C反应蛋白-白蛋白-淋巴细胞指数、C反应蛋白与淋巴细胞比值和C反应蛋白与血清钙比值对急性胰腺炎患者病情程度及预后的评估价值
DOI: 10.12449/JCH251222
Value of C-reactive protein-albumin-lymphocyte index, C-reactive protein-to-lymphocyte ratio, and C-reactive protein-to-serum calcium ratio in evaluating the severity and prognosis of patients with acute pancreatitis
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摘要:
目的 探讨C反应蛋白-白蛋白-淋巴细胞(CALLY)指数、C反应蛋白与淋巴细胞比值(CLR)和C反应蛋白与血清钙比值(CCR)与急性胰腺炎(AP)患者病情严重程度及预后的关系,并构建预后预测模型,为临床评估病情及判断预后提供参考。 方法 选取2021年6月—2024年6月在苏州大学附属第一医院诊治的407例AP患者为研究对象,根据2012年修订版亚特兰大分类标准和6个月内的预后情况,将患者分别分为轻症组(n=146)、中症组(n=137)和重症组(n=124),以及预后不良组(n=54)和预后良好组(n=353)。收集患者的临床资料,并计算CALLY指数、CLR和CCR。计量资料2组间比较采用成组t检验,3组间比较采用单因素方差分析。计数资料组间比较采用χ2检验。Pearson相关性分析CALLY指数、CLR和CCR与AP患者病情程度及预后的相关性,Cox回归分析AP患者预后不良的影响因素。Kaplan-Meier生存曲线分析CALLY指数、CLR和CCR对AP患者总生存期(OS)的影响,采用R软件基于多因素Cox回归分析筛选出的危险因素构建预测AP患者预后不良的列线图模型,并绘制受试者操作特征曲线分析各独立因素单独及联合对AP患者预后不良的预测价值。 结果 轻症组、中症组、重症组3组及预后良好组、预后不良组2组患者的CT严重指数(CTSI)评分、严重程度床边指数(BISAP)评分、急性生理学与慢性健康状况评价Ⅱ(APACHE Ⅱ)评分、血尿素氮、血清乳酸、血清淀粉酶、血清脂肪酶、CALLY指数、CLR和CCR比较,差异均有统计学意义(P值均<0.05)。Pearson相关性分析显示,CALLY指数与AP病情严重程度和预后呈负相关(rs=-0.134、-0.280),而CLR和CCR则呈正相关(rs=0.213~0.345)(P值均<0.05)。Cox回归分析证实,高BISAP评分(HR=2.246,95%CI:1.412~3.570)、高APACHE Ⅱ评分(HR=1.202,95%CI:1.089~1.327)、高血清淀粉酶水平(HR=1.004,95%CI:1.001~1.007)、高血清脂肪酶(HR=1.005,95%CI:1.002~1.008)、低CALLY指数(HR=0.536,95%CI:0.397~0.724)、高CLR(HR=1.033,95%CI:1.011~1.055)和高CCR(HR=1.144,95%CI:1.062~1.232)是AP预后不良的独立危险因素(P值均<0.05)。Kaplan-Meier生存曲线分析显示,低CALLY指数患者中位OS短于高CALLY指数患者(Log-rank χ2=31.934,P<0.001);高CLR、高CCR患者中位OS分别短于低CLR、低CCR患者(Log-rank χ2=34.201、28.023,P值均<0.001)。基于多因素分析构建的列线图模型展现出优异的预测效能(曲线下面积=0.977),显著优于各单项指标(P值均<0.05),当取Cut-off值0.107时,其灵敏度和特异度分别达0.963和0.898。内部验证证实模型稳定性良好(C-index=0.954),决策分析显示其具有理想的临床适用性。 结论 CALLY指数、CLR和CCR与AP患者病情严重程度及预后具有相关性。高BISAP评分、高APACHE Ⅱ评分、高血清酶水平、低CALLY指数、高CLR和高CCR是预后不良的独立危险因素,基于多因素构建的列线图模型具有较高的预测效能,能够实现对AP患者预后的早期、精准预测,为临床开展个体化干预和动态风险评估提供实用工具。 Abstract:Objective To investigate the association of C-reactive protein-albumin-lymphocyte (CALLY) index, C-reactive protein-to-lymphocyte ratio (CLR), and C-reactive protein-to-serum calcium ratio (CCR) with the severity and prognosis of patients with acute pancreatitis (AP), to construct a prognosis prediction model, and to provide a reference for clinical assessment of severity and prognosis. Methods A total of 407 AP patients who were diagnosed and treated in The First Affiliated Hospital of Soochow University from June 2021 to June 2024 were enrolled as subjects, and according to the 2012 revised edition of Atlanta classification standard and the prognosis within 6 months, the patients were divided into mild disease group with 146 patients, moderate disease group with 137 patients, and severe disease group with 124 patients, as well as into poor prognosis group with 54 patients and good prognosis group with 353 patients. Clinical data were collected from all subjects, and CALLY index, CLR, and CCR values were calculated. The independent samples t-test was used for comparison of continuous data between two groups, and a one-way analysis of variance was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. A Pearson correlation analysis was used to investigate the correlation of CALLY index, CLR, and CCR with the severity and prognosis of AP patients, and the Cox regression analysis was used to identify the influencing factors for poor prognosis of AP patients. The Kaplan-Meier survival curve was used to analyze the influence of CALLY index, CLR, and CCR on the overall survival (OS) of AP patients; R software was used to construct a nomogram model for predicting poor prognosis of AP patients based on risk factors identified by the multivariate Cox regression analysis. The receiver operating characteristic (ROC) curve was plotted to analyze the value of each independent factor used alone or in combination in predicting the poor prognosis of AP patients. Results There were significant differences between the mild, moderate, and severe disease groups in Computed Tomography Severity Index, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ) score, blood urea nitrogen, serum lactic acid, serum amylase, serum lipase, CALLY index, CLR, and CCR, and there were also significant differences in these indicators between the good prognosis group and the poor prognosis group (all P<0.05). The Pearson correlation analysis showed that CALLY index was negatively correlated with the severity and prognosis of AP (rs =-0.134 and -0.280,both P<0.05), while CLR and CCR were positively correlated with the severity and prognosis of AP (rs =0.213 — 0.345,all P<0.05). The Cox regression analysis confirmed that high BISAP score(HR=2.246,95%CI:1.412 — 3.570), high APACHE Ⅱ score(HR=1.202,95%CI:1.089 — 1.327), high serum amylase level(HR=1.004,95%CI:1.001 — 1.007),high serum lipase level(HR=1.005,95%CI:1.002 — 1.008), low CALLY inde(HR=0.536,95%CI:0.397 — 0.724), high CLR(HR=1.033,95%CI:1.011 — 1.055), and high CCR (HR=1.144,95%CI:1.062 — 1.232)were independent risk factors for the poor prognosis of AP (all P<0.05). The Kaplan-Meier survival curve analysis showed that the patients with low CALLY index had a shorter median OS than those with high CALLY index (Log-rank χ2=31.934, P<0.001), and the patients with high CLR and CCR had a significantly shorter median OS than those with low CLR and CCR, respectively (Log-rank χ2=34.201 and 28.023, both P<0.001). The nomogram model constructed based on the multivariate analysis showed excellent predictive efficiency, with an area under the ROC curve (AUC) of 0.977, which was significantly better than the AUC of each indicator used alone (P<0.05), when the cut-off