Background/Objectives: Wearable devices provide multidimensional measures of cardiometabolic health. We aimed to derive latent physiological dimensions from ECG and motion variables collected by a wearable device and evaluate their associations with the individual health metrics of the Longevity Check-Up 8+ (LC8+) programme. Methods: Community-dwelling adults voluntarily participating in four Longevity Check-Up 8+ (LC8+) events underwent 24-h multiparameter recording using a wearable device. Eight wearable-derived variables were entered into principal component analysis (PCA) to derive latent physiological dimensions. Component scores were subsequently evaluated for associations with overall LC8+ health, while exploratory analyses examined associations with individual health metric domains. Results: Ninety-seven participants (mean age 51.3 ± 13.4 years; 36% female) were enrolled. Among the 96 participants with complete data for the PCA, three latent physiological components were identified, explaining 70.1% of the total variance. PC1, which was characterised by high SDNN, high RMSSD, and low nocturnal heart rate, was independently associated with overall LC8+ health (LM: B = +0.402, 95% CI [+0.103, +0.700], p = 0.009). Among the eight LC8+ domains, only the association between PC1 and glycaemic health remained statistically significant after Benjamini-Hochberg correction in the primary fixed-effects analysis (95% CI [1.32, 4.62], adjusted p = 0.039). Conclusions: A wearable-derived autonomic component was associated with overall cardiometabolic health in community-dwelling adults. Among the individual LC8+ domains, the strongest association was observed for glycaemic health. These preliminary findings support further investigation of wearable device monitoring as a complementary tool for cardiovascular health assessment in preventive medicine.

Background: Population aging is accompanied by progressive immune remodeling, chronic low-grade inflammation, and increased susceptibility to neurodegenerative diseases. Although the microbiota-gut-brain axis is increasingly recognized as a regulator of neuroimmune homeostasis, mechanisms linking age-associated dysbiosis with immunosenescence, barrier dysfunction, and brain aging remain incompletely understood. This review integrates current evidence into the proposed Gut-Immune-Brain Resilience Axis (GIBRA), a systems-level model describing how microbial signaling shapes neuroimmune resilience during aging. Methods: A structured narrative review was conducted using PubMed and the Web of Science Core Collection from database inception up to July 2026. Evidence from systematic reviews, meta-analyses, consensus statements, mechanistic and translational studies, longitudinal cohorts, randomized clinical trials, and observational studies was synthesized. Results: Current evidence supports an important role for the disruption of microbial functional signaling in neuroimmune aging, while microbial taxonomy and functional profiles provide complementary levels of biological information. Reduced short-chain fatty acid production, dysregulated tryptophan metabolism, microbial translocation, endotoxin-mediated innate immune activation, and gut-conditioned adaptive immune responses promote immunosenescence, inflammaging, barrier dysfunction, and microglial priming. The proposed Double-Barrier Hypothesis links intestinal and blood-brain barrier dysfunction as complementary mechanisms underlying chronic neuroinflammation. GIBRA highlights functional microbiome endotypes, biomarkers, multi-omics, and artificial intelligence as emerging tools for precision medicine. Conclusions: GIBRA provides an integrated systems biology perspective connecting microbial signaling, immune resilience, barrier integrity, and brain resilience during aging. Prioritizing functional resilience over microbial taxonomy may improve biomarker discovery, patient stratification, and microbiome-targeted interventions for neurodegenerative disease prevention. Prospective longitudinal studies integrating multi-omics are needed to support clinical translation.

