Correlation between Progetto Cuore risk score and early cardiovascular damage in never treated subjects

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Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-δ. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, randomized, double-blind placebo-controlled trial of patients with nonalcoholic steatohepatitis (NASH). METHODS: Patients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and laboratory evaluations were performed every 2 months during this 1-year period. Liver biopsies were then collected and patients were assessed 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol-defined and modified definitions. Data from the groups given the different doses of elafibranor were compared with those from the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score. RESULTS: In intention-to-treat analysis, there was no significant difference between the elafibranor and placebo groups in the protocol-defined primary outcome. However, NASH resolved without fibrosis worsening in a higher proportion of patients in the 120-mg elafibranor group vs the placebo group (19% vs 12%; odds ratio = 2.31; 95% confidence interval: 1.02-5.24; P = .045), based on a post-hoc analysis for the modified definition. In post-hoc analyses of patients with nonalcoholic fatty liver disease activity score ≥4 (n = 234), elafibranor 120 mg resolved NASH in larger proportions of patients than placebo based on the protocol definition (20% vs 11%; odds ratio = 3.16; 95% confidence interval: 1.22-8.13; P = .018) and the modified definitions (19% vs 9%; odds ratio = 3.52; 95% confidence interval: 1.32-9.40; P = .013). Patients with NASH resolution after receiving elafibranor 120 mg had reduced liver fibrosis stages compared with those without NASH resolution (mean reduction of 0.65 ± 0.61 in responders for the primary outcome vs an increase of 0.10 ± 0.98 in nonresponders; P < .001). Liver enzymes, lipids, glucose profiles, and markers of systemic inflammation were significantly reduced in the elafibranor 120-mg group vs the placebo group. Elafibranor was well tolerated and did not cause weight gain or cardiac events, but did produce a mild, reversible increase in serum creatinine (effect size vs placebo: increase of 4.31 ± 1.19 μmol/L; P < .001). CONCLUSIONS: A post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients\u27 cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849

Livrable 3.2 Caractérisation physique des digestats bruts - Projet DIVA ANR-10-BIOE-007

Les travaux concernant la caractérisation physique des digestats bruts ont abordé trois aspects : (i) une analyse rhéologique des digestats se focalisant sur leurs propriétés de structure et d’écoulement ainsi que sur leurs points communs et spécificités, (ii) une analyse à dires d’experts de leur aptitude à l’épandage et (iii) l’étude de leur déshydratabilité (aptitude à la séparation de phase) via des mesures de cinétique de déshydratation en cellule de filtration compression et de siccité limite, tout en portant une attention particulière à l’étape de floculation. Du point de vue rhéologique, les digestats considérés dans le projet peuvent tous être définis comme des fluides non-Newtoniens, certains avec un seuil d’écoulement (c'est-à-dire qu’ils présentent des caractéristiques solides aux faibles contraintes et des caractéristiques liquides aux contraintes les plus élevées), d’autres sans seuil (ils ne présentent que des caractéristiques liquides, quelle que soit la contrainte appliquée). L’existence ou non du seuil de contrainte est liée à la fois à la concentration et à la composition des matières sèches : les deux paramètres clés permettant de distinguer le comportement rhéologique des digestats sont la concentration en matières sèches (MS) et le rapport MO/MS (où MO indique la teneur en matière organique). Ainsi, deux digestats de même MS et MO/MS ont le même comportement rhéologique. En termes d’épandabilité, les digestats les plus fluides (sans seuil de contrainte) peuvent, à dires d’expert, être épandus avec une tonne à lisier équipée de pendillards. Les autres digestats, à l’état brut, seront plus difficiles à épandre et une séparation de phase est préconisée. Concernant la déshydratation mécanique, une étape de floculation s’est avérée nécessaire en amont de la séparation de phase pour que des essais de laboratoires soient faisables : en effet, les digestats sont très chargés en matières colloïdales et la déshydratation en système de filtration sur toile ne donne des rendements exploitables que si un conditionnement chimique est utilisé pour favoriser la séparation eau/matières solides. Les résultats montrent également que la dose de polymère nécessaire pour une floculation optimale (si elle est réalisable) est 2 à 3 fois plus élevée que celle que l’on peut observer classiquement sur les boues résiduaires, ce qui est notamment dû à la forte salinité des digestats. On notera que les performances en déshydratation des digestats sont très variables selon la filière de digestion et les substrats digérés. Néanmoins, un lien a pu être établi entre la siccité limite des digestats et le ratio MO/MS des digestats considérés

The regular consumption of a polyphenol-rich apple doet not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adults

Background/objectives: Epidemiological studies suggest that apple consumption is associated with a reduction in cardiovascular disease risk. Apple polyphenols may contribute to explain these effects. Endothelial dysfunction has been associated with early stage of atherosclerosis and polyphenols from various dietary sources have been shown to reverse it. The aim of the present study was to investigate the effect of the consumption of a polyphenol-rich apple on endothelial function. Subjects/methods: In all, 30 hypercholesterolemic volunteers were included in a double-blind, randomized crossover trial. They successively consumed 40¿g of two lyophilized apples, polyphenol-rich and polyphenol-poor, providing respectively 1.43 and 0.21¿g polyphenols per day during two 4-week periods separated by a 4-week washout period. Results: Brachial artery flow-mediated vasodilation (FMD) was assessed at the beginning and at the end of each intervention period. FMD did not differ between the polyphenol-rich and the polyphenol-poor apples, neither did the other cardiovascular disease risk factors (plasma lipids, homocysteine, antioxidant capacity). Conclusions: These data suggest that over a 4-week period, the consumption of a polyphenol-rich apple does not improve vascular function in hypercholesterolemic patients