RESUMO
Background: Older age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI. Methods: This was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated. Results: Sixty patients were studied, 65% were males, their age was 76 years (IQR 70-80) and their admission GCS was 8 (IQR 6-11) with a GCS motor score of 5 (IQR 4-5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9-55.2), p < 0.0001 and 92% vs. 51% OR and 95% CI: 9.9 (2.1-46.3), p = 0.002]. In univariate analysis patients with unfavorable outcome were more frequently male and vulnerable-frail, had a higher prevalence of pre-existing neurodegenerative disease, abnormal pupil, lower GCS and had worst CT scan characteristics. At multivariate analysis, only CFS ≥ 4 and traumatic subarachnoid hemorrhage remained associated to 6-month outcome. Conclusion: Frailty was associated with 6 month-outcome, suggesting that the pre-injury functional status could represent an additional indicator to stratify patient's severity and to predict outcome.
RESUMO
The role of tumor necrosis factor (TNF) and its receptors after traumatic brain injury (TBI) remains unclear. We evaluated the effects of genetic deletion of either p55 or p75 TNF receptor on neurobehavioral outcome, histopathology, DNA damage and apoptosis-related cell death/survival gene expression (bcl-2/bax), and microglia/macrophage (M/M) activation in wild-type (WT) and knockout mice after TBI. Injured p55 (-/-) mice showed a significant attenuation while p75 (-/-) mice showed a significant worsening of sensorimotor deficits compared with WT mice over 4 weeks postinjury. At the same time point, contusion volume in p55 (-/-) mice (11.1±3.3 mm(3)) was significantly reduced compared with WT (19.7±3.4 mm(3)) and p75 (-/-) mice (20.9±3.2 mm(3)). At 4 hours postinjury, bcl-2/bax ratio mRNA expression was increased in p55 (-/-) compared with p75 (-/-) mice and was associated with reduced DNA damage terminal deoxynucleotidyl transferaseYmediated dUTP nick end labeling (TUNEL-positivity), reduced CD11b expression and increased Ym1 expression at 24 hours postinjury in p55 (-/-) compared with p75 (-/-) mice, indicative of a protective M/M response. These data suggest that TNF may exacerbate neurobehavioral deficits and tissue damage via p55 TNF receptor whose inhibition may represent a specific therapeutic target after TBI.