Serum Levels of Caspase-Cleaved Cytokeratin-18 in Patients with Severe Traumatic Brain Injury Are Associated with Mortality: A Pilot Study

Abstract

ObjectiveThere have been found apoptotic changes in brain tissue samples from animals and humans after a traumatic brain injury (TBI). The protein cytokeratin 18 (CK-18), present in epithelial cells, is cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK)-18. Circulating levels of CCCK-18, as biomarker of apoptosis, have been determined in patients with different processes; however, it has not been explored in TBI patients. Thus, the objective of this study was to determine whether there is an association between serum CCCK-18 levels and mortality and whether such levels could be used as a biomarker to predict outcomes in TBI patients.MethodsA prospective, observational, multicenter study carried out in six Spanish Intensive Care Units. We included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9; and were excluded those patients with Injury Severity Score (ISS) in non-cranial aspects higher than 9. We measured serum CCCK-18 levels at admission. The end-point of the study was 30-day mortality.ResultsSurviving patients (n = 73) showed lower serum CCCK-18 levels (P = 0.003) than non-survivors (n = 27). On ROC analysis, the area under the curve (AUC) for serum CCCK-18 levels as predictor of 30-day mortality was 0.69 (95% CI = 0.59–0.78; P = 0.006). We found in survival analysis that patients with serum CCCK-18 higher than 201 u/L had higher 30-day mortality than patients with lower levels (Hazard ratio = 3.9; 95% CI = 1.81–8.34; P<0.001). Regression analyses showed that serum CCCK-18 levels higher than 201 u/L were associated with 30-day mortality (OR = 8.476; 95% CI = 2.087–34.434; P = 0.003) after controlling for age and GCS.ConclusionsThe novel finding of our study was that serum CCCK-18 levels are associated with 30-day mortality and could be used as a prognostic biomarker in patients with severe TBI.

Serum keratin‐18 fragments as cell death biomarker in association with disease progression and prognosis in hepatitis B virus‐related cirrhosis

“…However, it should be emphasized that K18 and its caspase‐cleaved fragments detected in the circulation are not necessarily liver origin since K18 is also the major intermediate filaments of epithelial cells other than hepatocytes . Serum cK18 was significantly increased in patients with traumatic brain injury and malignant middle cerebral artery infarction . Therefore, our observation that the significantly higher level of serum K18 in patients with HE than that in those without HE was reasonable.…”

“…9 Serum cK18 was significantly increased in patients with traumatic brain injury and malignant middle cerebral artery infarction. 44,45 Therefore, our observation that the significantly higher level of serum K18 in patients with HE than that in those without HE was reasonable. However, such observation was not confirmed when similar analysis was performed only in patients without liver failure.…”

Nesfatin-1 and caspase-cleaved cytokeratin-18: Promising biomarkers for Alzheimer’s disease?

“…For example, Lorente et al showed that there is an association between early mortality and higher serum CCCK-18 levels in severe spontaneous intracerebral hemorrhage patients (22). They also showed that there are higher serum CCCK-18 levels in cases of severe malignant middle cerebral artery infarction, severe sepsis and severe traumatic brain injury (6,23,24). Besides that, Gu et al suggested that there is an association between increased serum CCCK-18 concentrations and late mortality in intracerebral hemorrhage (25).…”

Quantified EEG for the Characterization of Epileptic Seizures versus Periodic Activity in Critically Ill Patients

“…A very effective tool to evaluate the brain function in these conditions is electroencephalography (EEG). However, a dynamical evolution of injury is commonly observed in critically ill patients, due to the occurrence of epileptic seizures (ES), status epilepticus (SE), apoptosis, vasospasm or other different brain insults [2][3][4]. In this sense, continuous EEG (cEEG) is a non-invasive method that allows the functional assessment of the cerebral cortex in real time for prolonged periods of time.…”