Introduction: Substance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes. SP is released early following acute injury to the CNS, promoting a neurogenic inflammatory response characterized by an increase in the permeability of the blood–brain barrier and the development of vasogenic edema. High levels of SP could lead to an exacerbated inflammatory response that could be fatal for patients with traumatic brain injury (TBI). Thus, the main goal of the present study was to determine whether serum SP levels are associated with injury severity and mortality in patients with severe TBI.Methods: This multicenter, observational, prospective study was carried out in six Spanish intensive care units and included patients with Glasgow Coma Scale (GCS) scores ≤8. Patients with an Injury Severity Score ≥10 in non-cranial aspects were excluded. Blood samples were collected on day 1 of TBI to measure serum SP levels. The endpoint was 30-day mortality.Results: We found higher serum SP levels (P=0.002) in non-surviving patients (n =27) than in surviving patients (n =73). The area under the curve for serum SP levels with regard to predicting 30-day mortality was 0.70 (95% confidence interval (CI), 0.60 to 0.79;P299 pg/ml had higher 30-day mortality than patients with lower levels (hazard ratio =3.7; 95% CI, 1.75 to 7.94;P299 pg/ml were associated with 30-day mortality when we controlled for APACHE II score and Marshall computed tomography lesion classification (odds ratio (OR) =5.97; 95% CI, 1.432 to 24.851;P=0.01) and for GCS score and age (OR =5.71; 95% CI, 1.461 to 22.280;P=0.01). We found a negative association between serum SP levels and GCS score (Spearman’s ρ = −0.22;P=0.03).Conclusions: We report, for the first time to our knowledge, that serum SP levels were associated with injury severity and mortality in patients with severe TBI. These results open the possibility that SP antagonists may be useful in the treatment of patients with severe TBI.

Data on circulating total antioxidant capacity (TAC) levels in ischemic stroke patients compared with healthy controls are limited and provided conflicting findings. There are not data about the association between circulating TAC levels, peroxidation state and outcome in patients with severe ischemic stroke. The objective of this study was to examine the relationship of TAC with 30-day mortality after severe ischemic stroke. This multicenter study included 58 patients with coma (Glasgow Coma Scale < 9) following severe malignant middle cerebral artery infarction (MMCAI). We measured circulating levels of TAC and malondialdehyde (MDA, a biomarker of lipid peroxidation) on day 1 of severe MMCAI diagnosis. The study endpoint was 30-day mortality. Non-survivors (n = 29) showed higher serum TAC levels (p < 0.001) and higher serum MDA levels (p = 0.004) than survivors (n = 29). Multiple binomial logistic regression analysis showed that serum TAC levels were associated with 30-day mortality, after controlling for Glasgow Coma Scale and age (odds ratio 1.92; 95 % confidence interval 1.201–3.072; p = 0.006). There was a correlation between serum TAC and MDA levels (rho = 0.35; p = 0.008). This single-center study in severe MMCAI patients found an association between higher serum TAC levels and 30-day mortality and further identified a relationship between serum TAC levels, lipid peroxidation state and mortality after severe ischemic stroke.

Different apoptosis pathways activate caspase-3. In a study involving 27 patients with traumatic brain injury (TBI), higher caspase-3 levels were found in contusion brain tissue resected from non-survivors than from survivors. The objective of this study was to determine whether there is an association in TBI patients between serum caspase-3 levels (thus using an easier, quicker, less expensive and less invasive procedure) and mortality, in a larger series of patients. We carried out a prospective, observational and multicenter study in six Spanish Hospital Intensive Care Units including 112 patients with severe TBI. All had Glasgow Coma Scale (GCS) scores lower than 9. Patients with an Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Blood samples were collected on day 1 of TBI to measure serum caspas-3 levels. The endpoint was 30-day mortality. We found that non-surviving patients (n = 31) showed higher (p = 0.003) serum caspase-3 levels compared to survivors (n = 81). Kaplan-Meier survival analysis showed a higher risk of death in TBI patients with serum caspase-3 levels >0.20 ng/mL than in patients with lower concentrations (Hazard Ratio = 3.15; 95 % CI = 1.40 to 7.08; P < 0.001). Multiple logistic regression analysis showed that serum caspase-3 levels > 0.20 ng/mL were associated with mortality at 30 days in TBI patients controlling for Marshall CT classification, age and GCS (Odds ratio = 7.99; 95 % CI = 2.116 to 36.744; P = 0.001). The association between serum caspase-3 levels and mortality in TBI patients was the major novel finding of our study.

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.

Previously, circulating total antioxidant capacity (TAC) in traumatic brain injury (TBI) patients has been scarcely studied and only in studies of small sample size (lower than 55 TBI patients). In one study were found higher serum TAC in non-survivor than in survivor TBI patients; however, an association between circulating TAC and mortality in patients with TBI has not been previously reported. Thus, the objective of this study was to determine whether there is an association between circulating TAC, peroxidation state and mortality in patients with severe TBI. This was a multicenter, observational and prospective study was carried out in six Spanish Intensive Care Units. We included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9. We excluded patients with Injury Severity Score (ISS) in non-cranial aspects higher than 9. We measured serum TAC on day 1 of TBI. The 30-day mortality was established as endpoint. Non-surviving TBI patients (N = 27) showed higher serum TAC (P < 0.001) than survivor ones (N = 73). Logistic regression analyses showed that serum TAC higher than 2.59 nmol/mL were associated with 30-day mortality controlling for APACHE-II and CT classification (OR = 4.40; 95 % CI = 1.14–16.98; P = 0.03), controlling for GCS and age (OR = 5.88; 95 % CI = 1.57–22.06; P = 0.009), and controlling for CT classification and admission abnormal pupils (OR = 3.89; 95 % CI = 1.30–11.61; P = 0.02). There was an association between serum TAC and malondialdehyde (a biomarker of lipid peroxidation) levels (rho = 0.25; p = 0.01), APACHE-II score (rho = 0.23; p = 0.03) and GCS (rho = −0.21; p = 0.04). To our knowledge, our series is the largest reporting data on circulating TAC in patients with severe TBI. The most relevant and new findings of our study were that there is an association between circulating TAC and peroxidation state and mortality in patients with severe TBI.