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MDS-RS patients are characterized by chronic anemia and a low risk of Acute Myeloid Leukemia (AML) progression and they generally become Red Blood Cell (RBC) transfusion dependent (TD).We performed a retrospective "real-life" observational study of 6 months in 100 MDS-RS TD patients, recruited in 12 French centers, to describe transfusion characteristics, and evaluate the frequency and causes of hospitalizations, health costs, and morbidity, associated with transfusion dependency, in a French population of RBC transfusion-dependent MDS-RS patients.79% of the patients had high transfusion burden (HTB) and 21% low transfusion burden (LTB). HTB patients had a longer disease duration (6 vs. 3.7 years, p = 0.0078), more frequent iron chelation (82% vs. 50%, p = 0.0052) and higher serum ferritin (p = 0.03). During the 6-month study period, 22% of the patients required inpatient hospitalization, 36% of them for symptomatic anemia requiring emergency RBC transfusion. The 6-month median transfusion costs, including the cost of the day care facility, transportation to and from the hospital, iron chelation, and lab tests, was 16,188€/patient.MDS-RS represents the archetypal type of chronically transfused lower-risk MDS. Most of those patients have a high transfusion burden and thus frequently need visits to the hospital's day care facility, and frequent hospitalizations, with an overall high median treatment cost. Those costs should be compared with costs of new treatments potentially able to avoid RBC transfusion dependence and to reduce the complications of chronic anemia in MDS-RS patients.

Ce court article vise à faire le bilan de la mise en œuvre par la France, tant sur le plan national que sur le plan international, du Pacte mondial pour des migrations sûres, ordonnées et régulières, adopté en décembre 2018. Offrant un regard critique sur quatre années d’un engagement limité de la France envers les processus amorcés en 2018, il fait état d’un retard de la France pris dans l’émergence de la gouvernance mondiale des migrations, retard difficilement justifiable au regard des contraintes nationales, régionales et internationales. Appelant à une réaction française, il propose la voie de la mobilisation de la Commission nationale consultative des droits de l’homme (CNCDH), institution indépendante française chargée de veiller au respect par la France de ses obligations internationales possédant les compétences et le mandat nécessaires à un lancement véritable de la mise en œuvre française du Pacte.

Ce chapitre se propose d’étudier l’évolution de l’idée multilatérale dans le domaine des migrations internationales, et ses tentatives de réalisation, jusqu’à une dimension prospective sur la possible mise en œuvre d’une « gouvernance mondiale », annoncée. Il vise à démontrer que l’idée d’une coopération multilatérale existe depuis longtemps en la matière, et que sa réalisation serait au moins aussi légitime que la résistance souverainiste traditionnelle des États, qui semble pourtant dominante, aujourd’hui, en droit international.

International audience

International audience

International audience; Sommes-nous, comme certains le pensent, confrontés à la fin du multilatéralisme ? Quel peut être le devenir du multilatéralisme au XXIe siècle ? La Covid-19 a confirmé le mal-être profond que traverse le multilatéralisme depuis plusieurs années. Heurté par l’America first, confronté à la montée en puissance de la Chine, promu par l’Union européenne et le Canada, le multilatéralisme semble aujourd’hui confronté à la montée de l’unilatéralisme et à une remise en cause des valeurs qui le sous-tendent. La crise de la Covid-19 a agi comme un catalyseur, accélérant les transformations déjà en cours. Ainsi, Josep Borrel, Haut représentant pour la politique extérieure et la politique de sécurité commune de l’Union européenne, estime que « le monde d’après est déjà là ». Avec comme point de départ une réflexion sur l’état du multilatéralisme à l’heure de la Covid-19, cet ouvrage s’interroge sur la reconfiguration annoncée et attendue du multilatéralisme contemporain. Cette publication pluridisciplinaire riche d’une trentaine de contributions propose une réflexion sur les perspectives d’un multilatéralisme menacé mais indispensable face aux enjeux globaux contemporains.

International audience; Objectives: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.Methods: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow-up.Results: This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities.Conclusions: The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.

International audience

International audience

International audience

International audience; Physiopathology of myelodysplastic syndrome (MDS) remains poorly understood and the role of the microenvironment is increasingly highlighted. Recent studies in mouse models demonstrate that abnormalities of mesenchymal stromal cells (MSC) contribute to the physiopathology of MDS. In particular, genetic deletion of dicer1, a gene encoding a type III RNase essential for the genesis of miRNA, in murine MSC-derived osteoprogenitors led to a pathological microenvironment generating myelodysplastic features in hematopoietic progenitors and ultimately leading to acute myeloid leukemia [1]. In human, there is an increased susceptibility to senescence of the MDS mesenchymal stem cells and defects in the support properties of the growth of hematopoietic stem cells (HSC) [2]. These observations establish a causal relationship between deregulation of the hematopoietic niche and MDS pathogenesis. However, so far only few studies have addressed the mechanisms by microenvironmental MSC and HSC exchange signals that may interfere with miRNA processing, specifically in the human MDS microenvironment.

Background: We assessed the impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of patients over 60 with a new diagnosis of AML treated using the LAM-SA 2007 FILO trial protocol. Patients and methods: 424 patients with de novo AML diagnosis without adverse cytogenetic criteria and an Eastern Cooperative Oncology Group score ≤ 2 were included between February 2008 and December 2011. Three geriatric assessment (GA) domains were used for evaluation: nutritional status using the Mini Nutritional Assessment, cognitive status by the Mini Mental State Examination, and functional status by activity of daily living (ADL) and instrumental activities of daily living (IADL). Assessment was realized at diagnosis and then three times during the patient’s follow-up. Results: AML and its treatment didn’t impact cognitive (p=0.554) or functional status (p=0.842 for ADL and p=0.087 for IADL). AML ad a positive impact on nutritional status with improvement over time (p=0.041). The benefit was greatest for patients with poor performance status at diagnosis (p

Publication d'une version révisée du mémoire de Master 2.; International audience; In a global context where the importance of migration is increasingly recognized, the Global Compact for Safe, Orderly and Regular Migration, or Marrakech Compact on Migration, has been adopted by a majority of States in an attempt to collectively address this salient issue. Although non-binding, the Marrakech Compact on Migration is of considerable importance, since it can be analysed as the first legal instrument of such scope dealing with the migration issue, in the broad sense. This essay provides a first critical analysis of the Compact, comparing the current gaps in international migration law and international migration management with the Compact responses concerning the rights of migrants and global governance.; Dans un contexte mondial où l’importance du phénomène migratoire est de plus en plus reconnue, le Pacte mondial pour des migrations sûres, ordonnées et régulière, ou Pacte de Marrakech, a été adopté par une majorité d’Etats pour tenter de répondre, collectivement, à cet enjeu saillant. Bien que non contraignant, le Pacte de Marrakech possède une importance considérable, puisqu’il peut s’analyser comme le premier instrument juridique d’une telle ampleur traitant de la question migratoire, au sens large. Ce mémoire propose une première analyse critique du Pacte, comparant les manques actuels du droit international des migrations et de la gestion internationale des migrations à la réponse apportée par le Pacte, sur les volets des droits des migrants et de la gouvernance mondiale.

International audience

Background: MDS-RS are associated with a low risk of Acute Myeloid Leukemia (AML) progression and prolonged survival in most cases, but recurring anemia whose treatments, including Erythropoiesis Stimulating Agent (ESA), Lenalidomide, hypomethylating agents (HMAs), Luspatercept, and experimental drugs generally have transient effect and/or are not widely available. MDS-RS patients thus eventually have regular Red Blood Cells (RBC) transfusion dependency (TD) associated with mean low hemoglobin levels, and chronic anemia responsible for reduced quality of life, cardiovascular complications, and iron overload with organ dysfunction. We performed a retrospective observational study to describe transfusion characteristics and costs, along with clinical events, in a French population of RBC TD MDS-RS patients. Methods: Adult RBC-TD patients with MDS-RS from 12 hematology departments of the GFM were included. The number of RBC concentrates transfused was assessed over the last 6 months (during which no other treatment than transfusions was received), and patients categorized in low transfusion burden (LTB: 3 to 7 RBC/16 weeks) and high transfusion burden (HTB: ≥8 RBC concentrates /16 weeks). Data about iron chelation, full time hospitalization (differing from day care facility stays for programmed transfusions), causes of hospitalization, treatment of anemia before inclusion and transfusion costs was collected. Results: 100 patients MDS-RS were included, with a median time from diagnosis of 5 years (1 to 21 years). Median age was 78 years (57 to 99). Patients had received a median of 2 lines of treatment (including an ESA in 97% of them). 21% had LTB and 79% HTB. HTB patients had a longer disease duration, more frequent iron chelation (82% versus 50% in LTB patients, p=0.0052) and higher serum ferritin at inclusion (median 1958 µg/l versus 1176 µg/l, p=0.03). During the 6-month study period, 22% of the patients required full time hospitalization (in addition to day care facility for transfusions), including 25% of patients with HTB and 15% with LTB, and 43% during overall disease follow-up. Causes of full time hospitalization (figure) were symptomatic anemia (41%), general condition degradation (5%) or cardiac disease (8%), to both of which anemia potentially contributed, infection (23%), bleeding (8%), pulmonary (2%), 13% for other reasons. 15 HTB patients versus 1 LTB patient were hospitalized for symptomatic anemia. The 6-months average transfusion costs, including cost of the day care facility for RBC transfusion, transportation to and from the hospital, lab tests and iron chelation were $21459/patient, excluding costs of full-time hospitalization for complications. The average cost in HTB and LTB patients was $22829 and $7586/patient, respectively. Conclusion: Most MDS-RS patients currently become RBC-TD, often during several years, and most have high transfusion burden. The average cost of RBC transfusions and iron chelation was $21459/ 6 months. During this short observation time, 22% of the patients required full time hospitalization, due to complications of anemia in at least 50% of the cases, which also increased costs (comparison with rates of hospitalization in an age and sex matched general population will be presented). Poor quality of life associated with chronic anemia should also be taken into account in those RBC-TD patients. Widely available treatments, capable of avoiding RBC transfusion dependence and improving mean hemoglobin levels, are required in those MDS-RS patients. Disclosures Cony-Makhoul: BMS: Speakers Bureau; Incyte Biosciences: Speakers Bureau; BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria. Cluzeau:Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Menarini: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Stamatoulas Bastard:Takeda: Consultancy; Pfizer: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Honoraria. Fenaux:Jazz: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Park:Pfizer: Other: Travel expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees.

Chronic myelomonocytic leukemia (CMML) is a myeloid hematological malignancy with overlapping features of myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). The knowledge of the role of the tumor microenvironment (TME), particularly mesenchymal stromal cells (MSCs), in MDS pathogenesis is increasing. Generally, cancer is associated with a procoagulant state participating in tumor development. Monocytes release procoagulant, tissue factor (TF)–bearing microparticles. We hypothesized that MSCs and clonal monocytes release procoagulant extracellular vesicles (EVs) within the CMML TME, inducing a procoagulant state that could modify hematopoietic stem cell (HSC) homeostasis. We isolated and cultured MSCs and monocytes from CMML patients and MSCs from healthy donors (HDs). Their medium EVs and small EVs (sEVs) were collected after iterative ultracentrifugations and characterized by nanoparticle tracking analysis. Their impact on hemostasis was studied with a thrombin generation assay and fibrinography. CMML or HD HSCs were exposed to sEVs from either CMML or HD MSCs. CMML MSC sEVs increased HD HSC procoagulant activity, suggesting a transfer of TF from the CMML TME to HD HSCs. The presence of TF on sEVs was shown by electron microscopy and western blot. Moreover, CMML monocyte EVs conferred a procoagulant activity to HD MSCs, which was reversed by an anti-TF antibody, suggesting the presence of TF on the EVs. Our findings revealed a procoagulant “climate” within the CMML environment related to TF-bearing sEVs secreted by CMML MSCs and monocytes.

L’enjeu de l’agroécologie est aujourd’hui perçu et compris par une grande majorité du monde agricole et répond à une aspiration sociétale. En viticulture, il se cristallise autour de l’utilisation des produits phytosanitaires, mais aussi de la qualité et la fertilité des sols et la biodiversité des parcelles.

National audience; L’enjeu de l’agroécologie est aujourd’hui perçu et compris par une grande majorité du monde agricole et répond à une aspiration sociétale. En viticulture, il se cristallise autour de l’utilisation des produits phytosanitaires, mais aussi de la qualité et la fertilité des sols et la biodiversité des parcelles.

Contexte Les Concentres de Globules Rouges (CGR) transfuses contiennent tres majoritairement des globules rouges, mais aussi des proteines et surtout des vesicules extracellulaires (EV). La liberation d’EV est un mecanisme de communication intercellulaire interessant car les EV vehiculent divers signaux : acides nucleiques, microARN, molecules membranaires, phosphatidylserines, facteur tissulaire, recepteurs/ligands, enzymes, facteurs de transcription, etc. qui peuvent influencer les cellules cibles. Bien que depourvu de systeme endosomal, les globules rouges en fin de vie liberent des EV. Les patients atteints de syndromes myelodysplasiques souffrent majoritairement d’anemie et recevront au cours de leur maladie des transfusions de culots globulaires. Dans ce travail, nous analysons ex vivo les interactions des EV de CGR sur l’hematopoiese des SMD dans son environnement medullaire. Resultats et conclusion Nous avons purifie les EV de CGR par ultracentrifugations differentielles et les avons caracterisees par Nanoparticle Tracking Analysis (Malvern NanoSight). Les EV sont plus nombreuses dans les poches pres de la date de peremption et sont plus petites. En microscopie confocale, nous avons mis en evidence que les EV marquees par un fluorochrome lipophile penetrent dans les CSH et les cellules souches mesenchymateuses (MSC) obtenues de moelle osseuse de patients atteints de SMD. Nous analysons maintenant le profil des microARN contenus dans ces EV et l’impact potentiel des EV sur l’hematopoiese en contexte pathologique SMD dans des modeles de coculture a long terme.

Lipoprotein (a) [Lp(a)] is a lipoprotein which has a plasma concentration that is highly correlated with cardiovascular disease. In this study, the new Lp(a) assay for the Vitek Immuno-Diagnostic Assay System (VIDAS) developed by bioMerieux was evaluated. This method uses an enzyme linked fluorescent immunoassay (ELFIA) technique. Within-run and between-run reproducibility of the Vidass Lp(a) assay are characterized by coefficients of variation (CV) of 3 to 5.9% and 3.9 to 5.9%, respectively. Using analysis of variance, no statistical difference was shown between ELFIA and immunonephelometric assay (INA). When comparing results of the Vidas Lp(a) test with the INA, a highly significant correlation of r = 0.9708 and regression line equation y = 0.963x-0.037 was found. Interference of lipemia was studied: no influence was observed up to 12.3 mmol l(-1) triglycerides. No interference of haemoglobin was noted for Lp(a) > 0.20 g l(-1). Hyperbilirubinemia ( > 120 micromol l(-1)) led to results being underestimated for concentrations of Lp(a) which were < 0.20 g l(-1). No pre-analytical interference of citrate was measured but pre-analytical interference of EDTA was found. In conclusion, this new fully automated immunofluorimetric Lp(a) assay enables to the rapid, accurate and reliable determination of Lp(a) in blood samples.

A brief philatelic evocation of Louis Pasteur and of his disciples Philately is an important source of knowledge on numerous items. Evocation of Louis Pasteur's as well as his disciples life and works throughout stamp collection is a perfect example of this. Born in Dole in 1822, he spent his youth in Arbois. It is at the Ecole normale supérieure that he performed his work on cristals which led him to establish molecular dissymetry principles. Later, he studied of the fermentation process, he searched the reason of wines'disease and the means to prevent it (i.e. pasteurisation), he solved the problem of the silkworm disease and discovered agents of numerous infectious diseases. He demonstrated scientifically the vaccination principle. In 1885 he tried with success the first human antirabic vaccination. Three years later, the Pasteur Institute was inaugurated. After his death, his works survived in numerous institutes all over the world. Many pasteurians received the Nobel Prize., La philatélie évoque la vie et l'œuvre de Pasteur ainsi que celle de ses élèves. Toutes les étapes de sa carrière sont illustrées par des timbres ou des flammes., Jouzier Étienne. Brève évocation philatélique de Louis Pasteur et de ses disciples. In: Revue d'histoire de la pharmacie, 85ᵉ année, n°314, 1997. pp. 147-152.

Resume L'electrophorese des proteines demeure un examen simple et rapide fournissant des informations precieuses au diagnostic de nombreuses maladies. En particulier, elle permet de suspecter la presence d'une proteine monoclonale qui est ulterieurement confirmee par immunofixation. Cette etude evalue les performances de deux methodes d'electrophorese. Elle montre que la methode Sebia Hydrasys a une specificite de 94 % et une sensibilite de 100 % tandis que la methode Helena a une specificite de 94 % et une sensibilite de 63 %.

A potentiometric stripping analysis method for blood lead determination, using Radiometer Tracelab PSU 22, has been investigated. Hemoglobin precipitation by hydrochloric and perchloric acids mixture allows to obtain the same signal for the same lead concentrations in aqueous standards and various blood samples. Thus it is possible to use a time saving calibration procedure. Equilibration time increase improved method sensitivity and precision. The analysis time was 3 minutes per sample. The detection limit was 0.006 microM/L. The relative standard deviation was 3.6% for 1.351 microM/L and 6% for 0.203 microM/L. The results of 66 determinations obtained by this method and by graphite furnace atomic absorption spectrometry were compared (R=0.991). Potentiometric stripping analysis is less expensive and very convenient for clinical laboratories.

Lipoprotein (a) [Lp(a)] is a lipoprotein which has a plasma concentration that is highly correlated with cardiovascular disease. In this study, the new Lp(a) assay for the Vitek Immuno-Diagnostic Assay System (VIDAS) developed by bioMérieux was evaluated. This method uses an enzyme linked fluorescent immunoassay (ELFIA) technique. Within-run and between-run reproducibility of the Vidass Lp(a) assay are characterized by coefficients of variation (CV) of 3 to 5.9% and 3.9 to 5.9%, respectively. Using analysis of variance, no statistical difference was shown between ELFIA and immunonephelometric assay (INA). When comparing results of the Vidas Lp(a) test with the INA, a highly significant correlation of r = 0.9708 and regression line equation y = 0.963x-0.037 was found. Interference of lipemia was studied: no influence was observed up to 12.3 mmol l(-1) triglycerides. No interference of haemoglobin was noted for Lp(a)0.20 g l(-1). Hyperbilirubinemia (120 micromol l(-1)) led to results being underestimated for concentrations of Lp(a) which were0.20 g l(-1). No pre-analytical interference of citrate was measured but pre-analytical interference of EDTA was found. In conclusion, this new fully automated immunofluorimetric Lp(a) assay enables to the rapid, accurate and reliable determination of Lp(a) in blood samples.

Extraction of oyster lipids were carried out on total wet organic tissues with a mixture of chloroform-methanol. The different fractions of polar and not polar lipids were separated by thin layer chromatography (TLC) and the methyl esters of the constituant fatty acids has been prepared by transmethylation a cold for use in subsequent gas-liquid chromatography (open tubular gas chromatography). The oyster contained considerable proportions of C16:0 and heiglhly unsaturated acids (specially in lecithin and cephalin) of C20, C22 series which are characteristic of the lipids of most acquatic plants and animals. Studies were made of the seasonal variations.