Impact of nonphysician, technology-guided alert level selection on rates of appropriate trauma triage in the United States: a before and after study.

Purpose: Overtriage and undertriage rates are critical metrics in trauma, influenced by both trauma team activation (TTA) criteria and compliance with these criteria. Analysis of undertriaged patients at a level I trauma center revealed suboptimal compliance with existing criteria. This study assessed triage patterns after implementing compliance-focused process interventions. Methods: A physician-driven, free-text alert system was modified to a nonphysician, hospital dispatcher-guided system. The latter employed dropdown menus to maximize compliance with criteria. The preintervention period included patients who presented between May 12, 2020, and December 31, 2020. The postintervention period incorporated patients who presented from May 12, 2021, through December 31, 2021. We evaluated appropriate triage, overtriage, and undertriage using the Standardized Trauma Assessment Tool. Statistical analyses were conducted with an α level of 0.05. Results: The new system was associated with improved compliance with existing TTA criteria (from 70.3% to 79.3%, P=0.023) and decreased undertriage (from 6.0% to 3.2%, P=0.002) at the expense of increasing overtriage (from 46.6% to 57.4%, P<0.001), ultimately decreasing the appropriate triage rate (from 78.4% to 74.6%, P=0.007). Conclusions: This study assessed a workflow change designed to improve compliance with TTA criteria. Improved compliance decreased undertriage to below the target threshold of 5%, albeit at the expense of increased overtriage. The decrease in appropriate triage despite compliance improvements suggests that the current criteria at this institution are not adequately tailored to optimally balance the minimization of undertriage and overtriage. This finding underscores the importance of improved compliance in evaluating the efficacy of TTA criteria.

Transcriptional Regulation of Amino Acid Transport in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a deadly brain tumor with a large unmet therapeutic need. Here, we tested the hypothesis that wild-type p53 is a negative transcriptional regulator of SLC7A11, the gene encoding the System xc- (SXC) catalytic subunit, xCT, in GBM. We demonstrate that xCT expression is inversely correlated with p53 expression in patient tissue. Using representative patient derived (PDX) tumor xenolines with wild-type, null, and mutant p53 we show that p53 expression negatively correlates with xCT expression. Using chromatin immunoprecipitation studies, we present a molecular interaction whereby p53 binds to the SLC7A11 promoter, suppressing gene expression in PDX GBM cells. Accordingly, genetic knockdown of p53 increases SLC7A11 transcript levels; conversely, over-expressing p53 in p53-null GBM cells downregulates xCT expression and glutamate release. Proof of principal studies in mice with flank gliomas demonstrate that daily treatment with the mutant p53 reactivator, PRIMA-1Met, results in reduced tumor growth associated with reduced xCT expression. These findings suggest that p53 is a molecular switch for GBM glutamate biology, with potential therapeutic utility.

3D Printed Multiplexed Competitive Migration Assays with Spatially Programmable Release Sources.

Here, a 3D printed multiplexed competitive migration assay is reported for characterizing a chemotactic response in the presence of multiple spatially distributed chemoattractants. The utility of the assay is demonstrated by examining the chemotactic response of human glioblastoma cells to spatially opposing chemotactic gradients of epidermal growth factor (EGF) and bradykinin (BK). Competitive migration assays involving spatially opposing gradients of EGF and BK that are optimized in the absence of the second chemoattractant show that 46% more glioblastoma cells migrate toward EGF sources. The migration velocities of human glioblastoma cells toward EGF and BK sources are reduced by 7.6 ± 2.2% and 11.6 ± 6.3% relative to those found in the absence of the spatially opposing chemoattractant. This work provides new insight to the chemotactic response associated with glioblastoma-vasculature interactions and a versatile, user-friendly platform for characterizing the chemotactic response of cells in the presence of multiple spatially distributed chemoattractants.