• Comprehensive Intervention to Promote Healthy Lifestyles and Prevent Cardiometabolic Diseases in Low-Income School Children From Mexico: Protocol for the ESCOLARISANO Randomized Controlled Trial.
    1 week ago
    Obesity is a serious public health issue affecting children in a progressively alarming manner; thus, nutrition education and behavior change interventions during childhood are a priority. Eating and physical activity behaviors are mainly influenced by the environment; therefore, lifestyle changes are often successful when interventions are implemented in places such as the home and school. Schools are fundamental for ensuring the development of students' personalities, skills, abilities, and long-term behaviors.

    This study aims to measure the effect of an intervention designed for low-income Mexican schoolchildren, focused on promoting healthy lifestyles for the prevention of obesity and cardiometabolic diseases.

    The study design is a randomized clinical trial (NCT05945862), with intervention groups paired with control groups of the same grade. Four elementary schools were selected based on district socioeconomic status. The study will be carried out for 1 year in four phases: (1) initial measurements, including anthropometry, blood pressure, psychosocial diagnosis, family medical history, and behavior variables, such as nutrition knowledge, dietary intake, sleep time and quality, and physical activity; (2) intervention implementation based on social cognitive theory, the behavior change wheel with the capability, opportunity, and motivation influencing behavior theoretical framework, and the transtheoretical theory, covering topics related to nutrition and healthy eating, child health, personal and sleep hygiene, physical activity, psychosocial well-being, and motivation; (3) postintervention measurements, including initial and behavioral measurements and intervention indicators; and (4) 6-month postintervention evaluation using the same initial and behavioral measures as in phase 1. Baseline differences by age, sex, socioeconomic status, and location will be analyzed using chi-square tests (qualitative variables) and analysis of covariance (quantitative variables). Multiple linear regression will test potential baseline associations between dependent variables (anthropometrics and blood pressure) and independent variables (diet, exercise, sleep time, family interaction, psychosocial well-being, and perception of childhood obesity). For comparing changes between the intervention and control groups at postintervention and at 6-month postintervention in anthropometrics, blood pressure, and behavioral variables, we will use multilevel mixed-effects regression models, given the hierarchical structure of participants nested within schools and the repeated measurements over time. SPSS and STATA software will be used with a significance level of P<.05.

    From October 2023 to August 2024, a total of 451 participants were recruited from 4 different elementary schools in Sonora, México. As of February 2026, the data collected are in the process of being captured and analyzed.

    The protocol is a comprehensive program designed for schoolchildren in Mexico, intended to be an effective strategy for promoting healthy lifestyles and preventing cardiometabolic diseases. It is important to continuously adapt the intervention before implementation and to evaluate it to ensure its sustainability and expand its impact on other elementary schools, improving the health and well-being of schoolchildren.
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  • Electroactive microneedle augmented stem cell therapy in myocardial infarction.
    1 week ago
    Ischemic heart disease and related sequelae pose tremendous burdens on worldwide medical care. The excessive activation of cardiomyocytes and cardiac fibroblasts further exacerbates the prognosis after necrosis. Decades of stem cell therapy in preclinical studies suggested promising results in cardiomyocyte regeneration and tissue remodeling. However, few formulations achieved clinical translation due to the limited stem cell engraftment and insufficient arousal of resident cardiomyocytes. Here, we reported an implantable electroactive device to leverage stem cell therapy and cardiomyocyte restoration for effective heart recovery. Assisted by the piezoelectric microneedle patch with 80-cubic millimeter cavity, 1.5 × 105 mesenchymal stem cells could be delivered efficiently to the infarcted site and sustained longer for continuous paracrine effects. Meanwhile, the piezoelectric stimulation generated from the poly(l-lactic) acid microneedle matrix further potentiated the stem cells and elicited more vigorous self-repair responses in cardiomyocytes. This approach was validated to effectively suppress inflammatory monocytes, reduce cardiomyocyte necrosis, and improve heart remodeling in a rat heart infarction model.
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  • Sex differences in global burden of Congenital Heart Anomalies in children under five from 1990 to 2021.
    1 week ago
    Congenital heart anomalies (CHA) significantly contribute to childhood morbidity and mortality worldwide. Understanding sex-specific differences and their association with societal development levels is crucial for formulating effective health strategies.

    We extracted sex-stratified incidence, mortality, and disability-adjusted life years (DALYs) for CHA among children under five from the Global Burden of Disease Study 2021 for 204 countries and territories (1990-2021). Sex differences were quantified using male-to-female rate ratios with 95% uncertainty intervals. Temporal trends were evaluated using the estimated annual percentage change (EAPC) derived from log-linear regressions. We assessed the association between disease burden and development status using the Sociodemographic Index (SDI). To address confounding variables and geographic clustering, we fitted linear mixed-effects models with sex, SDI, and calendar year as fixed effects and GBD region as a random intercept, reporting adjusted coefficients with 95% confidence intervals.

    From 1990 to 2021, the global CHA burden declined. While descriptive analysis showed higher raw point estimates for males, a multivariable mixed-effects analysis-adjusted for SDI (as a proxy for macro-level development and health-system context) and temporal trends-confirmed that male sex was significantly associated with a higher CHA burden (DALYs Adjusted Coefficient: 876.4, P < 0.001; Mortality Adjusted Coefficient: 9.7, P < 0.001). This suggests a robust male disadvantage independent of socioeconomic status. The highest CHA burdens were observed in Sub-Saharan Africa, Southeast Asia, and South Asia, while improvements in SDI were significantly associated with overall reductions in burden.

    Despite overall reductions in CHA burden, profound regional disparities and observable sex differences persist, especially in resource-limited areas. Policy interventions focusing on gender-sensitive resource allocation, enhanced neonatal screening, and improved surgical access are critical to mitigating these disparities and advancing global pediatric health equity.
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  • Rationale and design of a multicenter, prospective, diagnostic clinical study: A study protocol for evaluating the diagnostic validation of deep learning-based noninvasive CT-FFR for in-stent restenosis.
    1 week ago
    Currently, there are many diagnostic strategies for in-stent restenosis (ISR) used clinically, including invasive coronary angiography (ICA), coronary computed tomography angiography (CCTA), and Fractional Flow Reserve (FFR). CCTA is not recommended for post-stent implantation patients owing to suboptimal image quality caused by artifacts. The FFR application is limited by its procedural complexity. Precise evaluation may be achieved by using computed tomography-derived fractional flow reserve (CT-FFR), which combines computational fluid dynamics (CFD) with CCTA. Anatomical and functional assessments of ISR lesions could be integrated effectively as well in this way. However, the computational complexity and prolonged processing time may hinder its utility in clinical use.

    This study is a multicenter, prospective, diagnostic study, aiming to establish a deep learning-based CT-FFR model for the accurate assessment of ISR and to validate its diagnostic performance using invasive FFR as the reference standard. This study will be carried out in Beijing Anzhen Hospital and 6 subcenters in China. We planned to prospectively enroll 331 post-stent implantation patients with available CCTA data since June 2022, and invasive FFR will be performed within 3 months when clinically indicated. Patient recruitment is currently ongoing. Among them, 250 patients from Beijing Anzhen Hospital will be used to adapt and extend the existing DEEPVESSEL model, a deep learning-based CT-FFR computational software designed for the non-invasive functional assessment of coronary artery disease and previously validated in de novo coronary lesions, for application in the assessment of in-stent restenosis (ISR), and 81 patients from the other 6 subcenters will be used in external validation. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value with their corresponding 95% confidence intervals (CIs) were calculated for CT-FFR. The receiver operating characteristic (ROC) curve was analyzed, and the area under the curve (AUC) was calculated. The McNemar test and Bland-Altman plot will be used to examine the diagnostic consistency between CT-FFR and invasive FFR. The correlation was analyzed by Spearman's correlation coefficient.

