RMD Open最新文献

{"title":"Induction of interleukin 21 receptor expression via enhanced intracellular metabolism in B cells and its relevance to the disease activity in systemic lupus erythematosus.","authors":"Masanobu Ueno, Shigeru Iwata, Kaoru Yamagata, Yasuyuki Todoroki, Koshiro Sonomoto, Atsushi Nagayasu, Ippei Miyagawa, Satoshi Kubo, Yusuke Miyazaki, Hiroko Miyata, Ryuichiro Kanda, Takafumi Aritomi, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1136/rmdopen-2024-004567","DOIUrl":"10.1136/rmdopen-2024-004567","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the association between the changes in intracellular metabolism in the early stage of B cell activation and systemic lupus erythematosus (SLE) pathogenesis.</p><p><strong>Methods: </strong>CD19⁺ or CD19⁺CD27^- (naïve) cells from the peripheral blood of healthy controls and lupus patients were cultured under different stimuli. The changes in intracellular metabolism and signalling pathways in these cells were evaluated.</p><p><strong>Results: </strong>Stimulation with CpG (Toll-like receptor 9 (TLR9) ligand) in vitro induced enhanced interleukin 21 (IL-21) receptor expression in CD19⁺CD27^- cells after 24 hours. The addition of IL-21 to the CpG stimulation enhanced the extracellular acidification rate, which indicates glycolysis, within 30 min. IL-21 receptor (IL-21R) expression induced by CpG stimulation was selectively inhibited by 2-deoxy-D-glucose (hexokinase 2 (HK2) inhibitor) and heptelidic acid (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibitor). RNA immunoprecipitation with anti-GAPDH antibody revealed that CpG stimulation dissociated the binding between IL-21R messenger RNA (mRNA) and GAPDH under no stimulation. HK2 and GAPDH expression were higher in CD19⁺CD27^- cells of lupus patients than in those of healthy controls, and GAPDH expression was correlated with the plasmocyte count and disease activity score.</p><p><strong>Conclusion: </strong>IL-21R mRNA-GAPDH binding dissociation associated with rapid glycolytic enhancement by the TLR9 ligand in B cells may induce plasmocyte differentiation through IL-21 signals and be involved in exacerbating SLE.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910439","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":"Does tocilizumab eliminate inflammation in GCA? A cohort study on repeated temporal artery biopsies.","authors":"Caterina Ricordi, Chiara Marvisi, Pierluigi Macchioni, Luigi Boiardi, Alberto Cavazza, Stefania Croci, Martina Bonacini, Giuseppe Malchiodi, Rexhep Durmo, Annibale Versari, Pamela Mancuso, Paolo Giorgi Rossi, Francesco Muratore, Carlo Salvarani","doi":"10.1136/rmdopen-2024-005132","DOIUrl":"10.1136/rmdopen-2024-005132","url":null,"abstract":"<p><strong>Background: </strong>Vascular inflammation persists in temporal artery biopsy (TAB) of giant cell arteritis (GCA) patients even after prolonged glucocorticoid (GC) therapy. We aimed to evaluate the histological impact of adding tocilizumab (TCZ) to GCs.</p><p><strong>Methods: </strong>We enrolled all consecutive GCA patients with an inflammed TAB at diagnosis who were treated with TCZ and GCs for ≥6 months and followed from December 2017 to December 2023. Within 2 weeks, all patients underwent a second TAB, positron emission 18-fluorodeoxyglucose tomography/CT (PET/CT) and vessel colour Doppler ultrasonography (CDUS). Results were compared with pretreatment findings.</p><p><strong>Results: </strong>13 patients repeated TAB after a median TCZ treatment of 2.4 years (Q1-Q3: 1.2-3.9 years). The first TAB showed transmural inflammation (TMI) in 11/13 patients (84.6%), inflammation limited to adventitia (ILA) in one patient (7.7%) and small vessel vasculitis (SVV) in another (7.7%). On repeated TABs, five patients (38.5%) still showed some degree of inflammation. Among the 11 patients with initial TMI, 2 had ILA, 1 had TMI, 1had SVV and 1 had vasa vasorum vasculitis at the second TAB. Nine patients had active vasculitis at baseline PET/CT, and three (33.3%) still showed activity at the last PET/CT, with a relevant reduction in mean PET vascular activity score (-6.5; 95% CI 1.54 to 11.45; p=0.017). The repeated quantitative CDUS revealed altered parameters suggestive of vasculitis in temporal arteries in about one-third of the patients.</p><p><strong>Conclusion: </strong>Our study, using pathological and imaging assessments, revealed that after TCZ and GCs, over one-third of patients still presented with vascular inflammation.