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

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Ontologías en disputa: Diálogos entre la antropología y la arqueología para la problematización de paisajes regionals

Objetivo/contexto: Hacia finales del siglo XX, el dualismo ontológico con el que antropólogos y arqueólogos nos hemos formado teórica y metodológicamente ha sido cuestionado y puesto en debate. En este contexto, nuestro objetivo es exponer críticamente los trabajos que se están realizando y que contribuyen a problematizar los paisajes enredados de existencias, materialidades, saberes, sentidos o prejuicios pasados y presentes, y con ello a restablecer el diálogo entre la antropología social y la arqueología. Metodología: Exponemos el estado actual de la apertura ontológica en clave latinoamericana. Problematizamos la noción de paisaje como concepto que permite diálogos teórico-metodológicos entre la antropología y la arqueología, así como con otras disciplinas. También presentamos ejes de comunicación y diálogo entre los artículos que forman parte del presente dossier para finalizar con los desafíos por delante en cuanto a traspasar fronteras disciplinarias, temporales y espaciales. Conclusiones: En contextos de históricas relaciones de poder, de profundas crisis socio-ambientales, los principales desafíos de la apertura ontológica serían: 1) generar referentes teóricos permeables a diversas disciplinas y saberes; 2) consolidar metodologías que integren lo etnográfico con lo arqueológico; 3) alentar diálogos constructivos hacia y con otras disciplinas y saberes, y 4) propiciar la comprensión del entramado político actual y la generación de políticas públicas que permitan diversas formas de relacionamiento con el entorno. Originalidad: El restablecimiento de diálogos entre la arqueología y la antropología social desde las aperturas ontológicas tiene el potencial de discutir cómo en determinados contextos se concretan y/o disputan paisajes y modos hegemónicos de habitar en el mundo, así como se problematizan los usos políticos del pasado y las políticas de uso del espacio y el ambiente.Objective/context: Towards the end of the 20th century, the ontological dualism with which anthropologists and archaeologists have trained us theoretically and methodologically has been questioned and debated. In this context, our objective is to critically expose the works that are being carried out and that contribute to problematizing the landscapes entangled with past and present existences, materialities, knowledge, senses or prejudices, and, with it, to re-establish the dialogue between social anthropology and archaeology. Methodology: We expose the current state of the ontological opening in Latin American code. We problematize the notion of landscape as a concept that allows theoretical-methodological dialogues between anthropology and archaeology, as well as with other disciplines. We also present axes of communication and dialogue between the articles that are part of this dossier, to end with the challenges ahead in terms of crossing disciplinary, temporal and spatial borders. Conclusions: In contexts of historical power relations, of deep socio-environmental crises, the main challenges for an ontological opening would be: 1) to generate theoretical referents permeable to various disciplines and fields of knowledge; 2) to consolidate methodologies that integrate the ethnographic with the archaeological; 3) to encourage constructive dialogues towards and with other disciplines and fields of knowledge; and 4) to propitiate the understanding of the current political framework and the generation of public policies that allow for diverse forms of relation with the environment. Originality: The re-establishment of dialogues between archaeology and social anthropology from ontological openings has the potential to discuss how, in certain contexts, landscapes and hegemonic ways of living are concretized and/or disputed, as well as the political uses of the past and the policies of use of space and the environment.Objetivo/contexto: No final do século XX, o dualismo ontológico com o qual antropólogos e arqueólogos se formaram teórica e metodologicamente vem sendo questionado e colocado em debate. Nesse contexto, nosso objetivo é expor criticamente os trabalhos que estão sendo realizados e que contribuem para problematizar as paisagens permeadas de existências, materialidades, saberes, sentidos ou preconceitos passados e presentes, e, com isso, reestabelecer o diálogo entre a antropologia social e a arqueologia. Metodologia: Expomos o estado atual da abertura ontológica no âmbito latino-americano. Problematizamos a noção de paisagem como conceito que permite diálogos teórico-metodológicos entre a antropologia e a arqueologia, assim como outras disciplinas. Também apresentamos eixos de comunicação e diálogo entre os artigos que fazem parte do presente dossiê para finalizar com os desafios que temos adiante sobre ultrapassar fronteiras disciplinares, temporais e espaciais. Conclusões: Em contextos de históricas relações de poder, de profundas crises socioambientais, os principais desafios para uma abertura ontológica seriam: 1) gerar referentes teóricos permeáveis a diversas disciplinas e saberes; 2) consolidar metodologias que integrem o etnográfico com o arqueológico; 3) promover diálogos construtivos com outras disciplinas e saberes; e 4) propiciar a compreensão da estrutura política atual e a geração de políticas públicas que permitam as diversas formas de relacionamentos com o ambiente. Originalidade: O reestabelecimento de diálogos entre a arqueologia e a antropologia social a partir das aberturas ontológicas tem o potencial de discutir como, em determinados contextos, se concretizam e/ou disputam paisagens e modos hegemônicos de habitar, bem como se problematizam os usos políticos do passado e as políticas de uso do espaço e do ambiente.Fil: Saldi, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Mafferra, Luis Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Barrientos Salinas, J. Alejandro. Universidad Mayor de San Andrés; Bolivi

