预测单核细胞干细胞为无选择关键肢体缺血患者的治疗性血管生成的反应者。

Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia.

机构信息

Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Institute of Vascular Surgery, Fudan University, Shanghai, China.

出版信息

Stem Cell Res Ther. 2019 Jan 11;10(1):15. doi: 10.1186/s13287-018-1117-5.

BACKGROUND

Although the mononuclear cell (MNC) transplantation could theoretically induce therapeutic angiogenesis in the patients with no-option critical limb ischemia (NO-CLI), the clinical responses to this approach are inconsistent among different clinical trials. The purpose of this study was to identify the prognostic factors of responders and develop a predictive nomogram to guide patient selection.

METHODS

We retrospectively reviewed a consecutive NO-CLI cohort who received peripheral blood-derived transplantation in our center. The patients who survived and achieved complete remission of CLI at 6 months post-transplantation were defined as responders. Logistic regression models were used to screen and identify the prognostic factors based on which predictive nomogram was developed. A receiver operating characteristic (ROC) curve and a calibration curve were drawn to determine the discrimination level and predictive accuracy.

RESULTS

The study ultimately enrolled 103 patients, including 58 responders and 45 non-responders. Based on the multivariate regression analysis, age ≥ 50 years (odds ratio [OR] 0.201, P = 0.004), blood fibrinogen > 4 g/L (OR 0.176, P = 0.003), arterial occlusion above the knee/elbow (OR 0.232, P = 0.010), the transcutaneous pressure of oxygen (TcPO) (OR 1.062, P = 0.006), and the Log total transplanted CD34 cell count (OR 3.506, P = 0.046) were identified as independent prognostic factors of the responders in the nomogram. An area under the ROC curve of 0.851 indicated good discrimination, and the calibration curve of the predicted probability showed optimal agreement with that of the observed probability.

CONCLUSIONS

Age, blood fibrinogen, arterial occlusion level, TcPO, and the total transplanted CD34 cell count were independent prognostic factors of the responders. A nomogram with high discrimination and accuracy was developed to provide individualized predictions.

TRAIL REGISTRATION

ChiCTR, ChiCTR1800019401 . Registered 9 November 2018-Retrospectively registered.

背景

虽然单核细胞（MNC）移植理论上可以在没有选择的严重肢体缺血（NO-CLI）患者中诱导治疗性血管生成，但不同临床试验之间的临床反应不一致。本研究的目的是确定反应者的预后因素，并开发预测列线图以指导患者选择。

方法

我们回顾性分析了在我们中心接受外周血源性移植的连续 NO-CLI 队列。在移植后 6 个月存活且 CLI 完全缓解的患者被定义为反应者。使用逻辑回归模型根据筛选和确定预后因素，并开发预测列线图。绘制受试者工作特征（ROC）曲线和校准曲线，以确定区分水平和预测准确性。

结果

该研究最终纳入了 103 例患者，其中 58 例为反应者，45 例为非反应者。基于多变量回归分析，年龄≥50 岁（比值比[OR]0.201，P=0.004）、血纤维蛋白原>4g/L（OR 0.176，P=0.003）、膝/肘以上动脉闭塞（OR 0.232，P=0.010）、经皮氧分压（TcPO）（OR 1.062，P=0.006）和 Log 总移植 CD34 细胞计数（OR 3.506，P=0.046）被确定为列线图中反应者的独立预后因素。ROC 曲线下面积为 0.851，表明具有良好的区分能力，预测概率的校准曲线与观察概率最佳吻合。