AAGBI/Anaesthesia Project Grant
The successful applicants for the AAGBI/Anaesthesia Departmental Project Grant were:
Principal Applicant
Dr Andrew Conway Morris
Clinical Lecturer, Critical Care Medicine, University of Edinburgh
Title
Characterising T-reg subgroup phenotypes in human sepsis
Amount
£23,968
Scientific Abstract
Sepsis, although classically described as a hyper-inflammatory disease, can result in profound immunosupression. The mechanisms underlying this immunosupression are poorly understood. The recent finding of elevated numbers of immunosuppressive regulatory T-cells (CD4+CD25+FOXP3+) in sepsis provides new insight into why this might happen. We recently identified elevated levels of CD4+CD25+FOXP3+ Treg cells in adult critically ill patients, and found they were associated with a higher incidence of subsequent ICU-acquired infection; a secondary analysis suggested a possible association with increased mortality in sepsis. The characterisation of Tregs in human sepsis has been basic and has not accounted for recent insights into Treg biology, including the presence of differently functional subtypes. Although it is clear that Tregs inhibit lymphocyte proliferation, their potential synergies with other immune cells such as monocytes and neutrophils remain unexplored in sepsis. We will characterise the subtypes of Tregs in human sepsis and further investigate their association with mortality. In addition, we will undertake a comprehensive characterization of Treg subtypes in human sepsis, including exploring functional responses to stimulation, suppressive effects on effector T-cells, and their effects on other immune cell functions including monocyte cytokine responses and phagocytosis and reactive oxygen species production by neutrophils.
First Year Report from Dr Conway Morris (103 KB)
Second Year Report from Dr Conway Morris (337 KB)
Principal Applicant
Dr Robert Sanders
MRC Clinical Training Fellow, Imperial College London
Title
The impact of statins on perioperative mortality in noncardiac surgery in a United Kingdom database.
Amount
£21,873
Scientific Abstract
Controversy plagues research into appropriate preoperative medication to reduce perioperative risk. Accumulating data suggest that patients taking statins have reduced postoperative complications and mortality compared to patients naïve to statins. However meta-analysis has highlighted that the current data are inconclusive. Furthermore the controversy surrounding Dr. Poldermanns' resignation casts doubt over one of the two randomized controlled trials conducted in non-cardiac surgery identified as part of our Cochrane review on perioperative statin therapy. Further data are also required to inform us about the perioperative impact of other cardiovascular agents. We have recently constructed perioperative risk models based on administrative hospital data; herein we will
extend these findings by studying a primary care database that incorporates pharmaceutical information to (i) investigate the impact of statins and other chronic cardiovascular medication on perioperative mortality and (ii) show the prevalence of drug use in the United Kingdom as feasibility data for a randomized controlled trial. We will analyze data from both the general (unselected) population and a population of patients indicated for secondary prevention (high risk) analyzing three surgical cohorts: abdominal aortic aneurysm repair (high risk), total hip or knee replacement (intermediate risk) or hysterectomy (low risk) surgery.
First Year Report from Dr R Sanders (80 KB)
Interim report from Dr R Sanders 2012 R1.pdf (57 KB)
