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PubMed2026

Risk factors of venous thromboembolism in ICU patients: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU). METHODS: A systematic literature search was conducted via PubMed, Embase, Web of Science, and Cochrane databases up to 25 April 2025, to identify studies examining the association between risk factors and the occurrence of venous thromboembolism (VTE) in ICU patients. Data were pooled using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2465 relevant studies were identified through the systematic search, of which 30 were included in the meta-analysis. The pooled data showed that the following were significant risk factors for venous thromboembolism (VTE) in ICU patients: central venous catheterization (OR = 2.67, 95% CI: 1.67-4.28; I2 = 28%), invasive mechanical ventilation (OR = 2.08, 95% CI: 1.46-2.96; I2 = 0%), advanced age (OR = 2.06, 95% CI: 1.28-3.31; I2 = 86%), length of ICU stay (OR = 4.24, 95% CI: 1.43-12.57; I2 = 98%), malignancy (OR = 2.30, 95% CI: 1.03-5.12; I2 = 67%), elevated D-dimer levels (OR = 2.46, 95% CI: 1.37-4.40; I2 = 34%), and a history of VTE (OR = 2.84, 95% CI: 1.45-5.55; I2 = 51%). According to the GRADE assessment, the quality of evidence was rated as moderate for invasive mechanical ventilation, low for central venous catheterization and D-dimer levels, and very low for the remaining factors. CONCLUSION: Invasive mechanical ventilation, central venous catheterization, and elevated D-dimer levels are associated with VTE risk, supported by relatively high-quality evidence. These findings may help identify ICU patients at higher risk of VTE, inform the development of risk assessment models for patient stratification, and ultimately contribute to improved prognosis through optimal screening and management strategies.

Humans↗

PubMed2026

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups.

BACKGROUND: Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3 mg/day(SMD = -7.57;95%C.I. = -8.25;-5.85); tamoxifen 160 mg/day(SMD = -1.73;95%C.I. = -2.32;-1.13); rivastigmine 3 mg/day(SMD = -1.13;95%C.I. = -1.06;-0.58); haloperidol 30 mg/day(SMD = -0.96;95%C.I. = -1.25;-0.75); valproate 750 mg/day(SMD = -0.76;95%C.I. = -1.48;-0.58); tamoxifen 40 mg/day(SMD = -0.75;95%C.I. = -1.41;-0.59); celecoxib 400 mg/day(SMD = -0.74;95%C.I. = -1.20;-0.38); paliperidone extended-release 12 mg/day(SMD = -0.62; 95%C.I. = -0.91;-0.32); olanzapine 15 mg/day(SMD = -0.59;95%C.I. = -0.60;-0.38); olanzapine 20 mg/day(SMD = -0.52;95%C.I. = -0.66;-0.38); risperidone 4 mg/day(SMD = -0.53;95%C.I. = -0.76;-0.29); allopurinol 600 mg/day(SMD = -0.54;95%C.I. = -0.67;-0.22); cariprazine 12 mg/day(SMD = -0.49;95%C.I. = -0.66;-0.33); risperidone 4.2 mg/day(SMD = -0.46;95%C.I. = -0.75;-0.17); lithium 1500 mg/day(SMD = -0.42;95%C.I. = -0.57;-0.28); ziprasidone 160 mg/day(SMD = -0.49;95%C.I. = -0.68;-0.31); asenapine 20 mg/day(SMD = -0.38;95%C.I. = -0.53;-0.22); haloperidol 8 mg/day(SMD = -0.34;95%C.I. = -0.63;-0.05); aripiprazole 15 mg/day(SMD = -0.33;95%C.I. = -0.61;-0.06) outperformed placebo. Ziprasidone 160 mg/day, celecoxib 200 mg/day, asenapine 20 mg/day, and asenapine 10 mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.

Humans↗

PubMed2026

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 ± 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans↗

PubMed2026

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1 mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest η2 = 0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p ≥ 0.05; η2 ≤ 0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p ≥ 0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed ≤8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1 mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

Humans↗

PubMed2026

The influence of organizational culture on medication safety practices and associated risk factors in the community setting: A systematic review.

