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Lemoine M.,Imperial College London | Eholie S.,Félix Houphouët-Boigny University | Lacombe K.,Saint Antoine Hospital | Lacombe K.,Paris-Sorbonne University
Journal of Hepatology | Year: 2015

The burden of liver disease may dramatically increase in the near future in Africa, where screening and access to care and treatment are hampered by inadequate disease surveillance, lack of high-quality tools to assess chronic liver disease, and underestimated needs for human and financial resources. Chronic hepatitis may be considered as silent and neglected killer, fuelled by many years of global inertia from stakeholders and policy makers alike. However, the global battle against viral hepatitis is facing a new era owing to the advent of highly effective drugs, innovative tools for screening and clinical follow-up, and recent signs that governments, advocacy groups and global health organizations are mobilizing to advocate universal accessto- treatment. This review details the barriers to prevention, screening and treatment of viral hepatitis on the African continent, focuses on the urgent need for operational and research programmes, and suggests integrated ways to tackle the global epidemic. © 2014 European Association for the Study of the Liver.


Bejaoui M.,Lariboisiere Hospital | Sokol H.,Paris-Sorbonne University | Sokol H.,Saint Antoine Hospital | Marteau P.,Lariboisiere Hospital | Marteau P.,Paris-Sorbonne University
Digestive Diseases | Year: 2015

Microorganisms present in the intestine possess proinflammatory or anti-inflammatory activities which may modulate inflammatory bowel disease (IBD). The concepts followed by researchers in trying to target the microbiota in IBD were to decrease pathogens or pathobionts, or only the microbial load, and more recently, to favor growth and persistence of favorable microorganisms. We review, here, those concepts and critically analyze the clinical data (especially randomized controlled trials) obtained using antibiotics and probiotics. We eventually present and criticize the rational and data obtained so far following new research strategies including the use of new probiotics, genetically modified organisms and fecal transplantation. © 2015 S. Karger AG, Basel.


Souied E.H.,University Paris Est Creteil | Delcourt C.,University of Bordeaux 1 | Delcourt C.,French Institute of Health and Medical Research | Querques G.,University Paris Est Creteil | And 7 more authors.
Ophthalmology | Year: 2013

Objective: To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). Design: The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. Participants: Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. Methods: Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. Main Outcome Measures: The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). Results: Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. Conclusions: In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same effect on CNV incidence in the second eye as did the placebo. However, RBCM fatty acid measurements revealed that CNV incidence was significantly reduced in DHA-supplemented patients showing a steadily high EPA plus DHA index over 3 years. © 2013 by the American Academy of Ophthalmology Published by Elsevier Inc.


Trivedi P.J.,University of Birmingham | Corpechot C.,Saint Antoine Hospital | Pares A.,University of Barcelona | Hirschfield G.M.,University of Birmingham
Hepatology | Year: 2016

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. © 2016 by the American Association for the Study of Liver Diseases.


Sokol H.,Saint Antoine Hospital | Seksik P.,Saint Antoine Hospital | Carrat F.,University Pierre and Marie Curie | Nion-Larmurier I.,Saint Antoine Hospital | And 3 more authors.
Gut | Year: 2010

Background and aims: Concomitant use of immunosuppressants (IS) with scheduled infliximab (IFX) maintenance therapy for Crohn's disease (CD) or ulcerative colitis (UC) is debated. The aim of this study was to assess whether IS co-treatment is useful in patients with inflammatory bowel disease (IBD) on scheduled IFX infusions. Methods: 121 consecutive patients with IBD (23 UC, 98 CD) treated by IFX and who received at least 6 months of IS co-treatment (azathioprine (AZA) or methotrexate (MTX)) were studied. In each patient, the IFX treatment duration was divided into semesters which were independently analysed regarding IBD activity. Results: Semesters with IS (n=265) and without IS (n=319) were analysed. IBD flares, perianal complications and switch to adalimumab were less frequently observed in semesters with IS than in those without IS (respectively: 19.3% vs 32.0%, p=0.003; 4.1% vs 11.8%, p=0.03; 1.1% vs 5.3%, p=0.006). Maximal C-reactive protein (CRP) level and IFX dose/kg observed during the semesters were lower in semesters with IS. Within semesters with IS, IBD flares and perianal complications were less frequently observed in semesters with AZA than in those with MTX. In multivariate analysis, IS co-treatment was associated with a decreased risk of IBD flare (OR 0.52; 95% CI 0.35 to 0.79) Conclusion: In patients with IBD receiving IFX maintenance therapy, IS co-treatment is associated with reduced IBD activity, IFX dose and switch to adalimumab. In this setting, co-treatment with AZA seems to be more effective than co-treatment with MTX. Benefit of such a combination treatment has to be balanced with potential risks, notably infections and cancers.


Mael-Ainin M.,Tenon Hospital | Mael-Ainin M.,Paris-Sorbonne University | Abed A.,Tenon Hospital | Abed A.,Paris-Sorbonne University | And 6 more authors.
Journal of the American Society of Nephrology | Year: 2014

Increased renal expression of periostin, a protein normally involved in embryonic and dental development, correlates with the decline of renal function in experimental models and patient biopsies. Because periostin has been reported to induce cell differentiation, we investigated whether it is also involved in the development of renal disease and whether blocking its abnormal expression improves renal function and/ or structure. After unilateral ureteral obstruction in wild-type mice, we observed a progressive increase in the expression and synthesis of periostin in the obstructed kidney that associated with the progression of renal lesions. In contrast, mice lacking the periostin gene showed less injury-induced interstitial fibrosis and inflammation and were protected against structural alterations. This protection was associated with a preservation of the renal epithelial phenotype. In vitro, administration of TGF-b to renal epithelial cells increased the expression of periostin several-fold, leading to subsequent loss of the epithelial phenotype. Furthermore, treatment of these cells with periostin increased the expression of collagen I and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery of antisense oligonucleotides to inhibit periostin expression protected animals from L-NAME-induced renal injury. These data strongly suggest that periostinmediates renal disease in response to TGF-b and that blocking periostinmay be a promising therapeutic strategy against the development of CKD. Copyright © 2014 by the American Society of Nephrology.


Mladenovic Z.,University Pierre and Marie Curie | Saurel A.-S.,Saint Antoine Hospital | Berenbaum F.,University Pierre and Marie Curie | Jacques C.,University Pierre and Marie Curie
Journal of Rheumatology | Year: 2014

Objective. To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1b (IL-1b) and related to cartilage catabolism in murine osteoblasts. Methods. Osteoblasts were obtained from Swiss mice and cultured for 3 weeks. HA-treated osteoblasts were incubated with 100 μg/ml HA during the last week of culture, then stimulated with IL-1b (10 ng/ml) for 24 h. The expression of matrix metalloproteinases 3 and 13 (MMP-3 and MMP-13), ADAMTS-4 and ADAMTS-5, tissue inhibitor of metalloproteinases (TIMP), osteo-protegerin, and receptor activator of nuclear factor-kB ligand (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13 release was assessed by Western blot analysis. Results. IL-1b increased the mRNA levels of MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5 and release of MMP-3 and MMP-13. Seven days of HA treatment significantly prevented the IL-1b-increased mRNA levels of MMP-3 (-61%, p < 0.01), MMP-13 (-56%, p <0.01), ADAMTS-4 (-58%, p < 0.05), ADAMTS-5 (-52%, p < 0.01), and RANKL (-49%, p < 0.05), but not TIMP. As well, IL-1b-induced production of MMP-3 and MMP-13 was inhibited, by 27% (p < 0.01) and 40% (p < 0.01), respectively. Conclusion. In an inflammatory context in murine osteoblasts, HA can inhibit the expression of MMP and ADAMTS. Because HA can counteract the production of these mediators in chondrocytes, its beneficial effect in osteoarthritis may be due to its action on cartilage and subchondral bone. © 2014. All rights reserved.


