Cardiovascular disease remains a leading cause of death among individuals with Type 2 diabetes mellitus (T2DM). To better direct preventative care, many risk assessment tools have been developed to determine whether T2DM patients will develop cardiovascular disease. This paper analyzes three specific tools: UKPDS (United Kingdom Prospective Diabetes Study), the Framingham Risk Score, and the QRISK (QRESEARCH cardiovascular risk algorithm) calculator, with a focus on their predictive utility and limitations in clinical practice. All these models were designed using a variety of patient information, including demographics, cholesterol levels, and blood pressure values; however, each has its own drawbacks. The UKPDS is based on an outdated study and does not account for patients with a history of baseline heart disease. The Framingham Risk Score is less accurate when determining the risk of cardiovascular events in underserved populations, as the database it was developed from lacks sufficient representation of these groups. While the QRISK calculator incorporates additional patient factors to better address the gaps of previous tools, resulting in more accurate predictions, none of these tools are perfectly individualized. Patient data is constantly changing, highlighting the need for models that utilize machine learning algorithms. Such approaches allow for greater adaptability and can integrate data from biomarkers and continuous glucose monitoring devices. Improving the accessibility and implementation of these newer tools is essential to better address existing healthcare gaps and enhance preventative care in high-risk populations.

Extensive Small-cell lung cancer (ES-SCLC) has a poor prognosis following the failure of first-line therapy based immune checkpoint inhibitors. This study aimed to evaluate the efficacy and safety of nab-paclitaxel combined with anlotinib as second-line treatment for relapsed SCLC.

Patients were divided into two groups: patients receiving 125 mg/m² of nab-paclitaxel on Days 1 and 8, repeated every 3 weeks for six cycles (the NAP group) and patients receiving 125 mg/m² of nab-paclitaxel on Days 1 and 8 accompanied with 12 mg/day of anlotinib for 14 days, repeated every 3 weeks for up to six cycles, followed by maintenance anlotinib until disease progression or unacceptable toxicity (the ANNAB group). The primary endpoints were progression-free survival (PFS) and overall response rate (ORR). The secondary endpoints were overall survival (OS) and safety.

Between January 1, 2023, and July 31, 2024, 48 patients were enrolled into the study. The median PFS was 6.0 months in the ANNAB group and 4.7 months in the NAP group (p = 0.0004). ORR was significantly higher in the ANNAB group than in the NAP group (37.5% vs. 8.3%, p = 0.0363). The median OS was 10.0 months in the ANNAB group compared to 7.3 months in the NAP group (p < 0.0001). There were no significant differences in adverse events between the two groups.

The combination of nab-paclitaxel and anlotinib as second-line treatment for recurrent SCLC demonstrated promising efficacy and an acceptable toxicity profile, suggesting its potential as a viable therapeutic strategy.

Noninvasive liver fibrosis indices, including the Fibrosis-4 (FIB-4) and AST-to-platelet ratio index (APRI), are widely used in clinical practice. We investigated whether admission FIB-4 and APRI, together with inflammatory markers and comorbidities, chest CT severity, and intensive care unit (ICU) admission, were associated with short- and long-term mortality in hospitalized COVID-19 patients. We retrospectively analyzed 691 adults hospitalized with PCR-confirmed COVID-19 between October and November 2020. Demographic characteristics, comorbidities, admission laboratory parameters, chest CT severity, length of stay, and intensive care unit (ICU) admission were recorded. Mortality during hospitalization, within 100 days, and within 4 years was obtained from the hospital database. FIB-4 and APRI were calculated using routine laboratory parameters. The cohort included 410 women (59.3%) and 281 men (40.7%); 79 patients (11.4%) required ICU admission, and 36 (5.2%) had malignancy. In-hospital, 100-day, and 4-year mortality rates were 12.0%, 14.6%, and 23.3%, respectively. Across all time points, mortality was associated with older age, higher inflammatory markers (including CRP), higher neutrophil counts and neutrophil-to-lymphocyte ratio (NLR), higher FIB-4 and APRI scores, severe chest CT findings, ICU admission, and comorbidities including malignancy, hypertension, and chronic renal failure. Lymphocyte count, hemoglobin, and platelet count were inversely associated with mortality. Admission inflammatory markers and noninvasive fibrosis indices (FIB-4 and APRI), combined with comorbidities and disease severity (CT and ICU requirement), are strong predictors of short- and long-term mortality up to 4 years in hospitalized COVID-19 patients.

Chronic subdural hematoma (CSDH) is a common neurosurgical condition in the elderly population, with an increasing incidence attributed to longer life expectancy, widespread use of anticoagulant or antiplatelet agents, and a higher risk of falls. Its diagnosis remains challenging due to its nonspecific and often subtle clinical presentation, typically including confusion, cognitive decline, gait disturbances, or somnolence, which may mimic other geriatric syndromes. Neuroimaging is essential, with non-contrast CT as the first-line modality, complemented by MRI in selected cases to better characterize complex or atypical lesions. Surgical evacuation via burr-hole trepanation remains the cornerstone of management in symptomatic patients, particularly when associated with significant mass effect. The addition of subdural drainage and intraoperative irrigation with warm saline (37 °C) has been shown to reduce postoperative recurrence. Recently, middle meningeal artery (MMA) embolization has emerged as a promising minimally invasive technique aimed at occluding the vascular supply of the neomembrane responsible for persistent microbleeding. Recent randomized controlled trials have demonstrated the efficacy and safety of MMA embolization in reducing recurrence rates, either as a primary or adjunctive therapy, particularly in high-risk or inoperable patients. Beyond the procedure itself, patient outcomes largely depend on a multidisciplinary approach encompassing neurosurgery, interventional neuroradiology, anesthesiology, geriatrics, and rehabilitation. Optimal perioperative management includes correction of coagulation disorders, monitoring of fluid balance, and individualized postoperative surveillance. The integration of novel endovascular strategies with traditional surgical treatment opens new avenues for personalized care and improved prognosis in this vulnerable population. Further research is warranted to refine patient selection criteria for embolization, evaluate long-term outcomes, and determine its place in treatment algorithms.

This paper describes the methodology and outcomes of the development of a trauma-informed protocol for cognitive behavioral therapy for insomnia (CBT-I). Methods included (a) convening an expert panel of U.S. Department of Veterans Affairs providers (n = 4) to identify trauma-related symptoms that may interfere with standard CBT-I delivery and to assess trauma-informed adaptations to an existing CBT-I protocol, (b) presenting adapted protocol materials to veteran engagement groups for feedback, and (c) sequentially delivering the trauma-informed CBT-I protocol to women veterans (n = 5) with iterative refinement of the intervention materials and evaluation of clinical improvement (Insomnia Severity Index and Pittsburgh Sleep Quality Index total scores and sleep diaries). Trauma-informed adaptations to CBT-I included posttraumatic stress disorder (PTSD) diagnosis psychoeducation, nighttime hyperarousal reduction strategies, nightmare/sleep avoidance psychoeducation, behavior tracking to challenge avoidance, psychoeducation about trauma-related thoughts, and orientation to PTSD treatments. Veteran engagement group consensus supported expert feedback. Women who completed trauma-informed CBT-I reported improved sleep outcomes from baseline to 3-month follow-up and high perceived acceptability and clarity regarding trauma-informed adaptations. This efficient, multistep approach resulted in an acceptable, efficacious protocol for use in a randomized clinical trial. These methods can be applied to other protocols to systematically adapt other psychotherapies for patients with PTSD.

The extensive genetic overlap between anxiety disorders (ANX) and major depression (MD) may partly reflect inclusion of comorbid cases in genome-wide association studies (GWAS). We investigated this genetic relationship between ANX and MD with and without mutual comorbidity.

