Post-operative immune suppression is mediated via reversible, Interleukin-10 dependent pathways in circulating monocytes following major abdominal surgery.

INTRODUCTION: Post-operative infections occur frequently following major surgery. The magnitude of the post-operative immune response is associated with an increased risk of post-operative infections, although the mechanisms driving post-operative immune-dysfunction and the potential reversibility of this response with immune stimulants are not well understood. This study aims to describe the immediate immune response to major surgery and establish links to both post-operative infection and functional aspects of immune dysregulation. We also investigate the potential of clinically available immune stimulants to reverse features of post-operative immune-dysfunction. METHODS: Patients over 45 years old undergoing elective gastro-intestinal surgery with planned post-operative surgical ICU admission were recruited. The expression of selected genes was determined pre-operatively and at 2, 24 and 48 hours post-operatively using qRT-PCR. Circulating levels of Interleukin-10 protein were determined by ELISA. Peri-operative cell surface monocyte HLA-DR (mHLA-DR) expression was determined using flow cytometry. Gene expression and mHLA-DR levels were determined in healthy monocytes cultured in peri-operative serum with and without neutralising antibodies and immune stimulants. RESULTS: 119 patients were recruited; 44 developed a post-operative infection. Interleukin-10 mRNA and protein increased 4-fold post-operatively (P<0.0001), peaking within 2 hours of the procedure. Higher post-operative Interleukin-10 mRNA (P = 0.007) and protein (P = 0.001) levels were associated with an increased risk of infection. Cell surface mHLA-DR expression fell post-operatively (P<0.0001). Reduced production, rather than intracellular sequestration, accounted for the post-operative decline in cell surface mHLA-DR expression. Interleukin-10 antibody prevented the decrease in mHLA-DR expression observed when post-operative serum was added to healthy monocytes. GM-CSF and IFN-γ prevented the decline in mHLA-DR production through distinct pathways. CONCLUSIONS: Monocyte dysfunction and features of immune suppression occur frequently after major surgery. Greater post-operative Interleukin-10 production is associated with later infection. Interleukin-10 is an important mediator of post-operative reductions in mHLA-DR expression, while clinically available immune stimulants can restore mHLA-DR levels.Royal College of Surgeons of England, The National Institute of Academic Anaesthesia (British Journal of Anaesthesia / Royal College of Anaesthetists Project Grant) European Society of Anaesthesiology

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Does major surgery induce immune suppression and increase the risk of postoperative infection?

Barts and the London Charity, the Intensive Care Society (ICS), the National Institute of Academic Anaesthesia (NIAA), the National Institute for Health Research (NIHR) and the Royal College of Surgeons of England

A single-centre observational cohort study of admission National Early Warning Score (NEWS)

Introduction Early warning scores are commonly used in hospitals to identify patients at risk of deterioration. The National Early Warning Score (NEWS) has recently been introduced to UK practice. However, it is not yet widely implemented. We aimed to compare NEWS to the early warning score currently used in our hospital – the Patient at Risk Score (PARS). Methods We conducted a prospective observational cohort study of all adult general medical patients admitted to a single hospital over a 20-day period. Physiological data and early warning scores recorded in bedside charts were collected on admission and a NEWS score was retrospectively calculated. The patient notes were reviewed at 48 h after admission. The primary outcome was a composite of critical care admission or death within 2 days of admission. The secondary outcome was hospital length of stay. Results NEWS was more strongly associated with the primary outcome than PARS (odds ratio 1.54, p < 0.001 compared to 1.42, p = 0.056). A NEWS of 3 or more was associated with the primary outcome (odds ratio 7.03, p = 0.003). Neither score was correlated with hospital length of stay. Conclusion NEWS on admission is superior to PARS for identifying patients at risk of death or critical care admission within the first 2 days of hospital stay. Current guidelines advocate a threshold of 5 for triggering a clinical review. However, since a score of 3 or more was associated with a poor outcome, this recommendation should be reviewed. Both scores were poor predictors of hospital length of stay