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Deep brain stimulation for the treatment of disorders of consciousness and cognition in traumatic brain injury patients: a review.
Kundu B, Brock AA, Englot DJ, Butson CR, Rolston JD
(2018) Neurosurg Focus 45: E14
MeSH Terms: Animals, Brain Injuries, Traumatic, Cognition, Consciousness, Deep Brain Stimulation, Epilepsy, Humans, Thalamus
Show Abstract · Added September 25, 2018
Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
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8 MeSH Terms
Prognosis of diffuse axonal injury with traumatic brain injury.
Humble SS, Wilson LD, Wang L, Long DA, Smith MA, Siktberg JC, Mirhoseini MF, Bhatia A, Pruthi S, Day MA, Muehlschlegel S, Patel MB
(2018) J Trauma Acute Care Surg 85: 155-159
MeSH Terms: Adult, Brain Injuries, Traumatic, Cohort Studies, Diffuse Axonal Injury, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Middle Aged, Prognosis, Quality of Life, Retrospective Studies, Tomography, X-Ray Computed
Show Abstract · Added June 26, 2018
BACKGROUND - Determine the prognostic impact of magnetic resonance imaging (MRI)-defined diffuse axonal injury (DAI) after traumatic brain injury (TBI) on functional outcomes, quality of life, and 3-year mortality.
METHODS - This retrospective single center cohort included adult trauma patients (age > 17 years) admitted from 2006 to 2012 with TBI. Inclusion criteria were positive head computed tomography with brain MRI within 2 weeks of admission. Exclusion criteria included penetrating TBI or prior neurologic condition. Separate ordinal logistic models assessed DAI's prognostic value for the following scores: (1) hospital-discharge Functional Independence Measure, (2) long-term Glasgow Outcome Scale-Extended, and (3) long-term Quality of Life after Brain Injury-Overall Scale. Cox proportional hazards modeling assessed DAI's prognostic value for 3-year survival. Covariates included age, sex, race, insurance status, Injury Severity Score, admission Glasgow Coma Scale Score, Marshall Head computed tomography Class, clinical DAI on MRI (Y/N), research-level anatomic DAI Grades I-III (I, cortical; II, corpus callosum; III, brainstem), ventilator days, time to follow commands, and time to long-term follow-up (for logistic models).
RESULTS - Eligibility criteria was met by 311 patients, who had a median age of 40 years (interquartile range [IQR], 23-57 years), Injury Severity Score of 29 (IQR, 22-38), intensive care unit stay of 6 days (IQR, 2-11 days), and follow-up of 5 years (IQR, 3-6 years). Clinical DAI was present on 47% of MRIs. Among 300 readable MRIs, 56% of MRIs had anatomic DAI (25% Grade I, 18% Grade II, 13% Grade III). On regression, only clinical (not anatomic) DAI was predictive of a lower Functional Independence Measure score (odds ratio, 2.5; 95% confidence interval, 1.28-4.76], p = 0.007). Neither clinical nor anatomic DAI were related to survival, Glasgow Outcome Scale-Extended, or Quality of Life after Brain Injury-Overall Scale scores.
CONCLUSION - In this longitudinal cohort, clinical evidence of DAI on MRI may only be useful for predicting short-term in-hospital functional outcome. Given no association of DAI and long-term TBI outcomes, providers should be cautious in attributing DAI to future neurologic function, quality of life, and/or survival.
LEVEL OF EVIDENCE - Epidemiological, level III; Therapeutic, level IV.
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Platelet transfusion does not improve outcomes in patients with brain injury on antiplatelet therapy.
Holzmacher JL, Reynolds C, Patel M, Maluso P, Holland S, Gamsky N, Moore H, Acquista E, Carrick M, Amdur R, Hancock H, Metzler M, Dunn J, Sarani B
(2018) Brain Inj 32: 325-330
MeSH Terms: Aged, Aged, 80 and over, Aspirin, Brain Injuries, Clopidogrel, Female, Humans, Injury Severity Score, Length of Stay, Male, Platelet Aggregation Inhibitors, Platelet Transfusion, Statistics, Nonparametric, Treatment Outcome
Show Abstract · Added June 26, 2018
INTRODUCTION - Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI.
METHODS - An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted.
RESULTS - Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p < 0.01), but had a non-significant impact on clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no differences in mortality.
CONCLUSION - Platelet transfusion significantly decreases platelet inhibition due to aspirin but is not associated with change in outcomes in patients on APM following TBI.
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14 MeSH Terms
Acute Management of Traumatic Brain Injury.
Vella MA, Crandall ML, Patel MB
(2017) Surg Clin North Am 97: 1015-1030
MeSH Terms: Brain Injuries, Traumatic, Humans, Intracranial Hypertension, Intracranial Pressure, Seizures
Show Abstract · Added June 26, 2018
Traumatic brain injury (TBI) is a leading cause of death and disability in patients with trauma. Management strategies must focus on preventing secondary injury by avoiding hypotension and hypoxia and maintaining appropriate cerebral perfusion pressure (CPP), which is a surrogate for cerebral blood flow. CPP can be maintained by increasing mean arterial pressure, decreasing intracranial pressure, or both. The goal should be euvolemia and avoidance of hypotension. Other factors that deserve important consideration in the acute management of patients with TBI are venous thromboembolism, stress ulcer, and seizure prophylaxis, as well as nutritional and metabolic optimization.
