CSF Bcl-2 and cytochrome C temporal profiles in outcome prediction for adults with severe TBI

Wagner, Amy K.; Amin, Krutika; Niyonkuru, Christian; Postal, Brett A; McCullough, Emily H.; Ozawa, Haishin; Dixon, C. Edward; Bayır, Hülya; Clark, Robert S. B.; Kochanek, Patrick M.; Fabio, Anthony

doi:10.1038/jcbfm.2011.31

Cited by 42 publications

(29 citation statements)

References 40 publications

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“…Age and, to a lesser degree, gender, have been associated with TRAJ group membership for serum hormone profiles studied in sTBI. 44,45 Older age has also been implicated in affecting other CSF biomarker levels after TBI, including BCL-2 and cytochrome C 44 as well as F2-isoprostane. 49 As with these other studies, older age was also independently associated with worse outcome, possibly resulting from increased medical complications and decreased repair mechanisms outside of the specific relationships with S100b and other markers.…”

Section: Discussionmentioning

confidence: 98%

S100b as a Prognostic Biomarker in Outcome Prediction for Patients with Severe Traumatic Brain Injury

Goyal

Failla

Niyonkuru

et al. 2013

Journal of Neurotrauma

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155

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As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) (n = 138 subjects) and serum (n = 80 subjects) samples across a 6-day time course. Long-bone fracture, Injury Severity Score (ISS), and isolated head injury status were variables used to assess extracerebral sources of S100b in serum. After TBI, CSF and serum S100b levels were increased over healthy controls across the first 6 days post-TBI (p ≤ 0.005 and p ≤ 0.031). Though CSF and serum levels were highly correlated during early time points post-TBI, this association diminished over time. Bivariate analysis showed that subjects who had temporal CSF profiles with higher S100b concentrations had higher acute mortality (p < 0.001) and worse Glasgow Outcome Scale (GOS; p = 0.002) and Disability Rating Scale (DRS) scores (p = 0.039) 6 months post-injury. Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores (p = 0.032), temporal serum profiles were associated with acute mortality (p = 0.015). High CSF S100b levels were observed in women (p = 0.022) and older subjects (p = 0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.

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Section: Discussionmentioning

confidence: 98%

S100b as a Prognostic Biomarker in Outcome Prediction for Patients with Severe Traumatic Brain Injury

Goyal

Failla

Niyonkuru

et al. 2013

Journal of Neurotrauma

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155

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“…In our published work, we have observed AvePP much greater than 0.7, suggesting that subjects with TBI can be very accurately placed into a trajectory group. 12,13 2. Odds of correct classification (OCC): for a trajectory group j,…”

Section: Evaluating Trajectory Model Fitmentioning

confidence: 99%

“…5,[9][10][11]20 Recent research from our group has assessed temporal biomarker profiles in evaluating TBI prognosis. 12,13,21,22 Based on this recent work, we hypothesized that temporal biomarker profiles can be more informative than single-point estimates in predicting outcome. Work has also identified demographic, premorbid, and psychosocial factors associated with functional impairments, disability, and community integration for those with TBI.…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we have applied group-based trajectory modeling to discern unique biomarker trends after TBI. 12,13 The specific aims of this article are to demonstrate a step-by-step process for this approach by (1) summarizing approaches for describing temporal trends of biomarker levels across time in persons with TBI and (2) comparing prediction potential of biomarker profiles to methodologies that use a single measure in predicting outcome after TBI. To provide a practical example of this novel approach in biomarker research, we use S100b data that were measured from CSF samples collected from adult subjects with severe TBI over the first 6 days after their injury.…”

Section: Introductionmentioning

confidence: 99%

“…Several cerebrospinal fluid (CSF) and serum biomarkers have shown promise in predicting long-term outcome after severe TBI. [3][4][5][6][7][8][9][10][11][12][13] One particular marker of interest in TBI is S100 calcium-binding protein B (S100b), a protein expressed in mature astrocytes whose foot processes contribute to the bloodbrain barrier (BBB). S100b easily extravasates into the serum as a result of BBB compromise, making it a potentially logical choice as a candidate biomarker for TBI diagnosis and prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Group-Based Trajectory Analysis Applications for Prognostic Biomarker Model Development in Severe TBI: A Practical Example

Niyonkuru

Wagner

Ozawa

et al. 2013

Journal of Neurotrauma

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Over the last decade, biomarker research has identified potential biomarkers for the diagnosis, prognosis, and management of traumatic brain injury (TBI). Several cerebrospinal fluid (CSF) and serum biomarkers have shown promise in predicting long-term outcome after severe TBI. Despite this increased focus on identifying biomarkers for outcome prognostication after a severe TBI, several challenges still exist in effectively modeling the significant heterogeneity observed in TBI-related pathology, as well as the biomarker-outcome relationships. Biomarker data collected over time are usually summarized into single-point estimates (e.g., average or peak biomarker levels), which are, in turn, used to examine the relationships between biomarker levels and outcomes. Further, many biomarker studies to date have focused on the prediction power of biomarkers without controlling for potential clinical and demographic confounders that have been previously shown to affect long-term outcome. In this article, we demonstrate the application of a practical approach to delineate and describe distinct subpopulations having similar longitudinal biomarker profiles and to model the relationships between these biomarker profiles and outcomes while taking into account potential confounding factors. As an example, we demonstrate a group-based modeling technique to identify temporal S100 calcium-binding protein B (S100b) profiles, measured from CSF over the first week post-injury, in a sample of adult subjects with TBI, and we use multivariate logistic regression to show that the prediction power of S100b biomarker profiles can be superior to the prediction power of single-point estimates.

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Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

et al. 2022

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IMPORTANCE Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment. OBJECTIVETo analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest. DESIGN, SETTING, AND PARTICIPANTSThe Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included 120 children aged 48 hours to 17 years who were resuscitated after cardiac arrest, had pre-cardiac arrest Pediatric Cerebral Performance Category scores of 1 to 3 points, and were admitted to an intensive care unit after cardiac arrest. EXPOSURE Cardiac arrest. MAIN OUTCOMES AND MEASURESThe primary outcome was an unfavorable outcome (death or survival with a Vineland Adaptive Behavior Scales, third edition, score of <70 points) at 1 year after cardiac arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCH-L1), neurofilament light (NfL), and tau concentrations were measured in blood samples from days 1 to 3 after cardiac arrest. Multivariate logistic regression and area under the receiver operating characteristic curve (AUROC) analyses were performed to examine the association of each biomarker with outcomes on days 1 to 3. RESULTS Among 120 children with primary outcome data available, the median (IQR) age was 1.0 (0-8.5) year; 71 children (59.2%) were male. A total of 5 children (4.2%) were Asian, 19 (15.8%) were Black, 81 (67.5%) were White, and 15 (12.5%) were of unknown race; among 110 children with data on ethnicity, 11 (10.0%) were Hispanic, and 99 (90.0%) were non-Hispanic. Overall, 70 children (58.3%) had a favorable outcome, and 50 children (41.7%) had an unfavorable outcome, including 43 deaths. On days 1 to 3 after cardiac arrest, concentrations of all 4 measured biomarkers were higher in children with an unfavorable vs a favorable outcome at 1 year. After covariate adjustment, NfL

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CSF Bcl-2 and cytochrome C temporal profiles in outcome prediction for adults with severe TBI

Cited by 42 publications

References 40 publications

S100b as a Prognostic Biomarker in Outcome Prediction for Patients with Severe Traumatic Brain Injury

S100b as a Prognostic Biomarker in Outcome Prediction for Patients with Severe Traumatic Brain Injury

Group-Based Trajectory Analysis Applications for Prognostic Biomarker Model Development in Severe TBI: A Practical Example

Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest

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