Supplementary Material for: Safety and efficacy of infusional perioperative Tacrolimus therapy in Crohn’s Disease patients undergoing intestinal resection

Introduction: Perioperative optimization of Crohn’s Disease (CD) patients is mandatory in order to ensure favorable outcomes and limit perioperative morbidity such as anastomosis-related complications. The use of perioperative tacrolimus may offer beneficial inflammatory control and improve postoperative outcome. However, it also may exhibit unwanted effects of immunosuppression on infectious complications and wound healing.

Methods: This is a single-center, retrospective study of CD patients undergoing intestinal resection between 2009 and 2018. Characteristics of CD patients receiving infusional perioperative Tacrolimus or not were systematically evaluated and exploratively compared. To investigate the impact of Tacrolimus and other predictors on postoperative infectious complications, simple regression with a threshold of p<0.05 was used. Significant predictors of the simple regression analysis, as well as Tacrolimus, were then included into multiple logistic regression.

Results: This analysis included 30 patients (34.88%) having received Tacrolimus perioperatively and 56 patients (65.12%) that were not treated with Tacrolimus. In median, 1mg/day of Tacrolimus was given intravenously for 11 days. Adverse events occurred in three patients (10%). The most common adverse events were headache and paresthesia. Tacrolimus showed no significant correlation to postoperative infectious complications. Furthermore, multiple regression analysis found no significant effect of Tacrolimus on postoperative infectious complications when controlling for previously identified confounders.

Conclusion: Administration of Tacrolimus showed no negative impact on postoperative infectious complications in the study cohort, indicating safety of perioperative Tacrolimus therapy. By describing in detail our study population of patients receiving perioperative Tacrolimus, we provide data guiding future prospective studies.

引言：为确保克罗恩病（Crohn’s Disease, CD）患者获得良好手术结局并降低围手术期并发症风险（如吻合口相关并发症），对其进行围手术期优化管理是必要举措。围手术期使用他克莫司（tacrolimus）或可实现有效的炎症控制，改善术后预后，但同时也可能引发免疫抑制相关的不良反应，增加感染并发症风险并延缓伤口愈合。

方法：本研究为一项单中心回顾性研究，纳入2009年至2018年间接受肠切除术的克罗恩病患者。系统评估并探索性对比了接受围手术期静脉输注他克莫司与未接受该治疗的患者的临床特征。为探究他克莫司及其他预测因素对术后感染并发症的影响，本研究采用P值阈值为0.05的简单回归分析；将简单回归分析中筛选出的显著预测因素及他克莫司纳入多因素logistic回归模型。

结果：本分析共纳入86例患者，其中30例（34.88%）接受了围手术期他克莫司治疗，56例（65.12%）未接受该治疗。受试者的他克莫司给药方案为中位每日静脉输注1mg，持续11天。共有3例患者（10%）出现不良事件，最常见的不良事件为头痛与感觉异常。他克莫司与术后感染并发症无显著相关性；此外，多因素回归分析显示，在控制既往确认的混杂因素后，他克莫司对术后感染并发症无显著影响。

结论：本研究队列数据显示，围手术期使用他克莫司对术后感染并发症无负面影响，表明该治疗方案具有安全性。本研究详细描述了接受围手术期他克莫司治疗的患者队列特征，可为未来的前瞻性研究提供参考数据。