Sustained high serum caspase-3 concentrations and mortality in septic patients.

Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.

Association between septic patient mortality and blood survivin concentrations.

OBJECTIVE: Survivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. DESIGN: Observational and prospective study. SETTING: Three Spanish Intensive Care Units. PATIENTS: Patients with sepsis or septic shock according to Sepsis-3 Consensus criteria. INTERVENTIONS: Serum survivin concentrations were determined at moment of sepsis diagnosis. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946-0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943-0.989; p=0.004). CONCLUSIONS: There is an association between septic patient mortality and low blood survivin concentrations.

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Serum caspase-3 levels during the first week of traumatic brain injury.

OBJECTIVE: Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality. DESIGN: A prospective observational study was carried out. SETTING: Six Spanish Intensive Care Units. PATIENTS: Patients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points). INTERVENTIONS: Serum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI. MAIN VARIABLES OF INTEREST: Thirty-day mortality was considered as the study endpoint. RESULTS: In comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61-0.78; p=0.001), 0.83 (0.74-0.89; p<0.001) and 0.87 (0.79-0.93; p<0.001), respectively. CONCLUSIONS: The novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality.

DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction.

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p<0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p=0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients.

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.