A Retrospective Clinical Analysis of the Serum Bile Acid Alteration Caused by Traumatic Brain Injury
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ABSTRACT:
SUBMITTER: Zhu Y
PROVIDER: S-EPMC8424180 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n?=?72) and controls (n?=?35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.
| S-EPMC5098187 | biostudies-literature
Project description:BackgroundsAcute kidney injury (AKI) is a prevalent nonneurological complication in patients with traumatic brain injury (TBI). We designed this study to explore the association between serum uric acid (SUA) level and the occurrence of AKI following TBI.MethodsThis is a retrospective single-center study. A total of 479 patients admitted with TBI were included in this study. We utilized SUA and other risk factors for AKI to construct a predictive model by performing multivariate logistic regression. 374 patients and 105 patients were, respectively, divided into a training set and validation set. The predictive value of the single SUA and constructed model was evaluated by drawing a receiver operating characteristic (ROC) curve. AKI was diagnosed according to the KIDGO criteria.Results79 (21.12%) patients were diagnosed with AKI in the training cohort. The patients in the AKI group are older than those in the non-AKI group (p = 0.01). And the Glasgow Coma Scale (GCS) of the AKI group was lower than that of the non-AKI group (p < 0.001). In a multivariate logistic regression analysis, we found that heart rate (p = 0.041), shock (p = 0.018), serum creatinine (p < 0.001), and serum uric acid (SUA) (p < 0.001) were significant risk factors for AKI. Bivariate correlation analyses showed that serum creatinine was moderately positively correlated with SUA (r = 0.523, p < 0.001). Finally, the area under the receiver operating characteristic curve (AUC) of SUA for predicting AKI in the training set and validation set was 0.850 (0.805-0.895) and 0.869 (0.801-0.938), respectively.ConclusionsSUA is an effective risk factor for AKI following TBI. Combining SUA with serum creatinine could more accurately identify TBI patients with high risk of developing AKI.
| S-EPMC7479452 | biostudies-literature
Project description:Traumatic brain injury (TBI) is one of the leading causes of morbidity, disability and mortality across all age groups globally. Currently, only palliative treatments exist, but these are suboptimal and do little to combat the progressive damage to the brain that occurs after a TBI. However, multiple experimental treatments are currently available that target the primary and secondary biochemical and cellular changes that occur after a TBI. Some of these drugs have progressed to clinical trials and are currently being evaluated for their therapeutic benefits in TBI patients. The aim of this study was to identify which drugs are currently being evaluated in clinical trials for TBI. A search of ClinicalTrials.gov was performed on 3 December 2021 and all clinical trials that mentioned "TBI" OR "traumatic brain injury" AND "drug" were searched, revealing 362 registered trials. Of the trials, 46 were excluded due to the drug not being mentioned, leaving 138 that were completed and 116 that were withdrawn. Although the studies included 267,298 TBI patients, the average number of patients per study was 865 with a range of 5-200,000. Of the completed studies, 125 different drugs were tested in TBI patients but only 7 drugs were used in more than three studies, including amantadine, botulinum toxin A and tranexamic acid (TXA). However, previous clinical studies using these seven drugs showed variable results. The current study concludes that clinical trials in TBI have to be carefully conducted so as to reduce variability across studies, since the severity of TBI and timing of therapeutic interventions were key aspects of trial success.
| S-EPMC9138587 | biostudies-literature
Project description:Repeated mild traumatic brain injury (rmTBI), the most common type of traumatic brain injuries, can result in neurological dysfunction and cognitive deficits. However, the molecular mechanisms and the long-term consequence of rmTBI remain elusive. In this study, we developed a modified rmTBI mouse model and found that rmTBI-induced transient neurological deficits and persistent impairments of spatial memory function. Furthermore, rmTBI mice had long-lasting detrimental effect on cognitive function, exhibiting memory deficits even 12 weeks after rmTBI. Microarray analysis of whole genome gene expression showed that rmTBI significantly altered the expression level of 87 genes which are involved in apoptosis, stress response, metabolism, and synaptic plasticity. The results indicate the potential mechanism underlying rmTBI-induced acute neurological deficits and its chronic effect on memory impairments. This study suggests that long-term monitoring and interventions for rmTBI individuals are essential for memory function recovery and reducing the risk of developing neurodegenerative diseases.
| S-EPMC5589921 | biostudies-literature
Project description:BackgroundTraumatic brain injury (TBI) involves several aspects of a patient's condition, including physical, mental, emotional, cognitive, social, and functional changes. Therefore, a clinical trial with individuals with TBI should consider outcome measures that reflect their global status.MethodsWe present the work of the National Institute of Child Health and Development-sponsored Traumatic Brain Injury Clinical Trials Network Outcome Measures subcommittee and its choice of outcome measures for a phase III clinical trial of patients with complicated mild to severe TBI.ResultsOn the basis of theoretical and practical considerations, the subcommittee recommended the adoption of a core of 9 measures that cover 2 different areas of recovery: functional and cognitive. These measures are the Extended Glasgow Outcome Scale; the Controlled Oral Word Association Test; the Trail Making Test, Parts A and B; the California Verbal Learning Test-II; the Wechsler Adult Intelligence Scale-III Digit Span subtest; the Wechsler Adult Intelligence Scale-III Processing Speed Index; and the Stroop Color-Word Matching Test, Parts 1 and 2.ConclusionsThe statistical methods proposed to analyze these measures using a global test procedure, along with research and methodological and regulatory issues involved with the use of multiple outcomes in a clinical trial, are discussed.
| S-EPMC2939167 | biostudies-literature
Project description:IntroductionThere is no widely used method for communicating the possible need for surgical intervention in patients with traumatic brain injury (TBI). This study describes a scoring system designed to communicate the potential need for surgical decompression in TBI patients. The scoring system, named the Surgical Intervention for Traumatic Injury (SITI), was designed to be objective and easy to use.MethodsThe SITI scale uses radiographic and clinical findings, including the Glasgow Coma Scale Score, pupil examination, and findings noted on computed tomography. To examine the scale, we used the patient database for the Progesterone for the Treatment of Traumatic Brain Injury III (ProTECT III) trial, and retrospectively applied the SITI scale to these patients.ResultsOf the 871 patients reviewed, 164 (18.8%) underwent craniotomy or craniectomy, and 707 (81.2%) were treated nonoperatively. The mean SITI score was 5.1 for patients who underwent surgery and 2.5 for patients treated nonoperatively (P<0.001). The area under the receiver operating characteristic curve was 0.887.ConclusionThe SITI scale was designed to be a simple, objective, clinical decision tool regarding the potential need for surgical decompression after TBI. Application of the SITI scale to the ProTECT III database demonstrated that a score of 3 or more was well associated with a perceived need for surgical decompression. These results further demonstrate the potential utility of the SITI scale in clinical practice.
| S-EPMC6625684 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma closely related to metabolic disorders is a common and aggressive liver malignancy. The dysregulation of bile acid homeostasis has emerged as a key factor for the development and progression of HCC. We aimed to investigate the relationship between bile acids and HCC diagnosis and progression.MethodsA total of 744 HBV-related patients (including 396 HCC patients and 348 patients with chronic liver diseases) were enrolled in the current study. The baseline characteristics of patients were collected from electronic medical records, and the levels of bile acid profiles were determined by LC-MS/MS. Propensity score matching analysis was conducted to reduce the effect of selection bias, and receiver operating characteristic analysis was performed to evaluate the clinical application values of bile acid.ResultsSignificant differences were observed for most characteristics between the HCC group and the CLD group before PSM analysis. Patients with HCC were older and fatter (p < 0.05). After adjusting with a 1:1 ratio for age, gender and BMI, 42 HCC patients and 42 non-HCC patients were matched in 2 groups, respectively. The total bile acid level in HCC patients was lower than that in patients with chronic liver diseases before and after PSM analysis (p < 0.05). However, patients with HCC had significantly higher levels of DCA, LCA, and GLCA and lower levels of TCDCA, GUDCA, and TUDCA (p < 0.05, respectively). Besides, the TCDCA, TUDCA, GLCA, and GUDCA were significantly correlated with tumor procession. Moreover, the BAs profiles had a superior predictive ability for predicting the development of HCC even in patients with low serum AFP levels.ConclusionPatients with HCC had significantly lower levels of total bile acid, but higher levels of secondary bile acids (DCA, LCA, and GLCA). The levels of primary bile acid (TCDCA) were closely related to tumor size and stage, which indicated that the bile acids were involved in the HCC procession and had important clinical application values.
