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ABCG2 c.421C>A Is Associated with Outcomes after Severe Traumatic Brain Injury.

ABSTRACT: Traumatic brain injury (TBI) is a leading cause of death with no pharmacological treatments that improve outcomes. Transporter proteins participate in TBI recovery by maintaining the central nervous system (CNS) biochemical milieu. Genetic variations in transporters that alter expression and/or function have been associated with TBI outcomes. The ATP-binding cassette transporter, ABCG2, is a uric acid (UA) transporter that effluxes UA from cells in the CNS and is responsible for systemic UA clearance. Uric acid is a CNS antioxidant and/or a biomarker that might support TBI recovery. Our objective was to investigate the impact of ABCG2 SNP: c.421C>A on TBI outcomes. Two cohorts (discovery [N?=?270] and replication [N?=?166]) were genotyped for ABCG2 c.421C>A. Glasgow Outcome Scale (GOS) scores were collected at 3, 6, 12, and 24 months post-injury and compared with mixed-effects multiple ordinal regression controlled for time post-injury, age, sex, time, post-injury imaging determined hemorrhage types, and Glasgow Coma Scale score. Variant alleles (genotype) were associated with better GOS scores (p?=?0.01 [discovery] and p?=?0.02 [replication]), whereas genotype*age interaction was associated with worse GOS scores (p?=?0.03 [discovery] and p?=?0.01 [replication]). Reversed coefficient directionality suggests variant allele(s) are protective up to approximately age 34 years. Overall, variant alleles at ABCG2 c.421C>A associate with better GOS scores post-injury in two independently sampled cohorts. This finding is mitigated by increasing subject age. This suggests that ABCG2 might have an age-dependent effect on TBI recovery and should be explored in future mechanistic studies.

SUBMITTER: Adams SM

PROVIDER: S-EPMC5757075 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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ABCG2 c.421C>A Is Associated with Outcomes after Severe Traumatic Brain Injury.

Adams Solomon M SM Conley Yvette P YP Ren Dianxu D Okonkwo David O DO Puccio Ava M AM Dixon C Edward CE Clark Robert S B RSB Kochanek Patrick M PM Empey Philip E PE

Journal of neurotrauma 20170919 1

Traumatic brain injury (TBI) is a leading cause of death with no pharmacological treatments that improve outcomes. Transporter proteins participate in TBI recovery by maintaining the central nervous system (CNS) biochemical milieu. Genetic variations in transporters that alter expression and/or function have been associated with TBI outcomes. The ATP-binding cassette transporter, ABCG2, is a uric acid (UA) transporter that effluxes UA from cells in the CNS and is responsible for systemic UA clea ...[more]

PMID: 28747144

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Project description:The effect of the 2003 severe pediatric traumatic brain injury (TBI) guidelines on outcomes has not been examined. We aimed to develop a set of acute care guideline-influenced clinical indicators of adherence and tested the relationship between these indicators during the first 72 hours after hospital admission and discharge outcomes.Retrospective multicenter cohort study.Five regional pediatric trauma centers affiliated with academic medical centers.Children under 18 years with severe traumatic brain injury (admission Glasgow Coma Scale score ? 8, International Classification of Diseases, 9th Edition, diagnosis codes of 800.0-801.9, 803.0-804.9, 850.0-854.1, 959.01, 950.1-950.3, 995.55, maximum head abbreviated Injury Severity Score ? 3) who received tracheal intubation for at least 48 hours in the ICU between 2007 and 2011 were examined.None.Total percent adherence to the clinical indicators across all treatment locations (prehospital, emergency department, operating room, and ICU) during the first 72 hours after admission to study center were determined. Main outcomes were discharge survival and Glasgow Outcome Scale score. Total adherence rate across all locations and all centers ranged from 68% to 78%. Clinical indicators of adherence were associated with survival (adjusted hazard ratios, 0.94; 95% CI, 0.91-0.96). Three indicators were associated with survival: absence of prehospital hypoxia (adjusted hazard ratios, 0.20; 95% CI, 0.08-0.46), early ICU start of nutrition (adjusted hazard ratios, 0.06; 95% CI, 0.01-0.26), and ICU PaCO2 more than 30 mm Hg in the absence of radiographic or clinical signs of cerebral herniation (adjusted hazard ratios, 0.22; 95% CI, 0.06-0.8). Clinical indicators of adherence were associated with favorable Glasgow Outcome Scale among survivors (adjusted hazard ratios, 0.99; 95% CI, 0.98-0.99). Three indicators were associated with favorable discharge Glasgow Outcome Scale: all operating room cerebral perfusion pressure more than 40 mm Hg (adjusted relative risk, 0.61; 95% CI, 0.58-0.64), all ICU cerebral perfusion pressure more than 40 mm Hg (adjusted relative risk, 0.73; 95% CI, 0.63-0.84), and no surgery (any type; adjusted relative risk, 0.68; 95% CI, 0.53- 0.86).Acute care clinical indicators of adherence to the Pediatric Guidelines were associated with significantly higher discharge survival and improved discharge Glasgow Outcome Scale. Some indicators were protective, regardless of treatment location, suggesting the need for an interdisciplinary approach to the care of children with severe traumatic brain injury.

Project description:ImportanceThe development and expansion of intracranial hematoma are associated with adverse outcomes. Use of tranexamic acid might limit intracranial hematoma formation, but its association with outcomes of severe traumatic brain injury (TBI) is unclear.ObjectiveTo assess whether prehospital administration of tranexamic acid is associated with mortality and functional outcomes in a group of patients with severe TBI.Design, setting, and participantsThis multicenter cohort study is an analysis of prospectively collected observational data from the Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) study in the Netherlands. Patients treated for suspected severe TBI by the Dutch Helicopter Emergency Medical Services between February 2012 and December 2017 were included. Patients were followed up for 1 year after inclusion. Data were analyzed from January 10, 2020, to September 10, 2020.ExposuresAdministration of tranexamic acid during prehospital treatment.Main outcomes and measuresThe primary outcome was 30-day mortality. Secondary outcomes included mortality at 1 year, functional neurological recovery at discharge (measured by Glasgow Outcome Scale), and length of hospital stay. Data were also collected on demographic factors, preinjury medical condition, injury characteristics, operational characteristics, and prehospital vital parameters.ResultsA total of 1827 patients were analyzed, of whom 1283 (70%) were male individuals and the median (interquartile range) age was 45 (23-65) years. In the unadjusted analysis, higher 30-day mortality was observed in patients who received prehospital tranexamic acid (odds ratio [OR], 1.34; 95% CI, 1.16-1.55; P < .001), compared with patients who did not receive prehospital tranexamic acid. After adjustment for confounders, no association between prehospital administration of tranexamic acid and mortality was found across the entire cohort of patients. However, a substantial increase in the odds of 30-day mortality persisted in patients with severe isolated TBI who received prehospital tranexamic acid (OR, 4.49; 95% CI, 1.57-12.87; P = .005) and after multiple imputations (OR, 2.05; 95% CI, 1.22-3.45; P = .007).Conclusions and relevanceThis study found that prehospital tranexamic acid administration was associated with increased mortality in patients with isolated severe TBI, suggesting the judicious use of the drug when no evidence for extracranial hemorrhage is present.

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ABCG2 c.421C>A Is Associated with Outcomes after Severe Traumatic Brain Injury.

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ABCG2 c.421C>A Is Associated with Outcomes after Severe Traumatic Brain Injury.

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