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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.This observational prospective study included patients with severe supratentorial SIH (defined as Glasgow Coma Scale9) 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.Nonsurviving patients (n = 46) showed higher serum TIMP-1 (P0.001) 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 levels223 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).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 circulating soluble cluster of differentiation 40 ligand (sCD40L) levels at admission of an ischemic stroke have been found in nonsurvivor than in survivor patients. The objectives of this study were to determine whether serum sCD40L levels during the first week of a severe malignant middle cerebral artery infarction (MMCAI) are higher in nonsurvivor than in survivor patients and whether they could be used as biomarker of mortality prediction.This multicenter study included patients with severe MMCAI (defined as Glasgow Coma Scale score9). We determined serum sCD40L concentrations at days 1, 4, and 8 and performed receiver operating characteristic analyses to determine their capacity for 30-day mortality prediction.Nonsurvivors (n = 34) showed higher sCD40L levels on days 1 (P0.001), 4 (P = 0.004), and 8 (P0.001) than did survivor patients (n = 34). Areas under the curve of serum sCD40L concentrations at days 1, 4, and 8 of severe MMCAI for 30-day mortality prediction were 83% (P 0.001), 89% (P0.001), and 87% (P0.001), respectively.The findings that nonsurvivors showed higher serum sCD40L levels during the first week of MMCAI than did survivors and that serum sCD40L levels during the first week of MMCAI could be used as a mortality predictor biomarker are 2 novel findings.

Substance P is a neuropeptide belonging to the tachykinin family and is involved in neuroinflammation. In a previous study by our team, we found higher serum substance P levels on day 1 of traumatic brain injury (TBI) in nonsurviving than in surviving patients. Thus, the objective of this study was to determine whether serum substance P levels during the first week of TBI could predict early mortality.This was a multicenter, observational, and prospective study. We included patients with an isolated severe TBI, defining isolated as9 points in non-cranial aspects of Injury Severity Score and severe as9 points of Glasgow Coma Scale. We determined serum substance P concentrations at days 1, 4, and 8 of TBI. We performed receiver operating characteristic analyses to determine the capacity of serum substance P levels at day 1, 4, and 8 of TBI to predict 30-day mortality.Nonsurviving (n = 34) compared with surviving patients (n = 90) had greater serum substance P levels on day 1 (P0.001), 4 (P0.001), and 8 (P0.001) of TBI. The areas under curve of serum substance P concentrations at days 1, 4, and 8 of TBI to predict 30-day mortality were 76% (P0.001), 87% (P0.001), and 89% (P0.001), respectively.The new finding of our study is that the presence of elevated serum substance P levels during the first week of TBI is associated with increased mortality.

Soluble cluster of differentiation 40 ligand (sCD40L) is a member of the tumor necrosis factor family with proinflamatory and procoagulant effects. A previous study found higher serum sCD40L levels at day 1 of traumatic brain injury (TBI) in nonsurviving than surviving patients. Thus the objective of this study was to compare serum sCD40L levels during the first week of a severe TBI between surviving and nonsurviving patients and to determine whether it could be used as a mortality predictor biomarker.In this multicenter study severe TBI patients (with Glasgow Coma Scale score9) with an Injury Severity Score in noncranial item9 were included. Serum sCD40L concentrations at days 1, 4, and 8 of TBI were determined. We performed receiver operating characteristic analyses to determine the capacity of 30-day TBI mortality prediction by serum sCD40L levels at days 1, 4, and 8 of TBI.We found that nonsurviving (n = 34) patients in comparison with surviving (n = 90) patients had higher sCD40L levels on days 1 (P0.001), 4 (P = 0.004), and 8 (P 0.001) of TBI. We also found that the areas under curve of serum sCD40L concentrations at days 1, 4, and 8 of TBI to 30-day mortality prediction were 82% (P0.001), 72% (P = 0.01) and 83% (P0.001), respectively.The existence of higher serum sCD40L levels in nonsurviving than surviving patients during the first week of TBI and fact that serum sCD40L levels during the first week of TBI can be used as a mortality predictor biomarker are the new findings of our study.