NEJM Group

The 𝘋𝘪𝘢𝘨𝘯𝘰𝘴𝘵𝘪𝘤 𝘢𝘯𝘥 𝘚𝘵𝘢𝘵𝘪𝘴𝘵𝘪𝘤𝘢𝘭 𝘔𝘢𝘯𝘶𝘢𝘭 𝘰𝘧 𝘔𝘦𝘯𝘵𝘢𝘭 𝘋𝘪𝘴𝘰𝘳𝘥𝘦𝘳𝘴, fifth edition, criteria for the diagnosis of neuroleptic malignant syndrome include exposure to a dopamine-blocking drug, severe muscular rigidity, fever, and at least two of the following features: diaphoresis, dysphagia, tremor, incontinence, an altered level of consciousness, mutism, tachycardia, elevated or labile blood pressure, leukocytosis, or an elevated serum creatine kinase level. In practice, the syndrome is easier to identify than this list of items suggests.     The history, medication list, and context usually make it apparent that the patient has been exposed to a drug implicated in neuroleptic malignant syndrome, but this is not always evident, particularly with medications that are not used primarily for the treatment of psychosis or delirium.    To learn more, read the Review Article “Neuroleptic Malignant Syndrome” by Eelco F.M. Wijdicks, MD, PhD, and Allan H. Ropper, MD, from Mayo Clinic: https://nej.md/3N31DL6 

Data from nonrandomized comparisons have suggested that survival might be better with long-term oxygen therapy used for 24 hours per day than with the typically recommended 15 hours per day.     Data from randomized trials directly comparing these two durations of oxygen therapy are lacking.    In the REDOX trial, researchers assessed hospitalization and mortality among patients with chronic severe hypoxemia who received long-term oxygen therapy for either 24 or 15 hours per day.    241 adults who were starting oxygen therapy for chronic severe hypoxemia at rest were randomly assigned to receive long-term oxygen therapy (LTOT) for either 24 or 15 hours per day. The primary outcome was a composite of hospitalization or death from any cause within 1 year.    Among patients with severe hypoxemia, long-term oxygen therapy used for 24 hours per day, as compared with 15 hours per day, did not reduce the risk of hospitalization or death within 1 year.    Read the full REDOX trial results and Plain Language Summary: https://nej.md/4cR3pK4    #ClinicalTrials #MedicalResearch 

The 2024 Albert Lasker Award for Basic Medical Research recognizes Dr. Zhijian (James) Chen for his elucidation of how DNA stimulates immune responses.    Figure 1 from the article illustrates the cGAS–STING DNA sensing pathway.    The cyclic GMP–AMP synthase (cGAS) enzyme binds to viral DNA, tumor DNA, or our own aberrant DNA. DNA binding activates cGAS to synthesize cyclic GMP–AMP (cGAMP) from ATP and GTP nucleotides. Bacteria also produce cyclic dinucleotides (CDNs). Bacterial cyclic dinucleotides and cGAMP bind to STING, a protein of the endoplasmic reticulum, which results in activation of a signaling pathway that stimulates the production of type I interferons. IRF3 denotes interferon regulatory factor 3, IκBα nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor alpha, NF-κB nuclear factor κB, and TBK1 TANK binding kinase 1.    Read the Clinical Implications of Basic Research article “How DNA Sensing Drives Inflammation” by Russell E. Vance, PhD, from the Howard Hughes Medical Institute (HHMI) and the University of California, Berkeley: https://nej.md/4e9pCEt 

𝗖𝗼𝗻𝗱𝗶𝘁𝗶𝗼𝗻𝗶𝗻𝗴 is a term used to describe a course of treatment comprising one or more medications administered to patients before transplantation of allogeneic or autologous hematopoietic stem cells. Typically, radiation and alkylating agents such as busulfan that eliminate the recipient’s hematopoietic cells are given to “make space” for the transplanted cells. For most allogeneic transplant recipients, additional agents are given to eliminate immune cells and prevent immunologic rejection of the graft. To learn more about this NEJM Illustrated Glossary term, read the editorial “CSF1R Blockade for Refractory Chronic Graft-versus-Host Disease” by Mohamad Mohty, MD, PhD, from Sorbonne Université, INSERM, CRSA PARIS, and Greater Paris University Hospitals - AP-HP: https://nej.md/3MOORQs      Explore more terms: https://nej.md/glossary    

Case Record of the Massachusetts General Hospital: A 47-year-old man was admitted to the hospital because of confusion, pneumonia involving the right lower lobe, and acute kidney failure. The creatine kinase level was 28,581 U per liter. A diagnosis was made.    Figure 2 from the case shows environmental sources, clinical manifestations, laboratory findings, and radiologic findings of legionella pneumonia.    Transmission typically occurs through aerosolization from an environmental source. Inhalation and inoculation result in prodromal symptoms, including fever, malaise, and headache. Over the course of several days, a cough develops that may or may not be productive of purulent sputum. Altered mental status is frequently described with severe cases. Nonpulmonary symptoms, such as headache and gastrointestinal symptoms, may be severe and lead to misdiagnosis. Laboratory findings are consistent with severe community-acquired pneumonia and may show leukocytosis or leukopenia, elevated levels of liver enzymes, lactate dehydrogenase, and creatine kinase, and hyponatremia; however, these findings lack specificity. Radiologic findings nearly always include a consolidating pneumonia at the time of presentation. Extrapulmonary infection is rare and occurs almost exclusively in immunocompromised patients.    Read more about this real-life case in “A 47-Year-Old Man with Confusion and Kidney Failure” by Sachin J. Shah, MD, MPH, Melissa C. Price, MD, and Sanjat Kanjilal, MD, MPH, from Massachusetts General Hospital, Harvard Medical School, Harvard Pilgrim Health Care Institute, and Brigham and Women's Hospital: https://nej.md/3B9Fx7e 

Clinicians are increasingly being asked to be more productive and efficient in the delivery of care. As a result, #DigitalHealth tools are playing a crucial role in helping meet those demands and are being leveraged within care organizations to help clinicians increase their effectiveness.    In this free, virtual event, we will discuss how key emerging technologies will positively impact patient care, and how you can leverage these new tools to be more proficient in your daily work.    Join NEJM CareerCenter to learn:    📈 The potential for growth in digital tools and ways organizations can successfully implement these technologies into their workdays  ✨ What advancements have been made with digital health tools that result in improved clinician well-being  💡 How these emerging technologies will impact clinicians’ careers and help support the health care workforce in building robust skillsets    📅 October 17, 2024, 12:00–1:00 PM ET   🔗 https://nej.md/47Ba0Hi     #HealthCare 

Most patients with newly diagnosed chronic myeloid leukemia (CML) are treated with one of four approved ATP-competitive tyrosine kinase inhibitors (TKIs): first-generation imatinib or second-generation nilotinib, dasatinib, or bosutinib.     However, many patients switch treatments within the first year because of troublesome adverse effects.    In the ASC4FIRST trial, researchers assessed the efficacy and safety of asciminib as compared with investigator-selected TKIs in patients with newly diagnosed CML.     405 patients were randomly assigned to receive either asciminib or an investigator-selected TKI: imatinib, nilotinib, dasatinib, or bosutinib. The two primary objectives of the trial were to compare the efficacy of asciminib with that of the investigator-selected TKIs considered together and with imatinib considered individually.     The primary end point for both objectives was major molecular response (defined by BCR::ABL1 transcript levels ≤0.1% on the International Scale) at week 48.    Asciminib showed superior efficacy and a favorable safety profile as compared with investigator-selected TKIs considered together, and with imatinib individually, in patients with newly diagnosed chronic myeloid leukemia. Whether asciminib is more effective than the second-generation TKIs is not clear.    Read the full ASC4FIRST trial results and Plain Language Summary: https://nej.md/4bNNr3c    #ClinicalTrials #MedicalResearch 