The posterior communicating artery (PComA) aneurysm is a challenging microsurgical problem due to multiple factors. These include the technical complexity of the surgery itself, potential injury to blood vessels during surgery, recovery of cranial nerve function, and overall neurological outcome after the operation. These are all related to the area where the PComA aneurysm is located, but they have fundamentally different biological determinants. Prior methods of describing aneurysms do not adequately describe how the relationships of the internal carotid artery (ICA) and PComA/P1 configuration influence the proximity of the aneurysm to other important structures such as the perforating arteries, the anterior choroidal artery (AChA), cranial nerve III (CN III), and the surgical corridor. We created PComA-CORE, an artificial intelligence-based framework designed to evaluate whether the elements of experienced microsurgeons' thought processes can be measured individually while still maintaining temporally valid predictions, human interpretability, and explicit estimates of predictive uncertainty. Methods: Using a highly detailed database of clinical, radiographic, anatomical, intraoperative, and longitudinal data from 687 adult patients who underwent microsurgical clipping of PComA aneurysms over the period 1997-2026, we applied PComA-CORE to predict separately: Microsurgical Complexity (C); Oculomotor Recovery (O); Neurovascular Preservation Risk (R); and Expected 90-Day Functional Outcome (E). The models used cases from 1997-2020 (n = 564) for development and cases from 2021-2026 (n = 123) for temporal evaluation. Several architectures, including penalized regression, machine-learning techniques, interpretable machine learning, and ensembles, were compared using nested cross-validation, discrimination metrics, calibration metrics, decision-curve analysis, explainability measures, uncertainty-aware prediction, inter-observer reproducibility, and model-to-score distillation. Results: Four discrete predictive architectures were identified by PComA-CORE. PComA-C was found to be highly dependent upon anatomy because the specific geometric characteristics of individual vascular segments and the presence or incorporation of branches around the aneurysm strongly influenced temporal predictions. PComA-R was found to behave as a distributed susceptibility phenotype based on neurovascular attributes rather than a deterministic injury model and achieved a temporal AUC of 0.703. Among patients with preoperative CN III palsy, PComA-O identified that recovery primarily depended upon the time course of neurological dysfunction and structural deformation of the affected nerve. Temporal validation was not feasible given the small number of recent non-recovery events. Conversely, PComA-E showed that global functional outcome continued to depend predominantly upon clinical neurological severity, with a temporally evaluated penalized model achieving an AUC of 0.878. Uncertainty-aware predictions indicated that some cases would benefit from greater caution in interpretation. High-resolution anatomical phenotypes demonstrated good inter-observer reproducibility. Score distillation demonstrated that simplification preserved predictive information, but did so differently depending on the endpoint. Conclusions: The problem of predicting the consequences of clipping a PComA aneurysm is multidimensional and does not exist as a single "risk" prediction problem. Technical complexity, neurovascular vulnerability, neural recovery, and global disability each exist within distinct predictive spaces and require different levels of anatomical detail and/or computational complexity. PComA-CORE establishes a human-supervised framework to transform expert microsurgical thought processes into explicit, reproducible, uncertainty-aware, and clinically interpretable representations. While prospective multicenter validation will be needed prior to clinical use, it has the potential to establish a basis for explainable AI, precision cerebrovascular neurosurgery, anatomy-informed risk stratification, and clinically interpretable decision-support systems in complex aneurysm surgery.

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery with cardiopulmonary bypass (CPB), increasing morbidity and prolonging hospitalization. This study aimed to develop and validate an exploratory prediction model that integrates perioperative inflammatory biomarkers with clinical and surgical variables to identify patients at risk of early POAF.

A prospective exploratory cohort of 89 patients undergoing coronary artery bypass grafting (CABG; n = 36), valve surgery (n = 40), or CABG-valve surgery (n = 13) was evaluated. Clinical, surgical, and proinflammatory serum biomarkers (IL-6, IL-8, IL-10, and CRP) were recorded preoperatively (T1) and at 24 h (T2) and 48 h (T3) postoperatively. Multiple-comparison adjustments were made using the Benjamini-Hochberg false discovery rate. Predictor selection was based on bootstrap-derived stability using LASSO-penalized logistic regression, and the final model was estimated using Firth's bias-reduced logistic regression.

POAF incidence was 8.3% in CABG, in contrast to 22.5% and 30.8% in valve and CABG-valve surgeries, respectively. After multiple-comparison corrections, only IL-6 at T2 postoperatively was significantly higher in patients who subsequently developed POAF. Bootstrap-based stability selection retained T2 postoperative IL-10 and magnesium concentrations in the final model, which achieved an apparent AUC of 0.776 and a bootstrap optimism-corrected AUC of 0.728, with acceptable calibration (Brier score = 0.103), negligible multicollinearity (VIF = 1.04), and a negative predictive value of 95.5% at the optimal Youden threshold.

Our findings support an exploratory prediction model with moderate discrimination for POAF after cardiac surgery with CPB, providing a methodological foundation for future multicenter validation studies.

Hypertensive disorders of pregnancy (HDPs) are established markers of later-life cardiovascular disease, but their association with dementia remains uncertain.

To investigate whether HDPs are associated with incident dementia in a nationwide population-based cohort with more than 2 decades of follow-up.

This retrospective cohort study used the Korean National Health Insurance Service database to identify females aged 16 years or older who delivered between January 1, 2002, and December 31, 2005, and followed up through December 31, 2024. Statistical analyses were conducted between October 2025 and May 2026.

HDPs were defined as gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, or eclampsia.

The primary outcome was incident dementia, including Alzheimer disease and vascular dementia. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% CIs.

Among 1 370 485 females (mean [SD] age, 29.2 [3.9] years), 28 747 (2.1%) experienced HDPs. The cumulative incidence of dementia was higher among females with HDPs than among those without HDPs (7.2 vs 2.8 per 10 000 females; P < .001), as was the incidence density of dementia (3.00 vs 1.05 per 100 000 person-years; P < .001). In model 1, HDPs were associated with an increased risk of incident dementia after adjustment for baseline maternal, socioeconomic, and obstetric factors (adjusted HR, 1.96; 95% CI, 1.19-3.23). In model 2, after additional adjustment for postdelivery hypertension, diabetes, myocardial infarction, and stroke, the association was attenuated and was no longer statistically significant (adjusted HR, 1.15; 95% CI, 0.70-1.91).

In this cohort study, HDPs were associated with an increased risk of incident dementia after adjustment for baseline maternal, socioeconomic, and obstetric factors. However, this association was no longer statistically significant after additional adjustment for postdelivery vascular and metabolic conditions. Given the small number of dementia events among females with HDPs, these findings should be interpreted cautiously. These findings suggest that HDPs may serve as an early-life marker of long-term neurovascular vulnerability.

Cardiovascular toxicity is an important complication of treatment for hematologic malignancies, but it is often discussed mainly in terms of direct myocardial injury. Endothelial injury may provide a common link between several cardiovascular complications seen in these patients. Endothelial dysfunction may already be present because of the malignancy itself and can be further increased by anticancer treatment, immune activation and haematopoietic stem cell transplantation. Oxidative stress, reduced nitric oxide availability, inflammation, increased vascular permeability and activation of coagulation can shift the endothelium from a protective to a pro-inflammatory and prothrombotic state. These changes could contribute to hypertension, thrombosis, atherosclerotic disease, coronary microvascular dysfunction, arterial stiffness and myocardial dysfunction. The role of endothelial injury is particularly relevant with BCR-ABL inhibitors, proteasome inhibitors, CAR-T-cell therapy, bispecific antibodies and transplantation, although the mechanisms and strength of evidence differ between treatments. Several circulating biomarkers and tools, including angiopoietin-2, von Willebrand factor, soluble thrombomodulin, adhesion molecules and the Endothelial Activation and Stress Index, may help identify endothelial injury, but their clinical roles still remain unclear. This review examines endothelial injury across hematologic malignancies and their treatments and discusses its role in cardiovascular toxicity, current approaches to vascular protection and the main gaps that need to be addressed before endothelial assessment can become part of routine cardio-oncology care.

(1) Background: In routine clinical practice, CHDs are occasionally diagnosed in adulthood, mostly relatively minor defects that become symptomatic later in life. Less frequently, adults may present with complex CHDs that, due to anatomical variations, remain undiagnosed until adulthood. Another important group comprises patients with previously unrecognized CHDs, particularly those from socioeconomically disadvantaged settings with limited access to healthcare. (2) Body: In adulthood, CHDs often present with nonspecific symptoms suggestive of other cardiovascular conditions (cardiomyopathy or coronary artery disease), including dyspnea, chest discomfort, signs of HF, syncope, palpitations, and paradoxical embolism. The initial manifestation may also be a malignant arrhythmia or sudden cardiac death; therefore, early recognition and diagnosis are crucial. TTE represents the first-line diagnostic modality. Reduced LVEF in young patients, particularly when accompanied by left atrial and right-sided cardiac chamber dilatation, should raise suspicion of an underlying CHD. The diagnostic evaluation may be supplemented by TEE, CMR imaging, and right heart catheterization. Familial forms of CHD and the risk of transmission to offspring have been extensively investigated, particularly for conditions with a strong genetic component, such as BAV. (3) Conclusions: In adult patients with newly diagnosed CHD, accurate recognition of clinical symptoms and completion of an appropriate diagnostic workup are essential for establishing the diagnosis and initiating timely treatment. Furthermore, identification of families at increased genetic risk is important to facilitate targeted genetic panel screening. Future research should focus on developing and validating appropriate screening strategies for the early detection of CHDs in resource-limited regions.

In addition to its contractile role, skeletal muscle has important secretory functions and communicates with local and distant tissues through myokines, a heterogeneous group of cytokines, chemokines, growth factors, peptides, and extracellular-matrix-associated proteins released by muscle cells. Their production is regulated by contraction, mechanical loading, energy availability, hypoxia, inflammation, injury, and mitochondrial or metabolic stress. Through autocrine, paracrine, and endocrine mechanisms, myokines influence satellite-cell activity, myogenesis, protein turnover, muscle mass, metabolism, mitochondrial function, angiogenesis, immune-cell recruitment, extracellular-matrix remodeling, and inter-organ communication. This review provides a structured overview of current knowledge on the production, regulation, and biological actions of approximately 25 major myokines, with particular emphasis on the strength of evidence supporting their classification as bona fide muscle-derived factors. We distinguish local muscle signaling from changes in circulating concentrations of uncertain tissue origin and highlight the context-dependent nature of myokine actions. The same mediator may support adaptation and repair when transiently and locally produced but contribute to inflammation, metabolic dysfunction, fibrosis, or muscle wasting when signaling is excessive, prolonged, or disease-associated. Defining cellular sources, temporal regulation, receptor availability, and interactions within the muscle secretome will be essential for clarifying physiological relevance and translating myokine biology into biomarkers and therapeutic strategies.

Controlling blood pressure (BP) is essential for slowing chronic kidney disease (CKD) progression. This study examined the associations between treatment burden, assessed by antihypertensive medication use, and health-related quality of life (HRQoL) in youth with CKD and hypertension.

Youth (aged 8 to 21 years) were identified through electronic health records from 15 institutions. Youth and caregivers completed an online questionnaire assessing healthcare experiences, medication use, physical symptoms, and BP monitoring. HRQoL and related well-being domains (fatigue, anxiety, sleep disturbance, global health, and life satisfaction) were assessed using PROMIS^® measures. Analyses focused on youth-reported outcomes. Linear regression estimated associations between antihypertensive medication use and HRQoL outcomes, and scores were compared to the general population.

The study included 395 youth (M_age = 16.8 years, 54% female) and 238 caregivers. Over 95% of caregivers reported generally positive healthcare experiences. Most youth (92%) reported at least one of the physical symptoms asssessed (median [IQR] = 5 [3, 8] symptoms). Twenty-one percent took no antihypertensive medications, 56% took one, and 23% took multiple. Use of multiple medications was associated with slightly lower global health (B = - 2.6; 95% CI: - 4.9, - 0.3) after adjustment for CKD stage. No associations were observed for other HRQoL domains. Overall, youth reported lower QoL than the general population, with the greatest impairments observed in global health and fatigue.

Youth with CKD and hypertension reported generally positive healthcare experiences, and antihypertensive medication use, one component of treatment burden, showed minimal association with HRQoL. Despite modest effects, continued attention to HRQoL remains an important aspect of care for youth with CKD and hypertension.

Extreme temperatures are emerging as major climate-sensitive drivers of chronic cardiovascular disease (CVD). Global warming has increased the frequency, duration, and intensity of heatwaves, while substantial cold-related risk persists, particularly in poorly insulated and socioeconomically vulnerable settings. Together, non-optimal temperatures account for millions of deaths annually, with a large and growing share attributable to CVD. In this narrative review, we synthesize epidemiological, mechanistic, and systems-level evidence linking heat and cold exposure to chronic cardiovascular outcomes, with a focus on ischemic heart disease, stroke, heart failure, and arrhythmias. We first outline key temperature metrics, shifting climate patterns, and challenges in exposure assessment, including the roles of humidity, diurnal variability, and indoor versus outdoor environments. We then summarize the epidemiology of temperature, CVD associations across diverse regions, highlighting U- and J-shaped exposure-response curves and disproportionate impacts in low- and middle-income countries, older adults, and socioeconomically disadvantaged communities. Mechanistic sections examine how heat and cold drive autonomic imbalance, endothelial dysfunction, oxidative stress, inflammation, haemoconcentration, changes in coagulation, renal injury, and myocardial oxygen supply-demand mismatch. We further discuss modifying effects of air pollution, wildfires, dust storms, and medication use, including clinically relevant drug-heat interactions in patients with chronic CVD. Finally, we review heat-health and cold-health action plans, health-system resilience frameworks, and emerging research gaps spanning exposure science, mechanistic studies, vulnerable populations, and policy evaluation. Recognising non-optimal temperature exposure as a modifiable environmental risk factor for chronic CVD is essential. Integrating climate-informed prevention, clinical care, and adaptation strategies offers substantial and timely opportunities to reduce cardiovascular burden in a warming and increasingly unstable climate.