Using UK Biobank, we performed disorder-specific GWAS for ANX-only (cases/controls = 9,980/179,442) and MD-only (cases/controls = 15,301/179,038) and derived polygenic risk scores (PRS). In the Norwegian Mother, Father, and Child Cohort (MoBa), we tested associations of PRS with MD-only (N=7,486), ANX-only (N=1,992), and comorbid (ANX-MD) (N=3,468) and controls (N=85,851). PRS associations with anxiety and depression symptoms were tested in MoBa (N=54,862). GWAS including comorbid cases (MD-comorbid or ANX-comorbid) were used for comparison. Genetic correlations were compared by comorbidity status, and Mendelian randomization was employed to assess causal relationships.

MD-comorbid and ANX-comorbid PRS showed stronger association with ANX-MD cases than with their primary disorders, MD-only (Z=-2.82; P_adjusted=0.01) and ANX-only (Z=-2.36; P_adjusted=0.03), respectively. MD-only PRS was more strongly associated with MD-only than with ANX-only cases (Z=3.63; P_adjusted=6.9e-04). The genetic correlation was lower between ANX-only and MD-only (rg=0.53, SE=0.11) than between ANX-comorbid and MD-comorbid (rg=0.91, SE=0.01). Bidirectional causal effects observed in comorbidity-inclusive analyses were attenuated to null when comorbid states were excluded. Gene sets of MD-comorbid, ANX-comorbid, and MD-only, but not of ANX-only, were enriched for the immune regulation pathway - interleukin-21 production.

The genetic distinction between ANX and MD becomes more pronounced when comorbid cases are excluded. The findings underscore the importance of disorder-specific genetic studies for advancing precision medicine.

The aim of this study was to facilitate the fine classification of diabetic complications and the prioritisation of drug targets via immune-cell-related gene expression data, distinguishing cell-type-related pleiotropy.

We analysed the combined clinical, genetic and immune-related features of diabetic complications, generating distinct clusters. Using 18,611 immune expression quantitative trait loci (eQTL) of 4487 genes, we investigated the causal effects of immune-cell-related gene expression on the risks of type 2 diabetes and its complications through Mendelian randomisation (MR) and colocalisation approaches. We then explored cell-type-related enrichment and specificity, and attenuated the cell-type-related pleiotropy for the top MR findings via multivariable MR methods.

Clustering analyses identified diabetic neuropathy as a distinct cluster of diabetes complications, with distinct immune-related features. MR and colocalisation analyses revealed the expression of 425 and 123 unique genes associated with type 2 diabetes and its complications, respectively, with external validation performed using single-cell RNA-seq data. We further quantified the impacts of cell-type-related pleiotropy, demonstrating that the percentage of pleiotropic genes increased from 40.0% (classic pleiotropy) to 71.1% (classic and/or cell-type-related pleiotropy). Applying six multivariable MR (MVMR) methods substantially attenuated the cell-type-related pleiotropy for the top findings. Finally, we integrated clinical trial evidence with genetic evidence and prioritised ten immune-related drug targets for diabetic complications.

Our study supports a key role for immune mechanisms in diabetic complications and highlights promising therapeutic targets by distinguishing and minimising the influence of cell-type-related pleiotropy.

Non-communicable diseases (NCDs) are a growing health crisis in Bangladesh and a leading cause of morbidity and mortality. This study assessed the capacity and service readiness of healthcare facilities for the management of NCDs, including hypertension (HTN), diabetes mellitus (DM), and chronic respiratory diseases (CRDs), in two selected districts of Bangladesh.

A cross-sectional study was conducted in 328 public and private health facilities utilising the World Health Organisation's Service Availability and Readiness Assessment manual. The study assessed the facilities' readiness to manage NCDs across four domains: trained staff & guidelines, basic equipment, diagnostics, and essential medicines. A composite mean readiness index (RI) score was calculated using these domains. A facility with a composite RI score of 70% or higher was considered ready to manage NCDs.

A total of 84% (n = 277) of facilities belong to the public sector. District hospitals (DH) and Upazila Health Complexes (UHCs) demonstrated high readiness for HTN (83% and 78%, respectively) and DM (78% and 71%, respectively), surpassing the 70% cutoff. However, no facilities met this criterion for CRDs. The highest RI scores were found for equipment for HTN and DM, and in staff & guidelines for CRDs. In contrast, the lowest RI scores were: medicines for HTN (8% in Union-level Facilities and 3% in Community Clinics (CCs)) and diagnostics for DM (4% and 2% respectively).

PHC-level health facilities, particularly Union-level Health Facilities and CCs in Bangladesh, are critically underprepared for NCD management, with key deficiencies in staffing, diagnostics, and medicine supply. This necessitates an effective, equity-driven approach to equip both public and private healthcare facilities and improve overall NCD care in the country.

This study aimed to investigate the functional recovery of an 8-gene-edited pig heart after orthotopic xenotransplantation, the characteristics of the recipient's immune responses, and the efficacy of postoperative complication management to provide comprehensive experimental evidence for the clinical translation of xenogeneic cardiac transplantation technology.

On December 27, 2025, an orthotopic heart was xenotransplanted from an 8-gene-edited pig to a rhesus macaque using the biatrial anastomosis technique. Postoperatively, comprehensive vital sign monitoring, immunosuppressive therapy, and complication interventions were implemented. Donor organ cardiac function, recipient immune indicators, and survival status were evaluated within 30 days after transplantation.

The recipient macaque survived for more than 30 days postoperatively. The cardiac function of the donor heart gradually stabilized, with the ejection fraction increasing from 58% in the early postoperative phase to 66%. No hyperacute immune rejection occurred. Postoperative complications, including infection, pleural effusion, and blood pressure fluctuations, were effectively controlled with symptomatic treatment.

An 8-gene-edited pig heart demonstrates good biocompatibility in xenogeneic cardiac transplantation. Standardized surgical procedures, precise immunosuppressive regimens, and comprehensive postoperative care can effectively ensure desirable transplantation outcomes. This study offers an important technical reference for clinical xenogeneic cardiac transplantation.

The co-occurrence of HIV and non-communicable diseases (NCDs), particularly hypertension, is a growing global health issue. As people living with HIV (PLHIV) live longer due to antiretroviral therapy (ART), they become more susceptible to NCDs like hypertension due to chronic inflammation, long-term drug side effects, and metabolic factors that compound their risk. The integrated HIV/HTN project implemented a feasible and cost-effective multi-component intervention in several public health facilities in Uganda. In this study, we sought to evaluate the program sustainability of the intervention by the public health delivery system.

A mixed-methods cross-sectional study was conducted across 26 public health facilities in 13 intervention districts of southwestern Uganda. Quantitative data were collected using the Program Sustainability Assessment Tool (PSAT) from District Health Officers (N = 15), HIV focal persons (N = 10), and Facility/Clinic in-charges (N = 25). Qualitative data were gathered through in-depth interviews with healthcare managers and analyzed using Stata and Dedoose software.

The PSAT Partnerships domain scored high (5.68), reflecting strong stakeholder engagement, communication, and leadership involvement. The Organizational Capacity domain also performed well (5.66), with strong integration of hypertension screening and data management, resource management and staff training rated at 4.24 and 4.9 respectively. Integration of HTN into HIV Care Evaluation scored (5.54), excelling in public communication but needing improvement in reporting and evaluation capacity. The Communications domain (5.51) showed moderate effectiveness, with room to enhance public engagement and feedback strategies. Environmental Support was the weakest domain (4.73), highlighting the need for better resource mobilization and training adequacy.

The sustainability of a multi-component care model was strongly influenced by strong partnerships and leadership. To ensure long-term success, environmental support, resource management, and sustainability planning is essential. Addressing these gaps will strengthen ongoing integration efforts in resource-limited settings.

ClinicalTrials.gov, TRN: NCT04624061, Registration date: 04 November 2022.