www.c4ts.qmul.ac.uk
C4TS Newsletter Summer 2019 Issue 19
C4TS RESEARCH NEWS SUMMER 2019 Welcome to the Centre for Trauma Sciences (C4TS) Summer 2019 newsletter. In this edition, Dr Hoffman discusses a new trauma outcomes study called ROWTATE, which is developing a return to work programme for survivors of serious injury. Dr Jennifer Ross gives an overview of the research we are undertaking in the pioneering field of trauma immunology. We highlight the achievements of Mr Martin Griffiths, which have led to his appointment as the NHS’s first clinical director for violence reduction. Finally, we report on some of our public engagement work, including the upcoming ACIT 2000 event which will celebrate achievements enabled by this landmark C4TS study into coagulopathy.
Returning to work after serious injury by Dr Karen Hoffman, head of C4TS Trauma Rehabilitation Research
New study aims to create an effective vocational rehabilitation programme for trauma survivors Background The ROWTATE (Return to Work After Trauma) study aims develop a programme to help moderately and severely injured patients return to work, and to assess how well the programme works. The six-year, £2.4 million project is funded by the National Institute for Health Research (NIHR), and is led by researchers at the University of Nottingham and clinicians at the East Midlands Major Trauma Centre, Nottingham University Hospitals NHS Trust. I am leading C4TS involvement in this important study. Many patients who suffer moderate to severe injury are sadly left with longterm physical, psychological and financial problems and one year on from their initial injury up to one-third of patients will still not have returned to work. Unfortunately, there is llittle specialised vocational rehabilitation support to enable these people to return to paid employment. Method The project will involve clinicians from the East Midlands Major Trauma Centre, the Clinical Trials Research Unit at the University of Leeds, Nottingham Trent University, Queen Mary University London, and four other major trauma centres across England: Addenbrooke’s Hospital, Cambridge; Leeds General Infirmary; Southmead Hospital, Bristol and The Royal London Hospital. The research team will work with patients affected by traumatic injury, NHS service providers and clinical commissioners to develop a rehabilitation programme that will meet the needs of patients and can be supported and delivered by the NHS.Trauma survivors with different kinds of injuries are being consulted on programme design and delivery methods. The pilot programme will then be rolled out at five major trauma centres around England, enrolling about 700 patients.
C4TS Newsletter Summer 2019
Dr Karen Hoffman Study objectives The study will measure how many injured people who receive ROWTATE have returned to work 12 months later, and compare this to people who have not had access to new specialist rehabilitation. The project will also assess the potential impact it has on patients’ physical, psychological and financial problems, to find out whether the new programme is a cost-effective way of reducing demand for NHS services. More info here
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What is trauma immunology? by Dr Jennifer Ross, Clinical Research Fellow Trauma affects the full spectrum of humanity, but the physiological response of affected individuals can vary from person to person. Whilst a lot of work has gone into improving outcomes from severe bleeding, uncontrolled haemorrhage in the acute phase of injury does not account for all trauma deaths. In fact, when patients die following severe trauma, around half of those deaths actually occur after 24hrs. Of these patients, the vast majority display immune system dysregulation that can lead to severe multiple organ dysfunction syndrome (MODS) and immunosuppression with subsequent recurrent infections. For this reason, understanding the immune response to severe injury, from initial drivers to eventual outcomes, is a priority for trauma research. Previous studies looking at the 24-72hr post injury window have shown a complex and widespread immune cell response termed the ‘genomic storm’, with both pro- and anti-inflammatory patterns. The activators of this response are generated by extensive injury-induced immunogenic cell death and include damage-associated molecular patterns (DAMPs or
alarmins) that are both passively and actively released by damaged or dying cells. Understanding such a huge response is difficult, but the potential to trace the cascade of immune responses back towards the point of injury opens up the possibility of identifying early targets for pathway modulation, influencing the clinical trajectory and outcomes for each patient. In order to look at this early window, we have previously performed pilot work using samples taken from trauma patients within 2 hours of injury (hyper-acute). Whole blood transcriptomic analyses of these samples displayed a focused activation of damage recognition-associated innate immune cell pathways, while flow cytometry also revealed increased neutrophils, monocytes, NK cells, and innate lymphocytes such as γδ T cells. Importantly, this study also revealed that almost the entire differential response associated with subsequent MODS (vs. noMODS) was present in the hyper-acute window and the hyper-acute response in patients who later developed MODS was markedly different to the response in individuals who did not get MODS, or indeed to patients with MODS at later time-points. (cont’d p3)
Figure 1: Immune system response to critical injury
Figure 1: From left to right, we see that DAMP and cytokine release in the hyper-acute window after critical injury activates components of the innate immune system via pattern recognition and cytokine (e.g IL-6) receptors. Our trauma immunology research seeks to ascertain whether adverse clinical outcomes result from exceeding a critical damage threshold, or from an abnormal damage response to a level of injury that in some individuals can be tolerated.
Trauma Immunology cont’d The results of our pilot work suggest that differential responses to severe injury in some individuals may lead to adverse clinical outcomes. However they do not rule out the possibility that patients who develop MODS may do so because they were more severely injured in the first place. This highlights the difficulty of assessing injury severity using ISS, as this anatomically based system may not be a good reflection of physiological injury burden related to the extent of actual tissue damage. Going forward, we aim to build on our previous work by attempting to answer a number of key outstanding questions. Crucially, are there differential immune responses to severe injury in the hyper-acute window that lead to distinct, and potentially unfavourable, clinical outcomes (e.g. MODS, infection)? Furthermore, can biomarkers (and potential modifiable targets) of subsequent adverse clinical outcomes be identified in the hyper-acute window? We will expand the transcriptomic analyses performed in our pilot study to a much larger cohort of trauma patients in order to further establish the presence of signatures related to patient outcomes. Analysing hyper-acute samples from the same cohort of patients, we will look for patterns of immune mediators and DAMPS (as objective indicators of tissue damage) that may relate to the physiological burden of injury. Using these results, we aim to clarify whether traumainduced immune dysregulation is simply a consequence of surpassing an injury threshold, or instead represents a non-physiological response to severe injury occurring only in certain individuals. We will also aim to identify drivers and potential modifiable targets of immune dysregulation leading to MODS, with the eventual target of improving clinical outcomes for patients affected by severe injury.
Barts Charity’s Trauma Appeal seeks to raise community awareness of the impact of traumatic injury and the need for further investment in trauma research and treatments. You can help by sharing the Charity’s videos on social media, starting your own fundraising activity or simpy donate by visiting the appeal page: https://www.justgiving.com/campaigns/ charity/blc/transformtrauma
C4TS fellow wins prestigous research awards
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C4TS clinical research fellow Anthony Thaventhiran has been awarded a Royal College of Surgeons of England (RCS) Surgical Research Fellowship and a British Medical Association (BMA) Foundation for Medical Research Lift into Research grant. These prestigous grants will help fund Anthony’s PhD into Acute Traumatic Coagulopathy Anthony Thaventhiran (ACT). The RCS received 96 applications this year and awarded only 20 fellowships. Anthony was competing against many other medical specialities for the BMA award. Anthony said: “My ambition is to become an academic trauma surgeon, and I hope that these two awards will be the launch-pad for my academic career and provide the ideal stepping stone for my research to lead to early clinical trials. Approximately one quarter of trauma patients develop ATC which is associated with a 50% mortality rate. Current therapy involves blood component therapy and tranexamic acid, however, these do not directly target ATC. My PhD aims to investigate novel therapeutics which target the underlying pathology of ATC. Ultimately, I hope to improve patient outcomes from traumatic haemorrhage through my research. “
Are you interested in getting involved with C4TS research? Then why not join the Patient/Public Advisors for Injury Research (PAIR) Group. You can help shape research priorities, communicate information to patients and much more. Contact Scarlett to find out more about this exciting group.
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NHS’S FIRST VIOLENCE REDUCTION CLINICAL DIRECTOR C4TS Trauma Sciences MSc faculty member & Royal London Hospital consultant trauma surgeon will lead the NHS on violence reduction Mr Martin Griffiths, a consultant trauma surgeon at the Royal London hospital major trauma centre and C4TS Trauma Sciences MSc faculty member, has been appointed the NHS’s first clinical director for violence reduction. Martin has spent over 15 years as an influential advocate for violence control, including visiting schools to warn pupils of the dangers of knife and gun crime. He established the innovative Barts Health violence reduction programme, a UK first, which enlists case workers to engage with young patients injured through gang crime while they’re still being treated in hospital, to help break the cycle of violence at the point of crisis. Martin’s enormous public contribution to violence reduction was most recently recognised when he won the NHS Hero Doctor award in 2018. In an interview with the London Evening Standard, Martin said “Every day I see the wasted opportunities of young people stuck on hospital wards with life-changing injuries. “We do everything we can for these patients but don’t just want to patch them up and send them back out to be injured again. By working across the NHS there is more we can do to prevent these attacks happening in the first place. I want to build a network that will empower communities across London to challenge the attitudes and behaviours that result in violence.” Martin’s appointment is part of a broader approach to violence minimisiation required across London. Along with other C4TS clinicians, Martin coauthored the London Major Trauma System’s policy on tackling knife violence, which calls for a public health approach to violence reduction. The policy can be found here.
ACIT 2000 May 2019 saw the recruitment of the 2000th patient into C4TS’s pioneering Activation of Coagulation and Inflamation in Trauma (ACIT) study. Established in 2008, ACIT collects blood and other clinical data from adult trauma patients and provides a platform for multiple analyses to better understand the body’s response to injury. Many of C4TS’s breakthoughs in coagulopathy, organ dysfunction and trauma immunology have been enabled by ACIT.
Mr Martin Griffiths Martin has taken up his new appointment on a part-time basis to enable him to retain his work at the Royal London Hospital and continue to provide invaluable input into C4TS education programmes.
London Trauma System News
by Dr Elaine Cole, Director of Research & Innovation
We have two excellent collaboration and training opportunities coming up! On 4 September, nurses, clinicians & therapists from all disciplines who work with rib injury patients are coming together to develop our first pan-London major trauma system rib injury toolkit.
To celebrate the achievements of this landmark study, C4TS will be holding a public event at the historic St Barts Great Hall, London on the evening of Tuesday evening 12 November 2019. ACIT 2000 will feature speakers from C4TS, trauma survivors and more, and include refreshments.
And on 11 & 12 November, our TORCH course will teach CT1-3 and ST3-6 clinicians how to lead, coordinate and cohere the care that complex polytrauma patients require post-critical care.
For more information please contact Richard Carden
More info & registration details here
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PUBLIC ENGAGEMENT & EDUCATION NEWS C4TS games popular at QMUL Festival Of Communities by Dr Scarlett Gillespie, Post-Doctoral Research Fellow C4TS was part of the QMUL’s Festival of Communities which ran over two days in June, attracting over 3500 members of the local community at the University’s Peoples Palace. The public engagement team had the pleasure of presenting several of the hands-on activities that we developed last year. Our Trauma Jenga game proved to be the biggest draw for adults and children alike! The game aims to highlight how trauma can affect all the different organs of the body. The game allows us to talk about what trauma is, and how our research and clinical trials are trying to improve patient outcomes. Also popular was our craft activity where children can design their own immune cell. Lots of beautiful, sparkly immune cells, catching bacteria and releasing protective chemicals and messengers, were created throughout the day, giving us the opportunity to talk about the important role the immune system plays in protecting the body and how this changes after injury. We loved seeing such a variety of people engaging with our stand, and taking away our leaflets and spare ‘immune cells’ to continuing learning at home! More pictures form the event can be seen on Twitter with the hash tag #immune2trauma.
C4TS researchers & children explore trauma immunology through games at Queen Mary University of London’s community festival.
More information about our public engagement and outreach resources here.
C4TS appoints new teaching fellow Jacqueline Rappoport has been appointed as C4TS’s first Teaching Fellow (Trauma Sciences). Jack will assist the Trauma Sciences MSc programme directors and administrator in day-to-day decision making whilst also helping to coordinate and undertake activities such as assessment design, marking, moderation, programme development and student supervision. Jack has a fascinating background in Counselling and Forensic Psychology, working in Esafety with children and young people, in forensic environments with psychologically co-morbid offenders and with military veterans with family re-integration challenges. She is in the final stages of completing a multi-disciplinary PhD around the wider sociological impact of PTSD on Military Veterans who have offended. Jack says “My academic experience includes teaching Sociology, Criminology and Psychology as well as supporting students with additional learning needs. I’ve joined C4TS at a very exciting time as we prepare for our annual Trauma Sciences MSc summer school, where esteemed faculty from all around the world will teach a huge range of topics including war surgery, orthopaedic injury management, traumatic arrest and thoracotomy, rehabilitation and more. I look forward to providing ongoing support to students during the summer school, providing teaching support to tutors and eventually engaging with research and publication interests.”