Antonia Pérez-Cejas

Higher serum caspase-cleaved cytokeratin-18 levels during the first week of sepsis diagnosis in non-survivor patients.

Abstract Background: Caspase-cleaved cytokeratin (CCCK)-18 is a protein released into the blood during apoptosis. Higher circulating CCCK-18 concentrations have been found in non-survivor than in survivor septic patients at moment of sepsis diagnosis. The following questions arise now: (1) How are serum CCCK-18 levels during the first week of sepsis? (2) Is there an association between sepsis severity and mortality and serum CCCK-18 levels during the first week? The aims of this study were to answer these questions. Methods: Multicenter study with 321 severe septic patients from eight Spanish intensive care units. We determined serum concentration of CCCK-18, tumor necrosis factor (TNF)-α, and interleukin (IL)-10 during the first week. Our end-point study was 30-day mortality. Results: Non-survivor (n=108) compared to survivor patients (n=213) showed higher serum CCCK-18 levels at days 1, 4 and 8 (p<0.001). ROC curve analyses showed that serum CCCK-18 levels at days 1 (AUC=0.77; 95% CI=0.72–0.82), 4 (AUC=0.81; 95% CI=0.76–0.85) and 8 (AUC=0.83; 95% CI=0.78–0.88) could predict mortality at 30 days (p<0.001). Logistic regression analyses showed that serum CCCK-18 levels at days 1 (OR=4.367; 95% CI=2.491–7.659), 4 (OR=10.137; 95% CI=4.741–21.678) and 8 (OR=8.781; 95% CI=3.626–21.268) were associated with 30-day mortality (p<0.001). We found a positive correlation between CCCK-18, SOFA, and lactic acid at days 1, 4 and 8. Conclusions: Non-survivor septic patients showed persistently during the first week higher serum CCCK-18 levels than survivor patients, and there is an association between sepsis severity and mortality and serum CCCK-18 levels during the first week.

Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma.

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301–73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%–84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.

Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and Mortality in Severe Septic Patients

The association between interleukin (IL)-6 promoter polymorphism (-174 G/C), circulating IL-6 levels and mortality in septic patients has scarcely been addressed, and then only in studies of small sample size, and a direct association among them has not been previously reported. Therefore, the purpose of our study was to determine whether this association exists. An observational, prospective and multicenter study including severe septic patients was undertaken and serum IL-6 levels at severe sepsis diagnosis and IL-6 promoter polymorphism (-174 G/C) were determined. The end-point of the study was 30-day mortality. The study included 263 patients with the following genotypes of IL-6 promoter polymorphism (-174 G/C): 123 (46.8%) GG, 110 (41.8%) GC and 30 (11.4%) CC. CC homozygous patients showed lower sepsis-related organ failure assessment (SOFA) score, serum IL-6 levels and mortality at 30 days compared to those with other genotypes (GC or GG). On regression analysis, CC homozygous patients showed lower 30-day mortality than those with genotype GG (odds ratio = 0.21; 95% CI = 0.053−0.838; p = 0.03) or GC (hazard ratio = 0.28; 95% CI = 0.074−1.037; p = 0.06). The most important results of our study were that CC might be a favorable genotype in septic patients showing lower serum IL-6 levels and lower risk of death within 30 days.

High serum soluble CD40L levels previously to liver transplantation in patients with hepatocellular carcinoma are associated with mortality at one year

Purpose: CD40L and its soluble form (sCD40L) are proteins of the tumor necrosis factor superfamily (TNFSF) that exhibit prothrombotic and proinflammatory properties when binding to CD40, which is a cell surface receptor of the tumor necrosis factor receptor superfamily (TNFRSF). High circulating levels of sCD40L have been associated with poor prognosis in patients with hepatocellular carcinoma (HCC). However, it is unknown whether there is an association between circulating sCD40L levels and survival in patients with HCC underwent to liver transplantation (LT), and this was the objective of that study. Methods: Serum sCD40L levels were measured in a total of 139 patients before LT (124 survivors at 1 year of LT and 15 non‐survivors). The end‐point study was 1 year survival after liver LT. Results: We found that 1‐year non‐surviving patients showed higher serum sCD40L levels than survivor patients (p = 0.02). We found in logistic regression analysis that serum sCD40L levels higher than 321 pg/mL (Odds Ratio = 6.86; 95% confidence interval = 2.06–22.76; p = 0.002) and age of LT deceased donor were associated with death at 1 year. Conclusions: The new finding of our study was that high serum sCD40L levels previously to LT in patients with HCC are associated with higher mortality at one year. Highlights:There are higher serum levels of sCD40L previously to LT in patients with HCC in 1‐year non‐survivor than in survivors.There is an association between serum levels of sCD40L previously to LT in patients with HCC and survival.Serum levels of sCD40L previously to LT in patients with HCC could be used as biomarker of survival.

Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke.

Patients with high serum substance P levels previously to liver transplantation for hepatocellular carcinoma have higher risk of one-year liver transplantation mortality

Purpose Substance P is a tachykinins family member with inflammatory effects. Higher circulating levels of substance P have been found in patients with liver diseases and in patients with higher severity of liver diseases. The objective of this study was to determine whether serum levels of substance P levels, prior to liver transplantation (LT) for hepatocellular carcinoma (HCC) are associated with one-year LT mortality. Material and Methods In this observational retrospective unicenter study were included patients with LT for HCC. Serum levels of substance P were measured before LT. The end-point of the study was one-year mortality after LT. Results We found that one-year survivor patients (n = 127) showed a lower age in liver donors (p = 0.03) and lower levels of serum substance P levels (p = 0.003) than non-survivor patients (n = 15). Logistic regression analysis showed that serum levels of substance P (levels) were associated with one-year mortality (Odds Ratio = 1.011; 95% CI = 1.004–1.018; p = 0.002) controlling for the age of the LT donor. Conclusions We believe that our study is the first study reporting data on circulating levels of substance P previously to LT for HCC, and an association between elevated levels of serum substance P before LT and mortality during the first year of LT.

Serum total antioxidant capacity prior to liver transplantation for hepatocellular carcinoma is associated with 1-year liver transplantation survival

Objective To determine whether there was an association between serum total antioxidant capacity (TAC) levels prior to in liver transplantation (LT) for hepatocellular carcinoma (HCC) and 1-year LT mortality. Methods This observational retrospective single-centre study of patients with LT for HCC measured serum levels of TAC and malondialdehyde (as a biomarker of lipid peroxidation) before LT. The study endpoint was 1-year LT mortality. Results This study included 142 patients who underwent LT for HCC. Patients who survived the first year (n = 127) had significantly lower aged liver donors, significantly higher serum TAC levels, and significantly lower serum malondialdehyde levels compared with the non-survivors (n = 15). Logistic regression analysis found that serum TAC levels (odds ratio [OR] 0.275; 95% confidence interval [CI] 0.135, 0.562) and the age of the LT donor (OR 1.050; 95% CI 1.009, 1.094) were associated with 1-year LT mortality. There was an inverse association between serum levels of TAC and malondialdehyde levels (rho = –0.22). Conclusions There was an association between low serum TAC levels prior to LT for HCC and mortality during the first year after LT. There was an inverse association between serum TAC levels and lipid peroxidation as measured by malondialdehyde levels.