Tentativa de sistematização da defesa do patrimônio histórico do Rio Grande do Sul: jazidas e monumentos

A moção que apresentamos em sessão de Assembléia Geral da Associação dos Professôres Universitários de História, núcleo do Rio Grande do Sul, tivemos a satisfação de vê-la transformada em ternário dêste encôntro. Decorrente de tal circunstância e na qualidade de signatários de tal moção, sentimo-nos impelidos a focalizar, perante êste Encôntro, as nossas idéias em tôrno da salvaguarda do Patrimônio Histórico do Rio Grande do Sul

Tentativa de sistematização da defesa do patrimônio histórico do Rio Grande do Sul: jazidas e monumentos

A moção que apresentamos em sessão de Assembléia Geral da Associação dos Professôres Universitários de História, núcleo do Rio Grande do Sul, tivemos a satisfação de vê-la transformada em ternário dêste encôntro. Decorrente de tal circunstância e na qualidade de signatários de tal moção, sentimo-nos impelidos a focalizar, perante êste Encôntro, as nossas idéias em tôrno da salvaguarda do Patrimônio Histórico do Rio Grande do Sul

KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing Genomic Loss in Small Cell Lung Cancer

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Epigenetic loss of the endoplasmic reticulum-associated degradation inhibitor SVIP induces cancer cell metabolic reprogramming

The endoplasmic reticulum (ER) of cancer cells needs to adapt to the enhanced proteotoxic stress associated with the accumulation of unfolded, misfolded and transformation-associated proteins. One way by which tumors thrive in the context of ER stress is by promoting ER-Associated Degradation (ERAD), although the mechanisms are poorly understood. Here, we show that the Small p97/VCP Interacting Protein (SVIP), an endogenous inhibitor of ERAD, undergoes DNA hypermethylation-associated silencing in tumorigenesis to achieve this goal. SVIP exhibits tumor suppressor features and its recovery is associated with increased ER stress and growth inhibition. Proteomic and metabolomic analyses show that cancer cells with epigenetic loss of SVIP are depleted in mitochondrial enzymes and oxidative respiration activity. This phenotype is reverted upon SVIP restoration. The dependence of SVIP hypermethylated cancer cells on aerobic glycolysis and glucose was also associated with sensitivity to an inhibitor of the glucose transporter GLUT1. This could be relevant to the management of tumors carrying SVIP epigenetic loss, because these occur in high-risk patients who manifest poor clinical outcomes. Overall, our study provides insights into how epigenetics helps deal with ER stress and how SVIP epigenetic loss in cancer may be amenable to therapies that target glucose transporters.This work was supported by the Health Department PERIS project number SLT/002/16/00374 and AGAUR project numbers 2017SGR1080, 2014SGR633, 2017SGR1033, and 2009SGR1315 of the Catalan Government (Generalitat de Catalunya); the Spanish Institute of Health Carlos III (ISCIII) project number DTS16/00153 and Ministerio de Economía y Competitividad (MINECO) project numbers SAF2014-55000-R, BFU2014-57466-P, SAF2017-89673-R, and SAF2015-70270-REDT co-financed by the European Development Regional Fund, A way to achieve Europe ERDF; the Cellex Foundation; and “la Caixa” Bank Foundation (LCF/PR/PR15/11100003). MC acknowledges the prize “ICREA Academia” for excellence in research, funded by ICREA foundation. We thank the Scientific and Technological Centre (CCiTUB) of the University of Barcelona for technical support with cell cytometry and sorting. We also thank the Regenerative Medicine Center (CMRB) Electron Microscopy and Histology facility

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial.

5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab. VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 then 2400 mg/m2) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS). The intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively. First-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy