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

Author:

Cho Young-Eun1,Kim Jeongmin2,Vorn Rany34,Cho Hyeonmi5,Baek Wonhee6,Park Hyunki5,Yun Sijung7,Kim Hyung-Suk4,Cashion Ann K8,Gill Jessica3,Koo Bon-Nyeo2,Lee Hyangkyu5ORCID

Affiliation:

1. College of Nursing, The University of Iowa , Iowa City, Iowa , USA

2. Department of Anesthesiology and Pain Medicine, Anesthesia Pain Research Institute, Yonsei University College of Medicine , Seoul , Republic of Korea

3. School of Nursing, Johns Hopkins University , Baltimore, Maryland , USA

4. National Institute of Nursing Research, National Institutes of Health , Bethesda, Maryland , USA

5. Mo-Im Kim Nursing Research Institute, College of Nursing, Yonsei University , Seoul , Republic of Korea

6. College of Nursing, Gyeongsang National University , Jinju, Gyeongnam , Republic of Korea

7. Predictiv Care, Inc , Sunnyvale, California , USA

8. College of Nursing, The University of Tennessee Health Science Center , Memphis, Tennessee , USA

Abstract

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.

Funder

National Research Foundation of Korea

Yonsei University College of Nursing

National Institute of Nursing Research

University of Iowa College of Nursing

Publisher

Oxford University Press (OUP)

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