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Dr Hew Torrance
hew.torrance19@imperial.ac.uk

Improving care for patients undergoing major surgery abdominal surgery

Every year in high-income countries, 1 in 10 adults undergo a non-cardiac surgical procedure, with a mortality rate in Europe as high as 4%. Postoperative infections are a major contributor to this unacceptably high death rate. Over 20% of surgical patients aged over 45 years suffer clinically significant infectious complications, with a patient who develops post-operative pneumonia having an almost five-fold increased risk of 30-day mortality.

The temporal changes in immune function following major abdominal surgery are complex and still remain poorly understood, although the phenomenon of post-operative immune suppression is thought to contribute to an enhanced susceptibility to nosocomial infection.

Presently there are no widely available, well-validated biomarkers to identify those most at risk of infection and once nosocomial infection has been recognised treatment options are limited. The two current strategies are either reactive (i.e. initiating antibiotic treatment once an infection is clinically suspected), or prophylactic, which involves the indiscriminate use of antibiotics, encouraging the development of antimicrobial resistance. 

Identifying inter-individual variation to sterile inflammatory processes

Professors’ Knight, Gordon and Hinds, through the UK Genomic Advances in Sepsis (GAinS)
Collaborative, have been successfully investigating the role of inter-individual variability in a patient’s ability to recover from (apparently) similar pathogen-associated molecular patterns (PAMPs) mediated infectious insults. This phenomenon is highly relevant when interpreting the postoperative immune response as it is increasingly apparent that there are parallels between the immune pathways activated following exposure to circulating PAMPs (from sepsis) and DAMPs (from (sterile) tissue damage).

Currently, it is unclear why only some individuals develop postoperative infectious complications despite a homogenous intra-operative insult. This work focuses on using a multi-‘omic approach to provide novel insights into the immune pathways and gene networks activated postoperatively following a homogenous sterile stimulus.

How will this benefit our patients?

The understanding of context-specific pathways and networks generated from this work aims to characterise inter-individual variation in the host response to a homogenous stimulus; identify novel diagnostic panels; guide the repurposing of existing drugs and provide insights into novel therapeutic targets.

The focus of this programme of research is to ultimately enable the development of a precision-medicine strategy for the prevention and management of post-operative nosocomial infections.

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Dr Hew Torrance

Dr Hew Torrance
Clinical Lecturer