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PubMed2026

Effects of free-weight resistance training based on hexagonal barbell deadlift in older women: A 24-week randomized controlled trial.

PURPOSE: This randomized controlled trial examined effects of a 24-week hexagonal barbell deadlift (HBDL)-based free-weight resistance training program on body composition, trunk muscle function, and functional performance in older women. METHODS: Thirty-two women (67.6 ± 6.3 years) were randomly assigned to an HBDL group (DG, n = 16) or control group (CG, n = 16). DG trained twice weekly for 24 weeks under supervision. Primary outcomes were body composition and isokinetic trunk peak torque and average power at 60°/s and 120°/s. Secondary outcomes were isokinetic knee function, mobility, and maximal isotonic strength. Between-group differences after the intervention were examined by analysis of covariance (α = 0.05). RESULTS: After intervention, DG showed greater trunk lean mass (+0.4 kg vs. -0.2 kg, p = 0.006) than CG, and reductions in body fat percentage (-1.4% vs. +0.3%, p = 0.003), total fat mass (-1.1 kg vs. +0.3 kg, p = 0.013), and regional fat mass (trunk, gluteal, thigh; all p < 0.05). Trunk extensor peak torque at 60°/s (+26.0% vs. -6.3%, p < 0.001) and average power at 60°/s (+38.1% vs. -7.6%, p < 0.001) and 120°/s (+33.2% vs. +0.1%, p = 0.002) improved significantly. DG also showed better eyes-closed static balance and 6-min walk performance (both p < 0.05). Whole-body lean mass and lower-limb isokinetic strength did not differ between groups. Attendance was 89.6% with no adverse events. CONCLUSION: HBDL-based free-weight resistance training is a safe, feasible, and effective strategy to improve body composition, trunk extensor function, and mobility in older women.

Humans↗

PubMed2026

Persistent cloaca without vaginal-common channel fistula: A Case series characterizing a rare phenotype.

INTRODUCTION: Persistent cloaca occurs in approximately 1 in 25,000 live births. Among patients with cloaca, the absence of a vaginal connection to the common channel represents a rare phenotype with distinct anatomic and management considerations. We describe the urologic, gynecologic, and surgical characteristics of this patient subset. METHODS: We performed a retrospective analysis of a single-institution cohort of patients with persistent cloaca managed at a quaternary-care children's hospital between 2019 and 2025. Patients were eligible if they underwent primary cloacal repair by our multidisciplinary team and met all three diagnostic criteria for absent vaginal-common channel fistula: no hydrocolpos on imaging, no identified vaginal opening on cystoscopy or cloacagram, and no visible lumen between müllerian and cloacal structures identified intraoperatively. RESULTS: Of 51 patients who underwent primary repair, 6 (12%) met criteria for absent vaginal-common channel fistula. All met criteria for VACTEGRLS association. Common channel length ranged from 1.1 to 7.0 cm and urethral length from 0.5 to 2.2 cm. Urologic anomalies were nearly universal: five patients (83%) had a solitary functional kidney and four (67%) had vesicoureteral reflux. All underwent posterior sagittal anorectoplasty (PSARP) for rectal repair with the common channel repurposed as the neourethra. Five (83%) underwent diagnostic laparoscopy during which the müllerian structures were examined but left in situ. At last follow-up (median 17.5 months, range 4-35 months), three patients (50%) had volitional voiding and three (50%) required assisted bladder emptying via vesicostomy or Mitrofanoff. CONCLUSION: Persistent cloaca without a vaginal-common channel fistula represents a rare but clinically distinct phenotype characterized by severe urologic anomalies. Recognition of this phenotype is essential for surgical planning and long-term urologic and gynecologic surveillance. Because there was no connection between the vagina and the urinary tract, delaying management of the müllerian structures did not adversely affect the urinary tract.

Humans↗

PubMed2026

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

BACKGROUND: Patients undergoing acoustic neuroma (AN) surgery often experience postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. METHODS: In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were assigned to esketamine (n = 42) or placebo (n = 42). The esketamine cohort received a continuous intravenous infusion of esketamine at 0.2 mg·kg-1·h-1 during anesthesia, followed by 1 mg·kg-1 esketamine as an adjuvant in patient-controlled intravenous analgesia (PCIA). The placebo group received saline. The primary outcome was the incidence of depression on postoperative day (POD1), defined as a Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score > 7. RESULTS: Seventy-seven patients completed the study (39 in the esketamine group, 38 in the placebo group). Esketamine significantly reduced the incidence of depression at POD1 (7.7% versus 31.6%; relative risk 0.24, 95% CI: 0.08-0.80, p = 0.008) and POD3 (0.0% versus 15.8%, relative risk 0.00, 95% CI: 0.00-0.47, p = 0.031) compared with placebo. The incidences of anxiety on POD1 and 3 and sleep disturbances on POD1 were also significantly reduced (p < 0.05). Notably, no significant differences were observed between the two groups in terms of immune function, postoperative pain scores, or intraoperative morphine equivalent. Adverse events did not differ between the groups. CONCLUSION: Perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety, and improve sleep quality after AN surgery, without significant effects on early immune function or acute postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400084537.

Humans↗

PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗

PubMed2026

Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials.

BACKGROUND: To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. METHODS: Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4 h (AUC0-4h) after nebulised 99mTc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV1 (litres), 15 min post dose (95% confidence intervals [CI]: lower limit >-10%, upper limit >0%). Both studies assessed safety. RESULTS: In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC0-4h geometric mean ratio [90% CI]: 1.00 [0.99, 1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV1 at 15 min: -0.37% [HFA-152a] vs -0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [-3.61, 4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. CONCLUSION: HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.

Humans↗

PubMed2026

Efficacy and Safety of Bimagrumab in Adults With Obesity and Metabolic Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

AIMS: This study aims to systematically evaluate the efficacy of bimagrumab on body composition and glucose parameters in adults with obesity and metabolic dysfunction and its safety profile. METHODS: We searched MEDLINE, PubMed, Embase, and the Cochrane Library on April 20, 2026, for randomized controlled trials (RCTs) assessing bimagrumab treatment in adults with obesity, insulin resistance, or type 2 diabetes mellitus (T2DM). The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and meta-analyses of efficacy and safety data were conducted using R software. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system was used to assess the strength of evidence. The study was registered with PROSPERO (CRD420261377110). RESULTS: Of the 134 retrieved records, 4 RCTs (enrolling 268 participants) were included. The included population represented a broad spectrum of metabolic dysfunction, from obesity and nondiabetic insulin resistance to established T2DM. Compared with placebo, bimagrumab treatment significantly reduced total weight (mean difference [MD] -4.85 kg, 95% confidence interval [CI] -6.82 to -2.88), fat mass (-4.72 kg [-8.05 to -1.40]), and glycated haemoglobin (HbA1c) (-0.13% [-0.23 to -0.03]) and significantly increased total lean mass (1.66 kg [0.81 to 2.51]). However, bimagrumab led to an increase in low-density lipoprotein (LDL) concentrations of 0.47 mmol/L [0.03 to 0.91] and significantly increased incidences of discontinuation (risk ratio [RR] 5.75 [1.61 to 20.46]), muscle spasms (RR 10.44 [4.23 to 25.75]), and diarrhoea (RR 4.91 [2.38 to 10.11]). CONCLUSION: Bimagrumab effectively reversed adverse effects on body composition in obese individuals, resulting in significant fat reduction, increased skeletal muscle mass, and improved glycemic control, suggesting that bimagrumab is a promising new target for personalized metabolic therapy.

Humans↗

PubMed2026

Interactive gaming during inhalational induction of anesthesia reduces pediatric patient anxiety and improves induction compliance: A randomized controlled trial.

