细胞 microRNAs 与多发伤患者的临床参数相关。

Cellular microRNAs correlate with clinical parameters in multiple injury patients.

机构信息

From the Surgical Critical Care Initiative (D.A.V., S.A.S., F.L., V.K., M.J.B., T.G.B., T.A.D., C.J.D., A.D.K., E.A.E.); Department of Surgery (D.A.V., S.A.S., F.L., H.R., V.K., M.J.B., T.A.D., E.A.E.), Uniformed Services University of the Health Sciences; Henry M Jackson Foundation for the Advancement of Military Medicine (S.A.S., F.L., V.K.), Bethesda, Maryland; Translational Molecular Pathology (S.A., M.S., G.A.C.), Houston, Texas; DecisionQ (H.H.), Arlington, Virginia; Department of Surgery (F.L., V.K., M.J.B., E.A.E.), Walter Reed National Military Medical Center, Bethesda, Maryland; Department of Surgery (T.G.B., C.J.D.), Emory University, Atlanta, Georgia; and Department of Surgery (A.D.K.), Duke University, Durham, North Carolina.

出版信息

J Trauma Acute Care Surg. 2022 Oct 1;93(4):427-438. doi: 10.1097/TA.0000000000003708. Epub 2022 Jul 7.

DOI:10.1097/TA.0000000000003708

PMID:35797620

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9488942/

Abstract

INTRODUCTION

The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs).

METHODS

Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization.

RESULTS

Polytrauma patients (n = 180) had high Injury Severity Score (26 [20-34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78.

CONCLUSION

Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation.

LEVEL OF EVIDENCE

Diagnostic Tests/Criteria; Level II.

摘要

简介

严重创伤后炎症反应的病理生理学较为复杂，其严重程度与组织损伤程度和结局相关。对感染介导的免疫途径的研究表明，细胞 microRNA 可能调节炎症反应。作者假设 microRNA 的表达与多发伤患者（PtP）的复杂康复相关。

方法

本研究纳入了前瞻性观察性组织和数据采集方案中损伤严重程度评分＞15 的多发伤患者。将多发伤患者分为复杂康复组和非复杂康复组。多发伤患者在入院时（T0）采集血液样本。使用基于多重 Luminex 的方法测量包括细胞因子和趋化因子在内的系统炎症的既定生物标志物，并使用多重 RNA 杂交法测量血浆样本中的新型 microRNA。

结果

多发伤患者（n=180）损伤严重程度评分高（26[20-34]），复杂康复率为 33%。PtP 患者在 T0 时的 microRNA 水平低于健康对照组，双变量分析表明 microRNA 的变化与年龄、种族、合并症、静脉血栓栓塞、肺部并发症、复杂康复和死亡率相关。microRNA 与白细胞介素 10、血管内皮生长因子、急性生理学和慢性健康评估以及序贯器官衰竭评估评分呈正相关。基于 microRNA、细胞因子和趋化因子的复杂康复预测因素的多变量 Lasso 回归分析显示，miR-21-3p 和单核细胞趋化蛋白 1 可预测复杂康复，曲线下面积为 0.78。