Podcasts about The New England Journal of Medicine

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

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.

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/  

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 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.

With Justyna Sokolska, Institute of Heart Diseases, Wroclaw Medical University, Wroclaw - Poland, and Maja Cikes, University of Zagreb School of Medicine, Head at the Unit for Heart Failure and Mechanical Circulatory Support, Department of Cardiovascular Diseases, University Hospital Center, Zagreb - Croatia. In this episode of HFA CardioTalk, Justyna Sokolska interviews Maja Cikes on the challenges in management of long-term left ventricular assist device in patients with advanced heart failure. The discussion emphasizes the importance of selecting appropriate patients at the optimal time, examines the adverse events and highlights major ongoing clinical trials.  Recommended readings:  Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial, Mehra MR, et al. JAMA. 2023 Dec 12;330(22):2171-81  Trends and Outcomes of Left Ventricular Assist Device Therapy: JACC Focus Seminar, Varshney AS, et al. J Am Coll Cardiol 2022 Mar 22;79(11):1092-1107 Cardiac implantable electronic devices with a defibrillator component and all-cause mortality in left ventricular assist device carriers: results from the PCHF-VAD registry, Cikes M, et al. Eur J Heart Fail 2019 Sep;21(9):1129-41 A Fully Magnetically Levitated Left Ventricular Assist Device — Final Report, Mehra MR, et al. N Engl J Med 2019 Apr 25;380(17):1618-27 This 2025 HFA Cardio Talk podcast series is supported by Bayer AG in the form of an unrestricted financial support. The discussion has not been influenced in any way by its sponsor.

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. 

Episode 188: RSV Management and PreventionDr. Sandhu and future Dr. Mohamed summarize the management of RSV and describe how to prevent it with chemoprophylaxis and vaccines. Dr Arreaza adds some comments about RSV vaccines.Written by Abdolhakim Mohamed, MSIV, Ross University School of Medicine. Comments by Ranbir Sandhu, MD, and Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.What is RSV? -The Respiratory syncytial Virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus genus within the Pneumoviridae family. -RSV is a major cause of acute respiratory tract infections, particularly bronchiolitis and pneumonia, in infants and young children, and it also significantly affects older adults and immunocompromised individuals. -RSV infections cause an estimated 58,000–80,000 hospitalizations among children younger than 5 years and 60,000–160,000 hospitalizations among adults older than 65 years each year.-RSV is highly contagious and spreads through respiratory droplets and direct contact with contaminated surfaces. The virus typically causes seasonal epidemics, peaking in the winter months in temperate climates and during the rainy season in tropical regions. -Virtually all children are infected with RSV by the age of two, and reinfections can occur throughout life, often with milder symptoms.-Per the 2014 Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis, from the American Academy of Pediatrics, the most common etiology of bronchiolitis is RSV. -About 97% of children are infected with RSV in the first 2 years of life, about 40% will experience lower respiratory tract infection during the initial infection. Other viruses that cause bronchiolitis include human rhinovirus, human metapneumovirus, influenza, adenovirus, coronavirus, and parainfluenza viruses.When is RSV season?-Classically, the highest incidence of infection occurs between December and March in North America. Per CDC, there were typical prepandemic RSV season patterns, but the COVID-19 pandemic disrupted RSV seasonality during 2020–2022. -Before we dive into the seasonality patterns, for context, in order to describe RSV seasonality in the US, data was gathered and analyzed from polymerase chain reaction (PCR) test results reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) during July 2017–February 2023. -Seasonal RSV epidemics were defined as the weeks during which the percentage of PCR test results that were positive for RSV was ≥3%. Per 2017–2020 data, RSV epidemics in the United States typically follow seasonal patterns, that began in October, peaked in December or January, and ended in April. -However, during 2020–21, the typical winter RSV epidemic did not occur. The 2021–22 season began in May, peaked in July, and ended in January. -The 2022–23 season started (June) and peaked (November) later than the 2021–22 season, but earlier than prepandemic seasons. CDC notes that the timing of the 2022–23 season suggests that seasonal patterns are returning toward those observed in prepandemic years, however, warn that clinicians should be aware that off-season RSV circulation might continue.Treatment of RSVSome key points of the 2014 pediatric guidelines from the American Academy of Pediatrics.-AAP strongly do not recommend beta agonists or steroids for viral associated bronchiolitis because of no significant improved outcomes. “Clinicians should not administer albuterol (or salbutamol) to infants and children with a diagnosis of bronchiolitis (Evidence Quality: B; Recommendation Strength: Strong Recommendation).”-Epinephrine is not recommended for infants and children with a diagnosis of bronchiolitis (Evidence Quality: B; Recommendation Strength: Strong Recommendation).-Nebulized hypertonic saline should not be administered to infants with a diagnosis of bronchiolitis in the emergency department (Evidence Quality: B; Recommendation Strength: Moderate Recommendation), but hypertonic saline may be administered when they are hospitalized (Evidence Quality: B; Recommendation Strength: Weak Recommendation [based on randomized controlled trials with inconsistent findings]).-Chest physiotherapy should not be used in infants and children with a diagnosis of bronchiolitis (Evidence Quality: B; Recommendation Strength: Moderate Recommendation).-Antibiotics should not be administered in bronchiolitis unless there is a concomitant bacterial infection, or a strong suspicion of one (Evidence Quality: B; Recommendation Strength: Strong Recommendation).-Oxygen therapy may not be administered if the oxyhemoglobin saturation exceeds 90% in infants and children with a diagnosis of bronchiolitis (Evidence Quality: D; Recommendation Strength: Weak Recommendation [based on low level evidence and reasoning from first principles]).-Clinicians should administer nasogastric or intravenous fluids for infants with a diagnosis of bronchiolitis who cannot maintain hydration orally (Evidence Quality: X; Recommendation Strength: Strong Recommendation).How do we prevent RSV?Infant Immuno-prophylaxis:A clinical trial in 2022 demonstrated that a single injection of nirsevimab (Beyfortus®), administered before the RSV season, protected healthy late-preterm and term infants from RSV-associated lower respiratory tract that required medical treatment. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life.Additionally, on August 3, 2023, the Advisory Committee on Immunization Practices (ACIP) recommended nirsevimab for all infants younger than 8 months who are born during or entering their first RSV season and for infants and children between 8-19 months who are at increased risk for severe RSV disease and are entering their second RSV season. On the basis of pre-COVID-19 pandemic patterns, nirsevimab could be administered in most of the continental United States from October through the end of March.Maternal Vaccination: The CDC recommends the administration of the RSVPreF vaccine to pregnant women between 32 0/7 and 36 6/7 weeks of gestation. This vaccination aims to reduce the risk of RSV-associated lower respiratory tract infection in infants during the first 6 months of life.At this time, if a pregnant woman has already received a maternal RSV vaccine during any previous pregnancy, CDC does not recommend another dose of RSV vaccine during subsequent pregnancies.Older individuals: -Each year in the U.S., it is estimated that between 60,000 and 160,000 older adults are hospitalized and between 6,000 and 10,000 die due to RSV infection-ABRYSVO's approval will help offer older adults protection in the RSV season.-On June 26, 2024, ACIP voted to give these recommendations: all adults older than 75 years and adults between 60–74 years who are at increased risk for severe RSV disease should receive a single dose of RSV vaccine (Abrysvo®).Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Hamid S, Winn A, Parikh R, et al. Seasonality of Respiratory Syncytial Virus — United States, 2017–2023. MMWR Morb Mortal Wkly Rep 2023;72:355–361. DOI: http://dx.doi.org/10.15585/mmwr.mm7214a1Hammitt LL, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Madhi SA, Muller WJ, Zar HJ, Brooks D, Grenham A, Wählby Hamrén U, Mankad VS, Ren P, Takas T, Abram ME, Leach A, Griffin MP, Villafana T; MELODY Study Group. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med. 2022 Mar 3;386(9):837-846. doi: 10.1056/NEJMoa2110275. PMID: 35235726.Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ, Zorc JJ, Stanko-Lopp D, Brown MA, Nathanson I, Rosenblum E, Sayles S 3rd, Hernandez-Cancio S; American Academy of Pediatrics. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014 Nov;134(5):e1474-502. doi: 10.1542/peds.2014-2742. Erratum in: Pediatrics. 2015 Oct;136(4):782. doi: 10.1542/peds.2015-2862. PMID: 25349312.CDC, per their published article Seasonality of Respiratory Syncytial Virus — United States for 2017–2023, in the United StatesWhat U.S. Obstetricians Need to Know About Respiratory Syncytial Virus.Debessai H, Jones JM, Meaney-Delman D, Rasmussen SA. Obstetrics and Gynecology. 2024;143(3):e54-e62. doi:10.1097/AOG.0000000000005492.Maternal Respiratory Syncytial Virus Vaccination and Receipt of Respiratory Syncytial Virus Antibody (Nirsevimab) by Infants Aged

N Engl J Med 2024;391:1673-1684Background: Non-ST elevation myocardial infarction (NSTEMI) is the most common acute coronary syndrome subtype in adults over 75 years old. However, these patients were underrepresented in landmark NSTEMI trials. Older adults with multiple comorbidities face an increased risk of mortality. While NSTEMI contributes to this risk, they also have competing risks such as advanced age, frailty, and chronic kidney disease. The presence of competing risks means that aggressively managing one condition may have a smaller impact on overall mortality compared to a younger, otherwise healthy adult with myocardial infarction, whose primary risk of death stems from the myocardial infarction itself. Additionally, comorbid conditions like advanced kidney disease and diffuse atherosclerosis can increase the risks associated with revascularization.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.A patient-level meta-analysis of smaller trials, including 1,479 patients, found that in elderly patients with NSTEMI, an invasive strategy reduced myocardial infarction and urgent revascularization but not mortality.The Older Patients with Non–ST-Segment Elevation Myocardial Infarction Randomized Interventional Treatment (SENRIOR-RITA) trial sought to assess invasive vs conservative management of elderly patients with NSTEMI, in a more pragmatic design.Patients: Eligible patients had to have type I NSTEMI and be 75 years or older.Patients were excluded if they had cardiogenic shock or life expectancy less than 1 year.Baseline characteristics: The trial randomized 1,518 patients from hospitals across England and Scotland – 753 randomized to invasive strategy and 765 to conservative strategy.The average age of patients was 82 years and 55% were men. Approximately 65% had hypertension, 31% had diabetes, 31% had hyperlipidemia, 31% had prior myocardial infarction, 15% had prior stroke or TIA, 21% had kidney disease, 15% had chronic obstructive pulmonary disease, and 5% were current smokers.The average Charlson comorbidity index was 5.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive or conservative strategy.In the invasive strategy, patients underwent coronary angiogram, and revascularization was performed as appropriate. In the conservative arm, patients were treated (unless contraindicated) with aspirin, a P2Y12 receptor antagonist, statin, beta-blocker and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Patients in the conservative arm were allowed to have a coronary angiogram if they had worsening clinical status.Endpoints: The primary end point was a composite of cardiovascular death or nonfatal myocardial infarction. Secondary outcomes included all-cause death, subsequent coronary revascularization, hospitalization for heart failure, stroke and bleeding.Analysis was performed based on the intention-to-treat principle. The trial aimed to detect a hazard ratio of 0.78, assuming a 20% risk of the primary outcome in the conservative arm. A sample size of 1,668 patients with at least 688 primary outcome events would provide 90% power at 5% alpha, while 520 events would provide 80% power.Results: Among the patient randomized to the invasive arm, 90% underwent coronary angiography and 50% underwent revascularization. The medium number of days from admission to coronary angiography was 5. Among patients randomized to the conservative arm, 5.6% underwent coronary angiography within 7 days. The median follow-up time was 4.1 years.The primary outcome was not significantly different between both groups (25.6% with invasive vs 26.3% with conservative, HR: 0.94, 95%: 0.77 - 1.14; p= 0.53).There was also no difference in all-cause death (36.1% vs 32.3%), cardiovascular death (15.8% vs 14.2%), stroke (4.2% vs 5.2%), hospitalization for heart failure (10.9% vs 10.7%), or major bleeding (8.2% vs 6.4%) “incidence for invasive mentioned first”. Future coronary revascularization was more frequent in the conservative arm (13.7% vs 3.9%). Non-fatal myocardial infarction was significantly lower with an invasive strategy (11.7% vs 15.0%).Procedural related complications occurred in less than 1% of the patients.There were no significant subgroup interactions for the primary outcome.Conclusion: In older patients with NSTEMI, an invasive strategy compared to conservative strategy, did not reduce the primary composite endpoint of cardiovascular death or nonfatal myocardial infarction, over a median of 4.1 years.The trial enrolled fewer patients than planned, and the lower-than-expected event rate reduced its statistical power. Additionally, the median 5-day delay before coronary angiography may have biased the results toward the conservative strategy.Despite its limitations, this trial demonstrates that a conservative approach is a reasonable option for selected older patients with NSTEMI. It also highlights that, although enrolling older patients with comorbidities in trials is challenging, it is feasible, and greater effort is needed to include more of this population in future trials.Finally, in this trial of patients with myocardial infarction, about one-third died over a median of 4.1 years, with less than half of these deaths attributed to cardiovascular disease. Even if an invasive strategy had reduced cardiovascular mortality, its impact on all-cause mortality would have been less significant. This concept extends beyond this trial; when interventions are applied to older patients with multiple competing risks, their overall benefit diminishes.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 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.

