Data_Sheet_1_High indirect bilirubin levels as an independent predictor of postoperative myasthenic crisis: a single-center, retrospective study.docx

BackgroundThymectomy is an efficient and standard treatment strategy for patients with myasthenia gravis (MG), postoperative myasthenic crisis (POMC) is the major complication related to thymectomy and has a strongly life-threatening effect. As a biomarker, whether the bilirubin level is a risk factor for MG progression remains unclear. This study aimed to investigate the association between the preoperative bilirubin level and postoperative myasthenic crisis (POMC).
MethodsWe analyzed 375 patients with MG who underwent thymectomy at Tangdu Hospital between January 2012 and September 2021. The primary outcome measurement was POMC. The association between POMC and bilirubin level was analyzed by restricted cubic spline (RCS). Indirect bilirubin (IBIL) was divided into two subgroups based on the normal upper limit of IBIL, 14 μmol/L.
ResultsCompared with non–POMC group, IBIL levels were significantly higher in patients with POMC. Elevated IBIL levels were closely associated with an increased risk of POMC (p for trend = 0.002). There was a dose-response curve relationship between IBIL levels and POMC incidence (p for non–linearity = 0.93). However, DBIL levels showed a U-shaped association with POMC incidence. High IBIL level (≥14 μmol/L) was an independent predictive factor for POMC [odds ratio = 3.47, 95% confidence interval (CI): 1.56–7.8, p = 0.002]. The addition of high IBIL levels improved the prediction model performance (net reclassification index = 0.186, 95% CI: 0.039–0.334; integrated discrimination improvement = 0.0345, 95% CI: 0.005–0.065).
ConclusionHigh preoperative IBIL levels, especially those exceeding the normal upper limit, could independently predict the incidence of POMC.

**背景** 胸腺切除术是重症肌无力（myasthenia gravis, MG）患者的有效标准治疗策略，术后肌无力危象（postoperative myasthenic crisis, POMC）是与胸腺切除术相关的主要并发症，具有极强的致死风险。作为一种生物标志物，胆红素水平是否为重症肌无力进展的危险因素目前尚不明确。本研究旨在探讨术前胆红素水平与术后肌无力危象（POMC）之间的关联。
**方法** 我们分析了2012年1月至2021年9月间在唐都医院接受胸腺切除术的375例重症肌无力患者。主要结局指标为术后肌无力危象（POMC）。采用限制性立方样条（restricted cubic spline, RCS）分析POMC与胆红素水平之间的关联。间接胆红素（indirect bilirubin, IBIL）依据其正常上限值14 μmol/L划分为两个亚组。
**结果** 与非POMC组患者相比，POMC组患者的间接胆红素（IBIL）水平显著升高。间接胆红素（IBIL）水平升高与POMC风险增加密切相关（趋势检验p=0.002）。间接胆红素（IBIL）水平与POMC发病率呈剂量-反应曲线关系（非线性检验p=0.93）。然而，直接胆红素（direct bilirubin, DBIL）水平与POMC发病率呈U型关联。术前高间接胆红素（IBIL）水平（≥14 μmol/L）是POMC的独立预测因素[比值比（odds ratio）=3.47，95%置信区间（confidence interval, CI）：1.56~7.8，p=0.002]。加入高间接胆红素（IBIL）水平指标可改善预测模型的性能（净重新分类指数（net reclassification index）=0.186，95%置信区间（CI）：0.039~0.334；综合判别改善指数（integrated discrimination improvement）=0.0345，95%置信区间（CI）：0.005~0.065）。
**结论** 术前高间接胆红素（IBIL）水平，尤其是超过正常上限值者，可独立预测术后肌无力危象（POMC）的发生。