Clinical Utility of Serum Levels of Ubiquitin C-Terminal Hydrolase as a Biomarker for Severe Traumatic Brain Injury

Abstract Background: Brain damage markers released in cerebrospinal fluid (CSF) and blood may provide valuable information about diagnosis and outcome prediction after traumatic brain injury (TBI). Objective: To examine the concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1), a novel brain injury biomarker, in CSF and serum of severe TBI patients and their association with clinical characteristics and outcome. Methods: This case-control study enrolled 95 severe TBI subjects (Glasgow Coma Scale [GCS] score, 8). Using sensitive UCH-L1 sandwich ELISA, we studied the temporal profile of CSF and serum UCH-L1 levels over 7 days for severe TBI patients. Results: Comparison of serum and CSF levels of UCH-L1 in TBI patients and control subjects shows a robust and significant elevation of UCH-L1 in the acute phase and over the 7-day study period. Serum and CSF UCH-L1 receiver-operating characteristic curves further confirm strong specificity and selectivity for diagnosing severe TBI vs controls, with area under the curve values in serum and CSF statistically significant at all time points up to 24 hours (P < .001). The first 12-hour levels of both serum and CSF UCH-L1 in patients with GCS score of 3 to 5 were also significantly higher than those with GCS score of 6 to 8. Furthermore, UCH-L1 levels in CSF and serum appear to distinguish severe TBI survivors from nonsurvivors within the study, with nonsurvivors having significantly higher and more persistent levels of serum and CSF UCH-L1. Cumulative serum UCH-L1 levels > 5.22 ng/mL predicted death (odds ratio, 4.8). Conclusion: Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI, including correlating to injury severity and survival outcome.

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Moderate and severe traumatic brain injury: effect of blood alcohol concentration on Glasgow Coma Scale score and relation to computed tomography findings

Journal of Neurosurgery ◽

10.3171/2014.9.jns14322 ◽

2015 ◽

Vol 122 (1) ◽

pp. 211-218 ◽

Cited By ~ 28

Author(s):

Nils Petter Rundhaug ◽

Kent Gøran Moen ◽

Toril Skandsen ◽

Kari Schirmer-Mikalsen ◽

Stine B. Lund ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Injury Severity ◽

Blood Alcohol Concentration ◽

Alcohol Concentration ◽

Dependent Manner ◽

Blood Alcohol ◽

Severe Tbi ◽

Gcs Score ◽

Dose Dependent

OBJECT The influence of alcohol is assumed to reduce consciousness in patients with traumatic brain injury (TBI), but research findings are divergent. The aim of this investigation was to study the effects of different levels of blood alcohol concentration (BAC) on the Glasgow Coma Scale (GCS) scores in patients with moderate and severe TBI and to relate the findings to brain injury severity based on the admission CT scan. METHODS In this cohort study, 265 patients (age range 16–70 years) who were admitted to St. Olavs University Hospital with moderate and severe TBI during a 7-year period were prospectively registered. Of these, 217 patients (82%) had measured BAC. Effects of 4 BAC groups on GCS score were examined with ordinal logistic regression analyses, and the GCS scores were inverted to give an OR > 1. The Rotterdam CT score based on admission CT scan was used to adjust for brain injury severity (best score 1 and worst score 6) by stratifying patients into 2 brain injury severity groups (Rotterdam CT scores of 1–3 and 4–6). RESULTS Of all patients with measured BAC, 91% had intracranial CT findings and 43% had BAC > 0 mg/dl. The median GCS score was lower in the alcohol-positive patients (6.5, interquartile range [IQR] 4–10) than in the alcohol-negative patients (9, IQR 6–13; p < 0.01). No significant differences were found between alcohol-positive and alcohol-negative patients regarding other injury severity variables. Increasing BAC was a significant predictor of lower GCS score in a dose-dependent manner in age-adjusted analyses, with OR 2.7 (range 1.4–5.0) and 3.2 (range 1.5–6.9) for the 2 highest BAC groups (p < 0.01). Subgroup analyses showed an increasing effect of BAC group on GCS scores in patients with Rotterdam CT scores of 1–3: OR 3.1 (range 1.4–6.6) and 6.7 (range 2.7–16.7) for the 2 highest BAC groups (p < 0.01). No such relationship was found in patients with Rotterdam CT scores of 4–6 (p = 0.14–0.75). CONCLUSIONS Influence of alcohol significantly reduced the GCS score in a dose-dependent manner in patients with moderate and severe TBI and with Rotterdam CT scores of 1–3. In patients with Rotterdam CT scores of 4–6, and therefore more CT findings indicating increased intracranial pressure, the brain injury itself seemed to overrun the depressing effect of the alcohol on the CNS. This finding is in agreement with the assumption of many clinicians in the emergency situation.

