SummaryAutoreactivity to heat shock protein 60 (Hsp60) has been implicated in the pathogenesis and regulation of chronic inflammation, especially in autoimmune diseases. In transplantation, there is a lack of information regarding the cytokine profile and specificity of cells that recognize self-Hsp60 as well as the kinetics of autoreactivity following transplantation. We studied the cellular reactivity of peripheral and graft-infiltrating lymphocytes against Hsp60 in renal transplant patients. Cytokine production induced by this protein in peripheral blood mononuclear cells indicated a predominance of interleukin (IL)-10 during the late post-transplantation period, mainly in response to intermediate and C-terminal peptides. Patients with chronic rejection presented reactivity to Hsp60 with a higher IL-10/interferon (IFN)-g ratio compared to long-term clinically stable patients. Graft-infiltrating T cell lines, cocultured with antigen-presenting cells, preferentially produced IL-10 after Hsp60 stimulation. These results suggest that, besides its proinflammatory activity, autoreactivity to Hsp60 in transplantation may also have a regulatory role.

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AimsTo assess treatment decision and outcome in patients referred for transcatheter aortic valve implantation (TAVI) in addition to predictive factors of mortality after TAVI.MethodsThree-centre prospective observational study including 358 patients. Endpoints were defined according to the Valve Academic Research Consortium.ResultsOf the 358 patients referred for TAVI, TAVI was performed in 235 patients (65%), surgical aortic valve replacement (AVR) in 24 (7%) and medical therapy (MT) in 99 (28%). Reasons to decline TAVI in favour of AVR/MT were patient preference (29%), peripheral vascular disease (15%) and non-severe aortic stenosis (11%). The logistic EuroSCORE was significantly higher in patients who underwent TAVI and MT in comparison with those undergoing AVR (19 vs. 10%, p = 0.007). At 30 days, all-cause mortality and the combined safety endpoint were 9 and 24% after TAVI and 8 and 25% after AVR, respectively. All-cause mortality was significantly lower in the TAVI group compared with the MT group at 6 months, 1 year and 2 years (12% vs. 22%, 21% vs. 33% and 31% vs. 55%, respectively, p < 0.001). Multivariable analysis revealed that blood transfusion (HR: 1.19; 95% CI: 1.05–1.33), pre-existing renal failure (HR: 1.18; 95% CI: 1.06–1.33) and STS score (HR: 1.06; 95% CI: 1.02–1.10) were independent predictors of mortality at a median of 10 (IQR: 3–23) months after TAVI.ConclusionsApproximately two-thirds of the patients referred for TAVI receive this treatment with gratifying short- and long-term survival. Another 7% underwent AVR. Prognosis is poor in patients who do not receive valve replacement therapy.

Introduction Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that other sirtuins could also be expressed in the CC. Expression of these enzymes in tissues is affected by aging, the main independent risk factor for erectile dysfunction besides other cardiovascular disease risk factors (CVDRF), such as diabetes or obesity. Aim The aim of this study was to characterize the expression of SIRT1-3 and SIRT5–7 in human CC relatively to age and CVDRF. Methods Samples of CC collected from patients submitted to programmed surgeries or organ donors were divided in three groups according to age and presence of CVDRF. Expression of SIRT1–3 and SIRT5–7 mRNAs was assessed by real-time polymerase chain reaction. Cellular localization and semi-quantification of sirtuins proteins were performed by immunofluorescence and Western blotting (WB), respectively. Nuclear factor kappa B (NFkB)-p65, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) levels were also assayed by WB. Main Outcome Measures The main outcome measure was to characterize the expression of SIRT1–3 and SIRT5–7 in human CC. Results SIRT1–3 and SIRT5–7 mRNAs were detected in all individuals, without statistical differences among groups, excepting SIRT7 that decreased four times in aged groups relatively to young (P = 0.013). WB analysis demonstrated that aged individuals with CVDRF presented higher levels of SIRT7 protein relatively to young (P = 0.0495) and lower levels of SIRT3 protein relatively to healthy aged (P = 0.0077). Expression of NFkB-p65 and iNOS were higher in aged than in young individuals (P = 0.0185; P = 0.004, respectively). No differences in other sirtuins or total eNOS were seen among groups although phospho eNOS Ser1177 levels decreased in groups of aged men relatively to young (P = 0.0043; P = 0.0099). Conclusions Our results demonstrate for the first time expression of SIRT2–3 and SIRT5–7 in the human CC. Aged individuals with CVDRF presented an increase in SIRT7 protein levels and a decrease in mitochondrial SIRT3. This finding suggests that CVDRF induces the loss of antioxidant defense mechanisms leading to endothelial injury.

Patients who die during the first three months on dialysis are not systematically included in the American and European statistics. In contrast, only a few patients survive more than 10 years on this modality of renal replacement therapy. The factors determining these two extreme forms of outcome are poorly understood. We tested the hypothesis that a few variables, easily obtainable at the initiation of dialysis, would identify those individuals at high and low risk of early death. We retrospectively studied 23 patients who died within 90 days of initiating dialysis and 20 patients who survived more than 10 years. These patients were admitted for dialysis to a Brazilian center between July 1, 1976 and February 28, 1997. The baseline variables assessed which were thought to influence survival, were: age, sex, race, body weight, etiology of renal disease, blood pressure, comorbid conditions, hematocrit and serum electrolytes, albumin, creatinine, urea, and urea/creatinine ratio. Univariate analysis showed that patients who died early were older (56.2 +/- 15.6 vs. 42.1 +/- 10.4 years, p < 0.01), had lower serum creatinine (10.6 +/- 2.9 vs. 13.7 +/- 3.7 mg/dL, p < 0.01) and albumin (3.3 +/- 0.9 vs. 4.0 +/- 0.5 g/dL) and a higher urea/creatinine ratio (18.4 +/- 5.8 vs. 13.5 +/- 4.8, p < 0.01) compared with subjects surviving more than 10 years. Early death patients also had more cases of diabetes (35% vs. 0%, p < 0.01) and less chronic glomerulonephritis (9% vs. 35%, p < 0.05). Multivariate analysis showed that age (p < 0.01, CI 1.02 to 1.15, odds ratio 1.1) and urea/creatinine ratio (p < 0.01, CI 1.03 to 1.38, odds ratio 1.2) were positively and independently related to outcome. In the early death group, malnutrition was an important cause of death (17% of all deaths). Compared to baseline data, long-term survivors, at the last follow up, presented reduced systolic blood pressure and increased hematocrit and unchanged body weight, serum albumin and urea/creatinine ratio. These results, based on easily accessible initial variables, suggest that early death on dialysis is influenced by age and by indices related to the nutritional condition of the patients. They also highlight the importance of a potentially correctable risk factor in a population with an elevated prevalence of premature death.