Salmon-Ceron D.,University of Paris Descartes |
Tubach F.,University Paris Diderot |
Lortholary O.,University of Paris Descartes |
Chosidow O.,UniversiteParis EST |
And 11 more authors.
Annals of the Rheumatic Diseases | Year: 2011
Background: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). Objective: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. Methods: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. Results: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3-72.9); p<0.0001) or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0);p=0.002). Conclusion: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.
Travert M.,French Institute of Health and Medical Research |
Travert M.,UniversiteParis Est |
Huang Y.,French Institute of Health and Medical Research |
Huang Y.,UniversiteParis Est |
And 16 more authors.
Blood | Year: 2012
The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most downexpressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents. © 2012 by The American Society of Hematology.
Sibon D.,University of Paris Descartes |
Fournier M.,Center Hospitalier Lyon Sud |
Briere J.,University Paris Diderot |
Lamant L.,French Institute of Health and Medical Research |
And 11 more authors.
Journal of Clinical Oncology | Year: 2012
Purpose: Systemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated. Patients and Methods: Patients treated in three Groupe d'Étude des Lymphomes de l'Adulte prospective clinical trials with confirmed systemic ALCL after immunohistopathologic review and defined ALK expression status were analyzed. Results: Among the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β2-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β2-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. Conclusion: Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment. © 2012 by American Society of Clinical Oncology.
Goreac D.,UniversiteParis Est
ESAIM - Control, Optimisation and Calculus of Variations | Year: 2012
We aim at characterizing viability, invariance and some reachability properties of controlled piecewise deterministic Markov processes (PDMPs). Using analytical methods from the theory of viscosity solutions, we establish criteria for viability and invariance in terms of the first order normal cone. We also investigate reachability of arbitrary open sets. The method is based on viscosity techniques and duality for some associated linearized problem. The theoretical results are applied to general On/Off systems, Cook's model for haploinsufficiency, and a stochastic model for bacteriophage λ. © EDP Sciences, SMAI, 2011.
Meunier F.,UniversiteParis Est
RAIRO - Operations Research | Year: 2013
A simple idea used in many combinatorial algorithms is the idea of pivoting. Originally, it comes from the method proposed by Gauss in the 19th century for solving systems of linear equations. This method had been extended in 1947 by Dantzig for the famous simplex algorithm used for solving linear programs. From since, a pivoting algorithm is a method exploring subsets of a ground set and going from one subset σ to a new one σ′ by deleting an element inside σ and adding an element outside σ: σ′ = σvaua, with vaσ and ua‰ σ. This simple principle combined with other ideas appears to be quite powerful for many problems. This present paper is a survey on algorithms in operations research and discrete mathematics using pivots. We give also examples where this principle allows not only to compute but also to prove some theorems in a constructive way. A formalisation is described, mainly based on ideas by Michael J. Todd. © 2013 EDP Sciences.