Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

Altres ajuts: Fundació La Marató de TV3 2016 (303/C/2016) (201602.31) (to J.J.) and (97/C/2016) (201605-31) (to A.F.V.).The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: −44%; NAM HD: −57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation

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Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasFac. de Bellas ArtesFALSEsubmitte

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)