Effects of an extended therapeutic strategy versus standard-of-care therapy on persistent acute kidney injury in high-risk patients after major surgery: study protocol for the randomised controlled single-centre PrevProgAKI trial

Introduction
Persistent acute kidney injury (AKI) is associated with an increased morbidity and mortality. In patients with an already established AKI, the new urinary biomarker C-C motif chemokine ligand 14 (CCL14) can predict a persistent AKI. However, it is still unknown whether the implementation of nephroprotective measures in patients with an already established moderate/severe AKI can positively influence the trajectory of AKI and patients’ outcome.

Methods and analysis
The PrevProgAKI trial is a randomised, controlled, single-centre trial designed to evaluate the effectiveness of nephroprotective measures in patients with established moderate/severe AKI. We aim to enrol 480 patients with moderate or severe AKI (Kidney Disease: Imroving Global Outcomes, KDIGO, stage 2 or 3) within 72 hours of major surgery. Eligible patients will be randomised to receive either standard of care (control group) or an extended therapeutic strategy that consists of different supportive measures (intervention group). The randomisation will be stratified by urinary CCL14 results (CCL14

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Effect of HPV integration on prognosis of young women with CIN2 in China: protocol for a multicentre prospective cohort study

Introduction
Cervical cancer, a major global health concern, is primarily caused by human papillomavirus (HPV) infection. Although cervical intraepithelial neoplasia grade 2 (CIN2), a precancerous lesion, exhibits high spontaneous regression rates (50%–60%), particularly in younger women, current clinical management lacks accurate risk stratification. This study examines HPV integration status as a prognostic biomarker in women aged 18–45 diagnosed with CIN2, with the objective of developing a predictive tool for personalised therapeutic strategies and minimising overtreatment in this high-regression population.

Method and analysis
This multicentre cohort study will be implemented across 20 tertiary Grade A hospitals in China, encompassing eastern, western, central and northern regions. It will recruit 240 CIN2 patients, collecting sociodemographic, lifestyle and medical history data via questionnaires. Clinical examinations will be performed at baseline and follow-up. Disease regression ((to cervical intraepithelial neoplasia grade 1 [CIN1] or lower)) and non-regression (persistent CIN2 or progression) will be evaluated. Prognostic factors will be analysed using Cox proportional hazards models, adjusting for confounders such as age, weight and socioeconomic status.

Ethics and dissemination
The cohort study protocol and informed consent procedures adhere to the Declaration of Helsinki and pertinent Chinese clinical research regulations. Ethical approval has been obtained from the Clinical Research Review Committee of the Fujian Maternal and Child Health Hospital (2022KYLLR01018) and from the participating hospitals. Written informed consent is secured from all participants prior to enrolment, with detailed information provided regarding study objectives, procedures, potential risks and benefits and participants’ rights. Results will be published in peer-reviewed scientific journals, presented at academic meetings and conferences and released to the public through press releases.

Trial registration number
ClinicalTrials.gov (NCT05282095); Pre-results.

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Association of Biomarkers With Intracerebral Hematoma Expansion and Arterial Thromboembolic Events in Patients With Acute Intracranial Hemorrhage: The ANNEXA-I Biomarker Substudy

Stroke, Ahead of Print. BACKGROUND:ANNEXA-I (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors) was a randomized trial that demonstrated that andexanet compared with usual care in patients with intracranial hemorrhage associated with FXa (factor Xa) inhibitor treatment reduces the risk of hematoma expansion and increases the risk of arterial thromboembolic events.METHODS:In a secondary analysis of the ANNEXA-I trial, we compared the effects of andexanet with usual care on change in anti-FXa activity and endogenous thrombin potential (ETP) using Wilcoxon rank-sum test. We examined the associations between 1-hour reduction in anti-FXa and 1-hour increase in ETP and hematoma expansion at 12 hours (≥12.5 mL or percentage volume change ≥35%) using logistic regression, both unadjusted and adjusted for time from symptom onset to baseline scan, baseline diastolic blood pressure, hematoma volume, baseline biomarker level and time from baseline scan to treatment, and association with arterial thromboembolic events (ischemic stroke, myocardial infarction, and systemic embolism) during 30 days of follow-up using Cox regression, both unadjusted and adjusted for age, baseline biomarker level, prior MI, and eligibility for treatment with high-dose andexanet.RESULTS:ANNEXA-I enrolled 530 patients. Among 438 patients with baseline anti-FXa results, andexanet compared with usual care reduced anti-FXa activity at 1 hour (median, 8.6 versus 97.5 ng/mL; median reduction from baseline, 98.3 versus 10.9 ng/mL;P

