Intestinal failure in children, when unresponsive to rehabilitation, requires intestinal transplantation as the only definitive therapy. In regions with limited availability of deceased donors, living-donor intestinal transplantation (LDIT) represents an important alternative. The early immunometabolic consequences of venous drainage configuration, however, remain insufficiently defined. Because ischemia-reperfusion injury is central to graft dysfunction, understanding how portal versus systemic venous outflow shapes the immediate postoperative response is essential to guide pediatric strategies.

A juvenile swine model (n = 14) was used to compare portal (n = 7) and systemic (caval, n = 7) venous drainage after LDIT. Animals were followed for 4 days with serial biochemical, histological, immunohistochemical, and molecular assessments. Analyses included linear mixed-effects models (LMM) for repeated measures and principal component analysis (PCA) to integrate multivariable data and identify global immunometabolic patterns.

Hepatic and renal function were preserved in both groups. Histology revealed only mild ischemia-reperfusion injury (Chiu/Park grades 1-2), with a trend toward greater lymphocytic infiltration in the systemic group. Caspase immunohistochemistry demonstrated early apoptotic activation in the portal group, which declined by day 4, suggesting a controlled adaptive response. IL-1α expression was selectively upregulated in intestinal tissue from the portal group, consistent with early mucosal immune activation. PCA confirmed a distinct immunometabolic profile under portal drainage, characterized by balanced inflammation, controlled apoptosis, and trends toward enhanced protein synthesis.

Venous drainage configuration modulates early biological responses after LDIT. Portal drainage was associated with a more regulated immunometabolic profile, supporting the hypothesis that physiological venous outflow promotes mucosal protection and immune balance.

 People with serious mental illness die 10-20 years earlier than the overall population, mainly from cardiovascular disease. Although effective interventions to manage cardiovascular disease risk in this population exist, they have not been widely implemented in community settings. IDEAL Goals is an empirically supported, cardiovascular risk reduction program tailored for people with serious mental illness (i.e., "clients") and designed to be delivered by clinicians and staff in community mental health settings. In this trial, we use Replicating Effective Programs (REP) as the foundational implementation strategy to test the effects of two additional strategies, Coaching and Facilitation, on improving the number of IDEAL Goals sessions clients receive in community mental health organizations in Maryland and Michigan.

 This cluster-randomized hybrid Type 3 effectiveness-implementation trial will use a non-restricted sequential, multiple-assignment randomized trial (SMART) design that randomizes organizations at two points, months 0 and 6, of the 18-month IDEAL Goals intervention. Organizations will receive one of four sequences of implementation strategies: (1) REP only; (2) REP + Coaching; (3) REP + Facilitation; or (4) REP + Coaching + Facilitation. The primary aim is to determine the effect of the most intensive sequence of strategies (REP + Coaching + Facilitation) versus REP only on the number of IDEAL Goals sessions clients receive over 18 months. The secondary aim is to determine the marginal effects of Coaching and Facilitation on the number of IDEAL Goals sessions clients receive over 18 months. Exploratory aims include: (1) assessing tailoring variables to inform a future adaptive implementation intervention to scale IDEAL Goals; (2) estimating the cost of delivering IDEAL Goals and implementation strategies; and (3) examining the relationship between different sequences of implementation strategies on: clients' receipt of cardiovascular disease risk factor management processes and outcomes over 18 months; and clients' receipt of IDEAL Goals over 30 months. Qualitative efforts will explore implementation strategy mechanisms, adaptations, and participants' experience of delivering and receiving IDEAL Goals.

To meaningfully reduce premature mortality for people with serious mental illness, it is imperative to test strategies that can facilitate optimal uptake and continued sustainability of cardiovascular risk reduction programs in community settings.

ClinicalTrials.gov identifier: NCT06674616 , registered on November 1, 2024.

Pseudoxanthoma elasticum (PXE) is a genetic disease with autosomal recessive inheritance, characterized by slowly progressive ectopic calcification in the elastic fibers of the skin, Bruch's membrane in the retina, and in the arteries. Etidronate was found to be effective in halting the progression of arterial calcification in an earlier trial, including middle-aged patients with PXE with manifest arterial disease. It is uncertain if there are similar effects in young adult patients with PXE.

The TEMP-PREVENT study is a randomized, double-blind, placebo-controlled clinical trial, investigating the effect of 20 mg/kg cyclical etidronate on ectopic calcification in PXE patients of ≥ 18 and ≤ 55 years. The study is conducted at the University Medical Center, Utrecht, the Netherlands. The primary endpoint is the change in arterial calcification volume between baseline and 24 months in the leg arteries and carotid siphons, as measured on low-dose unenhanced Computed Tomography. Secondary endpoints are changes in dermatological, ophthalmological, vascular, laboratory, cognitive and quality of life outcomes/parameters. Recruiting started in April 2023. Results are expected in 2027 and will be dispersed through peer-reviewed journals and international conferences.

PXE is a rare genetic disease for which there is currently no registered treatment. The TEMP-PREVENT trial is set out to evaluate the effects of etidronate in young adult patients with PXE.  TRIAL REGISTRATION: The trial is registered at the Dutch Central Committee on Research Involving Human Subjects (CCMO) (registration number: NL75350.041.21), European Union Clinical Trials Register (EudraCT number: 2021-000434-34), and at ClinicalTrials.gov (ID: NCT05832580, registration date 2023-04-14).

Patients with acute myocardial infarction (AMI) and multivessel disease are at elevated risk of recurrent events. Radial wall strain (RWS), a novel indicator derived from angiography, has emerged as a potentially useful adjunct to optical coherence tomography (OCT) for assessing plaque vulnerability. The NASCENT trial is a prospective, multicentre cohort study designed to assess the natural history of coronary plaque in this high-risk AMI population and investigate the predictive value of angiography-based RWS for lesion progression, compared with OCT-assessed vulnerable plaque.

Following successful culprit lesion revascularisation for AMI patients with multivessel disease, we assessed eligible non-culprit lesions (30%-80% diameter stenosis) in non-flow-limiting, non-infarct-related arteries (Murray law-based quantitative flow ratio >0.80) using OCT and offline RWS analysis. The primary endpoint is lesion progression at 1 year, defined as a ≥20% increase in diameter stenosis percentage measured by quantitative coronary angiography. Between April 2024 and April 2025, 131 patients were enrolled. The 1-year angiographic and OCT follow-ups will be completed by May 2026. Clinical follow-ups are planned at 1 month, 6 months, 1 year and annually up to 3 years. As the first prospective trial comparing angiography-based RWS with OCT for predicting lesion progression in the AMI population, this study may provide crucial evidence for RWS as a valuable tool for risk stratification and clinical decision-making.

The protocol has been approved by the Institutional Review Board and Ethics Committee (Fuwai Hospital Approval No. 2023-2039) and will be conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants. The study results will undergo peer-reviewed publication.

NCT06040073.

This research paper presents a study protocol for an exploratory clinical trial evaluating the safety and potential efficacy of autologous peripheral blood mononuclear cell (PBMNC)-loaded injectable cell scaffold (ICS-001) for angiogenic therapy in chronic limb-threatening ischaemia (CLTI). CLTI, the advanced stage of peripheral artery disease, presents significant therapeutic challenges.

Angiogenic therapy using ICS-001 with PBMNCs-a novel approach designed to enhance local cell retention and promote neovascularisation-will be explored. The study will address the pathophysiology of CLTI, the limitations of current treatments and the rationale for cell-based therapies, alongside the clinical trial design for evaluating the safety and efficacy of ICS-001. We hypothesise that ICS-001 will improve ulcer healing and reduce ischaemic rest pain in patients with CLTI. This paper outlines the methodology, including patient selection, CD34⁺ cell mobilisation, scaffold preparation, injection protocols, clinical assessments, data collection and safety monitoring. The anticipated results, discussion and conclusion will offer insight into the clinical significance and potential impact of ICS-001 as a pioneering angiogenic therapy for CLTI.

The institutional review boards of all participating hospitals approved this study protocol (latest version V.6.0, 5 June 2025). Final data will be made publicly available. A report detailing the study results will be submitted for publication in an appropriate peer-reviewed journal.

Data are available on reasonable request. Technical appendix, statistical code is available by contacting the corresponding author. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) licence, which permits others to distribute, remix, adapt, build on this work non-commercially, and licence their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ TRIAL REGISTRATION NUMBER: jRCT2052230115, Japan Registry of Clinical Trials.

