Riccardo G Abbasciano1, Florence Y Lai2, Marius A Roman2, Angelica Rizzello2, Suraj Pathak2, Joussi Ramzi3, Carla Lucarelli4, Georgia R Layton5, Tracy Kumar2, Marcin J Wozniak2, Bryony Eagle-Hemming2, Enoch Akowuah6, Chris A Rogers7, Gianni D Angelini8, Gavin J Murphy2. 1. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. Electronic address: rga8@leicester.ac.uk. 2. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. 3. Leicester Medical School, University of Leicester, Leicester, UK. 4. Department of Cardiac Surgery, University of Verona, Verona, Italy. 5. University Hospitals of Leicester NHS Trust, Leicester, UK. 6. South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK. 7. Clinical Trials and Evaluation Unit, Bristol Trials Centre, University of Bristol, Bristol, UK. 8. Bristol Heart Institute, University of Bristol, Bristol, UK.
Abstract
BACKGROUND: It is unclear whether the innate immune response represents a therapeutic target for organ protection strategies in cardiac surgery. METHODS: A systematic review of trials of interventions targeting the inflammatory response to cardiac surgery reporting treatment effects on both innate immune system cytokines and organ injury was performed. The protocol was registered at the International Prospective Register of Systematic Reviews: CRD42020187239. Searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were performed. Random-effects meta-analyses were used for the primary analysis. A separate analysis of individual patient data from six studies (n=785) explored sources of heterogeneity for treatment effects on cytokine levels. RESULTS: Searches to May 2020 identified 251 trials evaluating 24 interventions with 20 582 participants for inclusion. Most trials had important limitations. Methodological limitations of the included trials and heterogeneity of the treatment effects on cytokine levels between trials limited interpretation. The primary analysis demonstrated inconsistency in the direction of the treatment effects on innate immunity and organ failure or death between interventions. Analyses restricted to important subgroups or trials with fewer limitations showed similar results. Meta-regression, pooling available data from all trials, demonstrated no association between the direction of the treatment effects on inflammatory cytokines and organ injury or death. The analysis of individual patient data demonstrated heterogeneity in the association between the cytokine response and organ injury after cardiac surgery for people >75 yr old and those with some chronic diseases. CONCLUSIONS: The certainty of the evidence for a causal relationship between innate immune system activation and organ injury after cardiac surgery is low.
BACKGROUND: It is unclear whether the innate immune response represents a therapeutic target for organ protection strategies in cardiac surgery. METHODS: A systematic review of trials of interventions targeting the inflammatory response to cardiac surgery reporting treatment effects on both innate immune system cytokines and organ injury was performed. The protocol was registered at the International Prospective Register of Systematic Reviews: CRD42020187239. Searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were performed. Random-effects meta-analyses were used for the primary analysis. A separate analysis of individual patient data from six studies (n=785) explored sources of heterogeneity for treatment effects on cytokine levels. RESULTS: Searches to May 2020 identified 251 trials evaluating 24 interventions with 20 582 participants for inclusion. Most trials had important limitations. Methodological limitations of the included trials and heterogeneity of the treatment effects on cytokine levels between trials limited interpretation. The primary analysis demonstrated inconsistency in the direction of the treatment effects on innate immunity and organ failure or death between interventions. Analyses restricted to important subgroups or trials with fewer limitations showed similar results. Meta-regression, pooling available data from all trials, demonstrated no association between the direction of the treatment effects on inflammatory cytokines and organ injury or death. The analysis of individual patient data demonstrated heterogeneity in the association between the cytokine response and organ injury after cardiac surgery for people >75 yr old and those with some chronic diseases. CONCLUSIONS: The certainty of the evidence for a causal relationship between innate immune system activation and organ injury after cardiac surgery is low.
Authors: David Rene Steike; Michael Hessler; Eberhard Korsching; Florian Lehmann; Christina Schmidt; Christian Ertmer; Jürgen Schnekenburger; Hans Theodor Eich; Björn Kemper; Burkhard Greve Journal: Cells Date: 2022-02-21 Impact factor: 6.600
Authors: Daniel Galvis; Eder Zavala; Jamie J Walker; Thomas Upton; Stafford L Lightman; Gianni D Angelini; Jon Evans; Chris A Rogers; Kirsty Phillips; Ben Gibbison Journal: J R Soc Interface Date: 2022-04-27 Impact factor: 4.293