Gestermann N.,University Paris - Sud |
Mekinian A.,University Paris - Sud |
Comets E.,University Paris Diderot |
Loiseau P.,French Institute of Health and Medical Research |
And 5 more authors.
Genes and Immunity | Year: 2010
Signal transducer and activator of transcription 4 (STAT4) is a transcription factor mainly activated by interleukin 12, which promotes the secretion of type 2 interferon (IFN) by T-helper 1 cells. We assessed the association of STAT4 gene polymorphism and primary Sjögren's syndrome (pSS) and its functional relevance. We analyzed STAT4 rs7582694 polymorphism in an exploratory cohort of 186 pSS patients and 152 controls, and in a replication cohort of 192 pSS patients and 483 controls, all Caucasian. mRNA levels of STAT4α, STAT4Β, STAT1, and the type 1 IFN-induced genes PKR, MX1 and IFITM1 were assessed in peripheral blood mononuclear cells (PBMCs) from 30 pSS patients. STAT4 rs7582694 C allele was associated with pSS in both cohorts (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.27-1.93, P2.3 × 10 -5). The association was increased for homozygous subjects, which suggests a recessive effect of the STAT4 at-risk allele. STAT4α, STAT4Β and STAT1 mRNA levels in PBMCs were not significantly associated with rs7582694 genotypes, however the mRNA levels of STAT4α and type 1 IFN-induced genes were strongly correlated: PKR (P4 × 10-3, r0.51), MX1 (P2 × 10-4, r0.63) and IFITM1 (P8 × 10 3, r0.47), suggesting that STAT4 might be involved in not only type 2 IFN production but also in type 1 IFN-mediated effects. © 2010 Macmillan Publishers Limited All rights reserved.
Cherin P.,Medecine Interne |
Rose C.,Hematologie |
De Roux-Serratrice C.,Medecine Interne |
Tardy D.,Actelion Pharmaceuticals |
And 9 more authors.
Journal of Inherited Metabolic Disease | Year: 2010
Background: Gaucher disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. Type 1 GD (GD1), the most common variant, is classically considered non-neuronopathic. Methods: We performed a national cross-sectional observational survey-the French Observatoire on Gaucher Disease (FROG)-in patients with GD1 between March 2005 and September 2006. The study included all patients over 18 years of age with confirmed GD1 who attended participating centers for regular follow-up. Results: One hundred and five patients were included, in whom we studied the prevalence and characteristics of relevant neurological symptoms associated with the neuraxis. Of these, 51 (49%) GD1 patients presented at least one neurological symptom. Four patients (4%) had Parkinson disease and 22 (21%) presented with at least one parkinsonian sign or at least one sign frequently associated with Parkinson disease. Five patients (5%) had a previous diagnosis of peripheral neuropathy. Other central nervous system symptoms were recorded in 20 (19%) patients and other peripheral nervous system symptoms in 39 (37%) patients. Conclusions: These data challenge the current classification of GD, and suggest that the three forms of GD each involve a different profile of neurological manifestations. © 2010 SSIEM and Springer.
Bulletin de l'Academie Nationale de Medecine | Year: 2010
The objective of anti-osteoporotic treatments is the prevention of the first or recurrent fractures. Screening of at risk patients is the basis of improvement of osteoporosis management. Prevalent fractures are strong determinants of incident fractures. In patients without fractures screening of risk factors, and quantification of risk using FRA X®tool, allows detection of patients who should receive highest priority for treatment. Several drugs have shown that they are able to decrease the risk of fracture, providing persistence and compliance. Non pharmacological approach (including nutrition and physical activity) is part of optimal management of osteoporosis.
Gottenberg J.E.,Hopitaux Universitaires Of Strasbourg |
Ravaud P.,Center dEpidemiologie Clinique |
Cantagrel A.,Toulouse University Hospital Center |
Combe B.,Immuno rhumatologie |
And 14 more authors.
Annals of the Rheumatic Diseases | Year: 2012
Objectives: Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. Methods: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. Results: 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti- CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. Conclusions: Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.
Nicaise-Roland P.,UF Immunologie Autoimmunite et Hypersensibilites |
Nogueira L.,Biologie Cellulaire |
Nogueira L.,University Paul Sabatier |
Demattei C.,Biostatistiques et Epidemiologie |
And 14 more authors.
Annals of the Rheumatic Diseases | Year: 2013
Objectives: To compare the performance of anticitrullinated peptides/protein antibodies (ACPA) detected by three immunoassays in the French ESPOIR cohort of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) and to study the relationship between ACPA and disease activity. Methods: A diagnosis of RA (1987 American College of Rheumatology (ACR) criteria) was established at baseline in 497 patients and after a 2-year follow-up in 592 patients. At baseline, antibodies to citrullinated fibrinogen (AhFibA), antimutated citrullinated vimentin (anti-MCV) and anticyclic citrullinated peptide (anti-CCP2) were assayed and the individual and combined diagnostic sensitivities and predictive values of the tests were determined. Relationships between ACPA positivity and the 28-joint disease activity score and Health Assessment Questionnaire scores were analysed. Results: At a diagnostic specificity of at least 98%, the three tests exhibited similar diagnostic sensitivities (47-48.5%). When considering as positive patients with at least one positive test, the sensitivity increased to 53.5% with a probable loss of specificity. Among the patients classified as having UA at baseline, 30% were positive for one ACPA, the positive predictive values for RA of the three tests ranging from 73% to 80% but increasing when two tests were associated. Whatever the test used, the addition of ACPA positivity to the 1987 criteria enhanced their sensitivity by 6%, close to that of the 2010 ACR/European League Against Rheumatism (EULAR) criteria. Conclusions: In early arthritis, AhFibA, anti-MCV and anti-CCP2 showed similar diagnostic sensitivity with a high diagnostic specificity and a similar high positive predictive value for RA. Adding ACPA to the 1987 ACR criteria significantly increased the number of patients classified as having RA, confirming the validity of the recent inclusion of the serological criterion in the ACR/EULAR criteria.
Valat J.-P.,University of Tours |
Genevay S.,University of Geneva |
Marty M.,University Paris Est Creteil |
Rozenberg S.,Rhumatologie |
Koes B.,Erasmus Medical Center
Best Practice and Research: Clinical Rheumatology | Year: 2010
Sciatica is a symptom rather than a specific diagnosis. Available evidence from basic science and clinical research indicates that both inflammation and compression are important in order for the nerve root to be symptomatic. Tumour necrosis factor-alpha (TNF-α) is a key mediator in animal models, but its exact contribution in human radiculopathy is still a matter of debate. Sciatica is mainly diagnosed by history taking and physical examination. In general, the clinical course of acute sciatica is considered to be favourable. In the first 6-8 weeks, there is consensus that treatment of sciatica should be conservative. We review and comment on the levels of evidence of the efficacy of patient information, advice to stay active, physical therapy analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), epidural corticosteroid injections and transforaminal peri-radicular injections of corticosteroid. There is good evidence that discectomy is effective in the short term. but, in the long term, it is not more effective than prolonged conservative care. Shared decision making with regard to surgery is necessary in the absence of severe progressive neurological symptoms. Although the term sciatica is simple and easy to use, it is, in fact, an archaic and confusing term . For most researchers and clinicians, it refers to a radiculopathy, involving one of the lower extremities, and related to disc herniation (DH). As such, the term 'sciatica' is too restrictive as nerve roots from L1 to L4 may also be involved in the same process. However, even more confusing is the fact that patients, and many clinicians alike, use sciatica to describe any pain arising from the lower back and radiating down to the leg. The majority of the time, this painful sensation is referred pain from the lower back and is neither related to DH nor does it result from nerve-root compression. Although differentiating the radicular pain from the referred pain may be challenging for the clinician, it is of primary importance. This is because the epidemiology, clinical course and, most importantly, therapeutic interventions are different for these two conditions. It should, however, be emphasised that the quality of the available evidence is rather limited due to a considerable heterogeneity in the study populations included in the trials. This makes generalisation of findings across studies, and to routine clinical practice, a challenge . Prevalence estimates of radicular pain related to DH also vary considerably between studies, which is, in part, due to differences in the definitions used . A recent review showed that the prevalence of sciatic symptoms is rather variable, with values ranging from 1.6% to 43% . If stricter definitions of sciatica were used, for example, in terms of pain distribution and/or pain duration, lower prevalence rates were reported. Studies in working populations with physically demanding jobs consistently report higher rates of sciatica compared with studies in the general population. © 2009.