High serum levels of caspase-cleaved cytokeratin-18 are associated with malignant middle cerebral artery infarction patient mortality

BackgroundThere have been found apoptotic changes in brain tissue samples from humans after cerebral ischemia. Caspase-cleaved cytokeratin (CCCK)-18 could appears in blood during apoptosis. High circulating levels of CCCK-18 have been associated with a poor prognosis in patients with cerebral process, such as traumatic brain injury and spontaneous cerebral hemorrhage. However, they have not been explored in patients with ischemic stroke. Thus, the aim of this study was to determine whether there is an association between serum CCCK-18 levels and mortality in patients with severe malignant middle cerebral artery infarction (MMCAI).MethodsThis was an observational, prospective and multicentre study. We included patients with severe MMCAI. We considered MMCAI as severe when Glasgow Coma Scale (GCS) was lower than 9. We measured serum CCCK-18 levels at the diagnosis moment of the severe MMCAI.ResultsWe found that non-surviving severe MMCAI patients (n = 33) showed lower GCS and platelet count, and higher serum CCCK-18 levels than survivor ones (n = 33). We found an area under the curve (AUC) of serum CCCK-18 levels to predict 30-day mortality of 82% (95% CI = 71%–91%; p < 0.001). In the multiple logistic regression analysis was found that serum CCCK-18 levels were associated with 30-day mortality (OR = 1.023; 95% CI = 1.010–1.037; p = 0.001) after to control for platelet count and GCS.ConclusionsTo our knowledge, this is the first series reporting data on serum CCCK-18 levels in ischemic stroke patients. The novel findings of our study were that non-surviving severe MMCAI patients had higher serum CCCK-18 levels than surviving patients, and that there is an association between high serum CCCK-18 levels and MMCAI patients mortality.

Non-survivor septic patients have persistently higher serum sCD40L levels than survivors

Introduction: Soluble CD40 ligand (sCD40L) is a protein with proinflammatory and prothrombotic effects. Previously we found higher circulating sCD40L levels in non‐survivor than in survivor patients at sepsis diagnosis. Now some questions arise such as how are serum sCD40L levels during the first week of severe sepsis?, is there an association between serum sCD40L levels during the first week and mortality?, and serum sCD40L levels during the first week could be used as sepsis mortality biomarker? This study was developed to answer these asks. Methods: Study from 6 Spanish Intensive Care Units with 291 severe septic patients. There were determined serum levels of sCD40L and tumor necrosis factor (TNF)‐alpha during the first week. The end‐point study was 30‐day mortality. Results: We found that serum sCD40L at days 1, 4, and 8 could predict mortality at 30 days, and are associated with mortality. Conclusions: The novel findings of our study were that there were higher serum sCD40L levels persistently during the first week in non‐survivor than in survivor patients, that there is an association between serum sCD40L levels during the first week and sepsis mortality, and that serum sCD40L levels during the first week could be used as sepsis mortality biomarker. HIGHLIGHTSSerum sCD40L levels are persistently higher during the first week in non‐survivor than in survivor patients.There is an association between serum sCD40L levels during the first week and sepsis mortality.Serum sCD40L levels during the first week could be used as sepsis mortality biomarker.

Serum melatonin levels are associated with mortality in patients with malignant middle cerebral artery infarction

Objectives Lower serum melatonin levels are found in patients with ischaemic stroke compared with healthy controls. This study aimed to determine whether serum melatonin levels are associated with peroxidation status, antioxidant status, and mortality in patients with ischaemic stroke. Methods Patients with severe malignant middle cerebral artery infarction (MMCAI), defined as a Glasgow coma scale (GCS) score lower than 9, were included. Serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity at the time of diagnosing MMCAI were determined. We chose 30-day mortality as the endpoint of the study. Results We found significantly higher serum levels of melatonin, total antioxidant capacity, and malondialdehyde in non-survivors (n = 32) than in survivors (n = 32) with MMCAI. Serum melatonin levels were associated with 30-day mortality (odds ratio = 2.205; 95% confidence interval = 1.294–3.759) after controlling for GCS score and age. We found a positive association between serum melatonin levels and total antioxidant capacity (rho = 0.36), and between serum melatonin and malondialdehyde levels (rho = 0.35). Conclusions Our study shows that serum melatonin levels are associated with peroxidation status, antioxidant status, and mortality in patients with MMCAI.