OBJECTIVE: Dysregulation of Cholesterol homeostasis(CH) and NK cells proportion can increase risk of ST-Elevated Myocardial Infarction(STEMI) for Coronary atherosclerotic heart disease(CAD) patients. Hence, it is necessary for the investigation of CH and MC in pathogenesis of STEMI for CAD patients, providing additional choice for the prevention of STEMI for CAD patients. METHODS: By combining 5 peripheral blood bulk profiles of CAD patients with STEMI and integrative bioinformatic pipelines, such as ssGSEA, CIBERSORT, WGCNA, machine learning, consensus clustering, we first identified novel CH and NK cell(NCH)-associated molecular subgroup and hub genes for CAD patients with STEMI, and then estimated hub genes predictive performance for STEMI onset among CAD patients. Besides, the biological features of hub gene were estimated both in bulk and single-cell profiles of CAD patients with STEMI, especially in artificial intelligence(AI)-driven virtual cells. Indeed, AI-empowered therapeutic enrichment framework(DrugRefLector) and molecular docking were cross-performed for identification of optimal preventative agents targeting hub genes for CAD patients. Finally, in vitro study confirmed the differentially expressed level of hub genes. RESULTS: Integrated NCH can lead to the molecular stratification for CAD patients with AMI, which provides insights into the patient precision medicine. Besides, NAMPT and CLEC4D can be considered as up-regulated NCH-associated hub gene involved in STEMI pathogenesis of CAD patients with satisfied predictive efficacy, which was mainly distributed at NK cells. Novelty, BRD-K92455082 can be considered as optimal STEMI-preventative agent for the CAD patients by targeting NAMPT and CLEC4D. CONCLUSION: Our study provides integrative evidence suggesting a potential combined role of cholesterol homeostasis and NK cell-associated transcriptional programs of AMI for CAD patients, which offers novel insights into patient precision and personalized medicine.

INTRODUCTION: Despite the use of direct oral anticoagulants (DOACs), acute ischemic stroke can occur for several reasons. According to international data, 20% of patients with acute ischemic stroke take DOACs, but no comprehensive analysis of this occurrence has been available in Hungary to date. OBJECTIVE: Our aim was to determine the prevalence of DOAC users in Hungarian ischemic stroke patients. METHOD: We used retrospective analysis of the Semmelweis University stroke registry to evaluate DOAC use in patients with acute ischemic stroke treated consecutively between October 2020 and September 2024. RESULTS: Among the 2918 consecutive patients with acute ischemic stroke within 24 hours, 320 were taking DOAC (10,57%), of these, 276 (86,25%) had a history of atrial fibrillation. 183 patients (57%) were treated with apixaban, 72 (23%) with rivaroxaban, 38 (12%) with dabigatran, and 27 (8%) with edoxaban. Regarding thrombolysis time windows, 173 out of 1379 (12.54%) patients within the standard intravenous thrombolysis window (0-4.5 h) and 63 out of 656 (9.6%) patients within the extended thrombolysis window (4.5-9 h) were receiving DOAC treatment. Among acute ischemic stroke patients taking DOACs, the proportion of women was higher (56.7%), and the average age for was significantly greater (76 years) compared to the overall acute ischemic population (70 years). DISCUSSION: The 10.57% prevalence of DOAC use among acute ischemic stroke patients was significantly lower than the 20% observed in international data. This discrepancy may be attributable to the later introduction of DOACs in Hungary, differing reimbursement policies, and high drug costs. Further studies are needed to explore the factors explaining this difference and their impact on stroke prevention. CONCLUSION: The rate of DOAC use among Hungarian acute ischemic stroke patients was below the international average, which warrants targeted studies to optimize anticoagulation strategies. Orv Hetil. 2026; 167(20): 779-783.

Large language models (LLMs) represent a rapidly advancing subset of artificial intelligence with significant potential to augment clinical practice. These tools can assist in literature synthesis, documentation, clinical reasoning, and patient communication. Despite demonstrated capabilities, adoption in healthcare remains limited due to barriers such as limited AI literacy, trust concerns, integration challenges, and generational disparities in digital proficiency. This review critically examines the role of LLMs as cognitive adjuncts in medicine, emphasizing the need for calibrated trust, human oversight, structured implementation strategies, and robust regulatory governance. Evidence suggests that stepwise integration of LLMs, beginning with low-risk tasks, may enhance physician efficiency, reduce cognitive burden, and may support high-quality care. Key limitations, including hallucinations, data currency, environmental impact, and data security, have to be addressed, alongside the need for continuous model refinement. Rigorous clinical trials are needed to establish the efficacy of LLMs. This includes the recognition that LLMs trained on vast web data may contain personal health information, creating a significant privacy risk. Responsible adoption of LLMs is essential to meet the demands of modern medicine while preserving clinical accountability and patient-centered care.

IMPORTANCE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and age-standardized COPD mortality has increased substantially over the past few decades. Robust estimates of life expectancy and years of life lost (YLL) from COPD, which are important to patient care and policy decisions, are lacking. OBJECTIVE: To determine whether COPD is associated with lower life expectancy and whether the YLL are associated with disease severity. DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 8 US general population cohorts. Participants aged 17 to 98 years were enrolled from 1983 to 2011 and followed up longitudinally through 2020. Data analysis was conducted from January 1, 2025, to January 15, 2026. EXPOSURES: Presence of COPD, which was defined by a prebronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio of less than 0.70 and disease stages per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. MAIN OUTCOMES AND MEASURES: This study used a parametric proportional hazards model with a Gompertz baseline hazard function to estimate survival by GOLD stage from the time of initial spirometry. The multivariable hazards function was used to estimate life expectancy, adjusting for demographics, educational attainment, body mass index, smoking status, pack-years of smoking, diabetes, hypertension, and hypercholesterolemia. YLL was calculated in comparison with individuals with no airflow obstruction. RESULTS: Of 45 886 participants (mean [SD] age, 52.4 [15.8] years; 25 827 [56.3%] females), 13 869 (30.2%) died over a median follow-up of 15.2 (IQR, 9.7-27.1) years. COPD was present in 8058 participants (17.6%). In age-adjusted models, mean life expectancy for an individual aged 65 years was 21.5 (95% CI, 21.3-21.6) years without COPD, decreasing to 20.0 (95% CI, 19.7-20.4) years for GOLD stage 1, 16.4 (95% CI, 16.1-16.8) years for GOLD stage 2, 13.1 (95% CI, 12.5-13.8) years for GOLD stage 3, and 10.7 (95% CI, 8.9-12.6) years for GOLD stage 4. YLL were 0.71 (95% CI, 0.34-1.08) for GOLD stage 1, 2.58 (95% CI, 2.21-2.95) for GOLD stage 2, 5.07 (95% CI, 4.39-5.74) for GOLD stage 3, and 7.12 (95% CI, 5.21-9.04) for GOLD stage 4. Comparable decreases were noted for COPD in those who never smoked vs ever smoked. YLL for GOLD stages 2 to 4 were similar or greater than the YLL for hypertension (2.7; 95% CI, 2.4-3.0), diabetes (4.1; 95% CI, 3.7-4.4), obesity (0.5; 95% CI, 0.1-0.9), and cigarette smoking (5.5; 95% CI, 5.1-5.9). CONCLUSIONS AND RELEVANCE: In this cohort study, COPD was associated with lower life expectancy, including in adults who never smoked.

PURPOSE OF REVIEW: Heart failure (HF) is the leading cause of morbidity and mortality in adults with congenital heart disease (ACHD), yet evidence-based pharmacological options remain limited. Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have demonstrated robust benefits across the heart failure spectrum in acquired cardiovascular disease. This review is summarizing emerging data on the use of SGLT2I in ACHD, a population characterized by unique pathophysiology and unmet therapeutic needs. RECENT FINDINGS: Recent literature, predominantly comprising case reports, retrospective cohorts, and small prospective studies, suggests that SGLT2I are generally safe and well tolerated in adult congenital heart disease heart failure (ACHD-HF). Across heterogeneous ACHD populations, including those with a systemic right ventricle (SRV) and Fontan circulation, SGLT2I use has been associated with improvements in natriuretic peptides, functional status, exercise capacity, and reductions in HF hospitalizations. Early data support favourable safety and low discontinuation rates. SUMMARY: The use of SGLT2I in ACHD-HF is feasible, well tolerated and with potential clinical benefit. Further ACHD-specific randomized clinical trials to define efficacy, optimal patient selection, and long-term outcomes are warranted.

OBJECTIVES: To systematically synthesize evidence on the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and imaging biomarkers of subclinical atherosclerosis and hepatic steatosis/fibrosis, and to quantify the magnitude of these associations across study populations. METHODS: We systematically searched PubMed, Embase, Web of Science Core Collection, and Cochrane Library (January 2000-February 28, 2026) for observational studies enrolling adults with MASLD (or historical NAFLD/MAFLD) that reported atherosclerotic cardiovascular disease (ASCVD)-related imaging outcomes. Primary outcomes were continuous coronary artery calcium (CAC; Agatston units), epicardial adipose tissue (EAT; cm3), controlled attenuation parameter (CAP; dB/m), and liver stiffness measurement (LSM; kPa). Weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomized thresholds were pooled using random-effects models with restricted maximum likelihood (REML) estimation and Hartung-Knapp adjustment where applicable; heterogeneity was quantified with I2 and τ2. RESULTS: Sixteen observational studies (n = 34,713; 6 cohort, 10 cross-sectional) from North America, Asia, and Europe were included. In modality-specific threshold analyses, MASLD was associated with higher odds of subclinical disease: CAC (OR 1.41, 95% CI 1.32-1.51; I2=75.0%), high EAT (OR 1.44, 95% CI 1.21-1.68; I2=0%), high CAP (OR 1.47, 95% CI 1.35-1.58; I2=0%), and high LSM (OR 1.49, 95% CI 1.31-1.66; I2=0%). For continuous outcomes, CAC was higher by 49.2 Agatston units (95% CI 46.8-51.7; I2=75.4%) and LSM was higher by 0.57 kPa (95% CI 0.46-0.68; I2=0%) in MASLD versus comparators. EAT (k = 2; n = 4,306): WMD 76.18 cm³ (95% CI 5.04-147.32; I2=98.3%) (exploratory only; not suitable for point estimation). CAP (k = 2; n = 6,652): WMD 45.12 dB/m (95% CI 0.96-89.27; I2=98.1%) (exploratory only; not suitable for point estimation). CONCLUSIONS: MASLD is consistently associated with greater calcific coronary burden, pericoronary adiposity, hepatic steatosis, and hepatic stiffness relative to non-MASLD comparators. These findings represent between-group imaging differences and should be interpreted as evidence of concurrent adverse imaging burden rather than formal demonstration of incremental predictive value beyond validated clinical risk engines. Whether these biomarkers improve discrimination, reclassification, or net clinical benefit beyond established scores (Pooled Cohort Equations [PCE], SCORE2, Framingham Risk Score [FRS]) requires prospective validation with pre-specified incremental prediction analyses. ADVANCES IN KNOWLEDGE: This study provides a comprehensive quantitative, multimodality synthesis demonstrating that MASLD is consistently associated with concurrent adverse changes across four key imaging biomarkers spanning subclinical atherosclerosis (CAC, EAT) and hepatic disease burden (CAP, LSM), establishing a critical evidence base to motivate prospective studies on integrating standardized imaging protocols to refine ASCVD risk characterization in MASLD populations.

BACKGROUND: Optimal management of advanced thymoma remains uncertain. We compared the efficacy of first-line platinum-anthracycline chemotherapy with other platinum-based regimens in a large Japanese cohort. METHODS: We retrospectively analyzed 157 patients with unresectable or recurrent thymoma treated at 39 institutions (2000-2020). Regimens were categorized as platinum-anthracycline (n = 104) or non-anthracycline platinum (n = 53). Propensity score matching (PSM) balanced baseline characteristics (46 pairs). The primary endpoint was overall response rate (ORR); secondary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS). RESULTS: Median age was 58 years (24-79) and 53% were male; 62% had recurrent disease. Before PSM, ORR was higher with platinum-anthracycline than with non-anthracycline platinum (57% vs 31%; p = 0.0024), while rwPFS (median 15.0 vs 13.4 months; HR 1.07; p = 0.72) and OS (median 84.9 vs 111.9 months; HR 1.36; p = 0.24) did not differ. After PSM, ORR remained higher (58% vs 32%; p = 0.0014) with comparable rwPFS (12.1 vs 11.7 months; HR 0.98; p = 0.98) and OS (93.8 vs 113.5 months; HR 1.41; p = 0.31). Overall, 70% of patients received subsequent local therapy. Among fatal cases, paraneoplastic syndromes occurred in 50%, and infections and cardiovascular events were frequent causes of death in addition to tumour progression. CONCLUSIONS: Although platinum-anthracycline regimens achieved higher response rates, this did not translate into longer rwPFS or OS. Non-anthracycline platinum regimens may be reasonable for selected patients, particularly when treatment tolerability is a priority, within individualized multidisciplinary long-term management. TRIAL REGISTRATION: UMIN000048181.

BACKGROUND: Chair-based exercise may represent a practical alternative for individuals with chronic obstructive pulmonary disease (COPD) who experience balance limitations, fatigue, or difficulty performing standing exercises. OBJECTIVES: To compare the effects of chair-based and standard home-based exercise programmes in people with COPD. METHODS: In this randomized controlled trial, 64 clinically stable patients with COPD were allocated to a Standard Exercise Group (SGr,n = 32) or a Chair-Based Exercise Group (ChGr,n = 32). Both groups completed an 8-week home-based exercise programme (5 days/week) supported by exercise videos, two live online supervised sessions, and weekly follow-up calls; no blinding was applied. Outcomes included the 6-minute walk test (6MWT), modified Medical Research Council dyspnoea scale (mMRC), Fatigue Severity Scale (FSS), pulmonary function, maximal inspiratory and expiratory pressures (MIP/MEP), peripheral muscle strength, Hospital Anxiety and Depression Scale (HADS), International Physical Activity Questionnaire-Short Form (IPAQ-SF), and Saint George's Respiratory Questionnaire (SGRQ). Adverse events were monitored. RESULTS: Both groups showed significant improvements in dyspnoea, fatigue, HADS scores, total physical activity, and all SGRQ domains (p < 0.01). In the chair-based group, 6MWT distance (p = 0.003), MIP and MEP (p = 0.025 and p = 0.028), and peak expiratory flow percentage (PEF%; p = 0.044) increased significantly. Between-group differences were observed only for changes in MEP% (p = 0.032) and PEF% (p = 0.01), favouring the chair-based group. No adverse events were reported. CONCLUSION: Both interventions improved symptoms, physical activity, and quality of life, while significant improvements in functional capacity and selected respiratory parameters were observed only in the chair-based group.

BACKGROUND: Meteorin-like protein (Metrnl) is a novel secreted protein produced by multiple tissues, which is involved in metabolic regulation, immune homeostasis, and tissue repair. In recent years, research on the role of Metrnl in diabetes has advanced significantly. However, substantial controversies persist regarding its expression dynamics, protective roles, and underlying molecular mechanisms in diabetes and its complications. MAIN BODY: This review synthesizes current evidence to systematically analyze the complex roles of Metrnl in diabetes. Preclinical studies have demonstrated that Metrnl primarily improves insulin resistance, protects pancreatic β-cells, and mitigates diabetes related damage to kidney, heart, and skin through multiple pathways, including the KIT receptor, AMPK and Wnt/β-catenin signaling pathways.In contrast, clinical data exhibit significant heterogeneity. Reports on circulating Metrnl levels in patients with type 2 diabetes are highly inconsistent, with findings of decreased, increased, or no significant changes. Such discrepancies are largely attributed to methodological inconsistencies and clinical confounders. Similar inconsistencies are observed in studies on gestational diabetes. Importantly, Metrnl also displays markedly different or even opposing expression patterns across various diabetic complications, highlighting its tissue-specific regulatory characteristics. CONCLUSIONS: In summary, Metrnl is a pleiotropic molecule involved in the pathophysiological processes of diabetes and its complications, and it holds potential as a candidate biomarker or therapeutic target. However, its clinical translation faces key challenges, including insufficient standardization of detection methods, unclear characterization of receptor systems, and undefined pharmacological properties. Therefore, although Metrnl shows promise in preclinical models, its clinical utility requires rigorous validation, and its roles should be interpreted cautiously based on the current body of evidence.

BACKGROUND: Patient factors determining the benefit of prone positioning remain uncertain, resulting in the maneuver being applied indiscriminately among those with moderate-severe ARDS. We aimed to assess if baseline respiratory system elastance (Ers), or "stiffness", determines the treatment effect of prone positioning on mortality. METHODS: Bayesian logistic regression modeling of the PROSEVA Trial was used to estimate the posterior probability of prone positioning effect moderation by baseline Ers on 90-day mortality in patients with moderate-severe ARDS. As a secondary aim, we tested whether the absolute change in driving pressure of the respiratory system (∆DPrs ) in response to prone positioning predicted 90-day mortality, using logistic regression. RESULTS: The treatment effect of prone positioning on mortality did not meaningfully vary with baseline Ers (posterior probability of benefit OR < 0.95 = 52%; interaction OR 0.94, 90% credible interval, CrI, 0.74-1.20). Higher baseline Ers was associated with greater improvements in DPrs at the end of the first prone session (β= -3.3, 95% confidence interval (CI) -4.09, -2.49; p = < 0.001). However, this response was not associated with mortality benefit in adjusted models (OR 1.14, 95% CI 0.96, 1.37; p = 0.14). CONCLUSIONS: The effect of prone positioning on mortality did not vary with Ers in the PROSEVA trial. Similarly, prone positioning-induced improvement in DPrs was not predictive of mortality in this cohort of passively ventilated ARDS patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint destruction, driven by aberrantly activated fibroblast-like synoviocytes (RA-FLS). Mitochondrial dysfunction, particularly excessive mitochondrial fission, contributes to RA-FLS activation and apoptosis resistance, yet the impact of disease-modifying antirheumatic drugs (DMARDs) on mitochondrial dynamics remains unclear. Here, we examined the correlation between mitochondrial dynamics proteins and RA disease activity and investigated the effects of leflunomide and methotrexate (MTX) on mitochondrial dynamics, autophagy, and apoptosis in RA-FLS and collagen-induced arthritis (CIA) mice. Mitochondrial dynamics proteins in synovial fluid correlated more strongly with disease activity than those in peripheral blood, and were partially normalized in RA patients receiving leflunomide or MTX. Both leflunomide and MTX attenuated TNF-induced mitochondrial fragmentation and decreased mitochondrial membrane potential in RA-FLS. Notably, leflunomide, but not MTX inhibited DRP1 phosphorylation at Ser616, increased reactive oxygen species, and induced apoptosis via the BCL-2/BAX/caspase-3 pathway. Additionally, leflunomide influenced autophagy by promoting LC3B II/I and enhancing p62 expression. In CIA mice, leflunomide reduced the expression and phosphorylation of DRP1 on synovium, increased the expression of OPA1, and alleviated joint inflammation and destruction. These findings identify mitochondrial dynamics as a therapeutic target in RA and suggest that leflunomide promotes apoptosis of RA-FLS by modulating the mitochondrial fission-autophagy axis.

