Podcasts about The New England Journal of Medicine

Featuring articles on routine cerebral embolic protection for TAVI, and treatments for cirrhosis due to MASH, BRAF V600E metastatic colorectal cancer, and Pompe's disease; a new review article series on medical education; a case report of a woman with dyspnea on exertion; and Perspectives on addressing ultraprocessed foods, on the costs of dismantling DEI, and on a brother's keeper.

Dariush Mozaffarian is the director of the Food is Medicine Institute at the Friedman School of Nutrition Science and Policy at Tufts University and a professor of medicine at Tufts University School of Medicine. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. D. Mozaffarian. Regulatory Policy to Address Ultraprocessed Foods. N Engl J Med 2025;392:2393-2396.

Featuring articles on mismatch repair–deficient tumors, generalized myasthenia gravis, HER2-mutant non–small-cell lung cancer, a Corynebacterium diphtheriae outbreak, and hereditary and sporadic papillary kidney cancer; a review article on unruptured intracranial aneurysms; a case report of a man with respiratory failure and shock after kidney transplantation; and Perspectives on medical AI and clinician surveillance, on pathobiology, and on unrest.

I. Glenn Cohen is a professor of law and deputy dean at Harvard Law School and faculty director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard University. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. I.G. Cohen, I. Ajunwa, and R.B. Parikh. Medical AI and Clinician Surveillance — The Risk of Becoming Quantified Workers. N Engl J Med 2025;392:2289-2291.

Train the Best. Change EMS.Howdy, y'all, I'm Dr Jeff Jarvis, and I'm the host of the EMS lighthouse project podcast, but I'm also the medical director for the new EMS system we're building in Fort Worth Texas. We are looking for an experienced critical care paramedic who is an effective and inspiring educator to lead the initial and continuing training and credentialing of a new team of Critical Care Paramedics who will be responding to our highest acuity calls. The salary is negotiable but starts between $65,000 and $80,000 a year for this office position. Whether y'all wear cowboy boots or Birkenstocks, Fort Worth can be a great place to live and work. So if you're ready to create a world-class EMS system and change the EMS world with us, give us a call at 817-953-3083, take care y'all.The next time you go to intubate a patient, should you give the sedation before the paralytic or the paralytic before the sedative? Does it matter? And what the hell does Bayes have to do with any of this? Dr Jarvis reviews a paper that uses Bayesian statistics to calculate the association between drug sequence and first attempt failure. Then he returns to Nerd Valley to talk about how to interpret 95% confidence intervals derived from frequentists statistics compared to 95% credible intervals that come from Bayesian statistics. Citations:1.     Catoire P, Driver B, Prekker ME, Freund Y: Effect of administration sequence of induction agents on first‐attempt failure during emergency intubation: A Bayesian analysis of a prospective cohort. Academic Emergency Medicine. 2025;February;32(2):123–9. 2.     Casey JD, Janz DR, Russell DW, Vonderhaar DJ, Joffe AM, Dischert KM, Brown RM, Zouk AN, Gulati S, Heideman BE, et al.: Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2019;February 28;380(9):811–21.3.     Greer A, Hewitt M, Khazaneh PT, Ergan B, Burry L, Semler MW, Rochwerg B, Sharif S: Ketamine Versus Etomidate for Rapid Sequence Intubation: A Systematic Review and Meta-Analysis of Randomized Trials. Critical Care Medicine. 2025;February;53(2):e374–83.

Featuring articles on treatments for pulmonary fibrosis, for obesity and overweight, for severe hemophilia B, and for a rare genetic disease; a review article on malnutrition in older adults; a case report of a man with a nasopharyngeal mass; a Medicine and Society on John Collins Warren; and Perspectives on undermining women's health research, on addressing antifungal drug resistance, and on conversations that matter in maternal medicine.

Amanda Kallen is an associate professor in the Division of Reproductive Endocrinology and Infertility at the University of Vermont Larner College of Medicine and an adjunct professor at the Yale School of Medicine. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A.N. Kallen and Others. Undermining Women's Health Research — Gambling with the Public's Health. N Engl J Med 2025;392:2185-2187.

N Engl J Med 2001;345:1667-1675Background: Angiotensin II is a peptide hormone that is part of the renin–angiotensin–aldosterone system (RAAS). Angiotensin II is a potent vasoconstrictor and growth-stimulating hormone. Data suggested that it plays a role in ventricular remodeling and progression of heart failure. Although treatment with angiotensin-converting enzyme inhibitors (ACEi) reduce angiotensin II levels, physiologically active levels of angiotensin II may persist despite long-term therapy.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Valsartan Heart Failure Trial (Val-HeFT) sough to assess whether the angiotensin-receptor blocker valsartan, could reduce mortality and morbidity when added to optimal medical therapy in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction less than 40% and left ventricular dilation, in addition to having clinical heart failure for at least 3 months with NYHA class II, III or IV symptoms. Patient also had to have been receiving a fixed-dose drug regimen for at least two weeks, that could include ACEi, diuretics, digoxin, and beta-blockers.There were many exclusion criteria. We mention some here: Postpartum cardiomyopathy, acute myocardial infarction within 3 months, coronary artery disease likely to require intervention, serum creatinine >2.5 mg/dL and life expectancy less than 5 years.Baseline characteristics: Patients were recruited from 302 centers in 16 countries. The trial randomized 5,010 patients – 2,511 randomized to receive valsartan and 2,499 to receive placebo.The average age of patients was 63 years and 80% were men. The average left ventricular ejection fraction was 27%. Cardiomyopathy was ischemic in 57% of the patients. The NYHA class was II in 62% of the patients, III in 36% of the patients and IV in 2%.Approximately 26% had diabetes and 12% had atrial fibrillation.At the time of enrollment, 86% were taking a diuretic, 67% were taking digoxin, 35% were taking beta-blockers, and 93% were taking ACEi.Procedures: The trial was double-blinded. The trial had an initial run-in period for 2 - 4 weeks where patients received placebo twice daily. This was performed to confirm patients' eligibility, clinical stability and compliance.Patients were assigned in a 1:1 ratio to receive valsartan or placebo. Randomization was stratified according to whether or not they were receiving a beta-blocker.Valsartan was started at a dose of 40 mg twice a day, and the dose was doubled every two weeks to the target dose of 160 mg twice a day. Placebo doses were adjusted in a similar way.Follow up occurred at 2, 4, and 6 months and every 3 months thereafter.Endpoints: The trial had two primary end points. The first was all-cause mortality. The second was the combined end point of mortality and morbidity, which was defined as cardiac arrest with resuscitation, hospitalization for heart failure, or administration of intravenous inotropic or vasodilator drugs for four hours or more without hospitalization.The estimated sample size was 5,000 patients. The sample size calculation assumed 20% relative risk reduction in mortality with valsartan assuming 906 patients would die during the trial. This sample size would provide the trial 90% power at 0.02 alpha. Alpha was 0.02 instead of the traditional 0.05 since the trial had two primary endpoints and to adjust for the interim analyses.Results: The target valsartan dose of 160 mg twice a day was achieved in 84% of the patients. The reduction in systolic blood pressure was greater with valsartan vs placebo – mean of 5.2 ± 15.8 mm with valsartan compared to 1.2 ± 14.8 mm Hg with placebo, at 4 months.All-cause mortality was not different between both groups (19.7% with valsartan vs 19.4% with placebo, RR: 1.02, 95% CI: 0.88 – 1.18; p= 0.80). The second co-primary endpoint was reduced with valsartan (28.8% vs 32.1%, RR: 0.87, 95% CI: 0.77 – 0.97; p= 0.009). This was driven by reduction in hospitalizations for heart failure (13.8% vs 18.2%). Cardiac arrest with resuscitation was 0.6% with valsartan and 1.0% with placebo. All-cause hospitalization was numerically lower with valsartan, however, this was not statistically significance (2,856 vs 3,106; p= 0.14). The mean change in ejection fraction was higher with valsartan (4.0% vs 3.2%; p= 0.001). More patients had improvement in NYHA classification with valsartan (23.1% vs 20.7%; p

Featuring articles on metabolic dysfunction–associated steatohepatitis, lung nodules, breast cancer, and improving birth outcomes; a review article on hemoglobinopathies; a Clinical Problem-Solving on from where it stems; and Perspectives on U.S. research leadership at a crossroads, on health care in an evolving immigration landscape, and on carrying hope while facing a crisis.

Watch the NEJM In Studio video of this interview at NEJM.org. David Jones is the Ackerman Professor of the Culture of Medicine at Harvard University. Harleen Marwah, the interviewer, is an Editorial Fellow at the Journal. W. Xue and D.S. Jones. Debating Race and the Diagnosis of Anemia — How Medicine Moved Away from Race-Based Standards. N Engl J Med 2025;392:2168-2173.

Amar Kelkar is a physician at the Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A.H. Kelkar. U.S. Research Leadership at a Crossroads — The Impact of Reducing NIH Indirect-Cost Coverage. N Engl J Med 2025;392:2081-2084.

