J. Avouac - Academia.edu (original) (raw)

Papers by J. Avouac

Research paper thumbnail of Prevalence and predictors of small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis

Journal of gastroenterology, Jan 14, 2018

The reported prevalence of small intestinal bacterial overgrowth (SIBO) among individuals with ir... more The reported prevalence of small intestinal bacterial overgrowth (SIBO) among individuals with irritable bowel syndrome (IBS) is highly variable. The aim of the study is to estimate the prevalence and identify predictors of SIBO in IBS. PubMed, Cochrane Library, and EMBASE through July 2017 were searched to identify studies evaluating the prevalence of SIBO in IBS. The pooled prevalence of SIBO among individuals with IBS and the pooled odds ratio (OR) of SIBO among those with IBS compared with healthy controls were calculated. Predictors of SIBO among IBS patients were also evaluated. Fifty studies (8398 IBS, 1432 controls) met the inclusion criteria. Overall pooled prevalence of SIBO in IBS was 38% (95% CI 32-44) and was higher among individuals with IBS (OR 4.7, 95% CI 3.1-7.2) compared with controls. The pooled prevalence of SIBO in IBS was higher in studies diagnosed by breath tests (40%, 95% CI 33-46) compared with cultures (19%, 95% CI 8-30). Among those with IBS, female gende...

Research paper thumbnail of 505 Effects of Joint Lavage in Patients with Osteoarthritis of the Knee: Meta-Analysis of Randomized Controlled Trials

Osteoarthritis and Cartilage, 2008

was considered as efficient (a = 10% b = 10%)), the secondary criteria were: the results at 24 mo... more was considered as efficient (a = 10% b = 10%)), the secondary criteria were: the results at 24 months for arthroscopy, histology, MRI, and the evaluation of the surgical technique. Treatment: Biopsy of 200 to 300 mg of cartilage from a non bearing zone of the knee, cellular expansion and incubation in an agarose and alginate hydrogel with manufacturing of 10, 14 or 18 mm diameter implants distributed in the lesion. Results: 20 patients have been included, 17 have been implanted, (a chondrocalcinosis, a culture failure, a fibrocartilage reconstruction have not been implanted). Patients characteristics: Average age: 30 years old, 12 Men/5 Women, 10 OD, Average IKDC initial score: 37, Average lesions' surface 3 cm 2. Mean criterion: IKDC at 24 months: 77.8 (p 3 cm 2 , and almost significant for OD and grade 4 lesions. MRI: 10 patients on 15 presented an identical signal/normal cartilage, for 11 patients/15 no visible transition. Arthroscopies: 13 realized with an average ICRS score of 10 on 12. Histology: O'Driscoll Average score on 21: 16. 8 patients presented a mostly hyaline cartilage, 3 a mixed hyaline and 1 fibrocartilage. The average surgery time was 41 minutes. Conclusions: The cartilage graft in a CARTIPATCH ® hydrogel confirms a significant clinical improvement especially for deep and large lesions. The use of a matrix allowing a homogeneous distribution and no cellular leakage can explain the good histological results with over 60% of the repaired cartilage mostly hyaline at 24 months. Two phase III studies one versus osteochondral autografts and one versus microfracture have been started.

Research paper thumbnail of Comparaison de la progression radiologique dans la polyarthrite rhumatoïde sous anti TNF-alpha en fonction de l'ancienneté de la maladie

Revue du Rhumatisme, 2007

Research paper thumbnail of A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study

Annals of the Rheumatic Diseases, 2014

ABSTRACT In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with... more ABSTRACT In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes.

Research paper thumbnail of HIV-related nephropathies associated with changes in blood and kidney tissue virus load

Kidney International, 2008

CASE PRESENTATION A 39-year-old African woman was admitted to our Nephrology Department in June 2... more CASE PRESENTATION A 39-year-old African woman was admitted to our Nephrology Department in June 2004 for exploration of a nephrotic syndrome. Relevant past medical history included HIV-1-positive infection since 1997. She had been treated with a combination of nucleoside reverse transcriptase inhibitors (AZT, 3TC, and abacavir) since April 2002. One week before admission, her CD4 þ lymphocyte count was 350 mm À3 and the RNA viral load was undetectable. Findings at admission included blood pressure of 160/ 90 mm Hg and peripheral inferior limb edema. Clinical examination of the heart, abdomen, and nervous system was normal. Urinary protein excretion was 3.6 g per 24 h, hematuria 3 Â 10 4 red blood cells per 1 ml of urine, albumin 25 g l À1 , serum creatinine and creatinine clearance estimated by the Cockroft and Gault formula were, respectively, 88 mmol l À1 and 80 ml min À1 , and electrolytes were in the normal range, as were C-reactive protein and serum fibrinogen. Blood count gave hemoglobin at 10 g per 100 ml, white blood cells 6600 mm À3 , and platelets 287 Â 10 9 l À1 without schizocytes. Liver function tests were normal. Immunoelectrophoresis showed no serum monoclonal component, serum IgA and IgM were in the normal range, and IgG was increased to 41.6 g l À1 (normal range: 6.9-14 g l À1). Serological tests for hepatitis were negative. Antinuclear antibody (titer of 1:80) was considered insignificant. Immunological tests were negative for antineutrophil cytoplasm antibodies, and for antibodies against double-stranded DNA, extractable nuclear antigens, cardiolipin, and b-2-glycoprotein 1.

Research paper thumbnail of Association between the IRF5 rs2004640 functional polymorphism and systemic sclerosis: A new perspective for pulmonary fibrosis

Arthritis & Rheumatism, 2009

ObjectiveThere is now growing evidence that connective tissue diseases, including systemic sclero... more ObjectiveThere is now growing evidence that connective tissue diseases, including systemic sclerosis (SSc), share a common genetic background. Microarray studies support a pivotal role of type I interferon (IFN) in the pathophysiology of connective tissue diseases. Interferon regulatory factors coordinate the expression of type I IFNs, and the IRF5 gene has been identified as a susceptibility gene of systemic lupus and Sjögren's syndrome. The aim of this study was to determine whether the IRF5 rs2004640 single‐nucleotide polymorphism is associated with SSc.MethodsThe IRF5 rs2004640 (GT) functional polymorphism was genotyped in 1,641 subjects of French European Caucasian origin: a discovery set comprising 427 patients with SSc and 380 control subjects and a replication set comprising 454 patients with SSc and 380 control subjects.ResultsIn both the discovery set and the replication set, the TT genotype was significantly more common in patients with SSc than in control subjects, w...

Research paper thumbnail of Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review

Annals of the Rheumatic Diseases, 2005

To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagno... more To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a predictor of future development of RA in healthy subjects and in patients with early undifferentiated arthritis. Methods: A systematic analysis of the literature published between 1999 and February 2006 was conducted. Data were collected on the sensitivity and specificity of the two generations of anti-CCP antibodies for diagnosing RA and predicting future development of the disease. Results: Among 107 studies initially identified, 68 had interpretable data and were analysed. Diagnostic properties were assessed in 58 studies: mean (SD) sensitivity was 53 (10)% (range 41-68) and 68 (15)% (range 39-94) for anti-CCP1 and anti-CCP2, respectively; mean (SD) specificity was 96 (3)% (range 90-99) and 95 (5)% (range 81-100) for anti-CCP1 and anti-CCP2, respectively. Predictive properties were assessed in 14 studies; odds ratio (95% confidence interval) of anti-CCP1 and anti-CCP2 for the future development of RA were 20 (14 to 31) and 25 (18 to 35), respectively, among patients with early undifferentiated arthritis and 64.5 (8.5 to 489) and 28 (8 to 95), respectively, among healthy subjects. Conclusion: Sensitivity of the second generation of anti-CCP is close to that of rheumatoid factor, with a higher specificity, for distinguishing RA from other rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive of the future development of RA in both healthy subjects and patients with undifferentiated arthritis.

Research paper thumbnail of Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group

Annals of the Rheumatic Diseases, 2010

ObjectiveTo identify a core set of preliminary items considered as important for the very early d... more ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as foll...

Research paper thumbnail of A8.3 Deficit of S100A4 Prevents Joint Destruction and Systemic Bone Loss in hTNFtg Mouse Model

Annals of the Rheumatic Diseases, 2013

Background and Objectives Autoantibodies recognising citrullinated proteins (ACPA) are highly spe... more Background and Objectives Autoantibodies recognising citrullinated proteins (ACPA) are highly specific for rheumatoid arthritis (RA), precede the clinical onset of the disease by years and are the strongest known risk factor for bone loss. We have recently shown that ACPA specific for citrullinated vimentin directly interact with osteoclast precursors and induce bone loss. In patients with RA, ACPA-containing immune complexes can be detected in synovial fluid and tissue. We hypothesised that (I) immune complexes directly promote osteoclast maturation and, consecutively, bone loss and that (II) the type of IgG-glycan is important for the interaction with osteoclast precursors, since ACPA have been shown to be hyposialylated. Materials and Methods We differentiated preosteoclasts from human monocytes and stimulated them with artificial immune complexes generated by heat aggregation from pooled human IgG (IVIG). Part of the IgG had been pretreated with neuraminidase or PNGase F to remove sialic acid or the whole Fc glycan, respectively. For in vivo studies we injected murine immune complexes in the knee joints of C57-BL/6 mice. Results Stimulation of preosteoclasts with immune complexes resulted in their dramatically increased maturation to osteoclasts. This effect was even more pronounced with complexes formed from desialylated IgG. Monomeric IgG and fully deglycosylated immune complexes did not alter osteoclast maturation. qPCR and FACS-analyses revealed that all Fcγ receptors (FcγR) are upregulated during osteoclastogenesis with FcγR I and FcγR III being the most prominent ones. Desialylated immune complexes induced the activation of spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) as well as the upregulation of the transcription factor c-fos in preosteoclasts. Injection of murine immune complexes into the knee joints of C57-BL/6 mice caused accumulation of osteoclasts in the vicinity of the site of injection. Conclusions Our data show that IgG immune complexes promote osteoclastogenesis. They upregulate the pro-osteoclastogenic transcription factor c-fos, after binding to activating FcγRs on preosteoclasts. This interaction is highly dependent on the absence of sialic acid in the Fc-glycan of the IgG. Altogether, we propose a novel mechanism by which ACPA promote bone loss independent of inflammation.

Research paper thumbnail of Valeur diagnostique et prédictive des anticorps anti-peptides cycliques citrullinés (anti-CCP) dans la polyarthrite rhumatoïde: revue systématique de 68 études

Revue du Rhumatisme, 2006

concentration de protéines localement tout en évitant les effets secondaires liés au transfert de... more concentration de protéines localement tout en évitant les effets secondaires liés au transfert de gène et de protéines in vivo dans des maladies comme la polyarthrite rhumatoïde (PR). Les vecteurs viraux AAV sont de bons candidats pour la thérapie génique intraarticulaire, mais il existe chez l'homme des anticorps naturels anti-AAV dans le sang ou le liquide synovial (LS) qui peuvent entraver l'infection. Objectifs : Comparer la neutralisation exercée par différents sérotypes d'AAV : AAV1, AAV2, AAV5 et AAV8, et déterminer, dans un système de culture de synoviocytes humains in vitro, le sérotype le plus adapté à une thérapie génique intra-articulaire. Patients et Méthodes.-Le LS provenait de 10 patients atteints de PR et les synoviocytes humains de prélèvements chirurgicaux. Des AAV de sérotypes 1, 2, 5 et 8 codant le gène de l'interleukine (IL-) 4 ont été utilisés. L'efficacité d'infection des AAV sur les synoviocytes a été mesurée par ELISA sur IL-4 dans le surnageant de culture. L'activité neutralisante contre AAV-IL-4 a été déterminée en évaluant le pouvoir neutralisant du LS (ou du sang de patients PR) sur l'infection des synoviocytes par les 4 sérotypes d'AAV. Résultats.-Le sérotype 2 était celui qui infectait le plus efficacement les synoviocytes humains, suivi de près par le sérotype 1. Les sérotypes 5 et surtout le sérotype 8 étaient moins efficaces. L'infection des synoviocytes par les sérotypes 1 et 2 était fortement inhibée par le LS de patients PR, tandis qu'elle l'était beaucoup moins lorsqu'on utilisait les sérotypes 5 et 8. Les activités neutralisantes du sang et du LS étaient corrélées pour chaque sérotype. Enfin, la neutralisation de l'infection par le LS pouvait être levée en utilisant de plus fortes quantités d'AAV in vitro. Conclusion.-Les sérotypes qui infectent le mieux les synoviocytes (sérotypes 1 et 2) en absence de LS sont aussi ceux qui sont le plus fortement neutralisés par le LS. En conséquence, le sérotype 5 serait le mieux adapté à une thérapie génique intra-articulaire car, bien qu'infectant un peu moins efficacement les synoviocytes, l'immunité dirigée contre lui est beaucoup plus faible. L'ensemble de ces données pourrait être utile pour mettre au point un transfert de gène intra-articulaire individuellement adapté à chaque patient [1].

Research paper thumbnail of Effet taille des traitements médicamenteux sur l'atteinte périphérique des spondylarthrites ankylosantes: revue systématique de la littérature

Revue du Rhumatisme, 2007

Research paper thumbnail of Phenotype-Haplotype Correlation of IRF5 in Systemic Sclerosis: Role of 2 Haplotypes in Disease Severity

The Journal of Rheumatology, 2010

Objective.Identification of an association between IRF5 rs2004640 and systemic sclerosis (SSc) ha... more Objective.Identification of an association between IRF5 rs2004640 and systemic sclerosis (SSc) has highlighted a key role for type 1 interferon (IFN). Additional functional IRF5 variants have been identified as autoimmune susceptibility factors. Our aim was to investigate whether IRF5 haplotypes confer susceptibility to SSc, and to perform genotype haplotype-phenotype correlation analyses.Methods.We genotyped IRF5 rs377385, rs2004640, and rs10954213 in 1623 individuals of French European Caucasian origin. SSc patient subphenotypes were analyzed according to cutaneous subsets and for SSc-related pulmonary fibrosis.Results.Case-control studies of single markers revealed an association between IRF5 rs3757385, rs2004640, and rs10954213 variants and SSc. We identified an IRF5 risk haplotype “R” (padj = 0.024, OR 1.23, 95% CI 1.07–1.40) and a mirrored protective haplotype “P” (padj = 8.8 × 10−3, OR 0.78, 95% CI 0.68–0.90) for SSc susceptibility. Genotype-phenotype correlation analyses fai...

Research paper thumbnail of Severe Refractory Rheumatoid Arthritis Successfully Treated with Combination Rituximab and Anti-Tumor Necrosis Factor- -Blocking Agents

The Journal of Rheumatology, 2009

Research paper thumbnail of Cardiovascular risk in rheumatoid arthritis: effects of anti-TNF drugs

Expert Opinion on Pharmacotherapy, 2008

Patients with rheumatoid arthritis (RA) have an increased risk of atherosclerotic cardiovascular ... more Patients with rheumatoid arthritis (RA) have an increased risk of atherosclerotic cardiovascular disease which cannot be explained by traditional cardiovascular risk factors alone. Atherosclerosis is considered an inflammatory condition and inflammation experienced in RA may contribute to accelerated atherosclerosis. Thus, it should be hypothesized that treatment with antitumor necrosis factor alpha (anti-TNF-alpha), TNF-alpha being a pivotal component of the inflammatory cascade, may decrease concomitantly intra-articular inflammation and vessel inflammation. The purpose of this review is to examine the data regarding cardiovascular mortality and morbidity in RA and the evidence available to date evaluating the influence of anti-TNF-alpha treatments in RA on the occurrence of cardiovascular events, on surrogate markers of atherosclerosis and classical cardiovascular risk factors. Clinical trials, original studies and review articles were identified from a Medline search (1998 - December 2007). Articles in English were reviewed, with emphasis on those containing assessments of cardiovascular effects (i.e., biological, structural, clinical) of anti-TNF-alpha drug. The suppression of systemic inflammation favoring atherosclerosis may lead to an improvement in cardiovascular prognosis in inflammatory disorders. Thus, reduction of inflammatory joint disease in RA with anti-TNF-alpha therapy, as probably with any powerful disease-modifying antirheumatic drugs, seems to be, at least in part, associated with concomitant reduction of the risk of cardiovascular events.

Research paper thumbnail of High N-terminal pro–brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis

Arthritis & Rheumatism, 2007

Objective. To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohor... more Objective. To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). Methods. Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea. Results. Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P < 0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P ‫؍‬ 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P ‫؍‬ 0.08), and erythrocyte sedimentation rate >28 mm/hour (P ‫؍‬ 0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69-62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45-387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90-450.33]). Conclusion. This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.

Research paper thumbnail of Cardiac involvement in systemic sclerosis assessed by tissue-doppler echocardiography during routine care: A controlled study of 100 consecutive patients

Arthritis & Rheumatism, 2008

To assess the prevalence of primary cardiac complications in a large population of patients with ... more To assess the prevalence of primary cardiac complications in a large population of patients with systemic sclerosis (SSc), using recently developed echocardiographic techniques. We prospectively studied 100 consecutive patients (mean +/- SD age 54 +/- 14 years; 86 women) presenting with SSc without pulmonary arterial hypertension or clinical manifestations of heart failure. All patients underwent standard echocardiography, along with measurements of longitudinal velocities by tissue Doppler imaging (TDI) to assess left ventricular (LV) and right ventricular (RV) contractility and LV diastolic function. Results were compared with those in 26 age- and sex-matched healthy controls. Patients with SSc had a wider mean left atrial diameter and impaired relaxation compared with the controls. A trend was observed toward a smaller LV ejection fraction (EF) in the patients (mean +/- SD 64.9 +/- 0.6%) than in the controls (67.2 +/- 0.7%), as well as higher pulmonary artery pressure (mean +/- SD 33.3 +/- 0.6 mm Hg versus 30.8 +/- 1.0 mm Hg). LVEF was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;55% in 7 patients versus none of the controls. Peak systolic mitral annular velocity as measured by TDI was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5 cm/second in 14 patients versus none of the controls (P = 0.040). Mitral annulus early diastolic velocity was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 cm/second in 30 patients versus 2 of the controls (P = 0.022). Fifteen patients and none of the controls had reduced peak systolic tricuspid annular velocity (P = 0.039). The TDI results correlated with each other, but not with lung abnormalities or other disease characteristics. Depression of LV and RV systolic and LV diastolic function is common in patients with SSc and is due to primary myocardial involvement. Considering the major contributions of TDI, the addition of this simple technique to standard measurements may improve the detection of heart involvement in patients with SSc.

Research paper thumbnail of Enhanced expression of ephrins and thrombospondins in the dermis of patients with early diffuse systemic sclerosis

Annals of the Rheumatic Diseases, 2010

Research paper thumbnail of Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis

Annals of the Rheumatic Diseases, 2011

ObjectiveTo evaluate the possible merit of endothelial markers for the prediction of ischaemic di... more ObjectiveTo evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).MethodsCirculating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up.ResultsAfter the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p≤0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 2...

Research paper thumbnail of Lack of Specificity of the 6-Minute Walk Test as an Outcome Measure for Patients with Systemic Sclerosis

The Journal of Rheumatology, 2009

Objective.The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascular... more Objective.The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascular diseases and has been considered as a surrogate endpoint. However, conflicting results have been reported in systemic sclerosis (SSc). Our objective was to evaluate the relationships of the 6-min walking distance (6MWD) and organ damage in SSc.Methods.Eighty-seven consecutive patients with SSc were included and prospectively investigated; they underwent 6MWT in addition to conventional assessment of possible lung, heart, kidney, skin, and muscle involvement, and disease activity scoring, severity, and quality of life determination.Results.Twenty-six patients (30%) had an abnormal 6MWT and the mean 6MWD was 461.8 ± 103.0 m. When considering 6MWT as a binary variable — normal or abnormal — C-reactive protein (CRP) was the only independent variable associated with abnormal 6MWT. Considered as a continuous variable, the 6MWD was associated with measures of lung involvement and inflammation,...

Research paper thumbnail of SAT0467 The Five Prospective Observational Trials of the International Systemic Sclerosis FP7-Health Research Project Desscipher: A Interim Report

Annals of the Rheumatic Diseases, 2015

Background Due to lack of adequate clinical research data, drug treatment of the rare disease sys... more Background Due to lack of adequate clinical research data, drug treatment of the rare disease systemic sclerosis (SSc) is commonly off-label. The international EC-funded research project DeSScipher (acronym for “to decipher the optimal management of systemic sclerosis”) was designed to increase the evidence-based treatment strategies for SSc patients and subsequently to improve their long-term quality-of-life. Objectives The primary objective is to compare the outcomes of different treatments with respect to efficacy and safety of currently used off-label drugs from the early to the advanced phases of the main SSc-associated organ dysfunctions in a routine rheumatology in- and outpatient setting. Methods Five prospective observational trials (OTs), carried out within the EULAR Scleroderma Trials and Research (EUSTAR) group, have been designed to analyze current treatment approaches of early functionally relevant manifestations such as digital ulcers (OT1) and hand arthritis (OT2) to the morbidity and mortality-driving manifestations such as interstitial lung disease (OT3), pulmonary hypertension (OT4) and severe heart disease (OT5). The study protocols are accessible at clinicaltrials.gov Identifiers NCT01836263, NCT01834157, NCT01858259, NCT01840748, NCT01829126. Results Between April 2013 and January 2015, 1781 SSc patients have been screened at 27 contributing EUSTAR centers. 1577 (89%) patients have been enrolled into at least one of the five OTs. In particular, 1179, 127, 981, 237 and 716 patients have been enrolled into OT1-5, respectively (3240 in total; a given patient could be enrolled into multiple OTs), which represents a baseline patient recruitment rate of 79% of the target number of 4098 patients (accordingly 226%, 79%, 59%, 25% and 91% of the required number of 522, 160, 1670, 960, 786 patients for OT1-5, respectively). The completion of 1-year (OT3, OT5) and 2-year follow-up visits (OT1, OT2, OT4) are pending. Conclusions DeSScipher is currently the largest prospective observational research project ever for SSc. While patient recruitment is still ongoing, preliminary results of the five OTs are expected in late 2015 and the final results depending on the completion of follow-up visits are expected between 2017 and 2018. Acknowledgements The DeSScipher project was funded by the European Community's Framework Programme 7 (FP7-HEALTH-2012.2.4.4-2 - Observational trials in rare diseases) under grant agreement N° 305495. We acknowledge the contribution of the following EUSTAR centers: Wuppertal (member N°192), Lille (93), Bad Bramstedt (187), Moscow (78), Assiut (168), Moscow (190), Bucharest (100), Monserrato (142), Iasi (162), Cluj-Napoca (16), Frankfurt (124), Salford/Manchester (80), Tübingen (56), Ancona (34), Zagreb (51) and Roma (94). Disclosure of Interest None declared

Research paper thumbnail of Prevalence and predictors of small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis

Journal of gastroenterology, Jan 14, 2018

The reported prevalence of small intestinal bacterial overgrowth (SIBO) among individuals with ir... more The reported prevalence of small intestinal bacterial overgrowth (SIBO) among individuals with irritable bowel syndrome (IBS) is highly variable. The aim of the study is to estimate the prevalence and identify predictors of SIBO in IBS. PubMed, Cochrane Library, and EMBASE through July 2017 were searched to identify studies evaluating the prevalence of SIBO in IBS. The pooled prevalence of SIBO among individuals with IBS and the pooled odds ratio (OR) of SIBO among those with IBS compared with healthy controls were calculated. Predictors of SIBO among IBS patients were also evaluated. Fifty studies (8398 IBS, 1432 controls) met the inclusion criteria. Overall pooled prevalence of SIBO in IBS was 38% (95% CI 32-44) and was higher among individuals with IBS (OR 4.7, 95% CI 3.1-7.2) compared with controls. The pooled prevalence of SIBO in IBS was higher in studies diagnosed by breath tests (40%, 95% CI 33-46) compared with cultures (19%, 95% CI 8-30). Among those with IBS, female gende...

Research paper thumbnail of 505 Effects of Joint Lavage in Patients with Osteoarthritis of the Knee: Meta-Analysis of Randomized Controlled Trials

Osteoarthritis and Cartilage, 2008

was considered as efficient (a = 10% b = 10%)), the secondary criteria were: the results at 24 mo... more was considered as efficient (a = 10% b = 10%)), the secondary criteria were: the results at 24 months for arthroscopy, histology, MRI, and the evaluation of the surgical technique. Treatment: Biopsy of 200 to 300 mg of cartilage from a non bearing zone of the knee, cellular expansion and incubation in an agarose and alginate hydrogel with manufacturing of 10, 14 or 18 mm diameter implants distributed in the lesion. Results: 20 patients have been included, 17 have been implanted, (a chondrocalcinosis, a culture failure, a fibrocartilage reconstruction have not been implanted). Patients characteristics: Average age: 30 years old, 12 Men/5 Women, 10 OD, Average IKDC initial score: 37, Average lesions' surface 3 cm 2. Mean criterion: IKDC at 24 months: 77.8 (p 3 cm 2 , and almost significant for OD and grade 4 lesions. MRI: 10 patients on 15 presented an identical signal/normal cartilage, for 11 patients/15 no visible transition. Arthroscopies: 13 realized with an average ICRS score of 10 on 12. Histology: O'Driscoll Average score on 21: 16. 8 patients presented a mostly hyaline cartilage, 3 a mixed hyaline and 1 fibrocartilage. The average surgery time was 41 minutes. Conclusions: The cartilage graft in a CARTIPATCH ® hydrogel confirms a significant clinical improvement especially for deep and large lesions. The use of a matrix allowing a homogeneous distribution and no cellular leakage can explain the good histological results with over 60% of the repaired cartilage mostly hyaline at 24 months. Two phase III studies one versus osteochondral autografts and one versus microfracture have been started.

Research paper thumbnail of Comparaison de la progression radiologique dans la polyarthrite rhumatoïde sous anti TNF-alpha en fonction de l'ancienneté de la maladie

Revue du Rhumatisme, 2007

Research paper thumbnail of A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study

Annals of the Rheumatic Diseases, 2014

ABSTRACT In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with... more ABSTRACT In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes.

Research paper thumbnail of HIV-related nephropathies associated with changes in blood and kidney tissue virus load

Kidney International, 2008

CASE PRESENTATION A 39-year-old African woman was admitted to our Nephrology Department in June 2... more CASE PRESENTATION A 39-year-old African woman was admitted to our Nephrology Department in June 2004 for exploration of a nephrotic syndrome. Relevant past medical history included HIV-1-positive infection since 1997. She had been treated with a combination of nucleoside reverse transcriptase inhibitors (AZT, 3TC, and abacavir) since April 2002. One week before admission, her CD4 þ lymphocyte count was 350 mm À3 and the RNA viral load was undetectable. Findings at admission included blood pressure of 160/ 90 mm Hg and peripheral inferior limb edema. Clinical examination of the heart, abdomen, and nervous system was normal. Urinary protein excretion was 3.6 g per 24 h, hematuria 3 Â 10 4 red blood cells per 1 ml of urine, albumin 25 g l À1 , serum creatinine and creatinine clearance estimated by the Cockroft and Gault formula were, respectively, 88 mmol l À1 and 80 ml min À1 , and electrolytes were in the normal range, as were C-reactive protein and serum fibrinogen. Blood count gave hemoglobin at 10 g per 100 ml, white blood cells 6600 mm À3 , and platelets 287 Â 10 9 l À1 without schizocytes. Liver function tests were normal. Immunoelectrophoresis showed no serum monoclonal component, serum IgA and IgM were in the normal range, and IgG was increased to 41.6 g l À1 (normal range: 6.9-14 g l À1). Serological tests for hepatitis were negative. Antinuclear antibody (titer of 1:80) was considered insignificant. Immunological tests were negative for antineutrophil cytoplasm antibodies, and for antibodies against double-stranded DNA, extractable nuclear antigens, cardiolipin, and b-2-glycoprotein 1.

Research paper thumbnail of Association between the IRF5 rs2004640 functional polymorphism and systemic sclerosis: A new perspective for pulmonary fibrosis

Arthritis & Rheumatism, 2009

ObjectiveThere is now growing evidence that connective tissue diseases, including systemic sclero... more ObjectiveThere is now growing evidence that connective tissue diseases, including systemic sclerosis (SSc), share a common genetic background. Microarray studies support a pivotal role of type I interferon (IFN) in the pathophysiology of connective tissue diseases. Interferon regulatory factors coordinate the expression of type I IFNs, and the IRF5 gene has been identified as a susceptibility gene of systemic lupus and Sjögren's syndrome. The aim of this study was to determine whether the IRF5 rs2004640 single‐nucleotide polymorphism is associated with SSc.MethodsThe IRF5 rs2004640 (GT) functional polymorphism was genotyped in 1,641 subjects of French European Caucasian origin: a discovery set comprising 427 patients with SSc and 380 control subjects and a replication set comprising 454 patients with SSc and 380 control subjects.ResultsIn both the discovery set and the replication set, the TT genotype was significantly more common in patients with SSc than in control subjects, w...

Research paper thumbnail of Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review

Annals of the Rheumatic Diseases, 2005

To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagno... more To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a predictor of future development of RA in healthy subjects and in patients with early undifferentiated arthritis. Methods: A systematic analysis of the literature published between 1999 and February 2006 was conducted. Data were collected on the sensitivity and specificity of the two generations of anti-CCP antibodies for diagnosing RA and predicting future development of the disease. Results: Among 107 studies initially identified, 68 had interpretable data and were analysed. Diagnostic properties were assessed in 58 studies: mean (SD) sensitivity was 53 (10)% (range 41-68) and 68 (15)% (range 39-94) for anti-CCP1 and anti-CCP2, respectively; mean (SD) specificity was 96 (3)% (range 90-99) and 95 (5)% (range 81-100) for anti-CCP1 and anti-CCP2, respectively. Predictive properties were assessed in 14 studies; odds ratio (95% confidence interval) of anti-CCP1 and anti-CCP2 for the future development of RA were 20 (14 to 31) and 25 (18 to 35), respectively, among patients with early undifferentiated arthritis and 64.5 (8.5 to 489) and 28 (8 to 95), respectively, among healthy subjects. Conclusion: Sensitivity of the second generation of anti-CCP is close to that of rheumatoid factor, with a higher specificity, for distinguishing RA from other rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive of the future development of RA in both healthy subjects and patients with undifferentiated arthritis.

Research paper thumbnail of Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group

Annals of the Rheumatic Diseases, 2010

ObjectiveTo identify a core set of preliminary items considered as important for the very early d... more ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as foll...

Research paper thumbnail of A8.3 Deficit of S100A4 Prevents Joint Destruction and Systemic Bone Loss in hTNFtg Mouse Model

Annals of the Rheumatic Diseases, 2013

Background and Objectives Autoantibodies recognising citrullinated proteins (ACPA) are highly spe... more Background and Objectives Autoantibodies recognising citrullinated proteins (ACPA) are highly specific for rheumatoid arthritis (RA), precede the clinical onset of the disease by years and are the strongest known risk factor for bone loss. We have recently shown that ACPA specific for citrullinated vimentin directly interact with osteoclast precursors and induce bone loss. In patients with RA, ACPA-containing immune complexes can be detected in synovial fluid and tissue. We hypothesised that (I) immune complexes directly promote osteoclast maturation and, consecutively, bone loss and that (II) the type of IgG-glycan is important for the interaction with osteoclast precursors, since ACPA have been shown to be hyposialylated. Materials and Methods We differentiated preosteoclasts from human monocytes and stimulated them with artificial immune complexes generated by heat aggregation from pooled human IgG (IVIG). Part of the IgG had been pretreated with neuraminidase or PNGase F to remove sialic acid or the whole Fc glycan, respectively. For in vivo studies we injected murine immune complexes in the knee joints of C57-BL/6 mice. Results Stimulation of preosteoclasts with immune complexes resulted in their dramatically increased maturation to osteoclasts. This effect was even more pronounced with complexes formed from desialylated IgG. Monomeric IgG and fully deglycosylated immune complexes did not alter osteoclast maturation. qPCR and FACS-analyses revealed that all Fcγ receptors (FcγR) are upregulated during osteoclastogenesis with FcγR I and FcγR III being the most prominent ones. Desialylated immune complexes induced the activation of spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) as well as the upregulation of the transcription factor c-fos in preosteoclasts. Injection of murine immune complexes into the knee joints of C57-BL/6 mice caused accumulation of osteoclasts in the vicinity of the site of injection. Conclusions Our data show that IgG immune complexes promote osteoclastogenesis. They upregulate the pro-osteoclastogenic transcription factor c-fos, after binding to activating FcγRs on preosteoclasts. This interaction is highly dependent on the absence of sialic acid in the Fc-glycan of the IgG. Altogether, we propose a novel mechanism by which ACPA promote bone loss independent of inflammation.

Research paper thumbnail of Valeur diagnostique et prédictive des anticorps anti-peptides cycliques citrullinés (anti-CCP) dans la polyarthrite rhumatoïde: revue systématique de 68 études

Revue du Rhumatisme, 2006

concentration de protéines localement tout en évitant les effets secondaires liés au transfert de... more concentration de protéines localement tout en évitant les effets secondaires liés au transfert de gène et de protéines in vivo dans des maladies comme la polyarthrite rhumatoïde (PR). Les vecteurs viraux AAV sont de bons candidats pour la thérapie génique intraarticulaire, mais il existe chez l'homme des anticorps naturels anti-AAV dans le sang ou le liquide synovial (LS) qui peuvent entraver l'infection. Objectifs : Comparer la neutralisation exercée par différents sérotypes d'AAV : AAV1, AAV2, AAV5 et AAV8, et déterminer, dans un système de culture de synoviocytes humains in vitro, le sérotype le plus adapté à une thérapie génique intra-articulaire. Patients et Méthodes.-Le LS provenait de 10 patients atteints de PR et les synoviocytes humains de prélèvements chirurgicaux. Des AAV de sérotypes 1, 2, 5 et 8 codant le gène de l'interleukine (IL-) 4 ont été utilisés. L'efficacité d'infection des AAV sur les synoviocytes a été mesurée par ELISA sur IL-4 dans le surnageant de culture. L'activité neutralisante contre AAV-IL-4 a été déterminée en évaluant le pouvoir neutralisant du LS (ou du sang de patients PR) sur l'infection des synoviocytes par les 4 sérotypes d'AAV. Résultats.-Le sérotype 2 était celui qui infectait le plus efficacement les synoviocytes humains, suivi de près par le sérotype 1. Les sérotypes 5 et surtout le sérotype 8 étaient moins efficaces. L'infection des synoviocytes par les sérotypes 1 et 2 était fortement inhibée par le LS de patients PR, tandis qu'elle l'était beaucoup moins lorsqu'on utilisait les sérotypes 5 et 8. Les activités neutralisantes du sang et du LS étaient corrélées pour chaque sérotype. Enfin, la neutralisation de l'infection par le LS pouvait être levée en utilisant de plus fortes quantités d'AAV in vitro. Conclusion.-Les sérotypes qui infectent le mieux les synoviocytes (sérotypes 1 et 2) en absence de LS sont aussi ceux qui sont le plus fortement neutralisés par le LS. En conséquence, le sérotype 5 serait le mieux adapté à une thérapie génique intra-articulaire car, bien qu'infectant un peu moins efficacement les synoviocytes, l'immunité dirigée contre lui est beaucoup plus faible. L'ensemble de ces données pourrait être utile pour mettre au point un transfert de gène intra-articulaire individuellement adapté à chaque patient [1].

Research paper thumbnail of Effet taille des traitements médicamenteux sur l'atteinte périphérique des spondylarthrites ankylosantes: revue systématique de la littérature

Revue du Rhumatisme, 2007

Research paper thumbnail of Phenotype-Haplotype Correlation of IRF5 in Systemic Sclerosis: Role of 2 Haplotypes in Disease Severity

The Journal of Rheumatology, 2010

Objective.Identification of an association between IRF5 rs2004640 and systemic sclerosis (SSc) ha... more Objective.Identification of an association between IRF5 rs2004640 and systemic sclerosis (SSc) has highlighted a key role for type 1 interferon (IFN). Additional functional IRF5 variants have been identified as autoimmune susceptibility factors. Our aim was to investigate whether IRF5 haplotypes confer susceptibility to SSc, and to perform genotype haplotype-phenotype correlation analyses.Methods.We genotyped IRF5 rs377385, rs2004640, and rs10954213 in 1623 individuals of French European Caucasian origin. SSc patient subphenotypes were analyzed according to cutaneous subsets and for SSc-related pulmonary fibrosis.Results.Case-control studies of single markers revealed an association between IRF5 rs3757385, rs2004640, and rs10954213 variants and SSc. We identified an IRF5 risk haplotype “R” (padj = 0.024, OR 1.23, 95% CI 1.07–1.40) and a mirrored protective haplotype “P” (padj = 8.8 × 10−3, OR 0.78, 95% CI 0.68–0.90) for SSc susceptibility. Genotype-phenotype correlation analyses fai...

Research paper thumbnail of Severe Refractory Rheumatoid Arthritis Successfully Treated with Combination Rituximab and Anti-Tumor Necrosis Factor- -Blocking Agents

The Journal of Rheumatology, 2009

Research paper thumbnail of Cardiovascular risk in rheumatoid arthritis: effects of anti-TNF drugs

Expert Opinion on Pharmacotherapy, 2008

Patients with rheumatoid arthritis (RA) have an increased risk of atherosclerotic cardiovascular ... more Patients with rheumatoid arthritis (RA) have an increased risk of atherosclerotic cardiovascular disease which cannot be explained by traditional cardiovascular risk factors alone. Atherosclerosis is considered an inflammatory condition and inflammation experienced in RA may contribute to accelerated atherosclerosis. Thus, it should be hypothesized that treatment with antitumor necrosis factor alpha (anti-TNF-alpha), TNF-alpha being a pivotal component of the inflammatory cascade, may decrease concomitantly intra-articular inflammation and vessel inflammation. The purpose of this review is to examine the data regarding cardiovascular mortality and morbidity in RA and the evidence available to date evaluating the influence of anti-TNF-alpha treatments in RA on the occurrence of cardiovascular events, on surrogate markers of atherosclerosis and classical cardiovascular risk factors. Clinical trials, original studies and review articles were identified from a Medline search (1998 - December 2007). Articles in English were reviewed, with emphasis on those containing assessments of cardiovascular effects (i.e., biological, structural, clinical) of anti-TNF-alpha drug. The suppression of systemic inflammation favoring atherosclerosis may lead to an improvement in cardiovascular prognosis in inflammatory disorders. Thus, reduction of inflammatory joint disease in RA with anti-TNF-alpha therapy, as probably with any powerful disease-modifying antirheumatic drugs, seems to be, at least in part, associated with concomitant reduction of the risk of cardiovascular events.

Research paper thumbnail of High N-terminal pro–brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis

Arthritis & Rheumatism, 2007

Objective. To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohor... more Objective. To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). Methods. Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea. Results. Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P < 0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P ‫؍‬ 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P ‫؍‬ 0.08), and erythrocyte sedimentation rate >28 mm/hour (P ‫؍‬ 0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69-62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45-387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90-450.33]). Conclusion. This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.

Research paper thumbnail of Cardiac involvement in systemic sclerosis assessed by tissue-doppler echocardiography during routine care: A controlled study of 100 consecutive patients

Arthritis & Rheumatism, 2008

To assess the prevalence of primary cardiac complications in a large population of patients with ... more To assess the prevalence of primary cardiac complications in a large population of patients with systemic sclerosis (SSc), using recently developed echocardiographic techniques. We prospectively studied 100 consecutive patients (mean +/- SD age 54 +/- 14 years; 86 women) presenting with SSc without pulmonary arterial hypertension or clinical manifestations of heart failure. All patients underwent standard echocardiography, along with measurements of longitudinal velocities by tissue Doppler imaging (TDI) to assess left ventricular (LV) and right ventricular (RV) contractility and LV diastolic function. Results were compared with those in 26 age- and sex-matched healthy controls. Patients with SSc had a wider mean left atrial diameter and impaired relaxation compared with the controls. A trend was observed toward a smaller LV ejection fraction (EF) in the patients (mean +/- SD 64.9 +/- 0.6%) than in the controls (67.2 +/- 0.7%), as well as higher pulmonary artery pressure (mean +/- SD 33.3 +/- 0.6 mm Hg versus 30.8 +/- 1.0 mm Hg). LVEF was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;55% in 7 patients versus none of the controls. Peak systolic mitral annular velocity as measured by TDI was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5 cm/second in 14 patients versus none of the controls (P = 0.040). Mitral annulus early diastolic velocity was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 cm/second in 30 patients versus 2 of the controls (P = 0.022). Fifteen patients and none of the controls had reduced peak systolic tricuspid annular velocity (P = 0.039). The TDI results correlated with each other, but not with lung abnormalities or other disease characteristics. Depression of LV and RV systolic and LV diastolic function is common in patients with SSc and is due to primary myocardial involvement. Considering the major contributions of TDI, the addition of this simple technique to standard measurements may improve the detection of heart involvement in patients with SSc.

Research paper thumbnail of Enhanced expression of ephrins and thrombospondins in the dermis of patients with early diffuse systemic sclerosis

Annals of the Rheumatic Diseases, 2010

Research paper thumbnail of Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis

Annals of the Rheumatic Diseases, 2011

ObjectiveTo evaluate the possible merit of endothelial markers for the prediction of ischaemic di... more ObjectiveTo evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).MethodsCirculating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up.ResultsAfter the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p≤0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 2...

Research paper thumbnail of Lack of Specificity of the 6-Minute Walk Test as an Outcome Measure for Patients with Systemic Sclerosis

The Journal of Rheumatology, 2009

Objective.The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascular... more Objective.The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascular diseases and has been considered as a surrogate endpoint. However, conflicting results have been reported in systemic sclerosis (SSc). Our objective was to evaluate the relationships of the 6-min walking distance (6MWD) and organ damage in SSc.Methods.Eighty-seven consecutive patients with SSc were included and prospectively investigated; they underwent 6MWT in addition to conventional assessment of possible lung, heart, kidney, skin, and muscle involvement, and disease activity scoring, severity, and quality of life determination.Results.Twenty-six patients (30%) had an abnormal 6MWT and the mean 6MWD was 461.8 ± 103.0 m. When considering 6MWT as a binary variable — normal or abnormal — C-reactive protein (CRP) was the only independent variable associated with abnormal 6MWT. Considered as a continuous variable, the 6MWD was associated with measures of lung involvement and inflammation,...

Research paper thumbnail of SAT0467 The Five Prospective Observational Trials of the International Systemic Sclerosis FP7-Health Research Project Desscipher: A Interim Report

Annals of the Rheumatic Diseases, 2015

Background Due to lack of adequate clinical research data, drug treatment of the rare disease sys... more Background Due to lack of adequate clinical research data, drug treatment of the rare disease systemic sclerosis (SSc) is commonly off-label. The international EC-funded research project DeSScipher (acronym for “to decipher the optimal management of systemic sclerosis”) was designed to increase the evidence-based treatment strategies for SSc patients and subsequently to improve their long-term quality-of-life. Objectives The primary objective is to compare the outcomes of different treatments with respect to efficacy and safety of currently used off-label drugs from the early to the advanced phases of the main SSc-associated organ dysfunctions in a routine rheumatology in- and outpatient setting. Methods Five prospective observational trials (OTs), carried out within the EULAR Scleroderma Trials and Research (EUSTAR) group, have been designed to analyze current treatment approaches of early functionally relevant manifestations such as digital ulcers (OT1) and hand arthritis (OT2) to the morbidity and mortality-driving manifestations such as interstitial lung disease (OT3), pulmonary hypertension (OT4) and severe heart disease (OT5). The study protocols are accessible at clinicaltrials.gov Identifiers NCT01836263, NCT01834157, NCT01858259, NCT01840748, NCT01829126. Results Between April 2013 and January 2015, 1781 SSc patients have been screened at 27 contributing EUSTAR centers. 1577 (89%) patients have been enrolled into at least one of the five OTs. In particular, 1179, 127, 981, 237 and 716 patients have been enrolled into OT1-5, respectively (3240 in total; a given patient could be enrolled into multiple OTs), which represents a baseline patient recruitment rate of 79% of the target number of 4098 patients (accordingly 226%, 79%, 59%, 25% and 91% of the required number of 522, 160, 1670, 960, 786 patients for OT1-5, respectively). The completion of 1-year (OT3, OT5) and 2-year follow-up visits (OT1, OT2, OT4) are pending. Conclusions DeSScipher is currently the largest prospective observational research project ever for SSc. While patient recruitment is still ongoing, preliminary results of the five OTs are expected in late 2015 and the final results depending on the completion of follow-up visits are expected between 2017 and 2018. Acknowledgements The DeSScipher project was funded by the European Community's Framework Programme 7 (FP7-HEALTH-2012.2.4.4-2 - Observational trials in rare diseases) under grant agreement N° 305495. We acknowledge the contribution of the following EUSTAR centers: Wuppertal (member N°192), Lille (93), Bad Bramstedt (187), Moscow (78), Assiut (168), Moscow (190), Bucharest (100), Monserrato (142), Iasi (162), Cluj-Napoca (16), Frankfurt (124), Salford/Manchester (80), Tübingen (56), Ancona (34), Zagreb (51) and Roma (94). Disclosure of Interest None declared