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Associations of red blood cell fatty acids with personality traits: 10-year follow-up in the Kibbutzim Family Study (KFS).

BACKGROUND: The ability of hostility and type-A personality to predict cardiovascular outcomes makes understanding antecedents of these personality traits an important public health objective. OBJECTIVES: This study aimed to examine whether blood-measured fatty acids (the exposure) are associated with hostility and type-A personality (the outcome), while accounting for lifestyle, sociodemographic factors, and polygenic background. METHODS: Personality traits, sociodemographic, and lifestyle data were obtained in 1992-1993 from 452 family members living in kibbutz settlements in Israel (visit 1) and remeasured 8 to 10 y later in 379 individuals (visit 2). Red blood cell (RBC) fatty acid concentrations were determined in visit 1 by gas chromatography. Longitudinal associations of visit 1 fatty acids with visit 2 personality traits were examined using linear models, before and after controlling for baseline personality scores. The contribution of environmental factors to personality scores beyond heritability was estimated by variance decomposition. RESULTS: In longitudinal analysis, 1% increase in visit 1 total n-6 (ω-6) fatty acid was associated with a 0.328-unit decrease in visit 2 type-A score [95% confidence interval (CI): -0.571, -0.085]. After adjustment for baseline personality levels, the association was slightly attenuated (β= -0.204; CI: -0.399, -0.009). One percent higher total n-6 was also associated with 1.119 units lower visit 2 hostility score (CI: -2.777, 0.038; P = 0.055). Finally, independent of the genetic contribution (32%-38% of adjusted variability in hostility and type-A personality), 1% increase in total n-3 and total n-6 was associated with 2.539 (CI: -3.907, -1.171) and 0.201 (CI: -0.365, -0.037) units lower hostility and type-A scores, respectively. CONCLUSIONS: Higher RBC total n-6 fatty acid concentrations are associated with lower type-A personality scores. After adjustment for baseline personality levels, the associations between total n-6 and hostility and between total n-3 and hostility are attenuated. These findings support further investigation of the relationship between fatty acid biology and personality traits using study designs better suited to causal inference.

Humans

Reliability, Device Agreement and Validity of Load-Velocity Profiles: A Systematic Review with Meta-analysis.

BACKGROUND: For a valid one-repetition maximum (1RM) prediction via load-velocity (LV) relationships, high reliability and accuracy must be assumed. OBJECTIVE: Since individual study results indicate ambivalent prediction, this systematic review and meta-analysis was designed to provide a updated and comprehensive overview, extending knowledge about the validity and reliability of commercially available velocity sensors in Part I and the validity and reliability of velocity-based 1RM prediction models in Part II. METHODS: A systematic literature search was conducted in PubMed/MEDLINE, Web of Science, and Scopus. Validity and/or reliability studies or velocity-based 1RM prediction evaluations were included. Methodological quality was assessed using adapted COSMIN. The analysis was performed for intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), and Pearson's correlation coefficient (r). The review was preregistered in PROSPERO (CRD42025634595). RESULTS: Sixty-three studies were included for sensor validity and reliability and 38 for 1RM prediction models. Part I: Velocity sensors demonstrated good-to-excellent pooled validity and device agreement (ICC = 0.91-0.92 [0.83-0.97]; k = 55 and 439, respectively); intra- and inter-day reliability were classified as good to excellent with ICC = 0.90-0.91 [0.85-0.95] (k = 228 and 608, respectively), with sensor technology moderating the results. However, substantial heterogeneity and wide ranges of study-level estimates indicated considerable variability across moderators, linear position transducer (LPT) generally showing more consistent performance than inertial measurement units (IMU). Part II: Velocity-based 1RM prediction showed ICCs = 0.90 [0.83-0.94] (k = 124) and ICC = 0.91 [0.72-0.98] (k = 9); for reliability and validity, respectively. DISCUSSION: Commercial velocity sensors generally provide high relative validity and reliability. Results varied depending on exercise complexity, intensity, sensor technology, and modeling approach. While velocity-based 1RM prediction demonstrated high average validity, large heterogeneity in lower body exercises significantly biased the results. Furthermore, the dearth of measurement error and agreement analyses prohibits final conclusions. CONCLUSION: Therefore, velocity-based monitoring and 1RM prediction require cautious interpretation, as sensor- and exercise-specific evidence remains limited.

Load–velocity relationship

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 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 months and ThuFLEP at 6 and 12 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

Influence of Concave Versus Convex Emergence Profiles on Midfacial Mucosal Stability-A Systematic Review With Meta-Analysis.

OBJECTIVES: To systematically evaluate the influence of concave versus convex emergence profiles on midfacial mucosal stability in partially edentulous patients restored with implant-supported single restorations. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted and registered in PROSPERO (CRD420251139042). An electronic search in MEDLINE (PubMed) and Embase was performed up to May 7, 2026. Eligible studies included RCTs comparing concave (test group) and convex (control group) transmucosal prosthetic designs and reporting midfacial mucosal level changes (mm). Data extraction and risk of bias assessment (RoB 2) were performed independently. A random-effects meta-analysis was conducted using weighted mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: Four RCTs including 144 implants with a 12-month follow-up were included. Of these, 128 implants contributed to the quantitative synthesis, with 66 implants allocated to the concave/modified emergence profile group and 62 implants allocated to the convex/non-concave emergence profile group. The pooled analysis demonstrated a mean difference of -0.31 mm (95% CI -0.63 to 0.02; p = 0.064), indicating a trend toward greater midfacial mucosal recession with convex emergence profiles compared with concave designs. Between-study heterogeneity was low to moderate (I2 = 28%), suggesting consistent findings across studies. Sensitivity analyses confirmed the direction of the effect, with pooled estimates ranging from -0.12 to -0.43 mm. Exclusion of one study resulted in a statistically significant difference favoring concave emergence profiles (-0.43 mm; 95% CI -0.70 to -0.16; p = 0.002). CONCLUSIONS: Convex emergence profiles are associated with a tendency toward increased midfacial mucosal recession. Concave profiles are preferable to support peri-implant soft-tissue stability. CLINICAL RELEVANCE: Emergence profile design should be considered an integral component of prosthetic and surgical planning. The use of concave transmucosal contours during provisionalization and definitive restoration may contribute to improved peri-implant soft tissue stability and enhanced esthetic outcomes.

Humans

Maternal Intake of Vitamins A, C, D, and E During Pregnancy and Risk of Type 1 Diabetes in the Child: The Norwegian Mother, Father, and Child Cohort Study.

BACKGROUND: Dietary vitamins play a role in antioxidant defense and immunoregulation. However, prospective studies exploring the association between vitamin intakes during pregnancy and the child's risk of type 1 diabetes are limited. OBJECTIVES: This population-based prospective cohort study aimed to investigate the association between maternal intake of vitamins A, C, D, and E during pregnancy and risk of type 1 diabetes in children. METHODS: We included 85,244 children born between 2002 and 2009 in the Norwegian Mother and Child Cohort Study, with follow-up until 31 December, 2021. Maternal intake of vitamins from food and dietary supplements from conception to the 22nd week of pregnancy was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was used to estimate hazard ratios (HRs), adjusting for background factors. RESULTS: During follow-up, 529 (0.6%) children were diagnosed with type 1 diabetes at a mean age of 9.4 y (standard deviation: 4.1 y) No associations were observed between maternal pregnancy intake of vitamin A [HR: 0.993; 95% confidence interval (CI): 0.983, 1.003/100 μg], vitamin C (HR: 1.000; 95% CI: 0.993, 1.007/10 mg), vitamin D (HR: 0.991; 95% CI: 0.978, 1.003/1 μg), or vitamin E (HR: 0.999; 95% CI: 0.996, 1.004/10 mg) and risk of type 1 diabetes in the child when adjusted for potential confounders. The results were similar when intakes were assessed separately from food and dietary supplements and after restriction to children with human leukocyte antigen DQ2 and/or DQ8 risk haplotypes. CONCLUSIONS: This prospective cohort study does not support the hypothesis that higher maternal intake of vitamins A, C, D, and E during pregnancy would decrease risk of type 1 diabetes in the child. Corroborated with previous evidence, our findings support a general pattern of null associations.

Humans

Comparative effectiveness of game-based learning modalities in nursing and medical education: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Game-based learning (GBL) is increasingly used in healthcare education, but educators must choose among diverse modalities (e.g., quiz platforms, apps, serious games and metaverse environments). Comparative evidence on which modalities perform best across learning domains (knowledge, attitudes, and practice) remains limited. AIM: To compare the effects of distinct GBL modalities on knowledge, attitudes, and practice outcomes in nursing and medical education and to explore whether comparative effects differ by learner group (pre-licensure students and in-service professionals). DESIGN: PRISMA-NMA-aligned systematic review and Bayesian network meta-analysis. METHODS: We searched eight databases and trial registries through September 2, 2024, for randomized controlled trials comparing GBL with traditional teaching (TT). Outcomes were transformed to a 0-100 scale and analysed as change from baseline in Bayesian consistency models; random-effects models were selected using deviance information criterion (DIC). Risk of bias was assessed using RoB 2. We report mean differences (MDs) with 95% credible intervals (CrIs) versus TT, ranking probabilities, and subgroup NMAs by learner group. RESULTS: Thirty-one RCTs (n = 3439) were included; 15 contributed complete data to the network. Risk of bias was low in 15 trials and raised some concerns in 16. The network was modest for knowledge (11 trials) and sparse for attitudes (3) and practice (4). Compared with TT, metaverse-based learning showed improved attitudes (MD 15; 95% CrI 12 to 18), based on a single trial. For knowledge and practice, Kahoot-based quizzes (MD 9.1; 95% CrI -8.9 to 27) and app-based learning (MD 4.6; 95% CrI -4.4 to 14) had the highest estimated mean improvements, but credible intervals were wide and included the null for most comparisons. Subgroup rankings differed by learner group, but several comparisons were imprecise and uncertainty was substantial, particularly in sparse networks. CONCLUSIONS: GBL modalities may improve learning outcomes compared with TT, but relative effects appear domain-specific and the certainty of rankings is limited by sparse evidence and imprecision. Future trials should prioritise head-to-head comparisons, robust outcome measurement, and longer-term retention and transfer outcomes in both student and in-service populations.

Humans

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

BACKGROUND: Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (LTE) studies (NCT01093326; up to 8 years). Current study evaluated safety and efficacy of ponesimod using combined core and LTE studies data for up to 13 years. METHODS: Of 393 participants completing the core study, 353 (90%) entered LTE, having 3 treatment periods (TP). In TP1 (∼1.85 years), participants continued core treatment (ponesimod: 10, 20, or 40 mg QD) whereas placebo-treated participants were re-randomized (1:1:1) to respective ponesimod doses. In TP2 (TP2 and TP3 combined duration: ∼10.4 years), participants on 40 mg were re-randomized (1:1) to 10/20 mg, while others continued same dose; in TP3 all participants received 20 mg. Study outcomes included safety and efficacy (ARR, time-to 24-week confirmed-disability-accumulation [24-week CDA], total T1-weighted Gadolinium-enhanced (T1 Gd+) lesions, new/enlarging T2 lesions and Combined Unique Active Lesions [CUALs]). RESULTS: For 20 mg dose, total 92.4% participants experienced ≥1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study. Mean (95% CI) ARR=0.14 (0.10-0.20); Kaplan-Meier estimate (95% CI) of confirmed relapse and 24-week CDA=52.5% (42.3-63.5) and 31.3% (22.6-42.3). Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73). CONCLUSION: Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Humans

Nerve injury in revision total elbow arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Revision total elbow arthroplasty (TEA) is technically demanding and carries a substantial risk of postoperative neurological complications because of scarring, altered anatomy, implant removal, and repeated humeral and ulnar exposure. The incidence, nerve distribution, and recovery profile of nerve injury after revision TEA remain incompletely defined. This study aimed to systematically review the literature to define the incidence, recovery profile, and risk factors for nerve injury after revision TEA. METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Thirteen retrospective case series were included, comprising 282 revision TEAs in 271 patients. Random-effects meta-analysis of proportions was undertaken where the data permitted. The primary outcome was postoperative nerve injury following revision TEA. Secondary outcomes included nerve type, recovery, secondary nerve-related procedures, infection, triceps insufficiency, metallosis, periprosthetic fracture, and re-revision. RESULTS: The pooled incidence of postoperative nerve injury was 22.3% (95% confidence interval [CI] 16.3 to 29.6; I2 = 34.6%). The crude incidence was 60 of 282 revisions (21.3%, 95% CI 16.6 to 26.5). The ulnar nerve was involved in 66.7% of all nerve injuries, the radial nerve in 31.7%, and the median nerve in 1.7%. No significant difference in pooled nerve-injury incidence was identified between studies published before 2010 and those published from 2010 onwards (22.9% vs. 21.4%, P = .837). Recovery reporting was heterogeneous; among injuries with numerically extractable outcomes, 85.4% improved partially or completely (95% CI 72.2 to 93.9). Secondary nerve-related procedures were reported in 7 studies. Pooled complication estimates were 10.2% for infection, 13.6% for triceps insufficiency, 25.5% for metallosis, 15.9% for periprosthetic fracture, and 14.0% for re-revision. CONCLUSIONS: Postoperative nerve injury is a common and clinically important complication of revision TEA, affecting approximately 1 in 5 cases. The ulnar nerve is most frequently involved, although radial nerve injury accounts for a substantial proportion of cases. Many neuropathies improve during follow-up, but persistent deficits and the need for secondary nerve-related procedures are not uncommon. Future studies should adopt standardized neurological definitions and reporting to improve comparability and guide preventive surgical strategies.

Humans

ALID score for treatment-effect heterogeneity of adjunctive low-voltage area ablation in persistent atrial fibrillation: A post hoc analysis of SUPPRESS-AF.

BACKGROUND: In persistent atrial fibrillation (AF), the incremental benefit of adjunctive low-voltage area (LVA) ablation beyond pulmonary vein isolation (PVI) remains inconsistent. OBJECTIVE: To examine whether a simple clinical score characterizes treatment-effect heterogeneity of adjunctive LVA ablation among patients with mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 and to perform an exploratory supportive analysis in an independent randomized cohort. METHODS: In this post-hoc analysis of SUPPRESS-AF, which included patients with persistent AF and mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 after PVI, four variables-age&#xa0;&#x2265;&#xa0;75&#xa0;years, left atrial diameter&#xa0;>&#xa0;44&#xa0;mm, estimated glomerular filtration rate&#xa0;<&#xa0;60&#xa0;mL/min/1.73&#xa0;m2, and absence of diabetes-were combined into the ALID score (0-4). Patients were stratified into low (0-1), intermediate (2), and high (3-4) score groups. Because EARNEST-PVI did not use LVA-guided ablation or select patients based on mapped LVA, it was analyzed as an exploratory supportive cohort rather than as an external validation cohort. RESULTS: In SUPPRESS-AF (n&#xa0;=&#xa0;336), a significant treatment-by-score interaction was observed (P&#xa0;<&#xa0;0.001). Adjunctive LVA ablation was associated with increased recurrence in the low-score stratum (HR 3.92; 95% CI 1.50-10.20) and reduced recurrence in the high-score stratum (HR 0.48; 95% CI 0.26-0.86). In EARNEST-PVI (n&#xa0;=&#xa0;494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P&#xa0;=&#xa0;0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5&#xa0;cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

Humans

Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis-version 1.

