{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:50:49Z","timestamp":1790934649984,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NICHD","award":["R21 HD109119"],"award-info":[{"award-number":["R21 HD109119"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite significant advancements in medical and surgical care, the morbidity and mortality rates of neonates and infants undergoing congenital cardiac surgery remain high. To identify new pathomechanisms associated with postoperative organ dysfunction, extracellular vesicles (EVs) were isolated from plasma from neonates and infants with or without organ dysfunction at three different time points around congenital cardiac surgery, and the EV miRNA expression profiles in the plasma were analyzed. A clear distinction was observed between the organ dysfunction (OD) and non-organ dysfunction (NOD) groups based on their EV miRNA expression profiles. Apoptosis and proinflammatory pathways were consistently upregulated across all time points in the OD group. Complement and coagulation cascades unexpectedly displayed downregulation at the end of the surgery in the OD group, which was verified further at the proteomic level in an independent patient cohort. The neutrophil extracellular trap (NET) formation was enhanced in the OD group across all time points compared to that in the NOD group. As NETs are known to consume complement components, these observed events might be interconnected. A feature selection machine learning method identified miR-200b-5p, miR-4800-5p, miR-363-3p, and miR-483-5p as robustly linked to organ dysfunction following congenital cardiac surgery (accuracy score = 9; SD in accuracy = 0.3162). In conclusion, our study suggested that neonates and infants with postoperative organ dysfunction were associated with enhanced NET formation and complement consumption.<\/jats:p>","DOI":"10.3390\/ijms26083837","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T06:23:56Z","timestamp":1744957436000},"page":"3837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Extracellular-Vesicle-Derived miRNAs in Postoperative Organ Dysfunction in Neonates and Infants Undergoing Congenital Cardiac Surgery: An Exploratory Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-9781","authenticated-orcid":false,"given":"Fahd","family":"Alhamdan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Immunology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiriya","family":"Maisat","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LeeAnn","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-9927","authenticated-orcid":false,"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2096-5363","authenticated-orcid":false,"given":"Juan","family":"Ibla","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Yuki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Immunology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S234","DOI":"10.1161\/CIRCULATIONAHA.109.928325","article-title":"Sex differences in mortality in children undergoing congenital heart disease surgery: A United States population-based study","volume":"122","author":"Marelli","year":"2010","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1161\/CIRCULATIONAHA.120.046962","article-title":"National Variation in Congenital Heart Surgery Outcomes","volume":"142","author":"Pasquali","year":"2020","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s40001-024-01735-5","article-title":"Clinical characteristics and outcomes of patients who underwent neonatal cardiac surgery: Ten years of experience in a tertiary surgery center","volume":"29","author":"Zhang","year":"2024","journal-title":"Eur. 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