John Patrick Co is vice president of education at Mass General Brigham and an associate professor of pediatrics at Harvard Medical School. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. D.F. Weinstein, E. Olson, and J.P.T. Co. Addressing Socioeconomic Barriers to Residency Choice. N Engl J Med 2025;392:1353-1355.

Raphael Coelho e Ênio Macedo convidam Guilherme Kenzo para falar sobre abordagem de suicídio no PS em três casos.Precisa de ajuda? Ligue 188 - Centro de valorização da vida.Referências:1. Stene-Larsen, Kim, and Anne Reneflot. “Contact with primary and mental health care prior to suicide: A systematic review of the literature from 2000 to 2017.” Scandinavian journal of public health vol. 47,1 (2019): 9-17. doi:10.1177/14034948177462742. Walby, Fredrik A et al. “Contact With Mental Health Services Prior to Suicide: A Systematic Review and Meta-Analysis.” Psychiatric services (Washington, D.C.) vol. 69,7 (2018): 751-759. doi:10.1176/appi.ps.2017004753. Sher, L. “Preventing suicide.” QJM : monthly journal of the Association of Physicians vol. 97,10 (2004): 677-80. doi:10.1093/qjmed/hch1064. Domaradzki, Jan. “The Werther Effect, the Papageno Effect or No Effect? A Literature Review.” International journal of environmental research and public health vol. 18,5 2396. 1 Mar. 2021, doi:10.3390/ijerph180523965. https://www.planalto.gov.br/ccivil_03/leis/leis_2001/l10216.htm#:~:text=LEI%20No%2010.216%2C%20DE,modelo%20assistencial%20em%20sa%C3%BAde%20mental6. https://mpce.mp.br/wp-content/uploads/2018/04/20180061-OMS-Prevencao-do-Suicidio-Manual-para-profissionais-da-midia.pdf7. Niederkrotenthaler, Thomas et al. “Role of media reports in completed and prevented suicide: Werther v. Papageno effects.” The British journal of psychiatry : the journal of mental science vol. 197,3 (2010): 234-43. doi:10.1192/bjp.bp.109.0746338. Phillips, D P. “The influence of suggestion on suicide: substantive and theoretical implications of the Werther effect.” American sociological review vol. 39,3 (1974): 340-54.9. Jack, Belinda. “Goethe's Werther and its effects.” The lancet. Psychiatry vol. 1,1 (2014): 18-9. doi:10.1016/S2215-0366(14)70229-910. Jack, Belinda. “Goethe's Werther and its effects.” The lancet. Psychiatry vol. 1,1 (2014): 18-9. doi:10.1016/S2215-0366(14)70229-911. Guinovart, Martí et al. “Towards the Influence of Media on Suicidality: A Systematic Review of Netflix's 'Thirteen Reasons Why'.” International journal of environmental research and public health vol. 20,7 5270. 27 Mar. 2023, doi:10.3390/ijerph2007527012. Cipriani, Andrea et al. “Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis.” BMJ (Clinical research ed.) vol. 346 f3646. 27 Jun. 2013, doi:10.1136/bmj.f364613. BOTEGA, Neury Jose. Crise Suicida: Avaliação e manejo. Porto Alegre: Artmed, 2015.14. Seena Fazel, Bo Runeson. Suicide. N Engl J Med 2020;382:266-274. DOI: 10.1056/NEJMra190294415. Gustavo Turecki et al. Suicide and suicide risk. Nat Rev Dis Primers. 2019. Oct 24;5(1):74. doi: 10.1038/s41572-019-0121-0.16. https://www.setembroamarelo.com/17. Cartilha de prevenção de suicídio: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/cartilhas/2024/cartilha-prevencao-de-suicidios.pdf/view18. Baldaçara L, Rocha GA, Leite VDS, Porto DM, Grudtner RR, Diaz AP, Meleiro A, Correa H, Tung TC, Quevedo J, da Silva AG. Brazilian Psychiatric Association guidelines for the management of suicidal behavior. Part 1. Risk factors, protective factors, and assessment. Braz J Psychiatry. 2021 Sep-Oct;43(5):525-537. doi: 10.1590/1516-4446-2020-0994. PMID: 33111773; PMCID: PMC8555650. - https://pubmed.ncbi.nlm.nih.gov/33111773/19. Baldaçara L, Grudtner RR, da S Leite V, Porto DM, Robis KP, Fidalgo TM, Rocha GA, Diaz AP, Meleiro A, Correa H, Tung TC, Malloy-Diniz L, Quevedo J, da Silva AG. Brazilian Psychiatric Association guidelines for the management of suicidal behavior. Part 2. Screening, intervention, and prevention. Braz J Psychiatry. 2021 Sep-Oct;43(5):538-549. doi: 10.1590/1516-4446-2020-1108. Erratum in: Braz J Psychiatry. 2021 Sep-Oct;43(5):563. doi: 10.1590/1516-4446-2020-0025. PMID: 33331533; PMCID: PMC8555636. - https://pubmed.ncbi.nlm.nih.gov/33331533/20. https://cvv.org.br/wp-content/uploads/2023/08/manual_prevencao_suicidio_profissionais_saude.pdf21. https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/edicoes/2024/boletim-epidemiologico-volume-55-no-04.pdf

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.

N Engl J Med 2005;353:1095-1104Background: Prior trials on revascularization in patients with acute coronary syndromes without ST-segment elevation have yielded mixed results. While FRISC II and TACTICS-TIMI 18 demonstrated a significant reduction in myocardial infarction, this benefit was not observed in RITA 3. None of these trials showed a significant reduction in mortality. Further research is needed to guide treatment strategies in this population, particularly after the introduction of early use of clopidogrel and intensive lipid-lowering 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 Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial sough to test the hypothesis that an early invasive strategy is superior to selective invasive strategy for patients with non-ST elevation myocardial infarction (NSTEMI).Patients: Eligible patients had to have all of the following: Worsening symptoms of ischemia or symptoms at rest with the last episode being 24 hours before randomization, elevated cardiac troponin T level (≥0.03 μg per liter); and either ischemic EKG changes (defined as ST-segment depression or transient ST-segment elevation exceeding 0.05 mV, or T-wave inversion of ≥0.2 mV in two contiguous leads) or a documented history of coronary artery disease.Patients were excluded if they were older than 80 years, had an indication for primary percutaneous coronary intervention or fibrinolytic therapy, hemodynamic instability or overt congestive heart failure, oral anticoagulant drugs use in the past 7 days, fibrinolytic treatment within the past 96 hours, percutaneous coronary intervention within the past 14 days, elevated bleeding risk, plus others.Baseline characteristics: The trial randomized 1,200 patients from 42 Dutch hospitals – 604 randomized to early invasive strategy and 596 randomized to selective invasive strategy.The average age of patients was 62 years and 74% were men. Approximately 39% had hypertension, 14% had diabetes, 35% had hyperlipidemia, 23% had prior myocardial infarction and 41% were current smokers.Approximately 48% of the patients had ST deviation equal to or greater than 0.1 mV.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo early invasive vs selective invasive strategy.Patients received 300 mg of aspirin at the time of randomization, followed by at least 75 mg daily indefinitely, and enoxaparin (1 mg/kg for a maximum of 80 mg) subcutaneously twice daily for at least 48 hours. The early use of clopidogrel (300 mg immediately, followed by 75 mg daily) in addition to aspirin was recommended to the investigators after the drug was approved for acute coronary syndrome in 2002. Intensive lipid-lowering therapy, preferably atorvastatin 80 mg daily or the equivalent was recommended as soon as possible after randomization. All interventional procedures during the index admission were performed with the use of abciximab.Patients assigned to the early invasive strategy were scheduled to undergo angiography within 24 - 48 hours after randomization. Patients assigned to the selective invasive strategy underwent coronary angiography if they had refractory angina despite optimal medical therapy, hemodynamic or rhythm instability, or significant ischemia on pre-discharge exercise test.In both groups, percutaneous coronary intervention (PCI) was performed when appropriate, without providing more details in the manuscript.The level of creatine kinase MB was measured at 6-hour intervals during the first day, after each new clinical episode of ischemia, and after each percutaneous revascularization procedure.Endpoints: The primary endpoint was a composite of all-cause death, myocardial infarction, or rehospitalization for angina at 1-year.The estimated sample size to provide 80% power to detect 25% relative risk difference between the two treatment groups at 5% alpha was 1,200 patients. This assumed that 21% of the patients in the early invasive arm would experience the primary outcome.Results: During the index admission, 98% of the patients in the early invasive strategy arm underwent coronary angiogram compared to 53% in the selective invasive arm. At 1-year, 79% of the patients in the early invasive strategy arm underwent revascularization compared to 54% in the selective invasive arm.The primary outcome was not significantly different between both treatment groups (22.7% with early invasive vs 21.2% with selective invasive, RR: 1.07; 95% CI: 0.87 - 1.33; p= 0.33). All-cause death was the same in both groups (2.5%). Myocardial infarction was significantly higher with the early invasive strategy (15.0% vs. 10.0%, RR: 1.50, 95% CI: 1.10 – 2.04; p= 0.005), while rehospitalization for angina was lower with early invasive (7.4% vs. 10.9%, RR: 0.68, 95% CI: 0.47 – 0.98; p= 0.04). Most myocardial infarctions were revascularization related and these were significantly more frequent with early invasive (11.3% vs 5.4%). Spontaneous myocardial infarctions were 3.7% with early invasive and 4.6% with selective invasive and this was not statistically significant.Major bleeding, not related CABG, during the index admission was more frequent with the early invasive strategy (3.1% vs 1.7%).There were no significant subgroup interactions for the primary outcome, including based on ST deviation and troponin levels.Conclusion: In patients with NSTEMI, an early invasive strategy was not superior to selective invasive strategy in reducing the composite endpoint of all-cause death, myocardial infarction, or rehospitalization for angina at 1-year. An early invasive strategy was associated with more myocardial infarctions with a number needed to harm of 20 patients, which was secondary to revascularization related myocardial infarction. An early invasive strategy reduced rehospitalization for angina with a number needed to treat of approximately 29 patients.The ICTUS trial showed that revascularization can cause harm and highlighted how counting procedural myocardial infarctions can influence outcome estimates. While there is ongoing debate about the significance of periprocedural myocardial infarctions, evidence indicates an association with increased mortality. Whether periprocedural myocardial infarctions are 'less severe' than spontaneous myocardial infarctions remains controversial, as their impact varies based on infarct size and patient characteristics. This underscores the importance of including all-cause mortality or advanced systolic heart failure as endpoints in trials of revascularization.Patients in ICTUS received better background medical therapy compared to prior trials in this area. While this could be responsible for the divergent results compared to other prior trials. It also highlights the heterogeneity of NSTEMI patients and that an invasive strategy is not appropriate for all.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

