Mortality prediction by serum melatonin levels of patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: In one study, higher serum melatonin levels have been reported at diagnosis of spontaneous intracerebral hemorrhage (ICH) in non-surviving than in surviving patients. Now, we carried out this study with the aims to explore whether blood melatonin concentrations in the first 7 days of ICH are different in survivor and non-survivor patients and whether are useful in the prediction of mortality. METHODS: Six Spanish hospitals participated in this observational study of patients with severe supratentorial ICH (defining severe as Glasgow Coma Scale < 9). We determined serum melatonin levels during the first, fourth, and eighth day of severe ICH. RESULTS: Surviving (n = 64) compared to non-surviving (n = 53) patients showed lower serum melatonin levels during the first (p < 0.001), fourth (p < 0.001), and eighth day (p < 0.001) of severe ICH. We found in multiple logistic regression analysis an association between serum melatonin levels and 30-day mortality (odds ratio = 8.932; 95% CI = 2.442-32.665; p = 0.001) controlling for midline shift, ICH score, early evacuation of ICH, and glycemia. We found an AUC (95% CI) for the mortality prediction of 0.90 (0.83-0.95; p < 0.001), 0.94 (0.87-0.98; p < 0.001), and 0.90 (0.81-0.96; p < 0.001) by serum melatonin concentrations during the first, fourth, and eighth day. CONCLUSIONS: In our current study, it appears that novel findings of serum melatonin levels recollected at any moment during the first 7 days of a severe ICH were higher in non-survivor than in survivor patients and could help in mortality prediction.

Serum B cell lymphoma-2 concentrations and mortality of patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: There is scarce data on B cell lymphoma 2 (Bcl2), a member of the Bcl-2 family of antiapoptotic molecules of the intrinsic apoptosis pathway, in patients with spontaneous intracerebral hemorrhage (SIH). In one study, higher serum Bcl2 levels were found in patients with SIH than in healthy subjects. Thus, the objective of our study was to compare serum Bcl2 levels in surviving and non-surviving SIH patients. METHODS: Patients with severe supratentorial SIH (defined as Glasgow Coma Scale < 9) admitted from the Intensive Care Units of five Spanish hospitals were included in this observational and prospective study. Serum levels of Bcl2L were determined at the time of diagnosis. Thirty-day mortality was the end-point study. RESULTS: Non-surviving (n = 38) compared to surviving patients (n = 41) had higher intracerebral hemorrhage (ICH) score (p = 0.001), midline shift (p = 0.003), and serum Bcl2 levels (p < 0.001). In addition, non-surviving compared to surviving patients had lower early hematoma evacuation rate (p = 0.03). We found 77% area under curve in mortality prediction for serum Bcl2 levels (95% CI = 0.66-88%; p < 0.001). Patients showing serum Bcl2 levels > 16.5 ng/mL had higher risk of death according to analysis of Kaplan-Meier (HR = 5.2; 95% CI = 2.5-10.6; p < 0.001). An association, after control for ICH score, midline shift, and early hematoma evacuation, was found between serum Bcl2 levels and 30-day mortality (OR = 1.090; 95% CI = 1.030-1.154; p = 0.003) in the multiple logistic regression. CONCLUSIONS: As far as we know, our study is the first one reporting higher serum Bcl2 levels in non-surviving than in surviving SIH patients and the association between serum Bcl2 levels and SIH mortality.

Low blood caspase-8 levels in survivor patients of traumatic brain injury.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of the extrinsic pathway of apoptosis) have been found in brain tissue of patients with traumatic brain injury (TBI) and in the blood of patients with different diseases. However, blood caspase-8 concentrations in TBI patients have not been reported. Therefore, our aim was to analyze whether blood caspase-8 concentrations are associated with mortality in TBI patients. METHOD: Patients with isolated and severe TBI were included. TBI was considered isolated if it showed an Injury Severity Score (ISS) <10 points on non-cranial aspects. TBI was considered severe if it showed a Glasgow Coma Scale (GCS) <9 points. This prospective observational study was conducted in 5 Intensive Care Units. Serum caspase-8 concentrations were measured on day 1 of TBI. RESULTS: Surviving patients (n=59) had lower age (p=0.004), higher GCS (p=0.001), lower APACHE-II score (p<0.001), lower high-risk-of-death computed tomography (CT) findings (p=0.02), lower intracranial pressure (ICP) (p=0.01), and lower serum caspase-8 concentrations (p<0.001) than non-surviving patients (n=24). An association was found between serum caspase-8 levels and mortality after controlling for CT findings, GCS, and age (OR=1.037; 95% CI=1.013-1.062; p=0.002), and after controlling for CT findings, APACHE-II, and ICP (OR=1.042; 95% CI=1.013-1.071; p=0.004) in multiple logistic regression. CONCLUSIONS: To our knowledge, this is the first series describing blood caspase-8 concentrations in patients with TBI. The association of high blood caspase-8 concentrations with mortality was the main new finding of the study. However, further investigations are needed to validate the preliminary results of our study.

High serum levels of TAC and early mortality in patients with spontaneous intracerebral haemorrhage.

OBJECTIVE: Oxidation contributes to secondary brain injury after spontaneous intracerebral haemorrhage (SIH). One study found lower levels of total antioxidant capacity (TAC) in the blood in patients with SIH than in healthy subjects. However, there are no data on blood TAC levels and survival in patients with SIH. Therefore, the objective of our study was to determine if an association exists between serum TAC levels and mortality in patients with SIH. METHODS: We included patients with severe supratentorial SIH. We considered severe when Glasgow Coma Scale (GCS) < 9. Patients from 6 Spanish hospitals were included in this observational and prospective study. Serum TAC levels at days 1, 4 and 8 of SIH were determined. Thirty-day mortality was our end-point study. RESULTS: Non-surviving patients compared with surviving patients showed higher serum TAC levels at day 1 (p < 0.001), 4 (p < 0.001) and 8 (p = 0.001). An area under the curve was found for the prediction of 30-day mortality by serum TAC levels of 0.92 (95% CI = 0.85-96%; p < 0.001). Multiple logistic regression analysis showed an association of serum TAC levels with 30-day mortality (odds ratio = 16.513; 95% CI = 2.548-107.015; p = 0.003) controlling for midline shift, glycemia, early evacuation of SIH, intracerebral haemorrhage (ICH) score, age and volume of SIH. CONCLUSIONS: The new findings of this study are that serum TAC levels are higher in non-surviving than in surviving patients, and that they are associated with mortality and could be used to predict mortality.

High Serum Soluble Fas Ligand Levels in Non-survivor Traumatic Brain Injury Patients.

PURPOSE: Soluble Fas Ligand (sFasL) is one of the main ligands that activates the apoptosis extrinsic pathway. Higher expression of FasL in brain samples and higher cerebrospinal fluid FasL concentrations in traumatic brain injury (TBI) patients than in controls have been found. However, the potential association between blood sFasL concentrations and TBI mortality has not been reported. Therefore, the objective of this study was to determine whether that association exists. METHODS: We included patients with a severe isolated TBI, defined as < 9 points in Glasgow Coma Scale (GCS) and < 10 non-cranial aspects points in Injury Severity Score in this observational and prospective study performed in 5 Intensive Care Units. We measured serum sFasL concentrations on day 1 of TBI. RESULTS: We found that 30-day survivor (n = 59) in comparison to non-survivor patients (n = 24) had higher GCS (p = 0.001), lower age (p = 0.004), lower APACHE-II score (p < 0.001), lower intracranial pressure (ICP) (p = 0.01), lower computer tomography (CT) findings of high risk of death (p = 0.02) and lower serum sFasL concentrations (p < 0.001). The area under the curve for mortality prediction by serum sFasL levels was of 75% (95% CI = 63%-87%; p < 0.001). In Kaplan-Meier analysis was found that patients with serum sFasL levels > 29.2 pg/mL had a higher mortality rate (Hazard ratio = 6.2; 95% CI = 2.6-14.8; p < 0.001). Multiple logistic regression analysis found an association between serum sFasL levels and mortality after controlling for GCS, age and CT findings (OR = 1.055; 95% CI = 1.018-1.094; p = 0.004), and after controlling for APACHE-II, ICP and CT findings (OR = 1.048; 95% CI = 1.017-1.080; p = 0.002). CONCLUSIONS: The association between serum sFasL levels and 30-day mortality in TBI patients was the major novel finding of our study; however, future validation could be interesting to confirm those results.

Serum Levels of B-cell Lymphoma-2 Anti-Apoptotic Protein and Malignant Middle Cerebral Artery Infarction Mortality.

INTRODUCTION AND GOAL: There is scarce and contradictory data on B-cell lymphoma 2 (Bcl2), member of the Bcl-2 antiapoptotic molecules family of intrinsic apoptosis pathway, in ischemic stroke patients. The objective of this study was to determine whether there is an association between blood Bcl2 concentrations and mortality of ischemic stroke patients. MATERIAL AND METHODS: Five Intensive Care Units participated in this prospective and observational study of patients with severe malignant middle cerebral artery infarction (MMCAI). Severe MMCAI was diagnosed when acute infarction was present in 50% or more of said region and with a Glasgow Coma Scale (GCS) score of less than 9 points. Serum samples were collected at the time of MMCAI diagnosis. FINDINGS: Higher serum Bcl2 concentrations (p = 0.001), lower platelet count (p = 0.01) and lower GCS (p = 0.002) were found in non-survivors (n = 28) than in MMCAI survivors (n = 28). Serum Bcl2 levels had an area under the curve for mortality prediction of 75% (95% CI = 62%-88%; p < 0.001). Patients with serum Bcl2 levels > 43.6 ng/mL had higher mortality rate according to Kaplan-Meier analysis (Hazard ratio=10.0; 95% CI = 3.4-29.5; p < 0.001). Multiple logistic regression showed an association between serum Bcl2 and mortality at 30 days (OR = 1.041; 95% CI = 1.006-1.077; p = 0.02) controlling for GCS and platelet count. CONCLUSIONS: This study reports for the first time the higher blood Bcl2 concentrations in non-surviving ischemic stroke patients than in survivors and the association between elevated blood Bcl2 and mortality in ischemic stroke patients.

Mortality prediction of ischemic stroke patients without thrombectomy by blood total antioxidant capacity.

It has been previously established that total antioxidant capacity concentrations of blood on the first day of ischemic stroke could predict mortality. Therefore, our study objective was to determine whether total antioxidant capacity concentrations in the blood during the first week of a cerebral infarction could help predict mortality. We included severe and malignant middle cerebral artery infarction patients (affecting 50% or more of the territory in computed tomography and a score of nine or fewer points in the Glasgow Coma Scale). Serum total antioxidant capacity concentrations were determined on days first, fourth, and eighth of the diagnosis of a malignant middle cerebral artery infarction. Higher serum total antioxidant capacity concentrations at first (P < 0.001), fourth (P < 0.001), and eighth (P = 0.003) day were found in non-surviving patients than in surviving ones. Serum total antioxidant capacity concentrations on first, fourth and eighth day of malignant middle cerebral artery infarction had an area under curve (95% Confidence Intervals) for 30-day mortality prediction of 0.86 (0.75-0.93; P < 0.001), 0.87 (0.74-0.95; P < 0.001) and 0.79 (0.64-0.90; P = 0.004)), respectively. Thus, the potential use of serum total antioxidant capacity concentrations at any time during the first 7 days of a severe malignant middle cerebral artery infarction without thrombectomy to predict mortality was the main novel finding of our study.

Serum substance P levels and early mortality of spontaneous intracerebral haemorrhage patients.

INTRODUCTION AND GOAL: Substance P, a neuropeptide of the tachykinin family, is involved in the neuroinflammation of different diseases of the central nervous system. To our knowledge, there is no published data on the level of circulating substance P levels in the prognosis of patients with spontaneous intracerebral hemorrhage (ICH). Therefore, the objectives of this observational and prospective study were to determine whether serum substance P levels in ICH patients were associated with early mortality and whether could be used in the mortality prognostic. MATERIAL AND METHODS: We included patients with severe primary supratentorial ICH (defined as Glasgow Coma Scale < 9) from 6 Intensive Care Units of Spanish hospitals. We determined serum substance P levels at the time of severe ICH diagnosis, at fourth and at eighth day. Thirty-day mortality was considered the end-point study. FINDINGS: Non-surviving (n=53) compared to surviving ICH patients (n=64) showed higher serum substance P levels at day 1 (p<0.001), day 4 (p<0.001) and day 8 (p<0.001). The area under the curve for 30-day mortality prediction by serum substance P levels was of 79% (95% CI = 70-86%; p<0.001). Kaplan-Meier analysis showed a higher 30-day mortality in patients with serum substance P levels>503 pg/mL (Hazard ratio=14.7; 95% CI=6.88-31.55; p<0.001). Multiple logistic regression analysis showed an association between serum substance P levels and 30-day mortality (Odds Ratio=1.006; 95% CI=1.002-1.010; p=0.004) controlling for ICH score, midline shift, glycemia, early evacuation of ICH. CONCLUSIONS: Thus, the novel aspects our study include that serum substance P levels in severe primary ICH patients were higher in non-surviving than in surviving patients, that serum substance P levels were associated with early mortality controlling for other variables, and that serum substance P levels could be used as biomarkers of prognosis.