    ChiCTR2200058822.
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  • Long-Term Effectiveness of a Game-Based Mobile App for Training in Cardiopulmonary Resuscitation and Automated External Defibrillator Use: Nonrandomized Controlled Trial.
    1 week ago
    Bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use are critical for improving survival after out-of-hospital cardiac arrest. Although conventional training methods are initially effective, they are often hampered by rapid skill decay over time. Game-based mobile apps have emerged as a promising and scalable alternative for CPR and AED education; however, evidence of their long-term efficacy remains scarce.

    This study aimed to evaluate the integration of a game-based mobile app into traditional CPR and AED training. We assessed its impact on university students' theoretical knowledge, practical skills, and theoretical knowledge retention, as well as their willingness to perform CPR and their awareness of disseminating these skills.

    A nonrandomized controlled trial was conducted among university students in China from March 21 to September 21, 2024. Participants were assigned to either an experimental group, which received game-based mobile app training supplemented with traditional training, or a control group, which received traditional training only. The game-based app featured a simulated scenario that required users to execute the correct sequence of resuscitation procedures and operate a virtual AED under time constraints. The intervention period lasted for 6 months. Participants' theoretical knowledge and practical skills were assessed immediately after training (baseline) and at the 7-day follow-up. Long-term retention of knowledge, willingness to perform CPR, and dissemination awareness were evaluated at the 6-month follow-up. Data were analyzed using SPSS software (IBM Corp), employing the chi-square test, Mann-Whitney U test, and Wilcoxon signed-rank test.

    A total of 481 participants completed the entire survey (n=241 in the experimental group and n=240 in the control group). In the short-term (7-d) assessment, the experimental group demonstrated significantly higher scores in both theoretical knowledge (P=.02) and practical skills (P<.001) compared to the control group. This advantage was maintained in the long term, with the experimental group showing superior knowledge retention at the 6-month follow-up (median score: 9/10 vs 8/10; P<.001). Furthermore, a majority of all participants expressed willingness to perform CPR on strangers (70.9%, 341/481) and to disseminate first-aid knowledge (92.1%, 443/481). However, no significant intergroup differences were observed for these latter 2 outcomes (P=.85 and P=.97, respectively).

    Despite the methodological limitations inherent in this nonrandomized study, our findings indicate that supplementing traditional training with the game-based mobile app significantly enhanced short-term acquisition of theoretical knowledge and practical skills and promoted sustained knowledge retention. This supports the app's potential as an effective and promising complement to conventional CPR and AED training programs.
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  • Early adequate linezolid concentrations and clinical outcomes in confirmed Gram-positive infections: the role of therapeutic drug monitoring.
    1 week ago
    Due to the unpredictable exposure of linezolid with a standard dosing regimen, therapeutic drug monitoring (TDM) has been recommended to guide it despite limited evidence on clinical endpoints. The primary objective was to determine whether achieving therapeutic linezolid concentrations at the first TDM measurement is associated with clinical cure. Microbiological eradication and 7 day and 30 day mortality were also assessed.

    We conducted a retrospective study in a cohort of patients with confirmed Gram-positive (Enterococcus/Staphylococcus spp.) infections and undergoing TDM. A steady-state linezolid trough concentration (Cmin,ss) of 2-8 mg/L was considered therapeutic. A multivariable logistic regression model assessed predictive factors associated with clinical cure.

    Four hundred patients (median age 68 years, 66.5% male) were included. Infections were mainly intra-abdominal (29.3%), skin/soft tissue or bone/joint (25.5%) and respiratory (21%). At first measurement only 34% of patients reached the therapeutic range, with 34.5% below range and 31.5% above range. Clinical cure rate was 76.3% and 30 day all-cause mortality was 20%. Multivariable logistic regression showed that achieving therapeutic Cmin,ss significantly increased the likelihood of clinical cure (OR 1.78, 95% CI 1.02-3.19). Conversely, a higher Charlson index, liver cirrhosis and sepsis/septic shock requiring ICU admission were risk factors for failure. Other clinical outcomes were not independently related to Cmin,ss.

    This study suggests that achieving early therapeutic linezolid concentrations is associated with a higher likelihood of clinical cure and highlights the limitations of an initial standard dosing. In this scenario, an early TDM may help to identify patients out-of-range who need guided dosing to ensure the achievement of pharmacokinetic/pharmacodynamic targets. Further prospective studies are needed to assess the impact of TDM on survival, microbiological outcomes and cost-effectiveness.
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  • Clinical Utility of Mechanical Echocardiographic Dispersion to Assess Left Ventricular Function and Ischemia or Infarction Detected by Gated 99M-Tc Sestamibi-SPECT.
    1 week ago
    Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide. Echocardiographic assessment of left ventricular (LV) asynchrony may provide additional value for detecting ischemia or infarction.

    To assess the systolic and diastolic mechanical dispersion (MD) by 3D-echocardiography and its correlation with left ventricular ejection fraction (LVEF) and ischemia or infarction by myocardial perfusion study (MPS) gated 99m-Tc Sestamibi-SPECT.

    Cross-sectional study of patients with angina. Systolic and diastolic MD were defined as the standard deviation (SD) of the time to reach minimum ventricular volume, corrected for the R-R interval. Association with LVEF was assessed with correlation and linear regression. ROC curves identified ischemia or infarction and compared with E/A ratio, TRIVI, and E/e' ratio.

    205 patients were studied with median age 62 (IQR: 54-69) years. 51% (n = 104) presented ischemia or infarction. We observed a negative correlation with systolic (r = -0.343, 95% -0.459 to -0.215; p < 0.001) and diastolic (r = -0.184, 95% -0.314 to -0.047; p < 0.01) MD and MPS-LVEF, which contributes to 8.9% and 11.8% of variance, respectively. Both parameters displayed an area under the curve (AUC) of 0.634 (95% 0.559-0.709, p < 0.001) and 0.604 (95% CI 0.527-0.679, p < 0.001) are shown to detect ischemia/infarction. In patients with transmural infarction the AUC for systolic MD improved to 0.691 (95% 0.582-0.801, p < 0.05).

    Systolic and diastolic MD are useful and simple parameters for assessment of LV function and ischemia or infarction.
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  • Mycotic Aneurysms in Intestinal Transplantation: A Case Series.
    1 week ago
    Mycotic aneurysms (MA) are a potentially fatal complication following intestinal transplantation (ITx). Their occurrence arises from several factors, such as chronic abdominal sepsis, potential for contamination of the vascular grafts during enteric anastomoses and the heightened burden of immunosuppression.

    A retrospective review of a prospectively maintained database of all adult ITx from December 2007 to June 2025 was conducted.

    Among 168 ITx, six patients (3.6%) experienced eight MA episodes. MA occurred bimodally, early post-transplant (2-8 weeks) or in a later phase (55-377 weeks). Recurrence occurred in two patients, averaging 132.4 weeks after initial diagnosis. A history of hollow viscus perforation or anastomotic leak was present in 83.4%. Diagnosis was peri-operative in two cases due to rupture, while others were detected electively via angio-CT. Recurrences were subtler, identified incidentally or with mild symptoms. Apart from targeted antibiotic and antifungal treatment, management strategy pivoted around endovascular stent grafting (ESG) followed by an aneurysmectomy and creation of a new conduit. Post-operative mortality at first presentation occurred in 66.6% of patients, with 50% within a week. Two patients survived recurrence, with one remaining alive 6.5 years post-diagnosis.

    MA in ITx is rare but commonly fatal, often linked to bowel perforation or anastomotic complications. Diagnosis relies on angio-CT or intraoperative identification at the time of emergency laparotomy. Management involves ESG and conduit resection. Early aggressive control of potential contamination sources after ITx is crucial, though general conclusions are limited by low incidence.
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  • Uncovering the similarities of lipidome-wide markers of carotid artery plaque and metabolic dysfunction-associated fatty liver disease: the Young Finns study.
    1 week ago
    Metabolic dysfunction-associated fatty liver disease (MAFLD) and carotid artery plaque (CAP) are both linked to circulatory lipid and lipoprotein metabolism. However, the shared lipidome-wide mechanisms underlying these diseases remain unexplored. To identify plasma lipid species associated with both MAFLD and CAP to uncover their shared metabolic pathways. We analyzed data from the Young Finns Study cohort from the 2007 and 2018 follow-ups (n = 1496, aged 41-56 years, 56.3% females). Ultrasound was used to determine the prevalence of both CAP and MAFLD during the 2018 follow-up. The participants were categorized into three mutually exclusive groups: participants with CAP without MAFLD (n = 257), participants with MAFLD without CAP (n = 150), and a control group free from both diseases (n = 436). Lipidomic profiling of 437 lipid species from plasma was performed during the 2007 follow-up (aged 30-45 years) via liquid chromatography‒tandem mass spectrometry. Logistic regression models, both unadjusted and adjusted for age, sex, physical activity, alcohol consumption, and smoking, were used to assess lipid associations with both disease outcomes separately. Odds ratios (ORs) and confidence intervals (95% CIs) were calculated for each lipid species, and multiple testing corrections were performed via the false discovery rate (FDR) method (< 0.05). Additionally, we performed a hypergeometric enrichment analysis to determine whether certain lipid classes appear more often than expected among the lipids associated with disease. In the unadjusted models, there were a total of 51 significant (FDR < 0.05) overlapping lipids between the CAP and MAFLD groups. In the adjusted models, four lipids were significantly associated with CAP, and 202 lipids were significantly associated with MAFLD. Notably, only one lipid-phosphatidylcholine (PC) 40:4-was significantly associated with both diseases. PC 40:4 was associated with an increased risk of CAP (OR 2.59; 95% CI, 1.57-4.32) and MAFLD (OR 5.26; 95% CI, 2.81-9.85). Our findings highlight PC 40:4 as a novel shared lipid signature for both MAFLD and CAP. This dual association suggests that overlapping metabolic disturbances and potentially common lipid-based pathogenic mechanisms link liver and vascular health. PC 40:4 may serve as a promising early biomarker or therapeutic target for metabolic-vascular comorbidities.
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  • Longitudinal assessment of thrombin generation using calibrated automated thrombography in patients with continuous-flow left ventricular assist devices over a five-year period.
    1 week ago
    Despite improved survival, patients with advanced heart failure receiving long-term left ventricular assist device (LVAD) support remain at risk of serious complications, including pump thrombosis, ischemic stroke, and bleeding. LVAD therapy may contribute to persistent alterations in the hemostatic system, the impact of which on adverse clinical events remains unclear. The aim of the study was to characterize longitudinal alterations in coagulation in patients supported with continuous-flow LVADs, assessed using the Calibrated Automated Thrombogram (CAT) assay. Basic coagulation parameters were assessed at baseline, 3-4 months, 6-12 months, and every 6 months thereafter. Only patients completing all four scheduled follow-up visits were included in further analyses. Eighty-five patients were recruited; 22 met the inclusion criteria. Significant shift toward a hypocoagulable state was observed: increase in thrombin generation lagtime, decrease in endogenous thrombin potential and peak thrombin concentration (P < 0.001). Markers of persistent fibrinolytic activity were observed. LVAD support was associated with increased albumin and hemoglobin levels, decreased bilirubin, creatinine, and NT-proBNP concentrations (P < 0.05). No significant differences were observed between CAT parameters and adverse events in the investigated group. Long-term LVAD therapy was associated with progressive changes in coagulation parameters, despite a stable anticoagulant and antiplatelet treatment regimen.
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