Best Practice & Research in Clinical Rheumatology最新文献

{"title":"Explainable biology for improved therapies in precision medicine: AI is not enough","authors":"I Jurisica","doi":"10.1016/j.berh.2024.102006","DOIUrl":"10.1016/j.berh.2024.102006","url":null,"abstract":"<div><div>Technological advances and high-throughput bio-chemical assays are rapidly changing ways how we formulate and test biological hypotheses, and how we treat patients. Most complex diseases arise on a background of genetics, lifestyle and environment factors, and manifest themselves as a spectrum of symptoms. To fathom intricate biological processes and their changes from healthy to disease states, we need to systematically integrate and analyze multi-omics datasets, ontologies, and diverse annotations. Without proper management of such complex biological and clinical data, artificial intelligence (AI) algorithms alone cannot be effectively trained, validated, and successfully applied to provide trustworthy and patient-centric diagnosis, prognosis and treatment. Precision medicine requires to use multi-omics approaches effectively, and offers many opportunities for using AI, “big data” analytics, and integrative computational biology workflows.</div><div>Advances in optical and biochemical assay technologies including sequencing, mass spectrometry and imaging modalities have transformed research by empowering us to simultaneously view all genes expressed, identify proteome-wide changes, and assess interacting partners of each individual protein within a dynamically changing biological system, at an individual cell level. While such views are already having an impact on our understanding of healthy and disease conditions, it remains challenging to extract useful information comprehensively and systematically from individual studies, ensure that signal is separated from noise, develop models, and provide hypotheses for further research. Data remain incomplete and are often poorly connected using fragmented biological networks. In addition, statistical and machine learning models are developed at a cohort level and often not validated at the individual patient level.</div><div>Combining integrative computational biology and AI has the potential to improve understanding and treatment of diseases by identifying biomarkers and building explainable models characterizing individual patients. From systematic data analysis to more specific diagnostic, prognostic and predictive biomarkers, drug mechanism of action, and patient selection, such analyses influence multiple steps from prevention to disease characterization, and from prognosis to drug discovery. Data mining, machine learning, graph theory and advanced visualization may help identify diagnostic, prognostic and predictive biomarkers, and create causal models of disease. Intertwining computational prediction and modeling with biological experiments leads to faster, more biologically and clinically relevant discoveries.</div><div>However, computational analysis results and models are going to be only as accurate and useful as correct and comprehensive are the networks, ontologies and datasets used to build them. High quality, curated data portals provide the necessary foundation for translati","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 4","pages":"Article 102006"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of vasculitis","authors":"Miguel Ángel González-Gay ,&nbsp;Elena Heras-Recuero ,&nbsp;Teresa Blázquez-Sánchez ,&nbsp;Claritza Caraballo-Salazar ,&nbsp;Fernando Rengifo-García ,&nbsp;Santos Castañeda ,&nbsp;Javier Martín ,&nbsp;Ana Marquez ,&nbsp;Raquel Largo","doi":"10.1016/j.berh.2024.101969","DOIUrl":"10.1016/j.berh.2024.101969","url":null,"abstract":"<div><div>Systemic vasculitis encompasses a wide range of conditions characterized by varying degrees of inflammation in blood vessels. Although the etiology of vasculitis remains unclear, accumulated data suggest that it is triggered in genetically predisposed individuals by the concurrence of certain environmental factors. The importance of the genetic component has been consistently supported by evidence of familial aggregation, differential prevalence by ethnicity, and multiple genetic associations with disease susceptibility and severity reported in recent years. The strongest association signals in most vasculitides correspond to genetic variants within the <em>HLA</em> region, suggesting an important role of the immune system in its pathophysiology. However, each type of vasculitis has distinct defining <em>HLA</em> association markers, likely due to disease-specific differences in antigenic drivers. Furthermore, other genetic polymorphisms located outside the <em>HLA</em> region play an important role in susceptibility to different vasculitides. More recent research has assessed the shared genetic susceptibility evident across different vasculitides. Future studies should focus on the identification of genetic markers that can serve as reliable biomarkers for early diagnosis, prognosis, and treatment response in systemic vasculitis.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 4","pages":"Article 101969"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of functional genomics studies in precision rheumatology","authors":"Ana Pires Piedade ,&nbsp;Jake Butler ,&nbsp;Stephen Eyre ,&nbsp;Gisela Orozco","doi":"10.1016/j.berh.2024.101988","DOIUrl":"10.1016/j.berh.2024.101988","url":null,"abstract":"<div><div>Rheumatic diseases, those that affect the musculoskeletal system, cause significant morbidity. Among risk factors of these diseases is a significant genetic component. Recent advances in high-throughput omics techniques now allow a comprehensive profiling of patients at a genetic level through genome-wide association studies. Without functional interpretation of variants identified through these studies, clinical insight remains limited. Strategies include statistical fine-mapping that refine the list of variants in loci associated with disease, whilst colocalization techniques attempt to attribute function to variants that overlap a genetically active chromatin annotation. Functional validation using genome editing techniques can be used to further refine genetic signals and identify key pathways in cell types relevant to rheumatic disease biology. Insight gained from the combination of genetic studies and functional validation can be used to improve precision medicine in rheumatic diseases by allowing risk prediction and drug repositioning.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 4","pages":"Article 101988"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of osteoarthritis","authors":"Guangju Zhai,&nbsp;Jingyi Huang","doi":"10.1016/j.berh.2024.101972","DOIUrl":"10.1016/j.berh.2024.101972","url":null,"abstract":"<div><div>Osteoarthritis (OA) is the most common form of arthritis with well recognized multifactorial nature. While several environmental factors such as older age, obesity and previous joint injury are strongly associated with its development, a genetic influence on OA has been recognized for over 80 years. Identification of genes associated with OA has received considerable attention over the last two decades, aided by the rapidly evolving genotyping and sequencing technologies. More than 300 genomic loci have been identified to be associated with OA at different joints. These findings are likely to help our better understanding of the pathogenesis of OA and lead to important therapeutic and diagnostic advances in this most common disabling rheumatic disorder. This article will review the data that support the role of genetic factors in common idiopathic <span>OA</span>.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 4","pages":"Article 101972"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalised medicine in juvenile dermatomyositis: From novel insights in disease mechanisms to changes in clinical practice","authors":"Saskia R. Veldkamp ,&nbsp;Femke van Wijk ,&nbsp;Annet van Royen-Kerkhof ,&nbsp;Marc HA. Jansen","doi":"10.1016/j.berh.2024.101976","DOIUrl":"10.1016/j.berh.2024.101976","url":null,"abstract":"<div><div>Juvenile dermatomyositis is characterized by childhood-onset chronic inflammation of the muscles and skin, with potential involvement of other organs. Patients are at risk for long-term morbidity due to insufficient disease control and steroid-related toxicity. Personalised treatment is challenged by a lack of validated tools that can reliably predict treatment response and monitor ongoing (subclinical) inflammation, and by a lack of evidence regarding the best choice of medication for individual patients. A better understanding of the involved disease mechanisms could reveal potential biomarkers and novel therapeutic targets. In this review, we highlight the most relevant immune and non-immune mechanisms, elucidating the effects of interferon overexpression on tissue alongside the interplay between the interferon signature, mitochondrial function, and immune cells. We review mechanism-based biomarkers that are promising for clinical implementation, and the latest advances in targeted therapy development. Finally, we discuss key steps needed for translating these discoveries into clinical practice.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 3","pages":"Article 101976"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of JIA associated uveitis","authors":"Ilaria Maccora ,&nbsp;Gabriele Simonini ,&nbsp;Catherine M. Guly ,&nbsp;Athimalaipet V. Ramanan","doi":"10.1016/j.berh.2024.101979","DOIUrl":"10.1016/j.berh.2024.101979","url":null,"abstract":"<div><div><span><span>Juvenile Idiopathic Arthritis<span> (JIA) is the most common chronic rheumatic disease<span> in childhood, and is associated with uveitis<span> in up to 20–25% of cases. Typically, the uveitis is chronic, asymptomatic, non-granulomatous and anterior. For this reason, screening for uveitis is recommended to identify uveitis early and allow treatment to prevent sight-threatening complications. The management of JIA associated uveitis requires a multidisciplinary approach and a close collaboration between </span></span></span></span>paediatric rheumatologist and ophthalmologist. Starting the appropriate treatment to control uveitis activity and prevent ocular complications is crucial. Current international recommendations advise a step-wise approach, starting with </span>methotrexate<span> and moving on to adalimumab<span><span> if methotrexate alone is not sufficient to control the disease. If the uveitis remains active despite standard treatment other therapeutic options may be considered including anti-IL6 or other anti-TNF agents such as </span>infliximab, although the evidence for these agents is limited.</span></span></div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 3","pages":"Article 101979"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capillaroscopy in the daily clinic of the pediatric rheumatologist","authors":"D. Schonenberg-Meinema ,&nbsp;M. Cutolo ,&nbsp;V. Smith","doi":"10.1016/j.berh.2024.101978","DOIUrl":"10.1016/j.berh.2024.101978","url":null,"abstract":"<div><div>In the last decade, nailfold capillaroscopy is finding its way to the daily clinic of (pediatric) rheumatologist. This review will provide the necessary knowledge for the clinician performing this easy and non-invasive examination in children. In the first part, background information on type of capillaroscopy device and standardized (internationally validated) interpretations for the different capillary variables compared to healthy pediatric controls will be provided. The second part focusses on capillary changes that are observed in Raynaud's phenomenon with follow-up recommendations. This part will also cover capillaroscopy findings in juvenile systemic sclerosis, childhood-onset systemic lupus erythematosus, juvenile dermatomyositis and –mixed connective tissue disease, as well as correlations with disease severity. Lastly, a research agenda shows the current gaps we have in knowledge in this niche of nailfold capillaroscopy in pediatric connective tissue diseases.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 3","pages":"Article 101978"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiphospholipid syndrome in children","authors":"Mojca Zajc Avramovic ,&nbsp;Tadej Avcin","doi":"10.1016/j.berh.2024.101986","DOIUrl":"10.1016/j.berh.2024.101986","url":null,"abstract":"<div><div>Antiphospholipid syndrome (APS) in children is a rare disease associated with significant morbidity and mortality. In comparison with APS in adults, pediatric APS has a more severe presentation with frequent recurrences of thrombotic events and a higher probability of life-threatening catastrophic APS. Nonthrombotic manifestations are also more common in the pediatric age group and can precede thrombosis. New classification criteria have been introduced recently and have not yet been assessed in pediatric patients with APS. In addition to anticoagulation drugs, other novel therapies have emerged including the use of B cell and complement inhibitors, especially in catastrophic APS. The purpose of this review is to provide a broad overview of aPL-related clinical manifestations in pediatric patients based on the analysis of published cohorts and data from the international pediatric APS registry. We also aim to illustrate APS in infants caused by transplacentally transferred maternal aPL, which is very rarely associated with acute thrombotic events in the perinatal period and more frequently with long-term neurodevelopmental abnormalities.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 3","pages":"Article 101986"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lifelong journey: Long-term perspectives on Juvenile Idiopathic Arthritis","authors":"Filipa Oliveira Ramos ,&nbsp;Carolina Zinterl ,&nbsp;João Eurico Fonseca","doi":"10.1016/j.berh.2024.101984","DOIUrl":"10.1016/j.berh.2024.101984","url":null,"abstract":"<div><div>Juvenile Idiopathic Arthritis (JIA) represents a diverse group of chronic inflammatory conditions that begin in childhood or adolescence and continue into adulthood, with varying severity and outcomes.</div><div>This review discusses the complexities of transitioning JIA patients emphasizing that inadequate transition from pediatric to adult care leads to loss of follow-up, treatment discontinuation, and increased disease activity. Furthermore, challenges in disease classification hinder continuity of care across lifespan.</div><div>It is also pointed out that predicting long-term outcomes in JIA remains complex due to heterogeneity and evolving phenotypes. Factors such as disease category, joint involvement, and treatment influence disease activity, functional disability, and quality of life. Despite advancements in treatment strategies, a substantial proportion of patients experience long-term disability and joint damage.</div><div>Finally, it is underscored that optimising long-term outcomes in adults with JIA requires a multifaceted approach encompassing structured transition processes, personalised treatment strategies, and comprehensive management of comorbidities. Further research is needed to refine predictive models, enhance disease monitoring tools, and understand the complex interplay between disease activity, treatment response, and long-term outcomes.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 3","pages":"Article 101984"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferonopathies: From concept to clinical practice","authors":"Leonardo Oliveira Mendonça ,&nbsp;Marie-Louise Frémond","doi":"10.1016/j.berh.2024.101975","DOIUrl":"10.1016/j.berh.2024.101975","url":null,"abstract":"<div><div>The <em>horror autoinflammaticus</em> derived from aberrant type I interferon secretion determines a special group of autoinflammatory diseases named interferonopathies. Diverse mechanisms involved in nucleic acids sensing, metabolizing or the lack of interferon signaling retro-control are responsible for the phenotypes associated to Aicardi-Goutières Syndrome (AGS), Proteasome-Associated Autoinflammatory Diseases (PRAAS), STING-Associated Vasculopathy with Infancy Onset (SAVI) and certain forms of monogenic Systemic lupus erythematosus (SLE). This review approaches interferonopathies from the basic immunogenetic concept to diagnosis and treatment.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 3","pages":"Article 101975"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}