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Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA is well-recognized, their precise role in disease management remains an area of active research. Such a field is particularly heterogeneous, calling for regular analysis and summarizing of the data that constantly emerge in the scientific literature, often sparse and scant of integration. The aim of this study was to systematically identify and synthesize all new evidence that emerged in human and animal model studies published between 2020 and 2023. This was necessary because, to the best of our knowledge, articles published before 2019 (and partly 2020) had already been included in systematic reviews that allowed to identify the ones concerning the knee joint. The review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only peer-reviewed articles were considered for inclusion. A total of 40 studies were identified, showing promising results in terms either of biomarker identification, new insight in mechanism of action or potential therapeutic targets for knee OA. DNA methylation, histone modification and ncRNA were all mechanisms involved in epigenetic regulation of the knee. Most recent evidence suggests that epigenetics is a most promising field with the long-term goal of improving understanding and management of knee OA, but a variety of research approaches need greater consolidation.

Background: Clinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC., Objective: We aimed to evaluate the impact of disease clearance on long-term outcomes in UC patients., Methods: A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial-Mayo score ≤2), endoscopic (endoscopic-Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long-time follow-up (≥12 months), to compare the occurrence of negative outcomes., Results: A total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC-related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log-rank p < 0.0001) and surgery (log-rank p < 0.00095)., Conclusion: In UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)