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OBJECTIVE Core outcome sets (COSs) are needed to promote data consistency across studies as well as data synthesis and comparability. The aim of the current study was to use a modified Delphi process to develop a COS for lateral femoral cutaneous neuropathy (LFCN), hereafter COS-LFCN. METHODS A 5-stage approach was used to develop the COS-LFCN: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. This study followed the Core Outcome Set - STAndards for Development, (COS-STAD) recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 25 participants, all neurological surgeons, representing 14 countries. The final COS-LFCN consisted of 41 factors and outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS for LFCN and provided definitions, methods of implementation, and time points for assessment. The COS-LFCN should serve as the minimum data to be collected in all future neurosurgical studies on LFCN. Incorporation of this COS will help improve consistency in reporting, data synthesis and comparability, and minimize outcome reporting bias.

Abstract Background Health-related quality of life (HRQoL) is impaired in patients with Crohn’s disease (CD). Upadacitinib (UPA), a Janus kinase inhibitor, demonstrated efficacy and safety in the phase 3 U-EXCEED (NCT03345836) and U-EXCEL (NCT03345849) induction, and U-ENDURE (NCT03345823) maintenance trials in patients with moderately to severely active CD. We assessed the effect of UPA maintenance treatment on HRQoL in patients with moderately to severely active CD from the U-ENDURE long-term extension (LTE) study. Methods Patients who completed the 52-week U-ENDURE maintenance study were eligible to participate in the LTE study, continuing their previously assigned maintenance treatment. Of the 337 patients receiving UPA (168, UPA 30 mg; 169, UPA 15 mg) in the U-ENDURE maintenance trial, a total of 244 patients (137, UPA 30 mg; 107, UPA 15 mg) were included in this analysis. All 244 patients completed week 96 of the LTE. Endpoints included percentage of patients who achieved Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase from induction baseline), IBDQ remission (total score ≥170 points), a meaningful within-person change (MWPC) of ≥ 9point increase from baseline in the Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F) and a MWPC of ≥ 4.1- and ≥3.9-point increase from baseline on the 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) component summary score, respectively, at maintenance week 52 and LTE week 96. We also assessed MWPC in Work Productivity and Activity Impairment in CD (WPAI-CD) domains defined as a decrease of ≥ 6.1% in presenteeism, ≥6.5% in absenteeism, ≥7.3% in overall work impairment and ≥8.5% in activity impairment. Data were reported using nonresponder imputation. Results The proportion of patients in the UPA 30 mg group achieving HRQoL outcomes was maintained from maintenance week 52 to LTE week 96, including achievement of IBDQ response (61.3% vs 57.7%), IBDQ remission (53.3% vs 53.3%), MWPC improvement in FACIT-F (50.4% vs 40.9%), SF-36 PCS (56.9% vs 56.2%), SF-36 MCS (47.4% vs 40.9%) and MWPC improvements in WPAI-CD domains presenteeism (45.6% vs 48.1%), overall work impairment (49.4% vs 51.9%) and daily activity impairment (57.7% vs 56.9%). Patients in the UPA 15 mg group also maintained achievement of these HRQoL outcomes over time (Table). Conclusion UPA (15 and 30 mg) maintenance treatment over a 3-year period was associated with sustained and clinically meaningful disease-specific and generic HRQoL improvement in patients with moderately to severely active CD. Despite the overall trend favouring UPA 30 mg, differences in patient-reported outcomes between the 2 dose groups were small. Conflict of interest: Panés, Julián: Personal Fees: J. Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Boehringer Ingelheim, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Spyre Therapeutics, Surrozen, Takeda, and Wasserman, and has served on data safety monitoring boards for Alimentiv, Mirum, Roche, Sorriso, Sanofi, and Surrozen Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Joshi, Namita: Namita Joshi is a full-time employees/contractor of AbbVie and may own AbbVie stock or options. Xuan, Si: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Shukla, Nidhi: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Perkovic, Ashley: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB.