Published by Elsevier Inc.
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Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline.
Alali AS, Mukherjee K, McCredie VA, Golan E, Shah PS, Bardes JM, Hamblin SE, Haut ER, Jackson JC, Khwaja K, Patel NJ, Raj SR, Wilson LD, Nathens AB, Patel MB
(2017) Ann Surg 266: 952-961
MeSH Terms: Adrenergic beta-Antagonists, Brain Injuries, Bronchial Spasm, Cardiovascular Diseases, Hospital Mortality, Humans, Quality of Life, Treatment Outcome
Show Abstract · Added June 26, 2018
OBJECTIVE - To determine if beta-(β)-blockers improve outcomes after acute traumatic brain injury (TBI).
BACKGROUND - There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with β-blockers offers a potentially beneficial approach.
METHODS - Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was β-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I).
RESULTS - Data were extracted from 9 included studies encompassing 2005 unique TBI patients with β-blocker treatment and 6240 unique controls. Exposure to β-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified.
CONCLUSIONS - In adults with acute TBI, observational studies reveal a significant mortality advantage with β-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital β-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after β-blocker use for TBI.
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Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential.
Glykys J, Dzhala V, Egawa K, Kahle KT, Delpire E, Staley K
(2017) Trends Neurosci 40: 276-294
MeSH Terms: Animals, Brain Edema, Brain Injuries, Traumatic, Chlorides, Extracellular Matrix, Humans, Neurons, Seizures, Symporters
Show Abstract · Added May 3, 2017
Pharmacoresistant seizures and cytotoxic cerebral edema are serious complications of ischemic and traumatic brain injury. Intraneuronal Cl concentration ([Cl]) regulation impacts on both cell volume homeostasis and Cl-permeable GABA receptor-dependent membrane excitability. Understanding the pleiotropic molecular determinants of neuronal [Cl] - cytoplasmic impermeant anions, polyanionic extracellular matrix (ECM) glycoproteins, and plasmalemmal Cl transporters - could help the identification of novel anticonvulsive and neuroprotective targets. The cation/Cl cotransporters and ECM metalloproteinases may be particularly druggable targets for intervention. We establish here a paradigm that accounts for recent data regarding the complex regulatory mechanisms of neuronal [Cl] and how these mechanisms impact on neuronal volume and excitability. We propose approaches to modulate [Cl] that are relevant for two common clinical sequela of brain injury: edema and seizures.
Copyright © 2017 Elsevier Ltd. All rights reserved.
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9 MeSH Terms
Tracheostomy risk factors and outcomes after severe traumatic brain injury.
Humble SS, Wilson LD, McKenna JW, Leath TC, Song Y, Davidson MA, Ehrenfeld JM, Guillamondegui OD, Pandharipande PP, Patel MB
(2016) Brain Inj 30: 1642-1647
MeSH Terms: Adult, Age Factors, Brain Injuries, Traumatic, Cohort Studies, Female, Glasgow Coma Scale, Humans, Insurance Coverage, Logistic Models, Male, Postoperative Complications, Risk Factors, Tracheostomy, Young Adult
Show Abstract · Added June 26, 2018
OBJECTIVE - To determine risk factors associated with tracheostomy placement after severe traumatic brain injury (TBI) and subsequent outcomes among those who did and did not receive a tracheostomy.
METHODS - This retrospective cohort study compared adult trauma patients with severe TBI (n = 583) who did and did not receive tracheostomy. A multivariable logistic regression model assessed the associations between age, sex, race, insurance status, admission GCS, AIS (Head, Face, Chest) and tracheostomy placement. Ordinal logistic regression models assessed tracheostomy's influence on ventilator days and ICU LOS. To limit immortal time bias, Cox proportional hazards models assessed mortality at 1, 3 and 12-months.
RESULTS - In this multivariable model, younger age and private insurance were associated with increased probability of tracheostomy. AIS, ISS, GCS, race and sex were not risk factors for tracheostomy placement. Age showed a non-linear relationship with tracheostomy placement; likelihood peaked in the fourth decade and declined with age. Compared to uninsured patients, privately insured patients had an increased probability of receiving a tracheostomy (OR = 1.89 [95% CI = 1.09-3.23]). Mortality was higher in those without tracheostomy placement (HR = 4.92 [95% CI = 3.49-6.93]). Abbreviated injury scale-Head was an independent factor for time to death (HR = 2.53 [95% CI = 2.00-3.19]), but age, gender and insurance were not.
CONCLUSIONS - Age and insurance status are independently associated with tracheostomy placement, but not with mortality after severe TBI. Tracheostomy placement is associated with increased survival after severe TBI.
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ICU sedation with dexmedetomidine after severe traumatic brain injury.
Humble SS, Wilson LD, Leath TC, Marshall MD, Sun DZ, Pandharipande PP, Patel MB
(2016) Brain Inj 30: 1266-70
MeSH Terms: Adult, Analgesics, Non-Narcotic, Blood Pressure, Brain Injuries, Traumatic, Dexmedetomidine, Dose-Response Relationship, Drug, Female, Heart Rate, Humans, Intensive Care Units, Male, Middle Aged, Retrospective Studies, Young Adult
Show Abstract · Added June 26, 2018
OBJECTIVE - To comprehensively describe the use of dexmedetomidine in a single institutional series of adult ICU patients with severe TBI. This study describes the dexmedetomidine dosage and infusion times, as well as the physiological parameters, neurological status and daily narcotic requirements before, during and after dexmedetomidine infusion.
METHODS - This study identified 85 adult patients with severe TBI who received dexmedetomidine infusions in the Trauma ICU at Vanderbilt University Medical Center between 2006-2010. Demographic, haemodynamic, narcotic use and sedative use data were systematically obtained from the medical record and analysed for changes associated with dexmedetomidine infusion.
RESULTS - During infusion with dexmedetomidine, narcotic and sedative use decreased significantly (p < 0.001 and p < 0.05). Median MAP, SBP, DBP and HR also decreased significantly during infusion when compared to pre-infusion values (p < 0.001). Despite the use of dexmedetomidine, RASS and GCS scores improved from pre-infusion to infusion time periods.
CONCLUSIONS - The findings demonstrate that initiation of dexmedetomidine infusion is not associated with a decline in neurological functioning in adults with severe TBI. Although there was an observed decrease in haemodynamic parameters during infusion with dexmedetomidine, the change was not clinically significant and the requirements for narcotics and additional sedatives were minimized.
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Brain in Congenital Heart Disease Across the Lifespan: The Cumulative Burden of Injury.
Marelli A, Miller SP, Marino BS, Jefferson AL, Newburger JW
(2016) Circulation 133: 1951-62
MeSH Terms: Brain, Brain Injuries, Child, Child Development, Cost of Illness, Heart Defects, Congenital, Humans, Longevity, Risk Factors
Show Abstract · Added March 26, 2019
The number of patients surviving with congenital heart disease (CHD) has soared over the last 3 decades. Adults constitute the fastest-growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has been focused largely on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes mellitus, and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. Against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions.
© 2016 American Heart Association, Inc.
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Standardizing ICU management of pediatric traumatic brain injury is associated with improved outcomes at discharge.
O'Lynnger TM, Shannon CN, Le TM, Greeno A, Chung D, Lamb FS, Wellons JC
(2016) J Neurosurg Pediatr 17: 19-26
MeSH Terms: Adolescent, Brain Injuries, Child, Child, Preschool, Clinical Protocols, Critical Care, Female, Glasgow Outcome Scale, Humans, Infant, Intensive Care Units, Pediatric, Male, Outcome Assessment (Health Care), Patient Discharge, Practice Guidelines as Topic, Retrospective Studies
Show Abstract · Added February 22, 2016
OBJECT The goal of critical care in treating traumatic brain injury (TBI) is to reduce secondary brain injury by limiting cerebral ischemia and optimizing cerebral blood flow. The authors compared short-term outcomes as defined by discharge disposition and Glasgow Outcome Scale scores in children with TBI before and after the implementation of a protocol that standardized decision-making and interventions among neurosurgeons and pediatric intensivists. METHODS The authors performed a retrospective pre- and postprotocol study of 128 pediatric patients with severe TBI, as defined by Glasgow Coma Scale (GCS) scores < 8, admitted to a tertiary care center pediatric critical care unit between April 1, 2008, and May 31, 2014. The preprotocol group included 99 patients, and the postprotocol group included 29 patients. The primary outcome of interest was discharge disposition before and after protocol implementation, which took place on April 1, 2013. Ordered logistic regression was used to assess outcomes while accounting for injury severity and clinical parameters. Favorable discharge disposition included discharge home. Unfavorable discharge disposition included discharge to an inpatient facility or death. RESULTS Demographics were similar between the treatment periods, as was injury severity as assessed by GCS score (mean 5.43 preprotocol, mean 5.28 postprotocol; p = 0.67). The ordered logistic regression model demonstrated an odds ratio of 4.0 of increasingly favorable outcome in the postprotocol cohort (p = 0.007). Prior to protocol implementation, 63 patients (64%) had unfavorable discharge disposition and 36 patients (36%) had favorable discharge disposition. After protocol implementation, 9 patients (31%) had unfavorable disposition, while 20 patients (69%) had favorable disposition (p = 0.002). In the preprotocol group, 31 patients (31%) died while 6 patients (21%) died after protocol implementation (p = 0.04). CONCLUSIONS Discharge disposition and mortality rates in pediatric patients with severe TBI improved after implementation of a standardized protocol among caregivers based on best-practice guidelines.
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16 MeSH Terms