Rochelle Walensky is the Bayer fellow in health and biotech at the American Academy in Berlin, a senior fellow at the Harvard Kennedy School, and an executive fellow at Harvard Business School. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. R.P. Walensky and L.D. Walensky. Application Overload — A Call to Reduce the Burden of Applying to Medical School. N Engl J Med. DOI: 10.1056/NEJMp2414572. D.B. Holt and E.A. Elster. Rethinking Shadowing for Aspiring Physicians. N Engl J Med 2025;392:1249-1251. A.A. Iyer, D.A. Hirsh, and R.M. Schwartzstein. Medical School Grading — Is “Good Enough” Good Enough? N Engl J Med 2025;392:1254-1257.

Featuring articles on intensive blood-pressure control in patients with diabetes, IgG4-related disease, severe chronic rhinosinusitis, advanced breast cancer, and vaccinating against C. difficile infection; a review article on chronic cough in adults; a case report of a man with hepatocellular carcinoma; an editorial on order out of chaos; and Perspectives on health care bridges, on partnerships between pharmaceutical and telehealth companies, and on the definition of failure.

Erin Fuse Brown is a professor of health services, policy, and practice at the Brown University 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. E.C. Fuse Brown, O.J. Wouters, and A. Mehrotra. Partnerships between Pharmaceutical and Telehealth Companies — Increasing Access or Driving Inappropriate Prescribing? N Engl J Med 2025;392:1148-1151.

In this episode, we dive into the early therapies and how our understanding of vascular physiology drastically changed the management of pulmonary hypertension. Intro 0:12 In this episode 0:18 Recap of part 1 & 2 0:31 What part 3 is about 2:31 WHO conference in 1975: Treating pulmonary hypertension 3:48 The Discovery of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), Part 1 5:20 Epoprostenol 6:18 Prostacyclin 10:37 Endothelin antagonists 11:41 Phosphodiesterase type 5 (PDE5) inhibitors 14:08 Interaction of nerves and blood vessels 15:06 The Soups VS the Sparks 17:36 A dreamed experiment 19:06 Acetylcholine 23:23  Enter “the calabar bean” 24:45 Acetylcholine and vasodilation: 1976 26:01 Rabbit aorta 27:45 Nitric oxide 29:38 Why are we using nitric oxide to treat pulmonary hypertension? 31:31 Tachyphylaxis 33:48 TNT factories 35:09 Nitrous oxide and tachyphylaxis 36:52 Pfizer in the 1980s 38:06 Understanding the trigger of pulmonary hypertension 40:53 PDE5 and nitric oxide and pulmonary hypertension 43:07 The end of the ripping yarns 44:20 Coming up in part 4 46:17 Thanks for listening 47:29 We'd love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Bernard C. C R Soc Biol. 1851;3:163-164. Furchgott RF, et al. Nature. 1980;doi:10.1038/288373a0. Galiè N, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa050010. Ghofrani HA, et al. Nat Rev Drug Discov. 2006;doi:10.1038/nrd2030. Giordano D, et al. Biochim Biophys Acta. 2001;doi:10.1016/s0167-4889(01)00086-6. Guthrie F. Q J Chem Soc. 1859;doi:10.1039/QJ8591100245. Higenbottam T, et al. Lancet. 1984;doi:10.1016/s0140-6736(84)91452-1. Marsh N, et al. Clin Exp Pharmacol Physiol. 2000;doi:10.1046/j.1440-1681.2000.03240.x. Montastruc JL, et al. Clin Auton Res. 1996;doi:10.1007/BF02281906. Nejad SH, et al. Future Cardiol. 2024;doi:10.1080/14796678.2024.2367390. Tansey EM. C R Biol. 2006;doi:10.10116/j.crvi.2006.03.012. Warren JV. Trans Am Clin Climatol Assoc. 1988;99:10-6. Disclosures: Brown reports no relevant financial disclosures.

N Engl J Med 2001;344:1879-1887Background: Acute coronary syndrome is broadly categorized into unstable angina, non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). In unstable angina, there is no rise in cardiac biomarkers, although some challenge this clinical entity in the current era of high sensitivity troponins. In NSTEMI, there is elevation of cardiac biomarkers but no ST segment elevation on the electrocardiogram. In STEMI, there is an ST segment elevation on the electrocardiogram as well as a rise in cardiac biomarkers.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.In patients with STEMI, percutaneous coronary intervention (PCI) significantly improves outcomes. However, its role in acute coronary syndrome without ST-segment elevation is less clear for several reasons. Patients with NSTEMI tend to be older and have more comorbidities, increasing procedural risks. This also means that they have competing risks for mortality, potentially reducing the benefit of PCI. Another key challenge is that NSTEMI patients frequently have multivessel disease, making it more difficult to identify the culprit lesion; since there is usually only partial occlusion of the culprit coronary artery. In contrast, there is usually complete occlusion of a coronary artery in STEMI and ST-segment elevation on the electrocardiogram helps localize the infarcted area, making it relatively easy to identify the culprit artery.The findings from previous randomized trials of revascularization in unstable angina and NSTEMI, have been inconsistent. The TACTICS–Thrombolysis in Myocardial Infarction 18 trial sought to compare early invasive vs conservative strategy in patients with unstable angina or NSTEMI.Patients: Eligible patients had angina within 24 hours that was: >20 minutes in duration, accelerating angina, or recurrent episodes at rest or with minimal effort. Patients also had to have one of the following: ST-segment depression of at least 0.05 mV, transient ( 2.5 mg/dL.Baseline characteristics: The trial randomized 2,220 patients – 1,114 randomized to early invasive strategy and 1,106 randomized to conservative strategy.The average age of patients was 62 years and 66% were men. Approximately 28% had diabetes and 39% had prior myocardial infarction.Troponin T levels were elevated (>0.01 ng/ml) in 54% of the patients.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo early invasive vs conservative strategy.Patients received aspirin 325 mg daily, intravenous unfractionated heparin (5000U bolus, followed by an infusion at 1000U/ hour for 48 hours), and intravenous tirofiban (0.4 μg/kg/minute for 30 minutes followed by an infusion of 0.1 μg/kg/minute for 48 hours or until revascularization with tirofiban administered for at least 12 hours after PCI).Patients in the early invasive arm underwent coronary angiogram between 4 and 48 hours after randomization and underwent PCI as appropriate. Patients in the conservative arm were treated medically. If stable, they underwent an exercise-tolerance test before discharged (83% of these tests were with nuclear perfusion or echocardiography imaging). Patients in the conservative arm underwent coronary angiography with PCI if they had angina at rest associated with ischemic EKG changes or elevation in cardiac biomarkers, had clinical instability or had ischemia on their stress test.Endpoints: The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome, at six months.The estimated sample size to provide 80% power was 1,720 patients. This assumed that 22% of the patients in the conservative arm would experience the primary outcome and that the early invasive strategy would result in 25% relative risk reduction in the primary outcome. The sample size was later increased to 2,220 patients.Results: In the early invasive strategy, 97% of the patients underwent coronary angiogram after a medium of 22 hours after randomization, and 60% underwent PCI or CABG. In the conservative arm, 51% underwent coronary angiogram and 36% underwent revascularization during the index hospitalization.The primary composite endpoint was lower with the early invasive strategy (15.9% vs 19.4%, odds ratio: 0.78, 95% CI: 0.62 - 0.97; p= 0.025). The Kaplan-Meier curves started to separate at approximately one week. This benefit was driven by lower myocardial infarction and lower rehospitalization for an acute coronary syndrome with the early invasive strategy; (4.8% vs 6.9%) and (11.0% vs 13.7%), respectively. There was no difference in all-cause death (3.3% vs 3.5%).There were 3 important subgroup interactions. First is based on ST changes where patients with ST changes at presentation had all the benefit with an early invasive strategy (16.4% vs 26.3% [for patients with ST changes] and 15.6% vs 15.3% [for patients without ST changes]). Second is based on Troponin T levels where patients with troponin T> 0.1 ng/mL had significantly more benefit with an early invasive strategy (16.4% vs 24.5% and 15.1% vs 16.6%). The third is based on TIMI score where patients with higher TIMI score had more benefit with an early invasive approach. For a high TIMI score of 5-7, the event rate was 19.5% with early invasive vs 30.6% with conservative approach. Patients with TIMI score of 0-2 had no benefit with an early invasive strategy (12.8% with early invasive vs 11.8% with conservative strategy).Note to readers: TIMI score is a risk stratification tool used to predict 14-day adverse outcomes in patients with unstable angina or NSTEMI. The score ranges from 0 to 7 with higher scores indicating worse prognosis.Conclusion: In patients with unstable angina or NSTEMI, an early invasive strategy reduced the composite endpoint of death from any cause, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months with a number needed to treat of approximately 29 patients.The subgroup analysis of this trial is particularly important and biologically plausible, as the presence of ST changes and level of cardiac biomarkers elevation indicate more significant myocardial ischemia or necrosis. Patients without ST changes comprised 62% of the study participants, while those with negative cardiac biomarkers made up 59%, and the study results should not be generalized to these subgroups.Another key consideration is the lack of detailed criteria for what was deemed ‘appropriate' revascularization. Only 60% of patients in the early invasive strategy group underwent revascularization, underscoring that not all patients with unstable angina or NSTEMI benefit from coronary angiography and that further risk stratification is necessary.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 breast cancer, bloodstream infection, subarachnoid hemorrhage, scrub typhus, and birth-related mortality; a review article on the evaluation and treatment of infertility; a case report of a woman with altered mental status and acidemia; and Perspectives on advancing transgender health amid policy threats, on evidence-based work design, and on what an oncologist had wished she had done for a grieving father.

Alex Keuroghlian is an associate professor of psychiatry at Harvard Medical School and the director of the Division of Public and Community Psychiatry at Massachusetts General Hospital. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. D.R.A. Coelho, A.L. Chen, and A.S. Keuroghlian. Advancing Transgender Health amid Rising Policy Threats. N Engl J Med 2025;392:1041-1044.

In this audio interview, Editor-in-Chief Eric Rubin and Deputy Editor Lindsey Baden are joined by state public health leaders Robbie Goldstein and Jennifer Shuford to discuss action against H5N1 in Massachusetts and Texas and across the nation. Eric Rubin is the Editor-in-Chief of the Journal. Lindsey Baden is a Deputy Editor of the Journal. Robert Goldstein is the Massachusetts Commissioner of Public Health. Jennifer Shuford is the Commissioner of the Texas Department of State Health Services. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. E.J. Rubin and Others. NEJM Outbreaks Update — H5N1: A View from the States. N Engl J Med. DOI: 10.1056/NEJMe2502863.

