Replication FailureOpen accessMedicine
Fahimeh Varzideh, Pasquale Mone, Urna Kansakar et al. · 2026 · Nutrients
Vitamin D, a fat-soluble secosteroid traditionally recognized for skeletal health, exerts pleiotropic effects on cardiovascular physiology and disease. Circulating 25-hydroxyvitamin D [25(OH)D], the principal biomarker of vitamin D status, is frequently suboptimal worldwide, particularly in older adults, individuals with darker skin pigmentation, and populations at higher latitudes. Observational studies consistently associate low 25(OH)D concentrations with increased risk of hypertension, atherosclerosis, myocardial infarction, heart failure, arrhythmias, stroke, and cardiovascular mortality.
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Y Sakr, Axel Nierhaus, Ulrike Schumacher et al. · 2026 · JAMA Network Open
Importance: Albumin supplementation may reduce mortality in patients with septic shock; however, data from randomized clinical trials are limited. Objective: To assess the impact of albumin administration on outcomes in patients with septic shock. Design, Setting, and Participants: This multicenter, open-label randomized clinical trial was conducted between October 21, 2019, and May 2, 2022. Patients from 23 intensive care units in Germany enrolled within 24 hours of the onset of septic shock were followed up for outcome data up to 90 days. The statistical trial report was completed and filed
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Christopher C. Butler, Andrew Pinto, Victoria Harris et al. · 2026 · New England Journal of Medicine
BACKGROUND: Nirmatrelvir-ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir-ritonavir in persons who have been vaccinated, infected naturally, or both is unclear. METHODS: In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (≥50 years of age or ≥18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 day
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Junren Chen, Siqi Qin, Ziwei Xing et al. · 2026 · Cellular & Molecular Biology Letters
BACKGROUND: Diabetic wounds are a debilitating complication of diabetes mellitus with a high rate of amputation and mortality. 6-Hydroxyhyoscyamine hydrobromide (6-HH) is a belladonna alkaloid with smooth-muscle-relaxing and…
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Sara A. Hurvitz, Rachel M. Layman, Giuseppe Curigliano et al. · 2026 · Journal of Clinical Oncology
PURPOSE Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant.…
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Ambrose Agweyu, Paul Mwaniki, Vaishnavi Menon et al. · 2026 · Nature Medicine
Rigorous evidence on the performance of large language models (LLMs) in real-world, low-resource clinical settings remains limited. Here we conducted a pragmatic, cluster-randomized trial in 16 primary care facilities in Kenya. Clinical officers were randomized to use the electronic medical record with or without LLM assistance. The primary outcome was an expert-adjudicated composite of treatment failure events experienced within 14 days of enrollment. Between 22 April and 16 July 2025, 9,691 patients were enrolled, overseen by 103 clinical officers (52 in the LLM-assisted arm and 51 in the co
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Wungki Park, Catherine O’Connor, Joanne F. Chou et al. · 2026 · Nature Medicine
Homologous recombination deficiency (HRD) arising from BRCA1or BRCA2 or PALB2 mutations confers sensitivity to platinum chemotherapy and PARP inhibition in pancreatic cancer (PC) and may enable prolonged disease control with immune checkpoint blockade (ICB). The phase 2 POLAR trial evaluated maintenance pembrolizumab plus olaparib following platinum-based chemotherapy in biomarker-stratified metastatic PC. Sixty-three participants were enrolled into three cohorts: cohort A (BRCA1/BRCA2-mutated or PALB2-mutated HRD, n = 33), cohort B (non-core HRD, n = 15) and cohort C (platinum sensitive, HRD-
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Lizl Veldsman, GA Richards, D. G. Nel et al. · 2025 · Journal of Parenteral and Enteral Nutrition
BACKGROUND: Muscle wasting is a hallmark of critical illness. We evaluated the effect of amino acid supplementation and mobilization on early muscle loss in critically ill patients. METHODS: We conducted a randomized parallel-group trial…
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Nicholas A. Marston, Erin A. Bohula, Ajay Bhatia et al. · 2026 · JAMA
Importance: Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with…
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Mette Kruse Klausen, Signe Justesen, Julie Niemann Pedersen et al. · 2026 · The Lancet
BACKGROUND: Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity. METHODS: In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were ass
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Jennifer Duffecy, Arfa Rehman, Scott Gorman et al. · 2025 · JMIR mhealth and uhealth
Unlabelled: Background: Perimenopausal and menopausal symptoms affect many women's well-being and quality of life. Digital technologies, especially smartphones, allow self-management interventions for menopausal symptoms, but they are understudied., Objective: We evaluated whether a novel digital care app, Caria, effectively reduced vasomotor and behavioral health symptoms of menopause., Methods: We enrolled 149 women for a 6-week randomized controlled trial (app treatment: n=112; web-based educational control: n=37). Enrolled participants had problematic vasomotor symptoms and at least one el
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Robert W. Lentz, Tyler J. Friedrich, Patrick J. Blatchford et al. · 2024 · Clinical Cancer Research
PURPOSE: In this single-institution phase II investigator-initiated study, we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite-stable metastatic colorectal cancer (MSS mCRC).…
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Jason Smith, Rebecca Cardigan, Emily Sanderson et al. · 2026 · New England Journal of Medicine
BACKGROUND: Whole-blood transfusion has recently gained favor in the management of severe hemorrhage; however, data from large clinical trials evaluating its clinical effectiveness and safety are lacking. METHODS: We conducted a pragmatic,…
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Noor Wortelboer, Annemiek van Ommen-Nijhof, Inge R. Konings et al. · 2026 · JAMA Oncology
Importance: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy are widely used in hormone receptor (HR)-positive, ERBB2-negative advanced breast cancer (ABC). The SONIA trial evaluates the optimal…
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Mihir A Kelshiker, Patrik Bächtiger, Camille F Petri et al. · 2026 · The Lancet
BACKGROUND: Early detection of cardiovascular disease is a global public health priority. Artificial intelligence (AI)-enabled stethoscopes offer robust performance characteristics in point-of-care detection of heart failure, atrial fibrillation, and valvular heart disease (VHD). We conducted a pragmatic, cluster-randomised controlled implementation trial to determine the real-world effect and implementation challenges of AI-stethoscopes. METHODS: UK primary care practices were cluster randomised 1:1 to intervention (training and implementation in use of AI-stethoscopes in routine care) or con
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Chloe Stanley, Ritwika Mallik, Nausheen Hamid et al. · 2026 · Nature Medicine
A suboptimal clinical response after metabolic and bariatric surgery (MBS) is common and carries considerable health concerns. Here a double-blinded, randomized (1:1), placebo-controlled trial using semaglutide 2.4 mg weekly (BARI-STEP) recruited adult participants at least 1 year after gastric bypass or sleeve gastrectomy with a suboptimal clinical response, defined as less than 20% weight loss from surgery. This was an adjunct to lifestyle intervention with a 500-kcal daily energy deficit. The primary outcome was percentage weight loss after 68-week treatment on an intention-to-treat analysi
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Yang L, Zhuang H, Yang Z et al. · 2026 · Medical ultrasonography
Aims To evaluate the applicability of transluminal dual-plane shear wave elastography (SWE) for measuring the anal sphincter in healthy adult women. Material and methods This prospective study recruited 140 healthy women between January…
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Silva SJ, Romero F, Magder LS et al. · 2026 · Academic medicine : journal of the Association of American Medical Colleges
Purpose Interest in research careers among medical graduates is decreasing, and fewer physicians report research as their primary work activity. This study examines the implementation of a required scholarly research course at the…
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Van Brussel L, Geurden T · 2026 · Ticks and tick-borne diseases
Background Rapid and high efficacy against ticks after attachment has the potential to aid in the prevention of tick-borne pathogen transmission. The objective of the study was to assess the speed-of-kill of Simparica Trio® against Ixodes…
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Dong B, Xian Z · 2026 · Journal of visualized experiments : JoVE
Adolescent bipolar disorder is a severe psychiatric condition frequently complicated by school refusal behavior, a debilitating functional impairment that often persists even after the pharmacological stabilization of mood symptoms. While…
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Özdemir HE, Albayrak MT, Koçluk Y · 2026 · Journal of clinical medicine
Purpose : To investigate whether the season in which photorefractive keratectomy (PRK) with mitomycin C (MMC) is performed influences postoperative corneal transparency considering seasonal variations in ultraviolet (UV) exposure. Methods…
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Minkhorst K, Munn A, MacDermid J et al. · 2025 · Archives of physical medicine and rehabilitation
Objective To evaluate whether the addition of an orthosis improved the efficacy of cortisone injection for the nonoperative management of trigger finger. Design Block randomized controlled trial. Setting Outpatient hand clinic.…
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Sadeghpour M, Laughter M, Rizzo SI et al. · 2026 · Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]
Background Despite evidence supporting efficacy of low-fluence Q-switched (QS) neodymium-doped yttrium aluminum garnet (Nd:YAG) 1,064-nm lasers, treatment protocols are not standardized and limited to mostly retrospective, observational,…
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Arenas Hoyos J, Dalela D, Schlomer BJ et al. · 2026 · Journal of pediatric urology
Background There is insufficient evidence to support the effectiveness of preoperative antibiotic prophylaxis in reducing surgical site infections (SSI) during urgent testicular torsion (TT) surgeries. Objective The primary objective was…
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Wang J, Du L, Wang Y et al. · 2026 · Cellular oncology (Dordrecht, Netherlands)
Purpose Combinations of anti-PD-1/PD-L1 immunotherapy (IO) and anti-VEGF tyrosine kinase inhibitor (TKI) are recommended as first-line therapy for metastatic renal cell carcinoma (RCC). We aimed to evaluate the predictive value of tissue…
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Lin MC, Jiang X, Qiu ZC et al. · 2026 · Head & neck
Background Management of the clinically node-negative (cN0) neck in intermediate-grade mucoepidermoid carcinoma (MEC) of the head and neck remains controversial. Methods We retrospectively reviewed patients with cN0 intermediate-grade MEC…
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Baxi SM, Igbinosa II, Main EK et al. · 2026 · AJOG global reports
Background Postpartum hemorrhage (PPH) is the leading global cause of maternal morbidity and mortality. Tranexamic acid (TXA), an antifibrinolytic agent that has been shown to reduce hemorrhage-related mortality in trauma, is used…
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Wang C, Li S, Lu H et al. · 2026 · BMC gastroenterology
Background While routine use of abdominal drainage in cases of perforated appendicitis is not generally recommended, there exists a paucity of evidence regarding the detailed stratification of its necessity based on varying degrees of…
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Vukšić J, Kustić D · 2026 · Rheumatology international
To examine whether salivary gland ultrasonography (SGUS) and scintigraphy (SGS) reflect systemic disease activity (ESSDAI) and patient-reported index (ESSPRI) in primary Sjögren's disease (PSD). We retrospectively enrolled 118 patients…
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Can V, Polat F, Kaya AF et al. · 2026 · Journal of cardiovascular pharmacology
Abstract Mechanical heart valve replacement necessitates long-term warfarin anticoagulation to prevent thromboembolic complications, yet achieving adequate anticoagulation control remains challenging. This study evaluated whether mean…
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