Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.
Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.
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严重钝性创伤后，持续的炎症，免疫抑制和分解代谢综合征。
DOI：
10.1097/ta.0b013e3182ab1ab5
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Efron PA
中科院分区：
文献类型：
--
作者：
Vanzant EL;Lopez CM;Ozrazgat-Baslanti T;Ungaro R;Davis R;Cuenca AG;Gentile LF;Nacionales DC;Cuenca AL;Bihorac A;Leeuwenburgh C;Lanz J;Baker HV;McKinley B;Moldawer LL;Moore FA;Efron PA
背景我们最近提出一种新的综合征--持续性炎症、免疫抑制和紧张综合征（PICS）已取代晚期多器官功能衰竭成为慢性危重病的主要表型。我们的目标是验证这一点，确定是否严重受伤的创伤患者的复杂结果有证据PICS在genomic level. METHODS我们进行了二次分析的炎症和主机响应损伤数据库的成人严重钝伤。患者被分为复杂，中间，和不复杂的临床轨迹。现有的基因组微阵列数据进行了比较，队列之间使用Incentiity途径分析。同时分析了入院时、第7天和第14天队列间的流行病学数据和结局。与中度/无并发症患者相比，有并发症的患者年龄更大，病情更重，需要呼吸机的天数更长。与无并发症的患者相比，他们也有持续的白细胞增多以及低淋巴细胞和白蛋白水平。复杂患者的总白色血细胞白细胞分析显示，对照受试者的总体全基因组表达模式和第7天和第14天的模式比无复杂患者的模式更异常。在第7天和第14天，并发症患者还具有适应性免疫的显著下调和炎性基因的显著上调（相对于与对照相比的倍数变化的幅度和与无并发症患者相比的幅度）。在第7天，与无并发症的患者和对照组相比，并发症患者在参与抑制骨髓细胞分化的功能途径、炎症增加、趋化性降低和先天免疫缺陷方面发生了显著变化。单核细胞，中性粒细胞和T细胞的亚群分析支持这些findings.CONCLUSIONGenomic分析复杂的临床结果的患者表现出持续的基因组表达的变化与适应性免疫反应和炎症增加的缺陷相一致。临床数据显示持续性炎症、免疫抑制和蛋白质耗竭。总体而言，数据支持具有复杂临床结局的患者表现出PICS的假设。
BACKGROUNDWe recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.METHODSWe performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14.RESULTSComplicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings.CONCLUSIONGenomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS.