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Disparities in guideline-adherent cardiovascular preventive care for people with diabetes: A systematic review and meta-analysis.

BACKGROUND: Clinical practice guidelines offer guidance on delaying the progression of cardiovascular disease in people living with diabetes. We sought to determine whether guideline-recommended cardiovascular preventive care for people living with diabetes differs according to sociodemographic indicators, globally. METHODS: We conducted a systematic review of studies that compared the sociodemographic characteristics of people diagnosed with type 1 or 2 diabetes who received cardiovascular preventive care as recommended by guidelines to those who did not. Sociodemographic predictors were defined by PROGRESS+ (an equity framework). We searched MEDLINE, EMBASE, and APA PsychInfo from 2010 to January 21, 2026. Studies were screened independently by two people. One person assessed the risk of bias and extracted data, and another verified. We pooled results using a random-effects model and assessed the certainty of evidence using GRADE. RESULTS: Twenty-five studies were included. Meta-analyses showed female, Black, and Hispanic individuals had slightly lower odds of receiving guideline-recommended prescriptions for lipid-lowering medication compared to Male, and White individuals, respectively (OR:0.89, 95%CI:0.79,1.00, moderate certainty; OR:0.78, 95%CI:0.74,0.81, high certainty; OR:0.86, 95%CI:0.59,1.26, low certainty). Individuals aged 18-45 years had moderately lower odds (OR:0.33, 95%CI:0.19,0.57, moderate certainty), no observed association for Asian individuals. Asian individuals had moderately lower odds of antihypertensive medication prescription (OR:0.42, 95%CI:0.38,0.46, high certainty). Evidence suggests likely no association between HbA1c testing and sex/gender or between sex/gender and lipid panel testing. CONCLUSIONS: Some disparities in guideline-recommended cardiovascular preventive care among people living with diabetes were found. These results are consistent with previous reviews and highlight the need to ensure guidelines consider equity and with improved dissemination.

Humans

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

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p&#x2009;<&#x2009;0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p&#x2009;<&#x2009;0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans

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

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration &#xd7; intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans

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

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 &#x2265;1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans

Comprehensive assessment of vasospastic angina using coronary computed tomography angiography: synergistic value of the presence of myocardial bridge, perivascular inflammation, and myocardial extracellular volume fraction.

AIMS: Coronary computed tomography angiography (CCTA) has evolved beyond anatomical assessment to include sophisticated tissue characterization. While an elevated perivascular fat attenuation index around the right coronary artery (FAI-RCA) is known to reflect coronary inflammation in vasospastic angina (VSA), recurrent vasospasms may also induce chronic subclinical myocardial injury and subsequent remodelling, potentially associated with an increased myocardial extracellular volume fraction (ECV). However, the diagnostic integration of ECV and FAI-RCA for identifying VSA in patients with angina with non-obstructive coronary arteries (ANOCA) remains to be elucidated. METHODS AND RESULTS: This study included consecutive ANOCA patients who underwent CCTA with a dedicated ECV protocol, followed by an invasive spasm provocation test. Comprehensive CCTA analysis quantified both FAI-RCA and the transmural ECV gradient (the difference between endocardial and epicardial ECV: ECVEndo - ECVEpi). Of the 100 patients analysed (mean age: 65.3 &#xb1; 11.8 years; 55% male), 27 were diagnosed with VSA. Multivariable logistic regression analysis identified transmural ECV gradient [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.01-1.25], presence of myocardial bridging (MB) (OR: 3.49, 95% CI: 1.25-9.74), and high FAI-RCA (> -70.95 Hounsfield units [HU]) (OR: 5.79, 95% CI: 2.06-16.30) as significant independent predictors of VSA (all P < 0.05). Notably, the integration of transmural ECV gradient provided incremental diagnostic value beyond FAI-RCA and MB, as assessed by the Net Reclassification Improvement and Integrated Discrimination Improvement. CONCLUSION: A multi-parametric CCTA approach potentially identifies patients at high risk for VSA. The significant association of the transmural ECV gradient with VSA suggests that myocardial remodelling imaging provides a novel diagnostic window into the cumulative myocardial impact of vasospasm, independent of active adipose tissue inflammation and the presence of MB.

Humans

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy

Telmisartan-based monotherapy and combination regimens for blood pressure control in adults with hypertension: a systematic review, meta-analysis, and GRADE assessment.

PURPOSE: To evaluate the efficacy, safety, and certainty of evidence for telmisartan-based antihypertensive regimens in adults with hypertension. METHODS: This systematic review and meta-analysis followed PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to 2026. Eligible studies enrolled adults with hypertension and compared telmisartan monotherapy or telmisartan-containing combinations with placebo, usual care, non-telmisartan antihypertensive agents, or alternative telmisartan-based regimens. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs), using random-effects models, with additional subgroup analyses conducted by comparator type. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE. RESULTS: Twenty-five included reports (24 unique trials, since two reports present secondary outcomes from the same underlying trial) involving 6,521 participants were included, spanning placebo-controlled, usual-care-controlled, active-comparator, and telmisartan-combination-versus-telmisartan-monotherapy designs. Telmisartan-based therapy significantly reduced office systolic blood pressure (MD&#x2009;-&#x2009;6.39&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;7.86 to&#x2009;-&#x2009;4.93; low certainty) and office diastolic blood pressure (MD&#x2009;-&#x2009;4.88&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;6.67 to&#x2009;-&#x2009;3.09; low certainty), although the magnitude of effect was comparator-dependent. Based on only two trials, 24-h ambulatory systolic blood pressure (MD&#x2009;-&#x2009;7.16&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;10.61 to&#x2009;-&#x2009;3.72) and ambulatory diastolic blood pressure (MD&#x2009;-&#x2009;4.42&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;6.36 to&#x2009;-&#x2009;2.48) were reduced with moderate certainty. Telmisartan-based regimens improved blood pressure response (RR 1.68; 95% CI 1.31 to 2.16; moderate certainty) but not blood pressure control achievement (RR 1.44; 95% CI 0.92 to 2.24; very low certainty). Overall adverse events, dizziness, and headache were comparable (very low to low certainty), while edema was less frequent with telmisartan-based therapy (RR 0.33; 95% CI 0.15 to 0.73; moderate certainty). CONCLUSION: Telmisartan-based regimens, particularly fixed-dose and multidrug combinations, effectively reduce office and ambulatory blood pressure and improve blood pressure response, with broadly comparable short-term safety and less edema. These effect sizes are comparator-dependent, and certainty of evidence for absolute blood pressure control achievement and for major adverse events is very low; heterogeneity, limited long-term data, and a predominance of Asian-population trials warrant cautious interpretation pending larger, higher-quality, and more geographically diverse confirmatory studies.

Humans

Comparing the Efficacy of Mechanochemical Ablation Versus Radiofrequency Ablation for Treating Great Saphenous Vein Incompetence: A Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy of mechanochemical ablation (MOCA) and radiofrequency ablation (RFA) in the treatment of great saphenous vein (GSV) incompetence. METHODS: Online databases including PubMed, Cochrane Library, Embase, and Web of Science were searched to collect randomized controlled trials (RCTs) and cohort studies comparing MOCA and RFA in the treatment of varicose veins in lower extremities from database inception to October 2025. Primary outcome was anatomic success. Secondary outcomes were visual analog scale (VAS), Aberdeen Varicose Vein Questionnaire score (AVVQ), and complications. Two reviewers independently screened the retrieved literature, extracted data, and assessed the risk of bias in the included studies. Subsequent analysis was performed using RevMan 5.3. RESULTS: A total of four RCTs, one cohort study and retrospective cross-sectional study involving 737 patients (380 MOCA patients and 357 RFA patients) were included. The meta-analysis results showed that the RFA group was significantly better than the MOCA group in short term and long term of anatomical success rate [(odds ratio [OR] = 0.38; 95% confidence interval [CI] (0.20, 0.71), P = 0.003), (OR = 0.17, 95% CI (0.06, 0.45), P = 0.0003)], but patients in the MOCA group had significantly lower perioperative period pain (mean difference [MD] = -4.48, 95% CI (-7.58, -1.37), P = 0.005] and required fewer days to return to normal activities (MD = -0.76, 95% CI, (-0.95, -0.57), P < 0.001). No significant differences were observed between the two groups in minor and major complications [(OR = 0.93, 95% CI (0.66, 1.33), P = 0.70), (OR = 1.30, 95% CI (0.32, 5.28), P = 0.72)] or quality of life scores (MD = -0.45, 95% CI (-2.53 to 1.63), P = 0.67). CONCLUSION: MOCA of GSV incompetence is an effective and safe method. Compared with RFA, it has lower postoperative pain score and faster recovery time. However, the anatomical success rates were significantly lower with MOCA than with RFA. Therefore, long-term follow-up to evaluate the impact on clinical results is required.

