NEJM This Week — October 2, 2025

Interactive Transcript

spk_0 Welcome. This is the New England Journal of Medicine. I'm Dr. Michael Beerer.

spk_0 This week, October 2nd, 2025, we talk about severe acute malnutrition with gastroenteritis in

spk_0 children, medical imaging and pediatric cancer risk, moderate hyper-tri glyceridemia,

spk_0 preventing RSV disease in healthy infants, and treating hypertension in rural South Africa.

spk_0 A review article on monoclonal gamopathy of undetermined significance, a clinical problem-solving

spk_0 on a shifting frame and perspectives on insight into corporate governance,

spk_0 on pharmaceutical tariffs, and on OUD medications.

spk_0 A test for penicillin allergy? This new clinical decisions about a college student with strep throat

spk_0 who has an unconfirmed penicillin allergy offers a case vignette accompanied by two essays.

spk_0 One, supporting prescription of a non-penicillin antibiotic and referral to an allergist,

spk_0 and the other supporting administration of penicillin under Dr. Supervision. We want to know what you

spk_0 decide. Cast your vote at NEJM.org.

spk_0 Intravenous rehydration for severe acute malnutrition with gastroenteritis.

spk_0 By Catherine Mateland from Imperial College London and co-authors.

spk_0 Severe acute malnutrition, the most extreme form of undernourishment, is a leading cause of hospital

spk_0 admissions among children in Africa. Many children with severe malnutrition have additional complications,

spk_0 such as severe dehydration due to diarrhea, which is associated with high in-hospital mortality,

spk_0 27-41%. International recommendations advise against the use of intravenous rehydration therapy

spk_0 in children with severe acute malnutrition because of the concern about fluid overload.

spk_0 Although such guidance documents have been in place for more than two decades,

spk_0 no previous or subsequent evidence has supported these recommendations. Given the high mortality

spk_0 associated with the current recommendations, the adoption of intravenous rehydration strategies

spk_0 might improve outcomes. This trial conducted in four countries in Africa, assessed whether

spk_0 intravenous rehydration administered either rapidly or slowly would result in lower mortality

spk_0 than the standard oral rehydration strategy among 272 hospitalized children with severe acute

spk_0 malnutrition with gastroenteritis. The mortality rate was lower than expected in both arms of the trial.

spk_0 Among these children, no evidence of a difference in mortality at 96 hours was noted between the oral

spk_0 and intravenous rehydration strategies. Editorialist Mark Peters from the Great Ormond Street

spk_0 Hospital Biomedical Research Center, London writes that in 2024, a United Nations report estimated

spk_0 that one in 11 persons up to 757 million worldwide were facing hunger. Food insecurity and the risk

spk_0 of famine are exacerbated by conflict and climate change. Infants and children are frequently the

spk_0 most severely affected as shocking images from sub-Saharan Africa and Gaza currently attest. Infants

spk_0 and children with severe acute malnutrition frequently have the acute medical complication of

spk_0 dehydration from gastroenteritis. The trial by Mateland and co-authors should be viewed as a trial

spk_0 that seriously challenges the perceived risks from intravenous rehydration. The upper boundary

spk_0 of the 95% confidence interval for the actual incidence of heart failure from these data with

spk_0 intravenous rehydration is 2.3%. We still need data from future large trials to evaluate whether

spk_0 these strategies are truly equivalent, but to the best of our current knowledge, intravenous

spk_0 alternatives to oral rehydration result in similar survival rates. Mateland and co-authors have

spk_0 provided important alternative treatment strategies for colleagues working in the most challenging

spk_0 circumstances. If additional studies confirm these data, hundreds of thousands of the most

spk_0 vulnerable people on our planet may benefit. Medical imaging and pediatric and adolescent

spk_0 hematologic cancer risk by Rebecca Smith-Bindman from the University of California, San Francisco,

spk_0 and co-authors. Assessing the risk of radiation-induced hematologic cancer from medical imaging

spk_0 and children and adolescents might support informed decisions on the use of imaging. This retrospective

spk_0 cohort study quantified the association between cumulative radiation dose to active bone marrow

spk_0 from medical imaging and the risk of hematologic cancers among a cohort of over 3 million children

spk_0 in the United States and Ontario, Canada. Over a mean of 10.1 years per person, 2,961 hematologic

spk_0 cancers were diagnosed. The excess cumulative incidence of hematologic cancers by 21 years of age,

spk_0 among children exposed to at least 30 milligrays, mean 57 milligrays, was 25.6 per 10,000.