BACKGROUND: Preoperative anxiety affects up to 75% of pediatric surgical patients and is associated with adverse postoperative outcomes. Traditional anxiolytic strategies with premedication carry drawbacks including delayed recovery and paradoxical reactions, driving interest in non-pharmacologic alternatives. Audiovisual distraction represents one approach, encompassing passive methods (e.g. watching a video) and active modalities (e.g. interactive gaming). The Bedside Entertainment and Relaxation Theater (BERT) is a projection-based environment that enables audiovisual distraction during induction. Whether BERT-based interactive gaming reduces anxiety and improves induction compliance compared to standard perioperative care remains unknown. METHODS: This single-center RCT enrolled 74 pediatric patients aged 4 to 14 undergoing inhalational induction, randomized to standard care (SOC) or interactive gaming via BERT added to SOC during induction (BERT). The primary outcome was change in patient anxiety from baseline to induction, measured using the Modified Yale Preoperative Anxiety Scale (mYPAS). Secondary outcomes included caregiver anxiety, induction compliance, OR efficiency, opioid administration, and OR staff perceptions. RESULTS: Patients in the BERT group experienced significantly smaller increases in anxiety from baseline to induction than SOC (median mYPAS increase [IQR]: 0 [0 to 0] vs 10 [0 to 38], p < 0.001). Induction compliance improved, with lower Induction Compliance Checklist (ICC) scores indicating fewer induction-related disruptive behaviors than SOC (median: 0 vs 1, shift -1 [95% CI: -2 to 0]; p = 0.004). Caregiver anxiety increased less in the BERT group than SOC (mean STAI increase: 0.18 vs 1.89, difference - 1.7, [95% CI: -3.2 to -0.26]; p = 0.022). OR staff reported high acceptability, with 97% supporting continued use. No differences were observed in OR efficiency or opioid administration between groups. CONCLUSIONS: Interactive gaming via BERT attenuated increases in patient anxiety, improved induction compliance, and reduced the rise in caregiver anxiety without prolonging OR time. These findings support BERT as an effective, workflow-compatible anxiolytic strategy for pediatric inhalational induction.

Humans↗

PubMed2026

Higher versus Routine Intraoperative Blood Pressure Targets in Noncardiac Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis of Randomized Trials.

BACKGROUND: Observational studies consistently link intraoperative hypotension to adverse postoperative outcomes, leading guidelines to recommend maintaining mean arterial pressure 60 to 65 mmHg or greater during noncardiac surgery. Whether targeting higher intraoperative blood pressure values improves clinical outcomes remains uncertain. METHODS: The authors conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided search on PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Embase from inception to April 2026. Randomized trials comparing higher intraoperative blood pressure targets, either as fixed absolute thresholds or personalized to preoperative baseline, versus routine blood pressure management in adults undergoing elective noncardiac surgery with general anesthesia were included. Outcomes included in-hospital or 30-day mortality, postoperative delirium, acute kidney injury (AKI), 30-day major cardiovascular events, acute myocardial injury, stroke, length of stay, and intraoperative hypotension. RESULTS: Fifteen trials (15,603 patients) were included. Higher targets did not reduce AKI (risk ratio [RR], 0.95; 95% CI, 0.85 to 1.06; P = 0.36; I 2 = 16%) or acute myocardial injury (RR, 1.02; 95% CI, 0.94 to 1.12; P = 0.59; I 2 = 0%) compared with routine targets, with firm evidence from trial sequential analysis. Higher targets were associated with a significant reduction in postoperative delirium (RR, 0.73; 95% CI, 0.54 to 0.98; P = 0.04; I 2 = 26%), although trial sequential analysis indicated the cumulative evidence remained insufficient to draw firm conclusions. No significant effect was observed on in-hospital or 30-day mortality (RR, 1.00; 95% CI, 0.75 to 1.34; P = 1.00; I 2 = 0%); evidence on 30-day major cardiovascular events, stroke, and length of stay was similarly insufficient to draw firm conclusions. CONCLUSION: In adults undergoing elective noncardiac surgery, targeting higher intraoperative blood pressure values does not improve major postoperative outcomes compared with routine management. A potential reduction in postoperative delirium warrants confirmation in adequately powered trials.

Humans↗

PubMed2026

EffectS of Lifestyle Interventions in Older PEople With Obesity (Effective SLOPE): a Systematic Review With Network Meta-Analyses.

BACKGROUND/AIM: We conducted a systematic review with network meta-analyses (NMA) summarizing the effects and safety of lifestyle interventions containing nutrition (NUT; e.g., calorie restriction), exercise (EX; e.g., aerobic/resistance exercise) and behavior change interventions (BCI; e.g., behavioral therapy) on physical function, body composition, quality of life, psychosocial outcomes, health and adverse events in community-dwelling older adults with obesity. METHODS: We used the methodology proposed by Cochrane and searched six databases and one trial registry for eligible randomized controlled trials (RCTs; intervention duration ≥ 12 weeks) up to May 2022 with a full new search in MEDLINE and a re-assessment of previously identified eligible trial registry entries in October 2025. Random-effects NMA ((standardized) mean difference ((S)MD), 95% confidence intervals) were conducted if possible. RESULTS: We included 72 RCTs (n = 6716) for descriptive summaries and 54 RCTs (n = 4249) for NMA. NUT+EX+BCI improved physical function (performance batteries) compared to control (SMD 3.37 [1.76;4.97]; high certainty of evidence). NUT+EX+BCI may reduce body (MD -8.69 [-13.14;-4.25]) and fat mass (MD -6.58 [-10.44;-2.73]) while not negatively affecting fat-free mass (MD -1.38 [-3.52;0.76]) or bone mineral density (MD -0.01 [-0.05;0.02]) (evidence very uncertain). Other interventions (single/combined) may also be effective; however, effects were often imprecise. For psychosocial outcomes, quality of life, and health events, data were insufficient or too heterogeneous to derive clear results. CONCLUSION: The evidence suggests that NUT+EX+BCI interventions are most suitable for the management of obesity in older adults. Nevertheless, further RCTs-especially in frail populations and on patient-relevant outcomes-are needed.

Humans↗

PubMed2026

Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.

BACKGROUND: This randomized controlled trial examined whether short-term aerobic exercise provided additional clinical benefit over an active control in older inpatients with depression in geriatric psychiatry. METHODS: 100 patients (mean age 76 years) were randomized to 2-week supervised aerobic ergometer training (intervention group, IG) or a flexibility program (control group, CG), both delivered in addition to treatment as usual (TAU). Adherence, training exposure and adverse events were recorded to assess feasibility. The primary outcome was clinical improvement measured with the Clinical Global Impression of Change (CGI). Secondary outcomes included depressive symptom severity assessed by the Beck Depression Inventory-II (BDI-II) and clinician-rated Hamilton Rating Scale for Depression (HAMD), physical activity, 6-min walk test (6MWT) performance, and fluoxetine-equivalent antidepressant dose (FLX). RESULTS: Thirty-nine participants attended at least 80% of sessions, with lower adherence in the IG. Weekly training duration differed between groups (74.0 ± 31.9 vs. 95.0 ± 25.3 min/week, p = .003). CGI did not differ between groups (IG: MD -0.31, 95% CI -0.67 to 0.05; p = .069). Depressive symptom severity decreased over time in both groups (p < .001), without significant between-group differences for HAMD (MD -0.22, 95% CI -2.55 to 2.12) or BDI-II (MD -0.62, 95% CI -3.68 to 2.45). 6MWT and FLX increased over time (both p < .001), without group differences (6MWT: MD -1.08 m, 95% CI -20.04 to 17.89; FLX: MD 5.69 mg/day, 95% CI -2.40 to 13.77). CONCLUSION: Short-term aerobic exercise was deliverable, but showed no additional clinical benefit over low-intensity flexibility during TAU. Further research should determine dose, duration and adherence for clinically relevant effects.

Humans↗

PubMed2026

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased μ-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety‑four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5 mg, PCIA 0.55 mg/kg) or sufentanil group (loading dose 10 μg, PCIA 3 μg/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9 ± 3.1 versus 177.5 ± 3.9, p < 0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3 days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p > 0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p = 0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans↗

PubMed2025

Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p < 0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p < 0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗

PubMed2026

Transvalvular Flow Rate is Associated With Mortality Rate and Lifetime Loss in Aortic Valve Stenosis: A Meta-Analysis of Reconstructed Time-to-Event Data.

Low-flow states are associated with adverse outcomes in aortic stenosis (AS), but the prognostic value of transvalvular flow rate (TFR) has not been consistently established across studies. This study is a systematic review and meta-analysis of reconstructed time-to-event data was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed/MEDLINE, EMBASE, and Cochrane Library were searched for studies (published by November 14, 2025) comparing low versus normal TFR in AS. Data were collected from Kaplan-Meier curves. The primary endpoint was all-cause mortality. Survival was assessed using pooled Kaplan-Meier curves, Cox regression, flexible parametric survival models, and restricted mean survival time (RMST) analysis. A total of 9 studies including 6,494 patients were analyzed; 2,575 (39.7%) had low TFR. At 8 years of follow-up, estimated survival was 34.1% (95% confidence interval [CI] 24.7% to 47%) in the low-TFR group and 63% (95% CI 58.9% to 67.4%) in the normal-TFR group. Low TFR was associated with higher all-cause mortality (hazard ratio 1.59, 95% CI 1.45 to 1.74, p < 0.001). We observed a progressively greater hazard over time, with the hazard ratio approaching 1.9 by 8 years. At 8 years, RMST in the normal-TFR group was 7.37 years (95% CI 7.21 to 7.53 years) versus 5.07 years (95% CI 4.91 to 5.23 years) in the low-TFR group, representing a lifetime loss of 2.3 years in the low-TFR group (ΔRMST -2.30 years, 95% CI -2.53 to -2.07 years, p < 0.001). In patients with AS, low TFR is associated with significantly higher mortality and lifetime loss. These findings support TFR as a clinically meaningful marker for risk stratification in AS.

Aortic Valve Stenosis↗

PubMed2026

Penpulimab and Gemcitabine With or Without Anlotinib in Metastatic Nasopharyngeal Carcinoma: A Randomized, Open-Label, Multicenter Phase 2 Study.

This prospective exploratory phase 2 study employed a three-cohort, two-phase design to evaluate the potential of anlotinib as a substitute for cisplatin in gemcitabine-penpulimab combinations for metastatic nasopharyngeal carcinoma (NPC) patients who were previously treated with cisplatin-based chemoradiotherapy. Patients enrolled in the study were randomized in a 1:1:1 ratio during the lead-in phase to one of three treatment arms: gemcitabine, cisplatin, penpulimab, and anlotinib (GP-PA, n = 8); gemcitabine, cisplatin, and penpulimab (GP-P, n = 6); or gemcitabine, penpulimab, and anlotinib (GAP, n = 6). The expansion phase enriched the optimal cohort, with stratification based on PD-L1 expression. The primary endpoints were safety and objective response rate (ORR), while the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). In the lead-in phase, grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 87.5% (GP-PA), 100% (GP-P), and 66.7% (GAP) patients, predominantly hematologic toxicities. ORR/DCR were 62.5%/87.5% (GP-PA), 83.3%/100% (GP-P), and 100%/100% (GAP). At median 20.2-month follow-up, median PFS/OS were 4.1/18.4 months for GP-PA and not reached for GP-P/GAP. In the expansion phase, a total of 14 patients received GAP, with an ORR of 93.3% and grade ≥ 3 TEAEs in 71.4% of patients. At data cut-off point, the median PFS had not been reached, and the 12-month PFS and OS rates were 53.8% and 78.6%, respectively. The GAP regimen demonstrated a favorable safety and efficacy profile, compared to the GP-PA and GP-P regimens in patients with metastatic NPC. These findings suggest that substituting cisplatin with anlotinib may offer a viable therapeutic strategy for this patient population.

Humans↗

PubMed2026

Safety and immunogenicity of an mRNA COVID-19 vaccine administered to adults: A phase 2, randomized, active-controlled trial.

We conducted a phase 2, randomized, active-controlled, observer-blind study (NCT05960097) among healthy adults ≥18 y of age who completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months earlier. Participants were randomized (1:1:1:1:1) to either receive an investigational bivalent mRNA COVID-19 vaccine encoding ancestral D614G and Omicron BA.4-5 spike proteins (CV0701 mRNA vaccine) at one of three dose levels, an investigational monovalent mRNA COVID-19 vaccine encoding the Omicron BA.4-5 spike protein (CV0601 mRNA vaccine), or a licensed Original Wuhan/Omicron BA.4-5 bivalent mRNA COVID-19 vaccine. The primary objectives were to evaluate reactogenicity, safety and immunogenicity post-vaccination. Secondary and tertiary objectives were to further evaluate humoral and cell-mediated immunity post-vaccination. In total, 425 participants were vaccinated and 381 were included in the Day 29 per-protocol immunogenicity analysis. Most solicited events were mild to moderate. No vaccine-related serious adverse events or myocarditis/pericarditis cases were reported. For the CV0701 mRNA vaccine, a dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4-5 was observed. Neutralizing titers against ancestral D614G and Omicron BA.4-5 declined by Days 91 and 181, but remained above baseline. Similar immune responses were observed for the CV0601 mRNA vaccine. At Day 8, CD4+ T cells (Th1 profile) increased in all study groups and CD8+ T cells increased in all study groups, except the lowest CV0701 dose group. The CV0701 and CV0601 mRNA vaccines elicited robust humoral and cellular immunity with an acceptable safety profile, comparable to a licensed, bivalent mRNA vaccine. Clinical Trial Registration EU CT number: 2023-504596-25-00 ClinicalTrials.gov: NCT05960097.

Humans↗

PubMed2026

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 ≥1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