Castlebrook Clinical Trials Digest 2026-W15

Kuter et al. · N Engl J Med. 2026 Apr 9;394(14):1388-1398 · PMID 41950473 Why it matters: A Phase 2 double-blind RCT in NEJM evaluating mezagitamab — a novel anti-CD38 antibody targeting plasma cells and plasmablasts — in adults with persistent or chronic ITP refractory to standard therapy; this is the first controlled trial of an anti-CD38 approach in ITP and provides critical dose-finding and safety data for a potential new mechanism. Immune thrombocytopenia (ITP) is a disorder of increased platelet destruction and reduced platelet production and is associated with an increased bleeding risk and a compromised quality of life. Available therapies are ineffective in at least 20% of cases.

Lee et al. · N Engl J Med. 2026 Apr 9;394(14):1365-1375 · PMID 41910315 Why it matters: An open-label RCT in NEJM providing the first head-to-head randomized evidence comparing intensive LDL-C targeting (<55 mg/dL) versus conventional targeting (<70 mg/dL) for secondary prevention in ASCVD; results directly challenge current guideline conservatism and have immediate implications for lipid management strategy. Despite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited. In this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group).

<a name="cardiovascular"></a>

Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease Lee et al. · N Engl J Med. 2026 Apr 9;394(14):1365-1375 · PMID 41910315

Percutaneous coronary intervention versus coronary artery bypass grafting for unprotected left main stenosis: 10-year final results from the randomised, open-label, non-inferiority NOBLE trial · Lancet. 2026 · PMID 41936368

Electrical conditioning strategies in myocardial ischemia-reperfusion injury · Biomed Pharmacother. 2026 · PMID 41962230

Immune-endothelial crosstalk in cardiovascular inflammation: Canakinumab at the intersection of mechanism and precision therapy · Biomed Pharmacother. 2026 · PMID 41946303

Effects of diet-modulated gut microbiota and microbial metabolites in atherosclerosis · Biomed Pharmacother. 2026 · PMID 41946302

<a name="respiratory"></a>

All-Cause and Cause-Specific Mortality in Patients With Bipolar II Disorder · JAMA Netw Open. 2026 · PMID 41945344

<a name="endocrinology-metabolism"></a>

Airway management of adults in the acute care setting · BMJ. 2026 · PMID 41951238

<a name="neurology-stroke"></a>

Treatment for Brain Metastases With Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation: A Randomized Clinical Trial · JAMA. 2026 · PMID 41712219

Does This Patient Have Volume Overload?: The Rational Clinical Examination · JAMA. 2026 · PMID 41729549

Tenecteplase for Acute Non-Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke: The OPTION Randomized Clinical Trial · JAMA. 2026 · PMID 41642827

Risk Prediction Model for Taxane-Induced Peripheral Neuropathy in Early-Stage Cancer · JAMA Netw Open. 2026 · PMID 41961500

Focused ultrasound mediated gene therapy for glioblastoma: A preclinical in vivo systematic review and meta-analysis · Biomed Pharmacother. 2026 · PMID 41955864

<a name="infectious-diseases"></a>

Efficacy and safety of VPM1002 and Immuvac in preventing tuberculosis: phase 3 randomised clinical trial (PreVenTB trial) · BMJ. 2026 · PMID 41962942

Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial · N Engl J Med. 2026 · PMID 41950474

<a name="oncology"></a>

Setidegrasib in Advanced Non-Small-Cell Lung Cancer and Pancreatic Cancer · N Engl J Med. 2026 · PMID 41879829

Residential Radon Levels and Ovarian Cancer Among Postmenopausal Women · JAMA Netw Open. 2026 · PMID 41961496

Longitudinal Patterns of Symptoms in Patients Undergoing Chemotherapy: A Secondary Analysis of a Cluster Randomized Clinical Trial · JAMA Netw Open. 2026 · PMID 41941188

Total gastrectomy with splenectomy versus total gastrectomy with spleen preservation for gastric cancer · Cochrane Database Syst Rev. 2026 · PMID 41948983

Breast cancer and carotenoid- A comprehensive review of relationship insights, evidence, mechanisms, and future perspective · Biomed Pharmacother. 2026 · PMID 41955865

<a name="haematology"></a>

A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia Kuter et al. · N Engl J Med. 2026 Apr 9;394(14):1388-1398 · PMID 41950473

Pyruvate kinase activators in hereditary haemolytic anaemias: current evidence and clinical potential · Lancet. 2026 · PMID 41833294

<a name="gastroenterology-surgery"></a>

Non-drug perioperative interventions to reduce postoperative pulmonary complications after abdominal surgery: systematic review and meta-analysis · BMJ. 2026 · PMID 41956522

Celiac Disease · N Engl J Med. 2026 · PMID 41950475

High-Flow Nasal Oxygen Therapy After Cardiac Surgery: A Randomized Clinical Trial · JAMA Netw Open. 2026 · PMID 41949866

Penetrating versus non-penetrating mesh fixation in laparoscopic groin hernia repair · Cochrane Database Syst Rev. 2026 · PMID 41960697

<a name="musculoskeletal-orthopaedics"></a>

Antibiotic treatment for low back pain, radicular pain, or both · Cochrane Database Syst Rev. 2026 · PMID 41944232

<a name="trauma-emergency-medicine"></a>

Does This Child Have a Concussion?: The Rational Clinical Examination Systematic Review · JAMA. 2026 · PMID 41941197

Residential Therapy With Navigated Transcranial Magnetic Stimulation for Combat-Related PTSD: A Randomized Clinical Trial · JAMA Netw Open. 2026 · PMID 41945348

<a name="global-health"></a>

Multifaceted Strategies for Hypertension Control in Low-Income Patients · N Engl J Med. 2026 · PMID 41950472