Progression of transthyretin amyloid cardiomyopathy (ATTR-CM) can cause worsening congestion, requiring diuretic intensification (DI), heart failure (HF)-related hospitalizations (HFH), and death. Acoramidis and tafamidis are approved for ATTR-CM, but head-to-head trials are lacking. We evaluated the real-world comparative effectiveness of acoramidis versus tafamidis in newly treated patients with ATTR-CM.

Retrospective study using Komodo Healthcare Map® US claims data tokenized to Claritas. Patients aged ≥18 years newly initiating acoramidis or tafamidis between 12/11/2024 and 04/30/2025 with ≥1 prescription claim (first defined as index date), ≥6 months continuous enrollment preindex date, no multiple myeloma, light chain amyloidosis, or hematopoietic stem cell treatments, and no prior treatments for ATTR-CM were included and followed until disenrollment, death, treatment switch, or study end (07/31/2025). Outcomes included DI (initiation or dose-equivalent escalation of oral loop diuretics, parenteral loop diuretic use, or addition of thiazide-like diuretic) and composite of DI, HFH (inpatient admission with HF-related International Classification of Diseases, 10th Revision, Clinical Modification, diagnosis code in any position), and mortality. Propensity score weighting balanced baseline characteristics, disease severity, comorbidity burden, and baseline medication use. Time-to-event outcomes were assessed using weighted Cox proportional hazards models.

After weighting, patients treated with acoramidis (n = 170) and tafamidis (weighted sample size = 448) were comparable. Mean follow-up was 139 and 143 days, respectively. DI cumulative incidence curves separated early and remained divergent. Acoramidis significantly reduced the hazard of DI events by 43% versus tafamidis (11.8% vs. 20.5%; hazard ratio [HR], 0.57; 95% CI, 0.35-0.92; p = 0.021). Acoramidis had a significantly lower risk of composite events, with a 34% hazard reduction compared with tafamidis (17.6% vs. 26.4%; HR, 0.66; 95% CI, 0.44-0.99; p = 0.046).

In this first real-world comparative effectiveness study of newly treated patients, acoramidis had a significantly lower risk of DI events and composite events of DI, HFH, and mortality than tafamidis, potentially supporting improved clinical stability with acoramidis initiation. Additional evaluation with longer follow-up, larger cohorts, and/or prospective clinical outcomes is warranted. Graphical abstract available for this article.

We propose CardioTransfer-X, a cross-cohort transfer learning framework within a related clinical benchmark family for tabular CVD risk prediction that yields performance comparable to training from scratch while preserving transparency. Predictive models are pre-trained on a composite multi-hospital heart disease dataset to learn generalized risk patterns, then fine-tuned on the smaller, distributionally distinct Cleveland Heart Disease dataset. To mitigate dataset shift and class imbalance, we introduce a stability-aware, correlation-based feature selection strategy and apply SMOTE only during training. CardioTransfer-X is instantiated with XGBoost, TabNet, and a MLP, enabling systematic comparison across tree-based and neural models. SHAP-based explanations provide global interpretability across architectures, with consistent feature importance rankings before and after fine-tuning. Fine-tuned XGBoost achieves 80.65±4.08% accuracy and 81.74±3.71% F1-score on the Cleveland dataset while maintaining stable source-domain performance, showing performance competitive with training from scratch, while shifting the decision boundary toward higher sensitivity and maintaining clinically meaningful feature attributions.

To characterize the 30-day postoperative outcomes following craniotomy for AVM resection in pediatric patients and to elucidate independent predictors of adverse events using a large, multi-institutional database.

We performed a retrospective analysis utilizing the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2015-2023). Pediatric patients undergoing AVM resection were identified using a combination of CPT codes and ICD codes. The primary outcomes comprised a composite of 30-day mortality, complications, unplanned reoperation, readmission, non-home discharge, and extended length of stay. Multivariable logistic regression (Wald test; p < 0.05) was employed to identify independent predictors.

Analysis of 930 pediatric patients (median age 12.1 years, IQR 9.0-14.0) revealed that 34.3% experienced adverse outcomes within 30 days postoperatively. The observed mortality rate was 0.6%. Emergent surgical intervention demonstrated the strongest association with adverse outcomes (OR 8.58; 95% CI 5.12-14.37; p < 0.001), followed by preoperative ventilator dependence (OR 30.92; 95% CI 11.09-86.26; p < 0.001) and oxygen support requirements (OR 18.88; 95% CI 7.40-48.19; p < 0.001). Each additional minute of operative time conferred increased risk (OR 1.002/min; 95% CI 1.001-1.003; p < 0.001). Notably, we identified significant racial disparities, with African American/Black patients demonstrating an increased risk (OR, 1.65; 95% CI, 1.07-2.53; p = 0.023), while Hispanic ethnicity was associated with reduced adverse outcomes (OR, 0.73; 95% CI 0.53-1.00; p = 0.047).

These findings demonstrate that adverse outcomes following pediatric AVM resection are significantly influenced by surgical urgency, preoperative cardiopulmonary status, and operative complexity. The identification of potentially modifiable risk factors, particularly nutritional status and cardiopulmonary optimization, provides tangible targets for preoperative intervention. The observed racial disparities underscore the critical need for equitable, risk-stratified care paradigms in this vulnerable population.

Congestion is a central pathophysiological feature of heart failure (HF) and a major contributor to symptoms and prognosis. Despite the substantial mortality benefit of disease-modifying therapies [1], assessing and managing congestion remains challenging. Existing tools such as clinical examination, blood and urinary biomarkers, and cardiac and lung ultrasound are limited by observer variability, logistical constraints and the need for technical expertise [2]. Comorbidities such as chronic kidney disease (CKD), which co-exist in up to 60% of patients with heart failure and may contribute to congestion, further complicate assessments, which can lead to worse outcomes [3, 4]. Consequently, there is growing interest in objective, reproducible and accessible tools that complement conventional approaches to congestion assessment by providing additional information on fluid distribution within body compartments. Bioimpedance analysis (BIA) is a non-invasive technique that measures the electrical properties of biological tissues to estimate body composition and fluid distribution. Since the pioneering work of Nyboer in 1959 and Hoffer et al. in 1969 [5], BIA has evolved from a research tool for body composition into a broader clinical technology used across multiple specialties [6]. Advances in multifrequency, segmental, and spectroscopy-based systems have further expanded its potential for assessing fluid compartments in conditions such as HF and Chronic Kidney Disease (CKD). However, BIA encompasses heterogeneous technologies, parameters and prediction models, and its clinical role remains incompletely defined, with recommendations for further research [7]. This narrative review outlines the physiological principles of bioimpedance, evaluates its applications in HF diagnosis, prognostication, therapeutic guidance and remote monitoring, and explores the methodological and clinical barriers that have restricted its widespread adoption. We discuss its potential as an adjunctive tool for assessing congestion and highlight the key evidence gaps that must be addressed before bioimpedance can be more widely integrated into routine HF care.

Cardiovascular diseases (CVDs) represent the leading cause of morbidity and mortality worldwide, in Europe, and in Italy. Their onset can be prevented through a healthy lifestyle, including a balanced diet, regular physical activity, and abstention from smoking and alcohol consumption. The proactive cardiovascular screening program "Cardio50", provided for by the 2020-2025 Regional Prevention Plan of the Veneto Region, is positioned as a primary and secondary prevention intervention aimed at the early identification of modifiable risk factors in an apparently healthy population.

The study analysed the results of the "Cardio50" screening program conducted by the Prevention Department of AULSS 5 Polesana during the 2024-2025 two-year period on the cohort of subjects born in 1974-1975. Results were compared with data from the PASSI surveillance system relating to the same territory.

During the session of the cardiovascular screening, participants' lifestyle habits are investigated and anthropometric, blood pressure, and blood chemistry parameters are recorded, on the basis of which the software assigns a specific risk class (A, B1, B2, C, C1, D). Subjects in Class B2 are recalled for a six-month follow-up.

Out of 5481 potential participants, 2107 subjects (38.4%) took part, including 1109 women and 998 men. The distribution of risk classes showed a clear predominance of Class B2 (44.8%), followed by Class C (25.2%); overall, 85.2% of subjects required targeted interventions to address their risk factors. Six-month follow-up participation among subjects in Class B2 was 13.6%. Of the participants, 24.1% were smokers, 64.1% led a physically active lifestyle, 52.4% presented excess body weight and 12% consumed alcohol in a manner defined as higher-risk for health.

The clear predominance of subjects in Class B2, nearly one in two participants, highlights how a substantial proportion of the population exhibits at-risk behaviours despite the absence of overt clinical abnormalities, identifying a priority target for primary prevention. The low follow-up return rate represents a significant critical issue, as the sole initial detection of risk factors does not guarantee a genuine public health benefit without continuity of the preventive pathway. Comparison with PASSI showed consistency for smoking and excess body weight, a modest difference in physical activity levels and a discrepancy regarding alcohol consumption.

The study confirms the usefulness of the "Cardio50" program in the early detection of modifiable cardiovascular risk factors, but highlights the need to strengthen patient retention strategies during follow-up, including through greater involvement of general practitioners and local healthcare networks, in order to transform screening into a genuine long-term cardiovascular prevention pathway through integrated care.

Over the past few decades, advances in prenatal diagnosis, cardiac surgery, and perioperative management have substantially improved survival among individuals with congenital heart disease (CHD). As a result, CHD has evolved from a predominantly pediatric condition into a lifelong chronic disease requiring specialized follow-up tailored to disease complexity to prevent long-term complications, including arrhythmias, heart failure, and infective endocarditis [1]. The transition from pediatric to adult healthcare services represents a critical stage in the care pathway. Many adolescents transfer to adult care through unstructured processes, increasing the risk of discontinuity of care, loss to follow-up, and adverse clinical outcomes. Transition care is defined as a purposeful, planned, and coordinated process that ensures continuity of care, promotes patient autonomy, and facilitates transfer to specialized adult congenital heart disease (ACHD) services [2]. Although international guidelines strongly recommend structured transition programs, considerable heterogeneity persists regarding the timing of transition, intervention components, and the healthcare professionals involved. Consequently, standardized models and evidence-based recommendations for clinical practice remain limited. Therefore, a comprehensive synthesis of the available evidence is needed. The aim of this systematic review was to evaluate the effectiveness of transition care interventions for adolescents and young adults with CHD, with particular emphasis on clinical, educational, and organizational outcomes.

Transcatheter aortic valve implantation (TAVI) has become a viable option for patients with severe aortic valve stenosis across a broad range of surgical risk in recent years. The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score, a novel indicator of malnutrition and inflammation, has been discovered to be inversely linked with prognosis in several cancer types. The purpose of this study is to examine the performance of the HALP score in predicting one-month major adverse cardiac events and one-year mortality in patients treated with TAVI.

This study included 395 consecutive patients treated with TAVI, separated into two groups based on their HALP scores: low and high. Our study's primary endpoint was all-cause death within a year after discharge following the TAVI operation. The secondary endpoint was a composite endpoint that included periprocedural complications and events in one month.

Patients with a low median HALP score had a higher risk of one-month composite events and one-month death. In multivariate analysis, chronic kidney disease (odds ratio [OR]: 4.67, 95% confidence interval [CI]: 2.36 - 9.25, P < 0.001) and HALP score < 3.4 (OR: 1.235, 95% CI: 1.091 - 1.397, P < 0.001) were independent predictors of first-year mortality. Kaplan-Meier analysis for computing cumulative survival found that patients with low HALP scores based on a receiver operating characteristic curve cutoff of 3.4 had increased mortality rates throughout short-term follow-up.

The HALP score may be a significant independent predictor of short-term prognosis and mortality in patients treated with TAVI, beyond conventional risk-scoring tools for better disease management.

Lupus nephritis (LN) is a critical complication of systemic lupus erythematosus (SLE) and a leading cause of mortality in those affected. Abnormal energy metabolism of macrophages is closely associated with LN pathogenesis. Adenosine diphosphate (ADP) is known to regulate macrophage proinflammatory function; however, its specific role in SLE progression remains unexplored. We employed a spontaneous SLE mouse model and an integrated transcriptomic and metabolomic approach to investigate the effect of ADP on SLE disease progression and macrophage function. Our study revealed that ADP stimulates the AMPK signaling pathway, curtails macrophage senescence, and diminishes the release of senescence-associated secretory phenotype factors, ultimately alleviating SLE progression. Mechanistically, ADP promotes KLF10 expression, which binds to Sirtuin1 to facilitate deacetylation at the promoter region of Cdkn1a in macrophages. This process leads to reduced p21 expression and macrophage senescence. Collectively, the findings uncover a novel regulatory role of ADP in the pathogenesis of SLE and macrophage senescence, indicating its potential as a target for treatment.

Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro-atherogenic immune responses in aged atherosclerotic mice. 80- to 90-week-old male Ldlr^-/- mice with established atherosclerotic lesions were treated intraperitoneally with rapamycin or control triweekly for 8 weeks. Systemic and plaque immunity was assessed by flow cytometry or single-cell RNA-sequencing. Plaque morphology was evaluated by histology. Rapamycin treatment reduced plaque macrophage content (0.73 ± 0.07 × 10⁵ μm²) compared to control (ctrl: 0.95 ± 0.09 × 10⁵ μm², p < 0.05) and decreased total T cell numbers in vascular and lymphoid tissues. This was accompanied by a shift from effector to central memory phenotypes, particularly within the CD8⁺ compartment, and a relative enrichment of regulatory CD4⁺ T cells (Tregs). Single-cell transcriptomics of aortic Tregs revealed increased expression of suppressive genes (Foxp3, Tgfb1) upon rapamycin. Rapamycin also reduced T follicular helper cells, IL-21 expression, germinal center B cells, plasma cells, and total and oxidation-specific epitope-specific immunoglobulin levels. Additionally, age-associated B cells were diminished in spleen and lymph nodes, reflecting a broader anti-inflammatory effect on B cell immunity. Finally, aortic leukocytes displayed profoundly reduced senescent enrichment scores. Rapamycin remodels the immune landscape in aged atherosclerotic mice, promoting regulatory lymphocyte subsets and suppressing antigen-driven and inflammatory immune responses. These findings highlight the potential of immune-targeted rejuvenation to mitigate age-related atherogenic inflammation.

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerotic cardio-cerebrovascular disease. The role of impaired mitochondrial dynamics in the pathophysiological process of aging-related diseases is being actively researched. We discovered that targeting proteins related to mitochondrial dynamics, especially those involved in fission and fusion, may offer new treatment strategies for these diseases. Various approaches, including aerobic interval and treadmill training and the use of drugs such as the antidiabetic agents metformin and dapagliflozin, the antihypertensive agent irbesartan, and certain traditional Chinese medicine components, have shown potential in alleviating imbalances in mitochondrial dynamics in aging-related cardio-cerebrovascular diseases. In this review, we systematically summarize recent research on alterations in mitochondrial dynamics in age-related cardio-cerebral diseases and explore therapeutic strategies targeting these alterations, which may offer new directions for improving cardiac and brain health and guiding clinical practice.