Tissue specific and cell derived biomarkers in the early management of traumatic and thermal injuries

Although the major and immediate cause of death following severe trauma is bleeding, many patients die later following complications such as sepsis and organ failure.

Milestone n:0%

What does each milestone mean?

1 = Clinical need
2 = Idea
3 = Proof of concept
4 = Proof of feasibility
5 = Proof of value
6 = Initial clinical trials
7 = Validation of solution
8 = Approval and launch
9 = Clinical use
10 = Standard of care

Aim

The aims of our research are to improve our understanding of the physiological responses to both severe burn and traumatic injuries. By collecting pre-admission and daily samples from our patient cohorts (Golden Hour and SIFTI studies) we will measure key changes within the immune, inflammatory and haematological systems. This research aims to identify novel panels of biomarkers and therapeutic targets that will ultimately change clinical practice and decrease both morbidity and mortality.

Lay Summary

Although the major and immediate cause of death following severe trauma is bleeding, many patients die later following complications such as sepsis and organ failure. An individual’s immune response to injury significantly influences the chances of developing these life-threatening conditions. However, very little is known with regards to the immune and inflammatory status of trauma patients in the immediate aftermath of injury. We have shown that both Immune cell activation and the generation of inhibitory cells occurs within minutes of injury. This shows that the early response to injury is not only important for understanding the physiology of trauma but opens up the possibility of developing novel biomarkers and therapies. We are now also studying in detail the immune system for 2 weeks following severe burns injury and will confirm whether our unique panel of biomarkers can also predict sepsis and organ failure.

Background

Although the major cause of death following severe trauma is bleeding, many patients die later following complications such as sepsis and organ failure. These patients, therefore, consume large amounts of critical care and hospital resources. Human experimental research is required to better understand the hyper-acute immune response to damage before early stratification, identification of potential targets, and therapeutic modulation are possible. The identification of reliable outcome predictors in severe sepsis is vital for the early diagnosis and prognosis and for stratifying patients onto various treatment regimes. Our studies, therefore, focus on the immunological, inflammatory and haematological responses following both severe burns and traumatic injury. This has not only increased our understanding of the physiological responses following injury but resulted in the identification of candidate biomarkers and novel therapies.

Method

We are collecting and storing vast numbers of blood and urine samples from our 2 main patient cohorts (e.g. Golden Hour and SIFTI studies). This involves close collaboration with both our trauma and burns clinical teams. Immune function (e.g. a Neutrophil function) and Haematological parameters are immediately measured within fresh samples. Inflammatory and ageing biomarkers (e.g. cytokines, extracellular vesicles, DNA methylation, Neutrophil Extracellular Traps, metabolites etc) are regularly measured in batches from thawed cellular, plasma and serum samples. Validated sample results are entered into large clinical databases to enable a statistical analysis to determine the relationship of the biomarkers with the clinical status and outcomes of individual patients. New research findings are presented at national and international meetings and published within leading scientific journals.