Development and Validation of an OMERACT MRI Whole-Body Score for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE)

Objective: To develop a whole-body MRI-scoring system for peripheral arthritis and enthesitis. Methods: After consensus on definitions/locations of MRI pathologies, four multi-reader exercises were performed. Eighty-three joints were scored 0-3 separately for synovitis and osteitis, thirty-three entheses 0-3 separately for soft tissue inflammation and osteitis. Results: In the last exercise, reliability was moderate-good for musculoskeletal radiologists and rheumatologists with previously demonstrated good scoring proficiency. Median pairwise single-measure/average-measure ICCs were 0.67/0.80 for status scores and 0.69/0.82 for change scores; kappas ranged 0.35-0.77. Conclusion: WBMRI scoring of peripheral arthritis and enthesitis is reliable which encourages further testing and refinement in clinical trials

Standardisation of synovial biopsy analyses in rheumatic diseases: a consensus of the EULAR Synovitis and OMERACT Synovial Tissue Biopsy Groups

Following publication of the original article [1], the authors reported an error in the spelling of the ninth author’s name. Incorrect spelling: Soeren Andreas Just. Correct spelling: Søren Andreas Just. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: The aim of this global collaboration was to develop a consensual set of items for the analysis of synovial biopsies in clinical practice and translational research through the EULAR Synovitis Study Group (ESSG) and OMERACT Synovial Tissue Biopsy Group. Methods: Participants were consulted through a modified Delphi method. Three sequential rounds occurred over 12 months. Members were sent a written questionnaire containing items divided into two parts. Items were identified and formulated based on a scoping review. The first part of the questionnaire referred to synovial biopsies in clinical practice including five subsections, and the second part to translational research with six subsections. Every participant was asked to score each item on a 5-point Likert scale. Items with a median score above 3.5 and a >70% agreement were selected for the next round. The last round was conducted orally at EULAR in June 2017. Results: Twenty-seven participants from 19 centers were contacted by email. Twenty participants from 17 centers answered. Response rates for next rounds were 100%. For the first part relating to clinical practice, 20/44 items (45.5%) were selected. For the second part relating to translational research, 18/43 items (41.9%) were selected for the final set. Conclusions: We herein propose a consensual set of analysis items to be used for synovial biopsies conducted in clinical practice and translational research. Correction: Following publication of the original article [1], the authors reported an error in the spelling of the ninth author's name

Differential regulation of Nitric Oxide Synthase isoforms : in vitro and in vivo studies

Le développement de la dyalise péritonéale (DP) comme traitement substitutif de l'insuffisance rénale a été possible grâce à la structure unique de la membrane péritonéeale (MP). Malheureusement, l'utilisation de la MP à long terme est limitée par une altération de sa structure et de ses propriétés de transport lorsqu'elle est exposé à des concentrations élevées en glucose. L'urémie et les épisodes de péritonite contribuent aussi à la détérioration de la MP. Nous avons utilisé un modèle expérimental de péritonite chez le rat pour étudier comment les différentes isoformes de NOS, induites par l'infection, sont impliquées dans les modifications structurelles (y compris la nitrosylation des protéines) et fonctionnelles de la MP. La péritonite est caractérisée par une perte de l'ultrafiltration (UF), l'augmentation des activités de NOS liées à une surexpression de iNOS et eNOS, de même qu'un marquage plus intense pour la S-nitrosocystéine. L'ajout de L-NAME, un inhibiteur de NOS, dans le dialysat est capable de rétablir l'UF. Dans l'urémie, une prolifération vasculaire et une augmentation de la perméabilité de la membrane péritonéale ont été également retrouvées, cette fois-ci en association avec une surexpression de eNOS et nNOS. Dans les deux modèles, l'augmentation de la nitrosocysteine associée à une augmentation de l'activité NOS illustre le rôle important du NOS dans le MP, le production de radicaux peroxynitrites en présence des anions superoxyde ayant pour conséquence des modifications post-translationnelles des proteines. Dans le modèle de diabète induit par la streptozocine, le diabète est associé à une augmentation progressive de la perméabilité du péritoine pour les petites molécules, une augmentation significative de l'expréssion et de l'activité NOS ainsi qu'une densité capillaire accrue. Le traitement par insulin normalise les tests de la fonction péritonale et prévient la prolifération vasculaire et la surexpression de eNOS. Des études in vitro (cellules endothéliales aortiques bovines) et in vivo (rats soumis à un apport chronique en urée) nous ont permis d'excure un effet de l'hyperosmolarité per se à l'origine des modifications observées. Les hormones corticostéroïdes ont un effet modulateur connu sur la transcription du gène iNOS, mais leurs effets sur l'expression de eNOS ne sont pas clairement définis. Dans la MP, eNOS et l'aquaporine-1, qui forme le canal à eau (AQP1) sont tous deux exprimés au niveau de la membrane des cellules endothéliales qui tapissent les capillaires. Dans le même modèle, nous montrons que l'administration de dexaméthasone peut augmenter la perméabilité de l'eau à travers la membrane péritonéale par une augmentation de l'expression d'AQP1. Contrairement à AQP1, l'expression et l'activité de NOS n'est pas augmentée par l'administration de la dexaméthasone aux doses utilisées. Même si les hormones corticotéroïdes ont des nombreux effets secondaires, cette étude ouvre des perspectives pour modifier la perméabilité à l'eau et augmenter l'efficacité de la DP. La régulation différentielle de NOS a également été étudié dans d'autres systèmes (cellules thyroïdiennes en culture, vascularisation rénale, artères rénales dans la polykystose autosomique dominante).Thèse de doctorat en sciences biomédicales (physiologie, physiopathologie) -- UCL, 200

