-related TR. This is a team sport. Multidisciplinary discussions utilizing imaging (TTE/TEE, CT), risk scores (TRI-SCORE or TRIO), patient preference, and prior institutional experience are essential for the effective treatment of severe TR. Notes: What is the clinical importance of tricuspid regurgitation? TR is very common with approximately 4% of people over 75 having moderate or greater severity. TR (even mild) is associated with increased mortality. Those outcomes worsen as the TR severity worsens, and this phenomenon is independent of the mechanism of regurgitation. What is unique about the tricuspid valve compared to the other cardiac valves? It is at an anterior location which allows it to be imaged well with transthoracic echocardiography It is the largest valve and composed generally of 3 leaflets (but very often can have 4+ leaflets). Importantly, the RV is compliant and changes size and shape readily based on loading conditions. The TV annulus similarly changes size and shape based on hemodynamic conditions such as preload. What is a good framework for approaching the causes of tricuspid regurgitation? Determine the presence and define the severity of TR. Using TTE, we want to measure the right atrial size, the RV size, and any other concomitant valvular lesions.  Use TTE (2D and 3D) to characterize leaflet anatomy and characteristics. Subtypes of TR mechanisms (many times etiology is mixed). Primary: primary leaflet abnormality, occurs in ~10% of cases. Look for prolapse, flail, endocarditis, etc. Secondary/functional: leaflets normal but surrounding structures are abnormal. Atrial: RA and tricuspid annular dilation but normal RV size/shape, and can be related to arrhythmias like atrial fibrillation. Ventricular: RV dilated and/or dysfunctional with leaflet tethering. Can be related to pulmonary hypertension or primary RV disease. Cardiac implantable electronic device (CIED): Related to device (usually pacemakers or ICD) interaction with TV leaflets. Includes perforation, entanglement in subvalvular apparatus, impingement, etc. 3D TTE particularly helpful to evaluate How do we grade TR severity? It is very important to grade the severity of TR, and this is generally done with echocardiography. There are both quantitative and qualitative methods which use Doppler and various equations to estimate TR severity. Current recommendations have expanded TR severity beyond mild/moderate/severe to include “massive” and “torrential” categories. The most important parameters measured/calculated are vena contracta width, regurgitant volume, regurgitant fraction, and effective regurgitant orifice area. Helpful qualitative metrics include hepatic venous flow reversal. When should additional studies beyond transthoracic echocardiography, such as transesophageal echocardiography (TEE), cardiac computed tomography (CT), and cardiac magnetic resonance imaging (MRI) be pursued? TEE is particularly helpful if TTE views are poor. Since TEE is used during transcatheter intervention, a pre-procedure TEE to define anatomy, determine procedure candidacy, and plan for the procedure is critical.  CT is also helpful for procedure planning and has particular strengths in defining annulus size and geometry. A CT is required prior to transcatheter tricuspid valve replacement (TTVR). MRI is helpful for measuring RV volumes and function, but is not generally used to assess TR severity.  What is the approach to the treatment for severe tricuspid regurgitation? The first step is to try to determine the etiology. For secondary TR, treating the underlying condition is indicated. For example, pulmonary vasodilators for pulmonary HTN or guideline therapy for heart failure with reduced ejection fraction. Diuretics are the mainstay for treatment, with the goal to obtain euvolemia. This may require inpatient admission to optimize volume status and medication regimen. Once reversible etiologies are addressed, if the patient is still symptomatic from TR, additional therapies can be considered. What is the role of right heart catheterizations (RHC) in patients with severe TR? RHC is very helpful for many reasons. We use it in TR to help determine volume status, cardiac output, and RV function. Additionally, identifying and characterizing pulmonary hypertension (with pulmonary artery pressures and calculating pulmonary vascular resistance) is an important factor when choosing future therapies.  With severe tricuspid regurgitation, when should we refer for intervention (either with surgery or transcatheter repair or replacement)? Once reversible etiologies are addressed and euvolemia has been achieved, if the patient is still symptomatic from TR despite aggressive medical optimization, additional therapies can be considered. Once euvolemic, a repeat TTE should be ordered to reassess the severity of the TR. Use calculators (for example, either the TRI-SCORE or TRIO score) to predict operative mortality for isolated TR surgery. What are our transcatheter treatment options in severe tricuspid regurgitation, and how do we choose between them? The primary approved transcatheter treatment options for severe TR include transcatheter tricuspid edge-to-edge repair (T-TEER) and transcatheter tricuspid valve replacement (TTVR), of which the Edwards EVOQUE valve is the only one currently approved by the FDA. There are other TTVR device under investigation. These decisions should be made with a multi-disciplinary team including representation from cardiac imaging, interventional cardiology, and cardiothoracic surgery. Factors that go into the decision between T-TEER and TTVR include anatomy (annulus width, coaptation gap, leaflet length), RV reserve, pulmonary hypertension presence, ability to tolerate anticoagulation, patient preference, and institutional experience.  T-TEER is generally the first line with atrial functional and suitable anatomy. It is successful at reducing TR but does not generally eliminate it.  TTVR with EVOQUE is preferred in certain anatomic considerations like a large coaptation gap or when there is CIED-related TR (as this was excluded in T-TEER trials). Patients must be suitable for anticoagulation to receive TTVR as there is risk of leaflet thrombosis without it. If moderate/severe pulmonary hypertension is present, or there is poor RV function, TTVR may be avoided as the sudden elimination of TR causes a sudden increase in RV afterload which may not be tolerated. What is the role in advanced metrics for evaluating RV function? Advanced metrics like RV/PA coupling are under investigation but have not made it into the guidelines. The clinical utility is not yet known.  Assessing the RV function is important as stated above. Dr. Mankad prefers using 3D TTE to calculate an RVEF, or tracking RV longitudinal free wall strain. If you do encounter CIED-related TR, how do you treat it? Evaluate with TTE or TEE. 3D is very helpful to identify relative anatomy and leaflet-device interactions. There is no clear consensus about treatment if CIED-related TR is the primary mechanism of severe TR. If recently implanted, repositioning may be a valid option, but requires discussions with multiple teams including electrophysiology, advanced cardiac imaging, CT surgery, and interventional cardiology. References O’Gara PT, Lindenfeld J, Hahn RT, et al. 10 Issues for the Clinician in Tricuspid Regurgitation Evaluation and Management: 2025 ACC Expert Consensus Decision Pathway. J Am Coll Cardiol. 2025;S0735-1097(25)07047-0. O’Gara PT, Little SH, Badhwar V, et al. Operator and Institutional Recommendations and Requirements for Tricuspid Interventions: 2026 ACC/AHA/ASE/HRS/STS Expert Consensus Systems of Care Document. J Am Coll Cardiol. 2026;S0735-1097(26)05481-1. Hahn RT. Tricuspid Regurgitation. N Engl J Med. 2023;388(20):1876-1891. Davidson LJ, Tang GHL, Ho EC, et al. The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association. Circulation. 2024;149(22):e1223-e1238.

Dr Swapnil Pawar is joined by Dr Jose Chacko to discuss the LOGICAL trial, published in the New England Journal of Medicine in June 2026. Does limiting oxygen after cardiac arrest protect the brain from reperfusion injury? LOGICAL (the largest randomised trial of oxygen therapy after cardiac arrest to date) randomised 1,840 patients across 53 ICUs in Australia, New Zealand and Ireland to conservative versus liberal oxygen therapy. In this episode: – The pathophysiological rationale: hypoxic-ischaemic encephalopathy, reperfusion injury and free radical damage – Where LOGICAL sits alongside EXACT, ICU-ROX, HOT-ICU and the Danish BOX trial – The Mega-ROX master protocol design, and why the sepsis and non-HIE brain injury arms are still to come – Trial design: SpO₂ upper limit of 95% and FiO₂ down to 0.21 in the conservative arm versus no upper limit and a floor of FiO₂ 0.3 in the liberal arm – The results: no difference in favourable neurological outcome at 180 days (38.2% vs 39.7%), survival, length of stay, quality of life or cognitive function – Strengths, limitations, and what it means at the bedside, including why the hosts have landed in different places on titrating down to room air Reference: The LOGICAL Investigators and the ANZICS Clinical Trials Group. Conservative Oxygen for Unresponsive Patients after Cardiac Arrest. N Engl J Med. 2026 Jun 10. Full summary, outcome tables and references at critcareedu.com.au

This week, we feature new research on polymyalgia rheumatica, hypercholesterolemia, prostate cancer, and multiple myeloma. We review evidence-based strategies for tobacco cessation, and follow a case of a woman with nausea, dizziness, and metabolic acidosis. We discuss recent advances in gene editing for rare metabolic diseases. Perspectives address HIV care, health care quality, medical ethics, and finding resilience in the face of serious illness.

Eric Schneider is an adjunct professor of health policy and management at the Harvard T.H. Chan School of Public Health and a member of the Journal's Perspective Advisory Board. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. M. Chernew and E.C. Schneider. Rethinking the Role of Pay for Performance in Federal Health Care Quality Programs. N Engl J Med 2026;395:625-628.

HEADLINES: One Nation senators turned their backs during the Acknowledgement of Country in Parliament. The life-saving devices on every NSW ambulance have just been pulled from sale, and paramedics are demanding answers. A reality TV contestant accused of beheading her partner has pleaded not guilty to murder, flagging a mental health defence. Meta, Google, Tiktok and Snapchat to face 3000 lawsuits over how addictive their platforms are for young users. Andrew and Tristan Tate are pushing to be released from federal custody. A young girl’s quick thinking has helped save a stranded humpback whale, and good news for the Great Barrier Reef. GET IN TOUCHGot a story, news tip-off, feedback or dilemma?Send us a voice note or email us at thequicky@mamamia.com.au CREDITSHost: Charlotte Mortlock Audio Producer: Scott Stronach Group Executive Producer: Georgie Page Check out The Quicky Instagram here and our TikTok here Discover more Mamamia podcasts here Did you know some of our shows are now in video on the Apple Podcast app? Make sure your phone is up to date and check it out here! Mamamia acknowledges the traditional owners of the land on which we have recorded this podcast.Become a Mamamia subscriber: https://www.mamamia.com.au/subscribeSee omnystudio.com/listener for privacy information.

This week, we feature new research on chronic kidney disease, high-risk prostate cancer, peripheral artery disease, and oxygen therapy after cardiac arrest. We review the evaluation and management of syncope, follow a challenging case of immune-related inflammatory illness, and report on Perspectives exploring pandemic preparedness, the Bundibugyo Ebola outbreak, and physician mental health.

Jean Nachega is a professor of infectious diseases and the director of the Biomedical Research Institute at Stellenbosch University and an associate professor at the University of Pittsburgh School of Public Health. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A. Zumla and Others. Ebola at 50 — Lessons for Outbreak Response and Preparedness. N Engl J Med 2026;395:527-529. S. Tonen-Wolyec and L. Bélec. The Social Contract of Bundibugyo Ebola Isolation. N Engl J Med. DOI: 10.1056/NEJMp2607429.

Featuring perspectives from Dr Joshua K Sabari, including the following topics: Heymach JV et al. Zongertinib in previously treated HER2-mutant non-small cell lung cancer. N Engl J Med 2025;392(23):2321-33. (0:00) Popat S et al. Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG-1. ESMO 2025;Abstract LBA74. (5:25) Le X et al. Sevabertinib in advanced HER2-mutant non-small cell lung cancer. N Engl J Med 2025;393(18):1819-32. (12:37) CME information and select publications

This week, we feature advances that may change care for prostate cancer, multiple myeloma, acute pain, and IgA nephropathy. We review platelet factor 4 disorders and follow a case of persistent nasal ulceration. Perspectives explore medical aid in dying, federal authority in health care, public health and litigation, and the challenge of delivering life-changing news with honesty and compassion.

Jerry Avorn is a professor of medicine at Harvard Medical School and the codirector of the Program on Regulation, Therapeutics, and Law at Harvard Medical School and Brigham and Women's Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. J. Avorn. Products That Pose Health Risks — Can Litigation Protect Us When Government Fails? N Engl J Med 2026;395:421-423.

CardioNerds (Drs. Apoorva Gangavelli, Jenna Skowronski, and Hannah Every) discuss the continuum of prevention and heart failure with Drs. Anu Lala and Martha Gulati. Grounded in a clinical case of a 55-year-old woman with uncontrolled hypertension, type 2 diabetes, and obesity who is on the trajectory toward heart failure, this episode unpacks a paradigm-shifting framework from a joint HFSA/ASPC Scientific Statement. The discussion explores how prevention should not be siloed from heart failure management but rather integrated across a patient’s lifespan—from primary prevention in at-risk individuals, to secondary prevention in those with established heart failure, to tertiary prevention in patients with advanced therapies such as LVADs and heart transplantation. The experts highlight the importance of aggressive risk factor management, biomarker-guided screening, the AHA’s Life’s Essential 8, and the need for multidisciplinary collaboration and systems-level change to shift heart failure care from reactive to proactive. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls Systemic inflammatory diseases are associated with an elevated CVD risk that has significant implications for early detection, risk Heart failure prevention is a continuum, not a checkpoint. Prevention applies at every stage—from at-risk (Stage A) through advanced/post-transplant care—and every clinical encounter is an opportunity to intervene. The AHA’s Life’s Essential 8 (diet, physical activity, nicotine exposure, sleep, BMI, blood lipids, blood glucose, blood pressure) forms the foundation at every stage. Hypertension carries the highest population-attributable risk for heart failure of any modifiable risk factor. In the Framingham Heart Study, 91% of patients with newly diagnosed HF had pre-existing hypertension. The SPRINT trial demonstrated a 38% reduction in HF incidence with intensive blood pressure targets (30 ng/L or NT-proBNP >125 ng/L) identify individuals at heightened risk for progression to symptomatic HF. The ACC/AHA/HFSA guidelines give a Class IIa recommendation for natriuretic peptide screening in at-risk patients. Urine albumin-to-creatinine ratio (UACR) is an underutilized screening tool that provides additional insight into CKM risk. The heart failure label does not close the prevention window—it accentuates it. Secondary prevention through GDMT optimization (quadruple therapy in HFrEF) and continued risk factor management remains critical. Tertiary prevention extends to post-LVAD and post-transplant patients, where hypertension, diabetes, obesity, and CKD management remain essential to long-term outcomes. Show notes For a comprehensive review, please review the full HFSA/ASPC Joint Scientific Statement: Lala A, Beavers C, Blumer V, et al. The Continuum of Prevention and Heart Failure in Cardiovascular Medicine. J Card Fail. 2026;32:75-105. doi:10.1016/j.cardfail.2025.06.013 1. What is the “continuum of prevention” framework, and how does it differ from traditional approaches to heart failure prevention? Historically, prevention and heart failure management have been treated as separate disciplines—primary prevention handled by preventive cardiologists and treatment managed by heart failure specialists. This joint HFSA/ASPC Scientific Statement reframes prevention as a dynamic, continuous process that spans a patient’s entire lifespan, regardless of HF stage or ejection fraction. The framework maps onto the ACC/AHA HF staging system: Primary prevention targets Stage A (“at risk”) and Stage B (“pre-HF”) patients to reduce the burden of incident HF. Secondary prevention targets Stage C (symptomatic) and Stage D (advanced) patients to reduce the impact of established HF through GDMT optimization and ongoing risk factor management. Tertiary prevention encompasses risk factor management in patients with LVADs or heart transplants—populations where hypertension, diabetes, and obesity still drive outcomes. The Central Figure of the statement illustrates that Life’s Essential 8 (blood pressure and lipid control, diabetes management, exercise, sleep, smoking cessation, weight management, and diet/nutrition counseling) forms the foundation at every stage, with pharmacologic and device-based therapies layered on top as disease progresses (Figure) 2. How do traditional risk factors drive heart failure, and what should clinicians prioritize? Hypertension carries the greatest population-attributable risk for HF. In the Framingham Heart Study (N=5,143), HTN was associated with a 2- to 3-fold increased risk of HF, with a population-attributable risk of 39% in men and 59% in women. The SPRINT trial showed a 38% reduction in HF incidence and 25% reduction in the primary composite outcome with intensive BP targets (30 ng/L or NT-proBNP >125 ng/L) are associated with heightened risk for progression to symptomatic HF. In the ARIC study, incorporating NT-proBNP reclassified 20% of older adults without HF into Stage B. Factors that affect interpretation include age, sex, obesity (lower values), and CKD (higher values). High-sensitivity cardiac troponin (hs-cTn): Concentrations above the 99th percentile are now included in the definition of Stage B HF. Troponin testing may complement natriuretic peptides, particularly when BNP/NT-proBNP values are ambiguous. Risk scores: The PCP-HF equation predicts 10-year HF risk using traditional risk factors plus QRS duration. The AHA PREVENT score incorporates HF risk calculation and includes markers of kidney function (albuminuria, eGFR), though it may underestimate risk in men and Black adults. The CKM syndrome staging framework (Stages 0–4) provides a holistic approach to assessing systemic cardiovascular-kidney-metabolic risk. 4. What are the key nontraditional risk factors and cross-cutting themes in heart failure prevention? Genetics: Pathogenic cardiomyopathy variants exist in ~1 in 200 individuals in the general population. The HFSA and ACMG recommend cascade testing to identify at-risk family members. Polygenic risk scores for dilated cardiomyopathy show a 3.8-fold risk for DCM in the top 10th percentile compared with the median. Sex-specific considerations: Women have 2.8 times the odds of developing HFpEF, while men have similarly increased odds of HFrEF. A complete obstetric/gynecologic history is essential—preeclampsia is associated with a 4-fold increased risk of HF. Peripartum cardiomyopathy requires intentional screening in high-risk populations. Cardiotoxic exposures: Clinicians should be aware of medications that cause direct myocardial toxicity (e.g., anthracyclines, trastuzumab, tyrosine kinase inhibitors). A team-based approach with pharmacists can help optimize medication selection and risk factor modification. Social determinants of health: Environmental exposures (air pollution, arsenic, lead, cadmium), food insecurity, financial instability, and limited healthcare access contribute to HF risk and progression. Equity-focused, risk-based prevention strategies are needed. Psychological health: Depression is common in HF and independently associated with worse outcomes. Screening with brief questionnaires (e.g., PHQ-2) is recommended. Meditation, spirituality, and holistic wellness approaches remain underutilized. 5. What systems-level and policy changes are needed to move the needle on heart failure prevention? Multidisciplinary HF prevention clinics that bring together preventive cardiologists, HF specialists, endocrinologists, nephrologists, dietitians, pharmacists, exercise physiologists, and genetic counselors are advocated by the statement. EHR-embedded risk stratification could proactively flag patients on a trajectory toward HF—analogous to sepsis alerts or fall risk flags—enabling earlier intervention, particularly for patients who may not reach a cardiologist. Cardiac rehabilitation remains underutilized, particularly in HFrEF (Class 2b recommendation) and HFpEF (not yet covered by Medicare). The HF-ACTION trial showed quality-of-life benefits, and the REHAB-HF trial showed particular benefit in older patients with HFpEF. Policy priorities include expanding insurance coverage for preventive screening and novel therapies (SGLT2i, GLP-1 RAs, nsMRAs), reducing clinical inertia through team-based care models with closer follow-up intervals, and ensuring equitable access to evidence-based therapies across diverse populations. Digital health and AI hold promise for personalized risk prediction, remote monitoring (e.g., wearable devices, implantable PA pressure monitors), and virtual cardiac rehabilitation to overcome access barriers. Figure  Lala A, Beavers C, Blumer V, et al. The continuum of prevention and heart failure in cardiovascular medicine: a joint scientific statement from the Heart Failure Society of America and the American Society for Preventive Cardiology. J Card Fail. 2026;32(1):75-105. doi:10.1016/j.cardfail.2025.06.013) References Key references are bolded. Lala A, Beavers C, Blumer V, et al. The continuum of prevention and heart failure in cardiovascular medicine: a joint scientific statement from the Heart Failure Society of America and the American Society for Preventive Cardiology. J Card Fail. 2026;32(1):75-105. doi:10.1016/j.cardfail.2025.06.013 Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063 Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life’s Essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146(5):e18-e43. doi:10.1161/CIR.0000000000001078 SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116. doi:10.1056/NEJMoa1511939 Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275(20):1557-1562. doi:10.1001/jama.1996.03530440037034 Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997. doi:10.1001/jama.288.23.2981 Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153. doi:10.1056/NEJM200001203420301 Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720 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. doi:10.1056/NEJMoa2107038 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. doi:10.1056/NEJMoa2206286 Filippatos G, Anker SD, Agarwal R, et al. Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial. Circulation. 2022;145(6):437-447. doi:10.1161/CIRCULATIONAHA.121.057983 Solomon SD, McMurray JJV, Vaduganathan M, et al. Finerenone in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2024;391(16):1475-1485. doi:10.1056/NEJMoa2407107 Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563 Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10454):773-786. doi:10.1016/S0140-6736(24)01498-3  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. doi:10.1056/NEJMoa2306963 Ndumele CE, Neeland IJ, Tuttle KR, et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association. Circulation. 2023;148(20):1636-1664. doi:10.1161/CIR.0000000000001175 Khan SS, Matsushita K, Sang Y, et al. Development and validation of the American Heart Association’s PREVENT equations. Circulation. 2024;149(6):430-449. doi:10.1161/CIRCULATIONAHA.123.067626 Khan SS, Ning H, Shah SJ, et al. 10-year risk equations for incident heart failure in the general population. J Am Coll Cardiol. 2019;73(19):2388-2397. doi:10.1016/j.jacc.2019.02.057 Bozkurt B, Fonarow GC, Goldberg LR, et al. Cardiac rehabilitation for patients with heart failure: JACC expert panel. J Am Coll Cardiol. 2021;77(11):1454-1469. doi:10.1016/j.jacc.2021.01.030 Packer M. Leptin-aldosterone-neprilysin axis: identification of its distinctive role in the pathogenesis of the three phenotypes of heart failure in people with obesity. Circulation. 2018;137(15):1614-1631. doi:10.1161/CIRCULATIONAHA.117.032474 Lala A, Tayal U, Hamo CE, et al. Sex differences in heart failure. J Card Fail. 2022;28(3):477-498. doi:10.1016/j.cardfail.2021.10.006 Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and classification of heart failure. Eur J Heart Fail. 2021;23(3):352-380. doi:10.1002/ejhf.2115 Hershberger RE, Givertz MM, Ho CY, et al. Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline. J Card Fail. 2018;24(5):281-302. doi:10.1016/j.cardfail.2018.03.004 Levine GN, Cohen BE, Commodore-Mensah Y, et al. Psychological health, well-being, and the mind-heart-body connection: a scientific statement from the American Heart Association. Circulation. 2021;143(10):e763-e783. doi:10.1161/CIR.0000000000000947 Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022;399(10333):1391-1400. doi:10.1016/S0140-6736(22)00369-5

¿Has escuchado maravillas sobre medicamentos como Ozempic, Wegovy o Mounjaro, pero nadie te habla de las constantes náuseas y el malestar estomacal? La realidad clínica es que una gran parte de los pacientes abandonan estos tratamientos para la obesidad simplemente porque los efectos secundarios arruinan su calidad de vida. Pero la ciencia médica está a punto de dar un salto monumental. En este episodio, descubriremos a la AMILINA, una hormona producida por tu páncreas que está demostrando resultados asombrosos en ensayos clínicos: pérdida de peso significativa sin los severos vómitos ni malestares intestinales de los fármacos actuales. En este episodio aprenderás: → Cómo tu páncreas libera dos hormonas cada vez que comes. → Cómo la amilina bloquea el freno metabólico que hace que recuperes el peso perdido. → Cómo dos equipos de investigadores resolvieron el mismo problema químico de formas distintas. → Cómo la combinación CagriSema alcanza una reducción significativa del peso corporal. → Por qué la amilina resensibiliza tu cerebro a la leptina, algo que la semaglutida no logra.   Mi nombre es Dr. Mauricio González, médico internista y especialista en endocrinología en formación. Aquí comparto información basada en evidencia para que tomes decisiones de salud sin mitos ni marketing engañoso. Suscríbete a mi boletín informativo en: www.drmauriciogonzalez.com/   ⚠️ Este podcast tiene fines exclusivamente educativos e informativos y no constituye asesoramiento médico, diagnóstico ni tratamiento personalizado. Los medicamentos que se discuten en este episodio se encuentran en fase de investigación y no cuentan con aprobación de la FDA. Consulta siempre a tu médico o a un profesional de la salud calificado antes de cambiar tu régimen de tratamiento.   ¡Sigamos la conversación en redes sociales! Instagram

This week, we bring you advances in pancreatic and bladder cancer, preventing gonorrhea, a promising new therapy for adolescent hypertrophic cardiomyopathy, and a review of antiretroviral treatment for HIV. We also follow a striking case of vision loss that led to an unexpected diagnosis and discuss Perspectives on vaccine evidence, hepatitis C elimination, the endorsements of prescription drugs on social media, and the enduring intersection of love and loss in medicine.

Arnold Monto is a professor emeritus of epidemiology and of public health and codirector of the Center for Respiratory Virus Research and Response at the University of Michigan School of Public Health. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A.S. Monto and H.Y. Chu. The Best of Both Worlds — Using Clinical Trial and Observational Data to Evaluate Vaccine Protection. N Engl J Med 2026;395:313-316.

Long after acute infection has resolved, many survivors of severe COVID-19 experience persistent symptoms. Understanding the causes of long COVID and developing effective treatments pose a challenge for clinicians and researchers alike. In this episode of the Society of Critical Care Medicine (SCCM) Podcast, host Kyle B. Enfield, MD, speaks with Matthew Baldwin, MD, MS, about his article published in the March 2026 issue of Critical Care Explorations that examines post-acute sequelae of COVID-19 in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) survivors over a three-year period. One of the study's most notable findings is that approximately one in four study patients, many of whom were middle-aged and previously healthy, continued to meet criteria for long COVID three years after infection. This finding emphasizes the burden of chronic illness caused by COVID-19 infection and the need to focus research and treatment efforts on this population of ALI/ARDS survivors. Drs. Baldwin and Enfield discuss the relevance of inflammatory, thromboinflammatory, and endothelial biomarkers in understanding illness due to COVID-19. Surprisingly, the study found no association between long COVID symptoms and these biomarkers. Dr. Baldwin contextualizes this finding and encourages future studies to employ multiomics to better uncover the underlying mechanisms of these symptoms. The discussion emphasizes the patient-centered approach of the study, which examines functional outcomes as well as biomarkers. Dr. Baldwin encourages clinicians to validate the experiences of severe COVID-19 survivors and guide them towards the next step in their recovery as researchers continue to look for better therapies. Resources referenced in this episode: Baldwin M, Jones AE, McGroder CF, et al. Post-acute sequelae of COVID-19 persist over three years in acute lung injury/acute respiratory distress syndrome survivors but are not associated with persistent thromboinflammation or endothelial dysfunction. Crit Care Explor. 2026;8(3):e1390. Hodgson CL, Higgins AM, Bailey MJ, et al. Comparison of 6-month outcomes of survivors of COVID-19 versus non-COVID-19 critical illness. Am J Respir Crit Care Med. 2022;205(10):1159-1168. Herridge MS, Tansey CM, Matté A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293-1304. National Institutes of Health RECOVER Initiative. RECOVER: Researching COVID to Enhance Recovery. https://recovercovid.org Leisman DE, Mehta A, Thompson BT, et al. Alveolar, endothelial, and organ injury marker dynamics in severe COVID-19. Am J Respir Crit Care Med. 2022;205(5):507-519. Cervia-Hasler C, Brüningk SC, Hoch T, et al. Persistent complement dysregulation with signs of thromboinflammation in active long COVID. Science. 2024;383(6680). doi:10.1126/science.adg7942 Oelsner EC, Krishnaswamy A, Balte PP, et al. Collaborative cohort of cohorts for COVID-19 Research (C4R) Study: study design. Am J Epidemiol. 2022;191(7):1153-1173.

John Gerardi is joined by Jonathan Keller of California Family Council to unpack the disturbing expansion of Canada's euthanasia program, from proposals to euthanize infants with disabilities to recommendations that minors consent to their own deaths without parental input. This week's mystery clip reveals just how far the MAID program has gone, with roughly half of 2024 recipients citing feeling like a burden rather than terminal illness. The guys then break down how activists quietly corrupt language, sliding from physician assisted suicide to medical assistance in dying to simply assisted death, and why that shift matters. Finally, they take on a New England Journal of Medicine article arguing to contextualize the dead donor rule, a euphemism for harvesting organs from euthanasia patients before death, and explain why the slippery slope keeps proving pro-lifers right.

Continuing his exploration of once-weekly insulins, Neil Skolnik speaks with Aaron King, MD. Together, they cover the mechanisms, practical considerations, and the myriad benefits that this new therapy can have over daily basal insulin. This special episode is sponsored with support from Novo. Please listen to the episodes by clicking on the podcast player below or by freely subscribing to Diabetes Core Update via Apple Podcasts, Amazon Music, Spotify, or your preferred podcast platform. Presented by: Neil Skolnik, MD, Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health Aaron King, MD. Trained in the United States Navy in Family Medicine and certified by the American College of Diabetology, Dr. King practices outpatient diabetes management in San Antonio, Texas. Selected references: Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin. N Engl J Med 2023;389:297-308 Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy. N Engl J Med 2025;393:325-335

This week, we present advances in the treatment of multiple myeloma, systemic lupus erythematosus, and coronary artery disease, alongside new national data on health care–associated infections. We also review fibromyalgia and the emerging Bundibugyo virus outbreak, follow a surprising diagnostic case of alpha-gal syndrome, and explore Perspectives on caring for vulnerable patients, trustworthy health information, pharmacotherapeutic decisions in autism care, and the experience of caring for a parent with dementia.

Did you know that the average age of puberty onset in girls has been declining for decades, and that early puberty can have lasting psychological, social, and physical consequences? Roshni Patel, a fourth-year medical student at the Medical College of Georgia, and Bianca Forte, WHNP, a Women's Health Nurse Practitioner with a specialty in Pediatric and Adolescent Gynecology at Wellstar MCG Health, to discuss the recognition, evaluation, and management of precocious puberty in girls. Specifically, they will: Review the normal pubertal timeline and define precocious puberty in females Distinguish between premature thelarche, premature adrenarche, and precocious puberty through history and physical exam findings Discuss the initial diagnostic workup, including bone age studies, hormone levels, and the GnRH stimulation test Differentiate central precocious puberty from peripheral precocious puberty and outline appropriate management for each Address the mental health impact of early puberty and how to support young patients during the clinical encounter Identify when to refer patients to Pediatric Endocrinology or Pediatric and Adolescent Gynecology Special thanks to Dr. Rebecca Yang and Dr. Sarah Straka for peer reviewing this episode Free CME Available: Link Coming Soon! References: Aghaee S, Deardorff J, Quesenberry CP, Greenspan LC, Kushi LH, Kubo A. Associations Between Childhood Obesity and Pubertal Timing Stratified by Sex and Race/Ethnicity. Am J Epidemiol. 2022;191(12):2026-2036. doi:10.1093/aje/kwac148 Berberoğlu M. Precocious puberty and normal variant puberty: definition, etiology, diagnosis and current management. J Clin Res Pediatr Endocrinol. 2009;1(4):164-174. doi:10.4274/jcrpe.v1i4.3 Carel JC, Léger J. Clinical practice. Precocious puberty. N Engl J Med. 2008;358(22):2366-2377. doi:10.1056/NEJMcp0800459 Dinkelbach L, Grasemann C, Kiewert C, Leikeim L, Schmidt B, Hirtz R. Central Precocious Puberty and Psychiatric Disorders. JAMA Netw Open. 2025;8(6):e2516679. Published 2025 Jun 2. doi:10.1001/jamanetworkopen.2025.16679 Eckert-Lind C, Busch AS, Petersen JH, et al. Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020;174(4):e195881. doi:10.1001/jamapediatrics.2019.5881 Hampl SE, Hassink SG, Skinner AC, et al. Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity. Pediatrics. 2023;151(2):e2022060640. doi:10.1542/peds.2022-060640 Joinson C, Heron J, Lewis G, Croudace T, Araya R. Timing of menarche and depressive symptoms in adolescent girls from a UK cohort. Br J Psychiatry. 2011;198(1):17-2. doi:10.1192/bp.110.080861 Kaplowitz PB. For Premature Thelarche and Premature Adrenarche, the Case for Waiting before Testing. Horm Res Paediatr. 2020;93(9-10):573-576. doi:10.1159/000512764 Klein DA, Emerick JE, Sylvester JE, Vogt KS. Disorders of Puberty: An Approach to Diagnosis and Management. Am Fam Physician. 2017;96(9):590-599. Kota AS, Sharma L, Ejaz S. Precocious Puberty. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544313/

Yaara Zisman-Ilani is an associate professor in the Department of Social and Behavioral Sciences at the Barnett College of Public Health and in the Department of Psychiatry and Behavioral Science at the Lewis Katz School of Medicine, both at Temple University. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. Y. Zisman-Ilani and Others. Pharmacotherapeutic Decisions in Autism. N Engl J Med 2026;395:214-217.

CardioNerds co-chairs Dr. Dinu Balanescu and Dr. Billy Joe Mullinax, along with FIT lead Dr. Shiavax Rao, discuss the evolving landscape of randomized controlled trials in pulmonary embolism with Dr. Jay Giri, interventional cardiologist, Associate Professor of Medicine, and Director of the Cardiovascular Catheterization Laboratories at the Hospital of the University of Pennsylvania. This episode examines the historical evidence behind systemic thrombolysis, the emergence of catheter-directed therapies and mechanical thrombectomy, and the landmark RCTs – STORM-PE, PEERLESS, HI-PEITHO, and PEERLESS II – that are reshaping intermediate-risk PE management. The discussion highlights challenges in PE trial design, the critical importance of clinical deterioration as an endpoint, and why this era represents an unprecedented wave of evidence generation in PE. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes. Dr. Dinu Balanescu and Dr. Billy-Joe Mullinax are Co-chairs for the CardioNerds PE Series, developed in collaboration with the PERT Consortium.   Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Pulmonary Embolism PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls: Systemic thrombolysis in intermediate-risk PE reduces hemodynamic decompensation but at the cost of ~1.5–2% intracranial hemorrhage risk – a near-zero net benefit that has driven the search for safer catheter-based alternatives. “Focus on clinical deterioration, not mortality” – Due to crossover design in contemporary PE RCTs, control-arm patients who decompensate are rescued with advanced therapies, biasing mortality toward the null. Clinical deterioration is the most informative endpoint to watch in HI-PEITHO, PRAGUE-26, and PEERLESS II. HI-PEITHO is the first large RCT to demonstrate that catheter-directed fibrinolysis plus anticoagulation significantly reduces the composite of PE-related death, cardiorespiratory decompensation, or PE recurrence versus anticoagulation alone (RR 0.39; 95% CI 0.20–0.77; P=0.005), with no intracranial hemorrhage in either arm. The four major upcoming/recently reported PE RCTs (HI-PEITHO, PRAGUE-26, PEERLESS II, PE-TRACT) enroll progressively different risk populations – from the most enriched (HI-PEITHO) to the most permissive (PE-TRACT, which includes intermediate-low risk patients) – enabling a nuanced understanding of which patients benefit most from intervention. PE device clearance follows a fundamentally different FDA pathway than structural heart devices (single-arm safety/efficacy studies vs. mandated RCTs), yet market forces and clinical need have ultimately driven industry and government to sponsor large-scale RCTs – a lesson in how evidence development can evolve organically alongside regulatory frameworks. Notes: Notes drafted by Dr. Shiavax Rao. Question #1: What is the current evidence behind advanced PE therapies? Systemic thrombolysis: Sixteen RCTs over 40 years (1972–2014) enrolling nearly 2,000 patients have studied systemic thrombolysis in intermediate-risk PE. The landmark PEITHO trial (n=1,006) showed that tenecteplase reduced the composite of death or hemodynamic collapse (2.6% vs. 5.6%; P=0.015), driven primarily by reduced hemodynamic decompensation (1.6% vs. 5.0%; P=0.002). However, this came at the cost of increased major bleeding (6.3% vs. 1.5%; P

In our first summer series episode, we review a topic that keeps coming back. Hormone therapy for menopause. It was a thing, then it stopped being a thing, now it's a thing again.   Become a supporter of our show today either on Patreon or through PayPal! Thank you! http://www.patreon.com/thebodyofevidence/ https://www.paypal.com/donate?hosted_button_id=9QZET78JZWCZE   Email us your questions at thebodyofevidence@gmail.com.   Editor:    Robyn Flynn Theme music: “Fall of the Ocean Queen“ by Joseph Hackl Rod of Asclepius designed by Kamil J. Przybos Chris' book, Does Coffee Cause Cancer?: https://ecwpress.com/products/does-coffee-cause-cancer   Obviously, Chris is not your doctor (probably). This podcast is not medical advice for you; it is what we call information. References:  Geographic variability of menopausal symptoms   1) Nappi RE et al. Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden. Menopause. 2021 May 24;28(8):875-882. doi: 10.1097/GME.0000000000001793.    2) Nappi RE, et al.  Prevalence and quality-of-life burden of vasomotor symptoms associated with menopause: A European cross-sectional survey. Maturitas. 2023 Jan;167:66-74. doi: 10.1016/j.maturitas.2022.09.006.    What's the normal duration of symptoms   3) Avis NE, et al. Study of Women's Health Across the Nation. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015 Apr;175(4):531-9. doi: 10.1001/jamainternmed.2014.8063.  The Women's Health Initiative (WHI) studies   Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.    Anderson GL et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701.   Decline in HRT after WHI studies   Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999-2010. Obstet Gynecol. 2012 Sep;120(3):595-603. doi: 10.1097/AOG.0b013e318265df42.   Danish Osteoporosis Prevention Study Schierbeck LL metal. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012 Oct 9;345:e6409. doi: 10.1136/bmj.e6409.   Kronos Early Estrogen Prevention Study (KEEPS) Harman SM, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014 Aug 19;161(4):249-60. doi: 10.7326/M14-0353.   Kronos Early Estrogen Prevention Study (KEEPS) Hodis HN et al. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016 Mar 31;374(13):1221-31. doi: 10.1056/NEJMoa1505241.    Stopping hormonal therapy   Berman RS et al. Risk factors associated with women's compliance with estrogen replacement therapy. J Womens Health. 1997 Apr;6(2):219-26. doi: 10.1089/jwh.1997.6.219.   Grady D, Sawaya GF. Discontinuation of postmenopausal hormone therapy. Am J Med. 2005 Dec 19;118 Suppl 12B:163-5. doi: 10.1016/j.amjmed.2005.09.051.   Tapering vs. abrupt stop or hormonal therapy   Haimov-Kochman R et al. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Menopause. 2006 May-Jun;13(3):370-6. doi: 10.1097/01.gme.0000186663.36211.c0. PMID: 16735933.

This week, we present advances in the treatment of idiopathic pulmonary fibrosis, hypothalamic obesity, and lung cancer. We review nutrition in critical illness and follow a diagnostic case involving a patient who had a lung transplant. The Editors warn about the politicization of science. We discuss the dead donor rule in an era of voluntary euthanasia. Perspectives explore the forthcoming crisis in long-term care, reproductive medicine, and the realities of caring for loved ones at the end of life.

Mark Unruh is an associate professor of population health sciences at Weill Cornell Medical College. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. M.A. Unruh, V. Mor, and H.-Y. Jung. Colliding Forces — The Aging of the Baby Boom Generation and Contracting Nursing-Home Supply. N Engl J Med 2026;395:105-107. A.R. Olenski and D.C. Grabowski. Caring for an Aging America — The Looming Crisis of the Long-Term–Care Workforce. N Engl J Med 2026;395:107-110.

