N Engl J Med
· 2026 May · PMID 42202321
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Leishmaniases comprise clinically distinct diseases caused by the protozoan parasite leishmania, which is transmitted through the bite of infected sand flies. Cutaneous leishmaniasis is the most common form and manifests...Leishmaniases comprise clinically distinct diseases caused by the protozoan parasite leishmania, which is transmitted through the bite of infected sand flies. Cutaneous leishmaniasis is the most common form and manifests as a localized skin lesion. Mucosal leishmaniasis causes destructive nose, mouth, and throat lesions. Visceral leishmaniasis is a potentially life-threatening form that results from bloodborne dissemination of the parasites. The number of cases of cutaneous leishmaniasis is increasing, particularly in the Eastern Mediterranean region, and the prevalence of visceral leishmaniasis is decreasing globally. Laboratory diagnosis of the leishmaniases has shifted to the use of molecular methods to test tissue samples (e.g., skin or bone marrow), which can be used to identify infecting species. Treatment is challenged by limited drug choices. A recent advance is the use of combination therapies for visceral leishmaniasis. Two human leishmaniasis vaccines are undergoing preclinical testing or are ready for human testing.
Limbrick DD, Shannon CN, Bayman EO
… +79 more, Meehan T, Kallem M, Ackerman LL, Adelson PD, Ahmed R, Albert G, Aldana PR, Alden TD, Anderson RCE, Baird LC, Bauer D, Bethel-Anderson T, Bierbrauer K, Brockmeyer DL, Chern JJ, Couture DE, Daniels DJ, Dauser RC, Dlouhy BJ, Durham SR, Ellenbogen RG, Eskandari R, Gannon SR, Grant GA, Graupman PC, Greenberg JK, Greene S, Greenfield JP, Gross NL, Guillaume DJ, Hankinson TC, Heuer G, Iantosca M, Iskandar BJ, Jackson EM, Jallo GI, Johnston JM, Keating RF, Kelly MP, Kennedy E, Krieger MD, Kulkarni AV, Labuda R, Leonard JR, Maher CO, Mangano FT, McComb JG, McEvoy SD, McKinstry RC, Menezes AH, Niazi TN, Oakes J, Olavarria G, O'Neill BR, Poppe D, Ragheb J, Reeves S, Reynolds L, Selden NR, Shah MN, Shimony JS, Smyth MD, Spears S, Stone SSD, Strahle JM, Tamber M, Tramelli G, Tuite GF, Tyler-Kabara EC, Vance H, Wait SD, Wellons JC, Whitehead WE, Yahanda AT, Yan Y, Dacey RG, Park TS, Torner JC, Park-Reeves Syringomyelia Research Consortium Investigators
N Engl J Med
· 2026 May · PMID 42202320
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BACKGROUND: In children with Chiari type I malformation and syringomyelia, neurosurgical posterior fossa decompression (PFD) provides clinical improvement, but whether duraplasty (incising the dura and placing a dural gr...BACKGROUND: In children with Chiari type I malformation and syringomyelia, neurosurgical posterior fossa decompression (PFD) provides clinical improvement, but whether duraplasty (incising the dura and placing a dural graft) improves outcomes is unclear. METHODS: We conducted a multicenter, cluster-randomized, controlled trial of PFD with duraplasty (PFD-D) as compared with PFD alone. Persons 21 years of age or younger with cerebellar tonsillar ectopia of at least 5 mm and a maximum syrinx diameter of 3.0 to 9.9 mm were enrolled at 38 centers. Centers were cluster-randomized: all the participants within each center underwent the same intervention. The primary outcome was surgical complications within 6 months. Secondary outcomes were clinical improvement, syrinx reduction, and repeat decompression at 10 to 24 months and the change in overall health-related quality of life at 6 to 24 months. RESULTS: A total of 162 participants were included in the trial, of whom 78 were assigned to undergo PFD-D and 84 to undergo PFD alone. The percentage of participants with complications within 6 months was 14% with PFD-D and 6% with PFD (adjusted odds ratio, 2.59; 95% confidence interval [CI], 0.86 to 7.84; P = 0.11). At 24 months, the percentage of participants with clinical improvement was 58% with PFD-D and 46% with PFD; the mean (±SD) syrinx reduction was 3.08±2.33 mm and 1.22±1.79 mm, respectively; and the percentage of participants with repeat decompression was 3% and 14%. Changes in health-related quality of life were similar in the two groups. CONCLUSIONS: The percentage of participants with surgical complications did not differ significantly between those who underwent PFD-D and and those who underwent PFD alone. Larger trials are needed to determine the relative benefits and risks of these two procedures. (Funded by the Patient-Centered Outcomes Research Institute and others; ClinicalTrials.gov number, NCT02669836.).
