Publications by authors named "Georgios Filippou"

64 Publications

Identifying potential classification criteria for calcium pyrophosphate deposition disease (CPPD): Item generation and item reduction.

Arthritis Care Res (Hoboken) 2021 May 10. Epub 2021 May 10.

Division of Rheumatology, University of Alabama at Birmingham, Birmingham Veterans Affairs Medical Center, Birmingham, United States.

Objective: Classification criteria for calcium pyrophosphate deposition disease (CPPD) will facilitate clinical research on this common crystalline arthritis. We report on the first two phases of a four-phase process for developing CPPD classification criteria.

Methods: CPPD classification criteria development is overseen by a 12-member Steering Committee. Item generation (Phase I) included a scoping literature review of five literature databases and contributions from a 35-member Combined Expert Committee and two Patient Research Partners. Item reduction and refinement (Phase II) involved a Combined Expert Committee meeting, discussions among Clinical, Imaging, and Laboratory Advisory Groups, and an item rating exercise to assess the influence of individual items toward classification. The Steering Committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development.

Results: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The Advisory Groups eliminated items they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the Steering Committee recommended focusing on imaging of the knee, wrist, and one additional affected joint for calcification suggestive of CPP crystal deposition.

Conclusion: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.
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http://dx.doi.org/10.1002/acr.24619DOI Listing
May 2021

Experience and impact of crystal pyrophosphate deposition (CPPD) from a patient and caregiver perspective: A qualitative exploration from the OMERACT CPPD working group.

Semin Arthritis Rheum 2021 Jun 21;51(3):655-660. Epub 2021 Apr 21.

Academic Rheumatology, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Nottingham, UK.

Objective: To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives.

Methods: Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treatment experiences, and the impact of CPPD on their daily lives. Transcribed interviews were analysed using inductive thematic analysis.

Results: 28 patient interviews, six of which included a caregiver, were conducted across five countries. Acute CPP crystal arthritis flares resulted in temporary but profound disability for most patients, disrupting their ability to go about day-to-day activities, and they sought immediate medical attention. CPPD+OA and chronic CPP crystal inflammatory arthritis presented patients with longer term limitations in daily lives. Patients and their caregivers described these disruptions and limitations, which included a reduced ability or inability to complete household and self-care tasks, exercise, socialise, work and drive. They also described how arthritis pain and resulting limitations adversely impacted upon patients' psychological wellbeing. Delays in referral to specialists and diagnostic uncertainty were described by many. Lack of appropriate treatment or access to treatments only upon worsening of symptoms impacted upon the length of time some patients spent in pain and with functional limitations.

Conclusion: This study is the first to demonstrate the wide-ranging impact of CPPD, and highlights the need for improved diagnosis, physician training, as well as greater emphasis upon finding targeted therapies to specifically treat CPPD.
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http://dx.doi.org/10.1016/j.semarthrit.2021.04.010DOI Listing
June 2021

Consensus-based semi-quantitative ultrasound scoring system for gout lesions: Results of an OMERACT Delphi process and web-reliability exercise.

Semin Arthritis Rheum 2021 Jun 10;51(3):644-649. Epub 2021 Jan 10.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Objective: This study aimed to develop (1) a new ultrasound definition for aggregates and (2) a semi-quantitative ultrasound scoring system (0-3) for tophus, double contour and aggregates. Furthermore, the intra- and inter-reader reliabilities of both the re-defined aggregates and the semi-quantitative scoring system were assessed using static image exercises.

Methods: Thirty-seven rheumatologists were invited. A Delphi process was used for re-defining aggregates and for selecting a semi-quantitative scoring system with >75% agreement obligate for reaching consensus. Subsequently, a web-based exercise on static ultrasound images was conducted in order to assess the reliability of both the re-defined aggregates and the semi-quantitative scoring system.

Results: Twenty rheumatologists contributed to all rounds of the Delphi and image exercises. A consensual re-definition of aggregates was obtained after three Delphi rounds but needed an overarching principle for scoring aggregates in patients. A consensus-based semi-quantitative ultrasound scoring system for gout lesions was developed after two Delphi rounds. The re-definition of aggregates showed good intra- and inter-reader reliability (κ-values 0.71 and 0.61). The reliabilities of the scoring system were good for all lesions with slightly higher intra-reader (κ-values 0.74-0.80) than inter-reader reliabilities (κ-values 0.61-0.67).

Conclusion: A re-definition of aggregates was obtained with a good reliability when assessing static images. The first consensus-based semi-quantitative ultrasound scoring system for gout-specific lesions was developed with good inter- and intra-reader reliability for all lesions when tested in static images. The next step is to assess the reliabilities when scoring lesions in patients.
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http://dx.doi.org/10.1016/j.semarthrit.2020.11.011DOI Listing
June 2021

Outcome domains reported by patients, caregivers, healthcare professionals and stakeholders for calcium pyrophosphate deposition (CPPD): A content analysis based on semi-structured qualitative interviews from the OMERACT CPPD working group.

Semin Arthritis Rheum 2021 Jun 6;51(3):650-654. Epub 2021 Jan 6.

Academic Rheumatology, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Nottingham, UK.

Introduction: Although calcium pyrophosphate deposition (CPPD) disease is common, there are no validated outcome measures for clinical research in this condition. The aim of this study was to generate a list of outcome domains as reported by patients, their caregivers, healthcare professionals (HCPs) and stakeholders to inform the development of an Outcome Measures in Rheumatology (OMERACT) Core Domain Set for CPPD.

Methods: Patients with CPPD and their caregivers, HCPs and stakeholders took part in semi-structured qualitative interviews to explore potential outcome domains for CPPD clinical research relevant to their lived experience and knowledge of CPPD. Interviews were conducted in six countries across three continents. Data was analysed using manifest content analysis to identify outcome domains, which were tabulated and mapped to the core areas as defined by the OMERACT Filter 2.1.

Results: Thirty-six interviews were conducted in total. Participants comprised of 28 patients (six of which included a caregiver), seven HCPs and one stakeholder. The commonly identified (sub-) domains (d) across the 1) abnormalities/manifestations core area were joint pain (d = 35), joint swelling (d = 27), joint stiffness (d = 25), CPPD flares (d = 25); 2) life-impact core area were overall function (d=35), and specifically the ability to complete daily tasks (d = 25); and 3) societal/resource use core area were use of analgesic medicines (d = 26). Patients more commonly reported joint swelling, stiffness and range of movement, and use of analgesics while HCPs more commonly reported domains relating to presence of CPP crystals, radiologic calcification, joint damage, time to diagnosis and suitability of treatment.

Conclusion: Among a number of potential outcome domains identified, articular manifestations, function and analgesic use were most frequently mentioned by participants. These findings will be used to develop an OMERACT Core Domain Set for CPPD.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.021DOI Listing
June 2021

A critical review of the available evidence on the diagnosis and clinical features of CPPD: do we really need imaging?

Clin Rheumatol 2021 Jul 24;40(7):2581-2592. Epub 2020 Nov 24.

Academic Rheumatology, University of Nottingham, Nottingham, UK.

Imaging has been playing an important role in the pathogenetic and clinical characterisation of many rheumatic diseases, especially in the most recent years with the advent of many new, highly technological and promising techniques. Calcium pyrophosphate deposition disease (CPPD) benefited also from these new techniques, most of which can readily identify calcium crystals. Nowadays, imaging is used mainly to identify crystals in joints but given the complexity of CPPD, imaging should be used with an "holistic" approach in order to gain insights in the pathogenesis, spectrum of clinical manifestations and natural history of the disease. Furthermore, overlap or association of CPPD with other prevalent diseases of the elderly makes the differential diagnosis challenging. In this review, we provide a critical review of the current knowledge on the use of imaging both for the identification of crystals and for its application in clinical practice as an aid for determining the impact of the disease on patients.Key Points• CPPD is a complex disease with a wide spectrum of clinical manifestations and understanding of pathogenetic mechanisms and clinical phenotypes is essential for correct characterisation• Imaging has made important advances regarding identification of CPPD in recent years, and new, more sophisticated techniques are under investigation• Imaging has the potential to improve our knowledge on pathogenesis and clinical phenotypes of CPPD• Imaging techniques have to be tested thoroughly for reliability, discrimination and sensitivity to change before they can be implemented in clinical trials.
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http://dx.doi.org/10.1007/s10067-020-05516-3DOI Listing
July 2021

One-year efficacy and safety of single or one to three weekly injections of hylan G-F 20 for knee osteoarthritis: a systematic literature review and meta-analysis.

Clin Rheumatol 2021 Jun 27;40(6):2133-2142. Epub 2020 Oct 27.

ASST Fatebenefratelli, University Hospital "Luigi Sacco", Rheumatology Unit, Via Giovanni Battista Grassi, 74, 20157, Milan, Italy.

The aim of this study was to evaluate the long-term efficacy and safety of single or 1-3 weekly injections of hylan G-F 20 at 1 year following the first injection for knee osteoarthritis (OA). Searches were conducted in PubMed/MEDLINE, Embase, and CENTRAL and included relevant conference proceedings (January 1, 1995-August 17, 2020). Randomized controlled trials (RCTs), non-randomized trials, and observational studies investigating 1-year efficacy and safety of 1-3 weekly injections or single hylan G-F 20 injection for knee OA were included. Primary outcomes were WOMAC pain, physical function, and stiffness. Meta-analyses of RCTs and non-randomized studies were conducted separately. Our search identified 24 eligible studies. Hylan G-F 20, in the meta-analyses of RCTs, showed statistically significant improvement in WOMAC pain (SMCC - 0.98, 95% CI - 1.50, - 0.46), physical function (SMCC - 1.05, 95% CI - 1.28, - 0.83), and stiffness (SMCC - 1.07, 95% CI -1.28, -0.86). Improvement was also seen for VAS pain, SF-36 MCS (mental component summary), and SF-36 PCS (physical component summary). Analyses of non-randomized studies showed similar efficacy estimates. There were no significant differences in efficacy based on injection schedule, nor between RCT and non-randomized studies. Rates of adverse events (AEs) were low for most types of AEs. Hylan G-F 20 (either as single or 1-3 weekly injections) showed improvement in 1-year efficacy outcomes in comparison to baseline and was generally well tolerated. While further research will inform the medical field regarding viscosupplementation treatment options for knee OA, these findings show that hylan G-F 20 at both frequencies/dosages are efficacious and generally well tolerated for long-term use.
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http://dx.doi.org/10.1007/s10067-020-05477-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121739PMC
June 2021

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

Ann Rheum Dis 2021 02 28;80(2):261-267. Epub 2020 Sep 28.

Rheumatology Department, University of Medicine and Pharmacy of Craiova, Craiova, Romania.

Objective: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard.

Methods: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings.

Results: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation.

Conclusion: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.
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http://dx.doi.org/10.1136/annrheumdis-2020-217998DOI Listing
February 2021

Differential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A Systematic Literature Review.

Front Med (Lausanne) 2020 7;7:141. Epub 2020 May 7.

UOC e Sezione di Reumatologia - Dipartimento di Scienze Mediche, Università degli Studi di Ferrara, Ferrara, Italy.

Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.
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http://dx.doi.org/10.3389/fmed.2020.00141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221062PMC
May 2020

The two faces of the same medal… or maybe not? Comparing osteoarthritis and calcium pyrophosphate deposition disease: a laboratory and ultrasonographic study.

Clin Exp Rheumatol 2021 Jan-Feb;39(1):66-72. Epub 2020 Apr 9.

Section of Rheumatology, Department of Medical Sciences, University of Ferrara, Italy.

Objectives: Osteoarthritis (OA) and calcium pyrophosphate deposition disease (CPPD) are frequently associated but the real relation between these diseases is not still understood. The aim of this paper is to investigate the characteristics in terms of inflammation, anatomical changes and synovial fluid (SF) features in knees of patients with OA and CPPD.

Methods: Consecutive patients older than 55 years with knee pain and swelling were enrolled. All patients underwent a complete clinical examination, a US examination of the affected joint, arthrocentesis of the knee and analysis of synovial fluid, including dosing of inorganic ions and number of crystals. The gold standard for the diagnosis was the microscopic analysis of the SF.

Results: Sixty-seven patients were enrolled, 25 affected by OA and 42 by CPPD. At US, a significantly higher amount of effusion and synovitis was identified in patients with CPPD but there were no significant differences regarding structural changes. At the SF analysis, the white blood cell (WBC) count was higher in patients with CPPD who also presented a higher number of polymorphonuclear cells and a lower number of monocytes. Regarding the inorganic ion concentration, the statistical analysis did not reveal any differences. The number of crystals in the SF, correlated with a larger effusion, higher grade of synovitis and a higher WBC count.

Conclusions: A higher degree of inflammation was found in patients with CPPD. The findings suggest that longitudinal studies would be useful to better understand the evolution of the diseases and highlight the need for different treatment strategies.
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February 2021

Utility of Ultrasound and Dual Energy CT in Crystal Disease Diagnosis and Management.

Curr Rheumatol Rep 2020 04 15;22(5):15. Epub 2020 Apr 15.

Dipartimento Scienze Cliniche e Biologiche, Academic Rheumatology Centre, Università degli Studi di Torino, Turin, Italy.

Purpose Of Review: The objective of this review is to critically discuss the latest evidence on the use of ultrasound and dual energy computed tomography (DECT) for the assessment of microcrystalline arthritis.

Recent Findings: Both techniques have been included in the classification and diagnostic criteria for gout, while only ultrasound appears in the diagnostic recommendations for CPPD. Regarding the management of the diseases, there is encouraging evidence for the use of both techniques for the follow-up of gout patients, while very few or null data are available for CPPD. Ultrasound has been adequately validated for the diagnosis of CPPD, while some issues have still to be clarified regarding gout. DECT has also demonstrated to be accurate for gout diagnosis, but very few data are available regarding CPPD. Future research should aim to improve the reliability of both techniques and to create scoring systems for a more accurate follow-up of patients.
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http://dx.doi.org/10.1007/s11926-020-0890-1DOI Listing
April 2020

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

Ann Rheum Dis 2019 11 9;78(11):1592-1600. Epub 2019 Sep 9.

Department of Rheumatology, Hôpital Lariboisière, Paris, France.

Objective: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout.

Methods: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions.

Results: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus).

Conclusion: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.
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http://dx.doi.org/10.1136/annrheumdis-2019-215933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288724PMC
November 2019

Radiomics-Based Assessment of Primary Sjögren's Syndrome From Salivary Gland Ultrasonography Images.

IEEE J Biomed Health Inform 2020 03 18;24(3):835-843. Epub 2019 Jul 18.

Salivary gland ultrasonography (SGUS) has shown good potential in the diagnosis of primary Sjögren's syndrome (pSS). However, a series of international studies have reported needs for improvements of the existing pSS scoring procedures in terms of inter/intra observer reliability before being established as standardized diagnostic tools. The present study aims to solve this problem by employing radiomics features and artificial intelligence (AI) algorithms to make the pSS scoring more objective and faster compared to human expert scoring. The assessment of AI algorithms was performed on a two-centric cohort, which included 600 SGUS images (150 patients) annotated using the original SGUS scoring system proposed in 1992 for pSS. For each image, we extracted 907 histogram-based and descriptive statistics features from segmented salivary glands. Optimal feature subsets were found using the genetic algorithm based wrapper approach. Among the considered algorithms (seven classifiers and five regressors), the best preforming was the multilayer perceptron (MLP) classifier (κ = 0.7). The MLP over-performed average score achieved by the clinicians (κ = 0.67) by the considerable margin, whereas its reliability was on the level of human intra-observer variability (κ = 0.71). The presented findings indicate that the continuously increasing HarmonicSS cohort will enable further advancements in AI-based pSS scoring methods by SGUS. In turn, this may establish SGUS as an effective noninvasive pSS diagnostic tool, with the final goal to supplement current diagnostic tests.
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http://dx.doi.org/10.1109/JBHI.2019.2923773DOI Listing
March 2020

Video clip assessment of a salivary gland ultrasound scoring system in Sjögren's syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise.

Ann Rheum Dis 2019 07 29;78(7):967-973. Epub 2019 Apr 29.

Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.

Objective: To develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren's syndrome (pSS) and to test their intrareader and inter-reader reliability using US video clips.

Methods: Twenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren's syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1-5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions.

Results: Consensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen's kappa 0.81) and inter-reader reliability was good (Light's kappa 0.66).

Conclusion: New definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.
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http://dx.doi.org/10.1136/annrheumdis-2019-215024DOI Listing
July 2019

OMERACT agreement and reliability study of ultrasonographic elementary lesions in osteoarthritis of the foot.

RMD Open 2019 8;5(1):e000795. Epub 2019 Mar 8.

Scienze Cliniche e Biologiche, Università degli Studi di Torino, Rome, Italy.

Objective: To evaluate the level of agreement on ultrasonographic (US) lesions among highly experienced sonographers as well as the intraobserver and interobserver reliability of inflammatory and structural US lesions in patients with osteoarthritis (OA) of the foot.

Methods: After a systematic literature review, a Delphi survey was performed to test definitions of US lesions in OA of the foot, including inflammatory lesions (ie, synovial hypertrophy [SH], joint effusion [JE], power Doppler signal [PD]), and structural abnormalities (ie, cartilage damage [CD] and osteophytes). Subsequently, the reliability of US in assessing the aforementioned lesions was tested on static images as well as during a live exercise. Reliability was assessed by kappa analyses and prevalence-adjusted bias-adjusted kappa (PABAK) on a dichotomous and an ordinal scale.

Results: Intraobserver and interobserver reliability for SH and JE evaluated by binary scoring was good for both components, while the intraobserver reliability for semiquantitative scoring of SH ranged from moderate in the web-based exercise (PABAK 0.49) to good (PABAK 0.8) in the live exercise. Reliability for CD and PD assessments were respectively good and excellent in all exercises (ranged from PABAK 0.61 to 0.79 for CD and 0.88 to 0.95 for PD). The interobserver reliability for the semiquantitative scoring of osteophytes was fair in the live exercise (PABAK 0.36) and moderate in the static exercise (PABAK 0.60).

Conclusions: Consensual US definitions were found to be reliable for assessing inflammatory lesions in OA of the foot, while the use of US to assess structural damage requires further studies.
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http://dx.doi.org/10.1136/rmdopen-2018-000795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443136PMC
April 2020

OMERACT Definitions for Ultrasonographic Pathologies and Elementary Lesions of Rheumatic Disorders 15 Years On.

J Rheumatol 2019 10 1;46(10):1388-1393. Epub 2019 Feb 1.

From the Department of Rheumatology, MC Groep hospitals, Lelystad, the Netherlands; Academic Rheumatology Centre, Università degli Studi di Torino, Turin; Department of Medical Sciences, Section of Rheumatology, University of Ferrara; Azienda Ospedaliero-Universitaria Sant'Anna di Cona, Ferrara, Italy; Department of Rheumatology, Bone and Joint Research Unit, Hospital Universitario Fundación Jiménez Díaz, IIS Fundación Jiménez Díaz; Universidad Autónoma de Madrid; Rheumatology Department, Paediatric Rheumatology Unit, Hospital Universitario Severo Ochoa, Madrid, Spain; Rheumatology Department, National Institute of Rheumatology and Physiotherapy, Budapest, Hungary; Division of Musculoskeletal and Rheumatic Diseases, Instituto Nacional de Rehabilitacion, Mexico City, Mexico; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; Immanuel Krankenhaus Berlin, Medical Center for Rheumatology Berlin-Buch, Berlin, Germany; Rheumatology Department, Cavale Blanche Hospital; Brest Occidentale University, Brest; Rheumatology Department, AP-HP, Hôpital Ambroise Paré, INSERM U1173, Labex Inflamex, Université Versailles St-Quentin en Yvelines, Boulogne-Billancourt, France; Department of Rheumatology, Medical University of Vienna, Vienna, Austria; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds, UK; Department of Rheumatology, University of Adelaide, Adelaide, Australia; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark.

