早期免疫介质的动态调控可识别出对出血耐受或敏感的多发性创伤患者。
Early dynamic orchestration of immunologic mediators identifies multiply injured patients who are tolerant or sensitive to hemorrhage.
机构信息
From the Department of Orthopaedic Surgery, (T.O.M.), Indiana University School of Medicine, Indianapolis, Indiana; Department of Orthopaedic Surgery, INOVA Health System (G.E.G.), Fairfax, Virginia; Department of Surgery, (R.Z., R.A.N., T.R.B., Y.V.), University of Pittsburgh School of Medicine, Pittsburgh; Department of Biostatistics, Epidemiology and Informatics, School of Medicine (L.S.), University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Preventive Medicine, Keck School of Medicine, (Q.S.), University of Southern California, Los Angeles, California.
出版信息
J Trauma Acute Care Surg. 2021 Mar 1;90(3):441-450. doi: 10.1097/TA.0000000000002998.
BACKGROUND
Multiply injured patients (MIPs) are at risk of complications including infections, and acute and prolonged organ dysfunction. The immunologic response to injury has been shown to affect outcomes. Recent advances in computational capabilities have shown that early dynamic coordination of the immunologic response is associated with improved outcomes after trauma. We hypothesized that patients who were sensitive or tolerant of hemorrhage would demonstrate differences in dynamic immunologic orchestration within hours of injury.
METHODS
We identified two groups of MIPs who demonstrated distinct clinical tolerance to hemorrhage (n = 10) or distinct clinical sensitivity to hemorrhage (n = 9) from a consecutive cohort of 100 MIPs. Hemorrhage was quantified by integrating elevated shock index values for 24 hours after injury (shock volume). Clinical outcomes were quantified by average Marshall Organ Dysfunction Scores from days 2 to 5 after injury. Shock-sensitive patients had high cumulative organ dysfunction after lower magnitude hemorrhage. Shock-tolerant (ST) patients had low cumulative organ dysfunction after higher magnitude hemorrhage. Computational methods were used to analyze a panel of 20 immunologic mediators collected serially over the initial 72 hours after injury.
RESULTS
Dynamic network analysis demonstrated the ST patients had increased orchestration of cytokines that are reparative and protective including interleukins 9, 17E/25, 21, 22, 23, and 33 during the initial 0- to 8-hour and 8- to 24-hour intervals after injury. Shock-sensitive patients had delayed immunologic orchestration of a network of largely proinflammatory and anti-inflammatory mediators. Elastic net linear regression demonstrated that a group of five mediators could discriminate between shock-sensitive and ST patients.
CONCLUSIONS
Preliminary evidence from this study suggests that early immunologic orchestration discriminates between patients who are notably tolerant or sensitive to hemorrhage. Early orchestration of a group of reparative/protective mediators was amplified in shock-tolerant patients.
LEVEL OF EVIDENCE
Prospective clinical outcomes study, level III.
背景
多发伤患者（MIP）有发生感染和急性及长期器官功能障碍等并发症的风险。免疫反应对创伤后的结局有影响。计算能力的最新进展表明，免疫反应的早期动态协调与创伤后转归改善相关。我们假设对出血敏感或耐受的患者在损伤后数小时内，其免疫反应的动态协调会有差异。
方法
我们从连续的 100 例 MIP 队列中确定了两组对出血有明显不同临床耐受性（n=10）或明显不同临床敏感性（n=9）的 MIP。通过整合损伤后 24 小时内升高的休克指数值（休克量）来量化出血。临床结局通过损伤后 2 至 5 天的平均马歇尔器官功能障碍评分来量化。休克敏感患者在较小程度出血后会发生较高程度的累积器官功能障碍。休克耐受（ST）患者在较大程度出血后会发生较低程度的累积器官功能障碍。计算方法用于分析损伤后最初 72 小时内连续采集的 20 种免疫介质的面板。
结果
动态网络分析显示，在损伤后最初的 0 至 8 小时和 8 至 24 小时两个时间段，ST 患者的细胞因子网络（包括白细胞介素 9、17E/25、21、22、23 和 33）有更多的协调性，这些细胞因子具有修复和保护作用。休克敏感患者的一大类促炎和抗炎介质的免疫协调延迟。弹性网络线性回归表明，有一组五个介质可以区分休克敏感和 ST 患者。
结论
本研究的初步证据表明，早期免疫协调可以区分对出血明显耐受或敏感的患者。ST 患者的一组修复/保护介质的早期协调被放大。
证据等级
前瞻性临床结局研究，III 级。
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