N Engl J Med 2001;344:1651-1658Background: The MERIT-HF trial demonstrated the efficacy of the selective beta blocker metoprolol CR/XL for well selected patients with chronic systolic heart failure who were on optimal therapy with an ACEi and diuretic. The trial randomized nearly 4,000 patients and was stopped early due to the benefit of the drug on all-cause mortality but it also reduced major morbidity as indicated by significant reductions in hospitalization. It represented the first large scale trial to show a morbidity and mortality benefit for beta blockers in patients with chronic systolic heart failure. Prior to MERIT-HF, the nonselective beta blocker carvedilol reduced morbidity and mortality in a smaller trial of patients with chronic stable heart failure. Limitations of the trial included its size and the fact that it was not originally designed to test mortality. Furthermore, it was stopped early without clearly prespecified stopping rules and 8% of total patients selected for participation in the trial were excluded prior to randomization after a 2 week, open-label run-in phase with the study drug. During the run-in period, 24 patients (2%) experienced worsening heart failure or death and were excluded from participation in the trial - the difference in total deaths between groups was 9 when the trial was stopped. In our opinion, the results of this trial were far from definitive and there are theoretical reasons why selective and nonselective beta blockers could have different effects on cardiac outcomes.The primary difference between selective and nonselective beta blockers lies in their specificity of action; while both types block adrenaline from binding to beta receptors on nerves, selective beta blockers primarily affect those found in the heart whereas nonselective ones also impact those located in the lungs and blood vessels. In the lungs, adrenaline causes bronchodilation and in the blood vessels, vasoconstriction. Thus, nonselective beta blockers also reduce afterload, which can improve cardiac hemodynamics in the failing heart.The Carvedilol Prospective Randomized Cumulative Survival Study was a large-scale trial that sought to test the hypothesis that the nonselective beta blocker carvedilol reduces mortality in patients with chronic stable heart failure who are on optimal treatment.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: Patients with “severe chronic heart failure” were recruited from 334 sites in 21 countries. Severe chronic heart failure was defined by the presence of dyspnea or fatigue at rest or on minimal exertion for at least 2 months and a LVEF of

Featuring articles on pulmonary arterial hypertension, oral semaglutide and cardiovascular outcomes, giant-cell arteritis, the loss of subsidized drug coverage and mortality, and neutralizing venom toxins; a review article on cancer of unknown primary site; a case report of a man with fever, nausea, and respiratory failure; and Perspectives on primary care and the free market, federal cuts at the VA, the GINA gap, and the meaning of goodbye.

Zirui Song is an associate professor of health care policy and medicine at Harvard Medical School and a general internist at Massachusetts General Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. Z. Song and J.M. Zhu. Primary Care — From Common Good to Free-Market Commodity. N Engl J Med 2025;392:1977-1979.

Making strides against melanoma: how can medical oncologists and interventional oncologists join forces to deliver smarter, patient-centered care? In this episode of BackTable, Dr. Tyler Sandow, hosts Dr. Sunandana Chandra, medical oncologist at Northwestern, and Dr. Riad Salem, interventional oncologist at Northwestern to discuss the evolving management of advanced melanoma. --- This podcast is supported by an educational grant from Replimune. --- SYNPOSIS The doctors open the episode with an overview of melanoma and recent advances in its treatment, highlighting key trials such as DREAMseq and CheckMate 067. The discussion explores the shift from medical oncologist as solo primary providers to a dynamic, multidisciplinary approach to advanced cancer care—emphasizing cutting-edge treatments like immunotherapy and intratumoral oncolytic viruses. Dr. Salem shares practical insights on the procedural techniques of administering intratumoral oncolytics like Replimune, emphasizing the importance of thorough documentation and patient-centered care. The doctors also provide an overview of the ongoing IGNYTE-3 Trial, a Phase 3 study assessing the safety and efficacy of the oncolytic immunotherapy RP1 in combination with nivolumab for the treatment of advanced melanoma. The episode underscores the transformative potential of innovative melanoma treatments and the crucial role of integrated, team-based approaches in improving cancer patient outcomes. --- TIMESTAMPS 00:00 - Introduction03:48 - The Evolution of Melanoma Treatment: From Chemotherapy to Immunotherapy14:05 - The Role of Oncolytic Viruses in Melanoma Treatment20:14 - Interventional Radiology's Role in Cancer Treatment27:00 - Collaborative Approach to Cancer Care32:53 - Hyper Documentation and Communication Efficiency44:47 - Future of Intratumoral Oncolytics48:10 - Multidisciplinary Approach in Advanced Cancer Management51:46 - Conclusion and Final Thoughts --- RESOURCES DREAMseq Trial: Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. doi:10.1200/JCO.22.01763 CheckMate 067 trial: Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22. doi:10.1056/NEJMoa2407417

N Engl J Med 1999;341:709-717Background: The renin–angiotensin–aldosterone system (RAAS) is activated in patients with systolic heart failure. While this activation initially helps increase blood volume and maintains blood pressure, chronic activation promotes cardiac fibrosis and remodeling. In patients with systolic heart failure, inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEi) significantly reduced mortality and morbidity, as seen in the CONSENSUS and SOLVD trials.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Preliminary data suggested that adding the aldosterone-receptor blocker spironolactone to ACEi, reduced the levels of atrial natriuretic peptide and did not lead to serious hyperkalemia.The Randomized Aldactone Evaluation Study (RALES) sought to test the hypothesis that spironolactone would significantly reduce the risk of all-cause death in patients with severe systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 35% or less, had NYHA class IV heart failure within the 6 months before enrollment and NYHA class III or IV at the time of enrollment, and were treated with ACEi (if tolerated) and a loop diuretic.Patients were excluded if they had primary operable valvular disease (other than mitral or tricuspid regurgitation), congenital heart disease, unstable angina, primary liver failure, active cancer or any life-threatening condition, other than heart failure, prior heart transplant or awaiting heart transplant, serum creatinine >2.5 mg/dL, or serum potassium > 5.0 mmol/L.Baseline characteristics: Patients were recruited from 195 centers in 15 countries. The trial randomized 1,663 patients – 822 randomized to receive spironolactone and 841 to receive placebo.The average age of patients was 65 years and 73% were men. The average left ventricular ejection fraction was 25%. Cardiomyopathy was ischemic in 55% of the patients and non-ischemic in the rest. The NYHA class was III in 71% of the patients and IV in 29%.Data on baseline comorbid conditions were not provided.At the time of enrollment, 100% were taking loop diuretics, 94% were taking ACEi, 73% were taking digitalis, and 10% were taking beta-blockers. The mean daily dose of ACEi were as following: 63mg for captopril, 15mg for enalapril, and 14mg for lisinopril.Note: Max daily dose is 450mg for captopril, 40mg for enalapril, and 40mg for lisinopril.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive spironolactone 25mg PO daily or placebo.The dose could be increased to 50mg daily after 8 weeks of treatment, If the patient had worsening heart failure and had no evidence of hyperkalemia. In the event of hyperkalemia, the dose could be lowered to 25 mg every other day. Laboratory testing including potassium were performed every 4 weeks for the first 12 weeks, then every 3 months for up to 1 year and every 6 months thereafter until the end of the study.Endpoints: The primary outcome was all-cause death. Secondary end points included death from cardiac causes, hospitalization for cardiac causes and change in the NYHA class.Analysis was performed based on the intention-to-treat principle. The planned sample size was not mentioned in the methods. However, the results mention that recruitment was complete. The sample size calculation assumed 38% mortality rate in the placebo group and that spironolactone would reduce mortality by 17% (relative risk reduction). The power of the study was set at 90% with a two-sided alpha of 5%.Results: Recruitment was complete in Dec, 1996 with follow up planned through Dec, 1999. However, the study was stopped early on Aug, 1998 after interim analysis showed significant reduction in mortality with spironolactone. The mean follow up time was 24 months. After 24 months of follow up, the mean daily dose of spironolactone was 26 mg.Spironolactone reduced all-cause death (35% vs 46%, RR: 0.70, 95% CI: 0.60 - 0.82; p< 0.001). Death from cardiac causes was also reduced with spironolactone (27% vs 37%, RR: 0.69, 95% CI: 0.58 - 0.82; p

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Imlunestrant with or without abemaciclib in advanced breast cancer: Results of the Phase III EMBER-3 trial (0:00) Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract  Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the Phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1 and PTEN in HR-positive, HER2-negative metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice (7:00) Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat 2024;207(3):599-609. Abstract Camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), versus fulvestrant for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomized, Phase II trial (10:25) Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract Latest on SERDs: An education session at San Antonio Breast Cancer Symposium 2024 (13:57) Jeselsohn RM. Latest on selective estrogen receptor degraders (SERDs). San Antonio Breast Cancer Symposium 2024;Education Session 5. CME information and select publications

N Engl J Med 1997;336:525-33Background: Digoxin is a natural drug that comes from the Foxglove plant (Digitalis purpurea). It has been used for the treatment of congestive heart failure for over 200 years. At the time this trial was undertaken, it was given to the overwhelming majority of patients with severe congestive heart failure. The percentage of patients on digoxin was over 90% in all of the seminal heart failure trials we have reviewed thus far. However, despite its frequent use, it was unknown whether the drug improved major morbidity or mortality, and new drug classes were emerging with positive effects on hard outcomes. The primary aim of the Digitalis Investigation Group was to design a large, pragmatic trial to test the long-term effect of digoxin versus placebo on all-cause mortality as well as hospitalization for heart failure.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: The study enrolled 6,800 patients with congestive heart failure and an EF of 45% in an ancillary trial. The patient population in the trial was intended to be diverse with no upper age limit. If patients were already on an ACE inhibitor, and had been stable for at least 2 weeks, they could be randomized immediately. For patients not on an ACE inhibitor, they were prescribed the drug and reevaluated in 2 weeks, at which time they could be randomized, if stable. Patients could be randomized into the trial whether they were taking digoxin or not and there was no washout phase.Important exclusion criteria included an MI, cardiac surgery or percutaneous coronary intervention within 4 weeks; unstable or refractory angina for less than 1 month; 2nd or 3rd degree AV block or sick sinus syndrome without a pacemaker; atrial fibrillation or atrial flutter; cor pulmonale; acute myocarditis; amyloid cardiomyopathy; hypertrophic cardiomyopathy; complex congenital heart disease; current treatment with IV inotropes; potassium 5.5 mmol/L; need for cardiac surgery or percutaneous coronary intervention in near future; patients on heart transplant list; severe kidney (Cr >3.0 mg/dL) or liver disease; any non-cardiac disease that shortens life-expectancy to

Norton Healthcare's Parenting With You is the podcast that helps you keep your kids healthy and safe by providing practical, down to earth advice for parents of children of any age, from babies through the teen years. In this Episode: Revisting the Measles Unfortunately, the measles has been back in the news recently. In this episode our host, Dr Erin Frazier, speaks with pediatric infectious disease specialist Dr. Kristina Bryant. During the conversation, Dr's Frazier and Bryant cover all the ground parents need to know today regarding the measles. During today's discussion, a couple of research studies were mentioned: Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J, Melbye M. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. 2002 Nov 7;347(19):1477-82. doi: 10.1056/NEJMoa021134 Hviid A, Hansen JV, Frisch M, Melbye M. Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study. Ann Intern Med. 2019 Apr 16;170(8):513-520. doi: 10.7326/M18-2101.   About Norton Children's Center for Prevention and Wellness A healthy kid is a happy kid. Norton Children's Prevention & Wellness provides resources to help you and your child build healthy habits. Established in 1991, the Office of Child Advocacy of Norton Children's Hospital, now Norton Children's Prevention & Wellness, takes an active leadership role in teaching healthy habits in children, including injury prevention and educating children and their families on healthy lifestyle choices. Advocacy and outreach educational programs are at the heart of the Norton Children's mission. Norton Children's Prevention & Wellness is funded through donations to the Norton Children's Hospital Foundation. Our efforts are focused around: ·      Safety and injury prevention ·      Promoting healthy lifestyles ·      Key community partnerships ·      Government relations Norton Children's Prevention and Wellness Classes:  https://nortonchildrens.com/prevention-wellness/classes-events/ Find a pediatrician go to https://nortonchildrens.com/locations/pediatrician-offices/  or call 502-629-KIDS, option 3.

Featuring articles on multiple sclerosis, narcolepsy type 1, antiretroviral therapy in children with HIV, and porcine kidney xenotransplantation; a review article on Ph-positive acute lymphoblastic leukemia; a case report of a woman with peritonsillar swelling and bleeding; and Perspectives on the power of physicians in dangerous times, on community health centers, on AI-driven clinical documentation, and on driving Jackson.

Alice Chen is a primary care internist in Washington, DC, and former executive director of Doctors for America. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A.T. Chen and V.H. Murthy. The Power of Physicians in Dangerous Times. N Engl J Med 2025;392:1873-1875.

N Engl J Med 1996;334:1349-1355Background Before 1990, the prevailing idea held that the negative inotropy of beta-blockers would harm patients with impaired systolic function. Yet part of the progression of systolic heart failure involved over stimulation of the sympathetic nervous system. Norepinephrine can exert adverse effects on the circulation, both directly and indirectly. Smaller trials of beta-blockers in systolic heart failure found trends for benefit with beta-blockers, however, a mortality benefit had not yet been proven. The U.S. Carvedilol Heart Failure Study aimed to study mortality in patients with heart failure with a reduced ejection fraction.Cardiology Trial's Substack remains free of industry ads because of your support. Thank you. Please consider becoming a free or paid subscriber.Patients The study enrolled 1094 patients with chronic heart failure symptoms for at least 3 months, LVEF ≤ 0.35%, at least 2 months of treatment with diuretics and an angiotensin-converting enzyme (ACE) inhibitor (if tolerated). Treatment with digoxin, hydralazine, or nitrates was permitted but not required.Exclusion criteria were extensive and important to understand. These included any recent major cardiac events or surgery within the previous 3 months, uncorrected valvular disease, active myocarditis, sustained VT or higher degrees of AV block not controlled by pacing, systolic blood pressure of more than 160 or less than 85 mm Hg or diastolic blood pressure of more than 100 mm Hg, clinically significant kidney or liver disease or use of calcium-channel blockers, adrenergic agonists/antagonists, or class IC/III antiarrhythmic agents. Patients receiving β-adrenergic agonists or antagonists (presumably for another indication) were not enrolled.Baseline Characteristics The results of this and other beta-blocker trials in heart failure will be clear. One of the most important points for translating this evidence to patients will be the baseline characteristics. It is vital to understand who these patients were.The mean age was 58 years and approximately 76% were male. Most patients had mild to moderate heart failure, with 53% in NYHA Class II, 44% in Class III, and only 3% in Class IV. The etiology of heart failure was nearly evenly split between coronary artery disease (47%) and nonischemic cardiomyopathy (53%). Patients had significantly impaired cardiac function with a mean LVEF of 0.23. The mean six-minute walk distance ranged from 386 to 390 meters. Hemodynamic parameters were relatively stable, with mean systolic blood pressure of 116 mmHg, and mean heart rate of 83-84 beats per minute. Most patients were receiving standard heart failure therapy at baseline, including digitalis (90-91%), loop diuretics (95%), and ACE inhibitors (95%), while approximately one-third (32%) were on direct-acting vasodilators.Trial Procedures Patients were assessed for eligibility during a 3-week screening period during which exercise capacity was assessed with a 6-minute walk test. Notable was that these were outpatients able to complete a 6-minute walk test. Enrollment was stratified to one of four treatment protocols on the basis of the patients' performance on the exercise test: patients able to walk between 426 and 550 m when tested were assigned to the mild-heart-failure protocol; those able to walk between 150 and 425 m were assigned either to the moderate-heart-failure protocol or to a dose-ranging protocol, depending on the location of the study center; and those able to walk only less than 150 m were assigned to the severe-heart-failure protocol.After this base-line testing, all patients received 6.25mg of carvedilol twice daily for two weeks in an open-label run-in period. Those who tolerated this initial dose were then randomized to receive either placebo (n=398) or carvedilol (n=696) on a double-blind basis, in addition to their usual medications.The allocation ratio (carvedilol:placebo) was 2:1 in the mild and severe heart failure protocols and 1:1 in the moderate heart failure protocol. The dose was gradually increased to target levels of 25-50mg twice daily over 2-10 weeks, followed by maintenance therapy for an additional 6 months (12 months for mild heart failure).Endpoints At the time of trial planning, the original intent was safety. That is, to show that carvedilol did not increase mortality. The original intent was to enroll 1100 patients. As smaller trials on beta-blockers were published, the statistical plan included the possibility of beta-blocker benefit. The trialists therefore planned two sided statistical analysis.Cumulative survival curves were constructed as time-to-first-event plots by Kaplan–Meier survivorship methods and differences between the curves were tested for significance by the log-rank statistic with use of a Cox proportional-hazards regression model (which included the protocol as a covariate).Results Median follow-up was only 6.5 months due to early termination for benefit. The patients mean total daily dose of carvedilol was 45±27 mg. Overall mortality was 7.8% in the placebo group vs. 3.2% in carvedilol group. The relative risk reduction from carvedilol vs placebo was 65% (95% CI, 39-80%; p

Marcela Belleza e Raphael Coelho convidam Matheus Rezende, residente do último ano de Cardiologia - Incor, para conversar sobre manejo de doença coronariana crônica em tres tópicos:- Como realizar a investigação inicial?- Como fazer a terapia medicamentosa inicial?- O que fazer com o paciente que não melhora?Referências: 1. Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes [published correction appears in Eur Heart J. 2025 Feb 21:ehaf079. doi: 10.1093/eurheartj/ehaf079.]. Eur Heart J. 2024;45(36):3415-3537. doi:10.1093/eurheartj/ehae1772. Virani, Salim S 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 vol. 148,9 (2023): e9-e119. doi:10.1161/CIR.00000000000011683. Montone RA, Rinaldi R, Niccoli G, et al. Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions. J Am Coll Cardiol. 2024;84(8):744-760. doi:10.1016/j.jacc.2024.06.0154. Mortensen MB, Dzaye O, Steffensen FH, et al. Impact of Plaque Burden Versus Stenosis on Ischemic Events in Patients With Coronary Atherosclerosis. J Am Coll Cardiol. 2020;76(24):2803-2813. doi:10.1016/j.jacc.2020.10.0215. Doenst T, Haverich A, Serruys P, et al. PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73(8):964-976. doi:10.1016/j.jacc.2018.11.0536. Maron DJ, Hochman JS, Reynolds HR, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382(15):1395-1407. doi:10.1056/NEJMoa19159227. Rajkumar CA, Foley MJ, Ahmed-Jushuf F, et al. A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina. N Engl J Med. 2023;389(25):2319-2330. doi:10.1056/NEJMoa23106108. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377(14):1319-1330. doi:10.1056/NEJMoa17091189. Howlett JG, Stebbins A, Petrie MC, et al. CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial. JACC Heart Fail. 2019;7(10):878-887. doi:10.1016/j.jchf.2019.04.01810. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383(19):1838-1847. doi:10.1056/NEJMoa202137211. Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-1516. doi:10.1056/NEJMoa07082912. Ford TJ, Stanley B, Good R, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018;72(23 Pt A):2841-2855. doi:10.1016/j.jacc.2018.09.00613. Carvalho, Tales de et al. “Brazilian Cardiovascular Rehabilitation Guideline - 2020.” “Diretriz Brasileira de Reabilitação Cardiovascular – 2020.” Arquivos brasileiros de cardiologia vol. 114,5 (2020): 943-987. doi:10.36660/abc.20200407

Contributor: Jorge Chalit-Hernandez, OMS3 Educational Pearls: Psychedelics are being studied for their therapeutic effects in mental illnesses, including major depressive disorder, post-traumatic stress disorder, anxiety, and many others Classic psychedelics include compounds like psilocybin, LSD, and ayahuasca MDMA and ketamine are often included in psychedelic research, but have a different mechanism of action than the others Their mechanism of action involves agonism of the 5HT2A receptor, among others Given their resurgence, there is an increase in recreational use of these substances A recent study assessed the risks of recreational users developing subsequent psychotic disorders Individuals who visited the ED for hallucinogen use had a greater risk of being diagnosed with a schizophrenia spectrum disorder in the following 3 years Hazard ratio (HR) of 21.32 After adjustment for comorbid substance use and other mental illness, the hazard ratio was 3.53 - still a significant increase compared with the general population They also found an elevated risk for psychedelics when compared to alcohol (HR 4.66) and cannabis (HR 1.47) The study did not assess whether patients received antipsychotics or other treatments in the ED References Lieberman JA. Back to the Future - The Therapeutic Potential of Psychedelic Drugs. N Engl J Med. 2021;384(15):1460-1461. doi:10.1056/NEJMe2102835 Livne O, Shmulewitz D, Walsh C, Hasin DS. Adolescent and adult time trends in US hallucinogen use, 2002-19: any use, and use of ecstasy, LSD and PCP. Addiction. 2022;117(12):3099-3109. doi:10.1111/add.15987 Myran DT, Pugliese M, Xiao J, et al. Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder. JAMA Psychiatry. 2025;82(2):142-150. doi:10.1001/jamapsychiatry.2024.3532 Summarized & Edited by Jorge Chalit, OMS3 Donate: https://emergencymedicalminute.org/donate/  

N Engl J Med 1991;325:293-302N Engl J Med 1992;327:685-691Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Background: Systolic heart failure affects millions worldwide and is associated with high mortality and morbidity. If left untreated, the one-year mortality ranges from 15-50%, depending on the severity of the disease.The CONSENSUS trial found mortality benefit with the use of the angiotensin converting enzyme inhibitor (ACEi) enalapril in patients with New York Heart Association (NYHA) class IV heart failure. Data on less severe heart failure were lacking.The Studies of Left Ventricular Dysfunction (SOLVD) sought to assess whether an ACEi, enalapril, would reduce mortality in patients with low left ventricular ejection fractions defined as 35% of less.Patients: Eligible patients had left ventricular ejection fraction of 35% or less. The ejection fraction was measured using radionuclide techniques in 68% of the patients, contrast angiography in 11%, and two-dimensional echocardiography in 21%.Patients were excluded if they were over 80 years of age, or if they had significant valvular disease requiring surgery, unstable angina pectoris, angina requiring revascularization procedures, myocardial infarction during the previous month, severe pulmonary disease, serum creatinine >2 mg/ dl, or any other disease that might significantly impact survival.At the end of the run-in period for placebo, patients who had overt congestive heart failure were enrolled in the Treatment trial, and patients who were not having overt congestive heart failure were enrolled in the Prevention trial.Baseline characteristics: Patients were recruited from 83 hospitals linked to 23 centers in the United States, Canada, and Belgium.The Treatment trial randomized 2,569 patients – 1,285 patients randomized to receive enalapril and 1,284 randomized to receive placebo. The average age of patients was 61 years and 80% were men. The average left ventricular ejection fraction was 25%. Approximately 42% had hypertension, 26% had diabetes, 71% had ischemic heart disease and 22% were current smokers. The NYHA class was I in 11% of the patients, II in 57% of the patients, III in 30% and IV 2%. At the time of enrollment, 8% were taking beta-blockers, 67% were taking digitalis, 85% were taking diuretics, 9% were taking potassium-sparing diuretics and 51% were taking vasodilators (other than ACEi).The Prevention trial randomized 4,228 patients – 2,111 patients randomized to receive enalapril and 2,117 randomized to receive placebo. The average age of patients was 59 years and 89% were men. The average left ventricular ejection fraction was 28%. Approximately 37% had hypertension, 15% had diabetes, 83% had ischemic heart disease and 23% were current smokers. The NYHA class was I in 67% of the patients and II in 33%. At the time of enrollment, 24% were taking beta-blockers, 12% were taking digitalis, 17% were taking diuretics, 4% were taking potassium-sparing diuretics and 46% were taking vasodilators (other than ACEi).Procedures: A total of 7,402 patients were deemed eligible across both the Treatment and Prevention trials.Eligible patients for either trial entered a run-in and stabilization phase. Patients were given enalapril 2.5 mg twice daily in a single-blind fashion for 2 - 7 days to identify patients who could not tolerate even a small dose of the drug or those who were unable to comply with the regimen. A total of 310/7402 patients (4.2%) were excluded from the study during this phase. Following the active dosing phase, patients were placed on a regimen of matching placebo in a single-blind manner for 14 - 17 days. This allowed identification of individuals whose clinical condition deteriorated after drug withdrawal or who demonstrated poor compliance. During this phase, 295/ 7,092 patients (4.2%) were excluded from the study.At the end of the run-in period for placebo, patients who had overt congestive heart failure were enrolled in the Treatment trial, and patients who were not having overt congestive heart failure were enrolled in the Prevention trial.After that patients were randomized in a 1:1 ratio to receive enalapril or placebo.Treatment with enalapril or placebo was initiated at 2.5 mg or 5 mg twice daily, based on the patient's clinical status and physician judgment. The dose was titrated up to 10 mg twice daily if tolerated without symptomatic hypotension or worsening renal function. After randomization, follow-up visits occurred at two weeks, six weeks, four months, and every four months thereafter until study completion.Endpoints: The primary outcome for both trials was all-cause mortality. Heart failure hospitalization was assessed as a secondary outcome.The estimated sample size was 2,500 patients for the treatment trial and 4,600 for the prevention trial. These sample sizes would provide 90% power at 5% two-sided alpha to detect 25% relative risk reduction in mortality, with the use of enalapril. The estimated 3-year mortality in the control group was 32% in the Treatment trial and 17% in the Prevention trial.Authors reported risk reduction which was calculate as (1 – relative risk)*100.Results: A total of 39,924 patients with a left ventricular ejection fraction of 35% or less were identified. Of these, 6.4% were enrolled in the Treatment trial and 7.4% in the Prevention trial. Among the excluded patients, the main reasons were prior use of an ACEi (28%), cardiovascular problems (12%), contraindications to using ACEi (11%), lack of patient consent (11%), administrative reasons (21%), cancer or other life-threatening illnesses (12%), and other miscellaneous reasons (5%).The average follow up time was 41.4 months in the Treatment trial and 37.4 months in the Prevention trial.In the Treatment trial, enalapril reduced all-cause mortality (35.2% vs 39.7%, risk reduction: 16%, 95% CI: 5% – 26%; p< 0.0036). The majority of deaths (89%) were cardiovascular and the majority of these (79%) were heart failure or arrhythmia related. Enalapril also reduced all-cause hospitalization (69.5% vs 74.0%; p= 0.006). The total number of hospitalizations for heart failure was also reduced with enalapril – 683 vs 971. Subgroup analysis showed a numerical increase in death, with enalapril, in patients with an ejection fraction of 30-35% - this was not statistically significant.In the Prevention trial, enalapril did not have a significant effect on mortality (14.8% with enalapril vs 15.8% with placebo, risk reduction: 8%, 95% CI: -8% – 21%; p= 0.30). Enalapril significantly reduced the development of heart failure (20.7% vs 30.2%; p< 0.001). Total number of hospitalizations for heart failure was also significantly reduced with enalapril – 306 vs 454. The reduction in the development of heart failure was seen across all ejection fractions below 35%, although the benefit was larger with lower ejection fractions.In both trials, the benefit of enalapril was seen early after treatment initiation.Conclusion: In patients with left ventricular ejection fraction of 35% or less and overt congestive heart failure, enalapril reduced all-cause mortality with a number needed to treat of approximately 22 patients. In patients with a left ventricular ejection fraction of 35% or less and without overt congestive heart failure, enalapril had no significant effect on mortality but it reduced the development of heart failure with an number needed to treat of approximately 11 patients.The SOLVD trials provide strong evidence supporting the use of ACEi in patients with systolic heart failure. The role of ACEi in systolic heart failure has been examined across diverse patient groups, and the totality of evidence consistently supports their use. However, when examining the SOLVD trials in isolation, it is important to recognize the selective nature of enrollment, which limits the trials' external validity. Additionally, the use of a run-in period introduces bias in favor of enalapril, although this concern is less significant when the primary outcome is all-cause mortality.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring articles on high-risk smoldering multiple myeloma, M. tuberculosis infection, type 2 diabetes, uncontrolled hypertension, and lymphoma; a review article on the chemistry of food; a case report of a man with weight loss, weakness, and anorexia; and Perspectives on the dismantling of foreign-assistance efforts, on the crushing weight of nonclinical demands in primary care, and on the last dose.

Christopher Duggan is the director of the Center for Nutrition at Boston Children's Hospital, a professor of pediatrics at Harvard Medical School, and a professor in the Departments of Nutrition and Global Health and Population at the Harvard T.H. Chan School of Public Health. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. C.P. Duggan and Z.A. Bhutta. “Putting America First” — Undermining Health for Populations at Home and Abroad. N Engl J Med 2025;392:1769-1771.

N Engl J Med 1991; 325:303-10Background Enalapril was found to be superior to placebo for patients with severe, class IV heart failure in the CONSENSUS trial and the regimen of Hydralazine-Isosorbide dinitrate was found to be superior to Prazosin as well as placebo for stable patients with mild heart failure in the original V-HEFT I trial. No sufficiently powered trials in this space had been performed to assess whether Enalapril improved long-term morbidity or mortality for heart failure patients with milder symptoms and the CONSENSUS trial had important limitations. The V-HEFT II trial was undertaken to compare 2 vasodilator regimens (Enalapril and Hydralazine-Isosorbide dinitrate) in patients with chronic congestive heart failure. Besides comparing efficacy of these agents on mortality, investigators sought to understand how these agents affected physiologic endpoints. The trial was sponsored by the Veterans Administration and enrolled men and the patient population and methods were identical to the original V-HEFT trial.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Men between the ages of 18 and 75 were recruited from 13 participating Veterans Administration hospitals and had to have chronic congestive heart failure based on either evidence of cardiac dilatation or left ventricular dysfunction (EF

In this first-ever collaboration between Communicable and Breakpoints, the podcast of the US Society of Infectious Diseases Pharmacists, hosts Angela Huttner (Geneva, Switzerland) and Erin McCreary (Pittsburgh, USA) join trial investigators Josh Davis (Newcastle, Australia) and Steve Tong (Melbourne, Australia) to unpack the first results coming from the SNAP adaptive platform trial, which were recently presented at ESCMID Global in Vienna. Learn whether penicillin and cefazolin are non-inferior to—and maybe even safer than—flucloxacillin for penicillin-susceptible and methicillin-susceptible Staphylococcus aureus, respectively.This episode was edited by Julie Anne Justo, transcribed by Katie Lambert and Sarah Groom, and peer-reviewed by Megan Klatt and Lacy Worden. Note on conflict of interest for SNAP Data Safety Monitoring Committee (DSMC) members:Conflicts of interest were evaluated when choosing individuals to serve on the SNAP DSMC. Aside from being compensated for their duties on the committee, DSMC members have no ongoing financial relationships that relate to the trial and are not involved in the conduct of the trial in any role other than that of a DSMC member. DSMC members have no intellectual conflict of interest or bias and reviewed SNAP data in a fully objective manner. Literature:Steven Y. C. Tong, Joshua S. Davis, Emily Eichenberger et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015 Jul;28(3):603-61.SNAP Adaptive trial platform/results of the PSSA & MSSA domains: https://www.snaptrial.com.au/ESCMID Global April 2025 presentation:www.online.escmid.org *https://www.escmid.org/congress-events/escmid-global/programme/scientific-programme/CloCeBa trial results (ESCMID Global April 2025 presentation): www.online.escmid.org *https://www.escmid.org/congress-events/escmid-global/programme/scientific-programme/Note on access to online video of ESCMID Global presentations:In the six months following the congress:Non-ESCMID members have access if they registered for ESCMID GlobalMembers have access only if they registered for ESCMID GlobalSix months after the congress:Non-members do not have access, whatever their ESCMID Global registration statusAll members have access, whatever their ESCMID Global registration statusCAMERA 2 trial: Steven Y. C. Tong, David C. Lye, Dafna Yahav, et al. Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA BacteremiaA Randomized Clinical Trial. JAMA. 2020;323(6):527-537. doi:10.1001/jama.2020.0103 POET trial: Kasper Iversen, Nikolaj Ihlemann, Sabine U. Gill et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med 2019;380:415-424POET trial follow-up: Mia M. Pries-Heje, Christoffer Wiingaard, Nikolaj Ihlemann. Five-Year Outcomes of the Partial Oral Treatment of Endocarditis (POET) Trial. N Engl J Med 2022;386:601-602

N Engl J Med 1987; 314:1429-35Background Prior to the publication of this study, digoxin and diuretics were the mainstay of chronic heart failure management. No therapy had yet been shown to reduce mortality or improve heart failure outcomes in patients with severe disease. The results of the V-HEFT trial had been published in the prior year, which demonstrated that the vasodilator combination of hydralazine and isosorbide reduced death in patients with chronic, stable heart failure. CONSENSUS was the first study to test whether vasodilator therapy in general, and angiotensin converting enzyme inhibitors in particular could modify heart failure disease trajectory for those with severe disease when used as part of chronic disease management. The CONSENSUS trial was designed to test the hypothesis that Enalapril compared to placebo reduced mortality in patients with severe (NYHA IV) congestive heart failure.Patients Men and women with severe (NYHA IV) congestive heart failure and cardiomegaly based on heart size >600 ml/m2 in men or >550 ml/m2 in women were recruited from 35 centers in Finland, Norway and Sweden. Measurement of LV function was not required. Patients were excluded if they had 1) acute pulmonary edema, 2) hemodynamically important aortic or mitral valve stenosis, 3) MI within the previous 2 months, 4) unstable angina, 5) planned cardiac surgery, 6) right heart failure due to pulmonary disease, or 7) serum creatinine >3.4 mg/dL.It is not specified whether patients could be recruited from the inpatient or outpatient setting or both but prior to randomization, a 14-day period was allowed to stabilize patients on digoxin and diuretics. If during this period, their condition improved to NYHA class III or less they were not randomized.Baseline characteristics The majority of participants were male (70%) and their average age was 70. The average heart rate and blood pressure were 80 bpm and 120/75 mmHg and the average serum creatinine was about 1.5 mg/dL. Coronary artery disease was present in over 70% of participants and nearly 50% had suffered a previous heart attack. Hypertension and diabetes were present in over 20% and atrial fibrillation in 50%. The use of medications at baseline was evenly distributed between groups with nearly all patients being on digoxin and furosemide. About 50% of participants were also taking spironolactone as well as other vasodilator drugs. About 50% of patients had heart failure for more than 4 years.Procedures Treatment with enalapril or an identical placebo was initially started in the hospital with a dose of 5 mg twice a day. After 1 week it was increased to 10 mg twice a day if the patient did not have symptoms of hypotension or other side effects. According to the clinical response, a further increase in dosage could occur up to a maximum dose of 20 mg twice a day.Patients were evaluated after 1, 2, 3, 6, and 16 weeks, 6, 9, and 12 months and at the end of the study. In patients with worsening symptoms, additional vasodilator therapy with isosorbide dinitrate, hydralazine, or prazosin, in that sequence was recommended.Early in the trial the occurrence of symptomatic hypotension led to revision of the protocol after 67 patients had been randomized. No patient's treatment was unblinded but in patients with 1) serum sodium

