Barts c4ts winter 2017 newsletter

C4TS Newsletter Winter 2017 Issue 12 Welcome to the C4TS Winter 2017 newsletter. In this edition, we are pleased to announce that we have received funding for the CRYOSTAT-2 Randomised Control Trial (RCT). The trial will test the impact of delivering the clotting agent cryoprecipitate to trauma patients within 90 mins of admission, in the hope that this will reduce deaths from major haemorrhage. We have also commenced a Pan London prospective observational study called MODET, which will examine the incidence and impact of Multiple Organ Dysfunction (MODS) in elderly trauma patients. On the neuroscience front, Dr Ping Yip outlines his team’s discoveries about Galactin-3 in traumatic brain injury. We also welcome new starter Kerry Staab as our patient representative.

CRYOSTAT-2 Background As we noted in the Autumn 2016 issue, major haemorrhage is the most common preventable cause of death in the trauma population, with most deaths occurring within the first six hours after injury. As many as four in every 10 patients affected by severe trauma die from uncontrolled bleeding.

C4TS research has shown that low fibrinogen levels on admission to hospital are predictors of early mortality in trauma patients. Fibrinogen is a blood protein essential for forming clots and replacing it early with specific fibrinogen-rich blood transfusions may save lives.

Cryoprecipitate

Cryoprecipitate is a concentrated source of fibrinogen and is already used as a treatment for patients with major bleeding. However, transfusion typically occurs late (three hours or more) after arrival in the Emergency Department.

In 2013, C4TS working with NHS Blood & Transplant (NHSBT) undertook CRYOSTAT-1, a small Centre for Trauma Sciences

study that found it was feasible to deliver cryoprecipitate to trauma patients within an hour of admission, and that this appeared to reduce mortality.

Cryostat-1 outcomes: only two patients died in the cryoprecipitate study arm, compared to six patients given standard treatment

CRYOSTAT-2 We are pleased to announce that C4TS and NHSBT have been awarded ÂŁ2.4m from the National Institute for Health Research Health Technology Assessment Programme and Barts Charity to carry out a large multi-centre Randomised Controlled Trial (RCT) to evaluate early cryoprecipitate in major traumatic haemorrhage

Newsletter Winter 2017

www.c4ts.qmul.ac.uk

Dr Ross Davenport (Principal Investigator, CRYOSTAT-2)

by Dr Ross Davenport (Principal Investigator) (CRYOSTAT-2).

The trial will test the effect of early cryoprecipitate (within 90 minutes of admission) compared to standard blood transfusion therapy, on 1544 severely bleeding trauma patients at all Major Trauma Centres (MTCs) across England and at selected international partners in North America and Australia. Patient recruitment will commence in July 2017 and the trial will run for 36 months. The study will provide the answer to whether early cryoprecipitate transfused for major traumatic bleeding saves lives.

This will be the first national transfusion study in the UK since trauma networks were established in England and Wales.

Improved transfusion practices have the potential to save millions of lives globally.

More information can be found on our website or by contacting Dr Ross Davenport

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Multiple Organ Dysfunction in the Elderly Trauma Patient

By Dr Elaine Cole (Senior Investigator)

The MODET Study On 1st of February 2017, a Pan London Trauma System prospective observational study called MODET (Multiple Organ Dysfunction in Elderly Trauma) recruited its first patient. Funded by the Dunhill Medical Trust, MODET is a two year study which will examine the incidence and impact of Multiple Organ Dysfunction (MODS) in elderly trauma patients from London’s four Major Trauma Centres - Royal London Hospital, St Marys Hospital, Kings College Hospital and St Georges Hospital.

Background For the first time ever there are 11 million people aged 65 or over in the UK. As people live and remain active for longer, the number of older people suffering traumatic injury is increasing. In those who survive the initial period after major trauma, a significant proportion goes onto develop MODS. Many younger injured people who develop MODS will recover quickly, whereas older patients appear to suffer prolonged organ dysfunction, which is complicated by persistent immunosuppression, infectious episodes and extended hospital stays. MODS in older people is

associated with increased mortality, and the longer term recovery for survivors is currently unknown. The MODET study will run for two years and each London Major Trauma Centre will aim to enrol 130 older patients (>64 years) and 207 younger patients (< 64 years). More information can be found on our website or by contacting Dr Elaine Cole

A Possible TBI Therapy Target

By Dr Ping Yip (Lecturer in Neuroscience) Traumatic brain injury (TBI) is currently a major cause of morbidity and mortality, with an estimated 2.5 million people affected per year in Europe.

To date, there is no effective treatment for TBI, so there is a critical need to understand the disease and identify effective therapy.

Recently, it has been demonstrated that within the first 24 hours after TBI, several inflammatory response factors become increased, including a molecule from the lectin family called galectin-3.

Right: levels of Galectin-3 at 2 and 24 hours after murine TBI

MODET study objectives     

Identify the prevalence, severity and patterns of MODS in older patients (compared to younger controls) Determine predictors and risk factors of developing MODS in older patients (compared to younger controls) Identify age related characteristics that contribute to the development of MODS Examine the mode of mortality associated with MODS Analyse the relationship between MODS and longer term recovery and quality of life for older patients (compared to younger controls)

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Newsletter Winter 2017

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In a study carried out by myself and Dr Burguillos, we investigated the role of galectin-3 in TBI. In rodent studies, we showed a large increase in galectin-3 expression in microglia, a type of glial cell present in the central nervous system that is involved in the initial brain defence and immune system. Also, TBI resulted in an increase in the released form of galectin-3 at 24 hours in the cerebrospinal fluid, a fluid that bathes the brain and spinal cord.

These data suggest that when the brain is injured, microglia produces galectin-3. When a neutralising antibody against galectin-3 was administered, there was a decrease in the expression of pro-inflammatory markers in the brain. Furthermore, removal of galectin-3 promotes neuroprotection in the cortical and hippocampal cell populations after head injury.

In summary, these results suggest that following head trauma, released galectin-3 may act as an alarmin (molecule from a damaged cell that triggers an immune response), binding, and promoting inflammation and neuronal loss. Therefore, reducing the amount of galectin3 after TBI may be an effective method for the treatment of TBI. These findings require further pre-clinical trials.

More information on this study can be found in this Nature article, or by contacting Dr Ping Yip

Trauma Summit 2016: Putting Trauma On The Map On 13 December 2017, a Trauma Summit for past and present Trauma MSc students was held at the Gore Hotel, Kensington.

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Over 40 students and alumni attended the afternoon, which included a talk by Susanna Flood, former Media Director at Amnesty International, who shared her invaluable experience in creating successful public awareness campaigns. 2016 Summer School students also presented their group communications project #DontBreakTheChain, which promoted the importance of trauma systems.

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Newsletter Winter 2017

Congratulations to C4TS research fellow Rich Carden who has received a Young Investigator Award of ÂŁ1000 from the Royal College of Emergency Medicine. Rich won the award to help continue his research into inflammation and multiple organ failure in trauma patients.

Our new starters for February 2017 include Kerry Staab, who will be taking the lead on public and patient involvement (PPI) in the Centreâ&#x20AC;&#x2122;s research and patient supporting activities. As the carer of a son who suffered life-changed injuries due to a workplace accident several years ago, Kerry has first hand experience of trauma and its impact on patients and families. .

Welcome Kerry!

Congratulations are also due to the 46 students who graduated from the Centreâ&#x20AC;&#x2122;s MScs in Trauma Sciences and Orthopaedic Trauma Sciences in December 2016. This is the highest number of graduates from our pioneering distance learning programs since they were established in 2011.

On 14 December 2016, C4TS held the first ever Pan London Major Trauma System symposium at the Royal Geographic Society in Kensington.

Over 350 clinicians from all fields of London trauma care came together to share issues, research & innovation. Click here to watch the keynote address by Professor Sheldon Teperman from NYC. 3