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Objectives: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). Methods: A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. Results: One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). Conclusions: BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016 - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5 - Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621)., SCOPUS: ar.j, info:eu-repo/semantics/published

When designing innovative biomaterials, biocompatibility is regarded as a prerequisite for safe clinical use in humans. In this study, the biological safety of KiOmedine® CM-chitosan, which is a non-animal carboxymethyl chitosan biomaterial, was evaluated using a large panel of both in vitro and in vivo biocompatibility tests in accordance with the ISO 10993 series. KiOmedine® CM-chitosan was non-cytotoxic and non-genotoxic in vitro. The biomaterial was neither found to be haemolytic nor was it able to potentiate the activation of the central complement component C5a or the inflammatory mediators IL-1β and IL-8 in the presence of human whole blood. Furthermore, no evidence of any significant irritation, sensitization, pyrogenicity, and organ toxicity was detected in specific animal studies conducted with KiOmedine® CM-chitosan, and only minimal local tissue effects were observed after the intra-articular or intra-dermal injection of KiOmedine® CM-chitosan in the rabbit model. KiOmedine® CM-chitosan had minimal potential to induce immunotoxic reactions in the mouse air pouch model. Its biodegradation process was appropriately characterized at the histological level. In summary, our study represents an unprecedented body of work supporting the biological safety evaluation of KiOmedine® CM-chitosan, allowing its use in injectable medical devices.

Background Flexofytol is a Curcuma Longa extract with an increased bioavailibility (bio-optimised) by mixing curcuma extract with polysorbate. Objectives To demonstrate the effects of Flexofytol on OA symptoms and soluble biomarkers. Methods 141 patients with symptomatic knee OA (mean age 61.8 years [min.45-max.86]; 80.1% female; mean K and L grade of the knee 2.4; mean BMI 29.7 kg/m2) were randomised in a prospective double blinded, 3 parallel groups, comparative and multicenter, study (NCT02909621). At inclusion, all patients took pain killers or anti-inflammatory drugs which were authorised during the study. Patients received 6 months continuous treatment with either high dose Flexofytol (n=49, 140.01 mg Curcuma longa L. extract/treatment), low dose Flexofytol (n=47, 93.34 mg Curcuma longa L. extract/treatment) or placebo (n=45, Sunflower seed oil fill ingredient). Each treatment corresponded to 3 oral capsules two times a day to respect the blinding. All patients had clinical assessment (knee pain, knee function and patient global assessment of disease activity [PGADA]) and blood sampling for biomarkers measurements (usCRP and sColl2–1) at baseline (T0), 1 month (T1), 3 months (T3) and 6 months (T6). Additionally, patient compliance, satisfaction and tolerance were assessed at each timepoint following baseline. Primary outcome was the change at 3 months versus baseline in type II collagen degradation -specific biomarker sColl2–1 and VAS PGADA. Results Comparison of time evolution curves showed that sColl2–1 levels were lower in the treated groups but differences were not significant. The decrease in PGADA overtime was significantly more important in low dose group than in placebo group only at the 1 month evaluation timepoint (low dose ▵T1-T0, −12,5 mm vs placebo ▵T1-T0, −2 mm, p=0.035). Further, the knee pain relief was significantly higher in low dose group at T1 and T3 than in placebo (low dose ▵T1-T0, −16.5 mm vs placebo ▵T1-T0, −4 mm p=0.046; low dose ▵T3-T0, −36.5 mm vs placebo ▵T3-T0, −8 mm p=0.043). No difference was observed at T6. No differences were seen for any parameter when the high dose group was compared with the placebo group at any time point. The global KOOS score and its subscales significantly decreased overtime but changes were comparable in each group. Additionally, patient compliance was good and patient satisfaction remained stable overtime in each group. The ratio of patients with adverse events (AE) related to the product were similar in placebo and treated groups but the number of AE linked to the product was higher in the high dose group than in placebo (p=0.012). Conclusions Flexofytol, at a low dose, induced a rapid symptomatic relief on knee pain and a beneficial effect on the patient assessment of disease. This study also provides information on the dose to use and the design of a larger phase III clinical trial. Disclosure of Interest Y. Henrotin Consultant for: Tilman SA, M. Malaise: None declared, R. Wittoek: None declared, K. Devlam: None declared, J.-P. Brasseur: None declared, F. Luyten: None declared, Q. Jiangang: None declared, M. Van den Berghe : None declared, R. Uhoda: None declared, J. Bentin: None declared, T. De Vroey: None declared, L. Erpicum: None declared, Y. Dierckxsens Employee of: Tilman SA

