Association of Serum Bilirubin with the Severity and Outcomes of Intracerebral Hemorrhages

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, and it is often associated with a high mortality rate and significant morbidity among survivors. Recent studies have shown that bilirubin, a product of heme metabolism, can exhibit cytoprotective, antioxidant and, anti-inflammatory properties. However, little is known about the role of bilirubin in combating several pathophysiological pathways caused by intracerebral bleeding in patients with ICH. In this study, data were collected retrospectively on 276 patients with ICH who were admitted to a university hospital between 5 January 2014 and 31 December 2017. We assessed the relationship between levels of total, direct, and indirect serum bilirubin and assessments of initial stroke severity and clinical outcomes by using Spearman’s rank correlation and Kruskal-Wallis H tests. A secondary examination of the carrier protein albumin was also undertaken. Our study found that higher levels of direct bilirubin were correlated with worse admission Glasgow Coma Scales (GCS) (rs = −0.17, p = 0.011), worse admission ICH Scores (rs = 0.19, p = 0.008), and worse discharge modified Rankin Scales (mRS) (rs = 0.15, p = 0.045). Direct bilirubin was still significantly correlated with discharge mRS after adjusting for temperature at admission (rs = 0.16, p = 0.047), oxygen saturation at admission (rs = 0.15, p = 0.048), white blood cell count (rs = 0.18, p = 0.023), or Troponin T (rs = 0.25, p = 0.001) using partial Spearman’s correlation. No statistical significance was found between levels of total or indirect bilirubin and assessments of stroke severity and outcomes. In contrast, higher levels of albumin were correlated with better admission GCS (rs = 0.13, p = 0.027), discharge GCS (rs = 0.15, p = 0.013), and discharge mRS (rs = −0.16, p = 0.023). We found that levels of total bilirubin, direct bilirubin, and albumin were all significantly related to discharge outcomes classified by discharge destinations (p = 0.036, p = 0.014, p = 0.016, respectively; Kruskal-Wallis H tests). In conclusion, higher direct bilirubin levels were associated with greater stroke severity at presentation and worse outcomes at discharge among patients with ICH. Higher levels of albumin were associated with lower stroke severity and better clinical outcomes. Future prospective studies on the free bioactive bilirubin are needed to better understand the intricate relationships between bilirubin and ICH

The Role of Executive Functioning and Academic Achievement in the Academic Self-Concept of Children and Adolescents Referred for Neuropsychological Assessment

The current study evaluated a model of youth academic self-concept which incorporates practical executive functioning behaviors and academic achievement. Though greater academic achievement has been linked to both positive self-concept and better executive functioning, these constructs have not been examined simultaneously. It was hypothesized that academic achievement would mediate the association between problems with executive functioning and academic self-concept such that youth with more problems with executive functioning would have lower academic achievement and, in turn, lower academic self-concept. Clinical data was analyzed from a diagnostically heterogeneous sample of youth (n = 122) who underwent neuropsychological evaluation. Problems with executive functioning were assessed using the Behavior Rating Inventory of Executive Function. Academic achievement was assessed using the Woodcock–Johnson Tests of Achievement or Wechsler Individual Achievement Test. Academic self-concept was assessed using the youth-report version of the Behavioral Assessment System for Children. Surprisingly, findings indicate that academic achievement is not significantly associated with problems with executive functioning or academic self-concept. However, greater problems with executive functioning are associated with decreased academic self-concept. The overall model included several covariates and accounted for 10% of the variance in academic self-concept. Findings suggest that executive skills may be essential for aligning academic achievement with classroom performance. Though various child characteristic covariates were included, the model accounted for a small amount of variance suggesting that future studies should examine contributing contextual factors

Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2

Background Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction. Methods Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7-10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations. Results The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (beta = 0.488 p = 0.000) as well as reduced cognitive independence (beta = - 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (beta = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7-10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (beta = - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (beta = 0.679, p = 0.010). Conclusions Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes