Extracellular Vesicle MicroRNAs as Predictive Biomarkers in Postoperative Delirium After Spine Surgery: Preliminary Study.

Young-Eun Cho, Jeongmin Kim, Rany Vorn, Hyeonmi Cho, Wonhee Baek, Hyunki Park, Sijung Yun, Hyung-Suk Kim, Ann K Cashion, Jessica Gill, Bon-Nyeo Koo, Hyangkyu Lee
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Abstract

Postoperative delirium (POD) can cause poor patient outcomes in older adults who undergo surgery. In this study, we tested plasma extracellular vesicle (EV) miRNAs obtained before the delirium event to find predictive POD biomarkers after spine surgery. We recruited patients who are more than 70 years old and have undergone spine surgery. Finally, POD patients (n = 31) were included, with no-POD patients matched in age, sex, medical history, and type of surgery (n = 31). Peripheral blood was collected from patients in the operating room after the operation was completed. EVs were isolated from plasma, and the 798 miRNA expression level from EVs was measured using a NanoString platform. Sixty-two patients were included in the study; all were Korean, 67.7% were females, and the median age was 75 years. Preoperative medical history was not statistically different between no-POD and POD patients except for hypertension and the American Society of Anesthesiologists physical status. From the miRNA profiling, we identified 142 significantly differentially expressed miRNAs in POD patients compared with no-POD patients, which are associated with psychological/neurological disorders. The top 10 differentially expressed miRNAs including miR-548ar-5p and miR-627-5p were all upregulated in POD patients and the results were validated using qRT-PCR from the independent sets of samples (n = 96). We demonstrated the potential of plasma EV-miRNAs as predictive biomarkers to identify the risk group of POD after spine surgery. It also provides opportunities for future studies investigating the role of EV-miRNAs in delirium pathology.

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细胞外囊泡 MicroRNAs 作为脊柱手术后谵妄的预测性生物标记物;初步研究。
术后谵妄(POD)会导致接受手术的老年人预后不佳。在这项研究中,我们检测了在谵妄事件发生前获得的血浆细胞外囊泡 (EV) miRNA,以寻找预测脊柱手术后 POD 的生物标志物。我们招募了 70 岁以上接受过脊柱手术的患者。最后,POD 患者(31 人)与年龄、性别、病史和手术类型相匹配的非 POD 患者(31 人)被纳入其中。手术结束后,在手术室采集患者的外周血。从血浆中分离出 EVs,使用 NanoString 平台测量 EVs 中 798 个 miRNA 的表达水平。研究共纳入 62 名患者,均为韩国人,67.7% 为女性,中位年龄为 75 岁。除高血压和美国麻醉医师协会(ASA)身体状况外,无 POD 和 POD 患者的术前病史无统计学差异。通过 miRNA 图谱分析,我们在 POD 患者和非 POD 患者中发现了 142 个表达明显不同的 miRNA,这些 miRNA 与心理/神经紊乱有关。包括 miR-548ar-5p 和 miR-627-5p 在内的前 10 个差异表达的 miRNA 在 POD 患者中均出现了上调,这些结果通过来自独立样本集(n=96)的 qRT-PCR 得到了验证。我们证明了血浆 EV-miRNA 作为预测性生物标记物的潜力,可用于识别脊柱手术后 POD 的风险人群。这也为今后研究 EV-miRNA 在谵妄病理学中的作用提供了机会。
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