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Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury

Journal of Neurosurgery ◽

10.3171/2014.7.jns132474 ◽

2014 ◽

Vol 121 (5) ◽

pp. 1232-1238 ◽

Cited By ~ 47

Author(s):

Joshua W. Gatson ◽

Jennifer Barillas ◽

Linda S. Hynan ◽

Ramon Diaz-Arrastia ◽

Steven E. Wolf ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glasgow Coma Scale ◽

Injury Severity ◽

Area Under The Curve ◽

Serum Levels ◽

Clinical Findings ◽

Ct Scans ◽

Healthy Controls ◽

Scale Scores

Object In previous studies of traumatic brain injury (TBI), neural biomarkers of injury correlate with injury severity and predict neurological outcome. The object of this paper was to characterize neurofilament-H (NFL-H) as a predictor of injury severity in patients who have suffered mild TBI (mTBI). Thus, the authors hypothesized that phosphorylated NFL-H (pNFL-H) levels are higher in mTBI patients than in healthy controls and identify which subjects experienced a more severe injury such as skull fractures, intracranial hemorrhaging, and/or contusions as detected by CT scans. Methods In this prospective clinical study, blood (8 ml) was collected from subjects (n = 34) suffering from mTBI (as defined by the American Congress of Rehabilitation and Glasgow Coma Scale scores between 13 and 15) at Parkland Hospital, Dallas, Texas, on Days 1 and 3 after injury). Additional clinical findings from the CT scans were also used to categorize the TBI patients into those with and those without clinical findings on the scans (CT+ and CTgroups, respectively). The serum levels of pNFL-H were measured using the enzyme-linked immunosorbent assay. Results Compared with healthy controls, the mTBI patients exhibited a significant increase in the serum levels of pNFL-H on Days 1 (p = 0.00001) and 3 (p = 0.0001) after TBI. An inverse correlation was observed between pNFL-H serum levels and Glasgow Coma Scale scores, which was significant. Additionally, using receiver operating characteristic curve analysis to compare the mTBI cases with controls to determine sensitivity and specificity, an area under the curve of 100% was achieved for both (p = 0.0001 for both). pNFL-H serum levels were only significantly higher on Day 1 in mTBI patients in the CT+ group (p < 0.008) compared with the CT− group. The area under the curve (82.5%) for the CT+ group versus the CT− group was significant (p = 0.021) with a sensitivity of 87.5% and a specificity of 70%, using a cutoff of 1071 pg/ml of pNFL-H in serum. Conclusions This study describes the serum profile of pNFL-H in patients suffering from mTBI with and without CT findings on Days 1 and 3 after injury. These results suggest that detection of pNFL-H may be useful in determining which individuals require CT imaging to assess the severity of their injury.

