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PubMed2026

Preoperative Carbohydrate Supplementation Reduces Thirst and Improves Patient Satisfaction Before Elective Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND & AIMS: Prolonged preoperative fasting is a major source of patient discomfort, particularly thirst, before elective cesarean delivery. This study aimed to evaluate whether preoperative carbohydrate (CHO) supplementation could alleviate these discomforts and improve patient satisfaction without compromising safety. METHODS: In this single-center randomized controlled trial, 262 women scheduled for elective cesarean delivery under neuraxial anesthesia were randomly allocated to either the CHO group (Group CHO, n = 131), which received 355 mL of an oral carbohydrate solution on the night before and the morning of surgery, or the control group (Group C, n = 131), which followed conventional fasting. The primary outcome was the thirst Numeric Rating Scale (NRS, 0-10) score measured immediately before surgery. Secondary outcomes included hunger NRS, satisfaction NRS, and maternal and neonatal safety parameters. RESULTS: Baseline characteristics were comparable between groups. Despite a longer preoperative fasting duration in Group CHO (9.25 ± 1.05 vs. 8.74 ± 0.97 h, P < 0.001), this group exhibited significantly lower thirst NRS scores (1.69 ± 0.90 vs. 4.02 ± 0.99, P < 0.001) and hunger NRS scores (1.25 ± 0.94 vs. 2.09 ± 0.82, P < 0.001), as well as higher satisfaction NRS scores (7.70 ± 0.69 vs. 5.69 ± 1.17, P < 0.001). Subgroup analyses confirmed consistent benefits of CHO supplementation across most patient characteristics. Further analyses suggested that the maximum effect on thirst reduction occurred at approximately 9.2 h of solid fasting; however, the interaction between fasting duration and treatment group was not statistically significant (P = 0.187). CONCLUSION: Preoperative carbohydrate supplementation effectively reduces thirst and hunger and improves patient satisfaction before elective cesarean delivery without increasing maternal or neonatal risk. The beneficial effects were consistent across varying fasting durations, with exploratory spline analyses suggested a potential peak effect around 9.2 h, though this was not statistically significant and should be interpreted cautiously. These findings support the incorporation of carbohydrate loading into enhanced recovery protocols. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2500097956.

Humans↗

PubMed2026

Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study.

BACKGROUND: Patients undergoing minimally invasive esophagectomy (MIE) frequently experience moderate-to-severe postoperative pain and anxiety-depressive symptoms, compromising postoperative quality of recovery (QoR). Esketamine is a promising adjunct for analgesia and anxiolysis; however, the effect of low-dose esketamine on patient-centered recovery outcomes in MIE remains unclear. METHODS: In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) or placebo (equivalent volume and rate of saline). The primary outcome was the QoR-15 score on postoperative day (POD) 2. Secondary outcomes included QoR-15 scores on POD 1, 3, 7 and 30. Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) and Depression Subscale (HADS-D) scores, numeric rating scale (NRS) pain scores, and the Brief Pain Inventory (BPI) scores on POD 1 to 3, and safety evaluations. RESULTS: A total of 198 patients were analyzed (esketamine, n = 98; placebo, n = 100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9 ± 9.4 vs. 110.2 ± 9.8, p < 0.001) and POD 3 (123.6 ± 7.2 vs. 116.8 ± 8.4, p < 0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p < 0.001). Additionally, esketamine recipients reported significantly lower NRS scores at rest and during movement and BPI scores for pain severity and pain interference items (all p < 0.001). There were no significant between-group differences in safety outcomes. CONCLUSIONS: Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Register (identifier: ChiCTR2400088916).

Humans↗

PubMed2026

Intraocular Pressure Changes Following Intraluminal Stent Removal From the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressure (IOP) changes and to summarize its long-term efficacy and safety. CLINICAL RELEVANCE: Glaucoma remains one of the leading global causes of irreversible vision loss, necessitating effective surgical management for refractory cases. Glaucoma drainage devices are critical for these complex forms, and intraluminal stent removal from the PGI serves as a key strategy to titrate aqueous outflow and optimize long-term IOP control. METHODS: A systematic review was conducted by searching EMBASE, Medline, and CENTRAL. The meta-analysis ultimately included 5 observational studies. The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of the included studies. Continuous outcomes (eg, postremoval stent IOP reduction) were analyzed using the mean difference (MD) with 95% confidence intervals (CI); dichotomous outcomes (eg, hypotony incidence) were evaluated using pooled proportion with 95% CI. All meta-analyses employed a random-effects model. RESULTS: Our meta-analysis included 5 studies, involving a total of 283 eyes. The meta-analysis revealed that removal of the stent leads to a significant and immediate IOP reduction. The IOP reduction (immediate postremoval stent IOP minus preremoval stent IOP) was significant, with a pooled MD of -9.09 mm Hg IOP (MD = 9.09; 95% CI = [-11.77, -6.41]). In the preremoval stent high-IOP (>21 mm Hg) subgroup, the IOP reduction is -11.82 (95% CI = [-10.14, -13.51]). This reduction was significantly greater than the preremoval stent low-IOP (<21 mm Hg) subgroup, whose reduction is -6.66 mm Hg (95% CI = [-5.55, -7.77]). Regarding safety, the pooled proportion of clinically hypotony was low and highly consistent (I² = 0.00%) at only 0.03 (95% CI = [0.00, 0.15]). CONCLUSIONS: Intraluminal stent removal from the PGI is an effective and safe IOP-lowering intervention. Its IOP reduction effect is significantly more pronounced in patients with preremoval stent high IOP, providing crucial clinical guidance for managing persistently high IOP after PGI implantation.

Humans↗

PubMed2026

A two-center randomized clinical superiority trial of single-anastomosis sleeve ileal bypass versus sleeve gastrectomy for severe obesity: SASSY study protocol.

BACKGROUND: Single-anastomosis sleeve ileal bypass is a novel metabolic bariatric surgery intended to enhance metabolic outcomes and reduce the risk of postoperative complications. Although preliminary outcome data for single-anastomosis sleeve ileal bypass are promising, evidence from adequately powered, randomized head-to-head comparisons is scarce. This trial compares the efficacy and safety of single-anastomosis sleeve ileal bypass versus sleeve gastrectomy in patients with class II obesity (body mass index = 35.0-39.9 kg/m²) with at least one obesity‑related comorbidity or class III obesity (body mass index ⩾40.0 kg/m²). METHODS: This two-center randomized clinical superiority trial enrolls patients eligible for metabolic bariatric surgery at two specialized Norwegian centers. Included patients are randomly assigned (1:1) to either single-anastomosis sleeve ileal bypass or sleeve gastrectomy with standardized perioperative treatment and care. The primary endpoint is the between-group difference in change in body mass index from baseline to 2 years after single-anastomosis sleeve ileal bypass versus sleeve gastrectomy. Secondary endpoints include additional weight loss outcomes, the prevalence of gastroesophageal reflux disease, surgical and postoperative complications, obesity-related comorbidities, nutritional status, bone mineral density, gastrointestinal symptoms, quality of life, and rates of revisional and conversion surgery. All endpoints will be evaluated at 2 and 5 years after surgery. Statistical analyses utilize linear mixed models and analysis of covariance within an intention-to-treat framework. DISCUSSION: This trial will provide high-level evidence with robust and comparative outcome data on single-anastomosis sleeve ileal bypass and sleeve gastrectomy, aiming to clarify the clinical utility of single-anastomosis sleeve ileal bypass and inform surgical practice. Findings will address gaps in medium- and long-term evidence regarding weight loss, safety, comorbidity resolution, and quality of life following single-anastomosis sleeve ileal bypass.

Humans↗

PubMed2026

Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.

