Dr Hew Torrance
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.
Funders and related centres
- National Institute for Health Research (NIHR)
- NIHR Imperial Biomedical Research Centre
- The National Institute of Academic Anaesthesia (NIAA)
‘A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery’. Torrance HD, Zhang P, Longbottom ER, Mi Y, Whalley JP, Allcock A, Kwok AJ, Cano-Gamez E, Geoghegan CG, Antcliffe DB, Davenport EE, Pearse RM, O’Dwyer MJ, Hinds CJ, Knight JC, Gordon AC. MedRxiv 2023. https://doi.org/10.1101/2023.01.25.23284914 Preprint
‘High-throughput mass spectrometry maps the sepsis plasma proteome and differences in response’. Mi Y., Burnham KL, Charles PD, Heilig R, Vendrell I, Whalley J, Torrance HD, Antcliffe DB, May SM, Neville MJ, Berridge G, Hutton P, Goh C, Radhakrishnan J, Nesvizhskii A, Yu F, Davenport EE, McKechnie S, Davies R, O’Callaghan DJP, Patel P, Karpe F, Gordon AC, Ackland GL, Hinds CJ, Fischer R, Knight JC. MedRxiv 2022. http://doi.org/10.1101/2022.08.07.22278495 Preprint
‘The association of pre-operative anaemia with post-operative morbidity and mortality: An international prospective observational cohort study.’ Fowler AJ*, Ahmad T*, Abbott TEF, Torrance HD, Wouters PF, De Hert S, Lobo SM, Rasmussen LS, Beattie WS, Wijeysundera DN & Pearse RM; for the International Surgical Outcomes Study (ISOS) group. Br J Anaesth. 2018; 121:1227-1235. (*equal contributors). PMID: 30442249
‘Post-operative immune suppression is mediated via reversible, Interleukin-10 dependent pathways in circulating monocytes following major abdominal surgery.’ Torrance HD*, Longbottom ER*, Vivian ME, Lalabekyan B, Abbott TEF, Ackland GL, Hinds CJ, Pearse RM, O’Dwyer MJ. PLOS One. 2018; 13(9):e0203795. (*equal contributors). PMID: 30212506
‘Acute Kidney Injury in Trauma Patients Admitted to Critical Care: Development and Validation of a Diagnostic Prediction Model.’ Haines RW, Lin S-P, Hewson R, Kirwan CJ, Torrance HD, O’Dwyer MJ, West A, Brohi K, Pearse RM, Zolfaghari1 PJ, Prowle JR. Nature Scientific Reports. 2018; 8:3665. PMID: 29483607
‘Pre-hospital National Early Warning Score (NEWS) is associated with in-hospital mortality and critical care unit admission: a cohort study.’ Abbott TEF, Cron N, Vaid N, Ip D, Torrance HD, Emmanuel J. Annals of Medicine & Surgery. 2018; 27:17-21. PMID: 29511537
‘Signatures of Inflammation and Impending Multiple Organ Dysfunction in the Hyperacute Phase of Trauma: A Prospective Cohort Study.’ Cabrera CP*, Manson J*, Shepherd JM*, Torrance HD, Watson D, Longhi PM, Hoti M, Patel MB, O’Dwyer MJ, Nourshargh S, Pennington DJ, Barnes MR, Brohi K. Plos Med. 2017; 14(7): e1002352. PMID: 28715416 (*equal contributors)
‘A single-centre cohort study of National Early Warning Score (NEWS) and near patient testing in acute medical admissions.’ Abbott TEF, Torrance HD, Cron N, Vaid N, Emmanuel J. European Journal of Internal Medicine. 2016; 35:78-82. PMID: 27346295
‘Does major surgery induce immune suppression and increase the risk of postoperative infection?’ Torrance HD, Pearse RM, O’Dwyer MJ. Current Opinion in Anesthesiology. 2016; 29:376-83. PMID: 26963469
‘Artesunate Protects Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation.’ Sordi R, Nandra KK, Chiazza F, Johnson FL, Cabrera CP, Torrance HD, Yamada N, Patel NS, Barnes MR, Brohi K, Collino M, Thiemermann C. Annals of Surgery. 2016; 265:408-417. PMID: 26863400
‘Features of post-operative immune suppression are reversible with interferon gamma and independent of IL-6 pathways’ Longbottom ER*, Torrance HD*, Owen HC, Fragkou PC, Hinds CJ, Pearse RM, O’Dwyer MJ. Annals of Surgery. 2016; 264:370-7. PMID: 26445474. (*equal contributors)
‘Systemic inflammatory response syndrome (SIRS) after major abdominal surgery is predicted by early activation of TLR4 and TLR5.’ Lahiri R, Derwa Y, Bashir Z, Giles E, Torrance HD, Owen HC, O’Dwyer MJ, O’Brien A, Stagg AJ, Bhattacharya S, Foster GR, Alazawi W. Annals of Surgery. 2016; 263:1028-37. PMID: 26020106.
‘The perioperative immune response’ O’Dwyer MJ, Owen HC, Torrance HD. Current Opinion in Critical Care. 2015; 21:336-42. PMID: 26103142.
‘Epigenetic regulatory pathways involving micro-RNAs may modulate the host immune response following major trauma.’ Owen HC, Torrance HD, Jones TF, Pearse RM, Hinds CJ, Brohi K, O’Dwyer MJ. Journal of Trauma and Acute Care Surgery. 2015; 79:766-72. PMID: 26496100.
‘A single-centre observational cohort study of admission National Early Warning Score (NEWS).’ Abbott TF, Vaid N, Cron N, Wells M, Ip D, Torrance HD, Emmanuel J. Resuscitation. 2015; 92:89-93. PMID: 25943011.
‘Changes in gene expression following trauma are related to the age of transfused packed red blood cells.’ Torrance HD, Vivian ME, Brohi K, Prowle JR, Pearse RM, Owen HC, Hinds CJ, O’Dwyer MJ. Journal of Trauma and Acute Care Surgery. 2015; 78:535-42. PMID: 25710424.
‘Association between gene expression biomarkers of immunosuppression and blood transfusion in severely injured polytrauma patients.’ Torrance HD, Brohi K, Pearse RM, Mein CA, Wozniak E, Prowle, JR, Hinds CJ, O’Dwyer MJ. Annals of Surgery. 2015; 261:751-9. PMID: 24670848.
‘Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study.’ Fragkou PC*, Torrance HD*, Pearse RM, Ackland GL, Prowle JR, Owen HC, Hinds CJ and O'Dwyer MJ. Critical Care. 2014; 18:541 PMID: 25270110. (*equal contributors).
Dr Hew Torrance
Dr Hew Torrance