N Engl J Med 2024;390:1481-1492Background: In patients with ST-elevation myocardial infarction (STEMI), opening the culprit artery improves outcomes. Nearly half of STEMI patients have disease in other coronary arteries. Whether revascularizing these non-culprit arteries improves outcomes remained uncertain. The PRAMI trial showed improvement in outcomes with complete revascularization but was relatively small, included 465 patients, and did not require the use of fractional flow reserve (FFR).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 FFR-Guidance for Complete Nonculprit Revascularization (FULL REVASC) trial sought to assess if FFR-guided completed revascularization improves outcomes compared to culprit-only percutaneous coronary intervention (PCI).The COMPLETE trial was not published by the time the FULL REVASC trial started enrolling patients.Patients: Eligible patients had STEMI and were undergoing PCI or had high risk NSETMI undergoing urgent PCI. High risk NSTEMI included patients with dynamic ST–T-wave changes, ongoing chest pain, acute heart failure, hemodynamic instability independent of electrocardiographic changes, or life-threatening ventricular arrhythmias.Eligible patients had to have multivessel coronary artery disease, defined as one or more lesions in a nonculprit artery with a diameter of ≥ 2.5 mm and a visually graded stenosis of 50 - 99%.Patients were excluded if they had previous CABG, left main disease or cardiogenic shock.Baseline characteristics: The trial randomized 1,542 patients – 778 randomized to culprit-only PCI and 764 randomized to complete revascularization. Patients were recruited from 32 centers in 7 countries.Approximately 91% of the patients had STEMI and 9% had high risk NSTEMI.The average age of patients was 65 years and 76% were men. Approximately 51% had hypertension, 16% had diabetes, 23% were on treatment for hyperlipidemia, 8% had prior myocardial infarction, and 35% were current smokers.The number of residual coronary arteries with stenosis of 50-99% was 1 in 72% of the patients and 2 or more in the rest.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo culprit-only PCI or FFR-guide complete revascularization. The study was open label.Patients in the culprit-PCI only group did not receive further revascularization during the index hospitalization. Patients in the FFR-guided complete revascularization could receive further revascularization during the index procedure or during the index hospitalization. PCI of non-culprit lesion was recommended if FFR was 0.80 or less.Endpoints: The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The main secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularizationAnalysis was performed based on the intention-to-treat principle. The estimated sample size to achieve 80% with a two-sided alpha of 0.05 was 4,052 patients. This sample size would detect 0.75 risk ratio for the composite outcome of death or myocardial infarction at 1-year assuming 9.9% event rate in the culprit-only PCI. After the publication of the COMPLETE trial, the trial was stopped early due to ethical and feasibility concerns. Consequently, the original key secondary outcome (death from any cause, myocardial infarction, or unplanned revascularization) became the new primary outcome, and events after 1 year of follow-up were included in the primary analysis.Results: The trial was stopped after randomizing 38.1% of the original sample size. Among the patients assigned to the FFR-guided complete-revascularization arm, the procedure was followed in 95.9% of the patients, and among these patients, 17.9% underwent FFR-guided complete revascularization of non-culprit lesions during the primary PCI and the rest during the index hospitalization. Among the patients assigned to culprit-only arm, the assigned strategy was followed in 99.6% of the patients. The median follow-up time was 4.8 years.FFR was 0.8 or less in 392 (47.3%) of non-culprit vessels assessed, and PCI was performed in 369 (94.1%) of these vessels. In total, PCI was performed in 18.8% of the total non-culprit vessels. The average number of stents during the index hospitalization was 1 in the culprit-only PCI group and 2 in the complete revascularization group.The primary composite outcome was not significantly different between both treatment groups (19.0% with complete-revascularization vs 20.4% with culprit-only PCI, HR: 0.93, 95% CI: 0.74 - 1.17; p= 0.53). There were also no significant differences in composite endpoint of death from any cause or myocardial infarction (16.5% with complete revascularization vs 15.3% with culprit-only PCI) or unplanned revascularization (9.2% with complete revascularization vs 11.7% with culprit-only PCI).Stent thrombosis and stent restenosis were significantly more frequent in the complete revascularization arm (2.5% vs 0.9%, HR: 2.80, 95% CI: 1.18 – 6.67) and (4.2% vs 2.3%, HR: 1.84, 95% CI: 1.03 – 3.28), respectively.Baseline risk or coronary anatomy did not significantly affect subgroup interactions for the primary outcome.Conclusion: In patients with STEMI or high risk NSTEMI, FFR-guided complete revascularization compared to culprit-only PCI, did not improve the outcomes of death from any cause, myocardial infarction, or unplanned revascularization, over a median follow up time of 4.8 years. Complete revascularization resulted in more stent thrombosis and stent restenosis.The study lost some statistical power by stopping early, resulting in a final power of 74%. We disagree with the authors' decision to halt the trial prematurely based on the findings of the COMPLETE trial. COMPLETE was the first large trial to demonstrate a benefit in hard outcomes when revascularizing stable plaques, and its results warrant further confirmation. Furthermore, COMPLETE used different strategy as FFR was not required.Note to readers: Power measures the study's ability to avoid a Type II error (false negative) and it equals 1 - β with β being the probability of a Type II error. In other words, power represents the probability of correctly rejecting the null hypothesis (H₀) when the alternative hypothesis (H₁) is true. Most clinical trials aim for 80% or 90% power. For example, a study with 80% power has a 20% risk of failing to detect a real effect.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 bacterial vaginosis, diabetes prevention, Danon disease, chronic spontaneous urticaria, and VITT-like monoclonal gammopathy of thrombotic significance; a review article on micronutrients; a Clinical Problem-Solving on unveiling the unforeseen; and Perspectives on bankruptcy and genetic information, on drug development for rare diseases, on facing political attacks on medical education, and on sustaining equity efforts in the face of regression.

Sara Gerkeis an associate professor of law at the University of Illinois Urbana-Champaign. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. S. Gerke, M.B. Jacoby, and I.G. Cohen. Bankruptcy, Genetic Information, and Privacy — Selling Personal Information. N Engl J Med 2025;392:937-939.