BACKGROUND: Increasing attention has been given to the role of organizational culture in influencing medication safety practices across healthcare settings. The lack of widely accepted standardized instrumentation makes operational measurement of organizational culture and medication safety challenging. The purpose of this systematic review was to examine the impact of organizational culture on medication safety within community healthcare settings. METHODS: MEDLINE, CINAHL, Scopus, and Nursing & Allied Health were searched in August 2025 using keywords, subject terms, field codes, and Boolean operators to identify papers relevant to the review question; bibliographies of included studies were also reviewed. Screening and full-text review were completed independently by two reviewers with a third to adjudicate conflicts. The Critical Appraisal Skills Programme was used for quality assessment. The PRISMA statement guided the development and implementation of the review. RESULTS: Thirteen articles were included representing various community settings. Most studies reported on untoward medication events, but few measured systematically collected safety data before and after an intervention. Organizational culture was seldom defined or operationalized. Most studies were methodologically sound, but the overall level of evidence was weak to moderate. CONCLUSION: Organizational culture influences medication safety through aspects such as communication channels, teamwork, training, and an environment that allows error and near-miss reporting. Few studies explicitly evaluate the causal impact of culture interventions on measurable medication safety outcomes in community healthcare settings. Further research should incorporate standardized measurement tools and intervention-based, pre-post designs to better understand how organizational culture influences medication safety in community healthcare settings.

Organizational Culture↗

PubMed2026

Association between anaemia and osteoporosis: a systematic review and meta-analysis.

BACKGROUND: Osteoporosis significantly impacts global morbidity. Recent evidence suggests anaemia may contribute to osteoporosis risk. This systematic review and meta-analysis investigates this association. METHODS: PubMed, Scopus, EBSCO, and ScienceDirect were searched for papers. Studies with definition of anaemia and assessing osteoporosis outcomes were included. Meta-analysis utilized random-effects models (DerSimonian-Laird method), and study quality was assessed via Newcastle-Ottawa Scale (NOS). Analyses were performed using R Studio. RESULT: Eighteen studies (861,540 participants) were analyzed. Anaemia significantly increased osteoporosis risk in univariate analysis (OR 1.62; 95% CI 1.33-1.98; p < 0.001), despite high heterogeneity (I2 = 92.7%). The results remain significant in studies that reported multivariate analysis (OR 2.01; 95% CI 1.26-3.21; p = 0.004). Sensitivity analyses confirmed the robustness of our result. CONCLUSION: Anaemia significantly associated with osteoporosis, emphasizing the need for targeted screening in anaemic individuals. Further studies should consider incorporating anaemia into osteoporosis and fracture prediction tools.

Humans↗

PubMed2026

From human papillomavirus (HPV) infection to HPV-associated cancers in systemic lupus erythematosus: A systematic review and Meta-analysis.

OBJECTIVE: The current cervix-focused screening paradigm in systemic lupus erythematosus (SLE) may underestimate extra-cervical anogenital cancer risk. This meta-analysis aimed to quantify the risk of human papillomavirus (HPV) infection and HPV-associated cancers in SLE patients. METHODS: A comprehensive search was conducted in PubMed (2010), Embase (2010), and Cochrane Library (2010) to August 8, 2025. Odds Ratios (ORs) and Standardized Incidence Ratios (SIRs) with 95% Confidence Intervals (CIs) were calculated. The study protocol was registered with PROSPERO (CRD420251122192). RESULTS: SLE was associated with significantly increased odds of HPV infection (OR = 4.12, 95% CI 2.03, 8.32). We further assessed the risk of HPV-associated malignancies in SLE patients. SLE patients exhibited substantially elevated risks across multiple HPV-associated cancers (SIR = 1.90, 95% CI 1.51, 2.38). The risk of cervical cancer was more than doubled (SIR = 2.25, 95% CI 1.75, 2.89). Notably, even higher risks were observed for extra-cervical anogenital cancers, namely vulvar/vaginal cancers (SIR = 5.60, 95% CI 3.71, 8.43). CONCLUSIONS: SLE is associated with elevated risks of HPV infection and a broad spectrum of HPV-associated cancers. Subgroup analyses suggested that cyclophosphamide use, multiple sexual partners, and Asian populations may constitute higher-risk subgroups. These findings highlight the need for additional prospective evidence to better characterize HPV-associated cancer risks in SLE patients.