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: Original publications on definitions and scoring systems for pathophysiological manifestations and elementary lesions of various rheumatic disorders were reviewed from the onset of the WG research in 2005.

Results: Definitions and scoring systems according to new terminology are provided.

Conclusion: We have redefined OMERACT US pathology and elementary lesions as well as scoring systems, which are now proposed for OMERACT approval for application in clinical trials.
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http://dx.doi.org/10.3899/jrheum.181095DOI Listing
October 2019

The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study.

Ann Rheum Dis 2018 09 9;77(9):1283-1289. Epub 2018 Jun 9.

Rheumatology Unit, A.O.U. University Clinic Cagliari, Monserrato, Italy.

Objective: To define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation.

Methods: A multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models.

Results: 361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months.

Conclusions: PD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.
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http://dx.doi.org/10.1136/annrheumdis-2018-213217DOI Listing
September 2018

Identification of calcium pyrophosphate deposition disease (CPPD) by ultrasound: reliability of the OMERACT definitions in an extended set of joints-an international multiobserver study by the OMERACT Calcium Pyrophosphate Deposition Disease Ultrasound Subtask Force.

Ann Rheum Dis 2018 08 13;77(8):1194-1199. Epub 2018 Mar 13.

Lausanne University Hospital, Lausanne, Switzerland.

Objectives: To assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints.

Methods: A web-based exercise and subsequent patient-based exercise were carried out. A panel of 30 OMERACT members, participated at the web-based exercise by evaluating twice a set of US images for the presence/absence of CPPD. Afterwards, 19 members of the panel met in Siena, Italy, for the patient-based exercise. During the exercise, all sonographers examined twice eight patients for the presence/absence of CPPD at the same joints. Intraoberserver and interobserver kappa values were calculated for both exercises.

Results: The web-based exercise yielded high kappa values both in intraobserver and interobserver evaluation for all sites, while in the patient-based exercise, inter-reader agreement was acceptable for the TFC and the AC. TFC reached high interobserver and intraobserver k values in both exercises, ranging from 0.75 to 0.87 (good to excellent agreement). AC reached moderate kappa values, from 0.51 to 0.85 (moderate to excellent agreement) and can readily be used for US CPPD identification.

Conclusions: Based on the results of our exercise, the OMERACT US definitions for the identification of CPPD demonstrated to be reliable when applied to the TFC and AC. Other sites reached good kappa values in the web-based exercise but failed to achieve good reproducibility at the patient-based exercise, meaning the scanning method must be further refined.
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http://dx.doi.org/10.1136/annrheumdis-2017-212542DOI Listing
August 2018

The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology.

Ann Rheum Dis 2017 Dec 16;76(12):1974-1979. Epub 2017 Aug 16.

Department of Rheumatology, Sf. Maria Clinical Hospital, Bucharest, Romania.

Background: In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an update of these guidelines.

Objectives: To update the existing MSUS guidelines in rheumatology as well as to extend their scope to other anatomic structures relevant for rheumatology.

Methods: The project consisted of the following steps: (1) a systematic literature review of MSUS evaluable structures; (2) a Delphi survey among rheumatologist and radiologist experts in MSUS to select MS and non-MS anatomic structures evaluable by US that are relevant to rheumatology, to select abnormalities evaluable by US and to prioritise these pathologies for rheumatology and (3) a nominal group technique to achieve consensus on the US scanning procedures and to produce an electronic illustrated manual (ie, App of these procedures).

Results: Structures from nine MS and non-MS areas (ie, shoulder, elbow, wrist and hand, hip, knee, ankle and foot, peripheral nerves, salivary glands and vessels) were selected for MSUS in rheumatic and musculoskeletal diseases (RMD) and their detailed scanning procedures (ie, patient position, probe placement, scanning method and bony/other landmarks) were used to produce the App. In addition, US evaluable abnormalities present in RMD for each anatomic structure and their relevance for rheumatology were agreed on by the MSUS experts.

Conclusions: This task force has produced a consensus-based comprehensive and practical framework on standardised procedures for MSUS imaging in rheumatology.
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http://dx.doi.org/10.1136/annrheumdis-2017-211585DOI Listing
December 2017

Definition and Reliability Assessment of Elementary Ultrasonographic Findings in Calcium Pyrophosphate Deposition Disease: A Study by the OMERACT Calcium Pyrophosphate Deposition Disease Ultrasound Subtask Force.

J Rheumatol 2017 Nov 1;44(11):1744-1749. Epub 2017 Mar 1.

