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Background and Objectives Serratia marcescens is an emerging nosocomial pathogen, and the carbapenemase blaNDM has been reported in several surveys in Romania. We aimed to investigate the molecular epidemiology of S. marcescens in two Romanian hospitals over 2010–15, including a neonatal NDM-1 S. marcescens outbreak. Methods Isolates were sequenced using Illumina technology together with carbapenem-non-susceptible NDM-1-positive and NDM-1-negative Klebsiella pneumoniae and Enterobacter cloacae to provide genomic context. A subset was sequenced with MinION to fully resolve NDM-1 plasmid structures. Resistance genes, plasmid replicons and ISs were identified in silico for all isolates; an annotated phylogeny was reconstructed for S. marcescens. Fully resolved study NDM-1 plasmid sequences were compared with the most closely related publicly available NDM-1 plasmid reference. Results 44/45 isolates were successfully sequenced (S. marcescens, n = 33; K. pneumoniae, n = 7; E. cloacae, n = 4); 10 with MinION. The S. marcescens phylogeny demonstrated several discrete clusters of NDM-1-positive and -negative isolates. All NDM-1-positive isolates across species harboured a pKOX_NDM1-like plasmid; more detailed comparisons of the plasmid structures demonstrated a number of differences, but highlighted the largely conserved plasmid backbones across species and hospital sites. Conclusions The molecular epidemiology is most consistent with the importation of a pKOX_NDM1-like plasmid into Romania and its dissemination amongst K. pneumoniae/E. cloacae and subsequently S. marcescens across hospitals. The data suggested multiple acquisitions of this plasmid by S. marcescens in the two hospitals studied; transmission events within centres, including a large outbreak on the Targu Mures neonatal unit; and sharing of the pKOX_NDM1-like plasmid between species within outbreaks.

Background and Objectives: Serratia marcescens is an emerging nosocomial pathogen, and the carbapenemase blaNDM has been reported in several surveys in Romania. We aimed to investigate the molecular epidemiology of S. marcescens in two Romanian hospitals over 2010-2015; including a neonatal NDM-1- S. marcescens outbreak. Methods: Isolates were sequenced using Illumina technology together with carbapenem-non-susceptible NDM-1-positive and NDM-1-negative K. pneumoniae and E. cloacae to provide genomic context. A subset were sequenced with MinION to fully resolve NDM-1 plasmid structures. Resistance genes, plasmid replicons and insertion sequences were identified in silico for all isolates; an annotated phylogeny was reconstructed for S. marcescens. Fully resolved study NDM-1 plasmid sequences were compared with the most closely related publicly available NDM-1 plasmid reference. Results: 44/45 isolates were successfully sequenced (S. marcescens, n=33; K. pneumoniae, n=7; E. cloacae, n=4); ten with MinION. The S. marcescens phylogeny demonstrated several discrete clusters of NDM-1-positive and negative isolates. All NDM-1-positive isolates across species harboured a pKOX-NDM-1-like plasmid; more detailed comparisons of the plasmid structures demonstrated a number of differences, but largely conserved plasmid backbones across species and hospital sites. Conclusions: The molecular epidemiology is most consistent with the importation of a pKOX-NDM1-like plasmid into Romania and its dissemination amongst K. pneumoniae/E. cloacae and subsequently S. marcescens across hospitals. The data suggested multiple acquisitions of this plasmid by S. marcescens in the two hospitals studied; transmission events within centres, including a large outbreak on the Targu-Mures neonatal unit; and sharing of the pKOX-NDM-1-like plasmid between species within outbreaks.

© 2017 Elsevier Ltd Background Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. Methods In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. Findings Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4–63 years). The volumes of the accumbens (Cohen's d=−0·15), amygdala (d=−0·19), caudate (d=−0·11), hippocampus (d=−0·11), putamen (d=−0·14), and intracranial volume (d=−0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=−0·19 vs −0·10), amygdala (d=−0·18 vs −0·14), caudate (d=−0·13 vs −0·07), hippocampus (d=−0·12 vs −0·06), putamen (d=−0·18 vs −0·08), and intracranial volume (d=−0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). Interpretation With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. Funding National Institutes of Health.

Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients-two neighbouring countries with comparable treatment guidelines but with completely different traditions for routine surveillance imaging. Methods: Patients enroled in the Danish (LYFO) and Swedish population-based lymphoma registries were included by following criteria: (a) newly diagnosed DLBCL in the period 2007-2012, (b) age 18-65 years, and (c) CR after 1st line treatment with R-CHOP/CHOEP. We selected the age category 18-65 years, since 1st and 2nd line therapies are highly standardized for these patients (2nd line: high-dose therapy if feasible). The Danish and Swedish haematology/oncology services are fully publicly funded. Follow-up (FU) for Swedish patients included symptom assessment, clinical examinations, and blood tests with 3-month intervals for 2 years and with longer intervals later in follow-up. Imaging was only performed in response to suspected relapse. FU for Danish patients was equivalent but included additional routine surveillance imaging (usually half-yearly CT for 2 years as a minimum). Clinico-pathological features were retrieved from the national lymphoma registries, and vital status was updated using the civil registries. OS was defined as the time from end of treatment until death/censoring. Relapse data are continuously updated in the LYFO, and cumulative incidence rates for progression (relapse and death) were calculated for the Danish patients. Results: A total of 525 Danish and 696 Swedish patients were included. Danish and Swedish patients had similar male:female ratio, median age, and proportion of IPI high risk disease (IPI > 2). After a median FU of 51months, the 3-yr OS for the entire patient cohort was 92% (95% CI 90-93). There was no survival difference between Danish and Swedish patients (P = 0.5, log-rank). Age >60 years (HR 2.3, P 2 (HR 1.8, P = 0.04) at diagnosis were associated with inferior post-remission OS in multivariate Cox analysis, whereas an imaging-based FU strategy (country of FU) was not prognostic. An imaging-based FU strategy also had no impact on the post-remission OS for patients grouped according to the IPI scores (P = 0.2 for IPI 2). The cumulative 2-year progression rate was 6% (95% CI 4-9) for patients with IPI 2. Conclusions: The vast majority of young DLBCL patients in CR stay in remission, and only a small minority will benefit from a relapse-oriented FU program. More importantly, the post-remission survival rates were completely identical for Danish and Swedish patients despite the widespread use of routine imaging in Denmark, favouring a non-imaging-based FU strategy for DLBCL in 1st CR.