Shitara K, Elimova E, Liu T
… +27 more, Tabernero J, Lee KW, Schenker M, Tebbutt NC, Ajani J, Salimin N, Ku G, Gwang Kim J, Ales Diaz I, Zhang J, Pietrantonio F, Bai LY, Le Sourd S, Zhao J, Hierro C, Kiberu A, Van Herpe F, Bao Y, Zhang H, Yang L, Li V, Gartner EM, Chen Y, Grim J, Rha SY, Shen L, HERIZON-GEA-01 Investigators
N Engl J Med
· 2026 May · PMID 42202319
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BACKGROUND: Zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, plus chemotherapy both with and without tislelizumab (anti-programmed death 1), showed encouraging efficacy an...BACKGROUND: Zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, plus chemotherapy both with and without tislelizumab (anti-programmed death 1), showed encouraging efficacy and safety as first-line therapy in phase 2 studies involving patients with HER2-positive gastroesophageal adenocarcinoma. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The two primary end points were progression-free survival and overall survival. RESULTS: At a median follow-up of 25.9 months, progression-free survival was longer with zanidatamab-tislelizumab-chemotherapy (median among 302 patients, 12.4 months) and zanidatamab-chemotherapy (median among 304 patients, 12.4 months) than with trastuzumab-chemotherapy (median among 308 patients, 8.1 months) (hazard ratio for progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval {CI}, 0.51 to 0.78]; hazard ratio with zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons). Overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy (median, 26.4 vs. 19.2 months; hazard ratio for death, 0.72; 95% CI, 0.57 to 0.90; P = 0.004). At this interim analysis, overall survival did not differ significantly between zanidatamab-chemotherapy (median, 24.4 months) and trastuzumab-chemotherapy (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P = 0.06). The incidence of grade 3 or higher adverse events was 83.3% with zanidatamab-tislelizumab-chemotherapy, 73.8% with zanidatamab-chemotherapy, and 74.5% with trastuzumab-chemotherapy; diarrhea was the most common such event, in 24.8%, 20.0%, and 12.9% of patients, respectively. CONCLUSIONS: Zanidatamab plus chemotherapy, both with and without tislelizumab, led to longer progression-free survival than trastuzumab plus chemotherapy among patients with HER2-positive advanced gastroesophageal adenocarcinoma. At this interim analysis, overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy; further analyses are planned to assess zanidatamab-chemotherapy. Diarrhea was a common adverse event. (Funded by Jazz Pharmaceuticals and others; HERIZON-GEA-01 ClinicalTrials.gov number, NCT05152147.).
N Engl J Med
· 2026 May · PMID 42202318
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BACKGROUND: Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscula...BACKGROUND: Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction. METHODS: We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. All the patients received immunosuppression. Safety was assessed as adverse events related to the procedure. The primary efficacy end points were the change from baseline in the target heart-wall thickness, the left ventricular ejection fraction, and the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS). RESULTS: A total of 20 patients were treated in the study. Three patients died during the study (1 each from vasoplegia, coronavirus disease 2019, and aortic dissection). One patient underwent heart transplantation. Immunosuppression was discontinued in 4 patients because of implantation of a left ventricular assist device (in 2 patients), renal failure (in 1 patient), and urothelial carcinoma (in 1 patient). Of the 16 patients who were treated with the safe maximal dose (20 engineered-heart-muscle units), 12 patients completed the prespecified 3-month interim follow-up. The least-squares mean increase in the target-wall thickness was 4.5 mm (90% confidence interval [CI], 3.7 to 5.4; P<0.001), the increase in the left ventricular ejection fraction was 3.9 percentage points (90% CI, 0.9 to 6.8; P = 0.04), and the increase in the KCCQ-OSS was 6.7 points (90% CI, 1.0 to 12.5; P = 0.06). All the patients had at least one adverse event. CONCLUSIONS: In this interim analysis, cardiac remuscularization with BioVAT was associated with an increase in the target heart-wall thickness, left ventricular ejection fraction, and KCCQ-OSS at 3 months; all the patients had at least one adverse event. Longer-term follow-up and further clinical investigation are warranted. (Funded by the German Center for Cardiovascular Research and Repairon; BioVAT-HF ClinicalTrials.gov number, NCT04396899.).