Humans

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units

Vancomycin Effectiveness in Reducing Surgical Site Infection in Posterior Spinal Fusion Surgery: A Retrospective Data Analysis of the STRIVE Trial.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To re-evaluate vancomycin as a preventive measure for surgical site infection (SSI). SUMMARY OF BACKGROUND DATA: Intrawound vancomycin powder is used to prevent SSIs in spinal surgery. Prior studies, often limited to single institutions or small samples, have shown mixed efficacy and potential increases in non- S. aureus and Gram-negative infections. We hypothesized that SSIs rates would be similar with and without intrawound vancomycin in posterior spinal fusion (PSF) surgery. METHODS: Prospectively collected data from the 3595 patients in the STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) trial were stratified by intrawound antibiotic usage. Multivariate logistic regression assessed the effect of vancomycin use on SSI, adjusting for patient demographics and SSI-associated risk factors. Secondary outcomes included critical care stay, reoperation, sepsis, and hospital readmission. RESULTS: Of 3311 patients who underwent surgery, 847 (26%) received only intrawound vancomycin and 1534 (46%) received no intrawound antibiotics. Sixty (8%) patients developed postoperative SSI, of whom 20 (33%) had received intrawound vancomycin. Receiving intrawound vancomycin was not associated with SSI incidence versus no intrawound antibiotics [odds ratio (OR): 0.77; 95% CI: 0.42-1.42], critical care stay (OR: 0.94; 95% CI: 0.78-1.12), or sepsis (OR: 2.04; 95% CI: 0.62-6.73). However, intrawound vancomycin was associated with increased odds of hospital readmission (OR: 1.82; 95% CI: 1.28-2.6; P < 0.001) and reoperation (OR: 1.75; 95% CI: 1.18-2.6; P = 0.005). Factors significantly associated with intrawound vancomycin use included intraoperative antibiotic readministration (OR: 2.97; 95% CI: 1.36-6.5; P =0.006) and hospital location, lower odds in Europe (OR: 0.13; 95% CI: 0.06-0.29; P < 0.001) or Asia (OR: 0.02; 95% CI: 0-0.08; P < 0.001) versus North America. CONCLUSIONS: Intraoperative vancomycin use was not associated with reduced SSI incidence compared with no intrawound antibiotics after PSF surgery. LEVEL OF EVIDENCE: Level II.

Humans

Impact of smoking on structural failure after arthroscopic rotator cuff repair: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tears cause significant shoulder pain and functional limitation. Arthroscopic rotator cuff repair improves symptoms, yet structural failure rates remain substantial. Smoking may impair tendon-to-bone healing, but clinical studies report mixed findings due to heterogeneous methodology. Therefore, a systematic synthesis of imaging-confirmed outcomes is needed to clarify the association between smoking and structural failure after arthroscopic rotator cuff repair. METHODS: This review followed PRISMA 2020 and was registered in PROSPERO (CRD420251246197). PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 12 December 2025. Comparative clinical studies of adults undergoing arthroscopic rotator cuff repair that reported imaging-confirmed structural integrity (magnetic resonance imaging or ultrasonography) at &#x2265;6 months were included. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. The primary outcome (structural failure) was pooled as risk ratios using a random-effects model with the restricted maximum likelihood estimator and Hartung-Knapp adjustment. Secondary continuous outcomes were synthesized using Bayesian random-effects models; subgroup, sensitivity, and meta-regression analyses explored heterogeneity. RESULTS: Ten cohort studies (1,683 shoulders) were included. Smoking was associated with a higher risk of imaging-confirmed structural failure (risk ratio 1.53; 95% confidence interval 1.13-2.08; P = .011) with low heterogeneity (I2 = 24.7%). Subgroup and sensitivity analyses supported robustness, with no evidence of effect modification by region, follow-up duration, tear size, or smoking definition. Meta-regression showed no significant influence of age, smoking prevalence, or diabetes prevalence on the pooled effect. Secondary outcomes (3 studies) suggested slightly lower postoperative American Shoulder and Elbow Surgeons scores among smokers, while visual analog scale pain scores and forward flexion showed no clear between-group differences. No publication-bias signals were detected for the primary outcome. CONCLUSION: Smoking is associated with a higher risk of imaging-confirmed structural failure after arthroscopic rotator cuff repair. Functional outcomes were broadly similar between groups, with only a small, likely clinically negligible reduction in American Shoulder and Elbow Surgeons scores among smokers. These findings support careful smoking history assessment and perioperative risk modification, including smoking cessation strategies.

Humans

Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis.

BACKGROUND: In SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity), among 17&#x2009;604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes, randomization to the glucagon-like peptide-1 receptor agonist semaglutide significantly reduced the primary outcome of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (mean follow-up, 39.8 months). Inflammation, as indicated by plasma hsCRP (high-sensitivity C-reactive protein) level, is implicated as a biomarker predicting cardiovascular risk in obesity and atherosclerotic cardiovascular disease. SELECT provides a unique opportunity to study the relationship among hsCRP, obesity, weight loss, and MACE outcomes in semaglutide versus placebo groups. METHODS: In this prespecified SELECT substudy, we evaluated whether baseline hsCRP levels predicted MACE risk and examined the relationships between changes in hsCRP levels and time to first MACE, baseline body weight, weight loss, and other clinical measures among treatment groups over time (104, 208 weeks) using multiple approaches, including Cox modeling. RESULTS: Baseline hsCRP level, which was similar in the semaglutide (geometric mean 1.96 mg/L) and placebo (geometric mean 1.91 mg/L) groups, was prognostic of future MACE. The risk of MACE increased across baseline hsCRP level <2, 2-<10, and &#x2265;10 mg/L subgroups, including significant associations with cardiovascular and all-cause death. Semaglutide reduced hsCRP levels (-37.8% [104 weeks]) and risk of MACE across all hsCRP subgroups. Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss, but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss. Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria. hsCRP reductions were found to be prognostic of decreased risk of MACE. Modeling suggests decreased inflammation as contributing in part to the benefits seen with semaglutide in SELECT. CONCLUSIONS: In SELECT, hsCRP data at baseline and in response to treatment with semaglutide support inflammation as a potential prognostic factor associated with cardiovascular risk in these generally well-treated patients with atherosclerotic cardiovascular disease and overweight or obesity but not diabetes. These findings suggest that the MACE reduction observed with semaglutide versus placebo in SELECT may have partially involved a decrease in inflammation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03574597.

Humans

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72&#xa0;h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR&#xa0;=&#xa0;5.12; 95% CI: 2.57-12.24; p&#xa0;<&#xa0;0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity&#xa0;<&#xa0;0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p&#xa0;=&#xa0;0.045) and significantly improved risk reclassification (cNRI&#xa0;=&#xa0;0.4778, p&#xa0;<&#xa0;0.001; IDI&#xa0;=&#xa0;0.0240, p&#xa0;=&#xa0;0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85&#xa0;years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (&#x2265;30&#xa0;mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans

Toward personalized interventions for preventing depression in primary care: Qualitative and quantitative findings from the e-predictD pilot study.

BACKGROUND: The predictD intervention, delivered by family physicians (FPs), has demonstrated effectiveness and cost-efficiency in preventing depression and anxiety. The e-predictD study aims to design, develop, and evaluate a novel personalized intervention for depression prevention by integrating information and communication technologies (ICTs), risk prediction algorithms, and decision support systems (DSS) for both patients and FPs. OBJECTIVE: To evaluate the satisfaction, usability, and acceptability, of a beta version of the e-predictD intervention in primary care settings. METHODS: The e-predictD intervention follows a biopsychosocial approach, including an initial patient-FP interview, specific FP training, and an app. A &#x3b2;-version was tested in a pilot study without a control group over three months. The app integrates a validated depression risk prediction algorithm, decision algorithms, and a monitoring system supporting the DSS. The DSS generates a personalized prevention plan (PPP) from eight intervention modules: physical exercise, social relationships, problem-solving, communication skills, decision-making, assertiveness, sleep improvement, and cognitive restructuring. Patients and FPs discussed the PPP in a 15-minute baseline interview, selecting modules for implementation over three months. Semi-structured interviews gathered feedback. Assessments included depression (PHQ-9), anxiety (GAD-7), quality of life (SF-12), and major depression risk (predictD algorithm). RESULTS: Six FPs from six Spanish cities enrolled 56 non-depressed patients at moderate-to-high risk of depression; 47 (84%) completed follow-up. The app was used for a median of six days (interquartile range: 1-30). Both FPs and patients expressed satisfaction, leading to incorporated improvements. After three months, significant reductions in major depression risk and anxiety symptoms were observed, alongside improved mental quality of life. However, no significant changes were found in depressive symptoms or physical quality of life. CONCLUSION: This pilot study supports the feasibility and acceptability of the e-predictD &#x3b2;-version, despite lower-than-expected app usability. Health improvements were observed, warranting confirmation in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03990792.

Adult

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans

Association between SGLT2 inhibitors and reporting of phimosis/paraphimosis: a comparative pharmacovigilance analysis of the WHO database.

PURPOSE: Recent data have discussed occurrence of phimosis with Sodium-glucose co-transporter-2 (SGLT2) inhibitors. However, the potential risk among the different SGLT2 inhibitors is unknown. METHODS: Using Individual Case Safety Reports (ICSRs) registered in the WHO pharmacovigilance database (01/01/2000-30/06/2025), comparisons between the different SGLT2 inhibitors and versus other drugs used in diabetes (DUD) were performed. Results are shown as Reporting Odds Ratios (ROR). RESULTS: Among 11 342 810 ICSRs, 227 were phimosis/paraphimosis with SGLT2 inhibitors, mainly between 45 and 64 years. The higher ROR value was found with empagliflozin followed by dapagliflozin and canagliflozin. ROR for SGLT2 inhibitors was higher that of all other DUD [34.72 (25.86-46.62)]. The reporting risk of phimosis/paraphimosis with SGLT2 inhibitors was also higher than that of each pharmacological class of DUD. CONCLUSION: The results suggest an association between SGLT2 inhibitors use and phimosis ICSRs. Empagliflozin had the higher reporting risk.

Humans

Ultrasound-Guided Microwave Ablation Versus Open Surgery for Benign Breast Disease: Impact on Postoperative Lactation.

BACKGROUND: Benign breast disease (BBD) is common in adult women. While ultrasound-guided microwave ablation (MWA) is an established minimally invasive treatment, its comparative impact on postoperative lactation, particularly mastitis, remains understudied. This study aimed to evaluate mastitis outcomes following MWA versus open surgery for BBD. METHODS: In this retrospective study, 79 patients (105 nodules) treated between January 2018 and August 2023 were included 41 patients (62 nodules) underwent MWA and 38 patients (43 nodules) underwent open surgery. All patients lactated within 5 years post-procedure. The primary outcome was the incidence of lactational mastitis without systemic symptoms (MWoSS) and mastitis with systemic symptoms (MSS). Patient satisfaction was also assessed. RESULTS: The incidence of MWoSS was significantly lower in the MWA group (19.5%) than in the open surgery group (50.0%). Similarly, MSS occurred in 4.9% of the MWA group versus 34.2% of the open surgery group. Multivariate analysis identified open surgery as an independent risk factor, associated with a 4.13-fold increased risk of MWoSS (OR = 4.125, 95% CI: 1.517-11.218) and a 10.14-fold increased risk of MSS (OR = 10.140, 95% CI: 2.107-48.793). Patient satisfaction was significantly higher in the MWA group (9.29 &#xb1; 0.72 vs. 8.15 &#xb1; 1.13, p < 0.001). CONCLUSION: Compared to open surgery, ultrasound-guided MWA for BBD is associated with a significantly lower risk of postoperative mastitis and higher patient satisfaction, supporting its use for women of reproductive age, particularly when future breastfeeding is planned.

Humans