Gliomas are currently classified through integration of histology and mutation information, with new developments in DNA methylation classification. However, discrepancies exist amongst the major classification methods. This study sought to compare transcriptome-based classification to the established methods. RNAseq and microarray data were obtained for 1032 gliomas from the TCGA and 395 gliomas from REMBRANDT. Data were analyzed using unsupervised and supervised learning and other statistical methods. Global transcriptomic profiles defined four transcriptomic glioma subgroups with 91.4% concordance with the WHO-defined mutation subtypes. Using these subgroups, 168 genes were selected for the development of 1000 linear support vector classifiers (LSVC). Based on plurality voting of 1000 LSVC, the final ensemble classifier confidently classified all but 17 TCGA gliomas to one of the four transcriptomic profile (TP) groups. The classifier was validated using a gene expression microarray dataset. TP1 cases include IDHwt, glioblastoma high immune infiltration and cellular proliferation and poor survival prognosis. TP2a is characterized as IDHmut-codel, oligodendrogliomas with high tumor purity. TP2b tissue is mostly composed of neurons and few infiltrating malignant cells. TP3 exhibit increased NOTCH signaling, are astrocytoma and IDHmut-non-codel. TP groups are highly concordant with both WHO integrated histology and mutation classification as well as methylation-based classification of gliomas. Transcriptomic profiling provides a robust and objective method to classify gliomas with high agreement to the current WHO guidelines and may provide additional survival prediction to the current methods.
Background
Multiple blood cultures have been shown to improve pathogen yield and antimicrobial stewardship for adult patients with suspected serious bacterial infection (SBI). For children, the use of multiple blood cultures is less common and volume recommendations are more complicated, often resulting in single cultures with low volume.
Methods
In 2010, Children’s Hospital Colorado instituted electronic medical record (EMR) decision support to recommend collection of 2 blood cultures before administration of antibiotics for suspected SBI. Recommended blood culture volumes were calculated by age rather than weight. We evaluated all children admitted to inpatient units between 2008 and 2009 (pre-intervention) and 2011 and 2013 (postintervention) who received antibiotics in the hospital after having blood cultures drawn in the emergency department, excluding those with a length of stay >8 days. We compared blood culture yield, isolate classification (pathogen vs contaminant), and antimicrobial modifications before and after the interventions.
Results
A total of 3948 children were included in the study. EMR guidelines were associated with a significantly higher number of children with multiple blood cultures drawn before antibiotic administration (88.0% vs 12.3%; P < .001) and an increased percentage of blood cultures with the recommended volume (74.3% vs 15.2%; P < .001), resulting in a significantly higher pathogen isolation rate and improved antimicrobial decisions. Multiple cultures helped define the role of common contaminants in the clinical decision process.
Conclusions
Multiple blood cultures with age-based volumes taken before starting antibiotics increase pathogen isolation rates and appropriate modification of antimicrobial treatment in children.
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