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Objectives: To identify the prevalence of calcium pyrophosphate crystal deposition (CPPD) using ultrasound and conventional radiology at peripheral joints in patients with suspected or definite CPPD. Methods: A systematic literature search was performed in PubMed and Embase using pre-defined search strategies from inception to April 2021 to identify studies that evaluated conventional radiology and ultrasound in detecting CPPD at peripheral joints, including definite or suspected CPPD [Research question 1 (RQ1) and Research Question 2 (RQ2), respectively]. For the meta-analysis, the first, second, and third sub-analysis included studies with the knee, and knee or wrist as the index joint for CPPD (without restrictions on the reference standard) and synovial fluid analysis or histology as a reference standard (without restrictions on the index joint), respectively. Results: One-thousand eight hundred and twenty-seven manuscripts were identified, of which 94 articles were finally included. Twenty-two and seventy-two papers were included in RQ1 and RQ2, respectively. The knee had the highest prevalence for RQ1 and RQ2 by both conventional radiology and ultrasound, followed by the wrist with the highest prevalence for RQ1. The hand had the lowest CPPD prevalence. The third sub-analysis showed a higher CPPD prevalence on ultrasound than conventional radiology at the knee (only data available). Conclusion: Among all peripheral joints, the knees and wrists could be regarded as the target joints for CPPD detection by imaging. Furthermore, ultrasound seems to detect a higher number of calcium pyrophosphate deposits than conventional radiology, even when using a more restrictive reference standard.

Objectives: To assess the reliability and diagnostic accuracy of new radiographic definitions for calcium pyrophosphate deposition (CPPD) identification, developed by an international multidisciplinary working group. Methods: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and two rheumatologists assessed twice the images for presence/absence of CPPD on menisci, hyaline cartilage, tendons, joint capsule, synovial membrane, using the new definitions. In case of disagreement, a consensus decision was taken and considered for the assessment of diagnostic performance. Histological examination of specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa (PABAK) was used to assess the reliability. Diagnostic performance statistics were calculated. Results: Sixty-seven participants were enrolled for the reliability study. The inter-observer reliability was substantial in most of the assessed structures when considering all 4 readers (kappa range 0.59 – 0.90), substantial to almost perfect among radiologists (kappa range 0.70-0.91), and moderate to almost perfect among rheumatologists (kappa range 0.46 – 0.88). The intra-observer reliability was substantial to almost perfect for all the observers (kappa range 0.70 – 1). Fifty-one patients were enrolled for the accuracy study. Radiography demonstrated to be specific for CPPD (92%), but sensitivity remained low in all sites and in the overall diagnosis (54%). Conclusion: The new imaging definitions of CPPD are highly specific against the gold standard of histological diagnosis; when described findings are present these definitions allow for a definite diagnosis of CPPD, rather than other calcium-containing crystal depositions; instead a negative finding does not exclude the diagnosis.

Objective: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. Methods: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. Results: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). Conclusion: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

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.

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.

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 k was used for statistical analysis. Results: HC and FC of the knee yielded the highest interobserver k 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. The Journal of Rheumatology

Objective: Ultrasonography (US) demonstrated to be a promising tool for the diagnosis of calcium pyrophosphate dihydrate deposition disease (CPPD). The aim of this systematic literature review (SLR) was to collect the definitions for the US elementary lesions and to summarize the available data about US diagnostic accuracy in CPPD. Methods: We systematically reviewed all the studies that considered US as the index test for CPPD diagnosis without restrictions about the reference test or that provided definitions about US identification of CPPD. Sensitivity and specificity were calculated for each study and definitions were extrapolated. Subgroup analyses were planned by anatomical site included in the index text and different reference standards. Results: Thirty-seven studies were included in this review. All the studies were eligible for the collection of US findings and all definitions were summarized. US description of elementary lesions appeared heterogeneous among the studies. Regarding US accuracy, 13 articles entered in the meta-analysis. Considering each joint structure, the sensitivity ranged between 0.77 (0.63-0.87) and 0.34 (0.16-0.58) while the specificity varies between 1.00 (0.89-1.00) and 0.92 (0.16-1.00). Considering the reference standards used, the sensibility ranged between 0.34 (0.02-0.65) and 0.87 (0.76-0.99) while specificity ranged between 0.84 (0.52-1.00) and 1.00 (0.99-1.00). Conclusion: US is potentially a useful tool for the diagnosis of CPPD but universally accepted definitions and further testing are necessary in order to assess the role of the technique in the diagnostic process.

Objective 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. Conclusion 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.

Objective. To assess the efficacy of tidal irrigation in patients with Milwaukee shoulder syndrome (MSS). Methods. Ten patients with clinical diagnosis of MSS underwent ultrasound examination and tidal irrigation followed by instillation of methylprednisolone and tranexamic acid. A single shoulder was treated in 9 cases; in one patient with bilateral shoulder involvement, both shoulders were treated at different times. Six patients had longlasting disease (Group A) unsuccessfully treated with repeated joint fluid aspirations and intraarticular corticosteroid injections. Four patients had recent-onset illness without radiologic damage but with clinical findings similar to classic MSS (Group B), not previously treated with corticosteroid injections with symptoms dating from 3 months or less. Clinical examination including evaluation of adverse events, range of motion, and pain score by a 100 mm horizontal visual analog scale was scheduled just before tidal irrigation and after 2 and 6 months following the procedure in all cases. Results. Short- and longterm safety was excellent in all patients. Group A patients experienced short-lived improvement so that tidal irrigation had to be repeated within 6 to 10 months. No further therapy was necessary in any of the Group B patients during a mean followup of 16.5 months (range 12-24) due to a persistent clinical improvement without clinically detectable joint effusion. Conclusion. Closed-needle joint irrigation is a minimally invasive procedure, which led to a significant improvement in both pain and active motion in patients with longstanding symptoms. Patients with recent-onset disease recovered completely.