ORGAN DYSFUNCTION AND PROTECTION

Our current research programme projects are listed below.

Trauma Organ Protection using Artesunate (TOP-ART)

C4TS are conducting a Phase 2a clinical trial of Artesunate for the protection of organs in severely injured trauma patients with traumatic haemorrhage. We have discovered the drug enhances the protection of organs by reducing the body’s excessive response (i.e. inflammation) to injury and blood loss, and by activating well-known cell-survival pathways. 

A therapeutic agent that reduces the incidence and severity of multiple organ failure could have a major global impact on trauma patient outcomes and their demands for healthcare utilisation. The trial started at the Royal London Hospital in 2017.

More information about TOP-ART

TOP-ART on the ISRCTN trial registration site

MODET:  Multiple Organ Dysfunction in Elderly Trauma

It is not clear from the available international evidence if age-related characteristics or other factors such as frailty affect the development and severity of MODS. MODET (Multiple Organ Dysfunction in Elderly Trauma) is a Pan London Trauma System prospective observational study, funded by the Dunhill Medical Trust. A key objective is to identify the prevalence, severity and patterns of MODS in older patients, including predictors and risk factors.  Patients have been enrolled from the four Major Trauma Centres (Royal London Hospital, St Marys Hospital, Kings College Hospital and St Georges Hospital) over a two year period.

More information about MODET

ORDIT: Organ Dysfunction in Trauma: A National Point Prevalence study

Multiple organ dysfunction syndrome (MODS) is a dysfunctional systemic inflammatory response following major tissue trauma. Despite reductions in the reported incidence of MODS over recent years it remains a resource-intensive, morbid and potentially lethal sequelae following serious injury.  

ORDIT was a one month, prospective point prevalence cohort study of trauma patients (≥16 years) admitted to UK Major Trauma Centre (MTC) adult critical care units during Spring 2016. The primary outcome was to describe the patterns of single and multiple organ failure following trauma (identified using Sequential Organ Failure Assessment [SOFA] scoring). Data from the study is now being analysed. 

More information about ORDIT

Trauma Immunology

The human body's response to injury is complex and vital to survival.  Many of the 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. We are investigating the nature of the systemic immune-inflammatory response to trauma using gene expression profiling of blood samples taken from trauma patients on first admission to hospital and throughout their treatment.

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.

More information on our trauma immunology studies

Inhibitors of NF-kB

C4TS has developed an experimental model to test the effects of drugs during resuscitation on the development of organ injury and dysfunction.

Using this model, we have discovered that the activation of the transcription factor nuclear factor kappa B (NF-kB) occurs in all organs that later develop organ failure. We are now testing specific interventions which inhibit the activation of NF-kB when given at the time of resuscitation in order to evaluate whether such remedies also reduce the incidence or the severity of multiple organ failure.

Staff and Publications

Research Theme Leads:

Professor Chris Thiemermann (Discovery)

Professor Karim Brohi  (Clinical)

QM Co-investigators:

  • Professor Joanne Martin
  • Professor Norbert Avril 
  • Professor Magdi Yaqoob
  • Dr. Rupert Pearse
  • Dr Daniel Pennington
  • Dr. Michael O’Dwyer 

Research team:

Collaborators:

  • Dr. Mark Turner (Nottingham Trent)
  • Dr. Carl Hauser (Harvard)
  • Professor Michael Bauer (Germany) 
  • Dr. Anthony Cerami and Dr. Michael Brines (Netherlands)
  • Professor Peter Radermacher (Ulm)
  • Dr. Dan Traber (Texas)
  • Professor Marc Jeschke (Toronto)
  • Professor Helder Mota-Filipe (Lisbon)
  • Professor Shabbir Moochhala (Singapore)
 

Findings

Using experimental models, we have discovered that the intravenous injection of small doses of artesunate (1 to 4.8 mg/kg) upon resuscitation after severe haemorrhage reduces multiple organ failure

Findings

By analysing immune cell genes in blood from critically injured trauma patients, we have discovered that changes in the first few hours of injury can identify patients who go on to develop multiple organ dysfunction syndrome

 

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