妊娠合并胆囊结石发生急性胆胰并发症的危险因素分析及预测模型构建

Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model

  • 摘要:
    目的 探讨妊娠合并胆囊结石发生急性胆胰并发症的危险因素并构建预测模型。
    方法 采用回顾性病例对照研究方法。收集2011年9月至2022年10月兰州大学第一医院收治的98例和2014年5月至2021年10月甘肃省人民医院收治的53例妊娠合并胆囊结石患者的临床资料;年龄为29(25,32)岁。观察指标:(1)妊娠合并胆囊结石患者情况。(2)妊娠合并胆囊结石发生急性胆胰并发症的危险因素分析。(3)妊娠合并胆囊结石发生急性胆胰并发症的预测模型构建。正态分布的计量资料以x±s表示,组间比较采用独立样本t检验;偏态分布的计量资料以MQ1,Q3)表示,组间比较采用Mann‑Whitney U检验。计数资料以绝对数表示,组间比较采用χ²检验。等级资料比较采用秩和检验。单因素和多因素分析采用Logistic回归模型。构建列线图预测模型,绘制受试者工作特征曲线评估区分度,校准曲线、临床决策曲线评估模型的校准度和临床净获益。应用10折交叉验证对预测模型进行内部验证。
    结果 (1)妊娠合并胆囊结石患者情况。151例妊娠合并胆囊结石患者总胆固醇,甘油三酯,高密度脂蛋白胆固醇,低密度脂蛋白胆固醇,孕前体质量指数(<18.5 kg/m2、18.5~24.0 kg/m2、>24.0 kg/m2),孕期(早期、中期、晚期),初产妇(是、否),结石类型(单发、非单发),结石最大径(≤10 mm、 >10 mm),胆囊壁厚度(≥4 mm、<4 mm)分别为(4.9±1.4)mmol/L,1.88(1.22,2.93)mmol/L,1.48(1.22,1.83)mmol/L,(2.8±0.9)mmol/L,13、75、58例,37、45、69例,86、65例,37、114例,89、62例,38、113例。69例妊娠合并胆囊结石无症状患者和82例妊娠合并胆囊结石伴急性胆胰并发症患者年龄,孕前体质量指数(<18.5 kg/m2、18.5~24.0 kg/m2、>24.0 kg/m2),初产妇(是、否),结石类型(单发、非单发),结石最大径(≤10 mm、>10 mm),胆囊壁厚度(≥4 mm、<4 mm)分别为31(28,37)岁,3、30、36例,29、40例,32、37例,26、43例,4、65例和27(24,31)岁,10、45、22例,57、25例,5、77例,63、19例,34、48例,两者上述指标比较,差异均有统计学意义(Z=-3.636、-2.385,χ²=11.544、32.862、23.729、25.310,P<0.05)。82例妊娠合并胆囊结石伴急性胆胰并发症患者孕前体质量指数资料缺失5例。82例妊娠合并胆囊结石伴急性胆胰并发症患者中,单纯急性胆囊炎42例,胆总管结石和(或)急性胆源性胰腺炎40例(其中胆总管结石18例、急性胆源性胰腺炎13例、胆总管结石+急性胆源性胰腺炎9例)。(2)妊娠合并胆囊结石发生急性胆胰并发症的危险因素分析。多因素分析结果显示:初产妇、非单发结石、结石最大径≤10 mm、胆囊壁厚度≥4 mm是妊娠合并胆囊结石患者发生急性胆胰并发症的独立危险因素(优势比=3.102,6.305,3.674,6.686,95%可信区间为1.280~7.519,1.886~21.080,1.457~9.265,1.984~22.528,P<0.05)。进一步分析,多因素分析结果显示:初产妇、非单发结石、胆囊壁厚度≥4 mm是妊娠合并胆囊结石患者发生单纯急性胆囊炎的独立危险因素(优势比=3.671,8.905,7.137,95%可信区间为1.386~9.723,2.332~34.006,1.902~26.773,P<0.05);年龄、非单发结石、结石最大径≤10 mm、胆囊壁厚度≥4 mm是妊娠合并胆囊结石患者发生胆总管结石和(或)急性胆源性胰腺炎的独立危险因素(优势比=0.883,5.361,5.472,8.895,95%可信区间为0.789~0.988,1.062~27.071,1.590~18.827,2.064~38.325,P<0.05)。(3)妊娠合并胆囊结石发生急性胆胰并发症的预测模型构建。纳入年龄、初产妇、结石类型、结石最大径、胆囊壁厚度临床因素建立妊娠合并胆囊结石发生急性胆胰并发症预测模型列线图。预测模型受试者工作特征曲线的曲线下面积为0.869(95%可信区间为0.813~0.923),具有较好预测能力。Hosmer‑Lemeshow检验结果显示其拟合度良好(χ²=5.680,P>0.05),具有良好校准度。决策曲线分析结果显示该模型具有较高临床净获益。应用10折交叉验证对预测模型进行内部验证,交叉验证样本的受试者工作特征曲线的曲线下面积为0.833,表明该预测模型较稳定。
    结论 初产妇、非单发结石、结石最大径≤10 mm、胆囊壁厚度≥4 mm是妊娠合并胆囊结石患者发生急性胆胰并发症的独立危险因素。构建的预测模型具有良好预测效能。

     

    Abstract:
    Objective To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.
    Methods The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M(Q1,Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation.
    Results (1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m2, 18.5‒24.0 kg/m2, >24.0 kg/m2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m2, 18.5‒24.0 kg/m2, >24.0 kg/m2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them (Z=‒3.636, ‒2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone (odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280‒7.519, 1.886‒21.080, 1.457‒9.265, 1.984‒22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone (odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386‒9.723, 2.332‒34.006, 1.902‒26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone (odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789‒0.988, 1.062‒27.071, 1.590‒18.827, 2.064‒38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813‒0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit (χ²=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability.
    Conclusions Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.

     

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