GOSPEL 4 - Patients with early onset gout develop earlier severe joint involvement and metabolic comorbid conditions

International audienc

Difficult-to-treat gout flares eligibility for interleukin-1 inhibition in private practice is uncommon according to current EMA approval

International audienc

Improving cognition in people with multiple sclerosis: study protocol for a multiarm, randomised, blinded trial of multidomain cognitive rehabilitation using a video-serious game (E-SEP cognition)

Introduction Multiple sclerosis (MS) is a prevalent neurological disease characterised by disseminated areas of demyelination and atrophy within the central nervous system, inducing cognitive disorders in 45%–65% of persons with MS (PwMS). Neuropsychology and neuroimaging studies provide evidence of the effectiveness of cognitive rehabilitation interventions, including memory and attention. Recently, serious game therapy (SGT) has been used in rehabilitation to improve cognitive processing speed. The aim of this study is to describe the protocol of a randomised controlled trial (RCT) to test the efficacy of a tablet-based cognitive home intervention among ambulatory PwMS, in comparison to a standardised neuropsychological rehabilitation.Methods and analysis This will be a parallel-assignment, double-blinded, RCT. One hundred and fifty (75 per arm) PwMS will be randomly assigned to receive cognitive rehabilitation session over 4 months (four 20-min sessions/week) of either: (1) tablet-based SGT or (2) conventional cognitive exercises. The same assessor will evaluate outcome measures at three points: at baseline (T0), after the 16 therapy sessions weeks (T1), and 6 months after the end of treatment (T2). The primary outcomes were the scores from the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Data analysis will be performed to compare the efficacy of the two treatments. We expect superior efficiency of tablet-based SGT in contrast to conventional cognitive exercises, based on BICAMS measures of speed processing information and episodic memory.Ethics and dissemination The trial protocol is registered on ClinicalTrials.Gov (NCT04694534) and benefits from a favourable opinion from an ethics committee (RC-P0066-2018-A00411-54)

Ultrasonography and dual-energy computed tomography provide different quantification of urate burden in gout: results from a cross-sectional study

Abstract Background Ultrasonography (US) and dual-energy computed tomography (DECT) can assess urate burden in gout. The objective of this study was to compare the quantification of urate deposition provided by US to the one provided by DECT. Methods Patients with a diagnosis of gout were prospectively recruited to undergo quantification of urate deposition using US and DECT. US examination for tophi and the double contour (DC) sign was performed on the knees and feet and corresponding DECT scans provided volumes of tophi and of overall urate deposition. The primary endpoint was the intra-class correlation coefficient (ICC) of the volume of the index tophus measured by US and DECT and its 95% confidence interval (CI 95%). Results Of the 64 patients included, 34 presented with at least one tophus on US. DECT inter-reader agreement for urate deposition was perfect with an ICC of 1 (1–1) and good for the measurement of the index tophus with an ICC of 0.69 (0.47–0.83). The ICC for the measurement of the index tophus between the two techniques was poor with a value of 0.45 (0.1–0.71). The average ratio between the index tophi volume as assessed by DECT and US was 0.65. The number of DC-positive joints did not correlate with DECT volume of overall deposits (Spearman correlation coefficient of 0.23). Conclusions DECT measurements of tophi give smaller volumes to the same tophi measured with US, and US signs of urate deposition in joints do not correlate with overall DECT volumes of extra-articular deposition

The lack of association between the burden of monosodium urate crystals assessed with dual-energy computed tomography or ultrasonography with cardiovascular risk in the commonly high-risk gout patient

