Abstract

Extracellular cold-inducible RNA-binding protein (eCIRP) acting as a novel damage-associated molecular pattern molecule promotes systemic inflammatory responses, including neuroinflammation in cerebral ischemia. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC). A total of 73 patients after ROSC were divided into non-survivor (n = 48) and survivor (n = 25) groups based on 28-day survival. Healthy volunteers (n = 25) were enrolled as controls. Serum eCIRP, procalcitonin (PCT), the pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and high mobility group protein (HMGB1), the neurological damage biomarkers neuron-specific enolase (NSE), and soluble protein 100β (S100β) were measured on days 1, 3, and 7 after ROSC. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) were calculated concurrently. Cerebral performance category scores on day 28 after ROSC were recorded. Serum eCIRP, IL-6, TNF-α, PCT, and HMGB1, NSE and S100β were significantly increased within the first week after ROSC. The increased levels of eCIRP were positively correlated with IL-6, TNF-α, lactate, NSE, S100β, CPR time, SOFA score, APACHE II score, and HMGB1 after ROSC. Serum eCIRP on days 1, 3, and 7 after ROSC could predict 28-day mortality and neurological prognosis. Serum eCIRP on day 3 after ROSC had a biggest AUC [0.862 (95% CI: 0.741-0.941)] for 28-day mortality and a biggest AUC [0.807 (95% CI: 0.630-0.981)] for neurological prognosis. Systemic inflammatory response with increased serum eCIRP occurred in patients after ROSC. Increased eCIRP level was positively correlated with the aggravation of systemic inflammatory response and the severity after ROSC. Serum eCIRP serves as a potential predictor for 28-day mortality and poor neurological prognosis after ROSC.

Highlights

  • The annual incidence of sudden cardiac arrest (CA) in adults is about 550,000 in the United States [1]

  • For patients survived from initial resuscitation, the mortality is still high in the post-resuscitation phase due to a complex pathophysiological process so-called post–cardiac arrest syndrome (PACS), which includes post-cardiac arrest brain injury, post–cardiac arrest myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathology [4]

  • We observed that serum Extracellular cold-inducible RNA-binding protein (eCIRP) was significantly increased in patients after restoration of spontaneous circulation (ROSC) and were higher in non-survivors than in survivors

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Summary

Introduction

The annual incidence of sudden cardiac arrest (CA) in adults is about 550,000 in the United States [1]. The systematic inflammatory response after ROSC, which is induced by systemic ischemia/reperfusion and characterized by the absence of endotoxin in plasma, high levels of circulating cytokines and inflammatory mediators, mimics the process in sepsis [5]. This "sepsis-like" inflammatory response has been demonstrated to contribute to vital organs injury such as brain and heart [5, 6], which is closely associated with neurological disability and high mortality. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC)

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