{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:05:26Z","timestamp":1780499126856,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,16]],"date-time":"2025-03-16T00:00:00Z","timestamp":1742083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008728","name":"Japan Research Foundation for Clinical Pharmacology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008728","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>While endogenous cortisol secretion rises in the early morning, the number of lymphocytes in the blood is higher at night, thus exhibiting an antiphase pattern to cortisol secretion. Therefore, compared with the daytime, the infiltration of lymphocytes into immune\u2010reactive tissues is enhanced at night. This study aimed to determine whether the administration of methylprednisolone (mPSL) in the evening is more effective against T cell\u2010mediated rejection (TCMR) after liver transplantation compared with morning administration. This study used a randomized, open\u2010label, parallel\u2010group comparison design. Pediatric patients scheduled to undergo living\u2010donor liver transplantation were randomly divided into morning (8:00\u2009a.m.) and evening (8:00\u2009p.m.) mPSL administration groups. The primary endpoint was the occurrence of TCMR within 14\u2009days of surgery. Sixty\u2010two patients were enrolled between 2014 and 2023, and six patients were excluded from the analysis as their dose of mPSL deviated from the protocol within 14\u2009days after surgery. Of the 56 subjects analyzed, TCMR was detected in 10 of the morning group (<jats:italic>n<\/jats:italic>\u2009=\u200929) and three of the evening group (<jats:italic>n<\/jats:italic>\u2009=\u200927) within 14\u2009days after surgery. Stratified analysis of patients who did not receive preoperative rituximab treatment showed that none of the evening group and 36.4% of the morning group developed TCMR within 14\u2009days after surgery (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01, 95% confidence interval; 2.00\u2013infinity). Safety evaluation results were comparable between the two groups. This study shows that the evening administration of mPSL is an effective approach for suppressing TCMR. This study is hypothesis generating, and replication in further studies is needed.<\/jats:p>","DOI":"10.1002\/cpt.3640","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T02:24:36Z","timestamp":1742178276000},"page":"386-393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Night\u2010Time Chronotherapy with Methylprednisolone Prevents an Acute Rejection in Pediatric Patients with Liver Transplantation: A\u00a0Randomized Clinical Trial"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2637-3916","authenticated-orcid":false,"given":"Kentaro","family":"Ushijima","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Jichi Medical University  Tochigi Japan"},{"name":"Division of Pharmaceutics, Faculty of Pharmaceutical Sciences Sanyo\u2212Onoda City University  Yamaguchi 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