PubMed | Orgametrie Biostatistiques, Medecine Interne, Medecine Vasculaire, Rhumatologie and 7 more.
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2016
To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc).Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20mg or placebo, three times daily for 12weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05).Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.231.61 vs 1.792.40 p=0.04) and W12 (0.861.62 vs 1.512.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12).The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit.NCT01295736.
PubMed | Rhumatologie
Type: Journal Article | Journal: PloS one | Year: 2013
To provide a table indicating the risk for developing anti citrullinated protein antibody (ACPA) positive rheumatoid arthritis (RA) according to ones HLA-DRB1 genotype.We HLA-DRB1 genotyped 857 patients with ACPA positive RA and 2178 controls from South Eastern and Eastern France and calculated Odds Ratios (OR) for developing RA for 106 of 132 possible genotypes accounting for 97% of subjects.HLA-DRB1 genotypic ORs for developing ACPA positive RA range from 28 to 0.19. HLA-DRB1 genotypes with HLA-DRB1*04SE (HLA-DRB1*0404, HLA-DRB1*0405, HLA-DRB1*0408), HLA-DRB1*0401, HLA-DRB1*01 are usually associated with high risk for developing RA. The second HLA-DRB1 allele in genotype somewhat modulates shared epitope associated risk. We did not identify any absolutely protective allele. Neither the Reviron, nor the du Montcel models accurately explains our data which are compatible with the shared epitope hypothesis and suggest a dosage effect among shared epitope positive HLA-DRB1 alleles, double dose genotypes carrying higher ORs than single dose genotypes.HLA-DRB1 genotypic risk for developing ACPA positive RA is influenced by both HLA-DRB1 alleles in genotype. We provide an HLA-DRB1 genotypic risk table for ACPA positive RA.
PubMed | Caen University Hospital Center, Institute Of La Main Nantes Atlantique, Rhumatologie and Brest University Hospital Center
Type: Case Reports | Journal: Chirurgie de la main | Year: 2014
The authors report on a case of dynamic compression of the ulnar nerve in the wrist by a supernumerary hypothenar muscle in a twenty-six-year-old female patient. For eight months, she had been suffering from acroparesthesias in the territory of the ulnar nerve with pain upon effort irradiating into the forearm. The initial clinical examination was rather non-conclusive and the electromyogram found no anomaly. Faced with this dynamic symptomatology, a provisional ultrasonography was performed, revealing a picture of apparent muscular appearance, confirmed on the MRI. Surgical exploration also confirmed the presence of this muscle located between the ulnar artery at the front and the ulnar nerve, which it was pressing against, at the back. It was a supernumerary fascicle of the flexor digiti minimi brevis for which was performed a complete surgical removal. At three months from neurolysis of the ulnar nerve and removal of the muscle, the preoperative symptoms had completely disappeared. This observation reminds us of the primordial role that imaging plays in detecting ulnar nerve compression at the wrist. Although the precision of an MRI as regards the description of supernumerary muscle of the wrist is not discussed, this case emphasizes the interest of ultrasonography.
News Article | November 15, 2016
A study finds that smoking or being overweight makes it more difficult for patients with rheumatoid arthritis to achieve optimal control of inflammation and symptoms, despite standard of care treatment. American and Canadian researchers, who collected data on more than 1,100 patients at multiple sites, presented their findings at the American College of Rheumatology/Association of Rheumatology Health Professionals annual meeting on November 15 in Washington, DC. "Early, aggressive treatment to achieve remission is the primary goal of therapy and can be best achieved early on when treating patients with newly diagnosed rheumatoid arthritis, as early disease control is associated with improved long-term outcomes," said Vivian Bykerk, MD, senior investigator and director of the Inflammatory Arthritis Center of Excellence at Hospital for Special Surgery. "We have previously shown that individuals with excess weight are less likely to achieve sustained remission in the first three years after diagnosis. Here we explore the impact of smoking and being overweight or obese on the ability to achieve good control of symptoms and inflammation in men and women with rheumatoid arthritis." Data were collected at 19 sites across Canada as part of the CATCH (Canadian Early Arthritis Cohort) Study. The multicenter study included rheumatoid arthritis patients diagnosed within 12 months of symptom onset. Researchers looked at the patient's disease activity score, known as the DAS, when they entered the study and at follow-up visits. The DAS is based on the number of swollen and tender joints, a blood test that reflects inflammation, and the patient's own description of their arthritis symptoms over the prior week. After the initial enrollment, patients were seen by their rheumatologist as part of their usual care for follow up every three months in the first year, every six months in the second year, and annually thereafter. Data about their arthritis were collected at each visit. The researchers analyzed how gender, excess weight and smoking (current/former/never) affected symptoms when patients entered the study and over time. The study included 1,109 patients with a mean age of 54 at study onset. Almost all of them were being treated with methotrexate and/or another conventional oral medication when they enrolled. Most of the participants (72%) were female. Among the women, 31% were overweight, 32% were obese, and 15% currently smoked. Among the males, 44% were overweight, 35% were obese and 22% currently smoked. Sex, excess weight and smoking were not significantly associated with symptom severity early on, when patients entered the study. However, all three factors influenced how much symptoms improved over time. The average rate of improvement in the disease activity score was lower in women compared to men. Less symptom improvement was also seen in patients who were overweight or obese compared with those of a healthy weight. Current smokers also saw less symptom relief compared to nonsmokers over time. Former smokers, however, did not do worse than those who had never smoked. The most dramatic differences in symptoms were seen in patients who were overweight or obese and smoked. These patients had considerably worse outcomes over time compared to nonsmoking patients with a healthy weight. "These results contribute to growing evidence of how lifestyle impacts how well patients may respond to treatment and the potential value of referring them to proven community-based smoking cessation and weight management programs," Dr. Bykerk concluded. Authors: Susan J. Bartlett1,2, Orit Schieir3, Kathleen Andersen4, Gilles Boire5, Boulos Haraoui6, Carol Hitchon7, Edward Keystone8, Janet E. Pope9, J Carter Thorne10, Diane Tin11, Vivian P. Bykerk12 and Canadian Early Arthritis Cohort (CATCH) Investigators, 1Department of Medicine, Division of ClinEpi, Rheumatology, Respirology, McGill University, Montreal, QC, Canada, 2Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3University of Toronto, Toronto, ON, Canada, 4Rheumatology, Hospital for Special Surgery, New York, NY, 5Rheumatology Division, CHUS - Sherbrooke University, Sherbrooke, QC, Canada, 61551, Ontario Street East, Institut de Recherche en Rhumatologie de Montréal (IRRM), Montreal, QC, Canada, 7University of Manitoba, Winnipeg, MB, Canada, 8Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada, 9University of Western Ontario, St Joseph's Health Care, London, ON, Canada, 10Southlake Regional Health Centre, Newmarket, ON, Canada, 11The Arthritis Program, Southlake Regional Health Centre, Newmarket, ON, Canada, 12Divison of Rheumatology, Hospital for Special Surgery, New York, NY Hospital for Special Surgery (HSS) is the world's largest academic medical center focused on musculoskeletal health. HSS is nationally ranked No. 1 in orthopedics and No. 2 in rheumatology by U.S. News & World Report (2016-2017), and is the first hospital in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. HSS has one of the lowest infection rates in the country. HSS is an affiliate of Weill Cornell Medical College and as such all Hospital for Special Surgery medical staff are faculty of Weill Cornell. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at http://www. .