Tendon friction rubs in systemic sclerosis: a possible explanation--an ultrasound and magnetic resonance imaging study.

Objective. To assess the tendon and joint involvement at wrists and ankles of patients suffering from diffuse SSc and to identify the morphological substrate of tendon friction rubs (TFRs).Methods. Fifteen consecutive patients suffering from diffuse SSc were included. All patients had two musculoskeletal US (MSUS) examinations of the wrists and ankles. MRI was performed at the most affected joints as detected by MSUS and in all sites in which TFRs were present.Results. No clinically overt arthritis or tenosynovitis was detected in the wrists and/or ankles prior to MSUS. Synovitis, tenosynovitis and tendon tear were identified in 8, 4 and 2 of 15 patients, respectively, by both MSUS and MRI. At entry, 5 patients had palpable TFRs (4 bilateral and 1 unilateral) and 10 patients did not. Tenosynovitis was more frequently found in ankles with TFRs (3/9) than in those without TFRs (3/21), although the difference was not statistically different (P = 0.3). Using MRI, deep connective tissue infiltrates surrounding tendons were present in all sites with TFRs but in only one patient without TFRs.Conclusion. Both MSUS and MRI are effective in detecting synovitis and tenosynovitis in diffuse SSc patients. Tenosynovitis, synovitis and thickened retinacula are not infrequently seen in these patients. Our data suggest that juxta-tendinous connective tissue infiltrates might be the morphological substrate of tendon friction rubs, which may thus be a misnomer for tissue friction rubs

Regulation of NO synthase isoforms in the peritoneum: implications for ultrafiltration failure in peritoneal dialysis.

BACKGROUND: Ultrafiltration (UF) failure often complicates peritoneal dialysis (PD). At least two molecules might be involved in UF failure: aquaporin-1 (AQP1), a water channel thought to be the ultra small pore of the peritoneal membrane (PM), and nitric oxide (NO), which might regulate effective peritoneal surface area and microvascular permeability. METHODS: The contributions of AQP1 and NO in UF failure were evaluated by combining different experimental approaches. Specific antibodies were used to investigate the expression (immunoblotting) and localization (immunostaining) of AQP1 and NO synthase (NOS) isoforms in the peritoneum, in correlation with: (i) morphometric analyses; (ii) the l-citrulline assay, which specifically measures NOS enzymatic activities; and (iii) permeability parameters across the PM. RESULTS: AQP1 is located in the endothelium lining peritoneal capillaries, and its expression is remarkably stable in samples ranging from normal to highly inflamed peritoneum and even when transcellular water permeability is absent (loss of sodium sieving). A significant NOS activity, mediated by specific NOS isoforms, can be assayed in the peritoneum. The NOS activity significantly increases in conditions such as peritonitis and long-term PD, and this increase is mirrored by up-regulation of NOS isoforms, as well as angiogenesis and increased endothelial area. CONCLUSIONS: These data suggest that the NO-mediated increase in effective peritoneal surface area, followed by a dissipation of the osmotic gradient, is a major mechanism accounting for the loss of UF in PD. Other biological consequences of increased NO levels in the peritoneum might include initiation of angiogenesis or modification of functionally important proteins such as AQP1

Comparison between 3-point Dixon- and CHESS-based OMERACT-recommended MRI protocols in hands of patients with suspicion of early rheumatoid arthritis.