This study aims to identify the key factors driving excessive alcohol and salt consumption in Ghana, both of which are modifiable risk factors for diseases such as cardiovascular conditions and cancers. Using the socio-ecological model (SEM), we qualitatively examine stakeholder perspectives to gain a comprehensive understanding of the influences contributing to these unhealthy consumption patterns.

A qualitative study was conducted using semi-structured interviews. Transcripts were analysed thematically, with identified drivers mapped onto the corresponding levels of influence within the SEM.

The study included 21 purposively sampled stakeholders from government and academic institutions in Ghana, including policymakers, practitioners and researchers.

Drivers of excessive salt and alcohol consumption were identified across all five levels of the SEM. At the intrapersonal level, disregard for health risks was a key factor. Community-level drivers included easy access to unhealthy foods and cultural norms promoting alcohol use at social events and salt in traditional dishes. At the societal and policy levels, inadequate regulation of the alcohol and food industries was found to reinforce lower-level drivers, further encouraging unhealthy consumption.

This study highlights the multilevel influences on alcohol and salt consumption, emphasising the interactions across SEM levels. It highlights that addressing unhealthy consumption is not solely a matter of personal responsibility, demonstrating that societal and policy factors play a significant role in shaping health and dietary behaviours. The findings underscore the need for comprehensive public health strategies that address influences at multiple levels to effectively reduce excessive alcohol and salt intake.

This study aims to investigate the predictors of very poor outcomes in patients with acute ischaemic stroke due to large vessel occlusion after successful endovascular thrombectomy.

A multicentre, retrospective study.

Data were derived from tertiary care facilities in five cities of China.

This study included 1242 patients with anterior circulation large-vessel occlusion who underwent endovascular thrombectomy, and they were stratified by 90-day modified Rankin Scale (mRS) scores into a very poor outcome group (mRS 5-6) and a non-very poor outcome group (mRS 0-4).

The primary outcome was very poor outcomes. Data from 1242 patients were analysed for demographic, laboratory, imaging and perioperative data.

Among the 1242 recruited patients, 318 (25.60%) exhibited very poor outcomes. In multivariate analysis, predictors of very poor outcomes were higher age (OR 1.059, 95% CI 1.043 to 1.075, p<0.001), stroke history (OR 1.993, 95% CI 1.373 to 2.888, p<0.001), coronary heart disease history(CHD;OR=1.816,95% CI 1.291-2.552,P=0.001),higher baseline National Institute of Health Stroke Scale (NIHSS; OR 1.076, 95% CI 1.054 to 1.099, p<0.001), higher neutrophil count (OR 1.078, 95% CI 1.025 to 1.134, p=0.003), lower Alberta Stroke Program Early CT Score (ASPECTS; OR 0.901, 95% CI 0.845 to 0.962, p=0.002), higher malignant cerebral oedema (MCE, OR 3.246,95% CI 2.241 to 4.713, p<0.001) and symptomatic intracranial haemorrhage (sICH, OR 3.97, 95% CI 2.569 to 6.169, p<0.001) and receiving intravenous thrombolysis (IVT, OR = 0.600,95% CI 0.431-0.830, P =0.002) . The predictive model demonstrated a certain degree of accuracy (area under the curve 0.839, 95% CI 0.813 to 0.864).

The very poor outcomes were associated with advanced age, CHD history, stroke history, high NIHSS score, high neutrophil count, low ASPECTS and presence of MCE and sICH, while receiving intravenous thrombolysis was a protective factor. These poor outcome predictors might play a crucial role in informing clinical decision-making.

ClinicalTrials.gov (NCT06290076); pre-results.

Paediatric acute ischaemic stroke (AIS) is a rare but severe neurological condition, often leading to long-term disability and considerable societal burden. Compared with adults, paediatric AIS exhibits distinct clinical characteristics and aetiologies, making early identification and prevention more challenging. This study aims to systematically review the prevalence and risk factors of paediatric AIS, providing a comprehensive evidence base for clinical prevention and management.

A systematic search will be conducted across major databases, including PubMed, Embase, Web of Science and Cochrane Library, from inception to August 2025. We will include observational studies reporting on the prevalence or risk factors of paediatric AIS. Two independent reviewers will screen the literature, extract data and assess study quality using the Newcastle-Ottawa scale. Meta-analysis will be performed using RevMan 5.4 and StataMP 16.0. Heterogeneity will be evaluated using the I² statistic, and subgroup and sensitivity analyses will be conducted as needed. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the quality of evidence.