| S-EPMC10963458 | biostudies-literature
Project description:Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decreases orexin neuron activation during wakefulness. We gave mice a dietary supplement of branched-chain amino acids (BCAAs), precursors for de novo glutamate synthesis in the brain. BCAA therapy reinstated activation of orexin neurons and improved wake deficits in mice with mild brain injury. Our data suggest that dietary BCAA intervention, acting in part through orexin, can ameliorate injury-induced sleep disturbances and may facilitate cognitive rehabilitation after brain injury.
| S-EPMC3951738 | biostudies-literature
Project description:BackgroundThe extent and severity of traumatic brain injuries (TBIs) can be difficult to determine with current diagnostic methods. To address this, there has been increased interest in developing biomarkers to assist in the diagnosis, determination of injury severity, evaluation of recovery and therapeutic efficacy, and prediction of outcomes. Several promising serum TBI biomarkers have been identified using hypothesis-driven approaches, largely examining proteins that are abundant in neurons and non-neural cells in the CNS.New methodAn unbiased approach, phage display, was used to identify serum TBI biomarkers. In this proof-of-concept study, mice received a TBI using the controlled cortical impact model of TBI (1mm injury depth, 3.5m/s velocity) and phage display was utilized to identify putative serum biomarkers at 6h postinjury.ResultsAn engineered phage which preferentially bound to injured serum was sequenced to identify the 12-mer 'recognizer' peptide expressed on the coat protein. Following synthesis of the recognizer peptide, pull down, and mass spectrometry analysis, the target protein was identified as glial fibrillary acidic protein (GFAP).Comparison with existing methods and conclusionsGFAP has previously been identified as a promising TBI biomarker. The results provide proof of concept regarding the ability of phage display to identify TBI serum biomarkers. This methodology is currently being applied to serum biomarkers of mild TBI.
| S-EPMC5067197 | biostudies-literature
Project description:Severe traumatic brain injury continues to present complex management and prediction challenges for the clinician. While there is some evidence that better systems of care can improve outcome, multiple multi-centre randomised controlled trials of specific therapies have consistently failed to show benefit. In addition, clinicians are challenged in attempting to accurately predict which children will recover well and which children will have severe and persisting neurocognitive deficits. Traumatic brain injury is vastly heterogeneous and so it is not surprising that one therapy or approach, when applied to a mixed cohort of children in a clinical trial setting, has yielded disappointing results. Children with severe traumatic brain injury have vastly different brain injury pathologies of widely varying severity, in any number of anatomical locations at what may be disparate stages of brain development. This heterogeneity may also explain why clinicians are unable to accurately predict outcome. Biomarkers are objective molecular signatures of injury that are released following traumatic brain injury and may represent a way of unifying the heterogeneity of traumatic brain injury into a single biosignature. Biomarkers hold promise to diagnose brain injury severity, guide intervention selection for clinical trials, or provide vital prognostic information so that early intervention and rehabilitation can be planned much earlier in the course of a child's recovery. Serum S100B and serum NSE levels show promise as a diagnostic tool with biomarker levels significantly higher in children with severe TBI including children with inflicted and non-inflicted head injury. Serum S100B and serum NSE also show promise as a predictor of neurodevelopmental outcome. The role of biomarkers in traumatic brain injury is an evolving field with the potential for clinical application within the next few years.
| S-EPMC8578762 | biostudies-literature