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451 results on '"Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie"'

401. Creatinine index and transthyretin as additive predictors of mortality in haemodialysis patients

Author: Terrier, Nathalie, Jaussent, Isabelle, Dupuy, Anne-Marie, Morena, Marion, Delcourt, Cécile, Chalabi, Lotfi, Rouanet, Catherine, Canaud, Bernard, Cristol, Jean-Paul, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Renal Research and Training Institute, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Association Installation à Domicile Epurations Rénales (AIDER), Centre Hémodialyse Languedoc Méditerranée, CHLM, Service de Néphrologie, Dialyse et Soins Intensifs, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: hemodialysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, malnutrition, mortality, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, creatinine index, transthyretin
Abstract: BACKGROUND: Malnutrition and inflammation are recognized as important predictors of poor clinical outcome in haemodialysis (HD). This study was designed to estimate the relative contribution of known biological markers of inflammation, malnutrition and muscle mass in the prognosis of HD patients. METHODS: A total of 187 HD patients (100 women, 87 men, median age 66.7 years [22.3-93.5]) were followed-up yearly for 5 years. At baseline, pre-dialysis values of C-reactive protein (CRP), albumin, transthyretin, total HDL- and LDL-cholesterol and triacylglycerol were determined. Estimation of creatinine index (CI) as muscle mass marker was determined by creatinine kinetic modelling using pre- and post-dialysis creatinine values. RESULTS: During the follow-up period, 89 deaths (53 from cardiovascular causes) were observed. After adjustment for age, gender, dialysis vintage, smoking, diabetes mellitus and hypertension, the highest tertile of CRP and lowest tertile of transthyretin and CI were significantly associated with all-cause mortality (relative risk (RR) = 1.98 [1.12-3.47], 2.58 [1.48-4.50], 2.71 [1.42-5.19], respectively). In addition, low CI had an additive value to low levels of transthyretin. In contrast, high cholesterol (RR = 0.47 [0.27-0.83], P = 0.0091) and vitamin E concentrations (RR = 0.46 [0.26-0.80], P = 0.006) showed a protective trend for all-cause mortality. In the multivariate analysis, transthyretin appeared as the most predictive biological marker of non-CV mortality (RR = 3.78 [1.30-10.96], P = 0.014), and CI of CV mortality (RR = 2.61 [1.06-6.46], P = 0.038), respectively. Discussion. These results confirm that uraemic malnutrition constitutes an important risk factor for mortality in HD. Beyond transthyretin, CI seems to be an additional marker routinely available and monthly determined in HD patients.
Published: 2008

402. Lipids in elderly women

Author: Dupuy, Anne-Marie, Carrière, Isabelle, Scali, Jacqueline, Cristol, Jean-Paul, Ritchie, Karen, Dartigues, Jean-François, Gambert, Philippe, Ancelin, Marie-Laure, Villebrun, Dominique, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Laboratoire de biochimie médicale (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, transdermal estradiol, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, lipid lowering agent, cholesterol, lipids (amino acids, peptides, and proteins), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, cohort, triglycerides, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Objective: To evaluate plasmatic lipid levels in elderly women in the general population as a function of use of lipid lowering agents (LLA) and hormone therapy (HT) Methods: 4271 women over 65 were recruited from three French cities. Analyses were performed after stratification by LLA treatment and HT and adjusting for a large range of socio-demographic and clinical factors. Results: Fifteen percent of women currently used HT (78% transdermal estradiol), and 30% were taking LLA. In this population, 4.6% of women were taking both HT and LLA (fibrate for 2.4% and statin for 2.2%). In non-LLA treated women, current HT was associated with lower total cholesterol, LDL-C, and non-HDL-C compared to never users. Women treated with LLA, also had lower total cholesterol, LDL-C, and non-HDL-C compared to non-LLA users, whereas triglyceride levels were the highest in statin users and lowest in fibrate users. Fibrate was associated with a more favorable lipid pattern than statin independently of HT use. In women without coronary heart disease or diabetes HT, statin, or fibrate were associated with lower LDL-C level risk based on NCEP guidelines (adjusted OR=0.67 [IC95=0.53;0.85], 0.38 [0.29;0.47], and 0.32 [0.25;0.42], respectively) with a possible interaction between fibrate and HT (0.18 [0.10;0.30]). Conclusions: Estradiol-based HT may lower atherogenic lipoproteins in post-menopausal women. In primary prevention of coronary heart disease, combining HT and fibrate may provide additional benefits compared to fibrate use.
Published: 2008

403. Creatinine index and transthyretin as additive predictors of mortality in haemodialysis patients

Author: Terrier, Nathalie, Jaussent, Isabelle, Dupuy, Anne-Marie, Morena, Marion, Delcourt, Cécile, Chalabi, Lotfi, Rouanet, Catherine, Canaud, Bernard, Cristol, Jean-Paul, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Renal Research and Training Institute, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Association Installation à Domicile Epurations Rénales (AIDER), Centre Hémodialyse Languedoc Méditerranée, CHLM, Service de Néphrologie, Dialyse et Soins Intensifs, and Villebrun, Dominique
Subjects: hemodialysis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, malnutrition, mortality, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, creatinine index, transthyretin
Abstract: BACKGROUND: Malnutrition and inflammation are recognized as important predictors of poor clinical outcome in haemodialysis (HD). This study was designed to estimate the relative contribution of known biological markers of inflammation, malnutrition and muscle mass in the prognosis of HD patients. METHODS: A total of 187 HD patients (100 women, 87 men, median age 66.7 years [22.3-93.5]) were followed-up yearly for 5 years. At baseline, pre-dialysis values of C-reactive protein (CRP), albumin, transthyretin, total HDL- and LDL-cholesterol and triacylglycerol were determined. Estimation of creatinine index (CI) as muscle mass marker was determined by creatinine kinetic modelling using pre- and post-dialysis creatinine values. RESULTS: During the follow-up period, 89 deaths (53 from cardiovascular causes) were observed. After adjustment for age, gender, dialysis vintage, smoking, diabetes mellitus and hypertension, the highest tertile of CRP and lowest tertile of transthyretin and CI were significantly associated with all-cause mortality (relative risk (RR) = 1.98 [1.12-3.47], 2.58 [1.48-4.50], 2.71 [1.42-5.19], respectively). In addition, low CI had an additive value to low levels of transthyretin. In contrast, high cholesterol (RR = 0.47 [0.27-0.83], P = 0.0091) and vitamin E concentrations (RR = 0.46 [0.26-0.80], P = 0.006) showed a protective trend for all-cause mortality. In the multivariate analysis, transthyretin appeared as the most predictive biological marker of non-CV mortality (RR = 3.78 [1.30-10.96], P = 0.014), and CI of CV mortality (RR = 2.61 [1.06-6.46], P = 0.038), respectively. Discussion. These results confirm that uraemic malnutrition constitutes an important risk factor for mortality in HD. Beyond transthyretin, CI seems to be an additional marker routinely available and monthly determined in HD patients.
Published: 2008

404. Dietary fat and the risk of age-related maculopathy: the POLANUT Study

Author: Delcourt, Cécile, Carrière, Isabelle, Cristol, Jean-Paul, Lacroux, Annie, Gerber, Mariette, Study Group, Polanut, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Épidémiologie et prévention : environnement et efficacité des interventions (EPIPREV), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, and POLANUT Study Group
Subjects: age-related maculopathy, dietary fat, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, unsaturated fats
Abstract: POLANUT Study Group : Cécile Delcourt (Principal Investigator, Bordeaux, France), Annie Lacroux (Montpellier, France), Isabelle Carrière (Montpellier, France), Mariette Gerber (Montpellier, France), Jean-Paul Cristol (Montpellier, France), Bernard Descomps (Montpellier, France), Claude L Léger (Montpellier, France), Francis Delpeuch (Montpellier, France), Anne-Dominique Girard (Montpellier, France), Stéphanie Denayer (Montpellier, France), Marie-Hortense Rocolle (Montpellier, France), Agnès Mora (Montpellier, France).; International audience; This study aimed at assessing the associations of dietary fat with the risk of age-related maculopathy (ARM), in the framework of a population-based study from southern France. Nutritional data were collected using a dietitian-administered food-frequency questionnaire. ARM was classified from retinal photographs using the international classification and included neovascular age-related macular degeneration, geographic atrophy, soft indistinct drusen, soft distinct drusen associated with pigmentary abnormalities. After multivariate adjustment, high total, saturated and monounsaturated fat intake were associated with increased risk for ARM (odds ratio (OR)=4.74, P=0.007; OR=2.70, P=0.04; and OR= 3.50, P=0.03, respectively). Total polyunsaturated fatty acid was not significantly associated with ARM. Total and white fish intake was not significantly associated with ARM, but fatty fish intake (more than once a month versus less than once a month) was associated with a 60% reduction in risk for ARM (OR=0.42, P=0.01).European Journal of Clinical Nutrition (2007) 61, 1341-1344; doi:10.1038/sj.ejcn.1602685; published online 14 February 2007.
Published: 2007

405. Dietary fat and the risk of age-related maculopathy: the POLANUT Study

Author: Annie Lacroux, Jean-Paul Cristol, Cécile Delcourt, Mariette Gerber, Isabelle Carrière, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Épidémiologie et prévention : environnement et efficacité des interventions (EPIPREV), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, and POLANUT Study Group
Subjects: Male, medicine.medical_specialty, 030309 nutrition & dietetics, Population, Medicine (miscellaneous), Physiology, Drusen, Macular Degeneration, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dietary Fats, Unsaturated, Risk Factors, Surveys and Questionnaires, Confidence Intervals, Odds Ratio, Humans, Medicine, Risk factor, education, 2. Zero hunger, 0303 health sciences, education.field_of_study, Nutrition and Dietetics, business.industry, Incidence, Unsaturated fat, Odds ratio, Middle Aged, Macular degeneration, medicine.disease, unsaturated fats, Dietary Fats, Surgery, Age-related maculopathy, age-related maculopathy, chemistry, dietary fat, Multivariate Analysis, 030221 ophthalmology & optometry, Maculopathy, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract: POLANUT Study Group : Cécile Delcourt (Principal Investigator, Bordeaux, France), Annie Lacroux (Montpellier, France), Isabelle Carrière (Montpellier, France), Mariette Gerber (Montpellier, France), Jean-Paul Cristol (Montpellier, France), Bernard Descomps (Montpellier, France), Claude L Léger (Montpellier, France), Francis Delpeuch (Montpellier, France), Anne-Dominique Girard (Montpellier, France), Stéphanie Denayer (Montpellier, France), Marie-Hortense Rocolle (Montpellier, France), Agnès Mora (Montpellier, France).; International audience; This study aimed at assessing the associations of dietary fat with the risk of age-related maculopathy (ARM), in the framework of a population-based study from southern France. Nutritional data were collected using a dietitian-administered food-frequency questionnaire. ARM was classified from retinal photographs using the international classification and included neovascular age-related macular degeneration, geographic atrophy, soft indistinct drusen, soft distinct drusen associated with pigmentary abnormalities. After multivariate adjustment, high total, saturated and monounsaturated fat intake were associated with increased risk for ARM (odds ratio (OR)=4.74, P=0.007; OR=2.70, P=0.04; and OR= 3.50, P=0.03, respectively). Total polyunsaturated fatty acid was not significantly associated with ARM. Total and white fish intake was not significantly associated with ARM, but fatty fish intake (more than once a month versus less than once a month) was associated with a 60% reduction in risk for ARM (OR=0.42, P=0.01).European Journal of Clinical Nutrition (2007) 61, 1341-1344; doi:10.1038/sj.ejcn.1602685; published online 14 February 2007.
Published: 2007

406. Pharmacotherapy (excluding biotherapies) for ankylosing spondylitis: development of recommendations for clinical practice based on published evidence and expert opinion

Author: Thierry Schaeverbeke, Frédéric Lavie, Emmanuelle Dernis, Alain Cantagrel, René Marc Flipo, Xavier Le Loët, Pascal Claudepierre, Philippe Goupille, Alain Saraux, Daniel Wendling, Stephan Pavy, Bernard Combe, Jacques Tebib, Jean-Francis Maillefert, Xavier Mariette, Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'immunologie et rhumatologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Rhumatologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Bordeaux [Bordeaux], Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département de Rhumatologie[Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie
Subjects: Male, medicine.medical_specialty, Consensus, Alternative medicine, MEDLINE, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Rheumatology, MESH: Practice Guidelines as Topic, medicine, Humans, Spondylitis, Ankylosing, 030212 general & internal medicine, MESH: Consensus, Spondylitis, Randomized Controlled Trials as Topic, MESH: Treatment Outcome, 030203 arthritis & rheumatology, Ankylosing spondylitis, Evidence-Based Medicine, MESH: Humans, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Evidence-based medicine, MESH: Follow-Up Studies, medicine.disease, MESH: Spondylitis, Ankylosing, MESH: Anti-Inflammatory Agents, Non-Steroidal, MESH: Sensitivity and Specificity, MESH: Male, 3. Good health, MESH: France, Treatment Outcome, MESH: Randomized Controlled Trials as Topic, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Meta-analysis, Family medicine, Practice Guidelines as Topic, Physical therapy, Female, France, business, MESH: Female, Rheumatism, MESH: Evidence-Based Medicine, Follow-Up Studies
Abstract: International audience; OBJECTIVES: To develop recommendations about pharmacotherapy (excluding biotherapeutic agents) in patients with axial forms of ankylosing spondylitis (AS) seen in everyday clinical practice. METHODS: The recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points about which recommendations were needed. Then, a literature task force looked for relevant publications in the following: Cochrane, PubMed, and Ovid databases; and abstracts from the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on the data in these publications, recommendations were drafted then validated by a group of experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts. RESULTS: The four focal points were the best strategy for using nonsteroidal anti-inflammatory drugs, role for systemic glucocorticoid therapy, role for glucocorticoid injections into the sacroiliac joints and entheses, and role for slow-acting drugs (e.g., methotrexate, sulfasalazine, leflunomide, thalidomide, and pamidronate). Of the 661 promising publications identified by the literature search, 173 were found to be relevant. The evidence in these 173 papers was reported to experts during interactive workshops. At the end of the workshops, the experts drafted recommendations, which were then validated by having all panel participants vote during a final meeting. There were seven recommendations, whose strength ranged from A to D. CONCLUSION: Seven recommendations about pharmacotherapy in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS in France.
Published: 2007

407. Imaging for the diagnosis and follow-up of ankylosing spondylitis: development of recommendations for clinical practice based on published evidence and expert opinion

Author: Frédéric Lavie, Bernard Combe, Jean-Francis Maillefert, Thierry Schaeverbeke, Xavier Le Loët, Emmanuelle Dernis, Alain Saraux, René-Marc Flipo, Pascal Claudepierre, Stephan Pavy, Philippe Goupille, Alain Cantagrel, Daniel Wendling, Jacques Tebib, Xavier Mariette, Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Bordeaux [Bordeaux], Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Rhumatologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'immunologie et rhumatologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département de Rhumatologie[Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie
Subjects: Male, Delphi Technique, Alternative medicine, MESH: Monitoring, Physiologic, MESH: Delphi Technique, 030218 nuclear medicine & medical imaging, Scientific evidence, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, MESH: Practice Guidelines as Topic, Randomized Controlled Trials as Topic, computer.programming_language, Evidence-Based Medicine, MESH: Follow-Up Studies, Continuity of Patient Care, MESH: Spondylitis, Ankylosing, Magnetic Resonance Imaging, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Radiological weapon, Practice Guidelines as Topic, Female, France, MESH: Tomography, X-Ray Computed, Diagnostic Imaging, medicine.medical_specialty, MEDLINE, Sensitivity and Specificity, 03 medical and health sciences, Rheumatology, medicine, Humans, Spondylitis, Ankylosing, Medical physics, Monitoring, Physiologic, 030203 arthritis & rheumatology, Ankylosing spondylitis, MESH: Humans, business.industry, MESH: Diagnostic Imaging, Evidence-based medicine, medicine.disease, MESH: Sensitivity and Specificity, MESH: Male, MESH: France, MESH: Continuity of Patient Care, MESH: Randomized Controlled Trials as Topic, Physical therapy, Tomography, X-Ray Computed, business, computer, MESH: Female, Delphi, Rheumatism, MESH: Evidence-Based Medicine, Follow-Up Studies
Abstract: International audience; OBJECTIVE: To develop recommendations regarding imaging studies for the diagnosis and follow-up of patients with axial forms of ankylosing spondylitis (AS) seen in everyday practice. METHODS: Evidence from the literature and expert opinion were used to develop the recommendations. Using the Delphi consensus procedure, a scientific committee selected five areas of interest, about which scientific evidence was sought by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on this evidence, a panel of experienced rheumatologists drafted recommendations, using expert opinion if needed to supplement gaps in evidence. For each recommendation, the level of evidence and the extent of agreement among the experts were specified. RESULTS: The five areas of interest dealt with the usefulness of imaging studies for the diagnosis, follow-up, prognostic evaluation, and assessment of treatment responses in patients with AS. The literature search retrieved 144 articles based on titles and abstracts. After elimination of articles that did not include an analysis of the radiological evaluation of AS, 73 articles were left for review. Eight recommendations were drafted then validated by having all panel participants vote during a final meeting. CONCLUSION: Eight recommendations about the use of imaging studies in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.
Published: 2007

408. Clinical and laboratory follow-up for treating and monitoring patients with ankylosing spondylitis: development of recommendations for clinical practice based on published evidence and expert opinion

Author: Bernard Combe, Alain Cantagrel, Thierry Schaeverbeke, Emmanuelle Dernis, Alain Saraux, Frédéric Lavie, Xavier Mariette, Philippe Goupille, Pascal Claudepierrre, Jean Francis Maillefert, René-Marc Flipo, Daniel Wendling, Jacques Tebib, Xavier Le Loët, Stephan Pavy, Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Rhumatologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Bordeaux [Bordeaux], Service d'immunologie et rhumatologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département de Rhumatologie[Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie
Subjects: Male, MESH: Combined Modality Therapy, Delphi Technique, Delphi method, MESH: Monitoring, Physiologic, MESH: Risk Assessment, Severity of Illness Index, MESH: Delphi Technique, 0302 clinical medicine, MESH: Practice Guidelines as Topic, 030212 general & internal medicine, BASDAI, Randomized Controlled Trials as Topic, Evidence-Based Medicine, Continuity of Patient Care, MESH: Spondylitis, Ankylosing, Combined Modality Therapy, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Meta-analysis, Practice Guidelines as Topic, Female, France, medicine.medical_specialty, Consensus, MEDLINE, Clinical Chemistry Tests, Risk Assessment, Sensitivity and Specificity, 03 medical and health sciences, Rheumatology, MESH: Severity of Illness Index, medicine, Humans, Spondylitis, Ankylosing, Medical physics, MESH: Consensus, Spondylitis, Monitoring, Physiologic, 030203 arthritis & rheumatology, Ankylosing spondylitis, MESH: Humans, MESH: Clinical Chemistry Tests, business.industry, Evidence-based medicine, medicine.disease, MESH: Sensitivity and Specificity, MESH: Male, MESH: France, MESH: Continuity of Patient Care, MESH: Randomized Controlled Trials as Topic, Physical therapy, business, BASFI, MESH: Female, MESH: Evidence-Based Medicine
Abstract: International audience; OBJECTIVE: To develop French recommendations about the clinical and laboratory follow-up of patients with axial ankylosing spondylitis (AS) seen in everyday practice. METHODS: The recommendations were developed based on evidence from the literature and on expert opinion. A Delphi consensus procedure was used by a scientific committee to select five focal points, about which evidence was obtained by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. The results of the literature review were used by a panel of experienced rheumatologists to draft and to validate the recommendations, using expert opinion if needed to supplement gaps in published knowledge. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: The three focal points selected using the Delphi procedure dealt with choosing the best clinical and laboratory parameters for monitoring patients with AS; whether follow-up benefits from the use of composite indices (e.g., the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the BAS Functional Index [BASFI] and the BAS Metrology Index [BASMI]); and the clinical and laboratory parameters that predict functional or structural outcomes in patients with AS. The literature search retrieved 1510 relevant articles based on titles and abstracts, of which 322 were selected for in-depth review. Five recommendations about the clinical and laboratory follow-up of patients with AS were developed then validated by having all panel participants vote during a final meeting. CONCLUSION: Recommendations about the clinical and laboratory follow-up of patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.
Published: 2007

409. Waist Circumference Adds to the Variance in Plasma C-Reactive Protein Levels in Elderly Patients with Metabolic Syndrome

Author: Dupuy, Anne-Marie, Jaussent, Isabelle, Lacroux, Annie, Durant, Richard, Cristol, Jean-Paul, Delcourt, Cécile, Study Group, Pola, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Épidémiologie et prévention : environnement et efficacité des interventions (EPIPREV), Département de Gériatrie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, INSERM,Fondation de France, Department of Epidemiology of Ageing, Paris, the Fondation pour la Recherche Médicale, Paris, the Région Languedoc-Roussillon, Montpellier, France and the Association Retina-France, Toulouse, Rhônes Poulenc, Essilor and Specia, and the Centre de Recherche et d'Information Nutritionnelle, Paris., and Villebrun, Dominique
Subjects: Male, Aging, medicine.medical_specialty, Chronic bronchitis, Waist, Population, Blood Pressure, Disease, Sex Factors, Elderly, Internal medicine, Diabetes mellitus, medicine, Humans, education, National Cholesterol Education Program, Triglycerides, Aged, Metabolic Syndrome, Inflammation, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, biology, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Waist-Hip Ratio, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Cholesterol, HDL, Smoking, C-reactive protein, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Atherosclerosis, C-Reactive Protein, Endocrinology, Adipose Tissue, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, biology.protein, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Geriatrics and Gerontology, Metabolic syndrome, business
Abstract: Background: C-reactive protein (CRP), a nonspecific marker of the inflammatory status, is associated with cardiovascular disease risk factors and may be an important feature of the metabolic syndrome (MSX) in middle-aged subjects. Objectives: We assessed the relationship of CRP levels to specific components of MSX and other potential determinants in apparently healthy elderly subjects living in the South of France. Methods: In the framework of the population-based POLA (Pathologies Oculaires Liées à l’Age) Study, performed in 2,404 subjects aged 60 years or more, we measured the plasma CRP levels. All subjects with known systemic inflammatory diseases, such as chronic bronchitis, cardiovascular disease, and diabetes, and those who were on systemic steroid therapy as well as subjects with CRP levels >10 mg/l were excluded from the study, leaving 1,709 subjects for the statistical analyses. MSX was defined according to NCEP (National Cholesterol Education Program) criteria. Other potential determinants were assessed through interviewer-based questionnaire. Results: We grouped the subjects into three categories based on the 75th and 25th percentiles, corresponding to 3.05 and 0.82, respectively. We compared subjects in the highest quartile, i.e., with CRP ≧3.05 mg/l, with those in the two intermediate quartiles, i.e., with 0.82 < CRP < 3.05, and those in the lowest quartile, i.e., with CRP Conclusions: Abdominal adiposity adds to the variance in plasma CRP levels in elderly patients with MSX. This suggests that weight loss or other interventions targeted at adipocyte-related inflammation may represent an important means to prevent subclinical inflammation in the elderly, bearing a high risk of cardiovascular disease.
Published: 2007

410. Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma

Author: Thomas Moehler, Karène Mahtouk, Thierry Rème, Marion Larroque, Pierre Raynaud, John De Vos, Bernard Klein, Véronique Pantesco, Hartmut Goldschmidt, Dirk Hose, Eric Jourdan, Michael Hundemer, Jean-François Rossi, Michel Jourdan, Marion Baudard, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Clinical Hematology Department, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Nationales Centrum für Tumorerkrankungen, This work was supported by grants from the Ligue Nationale Contre Le Cancer (équipe labellisée), Paris, France. It is part of a national program called « Carte d'Identité des Tumeurs » (CIT) funded by the Ligue Nationale Contre le Cancer (http://www.ligue-cancer.net)., Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), and Frei, Monique
Subjects: Neutrophils, Osteoclasts, MESH: Multiple Myeloma, MESH: Neutrophils, MESH: Monocytes, Biochemistry, Monocytes, Syndecan 1, heparanase, 0302 clinical medicine, Bone Marrow, MESH: Osteoclasts, Gene expression, MESH: Glucuronidase, Glucuronidase, Regulation of gene expression, MESH: Aged, 0303 health sciences, Gene knockdown, MESH: Middle Aged, MESH: Bone Marrow Cells, MESH: Gene Expression Regulation, Enzymologic, Hematology, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, myeloma, 030220 oncology & carcinogenesis, MESH: Bone Marrow, Multiple Myeloma, Stromal cell, MESH: Cell Line, Tumor, MESH: Syndecan-1, Immunology, Bone Marrow Cells, Biology, Gene Expression Regulation, Enzymologic, Article, MESH: Prognosis, 03 medical and health sciences, Cell Line, Tumor, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Heparanase, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, 030304 developmental biology, MESH: Humans, syndecan-1, Cell Biology, Molecular biology, Transplantation, carbohydrates (lipids), Bone marrow
Abstract: The heparan sulfate (HS) proteoglycan, syndecan-1, plays a major role in multiple myeloma (MM) by concentrating heparin-binding growth factors on the surface of MM cells (MMCs). Using Affymetrix microarrays and real-time reverse transcriptase–polymerase chain reaction (RT-PCR), we show that the gene encoding heparanase (HPSE), an enzyme that cleaves HS chains, is expressed by 11 of 19 myeloma cell lines (HMCLs). In HSPEpos HMCLs, syndecan-1 gene expression and production of soluble syndecan-1, unlike expression of membrane syndecan-1, were significantly increased. Knockdown of HPSE by siRNA resulted in a decrease of syndecan-1 gene expression and soluble syndecan-1 production without affecting membrane syndecan-1 expression. Thus, HPSE influences expression and shedding of syndecan-1. Contrary to HMCLs, HPSE is expressed in only 4 of 39 primary MMC samples, whereas it is expressed in 36 of 39 bone marrow (BM) microenvironment samples. In the latter, HPSE is expressed at a median level in polymorphonuclear cells and T cells; it is highly expressed in monocytes and osteoclasts. Affymetrix data were validated at the protein level, both on HMCLs and patient samples. We report for the first time that a gene's expression mainly in the BM environment (ie, HSPE) is associated with a shorter event-free survival of patients with newly diagnosed myeloma treated with high-dose chemotherapy and stem cell transplantation. Our study suggests that clinical inhibitors of HPSE could be beneficial for patients with MM.
Published: 2007

411. B7-1 and 4-1BB ligand expression on a myeloma cell line makes it possible to expand autologous tumor-specific cytotoxic T cells in vitro

Author: Jean François Rossi, Marie Claude Delteil, Christophe Ferrand, Karin Tarte, Zhao-Yang Lu, L Nadal, Bernard Klein, Maud Condomines, Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Laboratoire de biologie moléculaire, EFS, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Frei, Monique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_treatment, chemistry.chemical_compound, 0302 clinical medicine, Transduction, Genetic, Cytotoxic T cell, 0303 health sciences, biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.anatomical_structure, 030220 oncology & carcinogenesis, B7-1 Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, Multiple Myeloma, medicine.drug, Interleukin 2, DNA, Complementary, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Genetic Vectors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, CD40, Cell Biology, Immunotherapy, Molecular biology, Coculture Techniques, CTL, 4-1BB ligand, 4-1BB Ligand, Retroviridae, chemistry, Gene Expression Regulation, biology.protein, Interleukin-2, CD8, T-Lymphocytes, Cytotoxic
Abstract: International audience; OBJECTIVE: The aim of this study was to confer an antigen-presenting cell (APC) ability on multiple myeloma cell lines (HMCLs) using B7-1 and/or 4-1BBL gene transfer. MATERIALS AND METHODS: HMCLs were retrovirally transduced with B7-1 and/or 4-1BBL cDNAs. Allogeneic or autologous T cells were stimulated by coculture with B7-1- and/or 4-1BBL-transduced HMCLs in the presence of interleukin-2. T cell clones were obtained by limiting dilution. T-cell activation was assessed by interferon-gamma Elispot assays and cytotoxicity by (51)Cr release assays. RESULTS: Neither primary multiple myeloma cells (MMCs) nor HMCLs expressed B7-1 or 4-1BBL, and these molecules could not be induced by CD40 triggering. HMCLs failed to stimulate allogeneic or autologous T cells. Transduction of HMCLs with B7-1 and/or 4-1BBL retroviruses induced a high expression of B7-1 and 4-1BBL molecules and a strong T-cell activation ability. Long-term cultured CD8(+) T-cell lines could be obtained by stimulation with the autologous B7-1/4-1BBL XG-19 HMCL. These cytotoxic T lymphocytes (CTL) efficiently killed the autologous parental XG-19 HMCL as well as autologous primary MMCs and allogeneic HMCLs. They did not kill autologous CD34 cells and autologous EBV cell line or natural killer target K562 cells. Cloned CTL could recognize allogeneic HMCLs, demonstrating that a shared anti-MMC repertoire was expanded. CONCLUSION: Transduction with B7-1 and 4-1BBL retroviruses turned HMCLs into efficient APCs. It permitted the long-term expansion of autologous anti-tumor CTL with a shared anti-MMC repertoire, for one HMCL. These data suggest developing an immunotherapy using modified tumor cells in patients with multiple myeloma.
Published: 2007

412. Pyruvate modifies glycolytic and oxidative metabolism of rat embryonic spinal cord astrocyte cell lines and prevents their spontaneous transformation

Author: Alain Privat, Didier Petite, Jacques Mercier, Christine Fabre, Pierre Baldet, Karen Lambert, Marcel Mersel, Caroline Rouleau, Keith Langley, Andrée Bonardet, Clovis Rakotoarivelo, Service d'Anatomie et Cytologie Pathologique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement de Physiologie des Interactions, Institut de Biologie, Laboratoire de Biochimie, Hôpital Lapeyronie, and Hamel, Christian
Subjects: Aging, MESH: Rats, Cellular respiration, MESH: Mitochondria, Respiratory chain, Oxidative phosphorylation, Mitochondrion, Biology, Biochemistry, MESH: Spinal Cord, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Oxygen Consumption, Pyruvic Acid, medicine, Animals, Glycolysis, MESH: Aging, MESH: Animals, MESH: Oxygen Consumption, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Pyruvic Acid, Cells, Cultured, 030304 developmental biology, 0303 health sciences, MESH: Embryo, Embryo, Mammalian, Cell biology, Mitochondria, Rats, MESH: Astrocytes, medicine.anatomical_structure, Electron Transport Chain Complex Proteins, Spinal Cord, Cell culture, Astrocytes, MESH: Glycolysis, Neuroglia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030217 neurology & neurosurgery, Astrocyte, MESH: Cells, Cultured, MESH: Electron Transport Chain Complex Proteins
Abstract: This study aimed to provide detailed data on mitochondrial respiration of normal astrocyte cell lines derived from rat embryonic spinal cord. Astrocytes in early passages (EP), cultured without pyruvate for more than 35 passages, defined here as late passages (LP), undergo spontaneous transformation. To study initial steps in cell transformation, EP data were compared with those of LP cells. LP cells had reduced glycolysis, fewer mitochondria and extremely low oxidative rates, resulting from a dysfunction of complexes I and II + III of the respiratory chain. Treatment of EP cells with pyruvate until they were, by definition, LP cultures prevented transformation of these cells. Pyruvate-treated EP cells had more mitochondria than normal cells but slightly lower respiratory rates. The increase of mitochondrial content thus appears to act as a compensatory effect to maintain oxidative phosphorylation in these LP 'non-transformed' cells, in which mitochondrial function is reduced. However, pyruvate treatment of transformed LP cells during additional passages did not significantly restore their oxidative metabolism. These data highlight changes accompanying spontaneous astrocyte transformation and suggest potential targets for the control of astrocyte proliferation and reaction to various insults to the central nervous system.
Published: 2007

413. In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma.: Anti-myeloma activity of amplified gamma delta T cells

Author: Burjanadze, Maka, Condomines, Maud, Rème, Thierry, Quittet, Philippe, Latry, Pascal, Lugagne, Cécile, Romagne, François, Morel, Yanis, Rossi, Jean-François, Klein, Bernard, Lu, Zhao-Yang, Frei, Monique, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Innate Pharma
Subjects: multiple myeloma, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.CAN] Life Sciences [q-bio]/Cancer, gamma delta T cells, cytotoxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, immunotherapy, cellular therapy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.
Published: 2007

414. Input of DNA microarrays to identify novel mechanisms in multiple myeloma biology and therapeutic applications.: DNA microarrays in multiple myeloma

Author: Mahtouk, Karène, Hose, Dirk, de Vos, John, Moreaux, Jérôme, Jourdan, Michel, Rossi, Jean François, Rème, Thierry, Goldschmidt, Harmut, Klein, Bernard, Frei, Monique, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of internal medicine V, Universität Heidelberg [Heidelberg], Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), and MSCNET, LNCC
Subjects: MESH: Gene Expression, MESH: Humans, MESH: Bone Marrow Cells, prognostic factors, MESH: Multiple Myeloma, therapeutic targets, microenvironment, MESH: Gene Expression Profiling, myeloma, hemic and lymphatic diseases, MESH: Oligonucleotide Array Sequence Analysis, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Animals, MESH: Bone Marrow, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, microarrays
Abstract: International audience; Multiple myeloma is a B-cell neoplasia characterized by the proliferation of a clone of malignant plasma cells in the bone marrow. We review here the input of gene expression profiling of myeloma cells and of their tumor microenvironment to develop new tumor classifiers, to better understand the biology of myeloma cells, to identify some mechanisms of drug sensitivity and resistance, to identify new myeloma growth factors, and to depict the complex interactions between tumor cells and their microenvironment. We discuss how these findings may improve the clinical outcome of this still incurable disease.
Published: 2007

415. Dietary fat and the risk of age-related maculopathy: the POLANUT Study

Author: Delcourt, Cécile, Carrière, Isabelle, Cristol, Jean-Paul, Lacroux, Annie, Gerber, Mariette, Study Group, Polanut, Mouillet, Evelyne, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Épidémiologie et prévention : environnement et efficacité des interventions (EPIPREV), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, and POLANUT Study Group
Subjects: age-related maculopathy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, dietary fat, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, unsaturated fats
Abstract: POLANUT Study Group : Cécile Delcourt (Principal Investigator, Bordeaux, France), Annie Lacroux (Montpellier, France), Isabelle Carrière (Montpellier, France), Mariette Gerber (Montpellier, France), Jean-Paul Cristol (Montpellier, France), Bernard Descomps (Montpellier, France), Claude L Léger (Montpellier, France), Francis Delpeuch (Montpellier, France), Anne-Dominique Girard (Montpellier, France), Stéphanie Denayer (Montpellier, France), Marie-Hortense Rocolle (Montpellier, France), Agnès Mora (Montpellier, France).; International audience; This study aimed at assessing the associations of dietary fat with the risk of age-related maculopathy (ARM), in the framework of a population-based study from southern France. Nutritional data were collected using a dietitian-administered food-frequency questionnaire. ARM was classified from retinal photographs using the international classification and included neovascular age-related macular degeneration, geographic atrophy, soft indistinct drusen, soft distinct drusen associated with pigmentary abnormalities. After multivariate adjustment, high total, saturated and monounsaturated fat intake were associated with increased risk for ARM (odds ratio (OR)=4.74, P=0.007; OR=2.70, P=0.04; and OR= 3.50, P=0.03, respectively). Total polyunsaturated fatty acid was not significantly associated with ARM. Total and white fish intake was not significantly associated with ARM, but fatty fish intake (more than once a month versus less than once a month) was associated with a 60% reduction in risk for ARM (OR=0.42, P=0.01).European Journal of Clinical Nutrition (2007) 61, 1341-1344; doi:10.1038/sj.ejcn.1602685; published online 14 February 2007.
Published: 2007

416. Acute respiratory failure in kidney transplant recipients: a multicenter study

Author: Georges Mourad, Jean-François Timsit, Benoît Schlemmer, Maryvonne Hourmant, David Osman, Denis Glotz, Bertrand Souweine, Anne-Elisabeth Heng, Antoine Durrbach, Christophe Guitton, Kada Klouche, Elie Azoulay, Christophe Legendre, Laurent Argaud, Jérôme Lambert, Eric Rondeau, Emmanuel Canet, Medical Intensive Care Unit and Biostatistics Departments, Saint-Louis Teaching Hospital, Service de Réanimation Médicale, Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de néphrologie adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Medical ICU, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Bioenergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de transplantation urologie-néphrologie ( ITUN ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Graft Rejection, Male, ARDS, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, 030230 surgery, Pneumocystis pneumonia, Critical Care and Intensive Care Medicine, law.invention, MESH: Kidney Transplantation, 0302 clinical medicine, law, MESH : Female, 030212 general & internal medicine, Hospital Mortality, Kidney transplantation, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Mortality rate, MESH : Acute Disease, MESH: Follow-Up Studies, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, Treatment Outcome, Acute Disease, MESH: Acute Disease, Female, Respiratory Insufficiency, MESH : Intensive Care Units, medicine.medical_specialty, MESH : Male, MESH: Graft Rejection, MESH : Treatment Outcome, MESH : Hospital Mortality, 03 medical and health sciences, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH: Hospital Mortality, Dialysis, Aged, Retrospective Studies, MESH: Humans, business.industry, Research, MESH : Humans, Bacterial pneumonia, MESH : Graft Rejection, MESH : Follow-Up Studies, MESH: Retrospective Studies, MESH : Respiratory Insufficiency, medicine.disease, Kidney Transplantation, MESH: Male, Surgery, Transplantation, MESH : Kidney Transplantation, MESH: Intensive Care Units, business, MESH: Female, MESH: Respiratory Insufficiency, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; INTRODUCTION: Data on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients. METHODS: We conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008. RESULTS: Of 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99). CONCLUSIONS: In kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss.
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417. Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy

Author: Rémy Gauzit, Christele Gras-Leguen, Anne-Marie Dupuy, Pierre-Emmanuel Charles, Jean-Pierre Bedos, Martin Chalumeau, Charles-Edouard Luyt, Christian Brun-Buisson, Yves Pean, Stéphanie Ruiz, Jean-Pierre Quenot, François Philippart, Yann-Eric Claessens, Jean-Paul Stahl, Nicolas Roche, Jérôme Pugin, Benoit Misset, Sigismond Lasocki, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Réanimation Médicale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Pneumologie et Soins Intensifs Respiratoires, Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpitaux Universitaires Paris Centre, Service de Pédiatrie Générale, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Département d'Urgences Médicales, Centre Hospitalier Princesse Grace, Pôle d'Anesthésie Réanimation, CHU Angers, Service de réanimation, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Centre Hospitalier de Versailles (CHV), Laboratoire de Microbiologie, Institut Mutualiste de Montsouris ( IMM ), Service de réanimation polyvalente, GH Saint-Joseph, Pôle d'Anesthésie-Réanimation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Clinique Médicale et Service d'Urgences Pédiatriques, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service de Biochimie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Intensive Care - SIRS Unit, University Hospitals of Geneva, Service de maladies infectieuses et tropicales, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Centre de Recherche Clinique, Université Paris Descartes - Paris 5 ( UPD5 ) -GH Saint-Joseph, Unité de Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Hôpitaux Universitaires Paris Centre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Mutualiste de Montsouris (IMM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Geneva University Hospital (HUG), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Paris Descartes - Paris 5 (UPD5)-GH Saint-Joseph, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), BMC, Ed., Brun-Buisson, Christian, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Pôle d'anesthésie Réanimation [CHU de Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre Hospitalier de Versailles (CHV), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: medicine.medical_specialty, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.drug_class, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Antibiotics, Review, pneumonia, meningitis, pancreatitis, infection, sepsis, emergency medicine, biomarkers, procalcitonin, C-reactive protein, Critical Care and Intensive Care Medicine, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, Procalcitonin, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Lower respiratory tract infection, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, Meningitis, 030212 general & internal medicine, Intensive care medicine, Infection, ddc:616, 0303 health sciences, 030306 microbiology, business.industry, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Pneumonia, medicine.disease, 3. Good health, Discontinuation, Pancreatitis, Emergency medicine, business, Biomarkers
Abstract: Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (80-90%, whether or not microbiological documentation has been obtained. For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended.
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418. A decision tree for genetic diagnosis of hereditary periodic fevers in unselected patients

Author: A. Le Quellec, L. Federici, Michel Rodière, Isabelle Koné-Paut, Christian Jorgensen, C Rittore-Domingo, I Touitou, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-IFR3, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, Genotype, Immunology, DNA Mutational Analysis, Familial Mediterranean fever, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Epidemiology, medicine, Immunology and Allergy, Humans, Child, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Retrospective Studies, 030203 arthritis & rheumatology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Decision Trees, Retrospective cohort study, Middle Aged, Pyrin, MEFV, medicine.disease, 3. Good health, Familial Mediterranean Fever, Extended Report, Cytoskeletal Proteins, Child, Preschool, Mutation, Female, Differential diagnosis, Genetic diagnosis, business
Abstract: Background: The diagnostic value of molecular analysis of the familial Mediterranean fever (FMF) gene (Mediterranean fever ( MEFV )) has been well established only in patients selected on the basis of ethnic background or clinical criteria. Genetic diagnosis for other hereditary periodic fever syndromes has been poorly evaluated. Objective: To determine the diagnostic contribution of genetic tests for hereditary periodic syndromes in a large, unselected series of patients. Methods: A retrospective study was conducted on 1941 patients referred to us for FMF genetic tests between 1997 and 2005. MEFV genotypes were compared with clinical data to appraise criteria for FMF diagnosis. Genetic tests for tumour necrosis factor receptor-associated periodic syndrome (TRAPS), hyperimmunoglobulinaemia D syndrome (HIDS) and cryopyrin-associated periodic syndromes (CAPS) were also reviewed. Results: 71% of the 1574 patients with enough data had a clinical diagnosis of FMF according to the widely used Israeli criteria. Two MEFV mutations were found in only 409 patients of this subgroup (sensitivity = 37%) and in 15 (3.3%) of the patients with an improbable clinical diagnosis of FMF (specificity = 97%). Molecular diagnosis for alternate hereditary periodic syndromes was carried out in 456 of the patients having a non-conclusive FMF genetic test. A positive diagnosis was obtained in 31 of these patients (TRAPS (n = 19), HIDS (n = 4) and CAPS (n = 8)). Conclusions: First-line MEFV mutation screening in patients with clinically typical FMF may be appropriate only in particular areas. To optimise genetic diagnosis, we propose a decision tree, which, with the advice of an expert practitioner, could help redirect test indications towards non-FMF hereditary periodic syndromes.
Published: 2006

419. Clinical practice format for choosing a second-line disease modifying anti-rheumatic drug in early rheumatoid arthritis after failure of 6 months' first-line DMARD therapy

Author: Meyer, Olivier, De Bandt, Michel, Berthelot, Jean-Marie, Cantagrel, Alain, Combe, Bernard, Fautrel, Bruno, Flipo, René-Marc, Lioté, Frédéric, Maillefert, Jean-Francis, Saraux, Alain, Wendling, Daniel, Guillemin, Francis, Le Loët, Xavier, Renseigné, Non, Hôpital Bichat - Claude Bernard, Service de Rhumatologie, Hôtel-Dieu, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Os et articulations, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)
Subjects: MESH: Antirheumatic Agents, MESH: Treatment Failure, Disease, Receptors, Tumor Necrosis Factor, Etanercept, Arthritis, Rheumatoid, 0302 clinical medicine, MESH: Practice Guidelines as Topic, 030212 general & internal medicine, Treatment Failure, skin and connective tissue diseases, MESH: Immunoglobulin G, MESH: Arthritis, Rheumatoid, Anti rheumatic drugs, 3. Good health, Clinical Practice, MESH: Methotrexate, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Antirheumatic Agents, Practice Guidelines as Topic, Drug Therapy, Combination, Leflunomide, musculoskeletal diseases, medicine.medical_specialty, MESH: Rheumatoid Factor, First line, MESH: Drug Administration Schedule, Drug Administration Schedule, Decision Support Techniques, 03 medical and health sciences, Rheumatology, Rheumatoid Factor, Dmard therapy, medicine, Rheumatoid factor, Humans, Intensive care medicine, 030203 arthritis & rheumatology, MESH: Humans, MESH: Sulfasalazine, business.industry, MESH: Biological Markers, MESH: Decision Support Techniques, Early rheumatoid arthritis, Isoxazoles, medicine.disease, MESH: Receptors, Tumor Necrosis Factor, Radiography, Sulfasalazine, MESH: Drug Therapy, Combination, Methotrexate, MESH: Isoxazoles, Immunoglobulin G, Physical therapy, business, Biomarkers
Abstract: International audience; BACKGROUND: The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. METHODS: A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. RESULTS: Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. CONCLUSION: Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.
Published: 2006

420. Microarray-based understanding of normal and malignant plasma cells

Author: de Vos, John, Hose, Dirk, Rème, Thierry, Tarte, Karin, Moreaux, Jérôme, Mahtouk, Karéne, Jourdan, Michel, Goldschmidt, Hartmut, Rossi, Jean-François, Cremer, Friedrich, Klein, Bernard, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universität Heidelberg [Heidelberg] = Heidelberg University, Université de Rennes (UR)-Hôpital Pontchaillou, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM)
Subjects: [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; Plasma cells (PCs) develop from B lymphocytes following stimulation by antigen and express a genetic program aimed at the synthesis of immunoglobulins. This program includes the induction of genes coding for transcription factors such as PRDM1, X-box-binding protein 1 and BHLHB3, cell-surface molecules such as CD138/syndecan-1, and for the unfolded protein response. We review how the microarray technology has recently contributed to the understanding of the biology of this rare but essential cell population and its transformation into premalignant and malignant PCs.
Published: 2006

421. Microarray-based understanding of normal and malignant plasma cells

Author: de Vos, John, Hose, Dirk, Rème, Thierry, Tarte, Karin, Moreaux, Jérôme, Mahtouk, Karéne, Jourdan, Michel, Goldschmidt, Hartmut, Rossi, Jean-François, Cremer, Friedrich, Klein, Bernard, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), and Frei, Monique
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; Plasma cells (PCs) develop from B lymphocytes following stimulation by antigen and express a genetic program aimed at the synthesis of immunoglobulins. This program includes the induction of genes coding for transcription factors such as PRDM1, X-box-binding protein 1 and BHLHB3, cell-surface molecules such as CD138/syndecan-1, and for the unfolded protein response. We review how the microarray technology has recently contributed to the understanding of the biology of this rare but essential cell population and its transformation into premalignant and malignant PCs.
Published: 2006

422. Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia

Author: Ducastelle, S., Adès, L., Gardin, C., Dombret, H., Prébet, T., Eric DECONINCK, Rio, B., Thomas, X., Debotton, S., Guerci, A., Gratecos, N., Stamatoullas, A., Fegueux, N., Dreyfus, F., Fenaux, P., Wattel, E., Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Hématologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Virologie et pathogenèse virale (VPV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Saas, Philippe
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, autologous stem cell transplantation, Adolescent, MESH: Survival Rate, Antineoplastic Agents, Transplantation, Autologous, Time, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, Aged, MESH: Adolescent, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Time, intensive chemotherapy, MESH: Adult, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Follow-Up Studies, Middle Aged, MESH: Transplantation, Autologous, MESH: Male, myelodysplastic syndrome, Survival Rate, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, MESH: Antineoplastic Agents, Female, MESH: Stem Cell Transplantation, MESH: Leukemia, Myeloid, Acute, MESH: Myelodysplastic Syndromes, MESH: Female, Follow-Up Studies, Stem Cell Transplantation
Abstract: International audience; We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS, autografted in first complete remission. Five (9.4%) died from the procedure whereas hematological reconstitution occurred in all the remaining patients. Forty patients (75%) relapsed, with 87.5% of the relapses occurring within 2 years of the autologous transplant. With a median follow-up of 6.2 years, the median actuarial disease-free survival and overall survival were 8 and 17 months after autograft, respectively. Karyotype was the only prognostic factor for disease-free and overall survival. The eight survivors (15%), including two patients with unfavorable or intermediate karyotype, remained in first complete remission 50+ to 119+ months after transplantation and are probably cured.
Published: 2006

423. Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination

Author: Badiou, Stéphanie, Jaussent, Isabelle, Terrier, Nathalie, Naudin, Estelle, Leray-Moragues, Hélène, Maurice, François, Dupuy, Anne-Marie, Rivory, Jean-Pierre, Canaud, Bernard, Cristol, Jean-Paul, Delcourt, Cécile, Villebrun, Dominique, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de nephrologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hémodialyse Languedoc Méditerranée (CHLM), Centre hémodialyse Languedoc Méditerranée, Epidémiologie, santé publique et développement, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED
Subjects: aminothiols, hemodialysis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, cardiovascular, chromatography, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, homocysteine, immunoassay, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Abstract: Background: Controversial results about hyperhomocysteinemia and cardiovascular (CV) risk in hemodialysis (HD) could be due in part to the methodology used for homocysteine (Hcy) determination. Objective: To compare the influence of the method used for Hcy determination (chromatography or immunoassay), in regard to the association of Hcy with CV mortality rate in HD patients in a 3 year prospective study. Methods: One hundred sixty-two patients undergoing HD were included in a cohort study. Baseline Hcy levels were measured by high performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA). Cysteine and cysteinylglycine were determined simultaneously to Hcy measure by HPLC. Results: Hcy levels obtained with both methods were highly correlated (r2=0.927, p
Published: 2006

424. Intradialytic parenteral nutrition: comparison of olive oil versus soybean oil-based lipid emulsions

Author: Anne-Marie Lorec-Penet, Jean-Paul Cristol, Denis Lairon, Philippe Atlan, Xavier Leverve, Yannick Saingra, Anne-Marie Dupuy, A L Alexia Le Brun, Noël Cano, Henri Portugal, Adrien Come, Hamant, Sarah, Service d'Hépatogastroentérologie et Nutrition, Clinique Résidence du Parc, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Laboratoire central, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Nutrition humaine et lipides : Biodisponibilité, métabolisme et régulation, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Université de Provence - Aix-Marseille 1-IFR125-Institut National de la Santé et de la Recherche Médicale (INSERM), Baxter SAS, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Male, Fat Emulsions, Intravenous, medicine.medical_specialty, Parenteral Nutrition, Fat Emulsions, [SDV]Life Sciences [q-bio], Serum albumin, Medicine (miscellaneous), chemistry.chemical_compound, Dietary Fats, Unsaturated, Double-Blind Method, Renal Dialysis, Internal medicine, medicine, Humans, Plant Oils, Prospective Studies, Olive Oil, Intradialytic parenteral nutrition, Phospholipids, Triglycerides, Aged, chemistry.chemical_classification, Unsaturated, Nutrition and Dietetics, biology, Cholesterol, Glutathione peroxidase, Albumin, Lipid metabolism, Malondialdehyde, Dietary Fats, Soybean Oil, Nutrition Disorders, [SDV] Life Sciences [q-bio], Oxidative Stress, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Biochemistry, biology.protein, lipids (amino acids, peptides, and proteins), Female, Intravenous, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Lipoprotein
Abstract: Lipid, oxidative and inflammatory parameters are frequently altered in dialysis patients and may be worsened by intravenous lipid emulsions (ILE). We assessed the efficacy and tolerance of olive as compared with standard soybean oil-based ILE during intradialytic parenteral nutrition (IDPN). IDPN mixtures containing amino acids, glucose, and either olive oil (OO group,n17) or soybean oil-based ILE (SO group,n18) were administered in a 5-week randomized, double-blind study. On days 0 and 35, patients' nutritional status was assessed by BMI, normalized protein catabolic rate, predialytic creatinine, serum albumin and transthyretin; lipid metabolism by plasma LDL- and HDL-cholesterol, triacylglycerols, phospholipids, apo A-I, A-II, B, C-II, C-III, E and lipoprotein (a); oxidative status by α-tocopherol, retinol, selenium, glutathione peroxidase, malondialdehyde and advanced oxidized protein products; inflammatory status by serum C-reactive protein, orosomucoid, IL-2 and IL-6. No serious adverse event was observed. Significant changes were observed from day 0 to day 35 (P
Published: 2006

425. Low doses of GM-CSF (molgramostim) and G-CSF (filgrastim) after cyclophosphamide (4 g/m2) enhance the peripheral blood progenitor cell harvest: results of two randomized studies including 120 patients

Author: Pascal Latry, Nathalie Fegueux, Ernesto Lopez, Jean-Pierre Daurès, Bernard Klein, Zhao-Yang Lu, Carole Exbrayat, Valérie Rouille, Patrice Ceballos, Philippe Quittet, Catherine Becht, Eric Legouffe, Jean-François Rossi, Damien Pouessel, Frei, Monique, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Unité de Thérapie Cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Thérapie Cellulaire et Génique, Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi
Subjects: Male, Antigens, CD34, MESH: Multiple Myeloma, Gastroenterology, Leukocyte Count, chemistry.chemical_compound, 0302 clinical medicine, Granulocyte Colony-Stimulating Factor, MESH: Aged, MESH: Filgrastim, Hematology, MESH: Middle Aged, Middle Aged, MESH: Granulocyte-Macrophage Colony-Stimulating Factor, Recombinant Proteins, Nitrogen mustard, Granulocyte colony-stimulating factor, Granulocyte macrophage colony-stimulating factor, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, Multiple Myeloma, medicine.drug, Adult, medicine.medical_specialty, Filgrastim, Cyclophosphamide, MESH: Leukapheresis, G-CSF, MESH: Peripheral Blood Stem Cell Transpl, Article, 03 medical and health sciences, Molgramostim, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Leukapheresis, Progenitor cell, Aged, Peripheral Blood Stem Cell Transplantation, Transplantation, MESH: Humans, business.industry, Granulocyte-Macrophage Colony-Stimulating Factor, MESH: Cyclophosphamide, GM-CSF, MESH: Adult, MESH: Antigens, CD34, MESH: Male, Surgery, MESH: Drug Therapy, Combination, chemistry, MESH: Leukocyte Count, business, MESH: Female, Hematopoietic stem cells, 030215 immunology
Abstract: International audience; The use of a combination of G-CSF and GM-CSF versus G-CSF alone, after cyclophosphamide (4 g/m2) was compared in two randomized phase III studies, including 120 patients. In study A, 60 patients received 5 x 2 microg/kg/day of G-CSF and GM-CSF compared to 5 mug/kg/day of G-CSF. In study B, 60 patients received 2.5 x 2 microg/kg/day G-CSF and GM-CSF compared to G-CSF alone (5 microg/kg/day). With the aim to collect at least 5 x 10(6)/kg CD34 cells in a maximum of three large volume leukapherises (LK), 123 LK were performed in study A, showing a significantly higher number of patients reaching 10 x 10(6)/kg CD34 cells (21/29 in G+GM-CSF arm vs 11/27 in G-CSF arm, P=0.00006). In study B, 109 LK were performed, with similar results (10/27 vs 15/26, P=0.003). In both the study, the total harvest of CD34 cells/kg was twofold higher in G-CSF plus GM-CSF group (18.3 x 10(6) in study A and 15.85 x 10(6) in study B) than in G-CSF group (9 x 10(6) in study A and 8.1 x 10(6) in study B), a significant difference only seen in multiple myeloma, with no significant difference in terms of mobilized myeloma cells between G-CSF and GM-CSF groups.
Published: 2006

426. Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination: aminothiols as predictive factors of hemodialysis outcome

Author: François Maurice, Jean-Pierre Rivory, Hélène Leray-Moragues, Estelle Naudin, Jean-Paul Cristol, Nathalie Terrier, Cécile Delcourt, Stéphanie Badiou, Isabelle Jaussent, Bernard Canaud, Anne-Marie Dupuy, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de nephrologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hémodialyse Languedoc Méditerranée (CHLM), Centre hémodialyse Languedoc Méditerranée, Epidémiologie, santé publique et développement, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED
Subjects: Male, Homocysteine, medicine.medical_treatment, Clinical Biochemistry, 030232 urology & nephrology, 030204 cardiovascular system & hematology, High-performance liquid chromatography, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, aminothiols, chemistry.chemical_compound, 0302 clinical medicine, Fluorescence Polarization Immunoassay, Prospective cohort study, Chromatography, High Pressure Liquid, Aged, 80 and over, chemistry.chemical_classification, hemodialysis, medicine.diagnostic_test, cardiovascular, General Medicine, Middle Aged, 3. Good health, Cardiovascular Diseases, Thiol, chromatography, Female, Hemodialysis, Cohort study, Adult, Hyperhomocysteinemia, 03 medical and health sciences, Renal Dialysis, medicine, Humans, Sulfhydryl Compounds, immunoassay, Aged, Chromatography, business.industry, Biochemistry (medical), homocysteine, medicine.disease, chemistry, Immunoassay, Kidney Failure, Chronic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background: Controversial results about hyperhomocysteinemia and cardiovascular (CV) risk in hemodialysis (HD) could be due in part to the methodology used for homocysteine (Hcy) determination. Objective: To compare the influence of the method used for Hcy determination (chromatography or immunoassay), in regard to the association of Hcy with CV mortality rate in HD patients in a 3 year prospective study. Methods: One hundred sixty-two patients undergoing HD were included in a cohort study. Baseline Hcy levels were measured by high performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA). Cysteine and cysteinylglycine were determined simultaneously to Hcy measure by HPLC. Results: Hcy levels obtained with both methods were highly correlated (r2=0.927, p
Published: 2006

427. Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects

Author: Philippe Quittet, Eric Legouffe, Jean-Pierre Daurès, Valérie Rouille, Marie-Cécile Bozonnat, Bernard Klein, Tarik Kanouni, Jean-François Rossi, Nathalie Fegueux, Carole Exbrayat, Ernesto Lopez, Zhao Yang Lu, John Widjenes, Robert Navarro, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Unité de Thérapie Cellulaire et Génique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Diaclone Research, Frei, Monique, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Melphalan, Male, medicine.medical_treatment, Anti-Inflammatory Agents, Pilot Projects, MESH: Multiple Myeloma, Pharmacology, Dexamethasone, autologous transplantation, MESH: Antibodies, Monoclonal, chemistry.chemical_compound, 0302 clinical medicine, Autologous stem-cell transplantation, Multiple myeloma, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Mucositis, Antibodies, Monoclonal, Hematology, MESH: Pil, Middle Aged, Nitrogen mustard, 3. Good health, multiple myeloma, C-Reactive Protein, 030220 oncology & carcinogenesis, MESH: Dexamethasone, Female, medicine.drug, Adult, Mucositis, medicine.medical_specialty, MESH: Myeloablative Agonists, Transplantation, Autologous, Article, Disease-Free Survival, 03 medical and health sciences, MESH: Melphalan, Internal medicine, MESH: C-Reactive Protein, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Autologous transplantation, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, anti-interleukin-6, 030304 developmental biology, Aged, MESH: Drug Evaluation, Transplantation, Chemotherapy, MESH: Humans, business.industry, Interleukin-6, MESH: Adult, Myeloablative Agonists, medicine.disease, MESH: Interleukin-6, MESH: Male, Endocrinology, chemistry, MESH: Anti-Inflammatory Agents, MESH: Disease-Free Survival, Drug Evaluation, business, MESH: Female, Stem Cell Transplantation
Abstract: International audience; Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m2) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m2. Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 microg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM.
Published: 2005

428. TNFalpha antagonist therapy in ankylosing spondylitis and psoriatic arthritis: recommendations of the French Society for Rheumatology

Author: Pham, Thao, Guillemin, Francis, Claudepierre, Pascal, Luc, Mathieu, Miceli-Richard, Corinne, Fautrel, Bruno, De Bandt, Michel, Breban, Maxime, Goupille, Philippe, Maillefert, Jean-Francis, Masson, Charles, Saraux, Alain, Schaeverbeke, Thierry, Wendling, Daniel, Mariette, Xavier, Combe, Bernard, Renseigné, Non, Service de Rhumatologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Bordeaux [Bordeaux], Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Anti-Inflammatory Agents, Disease, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Rheumatology, Sulfasalazine, Internal medicine, MESH: Rheumatology, medicine, MESH: Arthritis, Psoriatic, Humans, Spondylitis, Ankylosing, 030212 general & internal medicine, BASDAI, Leflunomide, 030203 arthritis & rheumatology, Ankylosing spondylitis, MESH: Humans, business.industry, Tumor Necrosis Factor-alpha, Arthritis, Psoriatic, medicine.disease, MESH: Spondylitis, Ankylosing, 3. Good health, MESH: France, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Anti-Inflammatory Agents, MESH: Tumor Necrosis Factor-alpha, Methotrexate, France, business, medicine.drug
Abstract: International audience; OBJECTIVES: To develop recommendations for TNFalpha antagonist therapy in patients with spondyloarthropathies. METHODS: The Delphi consensus procedure was used to select questions, to which evidence-based answers were sought in the literature. Expert opinion was used when needed to estimate the risks and benefits of TNFalpha antagonists. TNFalpha antagonists exert potent antiinflammatory effects but fail to provide a definitive cure. RESULTS: Recommendations were developed for patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). The following criteria for TNFalpha antagonist therapy were selected: definitive diagnosis of AS or PsA, active disease for at least 4 consecutive weeks documented during two physician visits, overall physician's assessment of disease activity>/=4/10 and BASDAI>/=4/10 in axial disease or at least three tender and swollen joints in peripheral disease, failure to respond adequately to at least three nonsteroidal antiinflammatory drugs given in optimal dosages for at least 3 months in axial disease or at least one disease-modifying antirheumatic drug (methotrexate, leflunomide, sulfasalazine) for at least 4 months, with local glucocorticoid injections if appropriate, in peripheral disease. Effectiveness and safety should be evaluated by a rheumatologist. The frequency of monitoring depends on the drug. Lack of effectiveness should be defined as inadequate improvement after 6-12 weeks, with a less than two-point decrease in the BASDAI in axial disease or a less than 30% decrease in the tender and swollen joint counts in peripheral disease. CONCLUSION: These clinical practice recommendations should help rheumatologists in their everyday decisions regarding the use of TNFalpha antagonist therapy in patients with AS or PsA.
Published: 2005

429. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rheumatoid arthritis synovial fibroblast proliferation through mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt

Author: Rachel Audo, J. Morel, B Combe, Michael Hahne, Immunopathologie de l'Inflammation, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Rhumatologie[Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie
Subjects: MAPK/ERK pathway, medicine.medical_specialty, p38 mitogen-activated protein kinases, Biology, Protein Serine-Threonine Kinases, Biochemistry, p38 Mitogen-Activated Protein Kinases, Receptors, Tumor Necrosis Factor, Arthritis, Rheumatoid, TNF-Related Apoptosis-Inducing Ligand, 03 medical and health sciences, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Internal medicine, Proto-Oncogene Proteins, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Phosphorylation, Protein kinase A, Extracellular Signal-Regulated MAP Kinases, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, 030304 developmental biology, Cell Proliferation, 0303 health sciences, Membrane Glycoproteins, Kinase, Akt/PKB signaling pathway, Tumor Necrosis Factor-alpha, Synovial Membrane, NF-kappa B, Cell Biology, Fibroblasts, 3. Good health, Protein Transport, Endocrinology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, Mitogen-Activated Protein Kinases, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt
Abstract: International audience; A hallmark of rheumatoid arthritis ( RA) is the pseudotumoral expansion of fibroblast- like synoviocytes ( FLSs), and the RA FLS has therefore been proposed as a therapeutic target. Tumor necrosis factor ( TNF)- related apoptosis- inducing ligand ( TRAIL) has been described as a pro- apoptotic factor on RA FLSs and, therefore, suggested as a potential drug. Here we report that exposure to TRAIL- induced apoptosis in a portion ( up to 30%) of RA FLSs within the first 24 h. In the cells that survived, TRAIL induced RA FLS proliferation in a dose-dependent manner, with maximal proliferation observed at 0.25 nM. This was blocked by a neutralizing anti- TRAIL antibody. RA FLSs were found to express constitutively TRAIL receptors 1 and 2 ( TRAIL- R1 and TRAIL- R2) on the cell surface. TRAIL- R2 appears to be the main mediator of TRAIL- induced stimulation, as RA FLS proliferation induced by an agonistic anti-TRAIL- R2 antibody was comparable with that induced by TRAIL. TRAIL activated the mitogen- activated protein kinases ERK and p38, as well as the phosphatidylinositol 3- kinase ( PI3K)/ Akt signaling pathway with kinetics similar to those of TNF-alpha. Moreover, TRAIL-induced RA FLS proliferation was inhibited by the protein kinase inhibitors PD98059, SB203580, and LY294002, confirming the involvement of the ERK, p38, and PI3 kinase/ Akt signaling pathways. This dual functionality of TRAIL in stimulating apoptosis and proliferation has important implications for its use in the treatment of RA.
Published: 2005

430. Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells

Author: Farida, Djouad, Claire, Bony, Thomas, Häupl, Gilles, Uzé, Najiba, Lahlou, Pascale, Louis-Plence, Florence, Apparailly, François, Canovas, Thierry, Rème, Jacques, Sany, Christian, Jorgensen, Danièle, Noël, Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Défenses antivirales et antitumorales (DAA), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie hormonale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, and Maylin, Françoise
Subjects: MESH: Extracellular Matrix Proteins, MESH: Cell Differentiation, Transcription, Genetic, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Immunophenotyping, Osteocalcin, Bone Marrow Cells, Immunophenotyping, Arthritis, Rheumatoid, MESH: Activins, MESH: Alkaline Phosphatase, Antigens, CD, Osteoarthritis, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Cell Lineage, Lectins, C-Type, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aggrecans, RNA, Messenger, Collagen Type II, MESH: Antigens, CD, Cells, Cultured, Inhibin-beta Subunits, Oligonucleotide Array Sequence Analysis, Extracellular Matrix Proteins, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Arthritis, Rheumatoid, MESH: Humans, MESH: Bone Marrow Cells, Synovial Membrane, MESH: Biological Markers, Cell Differentiation, Mesenchymal Stem Cells, MESH: Comparative Study, MESH: Collagen Type II, MESH: Cell Lineage, Alkaline Phosphatase, Activins, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM]Life Sciences [q-bio]/Immunology, Proteoglycans, Biomarkers, Research Article, MESH: Cells, Cultured
Abstract: Previous studies have reported that mesenchymal stem cells (MSC) may be isolated from the synovial membrane by the same protocol as that used for synovial fibroblast cultivation, suggesting that MSC correspond to a subset of the adherent cell population, as MSC from the stromal compartment of the bone marrow (BM). The aims of the present study were, first, to better characterize the MSC derived from the synovial membrane and, second, to compare systematically, in parallel, the MSC-containing cell populations isolated from BM and those derived from the synovium, using quantitative assays. Fluorescent-activated cell sorting analysis revealed that both populations were negative for CD14, CD34 and CD45 expression and that both displayed equal levels of CD44, CD73, CD90 and CD105, a phenotype currently known to be characteristic of BM-MSC. Comparable with BM-MSC, such MSC-like cells isolated from the synovial membrane were shown for the first time to suppress the T-cell response in a mixed lymphocyte reaction, and to express the enzyme indoleamine 2,3-dioxygenase activity to the same extent as BM-MSC, which is a possible mediator of this suppressive activity. Using quantitative RT-PCR these data show that MSC-like cells from the synovium and BM may be induced to chondrogenic differentiation and, to a lesser extent, to osteogenic differentiation, but the osteogenic capacities of the synovium-derived MSC were significantly reduced based on the expression of the markers tested (collagen type II and aggrecan or alkaline phosphatase and osteocalcin, respectively). Transcription profiles, determined with the Atlas Human Cytokine/Receptor Array, revealed discrimination between the MSC-like cells from the synovial membrane and the BM-MSC by 46 of 268 genes. In particular, activin A was shown to be one major upregulated factor, highly secreted by BM-MSC. Whether this reflects a different cellular phenotype, a different amount of MSC in the synovium-derived population compared with BM-MSC adherent cell populations or the impact of a different microenvironment remains to be determined. In conclusion, although the BM-derived and synovium-derived MSC shared similar phenotypic and functional properties, both their differentiation capacities and transcriptional profiles permit one to discriminate the cell populations according to their tissue origin.
Published: 2005

431. Abstract Suppression Signaling pathways involved in trail-induced HA synovial fibroblasts proliferation

Author: Morel, J., Audo, R., Combe, B., Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, and Adele, Sarah
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Published: 2005

432. Expression of EGF-family receptors and amphiregulin in multiple myeloma. Amphiregulin is a growth factor for myeloma cells

Author: Geneviève Fiol, Dirk Hose, Friedrich W. Cremer, Veronique Grau, Jean François Rossi, Bernard Klein, Hartmut Goldschmidt, Marion Moos, Eric Jourdan, Jérôme Moreaux, Karène Mahtouk, Thierry Rème, Michel Jourdan, Marion Baudard, Marc-Steffen Raab, John De Vos, Frei, Monique, Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Service de médecine interne B, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Institut für Humangenetik, and Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Cancer Research, medicine.medical_treatment, Apoptosis, MESH: Multiple Myeloma, medicine.disease_cause, ErbB Receptors, 0302 clinical medicine, Multiple myeloma, Oligonucleotide Array Sequence Analysis, 0303 health sciences, MESH: Plasma Cells, Reverse Transcriptase Polymerase Chain Reaction, MESH: Bone Marrow Cells, Gefitinib, 3. Good health, MESH: Quinazolines, 030220 oncology & carcinogenesis, Intercellular Signaling Peptides and Proteins, Multiple Myeloma, EGF Family of Proteins, Stromal cell, Plasma Cells, MESH: Glycoproteins, Antineoplastic Agents, Bone Marrow Cells, Biology, Amphiregulin, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, ErbB, MESH: Cell Proliferation, Genetics, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Intercellular Signaling Peptides and Proteins, Molecular Biology, 030304 developmental biology, Cell Proliferation, Glycoproteins, MESH: Humans, Cell growth, Growth factor, Gene Expression Profiling, MESH: Apoptosis, medicine.disease, MESH: Oligonucleotide Array Sequence Analysis, Cancer research, Quinazolines, MESH: Antineoplastic Agents, Carcinogenesis
Abstract: International audience; A hallmark of plasma cells is the expression of syndecan-1, which has major functions in epithelial cells, in particular as the coreceptor of heparin-binding growth factors. We previously found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a growth factor for malignant plasma cells. As amphiregulin (AREG) is another heparin-binding factor of the EGF family, we investigated its role in multiple myeloma (MM). Using Affymetrix DNA microarrays, we show here that the AREG gene was expressed by purified primary myeloma cells from 65 patients and that the expression was higher than in normal bone marrow (BM) plasma cells or plasmablastic cells. AREG stimulated IL-6 production and growth of BM stromal cells. Using real-time reverse transcriptase-polymerase chain reaction, we found that MM cells expressed ErbB receptors and that AREG promoted their growth. Furthermore, PD169540 (a pan-ErbB inhibitor) and IRESSA (an ErbB1-specific inhibitor) induced apoptosis of primary myeloma cells from 10/14 and 4/14 patients, respectively, and there was a synergistic effect with dexamethasone. Altogether, our data provide strong evidence that AREG plays an important role in the biology of MM and emphasize the advantages of using ErbB inhibitors, which might target myeloma cells as well as the tumor environment.
Published: 2005

433. Malnutrition in hemodialysis diabetic patients: evaluation and prognostic influence

Author: Cano, Noël, Roth, Hubert, Aparicio, Michel, Azar, Raymond, Canaud, Bernard, Chauveau, Philippe, Combe, Christian, Fouque, Denis, Laville, Maurice, Leverve, Xavier M, Nutrition In Dialysis (fsg-Nd), French Study Group For, Service d'Hépatogastroentérologie et Nutrition, Clinique Résidence du Parc, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Néphrologie, Centre Hospitalier Dunkerque, Service de Néphrologie, Dialyse et Soins Intensifs, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Hamant, Sarah, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble
Subjects: Male, dialysis in France, protein status, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Diabetic Nephropathies, MESH: Renal Dialysis, Longitudinal Studies, Prospective Studies, MESH: Incidence, MESH: Longitudinal Studies, 2. Zero hunger, MESH: Aged, MESH: Middle Aged, Mortality rate, Incidence, MESH: Follow-Up Studies, Middle Aged, Prognosis, MESH: Nutrition Assessment, 3. Good health, Nephrology, MESH: Survival Analysis, diabetes mellitus, Female, Hemodialysis, medicine.medical_specialty, MESH: Diabetic Nephropathies, malnutrition, Protein-Energy Malnutrition, MESH: Prognosis, Nephropathy, MESH: Body Mass Index, 03 medical and health sciences, MESH: Cross-Sectional Studies, Renal Dialysis, Diabetes mellitus, Internal medicine, diet and dialysis, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, death and diabetes, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, mortality and hemodialysis, Aged, Creatinine, MESH: Humans, business.industry, medicine.disease, Survival Analysis, MESH: Male, MESH: Prospective Studies, MESH: Protein-Energy Malnutrition, Endocrinology, Cross-Sectional Studies, Nutrition Assessment, chemistry, Lean body mass, business, Body mass index, MESH: Female, Kidney disease, Follow-Up Studies
Abstract: Malnutrition in hemodialysis diabetic patients: Evaluation and prognostic influence.BackgroundThis work aimed to evaluate the role of malnutrition in the increased mortality rate of hemodialysis diabetic patients from a French cooperative series.MethodsBody mass index (BMI), serum albumin, prealbumin, cholesterol, and pre-dialysis creatinine, normalized protein catabolic rate and lean body mass (LBM) were measured in 734 diabetic and 6389 non-diabetic patients (aged 63.4 ± 12.2 and 62.0 ± 15.9 years; 1.01 male to 1.40 female ratio). The outcome of 1610 of these patients, including 170 diabetics, was assessed during a 30-month follow-up.ResultsDiabetic as compared to non-diabetic patients showed a significant (P < 10-4) increased BMI (25.9 ± 5.2 vs. 23.1 ± 4.3) and cholesterol (5.5 ± 1.6 vs. 5.3 ± 1.5 mmol/L), and decreased albumin (37.8 ± 5.4 vs. 38.9 ± 5.3 g/L), prealbumin (317 ± 91 vs. 340 ± 94 mg/L), creatinine (711 ± 184 vs. 816 ± 217 μmol/L) and LBM (76 ± 18 vs. 87 ± 21%). Normalized protein catabolic rate was similar in the two groups (1.11 ± 0.31 vs. 1.13 ± 0.32 g/kg/L). One and two-year survival was 83.7 ± 2.9% and 65.5 ± 3.8% in diabetic patients versus 90.3 ± 0.8% and 79.9 ± 1.1% in non-diabetics (relative risk 1.26, P < 0.01). Independent predictors of survival were age, albumin and prealbumin in non-diabetics and only age in diabetics.ConclusionDiabetic patients compared to non-diabetics were characterized by an increased incidence of protein malnutrition and decreased survival. However, the higher death risk associated with diabetes was not related to malnutrition.
Published: 2002

434. p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis

Author: Paul Chuchana, Jacques Piette, Christian Jorgensen, Didier Philipot, Eleonora Olivotto, Anne Dorandeu, Yves-Marie Pers, David Guérit, Danièle Noël, Francisco Espinoza, Jean-Marc Brondello, Daniela Platano, Rosa Maria Borzì, Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratorio di immunoreumatologia e rigenerazione tissutale, Istituto di Ricerca Codivilla Putti-Istituto Ortopedico Rizzoli - Ior, Service de Médecine Légale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Unité d'Immunologie Clinique et de Thérapeutique des Maladies Ostéo-Articulaires, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), This work was supported by INSERM and by Fondation pour la Recherche Médicale (FRM) that was awarded to DN. DPh was a recipient of PhD program from 'Région Languedoc Roussillon-Université de Montpellier 1'., BMC, Ed., Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, and Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)
Subjects: Senescence, Cellular differentiation, Blotting, Western, Immunology, Enzyme-Linked Immunosorbent Assay, Real-Time Polymerase Chain Reaction, Transfection, Chondrocyte, Mice, 03 medical and health sciences, Chondrocytes, 0302 clinical medicine, Rheumatology, Matrix Metalloproteinase 13, Osteoarthritis, medicine, Animals, Humans, Immunology and Allergy, neoplasms, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Mice, Knockout, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, business.industry, Cartilage, Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, Middle Aged, Chondrogenesis, Arthritis, Experimental, Immunohistochemistry, Cell biology, MicroRNAs, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Knockout mouse, Matrix Metalloproteinase 1, business, Cell aging, Research Article
Abstract: Introduction Recent evidence suggests that tissue accumulation of senescent p16INK4a-positive cells during the life span would be deleterious for tissue functions and could be the consequence of inherent age-associated disorders. Osteoarthritis (OA) is characterized by the accumulation of chondrocytes expressing p16INK4a and markers of the senescence-associated secretory phenotype (SASP), including the matrix remodeling metalloproteases MMP1/MMP13 and pro-inflammatory cytokines interleukin-8 (IL-8) and IL-6. Here, we evaluated the role of p16INK4a in the OA-induced SASP and its regulation by microRNAs (miRs). Methods We used IL-1-beta-treated primary OA chondrocytes cultured in three-dimensional setting or mesenchymal stem cells differentiated into chondrocyte to follow p16INK4a expression. By transient transfection experiments and the use of knockout mice, we validate p16INK4a function in chondrocytes and its regulation by one miR identified by means of a genome-wide miR-array analysis. Results p16INK4a is induced upon IL-1-beta treatment and also during in vitro chondrogenesis. In the mouse model, Ink4a locus favors in vivo the proportion of terminally differentiated chondrocytes. When overexpressed in chondrocytes, p16INK4a is sufficient to induce the production of the two matrix remodeling enzymes, MMP1 and MMP13, thus linking senescence with OA pathogenesis and bone development. We identified miR-24 as a negative regulator of p16INK4a. Accordingly, p16INK4a expression increased while miR-24 level was repressed upon IL-1-beta addition, in OA cartilage and during in vitro terminal chondrogenesis. Conclusions We disclosed herein a new role of the senescence marker p16INK4a and its regulation by miR-24 during OA and terminal chondrogenesis.
Published: 2014

435. Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients

Author: Noël Cano, Raymond Azar, Christian Combe, Hubert Roth, Philippe Chauveau, Xavier Leverve, Maurice Laville, Michel Aparicio, Bernard Canaud, Denis Fouque, Hamant, Sarah, Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Médecine Interne B, Centre Hospitalier Dunkerque, Service d'Hépatogastroentérologie et Nutrition, Clinique Résidence du Parc, Service de Néphrologie, Dialyse et Soins Intensifs, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Bioénergétique fondamentale et appliquée, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, MESH: Kidney Transplantation, Body Mass Index, Cohort Studies, chemistry.chemical_compound, Hemoglobins, MESH: Bicarbonates, 0302 clinical medicine, Surveys and Questionnaires, Prealbumin, MESH: Renal Dialysis, Prospective Studies, MESH: Cohort Studies, MESH: Aged, 2. Zero hunger, Dialysis adequacy, education.field_of_study, MESH: Middle Aged, MESH: Follow-Up Studies, Middle Aged, MESH: Nutritional Status, 3. Good health, MESH: Hemoglobins, MESH: Kidney Failure, Chronic, Nephrology, MESH: Survival Analysis, Female, Hemodialysis, France, Adult, medicine.medical_specialty, Population, Urea reduction ratio, MESH: Serum Albumin, Nutritional Status, MESH: Body Mass Index, 03 medical and health sciences, MESH: Cross-Sectional Studies, Renal Dialysis, MESH: Prealbumin, Internal medicine, medicine, Humans, education, Dialysis, Serum Albumin, Aged, Creatinine, MESH: Humans, business.industry, MESH: Questionnaires, MESH: Adult, Kidney Transplantation, Survival Analysis, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, Bicarbonates, Cross-Sectional Studies, chemistry, Lean body mass, Kidney Failure, Chronic, business, MESH: Female, Body mass index, Follow-Up Studies
Abstract: International audience; Nutritional factors and dialysis adequacy are associated with outcome in hemodialyzed patients, but their relative contribution remains controversial, particularly when dialysis adequacy complies with current recommendations (Kt/V >1.2). Survival, clinical, and nutritional data from a cohort of prevalent 1,610 patients treated by hemodialysis in 20 centers in France have been collected over a 2.5-year period, from January 1996 to July 1998. Data including age, sex, cause of end-stage renal disease (ESRD), clinical outcome, time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were analyzed. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) from creatinine generation were computed from pre- and postdialysis urea and creatinine levels. The characteristics of the patients were as follows: age 59.6 +/- 16.5 years, 58.8% males, 11% of diabetics, time on dialysis 63.2 +/- 64.5 m. Weekly dialysis time was 12.18 +/- 1.78 hrs, Kt/V 1.34 +/- 0.34, nPCR 1.10 +/- 0.35 g/kg body weight/day. Albumin concentration was 39.4 +/- 5.3 g/L, prealbumin was 0.33 +/- 0.09 g/L, BMI was 23.0 +/- 4.5 kg/m(2). Overall survival was 89.7% +/- 0.8% and 78.4% +/- 1.1% after 1 and 2 years. In the Cox proportional hazard model, survival was significantly influenced by age, the presence of diabetes, and by concentrations of albumin and prealbumin, but not by other variables, including Kt/V and urea reduction ratio. These results indicate that nutritional protein concentrations were predictive of dialysis outcome, whereas variables reflecting actual body composition and dialysis dose were not. Furthermore, in this well-dialyzed population, dialysis adequacy had no influence on survival. In conclusion, when adequacy targets are met in hemodialyzed patients, survival is mainly dependent on age and nutritional status. Efforts should be focused on the most efficient ways to maintain nutritional status in these patients.
Published: 2001

436. Factors influencing survival in hemodialysis patients aged older than 75 years: 2.5-year outcome study

Author: Chauveau, Philippe, Combe, Christian, Laville, Maurice, Fouque, Denis, Azar, Raymond, Cano, Noël, Canaud, Bernard, Roth, Hubert, Leverve, Xavier, Aparicio, Maurice, Nutrition In Dialysis, French Study Group For, Hamant, Sarah, Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Médecine Interne B, Centre Hospitalier Dunkerque, Service de Néphrologie, Dialyse et Soins Intensifs, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Body Mass Index, Renal Dialysis, Internal medicine, medicine, Humans, Prospective Studies, Survival rate, Dialysis, Aged, Proportional Hazards Models, Aged, 80 and over, Univariate analysis, Dialysis adequacy, Analysis of Variance, business.industry, Proportional hazards model, Data Collection, Body Weight, Surgery, Nutrition Disorders, Survival Rate, [SDV] Life Sciences [q-bio], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, Nephrology, Lean body mass, Female, Hemodialysis, business, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Follow-Up Studies
Abstract: International audience; The incidence of malnutrition is widely held to be greater in the elderly, but this specific factor has not been extensively studied in elderly dialysis patients. In a 30-month follow-up prospective study, we evaluated the role of nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8 +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in January 1996, predialysis and postdialysis blood samples were collected according to recommended procedures for dialysis quantification. Normalized protein catabolic rate, dialysis adequacy parameters, and estimation of lean body mass (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from predialysis and postdialysis urea and creatinine levels. Overall survival rates were 80% and 65% after 1 and 2 years of follow-up, respectively, and were significantly less in patients with the lower quartile of obs/exp LBM. In univariate analysis using the Cox proportional hazards model, survival was significantly influenced by age, albumin level, prealbumin level, body mass index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable remained significant. Cardiovascular mortality accounted for 52.1% of the patient deaths. We conclude that in elderly HD patients, malnutrition influences overall survival despite adequate dialysis treatment.
Published: 2001

437. Acidosis and nutritional status in hemodialyzed patients. French Study Group for Nutrition in Dialysis

Author: Chauveau, Philippe, Fouque, Denis, Combe, Christian, Laville, Maurice, Canaud, Bernard, Azar, Raymond, Cano, Noël, Aparicio, Michel, Leverve, Xavier, Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Department of Nephrology, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Service de Néphrologie, Dialyse et Soins Intensifs, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de Médecine Interne B, Centre Hospitalier Dunkerque, Service d'Hépatogastroentérologie et Nutrition, Clinique Résidence du Parc, Bioénergétique fondamentale et appliquée, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Hamant, Sarah
Subjects: Adult, Male, MESH: Probability, Nutritional Status, MESH: Acidosis, MESH: Body Mass Index, Body Mass Index, MESH: Bicarbonates, MESH: Cross-Sectional Studies, Renal Dialysis, MESH: Analysis of Variance, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH: Renal Dialysis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, Probability, MESH: Aged, Analysis of Variance, MESH: Middle Aged, MESH: Humans, MESH: Adult, Middle Aged, MESH: Nutritional Status, MESH: Male, Bicarbonates, Cross-Sectional Studies, MESH: Kidney Failure, Chronic, Kidney Failure, Chronic, Female, Acidosis, MESH: Female
Abstract: International audience; In a cross-sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end-stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre- and postbicarbonate-dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (+/- 1 SD) were age 61 +/- 16 years, BMI 23.3 +/- 4.6 kg/m2, dialysis time 12.4 +/- 2.7 h/week, HCO3 22.8 +/- 3.5 mmol/L, albumin 38.7 +/- 5.3 g/L, prealbumin 340 +/- 90 mg/L, Kt/V 1.36 +/- 0.36, nPCR 1.13 +/- 0.32 g/kg BW/day, and LBM 0.86 +/- 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16-30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted between bicarbonate and Kt/V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.
Published: 2000

438. Tumor necrosis factor is a survival and proliferation factor for human myeloma cells

Author: Jourdan, Michel, Tarte, Karin, Legouffe, Eric, Brochier, Jean, Rossi, Jean-François, Klein, Bernard, Frei, Monique, Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: MESH: Recombinant Proteins, MESH: Humans, MESH: Cell Survival, MESH: Apoptosis, MESH: Tumor Necrosis Factor-alpha, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Cell Division, MESH: Multiple Myeloma, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Tumor Cells, Cultured, MESH: Interleukin-6, MESH: Antibodies, Monoclonal
Abstract: Interleukin-6 (IL-6) is a major survival factor for malignant plasma cells. In patients with multiple myeloma (MM), cell lines whose survival and proliferation are dependent upon addition of exogenous IL-6 have been obtained. We show here that tumor necrosis factor-alpha (TNF-alpha) is also a survival factor for myeloma cell lines, although less potent than IL-6. The survival activity of TNF-alpha is not affected by anti-IL-6 or anti-gp130 monoclonal antibodies (mAbs). TNF-alpha also induces myeloma cells in the cell cycle and promotes the long-term growth of malignant plasma cell lines. As TNF-alpha is produced in patients with MM and associated with a poor prognosis, these results suggest that anti-TNF-alpha therapies could be useful in this disease.
Published: 1999

439. Popliteal cysts from advanced amyloidosis in long-term haemofiltration / haemodiafiltration

Author: Dantoine, Thierry, Castro, R., Leblanc, M., Bosc, Jean-Yves, Vaussenat, F, Bouloux, C., Canaud, B., Handicap, Activité, Vieillissement, Autonomie, Environnement (HAVAE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 1997

440. Quantification directe de la dialyse sur site : utilisation du mimesis

Author: BOSC, JY, Vaussenat, F, Canaud, Bernard, Dantoine, Thierry, MION, C, Service de Néphrologie, Dialyse et Soins Intensifs, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Handicap, Activité, Vieillissement, Autonomie, Environnement (HAVAE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)
Subjects: [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 1996

441. MRI and serum biomarkers correlate with radiographic features in painful hand osteoarthritis

Author: Roux, Christian, Foltz, Violaine, Maheu, Emmanuel, Baron, Gabriel, Gandjbakhch, Frederique, Lukas, Cedric, Wendling, Daniel, Loeuille, Damien, Lafforgue, Pierre, Euler-Ziegler, Liana, Richette, Pascal, Chevalier, Xavier, on Osteoarthritis, French Section, HELLE, Déborah, CHU Nice, Hopital l'Archet 1, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Rhumatologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Hand Joints, Interleukin-6, Tumor Necrosis Factor-alpha, [SDV]Life Sciences [q-bio], Interleukin-1beta, education, Cartilage Oligomeric Matrix Protein, Middle Aged, Magnetic Resonance Imaging, Severity of Illness Index, [SDV] Life Sciences [q-bio], C-Reactive Protein, Osteoarthritis, Humans, Female, Hyaluronic Acid, Biomarkers, health care economics and organizations, Aged, Interleukin-1
Abstract: To explore the relationship between clinical findings, biologic biomarkers, conventional radiography and MRI in patients with painful hand OA.The following patient baseline data from the DORA study (evaluating anti-TNF-α agents against painful hand OA) were used: clinical assessment (pain, swelling, stiffness and function: Dreiser functional hand index [FIHOA] and Cochin hand functional scale [CHFS]); measurement of biomarkers (cartilage oligomeric matrix protein (COMP), type IIA collagen N-propeptid (PIINP), hyaluronic acid (HA), ultrasensitive C-reactive protein (usCRP), tumour necrosis factor (TNF), interleukin (IL)-6, IL-1β and urinary CTXII); radiological staging (Verbruggen, Kallman, Kellgren-Lawrence); anatomical evaluation by contrast-enhanced MRI of proximal and distal interphalangeal joints of dominant hand. Associations between clinical, biomarker and imaging findings were assessed using the Spearman correlation coefficient and test.18 patients were recruited, and 144 joints studied. A correlation was found between clinical features (pain, FIHOA, CHFS) and the Verbruggen score (respectively: p=0.05, r=0.47; p=0.05, r=0.48; p=0.05, r=0.48). Serum IL-1 level was strongly associated with loss of function (FIHOA: p=0.02, r=-0.73; CHFS: p=0.01, r=-0.76) and radiological erosions (p=0.03, r=0.7) as with urinary CTX2. A significant association was found between MRI osteophytes and usCRP (p=0.0026). MRI and radiological features were significantly correlated except for synovitis and bone marrow lesions.MRI synovitis was not correlated with radiological scores, clinical or biologic markers of inflammation. There was a strong correlation between other MRI features and radiological scores. Serum IL-1 level was associated with structural damage and function.
Published: 1996

442. Plasma Lutein and Zeaxanthin and Other Carotenoids as Modifiable Risk Factors for Age-Related Maculopathy and Cataract: The POLA Study

Author: Wolfgang Schalch, Isabelle Carrière, Pascale Barberger-Gateau, Martine Delage, Cécile Delcourt, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Research and Development, DSM Nutritional Products Ltd, Fondation de France, Fondation pour la Recherche Médicale, Région Languedoc-Roussillon, Association Retina-France, Rhônes Poulenc, Essilor, Specia et Centre de Recherche et d'Information Nutritionnelle., POLA Study Group, and Villebrun, Dominique
Subjects: Male, Lutein, genetic structures, 030309 nutrition & dietetics, Xanthophylls, MESH: Research Support, Non-U.S. Gov't, Macular Degeneration, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Chromatography, High Pressure Liquid, 0303 health sciences, education.field_of_study, MESH: Middle Aged, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, food and beverages, Middle Aged, beta Carotene, Zeaxanthin, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH: beta Carotene, Female, medicine.medical_specialty, Population, Drusen, MESH: Lutein, Cataract, 03 medical and health sciences, Zeaxanthins, Ophthalmology, medicine, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Risk factor, MESH: Chromatography, High Pressure Liquid, education, MESH: Macular Degeneration, MESH: Humans, business.industry, MESH: Xanthophylls, Macular degeneration, medicine.disease, MESH: Male, eye diseases, Surgery, Age-related maculopathy, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030221 ophthalmology & optometry, Maculopathy, MESH: Cataract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, business, MESH: Female
Abstract: PURPOSE. To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liees a l'Age (POLA) Study. METHODS. Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 μm) and/or soft distinct drusen (>125 μm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort. RESULTS. After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR = 0.07; 95% CI: 0.01-0.58; P for trend = 0.005), nuclear cataract (OR = 0.23; 95% CI: 0.08-0.68; P for trend = 0.003) and any cataract (OR = 0.53; 95% CI: 0.31-0.89; P for trend = 0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR = 0.21; 95% CI: 0.05- 0.79; P for trend = 0.01), and tended to be associated with plasma lutein (OR = 0.31; 95% CI: 0.09-1.07; P for trend = 0.04), whereas cataract showed no such associations. Among other carotenoids, only β-carotene showed a significant negative association with nuclear cataract, but not ARM. CONCLUSIONS. These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.
Published: 2006

443. Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first-line immunochemotherapy

Author: Ekaterina Gibiansky, Wolfgang Hiddemann, Robert Marcus, John F. Seymour, Georgina Meneses-Lorente, Guillaume Cartron, Nicolas Frey, Denis Sahin, Chantal E. Hargreaves, Günter Fingerle-Rowson, Candice Jamois, Vincent Buchheit, Leonid Gibiansky, Jonathan C. Strefford, F. Hoffmann-La Roche [Basel], North Potomac, Roche Innovation Center, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), King's College Hospital (KCH), Ludwig Maximilian University [Munich] (LMU), University of Melbourne, and University of Southampton
Subjects: Male, Oncology, Follicular lymphoma, CHOP, 030226 pharmacology & pharmacy, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Bendamustine Hydrochloride, Medicine, Pharmacology (medical), 030212 general & internal medicine, Lymphoma, Follicular, education.field_of_study, Population analysis, Hazard ratio, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Progression-Free Survival, 3. Good health, Treatment Outcome, B symptoms, Vincristine, Original Article, Female, Rituximab, medicine.symptom, medicine.drug, Bendamustine, medicine.medical_specialty, pharmacokinetic‐pharmacodynamic, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacokinetic-pharmacodynamic, Antibodies, Monoclonal, Humanized, Models, Biological, 03 medical and health sciences, Sex Factors, Internal medicine, Humans, Pharmacokinetics, education, Cyclophosphamide, Pharmacology, business.industry, Body Weight, Original Articles, medicine.disease, chemistry, Doxorubicin, Drug Resistance, Neoplasm, Prednisone, Monoclonal antibodies, business
Abstract: Aims: Obinutuzumab (G) is a humanized type II, Fc-glycoengineered anti-CD20 monoclonal antibody used in various indications, including patients with previously untreated front-line follicular lymphoma. We investigated sources of variability in G exposure and association of progression-free survival (PFS) with average concentration over induction (C meanIND ) in front-line follicular lymphoma patients treated with G plus chemotherapy (bendamustine, CHOP, or CVP) in the GALLIUM trial. Methods: Individual exposures (C meanIND ) were obtained from a previously established population pharmacokinetic model updated with GALLIUM data. Multivariate Cox proportional hazard models and univariate Kaplan–Meier plots investigated relationships of PFS with exposure and other potential prognostic factors. Results: Overall, G exposure was lower in high body-weight patients and in males, and slightly lower in patients with high baseline tumour burden. Analysis of clinical outcomes showed that variability in G exposure did not impact PFS in G-bendamustine-treated patients; PFS was inferior in males and patients with FCGR2a/2b T232 T low-affinity receptor variant, and superior in patients with FCGR2a/2b I232T variant. In G-CHOP/CVP arms, PFS improved with increasing C meanIND (hazard ratio = 1.74 and 0.394 at 5 th and 95 th percentile compared to median C meanIND ) and was inferior in patients with high baseline tumour size and B symptoms. Conclusions: It remains unclear whether for G-CHOP/CVP patients lower G exposure is a consequence of adverse disease biology and/or resistance to chemotherapy backbone (higher clearance in nonresponder patients, as demonstrated for rituximab) rather than being the cause of poorer clinical outcome. A study with >1 dose level of G could help resolve this uncertainty.
Published: 1970

444. TMEM187-IRAK1 Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisian and French Female Populations: Influence of Geographic Origin

Author: Khalifa, Olfa, Balandraud, Nathalie, Lambert, Nathalie, Auger, Isabelle, Roudier, Jean, Sénéchal, Audrey, Geneviève, David, Picard, Christophe, Lefranc, Gérard, Touitou, Isabelle, Mrenda, Bakridine M'Madi, Benedito, Cécilia, Pardoux, Etienne, Gagez, Anne-Laure, Pers, Yves-Marie, Jorgensen, Christian, Mahjoub, Touhami, Apparailly, Florence, CHU Saint-Eloi, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gènes HLA-DR, Autoanticorps et Microchimérisme dans la Polyarthrite Rhumatoïde et la Sclérodermie (HLA-DR), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SNECMA Villaroche [Moissy-Cramayel], Safran Group, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Unité clinique d'Immuno-Rhumatologie & Thérapeutique des maladies ostéo-articulaires, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, Université de Monastir - University of Monastir (UM), Université de Montpellier (UM), Clinical Department for Osteoarticular Diseases, University Hospital Lapeyronie, 34295 Montpellier, France, Inserm,University of Montpellier, the EU funding IMI- BTCure (no. 115142) and ERASMUS-Mundus (no. 2888), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: lcsh:Immunologic diseases. Allergy, Article Subject, [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC581-607, Research Article
Abstract: International audience; Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA). Here, we investigated the association between three polymorphisms in the Xq28 region containing TMEM187 and IRAK1 (rs13397, rs1059703, and rs1059702) in two unstudied populations: Tunisian and French. The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (= 408) compared with age-matched controls (= 471) in both Tunisian and French women. These results were confirmed by a meta-analysis replication study including two independent Greek and Korean cohorts. The rs1059702 C major allele was significantly associated with RA, only with French women. In the French population, the GTC haplotype displayed a protective effect against RA, while the ATC, GCC, and GTT haplotypes conferred significant risk for RA. No association for these haplotypes was found in the Tunisian population. Our results replicated for the first time the association of the three Xq28 polymorphisms with RA risk in Tunisian and French populations and suggested that RA susceptibility is associated with TMEM187-IRAK1 polymorphisms in women. Our data further support the involvement of X chromosome in RA susceptibility and evidence ethnicities differences that might be explained by differences in the frequencies of SE HLA-DRB1 alleles between both populations.

445. Evolving the comprehensive management of rheumatoid arthritis: identification of unmet needs and development of practical and educational tools

Author: Burmester, GR, Álvaro-Gracia, JM, Betteridge, N, Calvo Alén, J, Combe, B, Durez, P, Fautrel, B, Ferreira, RJO, Gabay, C, Iagnocco, A, Montecucco, C, Østergaard, M, Ramiro, S, Rubbert-Roth, A, Stamm, T, Szekanecz, Z, Taylor, PC, Van de Laar, M, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt-Universität zu Berlin, Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Universitario de Araba, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centro Hospitalar e Universitário [Coimbra], University of Geneva [Switzerland], Università degli studi di Torino (UNITO), Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Copenhagen = Københavns Universitet (KU), Leiden University Medical Center (LUMC), Zuyderland Hospital [Heerlen, The Netherlands], Brustzentrum Kantonsspital St. Gallen, Medizinische Universität Wien = Medical University of Vienna, University of Debrecen, University of Oxford [Oxford], University of Twente [Netherlands], Psychology, Health & Technology, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: ddc:616, MESH: Arthritis, Rheumatoid, MESH: Humans, Arthritis, Rheumatoid/diagnosis/therapy, Europe, Humans, Surveys and Questionnaires, Arthritis, Rheumatoid, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid, MESH: Rheumatology, MESH: Europe, MESH: Surveys and Questionnaires
Abstract: OBJECTIVES: Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs. METHODS: A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe. RESULTS: Five areas of priority need were identified: increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite of 14 eRA tools included educational slides, best-practice guidance, self‑assessment questionnaires, clinical checklists, a multidisciplinary team training exercise, an interactive patient infographic, and case scenarios. By April 2020, rheumatology professionals in 17 countries had been actively engaged in the eRA programme; in 11 countries, eRA tools were selected by national leaders in rheumatology and translated for local dissemination. A web platform, with country-specific pages, was developed to support access to the translated tools (https://www.evolvingthemanagementofra.com/). CONCLUSIONS: The eRA programme supports comprehensive management of RA across Europe through development and dissemination of practical educational tools. The eRA tools address priority needs and are available free of charge to the rheumatology community.

446. Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstrate the Efficacy of Biologics in Primary Sjogren's Syndrome?

Author: Jacques Morel, Sandrine Jousse-Joulin, Olivier Vittecoq, Anne Laure Fauchais, Emmanuel Nowak, Gilles Hayem, Aleth Perdriger, Pierre Yves Hatron, Laurent Chiche, Charles Zarnitsky, Jean Jacques Dubost, Xavier Mariette, Jacques-Eric Gottenberg, Divi Cornec, Jacques-Olivier Pers, Xavier Puéchal, Valérie Devauchelle-Pensec, Jean-Marie Berthelot, Vincent Goëb, Jean Sibilia, Claire Larroche, Alain Saraux, Raphaèle Seror, Eric Hachulla, Philippe Dieudé, Véronique Le Guern, Service de Rhumatologie, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Rhumatologie (Rhumato - HD - NANTES), Hôtel-Dieu de Nantes, Service de rhumatologie, Hôpital Sud, Département de Médecine Interne (DMP - LILLE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Département de Médecine Interne (DMI - MARSEILLE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Service de Rhumatologie - AMIENS (AMIENS - Rhumato), CHU Amiens-Picardie, Service de rhumatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut de Chimie du CNRS (INC), Département de Médecine Interne (DMI - BOBIGNY), chu bobigny, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Département de Rhumatologie (Rhumato - Ambroise Paré - PARIS), Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département de Rhumatologie, Hopital Jacques Monod, Département rhumatologie, CHU Clermont-Ferrand, Département de Rhumatologie (Rhumato - Bichat - PARIS), Hôpital Bichat Claude-Bernard, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de rhumatologie [CHU Rouen], Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: medicine.medical_specialty, Visual analogue scale, Endpoint Determination, [SDV]Life Sciences [q-bio], Population, lcsh:Medicine, Biologics, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Clinical endpoint, Humans, 10. No inequality, education, lcsh:Science, 030304 developmental biology, Randomized Controlled Trials as Topic, 030203 arthritis & rheumatology, 0303 health sciences, education.field_of_study, Multidisciplinary, business.industry, Patient Selection, lcsh:R, 3. Good health, Sjogren's Syndrome, Randomised Controlled Trials, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sample size determination, Cohort, Physical therapy, lcsh:Q, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Primary Sjögren's Syndrome
Abstract: OBJECTIVE:The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS). METHODS:We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. RESULTS:We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study. CONCLUSION:This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.

447. THE REFERENCE SITE COLLABORATIVE NETWORK OF THE EUROPEAN INNOVATION PARTNERSHIP ON ACTIVE AND HEALTHY AGEING

Author: Bousquet, J., Illario, M., Farrell, J., Batey, N., Carriazo, A. M., Malva, J., Hajjam, J., Colgan, E., Guldemond, N., Perala-Heape, M., Onorato, G. L., Bedbrook, A., Leonardini, L., Stroetman, V., Birov, S., Abreu, C., Abrunhosa, A., Agrimi, A., Alalaakkola, T., Allegretti, N., Alonso-Trujillo, F., Alvarez-Benito, M., Angioli, S., Apostolo, J., Armitage, G., Arnavielhe, S., Baena-Parejo, M., Bamidis, P. D., Balenovic, A., Barbolini, M., Baroni, I., Blain, H., Bernard, P. L., Bersani, M., Berti, E., Bogatyrchuk, L., Bourret, R., Brehm, J., Brussino, L., Buhr, D., Bultje, D., Cabeza, E., Cano, A., Capitani, C., Carantona, E., Cardoso, A., Coll Clavero, J., Combe, B., Conforti, D., Coppola, L., Corti, F., Coscioni, E., Costa, E., Crooks, G., Cunha, A., Daien, C., Dantas, Darpon Sierra, J., Davoli, M., Dedeu Baraldes, A., Luca, V., Nardi, L., Di Ciano, M., Dozet, A., Ekinci, B., Erve, S., Espinoza Almendro, J. M., Fait, A., Fensli, R., Fernandez Nocelo, S., Galvez-Daza, P., Gamez-Paya, J., Garcia Saez, M., Garcia Sanchez, I., Gemicioglu, B., Goetzke, W., Goossens, E., Geurdens, M., Gutter, Z., Hansen, H., Hartman, S., Hegendorfer, G., Heikka, H., Henderson, D., Heran, D., Hirvonen, S., Iaccarino, G., Jansson, N., Kallasvaara, H., Kalyoncu, F., Kirchmayer, U., Kokko, J. A., Korpelainen, J., Kostka, T., Kuna, P., Lajarin Ortega, T., Lama, C. M., Laune, D., Lauri, D., Ledroit, V., Levato, G., Lewis, L., Liotta, G., Lundgren, L., Lupianez-Villanueva, F., Mc Garry, P., Maggio, M., Manuel Keenoy, E., Martinez, C., Martinez-Domene, M., Martinez-Lozano Aranaga, B., Massimilliano, M., Maurizio, A., Mayora, O., Melle, C., Mendez-Zorilla, A., Mengon, H., Mercier, G., Mercier, J., Meyer, I., Millet Pi-Figueras, A., Mitsias, P., Molloy, D. W., Monti, R., Moro, M. L., Muranko, H., Nalin, M., Nobili, A., Nogues, M., O Caoimh, R., Pais, S., Papini, D., Parkkila, P., Pattichis, C., Pavlickova, A., Peiponen, A., Pereira, S., Pepin, J. L., Piera Jimenez, J., Portheine, P., Potel, L., Pozzi, A. C., Quinonez, P., Lauritsen, Ramirez X., Ramos, M. J., Rannali-Kontturi, A., Risino, A., Robalo-Cordeiro, C., Rolla, G., Roller, R., Romano, M., Romano, V., Ruiz-Fernandez, J., Saccavini, C., Sachinopoulou, A., Sanchez Rubio, M. J., Santos, L., simonetta scalvini, Scopetani, E., Smedberg, D., Solana-Lara, R., Soltysik, B., Sorlini, M., Stericker, S., Badiale, Stramba M., Taillieu, I., Tervahauta, M., Teixeira, A., Tikanmaki, H., Todo-Bom, A., Tooley, A., Tuulonen, A., Tziraki, C., Ussai, S., Veen, S., Venchiarutti, A., Verdoy-Berastegi, D., Verissimo, M., Visconti, L., Vollenbroek-Hutten, M., Weinzerl, K., Wozniak, L., Yorgancioglu, A., Zavagli, V., Zurkuhlen, A. J., Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Hydraulic and Environmental Engineering, University of Pavia, Department of Geriatrics - Efficiency and Deficiency Laboratory, Università degli Studi di Firenze [Firenze], Groupe d'étude de l'atmosphère météorologique (CNRM-GAME), Institut national des sciences de l'Univers (INSU - CNRS)-Météo France-Centre National de la Recherche Scientifique (CNRS), Mineralogisch-Petrographisches Institut (MPI), Mineralogisch-Petrographisches Institut, University of Coimbra [Portugal] (UC), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Laboratoire d'océanographie de Villefranche (LOV), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Istituto di Astrofisica Spaziale, Hôpital Lapeyronie [Montpellier] (CHU), Centre d’Expertise National des Technologies de l’Information et de la Communication pour l’autonomie - CENTICH (FRANCE), Center for Turbulence Research (CTR), Stanford University [Stanford], Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Station de Palavas, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de magnétisme et d'optique de Versailles (LMOV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Epidemiology Unit, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Nazionale di Geofisica e Vulcanologia, Sezione di Palermo, Centre d'EPistémologie et d'ERgologie Comparatives - UMR 7304 (CEPERC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Ethics, Law & Medical humanities, APH - Aging & Later Life, Bousquet, J, Illario, M, Farrell, J, Batey, N, Carriazo, A M, Malva, J, Hajjam, J, Colgan, E, Guldemond, N, Perälä-Heape, M, Onorato, G L, Bedbrook, A, Leonardini, L, Stroetman, V, Birov, S, Abreu, C, Abrunhosa, A, Agrimi, A, Alalääkkölä, T, Allegretti, N, Alonso-Trujillo, F, Álvarez-Benito, M, Angioli, S, Apóstolo, J, Armitage, G, Arnavielhe, S, Baena-ParejoI, M, Bamidis, P D, Balenović, A, Barbolini, M, Baroni, I, Blain, H, Bernard, P L, Bersani, M, Berti, E, Bogatyrchuk, L, Bourret, R, Brehm, J, Brussino, L, Buhr, D, Bultje, D, Cabeza, E, Cano, A, De Capitani, C, Carantoña, E, Cardoso, A, Coll Clavero, J I, Combe, B, Conforti, D, Coppola, L, Corti, F, Coscioni, E, Costa, E, Crooks, G, Cunha, A, Daien, C, Dantas, Null, Darpón Sierra, J, Davoli, M, Dedeu Baraldes, A, De Luca, V, De Nardi, L, Di Ciano, M, Dozet, A, Ekinci, B, Erve, S, Espinoza Almendro, J M, Fait, A, Fensli, R, Fernandez Nocelo, S, Gálvez-Daza, P, Gámez-Payá, J, García Sáez, M, Garcia Sanchez, I, Gemicioğlu, B, Goetzke, W, Goossens, E, Geurdens, M, Gütter, Z, Hansen, H, Hartman, S, Hegendörfer, G, Heikka, H, Henderson, D, Héran, D, Hirvonen, S, Iaccarino, G, Jansson, N, Kallasvaara, H, Kalyoncu, F, Kirchmayer, U, Kokko, J A, Korpelainen, J, Kostka, T, Kuna, P, Lajarín Ortega, T, Lama, C M, Laune, D, Lauri, D, Ledroit, V, Levato, G, Lewis, L, Liotta, G, Lundgren, L, Lupiañez-Villanueva, F, Mc Garry, P, Maggio, M, Manuel de Keenoy, E, Martinez, C, Martínez-Domene, M, Martínez-Lozano Aranaga, B, Massimilliano, M, Maurizio, A, Mayora, O, Melle, C, Mendez-Zorilla, A, Mengon, H, Mercier, G, Mercier, J, Meyer, I, Millet Pi-Figueras, A, Mitsias, P, Molloy, D W, Monti, R, Moro, M L, Muranko, H, Nalin, M, Nobili, A, Noguès, M, O'Caoimh, R, Pais, S, Papini, D, Parkkila, P, Pattichis, C, Pavlickova, A, Peiponen, A, Pereira, S, Pépin, J L, Piera Jiménez, J, Portheine, P, Potel, L, Pozzi, A C, Quiñonez, P, Ramirez Lauritsen, X, Ramos, M J, Rännäli-Kontturi, A, Risino, A, Robalo-Cordeiro, C, Rolla, G, Roller, R, Romano, M, Romano, V, Ruiz-Fernández, J, Saccavini, C, Sachinopoulou, A, Sánchez Rubio, M J, Santos, L, Scalvini, S, Scopetani, E, Smedberg, D, Solana-Lara, R, Sołtysik, B, Sorlini, M, Stericker, S, Stramba Badiale, M, Taillieu, I, Tervahauta, M, Teixeira, A, Tikanmäki, H, Todo-Bom, A, Tooley, A, Tuulonen, A, Tziraki, C, Ussai, S, Van der Veen, S, Venchiarutti, A, Verdoy-Berastegi, D, Verissimo, M, Visconti, L, Vollenbroek-Hutten, M, Weinzerl, K, Wozniak, L, Yorgancıoğlu, A, Zavagli, V, Zurkuhlen, A J, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Università degli Studi di Pavia = University of Pavia (UNIPV), Università degli Studi di Firenze = University of Florence (UniFI), Center for Turbulence Research [Stanford] (CTR), Stanford University, KYomed INNOV, Centre d'EPistémologie et d'ERgologie Comparatives (CEPERC), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Observatoire océanologique de Villefranche-sur-mer (OOVM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Active and healthy ageing, DG CONNECT, DG Santé, EIP on AHA, European Innovation Partnership on Active and Healthy Ageing, Allergic Rhinitis, Operational Definition, Program, Turkey, DG Sante, [SDV]Life Sciences [q-bio], Eip, Diseases, Articles, 03 medical and health sciences, 0302 clinical medicine, Synergies, 030228 respiratory system, Aha, Settore MED/42, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs.

448. Effects of biologic disease-modifying anti-rheumatic drugs on the radiographic progression of rheumatoid arthritis: a systematic literature review

Author: Combe, B., Lula, S., Boone, C., patrick durez, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, and Aiello, Mélisande
Subjects: Arthritis, Rheumatoid, musculoskeletal diseases, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Methotrexate, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Disease Progression, Humans, Drug Therapy, Combination, skin and connective tissue diseases
Abstract: International audience; OBJECTIVES:To evaluate the effect of biologic disease-modifying anti-rheumatic drugs (bDMARDs) on radiographic progression in patients with rheumatoid arthritis (RA).METHODS:A systematic review of electronic databases and conference proceedings was conducted through January 2015, to identify randomised controlled trials (RCTs) and observational studies that assessed the impact of bDMARDs [± conventional synthetic DMARDs (csDMARDs), mainly methotrexate (MTX)], versus csDMARDs alone, on radiographic progression in patients with RA.RESULTS:Following screening of >5000 records, 104 publications covering 63 studies were included. Of 34 RCTs in patients with early, active (n=13) or established RA (n=21) [abatacept (1, 2); adalimumab (4, 2); certolizumab pegol (1, 4); etanercept (3, 3); golimumab (1, 4); infliximab (1, 1); rituximab (1, 1); tocilizumab (1, 5)], combination therapy with a bDMARD and MTX had a significantly greater effect than placebo or MTX alone, in inhibiting radiographic progression. This included patients previously unresponsive, or who responded incompletely, to MTX treatment alone, and was supported by data from observational studies. Findings from a smaller subset of these and other RCTs supported superiority of combination therapy over bDMARD monotherapy, and bDMARD monotherapy over MTX, in slowing radiographic progression.CONCLUSIONS:There is evidence from RCTs with a range of bDMARDs that improvement in radiographic outcomes for patients with early or established RA, when used in combination with MTX and to a lesser extent as monotherapy, are significantly greater than MTX alone. There was no evidence of a difference between bDMARDs on inhibition of radiographic progression.

449. High Levels Of Natural Killer CELLS ARE Associated With Response To Tocilizumab In Patients With Severe Rheumatoid Arthritis

Author: Thibault Mura, Claire Daien, Jacques Morel, R. Audo, S. Gailhac, Bernard Combe, Michael Hahne, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CIC Montpellier, Institut National de la Santé et de la Recherche Médicale (INSERM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Herrada, Anthony, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Center of Experimental and Molecular Medicine
Subjects: Male, Severity of Illness Index, Receptors, Tumor Necrosis Factor, interleukin-6 inhibitor, regulatory T cells, Etanercept, Polyethylene Glycols, Arthritis, Rheumatoid, 0302 clinical medicine, Pharmacology (medical), Prospective Studies, skin and connective tissue diseases, perforin, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, natural killer cells, biology, Middle Aged, Natural killer T cell, 3. Good health, Killer Cells, Natural, Treatment Outcome, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Rheumatoid arthritis, Female, Rituximab, medicine.drug, Adult, musculoskeletal diseases, T cell, Antibodies, Monoclonal, Humanized, Immunoglobulin Fab Fragments, tocilizumab, 03 medical and health sciences, Rheumatology, medicine, Humans, Aged, 030203 arthritis & rheumatology, B cells, Lymphokine-activated killer cell, Tumor Necrosis Factor-alpha, business.industry, granzyme, Adalimumab, medicine.disease, Receptors, Interleukin-6, Granzyme B, Granzyme, Perforin, Immunoglobulin G, Immunology, Certolizumab Pegol, biology.protein, anti-TNF drug, business, 030215 immunology
Abstract: International audience; OBJECTIVES:We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls.METHODS:RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.RESULTS:We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.CONCLUSION:This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.

450. The role of mineral metabolism and inflammation on dialysis vascular access failure

Author: Nathalie Terrier, Hélène Leray-Moragues, Marion Morena, Cécile Delcourt, J L Flavier, François Maurice, Bernard Canaud, Anne Marie Dupuy, J Y Bosc, Isabelle Jaussent, Jean-Paul Cristol, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Renal Research and Training Institute, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de nephrologie, Centre hémodialyse Languedoc Mediterranée (CHLM), Hopital Béziers, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, and Villebrun, Dominique
Subjects: Male, Pathology, medicine.medical_treatment, 030232 urology & nephrology, Parathyroid hormone, Orosomucoid, Constriction, Pathologic, 030204 cardiovascular system & hematology, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, 0302 clinical medicine, Risk Factors, Ultrasonography, Aged, 80 and over, hemodialysis, cardiovascular risk, biology, Hyperparathyroidism, stenosis, Graft Occlusion, Vascular, Middle Aged, Thrombosis, mineral metabolism, Nephrology, Female, Adult, medicine.medical_specialty, Arteriovenous fistula, Veins, 03 medical and health sciences, Blood Vessel Prosthesis Implantation, Arteriovenous Shunt, Surgical, Osteoprotegerin, Renal Dialysis, Internal medicine, medicine, Humans, Dialysis, Vascular Patency, Aged, Inflammation, business.industry, vascular access, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Stenosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, biology.protein, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Thrombosis of arteriovenous fistula (AVF) is the leading cause of vascular access (VA) loss usually due to silent stenosis. Therefore, assessment of relevant risk factors of VA monitoring may provide insight into potential therapeutic targets for stenosis and thrombosis. The aim of this study was to evaluate the influence of cardiovascular risk factors (including inflammation and mineral metabolism dysfunctions) on the failure of internal AVF in HD patients. 128 HD patients with internal AVF were included in the study and followed up for two years. At baseline, VA morphology and function were followed by Doppler ultrasonography and serum albumin, prealbumine, C-reactive protein, orosomucoid, calcium, phosphorus, parathyroid hormone, bone-type alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor κB ligand were measured. At baseline, 50 stenoses were detected but none of them required any intervention. Age and biological parameters did not significantly differ between patients with or without VA stenosis. Over the two year- follow up, VA thrombosis occurred in 19 patients. Preexisting stenosis of VA was present in 9/19 patients (47.3% of cases) (chi-square = 3.708, p = 0.0538). Despite the low rate of events, phosphorus [1.75 (0.95–2.77) vs 1.42 (0.47–3.22) mmol/L, p = 0.0416], Calcium x Phosphorus product [4.00 (2.00–5.90) vs 3.40 (1.10–6.80) mmol2/L2, p = 0.0676] and parathyroid hormone [165.00 (1.00–944.00) vs 79.50 (1.00–846.60) ng/L, p = 0.0814) levels were higher in the 19 thrombotic patients whereas all other biological parameters did not significantly differ. These results, which confirm that VA thrombosis occurs more frequently upon preexisting stenosis, also demonstrate that mineral metabolism disorders, compared to inflammation, may contribute to VA dysfunction leading to thrombosis.

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