Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction

Rationale: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. Objective: To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c. Methods and Results: We prospectively assessed cytochrome c serum levels at hospital presentation in 2 cohorts: a diagnostic cohort of patients presenting with suspected AMI and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals 0.44-0.58; P=0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with nondetectable cytochrome c (6% versus 1%; P<0.001). This result was mainly driven by the high mortality rate observed in ST-segment-elevation AMI patients with detectable cytochrome c, as compared with those with nondetectable cytochrome c (11% versus 1%; P<0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% confidence interval 1.9-5.7; P<0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% confidence interval 1.20-13.38; P=0.02). Conclusions: Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Circulating cytochrome c as potential biomarker of impaired reperfusion in ST-segment elevation acute myocardial infarction

In patients with ST-segment elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), abrupt reperfusion can induce myocardial injury and apoptotic cell death. Reperfusion-induced myocardial damage, however, cannot be easily evaluated in clinical practice because of the lack of specific biomarkers. Cytochrome c, a mitochondrial protein, is released on reperfusion into the cytosol, where it triggers the apoptotic process. It can reach the external fluid and circulating blood when cell rupture occurs. We measured the cytochrome c circulating levels in patients with STEMI undergoing pPCI, and correlated them with the clinical signs of myocardial necrosis and reperfusion. The plasma creatine kinase-MB mass and serum cytochrome c (enzyme-linked immunosorbent assay method) were serially measured in 55 patients with STEMI undergoing pPCI. The angiographic and electrocardiographic signs of myocardial reperfusion were also assessed. Cytochrome c transiently increased in all patients with STEMI, with a curve that paralleled that of creatine kinase-MB. A significant relation was found between the peak values of the 2 biomarkers (R = 0.35, p = 0.01) and between the areas under the 2 curves (R = 0.33, p = 0.02). The creatine kinase-MB peak value correlated significantly with the clinical features of infarct extension. In contrast, the cytochrome c peak value correlated inversely with the myocardial blush grade. Patients with clinical signs of myocardial reperfusion injury had a significantly greater cytochrome c peak value than patients without reperfusion injury (median 1.65 ng/ml, interquartile range 1.20 to 2.20, vs 1.1 ng/ml, interquartile range 0.65 to 1.55; p = 0.04). In conclusion, serum cytochrome c is detectable in the early phase of STEMI treated with pPCI and is associated with clinical signs of impaired myocardial reperfusion