To compare fat suppression effectiveness, image quality and disease activity scores between MRI protocols based on the Dixon method and the Chemical Shift Selective (CHESS) technique in hands of patients with suspicion of early rheumatoid arthritis (RA). Both hands of 28 patients (19 women; mean age 45.2 years old) with suspicion of early RA were prospectively imaged with Dixon- and CHESS-based OMERACT recommended protocols at 1.5 T including fat-suppressed T2-weighted and contrast-enhanced T1-weighted imaging. Two radiologists (R1/R2) separately assessed effectiveness of fat suppression and determined RAMRIS scores woth the Dixon- and CHESS-based protocols. R1 repeated the RAMRIS scoring and measured contrast-to-noise ratios (CNRs) on Dixon and CHESS images. Statistics included 2-way ANOVA test for the comparison of CNRs and Bland-Altman methodology for inter-technique and intra-observer agreement (p < 0.05). Fat suppression failure occurred in up to 1 patient with the Dixon- and 25 patients with the CHESS-based protocols. CNRs were significantly higher on T1-weighted and lower on T2-weighted Dixon images than on the corresponding CHESS images (p ≤ 0.042). Median bias of the difference between Dixon- and CHESS-based RAMRIS scores was not significantly different from 0 (-0.8 to +1.0 and -1.1 to +1.4 for R1/R2). Median bias of the difference between RAMRIS scores at first and second readings was significantly different from 0 with the CHESS-based protocols (-0.8 to +1.7) but not with the Dixon-based protocols (+0.0 to +1.0). Dixon sequences yield more effective fat suppression and more reproducible RAMRIS scoring than CHESS sequences in hands with suspicion of early RA

MRI of Hands with Early Rheumatoid Arthritis: Usefulness of Three-Point Dixon Sequences to Quantitatively Assess Disease Activity.

The use of efficient treatment with a treat-to-target strategy combined with early detection of the disease completely changed the imaging presentation and outcome of newly diagnosed rheumatoid arthritis (RA) patients. Magnetic Resonance Imaging (MRI) has become the reference technique in clinical research to detect and quantify inflammatory involvement of the soft tissues (synovitis and tenosynovitis) and bone marrow (osteitis) along with structural damages of the bone (erosions) in hands of patients with RA. Three-point Dixon MRI may be a valuable alternative to the currently recommended sequences as it yields effective fat signal suppression, high imaging quality and reproducible assessment of disease activity

Contrast-enhanced T1-weighted Dixon water- and fat-only images to assess osteitis and erosions according to RAMRIS in hands of patients with early rheumatoid arthritis.

PURPOSE: To assess the agreement between readers using contrast-enhanced T1-weighted Dixon water- and fat-only images and OMERACT-recommended sequences for the scoring of osteitis and erosions according to the rheumatoid arthritis (RA) MRI scoring system (RAMRIS) in hands of patients with early RA. MATERIALS AND METHODS: Both hands of 24 patients (16 women, 8 men; mean age, 45.7±14.5 [SD] years; age range: 25-70 years) with early RA were prospectively imaged with fat-saturated T2-weighted sequences, non-Dixon T1-weighted imaging prior to contrast material injection and T1-weighted Dixon imaging after contrast material injection at 1.5T. There were Two radiologists separately quantified osteitis and erosions according to RAMRIS using contrast-enhanced T1-weighted Dixon water-only and fat-saturated T2-weighted images for osteitis and contrast-enhanced T1-weighted Dixon fat-only and T1-weighted images prior to contrast material injection for erosions. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique, intra-observer and inter-observer agreement. RESULTS: Mean ICC for the agreement between Dixon and non-Dixon images ranged from 0.68 (95%CI: 0.20-0.90) to 0.99 (95%CI: 0.95-1.00) for the scoring of osteitis and from 0.77 (95%CI: 0.38-0.93) to 0.99 (95%CI: 0.95-1.00) for the scoring of erosions. Mean ICC for the agreement between first and second readings ranged from 0.94 (95%CI: 0.81-0.98) to 0.97 (95%CI: 0.91-0.99) for the scoring of osteitis using Dixon and 0.91 (95%CI: 0.72-0.97) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images and from 0.80 (95%CI: 0.45-0.94) to 0.97 (95%CI: 0.91-0.99) for the scoring of erosions using Dixon and 0.72 (95%CI: 0.29-0.91) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images. CONCLUSION: Contrast-enhanced T1-weighted Dixon water- and fat-only images can serve as an alternative to fat-saturated T2-weighted and T1-weighted MRI sequences for the assessment of osteitis and erosions according to the RAMRIS scoring system in hands of patients with early RA