Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer

Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Growth performance of b?saro pigs in hoop barn and confinement housing systems, crecimiento de cerdos b?saros alojados en un sistema hoop barn y en confinamiento tradicional

The goal of this study was to compare the growth performance of growing/finishing pigs housed in a hoop barn system and in traditional confinement. A total of twenty B?saro breed pigs, with 98.6?5.71 days of age, and 25.4?4.87 kg of BW were used (beginning of experiment). The pigs were equally distributed in two groups: Gr1 ? hoop barn (3.0 m2/pig) with outdoor access (200 m2/pig); and Gr2 - traditional confinement with straw bedding (1.8 m2/pig). Both groups were fed with the same diet. During the next 98 days? period (growing phase) and until pigs reached approximately 80 kg LW, the animals were fed with a concentrate diet. In the finishing phase consisting of a final 70 days period until slaughter, the animals reached between 110-120 kg LW and were fed with concentrate and cornflour. The feed intake per group was registered daily and growth performances were collected every two weeks. During the growing phase no differences (P > 0.05) were observed in the average daily gain (ADG) between Gr1 (0.546?0.10 kg/day) and Gr2 (0.563?0.05 kg/day). However, a higher variability was observed in hoop barn group (CV of 18.1% vs. 8.8% in confinement). Similar results were observed during the finishing phase with ADG of 0.535?0.09 kg for Gr1 and 0.505?0.07 kg for Gr2 (P > 0.05). In both growing and finishing phases, the feed conversion rates (FCR) were 3.11 on the Gr1 versus 3.12 kg/kg on the Gr2, and 3.44 in Gr1 versus 3.53 in Gr2, respectively. Despite the different housing systems, ADG and FCR per period were identical in both systems. To the consumer's point of view, the positive aspects of the hoop barn system, such as the use of uncultivated land, product image and pig welfare, are sustainably attractive and therefore could be further reflected in the market.FE1B-06B2-126F | Jos? Pedro Pinto de Ara?joN/

Does Croton argyrophyllus extract has an effect on muscle damage and lipid peroxidation in rats submitted to high intensity strength exercise?

Many species of the genus Croton have been used for anti-inflammatory, antiproliferative, antidiabetic, and antitumor purposes. The objective was to evaluate the e ect of a hydroethanolic extract (HEE) from the inner bark of Croton argyrophyllus (Euphorbiaceae) on muscle damage and oxidative stress in rats after high intensity exercise. The animals were divided into four groups: (i) the sedentary group (SV; n = 7), (ii) the exercise vehicle group (EV, n = 7), (iii) the sedentary group HEE (SHG; n = 7) composed of sedentary animals and treated with the hydroethanolic extract of C. argyrophyllus (200 mg/kg, v.o.), and (iv) the HEE exercise group (HEE; n = 7) composed of animals submitted to resistance exercise (RE) and treated with the hydroethanolic extract of C. argyrophyllus (200 mg/kg, v.o.). In the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) test, the HEE showed lower values of inhibition potential (IP%) at 39.79% compared to gallic acid, 87.61%, and lipoperoxidation inhibition at 27.4% (100 ?g/mL) or 28.6% (200 ?g/mL) (p < 0.001). There was inhibition in free radicals in vivo. The HEE of C. argyrophyllus partially reduced the biomarkers of oxidative stress in muscle tissue and muscular damage (creatine kinase (CK) and Lactate Dehydrogenase (LDH)) (p < 0.05) in rats, and in this sense it can be an aid to the recovery process after exhaustive e orts