N Engl J Med 2019;381:1411-1421Background Percutaneous coronary intervention (PCI) had been clearly established as the standard of care for ST elevation myocardial infarction. Yet many patients taken for PCI have multiple lesions in addition to the culprit. The benefit of routinely treating additional significant lesions has been unclear, with previous smaller trials showing reductions in composite outcomes primarily driven by reduced revascularization rates.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 COMPLETE (Complete vs Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial investigated whether performing percutaneous coronary intervention (PCI) on non-culprit lesions reduces cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease.Patients The trial enrolled 4,041 patients from 140 centers in 31 countries between February 2013 and March 2017. Eligible patients had STEMI with successful culprit-lesion PCI and at least one non-culprit coronary artery lesion with ≥70% stenosis (or 50-69% stenosis with FFR ≤0.80) in a vessel ≥2.5mm in diameter. Patients were randomized within 72 hours after successful culprit-lesion PCI. Exclusion criteria included planned surgical revascularization and previous coronary bypass surgery.Baseline Characteristics The mean age was approximately 62 years, with about 80% being male. Approximately 19% had diabetes, 8% had previous MI, and 7% had previous PCI. Over 90% of patients underwent primary PCI (vs. pharmacoinvasive or rescue PCI), with 80% using radial access.The groups were well-balanced, with similar SYNTAX scores at baseline and similar culprit and non-culprit lesion characteristics. About 76% had one residual diseased vessel and 24% had two or more. Guideline directed medical therapy was robust and balanced, including more than 99% on dual antiplatelet therapy, 98% on statins, 88% on beta blocker, and 85% on ACEi or ARB.In patients in the complete revascularization group designated for non-culprit PCI during index hospitalization, the mean time to PCI was 1 day. In the group designated for non-culprit PCI after discharge, the mean time was 23 days.Trial procedures Patients were randomized to complete revascularization (n=2,016) or culprit-lesion-only PCI (n=2,025). In the complete revascularization group, investigators specified before randomization whether non-culprit PCI would occur during index hospitalization or after discharge (within 45 days).Everolimus-eluting stents were recommended for all procedures. Both groups received guideline-based medical therapy including dual antiplatelet therapy with aspirin and ticagrelor for at least one year.Endpoints The first coprimary outcome was cardiovascular death or new myocardial infarction. The second coprimary outcome was cardiovascular death, myocardial infarction, or ischemia-driven revascularization. Secondary outcomes included individual components of the composite outcomes, all-cause mortality, and safety outcomes like major bleeding, stroke, and stent thrombosis.Trialists estimated that a sample of 4000 patients would give 80% power to detect a 22% lower risk of the composite of cardiovascular death or myocardial infarction in the complete-revascularization group than in the culprit-lesion-only PCI group, assuming an event rate of 5% per year in the culprit-lesion-only PCI group. The first coprimary outcome was tested at a P value of 0.045 and the second at a P value of 0.0119.The co-primary endpoints were analyzed according to the time to first event approach. Confidence intervals for secondary and exploratory efficacy outcomes were not adjusted for multiple comparisons, and therefore inferences drawn from these intervals may not be reproducible.Results Over a median follow-up of 36.2 months, the first coprimary outcome occurred in 7.8% of the complete-revascularization group versus 10.5% of the culprit-lesion-only group (hazard ratio 0.74, 95% CI: 0.60-0.91; p= 0.004). Benefit was driven by reduced myocardial infarction rates (5.4% vs 7.9%) while cardiovascular death rates were similar (2.9% vs 3.2%).The second coprimary outcome was also reduced with complete revascularization (8.9% versus 16.7%, HR: 0.51, 95% CI: 0.43-0.61; p

In this NEJM Outbreaks Update, Editor-in-Chief Eric Rubin and Deputy Editor Lindsey Baden are joined by veterinarian and virologist Yoshihiro Kawaoka to discuss avian influenza and its current impact on chickens, cows, cats, and humans. Eric Rubin is the Editor-in-Chief of the Journal. Lindsey Baden is a Deputy Editor of the Journal. Yoshihiro Kawaoka is a veterinarian and virologist and a professor at the University of Wisconsin-Madison and the University of Tokyo. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. E.J. Rubin and Others. NEJM Outbreaks Update — H5N1. N Engl J Med. DOI: 10.1056/NEJMe2502267.

Featuring articles on H5N1 infection, chronic subdural hematoma, achondroplasia, and B-cell acute lymphoblastic leukemia; a review article on carceral health care; a case report of a woman with weakness, back pain, and pancytopenia; and Perspectives on the changing approach to addiction, on the moral injury of inhaler prescribing, and on how one size fits … some.

Join the Behind the Knife Surgical Oncology Team as we discuss the presentation, work-up, and management of neuroendocrine tumors of the small bowel. Learning Objectives: In this episode, we review the basics of neuroendocrine (NE) tumors of the small bowel, including how to evaluate patients with presenting symptoms consistent with NE tumors, initial work-up, staging, and management.  We discuss key concepts including DOTATATE scans and medical therapies high yield for direct patient care and board exams.  Hosts: Timothy Vreeland, MD, FACS (@vreelant) is an Assistant Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at Brooke Army Medical Center Daniel Nelson, DO, FACS (@usarmydoc24) is Surgical Oncologist/HPB surgeon at Kaiser LAMC in Los Angeles. Connor Chick, MD (@connor_chick) is a 2nd Year Surgical Oncology fellow at Ohio State University. Lexy (Alexandra) Adams, MD, MPH (@lexyadams16) is a 1st Year Surgical Oncology fellow at MD Anderson. Beth (Elizabeth) Barbera, MD (@elizcarpenter16) is a PGY-6 General Surgery resident at Brooke Army Medical Center Links to Paper Referenced in this Episode: Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427. PMID: 28076709; PMCID: PMC5895095. https://pubmed.ncbi.nlm.nih.gov/28076709/ ***SPECIALTY TEAM APPLICATION LINK: https://docs.google.com/forms/d/e/1FAIpQLSdX2a_zsiyaz-NwxKuUUa5cUFolWhOw3945ZRFoRcJR1wjZ4w/viewform?usp=sharing Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more.