Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation

AbstractBackground: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. Methods: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. Results: The VE LVAS–treated and non–VE LVAS–treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L · min–1 · m–2. Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS–related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS–treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS–treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). Conclusion: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation

Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates mesenchymal stem cells through let-7f microRNA and Wnt/β-catenin signaling

Tissue inhibitor of metalloproteinases 1 (TIMP-1) is a matrix metalloproteinase (MMP)-independent regulator of growth and apoptosis in various cell types. The receptors and signaling pathways that are involved in the growth factor activities of TIMP-1, however, remain controversial. RNA interference of TIMP-1 has revealed that endogenous TIMP-1 suppresses the proliferation, metabolic activity, and osteogenic differentiation capacity of human mesenchymal stem cells (hMSCs). The knockdown of TIMP-1 in hMSCs activated the Wnt/β-catenin signaling pathway as indicated by the increased stability and nuclear localization of β-catenin in TIMP-1–deficient hMSCs. Moreover, TIMP-1 knockdown cells exhibited enhanced β-catenin transcriptional activity, determined by Wnt/β-catenin target gene expression analysis and a luciferase-based β-catenin– activated reporter assay. An analysis of a mutant form of TIMP-1 that cannot inhibit MMP indicated that the effect of TIMP-1 on β-catenin signaling is MMP independent. Furthermore, the binding of CD63 to TIMP-1 on the surface of hMSCs is essential for the TIMP-1–mediated effects on Wnt/β-catenin signaling. An array analysis of microRNAs (miRNAs) and transfection studies with specific miRNA inhibitors and mimics showed that let-7f miRNA is crucial for the regulation of β-catenin activity and osteogenic differentiation by TIMP-1. Let-7f was up-regulated in TIMP-1–depleted hMSCs and demonstrably reduced axin 2, an antagonist of β-catenin stability. Our results demonstrate that TIMP-1 is a direct regulator of hMSC functions and reveal a regulatory network in which let-7f modulates Wnt/β-catenin activity

Involvement of a membrane pro-MMP 9 in TIMP-1 signalling pathway

3-8 Juille

Formation sur la valorisation de l'herbe dans les systèmes laitiers : le ressenti des enseignants

Le programme PSDR " Elevage Laitier, Territoires de l'Ouest et Prairies " (Laitop) vise à fournir des éléments et des innovations techniques et organisationnelles pour aider à maintenir la dynamique du secteur productif laitier et proposer des systèmes résilients face au risque économique. Il fait l'hypothèse que, si la prairie offre des atouts pour le maintien de la qualité des écosystèmes et la maîtrise des coûts, sa gestion et le conseil relatif à cette dernière restent difficiles. La formatiLe programme PSDR " Elevage Laitier, Territoires de l'Ouest et Prairies " (Laitop) vise à fournir des éléments et des innovations techniques et organisationnelles pour aider à maintenir la dynamique du secteur productif laitier et proposer des systèmes résilients face au risque économique. Il fait l'hypothèse que, si la prairie offre des atouts pour le maintien de la qualité des écosystèmes et la maîtrise des coûts, sa gestion et le conseil relatif à cette dernière restent difficiles. La formation initiale joue un rôle essentiel pour relancer une dynamique de valorisation de l'herbe au sein de systèmes laitiers plus durables en explicitant plus concrètement le concept de durabilité aux futurs acteurs et décideurs de la filière. L'information disponible sur la place de la prairie dans la formation initiale reste très partielle. L'objet du présent travail a été de faire un état des lieux de cet enseignement dans le Grand Ouest. Il s'agissait de déterminer comment le thème de l'herbe s'intègre dans les programmes, s'il existe ou non une certaine liberté des enseignants pour l'application des programmes, de connaître le positionnement des enseignants sur l'utilisation de l'herbe et sur les moyens disponibles pour enseigner la valorisation de ce fourrage