NEJM Group

There are approximately 20 essential micronutrients, and deficiency in one or more has distinct effects on the metabolome, proteome, and genome.    Since basic information about micronutrients is available in textbooks, reports on the ways in which requirements were established, reviews, and websites, the main purpose of a new Nutrition in Medicine article is to provide an overview of current issues in micronutrient assessment, interventions, and research that are of interest to health care practitioners.     In the United States, the prevalence of most micronutrient deficiencies is low. National surveys — namely, the National Health and Nutrition Examination Survey (NHANES), which assesses biochemical markers of nutritional status, as well as its interview component, What We Eat in America, which measures nutrient intakes — provide some data on micronutrient status in the general population.     However, these measures are made cross-sectionally, so it is difficult both to infer causality between micronutrient deficiencies and chronic diseases and to assess the health benefits of interventions such as supplementation.     In recent decades, there has been a concerted international effort to study micronutrient deficiencies and interventions in low- and middle-income countries and population groups in which the prevalence and severity of most deficiencies are highest. One third of the world’s population has one or more micronutrient deficiencies.    Continue reading “Micronutrients — Assessment, Requirements, Deficiencies, and Interventions” by Lindsay H. Allen, PhD, from the US Department of Agriculture (USDA) Agricultural Research Service (ARS) and University of California, Davis: https://nej.md/4ith0um    #PublicHealth 

Evidence-based treatments to benefit patients with bronchiectasis are lacking. Thus, the report by Chalmers et al. in NEJM is welcome. 👉 https://nej.md/4lBHwUr    In the ASPEN phase 3 trial, they found that fewer pulmonary exacerbations occurred in patients treated with an antiinflammatory drug called brensocatib than in patients who received placebo over the course of a year.    Learn more about brensocatib for the treatment of bronchiectasis in the editorial “Defanging the Neutrophil to Treat Bronchiectasis” by Adam T. Hill, MD, from The University of Edinburgh: https://nej.md/4cANv89    #Pediatrics #Pulmonology  

Does obinutuzumab, a humanized type II anti-CD20 monoclonal antibody, plus standard therapy provide better renal responses than standard therapy alone in patients with lupus nephritis? 👉 https://nej.md/3Eq6gxV    The addition of obinutuzumab to standard therapy was associated with a significantly better renal response than placebo in a recent phase 2 trial. The REGENCY phase 3 trial sought to confirm that result.    Patients who had systemic lupus erythematosus and biopsy-confirmed active class III or IV lupus nephritis, with a urinary protein-to-creatinine ratio of at least 1 (with protein and creatinine both measured in milligrams) and an antinuclear antibody (ANA) titer of 1:80 or greater (or an equivalent positive ANA test), were randomly assigned to receive intravenous infusions of obinutuzumab or placebo. All patients received standard therapy with mycophenolate mofetil plus oral prednisone. The primary end point was a complete renal response at week 76, defined by a urinary protein-to-creatinine ratio lower than 0.5, an eGFR of at least 85% of the baseline value, and absence of an intercurrent event.    Among patients with active lupus nephritis, the likelihood of a complete renal response at week 76 was higher with obinutuzumab added to standard therapy than with standard therapy alone.    Read the full REGENCY trial results and Research Summary: https://nej.md/3Eq6gxV    #ClinicalTrials  

How good are we at preventing HIV? How do efficacy and effectiveness differ? In the latest episode of Beyond Journal Club, the hosts journey from oral preexposure prophylaxis (PrEP) to long-acting injectables and then to the PURPOSE trials, which look at the use of long-acting lenacapavir as PrEP — a potential game-changer in the field of HIV.  🎧 Listen to the latest episode of Beyond Journal Club, a collaboration between CORE IM and NEJM Group: https://nej.md/4lDlNf2    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.    📖 Further reading  Original Article by L.-G. Bekker et al.: Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women (PURPOSE 1 trial) https://nej.md/3zRElVj    Original Article by C.F. Kelley et al.: Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons (PURPOSE 2 trial) https://nej.md/4fFWVzJ    #InfectiousDisease 

𝐆𝐞𝐧𝐨𝐦𝐞 𝐢𝐧𝐬𝐭𝐚𝐛𝐢𝐥𝐢𝐭𝐲 is a hallmark of cancer development and progression characterized by the accumulation of DNA damage; genome instability manifests as increased genetic alteration across the genome, including chromosomal translocations, structural variants, extrachromosomal DNAs, and aneuploidy. Replication stress, frequently observed in rapidly dividing cells, and exogenous factors, such as ultraviolet and ionizing radiation, tobacco smoke, and certain chemicals, can result in genome instability. Early genetic events in the life of cancer cells, such as changes in the maintenance of telomeric length, or the activation of an oncogene can lead to genome instability. Loss-of-function variants in genes encoding tumor suppressor proteins, such as those that mediate DNA repair and cell-cycle checkpoints, can also contribute to an unstable genome. To learn more about this NEJM Illustrated Glossary term, read the Clinical Implications of Basic Research article “Extrachromosomal DNA — Amping Up Cancer” by Lillian Siu, MD, and Trevor J. Pugh, PhD, from the University Health Network and the Ontario Institute for Cancer Research: https://nej.md/42jfYdH      Explore more terms: https://nej.md/glossary    #Oncology #MedicalResearch

