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

The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia

Expression of the MECOM (also known as EVI1) proto-oncogene is deregulated by chromosomal translocations in some cases of acute myeloid leukemia (AML) and is associated with poor clinical outcome. Here, through transcriptomic and metabolomic profiling of hematopoietic cells, we reveal that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs (shRNAs) identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive AML. EVI1 promotes CKMT1 expression by repressing the myeloid differentiation regulator RUNX1. Suppression of arginine-creatine metabolism by CKMT1-directed shRNAs or by the small molecule cyclocreatine selectively decreased the viability, promoted the cell cycle arrest and apoptosis of human EVI1-positive cell lines, and prolonged survival in both orthotopic xenograft models and mouse models of primary AML. CKMT1 inhibition altered mitochondrial respiration and ATP production, an effect that was abrogated by phosphocreatine-mediated reactivation of the arginine-creatine pathway. Targeting CKMT1 is thus a promising therapeutic strategy for this EVI1-driven AML subtype that is highly resistant to current treatment regimens. Keywords: AML; RUNX1; CKMT1; cyclocreatine; arginine metabolismNational Cancer Institute (U.S.) (NIH 1R35 CA210030-01)Stand Up To CancerBridge ProjectNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051

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

Inventory of current EU paediatric vision and hearing screening programmes

Background: We examined the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes relevant for comparison of screening programmes were derived from literature and used to compile three questionnaires on vision, hearing and public-health screening. Tests used, professions involved, age and frequency of testing seem to influence sensitivity, specificity and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists and audiologists involved in paediatric screening in all EU fullmember, candidate and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% more than once. First measurement of VA varies from three to seven years of age, but is usually before the age of five. At age three and four picture charts, including Lea Hyvarinen are used most, in children over four Tumbling-E and Snellen. As first hearing screening test otoacoustic emission (OAE) is used most in healthy neonates, and auditory brainstem response (ABR) in premature newborns. The majority of hearing testing programmes are staged; children are referred after one to four abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1-4) and funding sources (8)

Cognitive abilities and the effectiveness of hunt in relation to behavioural asymmetry in antlion larvae

Lateralizacja jest powszechnym w świecie zwierząt zjawiskiem polegającym na asymetrii w morfologii i funkcjonalności mózgu. Spekuluje się, że ma ona swoje odzwierciedlenie w asymetrii behawioralnej, czyli stronności w zachowaniu. Oba zjawiska, lateralizacja oraz asymetria behawioralna, mają dowiedzione doświadczalnie pozytywne skutki, ale mało wiadomo na temat kosztów tych zjawisk. Badania larw mrówkolwa (Myrmeleon bore, Neuroptera: Myrmeleontidae) wykazały, że część osobników wykazuje asymetrię i jednocześnie uczy się szybciej niż pozostała część, niewykazująca asymetrii. Mimo tego rodzaju pozytywnych poznawczych efektów asymetrii, larw ją wykazujących jest stosunkowo niewiele, co może być wynikiem jednocześnie występujących negatywnych skutków asymetrii. W przedstawionych tu badaniach przetestowano występowanie kompromisu między tempem uczenia się a skutecznością polowania u asymetrycznych i nieasymetrycznych larw M. bore. Wykazano, że osobniki asymetryczne uczą się szybciej, ale polują mniej skutecznie niż larwy nieasymetryczne, co świadczy o występowaniu wspomnianego kompromisu. Wyniki pomagają zrozumieć, dlaczego asymetria behawioralna jest stosunkowo rzadka w populacji larw mrówkolwa.Lateralization is a phenomenon common amongst animals; it involves asymmetry in morphology and brain functionality. Its reflection in behavioural asymmetry, being bias in behaviour, is subject to speculation. Both phenomena, lateralization and behavioural asymmetry, have experimentally proven positive effects. Research has shown that e.g. among antlion larvae (Myrmeleon bore, Neuroptera: Myrmeleontidae), some of the specimen exhibit asymmetry and simultaneously learn faster than those not exhibiting assymetry. Despite the same positive cognitive effects of asymmetry, the number of larvae that exhibit it is relatively low, which may be the result of the simultaneous occurrence of the asymmetry’s negative effects. Hence, the following study tests the occurrence of a compromise between the learning pace and another adaptation-wise significant quality - the effectiveness of hunt, among asymmetric and non-asymmetric M. bore larvae. It was established that asymmetric specimens learn faster but hunt more slowly than non-asymmetric larvae, which indicates the occurrence of the abovementioned compromise. It may explain why behavioural asymmetry is relatively rare among antlion larvae

Introgression of MHC class II genes in hybrid zones of pond turtles

Główny układ zgodności tkankowej (MHC) obejmuje geny mające podstawowe znaczenie w odpowiedzi swoistej kręgowców. Kodują glikoproteiny, których główną rolą jest prezentacja w organizmie obcych białek i inicjacja odpowiedzi odpornościowej. Wyjątkową cechą tych genów jest nadzwyczajny polimorfizm- występują w populacjach w wielu wariantach. Jednym z mechanizmów kształtujących zmienność genetyczną jest introgresja- przepływ genów między dwoma gatunkami, między którymi zachodzi hybrydyzacja i krzyżowania wsteczne. Introgresja adaptacyjna ma korzystny wpływ na dostosowanie organizmu i jest faworyzowana przez selekcję naturalną. Jest charakterystyczna dla genów będących pod wpływem ewolucyjnych procesów, które faworyzują zmienność genetyczną. Do takiej grupy należą właśnie geny układu zgodności tkankowej, będące pod wpływem doboru stabilizującego. Spekuluje się, że introgresja może wpływać na polimorfizm genów MHC.Celem badania było znalezienie odpowiedzi na pytanie, czy introgresja jest źródłem zmienności genów układu zgodności tkankowej klasy II u dwóch gatunków żółwi błotnych- Emys orbicularis i E. trinacris, zamieszkujących południe Włoch. Analizie poddano fragment sekwencji kodujący rowek (drugi egzon), który ze względu na swoją rolę w przyłączaniu antygenu cechuje się największą zmiennością genetyczną. Porównano liczbę alleli dzielonych między gatunkami w populacjach znajdujących się blisko strefy kontaktu (parapatrycznych) i oddalonych od niej (allopatrycznych). Potwierdzeniem przepływu genów byłaby większa liczba alleli dzielonych między gatunkami w populacjach parapatrycznych niż w populacjach allopatrycznych. Wbrew przewidywaniom, nie udało się stwierdzić zachodzenia introgresji między badanymi gatunkami. Może być to spowodowane przez brak adaptacyjnej wartości badanych sekwencji, istnienie bariery przeciwko mieszańcom lub brak zachodzenia hybrydyzacji. Nie udało się znaleźć jednoznacznego wyjaśnienia otrzymanego wyniku; zagadnienie to wymaga więcej badań.The Major Histocompatibility Complex (MHC) contains genes that play a crucial role in vertebrate adaptive immune response. They code glycoproteins responsible for presenting foreign antigens to host T cells and initiating the immune response. The unique feature of MHC genes is their extraordinary polymorphism – typically many variants occur in a population. One of the mechanisms that shapes MHC diversity may be introgression - gene flow that occurs between two species that hybridize and backcross. Adaptive introgression improves the fitness of the organism and is favored by natural selection. It is characteristic of genes that are influenced by evolutionary processes that favor genetic variation. This group includes the genes of the major histocompatibility complex, which are influenced by the stabilizing selection. It has been suggested that adaptive introgression may increase polymorphism of MHC genes.The main aim of this study was to answer the question whether introgression can be the source of MHC diversity in two species of pond turtles - Emys orbicularis and E. trinacris, inhabiting southern Italy. The fragment encoding a groove (second exon) was selected for analysis - due to its role in antigen binding, it is the most variable part of the sequence. The number of alleles shared between species in populations near the contact zone (parapatric) and in distant populations (allopatric) was compared. Gene flow would be confirmed by a greater number of alleles shared between species in parapatric populations than in allopatric populations. Contrary to our expectations, increased allele sharing in the proximity of the contact zone was not detected, indicating the lack of MHC introgression. The reason for such a result could be the lack of adaptive value of the tested alleles, the presence of a barrier against hybrids or the non-existence of hybridization between species. There was no clear explanation for the obtained result; this question requires further research

The Management of Peutz-Jeghers Syndrome : European Hereditary Tumour Group (EHTG) Guideline

The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when >= 80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.Peer reviewe