Responsiveness in Rheumatoid Arthritis. A Report from the OMERACT 11 Ultrasound Workshop

Objective.To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop.Methods.The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA.Results.The US-GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing.Conclusion.At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis.

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A Systematic Literature Review Analysis of Ultrasound Joint Count and Scoring Systems to Assess Synovitis in Rheumatoid Arthritis According to the OMERACT Filter

The Journal of Rheumatology ◽

10.3899/jrheum.110424 ◽

2011 ◽

Vol 38 (9) ◽

pp. 2055-2062 ◽

Cited By ~ 128

Author(s):

PETER MANDL ◽

ESPERANZA NAREDO ◽

RICHARD J. WAKEFIELD ◽

PHILIP G. CONAGHAN ◽

MARIA ANTONIETTA D’AGOSTINO

Keyword(s):

Rheumatoid Arthritis ◽

Construct Validity ◽

Task Force ◽

Power Doppler ◽

Scoring Systems ◽

Original Research ◽

Laboratory Findings ◽

Validity Data ◽

Wide Range ◽

Definition Of

Objective.The OMERACT Ultrasound Task Force is currently developing a global synovitis score (GLOSS) with the objective of feasibly measuring global disease activity in patients with rheumatoid arthritis (RA). In order to determine the minimal number of joints to be included in such a scoring system, and to analyze the metric properties of proposed global (i.e., patient level) ultrasound (US) scoring systems of synovitis in RA, a systematic analysis of the literature was performed.Methods.A systematic literature search of Pubmed and Embase was performed (January 1, 1984, to March 31, 2010). Original research reports written in English including RA, ultrasound, Doppler, and scoring systems were included. The design, subjects, methods, imaging protocols, and performance characteristics studied were analyzed, as well as the ultrasound definition of synovitis.Results.Of 3004 reports identified, 14 articles were included in the review. We found a lack of clear definition of synovitis as well as varying validity data with respect to the proposed scores. Scoring systems included a wide range and number of joints. All analyzed studies assessed construct validity and responsiveness by using clinical examination, laboratory findings, and other imaging modalities as comparators. Both construct validity and responsiveness varied according to the number and size of joints examined and according to the component of synovitis measured [i.e., gray-scale (GS) or power Doppler (PD) alone or in combination]. With regard to feasibility, time of evaluation varied from 15 to 60 min and increased with the number of joints involved in the examination.Conclusions.Ultrasound can be regarded as a valuable tool for globally examining the extent of synovitis in RA. However, it is presently difficult to determine a minimal number of joints to be included in a global ultrasound score. Further validation of proposed scores is needed.

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Ultrasound in clinically suspect arthralgia: the role of power Doppler to predict rheumatoid arthritis development

Arthritis Research & Therapy ◽

10.1186/s13075-021-02685-7 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Juan Molina Collada ◽

Katerine López Gloria ◽

Isabel Castrejón ◽

Juan Carlos Nieto-González ◽

Javier Rivera ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Power Doppler ◽

Independent Predictive Factor ◽

Logistic Regression Models ◽

Rheumatoid Arthritis Development ◽

Previous Diagnosis ◽

The Us ◽

Active Inflammation

Abstract Objective To determine the usefulness of power Doppler (PD) ultrasound (US) to predict rheumatoid arthritis (RA) development in patients with clinically suspect arthralgia (CSA). Methods Retrospective analysis of a US unit cohort over a 1-year period. Patients with CSA and no previous diagnosis of inflammatory arthritis (IA) were included for analysis. All underwent bilateral US examination of the hands and/or feet according to the EULAR guidelines. Active US inflammation was defined as PD synovitis and/or tenosynovitis ≥1 at any location. RA diagnosis according to clinician criteria 6 months after the US examination was checked. Univariate and multivariate logistic regression models were employed to investigate possible predictive factors of RA development. Results A total of 110 CSA patients (80 females, mean age 53.6 years) were included for analysis. After 6 months of follow-up, 14 (12.7%) developed RA and 34 (30.9%) IA. US active inflammation was present in 38 (34.5%) patients (28.2% showed PD synovitis and 18.2% PD tenosynovitis). Multivariate analysis showed that ACPA (OR 1.0003; 95% CI 1.002–1.006) and ESR (OR 1.054; 95% CI 1.016–1.094) were significantly associated with the detection of US active inflammation at baseline. Only PD tenosynovitis was found to be an independent predictive factor of an evolution towards RA (OR 6.982; 95% CI 1.106–44.057) and IA (OR 5.360; 95% CI 1.012–28.390). Conclusion US is able to detect features of subclinical inflammation in CSA patients, especially in those with higher ESR and ACPA values. Only PD tenosynovitis at baseline US assessment was found to be an independent predictor of RA and IA development in CSA patients.