Background The OMERACT Ultrasound scoring system (USSS) of joint in RA has been shown to be reliable and sensitive to change when used in clinical trial setting. However it is unclear whether this reliability is also achieved in clinical daily practice among Rheumatologists performing US in a non-research setting and using different machines. Objectives To assess agreement between non-research sonographers in scoring synovitis using the OMERACT USSS and using the scoring of an OMERACT expert as gold standard. To assess the reliability of the USSS by using different US machines. Methods First an OMERACT US expert presented the scoring method and supervised a training session. The wrist, MCP 2 and 3 joints of the left hand (dorsal aspect) of 3 RA patients were then successively evaluated by 9 Rheumatologists with 3 different US machines: Hitachi Arietta = H, GE Logic E9 = G, Esaote MyLab 7= E. The USSS included B-mode acquisition of synovial hypertrophy (SH), joint effusion (JE) and bone erosion (BE), and Power-Doppler (PD) activity. JE, SH and BE were scored binary; SH and PD were score semi quantitatively (0 to 3), by both the 9 participating Rheumatologists and the OMERACT US expert. The agreement between each participant with the scoring of the OMERACT US expert was quantified by proportions. The inter-US machine reproducibility was assessed by kappa statistics for discrete variables and weighted kappa9s for ordinate. Results The 3 joints of 3 patients each were evaluated on the 4 US items (SH, JF, BE, PD) on a different US machine. So 27 values were obtained for each joint within each item. The percentages of exact agreement (PEA) between these 27 values and the scores of the OMERACT US expert were calculated and ranged between 33% (9/27) for SH-MCP3, 37% for JF-MCP2 and PD-Wrist, 41% for SH-wrist, 48% BE-MCP3, 52% PD-MCP3, 56% PD-MCP3, 59 JF-wrist and BE-MCP2, 63% JF-MCP3, 67% SH-MCP2 and 78% (21/27) for BE-wrist. For the inter-US machines reproducibility, kappa between the 3 machines was calculated on 9 data (3 patients x 3 joints). The reliability was low for detecting JE ≤0.211. Acceptable reliability among machines was found for SH, BE and PD (table 1). Conclusions Non OMERACT-expert Rheumatologists can apply the USSS, and this score works well across different machines. The difference among machines and sonographers is mostly captured by the low reliability of JE. The OMERACT USSS could be used by sonographers in their everyday clinical practice to evaluate the activity of RA patients. Further studies in clinical-based settings will allow to define more precisely the applicability of this scoring system. Disclosure of Interest None declared

Objectifs Evaluer la concordance entre evaluation clinique (C) et echographie (ultrason–US) de la synovite (modes B, D et B + D) dans la polyarthrite rhumatoide (PR) active avant et apres traitement par anti-TNF, puis etudier les facteurs associes a une bonne concordance. Methodes Soixante-seize patients (necessitant une therapie anti-TNF) avec PR active (criteres ACR 1987) ont ete inclus dans une cohorte prospective, multicentrique avec 2 ans de suivi. Pour chaque patient, 38 articulations ont ete evaluees (2 poignets, 2 coudes, 2 epaules, 2 genoux, 10 MCP, 10 IPP, 10 MTP). Le grade de la synovite etait collecte a M0 en utilisant une variable semi-quantitative pour evaluation C (de 0 = pas de synovite de facon certaine a 3 = presence de synovite de facon importante), US mode B (de 0 = pas d’epaississement synovial a 3 = hypertrophie synoviale severe) et mode D (de 0 = aucun flux dans la synoviale a 3 = signaux de vaisseaux dans plus de la moitie de l’aire de la synoviale). Le coefficient kappa a ete determine pour evaluer la fiabilite des variables categorielles (synovite si grade ≥ 1). Les facteurs associes a une bonne concordance ont ete evalues par des analyses uni- et multivariees (tous les facteurs statistiquement significatifs et non correles dans le modele univarie ont ete inclus dans l’analyse multivariee). Resultats La concordance avant traitement anti-TNF entre evaluation C et US (kappa -0,08 a 0,51) ainsi que la concordance entre modes B et D (0,30 a 0,67) etaient variables en fonction du type d’articulation evaluee. La concordance entre C et US etait particulierement faible pour les articulations MTP et les epaules (kappa – mode B : faible DAS28, EVA clinique elevee et positivite des facteurs rhumatoides (FR) ; – mode D : pas d’evolution semi-recente de la PR (2–5 ans), activite moderee de la PR (DAS 3,2–5,1), âge entre 40 et 50 ans, etre une femme. Apres anti-TNF ces facteurs etaient : – mode B : site articulaire (genoux, coudes, MCP 4 et 5, IPP 2 a 5), etre un homme, faible IMC, pas d’evolution semi-recente de la PR (2–5 ans), incapacite moderee sur l’echelle HAQ et faible DAS28 ; – mode D : site articulaire (genoux, coudes, MCP 4 et 5, IPP 1 a 5), faible IMC, evolution recente de la PR, incapacite moderee sur l’echelle HAQ, faible DAS28, evaluation clinique faible et positivite des facteurs rhumatoides (FR). Conclusions La concordance entre les evaluations C et US depend du site articulaire. L’evaluation C sous-estime particulierement la synovite MTP et epaule. Les facteurs associes a une bonne concordance sur les autres sites articulaires sont nombreux et varient en fonction des modes US (les facteurs associes a une bonne concordance C-US modes B et D sont differents) et du traitement (site articulaire, HAQ, IMC faible sont associes a une bonne concordance C-US mais pas avant therapie TNF).

The economic burden of hip fractures is thought to be important, but the excess medical costs they induce remain largely unknown. We assessed the direct medical costs induced by hip fractures during and after hospitalization. Hospital costs of 170 consecutive Belgian women with hip fracture were gathered. During the year following discharge, all medical costs were collected for the 159 hip fracture women who survived the acute hospitalization stay. A similar collection of data was performed on a comparison group of 159 age-and residence-matched women without a history of hip fracture. The mean cost of the acute hospital stay was 8,667 Belgian francs and the mean 1-year hip-fracture-related extra costs after hospitalization was 6,636 Belgian francs. During the year following the acute hospital stay, 19% of the hip fracture women and 4% of the comparison women were newly admitted to nursing homes (p

Objectives To evaluate synovitis (clinical vs ultrasound (US)) to predict structural progression in rheumatoid arthritis (RA). Methods Patients with RA. Study design Prospective, 2-year follow-up. Data collected Synovitis (32 joints (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal)) at baseline and after 4 months of therapy by clinical, US grey scale (GS-US) and power doppler (PD-US); x-rays at baseline and at year 2. Analysis Measures of association (OR) were tested between structural deterioration and the presence of baseline synovitis, or its persistence, after 4 months of therapy using generalised estimating equation analysis. Results Structural deterioration was observed in 9% of the 1888 evaluated joints in 59 patients. Baseline synovitis increased the risk of structural progression: OR=2.01 (1.36-2.98) p, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective.Clinical joint examination (CJE) is less time-consuming than ultrasound (US) in rheumatoid arthritis (RA). Low concordance between CJE and US would indicate that the 2 tests provide different types of information. Knowledge of factors associated with CJE/US concordance would help to select patients and joints for US. Our objective was to identify factors associated with CJE/US concordance.Methods.Seventy-six patients with RA requiring tumor necrosis factor-α (TNF-α) antagonist therapy were included in a prospective, multicenter cohort. In each patient, 38 joints were evaluated. Synovitis was scored using CJE, B-mode US (B-US), and power Doppler US (PDUS). Joints whose kappa coefficient (κ) for agreement CJE/US was < 0.1 were considered discordant. Multivariate analysis was performed to identify factors independently associated with CJE/US concordance, defined as factors yielding p < 0.05 and OR > 2.Results.Concordance before TNF-α antagonist therapy varied across joints for CJE/US (κ = −0.08 to 0.51) and B-US/PDUS (κ = 0.30 to 0.67). CJE/US concordance was low at the metatarsophalangeal joints and shoulders (κ < 0.1). Before TNF-α antagonist therapy, a low 28-joint Disease Activity Score (DAS28) was associated with good CJE/B-US concordance, and no factors were associated with CJE/PDUS concordance. After TNF-α antagonist therapy, only the joint site was associated with CJE/B-US concordance; joint site and short disease duration were associated with CJE/PDUS concordance.Conclusion.Concordance between CJE and US is poor overall. US adds information to CJE, most notably at the metatarsophalangeal joints and shoulders. Usefulness is decreased for B-US when DAS28 is low and for PDUS when disease duration is short.

An 18-years old African girl, suffered for almost 4 years of polyarthralgia, joint contractures and a hardcover appearance of the skin suggestive of scleroderma. The clinical picture and a high level of CPK suggested Polymyositis (PM). Search for anti nuclear Antibody (ANA) showed speckled pattern at 1/2500 titre, and subscreening revealed isolated anti-Ku antibody. This was more often reported in association with PM - SSc overlap syndrome. Skin biopsy favored linear scleroderma. Interestingly, muscle biopsy showed features typical of dermatomyositis (DM). No endocrine disorder or underlying mitotic process was registered. Corticosteroid therapy was initiated followed by maintenance therapy with methotrexate; the outcome was favorable. This case illustrates the interest of anti-Ku screening in the diagnostic work-up. Our observation thus emphasizes the possible occurrence of isolated anti-Ku antibody expression in an overlap syndrome comprising SSc-DM association. Such association/linkage (implicating DM rather than PM) is, to our knowledge, very rarely well reported. Moreover, the therapeutic response seems favorable in such condition. We found one biopsy-confirmed observation of SSc-Inflammatory myositis (IM) overlap syndrome in an anti-Ku positive patient [1,2]. This later case was initially reported as SSc-PM overlap syndrome. Interestingly, follow-up showed evolution towards typical features of DM, and hence an overlap syndrome of SSc-DM association. Thus, our observation highlights the necessity/interest of biopsy to ascertain the precise nature of myositis in an overlap syndrome associating SSc and Myositis Clinico-pathological criteria in inflammatory myositis have been reviewed by Cherin P et al., [3]. Anti-ku Ab is knowingly reported in a context of myositis. Thus our observation and review of the literature suggest that in the presence of isolated anti-Ku Ab in a SSc-Myositis overlap context, muscle biopsy (that should be done) would tend to show DM (rather than PM) in association with the SSc. Such a finding may change the prognosis and the treatment approach of this syndrome. This can only be demonstrated after elaborate muscle biopsy in overlap syndromes, with or without the presence of anti-Ku antibodies.

Objective.To evaluate the intraobserver and interobserver reproducibility of B-mode and power Doppler (PD) sonography in patients with active long-standing rheumatoid arthritis (RA) comparatively with clinical data.Methods.In each of 7 patients being considered for a change in their RA treatment regimen, 7 healthcare professionals examined the 28 joints used in the Disease Activity Score 28-joint count (DAS28). Then 7 sonographers examined each of the 7 patients twice, using previously published B-mode and PD grading systems. The clinical reference standard was presence of synovitis according to at least 4/7 examiners. The sonographic reference standard was at least grade 1 (ALG1) or 2 (ALG2) synovitis according to at least 4/7 sonographers. Interobserver reproducibility of sonography was assessed versus the sonographer having the best intraobserver reproducibility. Agreement was measured by Cohen’s kappa statistic.Results.Intraobserver and interobserver reproducibility of B-mode and PD used separately was fair to good. Agreement between clinicians and sonographers at all sites using B-mode, PD, and both was 0.46, 0.37, and 0.36, respectively, for grade 1 synovitis; and 0.58, 0.19, and 0.19 for grade 2 synovitis. The number of joints with synovitis was smaller by physical examination (36.7%) than by B-mode with ALG1 (58.6%; p < 0.001). The number of joints with synovitis was higher by physical examination than by PD with both ALG1 (17.8%; p < 0.0001) and ALG2 (6.6%; p < 0.0001).Conclusion.PD findings explain most of the difference between clinical and sonographic joint assessments for synovitis in patients with long-standing RA.

Objectives To evaluate different global ultrasonographic (US) synovitis scoring systems as potential outcome measures of rheumatoid arthritis (RA) according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) filter. Methods To study selected global scoring systems, for the clinical, B mode and power Doppler techniques, the following joints were evaluated: 28 joints (28-joint Disease Activity Score (DAS28)), 20 joints (metacarpophalangeals (MCPs) + metatarsophalangeals (MTPs)) and 38 joints (28 joints + MTPs) using either a binary (yes/no) or a 0–3 grade. The study was a prospective, 4-month duration follow-up of 76 patients with RA requiring anti-tumour necrosis factor (TNF) therapy (complete follow-up data: 66 patients). Intraobserver reliability was evaluated using the intraclass correlation coefficient (ICC), construct validity was evaluated using the Cronbach α test and external validity was evaluated using level of correlation between scoring system and C reactive protein (CRP). Sensitivity to change was evaluated using the standardised response mean. Discriminating capacity was evaluated using the standardised mean differences in patients considered by the doctor as significantly improved or not at the end of the study. Results Different clinimetric properties of various US scoring systems were at least as good as the clinical scores with, for example, intraobserver reliability ranging from 0.61 to 0.97 versus from 0.53 to 0.82, construct validity ranging from 0.76 to 0.89 versus from 0.76 to 0.88, correlation with CRP ranging from 0.28 to 0.34 versus from 0.28 to 0.35 and sensitivity to change ranging from 0.60 to 1.21 versus from 0.96 to 1.36 for US versus clinical scoring systems, respectively. Conclusion This study suggests that US evaluation of synovitis is an outcome measure at least as relevant as physical examination. Further studies are required in order to achieve optimal US scoring systems for monitoring patients with RA in clinical trials and in clinical practice.

Objectives.To evaluate the reproducibility of clinical synovitis assessments in rheumatoid arthritis and the effect of variability on the Disease Activity Score-28 (DAS28).Methods.Seven healthcare professionals from different cities examined the same patients with active non-early rheumatoid arthritis (RA; duration > 4 yrs), for whom a treatment change was being considered. There was no training session and the examination was to be performed as quickly as possible. The healthcare professionals assessed the 28 joints of the DAS28 in 7 patients (196 joints), then reexamined the same 28 joints in 4 of these 7 patients (112 joints), who had been rendered unrecognizable. Then 7 sonographers examined each of the 7 patients twice, using B-mode and power Doppler ultrasound (PD). The reference standards were presence of synovitis according to at least 50% of clinical examiners and 50% of sonographers. Agreement was assessed by Cohen’s kappa statistic.Results.Intraobserver reliability ranged from 0.31 (least experienced research technician) to 0.77 (most experienced physician). Interobserver reliability ranged from 0.18 to 0.62. The largest difference between the lowest and the highest swollen joint counts in the same patient was 15, and the greatest variation in the DAS28 score was 0.92. Agreement between clinical and sonographic reference standards was 0.46, 0.37, and 0.36 for B-mode, PD, and both, respectively.Conclusion.Clinical inter- and intraobserver reliability is highly dependent on the examiner. Consequences on the DAS28 score can be substantial. Agreement with sonography is poor when both B-mode and PD are used but seems better, although low, when B-mode is used alone.

We investigated the effect of Polymorphonuclear neutrophils (PMN) on anti-CD3 mAb (OKT3 and anti-Leu4)-mediated T cell activation. In the absence of monocytes, purified E-rosette-positive cells (further referred to as “T cells”) require either solid-phase bound anti-CD3 or the combination of both a high concentration of soluble anti-CD3 and exogenous recombinant interleukin 2 (rIL-2) to proliferate. PMN cannot sustain T cell proliferation with soluble anti-CD3, but they markedly boost proliferation in the presence of soluble anti-CD3 and rIL-2. When PMN were added to T cell cultures stimulated with anti-CD3, this resulted in IL-2 receptor (IL-2R) expression and CD3 modulation. The mechanism of enhancement of anti-CD3-induced IL-2-responsiveness by PMN was further analyzed. A cellular T cell-PMN interaction was found to play a critical role and this was mediated through PMN Fc receptors (FcR). PMN bear two types of low-affinity FcR (FcRII and FcRIII). FcRII is known to bind mIgG1 (e.g., anti-Leu4) and FcRIII binds mIgG2a (e.g., OKT3). FcR involvement was demonstrated by two observations. Anti-FcRII mAb IV.3 inhibited the PMN signal for T cell activation with anti-Leu4. PMN bearing the second variant of FcRII which is unable to bind mIgG1 failed to promote anti-Leu4/IL-2-mediated T cell proliferation. Thus, PMN potentiate T cell responsiveness to IL-2 in the presence of anti-CD3 mAb and this potentiation by PMN requires interaction of anti-CD3 with PMN-FcR.