#ESMO24 Round Up: 11 articles were simultaneously published in NEJM and presented at this year’s ESMO - European Society for Medical Oncology Congress in Barcelona, Spain. Most of the articles included a podcast with NEJM Group editors discussing the significance of the trial results.     Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer (ADRIATIC)   📄 Full article: https://nej.md/4d0eZ5m    Pembrolizumab in HER2-Positive Gastric Cancer (KEYNOTE-811)  📄 Full article: https://nej.md/47BTmYp  🎧 Podcast: https://nej.md/3MKJrWw    Preoperative Chemoradiotherapy for Resectable Gastric Cancer (TOPGEAR)  📄 Full article: https://nej.md/4gg4gqv  🎧 Podcast: https://nej.md/4elNDb7    Ponsegromab for the Treatment of Cancer Cachexia  📄 Full article: https://nej.md/3XE645a  🎧 Podcast: https://nej.md/3zsPNXw    Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma (AMBASSADOR)  📄 Full article: https://nej.md/4gh1b9D  🎧 Podcast: https://nej.md/4go9Eb5    Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer (DESTINY-Breast06)  📄 Full article: https://nej.md/3TovTE9  🎧 Podcast: https://nej.md/3XHT4LS    Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma (CheckMate 067)  📄 Full article: https://nej.md/4dUqm0g  🎧 Podcast: https://nej.md/4gkKjPj    Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer (NIAGARA)  📄 Full article: https://nej.md/4gmAqk3  🎧 Podcast: https://nej.md/4e2bo8g    Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer (KEYNOTE-522)  📄 Full article: https://nej.md/3XzBOIS  🎧 Podcast: https://nej.md/4d3VCIV    Zolbetuximab in Gastric or Gastroesophageal Junction Adenocarcinoma   📄 Full article: https://nej.md/3ML9dtK  🎧 Podcast: https://nej.md/4dX7X2X    Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors (CABINET)   📄 Full article: https://nej.md/3AYuEoI  🎧 Podcast: https://nej.md/3ZFER3R 

Our October 2024 issue, guest edited by Rasu Shrestha MD MBA, is specially themed around digital health technology innovation: digital technology adoption, the uses of artificial intelligence, in-basket workflow, telehealth-enabled nursing, and digitally enabled care. 📖 View the issue: https://nej.md/3zjbwRS 🎧 Read or listen to the guest editor's letter: The Ongoing Challenge of Digital Technology Innovation: https://nej.md/47yfEKj 💻 Insights Report: Cautious Embrace of Digital Technologies for Health Care: https://nej.md/47rEbk8 with expert advisor Rasu Shrestha MD MBA Advocate Health 📧 In Depth: The “Inboxologist” — A Novel Approach to In-Basket Management in Primary Care: https://nej.md/3B5rLSZ 👨⚕️ Case Study: Virtual Nursing to Improve Patient and Team Member Experiences at NewYork-Presbyterian Hospital: https://nej.md/3B2mDyW 📈 Article: Standing on FURM Ground: A Framework for Evaluating Fair, Useful, and Reliable AI Models in Health Care Systems: https://nej.md/3zeENgn 📉 Article: Reducing Fraud, Waste, and Abuse Through Real-Time AI-Based Screening: Prospective Results in Deployment: https://nej.md/3zx76Xv 🤝 Commentary: The Digitally Enabled Care Framework: Leveraging Technology to Enhance the Physician–Patient Relationship: https://nej.md/3MKZ5l1 📺 Free Web event: Don't forget to tune into our gen AI and health IT event today or watch the recording after! https://nej.md/3M7HLWI #HealthIT #DigitalHealth #HealthCareAI #HealthCareDelivery #HealthCareInnovation

Primary central nervous system (CNS) vasculitis, also known as primary angiitis of the CNS, is a rare form of vasculitis that is limited to the brain and spinal cord and causes a variety of neurologic syndromes. Because of its rarity and the similarity of some of these syndromes to more common disorders, primary CNS vasculitis is often misidentified. Descriptions of this condition date back only to the mid-1950s. Primary CNS vasculitis may occur in children, although this is uncommon. In a new review, the authors focus on the disorder in adults.    Continue reading the Review Article “Primary Central Nervous System Vasculitis” by Carlo Salvarani, MD, Gene G. Hunder, MD, and Robert D. Brown, Jr., MD, MPH, from Mayo Clinic, Azienda Ospedaliera–IRCCS di Reggio Emilia, and Università degli Studi di Modena e Reggio Emilia: https://nej.md/3BaqxGh