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Age- and Severity-Related In-Hospital Mortality Trends and Risks of Severe Traumatic Brain Injury in Japan: A Nationwide 10-Year Retrospective Study

Journal of Clinical Medicine ◽

10.3390/jcm10051072 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1072 ◽

Cited By ~ 1

Author(s):

Chiaki Toida ◽

Takashi Muguruma ◽

Masayasu Gakumazawa ◽

Mafumi Shinohara ◽

Takeru Abe ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hospital Mortality ◽

Mortality Risk ◽

Injury Severity ◽

Mortality Trend ◽

Mortality Trends ◽

Age Related ◽

Severe Tbi ◽

Gcs Score

Traumatic brain injury (TBI) is the major cause of mortality and morbidity in severely-injured patients worldwide. This retrospective nationwide study aimed to evaluate the age- and severity-related in-hospital mortality trends and mortality risks of patients with severe TBI from 2009 to 2018 to establish effective injury prevention measures. We retrieved information from the Japan Trauma Data Bank dataset between 2009 and 2018. The inclusion criteria for this study were patients with severe TBI defined as those with an Injury Severity Score ≥ 16 and TBI. In total, 31,953 patients with severe TBI (32.6%) were included. There were significant age-related differences in characteristics, mortality trend, and mortality risk in patients with severe TBI. The in-hospital mortality trend of all patients with severe TBI significantly decreased but did not improve for patients aged ≤ 5 years and with a Glasgow Coma Scale (GCS) score between 3 and 8. Severe TBI, age ≥ 65 years, fall from height, GCS score 3–8, and urgent blood transfusion need were associated with a higher mortality risk, and mortality risk did not decrease after 2013. Physicians should consider specific strategies when treating patients with any of these risk factors to reduce severe TBI mortality.

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Modulated Neuroprotection in Unresponsive Wakefulness Syndrome after Severe Traumatic Brain Injury

Brain Sciences ◽

10.3390/brainsci11081044 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1044

Author(s):

Cristina Daia ◽

Cristian Scheau ◽

Aura Spinu ◽

Ioana Andone ◽

Cristina Popescu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glasgow Coma Scale ◽

Severe Traumatic Brain Injury ◽

Functional Independence ◽

Unresponsive Wakefulness Syndrome ◽

Coma Scale ◽

Severe Tbi ◽

Neuroprotective Treatment ◽

Gcs Score

Background: We aimed to assess the effects of modulated neuroprotection with intermittent administration in patients with unresponsive wakefulness syndrome (UWS) after severe traumatic brain injury (TBI). Methods: Retrospective analysis of 60 patients divided into two groups, with and without neuroprotective treatment with Actovegin, Cerebrolysin, pyritinol, L-phosphothreonine, L-glutamine, hydroxocobalamin, alpha-lipoic acid, carotene, DL-α-tocopherol, ascorbic acid, thiamine, pyridoxine, cyanocobalamin, Q 10 coenzyme, and L-carnitine alongside standard treatment. Main outcome measures: Glasgow Coma Scale (GCS) after TBI, Extended Glasgow Coma Scale (GOS E), Disability Rankin Scale (DRS), Functional Independence Measurement (FIM), and Montreal Cognitive Assessment (MOCA), all assessed at 1, 3, 6, 12, and 24 months after TBI. Results: Patients receiving neuroprotective treatment recovered more rapidly from UWS than controls (p = 0.007) passing through a state of minimal consciousness and gradually progressing until the final evaluation (p = 0.000), towards a high cognitive level MOCA = 22 ± 6 points, upper moderate disability GOS-E = 6 ± 1, DRS = 6 ± 4, and an assisted gait, FIM =101 ± 25. The improvement in cognitive and physical functioning was strongly correlated with lower UWS duration (−0.8532) and higher GCS score (0.9803). Conclusion: Modulated long-term neuroprotection may be the therapeutic key for patients to overcome UWS after severe TBI.

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Self-awareness four years after severe traumatic brain injury: discordance between the patient’s and relative’s complaints. Results from the PariS-TBI study

Clinical Rehabilitation ◽

10.1177/0269215517734294 ◽

2017 ◽

Vol 32 (5) ◽

pp. 692-704 ◽

Cited By ~ 6

Author(s):

Camille Chesnel ◽

Claire Jourdan ◽

Eleonore Bayen ◽

Idir Ghout ◽

Emmanuelle Darnoux ◽

...

Keyword(s):

Quality Of Life ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Significant Relationship ◽

Injury Severity ◽

Chronic Phase ◽

Functional Independence ◽

Severe Tbi

Objective: To evaluate the patient’s awareness of his or her difficulties in the chronic phase of severe traumatic brain injury (TBI) and to determine the factors related to poor awareness. Design/Setting/Subjects: This study was part of a larger prospective inception cohort study of patients with severe TBI in the Parisian region (PariS-TBI study). Intervention/Main measures: Evaluation was carried out at four years and included the Brain Injury Complaint Questionnaire (BICoQ) completed by the patient and his or her relative as well as the evaluation of impairments, disability and quality of life. Results: A total of 90 patient-relative pairs were included. Lack of awareness was measured using the unawareness index that corresponded to the number of discordant results between the patient and relative in the direction of under evaluation of difficulties by the patient. The only significant relationship found with lack of awareness was the subjective burden perceived by the relative (Zarit Burden Inventory) ( r = 0.5; P < 0.00001). There was no significant relationship between lack of awareness and injury severity, pre-injury socio-demographic data, cognitive impairments, mood disorders, functional independence (Barthel index), global disability (Glasgow Outcome Scale), return to work at four years or quality of life (Quality Of Life after Brain Injury scale (QOLIBRI)). Conclusion: Lack of awareness four years post severe TBI was not related to the severity of the initial trauma, sociodemographic data, the severity of impairments, limitations of activity and participation, or the patient’s quality of life. However, poor awareness did significantly influence the weight of the burden perceived by the relative.

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Relationship of “dose” of intracranial hypertension to outcome in severe traumatic brain injury

Journal of Neurosurgery ◽

10.3171/jns/2008/109/10/0678 ◽

2008 ◽

Vol 109 (4) ◽

pp. 678-684 ◽

Cited By ~ 127

Author(s):

Anne Vik ◽

Torbjørn Nag ◽

Oddrun Anita Fredriksli ◽

Toril Skandsen ◽

Kent Gøran Moen ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Hypertension ◽

Scale Score ◽

Severe Traumatic Brain Injury ◽

Injury Severity ◽

Area Under The Curve ◽

Term Outcome ◽

Long Term Outcome ◽

Scale Scores

Object It has recently been suggested that the degree of intracranial pressure (ICP) above the treatment goal can be estimated by the area under the curve (AUC) of ICP versus time in patients with severe traumatic brain injury (TBI). The objective of this study was to determine whether the calculated “ICP dose”—the ICP AUC—is related to mortality rate, outcome, and Marshall CT classification. Methods Of 135 patients (age range 1–82 years) with severe TBI treated during a 5-year period at the authors' institution, 113 patients underwent ICP monitoring (84%). Ninety-three patients with a monitoring time > 24 hours were included for analysis of ICP AUC calculated using the trapezoidal method. Computed tomography scans were assessed according to the Marshall TBI classification. Patients with Glasgow Outcome Scale scores at 6 months and > 3 years were separated into 2 groups based on outcome. Results Sixty patients (65%) had ICP values > 20 mm Hg, and 12 (13%) developed severe intracranial hypertension and died secondary to herniation. A multiple regression analysis adjusting for Glasgow Coma Scale score, age, pupillary abnormalities and Injury Severity Scale score demonstrated that the ICP AUC was a significant predictor of poor outcome at 6 months (p = 0.034) and of death (p = 0.035). However, it did not predict long-term outcome (p = 0.157). The ICP AUC was significantly higher in patients with Marshall head injury Categories 3 and 4 (24 patients) than in those with Category 2 (23 patients, p = 0.025) and Category 5 (46 patients, p = 0.021) TBIs using the worst CT scan obtained. Conclusions The authors found a significant relationship between the dose of ICP, the worst Marshall CT score, and patient outcome, suggesting that the AUC method may be useful in refining and improving the treatment of ICP in patients with TBI.

