Dataset Information

Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery-A Prospective Cohort Study.

ABSTRACT: Interleukin-6 (IL-6) can cause pro- and anti-inflammatory effects via different signaling pathways. This prospective study investigated the perioperative kinetics of IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in elective patients undergoing cardiopulmonary bypass (CPB). IL-6, sIL-6R, and sgp130 were measured simultaneously and consecutively at 19 timepoints until the 10th postoperative day (POD). The proportion of pro- and anti-inflammatory pathways were determined by calculating sIL-6R/IL-6 and sIL-6R/sgp130 ratios. We analyzed 93 patients. IL-6 increased during surgery with reaching a plateau two hours after CPB and peaking on POD 1 (188.5 pg mL-1 (IQR, 126.6; 309.2)). sIL-6R decreased at the beginning of the surgical procedure, reaching a nadir level on POD 2 (26,311 pg mL-1 (IQR, 22,222; 33,606)). sgp130 dropped immediately after CPB initiation (0.13 ng mL-1 (IQR, 0.12; 0.15)), followed by a continuous recovery until POD10. The sIL-6R/IL-6 ratio decreased substantially at the beginning of the procedure, reaching a nadir on POD 1 (149.7 (IQR, 82.4; 237.4)), while the sIL-6R/sgp130 ratio increased simultaneously until 6 h post CPB (0.219 (IQR 0.18; 0.27)). In conclusion, IL-6 exhibited high inter-individual variability reflecting an inhomogeneous inflammatory response. Pro-inflammatory effects and overwhelming inflammation were rare and predominantly anti-inflammatory effects were found.

SUBMITTER: Puchinger J

PROVIDER: S-EPMC8836792 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery-A Prospective Cohort Study.

Puchinger Jürgen J Ryz Sylvia S Nixdorf Larissa L Edlinger-Stanger Maximilian M Lassnigg Andrea A Wiedemann Dominik D Hiesmayr Michael M Spittler Andreas A Bernardi Martin H MH

Journal of clinical medicine 20220125 3

Interleukin-6 (IL-6) can cause pro- and anti-inflammatory effects via different signaling pathways. This prospective study investigated the perioperative kinetics of IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in elective patients undergoing cardiopulmonary bypass (CPB). IL-6, sIL-6R, and sgp130 were measured simultaneously and consecutively at 19 timepoints until the 10th postoperative day (POD). The proportion of pro- and anti-inflammatory pathways were determin ...[more]

PMID: 35160042

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Project description:IntroductionMore than 30 000 cardiac surgery procedures are performed in the UK each year, however, postoperative complications and long-term failure of interventions are common, leading to repeated surgeries. This represents a significant burden on the patient and health service.Routinely, patients are discharged to their general practitioner 6 weeks postoperatively and research studies typically only report short-term outcomes up to 1 year after surgery, together this makes long-term outcomes of cardiac surgery difficult to monitor. Further, traditional research methods have yet to advance understanding of what causes early complications and why surgical interventions fail.Methods and analysisThis prospective cohort study will characterise participants undergoing cardiac surgery at baseline, describe short-term, medium-term and long-term health outcomes postoperatively and collect tissue samples.All eligible adult patients undergoing cardiac surgery at the Bristol Heart Institute, UK will be approached for consent. Recruitment is expected to continue for up to 10 years resulting in the largest cohort of cardiac patients reported to date. Blood, urine and waste tissue samples will be collected during admission. Samples, along with anonymised data, will be used to investigate outcomes and inform predictive models of complications associated with cardiac surgery.Data about the surgical admission will be obtained from hospital databases and medical notes. Participants may be monitored up to 5 years postoperatively using data obtained from NHS digital. Participants will complete health questionnaires 3 months and 12 months postoperatively.The analysis of data and tissue samples to address specific research questions will require separate research protocols and ethical approval.Ethics and disseminationThis study was approved by the East Midlands Nottingham 2 Research Ethics Committee.Findings will be disseminated through peer-reviewed publications and presentation at national and international meetings. Participants will be informed of results in annual newsletters.Trial registration numberISRCTN90204321.

Project description:Postoperative delirium (POD) ranks among the most common complications in surgical patients. Blood-based biomarkers might help identify the patient at risk. This study aimed to assess how serum biomarkers with specificity for vascular and endothelial function and for inflammation are altered, prior to or following surgery in patients who subsequently develop POD. This was a study on a subcohort of consecutively recruited elective non-cardiac as well as cardiac surgery patients (age > 60 years) of the single-center PROPDESC trial at a German tertiary care hospital. Serum was sampled prior to and following surgery, and the samples were subjected to bead-based multiplex analysis of 17 serum proteins (IL-3, IL-8, IL-10, Cripto, CCL2, RAGE, Resistin, ANGPT2, TIE2, Thrombomodulin, Syndecan-1, E-Selectin, VCAM-1, ICAM-1, CXCL5, NSE, and uPAR). Development of POD was assessed during the first five days after surgery, using the Confusion Assessment Method for ICU (CAM-ICU), the CAM, the 4-'A's test (4AT), and the Delirium Observation Scale (DOS). Patients were considered positive if POD was detected at least once during the visitation period by any of the applied methods. Non-parametric testing, as well as propensity score matching were used for statistical analysis. A total of 118 patients were included in the final analysis; 69% underwent non-cardiac surgery, median overall patient age was 71 years, and 59% of patients were male. In the whole cohort, incidence of POD was 28%. The male gender was significantly associated with the development of POD (p = 0.0004), as well as a higher ASA status III (p = 0.04). Incidence of POD was furthermore significantly increased in cardiac surgery patients (p = 0.002). Surgery induced highly significant changes in serum levels of almost all biomarkers except uPAR. In preoperative serum samples, none of the analyzed parameters was significantly altered in subsequent POD patients. In postoperative samples, CCL2 was significantly increased by a factor of 1.75 in POD patients (p = 0.03), as compared to the no-POD cohort. Following propensity score matching, CCL2 remained the only biomarker that showed significant differences in postoperative values (p = 0.01). In cardiac surgery patients, postoperative CCL2 serum levels were more than 3.5 times higher than those following non-cardiac surgery (p < 0.0001). Moreover, after cardiac surgery, Syndecan-1 serum levels were significantly increased in POD patients, as compared to no-POD cardiac surgery patients (p = 0.04). In a mixed cohort of elective non-cardiac as well as cardiac surgery patients, preoperative serum biomarker profiling with specificity for vascular dysfunction and for systemic inflammation was not indicative of subsequent POD development. Surgery-induced systemic inflammation-as evidenced by the significant increase in CCL2 release-was associated with POD, particularly following cardiac surgery. In those patients, postoperative glycocalyx injury might furthermore contribute to POD development.

Project description:BackgroundElevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident.MethodsWe performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRT-PCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO).ResultsMicroRNAs were detectable in all 59 patients (median age 67 yr [61-75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95-8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94-10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n=48) and two (n=11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia.ConclusionsCirculating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.

Dataset Information

Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery-A Prospective Cohort Study.

Publications

Characteristics of Interleukin-6 Signaling in Elective Cardiac Surgery-A Prospective Cohort Study.

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