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There is no evidence of whether everolimus (EVR) reduces cytomegalovirus (CMV) events in patients receiving steroid-free regimens. Besides, studies evaluating a tacrolimus (TAC) and EVR regimen are limited to 1-year follow-up. In this single-center prospective randomized trial, the incidence of CMV and 3-year efficacy and safety outcomes of EVR were compared to those of mycophenolate sodium (MPS) in a steroid-free regimen based on low-exposure TAC. Both groups received rabbit anti-thymocyte globulin (r-ATG) induction (6 mg/kg) and the steroids were withdrawn at day 7. Maintenance immunosuppression consisted of TAC (4-7 ng/ml until month 3 and 2-4 ng/ml thereafter) plus EVR (3-8 ng/ml) in the EVR group (n = 59); and TAC (4-7 ng/ml during all follow-up) plus MPS (1440 mg) in the MPS group (n = 56). The EVR group presented with a lower incidence of CMV events (18.6% vs. 50%, P = 0.001). No differences were observed in biopsy-proven acute rejection (6.8% vs. 3.6%, P = 0.680),graft loss (0.0% vs. 1.8%, P = 0.487),death (6.8% vs. 1.8%, P = 0.365), or estimated glomerular filtration rate at 36 months (61.1 ± 25.4 vs. 66.3 ± 24 ml/min/1.73 m , P = 0.369). A higher proportion of patients discontinued MPS treatment (8.5% vs. 26.8%, P = 0.013) for safety issues. In conclusion, EVR was associated with lower rates of CMV events in patients induced with standard dose r-ATG and a maintenance steroid-free regimen based on TAC. This regimen effectively prevented acute rejection and demonstrated a more favorable safety profile. (ClinicalTrials.gov:NCT02084446).

PURPOSE: This study aimed to assess the effects of preconditioning with mixtures of oils containing high/low ratio of ω-6/ω-3 and ω-9/ω-6, respectively, in an experimental model of cerebral ischemia-reperfusion (I/R). METHODS: Forty-two Wistar rats were randomly distributed into two groups: control (n=24) and test (n=18). Control group was subdivided in 4 subgroups (n=6): G1: Sham-Water; G2: I/R-Water; G3: Sham-Isolipidic and G4: I/R-Isolipid. The animals received water or a isolipid mixture containing ω-3 oils (8:1 ratio) and ω-9/ω-6 (0.4:1 ratio) by gavage for seven days. Test group included 3 subgroups (n=6) G5: I/R-Mix1, G: 6 I/R-Mix2 and G7: I/R-Mix3. Test group animals received oily mixtures of ω-3 (1.4:1 ratio) and ω-6 (3.4:1 ratio), differing only in source of ω-3: G5 (alpha-linolenic acid); G6 (alpha-linolenic, docosahexaenoic and eicosapentaenoic acids), and G7 (alpha-linolenic and docosahexaenoic acids). On day 7 I/R rats underwent cerebral ischemia with bilateral occlusion of common carotid arteries for 1 hour followed by reperfusion for 3 hours. G1 and G3 animals underwent sham operation. Concluded the experiment, animals were decapitated and their brains sliced for red neurons (RN) count in CA3 area of the hippocampus. Variables were compared using ANOVA-Tukey test. RESULTS: The use of different mix preparations promoted a decrease in red cell count in all three groups (G5/G6/G7), compared with G2/G4, confirming the protective effect of different oil blends, regardless of ω-3 source. CONCLUSION: Pre-conditioning with mixtures of oils containing high ratio ω-6/ω-3 and low ω-9/ω-6 relationship protects brain neurons against I/R injury in an experimental model.