Humans↗

PubMed2026

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30‑day all‑cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged ≥ 60 years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K‑Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P < 0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR = 9.752), smoking (OR = 5.171), AIP (OR = 6.691), TyG index (OR = 4.393), HALP score (OR = 2.831), and ≥ 2 comorbidities (OR = 3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC = 0.884, accuracy = 0.829, sensitivity = 0.812, specificity = 0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30‑day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans↗

PubMed2026

Comprehensive source-risk assessment of organophosphate esters in surface water of the Dianchi Lake Basin, Yunnan, China.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, have been increasingly detected in aquatic environments. However, investigations of their distribution in high-altitude plateau lakes remain scarce. Identifying and quantifying the sources and associated risks of OPEs are crucial for subsequent water environment management. In this study, an integrated source-risk analysis approach was employed by combining the Positive Matrix Factorization (PMF) model, the Geodetector (GD) model, and risk quotient (RQ). Analysis of 14 OPEs in surface waters of the Dianchi Lake Basin (DLB) revealed 12 detectable compounds, with total OPEs concentrations (ΣOPEs) ranging from not detected (ND)-64.6 ng/L during the wet season and ND-35.8 ng/L during the dry season. Elevated ΣOPEs were primarily observed at inflow sites in the northern part of the lake and in urban rivers. Source apportionment indicated four major contributing sources: agricultural films containing flame-retardant and plasticizer additives, traffic-related particulate emissions, releases from household and personal care products, and industrial production and applications of flame retardants in plastics, electronics, and related products (the predominant source). The ecological impact caused by OPEs ranges from no risk to low risk, with tris(2-chloroethyl) phosphate emitted from industrial source being the primary driver of potential environmental risk. These findings highlight the necessity of prioritizing industrial sources in future management strategies. Overall, this study provides a methodological framework for source apportionment and risk assessment of OPEs and offers scientific evidence to support environmental management of OPEs in the DLB.

Environmental Monitoring↗

PubMed2026

Frequent readmissions after hospitalization for alcohol withdrawal: a systematic review and meta-analysis.

BACKGROUND: Alcohol use disorder and alcohol withdrawal syndrome impose substantial clinical and economic burdens, with repeated hospitalizations being common. We aimed to systematically review readmission rates following inpatient detoxification, assess variation across study designs and hospital settings, and identify key risk and protective factors. METHODS: We performed a literature search in Embase and Pubmed on 10/04/2026 focusing on studies assessing in hospital alcohol detoxification. Exclusion criteria included studies on substance use other than alcohol and outpatient or residential treatment. Main outcome was rehospitalization, and meta-analysis was performed to estimate pooled readmission proportions. Secondary outcomes were risk factors and protective factors influencing the rate of rehospitalization. RESULTS: Twenty-five studies were included. The pooled proportion of readmissions following alcohol detoxification was estimated at 17% (95% CI: 14%-21%; 13 studies, n = 287,896) within 1 month, increasing to 44% (95% CI: 36%-52%; 8 studies, n = 2,877) at 1 year. Substantial between-study heterogeneity was observed. Subgroup analyses found no significant differences by hospital setting or time period. Findings for study aim and study design were mixed and based on limited data A small number of studies suggested associations with housing stability, employment, and treatment engagement. CONCLUSIONS: This meta-analysis suggests that approximately one in six patients are readmitted within 1 month and nearly half within 1 year after inpatient alcohol detoxification. However, readmission rates varied considerably across settings and populations. Future research should evaluate targeted interventions to reduce readmissions among high-risk patient groups.

Humans↗

PubMed2026

Association of lipoprotein-associated phospholipase A2 with recurrence risk and its predictive value in large artery atherosclerotic stroke.

OBJECTIVE: To investigate the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with large artery atherosclerotic (LAA) stroke and its predictive value for recurrence. METHODS: We consecutively enrolled 412 acute LAA stroke patients. Using a cutoff of 200 ng/mL, patients were divided into high and low Lp-PLA2 groups, and into recurrence and non‑recurrence groups based on 1‑year follow‑up. Baseline characteristics, lipid profiles, National Institutes of Health Stroke Scale (NIHSS) scores, and vascular stenosis degree were compared. Binary logistic regression and Receiver Operating Characteristic (ROC) analysis were used to identify independent risk factors and evaluate predictive value. RESULTS: The high Lp-PLA2 group had significantly higher low-density lipoprotein cholesterol (LDL-C), small dense low-density lipoprotein cholesterol (sdLDL-C), prevalence of severe stenosis (≥70%), and proportion of NIHSS > 15 (all P < 0.05). The recurrence group showed elevated Lp-PLA2, higher LDL‑C and sdLDL-C, more severe neurological deficits, and more severe stenosis (all P < 0.001). Multivariable regression identified elevated Lp-PLA2 (per 10 ng/mL: OR = 1.139, 95% CI: 1.089-1.191), moderate (OR = 3.145) and severe (OR = 11.663) neurological deficits, and severe stenosis (OR = 9.390) as independent risk factors for recurrence (all P < 0.05). The Area Under the Curve (AUC) of Lp-PLA2 was 0.75 (95% CI: 0.69-0.82), with an optimal cutoff of 208.95 ng/mL. CONCLUSION: Elevated Lp-PLA2 is associated with adverse lipid profiles, more severe neurological deficits, and greater vascular stenosis in LAA stroke patients, and independently predicts 1‑year recurrence. Lp-PLA2 shows moderate predictive value, supporting its potential for risk stratification.