We describe a patient who developed acquired immunodeficiency syndrome-related complex, complicated by chronic, symmetric polyarthritis. Synovial biopsy showed large areas of plasma cell infiltration subjacent to the synovial lining. Ultrastructural study demonstrated tubuloreticular structures within endothelial cells, crystal-like inclusions in plasma cells, and virus-like particles located around synoviocyte fragments. Although immunologic and morphologic studies did not permit classification of these virus-like structures, the role of these possible virions in the pathogenesis of the observed synovitis remains to be determined. Surprisingly, the patient's chronic arthritis resolved with anti-retroviral treatment (azidothymidine: AZT).

Objectives To evaluate agreement between clinical (C) and ultrasound (US) assessment of synovitis (B, D and B+D mode) in active rheumatoid arthritis (RA) before and after treatment by antiTNF, and then to study factors associated with a good agreement. Methods 76 active (necessitating an anti-TNF therapy) RA (1987 ACR criteria) patients have been included in a prospective, 2 year follow-up multicenter cohort. For each patient, 38 joints were evaluated (2 wrists, 2 elbows, 2 shoulders, 2 knees, 10 MCP, 10 PIP, 10 MTP). Synovitis grade was collected at baseline using a semi-quantitative variable for both the physical examination (from 0=definitively no synovitis to 3=yes obvious and important), US Grey Scale (GS) (from 0=absence of synovial thickening to 3=marked synovial thickening) and US Power Doppler (PD) (from 0=absence of signal, no intra-articular flow to 3=marked signal in more than half of the synovial area. The kappa coefficient was determined to evaluate the reliability of categorical variables (synovitis if grade ≥1). Factors associated with a good agreement were evaluated using both uni and multivariate analysis (all items statistically significant in univariate model and not correlated with other items were included). Results Concordance before anti TNF between C and US assessment (kappa -0.08 to 0.51) as well as agreement between B and D mode (0.30 to 0.67) were variable according to the evaluated joint site. C and US agreement was particularly low on MTP and shoulders (kappa Conclusions Agreement between C and US assessment is joint site dependent. C assessment underestimates particularly MTP and shoulder synovitis. Factors associated to a good agreement on the other sites are numerous and variable according to US mode (factors associated to C-US mode B and D good agreement are different) and treatment (joint site, HAQ, low BMI are associated to a good C-US agreement after but not before TNF therapy). Disclosure of Interest None Declared

Background Presence of synovitis has been demonstrated to be predictive of subsequent structural deterioration in rheumatoid arthritis (RA). In comparison to physical examination, ultrasonography (US) seems to be more accurate (sensitive) for the detection of synovitis. Objectives To compare the predictive validity of synovitis with regard to the joint examination modality ( e.g. clinical versus US). Methods Patients: Definite active RA. Study design: Prospective, 2 year follow-up. Data collected: For each patient, 32 joints were evaluated (2 wrists, 10 MCP, 10 PIP, 10 MTP). Information of synovitis was collected at baseline at physical and US (Grey Scale (GS) and US Power Doppler (PD)) examinations by 2 distinct physicians. X-rays of the 32 joints performed at baseline and year 2 were evaluated (presence of both erosion and joint space narrowing) by another distinct physician. Analysis: Measures of association (odds ratio [OR]) and 95% confidence intervals [CI] were tested between the structural deterioration defined by an occurrence or a worsening of joint space narrowing or bone erosion and the presence of synovitis defined by clinical, US-GS or US-PD at baseline. These measures of association were tested using generalized estimating equation (GEE) analysis adjusting for within patient correlation and also other factors ( e.g. age, gender, disease duration, baseline DAS28 and baseline joint structural damage). Results Of the 77 recruited patients, 59 had a complete data set. After 2 years of follow-up, a structural deterioration was observed in 9% of the 1888 evaluated joints The increased probability to observe a structural progression in presence of synovitis was confirmed for the different joint examination modalities: OR =2.08 [1.39-3.11] p versus 1.64 [1.08-2.47] p =0.019 versus 1.80 [1.20-2.71] p =0.005 for the clinical versus US-GS versus US-PD evaluation respectively. In the 1101 joints with normal baseline clinical evaluation, an increased probability to observe a structural progression in presence of US synovitis was also observed (OR =2.22 [1.20-4.08] p 0.011 and 3.93 [1.93-7.99] p =0.001 for the US-GS and US-PD evaluation respectively). Inversely, in the 938 joints with normal baseline US evaluation (both GS and PD), an increased probability to observe a structural progression in presence of baseline clinical synovitis was still observed (OR =2.95 [1.50-5.81] p =0.002). Conclusions This study confirms the validity of synovitis to predict subsequent structural deterioration whatever the joint examination modality but suggests also that BOTH clinical AND ultrasonographic examinations are relevant to optimally evaluate the risk of subsequent structural deterioration Disclosure of Interest M. Dougados Grant/Research support from: abbott, V. Devauchelle-Pensec: None Declared, J.-F. Ferlet: None Declared, S. Jousse-Joulin: None Declared, M.-A. d’Agostino: None Declared, M. Backhaus: None Declared, J. Bentin: None Declared, G. Chales: None Declared, I. Chary-Valckenaere: None Declared, P. Conaghan: None Declared, F. Etchepare: None Declared, P. Gaudin: None Declared, W. Grassi: None Declared, D. van der Heijde: None Declared, X. Mariette: None Declared, E. Naredo: None Declared, M. Szkudlarek: None Declared, R. Wakefield: None Declared, A. Saraux: None Declared

Heterogenous population of cells, including macrophages, synoviocytes and lymphocytes play important roles in the immunopathogenesis of rheumatoid arthritis (RA). T cells, however, seem to be a common thread throughout the disease process. In inhibiting T lymphocytes, cyclosporin A presents a more selective form of therapy in RA. The immunosuppressive action of cyclosporin is primarily due to the inhibition of antigen/mitogen-induced secretion of lymphokines at the transcriptional level from T cell. The inhibition of Ca2(+)-dependent signaling pathways by cyclophilin-cyclosporin complexes in T cell appears to shut down lymphokine-gene transcription.

In the presence of interleukin 2 (IL2), soluble anti-CD3 monoclonal antibodies can stimulate highly purified normal T lymphocytes to proliferate. In these experiments HLADR+ T cells constituted 13 to 20% of the total cell population, and other HLADR+ cells, such as monocytes and B lymphocytes, constituted less than 1% of the population. When the HLADR+ T cells were removed from the total T cell population by cytofluorometric sorting, the residual HLADR- T cells failed to respond to soluble anti-CD3 plus IL2. When the separated HLADR+ T cells were recombined with the HLADR- T cells, a response was again found. This response was dependent on the dose of HLADR+ T cells added in the mixture. Irradiation individually of the HLADR+ and DR- T cells revealed that the proliferation in the cell mixture was predominantly, if not exclusively, by the HLADR- T cells. The ability of the HLADR+ T cells to provide a signal necessary to this proliferation was radioresistant. These data indicate that under the conditions of these experiments HLADR+ ("activated") T cells provide a signal necessary to the responsiveness of previously resting T cells.

SummaryTwo cases of chronic 3, 5, 3’-triiodo-thyroacetic acid (Triac) consumption (2.1 mg/day) are reported. Profound alterations of thyroid function were observed: thyroxine and free thyroxine concentrations were low, normal to excessively high triiodothyronine values were detected and thyroid stimulating hormone response to 200 fig thyroid releasing hormone i.v. was abolished.The literature concerning Triac use is reviewed, and the efficiency of the drug in the treatment of obesity is discussed.