{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:50:13Z","timestamp":1780419013004,"version":"3.54.1"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA244271"],"award-info":[{"award-number":["R01CA244271"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1TR004403"],"award-info":[{"award-number":["UM1TR004403"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG\u201020\u2010017\u201001\u2010CCE"],"award-info":[{"award-number":["RSG\u201020\u2010017\u201001\u2010CCE"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4\u2009years in 1970 to 53\u2009years in 2010. Despite the recent improvement in survival, there is little data about the prevalence of age\u2010related diseases, including age\u2010related malignancies, and the impact of standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age\u2010 and sex\u2010matched patients \u2265\u200915\u2009years old with and without Down syndrome using the TriNetX platform to identify the prevalence of malignancies and explore cardiovascular outcomes after treatment with anthracyclines. We further stratified the populations into adolescent and young adult (AYA, ages 15\u201339\u2009years old) and adult (\u2265\u200940\u2009years old) cohorts, given that treatment recommendations can be different. Down syndrome patients in the AYA cohort were more likely to be diagnosed with acute myeloid leukemia (OR 8.9, CI 4.99\u201315.89,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and lymphoid leukemia (OR 7.33, CI 4.82\u201311.15,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) The adult cohort with Down syndrome was more likely to be diagnosed with myelodysplastic syndromes (OR 12.25, CI 6.41\u201323.42,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), multiple myeloma (OR 1.66, CI 1.06\u20132.6,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.026), and testicular cancer (OR 2.73, CI 1.32\u20135.65,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005). Overall, Down syndrome patients (\u2265\u200915\u2009years old) treated with anthracyclines were more likely to be diagnosed with heart failure (OR 2.14, CI 1.07\u20134.27,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.042). Our study demonstrates adolescents and adults with down syndrome have a higher predisposition to several malignancies and an increased risk of cardiovascular disease after anthracycline treatment and may require specific screening guidelines to address their unique health risks.\n                  <\/jats:p>","DOI":"10.1002\/cph4.70037","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T04:29:48Z","timestamp":1757132988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cancer and Post\u2010Therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults With Down Syndrome"],"prefix":"10.1002","volume":"15","author":[{"given":"Michelle A.","family":"Buckman","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Vasileva","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa  Iowa City IA USA"},{"name":"Department of Health and Human Physiology University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Jedlicka","sequence":"additional","affiliation":[{"name":"Department of Health and Human Physiology University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik","family":"Kalra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Vasilyev","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Dickens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Tomasson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2605-0984","authenticated-orcid":false,"given":"Melissa L.","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa  Iowa City IA USA"},{"name":"Department of Pediatrics University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0143-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08062"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2023.283225"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00544.2022"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2013-0015"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)60660-0"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-1605"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15221-z"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.04.047"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2014.71"},{"key":"e_1_2_11_12_1","first-page":"475","article-title":"Doxorubicin\u2010Induced Oxidative Stress and Endothelial Dysfunction in Conduit Arteries Is Prevented by Mitochondrial\u2010Specific Antioxidant Treatment","volume":"2","author":"Clayton Z. 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