Abstract Background Endoscopic healing is an important treatment goal in Crohn’s disease (CD), in line with European Crohn’s and Colitis Organisation CD guidelines, as it is associated with improved long-term disease outcomes. We assessed the relationship between endoscopic healing and long-term clinical outcomes, patient-reported outcomes (PROs) and hospitalisations in patients (pts) with moderately to severely active CD receiving upadacitinib (UPA) maintenance treatment in the U-ENDURE long-term extension (LTE) study. Methods Pts completing the 52-week U-ENDURE maintenance study were eligible to participate in the LTE study, continuing their previously assigned maintenance treatment. Pts receiving UPA 15 mg or 30 mg once daily in LTE were included in this analysis. Clinical remission based on CD activity index (CDAI <150), CDAI response (≥100-point decrease in CDAI from induction baseline), clinical remission based on stool frequency/abdominal pain (SF/AP) score (average daily soft or liquid SF ≤ 2.8 and average daily AP ≤ 1.0, and neither greater than induction baseline), Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total IBDQ score from induction baseline) and remission (IBDQ total score ≥170 points), Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F) response (≥9-point increase from induction baseline), and economic outcomes (CD-related hospitalisations or surgeries) were evaluated at LTE week 96. Outcomes were compared between pts who achieved vs those who did not achieve endoscopic response, endoscopic remission, or ulcer-free endoscopy (endoscopic outcomes defined in Table footnote) at maintenance week 52 using chi-square testing (nominal P values). Pts with missing outcomes at LTE week 96 were imputed as nonresponders. Results Of 244 pts, 153/244 (62.7%), 112/244 (45.9%) and 89/242 (36.8%) achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at LTE week 0. Significantly (all nominal P≤0.05) more pts who achieved endoscopic response, endoscopic remission or had an ulcer-free endoscopy at LTE Week 0 achieved CDAI response, CDAI remission, SF/AP clinical remission, IBDQ response, IBDQ remission and FACIT-F response at LTE week 96 (Table). CD-related hospitalisations or surgeries at LTE week 96, were significantly (nominal P≤0.05) lower in pts with endoscopic remission and ulcer-free endoscopy at LTE week 0, and numerically lower in pts with endoscopic response. Conclusion A significantly higher proportion of pts who achieved endoscopic outcomes at 52 weeks and received up to 3 years of UPA maintenance treatment achieved long-term improvements in clinical and PROs and reduced CD-related hospitalisations or surgeries. Conflict of interest: Loftus, Jr, Edward: Edward V. Loftus, Jr. has received consulting fees from AbbVie, Abivax, Astellas, Avalo Therapeutics, Biocon, BMS, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Merck, Morphic Therapeutics, Ono Pharma, Spyre Therapeutics, Takeda, and TR1X Bio has received research support from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda and holds stock in Exact Sciences and Moderna. Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Joshi, Namita: Namita Joshi is a full-time employees/contractor of AbbVie and may own AbbVie stock or options. Shukla, Nidhi: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Perkovic, Ashley: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Panés, Julián: Personal Fees: J. Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Boehringer Ingelheim, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Spyre Therapeutics, Surrozen, Takeda, and Wasserman, and has served on data safety monitoring boards for Alimentiv, Mirum, Roche, Sorriso, Sanofi, and Surrozen

Abstract Background & Aims Central reading of endoscopy and histopathology is the current standard for disease activity assessment in inflammatory bowel disease (IBD) clinical trials but is limited by interreader and intrareader variability, operational delays, and cost. Artificial intelligence (AI) and machine learning (ML) offer the potential to improve accuracy, efficiency, and reproducibility. The International Organization for the Study of IBD (IOIBD) developed consensus statements on AI/ML use for endoscopic and histologic endpoint assessment in IBD trials. Methods As part of the IOIBD endpoints cluster initiative, a narrative, evidence-informed review with literature searches of Medline and Embase (January 2018-February 2025) identified studies applying AI/ML to endoscopy or histology in IBD. Relevant evidence informed 36 survey statements formulated by a steering committee. Seventy-two IOIBD members were invited to vote online; consensus required ≥80% agreement (score: 7-10 on a 10-point scale). Results Forty-five members completed the survey. Consensus was reached for 28 statements related to endoscopy, pathology, and trial design. Experts agreed that AI-based central reading could improve diagnostic accuracy, expedite processes, reduce costs, and enhance reproducibility. Combining human and AI assessments was favored over AI replacement. The key limitations identified included insufficient validation, generalizability concerns, and dependence on human-annotated training datasets. Conclusions This IOIBD consensus supports the integration of AI/ML into central reading for IBD clinical trials to improve objectivity, efficiency, and consistency, while maintaining human oversight. Further research should address validation, regulatory frameworks, and multimodal integration to enable broader adoption in both trials and clinical practice.

Abstract Background Spinal cord injury causes motor, sensory, and autonomic impairments. Transcutaneous spinal cord stimulation (tSCS) has shown potential to improve autonomic regulation, particularly cardiovascular and bladder control. Heart rate variability (HRV) serves as a non-invasive marker of autonomic balance, reflecting modulation of cardiac sympathetic and parasympathetic activity. The purpose of this study was to evaluate the effect of combined tSCS and physical therapy (tSCS + PT) on HRV and autonomic function metrics in chronic spinal cord injury. Methods. Eight participants (2 with tetraplegia, 6 with paraplegia) received tSCS at 30 Hz targeting T11–L1 or C5–T1, depending on injury level. Each underwent two tSCS + PT sessions per week for 12 weeks, followed by a 4-week washout period. Autonomic assessments included the Autonomic Standard Evaluation Form (ASAF), Neurologic Bladder Symptoms Score (NBSS), blood pressure, heart rate, SpO2%, and core temperature. Electrocardiograms were recorded pre- and post-tSCS + PT at baseline, 12, and 16 weeks. Results. Baseline effects of tSCS + PT revealed increased time-domain HRV parameters, suggesting enhanced cardiac parasympathetic activation (PSA). After 12 weeks, these parameters decreased, suggesting reduced cardiac PSA and enhanced sympathetic activation (SA). Similar results were found with frequency-domain parameters. Time-and frequency-domain parameters tended to return toward baseline after the 4-week therapy suspension. Two commonly reported HRV parameters, SDNN and RMSSD, showed large effects (g = 1.64, CI 95% [0.30, 2.98], and g = 1.23, CI 95% [0.11, 2.42], respectively) at 12 weeks when comparing pre- vs. post-tSCS + PT. Moderate, subject-related differences across evaluations were found in ASAF and NBSS (p > 0.05). Physiological metrics across time points did not show statistically significant differences (p > 0.05). Physiological metrics across time points did not show statistically significant differences (p > 0.05). Conclusions Combined tSCS + PT elicited improvements in autonomic clinical measures, without statistically significant changes in time-domain or frequency-domain HRV parameters. Nonetheless, trends and size effect in SDNN and RMSSD suggested that tSCS + PT induced midterm SA and a transient PSA immediately post-tSCS + PT. The partial recovery of HRV after tSCS withdrawal indicates that the observed autonomic changes were therapy-related.

ABSTRACT Obstructive sleep apnea (OSA) is a common, heritable disorder with diverse clinical presentations and etiologies. We conducted a genome-wide association meta-analysis of 492,107 individuals, including 46,028 OSA cases, identifying 14 genome-wide significant loci, eight of which are novel. Analyses adjusting for body mass index (BMI) revealed three loci independent of obesity, implicating alternative biological pathways contributing to disease. Integrative functional analyses, including chromatin interaction mapping, fine-mapping, and eQTL colocalization, prioritized candidate effector genes. Notably, implicated genes in chondrocytes were associated with craniofacial morphology in both mouse and human multivariate genotype-phenotype mapping, supporting a role for craniofacial structure in OSA risk. These findings highlight key genetic pathways (obesity-related, neurological, and craniofacial) underlying the development of OSA, offering new insights into its complex etiology.

ABSTRACT Immunoglobulin A nephropathy (IgAN) is an immune-mediated disease of B-cell origin and the most common primary glomerulonephritis worldwide, which often progresses to kidney failure within 10–20 years of diagnosis. Microscopic hematuria is frequently observed in IgAN; it is thought to result from damage to the glomerular filtration barrier caused by pathogenic immune complex deposits, allowing red blood cells to leak into the urinary space. Emerging evidence suggests that microscopic hematuria in IgAN may be linked to active glomerular inflammation, poorer disease prognosis and progressive kidney function decline. Despite this, it remains an underutilized biomarker for IgAN because of a lack of standardization (which can lead to preanalytical errors), challenging logistical considerations in large multicenter trials and non-glomerular hematuria as a confounding factor. The “proteinuria-centric” approach by the nephrology community may overlook that active forms of glomerulonephritis manifest with both proteinuria and hematuria, in contrast to primary podocytopathies where proteinuria is the main feature. When properly assessed, microscopic hematuria is a prognostically relevant biomarker in IgAN that may improve risk stratification and assessment of therapeutic response when evaluated alongside traditional biomarkers. This review evaluates the methods of assessment, pathophysiology and clinical utility of microscopic hematuria in IgAN.

Objectives: To identify factors associated with short-term mortality among patients receiving microaxial flow pump (mAFP) therapy for acute myocardial infarction-related cardiogenic shock (AMI-CS). Data Sources: We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from January 1, 2004, to January 1, 2025. Study Selection: We selected English-language studies that included adults with AMI-CS receiving mAFP and evaluated factors associated with short-term mortality. We excluded patients receiving concurrent venoarterial extracorporeal membrane oxygenation, as well as studies that solely included patients presenting with out-of-hospital cardiac arrest. Data Extraction: Two authors performed citation screening and data extraction. For each factor evaluated in at least two studies, we performed meta-analyses of adjusted odds ratios (aORs) using a random-effects model. Risk of bias was evaluated using the Quality in Prognosis Studies tool, and the certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. Data Synthesis: Our primary analysis included 18 studies, encompassing 20,617 patients. Median short-term mortality across studies was 50.7% (interquartile range 38.4–55.3%). Factors associated with short-term mortality based on high-certainty evidence included: increased age (aOR, 1.04 per year [95% CI, 1.03–1.05 per year] or ≥ 65 yr (aOR, 2.42 yr [95% CI, 0.77–7.64 yr]), female sex (aOR, 1.26 [95% CI, 1.09–1.45]), higher body mass index (aOR, 1.05 per point [95% CI, 1.04–1.07 per point]), higher heart rate (aOR, 1.02 per beats/min [95% CI, 1.01–1.02 per beats/min]), higher serum creatinine (aOR, 1.35 per mg/dL [95% CI, 1.08–1.70 per mg/dL]), mechanical ventilation (aOR, 2.53 [95% CI, 1.82–3.53]), vasopressors (aOR, 1.52 [95% CI, 1.11–2.08] for any vasopressors and aOR, 1.37 [95% CI, 1.18–1.58] per each vasopressor), presentation with ST-elevation myocardial infarction (aOR, 1.59 [95% CI, 1.11–2.26]), cardiac arrest (aOR, 2.85 [95% CI, 2.22–3.64]), and hypoxic-ischemic brain injury (aOR, 5.36 [95% CI, 3.03–9.47]). Conclusions: We identified several prognostic factors associated with short-term mortality in AMI-CS patients receiving mAFP support. This work may help inform clinicians, patients, and families regarding utilization of mAFP in AMI-CS.

Abstract Introduction Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population. Methods In a multicentre international double-blind placebo-controlled phase 2 study, we randomly assigned 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV). Results All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Baseline mean ECV 38.9 ± 10.9 ml, GLS −15.3 ± 3.6%, and LVEF 60.6 ± 9.9% were consistent with mild to moderate myocarditis and predominantly intact LV function. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of −3.7 ml, confidence interval (CI): −7.4 to 0.1; P = .0538; GLS was −16.0% in the active group and −15.9% in the placebo group, difference of −0.1, CI: −1.2 to 1.1; P = .90. Left ventricular mass was significantly reduced in the active group at 121.1 g compared to placebo 130.3 g, a difference of −9.2, CI: −16.4 to −2.1; P = .0117. In terms of remodelling, LAESV was significantly reduced in the active group (−8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (−7.4 ml; P = .098). Conclusion In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. In addition, improvement in other potential markers of myocardial recovery, including a significant reduction in LV mass, was seen in the active treatment group. Further investigation of the therapeutic potential of this therapy in inflammatory cardiac conditions is warranted.