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Abstract 230: Differential Effects of Prehospital Hypotension and Injury Severity in Isolated vs. Multisystem Major Traumatic Brain Injury

Circulation ◽

10.1161/circ.138.suppl_2.230 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Daniel W Spaite ◽

Chengcheng Hu ◽

Bentley J Bobrow ◽

Bruce J Barnhart ◽

Vatsal Chikani ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Injury Severity ◽

Treatment Effectiveness ◽

Guideline Implementation ◽

Body Region ◽

Head Region ◽

Differential Effects ◽

Severe Tbi

Background: In hospital-based studies, hypotension (HT, SBP <90) is more likely to occur in multisystem traumatic brain injury (MTBI) than isolated (ITBI). However, there are few EMS studies on this issue. Hypothesis: Prehospital HT is associated with differential effects in MTBI and ITBI and these effects are influenced by the severity of primary brain injury. Methods: Inclusion: TBI cases in the EPIC Study (NIH 1R01NS071049) before TBI guideline implementation (1/07-3/14). ITBI: Major TBI cases (CDC Barell Matrix Type 1) that had no injury with ICD9-based Regional Severity Score [RSS (AIS equivalent)] ≥3 in any other body region. MTBI: Type 1 TBI plus at least one non-head region injury with RSS ≥3. Results: Included were 13,435 cases [Excl: age <10 (5.9%), missing data (6.2%)]. 10,374 (77.2%) were ITBI, 3061 (22.8%) MTBI. Mortality: ITBI: 7.7% (797/10,374), MTBI: 19.2% (587/3061, p<0.0001). Prehospital HT occurred 3.5 times more often in MTBI (14.8%, 453/3061 vs 4.2%, 437/10,374; p<0.0001). Among HT cases, 40.8% (185/453) with MTBI died vs 30.9% with ITBI (135/437; p<0.0001). In the hypotensive moderate/severe TBI cohort (RSS-Head 3/4), MTBI mortality was 2.4 times higher (17.2%, 40/232) than ITBI (7.1%, 17/240, p = 0.001). However, in the hypotensive very/extremely severe TBI group (RSS-Head 5/6), mortality was almost identical in MTBI (73.4%, 141/192) and ITBI (72.1%, 116/161, p = 0.864). Conclusion: Among major TBI patients with prehospital HT, those with MTBI were much more likely to die than those with ITBI. However, this association varied dramatically with TBI severity. In mod/severe TBI cases with HT, MTBI mortality was 2.4 times higher than in ITBI. In contrast, in very/extremely severe TBI with HT, there was no identifiable mortality difference. Thus, in cases with substantial potential to survive the primary brain injury (mod/severe), outcome is markedly worse in patients with multisystem injuries. However, in very/extremely severe TBI, non-head region injuries have no apparent association with mortality. This may be because the TBI is the primary factor leading to death in these cases. The main EPIC study is evaluating whether this severity-based difference in “effect” has implications for TBI guideline treatment effectiveness.

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Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury

Biomarker Insights ◽

10.1177/11772719211053449 ◽

2021 ◽

Vol 16 ◽

pp. 117727192110534

Author(s):

Ker Rui Wong ◽

William T O’Brien ◽

Mujun Sun ◽

Glenn Yamakawa ◽

Terence J O’Brien ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Elevated Serum ◽