spk_0 The investigators estimated that in the cohort, 10.1 percent of the hematologic cancers may have

spk_0 been attributable to radiation exposure from medical imaging, with higher risks from the higher dose

spk_0 medical imaging tests such as CT. This study suggests an association between exposure to radiation

spk_0 from medical imaging and a small but significantly increased risk of hematologic cancer among children

spk_0 and adolescents. Lindsey Morton from the National Cancer Institute Bethesda, Maryland writes in

spk_0 an editorial that the report by Smith-Bindman and co-authors expands the understanding of health

spk_0 risks associated with low dose less than 100 milligrays radiation exposure, which can inform

spk_0 radiation protection standards and radiation-related carcinogenesis. The report is an important

spk_0 addition to the growing body of direct evidence regarding the small risks of cancer after low dose

spk_0 radiation exposure. It also confirms the relatively short latency interval between exposure and

spk_0 cancer diagnosis of radiation-related hematologic cancers as compared with solid tumors. More broadly,

spk_0 imaging is important for patient care and can be life-saving, but is also associated with some

spk_0 measurable risk. To provide evidence needed for decisions regarding imaging, long-term strategic

spk_0 support of radiation-related research and education should remain a high priority. Ultimately,

spk_0 we need to ensure that all involved in medical imaging, from radiologic professionals and referring

spk_0 physicians to caregivers and patients, wisely interpret the results of studies such as that of

spk_0 Smith-Bindman and co-authors, to understand the balance of the very small risks and the notable

spk_0 benefits of necessary imaging examinations to provide optimal patient care.

spk_0 Targeting APO-C3 with Olisarsin in moderate hyper-triglisoridemia by Brian Bergmark from Brighamon

spk_0 Women's Hospital Boston and co-authors. Highly effective therapies to reduce triglyceride levels

spk_0 are lacking. Olisarsin is an enacetylgalactosamine-conjugated anti-sense oligo nucleotide that targets the

spk_0 messenger RNA of APO-Lipo-protein C3, which inhibits triglyceride clearance. In this phase,

spk_0 three trial, 1,349 patients with moderate hyper-triglisoridemia and elevated cardiovascular risk,

spk_0 or with severe hyper-triglisoridemia, were enrolled and then randomly assigned in a 1-3 ratio

spk_0 to a 50-mg or 80-mg cohort. The patients were then randomly assigned in a 3-to-1 ratio to receive

spk_0 monthly subcutaneous Olisarsin or matching placebo within each cohort. Among these patients,

spk_0 treatment with Olisarsin resulted in significantly greater reduction in triglyceride levels at 6 months

spk_0 than placebo. The incidence of serious adverse events appeared to be similar across the trial groups.

spk_0 Kles Rovimab for Prevention of RSV Disease in Healthy Infants by Heather Zarr from the University of

spk_0 Cape Town, South Africa, and co-authors. Kles Rovimab is a long-acting investigational monoclonal

spk_0 antibody against site 4 of the respiratory sensitial virus RSV Fusion Protein. In this trial,

spk_0 3614 healthy pre-term and full-term infants entering their first RSV season were randomly

spk_0 assigned in a 2-to-1 ratio to receive one intramuscular 105-mg dose of Kles Rovimab or placebo.

spk_0 In the first 150 days, a single dose of Kles Rovimab reduced the incidence of RSV

spk_0 associated medically attended lower respiratory infection and RSV associated hospitalization with a

spk_0 safety profile similar to that of placebo. Home-based care for hypertension in rural South Africa

spk_0 by Mark Sidener from the Africa Health Research Institute, Durban, South Africa, and co-authors.

spk_0 Poorly controlled hypertension is a common problem worldwide, particularly in low-resource

spk_0 settings. In this randomized controlled trial of a home-based model of hypertension care in

spk_0 South Africa, 774 adults with hypertension were assigned to receive home-based care, which consisted

spk_0 of patient monitoring of blood pressure, home visits from a community health worker for data

spk_0 collection and medication delivery, and remote nurse-led decision-making supported by a mobile

spk_0 application, or enhanced home-based care, which consisted of the same intervention but with

spk_0 blood pressure machines transmitting readings automatically, or standard care with clinic-based

spk_0 management. The home-based models of hypertension care led to a significantly lower mean-sistolic

spk_0 blood pressure at six months than standard clinic-based care. I'm Deerntationman, a deputy editor

spk_0 at the New England Journal of Medicine. I've been a full-time medical journal editor for over

spk_0 15 years, but I've never stopped seeing patients. Just like the other full-time physician editors on

spk_0 our team, I continue to practice medicine for a couple of reasons. Most importantly, I love it.

spk_0 It's who I am. It's who I train to be. I've known many of my patients for over 20 years, and

spk_0 I don't want to lose those connections. I also think seeing patients makes me a better editor.

spk_0 When we sit around the table and discuss papers, my colleagues and I can understand why the

spk_0 questions asked by the research studies were considering are important or not to practicing

spk_0 clinicians because we see patients ourselves. I love this work because I always learn a lot,

spk_0 and the goal is simple, to help our authors clearly, honestly, and concisely communicate their

spk_0 findings to our readers, so they in turn can use what they read to help their patients.

spk_0 It certainly helps me take better care of my patients. We're published by the Massachusetts Medical

spk_0 Society, a not-for-profit publisher, and we rely on subscriptions from individual readers,

spk_0 medical schools, and libraries to fund what we do.

spk_0 Monoclonal Gammaopathy of Undetermined Significance, a review article by S. Vincent Raj Kumar

spk_0 and Sajji Kumar from the Mayo Clinic Rochester, Minnesota. Monoclonal Gammaopathy of

spk_0 Undetermined Significance, M. Gus, is a pre-malignant plasma cell disorder present in approximately

spk_0 5% of the general population over the age of 50 years. M. Gus is characterized by the presence of

spk_0 detectable monoclonal M proteins, which are identical copies of intact immunoglobulins,

spk_0 immunoglobulin light chains, or both, that are secreted by the clonal plasma cells.

spk_0 M. Gus is asymptomatic, but can progress to cancer, specifically multiple myeloma, lymphoblasmicidic

spk_0 lymphoma, formerly called Waldensromes macroglobulinemia, or solitary plasma cytoma, at a rate of 1%

spk_0 per year. A variety of systemic disorders referred to collectively as monoclonal Gammaopathy of

spk_0 clinical significance, M. G. C. S, can develop as a result of the secreted monoclonal immunoglobulin

spk_0 in persons with M. Gus. The diagnosis of progression to cancer or M. G. C. S usually requires

spk_0 histopathological confirmation to ensure that the clinical problem is attributable to the plasma cell

spk_0 disorder. No therapy is needed for M. Gus, and the schedule for clinical follow-up is dictated by

spk_0 underlying risk stratification. A shifting frame, a clinical problem solving by Alice

spk_0 Territ from Flinders Medical Center Bedford Park, South Adelaide, Australia, and co-authors.

spk_0 A 32-year-old woman was noted during early pregnancy to have some elevated liver enzyme levels

spk_0 on routine testing. She was asymptomatic, and her billi-roobin, alkaline phosphatase,

spk_0 and gamma glutamil transferase levels were normal. Her past medical history included postpartum

spk_0 myocarditis after her first delivery. Over time, persistently high amino transferase and creatine

spk_0 kinase levels raised suspicion for a muscle rather than liver disorder. She also had chronic

spk_0 neutropenia and later developed tender, hyperpigmented nodules on her shins, diagnosed as erythema

spk_0 indiratum, with evidence of tuberculosis infection. Despite TB treatment, she continued to have mild

spk_0 proximal muscle weakness and elevated creatine kinase levels. Imaging showed intramuscular edema

spk_0 and fatty atrophy, and a muscle biopsy revealed scattered necrotic fibers but no inflammatory infiltrate.

spk_0 Genetic testing ultimately identified a pathogenic, distrofen, DMD gene deletion,

spk_0 consistent with her being a symptomatic carrier of Duchens muscular dystrophy,

spk_0 with skeletal muscle and cardiac involvement. The majority of female carriers of a DMD variant

spk_0 on one chromosome are asymptomatic. However, a small number have symptoms ranging from mild

spk_0 muscle weakness to more severe clinical features, including cardiomyopathy, as was the case with

spk_0 this patient. Duchens muscular dystrophy is a rare, progressive, eventually fatal muscular disorder

spk_0 manifested initially by frequent falls, wadling gate, and difficulty climbing stairs.

spk_0 Insight into corporate governance, what motivates hospitals and delivery systems. A perspective on the

spk_0 corporatization of US healthcare by Stephen Lipstein from Denver, Colorado. Over the course of four

spk_0 decades, Mr. Lipstein held leadership positions at several prominent academic health systems.

spk_0 Yet, until he was asked to write this article, he notes that he had not heard the word corporatization

spk_0 used to describe what happens in his line of work. In part, the concern revolves around big corporations

spk_0 or private investors buying up and aggregating healthcare assets that previously were independently

spk_0 owned and operated. Critics of such large-scale combinations argue that when clinical assets are

spk_0 aggregated within contiguous geographic areas, there is market consolidation. And market consolidation

spk_0 leads to anti-competitive behaviors, resulting in higher prices without concomitant quality

spk_0 improvements. Fewer small innovative providers left to disrupt the status quo and depressed wages

spk_0 for healthcare workers. Delivery system leaders view asset aggregation in a different way,

spk_0 as a vehicle for efficient deployment of human, physical, and financial capital to achieve a

spk_0 healthcare mission. For example, expansion enables a healthcare system to diversify its

spk_0 payermix and maintain a financially healthy balance of all insurance types. Too many publicly

spk_0 insured patients and not enough privately insured patients within a healthcare system is a recipe

spk_0 for financial instability. The risks of pharmaceutical tariffs for generic drug availability,

spk_0 a perspective by Thomas Huang from Dana-Farber Cancer Institute, Boston, and co-authors.

spk_0 In April 2025, the Trump administration announced an investigation into the adverse effects of

spk_0 pharmaceutical imports on U.S. national security. Under section 232 of the Trade Expansion Act of 1962,

spk_0 the president has broad power to investigate and subsequently to adjust or restrict imports

spk_0 that threaten to impair national security. If finalized, the application of pharmaceutical tariffs

spk_0 under section 232 would upend long-standing trade conventions that have protected medicine imports

spk_0 from tariffs, increased costs for public healthcare payers, and potentially reduce the availability

spk_0 of important generic medicines in the United States. For example, applying tariffs under section 232

spk_0 would provide generic drug manufacturers with an incentive to marketly reduce or even discontinue

spk_0 product sales, that is for generic drugs that are disproportionately purchased by public payers,

spk_0 rather than absorbing the full cost of tariffs. Generic drugs, which account for roughly

spk_0 90% of total-filled prescriptions in the United States, generally have low profit margins and are

spk_0 mostly manufactured overseas. These authors believe that several changes to the administration's

spk_0 proposed policy on pharmaceutical tariffs are urgently needed to protect access to generic medicines.

spk_0 Goals for opioid use disorder medications, protection, remission, and recovery, a perspective by

spk_0 A. Thomas McLean from the University of Pennsylvania, Philadelphia, and Nora Falcov from the

spk_0 National Institutes of Health, Bethesda, Maryland. Medications such as methadone, nowtrexone,

spk_0 and buprenorphine are the first line treatment for opioid use disorder, OUD. Yet, most addiction

spk_0 treatment programs don't offer these medications, and most physicians don't prescribe them.

spk_0 The result is that only 20 to 25% of the patients who are at risk for overdose or other OUD-related

spk_0 harms receive medication for opioid use disorder. And even those patients are usually prescribed

spk_0 medication only for short-term detoxification. Along with stigma and lack of regulatory clarity,

spk_0 important barriers to broader prescribing include confusion and controversy about the appropriate

spk_0 clinical goals for OUD medications. A key question has been when, if ever, to taper and discontinue

spk_0 medication. At the systems level, the OUD cascade of care model is emerging as a standard tool for

spk_0 administrators of state and private healthcare organizations to monitor the management of OUD

spk_0 in their patient populations, by tracking the movement of patients from identification and

spk_0 diagnosis to prescription of OUD medications, sustained reduction in symptoms with these medications,

spk_0 and ultimately referral to recovery-oriented services. These authors believe operationalizing

spk_0 the stages of this model for use in the care of individual patients could offer practical

spk_0 guidance for prescribers and treatment programs, reduce ideological controversies hampering progress

spk_0 in the field of addiction medicine, and increase practitioners' willingness to treat OUD.

spk_0 In our images in clinical medicine, a 52-year-old woman with hypertension presented with fatigue,

spk_0 vomiting, and confusion. Examination was notable for powdery crystalline deposits on the arms,

spk_0 legs, trunk, and scalp. Testing of a skin scraping of the powdery crystals was positive for

spk_0 urea, a diagnosis of advanced end-stage kidney disease with uremic frost was made.

spk_0 Another image shows herpes' simplex virus isophagitis. A 29-year-old woman presented with a

spk_0 two-day history of painful swallowing. One week earlier, she had had a fever and sore throat.

spk_0 Upper endoscopy revealed multiple volcano-like ulcers in the middle isophagus.

spk_0 Read more from our issue at nejm.org. Let us know what you think about our podcast. Any comments

spk_0 or suggestions may be sent to audio at nejm.org. Thank you for listening.

NEJM This Week — October 2, 2025

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