From the University of Siena, Siena; Italian Society for Rheumatology (SIR) Epidemiology Unit, Milan; University of Pisa, Pisa; Università Politecnica delle Marche, Jesi; Internal Medicine Division, San Jacopo Hospital, Pistoia; Università degli Studi di Torino, Turin, Italy; University of Belgrade, Belgrade, Serbia; Department of Rheumatology, MC Groep, Lelystad, the Netherlands; APHP, Hôpital Ambroise Paré, Rheumatology Department, Boulogne-Billancourt; INSERM U1173, Laboratoire d'Excellence INFLAMEX, UFR Simone Veil, Versailles-Saint-Quentin University, Saint-Quentin en Yvelines, France; Division of Musculoskeletal and Rheumatic Diseases, Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra Ibarra, Mexico City, Mexico; Rehabilitation Clinical Hospital, Cluj-Napoca; Sf. Maria Hospital, Bucharest, Romania; Instituto Poal, University of Barcelona, Barcelona; Department of Rheumatology, Joint and Bone Research Unit, Hospital Universitario Fundación Jimenez Deaz and Autónoma University, Madrid, Spain; Immanuel Krankenhaus Berlin, Medical Center for Rheumatology Berlin-Buch Berlin, Berlin, Germany; Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark; Lausanne University Hospital, Lausanne, Switzerland.

Objective: To define the ultrasonographic characteristics of calcium pyrophosphate crystal (CPP) deposits in joints and periarticular tissues and to evaluate the intra- and interobserver reliability of expert ultrasonographers in the assessment of CPP deposition disease (CPPD) according to the new definitions.

Methods: After a systematic literature review, a Delphi survey was circulated among a group of expert ultrasonographers, who were members of the CPPD Ultrasound (US) Outcome Measures in Rheumatology (OMERACT) subtask force, to obtain definitions of the US characteristics of CPPD at the level of fibrocartilage (FC), hyaline cartilage (HC), tendon, and synovial fluid (SF). Subsequently, the reliability of US in assessing CPPD at knee and wrist levels according to the agreed definitions was tested in static images and in patients with CPPD. Cohen's κ was used for statistical analysis.

Results: HC and FC of the knee yielded the highest interobserver κ values among all the structures examined, in both the Web-based (0.73 for HC and 0.58 for FC) and patient-based exercises (0.55 for the HC and 0.64 for the FC). Kappa values for the other structures were lower, ranging from 0.28 in tendons to 0.50 in SF in the static exercise and from 0.09 (proximal patellar tendon) to 0.27 (triangular FC of the wrist) in the patient-based exercise.

Conclusion: The new OMERACT definitions for the US identification of CPPD proved to be reliable at the level of the HC and FC of the knee. Further studies are needed to better define the US characteristics of CPPD and optimize the scanning technique in other anatomical sites.
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http://dx.doi.org/10.3899/jrheum.161057DOI Listing
November 2017

The OMERACT Ultrasound Group: A Report from the OMERACT 2016 Meeting and Perspectives.

J Rheumatol 2017 Nov 1;44(11):1740-1743. Epub 2017 Feb 1.

From the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen; Department of Rheumatology, Zealand's University Hospital, Køge, Denmark; Dipartimento Scienze Cliniche e Biologiche - Reumatologia, Università degli Studi di Torino, Turin; Department of Medicine, Surgery and Neurosciences, Rheumatology Section, University of Siena, Siena; Pediatric Rheumatology Unit, IRCCS Ospedale Pediatrico Bambino Gesù, Rome; Internal Medicine Department, Azienda Socio Sanitaria Territoriale di Mantova, C. Poma Hospital, Mantua, Italy; Department of Rheumatology, MC Groep, Lelystad; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Rheumatology, Joint and Bone Research Unit, Hospital Universitario Fundación Jiménez Díaz; Autónoma University; Hospital Universitario Severo Ochoa, Madrid, Spain; Clinic Center, Faculty of Medicine, University of Niš, Niš; Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Rheumatology Research Group, The University of Birmingham, Birmingham; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK; Department of Rheumatology and Clinical Immunology, Faculty of Medicine, University of Freiburg, Freiburg; Charite University Hospital, Humboldt University; Immanuel Krankenhaus Berlin, Medical Center for Rheumatology Berlin-Buch; Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany; APHP, Department of Rheumatology, CHU Pitie-Salpetriere, Paris 6 University, GRC-UPMC 08, Pierre Louis Institute of Epidemiology and Public Health; APHP, Hôpital Ambroise Paré, Rheumatology Department, 92100 Boulogne-Billancourt; INSERM U1173, Laboratoire d'Excellence INFLAMEX, UFR Simone Veil, Versailles-Saint-Quentin University, 78180 Saint-Quentin en Yvelines, Paris, France; Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan; Department of Rheumatology, Royal Perth Hospital, Perth, Australia; Instituto Nacional de Rehabilitacion, Mexico City, Mexico; Rheumatology Institute of Rheumatology and Orthopedics, Royal Prince Alfred Hospital, Camperdown, Australia; Department of Rheumatology, Université catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires Saint Luc, Brussels, Belgium.

Objective: To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic arthritis (JIA).

Methods: For minimal disease activity, healthy controls (HC) and patients with early arthritis (EA) who were naive to disease-modifying antirheumatic drugs were recruited from 2 centers. US was performed of the hands and feet, and scored semiquantitatively (0-3) for synovial hypertrophy (SH) and power Doppler (PD). Synovial effusion (SE) was scored a binary variable. For JIA, a Delphi approach and subsequent validation in static images and patient-based exercises were used to developed preliminary definitions for synovitis and a scoring system.

Results: For minimal disease activity, 7% HC had at least 1 joint abnormality versus 30% in the EA group. In HC, the findings of SH and PD were predominantly grade 1 whereas all grades were seen in the EA cohort, but SE was rare. In JIA, synovitis can be diagnosed based on B-mode findings alone because of the presence of physiological vascularization. A semiquantitative scoring system (0-3) for synovitis for both B-mode and Doppler were developed in which the cutoff between Doppler grade 2 and grade 3 was 30%.

Conclusion: The first step has been taken to define the threshold for minimal disease activity in RA by US and to define and develop a scoring system for synovitis in JIA. Further steps are planned for the continuous validation of US in these areas.
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http://dx.doi.org/10.3899/jrheum.161240DOI Listing
November 2017

The big misunderstanding in rheumatology: Ultrasound is just equipment it cannot replace a doctor!

Med Ultrason 2016 Sep;18(3):273-4

Ultrasound Unit, Dipartimento Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.

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http://dx.doi.org/10.11152/mu.2013.2066.183.gefDOI Listing
September 2016

Ultrasound-detected tenosynovitis independently associates with patient-reported flare in patients with rheumatoid arthritis in clinical remission: results from the observational study STARTER of the Italian Society for Rheumatology.

Rheumatology (Oxford) 2016 Oct 27;55(10):1826-36. Epub 2016 Jun 27.

Rheumatology Unit, Bolzano Hospital, Bolzano.

Objectives: This study aimed to estimate the prevalence of US-detected tenosynovitis in RA patients in clinical remission and to explore its clinical correlates.

Methods: A total of 427 RA patients in clinical remission were consecutively enrolled from 25 Italian rheumatology centres. Tenosynovitis and synovitis were scored by US grey scale (GS) and power Doppler (PD) semi-quantitative scoring systems at wrist and hand joints. Complete clinical assessment was performed by rheumatologists blinded to the US results. A flare questionnaire was used to assess unstable remission (primary outcome), HAQ for functional disability and radiographic erosions for damage (secondary outcomes). Cross-sectional relationships between the presence of each US finding and outcome variables are presented as odds ratios (ORs) and 95% CIs, both crude and adjusted for pre-specified confounders.

Results: The prevalence of tenosynovitis in clinical remission was 52.5% (95% CI 0.48, 0.57) for GS and 22.7% (95% CI 0.19, 0.27) for PD, while the prevalence of synovitis was 71.6% (95% CI 0.67, 0.76) for GS and 42% (95% CI 0.37, 0.47) for PD. Among clinical correlates, PD tenosynovitis associated with lower remission duration and morning stiffness while PD synovitis did not. Only PD tenosynovitis showed a significant association with the flare questionnaire [OR 1.95 (95% CI 1.17, 3.26)]. No cross-sectional associations were found with the HAQ. The presence of radiographic erosions associated with GS and PD synovitis but not with tenosynovitis.

Conclusions: US-detected tenosynovitis is a frequent finding in RA patients in clinical remission and associates with unstable remission.
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http://dx.doi.org/10.1093/rheumatology/kew258DOI Listing
October 2016

Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept: results from the APPRAISE study.

RMD Open 2016 5;2(1):e000237. Epub 2016 May 5.

Medical Affairs , Bristol-Myers Squibb , Rueil-Malmaison , France.

Objectives: To explore whether changes in a composite (power Doppler/greyscale ultrasound (PDUS)) synovitis score, developed by the OMERACT-EULAR-Ultrasound Task Force, predict disease activity outcomes in rheumatoid arthritis (RA).

Methods: Patients with RA who were methotrexate inadequate responders starting abatacept were evaluated. Individual joint PDUS scores were combined in the Global OMERACT-EULAR Synovitis Score (GLOESS) for metacarpophalangeal joints (MCPs) 2-5, all joints (22 paired) and a reduced (9 paired) joint set. The predictive value of changes in GLOESS at week 1-16 evaluations for clinical status and response (Disease Activity Score (DAS)28 (C reactive protein, CRP) <2.6; DAS28(CRP) ≤3.2; DAS28(CRP) ≥1.2 improvement) up to week 24, and correlations between DAS28 and GLOESS were assessed.

Results: Eighty-nine patients completed the 24-week treatment period. Changes in GLOESS (MCPs 2-5) from weeks 1 to 16 were unable to predict DAS28 outcomes up to week 24. However, significant improvements in GLOESS (MCPs 2-5) were observed at week 12 in patients with DAS28 ≥1.2 improvement at week 24 versus those who did not achieve that clinical response. In patients achieving DAS28 ≥1.2 improvement or DAS28 ≤3.2 at week 24, changes in GLOESS (22 and 9 paired joint sets) were greater in patients who already achieved DAS28 ≥1.2 at week 12 than in those who did not. No significant correlations were found between changes in DAS28 and GLOESS definitions at any time point.