There is a fundamental link between diabetes and kidney care. But while there are many medications available to improve CKD outcomes in people with type 2 diabetes, the same options are not available for people with type 1. In this special episode, Dr. Neil Skolnik speaks with Janet McGill, MD, MA, FACE, FACP about the underdiscussed prevalence of CKD in type 1 and the importance of continued development in this area. This special episode is sponsored with support from Bayer. Please listen to the episodes by clicking on the podcast player below or by freely subscribing to Diabetes Core Update via Apple Podcasts, Amazon Music, Spotify, or your preferred podcast platform. Presented by: Neil Skolnik, MD, Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health Janet B. McGill, MD, MA, FACE, FACP, Professor of Medicine at the University of Washington's John T. Milliken Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research Selected References: Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026. The American Diabetes Association's Standards of Care 2026, Diabetes Care 2026;49 (Supplement_1):S246–S260 Finerenone in Type 1 Diabetes and Chronic Kidney Disease. N Engl J Med 2026;394:947-957 Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med 2020;383:2219-2229 Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020;383:1436-1446 Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med 2024;391:109-121

About our Guests: Fran Balamuth, MD, PhD, MSCE, is division chief of Pediatric Emergency Medicine at the Children's Hospital of Philadelphia. Dr. Balamuth's research interests focus on pediatric sepsis recognition using epidemiologic and translational approaches, for which she has received NIH and foundation funding. She is the co-PI of the PROMPT BOLUS trial, a multinational pragmatic trial comparing saline vs balanced fluids in pediatric sepsis, which will be the largest acute care pediatric trial in history. In addition, she co-leads the CHOP Pediatric Sepsis Program, which supports and promotes local clinical, research, educational, and quality-improvement initiatives related to sepsis. She is an internationally recognized sepsis leader, and has been invited to serve on the national steering committee for the Improving Pediatric Sepsis Outcomes quality collaborative through the US Children's Hospital Association, and 2 international task forces focused on defining pediatric sepsis through the US Centers for Disease Control and Prevention and the Society of Critical Care Medicine.Scott L. Weiss, MD, MSCE, FCCM, is a Professor of Pediatrics & Pathology and Genomic Medicine at Thomas Jefferson University and division chief of Critical Care Medicine at Nemours Children's Hospital, Delaware. Previously, Dr. Weiss was on the faculty at the Children's Hospital of Philadelphia, where he earned recognition as an international expert in pediatric sepsis. Dr. Weiss' NIH-funded research focuses on epidemiology, fluid resuscitation, and mitochondrial dysfunction in pediatric sepsis. Dr. Weiss is an international expert in pediatric sepsis and served as the co-PI of the PRoMPT BOLUS trial.Nathan Kuppermann, MD, MPH, is Executive Vice President and Chief Academic Officer of Children's National Hospital and Director of the Children's National Research Institute. He also serves as chair of the Department of Pediatrics and associate dean of Pediatric Academic Affairs at the George Washington University School of Medicine and Health Sciences. He is an internationally recognized clinical trialist in pediatric trauma, pediatric DKA, and acute pediatric infections. As the original chair of the Pediatric Emergency Medicine Applied Research Network (PECARN); his research is focused on clinical trials and clinical prediction rules using large cohorts of acutely ill and injured children. Dr. Kuppermann served as the senior investigator of the PRoMPT BOLUS trial.Selected References:Weiss SL, Balamuth F, Long E, Thompson GC, Hayes KL, Katcoff H, Cook M, Tsemberis E, Hickey CP, Williams A, Williamson-Urquhart S, Borland ML, Dalziel SR, Gelbart B, Freedman SB, Babl FE, Huang J, Kuppermann N; Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) Investigators of the PECARN, PERC, and PREDICT Networks. PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial. Trials. 2021 Nov 6;22(1):776. doi: 10.1186/s13063-021-05717-4. Erratum in: Trials. 2025 Oct 7;26(1):390. doi: 10.1186/s13063-025-09164-3. PMID: 34742327; PMCID: PMC8572061.Weiss SL, Balamuth F, Thurm CW, Downes KJ, Fitzgerald JC, Laskin BL. Major Adverse Kidney Events in Pediatric Sepsis. Clin J Am Soc Nephrol. 2019 May 7;14(5):664-672. doi: 10.2215/CJN.12201018. Epub 2019 Apr 18. PMID: 31000518; PMCID: PMC6500940.Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27. PMID: 29485925; PMCID: PMC5846085.Questions, comments or feedback? Please send us a message at this link (leave email address if you would like us to relpy) Thanks! -Alice & ZacSupport the showHow to support PedsCrit:Please complete our Listener Feedback SurveyPlease rate and review on Spotify and Apple Podcasts!Donations are appreciated @PedsCrit on Venmo , you can also support us by becoming a patron on Patreon. 100% of funds go to supporting the show.Please remember that all content during this episode is intended for educational and entertainment purposes only. It should not be used as medical advice. The views expressed during this episode by hosts and our guests are their own and do not reflect the official position of their institutions. If you have any comments, suggestions, or feedback-you can email us at pedscritpodcast@gmail.com.  You can also check out our website at http://www.pedscrit.com. Thank you for listening to this episode of PedsCrit!

This week, we discuss less-invasive approaches to guiding coronary intervention, new strategies for preventing kidney cancer recurrence, and head-to-head treatment data in multiple sclerosis. We review advances in multiple sclerosis, follow a diagnostic journey involving gait instability, and discuss correcting false narratives. Perspectives examine physicians and the body politic, chronic pain and OUD, and the often-overlooked burden of cognitive symptoms.

Justin Barr is a transplant surgeon at the Ochsner Clinic and a historian. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S.H. Podolsky, D.S. Jones, and J. Barr. Declarations of Independence — Physicians and the U.S. Body Politic, 1776–2026. N Engl J Med 2026;395:1-3.

In 2018, the ARIVE trial was published in the NEJM revealingthat induction of labor at 39 weeks reduced cesarean deliveries and gestational hypertension/preeclampsia in low-risk nulliparous women who had labor induced,compared to expectant management. Then, in 2025, and partly in response to L&D units across the country becoming saturated with low- risk, nulliparous patients awaiting their induction of labors at 39 weeks and 0 days, the ACOGreleased its clinical practice update in Jan 2025 stating, “The optimal timing of delivery for full-term pregnancies (39 0/7 to 40 6/7 weeks of gestation has not been determined”. Now there is new data, released as an article in press(June 26, 2026), out of the AJOG that raises some interesting questions about potential benefits of induction of labor LATER in the “full term” interval (40- 40 and 6 days) compared to earlier full term (39 weeks to 39 weeks 6 days). Thesefindings are “hypothesis- generating”.  Listen in for details. Strong Coffee Company - Protein Coffee PLUS MORE; Get 20%OFF | Promo Code: CHAPANOSPINOBG https://promocode.to/strong-coffee-company/chapanospinobg-hbv​     Grobman WA, Rice MM, Reddy UM, Tita ATN, et al;Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentMaternal–Fetal Medicine Units Network. Labor Induction versus ExpectantManagement in Low-Risk Nulliparous Women. N Engl J Med. 2018 Aug9;379(6):513-523. ​     Damri NT, Sheiner E, Wainstock T, GestationalAge at Full-Term Delivery and Long-Term Offspring Morbidity in Low-RiskPregnancies: A Population-Based Cohort Study, American Journal of Obstetricsand Gynecology (2026), ​     Management of Full-Term Nulliparous IndividualsWithout a Medical Indication for Delivery: ACOG Clinical Practice Update.Obstet Gynecol. 2025 Jan 1;145(1):e45-e50. doi: 10.1097/AOG.0000000000005783.Epub 2024 Nov 7. PMID: 39513607.

This week, we discuss a promising step toward a functional cure for chronic hepatitis B, first-line pulsed field ablation for persistent atrial fibrillation, reducing the demand for transfusion in surgery, treatment for rifampicin-resistant tuberculosis, and a decade-long look at CAR T-cell therapy outcomes. We review peanut allergy and discuss a case of a man with leg weakness, pain, and weight loss; Perspectives explore GLP-1 access, air-quality policy, and the human realities of homelessness.

Stacie Dusetzina is a professor of health policy and of cancer research at the Vanderbilt University School of Medicine. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S.B. Dusetzina. Access to GLP-1s for Medicare Beneficiaries — A Bridge to Nowhere? N Engl J Med 2026;394:2385-2387.

