Citations

Abstract In response to a Cochrane review (published in April 2026) on the clinical trials of monoclonal antibodies targeting beta amyloid, this perspective outlines a number of critiques. The scientists, methodologists, subject‐matter experts, and clinicians on this perspective strongly recommend that the Cochrane editorial board consider a call for editorial response, correction of press materials, or commissioned reply to this review for four overarching reasons: (1) decision to pool antibodies that do and do not clear beta amyloid, (2) decision to include studies from a time when biomarkers of Alzheimer's disease were not available, (3) analytical and methodological limitations of the approach used, (4) conflating the distinct roles and methodological processes of systematic review and guideline methodologies, (5) contextualizing the present critique within the existing evidence‐synthesis literature, and (6) mechanistic inference beyond the scope of the presented analyses. Conclusions that may not accurately reflect treatment‐specific effects could cause significant downstream clinical and psychosocial harm to those currently undergoing treatment and their family members as well as individuals considering participation in Alzheimer's clinical trials.

Abstract Inflammatory bowel diseases (IBD), principally Crohn’s disease (CD) and ulcerative colitis (UC), are common chronic disorders involving inflammation and often progressive tissue damage. Genome-wide association studies have mapped many risk signals, but the causal variants, effector genes and relevant cellular contexts remain difficult to resolve, limiting mechanistic interpretation and therapeutic translation. Here we performed a multi-ancestry GWAS meta-analysis of 125,992 individuals with IBD and more than 1.2 million controls, identifying 619 independent association signals (374 novel) at 420 IBD regions that account for 77–80% of SNP-based heritability. Fine-mapping resolved 81 high-confidence variants, 41 not previously reported. Although most signals were shared between CD and UC, 39% showed IBD subtype specificity, with UC signals showing stronger enrichment in functional annotations from intestinal epithelial, secretory and enteroendocrine cells, and CD showing stronger genetic correlations with circulating inflammatory biomarkers, including C-reactive protein and glycoprotein acetylation. Latent causal modelling supported a causal effect of decreased high-density lipoprotein on CD risk. By integrating bulk and single-cell eQTL and pQTL resources using colocalisation and Mendelian randomisation, together with coding-variant evidence from exome sequencing, we prioritised 664 candidate effector genes across 341 signals, including 390 newly implicated IBD genes, revealing new biological mechanisms and candidate therapeutic targets supported by human genetics.

Abstract Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract whose genetic basis is only partly resolved because most risk variants identified by genome-wide association studies (GWAS) lie in non-coding regions, limiting direct gene assignment and biological interpretation 1,2 . Here we analysed whole-exome and whole-genome sequencing data from 86,213 IBD cases and 478,363 controls of European ancestry. We identified 68 IBD genes directly implicated by conditionally independent protein-coding associations across the allele frequency spectrum. Many newly implicated IBD genes are supported by orthogonal genomic or pleiotropic evidence, pointing to disease-related pathways and nominating targets with therapeutic relevance. We further identified allelic series and non-additive effects at key loci such as NOD2 and TYK2. These results show that large-scale sequencing can resolve disease genes and pathways that remain ambiguous from non-coding association alone, providing a more direct route from human genetics to biological insight and therapeutic hypotheses.

Abstract Aims This systematic review evaluated the impact of metabolic and bariatric surgery (MBS) on weight loss, glycaemic control, insulin requirements and postoperative complications. Methods A PRISMA‐compliant, PROSPERO‐registered systematic review and meta‐analysis (CRD42025123500) was conducted. Medline, PubMed, Embase, Scopus and CENTRAL were searched. Primary outcomes were changes in body weight, BMI, HbA1c and insulin requirements following MBS. Risk of bias was assessed using ROBINS‐I and RoB‐2, and certainty of evidence using GRADE. Results Twenty‐two studies, including 1324 adults with type 1 diabetes mellitus (mean age 42.2 ± 11.6 years; mean follow‐up 31.6 ± 18.2 months), were analysed. Of 753 participants with reported sex, 74.6% were women ( n = 562). A total of 1304 procedures were performed, most commonly Roux‐en‐Y gastric bypass (44.5%; n = 580) and sleeve gastrectomy (39.2%; n = 512), followed by adjustable gastric banding (13.0%; n = 170). Meta‐analysis demonstrated significant reductions in body weight (mean difference 29.55 kg; 95% CI 25.72 to 33.39; I 2 = 20%) and BMI (11.35 kg/m 2 ; 95% CI 10.36 to 12.34; I 2 = 32%). HbA1c decreased by 4 mmol/mol (95% CI 2.05 to 6.78; I 2 = 19%), and insulin requirements declined by 43%–48% (0.20 U/kg; 95% CI 0.13 to 0.26; I 2 = 58%). Postoperative complications included diabetic ketoacidosis (15/182, 8%) and severe hypoglycaemia (21/516, 4%); any complication occurred in 21/495 (4%). Evidence quality was low. Conclusion MBS achieves weight loss and reduces insulin requirements in adults with type 1 diabetes mellitus and obesity, but glycaemic improvements are minimal. Given the observational evidence base and inconsistent safety reporting, true metabolic risk remains uncertain. High‐quality prospective studies with standardised outcome definitions are needed.

Rationale: Neuromuscular blocking agents (NMBAs) show potential benefits on mortality and other complications of acute respiratory distress syndrome (ARDS) in adult patients. Evidence-based decisions and processes ensure appropriate use of neuromuscular blockade in adult patients with ARDS. Objectives: The objective of these guidelines was to develop evidence-based recommendations for the administration of NMBAs in critically ill adult patients with ARDS. Design: The American College of Critical Care Medicine Board convened a 21-member multidisciplinary panel of experts in critical care medicine, nursing, respiratory therapy, pharmacology, surgery, neurology, and anesthesiology. The panel included two expert methodologists specialized in developing evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guidelines development including task force selection and voting. Methods: The panel members identified and formulated five Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and assessed the certainty of the evidence using the GRADE methodology. We used the GRADE evidence-to-decision framework to formulate the recommendations. Results: The panel generated two conditional recommendations. One recommendation is to use NMBAs in adults with ARDS with Pa o 2 /F io 2 less than 150. For the other recommendations, there was equipoise in the recommendation for and against using titratable vs. fixed-dose NMBA dosing, a monitoring-based strategy for assessing depth of sedation and analgesia in adults with ARDS before initiating or while receiving neuromuscular blockade, and administration of NMBAs for patients who are proned, due to overall lack of evidence in critically ill patients and due to considerations of patient safety and experience concerns. Conclusions: These guidelines provide additional perspectives on the use of NMBA in patients with ARDS, recognizing that institutional and patient-specific considerations must help to guide the decision-making process.

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) has been shown to have numerous benefits including lower costs, increased patient satisfaction, and decreased healthcare associated infections. Patient education is a crucial part of the OPAT process, as lack of understanding may lead to adverse drug events, emergency department visits, or hospital re-admission. A baseline survey of OPAT clinicians at a large multi-state health system revealed low awareness of existing OPAT education resources and consensus that the materials needed improvement. We hypothesized that an OPAT education video would improve OPAT staff satisfaction with the educational offerings.Figure 1.OPAT Video Link Engagement (2024)Figure 2.Patient Electronic Chart Message Methods Adult patients ( > 18 years of age) enrolled in OPAT programs at 4 sites within Mayo Clinic throughout Minnesota and Wisconsin from 5/1/23 - 8/1/24 were included. A standardized OPAT patient education video was developed using voice over PowerPoint slides. Video content included lab monitoring requirements, signs and symptoms of adverse effects including alarm symptoms, and intravenous catheter care. The video was available as a link for delivery via patient electronic chart message, to be played on clinic and hospital room computers, and accessed by patients via QR code on rack cards. We implemented inclusion rules built within our electronic health record which automated the delivery of these patient chart messages. The primary outcome was staff satisfaction with OPAT education materials. Secondary metrics included number of video patient accesses in hospital and clinic rooms, number of message deliveries, and frequency of message opening. Staff satisfaction with OPAT education was compared pre- and post-intervention using the Pearson chi-square test. Results The patient education video was accessed 73 times in hospital and clinic rooms and was delivered by automated patient chart message 157 times during the study period. Patient chart messages were opened 91.5% of the time. The percentage of staff who felt OPAT education materials needed improvement decreased from 90% pre-intervention to 38.1% post-intervention (p=0.05). Conclusion A standardized OPAT patient education video allowed for efficient electronic delivery of educational information to patients and improved OPAT staff satisfaction. Disclosures All Authors: No reported disclosures