Decisions regarding driving licence eligibility represents a complex medical and legal challenge, requiring careful consideration of both public safety and individual interests. The present paper provides a brief overview of the legal and administrative framework of fitness-to-drive evaluation, the roles of the professionals involved in the process, and key issues related to cognitive assessment. While physical symptoms associated with neurological conditions are generally objectively identifiable, cognitive impairments often remain less apparent and may significantly affect driving ability even in milder forms. The diagnostic accuracy of currently used neuropsychological tests is moderate, which limits the reliability of clinical decision-making. In this context, we present a prospective study conducted in stroke patients, in which a validated model based on the combination of multiple neuropsychological tests and logistic regression was developed. The model explicitly accounts for uncertainty and does not enforce categorical decisions in all cases, thereby allowing clinicians to refrain from definitive judgement in borderline cases. Although the method was validated in a stroke population, the proposed approach may be extended in future research to larger populations, such as older drivers. This would require the selection and validation of age-specific cognitive tests, which may support decision-making already at the level of primary care. Orv Hetil. 2026; 167(28): 1097-1104.

PURPOSE: Shunt thrombosis is an important complication after proximal splenorenal shunt (PSRS) in children with extrahepatic portal vein thrombosis (EHPVT). We evaluated whether preoperative vascular parameters are associated with postoperative PSRS patency. METHODS: Of 139 non-cirrhotic patients who underwent PSRS for EHPVT, 86 with adequate preoperative imaging and follow-up were included in this retrospective single-center study. The aortomesenteric angle, splenic and left renal vein diameter were measured on preoperative CT, and spontaneous splenorenal shunt presence was recorded. Shunt patency was assessed from postoperative imaging. Correlation, Firth penalized logistic regression, and ROC analyses were performed. RESULTS: Mean age was 114 ± 50 months; mean follow-up 81 ± 51 months. Patency was preserved in 69 patients (80.2%) and 17 (19.8%) developed thrombosis. No parameter was associated with patency: aortomesenteric angle (r = 0.035), splenic vein diameter (r = 0.039), left renal vein diameter (r = 0.111), or spontaneous splenorenal shunt (r = 0.005) (all p > 0.05). Firth regression identified no independent predictors, and the aortomesenteric angle showed non-significant discrimination (AUC = 0.64, 95% CI 0.485-0.795, p = 0.076). CONCLUSION: Preoperative vascular parameters were not associated with postoperative PSRS patency in pediatric EHPVT. Static anatomical measurements have limited predictive value for shunt outcomes.

Enterococcal bloodstream infections (BSI) are associated with high morbidity and limited treatment options, particularly in resource-limited settings where access to standard agents may be constrained. Comparative effectiveness data directly informing the choice among available agents for both vancomycin-resistant (VRE) and ampicillin-resistant, vancomycin-susceptible (VSE) enterococcal bacteremia are specifically lacking in such settings, where regimen selection is frequently dictated by drug availability and cost rather than guideline preference. We conducted a retrospective cohort study across three hospitals of a single university health system (Dr. Ziauddin University, Karachi, Pakistan) including hospitalized adults (≥ 18 years) with clinically significant enterococcal bacteremia (a positive blood culture together with clinical evidence of infection, as adjudicated by the treating physician) between January 1, 2010, and May 31, 2025. Only the first episode per patient was analyzed. VRE and VSE cohorts were compared for baseline characteristics and empiric therapy. Definitive monotherapy-receipt of a single study agent active against the isolate, assigned within the prespecified 48- to 72-h window after index blood culture (time-zero), by which time organism identification and susceptibility results were generally available-was assessed within the VRE and VSE cohorts. Because discharge alive is a competing event for in-hospital death, cumulative incidence functions (CIF) with Gray's test and an adjusted Fine-Gray competing-risks model (adjusted for age, Charlson Comorbidity Index, qPitt score, septic shock, and definitive antibiotic exposure (vancomycin, teicoplanin, daptomycin, tigecycline)) were used. Of 925 screened patients, 501 met inclusion criteria (VSE n = 404; VRE n = 97). VRE bacteremia presented with greater acute severity (higher APACHE II) and was more frequently catheter-associated, while VSE more often had urinary and intra-abdominal sources (all p < 0.001). In definitive monotherapy analyses among VRE (n = 67; tigecycline excluded, as it was used only as salvage therapy), 28-day mortality was numerically higher with teicoplanin (66.7%) but did not differ significantly across linezolid, teicoplanin, and daptomycin; CIF analysis similarly showed no difference in cumulative incidence of in-hospital death (Gray's p = 0.246). Tigecycline, used only as salvage therapy, was associated with higher 28-day mortality (80.0% vs 47.8%; p = 0.003; Supplementary Table S1). In VSE monotherapy (n = 404), teicoplanin exposure was associated with higher ICU admission and higher 28-day mortality, and CIF curves differed across vancomycin, teicoplanin, and linezolid (Gray's p < 0.001); however, the linezolid-exposed group had sparse/zero events for several endpoints, suggesting confounding by indication. In the adjusted Fine-Gray model, higher qPitt score was independently associated with mortality (sHR 2.21, 95% CI 1.62-3.01; p < 0.001). Tigecycline (sHR 4.00, 95% CI 2.11-7.60; p < 0.001) and daptomycin exposure (sHR 3.11, 95% CI 1.37-7.07; p = 0.007) were associated with higher subdistribution hazard of death, whereas vancomycin exposure was associated with lower hazard (sHR 0.36, 95% CI 0.20-0.67; p = 0.001). In this multi-hospital, single-system cohort, VRE bacteremia was more severe and more often catheter-associated than VSE. When accounting for discharge as a competing event, mortality differences across definitive monotherapy groups were not significant in VRE, while VSE comparisons were influenced by treatment selection and sparse outcome counts in some groups. Severity (qPitt score) was a key independent predictor of mortality, and observed antibiotic-mortality associations should be interpreted cautiously given confounding by indication.

PURPOSE: Acute portal vein thrombosis (PVT) poses a significant threat to life, with mortality rates ranging from 20% to 50%. However, a clear consensus on the management of acute PVT in children is lacking, and treatment strategies often rely on protocols established for adults. This study summarizes our experience and results in treating acute PVT with heparin combined with urokinase, providing reference data for the diagnosis and treatment of pediatric acute PVT. METHODS: From November 2017 to February 2026, 5 children (2 males and 3 females) experienced acute PVT after surgery in our hospital. The ages of these children ranged from 2 to 14 years (median: 13 years). Among the 5 patients, one had hereditary spherocytosis (HS), one had total splenic infarction caused by myeloproliferative neoplasms (MPNs), and three had Abernethy malformation. Splenectomy was performed in two patients with HS and MPN, and ligation of the portosystemic shunt was performed in the other three patients with Abernethy malformation. Abdominal ultrasound (US) and enhanced computed tomography (CT) were routinely performed at postoperative days 1-7 to detect PVT. An anticoagulant and thrombolytic treatment protocol involving the combined use of heparin and urokinase is implemented in cases of PVT involving the main portal vein and/or superior mesenteric vein (SMV); in this, intravenous heparin is administered continuously at an initial dosage of 20 U/kg per hour with an increased infusion rate to achieve APTT of 60-85 s, and intravenous urokinase is continuously administered at a dosage of 4400 U/kg per hour for 2-6 h every day. After the stabilization or disappearance of the PVT, oral medications, including aspirin and dipyridamole or rivaroxaban, were used for 6 months. The routine follow-up was performed after 1, 3, and 6 months, and every 6 months thereafter. RESULTS: The acute PVT was detected by US and CT in all patients at postoperative days 1-7 (median: 3 days). The thrombus was located in the main portal vein in 3 patients, in the SMV in 4 patients, in the IMV in 3 patients, and in the splenic vein in 4 patients. PVT occurred simultaneously in three or more branches of the portal vein system in 4 patients. One patient experienced severe abdominal pain caused by PVT, and there were no symptoms, including abdominal pain, hematochezia, nausea, or vomiting in the other 4 patients. When portal vein thrombosis is detected, there is a notable elevation in D-dimer levels. The level of D-dimer was gradually reduced, followed by the reduction of PVT after the anti-coagulation and thrombolysis therapy. The usage of heparin combined with urokinase therapy was successful in all patients; one patient developed CTPV but exhibited no symptoms of portal hypertension, whereas the PVT completely resolved in the remaining four patients between after 19 days to 6 months. There was no bleeding caused by anticoagulation or thrombolysis during therapy. The duration of hospitalization after surgery ranged from 15 to 34 days (median: 20 days). The duration of follow-up ranged from 2 months to 4 years (median: 1 year). There was no recurrence of PVT in all patients. CONCLUSIONS: The use of heparin combined with urokinase for the treatment of pediatric PVT is feasible and effective under the premise of ensuring safety. Nevertheless, further verification of its safety and effectiveness is still needed through increased sample size.

BACKGROUND: An estimated 1 in 500 people lives with hypertrophic cardiomyopathy (HCM), a disease for which genetic diagnosis can identify family members at risk and increasingly guide therapy. Variants in the gene, which encodes cardiac myosin-binding protein C (cMyBP-C), account for a significant proportion of HCM cases. However, many of these are classified as variants of uncertain significance, complicating clinical decision-making. Scalable methods for variant interpretation in disease-specific cell types are crucial for understanding variant impact and uncovering disease mechanisms. METHODS: We developed a scaled multidimensional mapping strategy to evaluate the functional impact of variants across a critical domain of cMyBP-C. We incorporate saturation base editing at the native locus, a long-read RNA sequencing-enabled assay of variant splice effects, and measurements of HCM-relevant phenotypes, including cMyBP-C abundance, hypertrophic signaling, and ubiquitin-proteasome function in human induced pluripotent stem cell-derived cardiomyocytes. RESULTS: Our multidimensional mapping strategy enabled high-resolution functional analysis of variants in induced pluripotent stem cell-derived cardiomyocytes. Our massively parallel splicing assay identified novel splice-disrupting variants. Targeted transient base editing generated a comprehensive variant library at the native locus, capturing diverse variant effects on cellular HCM-relevant phenotypes. Integration of functional assays revealed that decreased cMyBP-C abundance is a key driver of HCM-related phenotypes. In parallel, downregulation of protein degradation was observed to correlate with loss of function, and novel potential disease mechanisms were identified for missense variants near a critical binding domain. Bayesian estimates of variant effects enable the reclassification of clinical variants. CONCLUSIONS: This work provides a platform for extending genome engineering in induced pluripotent stem cells to multiplexed assays of variant effects across diverse disease-relevant cellular phenotypes, enhancing our understanding of variant pathogenicity and uncovering novel biological mechanisms that could inform therapeutic strategies.

BACKGROUND: Pressure-wire-based fractional flow reserve (FFR) is the gold standard for physiological assessment of intermediate coronary stenoses but remains underutilized owing to procedural complexity, cost, and the need for hyperemic agents. Angiography-derived physiology (ADP) platforms offer a wire-free, adenosine-free alternative. This systematic review and meta-analysis compared the clinical outcomes of ADP-guided versus FFR-guided revascularization in patients with coronary artery disease. METHODS: Comprehensive searches were performed in PubMed, Embase, ScienceDirect, and Cochrane CENTRAL from inception to April 2026. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals using random-effects models and robustness was checked with trial sequential analysis (TSA). RESULTS: Three multicenter randomized controlled trials involving 6165 patients were included. There was no significant difference in the primary composite endpoint (RR: 1.14, 95% CI: 0.85-1.54;  = 0.37;  = 57%), all-cause mortality (RR: 1.08, 95% CI: 0.75-1.56;  = .68), cardiac death (RR: 0.89, 95% CI: 0.53-1.49;  = .66), and any myocardial infarction (RR: 1.14, 95% CI: 0.66-1.98;  = .64) between ADP-guided and pressure-wire-based FFR-guided strategies. Clinically indicated revascularization was significantly higher with ADP (RR: 1.12, 95% CI: 1.05-1.20;  = .005;  = 0%). Trial sequential analysis confirmed that the accumulated evidence was sufficient to conclude no clinically meaningful difference in composite outcome. CONCLUSION: ADP-guided revascularization achieves broadly comparable clinical outcomes to pressure-wire-based FFR. Although ADP offers procedural advantages, certain platforms were associated with modestly higher revascularization rates. These findings support ADP as a practical alternative to conventional FFR in selected patients.

INTRODUCTION: Cardiac amyloidosis (CA), including transthyretin (ATTR) and light-chain (AL) subtypes, is an underrecognized mimic of heart failure with preserved ejection fraction. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) benefit general heart failure (HF) populations, their role in CA is unclear. This study evaluated the impact of SGLT2i on outcomes in patients with CA. METHODS: A systematic review and meta-analysis of seven observational studies ( = 13,303) compared patients with CA (AL and ATTR) receiving SGLT2i to matched controls. Outcomes included mortality, HF exacerbations, estimated GFR (eGFR), and NT-proBNP. Random-effects models were used to pool hazard ratios (HRs) and mean differences. RESULTS: In the primary analysis restricted to ATTR-CA, SGLT2i use was associated with lower observed all-cause mortality (the primary outcome; HR 0.71, 95% CI 0.58-0.87,  = 0.001). Among secondary outcomes in the ATTR-CA subgroup, SGLT2i use was associated with reduced NT-proBNP (-414 pg/mL, 95% CI -694 to -134,  = 0.004) and improved eGFR (+4.3 mL/min/1.73 m, 95% CI 1.4 to 7.2, p = 0.004). In a secondary, exploratory any-CA (AL + ATTR combined, 4 studies) analysis, the pooled mortality HR was 0.67 (95% CI 0.50-0.91,  = 0.010); between-study heterogeneity was substantial (I = 75%), and this combined estimate should not be interpreted as a single class effect across CA subtypes. CONCLUSIONS: In this meta-analysis of non-randomized observational studies, SGLT2 inhibitor use was associated with lower observed mortality and improved cardiac biomarkers in CA, with renal benefits most evident in ATTR. Because all included studies were observational and susceptible to confounding by indication, immortal time bias, and survivor bias, these findings are hypothesis-generating and should not be interpreted as evidence of efficacy; randomized trials are needed before treatment recommendations can be made.

INTRODUCTION: Smoking has been associated with disease risk; however, whether smoking is an independent predictor of long-term care (LTC) certification remains uninvestigated. Therefore, this study aimed to examine the association between smoking status and LTC certification. METHODS: This prospective cohort study was conducted using data from the Yamagata cohort study in Japan. Participants were followed for a mean of 7.6 years (SD=1.8). Individuals with available baseline data on smoking status and relevant covariates were included. The main exposure was baseline smoking status (current, former, and never smokers), and the primary outcome was LTC certification incidence during follow-up. Associations between smoking status and LTC certification were evaluated using Cox proportional hazards models, with sequential adjustment for potential confounders, including demographic factors, lifestyle habits, and comorbidities. RESULTS: At baseline, the overall smoking prevalence rate was 12.4% (22.4% in men, 4.6% in women). At a mean follow-up of 7.6 years (SD=1.8), LTC certification was issued to 262 (2.6%) individuals: 137 men (3.0%), and 125 women (2.1%). Unadjusted analysis using a Cox proportional hazards model indicated a higher hazard ratio (HR) for current smokers (HR=1.44; 95% CI: 1.03-2.02), which remained significant after adjustment for sex and age (AHR=1.81; 95% CI: 1.23-2.66). This persisted even after adjusting for sex, age, physical activity, alcohol consumption, hypertension, diabetes, and dyslipidemia (AHR=1.83; 95% CI: 1.25-2.69), and after accounting for nine factors, including stroke and ischemic heart disease (AHR=1.86; 95% CI: 1.27-2.73). Never and former smokers showed no differences in adjusted models. A sensitivity analysis excluding patients with a history of cardiovascular disease yielded similar AHRs. CONCLUSIONS: Overall, current smokers had a higher risk of LTC certification than never smokers, suggesting that smoking may be an independent risk factor.

BACKGROUND: Trisomy 18 is a common autosomal trisomy that is associated with high perinatal and infant mortality rates. With the widespread use of prenatal screening, many cases have been identified. In contrast, when the diagnosis occurs in the late prenatal period, that is, beyond the gestational limit for termination, or postnatally, careful planning for delivery and neonatal care is required. Emerging evidence suggests that intensive neonatal care can prolong survival and that the prenatal diagnosis may influence subsequent treatment choices. However, few studies have directly compared survival according to the timing of the diagnosis while accounting for treatment policy. Therefore, we compared survival between prenatally and postnatally diagnosed infants with trisomy 18, and examined whether diagnostic timing was associated with the selection of intensive care. METHODS: A retrospective study was conducted on 35 cases of trisomy 18 identified at our center between 2005 and 2024, including 25 prenatally diagnosed cases and 10 postnatally diagnosed liveborn infants. Among the prenatally diagnosed cases, 15 resulted in live births. Survival outcomes were compared between prenatally diagnosed liveborn infants ( = 15) and postnatally diagnosed liveborn infants ( = 10), and perinatal characteristics were evaluated. RESULTS: Among all liveborn infants, the Kaplan-Meier estimated 12-month survival rates were 8% (95% CI [0.5%-30.6%]) in the prenatal group and 40% (95% CI [12.3%-67.0%]) in the postnatal group, with poorer survival in the prenatal group (log-rank  = 0.02). Among liveborn infants, an intensive care policy was selected significantly less frequently in the prenatal group than in the postnatal group (33.3% [5/15] 90.0% [9/10],  = 0.01). In an exploratory subgroup analysis of infants who received intensive care, the Kaplan-Meier estimated 12-month survival rates were 20% (95% CI [0.8%-58.2%]) in the prenatal group and 44% (95% CI [13.6%-71.9%]) in the postnatal group. The confidence intervals were wide, and no statistically significant difference in survival was observed between the two groups (log-rank  = 0.30). CONCLUSIONS: Overall survival was poorer among infants with trisomy 18 diagnosed prenatally than among those diagnosed postnatally, and this difference may be partly associated with differences in treatment policies. These findings suggest that treatment policies following prenatal diagnosis may be associated with survival duration in trisomy 18.

BACKGROUND: Multivessel disease (MVD) represents a severe phenotype of coronary artery disease and is associated with poor prognosis. Early, non-invasive identification of MVD remains a clinical challenge. This study aimed to develop and validate a nomogram integrating cardiac function parameters and clinical characteristics for individualized prediction of MVD risk. METHODS: Clinical data were retrospectively collected from 353 patients with angiographically confirmed coronary artery disease at Guangzhou Red Cross Hospital between January 2023 and December 2024. Patients were randomly assigned to a training set (70%) and an internal validation set (30%). Least absolute shrinkage and selection operator (LASSO) regression was used to screen potential risk factors, followed by multivariate logistic regression to construct the predictive model and generate the nomogram. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). RESULTS: Seven predictors were ultimately included in the nomogram: age, gender, prior stent implantation, total cholesterol, left ventricular ejection fraction (LVEF), high-density lipoprotein, and albumin. The model exhibited good discrimination, with an AUC of 0.84 (95% CI [0.79-0.90]) in the training set and 0.79 (95% CI [0.68-0.89]) in the validation set. Accuracy was 0.81 in both datasets. Calibration curves and decision curve analysis demonstrated good predictive accuracy and clinical utility of the nomogram. Furthermore, the nomogram scores successfully stratified patients into high-risk (≥191) and low-risk (<191) groups, with significantly different score distributions between the MVD and non-MVD groups ( < 0.001). The developed nomogram provides an accurate and individualized tool for non-invasive prediction of MVD risk and may assist clinicians in identifying high-risk patients who could benefit from intensified intervention.

BACKGROUND: Diabetes markedly increases the risk of heart failure, yet the molecular signals connecting metabolic stress, myocardial fibrosis, and impaired cardiac repair remain incompletely understood. METHODS: We integrated bulk transcriptomic data from postischemic hearts (GSE26887), fibrosis-related genes from the CTD database, protein-protein interaction (PPI) analysis, and pathway enrichment (GO, KEGG, GSEA, and GSVA) to identify candidate mediators in diabetic versus nondiabetic heart failure. Single-cell RNA-sequencing datasets were analyzed with Seurat to map the cellular distribution of key genes. Pan-cancer analyses using TCGA cohorts were performed to evaluate prognostic, immune, and tumor mutation burden (TMB) correlations. Mechanistic validation was conducted in human cardiac progenitor cells (CPCs) exposed to normoglycemia or high glucose with S100A9 knockdown or overexpression, recombinant S100A8/A9, and a neutralizing S100A9 antibody. Cell viability (CCK-8); qPCR panels for fibrosis, inflammation, and metabolic genes; ROS production (DCF-DA and MitoSOX); and mitochondrial respiration were quantified. RESULTS: Differential expression and PPI network analyses identified S100A8 as a fibrosis-related hub specifically enriched in diabetic heart failure. Single-cell mapping revealed predominant S100A8 expression in CPCs rather than mature cardiomyocytes. Pathway analyses linked S100A8 to collagen fibril organization, ECM-receptor interaction, oxidative phosphorylation, and fatty acid -oxidation. Functionally, high glucose upregulated S100A8/S100A9 and profibrotic and proinflammatory genes in CPCs, increased total and mitochondrial ROS, and reduced basal, ATP-linked, and maximal respiration and spare capacity. S100A9 knockdown partially restored CPC proliferation, redox balance, and mitochondrial function, whereas S100A9 overexpression or recombinant S100A8/A9 further exacerbated oxidative stress and bioenergetic failure; S100A9 neutralization attenuated these effects. Pan-cancer analyses showed that high S100A8 expression was associated with adverse prognosis, altered immune infiltration, and increased TMB in several TCGA cohorts. CONCLUSIONS: S100A8/S100A9 emerges as a central mediator linking hyperglycemia-induced oxidative stress, metabolic inflexibility, and fibrotic reprogramming of CPCs, thereby promoting diabetic heart failure. S100A8/S100A9 may serve as a biomarker and therapeutic target at the interface of immunometabolism, cardiac regeneration, and cardio-oncology.