Diarrhea is one of the more common concerns in emergency medicine worldwide and in the United States, yet we often do not spend enough time understanding the breadth of causes and considerations for this syndrome. Do you know which patients benefit from Zinc? Would you like to review HUS? Can you mixup Oral Rehydration Solution if you needed to? We cover all of this and more in this “code brown” of a chapter! So come, get dirty with Alex and Venk in this truly crappy chapter of Always on EM!   CONTACTS X - @AlwaysOnEM; @VenkBellamkonda YouTube - @AlwaysOnEM; @VenkBellamkonda Instagram – @AlwaysOnEM; @Venk_like_vancomycin; @ASFinch Email - AlwaysOnEM@gmail.com REFERENCES & LINKS Shane AL, Mody RK, Crump JA, Tarr PI, Steiner TS, Kotloff K, Langley JM, Wanke C, Warren CA, Cheng AC, Cantey J, Pickering LK. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):e45-e80. doi: 10.1093/cid/cix669. PMID: 29053792; PMCID: PMC5850553. Gore JI, Surawicz C. Severe acute diarrhea. Gastroenterol Clin North Am. 2003 Dec;32(4):1249-67. doi: 10.1016/s0889-8553(03)00100-6. PMID: 14696306; PMCID: PMC7127018. Freedman SB, van de Kar NCAJ, Tarr PI. Shiga Toxin–Producing Escherichia coli and the Hemolytic–Uremic Syndrome. The New England Journal of Medicine. 2023;389(15):1402-1414. doi:10.1056/NEJMra2108739. Logan C, Beadsworth MB, Beeching NJ. HIV and diarrhoea: what is new? Curr Opin Infect Dis. 2016 Oct;29(5):486-94. doi: 10.1097/QCO.0000000000000305. PMID: 27472290. Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhoea. Drug Saf. 2000 Jan;22(1):53-72. doi: 10.2165/00002018-200022010-00005. PMID: 10647976. Schiller LR. Secretory diarrhea. Curr Gastroenterol Rep. 1999 Oct;1(5):389-97. doi: 10.1007/s11894-999-0020-8. PMID: 10980977. Gong Z, Wang Y. Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review. JCO Oncol Pract. 2020 Aug;16(8):453-461. doi: 10.1200/OP.20.00002. Epub 2020 Jun 25. PMID: 32584703. Do C, Evans GJ, DeAguero J, Escobar GP, Lin HC, Wagner B. Dysnatremia in Gastrointestinal Disorders. Front Med (Lausanne). 2022 May 13;9:892265. doi: 10.3389/fmed.2022.892265. PMID: 35646996; PMCID: PMC9136014. Expert Panel on Gastrointestinal Imaging; Chang KJ, Marin D, Kim DH, Fowler KJ, Camacho MA, Cash BD, Garcia EM, Hatten BW, Kambadakone AR, Levy AD, Liu PS, Moreno C, Peterson CM, Pietryga JA, Siegel A, Weinstein S, Carucci LR. ACR Appropriateness Criteria® Suspected Small-Bowel Obstruction. J Am Coll Radiol. 2020 May;17(5S):S305-S314. doi: 10.1016/j.jacr.2020.01.025. PMID: 32370974. Rami Reddy SR, Cappell MS. A Systematic Review of the Clinical Presentation, Diagnosis, and Treatment of Small Bowel Obstruction. Curr Gastroenterol Rep. 2017 Jun;19(6):28. doi: 10.1007/s11894-017-0566-9. PMID: 28439845. Modahl L, Digumarthy SR, Rhea JT, Conn AK, Saini S, Lee SI. Emergency department abdominal computed tomography for nontraumatic abdominal pain: optimizing utilization. J Am Coll Radiol. 2006 Nov;3(11):860-6. doi: 10.1016/j.jacr.2006.05.011. PMID: 17412185. Scheirey CD, Fowler KJ, Therrien JA, et al. ACR Appropriateness Criteria Acute Nonlocalized Abdominal Pain. Journal of the American College of Radiology : JACR. 2018;15(11S):S217-S231. doi:10.1016/j.jacr.2018.09.010. Atia AN, Buchman AL. Oral rehydration solutions in non-cholera diarrhea: a review. Am J Gastroenterol. 2009 Oct;104(10):2596-604; quiz 2605. doi: 10.1038/ajg.2009.329. Epub 2009 Jun 23. PMID: 19550407. Musekiwa A, Volmink J. Oral rehydration salt solution for treating cholera: ≤ 270 mOsm/L solutions vs ≥ 310 mOsm/L solutions. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD003754. doi: 10.1002/14651858.CD003754.pub3. PMID: 22161381; PMCID: PMC6532622. Centers for Disease Control and Prevention (CDC). Scombroid fish poisoning associated with tuna steaks--Louisiana and Tennessee, 2006. MMWR Morb Mortal Wkly Rep. 2007 Aug 17;56(32):817-9. PMID: 17703171. Résière D, Florentin J, Mehdaoui H, Mahi Z, Gueye P, Hommel D, Pujo J, NKontcho F, Portecop P, Nevière R, Kallel H, Mégarbane B. Clinical Characteristics of Ciguatera Poisoning in Martinique, French West Indies-A Case Series. Toxins (Basel). 2022 Aug 3;14(8):535. doi: 10.3390/toxins14080535. PMID: 36006197; PMCID: PMC9415704. Centers for Disease Control and Prevention (CDC). Ciguatera fish poisoning--Texas, 1998, and South Carolina, 2004. MMWR Morb Mortal Wkly Rep. 2006 Sep 1;55(34):935-7. PMID: 16943762. Thyroid Inferno EM Blog: https://emblog.mayo.edu/2014/11/01/thyroid-inferno/  Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016 Dec 20;12(12):CD005436. doi: 10.1002/14651858.CD005436.pub5. PMID: 27996088; PMCID: PMC5450879. Dhingra U, Kisenge R, Sudfeld CR, Dhingra P, Somji S, Dutta A, Bakari M, Deb S, Devi P, Liu E, Chauhan A, Kumar J, Semwal OP, Aboud S, Bahl R, Ashorn P, Simon J, Duggan CP, Sazawal S, Manji K. Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. N Engl J Med. 2020 Sep 24;383(13):1231-1241. doi: 10.1056/NEJMoa1915905. PMID: 32966722; PMCID: PMC7466932. Dalfa RA, El Aish KIA, El Raai M, El Gazaly N, Shatat A. Oral zinc supplementation for children with acute diarrhoea: a quasi-experimental study. Lancet. 2018 Feb 21;391 Suppl 2:S36. doi: 10.1016/S0140-6736(18)30402-1. Epub 2018 Feb 21. PMID: 29553435.   WANT TO WORK AT MAYO? EM Physicians: https://jobs.mayoclinic.org/emergencymedicine EM NP PAs: https://jobs.mayoclinic.org/em-nppa-jobs   Nursing/Techs/PAC: https://jobs.mayoclinic.org/Nursing-Emergency-Medicine EMTs/Paramedics: https://jobs.mayoclinic.org/ambulanceservice All groups above combined into one link: https://jobs.mayoclinic.org/EM-Jobs

Contributor: Aaron Lessen, MD Educational Pearls: What is a Rescue Inhaler? A rescue inhaler is a medication for people with asthma to quickly reverse the symptoms of an asthma attack. Historically albuterol (Short Acting Beta Agonist (SABA)) monotherapy has been the mainstay rescue inhaler. This is because albuterol works fast and is relatively cheap. What are Combination Rescue Inhalers? Combination rescue inhalers contain a fast-acting bronchodilator as well as an inhaled corticosteroid (ICS) The steroid helps to reduce some of the chronic airway inflammation that is worsening the asthma attack and can help to prevent future attacks Examples include budesonide-formoterol and albuterol-budesonide Global Initiative for Asthma (GINA), states that combination therapy is now the preferred reliever for adults and adolescents with mild asthma What are the drawbacks of Combination Rescue Inhalers? These inhalers are generally more expensive than just using a SABA inhaler which can be a barrier for some people Improper use can also lead to conditions like thrush due to the addition of the steroid References Krings JG, Beasley R. The Role of ICS-Containing Rescue Therapy Versus SABA Alone in Asthma Management Today. J Allergy Clin Immunol Pract. 2024 Apr;12(4):870-879. doi: 10.1016/j.jaip.2024.01.011. Epub 2024 Jan 17. PMID: 38237858; PMCID: PMC10999356. Papi A, Chipps BE, Beasley R, Panettieri RA Jr, Israel E, Cooper M, Dunsire L, Jeynes-Ellis A, Johnsson E, Rees R, Cappelletti C, Albers FC. Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. N Engl J Med. 2022 Jun 2;386(22):2071-2083. doi: 10.1056/NEJMoa2203163. Epub 2022 May 15. PMID: 35569035. Summarized by Jeffrey Olson, MS3 | Edited by Jorge Chalit, OMS3 Donate: https://emergencymedicalminute.org/donate/  

Featuring articles on lipoprotein(a), familial polycythemia, leukocyte adhesion deficiency, COPD, and on policies on reducing alcohol consumption; a review article on addressing alcohol use; a Clinical Problem-Solving on gazing into a crystal ball; and Perspectives on death and taxes, on cancer metastases, and on a good innings.

Arthur Robin Williams is an associate professor of clinical psychiatry at Columbia University and a research scientist at the New York State Psychiatric Institute. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. A.R. Williams. Death and Taxes — Is Alcohol the Solution? N Engl J Med 2025;392:1665-1667.

N Engl J Med 1986; 314:1547-52Background Into the mid-1980's, digoxin and diuretics were the mainstay of chronic disease management for congestive heart failure. Vasodilator agents were also commonly used based on limited data of their favorable hemodynamic effects. No sufficiently powered trials in this space had been performed to assess whether administration of vasodilators or any other agents improved long-term morbidity or mortality for heart failure patients. The V-HEFT trial was undertaken to test the hypotheses that 2 widely used vasodilator regimens (prazosin or a combination of hydralazine and isosorbide dinitrate) were superior for reducing death versus placebo. The trial was sponsored by the Veterans Administration and only enrolled men.Patients Men between the ages of 18 and 75 were recruited from 11 participating Veterans Administration hospitals and had to have chronic congestive heart failure based on either evidence of cardiac dilatation or left ventricular dysfunction (EF 0.7 ng/mL and euvolemic volume status. Clinical evaluations and exercise-tolerance tests on 2 consecutive visits, two weeks apart, had to reveal clinical and exercise stability before randomization could occur. Following randomization, patients continued to receive the optimal dose of digoxin and diuretic along with 1 of 3 study regimens. The placebo group was given placebo tablets and placebo capsules and instructed to take them 4 times a day. The prazosin group took 2.5 mg prazosin capsules and placebo tablets 4 times a day. The hydralazine-isosorbide dinitrate group took 37.5 mg hydralazine capsules and 20 mg isosorbide dinitrate tablets 4 times a day.In all groups, therapy began with 1 capsule and 1 tablet to be taken 4 times a day. In the absence of side effects, this was increased to 2 capsules and 2 tablets 4 times a day for a total of 20 mg of prazosin or 300-160 mg of hydralazine-isosorbide dinitrate. If drug-related side effects occurred, the dose could be reduced to half a tablet 4 times per day or to one capsule 2 times per day. If the dose was reduced, an attempt was made later to reinstitute the full dose.In order to limit dropouts, rigorous criteria were established for “treatment failures.” Physicians were advised to hospitalize patients with worsening symptoms, and, if appropriate, to use temporary intravenous vasodilator or inotropic interventions for stabilization. Physicians were encouraged to resume study medications upon discharge. At least 2 such hospitalizations were required, along with objective evidence of deterioration, before the study medications were discontinued and replaced with known therapy.Endpoints The primary endpoint was all-cause mortality.Results 642 patients were enrolled (273 in placebo group, 183 in prazosin group and 186 in the hydralazine-isosorbide dinitrate group). Excluding discontinuations that took place within 1 month before death, 47 patients (17%) discontinued one or both types of placebos, 43 patients (23%) discontinued prazosin, and 60 patients (32%) discontinued either one or both drugs in the hydralazine-isosorbide group. Six months after randomization, the average prescribed doses were 18.6 mg per day of prazosin, 270 mg per day of hydralazine, and 136 mg per day of isosorbide dinitrate. More than 85% of the prescribed drugs were taken in each treatment group.The mean follow-up was 2.3 years (range 6 months to 5.7 years). Only 4 patients were lost to follow up (2 in placebo group, 1 in prazosin group, and 1 in hydralazine-dinitrate group). There were 120 deaths in placebo group (44%; 19 per 100 patient years), 91 in the prazosin group (50%; 22 per 100 patient years), 72 in the hydralazine-dinitrate group (39%; 17 per 100 patient years). A reduction in mortality over the entire follow-up period was observed in the hydralazine-nitrate group compared with placebo (p = 0.093 on the log-rank test and p = 0.046 on the generalized Wilcoxon test, which gives more weight to treatment differences occurring in the earlier part of the mortality curves and less weight to the latter part, where the numbers are smaller). The absolute difference in mortality between these groups increased during three years and then began to diminish. The absolute difference in mortality between the placebo group and hydralazine-isosorbide groups at years 1 through 4 was 7%, 9%, 11% and 4%, respectively.Prespecified subgroup analysis in CAD vs no CAD stratification showed no significant treatment effect heterogeneity for hydralazine-nitrate among those with CAD although the absolute difference in mortality between groups was numerically higher for patients with CAD.At 8 weeks and 1 year, SBP (-4.1 and -4.6 mmHg) and DBP (-3.2 and -2.7 mmHg) decreased the most in the prazosin group compared to placebo. Hydralazine-nitrate was not associated with a statistically significant nor clinically significant difference in BP with exception of DBP at 8 weeks. The EF rose significantly at 8 weeks and 1 year in the hydralazine-nitrate group (+2.9 and +4.2) compared to placebo but not in the prazosin group.Side effects were reported in 4.0% of placebo patients, 11% of prazosin patients and 19% of hydralazine-nitrate patients, respectively. The most common side effects were headache and dizziness. Headache was reported in 12% of hydralazine-nitrate patients.Conclusions This study compared the combination of hydralazine-isosorbide dinitrate or prazosin to placebo in patients with chronic congestive heart failure who were optimized on digoxin and diuretic therapy. In what appears to be a young (58 years) and highly selected population of clinically stable, male veterans with dilated cardiomyopathies and low symptom burdens, the combination of hydralazine-isosorbide reduced death by 2 per 100 patient years, increased EF by 4% at 1 year and did not significantly alter BP compared to placebo. Side effects were reported in approximately 1 out of 5 patients with the most common being headache and approximately 1 out of 3 discontinued 1 or both study drugs. Prasozin did not reduce death or increase EF but did reduce BP compared to placebo. The internal validity of the study is high with only a few minor imbalances in baseline characteristics, which do not appear clinically relevant nor to consistently favor any one group. Less than 1% of patients were lost to follow up with no significant imbalances between groups. The external validity is limited by the fact that this is a population of male veterans and the etiologic distribution of cardiomyopathy and heart failure is likely different from a general heart failure population; etiologic causes of death are also likely to be different. Furthermore, the population is highly selected and its unclear how many patients from the general heart failure population would meet study criteria.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring articles on bronchiectasis, influenza, clonal hematopoiesis of indeterminate potential, and metachromatic leukodystrophy; a review article on biology of the Fc neonatal receptor; a case report of a woman with sore throat and rash; and Perspectives on HIV preexposure prophylaxis, on fossil fuels, and on Medicaid's mandate for children and adolescents.

Lauren Jatt is an infectious diseases fellow at the University of Washington. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. L.P. Jatt and Others. An HIV Vaccine in the Era of Twice-Yearly Lenacapavir for PrEP — Essential or Irrelevant? N Engl J Med 2025;392:1561-1563.

In this NEJM Outbreaks Update, Editor-in-Chief Eric Rubin and Deputy Editor Lindsey Baden are joined by Indiana Commissioner of Public Health Lindsay Weaver to discuss the current state of avian influenza in Indiana. Eric Rubin is the Editor-in-Chief of the Journal. Lindsey Baden is a Deputy Editor of the Journal. Lindsay Weaver is the Indiana Commissioner of Public Health. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. E.J. Rubin and Others. NEJM Outbreaks Updates — H5N1 in Indiana. N Engl J Med. DOI: 10.1056/NEJMe2503583.

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-429 Overview: Colorectal cancer screening saves lives, yet many patients remain unscreened. This episode explores current screening methods, the evidence behind the new DNA blood test, and how it compares to existing options. Gain practical insights to guide patient discussions and improve screening rates in your practice. Episode resource links: N Engl J Med. 2024 Mar 14;390(11):973-983. doi: 10.1056/NEJMoa2304714 N Engl J Med 2024;390:984-93. DOI: 10.1056/NEJMoa2310336 Guest: Jillian Joseph, MPAS, PA-C 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-429 Overview: Colorectal cancer screening saves lives, yet many patients remain unscreened. This episode explores current screening methods, the evidence behind the new DNA blood test, and how it compares to existing options. Gain practical insights to guide patient discussions and improve screening rates in your practice. Episode resource links: N Engl J Med. 2024 Mar 14;390(11):973-983. doi: 10.1056/NEJMoa2304714 N Engl J Med 2024;390:984-93. DOI: 10.1056/NEJMoa2310336 Guest: Jillian Joseph, MPAS, PA-C Music Credit: Matthew Bugos Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com   

Listen as we discuss the highly-awaited ESOPEC trial, which examines treatment regimens for esophageal and EGJ adenocarcinoma. Wildly impress your thoracic attendings or peers with your nuanced knowledge! FLOT who? You'll know. Pull out the paper and listen along! Learning Objectives: -Discuss the patient population in the ESOPEC trial -Discuss the main differences between the ESOPEC trial and the CROSS trial -Describe the main drawbacks between FLOT and the CROSS regimen. Hosts: Chloe Hanson MD, Brian Louie MD, and Peter White MD   Referenced Material https://www.nejm.org/doi/full/10.1056/NEJMoa2409408 Hoeppner J, Brunner T, Schmoor C, Bronsert P, Kulemann B, Claus R, Utzolino S, Izbicki JR, Gockel I, Gerdes B, Ghadimi M, Reichert B, Lock JF, Bruns C, Reitsamer E, Schmeding M, Benedix F, Keck T, Folprecht G, Thuss-Patience P, Neumann UP, Pascher A, Imhof D, Daum S, Strieder T, Krautz C, Zimmermann S, Werner J, Mahlberg R, Illerhaus G, Grimminger P, Lordick F. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. N Engl J Med. 2025 Jan 23;392(4):323-335. doi: 10.1056/NEJMoa2409408. PMID: 39842010. https://www.nejm.org/doi/full/10.1056/NEJMoa1112088 van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088. PMID: 22646630. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/abstract Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11. PMID: 30982686. ***Fellowship Application Link: https://forms.gle/PQgAvGjHrYUqAqTJ9 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://app.behindtheknife.org/listen

N Engl J Med 2017;377:2419-2432Background: A small fraction of patients with acute myocardial infarction (5-10%) have cardiogenic shock. These patients have a high baseline mortality. Early revascularization had been established as better than initial stabilization with medical therapy. Many patients with cardiogenic shock due to acute myocardial infarction (AMI) have multivessel disease. The question arises about whether to do culprit-only percutaneous coronary intervention (PCI) or more complete PCI at the time of the initial intervention.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was designed to test the hypothesis that PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, would result in better clinical outcomes than immediate multivessel PCI among patients who have multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock.Patients: The trial enrolled 706 patients with acute myocardial infarction (ST-segment elevation or non-ST-segment elevation) complicated by cardiogenic shock who had multivessel coronary artery disease. Cardiogenic shock was defined as SBP < 90 mmHg for more than 30 minutes or requiring pressors, clinical signs of pulmonary congestion, and signs of organ hypoperfusion (altered mental status, cold/clammy skin, oliguria, or lactate > 2 mmol/L).Exclusion criteria were extensive and designed to exclude patients with extremely poor prognosis: prolonged resuscitation, no intrinsic heart action, fixed dilated pupils, an indication for urgent CABG, a mechanical cause of shock, age > 90 years, massive pulmonary embolism, or severe renal insufficiency at baseline.Baseline Characteristics: The median age was 70 years, and approximately 75% were male. About 63% of patients had three-vessel disease. More than half the patients had ST-segment elevation myocardial infarction (about 62%), and anterior ST-segment elevation MI accounted for approximately 54% of these cases. About 53% of patients required resuscitation before randomization. The median left ventricular ejection fraction was between 30-33%.Procedures: In the culprit-lesion-only PCI group, only the culprit lesion was treated during the initial procedure, with staged revascularization encouraged based on residual ischemic lesions. In the multivessel PCI group, PCI of all major coronary arteries with >70% stenosis was performed, including attempts to recanalize chronic total occlusions. Crossover from the culprit-lesion-only PCI group to the multivessel PCI group occurred in 12.5% of patients, while crossover in the opposite direction happened in 9.4% of patients. The overall dose of contrast material was significantly higher and the duration of fluoroscopy significantly longer in the multivessel PCI group. Other interventional therapeutic measures were allowed, independent of the assigned treatment strategy.Endpoints: The primary endpoint was a composite of death from any cause or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Secondary endpoints included the individual components of the primary endpoint, recurrent myocardial infarction, rehospitalization for heart failure, repeat revascularization, time to hemodynamic stabilization, catecholamine therapy duration, ICU stay duration, and measurements of renal and myocardial injury. Safety end points included bleeding, which was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium (BARC) scale.Trialists estimated an event rate of the composite primary endpoint of 38% in the culprit-only group vs 50% in the complete group. Using a global type I error level of 0.05, the authors calculated that a sample of 684 patients would give the trial 80% power to rule out the null hypothesis of no difference between the two treatment groups in the event rate for the primary end point.Results: At 30 days, the composite primary endpoint occurred in 45.9% of patients in the culprit-lesion-only PCI group versus 55.4% in the multivessel PCI group (relative risk, 0.83; 95% CI, 0.71 to 0.96; P=0.01). Death occurred in 43.3% of the culprit-lesion-only PCI group versus 51.6% of the multivessel PCI group (relative risk, 0.84; 95% CI, 0.72 to 0.98; P=0.03). The rate of renal-replacement therapy was 11.6% in the culprit-lesion-only PCI group and 16.4% in the multivessel PCI group (relative risk, 0.71; 95% CI, 0.49 to 1.03; P=0.07).Rates of recurrent myocardial infarction, rehospitalization for heart failure, bleeding, and stroke did not differ significantly between groups. Subgroup analyses showed consistent results across all prespecified subgroups. The time to hemodynamic stabilization, the use of catecholamine therapy and the duration of such therapy, the duration of the ICU stay, and the use of mechanical ventilation and the duration of such therapy also did not differ significantly between the two groups.Conclusion: In patients with myocardial infarction and cardiogenic shock, culprit-only PCI was superior to multivessel PCI. Both components of the primary endpoint, death and severe renal failure were lower in the culprit-only arm. The authors and editorialists speculate why these findings contrast with trials in hemodynamically stable myocardial infarction patients, where early multivessel PCI showed benefit over culprit-only PCI.If you accept the thesis that multi-vessel PCI was superior to culprit-only PCI in stable AMI patients, the likely reason for the disparate results are that patients with cardiogenic shock differ substantially from stable patients. The sicker patients with cardiogenic shock benefit from a less-is-more approach where culprit-only PCI reduces treatment harm relative to multivessel PCI.We at CardiologyTrials, however, find the evidence for complete revascularization in stable AMI patients less than clear. The COMPLETE trial found benefit from multivessel PCI over culprit-only, but both composite endpoints were driven largely by non-fatal MI. CV death was not substantially different. The difference in MI could have been related to excluding procedure-related MI.What's more, the FULL-REVASC trial, which also compared culprit-only and multivessel PCI, failed to replicate the COMPLETE trial results. In FULL-REVASC the rates of the composite primary outcome of death, MI or unplanned revascularization were not significantly different. Sadly, FULL-REVASC was stopped early when COMPLETE results were published, which led to a possible loss of power.It's possible, likely even, that the null results of CULPRIT-SHOCK are not really that disparate from prior trials in patients with more stable AMI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring articles on obinutuzumab in active lupus nephritis, tecovirimat for mpox, treatments for paroxysmal atrial fibrillation, and gene therapy for hemophilia B; a review article on enteral nutrition in hospitalized adults; a case report of a woman with cough and weight loss; and Perspectives on withdrawal of the United States from the WHO, on what's next for nicotine, on the value zeitgeist, and on doctors in revolution and war.

Most of us know by now how important calcium is for people with calcium kidney stones. But what if you don't drink milk? Melanie shares what she recommends to non-dairy consumers. Blog: The Best Calcium Sources for Kidney Stones Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346(2):77-84.  Food Sources of Calcium (USDA)   Submit a question for Melanie to answer on the podcast! Connect with The Kidney Dietitian! Work with Us! |  Instagram | Facebook | Pinterest | Facebook Group | Newsletter www.thekidneydietitian.org All information in this podcast is meant for educational purposes only and should not be used in place of advice from a medical professional.  

Patricia Zettler is a professor of law at The Ohio State University Moritz College of Law. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. P.J. Zettler, T.L. Wagener, and M.L. Berman. What's Next for Nicotine? The Coming Legal and Political Battles over an FDA Proposal. N Engl J Med 2025;392:1461-1463.

In this special episode on Early Identification and Delay of Type 1 Diabetes, Dr. Neil Skolnik this emerging area with Dr. Jay Shubrook. This special episode is supported by an independent educational grant from Sanofi. 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 Jay Shubrook, D.O.  - Professor and Director of Diabetes Services, Touro University. Past  Chair, The American Diabetes Association Primary Care Advisory Group, Past Chair of the American College of Diabetology.   Selected References and Resources referred to the in the Podcast: Webinar Registration (Apr 28, 2025 10:00 AM): Early Detection Saves Lives: Implementing Type 1 Diabetes Screening in Pediatric and Primary Care References: Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care 2024;47(8):1276–1298 An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med 2019;381:603-613 Resources for Auto-antibody Testing: Type 1 Diabetes TrialNet Centers of Excellence Locations Type 1 Risk test         Trialnet  

Welcome to Simulcast! In this special episode, Victoria Brazil is joined by Hege Ersdal and Benjamin Kamala, the joint first authors of a ground-breaking study just published in the New England Journal of Medicine. Their program aimed to reduce birth-related mortality in Tanzania, with spectacular success. The Safer Births Bundle integrated key elements: innovative simulation training, data-driven quality improvements, advanced clinical devices, and international collaboration and local empowerment. Neonatal mortality was reduced by 40 % and maternal deaths reduced by 75%. Congratulations to all involved.  The article:  Kamala BA, Ersdal HL, Moshiro RD, Guga G, Dalen I, Kvaløy JT, Bundala FA, Makuwani A, Kapologwe NA, Mfaume RS, Mduma ER, Mdoe P; Safer Births Bundle of Care Study Group. Outcomes of a Program to Reduce Birth-Related Mortality in Tanzania. N Engl J Med. 2025 Mar 13;392(11):1100-1110. doi: 10.1056/NEJMoa2406295. 

Featuring articles on cancer-associated venous thromboembolism, endovascular treatment for stroke, dapagliflozin in patients undergoing TAVI, screening for prostate cancer, and extrachromosomal DNA; a review article on otitis media in young children; a case report of a woman with flank pain, fever, and hypoxemia; and Perspectives on some efforts toward equity and on breaking the sacred promise.

In this episode, we discuss the very early stages of drug targets and drug development with Dr. Mohd Shahid, PhD. Dr. Shahid's research involves the IER3 gene, which is an important modulator of the body's inflammatory response via its action in major immune cells, including macrophages and T-cells, and plays a role in metabolic disorders such as obesity, diabetes, and atherosclerosis, revealing a previously unknown function of this protein. Key Concepts Drug development is a multi-decade journey – human clinical trials occur very late in the process. Drug development often starts before a drug molecule is even conceived by identifying potential drug targets. Chronic inflammation is important for a variety of diseases, including obesity and atherosclerosis. Dr. Shahid's work focuses on a specific gene, Immediate Early Response 3 Gene (IER3 or IEX-1), and its role in modulating the inflammatory response in these disease states. The research process frequently leads to unexpected discoveries and new lines of inquiry. With Dr. Shahid, his work in obesity and inflammation actually led to a new understanding of the IER3's role in the interplay between macrophages, inflammation, and energy expenditure. References Shahid M, Javed AA, Chandra D, et al. IER3 deficiency induces browning of white adipose tissue and resists diet-induced obesity. Sci Rep. 2016;6:24135. Published 2016 Apr 11. doi:10.1038/srep24135 Shahid M, Hermes EL, Chandra D, et al. J Am Heart Assoc. 2018;7:e009261. DOI: 10.1161/JAHA.118.009261. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. doi:10.1056/NEJMoa0807646 Tardif JC, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497-2505. doi:10.1056/NEJMoa1912388

Featuring articles on HIV prevention, left atrial appendage closure after ablation for atrial fibrillation, timing of thrombolysis for stroke, congenital diarrhea and enteropathy, and the association between wealth and mortality in the United States and Europe; a review article on malaria; a Clinical Problem-Solving describing a “hot” cardiomyopathy; and Perspectives on physician shadowing, application overload, medical school grading, and impersonal personal statements.