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

Activação transcricional em mutantes GIM de Saccharomyces cerevisiae

Tese de mestrado, Biologia (Microbiologia Aplicada), 2009, Universidade de Lisboa, Faculdade de CiênciasEm Saccharomyces cerevisiae existem 6 genes GIM que codificam as subunidades do complexo GimC, um complexo citoplasmático que participa na biogénese dos componentes do citosqueleto, a actina e a tubulina. Em levedura estes genes não são essenciais. Diversos dados na literatura sugerem que a actina e as subunidades Gim2, Gim5 e Gim1 podem assumir um papel na regulação da transcrição. Juntamente com a observação de que os mutantes gim exibem fenótipos distintos e padrões de expressão genética distintos em condições de stress, estes dados fazem com que seja de toda a pertinência o estudo de potenciais relações entre as várias proteínas Gim e activadores da transcrição de genes de resposta ao stress. Yap1 e Gcn4 são activadores transcricionais que regulam a resposta celular ao stress oxidativo e nutricional, respectivamente. Perceber se a actividade de ambos os activadores é afectada em mutantes gim, e se este efeito se deve a possíveis relações com subunidades Gim, pode justificar a observação de fenótipos distintos entre mutantes gim quando sujeitos a diferentes stresses e contribuir para a identificação de novas funções as subunidades Gim. Os resultados obtidos sugerem que a activação da transcrição apresenta diferenças entre mutantes gim e estirpe selvagem e apoiam a ideia de diferentes importâncias de cada subunidade Gim na célula. A subunidade Gim2 parece exercer um efeito negativo na activação da transcrição por Yap1 e Gcn4, ao contrário da subunidade Gim1 que parece desempenhar um papel na indução da actividade do Gcn4. Adicionalmente, todos os mutantes gim, à excepção do mutante _gim1, exibem um fenótipo de resistência ao 3-aminotriazol que não se verifica para a estirpe selvagem.In Saccharomyces cerevisiae exist 6 GIM genes that encode the Gim subunits of the GimC complex, a cytoplasmatic complex that participates in the biogenesis of the cytoskeleton components, actin and tubulin. In yeast, these genes are not essential. Several data in the literature suggest that actin and Gim2, Gim5 and Gim1 subunits can assume a role in transcription regulation. Together with the observation that gim mutants exhibit distinct phenotypes and distinct patterns of gene expression in stress conditions, these data makes the study of potential relations between the several Gim proteins and transcription activators of genes involved in stress response extremely significant. Yap1 and Gcn4 are transcription activators that play central roles in the responses they regulate, respectively, in oxidative and nutritional stresses. Understanding if the activity of both activators is affected in gim mutants, and if this effect is due to possible relations with Gim subunits, can justify the distinct phenotypes among gim mutants when subject to different stresses and contribute to the identification of new functions for the Gim subunits. Results obtained suggest that transcription activation is different between gim mutants and wild type strain and backs up the idea of different importances for each Gim subunit in the cell. Gim2 subunit appears to have a negative effect on Yap1 and Gcn4, as opposing to Gim1 subunit that seems to assume a role in Gcn4 activity. Additionally, all gim mutants, except _gim1 mutant, exhibit a 3-aminotriazole resistence phenotype that is not observed for the wild type strain

Structural and biochemical characterization of a family 7 highly thermostable endoglucanase from the fungus Rasamsonia emersonii

Thermostable cellulases from glycoside hydrolase family 7 (GH7) are themain components of enzymatic mixtures for industrial saccharification oflignocellulose. Activity improvement of these enzymes via rational design isa promising strategy to alleviate the industrial costs, but it requires detailedstructural knowledge. While substantial biochemical and structural dataare available for GH7 cellobiohydrolases, endoglucanases are more elusiveand only few structures have been solved so far. Here, we report a newcrystal structure and biochemical characterization of a thermostableendoglucanase from the thermophilic ascomycete Rasamsonia emersonii,ReCel7B. The enzyme was compared with the homologous endoglucanasefrom the mesophilic model ascomycete Trichoderma reesei (TrCel7B),which unlike ReCel7B possesses an additional carbohydrate-binding module(CBM). With a temperature optimum of 80 °C, ReCel7B displayed anumber of differences in activity and ability to synergize with cellobiohydrolasescompared to TrCel7B. We improved both binding and kinetics ina chimeric variant of ReCel7B and a CBM, while we observe the oppositeeffect when the CBM was removed in TrCel7B. The crystal structure ofReCel7B was determined at 2.48 A resolution, with Rwork and Rfree factorsof 0.182 and 0.206, respectively. Structural analyses revealed that ReCel7Bhas increased rigidity in a number of peripheral loops compared toTrCel7B and fewer aromatics in the substrate-binding cleft. An increasednumber of glycosylations were identified in ReCel7B, and we propose a stabilizingmechanism for one of the glycans. Global structure–function interpretationsof ReCel7B highlight the differences in temperature stability,turnover, binding, and cellulose accessibility in GH7 endoglucanases