{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:07:16Z","timestamp":1789589236860,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21lk0201145h0001"],"award-info":[{"award-number":["21lk0201145h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The efficacy, safety, and optimal concentration of topical sirolimus gel for treatment of cutaneous lesions of vascular anomalies requires evaluation. This study was a multicenter, double\u2010blind, placebo\u2010controlled, parallel\u2010group, phase II randomized clinical trial. We enrolled patients with venous malformation (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200927), lymphatic malformation (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914), tufted angioma (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), or kaposiform hemangioendothelioma (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091). Patients applied either placebo or 0.2% or 0.4% topical sirolimus gel to the target lesion twice per day for 12\u2009weeks. The primary endpoint was the overall improvement score in the target lesion assessed from photographs by the independent review committee at Week 12. There was no statistically significant difference in the mean improvement score in the 0.2% group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.410) or the 0.4% group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.549) compared with in the placebo group. Thus, we could not prove the efficacy of topical sirolimus for cutaneous vascular anomalies in this protocol. Conversely, the improvement in target lesion size at Week 12 assessed by the committee as one of the 16 secondary endpoints was significantly higher in the 0.4% sirolimus gel group than in the placebo group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.031). In the post\u2010hoc analysis outside the protocol tracing the contour of the lesion, the percentages of patients with \u226520% reduction in the lesion area increased dose\u2010dependently (0%, 37.5%, and 65.0% in the placebo, 0.2%, and 0.4% group, respectively). Regarding safety, irritation and dermatitis at the application site occurred in the 0.4% gel group. Sirolimus gel reduced lesion size in our cohort. The safety data demonstrated topical sirolimus to have an acceptable safety profile.\n                  <\/jats:p>","DOI":"10.1111\/1346-8138.17688","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:50:05Z","timestamp":1741715405000},"page":"872-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Topical sirolimus therapy for cutaneous vascular anomalies: A randomized phase\n                    <scp>II<\/scp>\n                    clinical trial"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9230-6207","authenticated-orcid":false,"given":"Masatoshi","family":"Jinnin","sequence":"first","affiliation":[{"name":"Department of Dermatology Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"Department of Medical Data Science Graduate School of Medicine, Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Toranomon Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobukazu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Toranomon Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Nagahama","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine Kobe University Graduate School of Medicine  Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-3586","authenticated-orcid":false,"given":"Akiharu","family":"Kubo","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Medicine Kobe University Graduate School of Medicine  Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Ozeki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medicine, Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-3520","authenticated-orcid":false,"given":"Shuichi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomotaka","family":"Kawabata","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Yokohama City University Hospital  Yokohama\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Yokohama City University Hospital  Yokohama\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Yokohama City University Hospital  Yokohama\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumika","family":"Sawai","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Yokohama City University Hospital  Yokohama\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayato","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Yokohama City University Hospital  Yokohama\u2010shi Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-3950","authenticated-orcid":false,"given":"Mana","family":"Kurimoto\u2010Nishiguchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-5750","authenticated-orcid":false,"given":"Mariko","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8102-1193","authenticated-orcid":false,"given":"Kayo","family":"Kunimoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9317-7267","authenticated-orcid":false,"given":"Yuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23042358"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15189"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/JOVA.0000000000000064"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2019.01.011"},{"key":"e_1_2_9_6_1","first-page":"86","article-title":"Sirolimus in the treatment of vascular anomalies","volume":"27","author":"Triana P","year":"2017","journal-title":"Eur J Pediatr 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(sirolimus) Label (fda.gov). Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/021083s059 021110s076lbl.pdf. Accessed 02 Mar 2025."}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.17688","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1346-8138.17688","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.17688","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:39:27Z","timestamp":1772991567000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.17688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/1346-8138.17688"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.17688","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"2024-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}