C4TS AUTUMN 2014 NEWSLETTER
Issue 4
2
C4TS
AUTUMN 2014 newsletter
WELCOME
Welcome to the Autumn 2014 edition of the Barts Centre for Trauma Sciences (C4TS) Newsletter. In this edition, we outline some recent achievements and the current priorities for the Organ Failure and Protection research stream. Our recent article entitled “The systemic immune response to trauma: an overview of pathophysiology and treatment” (Lancet 2014: 384: 1455–65) provides a deeper context for Chris’ discussion below of trauma related multiple organ failure. We also highlight the preclinical work of our Experimental Models Research Core and update on the continuing growth and development of Trauma education activities.
Prof. Chris Thiemermann: Lead, Organ Failure and Protection Theme Lead, Brain and
Organ Failure and Protection
The human body’s response to injury is complex and vital to survival. Despite life-saving resuscitation in the emergency department, severe blood loss through traumatic injury can lead to the dysfunction of vital organs (i.e. kidney, lung, heart, liver, brain). Approximately 30% of trauma patients who survive the first 48 hours will develop multiple organ failure. This figure rises rapidly as the degree of haemorrhage and shock increases. Even modest improvements in these figures would have a significant impact on patient experience, quality of life and the overall cost of healthcare for seriously injured patients. As yet there are no effective organ protection agents in clinical use and current management is only supportive. Better early care, both in terms of blood transfusion and
Chris Thiemermann (Professor of Pharmacology) 0hr vs. 24hr Expression
novel prophylactic intervention may limit the severity of subsequent multiple organ failure. However, we may be close to the limit of what can be achieved with improvements in resuscitation and there remains a grave need for new effective treatment of trauma-haemorrhage mediated organ failure. New therapies, especially using acute organ protective agents that reduce the incidence and severity of multiple organ failure, will have a global impact on patient outcomes and resource utilization. Understanding the systemic immune response to trauma Complications after severe trauma injury are due to organ ischaemia and an excessive, inappropriate or dysfunctional immune-inflammatory response, and one of our research priorities is to better understand this complex process. The Organ Failure & Protection research theme is investigating the nature of the systemic immuneinflammatory response to trauma using gene expression profiling of blood samples taken from trauma patients (see Figure 1)
Biofunctions
Trauma and organ failure Our C4TS research is focused on further understanding the mechanisms by which the body suffers organ failure after trauma, with the aim of developing and trialing new organ protective agents and therapeutic strategies. .
By
Figure 1 ‘Heat map’ showing either upregulation (red) or down-regulation (green) of gene expression pathways associated with biofunction, comparing Admission and 24-hour post injury samples
These profiles can, for example, distinguish between the bloods of patients with similar injuries who go on to have good outcomes such as complete recovery, or those that sustain multiple organ dysfunction. Our research focuses on patients during the first life-saving hours of care, before widespread inflammation has been established. Other immune response studies to date have generally focused on patients’ pathophysiology at a much longer time period after the initial assault. As we collect samples immediately upon admission and through acute care (ie 3-6 hours) as well as data for up to 28 days after the initial trauma event, we believe we are addressing a key gap in research. Click here to find out more about C4TS research projects.