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Le Touquet – Paris-Plage, France

Bujan L.,EA 3694 Human Fertility Research Group | Bujan L.,Toulouse 1 University Capitole | Walschaerts M.,Toulouse 1 University Capitole | Moinard N.,Toulouse 1 University Capitole | And 15 more authors.
Fertility and Sterility

Objective: To determine the consequences of adjuvant testicular germ cell tumor treatment (TGCT) on sperm characteristics and sperm DNA, and to evaluate the predictors of sperm recovery. Design: Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting: University hospitals. Patient(s): One hundred twenty-nine volunteer TGCT patients and a control group of 257 fertile men. Intervention(s): Routine semen analyses, sperm DNA, and chromatin assessments. Main Outcome Measure(s): Comparisons of mean sperm characteristics before and after treatment, with sperm recovery analyzed by the Kaplan-Meier method. Result(s): The quantitative and qualitative sperm characteristics decreased after treatment, with lowest values at 3 and 6 months and with variations according to treatment type. The mean total sperm count recovered to pretreatment values at 12 months after treatment after two or fewer bleomycin, etoposide, and cisplatin (BEP) cycles, but not after radiotherapy or more than two BEP cycles. Only the treatment modalities and pretreatment sperm production were related to recovery of the World Health Organization reference sperm values. An increased proportion of patients had elevated high sperm DNA stainability at 6 months after radiotherapy. Conclusion(s): Adjuvant treatments for testicular germ cell tumor have drastic effects on spermatogenesis and sperm chromatin quality. These new data on both the recovery period according to treatment modalities and the post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive. © 2013 by American Society for Reproductive Medicine. Source

Sellmann C.,Friedrich - Schiller University of Jena | Jin C.J.,Friedrich - Schiller University of Jena | Degen C.,Friedrich - Schiller University of Jena | De Bandt J.,University of Paris Descartes | And 2 more authors.
Journal of Nutrition

Background: Genetic factors, a diet rich in fat and sugar, and an impaired intestinal barrier function are critical in the development of nonalcoholic steatohepatitis (NASH). The nonessential amino acid glutamine (Gln) has been suggested to have protective effects on intestinal barrier function but also against the development of liver diseases of various etiologies. Objective: The effect of oral Gln supplementation on the development of Western-style diet (WSD)-induced NASH in mice was assessed. Methods: Female 6- to 8-wk-old C57BL/6J mice were pair-fed a control (C) diet or a WSD alone or supplemented with 2.1 g L-Gln/kg body weight for 6 wk (C+Gln or WSD+Gln). Indexes of liver damage, lipid peroxidation, and glucose metabolism and endotoxin concentrations were measured. Results: Although Gln supplementation had no effect on the loss of the tight junction protein occludin, the increased portal endotoxin and fasting glucose concentrations found inWSD-fed mice,markers of liver damage (e.g., nonalcoholic fatty liver disease activity score and number of neutrophils in the liver) were significantly lower in the WSD+Gln group than in the WSD group (~47% and ~60% less, respectively; P < 0.05). Concentrations of inducible nitric oxide synthase (iNOS) protein and 3-nitrotyrosin protein adducts were significantly higher in livers of WSD-fed mice than in all other groups (~8.6- and ~1.9-fold higher, respectively, compared with the C group; P < 0.05) but did not differ between WSD+Gln-, C-, and C+Gln-fed mice. Hepatic tumor necrosis factor a and plasminogen activator inhibitor 1 concentrations were significantly higher in WSD-fed mice (~1.6- and ~1.8-fold higher, respectively; P < 0.05) but not in WSD +Gln-fed mice compared with C mice. Conclusion: Our data suggest that the protective effects of oralGln supplementation on the development ofWSD-inducedNASH in mice are associated with protection against the induction of iNOS and lipid peroxidation in the liver. © 2015 American Society for Nutrition. Source

Benjamin L.,University of Paris Descartes | Benjamin L.,EHESP School of Public Health | Benjamin L.,Glaxosmithkline | Buthion V.,University of Lyon | And 4 more authors.
BMC Health Services Research

Background: Oral anticancer drugs (OADs) allow treating a growing range of cancers. Despite their convenience, their acceptance by healthcare professionals and patients may be affected by medical, economical and organizational factors. The way the healthcare payment system (HPS) reimburses OADs or finances hospital activities may impact patients' access to such drugs. We discuss how the HPS in France and USA may generate disincentives to the use of OADs in certain circumstances. Discussion. French public and private hospitals are financed by National Health Insurance (NHI) according to the nature and volume of medical services provided annually. Patients receiving intravenous anticancer drugs (IADs) in a hospital setting generate services, while those receiving OADs shift a part of service provision from the hospital to the community. In 2013, two million outpatient IADs sessions were performed, representing a cost of 815 million to the NHI, but positive contribution margin of 86 million to hospitals. Substitution of IADs by OADs mechanically induces a shortfall in hospital income related to hospitalizations. Such economic constraints may partially contribute to making physicians reluctant to prescribe OADs. In the US healthcare system, coverage for OADs is less favorable than coverage for injectable anticancer drugs. In 2006, a Cancer Drug Coverage Parity Act was adopted by several states in order to provide patients with better coverage for OADs. Nonetheless, the complexity of reimbursement systems and multiple reimbursement channels from private insurance represent real economic barriers which may prevent patients with low income being treated with OADs. From an organizational perspective, in both countries the use of OADs generates additional activities related to physician consultations, therapeutic education and healthcare coordination between hospitals and community settings, which are not considered in the funding of hospitals activities so far. Summary. Funding of healthcare services is a critical factor influencing in part the choice of cancer treatments and this is expected to become increasingly important as economic constraints grow. Drug reimbursement systems and hospital financing changes, coupled with other accompanying measures, should contribute to improve equal and safe patient access to appropriate anticancer drugs and improve the management and care pathway of cancer patients. © 2014 Benjamin et al.; licensee BioMed Central Ltd. Source

Bujan L.,University Paul Sabatier | Walschaerts M.,University Paul Sabatier | Brugnon F.,Federation Francaise des CECOS | Brugnon F.,Universitary Hospital Estaing | And 13 more authors.
Fertility and Sterility

Objective To determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery. Design Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting University hospitals. Patient(s) Seventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men. Intervention(s) Semen analyses, and sperm DNA and chromatin assessments. Main Outcome Measure(s) Comparisons of sperm characteristics before and after treatment. Result(s) Patients already had altered sperm characteristics before lymphoma treatment, with no identified risk factor. Sperm count, total sperm count, motility, and vitality decreased after treatment, with lowest values at 3 and 6 months. Twelve months after treatment, mean sperm count recovered to pretreatment values after doxorubicin, bleomycin, vinblastine, darcarbacine (ABVD) or ABVD + radiotherapy, but not after doxorubicin, cyclophosphamide, vincristine, prednisone (CHOP) or mechlorethamine, oncovin, procarbazine, prednisone (MOPP) chemotherapies. It was noteworthy that 7% of patients remained azoospermic at 24 months. After 24 months, Kaplan-Meier estimates showed that more than 90% of patients will recover normal sperm count after ABVD or ABVD + radiotherapy vs. 61% for CHOP chemotherapies. In multivariate analyses including diagnosis and treatment protocol, only pretreatment total sperm count was related to recovery. Compared with a control group, lymphoma patients had higher sperm chromatin alterations and DNA fragmentation before any treatment. After treatment, DNA fragmentation assessed by TUNEL assay and sperm chromatin structure assay decreased from 3 and 6 months, respectively, while remaining higher than in the control group during follow-up. Conclusion(s) Lymphoma patients had altered sperm DNA and chromatin before treatment. Lymphoma treatment had damaging effects on spermatogenesis. These data on both the recovery period according to treatment modalities and the pre- and post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive. © 2014 by the American Congress of Rehabilitation Medicine. Source

Bobbio A.,Paris Center University Hospitals | Alifano M.,Paris Center University Hospitals | Alifano M.,University of Paris Descartes
Pharmacological Research

Surgery is still the best treatment option of lung cancer but only one third of patients are operable and prognosis remains mediocre in operated patients, with the exception of initial stages. Medical treatment is fast moving toward new frontiers. New insights in the biology of cancer development led to discovery of new drugs, which are more effective as compared to conventional platinum based chemotherapy. A new approach to immunotherapy based on immune-check point represents a remarkable innovation in lung cancer treatment. Initial trials with anti PD-1 antibodies in metastatic patients provided results never observed with previously known drug categories. Several key question need to be answered to identify patients most likely to respond to anti PD-1/anti PD-L1 treatments, to assess the role of combined treatment modalities including immune check point receptor block (associations with surgery, chemotherapy, ITKs), and to boost host immune response, possibly by lowering his systemic inflammation and improving nutritional status. © 2015 Elsevier Ltd. All rights reserved. Source

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