Yu Jiang-Zhou, Lindeblad Matt, Lyubimov Alex, Neri Flavia, Smith Brett, Szilagyi Erzsebet, Halliday Lisa, MacVittie Tom, Nanda Joy, Bartholomew Amelia
a Department of Surgery, University of Illinois at Chicago, Chicago, Illinois 60612;
b Department of harmacology, University of Illinois at Chicago, Chicago, Illinois 60612;
Radiat Res. 2015 Jul;184(1):46-55. doi: 10.1667/RR13918.1. Epub 2015 Jun 29.
In a mass casualty radiation event situation, individualized therapy may overwhelm available resources and feasibility issues suggest a need for the development of population-based strategies. To investigate the efficacy of a population-based strategy, Chinese macaques (n = 46) underwent total-body irradiation and received preemptive antibiotics, IV hydration on predetermined postirradiation days and were then compared to macaques (n = 48) that received subject-based care in which blood transfusions, IV hydration, nutritional supplementation and antibiotic supportive measures were provided. Estimated radiation doses for LD30/60, LD50/60 and LD70/60 of animals with subject-based care: 6.83 Gy (6.21, 7.59), 7.44 Gy (6.99, 7.88) and 8.05 Gy (7.46, 8.64), respectively, and for population-based care: 5.61 Gy (5.28, 6.17), 6.62 Gy (6.13, 7.18) and 7.63 Gy (7.21, 8.20), respectively. Analysis of four time periods, 0-9, 10-15, 16-25 and 26-60 days postirradiation, identified significant mortality differences during the period of 10-15 days. A subset analysis of higher radiation doses (6.75-7.20 Gy, n = 32) indicated hydration, nutrition and septic status were not significantly different between treatments. Whole blood transfusion treatment, administered only in subject-supportive care, was associated with significantly higher platelet and absolute neutrophil counts. Median platelet counts greater than 5,670 cells/μl and absolute neutrophil counts greater than 26 cells/μl during this period correlated with survival. We observed that the population-based treatment increased the LD50/60 compared to nontreatment (6.62 Gy vs. 4.92 Gy) and may be further optimized during days 10-15, where strategic blood transfusions or other strategies to achieve increases in neutrophil and platelet counts may further increase survival rates in subjects exposed to high doses of radiation.
在大规模伤亡辐射事件的情况下,个体化治疗可能会耗尽可用资源,可行性问题表明需要制定基于群体的策略。为了研究基于群体的策略的疗效,对46只中国猕猴进行全身照射,并在预定的照射后天数给予预防性抗生素、静脉补液,然后与48只接受个体化护理的猕猴进行比较,后者接受输血、静脉补液、营养补充和抗生素支持措施。接受个体化护理的动物的LD30/60、LD50/60和LD70/60的估计辐射剂量分别为6.83 Gy(6.21,7.59)、7.44 Gy(6.99,7.88)和8.05 Gy(7.46,8.64),而基于群体护理的分别为5.61 Gy(5.28,6.17)、6.62 Gy(6.13,7.18)和7.63 Gy(7.21,8.20)。对照射后0 - 9天、10 - 15天、16 - 25天和26 - 60天这四个时间段的分析发现,在10 - 15天期间存在显著的死亡率差异。对更高辐射剂量(6.75 - 7.20 Gy,n = 32)的亚组分析表明,治疗之间的补液、营养和败血症状态没有显著差异。仅在个体化支持护理中给予的全血输血治疗与显著更高的血小板和绝对中性粒细胞计数相关。在此期间,血小板计数中位数大于5670个细胞/μl和绝对中性粒细胞计数大于26个细胞/μl与存活相关。我们观察到,与未治疗相比,基于群体的治疗增加了LD50/60(6.62 Gy对4.92 Gy),并且在10 - 15天期间可能会进一步优化,在这个时间段进行策略性输血或其他提高中性粒细胞和血小板计数的策略可能会进一步提高高剂量辐射暴露受试者的存活率。