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POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3850 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 583-583

Author(s):

C. Garufi ◽

F. Ceccarelli ◽

F. R. Spinelli ◽

S. Mancuso ◽

C. Pirone ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Structural Damage ◽

Power Doppler ◽

Response To Treatment ◽

Jak Inhibitors ◽

Inflammatory Score ◽

Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

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AB0115 COMPARISON OF ULTRASOUND FINDINGS BETWEEN TNF INHIBITORS AND NON-TNF INHIBITORS AT FIRST BIOLOGICS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1377 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1086.2-1087

Author(s):

T. Okano ◽

T. Koike ◽

K. Inui ◽

K. Mamoto ◽

Y. Yamada ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Duration ◽

Power Doppler ◽

Tnf Inhibitors ◽

Tnf Inhibitor ◽

Significant Difference ◽

The Us ◽

Us Findings ◽

Improvement Ratio

Background:In rheumatoid arthritis (RA), biologics treatment is one of the effective treatment options. Usually, there is no difference in therapeutic effect regardless of which biologics is used, but the effect for joint synovitis is unknown. Recently, ultrasound (US) has played a role of sensitive imaging modality in the diagnosis and follow-up of patients with RA.Objectives:The aim of this study was to compare the improvement of US findings between TNF inhibitors and non-TNF inhibitors at first biologics in patients with RA.Methods:Fifty-four RA patients who started the first biologics from September 2016 to December 2018 were included in this longitudinal study (SPEEDY study, UMIN000028260). All the patients were performed clinical examination, blood test and US examination at baseline, 4, 12, 24, 36 and 52 weeks. A US examination was performed at the bilateral first to fifth metacarpophalangeal (MCP) joints, first interphalangeal (IP) and second to fifth proximal interphalangeal (PIP) joints, wrist joints (three part of radial, medial and ulnar) and first to fifth metatarsophalangeal (MTP) joints, by using HI VISION Ascendus (Hitachi Medical Corporation, Japan) with a multifrequency linear transducer (18-6 MHz). The gray scale (GS) and power Doppler (PD) findings were assessed by the semi-quantitative method (0-3). GS score and PD score (both 0-108 points) were defined as the sum of each score. The change of disease activity and US findings were compared between TNF group and non-TNF group.Results:Among 54 cases, 32 patients were used TNF inhibitor and 22 were non-TNF inhibitor. Age and duration of RA were significantly higher in the non-TNF group, and MTX dose was significantly lower in the non-TNF group. The baseline inflammatory markers tended to be higher in the non-TNF group and the disease activity was also higher in the non-TNF group. However, the US findings showed no significant difference in both GS and PD between two groups at baseline. US improvement ratio was no difference between TNF group and non-TNF group at 4, 12, 24, 36 and 52 weeks in both GS and PD score. Regardless of the type of biologics, patients with long-term disease duration tended to have poor improvement in US synovial fingings.Table 1.Baseline patient and disease characteristicsTNF (n=32)non-TNF (n=22)P valueFemale patients, n (%)21 (65.6)16 (72.7)0.767Age (years)63.5±15.471.0±9.00.030Disease duration (years)6.5±8.213.0±11.70.032CRP (mg/dl)1.8±2.53.0±3.20.170DAS28-ESR5.0±1.45.8±1.20.022GS score26.1±18.831.8±21.10.313PD score17.6±11.423.1±14.60.150Figure 1.GS and PD improvement ratio at 4, 12, 24, 36 and 52 weeksConclusion:There was no difference in the US findings improvement between patients with TNF inhibitor and non-TNF inhibitor at first biologics in patients with RA.References:[1]Grassi W, Okano T, Di Geso L, Filippucci E. Imaging in rheumatoid arthritis: options, uses and optimization. Expert Rev Clin Immunol. 2015;11:1131-46.[2]Nishino A, Kawashiri SY, Koga T, et al. Ultrasonographic Efficacy of Biologic andTargeted Synthetic Disease-ModifyingAntirheumatic Drug Therapy in RheumatoidArthritis From a Multicenter RheumatoidArthritis Ultrasound Prospective Cohort in Japan. Arthritis Care Res (Hoboken). 2018;70:1719-26.Acknowledgements:We wish to thank Atsuko Kamiyama, Tomoko Nakatsuka for clinical assistant, Setsuko Takeda, Emi Yamashita, Yuko Yoshida, Rika Morinaka, Hatsue Ueda and Tomomi Iwahashi for their special efforts as a sonographer and collecting data.Disclosure of Interests:None declared

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Jan Hornat: Transatlantic Democracy Assistance. Promoting Different Models of Democracy.

Mezinárodní vztahy ◽

10.32422/mv.1605 ◽

2019 ◽

Vol 54 (2) ◽

pp. 70-73

Author(s):

Veronika Bílková

Keyword(s):

Political Theory ◽

Democratic Governance ◽

Us Foreign Policy ◽

Democracy Promotion ◽

Democracy Assistance ◽

Constructivist View ◽

The Us ◽

Definition Of ◽

The Eu

The approaches of EU institutions and the US to democracy assistance often vary quite significantly as both actors choose different means and tactics. The nuances in the understandings of democracy on the part of the EU and the US lead to their promotion of models of democratic governance that are often quite divergent and, in some respects, clashing. This book examines the sources of this divergence and by focusing on the role of the actors’ "democratic identity" it aims to explain the observation that both actors use divergent strategies and instruments to foster democratic governance in third countries. Taking a constructivist view, it demonstrates that the history, expectations and experiences with democracy of each actor significantly inform their respective definition of democracy and thus the model of democracy they promote abroad. This book will be of key interest to scholars, students and practitioners in democracy promotion, democratization, political theory, EU and US foreign policy and assistance, and identity research.

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The role of public diplomacy in defending national and coalition interests (for example, the US, NATO and the EU)

10.33920/vne-01-2006-07 ◽

2020 ◽

pp. 61-69

Author(s):

V. I. Vinokurov

Keyword(s):

Public Diplomacy ◽

The Us ◽

Definition Of ◽

The Eu

The article gives a definition of public diplomacy, reveals the dualism of its functions, emphasizes the role and place of public diplomacy in upholding national and bloc interests.

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Rheumatoid Arthritis: Etiology and Pathogenesis

10.2310/im.1431 ◽

2014 ◽

Author(s):

Gary S. Firestein ◽

Anna-Karin H. Ekwall

Keyword(s):

Rheumatoid Arthritis ◽

Intracellular Signaling ◽

Cartilage Damage ◽

Signs And Symptoms ◽

American College Of Rheumatology ◽

European League Against Rheumatism ◽

Citrullinated Proteins ◽

Definition Of

Rheumatoid arthritis (RA) is among the most common forms of chronic inflammatory arthritis. It affects approximately 1% of adults and is two to three times more prevalent in women than in men. There are no specific laboratory tests for RA; diagnosis depends on a constellation of signs and symptoms that can be supported by serology and radiographs. The disease evolves over many years as a consequence of repeated environmental stress causing inflammation and immune activation followed by a breakdown of tolerance in individuals with a specific genetic background. This review describes the definition of RA; its etiology, including genetics, infections, the role of smoking and citrullination of proteins, and epigenetic mechanisms; and its pathogenesis, including synovial histopathology, bone and cartilage damage, adaptive and innate immunity, and the role of cytokines and intracellular signaling. Tables include the 1987 American Rheumatism Association criteria for the classification of RA and the 2010 American College of Rheumatology/European League Against Rheumatism classification for RA. Figures show citrullinated proteins in airway cells, a section of a proliferative synovium from a patient with a classic RA, and scalloped regions of erosion at the junction between a proliferative inflamed rheumatoid synovium and the bone. This review contains 3 highly rendered figures, 2 tables, and 71 references.

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Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218744 ◽

2021 ◽

pp. annrheumdis-2020-218744

Author(s):

Irina Gessl ◽

Mihaela Popescu ◽

Victoria Schimpl ◽

Gabriela Supp ◽

Thomas Deimel ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Power Doppler ◽

Joint Damage ◽

Joint Space ◽

Early Arthritis ◽

Damage Score ◽

Established Disease ◽

Active Inflammation

ObjectivesTo determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.MethodsPatients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.ResultsIn total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).ConclusionTenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

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1. Banks in the Financial System

Principles of Banking Law ◽

10.1093/he/9780199276080.003.0001 ◽

2018 ◽

Author(s):

Ross Cranston ◽

Emilios Avgouleas ◽

Kristin van Zweiten ◽

Theodor van Sante ◽

Christoper Hare

Keyword(s):

Financial Stability ◽

Regulatory Networks ◽

Financial System ◽

Capital Allocation ◽

Bank Supervision ◽

System P ◽

The Us ◽

Regulatory Coordination ◽

Definition Of

This chapter explains the economic functions and organizational structure of contemporary banking. It first discusses the role of banks in the economy, offering a brief account of the role of the financial system in capital allocation and risk management as well as key bank functions in this respect. It then details the rise and fall of the multifunctional bank in the era of globalization, and the different aspects of the too-big-to-fail bank problem and its possible causes. It explains the international nature of bank regulation and the standard-setting and regulatory coordination provided by key transnational regulatory networks such as the Basel committee on Bank Supervision and the Financial Stability Board; discusses the legal definition of the term ‘bank’ in the US and of ‘credit institution’ under EU legislation; advances a new understanding of what the term ‘bank’ means in the post-2008 era.

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