{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:08Z","timestamp":1792003688470,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart: Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UM1HL116885"],"award-info":[{"award-number":["UM1HL116885"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart: Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UL1TR000058"],"award-info":[{"award-number":["UL1TR000058"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart: Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P50AR072000"],"award-info":[{"award-number":["P50AR072000"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Center for Advancing Translational Sciences","award":["UM1HL116885"],"award-info":[{"award-number":["UM1HL116885"]}]},{"name":"National Center for Advancing Translational Sciences","award":["UL1TR000058"],"award-info":[{"award-number":["UL1TR000058"]}]},{"name":"National Center for Advancing Translational Sciences","award":["P50AR072000"],"award-info":[{"award-number":["P50AR072000"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["UM1HL116885"],"award-info":[{"award-number":["UM1HL116885"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["UL1TR000058"],"award-info":[{"award-number":["UL1TR000058"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["P50AR072000"],"award-info":[{"award-number":["P50AR072000"]}]},{"name":"VCU Investigational Drug Services, McGuff Pharmaceuticals, Santa Ana, CA","award":["UM1HL116885"],"award-info":[{"award-number":["UM1HL116885"]}]},{"name":"VCU Investigational Drug Services, McGuff Pharmaceuticals, Santa Ana, CA","award":["UL1TR000058"],"award-info":[{"award-number":["UL1TR000058"]}]},{"name":"VCU Investigational Drug Services, McGuff Pharmaceuticals, Santa Ana, CA","award":["P50AR072000"],"award-info":[{"award-number":["P50AR072000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng\/\u00b5L (SD 4.20 ng\/\u00b5L) and 2.65 ng\/\u00b5L (SD 3.87 ng\/\u00b5L), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng\/\u00b5L greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng\/mL (SD 5.57 ng\/mL) and 10.83 ng\/mL (SD 5.95 ng\/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng\/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng\/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.<\/jats:p>","DOI":"10.3390\/nu14204415","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T08:19:06Z","timestamp":1666599546000},"page":"4415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS"],"prefix":"10.3390","volume":"14","author":[{"given":"Xian","family":"Qiao","sequence":"first","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5184-3030","authenticated-orcid":false,"given":"Markos G.","family":"Kashiouris","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"L\u2019Heureux","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard J.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan W.","family":"Leichtle","sequence":"additional","affiliation":[{"name":"Division of Acute Care Surgical Services, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon D.","family":"Truwit","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Froedtert and the Medical College of Wisconsin, Aurora St. Luke\u2019s Medical Center, Milwaukee, WI 53215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Nanchal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Froedtert and the Medical College of Wisconsin, Aurora St. Luke\u2019s Medical Center, Milwaukee, WI 53215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Duncan","family":"Hite","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, University of Cincinnati, Cincinnati, OH 45221, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-7593","authenticated-orcid":false,"given":"Greg S.","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Sevransky","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpha A.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa050333","article-title":"Incidence and outcomes of acute lung injury","volume":"353","author":"Rubenfeld","year":"2005","journal-title":"N. 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