C4TS Newsletter www.c4ts.qmul.ac.uk Spring/Summer 2017 Issue 13 Welcome to the C4TS Spring/Summer 2017 newsletter. In this edition, we outline our discoveries about the widespread inflammatory response of the body’s immune system that occurs after severe trauma. Our analysis of the ‘genomic storm’ in the hyperacute phase sheds more light on the little understood problem of Multiple Organ Dysfunction Syndrome posttrauma which can be devastating for patients. We provide an update on our CRYOSTAT-2 Randomised Control Trial and an extract from Professor Brohi’s PLOS think-piece about the future of trauma research. Finally, Barts Charity has launched a major appeal to increase funding for trauma research with support from high profile rapper Professor Green.
The (C4TS Lead)
Professor Karim Brohi
Immune Response and Multiple Organ Dysfunction Background Multiple Organ Dysfunction Syndrome (MODS) is the failure of several organs (including lung, heart, kidney and liver), which contributes to the deaths and morbidity of many critically injured patients who survive their initial physical insult. It is a poorly understood condition with no proven therapies.
patients with minor injuries, and healthy volunteers.
by Professor Karim Brohi (C4TS Lead)
Out of 29,385 immune cell genes, we identified only 1,239 that were different between critical and control patients immediately after injury. However, by 24 hours after injury, this response had grown into a widespread immune reaction involving a ‘genomic storm’ of 6,294 genes.
Looking at the genes more closely, the team found that certain white blood cells, including ‘natural killer’ cells and ‘neutrophils’, emerged as potentially central to the immediate response to critical injury, while others, such as T-cells and B-cells, were less important.
A new C4TS study has found that testing blood samples within the first two hours of injury (the ‘hyperacute window’) could help predict which critically injured patients are more likely to develop multiple organ failure.
The study Our team studied blood samples from 70 critically injured patients, which were taken immediately on arrival in the resuscitation room (within two hours of injury). The team compared these samples with blood samples taken at 24 hours and 72 hours after injury, from
Centre for Trauma Sciences
Newsletter Spring-Summer 2017
Left: Cluster analysis of differentially expressed genes in MODS versus NoMODs patients in the hyperacute window.
When comparing the immune cell genes expressed in patients who later developed MODS to those who did not, most differences were seen immediately after injury.
Implications The first minutes or hours after a traumatic injury are a key window where a patient’s immune response may set the trajectory for whether they develop organ failure. If we can understand the mechanisms that lead to poor outcomes, we may be able to help bring dramatic improvements through better diagnostics and therapeutics. Read the full article here. 1
CRYOSTAT-2 Trial Update By Mr Ross Davenport (Senior Investigator)
The CRYOSTAT-2 Trial
from individual sites about how to maximise recruitment and running of the study to ensure we are able to deliver the trial within the specified timelines. Work to bring on study sites in North America continues with partners at The University of Texas Health Science Center and the Center for Translational Injury Research, Houston Texas. We hope to have up to ten Level 1 trauma centres in the USA and Canada on board and will start recruiting patients to the international arm of the study in early 2018.
In the last issue, we announced that C4TS and NHSBT had been awarded £2.4m from the National Institute for Health Research Health Technology Assessment Programme and Barts Charity to carry out CRYOSTAT-2, a large multi-centre Randomised Controlled Trial (RCT) to evaluate early cryoprecipitate in major traumatic haemorrhage. Our earlier study (CRYOSTAT-1) had suggested that early administration (within an hour of hospital admission) of this concentrated source of fibrinogen could save more lives. Fibrinogen is the key pro-coagulant factor needed for stable clot formation and the first clotting protein to fall during active major bleeding. 25% of all trauma patients have abnormal blood clotting, which causes higher rates of major haemorrhage and four fold increased risk of death. The primary clotting abnormalities in trauma are increased clot breakdown and low fibrinogen levels. CRYOSTAT-2 will test the effect of early cryoprecipitate (within 90 minutes of admission) compared to standard blood transfusion therapy on 1568 trauma patients, to determine whether in major traumatic haemorrhage it saves lives. .
Trial launch
May 2017: UK MTC CRYOSTAT-2 investigators gathered in London in May to prepare for patient recruitment
Centre for Trauma Sciences
Nationwide patient recruitment for the RCT launched this month (July). All 23 Major Trauma Centres (MTCs) have agreed to participate, the first time all MTCs have jointly participated in a clinical trial. At the first Investigators meeting in May, the study team were able to learn a lot Newsletter Spring-Summer 2017
CRYOSTAT-1 findings: Mr Ross Davenport discusses the impact of early cryoprecipitate administration on fibrinogen levels compared to standard transfusion practice
More information can be found on the C4TS website and the CRYOSTAT-2 website or by contacting Mr Ross Davenport.
Trauma research futures “Opportunities now exist not just for avoiding death but for returning survivors to full health and function. The global demand for solutions in reconstruction, regeneration, and rehabilitation across the patient’s journey is immense. The opportunities offered by bioengineering, regenerative medicine, robotics, and digital technologies are potentially transformative. Innovators in academia and industry can now collaborate and capitalise on more defined translational pathways, clearer regulatory frameworks, and access to patients through clinical research networks. This work is also likely to benefit a broad range of nontrauma conditions with components of tissue loss, healing, and loss of function.” Extract from Professor Brohi and Dr Schreibers’ forthcoming Perspectives piece for Public Library of Science (PLOS) Collections Trauma Special Issue. Professor Brohi and Dr Schreiber have co-edited this July 2017 PLOS edition.
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#TransformTrauma 2017! The two ‘Professors’: Professor Brohi talks to rapper Stephen Paul Manderson aka Professor Green about trauma research.
On 16 July, Barts Charity launched the #TransformTrauma appeal, the UK’s first national appeal to raise money for trauma research. The centerpiece of the appeal will be a fundraising concert in London on 9 September, headlined and curated by the rapper Professor Green (Stephen Paul Manderson). The Mirror group are media partners for the campaign. To date, Barts Charity have been major supporters of C4TS, and they are now wanting to create a step change in how the public perceives and engages with trauma research. CEO Fiona Miller Smith said “Nationally, only 1% of healthcare research funding is spent on trauma, despite injuries and violence being amongst the most prominent public health problems in the UK and globally.”
The 2nd annual Royal London Hospital Cyclethon was held on 17 May to mark Trauma Survivors Day. Over 100 clinicians, former patients, lawyers and other supporters static cycled for 12 hours to raise awareness of traumatic injury and encourage donations for research. Two level 1 trauma centres in the USA Vanderbilt (Nashville) and Jefferson (Philadelphia) - also joined in the fun and cycled in solidarity! Also in May, Professor Brohi addressed another sold out session at the popular Pint of Science public engagement series. Professor Brohi discussed the implications of evolutionary biology for how we treat major injury and took questions from a fascinated public.
“We’ve already seen here in London what can be achieved with applied research and maturing trauma system infrastructure – since 2010, there has been a 50% increase in survival rates, over 600 more new survivors. Now every week, someone survives who would have died 6 years ago” “Professor Brohi and his team are in a strong position to continue with world leading translational research and we hope this appeal will consolidate that.” Professor Green is a passionate supporter of the appeal, as he has suffered traumatic injury twice (knife injury and a car collision), and his life was saved by the Royal London Hospital trauma team. Another high profile trauma survivor supporting the appeal is amputee model Vicky Balch, who lost her leg in a rollercoaster ride accident at Alton Towers.
Our new starters include Bebhinn Lernihan, Robert Christie (below left), who are working on our Multiple Organ Dysfunction in Elderly Trauma study, and Esau Moreno Comacho (below right) who has taken on the position of C4TS Data Manager.
More information about the #TransformTrauma campaign including opportunities for involvement can be found here, or contact Nicole Skeltys, C4TS Communications Officer.
Centre for Trauma Sciences
Newsletter Spring-Summer 2017
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