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Vesicoureteral reflux and anorectal malformations.

BACKGROUND: Renal and urinary tract anomalies are frequently associated with anorectal malformations (ARMs) and may adversely affect long-term renal outcomes, if not detected early. However, reliable clinical predictors for significant urologic abnormalities across different ARM phenotypes remain poorly defined. OBJECTIVE: To determine the prevalence and grade distribution of vesicoureteric reflux (VUR) in neonates with ARMs, and to explore its association with renal and urinary tract anomalies, the complexity of the ARM phenotype, and other factors are associated with high-grade VUR. METHODS: In this retrospective cross-sectional study, medical records of 64 neonates diagnosed with ARMs and managed at a tertiary children's hospital between 2018 and 2025 were reviewed. All patients underwent renal and urinary tract ultrasonography. Voiding cystourethrography (VCUG) was performed for all neonates according to our institutional protocol, regardless of ultrasound findings or ARM phenotype. Demographic characteristics, ARM phenotype (less-complex vs. complex), urologic findings, urinary tract infection (UTI) history, and associated anomalies were analyzed. Multivariable logistic regression models were used to identify independent predictors of complex ARM phenotype and high-grade VUR. RESULTS: The cohort consisted of 64 neonates (75% male) with a mean gestational age of 37.36 ± 1.83 weeks and a mean birth weight of 2940 ± 601 g. Renal and urinary tract anomalies were common, with hydronephrosis observed in 48.4%, VUR of any grade in 39.1% and hydroureter in 35.9%,of patients. High-grade VUR was identified in 21.9% of patients, and a documented history of UTI was present in 18.8% of the entire cohort. In multivariable analyses, birth weight, presence of VUR, and UTI history were not independently associated with complex ARM phenotype. Additionally, no demographic or clinical variables reliably predicted high-grade VUR. The predictive performance of the regression model for high-grade VUR was limited (AUC = 0.60). CONCLUSION: Renal and urinary tract anomalies are highly prevalent among neonates with ARMs, with VUR representing a prominent finding. The lack of robust clinical predictors for complex ARM phenotype or high-grade VUR underscores the limitations of selective screening strategies and supports the role of comprehensive urologic evaluation in neonates with ARM, regardless of anatomic subtype.

Humans

Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group &#xd7; time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group &#xd7; time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

Humans

Intensive glycemic control in adults aged 80&#xa0;years and older: A randomized trial evaluating diabetes complications and competing mortality.

AIMS: To evaluate whether intensive glycemic control reduces microvascular or macrovascular events compared with conservative glycemic targets in independently ambulatory adults aged 80&#xa0;years or older with type 2 diabetes. METHODS: We conducted a prospective, randomized, open-label, single-center trial enrolling independently ambulatory adults aged&#xa0;&#x2265;&#xa0;80&#xa0;years with type 2 diabetes. Participants were assigned (1:1) to an intensive glycemic target (HbA1c&#xa0;<&#xa0;7&#xa0;%) or a conservative target (HbA1c&#xa0;<&#xa0;9&#xa0;%) and followed for 5&#xa0;years. Primary outcomes were composite microvascular and macrovascular events. Analyses were done by intention to treat. Cause-specific Cox models and Fine-Gray subdistribution hazard models were used to account for all-cause mortality as a competing event. This trial is registered with ClinicalTrials.gov, NCT00850798. FINDINGS: 206 participants were randomly assigned to intensive (n&#xa0;=&#xa0;102) or conservative (n&#xa0;=&#xa0;104) treatment. At 5&#xa0;years, mean HbA1c was lower in the intensive group than in the conservative group (7&#xb7;42&#xa0;% vs 8&#xb7;21&#xa0;%; p&#xa0;=&#xa0;0&#xb7;005). Intensive therapy did not reduce microvascular events (hazard ratio [HR] 1&#xb7;24, 95&#xa0;% CI 0&#xb7;76-2&#xb7;04) or macrovascular events (HR 1&#xb7;02, 0&#xb7;36-2&#xb7;92). Competing risk analyses showed no reduction in cumulative incidence of vascular outcomes (subdistribution HR approximately 1&#xb7;0 for both). The cumulative incidence of death exceeded that of vascular events, indicating that many participants died before potential glycemic benefits could be realized. Severe hypoglycemia requiring hospitalization was more frequent with intensive therapy (7 vs 1 event). INTERPRETATION: In adults aged 80&#xa0;years or older with type 2 diabetes, intensive glycaemic control improved glycaemic levels but did not reduce vascular events and increased the risk of severe hypoglycaemia. High competing mortality substantially limits the potential long-term benefit of intensive treatment, supporting conservative and individualized glycemic targets in very old adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00850798.

