{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:25:41Z","timestamp":1753878341401,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Wound Journal"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Non\u2010healing venous leg ulcers represent a significant healthcare problem that accounts for about $32 billion of spending in the US alone. Consequently, novel treatment strategies represent a major unmet need. The current study (part one of Phase II study [NCT04647240]) assesses the safety, tolerability and efficacy of the use of cell\u2010free human amniotic fluid in treating venous leg ulcers that did not heal following the correction of venous reflux. Patients received cell\u2010free amniotic fluid injections in and around the wound either weekly or biweekly over 12\u2009weeks. Primary outcomes included safety, tolerability and efficacy assessed by complete wound closure, wound area reduction and pain reduction. Eleven patients met enrollment eligibility, and nine completed the study. Five patients achieved complete wound closure by week 12. The average percent reduction in wound area was 83.7%, and pain scores were significantly lower by the study endpoint. No difference was observed in wound healing rates between weekly or biweekly treatment, but bi\u2010weekly treatment was associated with nominally faster recovery. Patients tolerated the treatment, and no side effects were reported. These results indicate that cell\u2010free amniotic fluid injection is a feasible, safe and effective treatment for non\u2010healing venous leg ulcers.<\/jats:p>","DOI":"10.1111\/iwj.70171","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T23:57:56Z","timestamp":1743033476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the Safety, Tolerability and Efficacy of Cell\u2010Free Amniotic Fluid in the Treatment of Non\u2010Healing Venous Ulcers: Initial Experience From a Prospective, Multicenter, Phase <scp>II<\/scp> Study"],"prefix":"10.1111","volume":"22","author":[{"given":"Frederick","family":"Ditmars","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Dermatology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Ducharme","sequence":"additional","affiliation":[{"name":"Compass Medical Research Center  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliza M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Podiatry Salem Veterans Affairs Health Care System  Salem Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u2010Anna","family":"Reems","sequence":"additional","affiliation":[{"name":"Merakris Therapeutics Inc., Research Triangle Park  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-1666","authenticated-orcid":false,"given":"William Samuel","family":"Fagg","sequence":"additional","affiliation":[{"name":"Merakris Therapeutics Inc., Research Triangle Park  Durham North Carolina USA"},{"name":"Department of Surgery University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovan N.","family":"Markovic","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2011.01.079"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2021.08.011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2019.12.075"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2004.09.027"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2002.121739"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2004.02456.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9113399"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10010029"},{"issue":"7","key":"e_1_2_9_10_1","first-page":"1039","article-title":"Diagnosis and Treatment of Venous Leg Ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V","volume":"22","author":"Valesky E. 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