BACKGROUND: We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.
METHODS: We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14.
RESULTS: Complicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings.
CONCLUSION: Genomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS.
LEVEL OF EVIDENCE: Epidemiologic study, level III.
Supplemental digital content is available in the article.
From the Departments of Surgery (E.L.V., R.U., R.D., A.G.C., L.F.G., D.C.N., A.L.C., J.L., B.M., L.L.M., F.A.M., P.A.E.), Molecular Genetics and Microbiology (C.M.L., H.V.B.), and Anesthesia (T.O-B., A.B.), and Institute on Aging (C.L.), University of Florida College of Medicine, Gainesville, Florida.
Submitted: August 2, 2013, Revised: October 11, 2013, Accepted: October 11, 2013.
This study was presented at the 72nd annual meeting of the American Association for the Surgery of Trauma, September 18–21, 2013, in San Francisco, California.
The work represents a secondary use of this public database, and the conclusions and discussion are the authors and do not necessarily represent the views of either the Glue Grant, Massachusetts General Hospital, or the National Institute of General Medical Sciences.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jtrauma.com).
Address for reprints: Philip A. Efron, MD, Department of Surgery, University of Florida College of Medicine, PO Box 10019, Gainesville, FL 32610-0019; email: firstname.lastname@example.org.