Aged, 80 and over

Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cognitive-behavioral interventions (CBIs) delivered by nonspecialist providers (NSPs) on perinatal depressive (PND) and anxiety symptoms, and to narratively synthesize their implementation processes and reported implementation outcomes, including acceptability, feasibility, fidelity, cost, and sustainability. METHODS: We systematically searched eight databases from inception to April 8, 2025. Eligible studies were randomised controlled trials (RCTs) assessing CBIs delivered by NSPs for PND and/or anxiety. Two reviewers independently screened, extracted, and assessed trials. Meta-analyses employed random-effects models, with subgroup, sensitivity, meta-regression, and publication bias analyses conducted in Stata 18.0. Implementation processes and outcomes were reported as frequencies or percentages across trials. RESULTS: A total of 47 trials (11, 357 participants) were included in the systematic review, of which 37 trials (8,709 participants) were included for meta-analyses. CBIs were conducted in 12 countries. Nurses and midwives delivered 45% of CBIs. CBIs were associated with reduced PND post-intervention compared with control conditions (standardized mean difference [SMD] -0.49, 95% CI -0.63 to -0.35; I&#xb2; = 86.8%). Limited evidence from four trials suggested a small sustained effect at 12 months (SMD -0.14, 95% CI -0.27 to -0.02; I&#xb2; = 26.4%). Reductions in anxiety symptoms were observed immediately post-intervention (SMD, -0.45, 95% CI -0.65 to -0.25; I&#xb2;=81%), but evidence for longer-term effects was limited. Subgroup analyses confirmed consistent effects across diverse settings, populations, and intervention characteristics. Reporting of implementation processes (e.g., training, supervision, fidelity) was limited, with only 23.4% of trials assessing fidelity and 10.6% evaluating costs. CONCLUSIONS: NSP-delivered CBIs showed beneficial effects on PND and anxiety, with generally encouraging evidence for acceptability and feasibility. However, evidence for sustained effects beyond the immediate post-intervention period remains limited. Future studies should strengthen long-term follow-up and improve reporting of implementation processes and outcomes, particularly in rural and adolescent perinatal populations, to inform scalable and equitable task-sharing models.

Humans

[A case of bilateral open-lip schizencephaly with West syndrome due to variant of PAFAH1B1 gene and literature review].

OBJECTIVE: To report the clinical manifestations, genetic features, diagnosis, treatment, and prognosis of a child with bilateral open-lip schizencephaly complicated by West syndrome due to a variant of PAFAH1B1 gene, and review the relevant literature. METHODS: Clinical data of a 4-month-old boy were retrospectively analyzed, and 35 previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of Gansu Provincial People's Hospital (Ethics No.: 2025-871). RESULTS: The 4-month-old boy presented with clustered flexor spasms, hypsarrhythmia on electroencephalography, and developmental regression. Brain magnetic resonance imaging revealed bilateral pachygyria, schizencephaly, and dysgenesis of the corpus callosum. Trio whole-exome sequencing identified a de novo heterozygous NM_000430.4: c.703_704delAG (p.Glu235Metfs*20) frameshift variant in the PAFAH1B1 gene. Sanger sequencing confirmed that neither parent carried this variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant has met the criteria for PVS1+PS2_Moderate+PM2_Supporting, and was classified as pathogenic. After treatment with adrenocorticotropic hormone combined with vigabatrin and other antiseizure medications, the epileptic spasms were controlled and the electroencephalographic abnormalities had improved. However, global developmental delay persisted at the 12-month follow-up. Analysis of the present case and 35 previously reported cases showed that PAFAH1B1-related phenotypes were highly consistent, mainly including infantile spasms (28/36), developmental delay/intellectual disability (29/36), and abnormal brain MRI findings (30/36), predominantly cortical malformations. The reported variant types included deletions, frameshift variants, nonsense variants, missense variants, and splice-site variants. CONCLUSION: PAFAH1B1 gene variants are an important cause for cortical malformations, including schizencephaly, and may lead to secondary West syndrome. This study has systematically summarized the genotypic and phenotypic features of bilateral open-lip schizencephaly complicated by West syndrome associated with a frameshift variant of the PAFAH1B1 gene. For infants with epileptic spasms or early-onset epilepsy accompanied by structural brain abnormalities, early genetic evaluation should be performed, and antiseizure treatment should be integrated with neurodevelopmental rehabilitation to facilitate long-term management.

Humans

Effectiveness of Internet-Delivered Cognitive Behavioural Therapy (ICBT) in Improving Weight-Loss and Psychosocial Well-Being Among Adults With High BMI: A Systematic Review.

AIM: To examine the effectiveness of Internet-delivered Cognitive Behaviour Therapy (ICBT) in improving psychosocial well-being and promoting weight-loss in adults &#x2265;&#x2009;18&#x2009;years with BMI &#x2265;&#x2009;25&#x2009;kg/m2. BACKGROUND: Global obesity engenders significant physical and psychosocial health consequences. Second-wave ICBT focused on restructuring negative thoughts and behaviours has been explored as a potential intervention for elevated BMI and mental health concerns, but its effectiveness remains to be fully established, making further evaluation essential. METHODS AND DATA SOURCES: Eight databases were searched from inception to January 2025 for randomised controlled trials (RCTs), including participants &#x2265;&#x2009;18&#x2009;years with BMI &#x2265;&#x2009;25&#x2009;kg/m2 and second-wave ICBT evaluating BMI, weight, depression, eating behaviours, and self-esteem. This review followed PRISMA 2020. Study quality was assessed using the Cochrane Risk of Bias (ROB 2) and GRADE. Data were extracted using a modified Cochrane form. Random-effects meta-analysis calculated Standardised Mean Differences (SMD) with 95% confidence intervals, with subgroup analyses exploring heterogeneity. RESULTS: Nine trials with 2278 participants were included. Significant improvements were seen in BMI, weight, and depressive symptoms while self-esteem effects were small and non-significant. Compared with passive controls, ICBT showed greater improvements in BMI and weight, whereas differences versus active control were smaller and inconsistent. Face-to-face CBT demonstrated superior outcomes for depression and self-esteem. Male-tailored interventions showed greater improvements. Shorter programmes yielded larger short-term weight loss, while longer programmes supported more sustained effects. Narrative synthesis indicated improvements in emotional and external eating, with increased mindful and restrictive eating behaviours. CONCLUSION: ICBT improved weight, BMI, and depressive symptoms, with limited evidence for self-esteem. Male-tailored interventions and longer programmes may enhance sustainable outcomes. IMPACT: Future ICBT programs should integrate strategies targeting sustainable weight loss and psychosocial well-being to support long-term outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or members of the public were not involved, as this study synthesised previously published data. TRIAL REGISTRATION: PROSPERO registration number: CRD42024497961.

Humans

Effects of single-injection vs. continuous brachial plexus blocks for shoulder surgeries on patient-reported outcomes: a systematic review and meta-analysis with trial sequential analysis of randomised controlled trials.

INTRODUCTION: Single-injection and continuous brachial plexus block techniques are used widely for postoperative analgesia in patients undergoing shoulder surgery. Although patient-reported outcomes are described in individual studies, their effects have not been synthesised comprehensively using a patient-centred framework. We sought to compare the effects of single-injection vs. continuous brachial plexus block techniques on patient-reported outcomes in adult patients following elective shoulder surgery. METHODS: Databases were searched from inception to October 2025 and randomised controlled trials reporting patient-reported outcomes were included. Co-primary outcomes were postoperative patient-reported pain intensity at rest and during movement at 12&#x2009;h, 24&#x2009;h and 48&#x2009;h post-surgery. Secondary outcomes included nausea and vomiting; sleep quality; patient satisfaction; opioid requests; and functional scores. Random-effects meta-analysis and trial sequential analysis were performed, with risk of bias and quality of patient-reported outcome reporting assessed. RESULTS: Twenty randomised controlled trials that included 1198 patients were analysed. Continuous brachial plexus blocks were associated with lower pain at rest at 12&#x2009;h, 24&#x2009;h and 48&#x2009;h, with mean differences (MD) of -1.96 (95%CI -2.81 to -1.11, p&#x2009;<&#x2009;0.001), -1.66 (95%CI -2.27 to -1.05, p&#x2009;<&#x2009;0.001) and&#x2009;-&#x2009;1.18 (95%CI -1.84 to -0.53, p&#x2009;<&#x2009;0.001), respectively. Pain on movement could only be pooled at 24&#x2009;h and 48&#x2009;h and showed MD -2.04 (95%CI -4.26-0.19, p&#x2009;=&#x2009;0.07) and&#x2009;-&#x2009;1.30 (95%CI -3.67-1.07, p&#x2009;=&#x2009;0.28) respectively. The co-primary outcomes approached or exceeded the predefined minimal clinically important difference for pain scores after shoulder surgery, in favour of continuous techniques. DISCUSSION: Continuous brachial plexus blocks are associated with better pain at rest and other patient-centred outcomes following shoulder surgery, while effects on dynamic pain and long-term functional recovery remain uncertain.

Humans

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000&#x2009;mg for 12&#x2009;weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p&#x2009;&#x2265;&#x2009;0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400&#x2009;mg (-2.6&#x2009;kg), 600&#x2009;mg (-1.2&#x2009;kg), and 1,000&#x2009;mg groups (-3.1&#x2009;kg). Compared with placebo, the 1,000&#x2009;mg dose resulted in the largest reductions in body weight (mean difference, -2.30&#x2009;kg; p&#x2009;=&#x2009;0.01) and BMI (mean difference, -0.85&#x2009;kg/m2; p&#x2009;=&#x2009;0.02). The 1,000&#x2009;mg dose showed preliminary efficacy for reducing body weight and BMI over 12&#x2009;weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans

Efficacy and safety of thulium fiber laser versus conventional holmium:YAG laser in anatomical endoscopic enucleation of the prostate: a systematic review and pairwise meta-analysis.

PURPOSE: Anatomical endoscopic enucleation is an established treatment for benign prostatic obstruction. Whether thulium fiber laser enucleation (ThuFLEP) improves outcomes over conventional holmium:YAG laser enucleation (HoLEP) remains uncertain. We compared the efficacy and safety of ThuFLEP versus non-MOSES-modulated HoLEP. METHODS: We performed a PRISMA-compliant systematic review and pairwise meta-analysis of randomised and comparative cohort studies comparing ThuFLEP and conventional HoLEP in adult men. Six databases were searched. Outcomes included International Prostate Symptom Score (IPSS), IPSS quality-of-life score, maximum urinary flow rate (Qmax), post-void residual volume, hospital stay, and complications. Risk of bias and certainty of evidence were assessed with RoB 2/ROBINS-I and GRADE. RESULTS: Seven non-overlapping comparative populations in eight publications included 3,509 patients. ThuFLEP was associated with a small statistically significant reduction in IPSS at 3&#xa0;months (mean difference [MD] -1.04 points, 95% confidence interval [CI] -1.81 to -0.28) of uncertain clinical relevance. Qmax differences were small and directionally inconsistent across follow-up (favouring HoLEP at 3&#xa0;months and ThuFLEP at 6 and 12&#xa0;months) and derived mainly from retrospective cohorts, with neutral randomised subgroups. Stress and urge urinary incontinence were less frequent overall (RR 0.75, 95% CI 0.58 to 0.96, and RR 0.39, 95% CI 0.22 to 0.68), but both estimates depended on one large registry cohort and were not robust to its exclusion. Most other complications and hospital stay showed no clear between-group difference. Limitations include few studies per outcome, heterogeneity, sparse safety events, inconsistent prostate-specific antigen reporting, and mostly low/very low certainty evidence. CONCLUSION: ThuFLEP and conventional HoLEP are clinically comparable with no definitive superiority of either laser. Platform selection should be individualised according to surgeon expertise, institutional resources, and patient characteristics. Future trials should standardise cost-effectiveness outcomes and investigate whether the distinct laser-tissue interactions impact adenoma clearance, PSA reduction, enucleation completeness, and long-term durability.

