202 research outputs found
Gastrointestinal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference
CONTEXT
Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction.
OBJECTIVES
Our objective was to evaluate current evidence and to develop consensus criteria for gastrointestinal dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and EMBASE were conducted from January 1992 to January 2020, using medical subject heading terms and text words to define gastrointestinal dysfunction, pediatric critical illness, and outcomes.
STUDY SELECTION
Studies were included if they evaluated critically ill children with gastrointestinal dysfunction, performance characteristics of assessment/scoring tools to screen for gastrointestinal dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, case series with sample size ≤10, and non-English language studies with inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment by a task force member.
RESULTS
The systematic review supports the following criteria for severe gastrointestinal dysfunction: 1a) bowel perforation, 1b) pneumatosis intestinalis, or 1c) bowel ischemia, present on plain abdominal radiograph, computed tomography (CT) scan, magnetic resonance imaging (MRI), or gross surgical inspection, or 2) rectal sloughing of gut mucosa.
LIMITATIONS
The validity of the consensus criteria for gastrointestinal dysfunction are limited by the quantity and quality of current evidence.
CONCLUSIONS
Understanding the role of gastrointestinal dysfunction in the pathophysiology and outcomes of MODS is important in pediatric critical illness
Necrotizing Enterocolitis: An Update on the Benefits of Breast Milk
Necrotizing enterocolitis (NEC) is the leading cause of death for preterm infants resulting from gastrointestinal disease. This review will focus on several components of human breast milk that may be beneficial in the prevention and treatment of NEC. The severe pathological features of NEC include inflammation, mucosal ulceration and disruption of the intestinal barrier. Despite maximal neonatal intensive care, the incidence and mortality rate of the disease remains high. Administration of breast milk, as well as donor breast milk, to preterm infants has been shown to reduce the incidence of NEC. Beyond this, there is no disease specific treatment for NEC. The immunomodulatory and protective properties of human breast milk have been evaluated in search of key components that may be utilized for the effective prevention and treatment of NEC
The Surgical Infection Society revised guidelines on the management of intra-abdominal infection
Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations.
Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council.
Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included.
Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline
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
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
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
Short-term movements and habitat preferences of sailfish, Istiophorus platypterus (Istiophoridae), along the southeast coast of Brazil
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
Assessment of gene-by-sex interaction effect on bone mineral density
To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic
NIH R01 AG18728
R01HL088119
R01AR046838
U01 HL084756
R01 AR43351
P01-HL45522
R01-MH-078111
R01-MH-083824
Nutrition and Obesity Research Center of Maryland P30DK072488
NIAMS/NIH F32AR059469
Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034
PI08/0183
Canadian Institutes of Health Research (CIHR)
NHLBI HHSN268201200036C
N01-HC-85239
N01-HC-85079
N01-HC-85086
N01-HC-35129
N01 HC15103
N01 HC-55222
N01-HC-75150
N01-HC-45133
HL080295
HL087652
HL105756
NIA AG-023629
AG-15928
AG-20098
AG-027058
N01AG62101
N01AG62103
N01AG62106
1R01AG032098-01A1
National Center of Advancing Translational Technologies CTSI UL1TR000124
National Institute of Diabetes and Digestive and Kidney Diseases DK063491
EUROSPAN (European Special Populations Research Network)
European Commission FP6 STRP grant 018947
LSHG-CT-2006-01947
Netherlands Organisation for Scientific Research
Erasmus MC
Centre for Medical Systems Biology (CMSB)
Netherlands Brain Foundation (HersenStichting Nederland)
US National Institute for Arthritis, Musculoskeletal and Skin Diseases
National Institute on Aging R01 AR/AG41398
R01 AR050066
R21 AR056405
National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195
Affymetrix, Inc. N02-HL-6-4278
Canadian Institutes of Health Research from Institute of Aging 165446
Institute of Genetics 179433
Institute of Musculoskeletal health 221765
Intramural Research Program of the NIH, National Institute on Aging
National Institutes of Health HHSN268200782096C
Hong Kong Research Grant Council HKU 768610M
Bone Health Fund of HKU Foundation
KC Wong Education Foundation
Small Project Funding 201007176237
Matching Grant
CRCG Grant
Osteoporosis and Endocrine Research Fund
Genomics Strategic Research Theme of The University of Hong Kong
Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011
911-03-012
Research Institute for Diseases in the Elderly 014-93-015
Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810
Erasmus Medical Center and Erasmus University, Rotterdam
Netherlands Organization for the Health Research and Development (ZonMw)
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture and Science
Ministry for Health, Welfare and Sports
European Commission (DG XII)
Municipality of Rotterdam
German Bundesministerium fur Forschung und Technology 01 AK 803 A-H
01 IG 07015
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