Victoria Warren

Detection of β-amyloid oligomers as a predictor of neurological outcome after brain injury

OBJECT Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (Aβ) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. METHODS Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecular-weight β-amyloid oligomers were measured using Western blot analysis. RESULTS Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. CONCLUSIONS Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.

Perspectives of surrogate decision makers for critically ill patients regarding gene variation research

Purpose:We undertook this investigation to explore the manner in which surrogate decision makers for critically ill patients perceived genetic data collected in the context of clinical investigation.Methods:Surrogate decision makers for critically ill patients cared for in intensive care units of two urban hospitals participated in focus groups designed to explore perceptions regarding gene variation research.Results:Surrogate decision makers were generally familiar with genetic concepts and reported that they could provide an informed opinion regarding permitting (or declining) the participation of their loved ones in gene variation research. Respondents perceived the risk associated with this type of research largely as the risk associated with acquiring the sample (i.e., whether it involved an invasive procedure or not) but appreciated that genetic samples could provide information not readily obtained from nongenetic sources. Concerns about potential misuse of genetic data largely centered on misconduct, paternity, forensic applications, and insurance and employment discrimination. Although surrogate decision makers expressed that their loved ones would have interest in return of results and being recontacted for future use, these interests were secondary to confidentiality concerns.Conclusion:Respondents perceived genetic and nongenetic data as comparable. Informed consent processes that provide clear information regarding confidentiality protections, specimen handling, and parameters for future use may enhance enrollment.Genet Med 2013:15(5):368–373

Critical illness research involving collection of genomic data: the conundrum posed by low levels of genomic literacy among surrogate decision makers for critically ill patients.

Critical illness clinical trials that entail genomic data collection pose unique challenges. In this qualitative study, we found that surrogate decision makers (SDMs) for critically ill individuals, such as those who would be approached for study participation, appeared to have a limited grasp of genomic principles. We argue that low levels of genomic literacy should neither preclude nor be in conflict with the conduct of ethically rigorous clinical trials.