Conclusions: PDUS was not correlated with clinical status or response as measured by DAS28-derived criteria, and PDUS changes were not predictive of clinical outcome. The discrepancies require further exploration.

Trial Registration Number: NCT00767325; Results.
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http://dx.doi.org/10.1136/rmdopen-2015-000237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860864PMC
May 2016

Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease.

Clin Exp Rheumatol 2016 Mar-Apr;34(2):254-60. Epub 2016 Feb 9.

Department of Medicine, Surgery and Neurosciences, Rheumatology Section, University of Siena, Italy.

Objectives: To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard.

Methods: We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee.

Results: 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests.

Conclusions: US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis.
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July 2016

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.

Ann Rheum Dis 2016 Oct 20;75(10):1763-9. Epub 2015 Nov 20.

Medical Affairs, Bristol-Myers Squibb, Rueil-Malmaison, France.

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.
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http://dx.doi.org/10.1136/annrheumdis-2015-207709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036216PMC
October 2016

Infantile perianal pyramidal protrusion: a case report with dermoscopy and ultrasound findings.

Dermatol Pract Concept 2015 Apr 30;5(2):125-8. Epub 2015 Apr 30.

Department of Medicine, Surgery and Neurosciences, Dermatology Section, University of Siena, Italy.

Infantile perianal pyramidal protrusion, it is a rare benign cutaneous condition described in relatively recent times. It is considered to be under-reported in the pediatric literature because it is often mistaken for other conditions. The unawareness of this lesion may be responsible for an excessive concern both in physician and in parents, which leads to overly aggressive and unnecessary treatments. Thus its recognition has many implications regarding proper management and treatment. We report a typical presentation of IPPP in which the diagnosis was based on the use of non-invasive diagnostic tools and in particular of dermoscopy and ultrasonography.
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http://dx.doi.org/10.5826/dpc.0502a25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462916PMC
April 2015

Subcutaneous fat necrosis in a newborn after brief therapeutic hypothermia: ultrasonographic examination.

Pediatr Dermatol 2015 May-Jun;32(3):427-9. Epub 2014 Dec 10.

Department of Dermatology, University of Siena, Siena, Italy.

A 7-day-old infant developed erythematous indurated plaques on the back, left shoulder, and arm a few days after therapeutic hypothermia. Ultrasonographic study along with Doppler blood flow analysis of lesional skin areas revealed flogistic fat involvement and calcifications. On the basis of clinical appearance, patient history, and ultrasonographic study, a diagnosis of subcutaneous fat necrosis of the newborn was established.
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http://dx.doi.org/10.1111/pde.12454DOI Listing
April 2016

A mimic of first dorsal interosseus atrophy revealed by ultrasound study.

Clin Neurophysiol 2015 Feb 20;126(2):423-4. Epub 2014 May 20.

Department of Medical, Surgical and Neurological Sciences, University of Siena, Italy.

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http://dx.doi.org/10.1016/j.clinph.2014.05.006DOI Listing
February 2015

Disease Activity and Bone Mineral Density of MCP Joints in Patients with Rheumatoid and Psoriatic Arthritis: Is There a Correlation?-A Study in Patients Treated with Methotrexate and an Anti-TNF α Agent.

ISRN Rheumatol 2013 7;2013:708323. Epub 2013 Dec 7.

Department of Medicine, Surgery and Neurosciences-Rheumatology Department, University of Siena, Policlinico le Scotte, Viale Bracci 16, 53100 Siena, Italy.

Background. Bone damage in rheumatoid arthritis (RA) and in psoriatic arthritis (PsA) includes an accelerated bone mineral density (BMD) reduction. The objective was to evaluate BMD variations of the metacarpophalangeal joints (MCPs) in patients starting treatment with methotrexate (MTX) or etanercept. Methods. Patients affected by RA or PsA with hand joints involvement and with moderate or high disease activity, were enrolled in this study. All patients underwent clinical examination, laboratory exams, and a DXA scan of the most affected hand, as assessed with an ultrasound examination at the baseline, at the time of enrolment and after 1, 3, 6, and 12 months. Patients non-responders to MTX received combination therapy, while patients with no previous treatment initiated MTX. Results. 22 patients were enrolled. In both RA and PsA groups, BMD increased independently of the treatment. However, in the patients affected by RA, a slight BMD decrease was observed at the last checkup. Globally, the BMD variations of the MCPs were strongly correlated with the disease activity. At the reduction of DAS28, the scores corresponded an increase of BMD. Conclusions. MCPs BMD is inversely correlated to disease activity. BMD increase seems to be correlated with the response to treatment and not with the drug itself.
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http://dx.doi.org/10.1155/2013/708323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871921PMC
January 2014