High 15-f-2t-isoprostane Levels In Patients With A Previous History Of Nonmelanoma Skin Cancer: The Effects Of Supplementary Antioxidant Therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background. Phase I of this study was aimed at comparing the profiles of oxidative stress biomarkers in patients with history of nonmelanoma skin cancer (NMSC), previously treated with surgery, to the healthy subjects. Phase II aimed to evaluate the effects of supplementary antioxidant therapy on the levels of biomarkers in the case group. Materials and Methods. In Phase I, oxidative stress biomarkers were measured in blood samples obtained from 24 healthy subjects and 60 patients with history of NMSC previously treated with surgery. In Phase II, the 60 patients with history of NMSC were randomized into two subgroups, one receiving placebo (n = 34) and the other (n = 26) receiving vitamin C, vitamin E, and zinc supplementation for 8 weeks, followed by reevaluation of biomarkers. Results. In Phase I, patients with history of NMSC showed increased plasma concentrations of all biomarkers, but only 15-F-2t-isoprostane was significantly higher than in the healthy subjects. Risk of NMSC increased by 4% for each additional 1 pg/mL increase in 15-F-2t-isoprostane. In Phase II, supplementation did not significantly reduce levels of oxidative stress biomarkers. Conclusion. Patients with history of NMSC had significantly high 15-F-2t-isoprostane plasma levels; supplementation did not result in significant reduction of oxidative stress biomarkers. This trial was registered with ClinicalTrials.gov (ID NCT02248584).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [482958/2011-1

High 15-f-2t-isoprostane levels in patients with a previous history of nonmelanoma skin cancer: the effects of supplementary antioxidant therapy

Phase I of this study was aimed at comparing the profiles of oxidative stress biomarkers in patients with history of nonmelanoma skin cancer (NMSC), previously treated with surgery, to the healthy subjects. Phase II aimed to evaluate the effects of supplementary antioxidant therapy on the levels of biomarkers in the case group. In Phase I, oxidative stress biomarkers were measured in blood samples obtained from 24 healthy subjects and 60 patients with history of NMSC previously treated with surgery. In Phase II, the 60 patients with history of NMSC were randomized into two subgroups, one receiving placebo (n = 34) and the other (n = 26) receiving vitamin C, vitamin E, and zinc supplementation for 8 weeks, followed by reevaluation of biomarkers. Results. In Phase I, patients with history of NMSC showed increased plasma concentrations of all biomarkers, but only 15-F-2t-isoprostane was significantly higher than in the healthy subjects. Risk of NMSC increased by 4% for each additional 1 pg/mL increase in 15-F-2t-isoprostane. In Phase II, supplementation did not significantly reduce levels of oxidative stress biomarkers. Patients with history of NMSC had significantly high 15-F-2t-isoprostane plasma levels; supplementation did not result in significant reduction of oxidative stress biomarkers. This trial was registered with ClinicalTrials.gov (ID NCT02248584)2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP482958/2011-1sem informaçã

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society