Dataset Information

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial.

ABSTRACT:

Objective

We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients.

Methods

Patients were randomly assigned into two groups (n = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days.

Results

NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 versus 18.09 ± 4.38 ng/mL, respectively (p = 0.008), and on day 7 were 12.3 ± 2.0 versus 16.43 ± 3.85 ng/mL, respectively (p = 0.003). Glasgow Coma Scale (GCS) on day 7 was 11.90 ± 2.83 versus 9.65 ± 3.44 in the doxycycline and control groups, respectively (p = 0.031). NSE serum levels and GCS scores were negatively correlated (r = -0.569, p < 0.001).

Conclusion

Adjunctive early use of doxycycline might be a novel option that halts the ongoing secondary brain injury in patients with moderate to severe TBI. Future larger clinical trials are warranted to confirm these findings.

SUBMITTER: Mansour NO

PROVIDER: S-EPMC8246481 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial.

Mansour Noha O NO Shama Mohamed A MA Werida Rehab H RH

Therapeutic advances in chronic disease 20210623

<h4>Objective</h4>We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients.<h4>Methods</h4>Patients were randomly assigned into two groups (<i>n</i> = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days.<h4>Results</h4>NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 <i>versus</i> 18.09 ± 4.38 ng/mL, r ...[more]

PMID: 34262678

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Project description:BackgroundSeveral studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury.MethodsPubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded.ResultsSixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66-0.80) for unfavorable outcome and 0.76 (95% CI, 0.62-0.90) for mortality.ConclusionsMortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies.

Project description:Background: Experimental evidence has indicated the benefits of intraoperative controlled decompression for the treatment of severe traumatic brain injury (sTBI). Intraoperative rapid decompression (conventional decompression) for the treatment of sTBI may result in intra- and post-operative complications. Controlled decompression may reduce these complications. Previous clinical trials in China have not yielded conclusive results regarding controlled decompression for sTBI. Therefore, we explored whether controlled decompression treatment decreases the rates of complications and improves the outcomes of patients with sTBI. Methods: We performed this randomized, controlled trial at our hospital. Patients with sTBI aged 18-75 years old were randomly (1:1) divided into controlled decompression surgery (n = 124) or rapid decompression surgery groups (n = 124). The primary outcome measures were the Extended Glasgow Outcome Scale (GOS-E) score at 6 months and 30-days all-cause mortality. The secondary outcomes were the incidences of intraoperative brain swelling, post-traumatic cerebral infarction, and delayed hematoma. Results: Compared with the rapid decompression group, the controlled decompression group had reduced 30-days all-cause mortality (18.6 vs. 30.8%, P = 0.035) and improved the 6-months GOS-E scores, and the difference was significant. In addition, the patients in the controlled decompression group had a lower intraoperative brain swelling rate (13.3 vs. 24.3%, P = 0.036), a lower delayed hematoma rate (17.7 vs. 29.0%, P = 0.048) and a relatively lower post-traumatic cerebral infarction rate (15.0 vs. 22.4%, P = 0.127) than those in the rapid decompression group. Conclusions: Our data suggest that controlled decompression surgery significantly improves sTBI outcomes and decreases the rates of sTBI-related complications. However, this was a single-hospital study, and well-designed multicenter randomized controlled trials are needed to evaluate the effects of controlled decompression surgery for the management of patients with sTBI. Clinical Trial Registration: Chinese Clinical Trial Registry; Date: 14/Dec/2013; Number: ChiCTR-TCC-13004002.

Project description:BackgroundPrognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury.MethodsWe searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses.ResultsWe screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data.InterpretationIn patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available.

Project description:The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary injuries following traumatic brain injury (TBI). Microvascular hyperpermeability and cerebral edema resulting from BBB dysfunction after TBI leads to elevation of intracranial pressure, secondary brain ischemia, herniation, and brain death. There are currently no effective therapies to modulate the underlying pathophysiology responsible for TBI-induced BBB dysfunction and hyperpermeability. The loss of BBB integrity by the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) is critical to TBI-induced BBB hyperpermeability, and doxycycline possesses anti-MMP-9 effect. In this study, the effect of doxycycline on BBB hyperpermeability was studied utilizing molecular modeling (using Glide) in silico, cell culture-based models in vitro, and a mouse model of TBI in vivo. Brain microvascular endothelial cell assays of tight junction protein immunofluorescence and barrier permeability were performed. Adult C57BL/6 mice were subjected to sham versus TBI with or without doxycycline treatment and immediate intravital microscopic analysis for evaluating BBB integrity. Postmortem mouse brain tissue was collected to measure MMP-9 enzyme activity. It was found that doxycycline binding to the MMP-9 active sites have binding affinity of -7.07 kcal/mol. Doxycycline treated cell monolayers were protected from microvascular hyperpermeability and retained tight junction integrity (p < 0.05). Doxycycline treatment decreased BBB hyperpermeability following TBI in mice by 25% (p < 0.05). MMP-9 enzyme activity in brain tissue decreased with doxycycline treatment following TBI (p < 0.05). Doxycycline preserves BBB tight junction integrity following TBI via inhibiting MMP-9 activity. When established in human subjects, doxycycline, may provide readily accessible medical treatment after TBI to attenuate secondary injury.

Project description:ObjectiveTo evaluate the efficacy of a novel intervention aimed at enhancing self-advocacy in individuals living with traumatic brain injury (TBI).SettingCommunity.ParticipantsSixty-seven (35 allocated to treatment, 32 to control) community-dwelling adults 9 months or more post-TBI (mean of 8.9 years postinjury); previously discharged from inpatient or outpatient TBI rehabilitation; able to travel independently in the community, indicating a level of independence needed to engage in self-advocacy.DesignLongitudinal randomized 2-arm controlled trial (NCT no. 03385824). Computer-generated block randomization allocated participants to treatment/intervention or control/no-intervention. All outcome assessments completed by blinded study staff.InterventionA manualized group intervention, Self-Advocacy for Independent Life (SAIL), addressing the self-efficacy beliefs, knowledge, and skills for self-advocacy following TBI.Main outcome measuresThe Self-Advocacy Scale (SAS) (primary); General Self-Efficacy Scale (GSE); Personal Advocacy Activity Scale (PAAS); Satisfaction With Life Scale (SWLS).ResultsThe treatment group showed significantly greater improvement than controls from baseline to posttreatment on the primary measure (SAS) of self-efficacy specific to self-advocacy after TBI (effect size = 0.22). Similar improvements were found on secondary measures of general self-efficacy and satisfaction with life from baseline to posttreatment. However, significant between-groups gains for primary and secondary measures were not maintained over 6- and 12-week follow-up.ConclusionsIndividuals living with chronic TBI sequelae can increase self-efficacy specific to self-advocacy, general self-efficacy, and satisfaction with life, through a TBI-specific intervention aimed at empowering individuals to advocate for their own needs and wishes. Sustaining gains over time may require ongoing community collaboration and support. This could involve community-based systems of self-advocacy education, resources, and peer support.

Dataset Information

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial.

Objective

Methods

Results

Conclusion

Publications

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial.

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