This week, we discuss endovascular therapy for post-thrombotic syndrome, new evidence on prehospital blood transfusion strategies in trauma patients, and a trial of cefazolin for Staph. aureus bacteremia. We examine evolving approaches to thyroid cancer and share a case of a man with pancytopenia after heart transplantation. Perspectives explore psychedelic therapy, the convergence of Down syndrome and Alzheimer's disease, and treating addiction.

Dr. Gillian L. Gordon Perue discusses asundexian and the OCEANIC-STROKE trial. Show citation:  Sharma M, Dong Q, Hirano T, et al. Asundexian for Secondary Stroke Prevention. N Engl J Med. 2026;394(15):1467-1479. doi:10.1056/NEJMoa2513880 

Marcus Hughes is an assistant professor of psychiatry at the Yale School of Medicine and an attending psychiatrist at Yale New Haven Psychiatric Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. M. Hughes. Psychedelic Therapies in the United States — Balancing State and Federal Oversight. N Engl J Med 2026;394:2281-2283. Y. Zisman-Ilani and R. Yehuda. Patient-Driven Care in Psychedelic Therapy. N Engl J Med 2026;394:2284-2286.

Join the Behind the Knife Surgical Oncology Team as we discuss clinical challenges through case-based examples including the diagnosis, workup, and management of patients with cutaneous melanoma. Learning Objectives:In this episode, we review the workup and management of patients with cutaneous melanoma and both microscopic and macroscopic nodal disease. References used in the making of this episode: Reijers, I.L.M., Menzies, A.M., van Akkooi, A.C.J. et al. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial. Nat Med 28, 1178–1188 (2022). https://doi.org/10.1038/s41591-022-01851-x Christian U. Blank et al. Neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in macroscopic, resectable stage III melanoma: The phase 3 NADINA trial.. J Clin Oncol 42, LBA2-LBA2(2024). DOI:10.1200/JCO.2024.42.17_suppl.LBA2 Faries MB, Thompson JF, Cochran AJ, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017;376(23):2211-2222. doi:10.1056/NEJMoa1613210   https://pubmed.ncbi.nlm.nih.gov/28591523/ National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma. Version 1.2026. Accessed April 8, 2026. NCCN Guidelines PDF   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: https://behindtheknife.org/premiumOral Board Review: https://behindtheknife.org/oral-boardOral Board Simulator: https://behindtheknife.org/oral-board/simulatorGeneral 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-reviewColorectal Surgery Oral Board Review Course: https://behindtheknife.org/premium/colorectal-surgery-oral-board-reviewSurgical Oncology Oral Board Review Course: https://behindtheknife.org/premium/surgical-oncology-oral-board-reviewCardiothoracic Oral Board Review Course: https://behindtheknife.org/premium/cardiothoracic-surgery-oral-board-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

This week, we present new evidence guiding coronary intervention, a molecular mechanism of inflammatory bowel disease, and gene therapy for a recessive disease. We review antidotes for anticoagulation reversal and discuss a case of hypertension in an adolescent patient. Perspectives examine cholera control, gambling-related harms, and race-based prescribing, alongside a reflection on medicine, motherhood, and what clinicians carry with them.

Edward Ryan is the director of global infectious diseases at Massachusetts General Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. E.T. Ryan, F. Qadri, and J.A. Lynch. Global Cholera-Control Efforts — Progress and Remaining Challenges. N Engl J Med 2026;394:2177-2180.

Whole blood is the current bright, shiny thing in EMS medicine. It works in the hospital and is what our patients are bleeding out onto the road so it just seems to make sense that we should put back what they're loosing. But… is it any better than blood components? That's the question the authors of TOWAR tried to answer. One of those authors, Dr Frank Guyette, joins us for a two episode interview about this trial and about trials in general. Dr Guyette is an EM and EMS physician, medical director for STATMedEvac, and Professor of Emergency Medicine at University of Pittsburgh. He is also a research leaders with the LITES network, the parent network for the TOWAR trial. We discuss the challenges of conducting large, multi-center randomized controlled trials in episode I, including funding and the ethics of prehospital research. In episode II, we'll jump into the details of the TOWAR trial itself.Reference:1. Sperry JL, Guyette FX, Cotton BA, et al.: Prehospital Resuscitation with Type O Whole Blood for Trauma and Hemorrhage. N Engl J Med. doi: 10.1056/NEJMoa2602167 (Epub ahead of print).

This week, we discuss left atrial appendage closure for atrial fibrillation, oxygen strategies in respiratory failure, an all-oral treatment for acute myeloid leukemia, CAR T-cell therapy enabling kidney transplantation, and a case of a neuroepithelial tumor that developed after gene therapy. We review childhood vaccine hesitancy, follow a complex diagnostic case, and examine Perspectives on corporatization in medicine, famine and war, and the future of health care systems.

Loren Adler is a fellow and the associate director at the Center on Health Policy at the Brookings Institution. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. L. Adler. Regulating Corporate Control in the U.S. Health Care System. N Engl J Med 2026;394:2073-2076.

Dr. Margarita Fedorova discusses the effectiveness of shunting for idiopathic normal pressure hydrocephalus.  Show citation:  Luciano MG, Williams MA, Hamilton MG, et al. A Randomized Trial of Shunting for Idiopathic Normal-Pressure Hydrocephalus. N Engl J Med. 2025;393(22):2198-2209. doi:10.1056/NEJMoa2503109   Show transcript:  Dr. Margarita Fedorova: Welcome to Neurology Minute. My name is Margarita Fedorova and I'm a neurology resident at the Cleveland Clinic. Today we're reviewing a randomized trial that provides high quality evidence for treatment we've been using for decades, shunting for idiopathic normal pressure hydrocephalus. The PENS trial, a placebo controlled effectiveness and iNPH shunting trial was published in the New England Journal of Medicine in December 2025 by Luciano and colleagues. This international multicenter study enrolled 99 patients across the United States candidate in Sweden. While idiopathic normal pressure hydrocephalus or iNPH is characterized by triad of gait impairment, cognitive decline in urinary continence, these findings can be non-specific and we mass factor in radiological findings too. Furthermore, while CSF shunting has long been the standard treatment, its effectiveness has never been rigorously confirmed in a large well-powered randomized trial. In this trial, patients with a clinical improvement in gait velocity after temporary CSF drainage were deemed eligible for shunting and randomizing the trial. What makes this trial particularly elegant is its blending strategy. All 99 participants underwent the same surgical procedure with the same commercially available programmable shunt valve. After surgery, the valve was set either to an open functioning position or to a high resistance placebo setting. Neither patients nor assessors knew who had a working shunt. This is about as close to a true double-blind design as neurosurgery can get. The primary outcome was changing gait velocity at three months. The open shunt group improved by 0.23 meters per second on average, while the placebo group showed essentially no change in 0.03 meters per second. That's a treatment difference of 0.21 meters per second, both statistically significant and clinically meaningful. To put that in perspective, a change of 0.10 meters per second is considered the threshold for substantial meaningful change in the elderly. 80% of the open shunt group exceeded that threshold compared to only 24% of the placebo group.  The Tenet scale, which measures gait imbalance, also showed significant improvement in the open shunt group. However, screening measures for good condition using the MoCA scale and bladder symptoms did not reach significance at three months, though tertiary outcomes for cognitive testing, quality of life and functional independence tended in favor of shunting. Importantly, falls were more common in the placebo group at 46% compared to 25% in the open shunt group. This is a meaningful safety signal given how dangerous falls are in older adults. There were also real risks with active shunting. Subdural hematomas occurred in 12% of the open shunt group versus 2% of placebo and three even required surgical intervention. Positional headaches from low CSF pressure were more common in the open shunt group at 59% versus 28%. The good news is that the adjustable valve allowed non-invasive management of many of these complications. While this trial gives us reasons to be cautiously optimistic about shunting for appropriately selected iNPH patients, it's worth noting that we only have evidence for improvement in gait and follow-up is only three months.  Longer-term data is still being collected so we don't know yet how durable these benefits are. If you want to read more, please find the paper by Mark G. Luciano, et al. It's titled A Randomized Trial of Shunting for Idiopathic Normal Pressure Hydrocephalus published in the New England Journal of Medicine in December 2025. That's your neurology menu for today. Keep exploring and we'll see you next time. 

