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Highly Accessed Commentary

Sepsis in transit: from clinical to molecular classification

Simone A Thair1* and James A Russell12

Author Affiliations

1 UBC James Hogg Research Centre, Heart + Lung Institute, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada

2 Division of Critical Care Medicine, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada

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Critical Care 2012, 16:173  doi:10.1186/cc11813


See related research by Maslove et al., http://ccforum.com/content/16/5/R183

Published: 14 November 2012

Abstract

In the previous issue of Critical Care, Maslove and colleagues studied circulating neutrophil transcriptional expression to discover and validate a molecular subclassification of adult patients with sepsis. The authors divided patients into small derivation (n = 55) and validation (n = 71) cohorts. Their complex methodology included partitioning around medoid and hierarchical clustering methods to define two transcriptionally distinct subtypes of sepsis. Pathway analysis found that chemokine and cytokine pathways as well as Toll-like receptor signaling were enhanced. Investigation of specific drug target genes relevant to sepsis found significantly different expression levels between the two molecular subtypes. Interestingly, most patient characteristics did not differ between groups, except for an increase in the proportion of severe sepsis in molecular subtype 1. Possible confounders of this study were the small sample size, population stratification, and lack of information regarding drug interventions, all of which support the need for more studies with larger cohorts that include transcriptional profiles. This thought-provoking hypothesis-generating study could lead to a new neutrophil expression-based molecular classification of adult sepsis.