Because no patients were involved, ethical approval was not required. The final results of this research will be submitted to a peer-reviewed journal or presented at relevant conferences, and any deviations from this protocol will be recorded and explained in the final report.

This study has been registered in the PROSPERO (PROSPERO Registration Number: CRD420251067538).

Rapid identification of high-risk and low-risk patients presenting to the emergency department (ED) influences clinical management and can help optimise patient outcomes as well as resource allocation. This study aims to externally validate the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) score in adult patients in the ED with suspected infection. Furthermore, generalisability was assessed by comparing the discriminatory ability of the RISE UP with the quick Sequential Organ Failure Assessment (qSOFA) as well as the Modified Early Warning Score (MEWS) and National Early Warning Score (NEWS).

Retrospective cohort study.

Single-centre study in the ED of a tertiary, university-affiliated hospital.

Adult patients with suspected infection presenting at the ED for internal medicine from 2016 to 2022.

The primary outcome was all-cause 30-day mortality. Secondary outcomes were all-cause 14-day mortality, 7-day mortality and intensive care unit (ICU) admission.

Prognostic performance was evaluated using discrimination (area under the receiver operating characteristic curve (AUC)) and a calibration plot.

Of the included 5038 ED visits, there was a 30-day mortality of 7.1%. Discrimination of RISE UP for 30-day mortality was good (AUC 0.809; 95% CI 0.786 to 0.832) and significantly higher than that for the other risk scores: qSOFA (AUC 0.675; 95% CI 0.644 to 0.707), MEWS (AUC 0.688; 95% CI 0.658 to 0.718) and NEWS (AUC 0.725; 95% CI 0.696 to 0.754) (p<0.001). For 14-day and 7-day mortality, RISE UP had the highest AUC, but NEWS performed best for ICU admission. The RISE UP score was well calibrated and had significantly better discriminatory ability in older patients aged ≥65 years (AUC 0.772; 95% CI 0.738 to 0.806; p<0.001) and patients with sepsis (AUC 0.746; 95% CI 0.695 to 0.798; p<0.05) compared with the other scores. Low-risk patients with a RISE UP score of <5% yielded a negative predictive value of 97.7% (95% CI 97.2 to 98.1) and a sensitivity of 79.3% (95% CI 74.7 to 83.4).

The RISE UP score outperformed the qSOFA, MEWS and NEWS in predicting 30-day mortality. It is generalisable to an adult infection-specific cohort and may facilitate distinction between high-risk and low-risk patients in the ED, particularly to rule out poor outcomes.

The National Association of Chronic Disease Directors (NACDD) is a nonprofit organization that supports state and territorial chronic disease prevention and health promotion efforts through capacity building and technical assistance. Each year, NACDD surveys health department leaders who oversee chronic disease prevention and health promotion work (hereafter, Chronic Disease Directors). In this paper, we report on the 2024 survey outcomes and place those findings into the broader public health policy context.

Fifty-one Chronic Disease Directors completed the organizational capacity and development needs survey. Responses were summarized in aggregate and by jurisdiction size.

State and territorial chronic disease units have varied responsibilities, but most address diabetes, cardiovascular diseases, and cancer screening and prevention. Chronic Disease Directors reported strong or improving capacity in most practice areas but ranked workforce development lower than other areas. Staffing decreased slightly during 2024 compared with 2023 (median of 1.1 and 1.3 employees per 100 000 jurisdiction population, respectively). Many Chronic Disease Directors expressed ongoing concerns about staff turnover and workforce development, funding limitations and stability, and the effects of the political climate on public health work. Despite these challenges, many respondents also conveyed success stories about program achievements, obtaining new funding, and building partnerships and collaborations. Looking forward to 2025, many Chronic Disease Directors expressed intentions to focus on leadership, policy, and technical training; on making structural and staffing changes within their units; and on continuing to build cross-sector relationships and collaborations.

Continued concerns about staff turnover and workforce development underscore the need to better understand and remove barriers to capacity building in this area to support job satisfaction and employee retention. Changes to federal infrastructure are likely to have substantial impacts and may increase reliance on cross-sector partnerships to continue advancing chronic disease prevention and health promotion.