NEJM Group

For patients with relapsed or refractory multiple myeloma, efficacious second-line combination treatments are needed.     Belantamab mafodotin — an antibody–drug conjugate targeting B-cell maturation antigen (BCMA) — has diverse mechanisms of antitumor activity and has shown activity as a single agent in these patients.    In the DREAMM-7 trial, researchers assessed the efficacy and safety of belantamab mafodotin in combination with standard-care therapies in patients with relapsed or refractory multiple myeloma.    494 adults with relapsed or refractory multiple myeloma were randomly assigned to receive belantamab mafodotin, bortezomib, and dexamethasone (BVd) or daratumumab, bortezomib, and dexamethasone (DVd). The primary end point was progression-free survival.    As compared with DVd, BVd therapy conferred a significant benefit with respect to progression-free survival in patients with relapsed or refractory multiple myeloma. Half the patients who received BVd had serious adverse events.    Read the full DREAMM-7 trial results and Plain Language Summary: https://nej.md/3wTS3pA    #ClinicalTrials #MedicalResearch 

A 𝗿𝗲𝗰𝗼𝗺𝗯𝗶𝗻𝗮𝗻𝘁 𝗵𝘂𝗺𝗮𝗻 𝗽𝗿𝗼𝘁𝗲𝗶𝗻 is a protein that is made with the aid of an expression vector containing a version of the gene encoding the desired protein. (Unlike the naturally occurring gene, it lacks introns and may have other changes.) The gene is then transcribed into RNA, which is translated into human protein. To learn more about this NEJM Illustrated Glossary term, read the editorial “Bioengineered Factor VIII — More Innovation for Hemophilia A” by Pratima Chowdary, M.D., from the Royal Free London NHS Foundation Trust: https://nej.md/3Y6RTWY    Explore more terms: https://nej.md/glossary  

A previously healthy 8-year-old girl was transferred to a Boston hospital from Nantucket (an island off the coast of Massachusetts) with a 12-day history of fevers, sore throat, and cervical lymphadenopathy.    After a thorough history taking that elicited exposure to rabbits and ticks and ingestion of well and spring water, the correct diagnosis of oropharyngeal tularemia was presumed, leading to directed therapy that resulted in resolution of symptoms.    Tularemia — also known as rabbit fever, hunter’s disease, and deer fever, among others — is a rare zoonotic infection that is endemic on multiple continents, including North America, Europe, and Asia.    In the United States, tularemia is most prevalent in south-central and western states and is relatively uncommon in Massachusetts. However, reported cases in Massachusetts often occur on Cape Cod, Martha’s Vineyard, or Nantucket, generally during the summer and early fall. As climate change affects animal hosts and insect vectors, the geographic range and incidence of tickborne illnesses (including tularemia) and other zoonotic diseases are expected to increase.    Tularemia manifests in six clinical syndromes: ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal. Ulceroglandular disease is the most common, whereas the typhoidal syndrome has the highest mortality. The syndrome at presentation corresponds with the mode of acquisition of the causative organism (shown in figure).    Learn more about the clinical case and tularemia in the Clinical Problem-Solving article “Going Down the Rabbit Hole” by Kendall Burdick, M.D., William Ealick, M.D., M.P.H., Hector Vargas Acevedo, M.D., Theodore Sectish, M.D., and Thomas J. Sandora, M.D., M.P.H.: https://nej.md/3A1vIaR 

Is the “Not Otherwise Specified” podcast “The Bear” for physicians? In a STAT First Opinion, Dr. Abraham Nussbaum shares the similarities of the restaurant drama “The Bear” to working in a hospital. Full article: https://lnkd.in/eV5e3iug Notably, the author points to the NEJM “Not Otherwise Specified” podcast by Dr. Lisa Rosenbaum in which she evaluates the current state of medical education and the generational differences that are leading to a quiet revolution in medical training. Listen to the “Not Otherwise Specified” podcast: https://nej.md/NOS Read the accompanying four-part article series, “Medical Training Today": https://nej.md/3uRKxL7

This editorial describes the science behind detecting and treating autoimmunity in kidney disease.    The blood in an average healthy adult is filtered through the approximately 2 million glomeruli contained within the kidneys — every 5 minutes! Thus, every 24 hours, an adult human produces the equivalent of eighteen 10-gallon fish tanks of filtrate. Ultimately, most of this filtrate is resorbed downstream in the kidney tubules, resulting in the net production of a liter or two of urine, which, in healthy persons, is nearly free of protein and large molecules but contains smaller waste substances (shown in figure). Impairment of the filtration process imposes a large burden: approximately 12% of persons with such impairment go on to have some form of kidney disease, and the majority of persons with kidney disease have dysfunctional glomeruli, characterized by reduced filtration of waste products from the bloodstream and increased loss of proteins that would otherwise maintain oncotic pressure within the circulation.    Read the editorial “Kidney Disease and Antinephrin Antibodies” by Jochen Reiser, M.D., Ph.D., and Julie Ingelfinger, M.D., from The University of Texas Medical Branch: https://nej.md/4fnl1zD   

Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death.     The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear.    In the SYNERGY-NASH trial, researchers assessed the efficacy and safety of once-weekly tirzepatide in persons with MASH and moderate or severe fibrosis.    190 adults with a body-mass index (BMI) between 27 and 50, histologically confirmed MASH, and moderate or severe fibrosis received once-weekly subcutaneous tirzepatide at one of three doses (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks.     The primary end point was resolution of MASH without worsening of fibrosis at week 52.    In participants with MASH and moderate or severe fibrosis, once-weekly tirzepatide at a dose of 5 mg, 10 mg, or 15 mg was more effective than placebo for resolution of MASH without worsening of fibrosis.    Read the full SYNERGY-NASH trial results and Plain Language Summary: https://nej.md/4c6h3su    #ClinicalTrials #MedicalResearch 

A 58-year-old woman with a history of obesity, hypertension, and hyperlipidemia comes to see you, her primary care doctor, for a follow-up visit, after having missed several appointments. She is currently taking atorvastatin, chlorthalidone, and lisinopril. On examination, her blood pressure is 128/86 mm Hg, her weight is 80 kg, and her body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) is 31.2. Her weight a year ago was 70 kg (with a BMI of 27.3). There are no other relevant findings. Recent laboratory testing showed an aspartate aminotransferase (AST) level of 45 U per liter (normal range, 8 to 33) and an alanine aminotransferase (ALT) level of 120 U per liter (normal range, 1 to 35) (both levels were normal 1 year ago), a total bilirubin level of 0.8 mg per deciliter (13.7 μmol per liter) (normal range, 0.1 to 1.2 mg per deciliter [1.7 to 20.5 μmol per liter]), an albumin level of 4.3 g per deciliter (normal range, 3.5 to 5.5), a platelet count of 198,000 (normal range, 150,000 to 450,000), and a glycated hemoglobin level of 7.5% (normal range, <5.7%). Her Fibrosis-4 index score is 1.20, which indicates a low risk of advanced fibrosis. Abdominal ultrasonography shows a fatty liver, with no liver nodularity or splenomegaly.    You tell her that her weight gain is probably contributing to the abnormal liver-enzyme levels and that she probably has metabolic dysfunction–associated steatotic liver disease (MASLD). She requests a referral to a dietitian to provide further resources on sustainable weight loss to address her metabolic syndrome. You wonder whether you should also refer this patient to a hepatologist for further management of MASLD.     Read more about the case and treatment options: https://nej.md/3YiYi1E 

A 𝗻𝗲𝗼𝗻𝗮𝘁𝗮𝗹 𝗙𝗰 𝗿𝗲𝗰𝗲𝗽𝘁𝗼𝗿 (𝗙𝗰𝗥𝗻) is a protein in rodents and humans that is responsible for the transfer of passive immunity from the mother to the newborn. The interaction between antibodies and the neonatal Fc (fragment crystallized) receptor, or FcRn, is crucial in maintaining and prolonging antibody plasma half-life. FcRn protects antibodies from normal lysosomal degradation inside cells, permitting them to recycle back into the circulation, thereby extending their half-life in the circulation. To learn more about this NEJM Illustrated Glossary term, read the editorial “Bioengineered Factor VIII — More Innovation for Hemophilia A” by Pratima Chowdary, M.D., from the Royal Free London NHS Foundation Trust: https://nej.md/3Y6RTWY    Explore more terms: https://nej.md/glossary 

“He casually passes me a sheet of stickers that read, ‘It was metastasized when I got here,’” writes Danielle Chammas, M.D., in a new Perspective.    “A chuckle escapes me as I imagine the social situation I’d find myself in if I let my daughters take these stickers to preschool for show-and-tell. I state the obvious: ‘I’m getting the sense that humor has been helping you get through all that’s going on.’    “‘Oh, I’m just getting started with the jokes, Dr. D.,’ he says, a glint in his eye. ‘This is just the tip of the iceberg.’    “Though I can’t suppress a smile in response to his energy, I wonder about the role humor plays in his coping. Like any defense, it’s clearly helping him keep himself together through an unthinkably difficult situation, but I don’t yet know what else it may be affecting. Is it keeping a distance between him and the painful truths he needs to integrate? Is it, on the contrary, allowing him to be more in contact with painful truths while staying psychologically intact? Before allowing myself to lean too far into the humor, I try to assess what we’re working with.”    Read the Perspective “Should I Laugh at That? Coping in the Setting of Serious Illness” by Danielle Chammas, M.D., from the University of California, San Francisco: https://nej.md/4cK3X5f 

The Covid-19 pandemic has been perceived mainly as a dangerous acute outbreak of infection that killed more than a million people in the United States and 7 million worldwide. However, in the pandemic’s wake, Covid-19 has left many millions more with a variety of chronic, systemic, and often disabling conditions collectively known as “long Covid.” In the United States alone, survey data indicate that approximately 7% of adults and more than 1% of children — numbering 15 to 20 million Americans and more than 60 million globally — have had long Covid.    Because of the novelty and diverse expression of this condition, a variety of terms and definitions have been advanced for long Covid, although none have gained wide acceptance and support from patients, clinicians, researchers, and government agencies. In recognition of the shortcomings of the existing definitions, the Administration for Strategic Preparedness and Response and the Office of the Assistant Secretary of Health in the Department of Health and Human Services tasked The National Academies of Sciences, Engineering, and Medicine with developing an improved definition for long Covid that would take into account the needs of patients as well as the views and understanding of a range of experts.    Learn more in the Sounding Board article “Long Covid Defined” by E. Wesley Ely, M.D., M.P.H., Lisa Brown, M.P.H., and Harvey Fineberg, M.D., Ph.D.: https://nej.md/3SvLlxw    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Editorial: From Evidence to Policy — Finding Authoritative Sources of Information on Health https://nej.md/4fi7B7U