La société civile mondiale reste à inventer

Utopie que de défendre un intérêt général mondial ? Non, mais en luttant pour une autre régulation des échanges économiques et des relations internationales, les altermondialistes occultent souvent le monde réel, où les visions divergent

Sortir du piège : la gauche face à la mondialisation / Philippe Frémeaux

Collection : Altérnatives économiques. Série PocheCollection : Altérnatives économiquesContient une table des matièresAvec mode text

Comprendre l'économie soviétique / Philippe Frémeaux, Christine Durand

Collection : Alternatives économiques ; 7Collection : Alternatives économiques ; 7Contient une table des matièresAvec mode text

Économie sociale et solidaire

Nos sociétés contemporaines sont traversées par des tensions sociales, économiques et environnementales d’ampleur. La succession des crises financières et écologiques, les excès du capitalisme, la financiarisation croissante des activités humaines ou encore la mondialisation des inégalités imposent de construire de nouveaux référentiels économiques pour penser les politiques publiques de demain. Dans ce contexte, alors que les recettes passées ont montré leurs limites, il semble pertinent de s’interroger sur le rôle que pourrait jouer une économie plus sociale et solidaire. Quels changements et nouveaux savoir-faire pourrait-on imaginer dans ce contexte socio-économique en mutation ? Comment pourrait-on répondre différemment aux besoins et promouvoir des formes d’actions alternatives à la logique de l’accumulation ? En invitant des chercheurs en sciences humaines et sociales à se pencher sur ces questions et en leur proposant de réfléchir à de nouvelles façons de comprendre le monde, pour mieux y agir, cet ouvrage se veut sortir des solutions conventionnelles et répétitives souvent suggérées par les experts proches de la science économique « dominante ». Il emprunte, dans une première partie, des chemins stimulants pour « repenser » l’économie. Les questions de mesure de la richesse, de confiance dans les relations économiques ou encore de gestion des biens communs sont ainsi abordées. Ce sont, ensuite, des pistes concrètes pour renouveler les fondements de l’État social qui sont envisagées. Se dessinent alors de nouveaux espaces de transformation que l’économie sociale et solidaire semble pouvoir développer

Atypical hemolytic and uremic syndrome due to C3 mutation in pancreatic islet transplantation: a case report

International audienceBackground: We here report on the first observation of a C3 mutation that is related to atypical hemolytic and uremic syndrome (aHUS), which occurred in a pancreatic islet transplant patient. Immunosuppressive treatments, such as calcineurin inhibitors, have been linked to undesirable effects like nephrotoxicity.Case presentation: A 40-year-old man with brittle diabetes, who was included in the TRIMECO trial, became insulin-independent 2 months after pancreatic islet transplantation. About 15 months after islet transplantation, the patient exhibited acute kidney injury due to aHUS. Despite plasma exchange and eculizumab treatment, the patient developed end-stage renal disease. A genetic workup identified a missense variant (p.R592Q) in the C3 gene. In vitro, this C3 variant had defective Factor I proteolytic activity with membrane proteins as cofactor proteins, which was thus classified as pathogenic. About 1 year after the aHUS episode, kidney transplantation was carried out under the protection of the specific anti-C5 monoclonal antibody eculizumab. The patient had normal kidney function, with preserved pancreatic islet function 4 years later.Conclusions: Pancreatic islet transplantation could have triggered this aHUS episode, but this link needs to be clarified. Although prophylactic eculizumab maintains kidney allograft function, its efficacy still needs to be studied in larger populations

Complement activation in sickle cell disease: Dependence on cell density, hemolysis and modulation by hydroxyurea therapy

International audienceThe complement system is an innate immune defense cascade that can cause tissue damage when inappropriately activated. Evidence for complement over activation has been reported in small cohorts of patients with sickle cell disease (SCD). However, the mechanism governing complement activation in SCD has not been elucidated. Here, we observe that the plasma concentration of sC5b-9, a reliable marker for terminal complement activation, is increased at steady state in 61% of untreated SCD patients. We show that greater complement activation in vitro is promoted by SCD erythrocytes compared to normal ones, although no significant differences were observed in the regulatory proteins CD35, CD55, and CD59 in whole blood. Complement activation is positively correlated with the percentage of dense sickle cells (DRBCs). The expression levels of CD35, CD55, and CD59 are reduced in DRBCs, suggesting inefficient regulation when cell density increases. Moreover, the surface expression of the complement regulator CD46 on granulocytes was inversely correlated with the plasma sC5b-9. We also show increased complement deposition in cultured human endothelial cells incubated with SCD serum, which is diminished by the addition of the heme scavenger hemopexin. Treatment of SCD patients with hydroxyurea produces substantial reductions in complement activation, measured by sC5b-9 concentration and upregulation of CD46, as well as decreased complement activation on RBCs in vitro. In conclusion, complement over activation is a common pathogenic event in SCD that is associated with formation of DRBCs and hemolysis. And, it affects red cells, leukocytes and endothelial cells. This complement over activation is partly alleviated by hydroxyurea therapy

Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre

International audienceBackground: Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). Methods: This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. Results: Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m 2 respectively in the eculizumab group and in the control group. Conclusions: These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery

BREAKTHROUGH IN THE MANAGEMENT OF ATYPICAL HEMOLYTIC UREMIC SYNDROME AFTER KIDNEY TRANSPLANTATION: A NATIONWIDE STUDY

International audienc

Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation

International audienceBACKGROUND AND OBJECTIVES: The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome.DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse.RESULTS: Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (<7 days) hematologic remission and a return of serum creatinine to baseline level in a median time of 26 days. At last follow-up, renal function remained unchanged in nonrelapsing and relapsing patients compared with baseline values before eculizumab discontinuation.CONCLUSIONS: Pathogenic variants in complement genes were associated with higher risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients