Characterization of digital annular pulleys and their entheses: an ultrasonographic study with anatomical and histological correlations

Objectives: Digital annular pulleys (DAP) are important anatomical structures for finger function. The anatomy, histology, and imaging assessment of DAP, particularly at the level of their entheses is still not clearly defined. The advent of high-frequency ultrasound (US) transducers opened new perspectives in evaluating sub-millimeter scale structures, such as pulleys, paving the way for their global assessment. The study aimed at characterizing DAP from an anatomical, histological, and US perspective, focusing on the detection and complete description of pulley entheses. Methods: US assessment and gross anatomy dissection were conducted on 20 cadaveric hands to study DAP thickness and structure including enthesis identification. The results of the US and anatomical measurements were correlated. DAP entheses identified by US were characterized via histological analysis. DAP in 20 healthy controls (HC) were detected and measured by US. The A1, A2, and A4 DAP entheses were assessed using a new dynamic maneuver to better evaluate those structures. Results: 1200 DAP (400 cadaveric, 800 HC) were analyzed. The cadaveric study demonstrated strong correlation between anatomical and US measurement of DAP (r = 0.96). At histological level, DAP entheses at the volar plate, sesamoid bones, or phalangeal ridges contained fibrous and fibrocartilaginous tissue. The US assessment of A1, A2, and A4 DAP in HC allowed the identification of 718/720 (99.73%) entheses. Conclusion: US is an effective tool to detect and study DAP. DAP entheses reveal both fibrous and fibrocartilaginous characteristics. A newly described maneuver to optimize DAP enthesis visualization enhances their detection by US

Core Domain Set Selection According to OMERACT Filter 2.1: The OMERACT Methodology

Objective: To describe the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 methodology for core domain set selection. Methods: The “OMERACT Way for Core Domain Set selection” framework consists of 3 stages: first, generating candidate domains through literature reviews and qualitative work, then a process of consensus to obtain agreement from those involved, and finally formal voting on the OMERACT Onion. The OMERACT Onion describes the placement of domains in layers/circles: mandatory in all trials/mandatory in specific circumstances (inner circle); important but optional (middle circle); or research agenda (outer circle). Five OMERACT working groups presented their core domain sets for endorsement by the OMERACT community. Tools including a workbook and whiteboard video were created to assist the process. The methods workshop at OMERACT 2018 introduced participants to this framework. Results: The 5 OMERACT working groups achieved consensus on their proposed core domain sets. After the Methodology Workshop training exercise at OMERACT 2018, over 90% of participants voted that they were confident that they understood the process of core domain set selection. Conclusion: The methods described in this paper were successfully used by the 5 working groups voting on domains at the OMERACT 2018 meeting, demonstrating the feasibility of the process. In addition, participants at OMERACT 2018 expressed increased confidence and understanding of the core domain set selection process after the training exercise. This methodology will continue to evolve, and we will use innovative technology such as whiteboard videos as a key part of our dissemination and implementation strategy for new methods

How does a cadaver model work for testing ultrasound diagnostic capability for rheumatic-like tendon damage?

To establish whether a cadaver model can serve as an effective surrogate for the detection of tendon damage characteristic of rheumatoid arthritis (RA). In addition, we evaluated intraobserver and interobserver agreement in the grading of RA-like tendon tears shown by US, as well as the concordance between the US findings and the surgically induced lesions in the cadaver model. RA-like tendon damage was surgically induced in the tibialis anterior tendon (TAT) and tibialis posterior tendon (TPT) of ten ankle/foot fresh-frozen cadaveric specimens. Of the 20 tendons examined, six were randomly assigned a surgically induced partial tear; six a complete tear; and eight left undamaged. Three rheumatologists, experts in musculoskeletal US, assessed from 1 to 5 the quality of US imaging of the cadaveric models on a Likert scale. Tendons were then categorized as having either no damage, (0); partial tear, (1); or complete tear (2). All 20 tendons were blindly and independently evaluated twice, over two rounds, by each of the three observers. Overall, technical performance was satisfactory for all items in the two rounds (all values over 2.9 in a Likert scale 1-5). Intraobserver and interobserver agreement for US grading of tendon damage was good (mean κ values 0.62 and 0.71, respectively), with greater reliability found in the TAT than the TPT. Concordance between US findings and experimental tendon lesions was acceptable (70-100 %), again greater for the TAT than for the TPT. A cadaver model with surgically created tendon damage can be useful in evaluating US metric properties of RA tendon lesions

OMERACT Definitions for Ultrasonographic Pathology and Elementary Lesions Of Rheumatic Disorders Fifteen Years On

Objective. The Outcome Measures in Rheumatology (OMERACT) ultrasound (US) working group (WG) operates research activities for the validation of US as an outcome measurement instrument according to the Filter 2.0 framework Methods. From the onset of the WG research in 2005 through now, original publications on definitions and scoring systems for pathophysiological manifestations and elementary lesions of various rheumatic disorders were reviewed Results. Definitions and scoring systems according to new terminology are provided Conclusions. We have redefined OMERACT definitions of US pathology and elementary lesions as well as scoring systems which are now proposed for OMERACT approval for application in clinical trial

Successful Stepwise Development of Patient Research Partnership:14 Years' Experience of Actions and Consequences in Outcome Measures in Rheumatology (OMERACT)

There is increasing interest in making patient participation an integral component of medical research. However, practical guidance on optimizing this engagement in healthcare is scarce. Since 2002, patient involvement has been one of the key features of the Outcome Measures in Rheumatology (OMERACT) international consensus effort. Based on a review of cumulative data from qualitative studies and internal surveys among OMERACT participants, we explored the potential benefits and challenges of involving patient research partners in conferences and working group activities. We supplemented our review with personal experiences and reflections regarding patient participation in the OMERACT process. We found that between 2002 and 2016, 67 patients have attended OMERACT conferences, of whom 28 had sustained involvement; many other patients contributed to OMERACT working groups. Their participation provided face validity to the OMERACT process and expanded the research agenda. Essential facilitators have been the financial commitment to guarantee sustainable involvement of patients at these conferences, procedures for recruitment, selection and support, and dedicated time allocated in the program for patient issues. Current challenges include the representativeness of the patient panel, risk of pseudo-professionalization, and disparity in patients' and researchers' perception of involvement. In conclusion, OMERACT has embedded long-term patient involvement in the consensus-building process on the measurement of core health outcomes. This integrative process continues to evolve iteratively. We believe that the practical points raised here can improve participatory research implementation.</p

Instrument Selection Using the OMERACT Filter 2.1: The OMERACT Methodology.

Objective: Outcome Measures in Rheumatology (OMERACT) Filter 2.1 revised the process used for core outcome measurement set selection to add rigour and transparency in decision making. This paper describes OMERACT’s methodology for instrument selection. Methods: We presented instrument selection processes, tools, and reporting templates at OMERACT 2018, introducing the concept of “3 pillars, 4 questions, 7 measurement properties, 1 answer”. Truth, Discrimination and Feasibility are the three original OMERACT pillars. Based on these, we developed four signaling questions. We introduced the Summary of Measurement Properties (SOMP) table which summarizes the seven measurement properties: Truth (domain match, construct validity), Discrimination (test-retest reliability, longitudinal construct validity (responsiveness), clinical trial discrimination, thresholds of meaning), and Feasibility. These properties address a set of standards which, when met, answer the one question: Is there enough evidence to support the use of this instrument in clinical research of the benefits and harms of treatments in the population and study setting described? The OMERACT Filter 2.1 was piloted on two instruments by the Psoriatic Arthritis Working Group Results: The methodology was reviewed in a full plenary session and facilitated breakout groups. Tools to facilitate retention of the process (i.e., “The OMERACT Way”) were provided. The two instruments were presented and the recommendation of the working group was endorsed in the first OMERACT Filter 2.1 Instrument Selection votes. Conclusion: Instrument Selection using OMERACT Filter 2.1 is feasible and is now being implemented

Improving Benefit-harm Assessment of Therapies from the Patient Perspective: OMERACT Premeeting Toward Consensus on Core Sets for Randomized Controlled Trials

Objective: Outcome Measures in Rheumatology (OMERACT) convened a premeeting in 2018 to bring together patients, regulators, researchers, clinicians, and consumers to build upon previous OMERACT drug safety work, with patients fully engaged throughout all phases. Methods: Day 1 included a brief introduction to the history of OMERACT and methodology, and an overview of current efforts within and outside OMERACT to identify patient-reported medication safety concerns. On Day 2, two working groups presented results; after each, breakout groups were assembled to discuss findings. Results: Five themes pertaining to drug safety measurement emerged. Conclusion: Current approaches have failed to include data from the patient’s perspective. A better understanding of how individuals with rheumatic diseases view potential benefits and harms of therapies is essential

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

Objectives: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number: NCT00767325

The Role of Neutrophils in Spondyloarthritis: A Journey across the Spectrum of Disease Manifestations

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils’ role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets