Citations

Lay Summary This article looks at how changes in bile acids and gut bacteria might contribute to chronic pouchitis, a condition that can develop after surgical removal of the colon and creation of a J-pouch for people with inflammatory bowel disease. The goal is to better understand pouchitis and find treatments to improve patients’ health.

Background: Young female patients undergoing hip arthroscopy have an increased prevalence of baseline capsular laxity of the hip joint. This laxity, along with superimposed postoperative iatrogenic capsular deficiency secondary to an unrepaired capsule, could potentially lead to worse outcomes after arthroscopic treatment of femoroacetabular impingement (FAI) in this population. Purpose: To compare outcomes and revision rates for young female patients undergoing hip arthroscopy for FAI and labral tear with capsular closure (CC group) versus capsular nonclosure (CNC group). Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review of prospectively collected data of patients who underwent index hip arthroscopy using interportal capsulotomies by a single surgeon between January 2014 and February 2020 was performed. Female patients aged 12 to 21 years who underwent hip arthroscopy with cam or pincer osteoplasty and labral repair with a 2-year minimum follow-up were included. The Beighton score was assessed. The Hip Outcome Score–Activities of Daily Living (HOS-ADL) and Hip Outcome Score–Sport-Specific Subscale (HOS-SSS) were obtained preoperatively and at 3 months, 1 year, and 2 years postoperatively. Data were analyzed using the Mann-Whitney U test and Fisher exact test. Results: A total of 23 hips (20 patients) were included in the CC group and 17 hips (16 patients) were included in the CNC group. The groups were not different regarding characteristics and preoperative patient-reported outcome scores. At all follow-up intervals postoperatively, the CC group scored significantly higher HOS-ADL and HOS-SSS. Fifteen of 17 (88.2%) patients in the CC group returned to sports versus 8 of 14 (57.1%) in the CNC group ( P = .03). Four (17.4%) hips in the CC group had revision surgery compared with 9 (52.9%) hips in the CNC group (odds ratio, 5.1; 95% CI, 1.2-22.5; P = .02). Conclusion: Young female patients treated with CC while undergoing arthroscopic FAI had improved outcomes, fewer revisions, and a higher return-to-sports rate than those treated without CC.

Abstract Objective We analyzed the long‐term safety and effectiveness of fenfluramine (FFA) in patients with Dravet syndrome (DS) in an open‐label extension (OLE) study after participating in randomized controlled trials (RCTs) or commencing FFA de novo as adults. Methods Patients with DS who participated in one of three RCTs or were 19 to 35 years of age and started FFA de novo were included. Key endpoints were: incidence of treatment‐emergent adverse events (TEAEs) in the safety population, and median percentage change in monthly convulsive seizure frequency (MCSF) from the RCT baseline to end of study (EOS) in the modified intent‐to‐treat (mITT) population. Post hoc analyses compared effectiveness in patients on concomitant stiripentol (STP) vs those not taking STP, and assessed safety (TEAEs) and effectiveness (Clinical Global Impression‐Improvement [CGI‐I] scale ratings) in patients enrolled as adults. Results A total of 374 patients, including 45 adults, received ≥1 FFA dose. Median FFA exposure was 824 days (range, 7–1280). TEAEs occurring in ≥10% of patients were pyrexia, nasopharyngitis, decreased appetite, seizure, decreased blood glucose, diarrhea, abnormal echocardiography (only physiologic regurgitation), upper respiratory tract infection, influenza, vomiting, and ear infection; no valvular heart disease or pulmonary arterial hypertension was observed over the OLE. In the mITT population ( n = 324), median percentage change in MCSF from baseline to EOS was −66.8% ( p < .001). The post hoc analyses of MCSF change from baseline to EOS in patients on concomitant STP ( n = 75) was −36.2% vs −71.6% in those not on concomitant STP ( n = 234) ( p < .0001). In adult patients, 29 of 41 (70.7%) and 29 of 42 patients (69.1%) demonstrated clinically meaningful improvement on CGI‐I at last visit as rated by caregivers and investigators, respectively. Significance Our OLE study of FFA in patients with DS confirmed previous positive findings and extended the exposure up to 3.5 years. No new or unexpected safety signals were observed and FFA demonstrated sustained and clinically meaningful reduction in MCSF.

Importance Excess body fat plays a pivotal role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). HU6 is a novel, controlled metabolic accelerator that enhances mitochondrial uncoupling resulting in increased metabolism and fat-specific weight loss. Objective To assess efficacy and safety of HU6 in reducing body weight, improving peak volume of oxygen consumption (VO 2 ) and body composition among patients with obesity-related HFpEF. Design, Setting, and Participants The Exploratory Phase 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of HU6 for Subjects With Obese HFpEF (HuMAIN-HFpEF) trial was a multicenter, dose-escalation randomized clinical trial among patients with chronic stable HFpEF and obesity. Data were analyzed from July to October 2024. Intervention HU6 treatment for 19 weeks, starting at 150 mg per day and potentially up titrated to 450 mg per day based on safety and tolerability vs placebo. Main Outcomes and Measures The primary end point was change in body weight. Results Of 66 participants randomized (mean [SD] age, 64.5 [12] years; 38 female [58%]; mean [SD] weight, 110.9 [22.4] kg), 56 completed the trial. HU6 (vs placebo) significantly decreased weight (between-group difference, −2.86 kg; 95% CI, −4.68 to −1.04 kg; P = .003), total fat mass (between-group difference, −2.96 kg; 95% CI, −4.50 to −1.42 kg; P &amp;lt; .001), and percentage visceral fat (between-group difference,−1.3%; 95% CI, −2.1 to −0.5%; P = .003), with no significant loss of muscle mass. There were no statistically significant changes in peak VO 2 , 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire score, high-sensitivity C-reactive protein level, N-terminal pro–brain natriuretic peptide level, or diastolic function. Serious adverse events were noted in 5 participants (4 in the HU6 group; 1 in the placebo group), including 1 death, all judged unrelated to treatment. Conclusions and Relevance Among patients with obesity-related HFpEF, treatment with HU6 for 19 weeks led to modest but statistically significant weight loss without significant changes in peak VO 2 . Larger trials of longer duration are warranted to determine whether longer-term administration of HU6 can improve exercise function, quality of life, and cardiovascular outcomes in this increasingly common disorder. Trial Registration ClinicalTrials.gov Identifier: NCT05284617

Précis: Patients with clinically uncontrolled open angle glaucoma submitted to isolated gonioscopy-assisted transluminal trabeculotomy or combined with phacoemulsification not only achieved low mean IOPs, but also demonstrated stable IOP patterns during a 24-month follow-up. Purpose: To assess the impact of gonioscopy-assisted transluminal trabeculotomy (GATT) on long-term intraocular pressure (IOP) variation. Patients and Methods: An unicentric retrospective study including 169 consecutive patients who had undergone standalone GATT or combined with phacoemulsification (PHACOGATT) due to clinically uncontrolled open angle glaucoma, with at least 12 months of follow-up was conducted. Long-term mean IOP, long-term IOP peak, long-term IOP fluctuation, coefficient of variation, mean-positive IOP variation, sustained clinically significant positive IOP variation, and number of follow-up visits with IOP ≥15 mm Hg were investigated. Results: One hundred sixty-nine eyes from 169 patients were included (GATT group=101 patients; PHACOGATT group=68 patients). Mean long term IOP (12.0±1.8 vs. 11.2±2.0 mm Hg), mean long-term IOP peak (12.9±2.6 vs. 11.8±3.5 mm Hg), and mean coefficient of variation (0.07±0.08 vs. 0.05±0.09) were lower in the PHACOGATT group, while mean IOP fluctuation (1.0±3.7 vs. 1.2±1.8 mm Hg) was lower in the GATT group. In addition, the overall mean-positive IOP variation was 0.79±1.64 mm Hg. Finally, only 6.5% of the patients presented sustained clinically significant positive IOP variation and IOP was ≥15 mm Hg in 5.9% of the follow-up visits. Conclusions: Patients with clinically uncontrolled open angle glaucoma submitted to GATT or PHACOGATT achieved low mean IOPs and demonstrated stable IOP patterns. Our results provide additional evidence supporting GATT and PHACOGATT as viable options for the treatment of medically uncontrolled glaucoma patients requiring low and stable IOPs.