BACKGROUND: Heart failure is a complex and dynamic clinical condition that requires continuous assessment, timely intervention, and re-evaluation in response to fluctuating patient status. Opportunities for nursing students to actively engage in such high-risk and rapidly changing situations during clinical practicum are often limited. Virtual reality (VR) simulation offers an immersive and interactive learning environment in which students can experience symptom progression and make nursing decisions within a safe yet realistic context. Given these characteristics, VR simulation is particularly well suited for heart failure nursing education. METHODS: This qualitative study employed Colaizzi's phenomenological method to explore the lived experiences of nursing students. The final analysis included reflection journals from 34 fourth-year nursing students. Data were collected through reflection journals written immediately after the instructor-led debriefing to capture immediate experiences and perceived meanings. Two qualitative researchers independently analyzed the data and reached consensus on themes following Colaizzi's procedure. The study adhered to COREQ guidelines. RESULTS: Five theme clusters emerged: (1) transitioning from technical practice to clinical presence, (2) clinical reasoning as situated action within a shared virtual space, (3) communicating within the reality of virtual accountability, (4) reorienting nursing through relational presence, and (5) navigating the boundaries of virtual and physical reality. CONCLUSIONS: VR-based simulation provided nursing students with multidimensional learning experiences extending beyond technical skill acquisition to include clinical reasoning, professional responsibility, communication, and patient-centered care. This study contributes qualitative evidence that elucidates how VR-based simulation supports integrated clinical reasoning and professional identity formation in heart failure nursing education, supporting its role as a complementary component within blended nursing education approaches. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 represent a critical window for preventing progression to overt cardiovascular disease (CVD). Insulin resistance (IR) is central to CKM pathophysiology, yet the comparative utility of longitudinal IR patterns (cumulative burden and longitudinal pattern groups) across multiple surrogates, and the mediating role of biological ageing, remain unexamined in this preclinical population. METHODS: We included 3948 participants with CKM stages 0-3 from the CHARLS 2011-2020. Twelve IR surrogates (TyG and derivatives, METS-IR, CTI, eGDR, TG/HDL-C) were assessed via cumulative exposure and K-means-derived pattern groups. Associations with incident CVD were evaluated using Fine-Gray competing risk models, spline regression, receiver operating characteristic analyses, and quantile-based models. Mediation analyses quantified the contribution of biological age acceleration. RESULTS: 756 (19.1%) of 3948 participants with CKM stages 0-3 developed incident CVD. Higher cumulative levels and the least favorable pattern groups of TyG-based indices, METS-IR, CTI, and TG/HDL-C were consistently associated with increased CVD risk, whereas elevated cumulative eGDR was protective. Cumulative eGDR demonstrated superior predictive performance for CVD risk (AUC: 0.613; all DeLong P < 0.05 vs. other indices) and was consistently identified as the top contributor by both WQS and Qgcomp analyses. Both KDM- and Light-BioAgeAccel partially mediated several IR-CVD associations (up to 45.8% and 25.9%, respectively). CONCLUSIONS: Sustained IR burden and unfavorable longitudinal IR patterns are linked to higher CVD risk in CKM stages 0-3, partly through accelerated biological aging. Integrating longitudinal IR profiling with aging metrics may sharpen early risk stratification and support scalable prevention targeting upstream metabolic drivers.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is characterized by marked clinical heterogeneity and poor prognosis. MYCN amplification drives NB tumorigenesis through epigenetic reprogramming and is frequently accompanied by a copy-number gain of the long arm of chromosome 17 (17q). Epigenetic dysregulation of enhancer landscapes-particularly large regulatory elements termed super‑enhancers (SEs), which are enriched for H3K27ac and bound by lineage-specific master transcription factors (TFs)-establishes distinct NB cellular identities and states. These SE domains demarcate oncogenes that function as critical regulators of cell proliferation and apoptosis. Therefore, SE-driven genes represent tumor vulnerabilities, offering selective therapeutic opportunities. METHODS: By integrating ATAC-seq data from 22 NB cell lines, the intratumoral heterogeneity of MYCN-amplified NB was characterized at the level of chromatin accessibility. Subsequently, based on H3K27ac ChIP-seq data from 38 NB cell lines, the ROSE algorithm was employed to identify SE-driven oncogenes. The synergistic mechanism between MYCN amplification and the 17q SE-driven gene MSI2 was investigated through genome‑wide CRISPR/Cas9 loss‑of‑function screens. At single‑cell resolution, we conducted a comprehensive analysis of the characteristics of heterogeneous tumor subpopulations and their immune microenvironment features. This analysis was performed using multiple bioinformatics workflows, including AUCell scoring, SCENIC analysis, copy‑number inference, cell differentiation‑state evaluation, neighborhood abundance tests, and separability tests. Finally, functional validation was performed using NB cell lines (MYCN‑amplified and non‑amplified) to assess gene perturbations. RESULTS: Pronounced epigenetic heterogeneity was observed within MYCN-amplified NB. MSI2 is an SE‑driven oncogene and is highly expressed in MYCN‑amplified NB. MSI2 and MYCN are co-expressed, may be mutually dependent, and are both correlated with cell cycle-related pathways. At the single-cell level, we identified and redefined an NB-MSI2 + MYCN+ subtype characterized by malignant transcriptional features, an immunosuppressive microenvironment, and poor patient prognosis. Building on this, combined targeting of MSI2 and MYCN markedly reduced proliferation and migration in MYCN‑amplified NB cells. CONCLUSIONS: The NB‑MSI2 + MYCN+ subtype defines a clinically aggressive, therapy‑refractory state characterized by high proliferation, metabolic reprogramming, and immunosuppression. For patients with MYCN-amplified NB, MSI2 is both a prognostic biomarker and a candidate therapeutic target.

BACKGROUND: Heart failure leads to adverse clinical and patient-reported outcomes. Its prevalence has increased markedly among adults aged 60 years and over. Transitional care interventions are recommended to address these issues; however, their effectiveness on health outcomes, particularly in older adults, remains limited and inconclusive. METHODS: This study aimed to systematically review and synthesise the existing evidence from randomised controlled trials on the effectiveness of transitional care interventions on health outcomes among older adults with heart failure. Only randomised controlled trials were included. This systematic review and meta-analysis were conducted according to the Cochrane Collaboration methodology and were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies from 2001 to the present were identified through searches of PubMed, the Cochrane Library, Web of Science Core Collection, and Cumulative Index to Nursing and Allied Health Literature Plus with full text. Risk ratios, mean differences, and standardised mean differences were calculated. Heterogeneity was evaluated with the I statistic. The certainty of the evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: Eight studies with 967 subjects (483 in the intervention group and 484 in the control group) were included in this systematic review and meta-analysis. Transitional care interventions were associated with improvements in self-care confidence and reductions in heart failure-specific readmission. There were no statistically significant effects on self-care maintenance, self-care management, or heart failure knowledge. Findings for health-related quality of life, functional status, and event-free survival varied across studies. The certainty of the evidence ranged from very low to moderate. CONCLUSIONS: Transitional care interventions were associated with improved self-care confidence and reduced heart failure-specific readmissions in older adults with heart failure. However, variations in the certainty of the evidence create uncertainty about the intervention's effect. The limited number of trials included in this review demonstrates an evidence gap in this area. Further high-quality studies with transparent reporting through prospective trial registration should be conducted to determine the optimal content of the transitional care intervention. REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021229464). CLINICAL TRIALS NUMBER: Not applicable.

