Validating the genomic signature of pediatric septic shock
Electronic searches were performed in Medline and Embase (1987 to October 2010), supplemented by additional searches in multiple microarray data repositories.We included studies that (1) used microarray, (2) were performed in humans and (3) investigated the host response mediated by circulating leukocytes.We identified 12 cohorts consisting of 784 individuals providing genome-wide expression data in early and late sepsis.Sepsis elicited an immediate activation of pathogen recognition receptors, accompanied by an increase in the activities of signal transduction cascades. However, changes in inflammation related genes were highly variable. Neither a distinctive pro/anti-inflammatory phase nor a clear transition from a pro-inflammatory to anti-inflammatory phase could be observed during sepsis.Complicating this uncertainty is the limited evidence to verify the two-phase model.Cytokine studies have been the mainstay evidence that provide support for the inflammation-based model.
As a result, concerns have been raised regarding the validity of treating sepsis simply as a pro-inflammatory or anti-inflammatory phenomenon.Forty-two children with a clinical diagnosis of septic shock and 15 normal controls served as the training data set, while 30 separate children with septic shock and 14 separate normal controls served as the test data set.Class prediction modeling using the training data set and the previously reported genome-wide expression signature of pediatric septic shock correctly identified 95-100% of controls and septic shock patients in the test data set, depending on the class prediction algorithm and the gene selection method. ; MONACO Marie ; ODOMS Kelli ; SAKTHIVEL Bhuvaneswari ; WONG Hector R.We searched in Medline and Embase, without language restriction, all publications on gene-expression studies between January 1987 and October 2010.In 1987 DNA array technology was first described, hence this year formed the starting point of our search .
NEW YORK (Genome Web) – Sepset Biosciences, a company spun out by the Centre for Drug Research and Development (CDRD), a Canadian national drug development and commercialization center, is developing a rapid diagnostic blood test to aid in the early, targeted treatment of sepsis.