Association between serum levels of caspase-cleaved cytokeratin-18 and early mortality in patients with severe spontaneous intracerebral hemorrhage

Leonardo Lorente,Luis Ramos,Jordi Solé-Violán,Victor García-Marín,Antonia Pérez-Cejas,Alejandro Jiménez,Mónica Argueso,Juan J Cáceres,María M Martín

doi:10.1186/s12868-018-0424-1

Abstract

BackgroundApoptotic changes after cerebral hemorrhage in brain samples of humans have been found. Caspase-cleaved cytokeratin (CCCK)-18 could be detected in the bloodstream during apoptosis. Higher circulating CCCK-18 levels have been associated with 6-month mortality in patients with basal ganglia hemorrhage. The aim of our study was to determine whether there is an association between serum CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH) patients. We performed an observational, prospective and multicentre study. There were included patients with severe SIH defined as Glasgow Coma Scale (GCS) lower than 9. We determined serum CCCK-18 levels at the severe SIH diagnosis moment.ResultsWe found that non-surviving SIH patients (n = 46) showed lower GCS, and higher serum CCCK-18 levels and APACHE-II score than survivor ones (n = 54). In ROC analysis was found that the area under the curve of serum CCCK-18 levels for 30-day mortality prediction was 90% (95% CI 82–95%; p < 0.001). In the multiple logistic regression analysis, we found an association between serum CCCK-18 levels and 30-day mortality (OR 1.034; 95% CI 1.013–1.055; p = 0.002).ConclusionsThe novel finding of our study was that there is an association between high serum CCCK-18 levels and 30-day mortality in severe SIH patients.

Highlights

Spontaneous intracerebral hemorrhage (SIH) results in a large amount of deaths, disabilities, and resource consumption [1,2,3]
We found that non-surviving spontaneous intracerebral hemorrhage (SIH) patients showed lower Glasgow Coma Scale (GCS), and higher serum CCCK18 levels, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, age, volume of SIH, midline shift, and glycemia than survivor ones (Table 1)
We found the following area under the curve for 30-day mortality prediction: serum Caspasecleaved cytokeratin (CCCK)-18 levels of 90% (Fig. 1), age of 72%, SIH volume of 68%, midline shift of 68%, GCS of 78%, APACHE-II score of 81%

Summary

Introduction

Spontaneous intracerebral hemorrhage (SIH) results in a large amount of deaths, disabilities, and resource consumption [1,2,3]. Secondary damage is induced by mitochondrial dysfunction, microglia activation and the release of neurotransmitter and inflammatory mediators; and those events lead to necrosis and to Between 1999 and 2005 in some animals models were found the presence of apoptosis after cerebral hemorrhage [8,9,10,11]. The aim of our study was to determine whether there is an association between serum CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH) patients. We determined serum CCCK-18 levels at the severe SIH diagnosis moment

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