Does intra-operative flexible endoscopy reduce anastomotic complications following left-sided colonic resections?

INTRODUCTION: Post-operative anastomotic leakage (AL) or bleeding (AB) significantly impacts on patient outcome following colorectal resection. To minimise such complications, surgeons can utilise different techniques perioperatively to assess anastomotic integrity. We aim to assess published anastomotic complication rates following left-sided colonic resection, comparing use of intra-operative flexible endoscopy against conventional tests used to assess anastomotic integrity. METHODS: PubMed/MEDLINE and EMBASE online databases were searched for non-randomised and randomised case-control studies that investigated post-operative AL and/or AB rates in left-sided colonic resections, comparing intra-operative flexible endoscopy against conventional tests. Data from eligible studies were pooled, and a meta-analysis using Review Manager 5.3 software was performed to assess for difference in AL and AB rates. RESULTS: Data from six studies were analysed to assess the impact of flexible endoscopy on post-operative AL and AB rates (1084 and 751 patients respectively). Use of flexible endoscopy was associated with reduced post-operative AL and AB rates, from 6.9% to 3.5% and 5.8% to 2.4% respectively. OR favoured intra-operative flexible endoscopy; 0.37 (95% CI 0.21-0.68, p=0.001) for AL and 0.35 (95% CI: 0.15-0.82, p=0.02) for AB. CONCLUSION: This meta-analysis showed that the use of intra-operative flexible endoscopy is associated with a reduced rate of post-operative anastomotic leakage and bleeding, compared to conventional anastomotic testing methods. This article is protected by copyright. All rights reserved

Distinct molecular signatures of clinical clusters in people with type 2 diabetes:an IMI-RHAPSODY study

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous diseas

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

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

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

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Nutritional, biochemical and microbiological composition of Borassus aethiopum Mart. sap in Burkina Faso

The palmyra palm Borassus aethiopum Mart. grow wild and gives natural stands in several localities of central-eastern and eastern regions of Burkina Faso. This work aimed to determine the nutritional, biochemical and microbiological composition of fresh palm sap from B. aethiopum Mart. during the first 4 days of tapping. The composition of palm sap was carried out by HPLC and standard methods. The sap collected during the first 4 days were sugary and contained less alcohol. The mean values of the pH, total and reducing sugars content were 4.84 +/- 0.5, 11.36 +/- 3.97 and 2.93 +/- 1.22% w/v respectively. Sucrose, glucose, fructose and Vitamin C values were 6.75% w/v, 4.99 g/L, 7.09 g/L, 8.93% w/v respectively. Galactose and xylose were not detected. Soluble proteins, arabinose, phenols and ethanol were present in low concentration. Calcium, potassium, magnesium and ammonium were present in palm sap with highest potassium content (13.26 g/L). Lactate (2.41 +/- 0.86 g/L), succinate (2.49 +/- 1.46 g/L), acetate (0.01 +/- 0.006 g/L), malate (0.17 +/- 0.31 g/L), propionate (0.07 +/- 0.04 g/L), citrate (0.19 +/- 0.11 g/L), tartrate (0.08 +/- 0.09 g/L) and pyruvate (0.05 +/- 0.03 g/L) were detected in palm sap. The microbiological analysis of sap gave 1.23 +/- 1.01 x 10(8) cfu/mL for total aerobic flora, 7.27 +/- 1.19 x 10(5) cfu/mL for yeasts, 1.86 +/- 1.63 x 10(7) cfu/mL for lactic acid bacteria and 3.75 +/- 0.75 x 10(5) cfu/mL for acetic acid bacteria. The fresh sap from B. aethiopum presents good nutritional value and its consumption can help to improve dairy food intake of rural population. It can be used for the manufacture of various products like palm wine, syrups, sugars, functional foods, etc

Sequelae and Quality of Life in Patients Living at Home 1 Year After a Stroke Managed in Stroke Units

International audienceIntroduction: Knowledge about residual deficiencies and their consequences on daily life activities among stroke patients living at home 1-year after the initial event managed in stroke units is poor. This multi-dimensional study assessed the types of deficiencies, their frequency and the consequences that the specific stroke had upon the daily life of patients.Methods: A cross-sectional survey, assessing, using standardized scales, 1 year post-stroke disabilities, limitations of activities, participation and quality of life, was carried out by telephone interview and by mail in a sample of stroke patients who returned home after having been initially managed in a stroke unit.Results: A total of 161 patients were included (142 able to answer the interview on their own; 19 needing a care-giver). Amongst a sub-group of the patients interviewed, 55.4% (95% Confidence Interval [47.1-63.7]) complained about pain and 60.0% (95% CI [51.4-68.6]) complained of fatigue; about 25% presented neuropsychological or neuropsychiatric disability. Whilst 87.3% (95% CI [81.7-92.9]) were independent for daily life activities, participation in every domains and quality of life scores, mainly in daily activity, pain, and anxiety subscales, were low.Conclusion: Despite a good 1-year post-stroke functional outcome, non-motor disabling symptoms are frequent amongst patients returned home and able to be interviewed, contributing to a low level of participation and a poor quality of life. Rehabilitation strategies focused on participation should be developed to break the vicious circle of social isolation and improve quality of life

BMC Health Serv Res

BACKGROUND: Stroke is a health problem with serious consequences, both in terms of mortality, and after-effects affecting patient quality of life. Stroke requires both urgent and chronic management involving the entire health care system. Although large variability in the management of stroke patients have been noticed, knowledge of the diversity and the scalability of post-stroke pathways, whether it is the care pathway or the life pathway, is currently not sufficient. Moreover the link between post-stroke pathways and patients sequelae have not been yet clearly defined. All this information would be useful to better target the needs to improve stroke patient management. The purposes are to identify the post-stroke life pathways components associated with sequelae (activity limitations - main purpose, cognitive disorders, anxio-depressive disorders, fatigue, participation restrictions) at 3 months and 1 year post-stroke, to define a typology of life pathways of patients during the post-stroke year and to analyze the social and geographical inequalities in the management of stroke. METHODS: Design: a prospective multicenter comparative cohort study with a follow up to 1 year after the acute episode. Participant centers: 13 hospitals in the Aquitaine region (France). STUDY POPULATION: patients diagnosed with a confirmed ischemic or hemorrhagic stroke included in the Aquitaine Observatory of Stroke (ObA2) cohort and voluntary to participate. Data sources are existing databases (ObA2 database and the French National Health Data System - SNDS) to collect information about care pathways, patient characteristics and stroke characteristics and Ad hoc surveys to collect information about life pathways and post-stroke sequelae. The endpoints of the study are post-stroke activity limitations evaluated by the modified Rankin score, other post-stroke sequelae (Cognitive disorders, anxio-depressive disorders, fatigue, restriction of participation) assessed by standardized and validated scales and Clusters of patients responding to pathways with common or similar characteristics.; DISCUSSION: By integrating a longitudinal dimension and relying on a large cohort, the project will make it possible to identify the sources of disturbances and the factors favorable to the outcome of the life pathways, important for the planning of the offer and the management of the public policies concerning stroke pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03865173 , March 6th, 2019

Replication and cross-validation of type 2 diabetes subtypes based on clinical variables : an IMI-RHAPSODY study

Aims/hypothesis Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic. Methods In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA(1c), random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort's cluster centres. Finally, we compared the time to insulin requirement for each cluster. Results Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6-90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requirement, while the MDH cluster showed the slowest progression. Conclusions/interpretation Clusters based on C-peptide instead of HOMA2 measures resemble those based on HOMA2 measures, especially for SIDD, SIRD and MOD. By adding HDL-cholesterol, the MARD cluster based upon HOMA2 measures resulted in the current clustering into two clusters, with one cluster having high HDL levels. Cross-validation between cohorts showed generally a good resemblance between cohorts. Together, our results show that the clustering based on clinical variables readily measured in the clinic (age, HbA(1c), HDL-cholesterol, BMI and C-peptide) results in informative clusters that are representative of the original ANDIS clusters and stable across cohorts. Adding HDL-cholesterol to the clustering resulted in the identification of a cluster with very slow glycaemic deterioration.Peer reviewe