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

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

A Step Toward NOTES Total Mesorectal Excision for Rectal Cancer

International audienceBackground: Previous publications have suggested that endoscopic transanalproctectomy (ETAP) is a promising technique and may be an alternative toconventional low anterior resection for rectal cancer. The aim of this studywas to evaluate the technical feasibility of ETAP, with a particular focus onpostoperative and oncological results and on functional outcomes.Methods: This study was a multicenter prospective study of unselected consecutive patients with low rectal cancer requiring proctectomy and coloanalanastomosis. All patients underwent a standardized procedure. The study endpoints were the safety and adequacy of the oncological resection criteria. Allpatients were evaluated with the Wexner Fecal Incontinence Questionnaireafter stoma closure.Results: Fifty-six consecutive patients (41 men) underwent ETAP betweenFebruary 2010 and June 2012. The median age was 65 years (39–83), andthe median body mass index was 27 (20-42). No intraoperative complicationswere encountered. There was no postoperative mortality, and the morbidityrate was 26%. The mesorectum was complete in 47 cases (84%) and nearlycomplete in 9 cases (16%). The median number of lymph nodes retrievedwas 12 (range, 7–29) per patient. The median radial and distal margins were8 mm (0–20) and 10 mm (3–40), respectively. R0 resection was achieved in53 patients (94.6%). The median Wexner score was 4 (3–12). Thirteen (28%)patients reported stool fragmentation and difficult evacuation.Conclusions: ETAP is a feasible alternative surgical option to conventionallaparoscopy for rectal resection and may represent a promising step towardrectal natural orifice transluminal endoscopic surgery (NOTES)

The Rescue of miR-148a Expression in Pancreatic Cancer: An Inappropriate Therapeutic Tool

<div><p>MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, <em>in vivo</em> data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both <em>in vitro</em> and <em>in vivo</em> thus suggesting a weak potential as a therapeutic tool.</p> </div

The E3 ubiquitin ligase TRIP12 participates in cell cycle progression and chromosome stability

International audienceSeveral studies have linked the E3 ubiquitin ligase TRIP12 (Thyroid hormone Receptor Interacting Protein 12) to the cell cycle. However, the regulation and the implication of this protein during the cell cycle are largely unknown. In this study, we show that TRIP12 expression is regulated during the cell cycle, which correlates with its nuclear localization. We identify an euchromatin-binding function of TRIP12 mediated by a N-terminal intrinsically disordered region. We demonstrate the functional implication of TRIP12 in the mitotic entry by controlling the duration of DNA replication that is independent from its catalytic activity. We also show the requirement of TRIP12 in the mitotic progression and chromosome stability. Altogether, our findings show that TRIP12 is as a new chromatin-associated protein with several implications in the cell cycle progression and in the maintenance of genome integrity

Transient over-expression of miR-148a in PDAC cell lines.

<p>(<b>A</b>) Capan-2, PANC-1, MIA PaCa-2 and BxPC-3 PDAC-derived cell lines and non-cancerous HPNE cell line were transiently transfected with miR-CT or miR-148a precursors. Four days after transfection, cell viability was assessed by colorimetric methods. For each cell line, the miR-148a-cell viability was compared to miR-CT cell viability (100%). The results are the mean of three independent experiments (±SEM) and are expressed as percentage of cell viability of control cells. (<b>B</b>), Cell cycle distribution was measured by propidium iodide staining followed by FACS analysis 72 hours after transfection of Capan-2 cells with miR-CT or miR-148a precursors.</p

Effect of stable miR-148a over-expression in PDAC cell line.

<p>MIA PaCa-2 cells were incubated with inducible lentiviral vectors encoding for scramble microRNA (miR-CT) or miR-148a (miR-148a). MIA PaCa-2 miR-CT or miR-148a proliferation rate was assessed in the presence or the absence of doxycycline in culture medium. For each condition, cell count was performed every 24 h and compared to the number of adherent cells at day 1. The results are the mean of three independent experiments (±SEM).</p

Murine orthotopic xenograft and tumor progression monitoring.

<p>(<b>A</b>) <i>In vivo</i> monitoring of xenograft tumor progression: MIA PaCa-2 cells expressing miR-148a and secreted Gaussia luciferase (Gluc) were injected in the pancreas of SCID mice. Mice received normal water (untreated, n = 10) or water supplemented with doxycycline (doxycycline, n = 12) for miR-148a expression induction until sacrifice. Gluc levels were measured in mice serum. The results are the mean of Gluc activities (±SEM) and are expressed as Arbitrary Light Unit (A.L.U.). (<b>B</b>) Tumors were removed and weighted the day of surgery. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055513#s3" target="_blank">Results</a> are mean (±SEM) of tumor weight in the untreated group (n = 10) and the doxycycline treated group (n = 12) (<b>C</b>) <i>In vivo</i> monitoring of xenograft tumor progression: MIA PaCa-2 cells expressing secreted Gaussia luciferase were injected in the pancreas of SCID mice (n = 10). Fifteen days later, lentiviral vectors encoding miR-148a (miR-148a, n = 7) or GFP only (GFP, n = 3) were injected in the tumors (the arrow indicates the lentiviral particles injection). The amount of Gluc was measured in mice serum and compared to the Gluc amount measured the day of lentivector injection (Day 0). The results are the mean of the Gluc level ratio in each group (±SEM) and are expressed as arbitrary light unit ratio. (<b>D</b>) Tumors receiving miR-148 (miR-148a, n = 7) or GFP (GFP, n = 3) were removed 10 days after lentiviral injection and were weighted. The graph represents the comparison of tumor weight expressing miR-148a (n = 7) or GFP (n = 3). The results are the mean of tumor weight in each group (±SEM).</p

Gemcitabine sensitivity of PDAC cell lines over-expressing miR-148a.

<p>(<b>A</b>) miR-148a endogenous expression level was measured by qRT-PCR in several PDAC cell lines and in hPDE and hPNE normal pancreatic cell lines. (<b>B</b>) Cell sensitivity to gemcitabine was measured after a 72 h-treatment in several PDAC cell lines and in normal hPNE pancreatic cells. Surviving cell fraction represents the number of treated cells during 72 h compared to the number of untreated cells (represented as 100%). The lethal concentration 50 (LC50) represents the dose of gemcitabine sufficient to obtain 50% of surviving cells compared to untreated cells. The results are the mean of three independent experiments (±SEM). (<b>C</b>) Cell sensitivity to gemcitabine was measured in MIA PaCa-2 cells stably over-expressing miR-148a (LV-TO-miR-148a) or a control miR (LV-TO-miR-CT) to gemcitabine in presence of doxycycline after a 72 h-treatment. Surviving cell fraction represents the number of treated cells during 72 h compared to the number of untreated cells (represented as 100%). The results are the mean of three independent experiments (±SEM).</p