Role of a high throughput biodosimetry test in treatment prioritization after a nuclear incident

Role of a high throughput biodosimetry test in treatment prioritization after a nuclear incident
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DOI:
10.1080/09553002.2018.1532615
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发表时间:
2020-01-02
影响因子:
2.6
通讯作者:
Terbrueggen, Robert
Terbrueggen, Robert
中科院分区:
医学3区
文献类型:
--
作者:
Jacobs, Aviva R.;Guyon, Timothy;Terbrueggen, Robert

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目的:我们介绍并评估了一种高通量生物剂量学测试系统(REDI-Dx),该系统适用于在核装置爆炸或核事故引起的大规模核事件后对数千名潜在辐射受害者进行测试,作为危机有效医疗管理总体战略的一部分。材料与方法:通过采集未经辐照的假定健康供体以及作为癌症治疗方案的一部分采集或从先前研究中储存的辐照受试者的样本,评价了高通量生物剂量测定试验的性能。该测试基于DxDirect(R)基因组平台测量一组辐射响应基因的基因表达。评价了REDI-Dx的潜在诊断准确性,作为实际辐射剂量的预测因子。虽然REDI-Dx检测已经过校准以提供实际吸收剂量的定量测量,但我们比较了REDI-Dx检测的性能(灵敏度和特异性),作为最常用阈值2.0戈伊和6.0戈伊的定性结果。结果:该试验特异性高,不受医疗条件的影响.使用受试者工作特征(ROC)曲线分析,REDI-Dx被证明是基于2.0或6.0戈伊确定治疗类别的实际剂量的良好预测因子,2.0戈伊的敏感性和特异性分别为98.5%和90%,6.0戈伊的敏感性和特异性分别为92%和84%。结果在临床实验室之间具有重现性,样本的SD为0.2戈伊
Purpose: We introduce and evaluate a high throughput biodosimetry test system (REDI-Dx) suitable for testing of thousands of potential radiation victims following a mass scale nuclear event caused by detonation of a nuclear device or a nuclear accident, as part of an overall strategy for effective medical management of the crisis. Materials and methods: The performance of a high throughput biodosimetry test was evaluated by collecting samples of both non-irradiated presumed healthy donors as well as irradiated subjects collected as part of either cancer treatment regimens or banked from previous studies. The test measures the gene expression of a set of radiation responsive genes based on the DxDirect (R) genomic platform. The potential diagnostic accuracy of REDI-Dx was evaluated as a predictor of actual dose of radiation. While the REDI-Dx test has been calibrated to provide a quantitative measure of actual absorbed dose, we compared the performance of the REDI-Dx test (sensitivity and specificity) as a qualitative result at the most commonly applied thresholds 2.0 Gy and 6.0 Gy. Results: The test demonstrated high specificity and lack of effect of medical conditions. Using receiver operating characteristic (ROC) curve analysis, REDI-Dx was shown to be a good predictor of actual dose for determining treatment category based on either 2.0 or 6.0 Gy, with a 98.5% sensitivity and 90% specificity for 2.0 Gy, and 92% sensitivity and 84% specificity for 6.0 Gy. Results were reproducible between clinical laboratories with an SD of 0.2 Gy for samples