Humans↗

PubMed2026

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n = 75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p = 0.02 to p < 0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans↗

PubMed2026

Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.

Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.

Humans↗

PubMed2026

Alcohol use disorder and childhood adversity in the association between polygenic risk and suicidality.

OBJECTIVE: Suicidal ideation (SI) and suicide attempt (SA) are both influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate the effects of genetic liability for suicidality. METHODS: Using data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime suicidality outcomes. We evaluated whether AUD partially accounted for these associations and ACEs moderated the direct and indirect associations. RESULTS: The SA PGS was significantly associated with SA (AFR: b = 0.36, SE = 0.01; EUR: b = 0.17, SE = 0.01; both ps < 2e-16), but the SI PGS was not associated with SI (p > 0.55). AUD statistically mediated the association between the SA PGS and SA, accounting for approximately 2% of the total association in AFR individuals and 10% in EUR individuals (both ps < 2e-16). Notably, the proportion of the association that was accounted for by AUD decreased as ACEs exposure increased, from 4.30% to 0.54% in AFR individuals and from 13.31% to 3.44% in EUR individuals. In contrast, there was only very modest mediation and no moderated mediation for SI. CONCLUSIONS: Particularly among individuals with lower ACEs exposure, AUD accounted for a meaningful proportion of the association between genetic liability to SA and lifetime SA. These findings highlight different correlates across suicidality phenotypes and suggest potential clinical relevance for AUD in the association between genetic liability and SA.

Adult↗

PubMed2026

Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.

INTRODUCTION: PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS: Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS: SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION: This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.

Humans↗

PubMed2026

Empagliflozin and functional aerobic capacity in individuals with increased risk of heart failure: The Empire Prevent Cardiac trial.

BACKGROUND: Higher maximal oxygen consumption (VO₂ max) is associated with lower risk of developing heart failure (HF). Empagliflozin improves VO2 max in HF with reduced ejection fraction, but the effect on VO2 max in individuals at risk of HF remain unknown. OBJECTIVE: This study aimed to evaluate the effect of 180 days treatment with empagliflozin compared to placebo on VO2 max, daily physical activity level, and quality of life (QoL) in individuals with overweight or obesity and risk of HF. METHOD: This investigator-initiated, double-blinded, randomized, placebo-controlled, multicenter trial included elderly individuals with body mass index >28 kg/m2 and at least one additional risk factor for HF, including hypertension, ischemic heart disease, stroke, or chronic kidney disease. Individuals with HF or type 2 diabetes mellitus were excluded. The primary endpoint was the mean difference in change of VO2 max. The secondary outcome was objectively measured physical activity level. QoL was an explorative outcome. RESULTS: Among 191 randomized individuals (94 empagliflozin, 97 placebo), 89% had hypertension and 66% ischemic heart disease. At baseline, 69% were male, median age was 68 years, median body mass index 31.9 kg/m², mean left ventricular ejection fraction 65 ± 9%, and mean VO₂ max 18.1 ± 4.3 mL/min/kg. Empagliflozin did not change VO2 max with an estimated treatment difference of -0.2 mL/min/kg (97.5% confidence interval -1.2 to 0.8), adjusted P = 1.00. No significant treatment differences were observed for neither daily physical activity nor QoL. CONCLUSIONS: Empagliflozin did not affect VO2 max, physical activity level, or QoL in elderly individuals with overweight or obesity and risk of HF.

Humans↗

PubMed2026

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans↗

PubMed2026

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS × RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans↗