{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:16:09Z","timestamp":1785208569625,"version":"3.55.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Foot Ankle Int."],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Persistent posttraumatic\/postsurgery ankle edema (PPAE) is edema that persists from 2\u2009weeks to 3\u2009months after injury or surgery. PPAE has negative effects on the healing process and quality of life. This study aimed to evaluate the efficacy of a phytochemical product containing diosmin, coumarin, and arbutin (Linfadren) in addition to the conventional treatment, in patients with PPAE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Between October 2018 and February 2020, 60 outpatients with PPAE (42 with ankle fractures and 18 with ankle sprains) were enrolled and randomized (1:1 ratio) to receive either 6-week conventional treatment plus Linfadren (study group) or conventional treatment alone (control group). Primary outcome was ankle edema as measured by the \u201cfigure-of-8-20\u201d method. Secondary outcomes were ankle function measured by the Lower Extremity Functional Scale (LEFS), and patient\u2019s overall perceived treatment efficacy. Tolerability of Linfadren was also evaluated. Assessments were performed at baseline, at end of treatment (6\u2009weeks after baseline), and 3\u2009months after the end of treatment (follow-up). A subgroup analysis was also conducted for the injury type (fracture\/sprain) to identify if this factor affected the results of the primary outcome measure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>At the end of treatment, the study group had a significantly greater improvement in ankle edema, improved ankle function, and more patients who considered this treatment effective compared with the control group. The measured difference in circumference by the figure-of-8-20 method averaged 4% at 6\u2009weeks and 5% at 3\u2009months. No difference between groups was seen in rescue medication. No adverse events were recorded. Subgroup analysis revealed no significant influence of the injury type on the primary outcome measure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Linfadren in addition to conventional treatment was more effective than conventional treatment alone in patients with PPAE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence:<\/jats:title>\n                    <jats:p>Level I, randomized controlled trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10711007231189679","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T08:52:46Z","timestamp":1695113566000},"page":"972-982","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and Safety of the Phytochemical Product Linfadren in the Management of Patients With Persistent Ankle Edema Following Trauma or Surgery: A Randomized Controlled Trial"],"prefix":"10.1177","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-7938","authenticated-orcid":false,"given":"Angelo","family":"Cacchio","sequence":"first","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, School of Medicine, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Calvisi","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, School of Medicine, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, School of Medicine, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Petralia","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, School of Medicine, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Angelozzi","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, School of Medicine, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"bibr1-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.200900281"},{"key":"bibr2-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2013.05.015"},{"key":"bibr3-10711007231189679","first-page":"899","volume-title":"Rehabilitation of the Hand and Upper Extremity","volume":"2002","author":"Artzberger S","edition":"5"},{"key":"bibr4-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1177\/0003319701052001S06"},{"issue":"4","key":"bibr5-10711007231189679","first-page":"371","volume":"79","author":"Binkley JM","year":"1999","journal-title":"Phys Ther"},{"key":"bibr6-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1159\/000179094"},{"issue":"1","key":"bibr7-10711007231189679","first-page":"3","volume":"32","author":"Burgos A","year":"1999","journal-title":"Lymphology"},{"key":"bibr8-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.08.001"},{"key":"bibr9-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1177\/0269215519829797"},{"key":"bibr10-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-018-4514-5"},{"key":"bibr11-10711007231189679","first-page":"143","volume-title":"Coumarins: Biology, Applications and Mode of Action","volume":"1997","author":"Casley-Smith JR"},{"issue":"3","key":"bibr12-10711007231189679","first-page":"190","volume":"21","author":"Casley-Smith JR","year":"1988","journal-title":"Lymphology"},{"issue":"2","key":"bibr13-10711007231189679","first-page":"76","volume":"29","author":"Casley-Smith JR","year":"1996","journal-title":"Lymphology"},{"key":"bibr14-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711330307"},{"key":"bibr15-10711007231189679","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199310143291604"},{"key":"bibr16-10711007231189679","unstructured":"CEN\/Technical Committee 205\/WG 2. 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