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Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients., Methods: Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated., Results: Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m 2 ), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups., Conclusions: Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies. Key Points • RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis. • RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis. • HCQ may provide a protective effect against liver fibrosis in RA patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study involves human participants, and the original study (FRANCIS) was approved by the medical ethical committee of the Maasstad hospital in Rotterdam, the Netherlands (The Dutch Trial register, NTR3873; ABR no. NL32669.101.10) and was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonisation Guidance for Good Clinical Practice. Participants gave informed consent to participate in the study before taking part. Consent for publication: Not applicable. Disclosures: None., (© 2025. The Author(s).)

Background: To explore whether healthy lifestyle factors (HLFs) predict a lower risk of major macrovascular and microvascular events and death in people with type 2 diabetes (T2D) with a high risk of vascular complications., Methods: Post hoc analyses of 11,133 participants with T2D in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial who were assigned a score ranging from 0 to 4 based on the number of baseline HLFs: never smoked, moderate-to-vigorous physical activity, ideal waist/hip ratio, and low-to-moderate alcohol consumption. Multivariable Cox models were used to determine associations of 0, 1, 2, and ≥ 3 HLFs with vascular events and all-cause mortality., Results: Compared to participants with no HLFs, hazard ratios for participants with 3 or 4 HLFs were 0.68 (95% confidence interval [CI] 0.57-0.81) for the composite of major macrovascular or microvascular events, 0.58 (0.46-0.75) for major macrovascular events, 0.78 (0.61-0.99) for microvascular events, and 0.48 (0.37-0.63) for all-cause mortality during a median follow-up of 5 years. Each increment in HLF score was significantly associated with lower rates of these outcomes. There was no heterogeneity in the effect on any outcome by HLF across randomized intensive blood glucose control and blood pressure lowering treatments., Conclusions: HLFs are associated with lower risks of major macrovascular and microvascular events and lower rates of death in high-risk adults with T2D., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval came from the institutional review board of each center as outlined in: • Patel A, MacMahon S, Chalmers J, et al.; ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007;370:829–840. • Patel A, MacMahon S, Chalmers J, et al.; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560–2572. All participants provided written informed consent to participate in ADVANCE. Consent for publication: This study was approved for publication by the ADVANCE Management Committee. Competing interests: SY holds China Scholarship Council (CSC) grant, the National Natural Science Foundation of China (82471226), Jiangsu Provincial Medical Key Discipline (ZDXK202217) and the 6th Jiangsu Province 333 High Level Talents Training Project. JC reports research grants from the NHMRC and from Servier International for the ADVANCE trial and the ADVANCE-ON follow-up study, all before 2014. MW also reports research support from the NHMRC, as well as consultancy work for Freeline in the recent past. CSA holds a Senior Investigator Fellowship of the NHMRC and reports receipt of advisory board fees from AstraZeneca, Australia. GM has received compensations as speaker/chairman/consultant from: Berlin Chemie, IPCA Laboratories, Medtronic Inc USA, Menarini Int, Merck Healthcare KGaA, Omnicuris, Recordati, Sanofi, Servier, Sun Laboratories. NP has received personal speaker fees from Servier, Takeda and Novo Nordisk, and advisory board activities from AstraZeneca and Novo Nordisk, and has received grants for his research group relating to diabetes mellitus from Diabetes UK, NIHR Efficacy and Mechanism Evaluation Programme (EME), Julius Clinical and the British Heart Foundation with a pending grant from Novo Nordisk. N.P. holds no stocks or shares in any such companies All other authors declare that they have no competing interest., (© 2025. The Author(s).)