Night-Time Chronotherapy with Methylprednisolone Prevents an Acute Rejection in Pediatric Patients with Liver Transplantation: A Randomized Clinical Trial.

IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Kentaro Ushijima, Yukihiro Sanada, Shinya Otomo, Keiko Ogaki, Taiichi Wakiya, Noriki Okada, Yuta Hirata, Yasuharu Onishi, Yasunaru Sakuma, Yukiyo Wada, Akio Fujimura, Koichi Mizuta
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Abstract

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-reactive 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-mediated rejection (TCMR) after liver transplantation compared with morning administration. This study used a randomized, open-label, parallel-group comparison design. Pediatric patients scheduled to undergo living-donor liver transplantation were randomly divided into morning (8:00 a.m.) and evening (8:00 p.m.) mPSL administration groups. The primary endpoint was the occurrence of TCMR within 14 days of surgery. Sixty-two 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 days after surgery. Of the 56 subjects analyzed, TCMR was detected in 10 of the morning group (n = 29) and three of the evening group (n = 27) within 14 days 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 days after surgery (P < 0.01, 95% confidence interval; 2.00-infinity). 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.

甲基强的松龙夜间计时疗法预防小儿肝移植患者急性排斥反应:一项随机临床试验
虽然内源性皮质醇分泌在清晨上升,但血液中淋巴细胞的数量在夜间较高,因此表现出皮质醇分泌的反相模式。因此,与白天相比,淋巴细胞向免疫反应组织的浸润在夜间增强。本研究旨在确定与早晨给药相比,晚上给药甲基强的松龙(mPSL)是否对肝移植后T细胞介导的排斥反应(TCMR)更有效。本研究采用随机、开放标签、平行组比较设计。将计划行活体肝移植的患儿随机分为上午(8:00)和晚上(8:00)给药组。主要终点是术后14天内TCMR的发生。2014年至2023年期间纳入了62名患者,其中6名患者因术后14天内mPSL剂量偏离方案而被排除在分析之外。在分析的56例受试者中,在术后14天内,晨起组10例(n = 29)和晚起组3例(n = 27)检测到TCMR。术前未接受利妥昔单抗治疗的患者的分层分析显示,夜间组和早晨组在术后14天内均无TCMR发生(P
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来源期刊
CiteScore
12.70
自引率
7.50%
发文量
290
审稿时长
2 months
期刊介绍: Clinical Pharmacology & Therapeutics (CPT) is the authoritative cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy, and evaluation of therapeutics. CPT welcomes original Articles in the emerging areas of translational, predictive and personalized medicine; new therapeutic modalities including gene and cell therapies; pharmacogenomics, proteomics and metabolomics; bioinformation and applied systems biology complementing areas of pharmacokinetics and pharmacodynamics, human investigation and clinical trials, pharmacovigilence, pharmacoepidemiology, pharmacometrics, and population pharmacology.
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