Serum Levels ◽

Long Bone ◽

Post Injury ◽

Neurofilament Light ◽

Peripheral Injury ◽

Long Bone Fracture ◽

Severe Tbi

Introduction: Serum neurofilament light (NfL) is an emerging biomarker of traumatic brain injury (TBI). However, the effect of peripheral injuries such as long bone fracture and skeletal muscle injury on serum NfL levels is unknown. Therefore, the aim of this study was to determine whether serum NfL levels can be used as a biomarker of TBI in the presence of concomitant peripheral injuries. Methods: Rats were randomly assigned to one of four injury groups: polytrauma (muscle crush + fracture + TBI; n = 11); peripheral injuries (muscle crush + fracture + sham-TBI; n = 12); TBI-only (sham-muscle crush + sham-fracture + TBI; n = 13); and triple-sham (n = 7). At 2-days post-injury, serum levels of NfL were quantified using a Simoa HD-X Analyzer. Results: Compared to triple-sham rats, serum NfL concentrations were higher in rats with peripheral injuries-only, TBI-only, and polytrauma. When compared to peripheral injury-only rats, serum NfL levels were higher in TBI-only and polytrauma rats. No differences were found between TBI-only and polytrauma rats. Conclusion: Serum NfL levels did not differ between TBI-only and polytrauma rats, indicating that significant peripheral injuries did not affect the sensitivity and specificity of serum NfL as a biomarker of moderate TBI. However, the finding of elevated serum NfL levels in rats with peripheral injuries in the absence of a TBI suggests that the presence of such injuries may limit the utility of NfL as a biomarker of less severe TBI (eg, concussion).

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White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury

Neurology ◽

10.1212/wnl.0000000000012222 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012222

Author(s):

Emily L Dennis ◽

Karen Caeyenberghs ◽

Kristen R Hoskinson ◽

Tricia L Merkley ◽

Stacy J Suskauer ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Behavioral Problems ◽

Child Behavior Checklist ◽

Injury Severity ◽

Meta Analysis ◽

Post Injury ◽

Severe Tbi ◽

Future Work

Objective:Our study addressed aims: (1) test the hypothesis that moderate-severe TBI in pediatric patients is associated with widespread white matter (WM) disruption; (2) test the hypothesis that age and sex impact WM organization after injury; and (3) examine associations between WM organization and neurobehavioral outcomes.Methods:Data from ten previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric msTBI working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.Results:Five hundred and seven children and adolescents (244 with complicated mild to severe TBI [msTBI] and 263 controls) were included. Patients were clustered into three post-injury intervals: acute/subacute - <2 months, post-acute - 2-6 months, chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral problems as indexed by the Child Behavior Checklist (CBCL). Our analyses revealed altered WM diffusion metrics across multiple tracts and all post-injury intervals (effect sizes ranging between d=-0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time post-injury. We observed a sex-by-group interaction: females with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (𝞫=0.043), which coincided with more parent-reported behavioral problems (𝞫=-0.0027).Conclusions:WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically-meaningful patient subtypes.

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High Serum Caspase-Cleaved Cytokeratin-18 Levels and Mortality of Traumatic Brain Injury Patients

Brain Sciences ◽

10.3390/brainsci9100269 ◽

2019 ◽

Vol 9 (10) ◽

pp. 269 ◽

Cited By ~ 1

Author(s):

Leonardo Lorente ◽

María M. Martín ◽

Agustín F. González-Rivero ◽

Antonia Pérez-Cejas ◽

Mónica Argueso ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glasgow Coma Scale ◽

Area Under The Curve ◽

High Serum ◽

Early Mortality ◽

Cytokeratin 18 ◽

New Findings ◽

Severe Tbi ◽

Time Of Admission

Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study was to analyze whether serum CCCK-18 levels determined during the first week after TBI could predict early mortality (at 30 days). Methods: Severe TBI patients were included (considering severe when Glasgow Coma Scale < 9) in this observational and multicentre study. Serum CCCK-18 levels were determined at day 1 of TBI, and at days 4 and 8 after TBI. Results: Serum CCCK-18 levels at day 1 of TBI, and in the days 4 and 8 after TBI were higher (p < 0.001) in non-surviving than in surviving patients (34 and 90 patients, respectively) and could predict early mortality (p < 0.001 in the area under the curve). Conclusions: The new findings from our study were that serum CCCK-18 levels at any moment of the first week of TBI were higher in non-surviving patients and were able to predict early mortality.

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