OBJECTIVE: This study focused on the correlations of lipoprotein-associated phospholipase A2 (Lp-PLA2) and angiotensin II (Ang II) levels with the severity of coronary artery stenosis (CAS) in elderly patients with suspected coronary heart disease (CHD). METHODS: This retrospective case-control study was conducted on 228 elderly patients suspected of CHD. Their clinical data were collected. Patients were grouped by CHD diagnosis and by CAS severity. Correlation analyses were performed between Lp-PLA2, Ang II, lipid profiles, and the atherogenic index of plasma (AIP). Influencing factors for moderate-to-severe CAS in elderly patients were identified by univariate/multivariate logistic regression models. Receiver operating characteristic curves were used to analyze diagnostic performance for the severity of CAS in elderly patients. RESULTS: Lp-PLA2 and Ang II levels were notably elevated in patients with CHD and were positively associated with the severity of CAS. Lp-PLA2 level correlated with lipid levels. Both Lp-PLA2 and Ang II were correlated with AIP. Elevated levels of Lp-PLA2 and Ang II were independent risk factors for moderate-to-severe CAS in elderly patients. Both Lp-PLA2 and Ang II demonstrated certain diagnostic value for identifying moderate-to-severe CAS in this population. The combination of Lp-PLA2 and Ang II demonstrated diagnostic performance comparable to AIP and superior to either marker alone for identifying moderate-to-severe CAS. CONCLUSIONS: Lp-PLA2 and Ang II are closely associated with AIP in elderly patients with CHD, are independent risk factors for moderate-to-severe CAS, and may serve as valuable biomarkers for diagnosis and risk stratification.

Hypertensive disorders of pregnancy, particularly pre-eclampsia, are recognized not only as major obstetric complications but also as early indicators of future maternal cardiovascular and renal risk. Despite this, postpartum care remains centered on blood pressure surveillance, whereas kidney assessment is not consistently incorporated into routine obstetric follow-up. This narrative review examines the renal implications of hypertensive disorders of pregnancy beyond delivery and translates guidance and observational evidence into a practical obstetric approach to postpartum kidney assessment. Available data indicate that a clinically meaningful subgroup of women have persistent renal abnormalities in the early postpartum period, most often as albuminuria or proteinuria rather than as overt reduction in estimated glomerular filtration rate. Reliance on blood pressure or serum creatinine alone may therefore fail to identify incomplete renal recovery, pregnancy-unmasked chronic kidney disease, or women requiring closer reassessment. We also emphasize pregnancy-associated acute kidney injury as a high-priority phenotype, operationalized by creatinine rise or oliguria using Kidney Disease: Improving Global Outcomes (KDIGO)-type criteria and interpreted against pregnancy-specific creatinine physiology. Patients meriting greater attention include those with severe or preterm disease, persistent hypertension, antenatal renal abnormalities, pregnancy-associated acute kidney injury, or relevant pre-existing comorbidity. We propose a feasible postpartum framework based on blood pressure measurement, serum creatinine with estimated glomerular filtration rate, and urinary assessment of albuminuria or proteinuria, with repeat testing or specialist evaluation guided by postpartum findings and clinical risk. Rather than creating a parallel nephrology pathway, this approach supports obstetric services in identifying women whose renal recovery may be incomplete.

BACKGROUND: Thyroid dysfunction has been associated with adverse postoperative outcomes, but little is known about its effects on patients undergoing coronary artery bypass grafting (CABG). Here, our goals were (1) to evaluate the incidence of CABG in patients with hypothyroidism receiving thyroid hormone replacement therapy, and (2) to assess short-term and long-term outcomes in patients with hypothyroidism undergoing CABG compared with controls without thyroid disease, and (3) to determine whether abnormal preoperative thyroid-stimulating hormone (TSH) levels modify postoperative surgical risk in this patient population. METHODS: Retrospective longitudinal study using the TriNetX Global Collaborative Network database. The incidence of CABG was evaluated in about 1.23 million patients with hypothyroidism during a 20-year observation period (median of 4.4 ± 5.9). Post-CABG outcomes, including mortality, cardiovascular events, and postsurgical complications, were evaluated in 6557 patients with hypothyroidism over 10 years after 1:1 propensity score-matching. RESULTS: Over 20 years, patients with a diagnosis of hypothyroidism had a higher incidence of CABG compared with controls (0.27% vs. 0.22%; hazard ratio [HR] 1.08; confidence interval [CI]: 1.03-1.14). Among patients who underwent CABG, the diagnosis of hypothyroidism was associated with mild increased risk of short-term postsurgical infections (HR:1.10, CI:1.01-1.20), CABG-specific complications (HR: 1.24, CI: 1.08-1.42), and critical care utilization (HR:1.14, CI:1.07-1.21). During long-term follow-up, these patients were at increased risk of incident heart failure (HR:1.15, CI:1.04-1.28), stroke (HR:1.18, CI:1.01-1.39), and major adverse cardiovascular events (MACE) (HR:1.15, CI:1.01-1.29). Sensitivity analysis, including only patients with hypothyroidism diagnosis, showed that abnormal preoperative TSH levels, particularly those with elevated TSH, had a higher risk of short-term mortality and long-term embolic events. CONCLUSIONS: Hypothyroidism is associated with a higher incidence of coronary disease requiring CABG and increased risks of postoperative complications, heart failure, stroke, and MACE. These findings support the potential value of preoperative thyroid function assessment and optimization to mitigate postoperative complications and improve surgical outcomes in this high-risk group.

