Association between sleep-disordered breathing and breast cancer aggressiveness

Background Sleep-disordered breathing (SDB) has been associated with cancer aggressiveness, but studies focused on specific tumors are lacking. In this pilot study we investigated whether SDB is associated with breast cancer (BC) aggressiveness. Methods 83 consecutive women <65 years diagnosed with primary BC underwent a home respiratory polygraphy. Markers of SDB severity included the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI4). The Ki67 proliferation index, lack of hormone receptors (HR-), Nottingham Histological Grade (NHG), and tumor stage were used as markers of BC aggressiveness. The association between SDB and molecular subtypes of BC was also assessed. Results The mean (SD) age was 48.8 (8.8) years and body mass index was 27.4 (5.4) Kg/m2. 42 women (50.6%) were post-menopausal. The median (IQR) AHI was 5.1 (2–9.4), and ODI4 was 1.5 (0.5–5.8). The median (IQR) AHI did not differ between the groups with Ki67>28% and Ki6728% and Ki67<29% (51.2% vs 52.3%, p = 0.90), HR- and HR+ (58.3% vs 49.1%, p = 0.47), NHG categories (p = 0.89), different tumor stages (p = 0.71), or molecular subtypes (p = 0.73). These results did not change when the ODI4 was used instead of the AHI. Conclusion Our results do not support an association between the presence or severity of SDB and BC aggressiveness.Asociación de Neumología y Cirugía Torácica del Sur (NEUMOSUR) 1/201

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Ultrahigh Energy Neutrinos at the Pierre Auger Observatory

The observation of ultrahigh energy neutrinos (UHEνs) has become a priority in experimental astroparticle physics. UHEνs can be detected with a variety of techniques. In particular, neutrinos can interact in the atmosphere (downward-going ν) or in the Earth crust (Earth-skimming ν), producing air showers that can be observed with arrays of detectors at the ground. With the surface detector array of the Pierre Auger Observatory we can detect these types of cascades. The distinguishing signature for neutrino events is the presence of very inclined showers produced close to the ground (i.e., after having traversed a large amount of atmosphere). In this work we review the procedure and criteria established to search for UHEνs in the data collected with the ground array of the Pierre Auger Observatory. This includes Earth-skimming as well as downward-going neutrinos. No neutrino candidates have been found, which allows us to place competitive limits to the diffuse flux of UHEνs in the EeV range and above.Fil: Allekotte, Ingomar. Comisión Nacional de Energía Atómica. Gerencia del Area Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche). Grupo de Partículas y Campos; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Almela, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Asorey, Hernán Gonzalo. Comisión Nacional de Energía Atómica. Gerencia del Area Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche). Grupo de Partículas y Campos; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica. Gerencia del Area Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche). Grupo de Partículas y Campos; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Dasso, Sergio Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio(i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: de la Vega, Gonzalo Andrés. Universidad Tecnológica Nacional. Facultad Regional de Mendoza; ArgentinaFil: Dova, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Filevich, Alberto. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigaciones y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Gamarra, R. F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; Argentina. Universidad Tecnológica Nacional. Facultad Regional de Mendoza; ArgentinaFil: Gitto, J.. Universidad Tecnológica Nacional. Facultad Regional de Mendoza; ArgentinaFil: Golup, Geraldina Tamara. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigaciones y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Gomez Albarracin, Flavia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Guardincerri, Yann. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Hansen, Patricia Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigaciones y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Jarne, Cecilia Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Josebachuili Ogando, Mariela Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Lucero, Luis Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Mariazzi, Analisa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Melo, Diego Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Micheletti, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Fisica de Rosario (i); ArgentinaFil: Mollerach, Maria Silvia. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigaciones y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Moreno, Juan Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Pallotta, Juan Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégicos para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Piegaia, Ricardo Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Pieroni, Pablo Emanuel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Platino, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Ponce, Victor Hugo. Universidad Nacional de Cuyo; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Quel, Eduardo Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégicos para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Ravignani Guerrero, Diego. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Ristori, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégicos para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Roulet, Esteban. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); ArgentinaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio(i); Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Sanchez, Federico Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Sciutto, Sergio Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Sidelnik, Iván Pedro. Comisión Nacional de Energía Atómica. Gerencia del Area Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche). Grupo de Partículas y Campos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Suarez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Supanitsky, Alberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio(i); ArgentinaFil: Tapia Casanova, Alex Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Tiffenberg, Javier Sebastian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Videla, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; Argentina. Universidad Tecnológica Nacional. Facultad Regional de Mendoza; ArgentinaFil: Wahlberg, Hernan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Instituto de Física La Plata; ArgentinaFil: Wainberg, Oscar Isaac. Comision Nacional de Energia Atomica. Gerencia del Area Investicaciones y Aplicaciones No Nucleares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: Wundheiler, Brian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnologías en Detección y Astropartículas; ArgentinaFil: The Pierre Auger collaboration

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication