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Critical Care
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Improvement of prognostic performance in severely injured patients by integrated clinico-transcriptomics: a translational approach

Authors: Daniel Rittirsch, Veit Schoenborn, Sandro Lindig, Elisabeth Wanner, Kai Sprengel, Sebastian Günkel, Barbara Schaarschmidt, Sonja Märsmann, Hans-Peter Simmen, Paolo Cinelli, Michael Bauer, Ralf A. Claus, Guido A. Wanner

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

Severe trauma triggers a systemic inflammatory response that contributes to secondary complications, such as nosocomial infections, sepsis or multi-organ failure. The present study was aimed to identify markers predicting complications and an adverse outcome of severely injured patients by an integrated clinico-transcriptomic approach.

Methods

In a prospective study, RNA samples from circulating leukocytes from severely injured patients (injury severity score ≥ 17 points; n = 104) admitted to a Level I Trauma Center were analyzed for dynamic changes in gene expression over a period of 21 days by quantitative RT-PCR. Transcriptomic candidates were selected based on whole genome screening of a representative discovery set (n = 10 patients) or known mechanisms of the immune response, including mediators of inflammation (IL-8, IL-10, TNF-α, MIF, C5, CD59, SPHK1), danger signaling (HMGB1, TLR2, CD14, IL-33, IL-1RL1), and components of the heme degradation pathway (HP, CD163, HMOX1, BLVRA, BLVRB). Clinical markers comprised standard physiological and laboratory parameters and scoring systems routinely determined in trauma patients.

Results

Leukocytes, thrombocytes and the expression of sphingosine kinase-1 (SPHK1), complement C5, and haptoglobin (HP) have been identified as markers with the best performance. Leukocytes showed a biphasic course with peaks on day 0 and day 11 after trauma, and patients with sepsis exhibited significantly higher leukocyte levels. Thrombocyte numbers showed a typical profile with initial thrombopenia and robust thrombocytosis in week 3 after trauma, ranging 2- to 3-fold above the upper normal value. ‘Relative thrombocytopenia’ was associated with multi-organ dysfunction, the development of sepsis, and mortality, the latter of which could be predicted within 3 days prior to the time point of death. SPHK1 expression at the day of admission indicated mortality with excellent performance. C5-expression on day 1 after trauma correlated with an increased risk for the development of nosocomial infections during the later course, while HP was found to be a marker for the development of sepsis.

Conclusions

The combination of clinical and transcriptomic markers improves the prognostic performance and may represent a useful tool for individual risk stratification in trauma patients.
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Metadata
Title
Improvement of prognostic performance in severely injured patients by integrated clinico-transcriptomics: a translational approach
Authors
Daniel Rittirsch
Veit Schoenborn
Sandro Lindig
Elisabeth Wanner
Kai Sprengel
Sebastian Günkel
Barbara Schaarschmidt
Sonja Märsmann
Hans-Peter Simmen
Paolo Cinelli
Michael Bauer
Ralf A. Claus
Guido A. Wanner
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-1127-y

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