Faculty Bibliography

OBJECTIVE:The aims of this study were to systematically review clinimetrics of commonly assessed ultrasound pathologies in knee, hip and hand osteoarthritis (OA), and to conduct a meta-analysis for each clinimetric. METHODS:Medline, Embase, and Cochrane Library databases were searched from their inceptions to September 2016. According to the Outcome Measures in Rheumatology (OMERACT) Instrument Selection Algorithm, data extraction focused on ultrasound technical features and performance metrics. Methodological quality was assessed with modified 19-item Downs and Black score and 11-item Quality Appraisal of Diagnostic Reliability (QAREL) score. Separate meta-analyses were performed for clinimetrics: (1) inter-rater/intra-rater reliability; (2) construct validity; (3) criteria validity; and (4) internal/external responsiveness. Statistical Package for the Social Sciences (SPSS), Excel and Comprehensive Meta-analysis were used. RESULT/RESULTS:Our search identified 1126 records; of these, 100 were eligible, including a total of 8542 patients and 32,373 joints. The average Downs and Black score was 13.01, and average QAREL was 5.93. The stratified meta-analysis was performed only for knee OA, which demonstrated moderate to substantial reliability [minimum kappa > 0.44(0.15,0.74), minimum intraclass correlation coefficient (ICC) > 0.82(0.73-0.89)], weak construct validity against pain (r = 0.12 to 0.27), function (r = 0.15 to 0.23), and blood biomarkers (r = 0.01 to 0.21), but weak to strong correlation with plain radiography (r = 0.13 to 0.60), strong association with Magnetic Resonance Imaging (MRI) [minimum r = 0.60(0.52,0.67)] and strong discrimination against symptomatic patients (OR = 3.08 to 7.46). There was strong criterion validity against cartilage histology [r = 0.66(-0.05,0.93)], and small to moderate internal [standardized mean difference(SMD) = 0.20 to 0.58] and external (r = 0.35 to 0.43) responsiveness to interventions. CONCLUSION/CONCLUSIONS:Ultrasound demonstrated strong criterion validity with cartilage histology, poor to strong correlation with patient findings and MRI, moderate reliability, and low responsiveness to interventions. PROSPERO REGISTRATION NO/UNASSIGNED:CRD42016039954.

Tophaceous gout is painful and impairs quality of life. The optimal modality for assessing tophus resolution in response to urate-lowering treatment remains poorly defined. Using pegloticase as a model system for resolving tophi, we compared multiple imaging and physical diagnostic strategies for assessing tophus resolution. A 32-year-old subject with chronic refractory tophaceous gout was enrolled and received 6 months of pegloticase treatment. Measurements of tophi using vernier calipers (monthly), photographs and musculoskeletal ultrasound (MSK-US; every 3 months), and dual-energy CT (DECT) were compared. Pegloticase persistently lowered the patient's sUA to <0.5 mg/dl. After 6 months, caliper measurements revealed 73, 60, and 61% reductions of three index tophi, while MSK-US revealed 47, 65, and 48% reductions. In contrast, DECT revealed 100% resolution of monosodium urate deposition in all three index tophi, and resolution or improvement of all other tophi identified. On caliper and MSK-US measurement, index tophus size fluctuated, with some lesions enlarging before ultimately contracting. Correlation between assessment modalities during tophus resolution may be poor. DECT identifies urate deposits invisible to physical exam and reveals that some urate deposits completely resolve even as their physically/sonographically measurable lesions persist. Recognition of urate resorption during the urate-lowering process may be confounded by fluctuating lesion volumes during initial tophus breakdown. While DECT was superior for identifying total (including occult) urate deposition, and assessing volume of deposits, other modalities may permit better assessment of non-urate tophus components.

OBJECTIVE: OA pathogenesis includes both mechanical and inflammatory features. Studies have implicated synovial fluid urate (UA) as a potential OA biomarker, possibly reflecting chondrocyte damage. Whether serum urate (sUA) levels reflect/contribute to OA is unknown. We investigated whether sUA predicts OA progression in a non-gout knee OA population. METHODS: Eighty-eight subjects with medial knee OA (BMI <33) but without gout were included. Baseline sUA was measured in previously banked serum. At 0 and 24 months, subjects underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs to determine joint space width (JSW) and Kellgren-Lawrence (KL) grades. Joint space narrowing (JSN) was determined as JSW change from 0 to 24 months. Twenty-seven subjects underwent baseline contrast-enhanced 3T knee MRI for synovial volume (SV) assessment. RESULTS: sUA correlated with JSN in both univariate (r=0.40, p/=6.8; JSN of 0.31 mm for sUA<6.8, p<0.01). Baseline sUA distinguished progressors (JSN>0.2mm) and fast progressors (JSN>0.5mm) from nonprogressors (JSN