Vafai SB, Täubel J, Ashdown T
… +28 more, Patel RS, Diamondali S, Cegla J, Soran H, Bashir B, Abitbol A, Gaudet D, Lauzière A, Brunham LR, Newby DE, Nicholls SJ, Scott RS, Kerr J, Tardif JC, Lunken C, Humphries SE, Karsten V, Tyler PD, Zhang X, Huniti N, Flight PA, Jensen CL, Falzone R, Biedenkapp JC, Lister T, Stolz LE, Khera AV, Kathiresan S
N Engl J Med
· 2026 May · PMID 42187087
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BACKGROUND: Persons carrying loss-of-function variants of proprotein convertase subtilisin-kexin type 9 () have reduced levels of low-density lipoprotein (LDL) cholesterol and fewer atherosclerotic cardiovascular disease...BACKGROUND: Persons carrying loss-of-function variants of proprotein convertase subtilisin-kexin type 9 () have reduced levels of low-density lipoprotein (LDL) cholesterol and fewer atherosclerotic cardiovascular disease events than persons without such variants. VERVE-102 is an investigational base-editing therapy designed to durably inactivate in the liver. METHODS: In this phase 1, open-label, single-ascending-dose study, we administered one intravenous infusion of VERVE-102 at one of six doses (ranging from 0.3 to 1.0 mg of total RNA per kilogram of body weight [mg per kilogram]) to adults with heterozygous familial hypercholesterolemia or premature coronary artery disease. VERVE-102 consists of a messenger RNA encoding an adenine base-editor protein and a guide RNA targeting , which are encapsulated in a lipid nanoparticle incorporating -acetylgalactosamine. The objectives were to assess safety and changes in blood PCSK9 protein and LDL cholesterol levels. RESULTS: A total of 35 participants across the six dose cohorts received VERVE-102 and had at least 28 days of follow-up. No dose-limiting toxic effects occurred. Mild-to-moderate infusion-related reactions and transient elevations in alanine aminotransferase levels were observed. Aspiration pneumonitis occurred in a participant with gastroesophageal reflux disease. Dose-dependent mean reductions in the PCSK9 level ranged from 51% at the 0.3-mg-per-kilogram dose to 88% at the 1.0-mg-per-kilogram dose. Corresponding reductions in the LDL cholesterol level ranged from 9% at the 0.3-mg-per-kilogram dose to 62% at the 1.0-mg-per-kilogram dose, with an absolute reduction of 78 mg per deciliter at the highest dose. Reductions appeared to be durable throughout follow-up, which was at least 1 year in 15 participants. CONCLUSIONS: One dose of VERVE-102 led to dose-dependent, substantial, and sustained reductions in PCSK9 and LDL cholesterol levels. (Funded by Verve Therapeutics; ClinicalTrials.gov number, NCT06164730.).
N Engl J Med
· 2026 Jun · PMID 42160716
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Vaccine hesitancy exists along a spectrum; most parents with hesitancy are motivated to protect their children but are often concerned about safety. Routine childhood vaccines recommended by the American Academy of Pedia...Vaccine hesitancy exists along a spectrum; most parents with hesitancy are motivated to protect their children but are often concerned about safety. Routine childhood vaccines recommended by the American Academy of Pediatrics have substantially reduced the incidence of disease and maintain a strong safety record. Clinicians are the most trusted source of vaccine information, and clear, confident recommendations are closely linked to higher uptake. Presumptive communication approaches are more effective than open-ended approaches, especially when paired with respectful dialogue. Empathy-driven, patient-centered strategies, including motivational interviewing, help address concerns, counter misinformation, and build trust while preserving relationships that may encourage future vaccination decisions.