Computational evidence for an early, amplified systemic inflammation program in polytrauma patients with severe extremity injuries
Computational evidence for an early, amplified systemic inflammation program in polytrauma patients with severe extremity injuries
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DOI：
10.1371/journal.pone.0217577
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发表时间：
2019-06-04
期刊：
影响因子：
3.7
通讯作者：
Vodovotz, Yoram
中科院分区：
文献类型：
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作者：
Almahmoud, Khalid;Abboud, Andrew;Vodovotz, Yoram
肢体和软组织损伤对创伤幸存者的炎症和不良住院结果有显著影响；因此，我们使用硅胶工具研究了这种情况下炎症反应与临床结果之间的复杂关联。从472名钝性创伤幸存者的队列中回顾得出了两个严格倾向匹配的中/重度损伤(损伤严重程度评分16)患者亚队列，每个患者类似于30名患者，并根据他们的肢体损伤严重程度(在简化损伤评分中高于或低于3)进行了分类。对系列血样进行了31种血浆炎症介质的分析。除了标准的统计分析外，还使用了动态网络分析(DYNA)和主成分分析(PCA)来模拟创伤后的全身炎症。与轻中度肢体损伤亚组相比，严重肢体损伤亚组患者在伤后前7天经历了更长的重症监护病房住院时间(LOS)、总LOS和使用机械呼吸机的天数，马歇尔多器官功能障碍(MOD)评分更高。在严重程度较高的队列中，首次抽血时乳酸、碱基缺失和肌酸磷酸激酶显著升高，同时多种循环炎症介质也发生显著变化。迪纳指出，17型免疫在两个亚队列中都发挥了持续的作用，严重肢体损伤组中也有干扰素-γ的作用。在严重损伤组中，DYNA网络复杂性在损伤后7天内增加，而在轻/中度损伤组中，在同一时间段内总体上降低。主成分分析显示，与轻中度损伤组相比，严重肢体损伤组的多条通路的激活更为强烈。因此，这些研究指出，严重四肢损伤后的自持性炎症与较轻的四肢损伤后消退炎症的可能性。
Extremity and soft tissue injuries contribute significantly to inflammation and adverse in-hospital outcomes for trauma survivors; accordingly, we examined the complex association between clinical outcomes inflammatory responses in this setting using in silico tools. Two stringently propensity-matched, moderately/severely injured (Injury Severity Score > 16) patient sub-cohorts of similar to 30 patients each were derived retrospectively from a cohort of 472 blunt trauma survivors and segregated based on their degree of extremity injury severity (above or below 3 on the Abbreviated Injury Scale). Serial blood samples were analyzed for 31 plasma inflammatory mediators. In addition to standard statistical analyses, Dynamic Network Analysis (DyNA) and Principal Component Analysis (PCA) were used to model systemic inflammation following trauma. Patients in the severe extremity injury sub-cohort experienced longer intensive care unit length of stay (LOS), total LOS, and days on a mechanical ventilator, with higher Marshall Multiple Organ Dysfunction (MOD) Scores over the first 7 days post-injury as compared to the mild/moderate extremity injury sub-cohort. The higher severity cohort had statistically significant elevated lactate, base deficit, and creatine phosphokinase on first blood draw, along with significant changes in multiple circulating inflammatory mediators. DyNA pointed to a sustained role for type 17 immunity in both sub-cohorts, along with IFN-gamma in the severe extremity injury group. DyNA network complexity increased over 7 days post-injury in the severe injury group, while generally decreasing over this same time period in the mild/moderate injury group. PCA suggested a more robust activation of multiple pathways in the severe extremity injury group as compared to the mild/moderate injury group. These studies thus point to the possibility of self-sustaining inflammation following severe extremity injury vs. resolving inflammation following less severe extremity injury.