• Lei Li, Qichen Zhang, Yongpu Feng, Fanyang Kong, Fengyuan Sun, Pei Xie, Jiangman Zhao, Hang Yu, Jiahuan Zhou, Shouxin Wu, Shengbing Zhao, Zhaoshen Li, Feng Liu, Yiqi Du, and Xiangyu Kong.
• National Key Laboratory of Immunity and Inflammation, Changhai Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
• Ann. Surg. 2024 Feb 7.

ObjectiveCurrent study aims to investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting APs with POF at early phase.BackgroundNovel biomarkers are sorely needed for early prediction of persistent organ failure (POF) in acute pancreatitis (AP) patients.MethodsIn the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs. 5) using microarrays. POF-associated miRNA signatures then were assessed in training cohort (n=227) and further validated in three independent cohorts (n=516), including one nested case-control cohort.ResultsA total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort, and was further evaluated in two validation cohorts for their predictive value for POF. AUCs for Cmi ranged from 0.88 to 0.90, which was statistically superior to AUCs of APACHE-II and BISAP, and outperformed BUN and creatinine in POF prediction across all cohorts (P<.05). Higher levels of Cmi indicated increased need for ICU admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in post-ERCP pancreatitis cases within "golden hours" after ERCP with high efficacy.ConclusionsSerum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset.Trial RegistrationClinicalTrials.gov (NCT02602808).Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

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