OBJECTIVE: To evaluate the association of paternal use of valproate during spermatogenesis compared with paternal use of lamotrigine or levetiracetam on offspring risk of neurodevelopmental disorders (NDDs). METHODS: Eligibility criteria: observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate vs lamotrigine or levetiracetam during spermatogenesis. INFORMATION SOURCES: the databases PubMed, Embase, Cochrane Library and Web of Science were systematically searched from January 1995 to October 2025.Synthesis of results and risk of bias: a random-effects model was used to estimate pooled HRs and 95%&#x2009;CI, with heterogeneity assessed using I2 statistic for any NDD.We present a meta-analysis of observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate versus lamotrigine or levetiracetam during spermatogenesis. Given the major regulatory implications of paternal valproate safety, the recent emergence of new population-based data, and the expectation of further large studies, we designed this work as a living systematic review and meta-analysis that will be updated as new eligible evidence becomes available. RESULTS: We identified three eligible studies based on data from (1) Norway and Sweden, (2) Norway and Taiwan and (3) Denmark. As two studies included Norwegian data, their results are referred to as 'Norway 1' and 'Norway 2' for clarity. In the meta-analysis of data from Denmark, Sweden and Norway 1, the pooled HR of offspring NDDs was 1.05 (95% CI 0.87 to 1.27; I2=0.0%), and in meta-analysis of data from Denmark, Sweden and Norway 2, it was 1.03 (95% CI 0.85 to 1.24; I2=0.0%).In the meta-analysis including Taiwan, Denmark, Sweden and Norway 1, the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), and when including data from Taiwan, Denmark, Sweden and Norway 2, the pooled HR was 1.04 (95% CI 0.87 to 1.25; I2=0.0%). CONCLUSIONS: In this living meta-analysis, we found no evidence that paternal exposure to valproate compared with lamotrigine/levetiracetam during spermatogenesis was associated with increased risk of NDDs in offspring.

Humans

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate &#x2265;&#x2009;90; 60-<&#x2009;90; 30-<&#x2009;60; <&#x2009;30&#x2009;mL/min/1.73&#x2009;m2) and liver (total bilirubin &#x2264;&#x2009;21&#x2009;&#x3bc;mol/L or aspartate aminotransferase [AST] &#x2264;&#x2009;31/&#x2264;&#x2009;37 [female/male] U/L; total bilirubin >&#x2009;21&#x2009;&#x3bc;mol/L or AST >&#x2009;31/>&#x2009;37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p&#x2009;>&#x2009;0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c <&#x2009;7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p&#x2009;<&#x2009;0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p&#x2009;<&#x2009;0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans

Evaluation of three Aspergillus antibody assays for screening of chronic pulmonary aspergillosis: prospective diagnostic accuracy study.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a frequent complication of pulmonary tuberculosis (PTB), particularly in high-burden settings where access to reliable serological diagnostics remains limited. We evaluated the diagnostic performance of two immunochromatographic technology (ICT) lateral flow assays (LFAs) and an ELISA for CPA screening among patients with active or previously treated PTB. METHODS: In this two-year prospective multicentre diagnostic evaluation, serum from adults with prior or active PTB was tested using the Era Biology Aspergillus IgG ICT LFA, LDBio Aspergillus IgG/IgM ICT LFA, and Bordier Aspergillus fumigatus IgG ELISA. CPA diagnosis was established using a consensus composite reference standard incorporating clinical, immunological, radiological, and microbiological criteria. The Bordier ELISA was used as part of the immunological component of the consensus CPA diagnosis, with a cutoff optical density of &#x2265;1.0. Diagnostic accuracy, agreement statistics, receiver operating characteristic analysis, and latent class analysis (LCA) were performed. RESULTS: Among 340 participants, 24 (7.06%) had CPA. Proportion of participants with positive antibody tests among all tested individuals were 6.76% for LDBio ICT LFA, 20.0% for Era Biology ICT LFA, and 11.47% for Bordier ELISA. Against consensus CPA diagnosis, Bordier ELISA showed 87.50% sensitivity and 94.30% specificity, LDBio ICT LFA 58.33% sensitivity and 97.15% specificity, and Era Biology LFA 66.67% sensitivity and 83.54% specificity. LCA estimated CPA prevalence at 7.72%. LCA-derived sensitivities and specificities were 86.58% and 99.92% for LDBio ICT LFA, 83.39% and 85.31% for Era Biology LFA, and 79.10% and 94.19% for Bordier ELISA. CONCLUSIONS: The Bordier ELISA showed high sensitivity and specificity, while the LDBio ICT LFA demonstrated very high specificity with strong LCA-derived performance. These findings support the use of ELISA for laboratory diagnosis and ICT as a point-of-care screening tool for CPA in resource-limited settings. Era Biology Aspergillus IgG LFA demonstrated moderate sensitivity and acceptable diagnostic performance, indicating its potential utility as a supplementary screening assay for CPA in settings where rapid, point-of-care testing is required.

Humans

Accelerated Biological Aging Increases the Risk of Head and Neck Cancer: Insights From Genetic Instruments of Epigenetic Clocks.

Epigenetic clocks are robust biomarkers of biological aging and have been associated with cancer susceptibility. However, the relationship between genetically predicted epigenetic age acceleration and head and neck cancer risk remains unclear. Using a large case-control study of 2189 head and neck squamous cell carcinoma (HNSCC) cases and 2189 age- and sex-matched controls, we investigated the associations between polygenic scores (PGSs) for multiple epigenetic clocks and HNSCC risk, and evaluated their potential causal roles using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) associated with four epigenetic clocks (HannumAge, HorvathAge, GrimAge, and PhenoAge) were used to construct clock-specific PGSs. Logistic regression models were applied to assess associations between PGSs and HNSCC risk, while MR analyses, including inverse-variance weighted (IVW), weighted median, and MR-Egger methods, were used to infer potential causal relationships. Among the 48 epigenetic clock-associated SNPs, 12 showed nominal associations with HNSCC risk, and one variant (rs2275558 in PBX1) remained significant after Bonferroni correction (OR&#x2009;=&#x2009;0.67, 95% CI: 0.60-0.76). PGSs for all four epigenetic clocks were higher in cases than in controls. In logistic regression analyses, each standard deviation increase in HannumAge PGS was associated with a 25% higher risk of HNSCC (OR&#x2009;=&#x2009;1.25, 95% CI: 1.10-1.41), whereas HorvathAge, GrimAge, and PhenoAge PGSs showed weaker positive associations (ORs ranging from 1.06 to 1.10). Individuals in the highest PGS quartile for all four epigenetic clocks exhibiting 14%-25% higher risk than those in the lower three quartiles. MR analyses supported potential causal effects of genetically predicted HannumAge (IVW OR&#x2009;=&#x2009;1.24 per SD increase, 95% CI: 1.09-1.42) and GrimAge (IVW OR&#x2009;=&#x2009;1.23 per SD increase, 95% CI: 0.98-1.56) on HNSCC risk, with consistent estimates in weighted median analyses. Our results highlight biological aging as a potential etiologic mechanism for HNSCC and suggest that epigenetic clock-related genetic profiles may improve HNSCC risk stratification.

Humans

2024-2025 BNT162b2 KP.2 COVID-19 full season vaccine effectiveness from vaccine registries linked to administrative claims in two states: A cohort study in non-immunocompromised adults.

BACKGROUND: Data on effectiveness of COVID-19 vaccinations during the 2024-2025 respiratory season are limited, particularly among those with underlying medical conditions (UMC). We estimated BNT162b2 KP.2 vaccine effectiveness (VE) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits in two U.S. states. METHODS: Retrospective cohort study of non-immunocompromised adults living in Louisiana or California, with &#x2265;1&#xa0;year prior continuous enrollment in insurance plans contributing to the HealthVerity claims database beginning August 22, 2024. The effectiveness of BNT162b2 KP.2 vaccine (2024-2025 formulation, hereafter referred to as BNT162b2), measured as a time-varying exposure against hospital admission, ED, or UC encounters with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 was calculated as 1 - adjusted hazard ratio using Cox proportional hazard models adjusted for age group, sex, state, insurance payor, presence or absence of UMCs, and pre-index healthcare utilization. Stratifications included those aged 65&#xa0;years and older, those aged 18-64&#xa0;years with UMCs, and those aged 18-64&#xa0;years without UMCs. RESULTS: The cohort included 6,256,421 individuals (93% California, 7% Louisiana); 330,565 (5%) received the BNT162b2 vaccine. Vaccinated individuals were older and had more comorbidities, wellness visits, and prior influenza vaccination. Overall, 66% of the study population had &#x2265;1 UMC; the most prevalent conditions were obesity (25%), history of immunocompromised conditions (23%), and mental health conditions (19%). COVID-19-related encounter rates for ED, UC or hospitalization were lower among vaccinated compared to unvaccinated persons (25.1 vs 36.3 per 100,000 person-months). Among all adults, VE was 37% against hospitalization, 12% against ED/UC encounters, and 16% against ED/UC/hospitalization encounters. Results were similar across age groups and UMCs. CONCLUSIONS: BNT162b2 provided protection against COVID-19-associated outcomes of ED, UC or hospitalization among non-immunocompromised U.S. adults, including those with UMCs, over the course of the 2024-2025 respiratory virus season, supporting continued vaccine recommendations. REGISTRATION: This study was posted on clinicaltrials.gov prior to analyses (NCT06923137).

Adolescent

Comparison of Traditional Chinese Exercise and Equipment-Based Exercise on Glycaemic Control and Vitamin D Levels in Middle-Aged and Elderly Patients With Prediabetes: A Randomised Controlled Trial.

BACKGROUND: Prediabetes is a critical window for preventing progression to type 2 diabetes mellitus (T2DM). Both vitamin D deficiency and physical inactivity are associated with impaired glucose metabolism. This study compared the effects of Traditional Chinese Exercise (TCE) and Kuanle Equipment Exercise (KEE) on glycaemic measures, lipid profiles, body composition and serum 25-hydroxyvitamin D3 [25(OH)D3] in middle-aged and elderly adults with prediabetes. METHODS: We conducted a 12-week, single-centre, randomised controlled trial involving 62 participants with prediabetes (mean age 55.2&#x2009;&#xb1;&#x2009;8.4&#x2009;years; 88.7% female). Participants were randomly assigned to control (usual care, n&#x2009;=&#x2009;21), TCE (n&#x2009;=&#x2009;20), or KEE (n&#x2009;=&#x2009;21). Primary outcomes included fasting plasma glucose (FPG), 2-h OGTT glucose, glycated haemoglobin (HbA1c) and serum 25(OH)D3. Secondary outcomes comprised triglycerides, total cholesterol, LDL-C, HDL-C and body composition. RESULTS: At baseline, mean serum 25(OH)D3 was 21.53&#x2009;&#xb1;&#x2009;3.90&#x2009;nmol/L. At 12&#x2009;weeks, both TCE and KEE improved FPG, 2-h OGTT glucose, HbA1c and 25(OH)D3 versus control (all p&#x2009;&#x2264;&#x2009;0.001). Relative changes in FPG were -9.4% (TCE) and -15.2% (KEE) versus -1.5% (control); corresponding changes were -14.6% and -21.2% for 2-h OGTT glucose, -6.7% and -12.9% for HbA1c, and +60.6% and +81.9% for 25(OH)D3. Direct TCE-KEE comparisons were not significant (all p&#x2009;>&#x2009;0.05). In an exploratory analysis, change in 25(OH)D3 was inversely associated with change in 2-h OGTT glucose (partial r&#x2009;=&#x2009;-0.358, p&#x2009;=&#x2009;0.006), but not with FPG, HbA1c, or triglycerides. CONCLUSIONS: Both TCE and KEE improved glycaemic outcomes and increased serum 25(OH)D3 compared with usual care in middle-aged and elderly adults with prediabetes. Although KEE produced numerically larger estimates, direct between-group comparisons were not significant, and the superiority of KEE over TCE was not established. These vitamin D findings require confirmation in trials that quantify sunlight exposure and dietary vitamin D intake.

Aged

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes.&#xa0;This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed.&#xa0;Eight studies (n&#x2009;=&#x2009;4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1&#xa0;month (RR 0.49, 95% CI 0.17-1.42), after 1&#xa0;month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD&#x2009;-&#x2009;1.75, 95% CI&#x2009;-&#x2009;3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD&#x2009;-&#x2009;0.99, 95% CI&#x2009;-&#x2009;1.86 to&#x2009;-&#x2009;0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION: &#xa0;Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: &#x2022; Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: &#x2022; This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans

Exploring the role of successful exercise-induced body weight loss on cardiometabolic health in individuals with metabolic syndrome.

BACKGROUND AND AIM: High-intensity interval training (HIIT) is known to improve cardiorespiratory fitness (i.e., VO2MAX), a key marker of cardiometabolic health in individuals with metabolic syndrome (MetS). Nonetheless, body weight loss is widely recognized as a crucial factor in reducing insulin resistance and improving metabolic risk factors. Thus, we aimed to determine the importance of body weight loss following exercise training on improving MetS. METHODS AND RESULTS: Two hundred and twenty-eight adults (55.3&#xa0;&#xb1;&#xa0;7.9&#xa0;yr) with overweight/obesity (32.5&#xa0;&#xb1;&#xa0;4.6&#xa0;kg&#xb7;m-2) and MetS were randomized to: a) standard health care non-exercise group (CONTROL group, N=58) or b) standard health care plus 16 weeks of HIIT (EXER group, N=170). MetS (MetS z-score), insulin resistance (HOMA-IR), cardiorespiratory fitness (VO2PEAK), maximal cycling power (WPEAK), and body weight/composition were assessed. After intervention, EXER group participants were divided according to their weight loss response to training: i) those achieving the weight loss predicted from estimated exercise energy expenditure (-BW group, n=78; -3.3&#xa0;&#xb1;&#xa0;2.2&#xa0;kg); ii) those not reaching the expected weight loss (=BW group, n=38; -0.7&#xa0;&#xb1;&#xa0;0.5&#xa0;kg); iii) and those who gained weight (+BW group, n=54; 1.1&#xa0;&#xb1;&#xa0;1.0&#xa0;kg). VO2PEAK significantly improved regardless of body weight loss response (-BW, 0.3&#xa0;&#xb1;&#xa0;0.3; =BW, 0.2&#xa0;&#xb1;&#xa0;0.3; +BW, 0.3&#xa0;&#xb1;&#xa0;0.2&#xa0;L&#xb7;min-1; all p&#xa0;<&#xa0;0.001) compared to CONTROL group (0.0&#xa0;&#xb1;&#xa0;0.3&#xa0;L&#xb7;min-1). However, significant improvements in MetS z-score (-0.31&#xa0;&#xb1;&#xa0;0.41) and HOMA-IR (-0.7&#xa0;&#xb1;&#xa0;1.6) were observed only in the -BW group (both p&#xa0;<&#xa0;0.001). CONCLUSIONS: Exercise recommendations should consider that greater improvements in MetS are observed when interventions are accompanied by successful body weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05120778.

Humans

Effectiveness of Multidomain Cardiac Rehabilitation After Myocardial Infarction by Patient Frailty: Prespecified Subgroup Analysis of the PIpELINe Trial.

BACKGROUND: Frailty is common among older patients surviving myocardial infarction, is associated with adverse outcomes, and is often perceived as a barrier to cardiac rehabilitation (CR). The aim of this study is to determine whether frailty influences prognosis after myocardial infarction, and whether frailty modifies the clinical benefit of multidomain CR. METHODS: We performed a prespecified subgroup analysis of the PIpELINe (Physical Activity Intervention in Elderly Patients With Myocardial Infarction) randomized clinical trial conducted in Italy, which enrolled 512 patients aged &#x2265;65 years recovering from myocardial infarction and randomized them in a 2:1 ratio to CR or usual care. Frailty was assessed using the Fried Frailty Phenotype, and patients were categorized as nonfrail (robust) or prefrail/frail. Time-to-event outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models, including treatment-by-frailty interaction terms to evaluate effect modification of the multidomain CR. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for cardiovascular causes within 1 year after randomization. RESULTS: Overall, 350 patients (68.4%) were classified as prefrail/frail, of whom 232 were randomized to intervention arm (66%). Frail patients were older (median age, 80 [75-85] years) and more frequently female (41.7% versus 24.7%). Compared with robust patients, prefrail/frail patients had a higher risk of the primary outcome (16 [9.9%] versus 62 [17.7%]; hazard ratio, 1.59 [95% CI, 0.89-2.82]; adjusted P=0.117). Among prefrail/frail patients, assignment to multidomain CR was associated with a lower risk of the primary outcome compared with usual care (hazard ratio, 0.57 [95% CI, 0.34-0.94]; P=0.028), with no statistically significant interaction in the treatment effect on the primary end point (P=0.57). CONCLUSIONS: Among older patients recovering from myocardial infarction, frailty is associated with worse prognosis but does not diminish the benefit of multidomain CR. These findings support the use of frailty assessment to guide rather than limit access to CR. REGISTRATION: ClinicalTrials.gov; Unique identifier: NCT04183465.

Humans