Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients

Les flux d'azote en élevage de ruminants

L'élevage transforme l'azote des végétaux en produits animaux et en rejette une partie sous forme de déjections, qui peuvent être utilisées comme engrais. Toutefois le développement des productions animales a conduit dans certains territoires à une concentration des apports et rejets d'azote, et une pollution des eaux, du sol et de l'atmosphère. Cette problématique est traitée depuis une vingtaine d'années par les politiques européennes. Que sait-on aujourd'hui de la dynamique des flux d'azote issus des élevages ? Quelles sont les pistes et les échelles pertinentes d'action pour réduire les émissions et leurs impacts sur l'environnement tout en préservant la compétitivité des productions animales ? Ces questions ont motivé de la part des ministères en charge de l'Agriculture et de l'Ecologie, au printemps 2010, une demande d'expertise scientifique collective auprès de l'INRA pour disposer d'un bilan des connaissances sur les différents flux d'azote associés aux activités d'élevage. Nous relatons ici les éléments majeurs concernant l'élevage des ruminants

Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease. Methods: This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment. Results: Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab. Conclusion: In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD

Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome

Background: Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination. Objectives: To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome. Methods: We analysed an international historical cohort of 61 children with radiologically isolated syndrome (18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria. Results: Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4\u201388.2%) versus 72.7% (49.8\u201389.3%); specificity 83.3% (58.6\u201396.4%) versus 53.9% (37.2\u201369.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1\u201393.2%) versus 100% (84.6\u2013100%); specificity 72.7% (49.8\u201389.3%) versus 25.6% (13.0\u201342.1%). Conclusions: Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Importance: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants: The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions: HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures: The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results: A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance: Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration: isrctn.org Identifier: ISRCTN5437125

Les peuplements benthiques du plateau insulaire de la Martinique et des zones bathyales adjacentes. Cas particulier de la malacofaune

Several oceanographic surveys in Martinique waters with, as main objectives, either geological mapping and evaluating marine aggregate resources of research into deep water carcinologie resources, nafe produced interesting informtion on benthic pppulations situated from the infralittoral to the bathyal shelf, for the wole of faunistic groups and more specifically for the malacofauna. The distribution of the various faunistic group has been analysed in function to the bathymetric, edaphic and possibly, thermic factors. The infralittoral zones, up to the 20 metres isobath, and circalittoral, between 60  and 80 metres, are known to have the richest populations. Corals, sponges, polychaete annelida and molluscs are the best represented, numerically as well as in diversity. Above the insular shelf, at slope level and towards the bathyal zones, faunistic desity decreases except in certain localised areas. The edaphic distribtion shows that the coral reef or those characterised by mixed sediments are the richest as are the loose grounds where the pelite density is relatively high. The highest indexes of abondance are spread over the upper part of the plateau, to the east, and at the entrance to Fort-de-France bay, to the west. Malacofauna distribution which makes a non-negligible contribution to benthic populations, follows the same pattern. Using multivarious analysis, several mollusc communities or gatherings have been identified in function the the three principal environmental factors : bathymetric, edaphic structure and temperature. The gasteropos were more abundant and varied on hard or coarse bottoms and bivalves, notably the soil-dwelling forms, on loose gronds. Diversity is maximal on the various substrata, particularly where they are composed of biodetric elements and heterometric mineral elements. Fairly distinctive communiteis have been found in the shallows and especially in deep water. Shelf communites, characterised by a greater number of ubiquitous forms, have less precise contours. The malacologic fauna of the slope, as far as the insular rise, appeared much poorer, due perhaps to the pronounced incline and a certain substratum instality. .Plusieurs c:unpagnes océanographiques effectuées dans les eaux de la Martinique avec pour objectifs principaux soit, la cartographie géologique et l'évaluation des ressources en granulats marins, soit, des recherches sur les ressources carcinologiques profondes, ont permis d'obtenir d'intéressantes informations sur les peuplements benthiques des fonds situés depuis l'infralittoral jusqu'à l'étage bathyal, pour l'ensemble des groupes faunistiques et plus particulièrement pour la malacofaune. La distribution des divers groupes faunistiques a été analysée en fonction des facteurs bathymétrique, édaphique et éventuellement thermique. Les aires infralittorales, jusqu'à l'isobathe 20 mètres, et circallitorales. entre 60 et 80 mètres se sont avérées avoir les populntions les plus riches. Les coraux, les spongiaires, les annélides polychètes et les mollusques sont les groupes les mieux représentés aussi bien numériquement qu'en diversité. Au-delà du plateau insulaire, au niveau du talus et vers les zones bathyales, la densité faunistique diminue sauf dans quelques aires très localisées. La distribution édaphique montre que les zones coralliennes ou caractérisées par des sédiments mélangés, sont les plus riches ainsi que les fonds meubles où la densité de pélites est relativement importante. Les indices d'abondance les plus élevés se répartissent sur la partie supérieure du plateau à l'est, et à l'entrée de la baie de Fort-de-France. à l'ouest. La distribution de la malacofaune, qui participe pour une part non négligeable aux peuplements benthiques, suit le même schéma. Par les analyses multivariées, plusieurs assemblages ou communautés de mollusques ont pu être identifiés en fonction des 3 principaux facteurs d'environnement : bathymétrie,  strucrure édaphique et température. Les gastéropodes sont apparus plus abondants et variés sur les fonds durs ou grossiers et les bivalves, notamment les formes endogées, sur les fonds meubles. La diversité est maximale sur les substrats variés, notamment sur ceux constitués d'éléments biodétritiques et d'éléments minéraux hétérométriques. Des communautés assez bien individualisées ont été trouvées sur les petits fonds et surtout dans les eaux profondes. Les communautés du plateau, caractérisées par un plus grand nombre de formes ubiquistes, ont des contours moins nets. La faune malacologique du talus, jusqu'au glacis insulaire, est apparue beaucoup plus pauvre, peut être à cause de la déclivité prononcée et d'une certaine instabilité du substratum

CHIMIOTHERAPIE ASSOCIANT VM-26 ET CCNU APRES RADIOTHERAPIE DANS LE TRAITEMENT DES ASTROCYTOMES DE HAUT GRADE (UNE SERIE DE TRENTE ET UN PATIENTS)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF