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 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.

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.

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.

High Serum Levels of Caspase-3 and Early Mortality in Patients with Severe Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Apoptotic cell death leads to secondary brain injury after spontaneous intracerebral hemorrhage (SIH). There is an association between serum caspase-3 levels and late mortality (at 6 months) in patients with SIH in basal ganglia. The new objective of this study was to determine whether there exists an association between serum caspase-3 levels and early mortality (at 30 days) in patients with SIH at different sites and not only in basal ganglia. METHODS: Patients with severe supratentorial SIH (defined as Glasgow Coma Scale < 9) admitted in 6 Spanish hospitals were included in this observational and prospective study. Patients with SIH due to aneurysm, arteriovenous malformation, and anticoagulant or fibrinolytic treatment were excluded. Serum caspase-3 levels at days 1, 4, and 8 of SIH were determined. Thirty-day mortality was the end-point study. RESULTS: Non-surviving (n = 53) showed higher serum caspase-3 levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001) than survivor patients (n = 64). Multiple logistic regression analysis showed an association of serum caspase-3 levels > 0.167 ng/mL with 30-day mortality (Odds Ratio = 47.007; 95% CI = 4.838-456.727; p = 0.001). CONCLUSIONS: The new findings of our study are that serum caspase-3 levels are associated with early mortality in patients with severe supratentorial SIH at different sites and that those levels during the first week of SIH are higher in non-survivors than in survivors.

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.

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.

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.

Red blood cell distribution width and mortality of spontaneous intracerebral hemorrhage patients.

OBJECTIVES: Two studies have found an association between hematoma expansion and red blood cell distribution width (RDW) in the diagnosis of spontaneous intracerebral hemorrhage (SIH); however, its association with SIH mortality has been not reported. Thus, the objectives of this study were to determine whether RDW in patients with SIH could be associated with mortality and could be used as mortality biomarker. PATIENTS AND METHODS: Observational and prospective study of patients with severe supratentorial SIH (Glasgow Coma Scale < 9) from Intensive Care Units of 6 Spanish hospitals. RDW was recorded at days 1, 4 and 8 of SIH. Thirty-day mortality was considered the end-point study. RESULTS: Non-surviving patients (n = 54) compared to surviving patients (n = 63) had higher RDW (p ≤ 0.001) at days 1, 4 and 8 of SIH. The area under curve (95 % confidence interval) to predict 30-day mortality by RDW at days 1, 4, and 8 of SIH was 0.87 (0.79-0.92; p < 0.001), 0.74 (0.64-0.83; p < 0.001) and 0.79 (0.68-0.87; p < 0.001) respectively. In the regression analysis an association between RDW and 30-day mortality was found controlling for early evacuation of SIH, midline shift, ICH score and glycemia (Odds ratio = 1.159; 95 % CI = 1.046-1.284; p = 0.005). CONCLUSIONS: The higher RDW during the first week of SIH in non-surviving than in surviving patients, and the potential role of RDW at any time during the first week as mortality biomarker are the main novelties 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.

Early Mortality of Brain Infarction Patients and Red Blood Cell Distribution Width.

BACKGROUND: Meta-analysis has found that high baseline red blood cell distribution width (RDW) is associated with increased long-term mortality (mortality at one year or more) in ischemic stroke. The objectives of this study were to determine whether there is an association between RDW and 30-day mortality, and to explore whether RDW during the first week of ischemic stroke could be a 30-day mortality biomarker. METHODS: We included patients with malignant middle cerebral artery infarction (MMCAI). RDW at days 1, 4, and 8 of MMCAI were determined. The end-point study was 30-day mortality. RESULTS: We found that survivor (n = 37) in respect to non-survivor patients (n = 37) had lower RDW at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.02). The area under curve (95% CI) for prediction of 30-day mortality by RDW at days 1, 4, and 8 of MMCAI were 0.80 (0.69-0.89; p < 0.001), 0.79 (0.66-0.89; p < 0.001), and 0.73 (0.58-0.84; p = 0.02). Regression analysis showed an association between RDW (odds ratio = 1.695; 95% CI = 1.230-2.335; p < 0.001) and 30-day mortality. CONCLUSIONS: The association between RDW and early mortality, and the potential role of RDW during the first week of MMCAI as a prognostic biomarker of early mortality were the main novelties of our study.

Non-Survivor Ischemic Stroke Patients Maintain High Serum Caspase-Cleaved Cytokeratin-18 Levels.

OBJECTIVE: Caspase-cleaved cytokeratin (CCCK)-18 could appear in blood during apoptosis. In two different studies, on day 1 of cerebral infarction and at 72 hours of cerebral infarction, respectively, higher circulating CCCK-18 levels were found in non-surviving than in surviving patients. The objective of this study was to analyze the ability of these levels to predict mortality at any time during the first week of cerebral infarction. METHODS: Patients with malignant middle cerebral artery infarction (MMCAI) were included and the diagnosis criteria were the presence, observed in a computed tomography, of an acute cerebral infarction in at least 50% of this territory and midline shift, and an acute neurological deterioration with a Glasgow Coma Scale ≤ 8. Serum CCCK-18 levels at days 1, 4 and 8 of MMCAI were determined. RESULTS: Serum concentrations of CCCK-18 at days 1, 4 and 8 of MMCAI were higher in non-surviving (n = 34) than in surviving patients (n = 34). Serum CCCK-18 concentrations at days 1, 4 and 8 of MMCAI had an area under curve (95% CI) used to predict a 30-day mortality of 0.83 (0.72--0.91; p < 0.001), 0.78 (0.65-0.89; p < 0.001) and 0.82 (0.68-0.92; p < 0.001). CONCLUSIONS: The novel finding is that serum levels of CCCK-18 levels at any time after the first week of MMCAI could help predict 30-day mortality.

Traumatic Brain Injury Patients Mortality and Serum Total Antioxidant Capacity.

OBJECTIVE: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to determine the role of serum TAC levels at any time during the first week of TBI for the prediction of early mortality. METHODS: Isolated (<10 points in non-cranial aspects of Injury Severity Score) and severe (<9 points in Glasgow Coma Scale) TBI patients were included. Serum TAC concentrations at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. RESULTS: Higher serum TAC levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.002) of TBI were found in non-surviving (n = 34) than in surviving patients (n = 90). The area under curve (95% Confidence Interval) for prediction of 30-day mortality by serum TAC concentrations at days 1, 4, and 8 of TBI were 0.79 (0.71-0.86; p < 0.001), 0.87 (0.79-0.93; p < 0.001), and 0.76 (0.67-0.84; p = 0.006) respectively. CONCLUSIONS: The novelty of our study was the ability to predict 30-day mortality by serum TAC concentrations at any time during the first week of TBI.

High serum substance P levels and mortality after malignant middle cerebral artery infarction.

PURPOSE: Previously our team found higher serum substance P concentrations at day 1 of a malignant middle cerebral artery infarction (MMCAI) in non-surviving than in surviving patients. Thus, the objective of this study was to determine whether serum substance P levels during the first week of MMCAI could predict mortality. METHODS: We included patients with MMCAI defined as computed tomography findings of acute infarction in at least of 50% of the territory and Glasgow Coma Scale ≤8. We determined serum concentrations of substance P on days 1, 4 and 8 of MMCAI. Thirty-day mortality was the study end-point. RESULTS: Serum substance P concentrations at days 1 (p < .001), 4 (p < .001), and 8 (p = .001) of MMCAI in non-surviving (n = 34) were higher than in surviving patients (n = 34). Receiver operating characteristic analyses showed that serum substance P concentrations at days 1, 4, and 8 of MMCAI had an area under curve (95% confidence intervals) to predict 30-day mortality of 0.77 (0.66-0.87; p < .001), 0.82 (0.69-0.91; p < .001) and 0.85 (0.72-0.94; p < .001) respectively. CONCLUSIONS: The two new findings of our study are that non-surviving MMCAI patients showed higher serum substance P levels at day 1, 4 and 8 than surviving, and that those levels could predict 30-day mortality.

Association Between DNA and RNA Oxidative Damage and Mortality of Patients with Traumatic Brain Injury.

BACKGROUND: The hyperoxidative state in traumatic brain injury (TBI) could produce oxidative damage on the ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Oxidative damage to nucleic acids in TBI patients has been studied, and higher concentrations of 8-OHdG were found in postmortem brain samples of subjects who died following TBI than in subjects who died from sudden cardiac death. Thus, the objective of this study was to determine whether there is an association between serum DNA and RNA oxidative damage and mortality in TBI patients. METHODS: We included patients with severe isolated TBI defined as a lower score than 9 points in the Glasgow Coma Scale (GCS) and lower than 9 points in non-cranial aspects in the Injury Severity Score. We determined serum concentrations of the three oxidized guanine species (OGS) (8-OHdG from DNA, 8-hydroxyguanosine from RNA, and 8-hydroxyguanine from DNA or RNA) and malondialdehyde (to estimate lipid peroxidation) on the day of TBI. Mortality at 30 days was the end-point study. RESULTS: We found higher serum concentrations of OGS (p < 0.001) and malondialdehyde (p < 0.001) in non-surviving (n = 34) than in surviving patients (n = 90), an association between serum OGS levels and 30-day mortality after control for CGS, age, and computed tomography findings (OR = 1.397; 95% CI = 1.137-1.716; p = 0.001), and a positive correlation between serum levels of OGS and malondialdehyde (rho = 0.24; p = 0.01). CONCLUSIONS: To our knowledge, our study is the largest series reporting data on DNA oxidative damage in TBI patients and is the first reporting DNA and RNA oxidative damage in TBI patients associating lipid peroxidation and mortality.

High Serum DNA and RNA Oxidative Damage in Non-surviving Patients with Spontaneous Intracerebral Hemorrhage.

PURPOSE: One study found higher leukocytes 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with spontaneous intracerebral hemorrhage (ICH) than in healthy subjects due to the oxidation of guanosine from deoxyribonucleic acid (DNA). The objective of this study was to determine whether there is an association between oxidative damage of serum DNA and ribonucleic acid (RNA) and mortality in patients with ICH. METHODS: In this observational and prospective study, patients with severe supratentorial ICH (defined as Glasgow Coma Scale < 9) were included from six Intensive Care Units of Spanish hospitals. At the time of severe ICH diagnosis, concentrations in serum of malondialdehyde (as lipid peroxidation biomarker) and of the three oxidized guanine species (OGS) (8-hydroxyguanosine from RNA, 8-hydroxyguanine from DNA or RNA, and 8-OHdG from DNA) were determined. Thirty-day mortality was considered the end-point study. RESULTS: Serum levels of OGS (p < 0.001) and malondialdehyde (p = 0.002) were higher in non-surviving (n = 46) than in surviving patients (n = 54). There was an association of serum OGS levels with serum malondialdehyde levels (rho = 0.36; p = 0.001) and 30-day mortality (OR = 1.568; 95% CI 1.183-2.078; p = 0.002). CONCLUSIONS: The novel and most important finding of our study was that serum OGS levels in ICH patients are associated with mortality.

High Serum Tissue Inhibitor of Matrix Metalloproteinase-1 Levels and Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Matrix metalloproteinase (MMP)-9, a member of the endoproteinase family, is involved in the neuroinflammation of spontaneous intracerebral hemorrhage (SIH). High circulating MMP-9 levels have been associated with poor functional outcome in patients with SIH. The objectives of this study were to determine whether serum MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 levels in SIH patients were higher in nonsurviving than surviving patients, if they were associated with early mortality, and if they could be used as biomarkers of prognosis. METHODS: This observational prospective study included patients with severe supratentorial SIH (defined as Glasgow Coma Scale <9) from 6 Spanish Intensive Care Units. Serum MMP-9 and TIMP-1 levels were determined at the time of severe SIH diagnosis. Thirty-day mortality was the endpoint study. RESULTS: Nonsurviving patients (n = 46) showed higher serum TIMP-1 (P < 0.001) and MMP-9 levels (P = 0.01) than surviving patients (n = 54). The area under the curve by serum TIMP-1 levels for the prediction of 30-day mortality was 74% (95% confidence interval = 64%-82%; P < 0.001). Multiple logistic regression analysis showed an association between serum TIMP-1 levels >223 ng/mL and 30-day mortality (odds ratio = 13.993; 95% confidence interval = 2.864-68.356; P = 0.001) after controlling for intracerebral hemorrhage score, glycemia, midline shift, and early evacuation of SIH. There was an association between circulating levels of TIMP-1 and MMP-9 (rho = 0.25; P = 0.01). CONCLUSIONS: The novel aspects our study include that serum TIMP-1 and MMP-9 levels in SIH patients were higher in nonsurviving than in surviving patients and that serum TIMP-1 levels were associated with early mortality and could be used as biomarkers for predicting mortality.

Higher Serum Melatonin Levels during the First Week of Malignant Middle Cerebral Artery Infarction in Non-Surviving Patients.

OBJECTIVE: The activation of different physiopathological pathways (neuroinflammation, apoptosis, and oxidation) can lead to secondary brain injury in ischemic stroke, and in animal models the administration of melatonin has reduced that secondary injury. Lower levels of serum melatonin were found at the time of admission of cerebral infarction in surviving patients than in non-surviving patients. Thus, we carried out this prospective and observational study with the aim of exploring serum melatonin levels in the first week of a malignant middle cerebral artery infarction (MMCAI) in surviving and non-surviving patients, and to explore the capacity of those levels to predict mortality. METHODS: Patients with severe MMCAI, defined as computed tomography showing acute infarction in more than 50% of the territory and Glasgow Coma Scale (GCS) lower than 9, were included in the study. We measured serum melatonin concentrations at days 1, 4, and 8 of MMCAI. Mortality at 30 days was the endpoint of our study. RESULTS: Non-surviving patients (n = 34) compared to surviving patients (n = 34) showed higher serum melatonin levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.001) of MMCAI. Serum melatonin concentrations at days 1, 4, and 8 of MMCAI had an area under the curve (AUC) (95% confidence interval (CI)) in the prediction of mortality of 0.89 (0.80-0.96; p < 0.001), 0.81 (0.68-0.91; p < 0.001), and 0.82 (0.68-0.92; p < 0.001), respectively. CONCLUSIONS: The novel findings of our study were that serum melatonin levels in the first week of MMCAI were higher in non-surviving patients, and were able to predict mortality.