BACKGROUND: Heart failure (HF) is a clinical syndrome characterized by impaired cardiac diastolic and systolic function due to structural or functional damage to the myocardium. HF represents the end-stage manifestation of many cardiac diseases. Therefore, early identification of high-risk patients is crucial. This study aims to utilize machine learning (ML) methods to develop and validate a model to predict major adverse cardiovascular and cerebrovascular events (MACCE) in patients with HF and identify its key predictive features. METHODS: This study is a retrospective cohort study. We enrolled a total of 271 patients, who were divided into training and testing sets. Baseline data, including cardiopulmonary exercise testing (CPET) parameters and laboratory tests, were collected for all participants. Based on the presence or absence of MACCE during follow-up, they were categorized into a No-event group and MACCE group. We developed seven ML models to predict the incidence of MACCE in patients with chronic heart failure (CHF) using CPET parameters. The predictive performance of these models was systematically compared, and model interpretability was evaluated using Shapley Additive exPlanations (SHAP). Subsequently, retaining only those with HF with preserved ejection fraction (HFpEF) for a sensitivity analysis. Additionally, a subgroup analysis was conducted between No-event group and Worsening HF (WHF) group. RESULTS: We used Boruta feature selection, four important predictive features were identified. Among the ML models constructed with these features, the Categorical Boosting (CatBoost) model demonstrated the best performance. SHAP analysis was applied to interpret the optimal model, revealing that lower values of heart rate recovery at 1 min (HRR1), as well as a higher carbon dioxide ventilation equivalent slope (VE/VCO slope), were associated with higher SHAP values-indicating greater importance in predicting adverse outcomes. CONCLUSION: HRR1 and VE/VCO slope can serve as independent predictors for the incidence of MACCE in patients with CHF.

The absence of induced pluripotent stem cell (iPSC) lines derived from Emirati patients with developmental disease hampers region-specific disease modeling and therapeutic research. Herein, we describe the creation of an iPSC line from peripheral blood mononuclear cells obtained from a 21-year-old Emirati female patient with ventricular septal defect (VSD) using Sendai virus-mediated delivery of reprogramming factors. The resulting line, UAEUi001-A, exhibited typical colony morphology, was mycoplasma negative, successfully generated embryoid bodies), and demonstrated strong alkaline phosphatase activity. These iPSCs were further characterized for pluripotency potential and their differentiation potential into the three germ layers under culture conditions through immunostaining using stage-specific markers. To the best our knowledge, this is the first reported generation of an iPSC line from an Emirati patient with VSD. Overall, this iPSC line may serve as a valuable model for establishing an Emirati-specific iPSC repository, supporting disease modeling and drug discovery relevant to the Emirati population.Impact StatementThis study establishes the first induced pluripotent stem cell (iPSC) line derived from an Emirati patient with ventricular septal defect, addressing a critical gap in region-specific disease models. It provides a valuable platform for understanding developmental cardiac disorders in underrepresented populations and supports the development of precision medicine and targeted therapeutic strategies relevant to the Emirati population.

Congenital Generalized Lipodystrophy (CGL), usually caused by pathogenic variants in AGPAT2 (CGL1) and BSCL2 (CGL2), is characterized by near-total loss of subcutaneous adipose tissue, low leptin levels and severe metabolic and systemic comorbidities. Skeletal abnormalities including diffuse sclerosis, lytic-appearing bone lesions, and high bone mineral density have been recognized in CGL, but the prevalence and clinical and radiological features of these bone phenotypes remain ill-defined. The aim of this single-institution case series and systematic review was to evaluate bone manifestations and radiological findings associated with CGL1 and CGL2. Data sources were PubMed, Scopus, Embase, CINAHL Plus, Global Index Medicus, Web of Science: Core, National Institutes of Health medical records. Articles were screened utilizing a dual reviewer process in Covidence. Included publications reported primary bone and radiologic findings in patients with CGL1 or CGL2. Two reviewers extracted data using REDCap and assessed risk of bias. 43 articles were included in the review, presenting 214 cases of CGL (90 CGL1, 81 CGL2, and 43 genetics not reported). Data from NIH patients was extracted by retrospective chart review. The NIH cohort had 60 CGL patients (40 CGL1, 20 CGL2). Skeletal imaging included radiographs, MRI, CT, and NaF PET scans. In the literature and NIH cases, respectively, diffuse osteosclerosis was reported in 37% and 39%, lytic-appearing lesions in 64% and 53%, and high bone mineral density in 68% and 43%. Individuals with CGL1 and CGL2 present with distinct and heterogeneous bone phenotypes including lytic-appearing lesions primarily affecting long bones, diffuse osteosclerosis, and high bone mineral density. These bone manifestations are often overlooked despite high prevalence and clinical relevance. Potential mechanisms include increased differentiation of bone marrow mesenchymal cells into osteocytes and effects of increased insulin or decreased leptin signaling.

Chronic systemic inflammation is a key driver of disease progression in rheumatoid arthritis and chronic kidney disease (CKD), particularly in patients undergoing long-term hemodialysis. Persistent elevation of proinflammatory cytokines contributes to pain, anemia, endothelial dysfunction, and increased cardiovascular risk, while therapeutic options are often limited by comorbidities and drug intolerance. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may offer an alternative strategy for systemic inflammatory control. We report on the case of a 56-year-old woman with juvenile-onset rheumatoid arthritis and dialysis-dependent CKD who received three consecutive systemic administrations of MSCs. Baseline evaluation demonstrated elevated inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Following treatment, inflammatory parameters were consistently reduced, which was accompanied by improvement in hemoglobin levels and favorable trends in renal function markers. Additionally, pain assessment scores (Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Visual Analogue Scale) showed clinically significant improvement. The patient also reported significant subjective pain relief and improved overall well-being. Although limited by its single-case design, this report supports the biological plausibility of systemic MSC therapy as a potential immunomodulatory approach in patients with overlapping autoimmune and uremia-associated chronic inflammation. Further controlled studies are warranted.

The human microbiome, comprising trillions of bacteria, viruses, fungi, and archaea, represents an essential partner in human biology rather than a passive collection of microbes. These microbial communities inhabit diverse niches, including the gut, skin, oral cavity, respiratory tract, and urogenital system, where they contribute to digestion, vitamin biosynthesis, immune development, and regulation of host metabolism. Their dynamic interactions form a complex ecosystem that profoundly shapes health across the lifespan. However, with ever increasing reports on the microbiome including perceived health benefits, diagnostic use, detrimental species and immune modulation, we synthesize findings from multiple biomedical fields for this review. It first describes beneficial functions of commensal microbes in maintaining immune tolerance and metabolic balance, then analyzes the effect of diet, geography and medication exposure, the consequences of dysbiosis in gastrointestinal, metabolic, neurological, cardiovascular, autoimmune, and oncological disorders. The article examines the functional potency of the gut microbiome, keystone taxa as well as disease-stage-specific and general dynamics, how microbiomes modulate drug absorption, metabolism, and efficacy, thereby influencing individualized responses to therapy. Furthermore, it evaluates therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial strategies that seek to restore microbial equilibrium. The significance of this review lies in its integrative perspective, as it links microbiome research to precision medicine, emphasizing that safeguarding microbial diversity is crucial for prevention, early diagnosis, and the personalization of future medical interventions.

BACKGROUND: Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti-inflammatory, and anti-apoptosis. This research seeks to investigate whether CHR can protect against pressure overload-induced myocardial remodeling and to explore the underlying mechanism. METHODS: Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established. RESULTS: The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF-α and IL-1β, suppressed cell apoptosis rate, downregulated the levels of Bcl-2 Associated X protein (BAX) and Cleaved-Caspase-3, and upregulated B-cell lymphoma/leukemia 2 (BCL-2) expression in TAC surgical mice or Ang II-treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO-1 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol‑3‑kinase (PI3K)/serine/threonine-protein kinase B (AKT) signaling pathway. CONCLUSIONS: Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload-induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K/AKT/NRF2 pathway-mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.

Pulmonary vein stenosis after repair of total anomalous pulmonary venous connection (TAPVC) is a life-threatening complication that frequently recurs, particularly in patients with asplenia. Although intrinsic mechanisms such as ostial narrowing and progressive neointimal proliferation are well recognized, extrinsic mechanical factors are less commonly emphasized in congenital heart disease. We report a case of recurrent pulmonary vein stenosis in a patient with asplenia in whom intrinsic susceptibility and possible posterior extrinsic compression may have acted synergistically. Serial computed tomography demonstrated persistent proximity between the left pulmonary vein and indwelling enteral feeding tubes. Sustained improvement was achieved after surgical relocation of the left pulmonary vein orifice to a site remote from the tubes. This case suggests that external mechanical influences may represent an underrecognized and potentially modifiable contributor to postoperative pulmonary vein stenosis in high-risk pediatric patients.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance is a major clinical challenge in children with Kawasaki disease (KD) and is associated with an increased risk of coronary artery lesions. Early identification of patients at high risk of IVIG resistance remains clinically important. METHODS: Medical data were collected from KD patients at Anhui Provincial Hospital between January 2018 and December 2023. Multivariable logistic regression was performed to identify independent risk factors for IVIG resistance in KD. The study further performed subgroup analyses and restricted cubic spline (RCS) to visualize the dose-response association between hemoglobin-albumin-lymphocyte-platelet score (HALP) and IVIG resistance. The predictive performance of HALP was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA), and internal validation was performed using bootstrap resampling. RESULTS: A total of 598 patients were included, of whom 58 (9.7%) were identified as IVIG-resistant. Patients with IVIG-resistant KD had significantly lower HALP scores, and low HALP was identified as an independent risk factor for IVIG resistance. The association was consistent across subgroups defined by age, sex, and incomplete KD (IKD). The area under the curve (AUC) for HALP in predicting IVIG resistance was 0.854, outperforming NLR (AUC = 0.751), PLR (AUC = 0.793), and SII (AUC = 0.759). In addition, DCA showed that HALP provided greater net benefit when the threshold probability ranged from 0.02 to 0.63. Moreover, subgroup ROC indicated that HALP had higher predictive value in patients aged ≤ 6 months (AUC = 0.934) and ≥ 48 months (AUC = 0.947). CONCLUSIONS: HALP is independently associated with IVIG resistance in children with KD and demonstrated good performance for early risk stratification, particularly in patients aged ≤ 6 months and ≥ 48 months. As a simple and readily available biomarker, HALP may serve as a useful complementary tool in routine pediatric clinical practice.

BACKGROUND: Hypertension is a leading risk factor for cardiovascular diseases, and its relationship with sleep quality and duration remains a topic of growing interest. Poor or insufficient sleep may contribute to the development of hypertension. This study aimed to investigate the association between sleep duration, sleep quality, and hypertension in community-dwelling adults using data from the Ardakan Cohort Study on Ageing (ACSA). METHODS: A cross-sectional analysis was conducted using ACSA data collected between 2020 and 2022, including 5,872 participants aged 50 years and older from Ardakan, Iran. Sleep quality was assessed using the validated Pittsburgh Sleep Quality Index (PSQI), and blood pressure was measured following standard protocols. Hypertension was defined according to the American Heart Association guidelines. Logistic regression models were employed to assess associations between sleep quality and hypertension. RESULTS: Hypertensive participants (n = 2,967) showed poorer sleep quality than non-hypertensive individuals (n = 2,905), as indicated by a higher mean PSQI score (8.13 ± 4.23 vs. 6.93 ± 4.06; P < 0.001), a higher prevalence of poor sleep (76.99% vs. 66.53%; P < 0.001), longer sleep latency (50.69% vs. 42.62%; P < 0.001), and a greater proportion of insufficient sleep (P < 0.001). Logistic regression analysis showed that a sleep duration of 6-7 h was associated with 28% lower odds of hypertension (OR = 0.78, 95% CI: 0.64-0.94, P = 0.01). Poor sleep quality was borderline associated with hypertension in the total population (OR = 1.16, 95% CI: 0.99-1.35, P = 0.05). Sleep latency categories were not significantly associated with hypertension in adjusted models. CONCLUSION: In this cross-sectional study, a sleep duration of 6-7 h was associated with lower odds of hypertension, while poor sleep quality showed a borderline association. No significant association was observed between sleep latency and hypertension in the fully adjusted models. These findings warrant further investigation in longitudinal studies to clarify causality.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is a critical complication in the treatment of cardiovascular diseases, and its pathogenesis is closely associated with mitochondrial dysfunction and the imbalance of glucose/lipid metabolism. This study aims to investigate the molecular mechanisms underlying glucose/lipid metabolism in MIRI and identify potential therapeutic targets. METHODS: Key genes and prognostic biomarkers related to MIRI were identified through bioinformatics analysis, and a hypoxia/reoxygenation (H/R) model using HL-1 cardiomyocytes was employed to simulate the pathological process of MIRI. RNA interference was used to knock down ATF4, and bioinformatics analysis identified key molecules involved in mA methylation. The regulatory mechanism of ATF4 mRNA stability mediated by RBM15 was further explored. Flow cytometry, mitochondrial membrane potential, and ATP assays were conducted to evaluate cell apoptosis, glucose uptake, fatty acid oxidation, and mitochondrial function. RESULTS: Bioinformatics analysis and the H/R model experiments in HL-1 cardiomyocytes revealed that ATF4 was highly expressed in MIRI. Knockdown of ATF4 exacerbated H/R-induced cell apoptosis and metabolic disturbances. mA methyltransferase RBM15 modulated the stability and expression of ATF4 mRNA through methylation. Further investigation showed that ATF4 upregulates Sestrin2 to inhibit GSK3β activity, thereby maintaining mitochondrial membrane potential and ATP production, promoting glucose uptake, and enhancing fatty acid oxidation. CONCLUSION: This study is the first to reveal the molecular mechanism by which the mA modified ATF4-Sestrin2/GSK3β signaling axis alleviates MIRI through dual regulation of glucose/lipid metabolism homeostasis and mitochondrial energy supply. It elucidates the bridging role of RBM15-mediated mA epigenetic modification in this process. These findings provide a new strategy for targeting metabolic reprogramming in MIRI therapy and suggest that ATF4 may serve as an intervention target.

BACKGROUND: Non‑communicable diseases (NCDs) pose a significant health challenge in Saudi Arabia, where 18.95% of adults report at least one chronic condition, including diabetes (9.1%), hypertension (7.9%), and cardiovascular diseases (1.5%). This burden highlights the need for reliable, national‑level estimation of dietary intake and nutrient adequacy to inform evidence‑based nutrition policy. Therefore, this study aimed to estimate dietary intake, nutrient exposure, and adequacy among Saudi adults using an updated, locally developed probabilistic model (NNC‑v2). METHODS: This modeling study was developed a model using nationally published data from Saudi Arabia starting in 2010. The model was designed to generate probabilistic estimates that account for uncertainty and variability by linking food supply data to population-level intake and nutrient exposure. Model parameters were specified as statistical distributions rather than fixed values, allowing variability and uncertainty to propagate through the estimation process. Age-related intake adjustment and routine variation were incorporated within the model structure. Nutrient adequacy was evaluated using a Monte Carlo-based Average Requirement cut-point approach (10,000 iterations). Predictive performance was assessed indirectly by comparing model-derived food expenditure with national survey data. RESULTS: Grains estimated intake (mean 278 g/day), followed by protein foods (120 g/day). Median energy intake was 2399 kcal/day in males and 2366 kcal/day in females. Estimated intake levels were evaluated against the Average Requirement (AR) values of 320 µg/day for folate and 75-90 mg/day for vitamin C. Among individuals with intake below the AR, the mean intake gaps were approximately 97 µg/day for folate and 27 mg/day for vitamin C. Magnesium intake was evaluated relative to AR values of 350 mg/day for males and 255 mg/day for females. Model-estimated monthly food expenditure closely aligned with national data (7% difference in 2018; 2% in 2023). CONCLUSIONS: NNC-v2 offers a probabilistic framework for estimating dietary intake and nutrient adequacy at the national level in Saudi Arabia within the available data sources.