UNLABELLED: Adolescent obesity requires time-efficient school-based exercise strategies that improve fitness and body composition within routine physical education settings. This randomized controlled trial compared two 12-week exercise sequences combining repeated sprint exercise and bodyweight resistance exercise in adolescents with obesity: bodyweight resistance followed by repeated sprint exercise (CRS) and repeated sprint exercise followed by bodyweight resistance (CSR), alongside a non-exercising control group. Fifty-nine participants completed the trial. After adjustment for baseline values, both CRS and CSR showed more favorable post-intervention outcomes than the control group for VOmax, BMI, body fat percentage, waist circumference, 20-m shuttle run performance, sit-ups, rope skipping, fat-free mass, and resting heart rate. Most outcomes were similar between CRS and CSR, but CRS produced greater improvement in VOmax. These findings support flexible school-based combined high-intensity exercise programming, while suggesting that resistance-before-sprint sequencing may better target cardiorespiratory fitness. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2500103429; ethics approval PN-202400005.

Heart failure (HF) patients exhibit autonomic dysfunction. Orthostatic hypotension occurs often in HF and may be linked with altered cardiovascular responsiveness in HF. However, the cardiovascular response to acute hypotension in HF patients compared to healthy adults is unknown. Therefore, data were retrospectively analysed from eight patients with HF with reduced ejection fraction (7 male/1 female) and seven healthy adults (CON; 6 male/1 female) who underwent acute hypotension via thigh cuff deflation following 7.5 min of unilateral lower limb occlusion. Mean arterial blood pressure (MAP; photoplethysmogram) and heart rate (HR; electrocardiogram) were continuously recorded. Statistical analysis involved independent-samples -tests. Baseline cardiovascular values were not different between groups (all > 0.05). The magnitudes of the MAP peak decrease during acute hypotension and consequent HR peak increase were not different between groups (MAP: HF -11 ± 3 mmHg vs. CON -12 ± 5 mmHg, = 0.756; HR: HF 3 ± 2b · min vs. CON 4 ± 3b · min, = 0.243). However, the MAP time to peak decrease and HR time to peak increase were longer in HF than CON (MAP: HF 11 ± 5 s vs. CON 6 ± 3 s, = 0.041; HR: HF 10 ± 4 s vs. CON 6 ± 2 s, = 0.044). HF patients exhibit a delayed cardiovascular response to acute hypotension compared to healthy adults, which may be linked with more frequent orthostatic hypotension in HF.

Pectus excavatum (PE) is the most common congenital chest wall deformity but its association with atrial fibrillation (AF) remains underrecognized. We present a case where surgical correction of PE resulted in complete resolution of AF, highlighting the role of structural compression in lone AF and other arrhythmias. A 25-year-old male with PE presented with recurrent symptomatic AF without prior cardiovascular disease. Despite initial treatment with metoprolol and apixaban, episodes persisted. Chest CT demonstrated severe deformity (Haller index 5.6) and right atrial compression. Echocardiography showed a reduced ejection fraction (40%-45%). He underwent a Nuss procedure with dual bars and intercostal nerve cryoablation, resulting in immediate intraoperative relief of compression. There was no recurrence of AF at 9 months follow up. Severe PE may contribute to lone AF through mechanical compression. Surgical correction can provide symptom resolution in appropriate patients.

OBJECTIVE: Atrial fibrillation (AF) is a common arrhythmia affecting a large fraction of patients in intensive care units (ICUs). Predicting patients at risk of AF in the ICU is a challenging task and is not commonly practiced but could have clinical implications considering that AF is a proxy for poorer outcomes. Our goal is to develop a real-time AF prediction model using ICU numerical data to improve alarm quality, helping clinicians to identify at-risk patients and intervene before AF onset, thereby potentially improving clinical outcomes. METHODS: We employed AmsterdamUMCdb, Europe's first openly accessible ICU dataset. The dataset includes static features, including demographics, as well as dynamic bedside monitoring data, like blood pressure and respiratory rate, along with detailed records of medication and fluid administration. To enhance generalizability across diverse ICU patients, we trained a long short-term memory (LSTM) model combined with a Model-Agnostic Meta-Learning (MAML) approach. Model performance was tested on an imbalanced test set, reflective of the real-world ratio of AF to non-AF patients. Direct external validation was performed using the MIMIC-IV database to test generalizability across different clinical settings. RESULTS: The LSTM-MAML model achieved an AUC of 0.92, accuracy of 0.89, and precision of 0.29 on the internal validation set. In external validation with MIMIC-IV, it showed near-equivalent performance with an AUC of 0.89, accuracy of 0.85, and precision of 0.18. CONCLUSIONS: The real-time prediction model demonstrated predictive value for AF and has potential for future clinical benefits. However, for clinical implementation, further refinement is necessary to improve its performance in identifying patients at risk for AF.

PURPOSE: Microalbuminuria and urine albumin-to-creatinine ratio (UACR) are important markers for early diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Aspirin (acetylsalicylic acid; ASP) has been associated with anti-inflammatory and metabolic effects in patients with T2DM. This study investigated the association between low-dose ASP use and renal injury markers in patients with T2DM. METHODS: A retrospective matched cohort study was conducted in 60 Taiwanese patients with T2DM. Patients receiving low-dose ASP (100 mg/day) were matched 1:1 with controls according to sex, age, height, weight, body mass index, and duration of diabetes. Metabolic outcomes and renal injury markers, including serum creatinine, urine microalbumin, and urine albumin-to-creatinine ratio (UACR), were evaluated during follow-up. RESULTS: Compared with the DM group, the ASP group demonstrated lower HbA1c and total cholesterol levels during follow-up. In renal outcome analysis, urine microalbumin levels were significantly lower in the ASP group than in the DM group at follow-up (p = 0.039). A trend toward improved UACR was also observed in the ASP group. CONCLUSION: Low-dose ASP use was associated with favorable changes in glycemic control and early renal injury markers in patients with T2DM. Lower urine microalbumin levels and a trend toward improved UACR were observed in the ASP group during follow-up. Although microalbuminuria may be influenced by multiple metabolic and cardiovascular factors, the present findings suggest that low-dose ASP therapy may have potential metabolic and renal associations in patients with T2DM. Further prospective studies are warranted to validate these findings and to explore the underlying mechanisms and their clinical relevance.

BACKGROUND: Shift work can disrupt circadian rhythms and is postulated to play a role in cardiovascular diseases (CVD). In the German prospective population-based Heinz Nixdorf Recall Study, we analyzed longitudinal associations between shift work and night-shift work with CVD. METHODS: CVD was defined as a fatal or non-fatal cardiac or cerebrovascular event or interventional coronary revascularization during an average follow-up of 15 years. Retrospective shift-work information was assessed as binary and as lifetime duration in years. Adjusted log-linear Poisson regression models were applied to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for the effect of shift and night-shift work on incident events. Stratified analyses by sex, diurnal preference, and blue-collar status were also performed. RESULTS: Incident CVD was not associated with shift work (N = 3024; shift work for at least 1 year: IRR = 0.87, 95% CI = 0.68-1.10; night-shift work for at least 1 year: IRR = 0.87, 95% CI = 0.66-1.14). However, we observed sex differences with reduced incidence of CVD for long duration of night-shift work among men (N = 1369 with 380 night-shift workers; model for duration of night-shift work: 1- < 10 years: IRR = 1.08, 95% CI = 0.74-1.57; 10+ years: IRR = 0.64, 95% CI = 0.42-0.96). For women, we found slightly elevated IRRs (N = 1438 with 91 night-shift workers; model for duration of night-shift work: 1- < 10 years: IRR = 1.11, 95% CI = 0.35-3.50; 10+ years: IRR = 2.05, 95% CI = 0.75-5.61). These estimates were stronger in women that never worked in blue-collar jobs (10+ years night-shift work: IRR = 3.22, 95% CI = 1.17-8.92). CONCLUSIONS: We did not observe consistently increased risks of CVD with shift and night workers. However, stratified analyses pointed toward sex- and job-specific vulnerable subgroups.

BACKGROUND The clinical manifestations of infective endocarditis (IE) are highly varied, and diagnostic delays are common and potentially life-threatening. Due to their overlapping clinical presentations, IE may be misdiagnosed as giant cell arteritis (GCA). Although IE mimics GCA, scalp allodynia associated with IE has not previously been reported. CASE REPORT A 60-year-old man with mitral valve prolapse presented with fever, generalized stiffness, and low back pain refractory to oral antibiotics and low-dose glucocorticoids. He also reported a stinging sensation on his scalp while washing his hair, consistent with scalp allodynia. Prednisolone was initiated for presumed GCA. However, blood cultures subsequently grew Streptococcus parasanguinis, and imaging studies showed hematogenous dissemination. Ultimately, IE was confirmed based on the modified Duke Criteria. All symptoms, including scalp allodynia, resolved completely following the initiation of antibiotic therapy. CONCLUSIONS This case highlights that scalp allodynia, while characteristic of GCA, can also occur in IE, and underscores the limitations of relying solely on clinical symptoms when differentiating GCA from infectious etiologies. In patients with fever and scalp allodynia-particularly those with predisposing cardiac conditions-IE warrants strong consideration. Blood cultures should be obtained before initiating glucocorticoid therapy, and early clinical reassessment is critical to avoid the potentially catastrophic consequences of missed or delayed IE diagnosis.

Chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) are driven by the BCR:ABL1 fusion and remain highly responsive to tyrosine kinase inhibitors (TKIs). Ponatinib, a third-generation TKI, uniquely retains activity against the T315I 'gatekeeper' mutation and most other BCR:ABL1 variants, producing deep cytogenetic and molecular responses in resistant CML and improving survival in Ph+ ALL. Across the PACE and OPTIC programs, frontline Ph+ ALL combinations (hyper-CVAD- and blinatumomab-based), and real-world cohorts, ponatinib demonstrates robust antileukemic efficacy in diverse settings and after multiple prior TKIs. However, its multikinase profile confers a clinically meaningful risk of arterial occlusive events (AOEs)-including coronary, cerebrovascular, and peripheral arterial complications-whose incidence is shaped by baseline cardiovascular risk and overall drug exposure. Mechanistic studies suggest that endothelial dysfunction, pro-inflammatory signaling, impaired nitric oxide bioavailability, and microvascular rarefaction contribute to ponatinib-associated vascular toxicity. Clinically, response-based dosing-such as step-down from 45→30→15 mg in CML or 30→15 mg in Ph+ ALL upon molecular milestones-preserves efficacy while reducing exposure-related AOE risk, though events are not eliminated. Emerging cardio-oncology strategies can further mitigate harm: baseline risk stratification (e.g. SCORE2/SCORE2-OP, HFA-ICOS), aggressive management of blood pressure and lipids, selective antiplatelet prophylaxis in high-risk profiles, and close longitudinal surveillance. Overall, contemporary evidence supports ponatinib as a high-potency option for T315I disease and multi-tyrosine kinase inhibitor (TKI) resistance, and as a practical component of modern Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) therapy, provided that dosing is individualized and cardiovascular risk is proactively managed. Future priorities include refining patient selection, validating preventive cardio-oncology bundles, and defining minimal-effective exposure thresholds that sustain durable disease control with the lowest feasible vascular liability.