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910436","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":"Biomarkers reflecting disturbed gut barrier under treatment with TNF inhibitors in radiographic axial spondyloarthritis.","authors":"Judith Rademacher, Murat Torgutalp, Christine Maria Hempel, Fabian Proft, Hildrun Haibel, Mikhail Protopopov, Laura Spiller, Denis Poddubnyy, Valeria Rios Rodriguez","doi":"10.1136/rmdopen-2024-004752","DOIUrl":"10.1136/rmdopen-2024-004752","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.</p><p><strong>Methods: </strong>Patients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy. We analysed the longitudinal association between biomarkers and disease activity, and the relationship between biomarkers and treatment response with regression analysis.</p><p><strong>Results: </strong>121 patients with r-axSpA were compared with 63 controls. At baseline, patients with r-axSpA had higher levels of LBP and calprotectin than controls, which decreased significantly during TNFi treatment. LBP showed a positive association in longitudinal analyses with Axial Spondyloarthritis Disease Activity Score (ASDAS) (ß=0.08, 95% CI 0.06 to 0.10), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (ß=0.08, 95% CI 0.04 to 0.12) and C reactive protein (CRP) (ß=1.69, 95% CI 1.04 to 2.34). Calprotectin was associated with ASDAS (ß=0.04, 95% CI 0.01 to 0.07) and CRP (ß=0.82, 95% CI 0.27 to 1.37). Furthermore, LBP and calprotectin levels at baseline showed an association with a subsequent change in BASDAI. Baseline zonulin levels were not significantly associated with disease activity or treatment response.</p><p><strong>Conclusion: </strong>Serum levels of LBP and calprotectin are associated with disease activity in patients with r-axSpA and decrease with TNFi response. In contrast, serum zonulin levels showed no association with disease activity or treatment response, arguing against a strict correlation between intestinal permeability and disease activity in axSpA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910435","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":"Synovitis scoring in hand osteoarthritis with ultrasonography: the performance of the Global OMERACT/EULAR Ultrasound Synovitis Score (GLOESS) is comparable to synovial thickening alone.","authors":"Coen van der Meulen, Marion C Kortekaas, Maria Antonietta D'Agostino, Féline P B Kroon, Frits R Rosendaal, Margreet Kloppenburg","doi":"10.1136/rmdopen-2024-005002","DOIUrl":"10.1136/rmdopen-2024-005002","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is increasingly recognised as a treatment target in hand osteoarthritis, and therefore correct measurement of local inflammation is essential. This study aimed to assess ultrasound scoring of synovitis and the additional value of the Global OMERACT/EULAR Ultrasound Synovitis Score (GLOESS) in hand osteoarthritis.</p><p><strong>Methods: </strong>Data from the randomised, double-blinded Hand Osteoarthritis Prednisolone Efficacy (HOPE) trial were used. The HOPE trial included patients with painful, inflammatory hand OA, treated with prednisolone or placebo (1:1). Ultrasound was performed in 30 hand joints at weeks 0, 6 and 14. Effusion, synovial thickening and Doppler signal were measured, the GLOESS was calculated from the latter two. Joint tenderness on palpation was assessed semiquantitatively (0-3), soft swelling as present/absent. Changes in ultrasound scores, and their association with change in joint tenderness or soft swelling, were investigated using generalised estimating equations. Effect sizes were calculated.</p><p><strong>Results: </strong>Of 92 included patients 79% were women, with mean (SD) age 63.9 (8.8) and body mass index 27.2 (4.6). Synovial thickening was the most prevalent. All ultrasound scores were strongly associated with joint tenderness and soft swelling cross-sectionally. There was no association of change in ultrasound scores with change in tenderness, but there was with change in soft tissue swelling. Synovial thickening and the GLOESS responded to treatment (effect size -0.39 (-0.72 to -0.07), -0.39 (-0.71 to -0.07), respectively).</p><p><strong>Discussion: </strong>Various ultrasound scores were associated with joint tenderness and soft swelling. The GLOESS and synovial thickening were both responsive to treatment, but GLOESS was not superior to synovial thickening alone.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910440","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":"Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study.","authors":"Bas Dijkshoorn, Romy Hansildaar, Daisy Vedder, Nida Soutari, Anna Rudin, Dan Nordström, Bjorn Gudbjornsson, Kristina Lend, Till Uhlig, Espen A Haavardsholm, Gerdur Grondal, Merete Lund Hetland, Marte Schrumpf Heiberg, Mikkel Østergaard, Kim Hørslev-Petersen, Jon Lampa, Ronald F van Vollenhoven, Aleksandra Antovic, Michael T Nurmohamed","doi":"10.1136/rmdopen-2024-004838","DOIUrl":"10.1136/rmdopen-2024-004838","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays-overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors-fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.</p><p><strong>Results: </strong>At baseline, patients had elevated levels of the following biomarkers compared with reference values: fibrinogen, F1+2, D-dimer and parameters of the two global haemostatic assays, that is, ETP and OHP. After 24 weeks we observed a significant reduction in F1+2 (p<0.01), fibrinogen (p<0.01), D-dimer (p<0.01), OHP (p<0.01), ETP (p<0.01), CLT (p<0.01), TAFI (p<0.01) and an increase of OFP (p<0.01). Tocilizumab treatment resulted in the most significant reduction of global haemostatic assays after 24 weeks, that is, a reduction of OHP 73% (p<0.01) compared with certolizumab pegol arm 32% (p<0.01), abatacept arm 24% (p=0.25) or conventional treatment arm 7% (p=0.66).</p><p><strong>Conclusion: </strong>Newly diagnosed RA patients have enhanced coagulation activation and impaired fibrinolysis as demonstrated by our results. Effective antirheumatic treatments during the first 24 weeks after diagnosis improved this haemostatic imbalance, with prominent effects of biological drugs and especially tocilizumab, compared with conventional treatment.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910438","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":"Changes in serum cholesterol loading capacity are linked to coronary atherosclerosis progression in rheumatoid arthritis.","authors":"George Athanasios Karpouzas, Bianca Papotti, Sarah R Ormseth, Marcella Palumbo, Elizabeth Hernandez, Maria Pia Adorni, Francesca Zimetti, Nicoletta Ronda","doi":"10.1136/rmdopen-2024-004991","DOIUrl":"10.1136/rmdopen-2024-004991","url":null,"abstract":"<p><strong>Objective: </strong>Excess cholesterol loading on arterial macrophages is linked to foam cell formation, atherosclerosis and cardiovascular risk in rheumatoid arthritis (RA). However, the effect of changes in cholesterol loading on coronary plaque trajectory and the impact of RA therapies on this relationship are unknown. We investigated the association between variations in cholesterol loading capacity (CLC) over time and atherosclerosis progression.</p><p><strong>Methods: </strong>In a prospective observational cohort study, coronary CT angiography evaluated atherosclerosis (non-calcified, partially calcified or fully calcified plaques and coronary artery calcium (CAC) score) in 100 patients with RA without cardiovascular disease at baseline and 6.9±0.4 years later. The presence of ≥5 plaques and lesions rendering >50% stenosis was considered an extensive and obstructive disease, respectively. Serum CLC was measured on human THP-1 monocyte-derived macrophages with a fluorometric assay.</p><p><strong>Results: </strong>Mean CLC change (follow-up CLC-baseline CLC) was 1.54 (SD 3.69) μg cholesterol/mg protein. In models adjusting for atherosclerotic cardiovascular disease risk score, baseline plaque and other relevant covariates, CLC change (per SD unit increase) is associated with a higher likelihood of progression of non-calcified (OR 2.55, 95% CI 1.22 to 5.35), fully calcified plaque (OR 3.10, 95% CI 1.67 to 5.76), CAC (OR 1.80, 95% CI 1.18 to 2.74) and new extensive or obstructive disease (OR 2.43, 95% CI 1.11 to 5.34). Exposure to prednisone unfavourably influenced, while biologics and statins favourably affected the relationship between CLC change and atherosclerosis progression (all p-for-interactions ≤0.048).</p><p><strong>Conclusion: </strong>CLC change is associated with atherosclerosis progression in a dose-dependent manner, including lipid-rich non-calcified plaques and extensive or obstructive disease that yield the greatest cardiovascular risk.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885386","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":"Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases.","authors":"Martin Aringer, Oliver Distler, Anna-Maria Hoffmann-Vold, Masataka Kuwana, Helmut Prosch, Elizabeth R Volkmann","doi":"10.1136/rmdopen-2024-004704","DOIUrl":"10.1136/rmdopen-2024-004704","url":null,"abstract":"<p><p>Interstitial lung disease (ILD) associated with rheumatoid arthritis or with connective tissue diseases such as systemic sclerosis can be collectively named systemic autoimmune rheumatic disease-associated ILDs (SARD-ILDs) or rheumatic musculoskeletal disorder-associated ILDs. SARD-ILDs result in substantial morbidity and mortality, and there is a high medical need for effective therapies that target both fibrotic and inflammatory pathways in SARD-ILD. Phosphodiesterase 4 (PDE4) hydrolyses cyclic AMP, which regulates multiple pathways involved in inflammatory processes. PDE4 is overexpressed in peripheral blood monocytes from patients with inflammatory diseases. However, clinical data on pan-PDE4 inhibition in fibrotic conditions are lacking. The PDE4B subtype is highly expressed in the brain, lungs, heart, skeletal muscle and immune cells. As such, inhibition of PDE4B may be a novel approach for fibrosing ILDs such as idiopathic pulmonary fibrosis (IPF) and SARD-ILD. Preclinical data for PDE4B inhibition have provided initial evidence of both anti-inflammatory and antifibrotic activity, with reduced potential for gastrointestinal toxicity compared with pan-PDE4 inhibitors. In a proof-of-concept phase II trial in patients with IPF, nerandomilast (BI 1015550), the only PDE4B inhibitor currently in clinical development, prevented a decline in lung function over 12 weeks compared with placebo. The potential clinical benefit of PDE4B inhibition is now being investigated in the phase III setting, with two trials evaluating nerandomilast in patients with IPF (FIBRONEER-IPF) or with progressive pulmonary fibrosis other than IPF (FIBRONEER-ILD). Here, we review the preclinical and clinical data that provide rationale for PDE4B inhibition as a treatment strategy in patients with SARD-ILD.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885670","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":"Anatomy-centred deep learning improves generalisability and progression prediction in radiographic sacroiliitis detection.","authors":"Felix J Dorfner, Janis L Vahldiek, Leonhard Donle, Andrei Zhukov, Lina Xu, Hartmut Häntze, Marcus R Makowski, Hugo J W L Aerts, Fabian Proft, Valeria Rios Rodriguez, Judith Rademacher, Mikhail Protopopov, Hildrun Haibel, Kay-Geert Hermann, Torsten Diekhoff, Lisa C Adams, Murat Torgutalp, Denis Poddubnyy, Keno K Bressem","doi":"10.1136/rmdopen-2024-004628","DOIUrl":"10.1136/rmdopen-2024-004628","url":null,"abstract":"<p><strong>Purpose: </strong>To examine whether incorporating anatomy-centred deep learning can improve generalisability and enable prediction of disease progression.</p><p><strong>Methods: </strong>This retrospective multicentre study included conventional pelvic radiographs of four different patient cohorts focusing on axial spondyloarthritis collected at university and community hospitals. The first cohort, which consisted of 1483 radiographs, was split into training (n=1261) and validation (n=222) sets. The other cohorts comprising 436, 340 and 163 patients, respectively, were used as independent test datasets. For the second cohort, follow-up data of 311 patients was used to examine progression prediction capabilities. Two neural networks were trained, one on images cropped to the bounding box of the sacroiliac joints (anatomy-centred) and the other one on full radiographs. The performance of the models was compared using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity.</p><p><strong>Results: </strong>On the three test datasets, the standard model achieved AUC scores of 0.853, 0.817, 0.947, with an accuracy of 0.770, 0.724, 0.850. Whereas the anatomy-centred model achieved AUC scores of 0.899, 0.846, 0.957, with an accuracy of 0.821, 0.744, 0.906, respectively. The patients who were identified as high risk by the anatomy-centred model had an OR of 2.16 (95% CI 1.19, 3.86) for having progression of radiographic sacroiliitis within 2 years.</p><p><strong>Conclusion: </strong>Anatomy-centred deep learning can improve the generalisability of models in detecting radiographic sacroiliitis. The model is published as fully open source alongside this study.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885369","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":"Different disease activity trajectories in early axial spondyloarthritis lead to significantly different long-term outcomes: a trajectory-based analysis of the DESIR cohort over 10 years.","authors":"Elodie Portier, Leslie Benattar, Matthieu Resche-Rigon, Maxime Dougados, Laure Gossec, Anna Molto","doi":"10.1136/rmdopen-2024-004910","DOIUrl":"10.1136/rmdopen-2024-004910","url":null,"abstract":"<p><strong>Introduction: </strong>The study aimed to identify and describe disease activity trajectories over 10 years in patients with recent-onset axial spondyloarthritis (axSpA) and determine their impact on long-term outcomes.