BACKGROUND: The triglyceride-glucose (TyG) index is an accessible marker of insulin resistance and may reflect metabolic susceptibility to kidney stone disease (KSD). This review synthesizes observational evidence on TyG and KSD and examines whether the association varies with increasing TyG. METHODS: PubMed, Embase, Web of Science, Scopus, the Cochrane Library, and ProQuest were searched up to May 22, 2026 according to PRISMA 2020 and a PROSPERO-registered protocol. Eligible studies enrolled adults, assessed TyG as either a continuous or categorical exposure, reported KSD as the outcome, and provided extractable effect estimates. Study quality was evaluated using the Joanna Briggs Institute (JBI) tools. Maximally adjusted odds ratios (ORs) were synthesized using the restricted maximum likelihood (REML) random-effects model. One-stage dose-response meta-analyses using linear and restricted cubic spline models were also conducted, and the certainty of evidence was judged using GRADE. RESULTS: Fourteen studies (total n = 1,066,215; KSD cases = 50,286) met the inclusion criteria. In the continuous analysis, each 1-unit increment in TyG corresponded to higher KSD odds (pooled adjusted OR: 1.33; 95% confidence interval [CI]: 1.15-1.54). Compared with the lowest TyG category, the highest had 52% higher odds of KSD (OR: 1.52; 95% CI: 1.26-1.84). In a one-stage random-effects dose-response meta-analysis, restricted cubic spline models provided the best fit but showed no statistical evidence of non-linearity, supporting a linear association with a 26% increase in odds per 1-unit increase in TyG (OR: 1.26; 95% CI: 1.12-1.42; 95% PI: 0.91-1.75). CONCLUSION: A higher TyG index was associated with greater odds of KSD in a broadly linear manner; however, the marked heterogeneity across studies suggests that TyG should be viewed as a potential metabolic risk marker rather than a routine screening tool. These findings may support broader cardiometabolic risk assessment and standard preventive counseling in patients at risk of KSD.

BACKGROUND: Cardiovascular disease (CVD) remains a major global health challenge. The triglyceride-glucose (TyG) index and its derived indices serve as indicators of insulin resistance (IR) and are closely associated with CVD incidence. This study aimed to compare the predictive value of different TyG-related indices for CVD incidence and assess the impact of the TyG-BMI across various subgroups, including potential interaction effects. METHODS: This study conducted a secondary analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), which included 5,382 participants aged 45 years and older. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and Cox proportional hazards regression models were employed to evaluate the associations between TyG-related indices and CVD incidence. Subgroup analyses were performed to evaluate the predictive performance of the TyG-BMI across different population categories and assess potential interactions. RESULTS: Cox proportional hazards regression indicated a significantly increased risk of CVD among participants in the highest quartile of the TyG-BMI, with a hazard ratio (HR) of 1.60 (95% CI: 1.33-1.99). Subgroup analyses confirmed this association across multiple demographic and clinical subgroups, including sex, residence, education level, alcohol consumption, smoking history, and history of hypertension, diabetes, stroke, liver disease, and kidney disease. Restricted cubic spline (RCS) analysis revealed a nonlinear relationship between the TyG-BMI and CVD incidence. Interaction analysis revealed a significant positive interaction between kidney disease and the TyG-BMI. CONCLUSIONS: The TyG-BMI demonstrated a modestly higher predictive value than other TyG-related indices in predicting CVD risk, establishing it as a valuable tool for clinicians assessing the incidence of CVD.

BACKGROUND: Cardiovascular disease (CVD) and cancer share common risk factors, and cancer survivors experience elevated long-term cardiotoxicity. Traditional risk-based metrics require person-time denominators that are unavailable in aggregate public health databases. This study introduces a proportional co-listing framework to detect population-level cardiovascular surveillance signals on death certificates across cancer types and demographic strata. METHODS: We conducted a national cross-sectional surveillance analysis using CDC WONDER Multiple Cause-of-Death data from 1999 to 2020 for decedents aged ≥ 15 years. Utilizing an "any-mention" framework, we calculated the Proportional Mortality Ratio (PMR), defined as the ratio of CVD co-listing on cancer-related death certificates to CVD listing on non-cancer certificates. Temporal trends were evaluated using joinpoint regression to estimate the average annual percent change (AAPC). Analyses were stratified by age, sex, race/ethnicity, geography, and index cancer subtypes (lung, colon, and leukaemia). RESULTS: Of 56,014,102 death certificates analyzed, 13,917,133 (24.8%) listed a malignant neoplasm, of which 3,997,238 (28.7%) co-listed CVD. Across the lifespan, the overall PMR followed a reverse J-shaped curve. Proportional co-listing was highest in the youngest cohort (ages 15-24: PMR 1.828, 95% CI: 1.778-1.879), declined to a nadir at ages 55-64 (PMR 0.336, 95% CI: 0.335-0.337), and rose modestly in older adulthood. From 1999 to 2020, PMRs increased significantly across all adult age groups, peaking at ages 55-64 (AAPC 1.69%, 95% CI: 1.52-1.83, p < 0.001). Young-adult PMR elevations were consistently higher in male, metropolitan, and Hispanic/Latino decedents. Among subtypes, leukaemia demonstrated the highest relative CVD co-listing in young adults (PMR 2.174), whereas colon cancer showed no statistically significant elevation (PMR 1.173, 95% CI: 0.951-1.447). CONCLUSIONS: Cardiovascular co-listing on US cancer death certificates is highly patterned by age, demographics, and cancer subtype. While elevated PMRs in young adults are consistent with patterns previously reported in cardio-oncology literature, sub-unity PMRs in middle-aged and older adults may reflect under-documentation of cardiovascular comorbidities in oncology settings alongside denominator effects arising from frequent CVD listing on non-cancer certificates. Improving comorbidity documentation on death certificates may enhance the utility of national administrative data for cardio-oncology surveillance and research.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular disease. The endothelial glycocalyx (eGCX) is a shear-sensitive intravascular barrier. The relevance of OSA and intermittent hypoxia (IH) for eGCX perturbation and cardiovascular disease in humans remains unclear. METHODS: In a prospectively recruited observational cohort with cross-sectional biomarker analysis in men (n = 60), polysomnography quantified apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and hypoxic burden (HB). Using single-time-point plasma sampling, eGCX glycosaminoglycans hyaluronan (HA) and heparan sulfate (HS) and the proteoglycan syndecan-1 (SDC-1) were related to OSA severity and repetitive hypoxemia, including multivariable adjustment for cardiometabolic, inflammatory, and renal determinants. Plasma proteomics defined pathways associated with OSA and HA/HS. Shear-matured primary human endothelial cells were exposed to OSA-characteristic IH cycles under arterial flow to assess eGCX structure, oxidative stress, nitric oxide (NO) signaling, thromboinflammatory status, and antioxidant treatment with N-acetylcysteine. RESULTS: Plasma HA and HS were higher in OSA than in non-OSA individuals and increased stepwise with disease severity, tracking AHI, ODI, and HB. These associations persisted in multivariable analyses adjusting for age, BMI, hypertension, hs-CRP, fasting glucose, and eGFR. Plasma SDC-1 did not differ between groups and remained non-associated in adjusted analyses. Proteomics revealed enrichment of inflammatory, coagulation, and oxidative stress-related pathways that strengthened with increasing OSA burden and higher HA/HS levels. Experimentally, IH caused loss of endothelial surface HA/HS with increased shedding, increased reactive oxygen species, reduced redox capacity, impaired NOS3/eNOS signaling and reduced NO bioavailability. IH or enzymatic eGCX digestion each enhanced monocyte and platelet adhesion, tissue factor expression, and fibrin deposition under shear, while N-acetylcysteine attenuated oxidative stress and partially restored surface HA expression. CONCLUSIONS: Integrated patient and IH-model data show that OSA severity and repetitive hypoxemia are associated with circulating markers consistent with eGCX perturbation, while the endothelial IH model supports induction of oxidative-inflammatory stress and a proadhesive, prothrombotic phenotype by intermittent hypoxia. Together, circulating HA and HS emerge as candidate biomarkers associated with OSA-related eGCX perturbation, warranting further evaluation in longitudinal and interventional studies of eGCX-stabilizing adjunct therapies. These findings derive from an all-male cohort and require validation in women and more diverse populations.

BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne flavivirus infection endemic to much of Asia and the Western Pacific. Although most infections are asymptomatic, less than 1% progress to clinical disease, typically presenting as acute encephalitis. The case fatality rate ranges from 20 to 30%, and up to half of survivors develop long-term neurological or psychiatric sequelae. While uncommon among travelers from non-endemic regions, risk increases with prolonged rural exposure or lack of vaccination. Immunocompromised individuals, including those with hematologic malignancies, may experience severe and rapidly progressive diseases. Awareness of this rare but life-threatening infection is essential when evaluating returning travelers with acute encephalopathy. CASE PRESENTATION: A 70-year-old Lao male living in the California Central Valley with a history of multiple myeloma, hypertension, and congestive heart failure presented with progressive confusion and weakness after travel to rural Laos. His trip exceeded the recommended duration, and his Japanese encephalitis virus (JEV) vaccination status was unknown. On admission, he was febrile and encephalopathic with new-onset rigidity. Computed tomography showed chronic calcifications consistent with prior neurocysticercosis, while magnetic resonance imaging revealed bilateral frontal and left insular cortical hyperintensities without thalamic involvement. Cerebrospinal fluid analysis conducted 9 days after his cognitive decline showed elevated protein without pleocytosis, and infectious and autoimmune panels were negative. Despite empiric antibiotics and supportive care, his condition deteriorated to coma, requiring intubation. Serologic testing later confirmed recent JEV infection with positive Immunoglobulin G (IgG) and low-titer Immunoglobulin M (IgM). After multidisciplinary discussions, comfort care was initiated, and he died in inpatient hospice. CONCLUSIONS: This case illustrates the diagnostic challenge of acute encephalopathy in immunocompromised travelers. Myeloma-related immune dysfunction, as suggested by his lack of pleocytosis, likely contributed to impaired viral clearance, leading to rapid progression. The absence of typical thalamic lesions and the presence of frontal and insular involvement represent an uncommon neuroimaging pattern in JE. Pre-existing neurocysticercosis may have further worsened neurologic outcomes, as prior studies suggest JEV co-infection can lead to worse prognosis. Our case highlights the importance of having a broad differential in an undifferentiated patient and the value of investigating a patient's history holistically. Imported JE should be considered in travelers returning from endemic regions, particularly those who are immunocompromised. A detailed travel history, broad infectious workup, and recognition of atypical imaging findings are key to diagnosis. Vaccination and mosquito precautions remain the most effective preventive measures against this often-fatal disease.

BACKGROUND: Obesity increases the risk of heart failure (HF), potentially through low-grade inflammatory processes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been suggested to attenuate inflammation, although data in patients without diabetes and HF are lacking. Moreover, it is unknown whether SGLT2 inhibitors affect adipose tissue dysfunction. We aimed to investigate the effect of the SGLT2 inhibitor empagliflozin on systemic inflammation, uric acid, and adipose tissue dysfunction in high-risk patients with overweight or obesity. METHODS: Pre-defined secondary analysis of the Empire Prevent Metabolic trial. Outpatients with body mass index (BMI) > 28 kg/m and risk factors for HF, excluding diabetes, were randomised to 180 days treatment with empagliflozin 10 mg or placebo. Patients completed blood sampling and subcutaneous abdominal adipose tissue biopsies at baseline and follow-up. Pre-defined endpoints were the baseline-adjusted estimated treatment differences (ETD) or ratios (ETR) for interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), and uric acid. Furthermore, we explored gene expression changes in selected markers of adipose tissue dysfunction, including inflammation. RESULTS: We randomised 92 patients (empagliflozin: 44, placebo: 48). Median age was 68 years, median BMI was 31.6 kg/m, while 21 (23%) and 54 (59%) patients presented with IL-6 > 7 pg/ml and hsCRP of at least 3 mg/l, respectively. Empagliflozin did not affect IL-6 (ETR: 1.03, 95% CI 0.82-1.30, p = 0.78) or hsCRP (ETR: 1.15, 95% CI 0.87-1.51, p = 0.33) compared to placebo. Meanwhile, uric acid decreased (ETD: - 0.06 mmol/l, 95% CI - 0.08 to - 0.04, p < 0.0001), whereas no changes in adipose tissue gene expression were observed. CONCLUSIONS: In this study, empagliflozin did not demonstrate anti-inflammatory effects but yielded possibly meaningful uricosuric effects in non-diabetic patients with overweight or obesity. Moreover, adipose tissue dysfunction remained unaltered. Trial registration clinicaltrials.gov NCT05042973.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a circulating biomarker reflecting oxidative stress, inflammation, and cellular aging. However, its role in disease risk assessment amongst individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 remains unclear. METHODS: This study included 29,697 UK Biobank participants with CKM stages 0-3 defined in accordance with the American Heart Association criteria. Associations of GDF-15 with metabolic, inflammatory and liver fibrosis markers and CKM stage were examined using linear or multinomial logistic regression models. Fine-Gray competing risk regression models were used to evaluate associations with incident atherosclerotic cardiovascular disease (ASCVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and their comorbidity (coexistence of both conditions). Bidirectional disease transitions were assessed using a multi-state Markov model. The relative importance of GDF-15 was evaluated using SHapley Additive exPlanations (SHAP) and likelihood ratio (LR) statistics. Improvements in risk prediction models were assessed using time-dependent area under the receiver operating characteristic curve, Brier score, integrated discrimination improvement and continuous net reclassification improvement. RESULTS: Amongst 29,697 participants (mean age of 56.16 years; 57.32% female), 2,786 developed ASCVD and 456 developed MASLD during follow-up. Higher GDF-15 levels were associated with poorer CKM health and showed the strongest associations with renal function markers, followed by insulin resistance indices. Each 1-unit increase in GDF-15 (normalised protein expression, log2 scale) was associated with increased risks of ASCVD (HR = 1.25, 95%CI 1.15-1.36, P = 1.35 × 10), MASLD (HR = 1.62, 95%CI 1.41-1.86, P = 2.06 × 10) and their comorbidity (HR = 1.62, 95%CI 1.32-2.18, P = 4.36 × 10) after multivariable adjustment for age, sex, smoking status, body mass index, diabetes mellitus, glycated haemoglobin, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, cystatin C, Townsend deprivation index, physical activity, and CKM stage. These associations remained consistent across subgroup analyses. Multi-state analyses indicated that GDF-15 predicted bidirectional progression between ASCVD and MASLD, with 10-year cumulative incidences of ASCVD and MASLD reaching 15.75% and 2.03%, respectively, among individuals in the top 10% of GDF-15 levels, and further increasing to 20.05% and 2.32% in those in the top 5%. SHAP and LR analyses showed that GDF-15 had high relative importance in predicting ASCVD and MASLD. Incorporating GDF-15 into established risk scores (PREVENT, SCORE2, FLI, FIB-4 and ARPI) showed modest improvements in risk discrimination, reclassification, and prediction error, particularly for ASCVD. In several settings, GDF-15 outperformed established biomarkers, including insulin resistance, systemic inflammation, apolipoprotein A/B, lipoprotein(a), cardiac troponin I, and N-terminal prohormone of brain natriuretic peptide. CONCLUSIONS: GDF-15 may serve as a promising biomarker for cardiovascular-kidney-liver-metabolic syndrome risk stratification and management.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), despite guideline-directed lipid-lowering therapy. Apolipoprotein B100 (ApoB100), reflecting total atherogenic particle number, may identify residual risk beyond LDL-cholesterol (LDL-C). Therefore, we investigated whether baseline ApoB100 levels independently predict MACE and MALE beyond conventional risk factors in this high-risk population. METHODS: In this prospective cohort study, 167 T2DM patients with CLTI undergoing LER were followed for 12 months with visits at 1, 3, 6, and 12 months post-procedure. We measured baseline ApoB100 and assessed its ability to predict MACE, MALE, and composite endpoints, adjusting for clinical covariates. RESULTS: Composite events occurred in 49.1% of patients, MACE in 24%, and MALE in 35.3%. ApoB100 levels were significantly higher in event groups (composite: 62.1 vs 38.0 mg/dL, p < 0.01; MACE: 66.1 vs 44.4 mg/dL, p < 0.01; MALE: 61.0 vs 42.4 mg/dL, p < 0.01). Multivariable analyses confirmed ApoB100 as an independent predictor (composite OR 1.14 per mg/dL, 95% CI 1.08-1.20, p < 0.01; MACE OR 1.10, p < 0.01; MALE OR 1.05, p < 0.01). ROC analysis demonstrated excellent predictive accuracy for ApoB100 (AUC 0.86, 95% CI 0.80-0.91), with optimal ROC-derived cut-off of 56.6 mg/dL. Adding baseline ApoB100 to conventional risk factors significantly improved model discrimination (AUC gains 0.08-0.15, all p < 0.01), while Kaplan-Meier curves by cut-off effectively stratified early events (log-rank p < 0.001). CONCLUSIONS: Elevated baseline ApoB100 independently predicted MACE, MALE, and composite events post-LER in T2DM-CLTI patients, substantially improving clinical risk models. Integrating ApoB100 into post-LER management algorithms could refine individualized therapeutic strategies, especially in patients with residual atherogenic risk despite optimal LDL-C control.

BACKGROUND: Congenital heart disease affects approximately 1% of live births worldwide and remains among the most significant contributors to neonatal morbidity and mortality. Approximately half of them require surgical or percutaneous interventions at some stage. Patient care involves critical situations including clinical, psychological, social, regional, and cultural practices. Family and patients go through stressful experiences. Through this review, we aim to highlight issues faced by the patients or their families during management of complex cardiac conditions and hope that medical personnel, health authorities and institutions will benefit from the information provided. This will result in a better patient experience and outcomes. METHOD: To identify patient and family concerns, this narrative review is based on daily observations and literature reviews (Google, Google Scholar, PubMed) between 2013 and 2026, and regional perspectives. Key areas included parental and patient stress, communication breakdowns, health care coverage, regional cultural influence, family dynamics, and socio-economic considerations. RESULTS: Patient-centered concerns in pediatric cardiac surgery include clinical, psychological, socioeconomic, and regional factors. In addition, communication, stress, interruptions in education or employment, funding, and logistics also influence patient's experience. Effective interprofessional care, psychosocial counseling, finding ways to support the cost of treatment, and appropriate use of technology can foster a better patient experience. This is particularly imperative in the Middle East region, where family cohesion, religious beliefs, language diversity, and healthcare inequities shape the recovery path. CONCLUSIONS: Our review shows that pediatric cardiac care requires a multidimensional, culturally attuned model that incorporates interprofessional care, empathy, innovation, community support, and system-level solutions involving various professional agencies in health insurance, finance, hospital management, research, and medical education. In addition, healthcare communication, access, support, cultural and spiritual identity plays a significant role in shaping patient and family experience during medical management.

BACKGROUND: People with disabilities (PWDs) have higher incidence and mortality rates of cardiovascular disease than non-PWDs. Considering the mutual influence of cardiovascular diseases and disabilities, careful observation and complementary management beyond standard treatments are essential when ischemic heart disease (IHD) occurs in PWDs. This study investigated the association between acupuncture treatment and reduced mortality in PWDs diagnosed with IHD. METHODS: Using a database from the National Health Insurance Service of Korea, PWDs newly diagnosed with IHD were included in this study. Exposure to acupuncture treatment within one year after diagnosis was used to classify participants into the exposure and non-exposure groups, with follow-up for three years or until death. Propensity score matching (PSM) was used to adjust for group imbalances, and survival analysis was conducted using the Cox proportional hazards model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Dose-response and subgroup analyses were also performed. RESULTS: After PSM, 38,157 PWDs were included in each group. The acupuncture group showed a significantly lower hazard of mortality, approximately 22% lower than that of the control group (adjusted HR 0.78, 95% CI 0.74-0.81). In the dose-response analysis, the group receiving the highest dose of acupuncture demonstrated the lowest hazard of mortality (adjusted HR 0.67, 95% CI 0.62-0.72). Most subgroups also showed a reduced mortality hazard in the acupuncture-treated groups, with the highest dose group exhibiting the lowest hazard. CONCLUSION: This study is a foundational investigation suggesting that acupuncture treatment is associated with reduced mortality in PWDs diagnosed with IHD. Although future research is needed to establish causality, acupuncture should be considered a beneficial option for managing IHD in PWDs.

BACKGROUND: Early-stage (0-3) cardiovascular-kidney-metabolic (CKM) syndrome populations require urgent cardiovascular disease (CVD) prevention. Chronic inflammation, insulin resistance, and visceral adiposity are three core interactive CVD pathogenic pathways, while current biomarkers fail to integrate all three. This study aimed to explore the association of the novel three-dimensional composite index CTI-CVAI with incident CVD and its predictive value in Chinese adults with CKM stages 0-3. METHODS: This nationwide prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), including 6728 participants aged ≥ 45 years with CKM stages 0-3. CTI-CVAI was calculated by combining the C-reactive protein-triglyceride-glucose index (CTI) and Chinese visceral adiposity index (CVAI). Cox regression, restricted cubic spline, survival analysis, ROC curves, and reclassification analysis were used to evaluate its value. Subgroup and multiple sensitivity analyses, including competing-risks models, were conducted to assess the robustness of the results. RESULTS: During a median follow-up of 9 years, the overall CVD incidence was 23.83%. CTI-CVAI elevation showed a linear, dose-dependent correlation with increased CVD risk (P < 0.001). After full confounder adjustment, per 1-SD CTI-CVAI increment increased CVD risk by 32% (HR = 1.32, 95% CI 1.26-1.39, P < 0.001), and the highest quartile exhibited 2.07-fold higher risk than the lowest (HR = 2.07, 95% CI 1.77-2.42, P < 0.001). Restricted cubic spline analysis revealed a linear association between CTI-CVAI and incident CVD (P for non-linearity > 0.05). CTI-CVAI demonstrated improved risk reclassification (NRI = 0.0566, P < 0.001) compared with single biomarkers. The association was stable across most subgroups. All sensitivity analyses yielded reliable, robust results. CONCLUSIONS: CTI-CVAI is independently and linearly associated with incident CVD risk in Chinese adults with CKM stage 0-3. As a low-cost, accessible biomarker integrating three key pathological pathways, it optimizes early CVD risk stratification and reclassification, providing a promising tool for targeted CVD prevention in CKM high-risk populations.