Mansiaux Y.,French Institute of Health and Medical Research | Mansiaux Y.,Paris-Sorbonne University | Carrat F.,French Institute of Health and Medical Research | Carrat F.,Paris-Sorbonne University | Carrat F.,Saint Antoine Hospital
BMC Medical Research Methodology | Year: 2014

Background: Big data is steadily growing in epidemiology. We explored the performances of methods dedicated to big data analysis for detecting independent associations between exposures and a health outcome. Methods. We searched for associations between 303 covariates and influenza infection in 498 subjects (14% infected) sampled from a dedicated cohort. Independent associations were detected using two data mining methods, the Random Forests (RF) and the Boosted Regression Trees (BRT); the conventional logistic regression framework (Univariate Followed by Multivariate Logistic Regression - UFMLR) and the Least Absolute Shrinkage and Selection Operator (LASSO) with penalty in multivariate logistic regression to achieve a sparse selection of covariates. We developed permutations tests to assess the statistical significance of associations. We simulated 500 similar sized datasets to estimate the True (TPR) and False (FPR) Positive Rates associated with these methods. Results: Between 3 and 24 covariates (1%-8%) were identified as associated with influenza infection depending on the method. The pre-seasonal haemagglutination inhibition antibody titer was the unique covariate selected with all methods while 266 (87%) covariates were not selected by any method. At 5% nominal significance level, the TPR were 85% with RF, 80% with BRT, 26% to 49% with UFMLR, 71% to 78% with LASSO. Conversely, the FPR were 4% with RF and BRT, 9% to 2% with UFMLR, and 9% to 4% with LASSO. Conclusions: Data mining methods and LASSO should be considered as valuable methods to detect independent associations in large epidemiologic datasets. © 2014 Mansiaux and Carrat; licensee BioMed Central Ltd.


Van Vre E.A.,French Institute of Health and Medical Research | Ait-Oufella H.,French Institute of Health and Medical Research | Ait-Oufella H.,Saint Antoine Hospital | Tedgui A.,French Institute of Health and Medical Research | And 2 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

Apoptotic cell death is an important feature of atherosclerotic plaques, and it seems to exert both beneficial and detrimental effects depending on the cell type and plaque stage. Because late apoptotic cells can launch proatherogenic inflammatory responses, adequate engulfment of apoptotic cells (efferocytosis) by macrophages is important to withstand atherosclerosis progression. Several efferocytosis systems, composed of different phagocytic receptors, apoptotic ligands, and bridging molecules, can be distinguished. Because phagocytes in atherosclerotic plaques are very much solicited, a fully operative efferocytosis system seems to be an absolute requisite. Indeed, recent studies demonstrate that deletion of just 1 of the efferocytosis pathways aggravates atherosclerosis. This review discusses the role of apoptosis in atherosclerosis and general mechanisms of efferocytosis, to end with indirect and direct indications of the significance of effective efferocytosis in atherosclerosis. © 2012 American Heart Association, Inc.


Michon M.,Saint Antoine Hospital | Maheu E.,Saint Antoine Hospital | Berenbaum F.,Saint Antoine Hospital
Annals of the Rheumatic Diseases | Year: 2011

Background Hand osteoarthritis (HOA) is a common disease that affects up to 40% of adults and may severely impair their health-related quality of life (HRQL). Objectives To assess how HRQL has been evaluated in HOA, focusing on a comparison of HRQL impairment in HOA and rheumatoid arthritis (RA), differences between erosive and non-erosive HOA and differences between OA of the thumb base (TB) and interphalangeal (IP) OA. Methods A systematic review of the literature. Results The authors screened 167 articles and retained 33. The outcome subsets usually reported were pain, function and stiffness. Overall HRQL was rarely assessed and the tools used differed greatly. Aesthetic damage was never studied in published articles, although this is a major complaint in daily practice. Three articles compared symptomatic HOA and RA; whereas pain and subjective health did not differ significantly, there is conflicting evidence of the difference between disability and stiffness between these groups. Two papers compared erosive and non-erosive HOA and found divergent elements concerning functional impairment; patients with erosive HOA reported more aesthetic damage. Three papers compared TB and IP OA with divergent results in terms of pain and function. Conclusion Overall HRQL is a broad concept involving domains beyond pain, function and stiffness. Few data are presently available on HOA, but it seems to have almost as great an impact as RA on HRQL. Further studies on HRQL in patients with HOA are required. Aesthetic damage should also be assessed withspecifically designed tools.

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