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Omics Approach for Personalised Prevention of Type 2 Diabetes Mellitus for African and European Populations (OPTIMA): a protocol paper

Introduction
The prevalence of type 2 diabetes (T2D) within sub-Saharan Africa (SSA) is increasing. Despite the pathophysiology of T2D differing by ethnicity and sex, risk stratification and guidelines for the prevention of T2D are generic, relying on evidence from studies including predominantly Europeans. Accordingly, this study aims to develop ethnic-specific and sex-specific risk prediction models for the early detection of dysglycaemia (impaired glucose tolerance and T2D) to inform clinically feasible, culturally acceptable and cost-effective risk management and prevention strategies using dietary modification in SSA and European populations.

Methods and analysis
This multinational collaboration will include the prospective cohort data from two African cohorts, the Middle-Aged Soweto Cohort from South Africa and the Research on Obesity and Diabetes among African Migrants Prospective cohort from Ghana and migrants living in Europe, and a Swedish cohort, the Pre-Swedish CArdioPulmonary bioImage Study. Targeted proteomics, as well as targeted and untargeted metabolomics, will be performed at baseline to discover known and novel ethnic-specific and sex-specific biomarkers that predict incident dysglycaemia in the different longitudinal cohorts. Dietary patterns that explain maximum variation in the biomarker profiles and that associate with dysglycaemia will be identified in the SSA and European cohorts and used to build the prototypes for dietary interventions to prevent T2D. A comparative cost-effectiveness analysis of the dietary interventions will be estimated in the different populations. Finally, the perceptions of at-risk participants and healthcare providers regarding ethnic-specific and sex-specific dietary recommendations for the prevention of T2D will be assessed using focus group discussions and in-depth interviews in South Africa, Ghana, Germany (Ghanaian migrants) and Sweden.

Ethics and dissemination
Ethical clearance has been obtained from all participating sites. The study results will be disseminated at scientific conferences and in journal publications, and through community engagement events and diabetes organisations in the respective countries.

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Role of NT-proBNP for Atrial Fibrillation Detection After Ischemic Stroke: A Time-Dependent Relationship

Stroke, Ahead of Print. BACKGROUND:Atrial fibrillation detected after stroke (AFDAS) affects secondary stroke prevention, yet identification can be challenging. Easily accessible cardiac blood biomarkers such as NT-proBNP (N-terminal pro-B-type natriuretic peptide) could guide diagnostic workup, but optimal cutoff values and the time-dependent relationship between NT-proBNP and AFDAS are unclear. We aimed (1) to externally validate earlier presented NT-proBNP cutoffs for atrial fibrillation prediction and (2) to assess the time-dependent relationship of NT-proBNP and early in-hospital AFDAS versus AFDAS after discharge.METHODS:We conducted a pooled data analysis of patients with ischemic stroke from the prospective international multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study (European Stroke Centers from October 2014 to October 2017) and the prospective single-center Graz stroke pathway study (Austria from May 2018 to August 2020). AFDAS was defined as ≥30-s atrial fibrillation/flutter diagnosed within 1 year post-admission and categorized in in-hospital versus after discharge. NT-proBNP was assessed ≤24 hours of symptom onset. The association between NT-proBNP and AFDAS was evaluated by a multivariable logistic regression analysis.RESULTS:AFDAS was diagnosed in 374 (16%) of 2292 patients with ischemic stroke (median age, 74 years; 42% female), 268 (72%) during hospitalization, and 106 (28%) after discharge (median duration of hospitalization, 15 days). NT-proBNP levels at admission had a good predictive capacity for in-hospital AFDAS (area under the receiver operating characteristic curve, 0.83 [95% CI, 0.81–0.86]). For patients diagnosed with AFDAS after discharge, the predictive capacity of NT-proBNP was poor (area under the receiver operating characteristic curve, 0.65 [95% CI, 0.60–0.70]), and 20% had normal NT-proBNP values

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