NEJM Group

In the report, investigators assessed the efficacy of levofloxacin for the prevention of secondary cases of tuberculosis among household contacts of persons with multidrug-resistant tuberculosis.

The January 2025 issue of NEJM Catalyst Innovations in Care Delivery is a special issue guest edited by Frederick P. Cerise, MD, MPH, exploring health care workforce innovations: workforce challenges, a worksite health scorecard, well-being committees, physician peer support, a coaching program, positive psychology for team building, and reflective writing workshops. 📖 View the special issue: https://nej.md/3VDD24o 🎧 Read or listen to the guest editor's letter: Caring for the Health Care Workforce https://nej.md/3VD4Ohx 🦠 Insights Report: Health Care Workforce Challenges Persist as a Legacy of Covid-19 https://nej.md/3ZFMBAT 🏥 In Depth: A Model for System-Level Change to Improve Workforce Well-Being https://nej.md/3P0scSm ❤️ Case Study: Team Building Through Positive Psychology Principles in the Pediatric Cardiac Operating Room https://nej.md/3ZTeczY ⚕️ Case Study: Creating Systemwide Interdisciplinary Well-Being Committees to Reduce Physician Burnout https://nej.md/3OZcZB2 🤝 Article: A Coaching Program to Improve Employee Engagement, Culture of Safety, and Patient Experience https://nej.md/41HxpGp ✍️ Commentary: VA Writes: A Reflective Writing Workshop to Improve Well-Being in Health Care Employees https://nej.md/3VH5qT7 👂 Commentary: How Peer Support Helps Heal the Culture of Medicine from Within https://nej.md/4ivoIF8

Are proton-pump inhibitors beneficial or harmful for stress ulcer prophylaxis in mechanically ventilated patients?    What do more recent studies like REVISE reveal about PPIs and possible harmful side effects of aspiration pneumonia and C. difficile colitis?    The latest episode of the Beyond Journal Club podcast, a collaboration between Core IM and NEJM Group, takes a deep dive into the REVISE trial (published in NEJM in 2024).     This podcast series puts #ClinicalTrials into context, telling the story of how we arrived at the current standard of care, appreciating the clinical question of the trial at hand, and interpreting what the findings may mean for these patients.    Listen now: https://nej.md/3BdvNt9    Read the full REVISE trial results published in NEJM: https://nej.md/3KD01Xp    #MedicalResearch 

Atrial fibrillation is common among patients with atherosclerotic coronary artery disease, but choosing the appropriate antithrombotic therapy for patients with both conditions is challenging.     Patients with atrial fibrillation need oral anticoagulants to prevent stroke or systemic embolism, whereas antiplatelet therapy is indicated to prevent ischemic events in patients with coronary artery disease. However, the combined use of an antiplatelet regimen and an anticoagulant regimen in patients with atrial fibrillation and concomitant coronary artery disease increases the risk of bleeding.    Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease who are receiving oral anticoagulants are lacking.    In the EPIC-CAD trial, researchers compared edoxaban monotherapy with dual antithrombotic therapy as long-term antithrombotic treatment in patients with atrial fibrillation and stable coronary artery disease.    Adults at high risk for thromboembolism were assigned to receive monotherapy with standard-dose edoxaban or dual antithrombotic therapy with edoxaban plus a single antiplatelet agent (aspirin or a P2Y12 inhibitor, according to the discretion of the treating physician).     The primary outcome was net adverse clinical events — a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major or clinically relevant nonmajor bleeding at 12 months.    In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy.    Read the full EPIC-CAD trial results and Plain Language Summary: https://nej.md/3Z1D1d3    #ClinicalTrials #MedicalResearch 

A recent Double Take video presents the case of a 42-year-old woman presenting with cough, fatigue, fevers, and shortness of breath. Based on a Clinical Problem-Solving article, the video explores the differential diagnosis for shortness of breath and highlights the importance of maintaining a broad differential when first-line therapies fail to improve a patient’s condition.    📺 Video:  A Diagnostic Sequence https://nej.md/4g7I8hq    📖 Further reading:  Clinical Problem-Solving: A Diagnostic Sequence (Giannini et al., May 4, 2023) https://nej.md/3LpDfT2 

A 𝗵𝗲𝗽𝗮𝘁𝗼𝗰𝘆𝘁𝗲 is a primary cell of the liver. Hepatocytes make up 70 to 80% of the liver’s mass and are involved in many of the liver’s key functions, including detoxification and the metabolism of carbohydrates and lipids.     In addition, they are involved in the production of proteins, such as albumin, clotting factors and various complement factors, and bile. They can be infected by hepatotropic viruses including hepatitis A, B, C, D, and E viruses.     The liver has a remarkable ability to regenerate because hepatocytes can reenter the cell cycle from a quiescent phase. Nevertheless, in the context of chronic liver disease, such as chronic hepatitis B virus infection, they are slowly displaced by fibrous tissue, eventually leading to cirrhosis, liver failure, and liver cancer.    To learn more about this term, read the editorial “Combination Therapy for Chronic HBV Infection” by Harry L.A. Janssen, MD, PhD, and Milan J. Sonneveld, MD, PhD, from Erasmus MC and University Health Network: https://nej.md/49nfu9F      #MedicalResearch 

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a T-cell–mediated severe cutaneous adverse reaction characterized by rash, fever, internal organ involvement, and systemic manifestations after prolonged exposure to a medication.     DRESS is also known as drug-induced hypersensitivity syndrome and was formerly known as anticonvulsant hypersensitivity syndrome, given its connection to such drugs.    DRESS has an estimated prevalence of approximately 2 cases per 100,000 population and an incidence of 1 in 1000 to 1 in 10,000 cases in patients who received a medication, depending on the culprit medication.     Aromatic anticonvulsants confer the highest risk of associated DRESS, followed by allopurinol and sulfonamide antibiotics. In the United States, five drugs account for most cases of DRESS; in order of decreasing prevalence in causing DRESS, these drugs are allopurinol, vancomycin, lamotrigine, carbamazepine, and trimethoprim–sulfamethoxazole.     Although DRESS is uncommon, it accounts for up to 23% of cutaneous drug eruptions in hospitalized patients. Recent studies suggest that worldwide mortality from DRESS ranges from 1.2 to 7.1%, and U.S.-specific mortality of 5% was documented in 2019.     A current conservative cost estimate for a single case of DRESS that results in hospitalization in the United States is $22,493.    Continue reading the Review Article “Drug Reaction with Eosinophilia and Systemic Symptoms” by Daniela Kroshinsky, MD, MPH, Adela Rambi G. Cardones, MD, MHSc, and Kimberly Blumenthal, MD, from the Duke University Health System, the University of Kansas Medical Center, Harvard Medical School, and Massachusetts General Hospital: https://nej.md/3ONkyL9  

A recent study unpicks a key immune-mediated mechanism of mutant IDH–blocking drugs such as vorasidenib in the treatment of IDH-mutant glioma.    Figure 1 from the article shows immunity, transcriptional activity, and growth of IDH-mutant tumors.     Mutant isocitrate dehydrogenase (mIDH) catalyzes the conversion of α-ketoglutarate (α-KG) into the R enantiomer of 2-hydroxyglutarate (R-2-HG), which blocks the activity of the DNA demethylase TET2 (Panel A, 1). As a result, the transcription of transposable elements and the DNA-sensing protein cyclic GMP–AMP synthase (cGAS) is blocked (Panel A, 2), which results in hyporesponsiveness to immunostimulatory activity of interferon-γ (Panel A, 3) and decreased antitumor immunity.     When the neomorphic enzymatic activity of mIDH is blocked by the isocitrate dehydrogenase (IDH) inhibitors ivosidenib or vorasidenib, α-KG levels are restored, R-2-HG levels are normalized (Panel B, 1), and TET2 demethylase activity derepressed. This process (Panel B, 2) results in the expression of cGAS and subclasses of transposable elements that are converted to double-stranded DNA (dsDNA) in the cytosol (Panel B, 3).     These double-stranded transposable elements bind and activate the cGAS-STING (stimulator of interferon genes) complex (Panel B, 4), which in turn activates interferon-stimulated genes (ISG) that encode interferons and other cytokines and chemokines (Panel B, 5), which attract T cells that produce interferon-γ (Panel B, 6) and sustain a feed-forward loop of interferon-γ hyperresponsiveness and enhanced antitumor immunity (Panel B, 7 through 10).     The abbreviation cGAMP denotes cyclic guanosine monophosphate–adenosine monophosphate, IRF3 interferon regulatory factor 3, mRNA messenger RNA, and STAT signal transducer and activator of transcription.    Learn more in the Clinical Implications of Basic Research article “Heating Up IDH-Mutant Gliomas” by Michael Platten, MD, and Lukas Bunse, MD, PhD, from Heidelberg University and the DKFZ German Cancer Research Center: https://nej.md/4f3dIMf 

Treatment of triple-negative breast cancer has traditionally been challenging because of the lack of therapeutic targets.     The programmed death 1 inhibitor pembrolizumab is approved for early-stage disease on the basis of findings from the KEYNOTE-522 trial, in which neoadjuvant and adjuvant pembrolizumab resulted in improvements in pathological complete response and event-free survival. The findings on overall survival, a key secondary end point, are now reported.    Researchers assessed the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab — as compared with neoadjuvant chemotherapy alone — in patients with early-stage triple-negative breast cancer.    Patients were assigned, in a 2:1 ratio, to a pembrolizumab–chemotherapy group or a placebo–chemotherapy group.     In the neoadjuvant phase, patients received pembrolizumab or placebo for four cycles plus paclitaxel and carboplatin, followed by pembrolizumab or placebo for four cycles plus doxorubicin–cyclophosphamide or epirubicin–cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab or placebo for up to nine cycles.    In patients with early-stage triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab improved overall survival as compared with neoadjuvant chemotherapy alone.    Read the full KEYNOTE-522 trial results and Plain Language Summary: https://nej.md/3XzBOIS    #ClinicalTrials #MedicalResearch 

A 𝗱𝗼𝘂𝗯𝗹𝗲-𝘀𝘁𝗿𝗮𝗻𝗱 𝗯𝗿𝗲𝗮𝗸 is a break that cleaves both strands of the DNA in a chromosome. If a break is not repaired, chromosomal integrity is lost, which usually leads to cell death. Double-strand breaks are caused naturally by certain chemicals endogenous to cells (e.g., reactive oxygen species), environmental exposures (e.g., ionizing radiation), and other natural processes. A normally dividing cell undergoes approximately 20 to 40 naturally occurring double-strand breaks every day.    Double-stand breaks are also created by endonucleases. These nucleases may be natural enzymes or enzymes engineered to stimulate genome editing. Natural nucleases are used by cells to generate genetic diversity. In the development of the immune system, for example, a nuclease, the RAG1-RAG2 complex, initiates a recombination of DNA segments that leads to the development of antibodies and T-cell receptors. In meiosis, the SPO11 nuclease creates double-strand breaks that allow homologous recombination, in which DNA is shuffled between chromosomes, creating genetic diversity. To learn more about this NEJM Illustrated Glossary term, read the 2019 Review Article “A New Class of Medicines through DNA Editing” by Matthew Porteus, MD, PhD: https://nej.md/2H4ra6X    Explore more terms: https://nej.md/glossary