NEJM Group

Combination chemotherapy has been the standard treatment of advanced-stage classic Hodgkin’s lymphoma for decades.    Adding brentuximab vedotin, a CD30-directed antibody drug conjugate, to chemotherapy improves outcomes in advanced-stage classic Hodgkin’s lymphoma as compared with standard ABVD chemotherapy (doxorubicin, vinblastine, and dacarbazine plus bleomycin).     However, brentuximab vedotin is associated with increased toxic effects in adults, and relapses remain problematic. How treatment with nivolumab, a programmed death receptor 1 (PD-1) inhibitor, compares with brentuximab vedotin is unknown.    In the S1826 trial, researchers assessed the efficacy and safety of nivolumab plus chemotherapy with doxorubicin, vinblastine, and dacarbazine (N+AVD), as compared with brentuximab vedotin plus AVD (BV+AVD), in patients with newly diagnosed classic Hodgkin’s lymphoma.    Patients 12 years of age or older with newly diagnosed, advanced-stage classic Hodgkin’s lymphoma were assigned to receive N+AVD or BV+AVD for six cycles.     Radiation therapy directed to residual lesions that were metabolically active after treatment was permitted. The primary end point was progression-free survival.    In adolescents and adults with previously untreated, stage III or IV classic Hodgkin’s lymphoma, N+AVD improved progression-free survival, as compared with BV+AVD, and had a better side-effect profile.    Read the full S1826 trial results and Plain Language Summary: https://nej.md/3A00MYS    #ClinicalTrials #MedicalResearch 

A 𝗺𝗲𝘀𝗲𝗻𝗰𝗵𝘆𝗺𝗮𝗹 𝘀𝘁𝗲𝗺 𝗰𝗲𝗹𝗹 is an adult stem cell, present in a wide variety of tissues, that can renew itself by dividing and can differentiate into specialized cell types that make up tissues such as bone, cartilage, muscle, fat, and connective tissue.   To learn more about this NEJM Illustrated Glossary term, read the 2019 Clinical Implications of Basic Research article “How Stem Cells Turn into Bone and Fat” by Arjun Deb, MD, from UCLA: https://nej.md/2QTUK18    Explore more terms: https://nej.md/glossary  

In this Double Take video, Dr. Nathaniel Morris examines the complex relationship between #mentalhealth and #incarceration, and William Palmer and Philip Jones recount their own personal experiences with incarceration and its impact on their mental health. The video explores the need to invest in diversion programs, general medicine, and mental health services for people who are incarcerated or at risk for incarceration.    Further reading: Injustice Disorder (Morris, November 26, 2022, issue) https://nej.md/3FmtO53    #PublicHealth #Psychiatry #NEJM 

Neurodevelopmental disorders are complex diseases that typically manifest during early childhood.     Patients often present with a spectrum of clinical features, such as craniofacial anomalies and impairments in cognitive, behavioral, or motor skills. The current understanding of these disorders and their causes is far from complete.    Of interest, then, is a report by Ganesh et al. in NEJM. They describe the cause of a severe neurodevelopmental disorder involving developmental delay, facial dysmorphisms, and cerebral hypomyelination affecting three children: heterozygous de novo deletions in a gene (𝘊𝘏𝘈𝘚𝘌𝘙𝘙) that encodes a long noncoding RNA (lncRNA).     This gene lies immediately upstream of the gene 𝘊𝘏𝘋2 and on the same strand of DNA; 𝘊𝘏𝘋2 is overexpressed in the three affected children.    Research shows that lncRNAs regulate gene expression, but understanding their modes of action has been challenging, owing to their large size, flexible conformation, and various interacting proteins.     However, their subcellular localization patterns often provide clues. For example, the location of the 𝘊𝘏𝘈𝘚𝘌𝘙𝘙 lncRNA (at the site of its own transcription) suggests that it may regulate 𝘊𝘏𝘋2 (panel A in image).  A heterozygous de novo pathogenic variant in 𝘊𝘏𝘋2 has been linked to neurodevelopmental disorders (panel B in image). Indeed, altered transcriptional activity at the 𝘊𝘏𝘈𝘚𝘌𝘙𝘙 locus may be the pathogenic event in persons with haploinsufficiency for 𝘊𝘏𝘈𝘚𝘌𝘙𝘙.     Learn more about the science behind the study in the editorial “Linking a Neurodevelopmental Disorder with a lncRNA Deletion” by Ling-Ling Chen, PhD: https://nej.md/4hkctuu  

Cryoglobulinemia is caused by the precipitation of immunoglobulin molecules when plasma or blood cools to 4°C. The term is routinely applied to two distinct disease entities that need to be distinguished from one another.    The clinical manifestations associated with cryoglobulinemia syndrome are highly diverse and can potentially affect virtually any organ; thus, the syndrome is categorized as a genuine systemic disease. However, not all manifestations are common to both types of cryoglobulinemia, and certain subtle differences can be helpful for clinicians in differentiating between type I cryoglobulinemia and mixed cryoglobulinemia. Data characterizing patients with type I cryoglobulinemia have been derived from retrospective cohorts that pooled cases involving IgG and IgM,7-12 whereas data on patients with mixed cryoglobulinemia have come mainly from cases of HCV-related vasculitis; both types are summarized in the figure shown.    Read the Review Article “Cryoglobulinemia — One Name for Two Diseases” by Patrice Cacoub, MD, Matheus Vieira, MD, and David Saadoun, MD, PhD, from Sorbonne Université, Groupe Hospitalier Pitié–Salpêtrière, Assistance Publique–Hôpitaux de Paris, and elsewhere: https://nej.md/48efBDN 

