{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:21:03Z","timestamp":1791231663498,"version":"4.1.0"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Various therapeutic strategies for angiogenesis are performed to improve symptoms in patients with critical limb ischemia (CLI). Pre-clinical studies have shown that low-intensity pulsed ultrasound (LIPUS) exposure induces angiogenesis. LIPUS may be a new stratergy for treatment of CLI. The purpose of this pilot trial was to evaluate outcomes in patients with CLI who were treated with LIPUS. Fourteen patients with CLI, who were not candidates for angioplasty or surgical revascularization, were enrolled in this study. Historical control data were obtained from the Hiroshima University PAD database. The primary endpoints were major amputation and death. The outcomes were compared in 16 lower limbs of the 14 patients with CLI who were treated with LIPUS and in 14 lower limbs of 14 patients with CLI as historical controls. All patients were followed for after 5 years after treatment with LIPUS. The mean duration of LIPUS exposure in the LIPUS group was 381\u00b1 283 days. During the 5-year follow-up periods, there were 3 major amputations and 7 deaths in the LIPUS group and there were 14 major amputations and 7 deaths in the historical control group. The overall amputation-free survival rate was significantly higher in patients who were treated with LIPUS than in historical controls. There was no significant difference between overall mortality-free survival rates in the LIPUS group and historical control group. LIPUS is a noninvasive option for therapeutic angiogenesis with the potential to reduce the incidence of major amputations in patients with CLI.<\/jats:p>","DOI":"10.1371\/journal.pone.0256504","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T18:23:42Z","timestamp":1629397422000},"page":"e0256504","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Low-intensity pulsed ultrasound decreases major amputation in patients with critical limb ischemia: 5-year follow-up study"],"prefix":"10.1371","volume":"16","author":[{"given":"Farina","family":"Mohamad Yusoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Kajikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yamaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Takaeko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Mizobuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kishimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Maruhashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-1494","authenticated-orcid":true,"given":"Ayumu","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-3672","authenticated-orcid":true,"given":"Yukihito","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"pone.0256504.ref001","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1056\/NEJMcp1709326","article-title":"Chronic limb-threatening ischemia","volume":"379","author":"A. 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