Abstract Background Gout is associated with higher cardiovascular risk that increases with disease severity. The objective of this study was to explore the relationship between the extent of monosodium urate (MSU) crystal deposition, assessed with ultrasonography (US) and dual-energy computed tomography (DECT), and cardiovascular risk. Methods Gout patients were included in this cross-sectional study to undergo DECT scans for the assessment of total MSU volume deposition in the knees and feet, and US to evaluate the number of joints with the double contour (DC) sign. Participants were screened for traditional cardiovascular risk factors, and levels of the American College of Cardiology (ACC)/American Heart Association (AHA) 10-year risk for heart disease or stroke were calculated. The primary endpoint was the Spearman correlation coefficient ρ between DECT MSU volume and cardiovascular risk. Results A total of 42 patients were included; they were predominantly male (40/42) and aged 63.0 ± 13.2 years. Overall, 28/42 patients presented with the metabolic syndrome and the average 10-year coronary event or stroke risk according to the ACC/AHA (n = 33) was 21 ± 15%. Correlations between DECT volumes of MSU deposits in the knees, feet, and knees + feet and cardiovascular risk according to the ACC/AHA were very poor, with ρ = 0.18, −0.01, and 0.13, respectively. The was no correlation between the number of joints with the DC sign and cardiovascular risk (ρ = −0.07). DECT MSU deposit volume was similar in patients with and without metabolic syndrome (p = 0.29). Conclusions The extent of MSU burden does not increase the estimated risk of cardiovascular events in gout patients

Monosodium urate burden assessed with dual-energy computed tomography predicts the risk of flares in gout: a 12-month observational study

Abstract Background Predicting the risk of flares in patients with gout is a challenge and the link between urate burden and the risk of gout flare is unclear. The objective of this study was to determine if the extent of monosodium urate (MSU) burden measured with dual-energy computed tomography (DECT) and ultrasonography (US) is predictive of the risk of gout flares. Methods This prospective observational study recruited patients with gout to undergo MSU burden assessment with DECT (volume of deposits) and US (double contour sign) scans of the knees and feet. Patients attended follow-up visits at 3, 6 and 12 months. Patients having presented with at least one flare at 6 months were compared to those who did not flare. Odds ratios (ORs) (95% confidence interval) for the risk of flare were calculated. Results Overall, 64/78 patients included attended at least one follow-up visit. In bivariate analysis, the number of joints with the double contour sign was not associated with the risk of flare (p = 0.67). Multivariate analysis retained a unique variable: DECT MSU volume of the feet. For each 1 cm3 increase in DECT MSU volume in foot deposits, the risk of flare increased 2.03-fold during the first 6 months after initial assessment (OR 2.03 (1.15–4.38)). The threshold volume best discriminating patients with and without flare was 0.81 cm3 (specificity 61%, sensitivity 77%). Conclusions This is the first study showing that the extent of MSU burden measured with DECT but not US is predictive of the risk of flares

Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization.

To determine changes of subchondral bone composition, micro-structure, bone marrow adiposity and micro-vascular perfusion in end-stage osteonecrosis of the femoral head (ONFH) compared to osteoarthritis (OA) using a combined in vivo and ex vivo approach. Male patients up to 70 years old referred for total hip replacement surgery for end-stage ONFH were included (n=14). Fifteen patients with OA were controls. Pre-operative MRI was used to assess bone perfusion (dynamic contrast-enhanced (DCE) sequences) and marrow fat content (chemical shift imaging). Three distinct zones of femoral head subchondral bone - necrotic, sclerotic, distant - were compared between groups. After surgery, plugs were sampled in these zones and Raman spectroscopy was applied to characterize bone mineral and organic components (old and newly-formed), and contrast-enhanced micro-computed tomography (CE-μCT) to determine bone micro-structural parameters and volume of bone marrow adipocytes, using conventional 2D histology as a reference. In the necrotic zone of ONFH patients compared to OA patients: i) the subchondral plate did not exhibit significant changes in composition nor structure; ii) the volume fraction of subchondral trabecular bone was significantly lower; iii) type-B carbonate substitution was less pronounced, iv) collagen maturity was more pronounced; and v) bone marrow adipocytes were significantly depleted. The sclerotic zone from the ONFH group showed greater trabecular thickness, and higher DCE-MRI AUC and K. Volume fraction of subchondral bone, trabecular number, and K were significantly lower in the distant zone of the ONFH group. This study demonstrated alterations of subchondral bone microstructure, composition, perfusion and/or adipose content in all zones of the femoral head