Castlebrook Clinical Trials Digest

The two highest-impact studies this week.

Wilhelm F et al. · Lancet Infect Dis. 2026 Apr;26(4):e220-e230 · PMID 40934937 Why it matters: Lancet Infect Dis systematic review of autoantibody evidence in long COVID; advances mechanistic understanding of post-acute sequelae and identifies immunotherapy targets for a condition affecting millions. Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers.

Chosidow A et al. · Lancet Infect Dis. 2026 Apr;26(4):374-383 · PMID 41274297 Why it matters: ORIGAMI documents post-COVID resurgence of Mycoplasma pneumoniae in French children across both prospective and retrospective cohort arms; direct antimicrobial stewardship and diagnostic implications. Chikungunya outbreaks have recurred in Brazil since 2014. This multicentre cohort study reports the post-COVID resurgence of Mycoplasma pneumoniae infections in French children, with microbiological confirmation and clinical characterisation across multiple centres.

High-Frame-Rate Echocardiography: A New Frontier in Noninvasive Functional Assessment · J Clin Med, 2026 · PMID 41899383

Echocardiographic Assessment Before, During, and After Impella Positioning: State of the Art · J Clin Med, 2026 · PMID 41899330

Mechanical Complications After Acute Myocardial Infarction: A Shock-Stage and Timing-Based Management Framework · J Clin Med, 2026 · PMID 41899321

Clonal Hematopoiesis in Cardiovascular Risk: Focus on Inflammatory Mechanisms · J Clin Med, 2026 · PMID 41899316

Transcatheter Valve Replacement for Mitral Stenosis: A State of the Art Review · J Clin Med, 2026 · PMID 41899297

Assessment of Right Ventricular Adaptability to Pressure Overloading for Critical Therapeutic Decision-Making Processes · J Clin Med, 2026 · PMID 41899292

Echocardiographic Assessment of Right Ventricular-Pulmonary Arterial Coupling in Heart Failure: Prognostic Insights from a Systematic Review · J Clin Med, 2026 · PMID 41899258

Revisiting the Genetics of Hypertrophic Cardiomyopathy: From Sarcomeres to Polygenic Modulation and Clinical Translation · J Clin Med, 2026 · PMID 41899251

Optimal Antithrombotic Regimens Across Atherosclerotic Vascular Beds: Toward Mechanism and Risk-Oriented Strategies · J Clin Med, 2026 · PMID 41899248

Lifetime Management of Aortic Stenosis: Evolving Strategies and Personalized Decision-Making · J Clin Med, 2026 · PMID 41899193

SGLT2 Inhibitors After Myocardial Infarction: Evidence, Mechanisms and Gaps in Knowledge · J Clin Med, 2026 · PMID 41899183

Cardiovascular Consequences of E-Cigarettes: A New Challenge for Cardiologists · J Clin Med, 2026 · PMID 41899150

Evidence on SGLT2 Inhibitors' Efficacy in Older and Frail Patients · J Clin Med, 2026 · PMID 41899142

Existing and Potential Therapeutic Strategies for Lowering Lipoprotein(a) Levels: An Update · J Clin Med, 2026 · PMID 41899103

Hemodynamic Changes During Cesarean Section Under Spinal Anesthesia in Normotensive and Hypertensive Pregnant Women-A Narrative Review · J Clin Med, 2026 · PMID 41899085

Out-of-Hospital Cardiac Arrest: Public-Access Defibrillation and System Approaches to Minimize Avoidable Delay · J Clin Med, 2026 · PMID 41899066

Continuous vs Intermittent Postoperative Vital Sign Monitoring: A Cluster Randomized Crossover Trial · JAMA Netw Open, 2026 · PMID 41885865

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis at 10 Years · N Engl J Med, 2026 · PMID 41880613

A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide · N Engl J Med, 2026 · PMID 41879224

The Inherited Basis of Coronary Artery Disease · N Engl J Med, 2026 · PMID 41870454

Lysophosphatidylcholine as a mechanistic and therapeutic nexus in atherosclerotic cardiovascular disease · Biomed Pharmacother, 2026 · PMID 41780255

Beta-Blockers after Myocardial Infarction with Normal Ejection Fraction · N Engl J Med, 2026 · PMID 41211954

Oncofertility in Women with Renal Cell Carcinoma in the Immune Checkpoint Inhibitors Era: A Multidisciplinary Perspective · J Clin Med, 2026 · PMID 41899374

The Current Landscape of Artificial Intelligence in Positron Emission Tomography (PET) Imaging Across the Cancer Continuum · J Clin Med, 2026 · PMID 41899368

Molecular Targeting of EGFR, BRAF, and HER2 Signaling in Colorectal Cancer: Contemporary Advances with Panitumumab, Encorafenib, and Tucatinib · J Clin Med, 2026 · PMID 41899309

Radiation-Induced Meningiomas: Systematic Review with Pooled Case Analysis and Case Series of Long Latency, Aggressive Behavior, and Clinical Outcomes · J Clin Med, 2026 · PMID 41899280

Overcoming Chemotherapy Resistance in Triple-Negative Breast Cancer with Nanocarrier-Delivered siRNA Therapeutics · J Clin Med, 2026 · PMID 41899235

Evaluating the Efficacy and Safety of TACE Combined with Iodine-125 Brachytherapy Versus TACE Monotherapy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899191

Chemotherapy for Older Adults with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899178

Expression of Molecular Markers Associated with Tenosynovial Giant Cell Tumours and Bone Destruction: A Systematic Review · J Clin Med, 2026 · PMID 41899159

Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies · J Clin Med, 2026 · PMID 41899095

Clinical, Dermatoscopic, Histological and Molecular Prognostic and Predictive Factors of Metastatic Melanoma Response to Immunotherapy: A Systematic Review and Drug Class Meta-Analysis · J Clin Med, 2026 · PMID 41899070

Beyond Visual Inspection: A Systematic Review of Adjunctive Aids for the Early Detection of Oral Squamous Cell Carcinoma · J Clin Med, 2026 · PMID 41899069

Open Anterolateral Cordotomy for Cancer Pain: Indication, Efficacy, and Safety: A Systematic Literature Review · J Clin Med, 2026 · PMID 41899036

The trophoblastic theory of cancer: Progesterone-dependent immune tolerance and modulation by synthetic and natural antagonists · Biomed Pharmacother, 2026 · PMID 41895062

Long-Term Outcomes of Concurrent Chemoradiotherapy With S-1 in Older Patients With Esophageal Cancer: A Secondary Analysis of a Randomized Clinical Trial · JAMA Netw Open, 2026 · PMID 41893843

Atezolizumab plus FOLFOX for Stage III Mismatch Repair-Deficient Colon Cancer · N Engl J Med, 2026 · PMID 41880612

Five tenets for advancing evidence-based precision medicine · Nat Med, 2026 · PMID 41872601

Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer · N Engl J Med, 2026 · PMID 41160818

Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer · N Engl J Med, 2026 · PMID 41124201

Safety and Efficacy of Octyl 2-Cyanoacrylate (Dermabond) in Breast Surgery: A Systematic Review · J Clin Med, 2026 · PMID 41899385

Reporting Standards and Quality Assurance Methods for Pancreatoduodenectomy in Randomised Controlled Trials: A Structured Narrative Review · J Clin Med, 2026 · PMID 41899376

Restoration of Muscle Function Following Distal Biceps Tendon Reinsertion: A Narrative Review · J Clin Med, 2026 · PMID 41899352

Western University Protocol for Obstructive Sleep Apnea · J Clin Med, 2026 · PMID 41899308

Prognostic Impact and Postoperative Management Following Poor Pathological Response to Perioperative FLOT in Resectable Gastric and GEJ Adenocarcinoma: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899291

Interventional Endoscopy for the Management of Post-Surgical Leaks and Fistulas: A Scoping Review · J Clin Med, 2026 · PMID 41899214

Surgical Necrotising Enterocolitis (S-NEC): Where We Stand Today: A Narrative Review · J Clin Med, 2026 · PMID 41899162

Myocardial Injury After Non-Cardiac Surgery in Otolaryngology: Evidence Gaps and a Systematic Review · J Clin Med, 2026 · PMID 41899110

Can Intraoperative Anesthesiological Management Reduce the Risk of Acute Kidney Injury After Liver Transplantation? A Systematic Review · J Clin Med, 2026 · PMID 41899104

Artificial Intelligence in Esophagectomy: A Systematic Review · J Clin Med, 2026 · PMID 41899094

The Development of Spinal Deformity in Patients with Duchenne Muscular Dystrophy: Clinical Assessment, Surgical Considerations and Recommendations for Treatment · J Clin Med, 2026 · PMID 41899042

From Biomaterial Innovation to Surgical Practice: A Systematic Review of RADA16 Self-Assembling Peptide Hydrogel in Otolaryngology and Head & Neck Surgery · J Clin Med, 2026 · PMID 41899038

Feeding Bottles With Different Venting Methods and Gastrointestinal Discomfort in Infants: A Randomized Clinical Trial · JAMA Netw Open, 2026 · PMID 41885859

An oral allopregnanolone prodrug bypasses liver metabolism via lymphatic transport enabling bioavailability in animals and humans · Sci Transl Med, 2026 · PMID 41880520

Primary sclerosing cholangitis · Lancet, 2026 · PMID 41871593

The Effects of Helicobacter pylori on the Treatment Outcomes of Peptic Ulcer in Patients with Liver Cirrhosis: A Systematic Review and Network Meta-Analysis · J Clin Med, 2026 · PMID 41899206

Sulbactam-Durlobactam in the Treatment of Bloodstream Infection Due to Carbapenem-Resistant Acinetobacter baumannii: A Case Series and Literature Review · J Clin Med, 2026 · PMID 41899205

Methodological quality assessment tool for observational studies comparing treatment effectiveness in infectious diseases: a Delphi consensus and application to studies on bloodstream infections due to carbapenem-resistant Enterobacterales · Lancet Infect Dis, 2026 · PMID 41887234

Umbilical cord antiseptics for preventing sepsis and death among newborns · Cochrane Database Syst Rev, 2026 · PMID 41881430

Prevention of Recurrent Nephrolithiasis in Adults and Children : A Systematic Review · Ann Intern Med, 2026 · PMID 41871357

Lipidomic insights into infectious meningitis: Pathogen-specific alterations and therapeutic implications · Biomed Pharmacother, 2026 · PMID 41865629

Macrophage extracellular traps in autoimmunity: In vivo definition, pathogenic circuits, and therapeutic targeting · Biomed Pharmacother, 2026 · PMID 41780256

Dengue Suppression by Male Wolbachia-Infected Mosquitoes · N Engl J Med, 2026 · PMID 41671481

Antibiotic Therapy for Uncomplicated Acute Appendicitis: Ten-Year Follow-Up of the APPAC Randomized Clinical Trial · JAMA, 2026 · PMID 41563747

Safety and immunogenicity of a live-attenuated chikungunya virus vaccine in adolescents: final results from a 12-month, double-blind, randomised, placebo-controlled, phase 3 trial in endemic areas of Brazil · Lancet Infect Dis, 2026 · PMID 41380703

Post-COVID-19 resurgence of Mycoplasma pneumoniae infections in French children (ORIGAMI): a retrospective and prospective multicentre cohort study Chosidow A et al. · Lancet Infect Dis. 2026 Apr;26(4):374-383 · PMID 41274297 Author information: (1)Department of General Paediatrics, Centre Hospitalier Intercommunal de Villeneuve-Saint-Georges, Villeneuve-Saint-Georges, France; GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France. Electronic address: [email protected]. (2)Department of General Paediatrics, Hôpital Clocheville, Tours, France; GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.

Core outcome measurement set for clinical trials in dengue: an international Delphi consensus study (DEN-CORE) · Lancet Infect Dis, 2026 · PMID 41072450

Autoantibodies in long COVID: a systematic review Wilhelm F et al. · Lancet Infect Dis. 2026 Apr;26(4):e220-e230 · PMID 40934937 Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers.

Constraint-Induced Movement Therapy in the Rehabilitation of Adults After Stroke: An Umbrella Review · J Clin Med, 2026 · PMID 41899381

Non-Invasive Radiofrequency Therapy for Musculoskeletal, Neurological, and Vascular Conditions of the Lower Limb: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899351

Imaging-Based Diagnostic Approaches in Moyamoya Disease: A Scoping Review · J Clin Med, 2026 · PMID 41899333

Managing Osteoarthritis Pain in Underrepresented Populations: Insights from Mexico and Latin America · J Clin Med, 2026 · PMID 41899318

Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets · J Clin Med, 2026 · PMID 41899281

Standardizing Periocular Surface Electromyography: A Scoping Review of Methods and Emerging Applications · J Clin Med, 2026 · PMID 41899180

Cone Beam Computed Tomography (CBCT) Prevalence and Morphometry of Foramen Vesalius: A Systematic Review, Meta-Analysis, and Update of the Literature · J Clin Med, 2026 · PMID 41899119

Racial and Ethnic Reporting and Representation in US Alzheimer Clinical Trials: A Systematic Review · JAMA Netw Open, 2026 · PMID 41893846

Advances in the pathophysiology and treatment of diabetic peripheral neuropathy · BMJ, 2026 · PMID 41887652

Home based, tailored intervention to reduce rate of falls after stroke (FAST): randomised trial · BMJ, 2026 · PMID 41876122

Therapeutic antagonism of a key toxin driving Alzheimer's disease: Comparison of a peptide variant and small molecule · Biomed Pharmacother, 2026 · PMID 41780257

A Pharmacovigilance Analysis of Ocular Adverse Events Associated with GLP-1 Receptor Agonists · J Clin Med, 2026 · PMID 41899386

The Cardiovascular Burden of Diabetes: Risk Factors, Clinical Phenotypes, and Personalized Cardiometabolic Management · J Clin Med, 2026 · PMID 41899282

Combined Role of Spirulina and Exercise-Based Interventions in Individuals with Overweight and Obesity: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899062

SGLT2 Inhibitors as a Novel Therapeutic Strategy in SIADH-Induced Hyponatraemia: Emerging Evidence and Clinical Implications · J Clin Med, 2026 · PMID 41899044

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials · JAMA Netw Open, 2026 · PMID 41885866

Beyond bystanders: How β cell stress shapes the autoimmune response in T1D · Sci Transl Med, 2026 · PMID 41880519

Injectable thermosensitive hydrogel-based sustained delivery system for anti-diabetic peptides in type 2 diabetes mellitus therapy: A review · Biomed Pharmacother, 2026 · PMID 41875502

Type 1 Diabetes: A Review · JAMA, 2026 · PMID 41697686

Artificial Intelligence in Asthma and COPD: Current Status and Future Potential · J Clin Med, 2026 · PMID 41899367

The Role of CEUS in the Diagnosis and Follow-Up of Pleuropulmonary Diseases and Interventional Procedures · J Clin Med, 2026 · PMID 41899217

Growth-Based Decision-Making in Congenital Scoliosis with Multiple Vertebral Anomalies · J Clin Med, 2026 · PMID 41899122

Nerandomilast in Autoimmune-Associated Interstitial Lung Diseases: Translating Evidence from Progressive Pulmonary Fibrosis Studies · J Clin Med, 2026 · PMID 41899090

Liberation from Non-Invasive Ventilation in Complex Intensive Care Unit Patients · J Clin Med, 2026 · PMID 41899073

Clinical Outcomes with the Use of Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Among Patients with Diabetes Mellitus and COVID-19: A Systematic Review of Observational Studies · J Clin Med, 2026 · PMID 41899041

Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial · JAMA, 2026 · PMID 41569557

Machine Learning Models for Predicting Bleeding Risk in Anticoagulated Patients with Atrial Fibrillation and Venous Thromboembolism: A Comparative Evidence Synthesis · J Clin Med, 2026 · PMID 41899294

Safety-First Framework for AI-Enabled Anamnesis in Head and Neck Surgery: Evidence Synthesis from a Narrative Review · J Clin Med, 2026 · PMID 41899141

Artificial Intelligence Applications in Gastric Cancer Surgery: Bridging Early Diagnosis and Responsible Precision Medicine · J Clin Med, 2026 · PMID 41899133

Deep Vein Thrombosis Prevention in Acute Ischemic Stroke Patients with Lower Limb Paralysis: A Narrative Review · J Clin Med, 2026 · PMID 41899016

Large Language Models Using Clinical Text in Pediatrics: A Scoping Review · JAMA Netw Open, 2026 · PMID 41879783

Medical Treatment for Endometriosis: One Size Does Not Fit All · J Clin Med, 2026 · PMID 41899332

Fascial Plane Blocks for Analgesia in Non-Operating Room Anesthesia Settings · J Clin Med, 2026 · PMID 41899068

Brief Prescribing Support and Buprenorphine Adoption in Rural Primary Care: A Cluster Randomized Clinical Trial · JAMA Netw Open, 2026 · PMID 41879782

Methadone Dose and Patient-Directed Discharge in Hospitalized Patients With Opioid Use Disorder · JAMA Netw Open, 2026 · PMID 41879780

The Limited Evidence Base for Multilevel Lumbar Interbody Fusion and Its Consequences for Clinical Conclusions: A Systematic Review · J Clin Med, 2026 · PMID 41899212

A Narrative Review of Spinopelvic Alignment Changes After Total Hip Arthroplasty · J Clin Med, 2026 · PMID 41899152

Who Is the Surgeon Now: Human Hands or Machine Minds? Artificial Intelligence in Orthopedics from Diagnosis to Follow-Up-A Structured Narrative Review · J Clin Med, 2026 · PMID 41899089

Radiation Exposure in Robotic-Assisted Versus Conventional and Navigation-Assisted Spine Surgery: A Systematic Review, Meta-Analysis, and Meta-Regression of 3205 Patients · J Clin Med, 2026 · PMID 41899071

Parental Acceptance of Passive Protective Stabilization During Pulp Therapy in Primary and Young Permanent Dentition: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899127

Pattern of Oculomotor Findings in Children with Attention Deficit/Hyperactivity Disorder in Relation to Methylphenidate Treatment · J Clin Med, 2026 · PMID 41899034

Clinical Implications of Minipuberty · N Engl J Med, 2026 · PMID 41880614

Paediatric case of invasive group A streptococcal necrotising myositis: diagnostic challenges and lessons learned · Lancet Infect Dis, 2026 · PMID 40819649

Celocentesis: Current Evidence and Future Directions · J Clin Med, 2026 · PMID 41899120

The Role of Hysteroscopy for the Treatment of Interstitial Ectopic Pregnancy: A Systematic Review · J Clin Med, 2026 · PMID 41899081

Hemophilia's Overlooked Female Face · J Clin Med, 2026 · PMID 41899079

Association Between Maternal C-Reactive Protein (CRP) Levels and Adverse Neonatal Outcomes: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899039

Setting research priorities to understand and address the impact of climate change on the health of women and children in low-income and middle-income countries using the Child Health and Nutrition Research Initiative method · Lancet Glob Health, 2026 · PMID 41903554

Comparison of the performance and costs of testing algorithms using rapid diagnostic tests for detection and treatment of syphilis among pregnant individuals and men who have sex with men: a modelling study · Lancet Infect Dis, 2026 · PMID 41285141

Breaking the under-reporting cycle for zoonotic diseases in low-income and middle-income countries through national-level integration of community-based surveillance and response: insights from Cameroon, Chad, Côte d'Ivoire, and Mali · Lancet Infect Dis, 2026 · PMID 40975107

Artificial Intelligence in the Diagnosis of Odontogenous Cysts and Ameloblastomas-A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899372

Oral nutritional interventions in hospitalised older people at nutritional risk: a network meta-analysis of individual participant data · Cochrane Database Syst Rev, 2026 · PMID 41886673

Slow-Release Oral Morphine vs Methadone for Opioid Use Disorder in the Fentanyl Era · JAMA Netw Open, 2026 · PMID 41874507

Alternate and Emerging Anticoagulation Strategies for Extracorporeal Membrane Oxygenation: A Scoping Review · J Clin Med, 2026 · PMID 41899262

Navigating the Hemostatic Balance: Anticoagulation and Antiplatelet Therapy in Patients with Thrombocytopenia · J Clin Med, 2026 · PMID 41899195

Non-clotting factor therapies for preventing bleeds in people with congenital hemophilia A or B · Cochrane Database Syst Rev, 2026 · PMID 41873813

Ocular Color Doppler Ultrasound (OCDUS) in Diagnosis and Monitoring of Ophthalmological, Cerebrovascular and Systemic Diseases: A Narrative Review · J Clin Med, 2026 · PMID 41899384

Anterior Segment Optical Coherence Tomography with Angiography for the Cornea and Ocular Surface · J Clin Med, 2026 · PMID 41899324

E-Scooter-Associated Injury Types and Injury Severity: A Systematic Review and Meta-Analysis · J Clin Med, 2026 · PMID 41899078

Enhanced Weight Management Program for Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial · JAMA Netw Open, 2026 · PMID 41893847

The Effects of Periodontal Treatment on Psoriasis: A Systematic Review of Limited Clinical and Preclinical Evidence · J Clin Med, 2026 · PMID 41899357

Impact of Gender-Affirming Surgery on Psychiatric Outcomes and Quality of Life in Transgender Individuals: A Systematic Review of Longitudinal Cohort Studies · J Clin Med, 2026 · PMID 41899136

Transcutaneous Electrical Nerve Stimulation and Pain With Movement in People With Fibromyalgia: A Cluster Randomized Clinical Trial · JAMA Netw Open, 2026 · PMID 41893844

Prednisolone Once Daily vs Hydrocortisone Thrice Daily in Hypoadrenalism: A Randomized Clinical Trial · JAMA Netw Open, 2026 · PMID 41874506

Prime Editing for p47(phox)-Deficient Chronic Granulomatous Disease · N Engl J Med, 2026 · PMID 41358590

Prescription Drug Promotion by Social Media Influencers: A Systematic Scoping Review · JAMA Netw Open, 2026 · PMID 41870429

AAV9 Gene Therapy in Type II GM1 Gangliosidosis - A Phase 1-2 Trial · N Engl J Med, 2026 · PMID 41665410

Electronic Health Record Intervention and Deprescribing for Older Adults: A Randomized Clinical Trial · JAMA, 2026 · PMID 41609788