Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine

Peer reviewe

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

Epstein-Barr Virus and immune status imprint the immunogenomics of non-Hodgkin lymphomas occurring in immune-suppressed environments

Non-Hodgkin lymphomas (NHL) commonly occur in immune-deficient (ID) patients, both HIV-infected and transplanted, and are often EBV-driven with cerebral localization, raising the question of tumor immunogenicity, a critical issue for treatment responses. We investigated the immunogenomics of 68 lymphoproliferative disorders from 51 ID (34 posttransplant, 17 HIV+) and 17 immunocompetent patients. Overall, 72% were Large B Cells Lymphoma (LBCL) and 25% were primary central-nervous-system lymphoma (PCNSL) while 40% were EBV-positive. Tumor whole-exome and RNA sequencing, along with a bioinformatics pipeline allowed analysis of tumor mutational burden (TMB), tumor landscape and microenvironment (TME) and prediction of tumor neoepitopes. Both TMB (2.2 vs 3.4/Mb, p=0.001) and neoepitopes numbers (40 vs 200, p=0.00019) were lower in EBVpositive than in EBV-negative NHL, regardless of the immune status. In contrast both EBV and the immune status influenced the tumor mutational profile, with HNRNPF and STAT3 mutations exclusively observed in EBV-positive and ID NHL, respectively. Peripheral blood T-cell responses against tumor neoepitopes were detected in all EBV-negative cases but in only half EBV-positive ones, including responses against IgH-derived MHC-class-II restricted neoepitopes. The TME analysis showed higher CD8 T cell infiltrates in EBVpositive vs EBV-negative NHL, together with a more tolerogenic profile composed of Tregs, type-M2 macrophages and an increased expression of negative immune-regulators. Our results highlight that the immunogenomics of NHL in patients with immunodeficiency primarily relies on the tumor EBV status, while T cell recognition of tumor- and IgH-specific neoepitopes is conserved in EBV-negative patients, offering potential opportunities for future T cell-based immune therapies

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

Dialogue between mammary tumour cells and adipose cells : involvement of the fatty acid transporter CD36

Le cancer du sein est le cancer le plus fréquent chez la femme dans le monde. Le sein se compose d’une glande mammaire organisée en canaux et lobules et entourée d’une fraction stromale, majoritairement composée de tissu adipeux. Les tumeurs mammaires dérivent des cellules épithéliales de la glande mammaire, et se développent dans un stroma riche en tissu adipeux, avec lequel il existe une communication dynamique et réciproque via des facteurs secrétés. De nombreux facteurs de risque augmentent l’incidence des cancers du sein. En utilisant des adipocytes mammaires issus de prélèvement humains, différenciés in vitro, nous montrons dans ces travaux que l’obésité, le statut ménopausique, et la densité mammaire, n’ont pas d’effet local dans le dialogue entre adipocytes mammaires et cellules tumorales mammaires. Nous montrons également que les adipocytes mammaires libèrent des acides gras qui peuvent être captés par les cellules tumorales mammaires, via le transporteur CD36, stimulant leur croissance et leur invasion. Nos travaux montrent aussi que l’expression de CD36 suffit à induire ces effets, et à activer la voie d’oxydation des acides gras in vitro. La compréhension des mécanismes qu’induit CD36 sur l’agressivité des cellules tumorales permettra d’envisager cette protéine comme un biomarqueur ou une cible thérapeutique dans les cancers du sein.Breast cancer is the most common cancer in women worldwide.The breast consists of a mammary gland organised into ducts and lobules and surrounded by a stromal fraction, mostly composed of adipose tissue. Breast tumours derive from epithelial cells of the mammary gland, and develop in a stroma, rich in adipose tissue, with which there is dynamic and reciprocal communication via secreted factors.Many risk factors increase the incidence of breast cancer. Using breast adipocytes from human samples, differentiated in vitro, we show in this work that obesity, menopausal status, and breast density have no local effect in the dialogue between breast adipocytes and breast tumour cells. We also show that mammary adipocytes release fatty acids which can be captured by mammary tumour cells, via the CD36 transporter, stimulating their growth and invasion. Our work also shows that the expression of CD36 is sufficient to induce these effects, and to activate the fatty acid oxidation pathway in vitro. Understanding the mechanisms induced by CD36 on the aggressiveness of tumour cells will allow us to consider this protein as a biomarker or a therapeutic target in breast cancer

Dialogue entre cellules tumorales mammaires et cellules adipeuses : implication du transporteur d'acides gras CD36

Breast cancer is the most common cancer in women worldwide.The breast consists of a mammary gland organised into ducts and lobules and surrounded by a stromal fraction, mostly composed of adipose tissue. Breast tumours derive from epithelial cells of the mammary gland, and develop in a stroma, rich in adipose tissue, with which there is dynamic and reciprocal communication via secreted factors.Many risk factors increase the incidence of breast cancer. Using breast adipocytes from human samples, differentiated in vitro, we show in this work that obesity, menopausal status, and breast density have no local effect in the dialogue between breast adipocytes and breast tumour cells. We also show that mammary adipocytes release fatty acids which can be captured by mammary tumour cells, via the CD36 transporter, stimulating their growth and invasion. Our work also shows that the expression of CD36 is sufficient to induce these effects, and to activate the fatty acid oxidation pathway in vitro. Understanding the mechanisms induced by CD36 on the aggressiveness of tumour cells will allow us to consider this protein as a biomarker or a therapeutic target in breast cancer.Le cancer du sein est le cancer le plus fréquent chez la femme dans le monde. Le sein se compose d’une glande mammaire organisée en canaux et lobules et entourée d’une fraction stromale, majoritairement composée de tissu adipeux. Les tumeurs mammaires dérivent des cellules épithéliales de la glande mammaire, et se développent dans un stroma riche en tissu adipeux, avec lequel il existe une communication dynamique et réciproque via des facteurs secrétés. De nombreux facteurs de risque augmentent l’incidence des cancers du sein. En utilisant des adipocytes mammaires issus de prélèvement humains, différenciés in vitro, nous montrons dans ces travaux que l’obésité, le statut ménopausique, et la densité mammaire, n’ont pas d’effet local dans le dialogue entre adipocytes mammaires et cellules tumorales mammaires. Nous montrons également que les adipocytes mammaires libèrent des acides gras qui peuvent être captés par les cellules tumorales mammaires, via le transporteur CD36, stimulant leur croissance et leur invasion. Nos travaux montrent aussi que l’expression de CD36 suffit à induire ces effets, et à activer la voie d’oxydation des acides gras in vitro. La compréhension des mécanismes qu’induit CD36 sur l’agressivité des cellules tumorales permettra d’envisager cette protéine comme un biomarqueur ou une cible thérapeutique dans les cancers du sein

Dialogue entre cellules tumorales mammaires et cellules adipeuses : implication du transporteur d'acides gras CD36

Breast cancer is the most common cancer in women worldwide.The breast consists of a mammary gland organised into ducts and lobules and surrounded by a stromal fraction, mostly composed of adipose tissue. Breast tumours derive from epithelial cells of the mammary gland, and develop in a stroma, rich in adipose tissue, with which there is dynamic and reciprocal communication via secreted factors.Many risk factors increase the incidence of breast cancer. Using breast adipocytes from human samples, differentiated in vitro, we show in this work that obesity, menopausal status, and breast density have no local effect in the dialogue between breast adipocytes and breast tumour cells. We also show that mammary adipocytes release fatty acids which can be captured by mammary tumour cells, via the CD36 transporter, stimulating their growth and invasion. Our work also shows that the expression of CD36 is sufficient to induce these effects, and to activate the fatty acid oxidation pathway in vitro. Understanding the mechanisms induced by CD36 on the aggressiveness of tumour cells will allow us to consider this protein as a biomarker or a therapeutic target in breast cancer.Le cancer du sein est le cancer le plus fréquent chez la femme dans le monde. Le sein se compose d’une glande mammaire organisée en canaux et lobules et entourée d’une fraction stromale, majoritairement composée de tissu adipeux. Les tumeurs mammaires dérivent des cellules épithéliales de la glande mammaire, et se développent dans un stroma riche en tissu adipeux, avec lequel il existe une communication dynamique et réciproque via des facteurs secrétés. De nombreux facteurs de risque augmentent l’incidence des cancers du sein. En utilisant des adipocytes mammaires issus de prélèvement humains, différenciés in vitro, nous montrons dans ces travaux que l’obésité, le statut ménopausique, et la densité mammaire, n’ont pas d’effet local dans le dialogue entre adipocytes mammaires et cellules tumorales mammaires. Nous montrons également que les adipocytes mammaires libèrent des acides gras qui peuvent être captés par les cellules tumorales mammaires, via le transporteur CD36, stimulant leur croissance et leur invasion. Nos travaux montrent aussi que l’expression de CD36 suffit à induire ces effets, et à activer la voie d’oxydation des acides gras in vitro. La compréhension des mécanismes qu’induit CD36 sur l’agressivité des cellules tumorales permettra d’envisager cette protéine comme un biomarqueur ou une cible thérapeutique dans les cancers du sein

Dialogue entre cellules tumorales mammaires et cellules adipeuses : implication du transporteur d'acides gras CD36

Breast cancer is the most common cancer in women worldwide.The breast consists of a mammary gland organised into ducts and lobules and surrounded by a stromal fraction, mostly composed of adipose tissue. Breast tumours derive from epithelial cells of the mammary gland, and develop in a stroma, rich in adipose tissue, with which there is dynamic and reciprocal communication via secreted factors.Many risk factors increase the incidence of breast cancer. Using breast adipocytes from human samples, differentiated in vitro, we show in this work that obesity, menopausal status, and breast density have no local effect in the dialogue between breast adipocytes and breast tumour cells. We also show that mammary adipocytes release fatty acids which can be captured by mammary tumour cells, via the CD36 transporter, stimulating their growth and invasion. Our work also shows that the expression of CD36 is sufficient to induce these effects, and to activate the fatty acid oxidation pathway in vitro. Understanding the mechanisms induced by CD36 on the aggressiveness of tumour cells will allow us to consider this protein as a biomarker or a therapeutic target in breast cancer.Le cancer du sein est le cancer le plus fréquent chez la femme dans le monde. Le sein se compose d’une glande mammaire organisée en canaux et lobules et entourée d’une fraction stromale, majoritairement composée de tissu adipeux. Les tumeurs mammaires dérivent des cellules épithéliales de la glande mammaire, et se développent dans un stroma riche en tissu adipeux, avec lequel il existe une communication dynamique et réciproque via des facteurs secrétés. De nombreux facteurs de risque augmentent l’incidence des cancers du sein. En utilisant des adipocytes mammaires issus de prélèvement humains, différenciés in vitro, nous montrons dans ces travaux que l’obésité, le statut ménopausique, et la densité mammaire, n’ont pas d’effet local dans le dialogue entre adipocytes mammaires et cellules tumorales mammaires. Nous montrons également que les adipocytes mammaires libèrent des acides gras qui peuvent être captés par les cellules tumorales mammaires, via le transporteur CD36, stimulant leur croissance et leur invasion. Nos travaux montrent aussi que l’expression de CD36 suffit à induire ces effets, et à activer la voie d’oxydation des acides gras in vitro. La compréhension des mécanismes qu’induit CD36 sur l’agressivité des cellules tumorales permettra d’envisager cette protéine comme un biomarqueur ou une cible thérapeutique dans les cancers du sein