In praise of arrays

Microarray technologies have both fascinated and frustrated the transplant community since their introduction roughly a decade ago. Fascination arose from the possibility offered by the technology to gain a profound insight into the cellular response to immunogenic injury and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced. Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analyses, and difficulties associated with actually recognizing signature gene-expression patterns and discerning mechanisms. To aid the understanding of this powerful tool, its versatility, and how it is dramatically changing the molecular approach to biomedical and clinical research, this teaching review describes the technology and its applications, as well as the limitations and evolution of microarrays, in the field of organ transplantation. Finally, it calls upon the attention of the transplant community to integrate into multidisciplinary teams, to take advantage of this technology and its expanding applications in unraveling the complex injury circuits that currently limit transplant survival

A Genome-Wide Scan of Ashkenazi Jewish Crohn's Disease Suggests Novel Susceptibility Loci

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10−6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10−8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10−9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10−8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10−8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10−9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim

Use of a p64 MW Flow Diverter with Hydrophilic Polymer Coating (HPC) and Prasugrel Single Antiplatelet Therapy for the Treatment of Unruptured Anterior Circulation Aneurysms: Safety Data and Short-term Occlusion Rates

Purpose To assess the safety and short-term occlusion rates in procedures using the p64 MW hydrophilic polymer-coated (HPC) flow diverter (FD) with prasugrel single antiplatelet therapy (SAPT) for the treatment of anterior circulation saccular aneurysms. Methods We retrospectively identified patients who underwent treatment of one or more intracranial anterior circulation saccular aneurysms between March 2020 and December 2021 with a p64 MW HPC FD and prasugrel SAPT with verified P2Y12 platelet receptor inhibition. Patients diagnosed with fusiform, dissecting, or recently ruptured aneurysms were excluded. Periprocedural and postprocedural complications, clinical outcomes, and angiographic follow-up results were evaluated. Results One hundred and two patients with 132 intracranial aneurysms met the inclusion criteria. Previous or concomitant treatments (e.g., coil occlusion) had been performed on 18 of these aneurysms. The technical success rate (i.e., implantation of the intended FD) was 100% with an average of 1.1 devices implanted per patient. Periprocedural and postprocedural complications occurred in 13.6% and 6.8% of these patients, respectively. No mortality or permanent clinical deterioration (i.e., modified Rankin scale score >= 3) were reported. Early follow-up digital subtraction angiography revealed aneurysmal occlusion rates of 72.6% and 83.8% at four and nine months, respectively. Conclusions The implantation of a p64 MW HPC FD with prasugrel SAPT is safe and results in rapid, reliable and effective aneurysmal occlusion

B-Lines for the assessment of extravascular lung water: Just focused or semi-quantitative?

Background B-lines as typical artefacts of lung ultrasound are considered as surrogate measurement for extravascular lung water. However, B-lines develop in the sub-pleural space and do not allow assessment of the whole lung. Here, we present data from the first observational multi-centre study focusing on the correlation between a B-lines score and extravascular lung water in critically ill patients suffering from a variety of diseases. Patients and Methods In 184 adult patients, 443 measurements were obtained. B-lines were counted and expressed in a score which was compared to extravascular lung water, measured by single-indicator transpulmonary thermodilution. Appropriate correlation coefficients were calculated and receiver operating characteristics (ROC-) curves were plotted. Results Overall, B-lines score was correlated with body weight-indexed extravascular lung water characterized by r = .59. The subgroup analysis revealed a correlation coefficient in patients without an infection of r = .44, in those with a pulmonary infection of r = .75 and in those with an abdominal infection of r = .23, respectively. Using ROC-analysis the sensitivity and specificity of B-lines for detecting an increased extravascular lung water (>10 mL/kg) was 63% and 79%, respectively. In patients with a P/F ratio <200 mm Hg, sensitivity and specificity to predict an increased extravascular lung water was 71% and 93%, respectively. Conclusions Assessment of B-lines does not accurately reflect actual extravascular lung water. In presence of an impaired oxygenation, B-lines may reliably indicate increased extravascular lung water as cause of the oxygenation disorders

Introduction and spread of vancomycin-resistant Enterococcus faecium (VREfm) at a German tertiary care medical center from 2004 until 2010: a retrospective whole-genome sequencing (WGS) study of the molecular epidemiology of VREfm

Abstract Background In most of Europe and especially in Germany, there is currently a concerning rise in the number of hospital-acquired infections due to vancomycin-resistant Enterococcus faecium (VREfm). Therefore, there is a need to improve our understanding of the way VREfm spreads in hospitals. In this study, we investigated the molecular epidemiology of VREfm isolates from the first appearance at our university hospital in 2004 until 2010. There is only very scarce information about the molecular epidemiology of VREfm from this early time in Germany. Methods Our analysis includes all available first VREfm isolates of each patient at our tertiary care center collected during the years 2004–2010. If available, additional consecutive VREfm isolates from some patients were analyzed. We used multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) for the analysis and description of nosocomial transmission pathways as well as the detection of outbreaks. Results VREfm isolates from 158 patients and 76 additional subsequent patient isolates were included in the analysis. Until 2006, detections of VREfm remained singular cases, followed by a peak in the number of VREfm cases in 2007 and 2008 with a subsequent decline to baseline in 2010. MLST and cgMLST analysis show significant changes in the dominant sequence types (STs) and complex types (CTs) over the study period, with ST192 and ST17 being responsible for the peak in VREfm cases in 2007 and 2008. The four largest clusters detected during the study period are comprised of these two STs. Cluster analysis shows a focus on specific wards and departments for each cluster. In the early years of this study (2004–2006), all analyzed VREfm stemmed from clinical specimens, whereas since 2007, approximately half of the VREfm were detected by screening. Of the 234 VREfm isolates analyzed, 96% had a vanB and only 4% had a vanA resistance genotype. Conclusions This retrospective study contributes significant knowledge about regional VREfm epidemiology from this early VREfm period in Germany. One remarkable finding is the striking dominance of vanB-positive VREfm isolates over the entire study period, which is in contrast with countrywide data. Analysis of cgMLST shows the transition from sporadic VRE cases at our institution to a sharp increase in VRE numbers triggered by oligoclonal spread and specific outbreak clusters with the dominance of ST192 and ST17

Rupture of anterior communicating artery aneurysms during computed tomography angiography: description of the pathway for intraseptal and intraventricular hemorrhage.

Intraventricular hemorrhage is common after the rupture of anterior communicating artery (ACoA) aneurysms, although the anatomical pathway has not been described. Knowledge of the mechanism of hemorrhage may enhance understanding of its prognosis. Using CT angiography, the authors analyzed this pathway in 2 cases of ACoA aneurysm rupture associated with intraventricular hemorrhage. The initial hemorrhages created a hyperdense ventriculographic image on which the subsequent contrast medium ejection could be followed. The contrast medium entered the subarachnoid space of the anterior interhemispheric fissure and broke through the lamina rostralis into the septum pellucidum and into the frontal horns of the lateral ventricles. Thus, the authors provide an explanation for bleeding from ACoA aneurysms into the ventricular system in the presence of an intact lamina terminalis. The septum pellucidum may act as a buffer before extension of the bleeding into the ventricular system