Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.

Background Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19. Methods After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group. Results Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively. Conclusion Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.

Twenty-four studies conformed to the inclusion criteria for inclusion in the systematic review. In total, 4986 patients underwent aortic valve repair. 7 studies represented bicuspid aortic valve (BAV) repair, 5 studies represented cusp prolapse, and 3 studies represented valve repair with root dilation or aneurysm. Overall weighted in-hospital mortality for all studies was low (1.46% ± 1.21). Preoperative aortic insufficiency (AI) ≥ 2+ did not correlate to reoperation for valve failure (Pearson's Rs 0.2705, P = 0.2585). AI at discharge was reported in 9 studies with a mean AI ≥ 2+ in 6.1% of patients. Weighted average percentage for valve reoperation following BAV repair was 10.23% ± 3.2. Weighted average reoperation following cusp prolapse repair was 3.83 ± 1.96. Weighted average reoperation in aortic valve sparing procedures with root replacement was 4.25% ± 2.46. Although there are limitations and complications of prosthetic valves, especially for younger individuals, there is ample published literature that confers strong evidence for AVR. On the contrary, aortic valve repair may be a useful option for selected patients, but there is lack of uniformity in data and absence of compelling supporting evidence. An international multi-center study comparing and assessing the results between AVR & AVr is the next step required. Currently, higher levels of evidence do not exist for aortic valve repair.