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to type 2 diabetes mellitus (T2DM) through a common root in insulin resistance. The more severe stage, metabolic dysfunction-associated steatohepatitis (MASH), increases the risk for cardiovascular complications, liver cirrhosis and hepatocellular carcinoma. Several trials investigating established antidiabetic-drugs in patients with T2DM and MASLD have yielded promising results. Therefore, we aimed to systematically review the effect of T2DM-drug treatment on MALSD parameters., Methods: Medical databases were searched until January 2025 for controlled trials in patients with T2DM and MASLD/MASH. Studies that evaluated the effect of T2DM-medication on the severity of MASLD/MASH in T2DM patients were included. The quality of the studies was assessed by three independent reviewers using a set of Cochrane risk-of-bias tools., Results: Of 1748 references, 117 studies fulfilled the inclusion-criteria and were assessed for eligibility in full-text. Fifty-two articles were included. Data included a total of 64.708 patients and study populations ranged from 9 to 50.742. Heterogeneity in study-design and analysis hampered the comparability of the results. Most evidence was present for GLP-1 receptor agonists, SGLT2-inhibitors and PPAR-γ-agonists for regression of liver fibrosis and MASH., Conclusion: Studies on the value of T2DM-drug treatment in the improvement of MASLD vary significantly in study design, size and quality. GLP-1 receptor agonists, PPAR-γ-agonists, SGLT2-inhibitors may all be preferred pharmacological interventions for patients with MASLD/MASH and T2DM. Newer agents like dual GLP-1/GIP or triple GLP-1/GIP/Glucagon agonists will likely play an important role in the treatment of MASLD/MASH in the near future., (© 2025 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Introduction: Sub-Saharan Africa has the highest malaria burden in the world. Several vector control strategies are being implemented to reduce mosquito density and protect the most vulnerable populations, such as children under 5 and pregnant women. This systematic review is designed to assess the effectiveness of integrated vector control versus single vector control interventions on malaria incidence and prevalence to guide decisions on controlling malaria vectors in sub-Saharan Africa., Methods and Analyses: We will systematically retrieve published and grey literature from electronic databases and clinical trial registries. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines will guide us in applying a systematic approach to screening, reviewing and extracting data. An inclusion criterion will be used to independently assess full-text copies of potentially relevant articles by two review authors. Risk of bias will be assessed using the Cochrane Risk of Bias Tool V.2 for randomised controlled trials and the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool for non-randomised intervention studies. A meta-analysis will be conducted based on studies that have reported a high level of evidence (risk ratios or ORs with 95% CIs). If substantial heterogeneity is encountered, subgroup analyses will be explored., Ethics and Dissemination: This review does not require ethical approval. The findings will be shared through open-access publications in peer-reviewed journals and presentations to stakeholders and international policymakers for malaria control., Prospero Registration Number: CRD42024559088., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

HIV majorly contributes to the disease burden in South Africa. Depressive symptoms are common in people living with HIV (PLHIV). Few studies compared depressive symptoms between PLHIV and those without HIV. The aim of the study was to examine the association of HIV status and depressive symptoms. Moreover, the study aimed to explore the comparison between HIV-negative participants and the different HIV-positive sub-groups regarding their depressive symptoms. A cross-sectional analysis was conducted among PLHIV and HIV-negative participants in rural South Africa, using the baseline data of the Ndlovu Cohort study. Data was collected on demographics, socioeconomic status, and depressive symptoms using the PHQ-9 questionnaire. A score of 10 and above indicated depressive symptoms. Logistic regression analysis on the relationship between HIV status and depressive symptoms was used while adjusting for age, sex, level of education, employment status, income, and ever smoking. The study included 1,927 participants; 46% were PLHIV and 239 (12.5%) had depressive symptoms. PLHIV were more likely to have depressive symptoms than HIV-negative participants (OR 1.34, 95% CI 1.01-1.77). This association was not statistically significant after adjusting for confounders (OR 1.22, 95% CI 0.92-1.63). Compared to HIV-negative participants, ART (antiretroviral treatment) naïve participants had statistically significant higher odds of depressive symptoms (OR 1.84, 95% CI 1.20-2.78). This association remained after adjusting for confounders (OR 1.72, 95% CI 1.11-2.61). There was no statistically significant difference in depressive symptoms between HIV-negative participants and those on ART, regardless of treatment regimen. In general, higher odds of depressive symptoms in ART-naïve PLHIV could reflect poor coping with diagnosis of HIV. Future research to investigate the relation between ART regimen and depressive symptoms, to establish causality and to identify changes over time, is warranted., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Human Research Ethics Committee at the University of Pretoria, Pretoria, South Africa, and the Limpopo Department of Health Ethics Committee (ethics reference number: 227/2014). Written informed consent was obtained from all participants prior to study participation., (© 2025. The Author(s).)