Enteral nutrition is defined as the provision of essential nutrients through an enteral tube to prevent or treat disease-related malnutrition in patients who are unable to consume adequate nutrients by mouth. 👉 https://nej.md/43PVxHO    The interplay of inadequate dietary intake and inflammation that characterizes disease-related malnutrition affects a patient’s response to medical nutrition therapy, including enteral nutrition.     Randomized, controlled trials performed over the past 15 years, involving mainly critically ill patients, as well as recent studies involving medical and surgical patients who were not critically ill, have informed our current understanding of enteral nutrition.     In a new review, Leah Gramlich, MD, and Peggi Guenter, PhD, RN, consider enteral nutrition in the context of disease-related malnutrition, provide evidence for the use of enteral nutrition in hospitalized patients, and discuss practice considerations.    Read the Review Article “Enteral Nutrition in Hospitalized Adults,” the latest in the Nutrition in Medicine series, from the University of Alberta and the American Society for Parenteral & Enteral Nutrition (ASPEN): https://nej.md/43PVxHO    #Gastroenterology  

Would thrombectomy benefit patients with medium-sized or distal vessel occlusion stroke? NEJM Editorial Fellow Sarah Gorey, MB, breaks down the ESCAPE-MeVO and DISTAL clinical trials. 📖 Further reading: ESCAPE-MeVO trial: https://nej.md/40LTUaL DISTAL trial: https://nej.md/4jYWV0z #ClinicalTrials #Neurology

For patients with cancer-associated venous thromboembolism (VTE), anticoagulation with a direct oral anticoagulant or low-molecular-weight heparin is recommended for 6 months, but are there any appropriate and effective regimens beyond that period?    In the API-CAT trial, patients with active cancer and proximal deep-vein thrombosis or pulmonary embolism who had completed at least 6 months of anticoagulant treatment were assigned to receive oral apixaban at a reduced (2.5 mg) or full (5.0 mg) dose twice daily for 12 months.     The primary efficacy outcome was centrally adjudicated fatal or nonfatal recurrent VTE over 12 months of follow-up (noninferiority margin, 2.00 for the upper boundary of the 95% CI of the subhazard ratio).    Among patients with active cancer and VTE who had received at least 6 months of anticoagulant treatment, extended treatment with low-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent VTE and the incidence of clinically relevant bleeding was lower with the reduced dose of apixaban than with the full dose.    Read the full API-CAT trial results and Research Summary: https://nej.md/41YkRZK    #Cardiology #ClinicalTrials  

An 𝐚𝐧𝐚𝐭𝐨𝐦𝐢𝐜𝐚𝐥 𝐜𝐨𝐧𝐧𝐞𝐜𝐭𝐢𝐯𝐢𝐭𝐲 𝐦𝐚𝐩 is a map of reconstructed white-matter pathways in the human brain based on diffusion-weighted MRI sequences. To learn more about this NEJM Illustrated Glossary term, read the 2018 Review Article “Mapping Symptoms to Brain Networks with the Human Connectome”: https://nej.md/2FYkgAc    Explore more terms: https://nej.md/glossary  

Does extrachromosomal DNA contribute to tumor heterogeneity and drive cancer progression? A new Clinical Implications of Basic Research article addresses that question. 👉 https://nej.md/42jfYdH    Extrachromosomal DNAs (ecDNAs) are circular DNA structures located in the nuclei of cells outside chromosomes.     They were originally discovered in chromosome spreads of cells obtained from embryonal tumors in the 1960s and were called “double minutes” because of their minuscule appearance.     Since then, molecular biologic and genome technologies have shown ecDNAs to be a driver of carcinogenesis, tumor heterogeneity, genome instability, immune evasion, and therapy resistance.    Proposed mechanisms for the formation of ecDNAs include complex chromosomal-shattering and genome-rearrangement events.     The ecDNAs lack centromeres and originate from chromosomal loci that can contain oncogenes, regulatory elements, and immunomodulatory genes. The current understanding is that ecDNAs are unique to cancer cells and are not found in healthy cells.     The segregation of ecDNA into daughter cancer cells is random and uneven, which creates opportunities for genetic advantage to accrue to one daughter cell over the other (seen in figure).     Recent studies revealed the landscape of ecDNA in human cancer and showed that coordinated inheritance of specialized ecDNA combinations can occur under selective pressures, such as cancer treatment.     In addition, the investigators found that clusters of cooperative ecDNA (called hubs) in the nucleus facilitate the efficient transcription of genes in ecDNA and on chromosomes, which further promotes the aggressive behavior of tumor cells.    Learn more in the Clinical Implications of Basic Research article “Extrachromosomal DNA — Amping Up Cancer” by Lillian Siu, MD, and Trevor J. Pugh, PhD, from the University Health Network and the Ontario Institute for Cancer Research: https://nej.md/42jfYdH    #Oncology #MedicalResearch