</p><p><strong>Methods: </strong>This prospective, multicentre study (Devenir des Spondylarthropathies Indifférenciées Récentes cohort, ClinicalTrials.gov NCT) followed patients with early axSpA for 10 years. Only patients with at least three Axial Spondylitis Disease Activity Score (ASDAS) values were included. Long-term outcomes assessed were TNF inhibitors (TNFi) exposure, structural progression, function (Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index), quality of life (36-items Short Form Survey), sick leave days and cardiovascular (CV) events. ASDAS trajectories were identified using k-means clustering. Multinomial multivariable regression estimated associations between baseline characteristics and trajectories. Long-term outcomes for each trajectory were described.</p><p><strong>Results: </strong>Among 601 patients, five ASDAS trajectories were identified: persistent low disease activity/remission (tA), clinically important improvement (tD) and persistent moderate (tB), high (tC) or very high (tE) disease activity. Patients in tA were more likely to be male, have a university degree, have white-collar jobs, have positive HLA B27 status and have less fibromyalgia. Trajectory tE was linked to poorer function (BASFI 50/100 vs 7/100 for lower ASDAS trajectory), higher TNFi exposure (74% vs 29%) and more CV events (5.7% vs 0). Structural progression was low but comparable across trajectories, except for higher sacroiliac joint progression in tB.</p><p><strong>Conclusion: </strong>The k-means method revealed distinct disease activity trajectories in axSpA. Higher disease activity trajectories were associated with a higher prevalence of fibromyalgia and poorer outcomes, except for structural progression, which was comparable across trajectories.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877872","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":"Large language models for accurate disease detection in electronic health records: the examples of crystal arthropathies.","authors":"Nils Bürgisser, Etienne Chalot, Samia Mehouachi, Clement P Buclin, Kim Lauper, Delphine S Courvoisier, Denis Mongin","doi":"10.1136/rmdopen-2024-005003","DOIUrl":"10.1136/rmdopen-2024-005003","url":null,"abstract":"<p><strong>Objectives: </strong>We propose and test a framework to detect disease diagnosis using a recent large language model (LLM), Meta's Llama-3-8B, on French-language electronic health record (EHR) documents. Specifically, it focuses on detecting gout ('goutte' in French), a ubiquitous French term that has multiple meanings beyond the disease. The study compares the performance of the LLM-based framework with traditional natural language processing techniques and tests its dependence on the parameter used.</p><p><strong>Methods: </strong>The framework was developed using a training and testing set of 700 paragraphs assessing 'gout' from a random selection of EHR documents from a tertiary university hospital in Geneva, Switzerland. All paragraphs were manually reviewed and classified by two healthcare professionals into disease (true gout) and non-disease (gold standard). The LLM's accuracy was tested using few-shot and chain-of-thought prompting and compared with a regular expression (regex)-based method, focusing on the effects of model parameters and prompt structure. The framework was further validated on 600 paragraphs assessing 'Calcium Pyrophosphate Deposition Disease (CPPD)'.</p><p><strong>Results: </strong>The LLM-based algorithm outperformed the regex method, achieving a 92.7% (88.7%-95.4%) positive predictive value, a 96.6% (94.6%-97.8%) negative predictive value and an accuracy of 95.4% (93.6%-96.7%) for gout. In the validation set on CPPD, accuracy was 94.1% (90.2%-97.6%). The LLM framework performed well over a wide range of parameter values.</p><p><strong>Conclusion: </strong>LLMs accurately detected disease diagnoses from EHRs, even in non-English languages. They could facilitate creating large disease registers in any language, improving disease care assessment and patient recruitment for clinical trials.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966415","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}