Elsevier

The Lancet

Volume 363, Issue 9426, 19 June 2004, Pages 2076-2083
The Lancet

Series
Injury research in the genomic era

https://doi.org/10.1016/S0140-6736(04)16460-XGet rights and content

Summary

With the development of trauma systems, improved resuscitation, and organ system support, survival after severe injury is common, but is often complicated by nosocomial infection and organ failure. These complications are costly, and can lead to death or disability. Although much is known about the pathophysiology of posttraumatic nosocomial infection and organ failure, findings have been limited by our ability to generate and analyse large amounts of experimental and observational data. However, technological advances in nucleic acid and protein analysis, coupled with increased computational capacity, provide an opportunity to characterise the determinants of and the responses to injury and sepsis on a genome-wide scale. New large-scale collaborative efforts aim to investigate the genome for variation (gene polymorphisms), characterise multiple levels of the biological response to injury (transcriptome and proteome), and relate these to clinical phenotypes. In this article, we summarise recent findings and explore where promising new technologies might have the greatest potential for increasing our knowledge. It will now be important to determine how these recent technological advances can be used and integrated with our existing approaches, to reduce death, disability, and the economic consequences of trauma.

Section snippets

SIRS model

Systemic injury, shock, or infection incites physiological responses of fever, tachycardia, tachypnoea, and leucocytosis that collectively have been used to define the systemic inflammatory response syndrome (SIRS).8 This concept has been extrapolated, in part, from carefully controlled, but potentially insufficient, experimental models to describe the physiological and biological response in patients with a range of clinical conditions.9, 10 For example, the physiological and biological

Alternative model

We propose an alternative model of the systemic response to tissue injury; in which the usual systemic response to tissue injury and infection serves to prevent systemic inflammation and maintain homoeostasis.24 figure 3B illustrates this concept, albeit in a simplistic two-dimentional way. Homoeostasis is influenced by the net effect of extracellular mediators and alterations in intracellular signalling pathways. This model differs from the SIRS/CARS (systemic inflammatory response

Functional genomics and biocomplexity

Recent advances in computational biology and high-throughput technologies for biomedical research are creating a growing interest in a more global, complex biological systems approach to the study of host responses in critical illness and injury.39, 40 Clinical phenotypes are determined by complex, dynamic interactions from the molecular to the organ system level (figure 1). Although accepted for decades, this tenet has been largely avoided until recently because the tools to map these

Future directions

Trauma is a major source of morbidity and mortality, with associated societal costs in the United States that exceed US$469 billion annually (data from the US National Safety Council). In fact, based on the best available data, injury will equal or surpass communicable disease in the year 2020 as the number one cause of disability-adjusted-life-years worldwide.96 The prevention and treatment of injury-induced organ dysfunction is an international priority. Despite these alarming statistics,

Glossary of terms

cDNA
Complementary DNA
cRNA
Complementary RNA
Genome
The genetic material (DNA) of an organism
Haplotype
A set of genes that are inherited as a unit
Mircosatellite
Regions of DNA where short sequences are repeated
Phenotype
The observable properties of an organism
Proteome
The complete protein complement of the genome
Single nucleotide poymorphism
A common, single-base variation in DNA sequence
Transcriptome
The complete RNA complement of the genome

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