BACKGROUND: This study aimed to characterize comorbidity distribution patterns and assess their clinical impact on therapeutic effectiveness in elderly pulmonary tuberculosis (PTB) patients, establishing an evidence base for risk-stratified clinical decision-making. METHODS: A retrospective cohort study was conducted among 1,340 hospitalized PTB patients (aged ≥ 60 years) from January 2020 to January 2024. Demographic characteristics, comorbidity data, and treatment outcomes were extracted from electronic medical records. Patients were categorized into treatment success (n = 1,105) and adverse outcome (n = 235) groups according to WHO criteria. Propensity score matching (PSM) was employed to balance baseline confounders, followed by multivariate logistic regression to evaluate associations between comorbidities and adverse outcomes. RESULTS: Comorbidities were prevalent in 81.64% (1,094/1,340) of patients, with stratification as follows: single comorbidity (30.67%, 411), dyad (26.64%, 357), triad (18.13%, 243), and complex multimorbidity (≥4 conditions: 6.19%, 83). The most frequent comorbidities were chronic heart diseases (31.12%), chronic lung diseases (27.84%), and hypertension (26.49%), followed by diabetes mellitus(20.30%) and psychiatric disorders (15.07%). The adverse outcome rate was 17.54% (235/1,340), comprising 98 treatment failures (7.31%), 89 deaths (6.64%), and 48 treatment terminations (3.58%).Multivariate analysis identified the following independent risk factors: diabetes mellitus(adjusted odds ratio [aOR]=2.73, 95% confidence interval [CI]:1.91-3.90), chronic kidney diseases (aOR = 6.31, 95% CI:4.00-9.96), active malignancy (aOR = 3.27, 95% CI:2.07-5.14), and multimorbidity (≥3 comorbidities; aOR = 1.71, 95% CI:1.20-2.46) (all p < 0.05). CONCLUSIONS: Elderly PTB patients exhibit a high comorbidity burden. Diabetes mellitus, chronic kidney diseases, active malignancy, and multimorbidity significantly increase the risk of adverse treatment outcomes. These findings underscore the necessity for multidisciplinary collaborative management models and early comorbidity screening to optimize clinical interventions. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Perioperative management of pediatric patients with congenital heart disease (CHD) and severe pulmonary arterial hypertension (PAH) remains challenging because of limited evidence-based guidelines. CASE PRESENTATION: We present the case of a 14-year-old female with a complete atrioventricular septal defect (Rastelli type A) and a single atrium with a biventricular connection. The preoperative pulmonary vascular resistance (PVR) was 6.3 Wood units after oxygen inhalation. Following a multidisciplinary evaluation, fenestrated patch closure was performed to reduce the right ventricular afterload. With standard perioperative management in place, early intravenous Treprostinil was initiated and carefully titrated. Thereafter, the patient maintained hemodynamic stability, was successfully extubated, and was discharged in stable condition. CONCLUSIONS: Early intravenous treprostinil, combined with individualized surgical protection, may help maintain hemodynamic stability and support recovery in high-risk pediatric patients with CHD-associated PAH.

BACKGROUND: To explore the expression characteristics, diagnostic value, and regulatory role of miR-148b-3p in hypertensive patients with left ventricular hypertrophy (LVH), providing preliminary evidence for mechanism research and clinical intervention. METHODS: 108 patients with hypertension, 105 patients with hypertension-related LVH, and 112 healthy controls were enrolled. Serum miR-148b-3p levels were detected by RT-qPCR. ROC curve analysis evaluated its diagnostic value, and logistic regression identified risk factors for hypertension with LVH. H9c2 cell experiments and Ang II-induced myocardial hypertrophy models were used to verify miR-148b-3p's functional role via CCK-8 (cell viability) and ELISA (ANP/BNP levels). RESULTS: Serum miR-148b-3p was higher in the hypertension with LVH group than in the hypertension and healthy controls. miR-148b-3p could effectively distinguish hypertensive patients with LVH (AUC = 0.821, 95%CI: 0.761-0.882). Additionally, elevated miR-148b-3p expression emerged as an independent risk factor for LVH and was strongly positively correlated with LVMI. In cellular experiments, overexpressing miR-148b-3p led to reduced cell proliferation and increased ANP and BNP expression; in contrast, the miR-148b-3p inhibitor reversed the above effects and alleviated Ang II-induced myocardial hypertrophy. Mechanistically, miR-148b-3p promotes myocardial hypertrophy by directly targeting KLF4. CONCLUSIONS: miR-148b-3p is highly expressed in hypertension with LVH, has diagnostic potential, and promotes myocardial hypertrophy by targeting KLF4 and regulating cell function, serving as a novel molecular marker and therapeutic target.

INTRODUCTION: Metabolic syndrome (MetS) is a series of health conditions, including insulin resistance, abdominal obesity, hypertension, and dyslipidemia. In diabetic patients, MetS elevates the risks of cardiovascular disease, stroke, and cardiovascular mortality. Its predictors are context-dependent, varying by diagnostic criteria and population characteristics, thus requiring localized studies to identify specific determinant factors. OBJECTIVE: To assess predictors of MetS among type II diabetic patients (T2DM) visiting public hospitals in Sidama Region, Ethiopia, from January 25- March 25, 2025. METHODS: An institutional unmatched case control study design was employed among 132 cases and 268 controls. Data were collected using a structured, interviewer-administered questionnaire adapted from the World Health Organization (WHO) STEPS instrument, complemented by laboratory investigations and standardized anthropometric measurements. MetS was diagnosed using the International Diabetes Federation (IDF) criteria. Bivariable and multivariable logistic regression models were fitted to determine predictors of MetS. Results were presented using adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULT: The mean age (± standard deviation) of the cases and controls was 56.9 (± 8.2) and 49.5 (± 8.1) years, respectively. MetS was found to be higher in female (61.4%) study participants than in male (38.6%). The identified predictors of MetS with 95% CI (AOR) were older age: 5.74 (2.56, 12.88), female sex: 2.91 (1.61, 5.26), urban residence: 2.59 (1.41, 4.75), monthly income > 3500 Ethiopian Birr: 4.30 (2.23, 8.28), family history of hypertension: 2.79 (1.47, 5.29), duration with DM: 5-9 years: 3.06 (1.57, 5.99) and ≥ 10 years: 3.61 (1.54, 8.48), and poor glycemic control: 3.93 (2.17, 7.13). CONCLUSION: The findings call for prioritizing targeted screening, lifestyle interventions, health education, and community-based programs to enhance the prevention, early detection, and management of MetS among T2DM patients.

OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score ≤10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.

INTRODUCTION: Non-cancer patients with advanced illnesses often experience delayed hospice referral and high-intensity care near the end of life, yet cross-diagnosis comparisons remain limited. This study examined diagnosis-specific patterns in hospice use and care intensity among non-cancer decedents. MATERIALS AND METHODS: We conducted a 10-year retrospective cohort study of adults with hospice-eligible non-cancer diagnoses who died or were discharged in a moribund condition between 2010 and 2019 at a tertiary referral hospital in Taiwan. Primary outcomes were place of death and an aggressive-care score (0-5) based on five EOL indicators in the last 28 days: hospitalisation >14 days, ≥1 intensive care unit (ICU) admission, ≥1 emergency department (ED) visit, cardiopulmonary resuscitation (CPR), and intubation with mechanical ventilation. Multivariable logistic regression identified factors associated with high aggressive-care scores (≥4). RESULTS: Among 5,127 non-cancer decedents, 7% received hospice care, with rates varying across diagnostic groups. Most hospice enrolments (60.2%) occurred within 7 days before death. Hospice recipients had lower median aggressive-care scores (2 vs. 3,  < 0.001) and lower ICU admissions (39.7% vs. 63.7%), ED visits (62.2% vs. 75.1%), CPR (1.7% vs. 10.1%), and mechanical ventilation (9.2% vs. 23.2%). Advanced heart disease (aOR 1.95) and end-stage renal disease (aOR 1.96) were associated with high aggressive-care scores, while hospice enrolment was associated with lower odds of such scores (aOR 0.46). CONCLUSION: Hospice care among hospitalised non-cancer decedents was infrequent and often initiated in the final week across diagnoses. These findings highlight diagnostic differences in end-of-life care intensity and support referral strategies for earlier palliative care integration.

BACKGROUND: Despite undertaking large volumes of structured exercise training, evidence suggests that masters athletes (MAs) remain susceptible to coronary artery disease (CAD). This review evaluated the prevalence and nature of CAD in MAs. METHODS: PubMed, Medline, EMBASE, Web of Science and Cochrane Library were searched on 23 November 2024, from 1 January 2000. MAs were defined as apparently healthy individuals aged ≥ 35 years with an exercise training history indicative of regular engagement in sporting activity. The Appraisal tool for Cross-Sectional Studies (AXIS) was used to assess study quality. RESULTS: A total of 17 studies reporting various measures of CAD in 2749 MAs (2127 male, 622 female) were included. Coronary artery calcium (CAC) was present in a significant proportion, with 565 MAs scoring > 0, and 179 and 43 MAs exceeding thresholds of > 100 and > 400, respectively. Evidence of plaque was detected in at least 458 MAs. This was predominantly calcified in the majority of cases. Obstructive disease (> 50% stenosis) was also identified in at least 51 MAs. Conventional cardiovascular (CV) risk factors such as smoking, dyslipidaemia, hypertension and diabetes were prevalent in this population. DISCUSSION: Clinical and methodological heterogeneity made it challenging to perform accurate quantitative analyses. However, our data reiterate that MAs are not invulnerable to CAD. Long-term and high-intensity endurance training may be associated with changes that predispose to atherosclerotic disease. Female MAs, and those from low- and middle-income countries, are markedly underrepresented in literature. CONCLUSION: A more individualised approach to CV risk assessment may be warranted in the future to guide early CAD detection and subsequent management. REGISTRATION: PROSPERO 2024 CRD42024607539.

BACKGROUND: The impact of age on outcomes in patients with large ischemic stroke [defined as Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≤ 5] remains unclear. This study aimed to explore the effect of age on clinical outcomes after endovascular therapy (EVT) for acute anterior circulation large ischemic stroke. METHODS: This subanalysis enrolled patients with acute large ischemic stroke from a prospective multicenter cohort registry from 38 stroke centers across China between November 2021 and February 2023. Patients were stratified into the EVT and standard medical treatment (SMT) groups. The effectiveness outcomes included the distribution of modified Rankin Scale (mRS) score and functional outcomes (mRS 0-2, 0-3, and 0-4) at 90 days. Safety outcomes included 90-day mortality, symptomatic intracranial hemorrhage (ICH) within 48 h, and any ICH. RESULTS: A total of 745 eligible patients were included in the analysis. Compared with SMT, EVT showed improved 90-day outcomes across different age groups [aged ≤ 65 years, adjusted common odds ratio (acOR): 2.11, 95% confidence interval (CI) 1.16-3.81, P = 0.01; aged 66-79 years, acOR: 1.23, 95% CI 0.79-1.92, P = 0.36; aged ≥ 80 years, acOR: 2.80, 95% CI 1.26-6.22, P = 0.01], while the predicted probabilities of achieving mRS 0-3 decreased and mortality rate increased both in the EVT and SMT groups with advancing age (P  = 0.88 and 0.84, respectively). CONCLUSIONS: In conclusion, age is a significant predictor of clinical outcomes in anterior circulation large ischemic stroke. While EVT benefits show progressive age-related decline, meaningful advantages persist even in patients aged ≥ 80 years, suggesting that age alone should not contraindicate EVT. However, further validation through large-scale randomized controlled trials is warranted.

Coronary artery disease (CAD) is a major risk factor for the development of heart failure (HF) with preserved ejection fraction (HFpEF) and is associated with increased mortality. However, an optimal strategy to screen for HFpEF among patients with CAD has not yet been established. The HFpEF-ABA score was introduced to estimate the pretest probability of HFpEF and was shown to predict adverse HF events. This retrospective multicenter cohort study included patients registered in the Clinical Deep Data Accumulation System database who underwent percutaneous coronary intervention from April 2013 to March 2019. Patients with a left ventricular (LV) ejection fraction ≥ 50% and no known history of HF were included. Age, body mass index, and a history of atrial fibrillation were used to calculate the HFpEF-ABA score, and patients were dichotomized at a 50% threshold for descriptive risk stratification. The primary endpoint was a composite of all-cause death and unplanned HF hospitalization. Among 3307 patients, those with high HFpEF-ABA scores were more likely to have hypertension, renal dysfunction, anemia, larger left atrial size, higher LV mass index, and elevated brain natriuretic peptide levels, consistent with an HFpEF phenotype. Over a median follow-up of 721 days, 275 patients experienced the primary endpoint. The HFpEF-ABA score was independently associated with the primary endpoint as both a continuous and a categorical variable (hazard ratio: 1.07 [95% confidence interval: 1.00-1.14], P = 0.043, and 1.37 [1.07-1.76], P = 0.015, respectively). The HFpEF-ABA score identifies CAD patients with an HFpEF phenotype and predicts adverse outcomes.

BACKGROUND: Prematurity and congenital heart disease (CHD) are risk factors for neonatal morbidity, including necrotising enterocolitis (NEC), and mortality. We describe the rates of NEC and survival in very preterm babies with severe CHD (sCHD), requiring cardiac intervention before discharge. METHODS: Retrospective cohort study utilizing the National Neonatal Research Database that included babies born <32weeks' gestation admitted to neonatal units in England and Wales, 2012-2020. EXPOSURE: Babies born <32weeks' gestation with sCHD, that require intervention before discharge (excluding patent arterial ducts). OUTCOMES: rates of sCHD, severe NEC (requiring surgery or death) and mortality (death before 37 weeks' CGA or neonatal discharge, whichever occurred first). RESULTS: 438/68,423 babies had a sCHD diagnosis (6.4 per 1000 admissions <32weeks). Compared to non-CHD infants, sCHD infants had a higher rate of severe NEC (7.1% (95% CI 5.0-9.9%) vs.3.7% (95% CI 3.6-3.8%), (p < 0.001)) and higher mortality before 37weeks' corrected gestational age (CGA) (31%, (95% CI 26.8-35.4%) vs. 10% (95% CI, 9.7, 10.2%) (p < 0.001)). Adjusted models showed that very preterm sCHD babies were two times more likely to develop NEC and six times more likely to die before 37weeks' CGA. CONCLUSION: Very preterm babies with sCHD have higher rates of NEC and mortality before cardiac intervention. IMPACT: Prematurity and severe congenital heart disease increase the risk of necrotising enterocolitis (NEC) and death. We found that in very preterm babies with severe CHD the odds of developing severe NEC were twice as high, and the odds of death were six times greater, compared to very preterm babies without sCHD. Careful planning and counselling are needed in preterm deliveries of babies with severe CHD to reduce the odds of NEC and mortality.