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.
C4TS AUTUMN 2014 NEWSLETTER | Issue 4
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Research Project Spotlight “Preclinical Research: A Necessity for Clinical Discovery” By
Dr Jordi Lopez-Tremoleda:
Experimental Models Core Manager
Background Preclinical studies utilizing animal models remain vital for characterizing the body’s reaction to injury, investigating the pathophysiological mechanisms of trauma and testing novel therapeutics and interventions. Model standardization and quality assurance, along with implementation of clinically relevant readouts are priorities to ensure research findings can be rapidly translated into practice.
Challenges and opportunities Trauma is a very complex and heterogeneous condition. Good models need to simulate immediate post-injury response to both injury itself and the management of a severely injured patient.
Dr Jordi Lopez-Tremoleda analysis, ExMoCo research is continuously developing as an integral part of our Centre’s focused research strategy to improve acute diagnosis, treatment and outcomes for trauma patients.
No single model can completely simulate the complex clinical scenario associated with traumatic injury. Stratified studies are conducted in different animal species that model various types of injury and clinical scenarios.
Objectives The Experimental Models Core (ExMoCo) provides various preclinical models targeting mechanisms of disease and drug efficacy. Most work is based on mice and rats models of trauma, since they are well characterized (from genome to physiology), accessible and readily amenable to genetic manipulation to support discovery research. The use of clinically relevant readouts is crucial to accelerate translation of any research findings from experimental models into patients. By combining these measures with
Education is another major focus of ExMoCo, to provide training that ensures the best preclinical research, with the principles of the 3Rs (Replacement, Reduction and Refinement) and providing the framework for humane animal research, always ensuring compliance with national and international legislation regulating the use of animals in scientific procedures.
Working closely with the clinical expertise within the C4TS, the ExMoCo is leading on the optimisation of regulatory path finding studies for developing new drug and treatment strategies in trauma. In parallel, the Core has been fostering close links with other key partners across the College (e.g. BSUs, Genome Centre). Externally ExMoCo has also been fostering a likeminded international network of academic and industrybased preclinical expertise, to ensure our models and tools more closely reflect human biology and predict the efficacy and safety of new medicines for trauma patients. Click here for more information about the C4TS experimental models core.
WHAT THE UNIT MEASURES
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ExMoCo brings together a diversity of veterinary and scientific expertise to capture clinically-relevant data in various models of trauma (i.e. haemorrhage, shock, brain & spinal cord injury).
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Translatable measures include full haematology, functional coagulation profiles, prognostic biomarkers, in vivo anatomical and functional imaging, organ biochemistry and histopathology.
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We also perform behavioral assessments looking at functional deficits with a view to better informing clinical prognosis and rehabilitation programs.
C4TS AUTUMN 2014 NEWSLETTER | Issue 4
3 NEW RESEARCH STAFF
Trauma Education C4TS has enrolled a record number of students to our 2014/15 Trauma Masters courses. We have attracted 64 new students to the MSc Trauma Sciences program which includes, Military & Austere and Orthopaedic specialties. We have 45 Year 2 students who will make up our second successful cohort of programme alumni this December. C4TS’s reputation for excellence in education, as well as research, continues to grow, attracting applications from as far afield as Australia, China, Singapore, Nigeria, Canada, Trinidad & Tobago and Thailand! For more Education information, click here.
ENGAGE WITH US ENGAGE WITH US ENGAGE WITH US ENGAGE WITH US ENGAGE WITH US ENGAGE WITH US
Outreach Activities On the 28 August, C4TS ran The Trauma Show as part of the Centre of the Cell’s program of summer events. The Trauma Show was developed by C4TS as a fun and informative outreach tool targeted at children 7 years and up.
(Above - starting from the top)
Joanna Shepherd “'I am a general surgery trainee and have recently joined the C4TS team as a Trauma Research Fellow. I have completed Year 1 of the Trauma Sciences MSc, and hope to continue to develop my interest in trauma through higher studies with the department.”
It is an interactive science show which includes demonstrations about blood and traumatic injuries. Participants are shown what blood is and the science and impact of blood loss, including coagulopathy, is explained. Each session also offers children and their families the opportunity to take part in a multimedia show inside the cell-shaped Pod venue, suspended over the laboratories of the Blizard Institute where C4TS is based. Outreach programs are an important part of C4TS’s mission to inspire and encourage the next generation of trauma scientists and clinicians. Please contact s.gillespie@qmul.ac.uk if you or your family would like to know more about our shows.
ANNOUNCEMENTS
Fabrizio Marreno “I am replacing the former Clinical Trial Coordinator (Claire) during her maternity leave. I am a nurse with background in clinical research and my last appointment was at the Imperial Clinical Research Facility. “ Somayyeh Mossadegh After 10 years in the RAF, I have just left having completed my commission and am looking forward to the next chapter of my life. My aim during the next few months is to work in conjunction with QMUL computer scientists to develop a governance tool for the Defence Medical Services using Bayesian Networks.
Congratulations to C4Ts Lead, Professor Karim Brohi upon his appointment as the Pan London Clinical Director of the Major Trauma Operational Delivery Network. The London Trauma Research Forum is happening at the Royal Geographical Society, th London on 9 December 2014, as part of the annual London Trauma Conference. We will shortly be launching a website called After Trauma which will connect and support survivors of traumatic injury. More information in the next newsletter.
ENGAGE WITH US Please do connect with us via our website (www.C4TS.qmul.ac.uk) and via Twitter (@CommsC4TS).