Vanzant Erin L, Hilton Rachael E, Lopez Cecilia M, Zhang Jianyi, Ungaro Ricardo F, Gentile Lori F, Szpila Benjamin E, Maier Ronald V, Cuschieri Joseph, Bihorac Azra, Leeuwenburgh Christiaan, Moore Frederick A, Baker Henry V, Moldawer Lyle L, Brakenridge Scott C, Efron Philip A
Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA.
Department of Surgery, Anesthesia, University of Florida, PO Box 100254, Gainesville, FL, 32610-0254, USA.
Crit Care. 2015 Mar 4;19(1):77. doi: 10.1186/s13054-015-0788-x.
We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.
We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.
We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts. However, aged patients had more comorbidities. Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities. Additionally, advanced age was an independent predictor of a complicated recovery and 28-day mortality. Acutely after trauma, blood neutrophil genome-wide expression analysis revealed an attenuated transcriptomic response as compared to the young; this attenuated response was supported by the patients' plasma cytokine and chemokine concentrations. Later, these patients demonstrated gene expression changes consistent with simultaneous, persistent pro-inflammatory and immunosuppressive states.
We concluded that advanced age is one of the strongest non-injury related risk factors for poor outcomes after severe trauma with hemorrhagic shock and is associated with an altered and unique peripheral leukocyte genomic response. As the general population's age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.
我们希望描述高龄与严重钝性创伤合并失血性休克后的临床结局及转录组反应之间的关系。
我们对1928例严重受伤患者的前瞻性多中心队列进行了流行病学、细胞因子和转录组分析。
我们发现老年（年龄≥55岁，n = 533）和年轻（年龄<55岁，n = 1395）队列之间的损伤严重程度没有差异。然而，老年患者有更多的合并症。高龄与更严重的器官衰竭、感染并发症、呼吸机使用天数和重症监护病房住院时间相关，以及增加了出院至专业护理或长期护理机构的可能性。此外，高龄是恢复复杂和28天死亡率的独立预测因素。创伤后急性期，血液中性粒细胞全基因组表达分析显示与年轻患者相比转录组反应减弱；患者血浆细胞因子和趋化因子浓度支持了这种减弱的反应。后来，这些患者表现出与同时存在的持续性促炎和免疫抑制状态一致的基因表达变化。
我们得出结论，高龄是严重创伤合并失血性休克后不良结局最强的非损伤相关危险因素之一，并且与外周白细胞基因组反应的改变和独特性相关。随着普通人群年龄的增加，针对这一高风险队列个性化预测模型和治疗靶点将很重要。