BACKGROUND: Citicoline is a promising therapeutic option for improving both motor and non-motor symptoms in Parkinson's disease (PD) beyond levodopa and other standard dopaminergic treatments. OBJECTIVES: The CITIPARK study evaluated the efficacy and safety of citicoline in improving clinical outcomes and quality of life (QOL) in PD patients on dopaminergic therapies. METHODS: The randomized, double-blind, multicenter trial compared citicoline (1000 mg/day intramuscular, two six-week cycles) with placebo for 24 weeks in PD under stable medications. The primary endpoint was change in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score; secondary endpoints included motor and non-motor subscores, QOL, clinical global impression (CGI) and safety. RESULTS: The study enrolled 485 participants, randomizing 474 (citicoline: 303; placebo: 171). Citicoline significantly increased the likelihood of achieving a minimal clinically important difference compared with placebo (OR 2.06, 95% CI 1.06-3.99; P = 0.031) on the MDS-UDPRS total score in the modified intention-to-treat population. Among secondary outcomes, the citicoline group showed greater improvement in motor function (MDS-UPDRS III -2.97 vs -0.13; p = 0.009) and a greater improvement on CGI -II and CGI-III (3.26 vs 3.59; p = 0.021 and 9.30 vs 10.38; p = 0.018, respectively). AEs occurred in 22.1% and 27.1% of the citicoline and placebo groups, respectively. CONCLUSIONS: Citicoline was well tolerated and associated with motor benefits compared with placebo in a highly compliant population. The results suggest a role of citicoline as a safe and possibly effective supportive therapy in PD treated with concomitant dopaminergic agents.

Humans↗

PubMed2026

Effect of an oral complementary medicine combination for symptomatic knee osteoarthritis: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Many individuals use complementary medicine therapies for osteoarthritis, despite limited scientific supporting evidence. These therapies have demonstrated anti-inflammatory, antioxidative, and chondroprotective effects via different molecular pathways, suggesting potential therapeutic benefits. This trial aimed to evaluate the efficacy and safety of a novel oral complementary medicine combination in adults with symptomatic knee osteoarthritis at 12 weeks. DESIGN: The 12-week, double-blind, randomized, placebo-controlled ATLAS trial was conducted in Australia from July 2024 to April 2025 (ACTRN12623000380695). Eligible participants were aged ≥40 years with symptomatic knee osteoarthritis and radiographic Kellgren-Lawrence grade ≥2. Participants were randomized 1:1 to receive the complementary medicine combination, comprising a total daily dose of Boswellia serrata extract 250 mg, pine bark extract 100 mg, methylsulfonylmethane 1500 mg, curcumin 500 mg, and piperine 5 mg, or placebo. The primary outcome was the 12-week change in knee pain (0-100 mm visual analogue scale (VAS)). A 95% confidence interval excluding differences >18 mm between groups was interpreted as the absence of a clinically meaningful difference. Harms were monitored weekly. RESULTS: Eighty-four participants were recruited (mean [SD], age 63.7 [8.0] years, BMI 29.0 [5.5] kg/m2), and 57% were female. At 12-weeks, both groups (intention-to-treat population: complementary medicine, n=42; placebo, n=41) showed a decrease in VAS pain (least squares means: complementary medicine 20.1 mm vs placebo 20.3 mm), however with no difference between groups: 0.16 mm (95% CI -6.81 to 7.12). The safety profile of experiencing any AE was similar between groups (risk difference, -3.4% [95% CI -24.8-17.9%]); and most adverse events were mild or moderate. Four participants experienced serious adverse events, unrelated to the treatment. CONCLUSIONS: The complementary medicine combination was not superior to placebo for improving pain over 12 weeks, and the evidence does not support the use of this combination to treat people with symptomatic knee osteoarthritis.

Humans↗

PubMed2026

Ultrasound-guided high-voltage vs conventional pulsed radiofrequency in elderly cervical radiculopathy: A randomized controlled trial.

BACKGROUND: Elderly patients with cervical radiculopathy present therapeutic challenges owing to comorbidities and medication-related risks. Long-term pharmacotherapy and surgical interventions are often suboptimal, necessitating evaluation of optimized pulsed radiofrequency strategies under image guidance. OBJECTIVES: This superiority trial compared the efficacy and safety of ultrasound-guided cervical nerve root high-voltage pulsed radiofrequency (HVP-PRF) versus conventional pulsed radiofrequency (C-PRF) for pain management in elderly patients with cervical radiculopathy. METHODS: This single-center, parallel-group, assessor-blinded randomized controlled trial enrolled patients aged 60-85 years with cervical radiculopathy, randomly assigned (1:1) to HVP-PRF (70 V) or C-PRF (45 V). Procedures were performed under ultrasound guidance with sensory/motor stimulation confirmation and temperature ≤42°C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (ΔNRS) from baseline to 3 months. Secondary outcomes included Neck Disability Index (NDI), neck pain NRS, Patient Global Impression of Change, responder rates, rescue analgesia use, and adverse events. Follow-up occurred at 1 week, 1, and 3 months. RESULTS: A total of 104 patients were randomized and 101 received treatment. At 3 months, HVP-PRF demonstrated significantly greater radiating pain improvement versus C-PRF (adjusted mean difference 1.24, 95% CI 0.46-2.02, P=0.002). Functional improvement (NDI) was superior in the HVP-PRF group at 3 months (AMD 6.47, 95% CI 2.11-10.83, P=0.004). Responder rates (≥50% pain reduction) were higher with HVP-PRF at 3 months (68.75% vs. 42.22%, OR 3.01, P=0.011) and 6 months (65.22% vs. 43.18%, OR 2.52, P=0.035). Rescue analgesic use was lower in the HVP-PRF group during 1-3 months intervals (both P<0.05). Adverse event rates were comparable (27.45% vs. 32.00%). CONCLUSION: Under ultrasound visualization and electrical stimulation-based target confirmation with temperature control ≤42°C, HVP-PRF provided greater and more durable relief of upper limb radiating pain compared with C-PRF in elderly patients with cervical radiculopathy, with a comparable safety profile.

Humans↗

PubMed2026

Endovascular treatment after stroke beyond 24 h vs 6-24 h: a propensity score-matched cohort study.

BACKGROUND: Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) within 6-24 h. However, the safety and feasibility of EVT for anterior circulation strokes beyond 24 h remain uncertain. METHODS: We conducted a retrospective cohort study of consecutive patients with anterior circulation LVO who underwent EVT at Changhai Hospital from 2018 to 2023. Patients were stratified into late (6-24 h) and very late (>24 h) windows. Propensity score matching (PSM) was performed to adjust for baseline imbalances, including age, sex, NIHSS, ASPECTS, occlusion location, perfusion parameters, and vascular risk factors. The primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2) at 3 months. Secondary outcomes included successful reperfusion (TICI 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 1043 screened patients, 429 patients with anterior circulation LVO were included after exclusions, comprising 373 in the late window and 56 in the very late window. PSM yielded 42 matched pairs. Compared with the late window group, the very late window group showed no statistically significant differences in functional independence (54.8% vs. 57.1%; OR = 0.908, 95% CI 0.382-2.153, p = 0.830), successful reperfusion (88.1% vs. 92.9%; OR = 1.800, 95% CI 0.481-7.096, p = 0.460), sICH (2.4% vs. 9.5%; OR = 0.232, 95% CI 0.012-1.652, p = 0.200), intraprocedural complications (26.2% vs. 19.0%; OR = 1.508, 95% CI 0.540-4.362, p = 0.440), or postoperative complications (33.3% vs. 35.7%; OR = 0.900, 95% CI 0.363-2.219, p = 0.820). CONCLUSIONS: In this selected, single-center cohort of anterior circulation LVO patients undergoing EVT, treatment initiated beyond 24 h appeared to have comparable effectiveness and safety to treatment initiated within 6-24 h. Definitive evidence requires confirmation from adequately powered randomized controlled trials.

Humans↗

PubMed2026

Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.

PURPOSE: Transforming growth factor β (TGFβ) plays a dual role in cancer, acting as a tumor suppressor early in the disease but promoting progression and immune evasion when dysregulated. In pancreatic ductal adenocarcinoma (PDAC), TGFβ-driven desmoplasia fosters chemoresistance and immunosuppression, limiting therapeutic efficacy. NIS793, a fully human mAb targeting TGFβ, demonstrated antifibrotic and immunomodulatory activity in preclinical models and early-phase trials. PATIENTS AND METHODS: We conducted a randomized, open-label, phase II study in treatment-naïve patients with metastatic PDAC (mPDAC) to evaluate NIS793 ± spartalizumab (anti-PD-1) combined with nab-paclitaxel (or Abraxane)/gemcitabine (ABRA/GEM) versus ABRA/GEM alone. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, pharmacokinetics, and biomarker analyses. Exploratory assessments included paired tumor RNA sequencing, cell-free DNA profiling, and plasma proteomics. RESULTS: NIS793 demonstrated target engagement and suppression of TGFβ signaling, confirmed by transcriptomic and proteomic analyses. Stromal remodeling was evident, with significant downregulation of cancer-associated fibroblast markers (Acta2, Fap) and collagen-related signatures. Despite proof of mechanism, clinical efficacy was not observed: Median PFS and OS were comparable or numerically worse in the NIS793 arm versus control (HR for OS in NIS793 + ABRA/GEM vs. ABRA/GEM: 1.32; 95% confidence interval, 0.84-2.07). The safety profile was manageable, with no unexpected toxicities. Biomarker data revealed increased expression of neutrophil-related genes after treatment, suggesting potential induction of tumor-promoting inflammation. CONCLUSIONS: NIS793 effectively inhibited TGFβ signaling and led to stromal remodeling but failed to improve outcomes in mPDAC. These findings highlight the complexity of TGFβ biology and caution against its blockade in combination with chemotherapy for PDAC. Future strategies should consider context-dependent effects of TGFβ inhibition.

Humans↗

PubMed2026

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (∼19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (∼6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans↗

PubMed2026

Prothrombin complex concentrate (PCC) vs. non-PCC strategies for warfarin reversal in left ventricular assist device recipients: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) prolong survival in end-stage heart failure, and warfarin thromboprophylaxis is recommended to prevent device thrombosis and thromboembolic complications. When bleeding occurs or emergency surgery is required, rapid anticoagulation reversal is critical. Prothrombin complex concentrate (PCC) provides rapid reversal; however, its risk-benefit profile in LVAD recipients remains unclear. We conducted a systematic review and meta-analysis comparing PCC with non-PCC strategies for warfarin reversal in LVAD recipients. METHODS: MEDLINE, Embase, and Scopus were searched through June 2025 for studies of PCC versus non-PCC strategies for warfarin reversal in LVAD recipients. Two reviewers independently extracted data. Random-effects models were used to pool arm-level estimates and to pool head-to-head comparisons using mean differences or risk ratios (RRs). RESULTS: Eighteen studies involving 779 patients were included. Arm-level pooled estimates for PCC versus non-PCC comparators were 24.0% versus 15.8% for mortality, 16.5% versus 12.1% for thrombotic events, and 3.1 versus 5.7 for FFP units. Arm-level time to INR correction was longer with PCC overall (16.5 versus 13.6 h), driven by one elective cohort, but faster within the ICH subgroup (6.0 versus 13.7 h). In head-to-head comparisons, PCC achieved faster INR correction than non-PCC comparators (mean difference - 7.6 h; p = 0.001) and required fewer FFP units (-2.6 units; p = 0.019), with no significant difference in all-cause mortality (RR 1.14; p = 0.490) or thrombotic events (RR 1.43; p = 0.176). CONCLUSIONS: In head-to-head studies, PCC was associated with faster INR correction and lower FFP requirements than non-PCC strategies, whereas mortality and thrombotic events did not differ significantly. Given the observational evidence, wide confidence intervals, and heterogeneity, equivalent safety cannot be established, and prospective studies are needed to define the relative safety and effectiveness of the two approaches. IMPLICATIONS FOR CLINICAL PRACTICE: PCC-based strategies may be considered for urgent warfarin reversal in LVAD recipients, particularly when rapid INR reduction or avoidance of large-volume plasma transfusion is clinically important. Treatment decisions should account for the indication, bleeding severity, and underlying thrombotic risk. TRIAL REGISTRATION: CRD42024573925.

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PubMed2026

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 × 10⁹ vg/eye), medium (3 × 10⁹ vg/eye), or high (1 × 10¹⁰ vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (≥100 vs <90 µV in controls at 10 cd·s/m²) and photopic b-wave amplitudes (49-66 vs 31-46 µV at 30 cd·s/m²) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

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PubMed2026

Complete Revascularization Guided by Functional Coronary Angiography in STEMI.

BACKGROUND: Complete coronary-artery revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the preferred strategy for identifying nonculprit lesions that warrant treatment remains uncertain. METHODS: In this international, randomized trial, we assigned patients with STEMI and multivessel disease in whom the culprit lesion had been successfully treated to undergo complete coronary-artery revascularization guided by functional coronary angiography (physiology-guided group) or by conventional angiography (angiography-guided group). The primary outcome was a composite of death from any cause, myocardial infarction, cerebrovascular accident (stroke or transient ischemic attack), or ischemia-driven revascularization, assessed in a time-to-event analysis. The primary safety outcome was a composite of contrast-associated acute kidney injury or major bleeding. RESULTS: A total of 1823 patients underwent randomization; 913 were assigned to the physiology-guided group and 910 assigned to the angiography-guided group. The median age of the patients was 66 years (interquartile range, 58 to 76), and 24% were women. At a median follow-up of 17.9 months, a primary-outcome event had occurred in 81 patients (8.9%) in the physiology-guided group and in 125 patients (13.7%) in the angiography-guided group (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.83; P<0.001). A primary-safety-outcome event occurred in 42 patients (4.6%) in the physiology-guided group and in 65 patients (7.1%) in the angiography-guided group (hazard ratio, 0.63; 95% CI, 0.43 to 0.93; P = 0.02). CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease, a strategy of complete coronary-artery revascularization guided by functional coronary angiography resulted in a lower risk of a primary-outcome event (death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization) than a strategy guided by conventional angiography. (Funded by the Italian Health Ministry and others; AIR-STEMI ClinicalTrials.gov number, NCT05818475.).

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PubMed2026

Unanticipated Effects of Parental Social Media Use: Guidance for Clinicians.

"Sharenting," the practice of parents posting photographs, videos, and information about their children on social media, has an ever-growing presence in modern society. However, researchers and the public are now recognizing the potential consequences of sharing, including creation of permanent digital footprints, strained familial relationships, and threats to children's safety. Despite this emerging evidence, no U.S. clinical or legal guidelines exist for parents on safe sharing. Visits with behavioral health providers and family physicians can serve as key points for intervention. This column aims to provide clinicians with a better understanding of sharenting and its potential effects on patients and families, guidance on discussing safe online sharing, and a tool for parents and other caregivers to use when deciding whether to post.

Humans↗

PubMed2026

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50 mg/day) or placebo for 12 weeks. The primary endpoint was point-prevalence abstinence at 12 weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3 years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12 weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p < 0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3 months (28% vs. 54%, p = 0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p = 0.07). Maintenance of abstinence at 6 months favoured naltrexone (22% vs. 8%, p = 0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5× ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63 ± 1.16 vs. 9.29 ± 1.78, p < 0.01) and OCDS-C score (6.35 ± 1.23 vs. 9.02 ± 1.86, p < 0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

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PubMed2026

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult↗

PubMed2026

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma.

PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC. METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint. RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo. CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

Adult↗

PubMed2026

ZrO₂@C-based colorimetric/photothermal dual-mode immunosensor coupled with a novel monoclonal antibody for quantification of Aspergillus ochraceus biomass.

Aspergillus ochraceus contaminates agricultural products and produces nephrotoxic, carcinogenic ochratoxin A (OTA), posing severe food safety hazards. A dual-signal lateral flow immunochromatographic assay (dLFIA) based on ZrO₂@C nanoprobes was established for quantitative detection of A. ochraceus biomass. A novel monoclonal antibody (mAb 4B4) was prepared as the capture antibody to immobilize A. ochraceus mycelial lysate antigen on the test line, and a rabbit polyclonal antibody (pAb G2801) as the detection antibody to modify ZrO₂@C composites (synthesized via UiO-66 pyrolysis) into 200 nm colorimetric/photothermal nanoprobes. This dLFIA achieved limits of detection of 0.164 μg/mL (colorimetric) and 0.517 μg/mL (photothermal). This efficient and reliable method allows quantitative analysis of A. ochraceus biomass, which is suitable for routine monitoring of fungal contamination in agro-food matrices.

Antibodies, Monoclonal↗