Over the past decade, significant advances have been made in the definition, epidemiology, identification of high-risk populations, aetiology, pathophysiology, clinical classification, risk stratification, and diagnostic and therapeutic strategies for pulmonary hypertension. Echocardiography remains the primary first-line screening tool and the most widely used initial diagnostic modality, and it is essential for longitudinal follow-up and assessment of treatment response. However, to date, a unified, standardized, and protocol-based echocardiographic pathway for screening and diagnosing pulmonary hypertension remains lacking in China, resulting in marked inter-center and inter-operator variability in echocardiographic parameters and reporting. Differences among clinical experts in the selection and interpretation of echocardiographic measurements have further limited the broad application of echocardiography in guiding the diagnosis and management of pulmonary hypertension. To improve the accuracy and consistency of standardized echocardiographic screening, diagnosis, risk assessment, treatment target setting, and therapeutic response evaluation in adult pulmonary hypertension in China, experts in cardiology, pulmonary vascular medicine, respiratory medicine, and echocardiographic imaging were convened by the Pulmonary Vascular Group of Chinese Medical Doctor Association of Cardiology, Chinese Society of Echocardiography, and Specialized Committee of Cardiovascular Disease Prevention and Rehabilitation of the Chinese Association of Rehabilitation Medicine to develop this guideline based on the latest domestic and international evidence, as well as recent international guidelines and consensus statements.This guideline provides stratified recommendations according to hospital capabilities and the expertise of pulmonary vascular physicians and echocardiographic technicians, and integrates echocardiographic workflows and acquisition parameters applicable to different levels of medical institutions. The workflow spans the entire disease course, including screening, diagnosis, assessment, and follow-up. This guideline aims to establish a unified pathway for echocardiographic application and parameter acquisition across institutions and physicians of varying backgrounds and levels, and to serve as a reference for further standardizing echocardiographic evaluation of adult pulmonary hypertension in China.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disease resulting in decreased circulating functional levels of alpha-1 antitrypsin (AAT), an important protease inhibitor that protects tissue, particularly the lungs, from protease-mediated degradation. Individuals with AATD-associated emphysema have historically been treated with plasma-derived AAT, requiring weekly infusions. A recombinant AAT-Fc fusion protein, efdoralprin alfa, is currently being studied in clinical trials. Here, we sought to delineate a normal range of functional AAT (fAAT) that can be used to assess how effectively therapies restore fAAT to the normal range.

Self-reported healthy individuals from Massachusetts were recruited to serve as donors to delineate a reference interval (RI), with requirements for ≥ 75% of individuals to be White. The Mayo Clinic analyzed blood samples from each donor to confirm wildtype Pi*MM phenotype and assess total AAT protein levels using the A1ALC test and a Siemens nephelometry assay, respectively. Samples were assessed for fAAT at BioAgilytix using a validated anti-neutrophil elastase capacity assay with WHO International AAT standards. Verification cohorts were recruited from geographically distinct regions (Florida and California) to confirm that the Massachusetts cohort was representative of the broader population.

Of 237 individual donors in the RI cohort, 211 with confirmed wildtype Pi*MM phenotype were used to calculate the RI. The central 95% range (2.5th percentile to 97.5th percentile) of fAAT concentration was 23.8-42.4 µM, with 23.8 µM designated as the lower limit of normal (LLN). Although one of the Florida verification cohorts was not included because of inability to verify sample-handling procedures, the LLN determined from the RI cohort was in alignment with the other two verification cohorts. In addition, the lower bound for total AAT protein from the RI cohort was 106 mg/dL. This value was consistent with two larger published datasets, supporting the representativeness of the RI cohort.

The fAAT RI and LLN delineated by this study can be applied directly to clinical trials to evaluate the pharmacodynamic effect of AATD therapies, and, in conjunction with clinical trial pharmacokinetic data, can be used to support dosing decisions for patients with AATD.

Carbon black (CB) exposure is a well-established cause of pulmonary injury, yet sensitive and practical biomarkers for early detection remain lacking. This study aims to address this gap. Here, we investigate whether urinary metabolomics can provide noninvasive signatures for the early identification and risk stratification of CB-associated airway injury.

In 2018, we enrolled 45 CB-exposed packing workers from a CB factory in Henan Province and 45 municipal waterworks employees without occupational particulate exposure as controls from the same city. After accounting for environmental confounding, participants completed baseline questionnaires; internal exposure dose, lung function, and airway structure were assessed, and urine was collected concurrently. Urinary metabolomes were quantified by UPLC-Orbitrap-MS, and covariate-adjusted linear regression identified metabolites associated with CB exposure and airway remodeling, which informed development of an exposure-related small-airway injury prediction model.

CB-exposed workers showed significantly higher lung CB burden, impaired pulmonary ventilatory function (reduced FEF₂₅ and FEF₂₅P), and increased 6th-generation airway wall thickness (WA%), with untargeted metabolomics identifying 210 differential metabolites primarily enriched in the purine metabolism pathway. Correlation analysis between differential metabolites and 6th-generation WA% (LB1+2) further identified four key endogenous metabolites, namely creatine, citric acid, Prostaglandin E2, and 3 beta-Hydroxy-5-cholestenoate. A KNN classifier incorporating these four metabolites demonstrated mean AUCs of 0.782 ± 0.06 and 0.631 ± 0.138 in the training and test sets, respectively.

Urinary metabolomics identified four candidate biomarkers for carbon black-related airway injury, and a metabolite-based predictive model may offer a noninvasive, cost-effective approach for early screening in occupationally exposed populations.

MiR-501-3p, a small non-coding RNA, has been linked to vascular damage and arterial stiffness, but its role in abdominal aortic aneurysm (AAA) remains unknown. Blood exosomal microRNAs were extracted, and RNA was also extracted from tissue samples, including both the region of maximum aortic dilation and the transition zone between normal and aneurysmal tissue. The low blood miR-501-3p expression group included more AAA patients and greater size than the high group. Multivariate analysis revealed a significant association between the presence of AAA and low blood miR-501-3p (OR = 6.467, p < 0.05). In AAA tissue, miR-501-3p was lower in the maximum point compared to the border point and correlated with larger AAA sizes. All low expression cases at the maximum point had an AAA ≥ 55 mm, whereas only 9.5% of cases in the high expression group had an AAA ≥ 55 mm (P < 0.01). miR-501-3p was identified as a potential key indicator and regulator of AAA presence and expansion.

Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden characterized by progressive cardiac dysfunction and high mortality. Emerging evidence suggests that epigenetic modifications, especially DNA methylation of antioxidant-related genes, may influence the molecular mechanisms underlying heart failure. This study aimed to investigate the methylation status of the glutathione peroxidase 4 (GPX4) promoter region in patients with HFrEF and to explore its associations with clinical and biochemical indicators.

A total of 125 patients with HFrEF (LVEF < 50%) and 350 healthy controls were enrolled. Peripheral blood genomic DNA was extracted, and CpG methylation levels within the GPX4 promoter (FA3 and FA20 regions) were quantified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Statistical analyses were performed using t-tests, Mann-Whitney U tests, and χ² tests. Restricted cubic spline (RCS) models were then applied to assess potential nonlinear dose-response relationships between methylation levels and clinical variables.

Methylation at GPX4_FA3_CpG_5 was significantly higher in HFrEF patients than in healthy controls (P = 0.019). Stratified analysis by NYHA class revealed increased methylation at GPX4_FA20_CpG_6 in patients with class I/II heart failure compared with those with class III/IV disease (P = 0.017). RCS modeling identified nonlinear U-shaped or multiphasic associations between GPX4_FA3_CpG_5 methylation and several clinical indicators, including total bile acid (TBA), fibrinogen (FG), fibrin degradation products (FDP), and eosinophil percentage (EO%). No significant associations were detected between GPX4 methylation and blood lipid or routine hematologic parameters.

In HFrEF patients, GPX4 promoter methylation is closely associated with clinical and biochemical alterations. Site-specific changes suggest that dysregulation of the GPX4-mediated antioxidant network and ferroptosis-related pathways may contribute to cardiac dysfunction. The nonlinear dose-response relationships with hepatic and coagulation markers indicate complex metabolic interplay. These findings support GPX4 promoter methylation as a potential epigenetic marker for HFrEF.

Pediatric patients undergoing cardiac surgery are at risk for developing positive cumulative fluid balance (CFB). Our goal was to study postoperative CFB in this population, its explanatory variables, and its effect on clinical outcomes during pediatric intensive care unit (PICU) stay and follow-up.

Retrospective single center study of 200 consecutive children undergoing congenital heart surgery with cardiopulmonary bypass (CPB). A clinically relevant CFB was defined as ≥ 5% at the end of postoperative day 1 (CFB POD1 ≥ 5%).

A CFB POD1 ≥ 5% was observed in 36% of the patients. Lower weight and longer CPB time were identified as explanatory variables for developing CFB POD1 ≥ 5%. Patients with CFB POD1 ≥ 5% showed more acute kidney injury, higher vasoactive inotropic scores, and prolonged invasive ventilation and PICU length of stay (LOS). A 1% increase in CFB POD1 lengthened PICU LOS by 0.8 days (CI 0.588 - 1.001, p < 0.001). Furthermore, patients with CFB POD1 ≥ 5% had lower cardiac event free survival time (p < 0.001).

This study confirms that even a minor positive CFB ≥ 5% is common in pediatric cardiac patients and associated with adverse PICU outcomes. Lower body weight and prolonged CPB duration increased the risk for positive CFB, warranting close fluid monitoring. Positive CFB was also associated with cardiac events during long-term follow-up and may help identify patients at increased risk for a complicated clinical trajectory, underscoring the importance of timely recognition and structured cardiac follow-up.

• Positive cumulative fluid balance (CFB) is associated with adverse outcomes in critically ill pediatric patients, including those undergoing congenital heart surgery, though causality remains unclear. • Evidence on optimal fluid management and clinically relevant CFB thresholds remains limited.

• This study confirms that a seemingly minor CFB of 5% is common and associated with adverse outcomes in a heterogenous pediatric cardiac cohort. • Positive CFB was additionally associated with adverse long-term outcomes, identifying positive CFB as a potential early marker of a complicated clinical course.

Drug therapy problems (DTPs), unintended events in pharmacotherapy that impede therapeutic goals and risk patient harm, are critical barriers to effective cardiovascular disease (CVD) management. Ambulatory cardiac patients are highly vulnerable to DTPs primarily due to complex comorbidities, but the prevalence and specific drivers of these problems within chronic care settings in Ethiopia are poorly characterized. Therefore, this study aimed to determine the prevalence and predictors of DTPs among adult ambulatory CVD patients at Wolaita Sodo University Comprehensive Specialized Hospital from May 9 to July 8, 2022. We conducted an institution-based cross-sectional study among ambulatory cardiac patients receiving chronic care. Data were collected through structured patient interviews and comprehensive medical record reviews. DTPs were systematically identified and classified using Cipolle's validated methodology, adapted for the local patient population. Binary logistic regression was used to assess the associations between predictor variables and DTPs, followed by multiple logistic regression to control for potential confounders. Statistical significance was determined at p≤0.05, with 95% confidence intervals used to estimate precision of effect measures. Among 195 ambulatory CVD patients, hypertension (59.5%, n=116) and heart failure (47.2%, n=92) were the most prevalent conditions. The study identified DTPs in 69.7% of patients (n=136), totaling 168 DTPs (mean: 1.3, standard deviation: 0.461) per affected patient. Unmet therapeutic needs (41.0%) and medication non-adherence (24.4%) emerged as the most common DTP categories. ASCVD risk assessment classified 40% of evaluated patients as high-risk (10-year risk ≥20%). Significant predictors of DTPs included polypharmacy [adjusted odds ratio (AOR): 3.48, 95% confidence interval: 1.47-8.24] and age (25-64 years: AOR=16.38), while prior hospitalization (AOR: 0.31) demonstrated protective effects. This study identifies unmet therapeutic needs and medication non-adherence as the predominant DTPs and polypharmacy as the most significant predictor among ambulatory CVD patients at Wolaita Sodo University Comprehensive Specialized Hospital, calling for systematic medication reviews, pharmacist-led interventions for high-risk groups, and enhanced adherence support programs to optimize treatment outcomes.

BackgroundHospital-associated venous thromboembolism (HA-VTE) is the leading preventable cause of death among patients undergoing gynecological surgery. Standard risk assessment methodologies, such as the Caprini score, which is a commonly utilized tool for risk assessment, do not sufficiently account for the unique vulnerabilities inherent to this specialty. To address these deficiencies, we aimed to develop a preliminary machine learning framework for predicting venous thromboembolism (VTE) in gynecological contexts.MethodsIn this retrospective case-control investigation, we identified 75 patients who were consecutively diagnosed with postoperative VTE after undergoing gynecological surgery at Ningbo NO.2 Hospital between March 2020 and February 2025. Controls were chosen using a matching protocol at a ratio of 1:3, resulting in the random selection of 225 patients free from VTE within the same surgical cohort during the same period. An Extremely Randomized Trees (Extratrees) machine learning classifier was constructed, incorporating 22 clinically relevant predictors identified by univariate analyses. We utilized the new model to compare it against the Caprini score.ResultsThe model was trained and validated with a class-stratified 70:30 split and exhibited remarkable discriminative ability, achieving an area under the curve (AUC) of 0.907 [95% confidence interval (CI): 0.833-0.972], significantly exceeding the performance of the Caprini score (AUC 0.731, 95% CI: 0.660-0.803). The model showed consistent discrimination across validation groups, yielding an accuracy of 0.833.ConclusionThis preliminary machine learning framework, tailored specifically for gynecology, provides enhanced risk stratification for VTE.

A substantial proportion of people with HIV and established atherosclerotic cardiovascular disease (ASCVD) meet criteria for extreme cardiovascular risk, yet low-density lipoprotein cholesterol (LDL-C) target achievement remains markedly suboptimal. Bridging the gap between updated guideline recommendations and real-world practice is essential to reduce recurrent ASCVD in this high-risk population.

Goltz-Gorlin syndrome, also known as focal dermal hypoplasia (FDH), is an uncommon X-linked dominant mesoectodermal dysplasia that predominantly affects females, with most nonmosaic males presumed to be nonviable. The disorder arises from abnormal development of mesodermal and ectodermal tissues and manifests as a broad spectrum of multisystem abnormalities. It is characterized by distinctive cutaneous findings and extracutaneous involvement involving the ocular, dental, skeletal, GI, genitourinary, cardiovascular, and central nervous systems. We report the case of a 49-year-old woman who presented with multiple papillomatous lesions initially involving the oral cavity and progressively spreading to other areas. Physical examination revealed innumerable millimetric verruciform papules, as well as multiple soft, yellowish, smooth oval papules over a hyperpigmented macule distributed along Blaschko lines. Additional findings included telangiectasias, patchy alopecia, dental anomalies, strabismus, and syndactyly/ectrodactyly of the left hand and right foot. Histopathological examination of verruciform and yellow papules confirmed FDH. PCR testing for human papillomavirus from oral and heel lesions was negative. The diagnosis of Goltz-Gorlin syndrome was established based on clinical criteria and histopathological findings. Multidisciplinary management included dental excision of papillomas and treatment with topical 5-fluorouracil and oral isotretinoin, resulting in complete remission. To date, approximately 200-300 cases have been reported worldwide. A retrospective institutional review identified only two additional cases between 2010 and 2025, underscoring the rarity of this condition. This case highlights the importance of early recognition of Goltz-Gorlin syndrome through characteristic cutaneous and extracutaneous findings and suggests that combined topical 5-fluorouracil and oral isotretinoin may be an effective therapeutic option for extensive papillomatous lesions.