SeriesInjury research in the genomic era
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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Cited by (87)
Inflammation and disease: Modelling and modulation of the inflammatory response to alleviate critical illness
2018, Current Opinion in Systems BiologyCitation Excerpt :Though numerous promising candidate therapies have emerged from decades of pre-clinical studies, none have stood up under rigorous examination in the context of Phase III clinical trials as the elusive “golden bullet” therapy [5,16]. We and others have hypothesized that the very features that make acute inflammation and critical illness a complex system are a key part of this failure, and that precision medicine for critical illness will necessitate the use of systems and computational biology approaches in order to arrive at effective treatment strategies [6,17–20]. Combining the tools of data-driven and mechanistic modelling with experimental studies has provided a deeper understanding of the dynamically changing nature of the acute inflammatory response and introduced methods for discovering effective control modalities [20–26].
Frequency and perforin expression of different lymphocyte subpopulations in patients with lower limb fracture and thoracic injury
2017, InjuryCitation Excerpt :In patients with isolated, uncomplicated injuries, the inflammatory response is temporary, predictable and well-balanced between proinflammatory and anti-inflammatory factors, whereas in patients with multiple injuries, the inflammatory response is markedly enhanced and can lead to the development of SIRS [7,8]. With the development of MODS, the mortality rate of patients with multiple body injuries increases to 50–80% [9–12]. When there is an excessive inflammatory response, an anti-inflammatory response is activated in an attempt to maintain body balance.
From data patterns to mechanistic models in acute critical illness
2014, Journal of Critical CareCitation Excerpt :However, despite the demonstrated validity and usefulness of these types of biological patterns and physiologic signal analyses, these methods remain primarily phenomenologic in nature, in essence connecting physiologic patterns with clinical outcome through the use of statistical methods [36]. As in HRV, inflammation in acute critical illness manifests in patterns evident at the genomic [37-40], proteomic [41-44], and metabolomic [43-45] levels. The growing number of these studies has resulted in a “data deluge [46].”
The New Revised Classification of Acute Pancreatitis 2012
2013, Surgical Clinics of North AmericaAcomputer-based education intervention to enhance surrogates' informed consent for genomics research
2015, American Journal of Critical Care