Humans

Oblique Lateral Interbody Fusion With Lateral Vertebral Screw Fixation Versus Transforaminal Lumbar Interbody Fusion for Severe Lumbar Stenosis: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The benefits of oblique lateral interbody fusion (OLIF) vs transforaminal lumbar interbody fusion (TLIF) in severe lumbar stenosis (Schizas C/D) remain uncertain. This randomized trial compared clinical, radiographic, and safety outcomes of OLIF and TLIF. METHODS: From November 2018 to December 2021, a prospective, multicenter, randomized controlled trial enrolled 260 adults with single-level severe stenosis and instability. In total, 224 patients were randomized to OLIF or TLIF. Prespecified outcomes followed consolidated standards of reporting trials. Primary outcomes were visual analog scale back/leg pain and Oswestry Disability Index (ODI), with minimal clinically important difference thresholds of ODI &#x2265;12-13 points or &#x2265;30% improvement, and visual analog scale &#x2265;1.5-2.0 points. Radiographic measures included disc height, lumbar and segmental lordosis, and canal cross-sectional area (CSA). Complications were recorded. Ethics approval was obtained from the institutional review board, the trial was registered with ISRCTN.com , and all patients provided written informed consent. RESULTS: In total, 224 patients were randomized, 5 were lost to follow-up (TLIF n = 2, OLIF n = 3). Baseline features were comparable. OLIF was associated with shorter operative time, less blood loss, earlier ambulation, and shorter hospital stay (all P < .05). Both groups achieved significant, clinically meaningful improvements. OLIF showed greater back pain reduction at 3-6 months and 2 years ( P < .05) and superior ODI improvement at 3 and 6 months ( P < .001), although long-term ODI scores were similar. Radiographically, OLIF provided greater restoration of disc height and segmental lordosis (all P < .001) and demonstrated progressive CSA increase (dynamic decompression), whereas TLIF achieved immediate, sustained CSA enlargement. Fusion rates were comparable at 1-2 years. Complication rates were low and similar (7.3% TLIF vs 5.5% OLIF), with most OLIF-specific events transient. CONCLUSION: Both OLIF and TLIF yield improvements in severe lumbar stenosis. OLIF offers perioperative advantages, earlier functional recovery, radiographic restoration, and dynamic canal remodeling, supporting its role as an equivalent alternative for lumbar spinal stenosis with some secondary advantages.

Humans

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid &#x3b1;-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient &#x2264;66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score &#x2265;7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article

Temporal shifts in gyrA mutation types and sublineage replacement in ST11 Salmonella enterica&#xa0;serovar Enteritidis over a decade (2014-2023): A genomic epidemiological study in Guangxi, China.

The overuse or abuse of antibiotics drives the global health threat of antimicrobial resistance. Although bans on certain veterinary antibiotics, such as colistin, have proven effective, the impact of fluoroquinolone stewardship on the evolution of the foodborne pathogen Salmonella enterica serovar Enteritidis (S. Enteritidis) remains unclear. Here, we conducted a decade-long (2014-2023) retrospective longitudinal genomic epidemiological analysis of 441&#xa0;ST11 S. Enteritidis isolates from Guangxi, China, alongside a global reference dataset of 4297 genomes. Our aim was to elucidate the effect of real-world antibiotic stewardship on the shift of gyrA point mutations and lineage distribution. Surveillance identified three global epidemic clade sublineages (GEC-L2, L3, L4), with the multidrug-resistant GEC-L4 (i.e., GC-c or MMC2), characterized by the gyrA mutation with amino acid substitution D87Y, being domestically dominant (70.07%, 309/441). Following China's 2016 ban on the veterinary use of critical fluoroquinolones, the proportion of the highly resistant GEC-L4 sublineage decreased continuously (from 86.84% in 2017 to 56.00% in 2023), while the less resistant GEC-L3 sublineage (i.e., GC-b or MMC1), mainly characterized by gyrA D87G, increased simultaneously (from 13.16% to 44.00%). This phenomenon might be attributed to the fact that the GEC-L4 sublineage exhibited a higher fitness cost compared with the GEC-L3 sublineage, as confirmed by the competition assay. A Random Forest Model validated that the gyrA mutation with amino acid substitution&#xa0;D87Y was the paramount feature for these sublineages' identification. In contrast, global data showed a continuous increase in gyrA mutations (from 8.63% in 2006 to 68.85% in 2024), primarily D87Y (from 1.44% to 31.15%) and D87N (from 4.32% to 22.95%), correlating with rising average fluoroquinolone consumption. This study provides direct genomic evidence that national-level antibiotic stewardship can drive the replacement of highly resistant sublineages with moderately resistant ones. These findings offer crucial scientific evidence for evaluating the impact of antibiotic management policies and inform strategies for the rational use of antimicrobials.

China

Sex modifies the association of high-altitude hypoxia with poor sleep quality and depression in school-age children and adolescents.

BACKGROUND: While chronic exposure to high-altitude hypoxia is known to impair sleep and mental health, whether these effects are sex-dependent remains unclear. This study addresses a critical gap by investigating how sex modifies the association between high-altitude hypoxia and risks of poor sleep quality, depressive symptoms, and their co-occurrence in children and adolescents. METHODS: In this cross-sectional study (March-May 2024), we enrolled 1,345 long-term residents of the Shannan Tibet Autonomous Prefecture (altitude: 3,650-4,800&#xa0;m) and 2,909 age-matched controls from low-altitude plains (Anhui Province, China). Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Montgomery-Asberg Depression Rating Scale (MADRS), respectively. Sex-stratified analyses and interaction metrics (RERI/AP/SI) were employed to evaluate additive and multiplicative effects. RESULTS: High-altitude residents exhibited significantly higher prevalence of poor sleep (24.2% vs. 18.7%, P&#x2009;<&#x2009;0.001), depression (23.6% vs. 15.3%, P&#x2009;<&#x2009;0.001), and their co-occurrence (12.6% vs. 8.6%, P&#x2009;<&#x2009;0.001) compared to low-altitude controls. A significant negative additive interaction (RERI&#x2009;=&#x2009;-&#x2009;0.78, 95% CI: -1.35 to -&#x2009;0.3; P&#x2009;<&#x2009;0.001) indicated that sex modifies the altitude-outcome association. Specifically: (1) high-altitude residence significantly increased poor sleep risk in males (OR&#x2009;=&#x2009;1.60, 95% CI: 1.26-2.03) but not in females (OR&#x2009;=&#x2009;1.39, 95% CI: 1.07-1.79); and (2) the expected female predominance in poor sleep observed in the plain region (OR&#x2009;=&#x2009;1.452, 95% CI: 1.191-1.769) disappeared in the plateau region (OR&#x2009;=&#x2009;0.865, 95% CI: 0.667-1.121). Similar patterns were independently replicated for depressive symptoms. These findings confirm that high-altitude exposure differentially increases risk in males rather than protecting females. CONCLUSION: Males show marked vulnerability to high-altitude-associated sleep and mood impairments, while females demonstrate resilience. Sex-tailored interventions for high-altitude populations, particularly targeting male adolescents, are urgently needed.

Humans

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 &#x2264;42&#xb0;C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (&#x394;NRS) 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 (&#x2265;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 &#x2264;42&#xb0;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

Physician-Modified Fenestrated Stent-Grafts Planned Using Three-Dimensional Techniques for Complex Aortic Pathology: A Systematic Review and Meta-Analysis.

BACKGROUND: Complex aortic pathology involving the visceral arteries remains a significant therapeutic challenge. Open repair is associated with considerable perioperative risk, particularly in patients with multiple comorbidities, while standard endovascular aneurysm repair (EVAR) is often not feasible because of inadequate proximal sealing zones. Fenestrated and branched endovascular repair (F/BEVAR) represents an established treatment strategy; however, the use of custom-made devices is limited by manufacturing time and availability. Physician-modified stent grafts (PMSGs) have therefore emerged as a pragmatic alternative. Three-dimensional planning techniques have been increasingly used to facilitate accurate graft modification. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of PMSG procedures planned with three-dimensional techniques. Technical success, target vessel patency, early mortality, endoleak occurrence, and reintervention rates were analyzed. METHODS: A systematic search was conducted in the PubMed/MEDLINE and Embase databases. Studies describing the use of physician-modified fenestrated stent grafts planned with three-dimensional tools were included. Meta-analyses were performed using a random-effects model with restricted maximum likelihood estimation. A logit transformation was used for the analysis of proportions. RESULTS: The analysis included five studies involving 172 patients. The estimated weighted mean follow-up duration was 14.9 months. The overall technical success rate was 92.9% (95% confidence interval [CI]: 84.5-96.9%), with low-to-moderate heterogeneity. Target vessel patency was 96.9% (95% CI: 93.6-98.5%). Early mortality was 5.5% (95% CI: 2.1-13.3%). The incidence of endoleaks was 13.3% (95% CI: 5.8-27.4%), with significant heterogeneity among studies. Reinterventions were reported in 6.6% of patients (95% CI: 2.3-17.5%). CONCLUSION: The results indicate that PMSG procedures planned with three-dimensional techniques are associated with a high rate of technical success and preserved patency of target vessels in patients with complex aortic pathology. The observed variability in endoleak and reintervention rates likely reflects differences in anatomical complexity and patient selection among studies. Further prospective studies are needed to confirm long-term outcomes.

Humans

The relationship between food intake and outdoor temperature in a longitudinal study: a public health perspective in the context of global warming.

BACKGROUND: Climate change affects human health and nutrition. Rising temperatures may significantly impact diets, but research on their influence on dietary habits in large populations remains limited. OBJECTIVES: We aimed to study the link between outdoor temperature and energy-adjusted food consumption across profiles in a longitudinal study. METHODS: This study included 100,851 participants from the NutriNet-Sant&#xe9; study (2009-2023) with 1,716,046 24-h dietary records linked to daily maximum outdoor temperature at the residence, from the nearest M&#xe9;t&#xe9;o-France station. Associations were analyzed using linear mixed models with interactions tested for sex and 6 socioeconomic profiles (employees, privileged, intermediate, young, disadvantaged, and retirees) derived from clustering. RESULTS: Across all subgroups, higher outdoor temperature was associated with higher consumption of fruits, vegetables, processed meats, sweet products, water, alcoholic beverages, and sugar-sweetened beverages, whereas consumption of red meat, pulses, and dairy products decreased. From 25&#xb0;C to 35&#xb0;C, the increase in alcohol consumption with temperature was more pronounced in males {150 g/d [95% confidence interval (CI): 147 g/d, 153 g/d] to 166 g/d [95% CI: 162 g/d, 171 g/d], +11%} than in females [101 g/d (95% CI: 98 g/d, 103 g/d) to 107 g/d (95% CI: 104 g/d, 109 g/d), +6%]. Across socioeconomic profiles, changes shared similar directions, but some trends were more marked, notably for alcoholic beverages among employees (95% CI: 114 g/d, 130 g/d; +14%) and sugar-sweetened beverages in young (95% CI: 56 g/d, 72 g/d; +29%). Consumption of fruits increased more modestly in the young (95% CI: 227 g/d, 248 g/d; +9%) than in employees (95% CI: 194 g/d, 227 g/d; +17%). These changes, although variable in magnitude, were not accompanied by substantial modifications in energy intake or overall diet quality scores. CONCLUSIONS: These results emphasize the importance of targeted prevention messages when temperatures exceed 25&#xb0;C, especially concerning alcoholic and sugar-sweetened beverages, and offer insight into potential long-term food consumption patterns (beyond seasonal changes) in the context of global warming.

Humans

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1&#xa0;m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p&#x2009;<&#x2009;0.001) and stance ratio (p&#x2009;=&#x2009;0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p&#x2009;<&#x2009;0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p&#x2009;<&#x2009;0.001) and foot (p&#x2009;=&#x2009;0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These&#xa0;results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Humans