Dr. Casandra MacLeod discusses central retinal artery occlusions, recent trials, and those anticipated in the future.  Show citation:  Préterre C, Gaultier A, Obadia M, et al. Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4·5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial. Lancet Neurol. 2025;24(11):909-919. doi:10.1016/S1474-4422(25)00308-4  Poli S, Grohmann C, Wenzel DA, et al. Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial. Int J Stroke. 2024;19(7):823-829. doi:10.1177/17474930241248516  Ryan SJ, Jørstad ØK, Skjelland M, et al. A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. N Engl J Med. 2026;394(5):442-450. doi:10.1056/NEJMoa2508515 Show transcript:  Dr. Casandra MacLeod Hello, this is Casandra MacLeod, a neurology resident at Cleveland Clinic with today's Neurology Minute. Today we will be discussing central retinal artery occlusions, or CRAOs, and the recent trials that have come out and even those further on the horizon. The 2026 American Heart Association and American Stroke Association guidelines for the early management of patients with acute ischemic stroke were recently published and in them highlight the uncertainty around the treatment of acute CRAOs with intravenous thrombolysis, even when the patient presents within four and a half hours and is otherwise eligible. These guidelines come after two recent trials, which we will further discuss. The thrombolysis in patients with acute central retinal artery occlusion, or the THEIA trial, was published in the November issue of Lancet Neurology. This multicenter trial out of France randomized 70 patients with acute CRAOs presented within four and a half hours of time from last known well to either receive IV alteplase and oral placebo or IV placebo and oral aspirin. While safety measures showed no symptomatic hemorrhage event, although they did have one asymptomatic intracerebral hemorrhage occur, the primary outcomes, which included visual acuity improvement at one month, showed some evidence for a trend of improved acuity in the IV thrombolytic group at 66% compared to 48 in the aspirin group, it did not reach significant. And now more recently, the Tenecteplase in central retinal artery occlusion study, or TenCRAOs, was published in the January 2026 issue of The New England Journal of Medicine. TenCRAOs was a six European country multicenter trial that randomized 78 patients with CRAOs all presenting within four and a half hours of time from last known well to either receive IV Tenecteplase or aspirin, both with placebo-matching as in THEIA. The primary outcomes of TenCRAOs also included visual acuity at one month, but unfortunately this trial also did not show [inaudible 00:02:07]. They showed 20% in the IV TNK group compared to 24% in aspirin. And additionally, there was one fatal intracerebral hemorrhage in the TNK group that should be considered. Overall, the AHA and ASA guidelines state the usefulness of treatment with intravenous thrombolysis is uncertain. And this is based largely on these studies as neither trial showed improved visual recovery. Although both of these trials are underpowered, leading many to believe that the jury is still out on the use of IV thrombolytics in CRAOs. But importantly, stay on the lookout for one last trial. The early reperfusion therapy with intravenous alteplase for recovery of vision and acute central retinal artery occlusion, or the Revision trial, is actively recruiting. Revision is similar in design as THEIA, but with a goal of up to 422 total patients for a goal of a well-powered study to guide decision making. 

MCAS is one of those diagnoses that can make it feel like your body is telling a dozen stories at once—and no one is listening. If you're experiencing GI symptoms alongside flushing, hives, brain fog, fatigue, palpitations, medication sensitivities, or a persistent "fight-or-flight" feeling, this episode is designed to help connect the dots without oversimplifying your experience.In this episode, we sit down with gastroenterologist Dr. Zachary Spiritos to unpack mast cell activation syndrome (MCAS) and explore the connections between immune activation, the gut-brain axis, and symptoms that can affect nearly every system in the body. We discuss why patients are often dismissed, how stress and hormonal changes can amplify symptoms, and what a realistic, stepwise treatment approach looks like when the evidence base is still evolving.In this episode, we discuss:• What mast cells do and why MCAS can affect multiple organ systems • Why MCAS is often missed in siloed medical care and mislabeled as anxiety • Barrier dysfunction, environmental triggers, and intestinal permeability as a useful framework • Histamine as one mediator among many and why antihistamines are not a perfect treatment for all• Links between MCAS, IBS, visceral hypersensitivity, dysautonomia, and POTS • Hypermobility, pelvic floor dysfunction, and neck tension as common clinical clues • Treatment principles including start low and go slow, informed consent, and layered individualized plans • Dietary approaches patients commonly explore, including low-histamine, low-FODMAP, and gluten-free patterns • Hormonal influences across the menstrual cycle and during perimenopause• The role of sleep, nervous system regulation, and stress reduction in decreasing symptom reactivity If you've ever felt like your symptoms don't fit neatly into a single diagnosis, this episode will help you make sense of the bigger picture and explore what healing can look like when the gut, immune system, and nervous system are all part of the conversation. References:Ford AC, Staudacher HM, Talley NJ. Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target. Gut. 2024;73(7):1199-1211. Published 2024 Jun 6. doi:10.1136/gutjnl-2023-331833Walker MM, Warwick A, Ung C, Talley NJ. The role of eosinophils and mast cells in intestinal functional disease. Curr Gastroenterol Rep. 2011;13(4):323-330. doi:10.1007/s11894-011-0197-5Pasricha PJ, Talley NJ. Functional Dyspepsia. N Engl J Med. 2026;394(2):166-176. doi:10.1056/NEJMcp2501860Find Dr. Spiritos on IG @drzacspiritosSo please like and subscribe and share the gut health podcast. Don't forget to subscribe, rate, and leave us a comment. Learn more about Kate and Dr. Riehl:Website: www.katescarlata.com and www.drriehl.comInstagram: @katescarlata @drriehl and @theguthealthpodcastOrder Kate and Dr. Riehl's book, Mind Your Gut: The Science-Based, Whole-body Guide to Living Well with IBS.  The information included in this podcast is not a substitute for professional medical advice, examination, diagnosis or treatment.  Always seek the advice of your physician or other qualified health care provider before starting any new treatment or making changes to existing treatment.

This week, we present new research guiding treatment of pulmonary embolism, early progress in cardiac regeneration with engineered heart tissue, and treatments for gastroesophageal cancer and Chiari malformation. We review leishmaniasis and follow a revealing neurologic case. Perspectives discuss nutrition policy, tickborne illness, structural competence in medicine, and the arrival of closure.

Deirdre Tobias is an associate professor in the Department of Nutrition at the Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. D.K. Tobias and F.B. Hu. The 2025–2030 Dietary Guidelines for Americans — Progress, Pitfalls, and the Path Forward. N Engl J Med 2026;394:1969-1971.

Whole blood is the current bright, shiny thing in EMS medicine. It works in the hospital and is what our patients are bleeding out onto the road so it just seems to make sense that we should put back what they're loosing. But… is it any better than blood components? That's the question the authors of TOWAR tried to answer. One of those authors, Dr Frank Guyette, joins us for a two episode interview about this trial and about trials in general. Dr Guyette is an EM and EMS physician, medical director for STATMedEvac, and Professor of Emergency Medicine at University of Pittsburgh. He is also a research leaders with the LITES network, the parent network for the TOWAR trial. We discuss the challenges of conducting large, multi-center randomized controlled trials in episode I, including funding and the ethics of prehospital research. In episode II, we'll jump into the details of the TOWAR trial itself.Reference: 1. Sperry JL, Guyette FX, Cotton BA, et al.: Prehospital Resuscitation with Type O Whole Blood for Trauma and Hemorrhage. N Engl J Med. doi: 10.1056/NEJMoa2602167 (Epub ahead of print).

Eric Rubin is the Editor-in-Chief of the Journal. Lindsey Baden is a Deputy Editor of the Journal. Angela Hewlett is Director of the Nebraska Biocontainment Unit. Steven Kornfeld is a physician who was a passenger on the MV Hondius. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. E.J. Rubin and Others. NEJM Outbreaks Update — Andes Hantavirus. N Engl J Med. DOI: 10.1056/NEJMe2505379.

This week, we present a promising new therapy for dermatomyositis, evolving approaches to stroke care, the prevention of Covid-19 after household exposure, and new treatments for kidney disease. We review inflammatory myopathies and follow a complex case of multisystem illness. Perspectives discuss AI and uncertainty in clinical care, health equity, the forces shaping affordability in health care, and on unpacking the ordinary.