It is estimated that 2 million persons every year in the United States and Europe have an acute myocardial infarction.    The lack of contemporary large-scale randomized trials and of consensus recommendation on the duration of beta-blocker therapy after myocardial infarction has resulted in lifelong therapy in many patients, making this class of drugs one of the most prescribed worldwide.     Beta-blocker therapy is not only a standard of care for patients after myocardial infarction but also a quality indicator of secondary prevention, with a prescription rate that has reached over 90% in most Western registries.    In the ACTION trial, researchers examined whether interruption of beta-blockers was safe and might improve quality of life in patients with a history of uncomplicated myocardial infarction.    Patients with a history of myocardial infarction who were receiving treatment with any type or dose of beta-blocker were randomly assigned to interruption or continuation of beta-blocker therapy.     The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons. The main secondary end point was the change in quality of life as measured with the European Quality of Life–5 Dimensions questionnaire.    In patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not shown to be noninferior to a strategy of beta-blocker continuation with respect to a composite outcome of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons.    Read the full ACTION trial results and Plain Language Summary: https://nej.md/3MeRHOi    #MedicalResearch #ClinicalTrials  

𝗛𝗲𝘁𝗲𝗿𝗼𝘇𝘆𝗴𝗼𝘀𝗶𝘁𝘆 is the presence of different alleles at one or more loci on homologous (paired) chromosomes. To learn more about this NEJM Illustrated Glossary term, read the 2022 Review Article “Hemochromatosis” by John Olynyk, MD, and Grant A. Ramm, PhD, from South Metropolitan Health Service, Edith Cowan University, and the QIMR Berghofer Medical Research Institute: https://nej.md/3VzNVSB Explore more terms: https://nej.md/glossary

In the November issue: a multinational registry, a culture of respect, eliminating race-based clinical algorithms, improving racial health equity, complex care for hard-to-reach patients, engaging pharmacists in preventive care, and health policy. 📖 View the issue: https://nej.md/3zTAzv8 🎧 Letter from our editors: The Power of Collaboration to Improve Care Delivery: https://nej.md/3BA5nBp 🏛️ Insights Report: Making the Case for Government Regulation: https://nej.md/3NnHxLS with expert advisor Mark McClellan, Duke-Margolis Institute for Health Policy 📈 In Depth: The Racial Health Equity Progress Report: A Data-Driven Equity Action Tool: https://nej.md/3BGirp3 👩⚕️ Case Study: Supporting Rising-Risk Medicaid Patients Through Early Intervention: https://nej.md/482n9cC 🤝 Case Study: Codesigning Solutions with Health Care Team Members to Foster a Culture of Respect: https://nej.md/484Kw5u 📊 Article: New York City’s Public Health Approach to Reexamining Race-Based Clinical Algorithms: https://nej.md/4eVuuNm 💉 Commentary: Limited RSV Vaccine Administration: A Case for Redesigning the Preventive Care Model: https://nej.md/4dHHzco 👁️ Commentary: The European Registry of Quality Outcomes for Cataract and Refractive Surgery: Benefits and Lessons of a Multinational Registry: https://nej.md/3Y6ye8b

What does it take to get into the fast-developing field of medical #ArtificialIntelligence research and entrepreneurship?      Find out in the latest episode of the NEJM AI Grand Rounds podcast, where David Ouyang, MD, a cardiologist and AI researcher at Cedars-Sinai Medical Center, discusses his journey from medical training to AI research and entrepreneurship, as well as his groundbreaking work in applying AI to cardiology imaging and the challenges of bringing AI innovations from academia to clinical practice.      The conversation with hosts Arjun Manrai, PhD, and Andrew Beam, PhD, also explore his experience conducting randomized controlled trials for AI algorithms in echocardiography, the process of commercializing research through Y Combinator, and the hurdles in reimbursement for AI-based medical devices.       The episode also considers the future of AI in cardiology, the importance of clinician involvement in AI development, and the potential impact of large language models on medical practice.       Dr. Ouyang shares insights on balancing clinical value with business considerations in health care AI and offers advice for researchers looking to conduct clinical trials for AI technologies.      Listen to the full episode hosted by NEJM AI Deputy Editors Arjun Manrai, PhD, and Andrew Beam, PhD: https://nejm.ai/ep23    #AIinMedicine 

The MINT trial changed how many clinicians think about transfusions in acute MI. But it was neutral.    The latest episode of the Beyond Journal Club podcast, a collaboration between Core IM and NEJM Group, takes a deep dive into interpreting the MINT trial (published in NEJM in 2023). This podcast series puts #ClinicalTrials into context, telling the story of how we got to where we are, appreciating the clinical question of the trial at hand, and interpreting what the findings may mean for our patients.    Listen now: https://nej.md/4eRNY5K    Read the full MINT trial results published in NEJM: https://nej.md/49rFHDG    #MedicalResearch