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage.

BACKGROUND: Several studies of spontaneous intracerebral hemorrhage (SICH) patients have shown apoptotic changes in brain samples after hematoma evacuation. However, there have been no data on the association between blood concentrations of soluble fas (sFas) (the main surface death receptor of the extrinsic apoptosis pathway) and the prognosis of spontaneous intracranial hypotension (SIH) patients. AIM: To determine whether there is an association between blood sFas concentrations and SICH patient mortality. METHODS: We included patients with severe and supratentorial SIH. Severe was defined as having Glasgow Coma Scale < 9. We determined serum sFas concentrations at the time of severe SICH diagnosis. RESULTS: We found that non-surviving patients (n = 36) compared to surviving patients (n = 39) had higher ICH score (P = 0.001), higher midline shift (P = 0.004), higher serum sFas concentrations (P < 0.001), and lower rate of early hematoma evacuation (P = 0.04). Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality (odds ratio = 1.070; 95% confidence interval = 1.014-1.129; P = 0.01) controlling for ICH score, midline shift, and early hematoma evacuation. CONCLUSION: The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.

High blood Fas concentrations in non-survivor patients with traumatic brain injury.

Fas is one of the main death receptors of the extrinsic pathway of apoptosis. A study has reported higher Fas expression in brain samples of non-surviving TBI patients than in survivors. The objective of our current study was to determine whether there is an association between Fas concentrations in blood and mortality of isolated TBI patients. Patients with severe TBI [< 9 points in Glasgow Coma Scale (GCS)] and isolated TBI (< 10 non-cranial aspects points on the Injury Severity Score) were included from 5 Intensive Care Units. We measured serum Fas concentrations on the day of TBI. Non-surviving (n = 23) compared to surviving patients (n = 57) had higher age (p = 0.01), lower GCS (p = 0.001), higher APACHE-II score (p < 0.001), higher ICP (p = 0.01), higher CT findings with high risk of death (p = 0.02) and higher serum Fas concentrations (p < 0.001). We found in regression analyses an association between serum Fas levels and mortality of TBI patients after controlling for CT findings, age and CGS (OR = 1.006; 95% CI 1.001-1.011; p = 0.02), and after controlling for CT findings, ICP and APACHE-II (OR = 1.007; 95% CI 1.001-1.012; p = 0.02). Thus, the most interesting and novel finding in this study is the association between high blood Fas concentrations and mortality in TBI patients.

Association between serum concentrations of anti-apoptotic B-cell lymphoma-2 protein and traumatic brain injury mortality.

BACKGROUND: There are scarce and contradictory data existing about B-cell lymphoma 2 (Bcl2), one of the Bcl2 family of anti-apoptotic proteins, in traumatic brain injury (TBI) patients. Thus, the objective of this study was to analyze whether blood concentrations of Bcl2 are associated with mortality. METHODS: Patients with isolated and severe TBI, defined as <10 points of the Injury Severity Score (ISS) in non-cranial aspects and <9 points in Glasgow Coma Scale (GCS), were included. This was an observational and prospective study carried out in five Intensive Care Units. Serum Bcl2 concentrations on day 1 of TBI were determined. RESULTS: Serum Bcl2 concentrations were lower (p < 0.001) in surviving patients (n = 59) compared to non-survivors (n = 24). We found an association between serum Bcl2 levels and mortality controlling for age and GCS (OR = 1.149; 95% CI = 1.056-1.251; p = 0.001) and controlling for computer tomography findings (OR = 1.147; 95% CI = 1.056-1.246; p = 0.001). CONCLUSIONS: This study reports for the first time an association between serum Bcl2 levels and 30-day mortality in TBI patients.

Mortality prediction of patients with spontaneous intracerebral hemorrhage by serum soluble Fas ligand concentrations.

BACKGROUND: A study of patients with spontaneous intracerebral hemorrhage (SIH) found a higher content of Fas ligand in the perihematomic brain area compared to healthy brain areas. The objective of this study was to analyze whether blood soluble Fas ligand (sFasL) concentrations could be used to estimate the prognosis of SIH patients. METHODS: Observational and prospective study performed in five Spanish Intensive Care Units. Patients with severe supratentorial SIH, defined as Glasgow Coma Scale (GCS) <9, were included. Serum sFasL levels were determined at the time of diagnosis of severe SIH. Mortality at 30 days was the end-point study. RESULTS: Surviving SIH patients (n = 41) compared to nonsurvivors (n = 38) showed lower serum sFasL levels (p < 0.001). The area under curve of mortality prediction for serum sFasL levels was 0.79 (95% CI = 0.70-0.89; p < 0.001). Multiple logistic regression analysis found an association of serum sFasL concentrations with 30-day mortality (ORo = 1,034; 95% CI = 1,010-1,058; p = 0,006) after controlling for midline shift, early hematoma evacuation, and intracerebral hemorrhage score. CONCLUSIONS: The capability of serum sFasL to predict SIH patient mortality is the main novel finding of our study. ABBREVIATIONS: APACHE II: Acute Physiology and Chronic Health Evaluation; aPTT: activated partial thromboplastin time; FIO2: fraction of inspired oxygen; GCS: Glasgow Coma Scale; ICU: Intensive Care Unit; INR: international normalized ratio; PaO2: pressure of arterial oxygen.

Blood soluble Fas concentrations and ischemic stroke patient mortality.

BACKGROUND: Fas is a major receptor for cell death by apoptosis. Higher blood concentrations of soluble Fas (sFas) have been reported in patients with ischemic stroke compared to control subjects. The aim of this study was to explore the existence or not of an association between blood sFas concentrations and mortality in patients with ischemic stroke. METHODS: This study included patients admitted to Intensive Care Units with severe and malignant middle cerebral artery infarction (MCAI), defined as acute infarction, in more than 50% of this territory on computed tomography and less than 9 points on the Glasgow Coma Scale (GCS). Serum sFas levels were determined at the time of diagnosis of MMCAI. RESULTS: Non-surviving severe MMCAI patients (n = 27) showed lower platelet count (p = 0.004), higher serum sFas (p < 0.001), and lower GCS (p = 0.001) compared to surviving patients (n = 27). Multiple logistic regression found an association of serum sFas levels and mortality at 30 days (OR = 1.015; 95% CI = 1.002-1.027; p = 0.02) after control for CGS and platelet count. CONCLUSIONS: The main novelty of our study was the existence of an association between high blood sFas concentrations and mortality in patients with ischemic stroke.

Blood concentrations of proapoptotic sFas and antiapoptotic Bcl2 and COVID-19 patient mortality.

Background: There are no data on circulating concentrations of sFas (proapoptotic protein of extrinsic pathway) and Bcl2 (antiapoptotic protein of intrinsic pathway) in COVID-19 patients. Thus, our objective study was to determine whether an association exists between serum concentrations of sFas and Bcl2 and COVID-19 patient mortality.Methods: This observational and prospective study of COVID-19 patients was performed in eight Intensive Care Units (ICU) from Canary Islands (Spain). Serum levels of sFas and Bcl2 at ICU admission were determined. Mortality at 30 days was the end-point study.Results: Surviving patients (n = 42) compared to non-surviving (n = 11) had lower APACHE-II (p < 0.001), lower SOFA (p = 0.004), lower serum sFas levels (p = 0.001) and higher serum Bcl2 levels (p < 0.001). Logistic regression showed an association between high serum sFas levels and mortality after controlling for APACHE-II (OR = 1.004; 95% CI = 1.101-1.007; p = 0.01) or SOFA (OR = 1.003; 95% CI = 1.101-1.106; p = 0.004), and between low serum Bcl2 levels and mortality after controlling for APACHE-II (OR = 0.927; 95% CI = 0.873-0.984; p = 0.01) or SOFA (OR = 0.949; 95% CI = 0.913-0.987; p = 0.01).Conclusions: Thus, to the best of our knowledge, this is the first study reporting blood levels of sFas and Bcl2 in COVID-19 patients and its association with mortality.

Serum tissue inhibitor of MMP-1 levels at any moment of the first week of spontaneous intracerebral hemorrhage may predict early mortality.

Aim: To determine whether serum levels of MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 during the first week after spontaneous intracerebral hemorrhage (SIH) could be used for mortality prediction. Materials & methods: We included 117 patients with severe supratentorial SIH (defined as Glasgow Coma Scale <9). We determined serum concentrations of MMP-9 and TIMP-1 at days 1, 4 and 8 of severe SIH diagnosis. Results: The area under curve of serum TIMP-1 concentrations at days 1, 4 and 8 to predict 30-day mortality of 75% (p < 0.001), 82% (p < 0.001) and 73% (p < 0.001). Conclusion: Thus, the novel findings of our study were that serum levels of TIMP-1 during the first week of SIH may be used for mortality prediction.

Serum melatonin levels in predicting mortality in patients with severe traumatic brain injury.

PURPOSE: A secondary brain injury could appear after traumatic brain injury (TBI) due to neuroinflammation, oxidation and apoptosis. Higher levels of serum melatonin have been found on admission for TBI in non-surviving than in surviving patients. Thus, the objective of this study was to know serum melatonin levels during the first week of TBI in surviving and non-surviving patients, and to know if serum melatonin levels during the first week of TBI can be used to predict mortality. METHODS: Patients with an isolated and severe TBI were included; that is, if they scored < 10 points in non-cranial aspects of Injury Severity Score and < 9 points in the Glasgow Coma Scale. We measured serum melatonin concentrations at days 1, 4 and 8 of TBI. Thirty-day mortality was the end-point study. RESULTS: Lower serum melatonin levels were found in the surviving patients (n = 90) than in the non-survivors (n = 34) on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.02) of TBI. Serum melatonin concentrations on days 1, 4, and 8 of TBI had an area under curve (95% Confidence Interval) for the prediction of 30-day mortality of 0.85 (0.77-0.91; p < 0.001), 0.82 (0.74-0.89; p < 0.001) and 0.71 (0.61-0.79; p = 0.06) respectively. CONCLUSIONS: The new findings of this study were the presence of higher levels of serum melatonin on days 1, 4 and 8 of TBI in non-survivors than in survivors, and the ability to predict 30-day mortality for serum melatonin levels measured at these time points. However, more research is necessary to confirm our results.

Mortality of spontaneous intracerebral haemorrhage patients and high serum caspase-8 concentrations.

PURPOSE: Apoptotic changes in brain samples have been found in haematoma areas of patients with spontaneous intracerebral haemorrhage (SIH) undergoing surgical haematoma evacuation. However, circulating caspase-8 concentrations in SIH patients have not been described. Thus, we carried out this study with the aim to explore whether there is an association of circulating caspase-8 concentrations and mortality in patients with SIH. METHODS: We included patients with severe and supratentorial SIH. We established that the SIH was severe if Glasgow Coma Scale (GCS) was lower than 9. Intensive Care Units from 5 Spanish hospitals carried out the recruitment of patients of this observational and prospective study. We registered serum caspase-8 levels at moment of severe SIH diagnosis and 30-day mortality. RESULTS: Surviving (n = 41) in respect to non-surviving SIH patients (n = 38) showed lower serum caspase-8 levels (p < 0.001). The area under the curve to estimate 30-day mortality ability by serum caspase-8 levels was 0.75 (95% CI = 0.64-86; p < 0.001). Kaplan-Meier analysis found that patients with serum caspase-8 levels > 17.8 ng/mL showed higher death risk (Hazard ratio = 3.9; 95% CI = 1.99-7.63; p < 0.001). Multiple logistic regression analysis revealed the association of serum caspase-8 concentrations (controlling for intracerebral haemorrhage score, midline shift and early haematoma evacuation) with mortality at 30 days (Odds Ratio = 1.048; 95% CI = 1.018-1.079; p = 0.002). CONCLUSIONS: The association of serum caspase-8 concentrations with mortality of SIH patient mortality is the main of novel findings that have been revealed in our study.

DNA and RNA Oxidative Damage and Mortality of Patients With COVID-19.

BACKGROUND: Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) oxidative damage is associated with mortality of patients with different diseases. However, there are no data about DNA and RNA oxidative damage from coronavirus disease 2019 (COVID-19) patients. Thus, the objective of this study was to explore DNA and RNA oxidative damage in surviving and non-surviving COVID-19 patients. MATERIALS AND METHODS: Eight Intensive Care Units from 6 hospitals in the Canary Islands (Spain) participated in this prospective and observational study. We recorded the serum levels at ICU admission of the three guanine oxidized species (OGS) because guanine is the nucleobase that forms the DNA and RNA most prone to oxidation. Survival at 30 days was our end-point study. RESULTS: Non-surviving (n = 11) compared to surviving patients (n = 42) had higher APACHE-II (p < 0.001), SOFA (p = 0.004) and serum OGS levels (p = 0.001). In logistic regression analyses an association between serum OGS levels and 30-day mortality after controlling for SOFA (OR=2.601; 95% CI=1.305-5.182; p = 0.007) or APACHE-II (OR=2.493; 95% CI=1.274-4.879; p = 0.008) was found. The area under curve (AUC) for mortality prediction by serum OGS levels was 83% (95% CI=70-92%; p < 0.001), by APACHE II was 85% (95% CI=75-96%; p < 0.001), and by SOFA was 80% (95% CI=66-94%; p < 0.001). No significant differences were found in the AUC between serum OGS levels and SOFA (p = 0.91), and serum OGS levels and APACHE-II (p = 0.64). CONCLUSIONS: To our knowledge, this is the first study reporting on oxidative DNA and RNA damage in COVID-19 patients, and the main new finding was that serum OGS concentration was associated with mortality.

Red blood cell distribution width as mortality biomarker in patients with traumatic brain injury.

One study found higher red blood cell distribution width (RDW) on the admission of traumatic brain injury (TBI) in non-surviving patients; however, a regression analysis was not carried out to establish an association between RDW and TBI mortality. Thus, the objectives of this study were to determine whether there is an association between RDW and TBI mortality, and to describe the temporal profile of RDW during the first week. Isolated (< 10 points in non-cranial aspects of Injury Severity Score) and severe (< 9 points in Glasgow Coma Scale) TBI patients were included. RDW at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Ninety-seven surviving patients compared to the 38 non-surviving patients had higher RDW at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). The area under the curve (95% CI) for prediction of mortality by RDW at days 1, 4, and 8 was 0.81 (0.73-0.87; p < 0.001), 0.92 (0.85-0.96; p < 0.001) and 0.94 (0.88-0.98; p < 0.001). Regression analysis showed an association between RDW and mortality (odds ratio = 1.778; 95% CI 1.312-2.409; p < 0.001). The association found between RDW on admission and mortality is the main new finding of our study. Regarding the temporal profile of RDW, the fact that RDW during the first week of TBI may help in estimating prognosis is another interesting finding of our study.

Association between red blood cell distribution width and mortality of COVID-19 patients.

PURPOSE: We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. METHODS: Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. RESULTS: We found that patients who did not survive (n=25) compared to surviving patients (n=118) were older (p=0.004), showed higher RDW (p=0.001), urea (p<0.001), APACHE-II (p<0.001) and SOFA (p<0.001), and lower platelet count (p=0.007) and pH (p=0.008). Multiple binomial logistic regression analysis showed that RDW was associated with 30-day mortality after controlling for: SOFA and age (OR=1.659; 95% CI=1.130-2.434; p=0.01); APACHE-II and platelet count (OR=2.062; 95% CI=1.359-3.129; p=0.001); and pH and urea (OR=1.797; 95% CI=1.250-2.582; p=0.002). The area under the curve (AUC) of RDW for mortality prediction was of 71% (95% CI=63-78%; p<0.001). We did not find significant differences in the predictive capacity between RDW and SOFA (p=0.66) or between RDW and APACHE-II (p=0.12). CONCLUSIONS: Our study provides new information regarding the ability to predict mortality in patients with COVID-19. There is an association between high RDW and mortality. RDW has a good performance to predict 30-day mortality, similar to other severity scores (such as APACHE II and SOFA) but easier and faster to obtain.