BACKGROUND: Exercise-induced pulmonary hypertension (EiPH) represents an early stage of pulmonary vascular disease that remains challenging to identify noninvasively, particularly in patients with borderline resting haemodynamics. We aimed to develop and validate a multimodal non-invasive model integrating clinical characteristics, exercise echocardiography, and cardiopulmonary exercise testing (CPET) to accurately predict invasively confirmed EiPH. METHODS: This prospective cohort study consecutively enrolled adult patients who presented with exercise limitation following chronic pulmonary artery thrombosis or who exhibited increased tricuspid regurgitation velocity on transthoracic echocardiography. All patients underwent comprehensive clinical evaluation, stress echocardiography, CPET, and invasive exercise right heart catheterization as the diagnostic gold standard. To minimize the impact of physiological variability on the results, all three tests were conducted at the same time. Feature selection was conducted sequentially using Spearman correlation analysis, statistical testing, and LASSO regression to identify core features associated with EiPH. Subsequently, a logistic regression model with elastic net regularization was used. Five-fold cross-validation and grid search were employed to optimize model parameters and evaluate the diagnostic performance of different models. In addition, the DeLong test was used to assess whether the AUC differed significantly between models. Finally, subgroup analyses were performed to validate the robustness of the model. RESULTS: The study included a total of 78 patients, comprising 34 cases of EiPH and 44 cases without EiPH. Patients in the EiPH group were significantly older (68.5 vs. 51.5 years, P < 0.001) and demonstrated reduced exercise capacity, impaired pulmonary function, abnormal right ventricular function, and increased pulmonary vascular resistance. After integrating multimodal data from clinical features, stress echocardiography, and cardiopulmonary exercise testing, the Clinical+Echo+CPET model achieved the best performance, with an AUC of 0.951 (95% CI: 0.902-0.987), an accuracy of 0.871, and a Brier score of 0.128, indicating strong discriminative ability and good calibration. The model maintained high stability in the internal validation cohort, with an AUC of 0.900, a sensitivity of 0.833, and a specificity of 0.700. The DeLong test showed that the multimodal model (Clinical+Echo+CPET) had superior discriminative performance compared with the unimodal models (Clinical, Echo, or CPET). Subgroup analysis demonstrated that the model maintained good diagnostic performance across different age and sex groups. CONCLUSIONS: A non-invasive multimodal model integrating clinical indicators, exercise echocardiography, and cardiopulmonary metabolic parameters can reliably identify EiPH.

BACKGROUND: Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is a high-risk phenotype primarily driven by metabolic syndrome, with a significantly increased incidence and risk of adverse outcomes. A fundamental reason for this is the lack of early clinical diagnosis. As a tool capable of accurately capturing pathophysiological states, metabolomics provides a critical entry point for addressing this issue; however, studies focusing on the metabolic characteristics of this population remain limited. METHODS: This study integrated a clinical cohort and untargeted metabolomics to compare serum metabolic profiles between patients with cardiometabolic HFpEF and those with metabolic syndrome (MetS). Baseline characteristics were balanced using propensity score matching (PSM). Differential metabolites were identified by untargeted metabolomics, followed by KEGG pathway enrichment analysis. Machine-learning approaches were further applied to screen candidate metabolites with potential diagnostic efficacy, and weighted gene co-expression network analysis (WGCNA) together with SHapley Additive exPlanations (SHAP) were used to evaluate phenotype association and feature contribution. In an independent clinical cohort, total sphingomyelin (SM) levels were assessed by ELISA as an external evaluation strategy based on clinical applicability. RESULTS: Differential metabolites between the two groups were mainly enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Through multi-method screening, C24:1 Sphingomyelin was identified as a candidate metabolite with potential diagnostic efficacy. The co-expression module containing C24:1 Sphingomyelin was significantly correlated with NT-proBNP, a key biomarker of heart failure, and SHAP analysis indicated that C24:1 Sphingomyelin contributed substantially to the classification model. In the external cohort, total SM levels were associated with disease status, suggesting the potential clinical association of sphingolipid-related signals. CONCLUSION: This study preliminarily characterized the metabolic features distinguishing cardiometabolic HFpEF from MetS alone, suggesting that sphingolipid dysregulation is associated with the development and progression of this phenotype. Among the identified metabolites, C24:1 Sphingomyelin was identified as a candidate metabolite with potential diagnostic performance, and SM showed potential clinical applicability. These findings provide new clues for biomarker discovery and preliminary clinical translational exploration in cardiometabolic HFpEF.

BACKGROUND: Atherosclerosis (AS) is a primary driver of cardiovascular diseases, with vascular smooth muscle cell (VSMC) fate being critical for plaque stability. Macrophage extracellular traps (METs) are implicated in AS, but their precise impact on VSMCs remains unclear. This study investigated the role of METs in VSMC necroptosis, phenotypic switching, and AS progression. METHOD: An ApoE mouse model was utilized, with intraperitoneal injection of exogenous METs. Atherosclerotic plaque burden was assessed via Oil Red O, H&E, and Masson staining. MPO-DNA complexes, inflammatory cytokines, and necrotic markers were quantified by ELISA. In vitro, VSMCs were treated with ox-LDL, METs, and pathway inhibitors to evaluate necroptosis, contractile/synthetic phenotype markers, and Rap1 signaling pathway activation. RESULTS: Exogenous METs administration exacerbated AS plaque burden in ApoE mice, characterized by increased plaque area, reduced collagen content, and thinner fibrous caps. METs also amplified systemic inflammation, dyslipidemia, and necroptosis-driven plaque destabilization. Bioinformatic analysis revealed a strong association between METs and necroptosis in unstable plaques. In vitro, METs triggered VSMC necroptosis and upregulated synthetic phenotype markers. Mechanistically, the Rap1-MEK5-ERK5/p38 signaling axis was activated in METs-treated VSMCs and AS plaques. Pharmacological inhibition of Rap1 signaling attenuated plaque progression and suppressed VSMC necroptosis and phenotypic switching. Additionally, METs were internalized by VSMCs via endocytosis. CONCLUSION: Our findings demonstrate that METs are endocytosed by VSMCs, activating the Rap1-MEK5-ERK5/p38 cascade to drive necroptosis and synthetic phenotypic transition, thereby accelerating AS progression. These insights provide a molecular foundation for developing novel therapies targeting METs or the Rap1 pathway to stabilize vulnerable plaques.

BACKGROUND: While metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently associated with increased cardiovascular risk in the general population, its association with cardiovascular disease (CVD) mortality in adults with established cardiometabolic risk factor (including obesity, hypertension, diabetes mellitus, or dyslipidemia) remains inconsistent. We aimed to determine whether frailty confounds the MASLD-CVD mortality association. METHODS: We analyzed 10,413 US NHANES III adults with ≥ 1 cardiometabolic risk factor. Frailty was quantified using a 49-item frailty index (FI, ranging from 0 [maximal robustness] to 1 [severe frailty]) and categorized into quartiles. Associations between MASLD and CVD mortality were assessed using multivariable Cox proportional hazards models with and without frailty adjustment. Interaction and mediation analyses were also performed. RESULTS: Over a mean follow-up of 23.36 years, 1,375 (13.20%) CVD deaths occurred. Frailty was significantly associated with both MASLD and CVD mortality. There was no evidence of interaction between MASLD and frailty, and mediation analysis showed no indirect effect of MASLD on CVD mortality through frailty. In absence of frailty adjustment, MASLD was not associated with CVD mortality (HR = 0.92, 95% CI: 0.78-1.10). After adjustment for frailty, MASLD was independently associated with higher CVD mortality (HR = 1.19, 95% CI: 1.07-1.32). Stratified by FI quartiles, significant associations were observed only in the higher frailty quartiles (Q3: HR = 1.35, 95% CI: 1.03-1.77; Q4: HR = 1.70, 95% CI: 1.07-2.69). The population attributable fraction of MASLD for CVD mortality was 10.1-12.5% after frailty adjustment. CONCLUSIONS: Frailty may confound the MASLD-CVD mortality relationship in people with cardiometabolic risk factors. The association between MASLD and CVD mortality is detected only when frailty is adjusted for.

BACKGROUND: High lipoprotein(a) [Lp(a)] levels and insulin resistance (IR) are both established risk factors for atherosclerosis. Nevertheless, the interrelationship between these two factors and their combined effects on atherosclerosis remain poorly understood. This research aimed to explore the distribution characteristics of Lp(a) across individuals at varying IR degrees and to evaluate the combined ability of Lp(a) levels and the IR surrogate marker, estimated glucose disposal rate (eGDR), in predicting atherosclerosis. METHODS: This retrospective study involved data from 10,753 participants who received health examinations at the Third Xiangya Hospital (2017-2025). Carotid ultrasound was employed to diagnose atherosclerotic plaques. Logistic regression and restricted cubic spline (RCS) analysis were used across eGDR quartiles to examine the relationship between Lp(a) and plaque risk. The incremental benefits of incorporating both Lp(a) and eGDR in predicting atherosclerosis were further assessed via machine learning-based analyses. RESULTS: In this study, the median Lp(a) concentration of the participants was 12.4 mg/dL, with 14.4% exhibiting values greater than 30 mg/dL. RCS analysis identified a significant nonlinear (U-shaped) relationship of Lp(a) with eGDR, whereas peak Lp(a) levels were observed within the uppermost eGDR quartile (Q4). Lp(a) levels demonstrated an independent positive link to atherosclerotic plaque risk; notably, this association remained significant in both the lowest and highest eGDR quartiles. Furthermore, machine learning analyses indicated that the incorporation of Lp(a) and eGDR conferred a modest gain in the model's discriminative capacity when forecasting atherosclerotic plaque, with the AUROC value increasing slightly from 0.7810 to 0.7820. CONCLUSIONS: Lp(a) levels exhibited a positive linear association with atherosclerotic plaques in the overall population, which varied across eGDR strata. Furthermore, the interaction between Lp(a) and eGDR was significantly relevant for the prediction of this condition. The integration of Lp(a) levels and the eGDR into machine learning models modestly improved the identification of high-risk individuals. This strategy supports more precise clinical interventions, ultimately contributing to improved cardiovascular health outcomes.