value is 0.107,the sensitivity and specificity of the nomogram model reached 0.963 and 0.898, respectively. Internal validation confirmed that the model had good stability, with a C-index of 0.954, and the decision curve analysis showed that it had satisfactory clinical applicability. Conclusion CALLY index, CLR, and CCR are correlated with the severity and prognosis of AP patients. High BISAP score, high APACHE II score, high serum enzyme level, low CALLY index, high CLR, and high CCR are independent risk factors for poor prognosis, and the nomogram model constructed based on multiple factors has high predictive efficiency and can achieve early accurate prediction of the prognosis of AP patients, thereby providing a practical tool for individualized intervention and dynamic risk assessment in clinical practice. -
Key words:
- Pancreatitis /
- Patient Acuity /
- Prognosis
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表 1 不同病情程度患者的临床资料比较
Table 1. Comparison of clinical data of patients with different degrees of disease
指标 轻症组(n=146) 中症组(n=137) 重症组(n=124) 统计值 P值 性别[例(%)] χ2=0.924 0.630 男 67(45.89) 68(49.64) 64(51.61) 女 79(54.11) 69(50.36) 60(48.39) 年龄[例(%)] χ2=3.801 0.150 <60岁 87(59.59) 66(48.18) 69(55.65) ≥60岁 59(40.41) 71(51.82) 55(44.35) BMI(kg/m2) 23.63±2.73 24.13±2.70 23.67±2.82 F=1.394 0.249 糖尿病[例(%)] χ2=0.220 0.896 无 134(91.78) 127(92.70) 113(91.13) 有 12(8.22) 10(7.30) 11(8.87) 高血压[例(%)] χ2=1.681 0.432 无 133(91.10) 123(89.78) 107(86.29) 有 13(8.90) 14(10.22) 17(13.71) 病因[例(%)] χ2=4.795 0.309 高脂血症 41(28.08) 29(21.17) 29(23.39) 胆源性 79(54.11) 70(51.09) 68(54.84) 酒精性 26(17.81) 38(27.74) 27(21.77) CTSI评分(分) 5.45±1.07 5.95±0.86 5.98±0.92 F=13.856 <0.001 BISAP评分(分) 2.52±0.70 2.95±0.67 3.11±0.69 F=27.447 <0.001 APACHE Ⅱ评分(分) 8.34±2.11 9.96±3.02 11.55±3.19 F=44.633 <0.001 空腹血糖(mmol/L) 7.92±2.39 7.68±2.39 7.99±2.49 F=0.589 0.555 WBC(×109/L) 14.31±4.59 14.99±4.29 14.79±4.49 F=0.879 0.416 BUN(mmol/L) 5.45±0.84 5.66±0.91 5.83±1.01 F=5.921 0.003 血清乳酸(mmol/L) 9.72±1.45 9.84±1.58 10.37±1.54 F=6.917 0.001 Cr(μmol/L) 79.66±12.20 78.27±10.61 79.34±11.36 F=0.567 0.568 TBil(mg/dL) 2.94±0.98 3.01±0.98 3.06±1.03 F=0.472 0.624 血清淀粉酶(U/L) 219.03±77.48 235.52±98.08 308.81±100.46 F=35.204 <0.001 血清脂肪酶(U/L) 362.38±72.35 374.31±98.77 438.34±103.10 F=25.886 <0.001 CALLY指数 4.67±1.13 4.77±1.24 4.21±1.13 F=8.396 <0.001 CLR 63.30±11.39 63.31±10.52 71.14±14.57 F=17.850 <0.001 CCR 15.28±3.51 17.10±2.92 18.75±4.18 F=32.180 <0.001 注:BMI,体重指数;CTSI,CT严重指数;BISAP,严重程度床边指数;APACHE Ⅱ,急性生理学与慢性健康状况评价Ⅱ;WBC,白细胞计数;BUN,血尿素氮;Cr,肌酐;TBil,总胆红素;CALLY,C反应蛋白-白蛋白-淋巴细胞;CLR,C-反应蛋白与淋巴细胞比值;CCR,C-反应蛋白与血清钙比值。
表 2 预后不良组和预后良好组的临床资料比较
Table 2. Comparison of clinical data between the poor prognosis group and the good prognosis group
指标 预后良好组(n=353) 预后不良组(n=54) 统计值 P值 性别[例(%)] χ2=0.218 0.641 男 171(48.44) 28(51.85) 女 182(51.56) 26(48.15) 年龄[例(%)] χ2=0.026 0.873 <60岁 192(54.39) 30(55.56) ≥60岁 161(45.61) 24(44.44) BMI(kg/m2) 23.78±2.75 24.03±2.81 t=-0.623 0.533 糖尿病[例(%)] χ2=1.970 0.160 无 327(92.63) 47(87.04) 有 26(7.37) 7(12.96) 高血压[例(%)] χ2=2.214 0.137 无 318(90.08) 45(83.33) 有 35(9.92) 9(16.67) 病因[例(%)] χ2=0.756 0.685 高脂血症 88(24.93) 11(20.37) 胆源性 188(53.26) 29(53.70) 酒精性 77(21.81) 14(25.93) CTSI评分(分) 5.74±1.01 6.04±0.78 t=-2.071 0.039 BISAP评分(分) 2.76±0.69 3.37±0.73 t=-5.925 <0.001 APACHE Ⅱ评分(分) 9.32±2.61 13.41±3.52 t=-8.211 <0.001 空腹血糖(mmol/L) 7.82±2.37 8.09±2.69 t=-0.763 0.446 WBC(×109/L) 14.59±4.43 15.33±4.65 t=-1.137 0.256 BUN(mmol/L) 5.58±0.87 6.03±1.16 t=-2.783 0.007 血清乳酸(mmol/L) 9.89±1.51 10.43±1.71 t=-2.409 0.016 Cr(μmol/L) 78.91±11.57 80.33±10.33 t=-0.851 0.395 TBil(mg/dL) 2.98±0.99 3.16±1.03 t=-1.310 0.191 血清淀粉酶(U/L) 236.94±89.95 349.98±103.63 t=-8.422 <0.001 血清脂肪酶(U/L) 376.33±86.50 475.91±117.38 t=-7.478 <0.001 CALLY指数 4.69±1.19 3.79±0.81 t=7.061 <0.001 CLR 63.99±11.31 76.85±15.37 t=-5.907 <0.001 CCR 16.36±3.35 20.87±4.39 t=-7.241 <0.001 注:BMI,体重指数;CTSI,CT严重指数;BISAP,严重程度床边指数;APACHE Ⅱ,急性生理学与慢性健康状况评价Ⅱ;WBC,白细胞计数;BUN,血尿素氮;Cr,肌酐;TBil,总胆红素;CALLY,C反应蛋白-白蛋白-淋巴细胞;CLR,C-反应蛋白与淋巴细胞比值;CCR,C-反应蛋白与血清钙比值。
表 3 多因素Cox回归分析AP患者预后不良的独立危险因素
Table 3. Multivariate Cox regression analysis of independent risk factors of poor prognosis in AP patients
变量 β值 SE Wald P值 HR(95%CI) CTSI评分 0.184 0.164 1.265 0.261 1.202(0.872~1.658) BISAP评分 0.809 0.237 11.691 0.001 2.246(1.412~3.570) APACHE Ⅱ评分 0.184 0.050 13.386 <0.001 1.202(1.089~1.327) BUN 0.175 0.158 1.217 0.270 1.191(0.873~1.624) 血清乳酸 0.039 0.091 0.183 0.669 1.040(0.870~1.242) 血清淀粉酶 0.004 0.002 6.290 0.012 1.004(1.001~1.007) 血清脂肪酶 0.005 0.002 9.003 0.003 1.005(1.002~1.008) CALLY指数 -0.623 0.153 16.515 <0.001 0.536(0.397~0.724) CLR 0.032 0.011 8.842 0.003 1.033(1.011~1.055) CCR 0.134 0.038 12.662 <0.001 1.144(1.062~1.232) 注:CTSI,CT严重指数;BISAP,严重程度床边指数;APACHE Ⅱ,急性生理学与慢性健康状况评价Ⅱ;BUN,血尿素氮;CALLY,C反应蛋白-白蛋白-淋巴细胞;CLR,C-反应蛋白与淋巴细胞比值;CCR,C-反应蛋白与血清钙比值。
表 4 各项因素及列线图模型预测AP患者预后不良的效能
Table 4. Efficacy of various factors and nomogram models in predicting poor prognosis in AP patients
指标 AUC SE P值 95%CI Cut-off 约登指数 灵敏度 特异度 BISAP评分 0.705 0.038 <0.001 0.631~0.779 3.500 0.280 0.407 0.873 APACHE Ⅱ评分 0.830 0.031 <0.001 0.768~0.891 10.500 0.524 0.833 0.691 血清淀粉酶 0.792 0.034 <0.001 0.724~0.859 316.300 0.443 0.630 0.813 血清脂肪酶 0.775 0.039 <0.001 0.699~0.852 471.100 0.523 0.667 0.856 CALLY指数 0.738 0.030 <0.001 0.680~0.797 4.405 0.430 0.615 0.815 CLR 0.765 0.039 <0.001 0.688~0.842 72.445 0.503 0.704 0.799 CCR 0.787 0.034 <0.001 0.719~0.854 19.200 0.423 0.630 0.793 列线图模型 0.977 0.007 <0.001 0.963~0.991 0.107 0.861 0.963 0.898 注:BISAP,严重程度床边指数;APACHE Ⅱ,急性生理学与慢性健康状况评价Ⅱ;CALLY,C反应蛋白-白蛋白-淋巴细胞;CLR,C-反应蛋白与淋巴细胞比值;CCR,C-反应蛋白与血清钙比值;AUC,受试者操作特征曲线下面积。
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