{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:58:41Z","timestamp":1790585921382,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microsurgery"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ischemia\u2013reperfusion injury due to vascular pedicle occlusion is one of the most common causes of free flap failure in head and neck cancer reconstruction. Remote ischemic preconditioning (RIPC) has been proposed as an experimental, non\u2010invasive intervention to attenuate flap ischemia\u2013reperfusion injury; however, the tissue\u2010protective mechanisms remain unclear. RIPC may have multiple effects on the inflammatory system, which plays a central part in the pathophysiology of ischemia\u2013reperfusion injury. The aim of the present study was to evaluate the effect of RIPC on inflammatory cytokine plasma levels during free flap reconstruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Head and neck cancer patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200960) undergoing tumor resection and subsequent free flap reconstruction between August 2015 and November 2017 at Aarhus University Hospital, Denmark were randomized 1:1 to RIPC or sham intervention in a single\u2010center, single\u2010blinded, randomized controlled trial (RCT) (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov:<\/jats:ext-link>\n                      NCT02548377). The study was approved by The Central Denmark Region Committees on Health Research Ethics (journal no. 1\u201010\u201072\u2010140\u201015) and reported following the CONSORT guidelines. RIPC was administered intraoperatively as four 5\u2010min\u2009cycles of upper extremity occlusion and reperfusion with an inflatable tourniquet. Blood samples were collected before surgery, 6\u2009h after RIPC\/sham intervention, and on the 1st postoperative day. Tumor necrosis factor (TNF)\u2010\u03b1, interleukin (IL)\u20101\u03b2, IL\u20102, IL\u20104, IL\u20106, IL\u20108, IL\u201010, IL\u201012p70, IL\u201013, and interferon (IFN)\u2010gamma were analyzed using a multiplex immunoassay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The average age of the RIPC group was 67\u2009years (\u00b110) and 64\u2009years (\u00b112) in the sham group. Plasma levels of the pro\u2010inflammatory cytokines changed significantly between preoperative measures to 1\n                      <jats:sup>st<\/jats:sup>\n                      postoperative day between RIPC and sham; TNF\u2010\u03b1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), IL\u20106 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), IL\u20108 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), IL\u201012p70 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and IFN\u2010\u03b3 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). No significant differences in cytokine levels were shown between groups at any specific time points.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RIPC does not attenuate pro\u2010inflammatory cytokine release in head and neck cancer patients undergoing free flap reconstruction.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT02548377\n                    <\/jats:p>\n                  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