{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:09:11Z","timestamp":1777511351147,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institutes of Health,National Center for Research Resources, National Institute of Diabetes and Kidney Diseases","award":["U42-RR16607"],"award-info":[{"award-number":["U42-RR16607"]}]},{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","award":["31-2008-616"],"award-info":[{"award-number":["31-2008-616"]}],"id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Herein, we characterized the percentage of tacrolimus to the combined sirolimus and tacrolimus trough levels (tacrolimus %) observed during islet transplant-associated immune suppression therapy with post-transplant skin cancer. Although trough levels of tacrolimus and sirolimus were not different ( P = 0.79, 0.73, respectively), high tacrolimus % resulted in a 1.32-fold increase in skin cancer odds when adjusting for age, sex, body mass index (BMI), and use of mycopheonlate mofetil (MMF; p = 0.039). Skin cancer patients were likely to have been older but not differ significantly (mean difference 12 years, P = 0.056), but age was significantly associated with a 1.22-fold increase in adjusted skin cancer odds ( P = 0.046). BMI was inversely associated with skin cancer, with an adjusted odds ratio (OR) of 0.40 ( P = 0.022). High tacrolimus % (&gt;35) resulted in a 4.6-fold increase in skin cancer frequency, whereas sirolimus above 75% of the combined therapy led to a 5.2-fold increase in islet graft dysfunction (IGD) events\/year. By calculating the maximum safe exposure (MSE) to tacrolimus % according to patient age and BMI, we found that cumulative months spent above MSE was predictive of skin cancer (1.20-fold increase, P = 0.003). Individuals exceeding the MSE for 1 year were 9.2 times more likely to develop skin cancer ( P = 0.008). Results suggest that strategies targeting immunosuppression ratios based on age and BMI may minimize cancer risk while improving graft survival and function.<\/jats:p>","DOI":"10.1177\/09636897241309412","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:47Z","timestamp":1736380847000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Tacrolimus, Sirolimus, Age, and Body Mass Index on the Occurrence of Skin Cancer and Islet Dysfunction After Transplantation"],"prefix":"10.1177","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9123-5101","authenticated-orcid":false,"given":"Christopher","family":"Orr","sequence":"first","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannette","family":"Stratton","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"El-Shahawy","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Forouhar","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Peng","sequence":"additional","affiliation":[{"name":"Kidney & Pancreas Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA. USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gagandeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meirigeng","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fouad","family":"Kandeel","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"bibr1-09636897241309412","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05804-4"},{"key":"bibr2-09636897241309412","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000081399.75231.3B"},{"key":"bibr3-09636897241309412","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.455"},{"key":"bibr4-09636897241309412","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061267"},{"key":"bibr5-09636897241309412","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.6691"},{"key":"bibr6-09636897241309412","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2015.5548"},{"key":"bibr7-09636897241309412","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.11.2731"},{"key":"bibr8-09636897241309412","unstructured":"Collaborative Islet Transplant Registry. 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