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

Le cancer colorectal: dix années d'illusion de progrès mais des avancées sont à l'horizon

Recent years have basically been marked by a modest progress in digestive oncology. Biologic drugs such as anti-EGFR and antiangiogenic antibodies have improved the overall survival of patients with advanced colorectal cancer for a few months, but did not alter adjuvant treatment paradigms after curative resection of a locally advanced colon cancer or of liver metastases. With the exception of the RAS gene mutations, predictive of lack of effectiveness to anti-EGFR antibodies, our knowledge of colon cancer tumor biology has hardly evolved. Long-awaited novelties come rather from fundamental discoveries about the different genomic subtypes of colorectal cancer and new immunotherapy approaches which both announce hopefully real giant leaps in the near future.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Nonbacterial thrombotic endocarditis in a patient with gastric cancer and SARS-CoV-2 infection.

Nonbacterial thrombotic endocarditis, formerly known as marantic endocarditis, is a very rare complication of advanced malignancy and other hypercoagulable states in which sterile, fibrin vegetations develop on heart valve leaflets. The most common malignancies associated with this entity are lung, pancreatic and gastric cancer. It has also been described as a presentation of COVID-19, which is known to be frequently complicated with coagulopathy and thromboembolic events. We report the case of a 62 year-old female patient newly diagnosed with stage IV gastric cancer and acute SARS-CoV-2 infection, presenting with confusion and homonymous hemianopsia in the setting of multiple acute ischemic strokes complicating a nonbacterial thrombotic mitral endocarditis. Herein, we discuss the underlying pathophysiology and make the hypothesis that SARS-CoV-2 infection could have participated in the pathogenesis of nonbacterial thrombotic endocarditis in our patient suffering from a gastric cancer

In Deciphering the Future of Adjuvant Treatment in Colon Cancer, the Journey Matters More than the Achievements

The development of adjuvant treatment in colon cancer has followed the same paradigm as in other solid tumors, transposing the drug regimens found to perform the best in the advanced setting into the adjuvant setting. However, despite numerous studies, no progress has been recorded for patients with stage II and III colon cancer since the publication of the MOSAIC trial more than 10 years ago. We performed a comprehensive review of randomized phase III trials both already published and currently recruiting, and revisited the scientific rationale of adjuvant treatment in colon cancer and the philosophical roots of its development in order to challenge the current paradigms and to consider future perspectives. This analysis provides ground for new approaches based on the identification of patients unlikely to benefit from standard therapies with the aim to spare them needless toxicities and to identify a subgroup of patients who would be candidates for advanced research with new therapies.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Grey areas and evidence gaps in the management of rectal cancer as revealed by comparing recommendations from clinical guidelines

Background: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. Methods: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e. identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e. substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence by using the χ2 statistic test. Results: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 3/10 cases (30%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 2.6, p = 0.106). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. Conclusions: Substantial variation exists across clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Comparative analysis of ESD versus EMR in a large European series of non-ampullary superficial duodenal tumors

Background and study aims : The choice of endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) in non-ampullary superficial duodenal tumors (NASDTs) is challenging and the benefits of ESD remain unclear. The aim was to comparatively analyze the feasibility, outcomes and safety of these techniques in these lesions. Patients and methods:  This is an observational and retrospective study. All consecutive patients presenting with NASDTs who underwent EMR or ESD between 2005 and 2017 were included. The following main outcomes were comparatively evaluated: en-bloc and complete (R0) resection rates, and local recurrence. Secondary outcomes were perforation and delayed bleeding. Results : One hundred sixty-six tumors in 150 patients (age: 66 years, range: 31 - 83, 42.7 % males) were resected by ESD (n = 37) or EMR (n = 129) and included. The median procedure time (81 vs. 50 min, P  = 0.007) and tumor size (25 vs. 20 mm, P  = 0.01) were higher in the ESD group. The global malignancy rate was 50.3 %. There were no differences in en-bloc resection (29.7 % vs. 44.2 %, P  = 0.115), complete resection (19.4 % vs. 35.5 %, P  = 0.069), and local recurrence (14.7 % vs. 16.7 %, P  = 0.788) rates. Tumor size was associated with recurrence (28 vs. 20 mm, P  = 0.008), with a median follow-up of 6.5 months. Focal recurrence (n = 22, 13.3 %) was treated endoscopically in 86.4 %. En-bloc resection in the ESD group was comparable in large ( ≥ 20 mm) and small lesions (27.6 % vs. 37.5 %, P  = 0.587), while this outcome decreased significantly in large lesions resected by EMR (17.4 % vs. 75 %, P  < 0.001). Nine perforations were confirmed in 6 lesions (16.2 %) resected by ESD and 3 (2.3 %) by EMR ( P  = 0.001). Endoscopic therapy was successful in all but 1 patient (88.9 %) presenting with a delayed perforation. Conclusions : ESD may be an alternative to EMR and surgery in selected NASDTs, such as large duodenal tumors where EMR achieves low en-bloc resection rates and the local recurrence may be higher. However, this technique may have a higher risk of perforations

Prognostic value of a three-scale grading system based on combining molecular imaging with 68Ga-DOTATATE and 18F-FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias

info:eu-repo/semantics/publishe

612TiPPhase I studies assessing the safety and clinical activity of multiple doses of a NKG2D-based CAR-T therapy, CYAD-01, in metastatic colorectal cancer

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A phase I study assessing the safety and clinical activity of multiple doses of a NKG2D-based CAR-T therapy, CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with potentially resectable liver metastases from colorectal cancer

We recently developed a novel chimeric antigen receptor (CAR) T-cell therapy, called CYAD-01 (a.k.a. NKR-2), incorporating the full-length human natural killer receptor NKG2D fused with the human CD3 zeta signaling domain, which associates with the adaptor molecule DAP10 to provide co-stimulatory signal upon ligand binding. CYAD-01 is currently evaluated in the ongoing THINK study (NCT03018405) without preconditioning therapy in both hematological and solid indications. Classical CAR-Ts has yet to demonstrate positive results in the context of solid tumors. Underlying reasons for this reduced clinical activity include the need to extravasate from the peripheral circulation, infiltrate into the tumor and overcome the hostile immune suppressive tumor microenvironment (TME) to deliver anti-tumor effector responses. To address the challenge related to the immunosuppressive TME, the SHRINK trial (Standard cHemotherapy Regimen and Immunotherapy with NKR-2) has been developed to assess the safety and clinical activity of multiple infusion CYAD-01 treatment (every 2 weeks x 3 infusions) in patients undergoing standard-of-care FOLFOX (Folinic acid, Fluorouracil (5-FU) and Oxaliplatin) chemotherapy, as neoadjuvant treatment, for the treatment of colorectal metastatic disease with potentially resectable metastases (NCT03310008). The FOLFOX treatment is given every two weeks for six cycles and CYAD-01 cells are infused shortly after chemotherapy on cycles 3, 4 and 5. This concurrent administration of chemotherapy and CYAD-01 treatments would not only (i) favor infiltration into the immunosuppressive TME due to the effect of chemotherapy on TME and cancer cells but also (ii) provide an opportunity for the CYAD-01 cells to better engraft due to the lymphodepletion induced by the standard chemotherapy administration, and likely (iii) increase the NKG2D ligand expression in tumor tissues targeted by CYAD-01, even in patients presenting heterogeneity and/or low ligand expression. The study contains two consecutive segments. The dose escalation segment will enroll 9 patients and will evaluate 3 dose levels of CYAD-01 (1x108, 3x108 and 1x109 CYAD-01 per injection) following a 3+3 design. The expansion segment will then enroll 21 additional patients to further evaluate the safety and potential signs of activity of the CYAD-01 therapy when administered concurrently with chemotherapy. Peripheral blood samples, as well as tumor biopsies from patients at baseline and at resection, will be collected to determine, among others, CYAD-01 persistence, NKG2D ligand expression and systemic cytokine levels in peripheral blood post-infusion