Prognostic Study Of Spontaneous Supratentorial Intracerebral Hemorrhage For Patients With Minimally Invasive Surgery

Part I Development of prediction models to predict the prognosis of intracerebral hemorrhage patients with minimally invasive surgeryObjective: Spontaneous intracerebral hemorrhage is a severe cerebrovascular disease with high mortality and disability rate.Minimally invasive surgery(MIS)has been widely used in the treatment of intracerebral hemorrhage(ICH),since it can reduce the mortality within one month and may improve the long-term prognosis of intracerebral hemorrhage patients.Even through the application of MIS is relatively mature at present,but the prediction model of clinical outcome is not definite yet.Therefore,it is necessary to develop effective prediction models which are capable of predicting the postoperative outcome of MIS in patients with ICH.The aim of this study was to develop and internally validate models for predicting the one-month mortality and long-term prognosis of ICH patients with MIS.Methods: We collected the clinical data of patients with MIS for ICH evacuation in Tongji Hospital of Wuhan from January 2012 to June 2016.A multivariate regression analysis was employed to develop the nomograms and clinical predictive scales.The discrimination and calibration ability of the nomograms and clinical predictive scales were evaluated by AUC(area under curve)and calibration curve.Using R language programming,the web page predictive tools which were capable of predicting the postoperative clinical outcome of ICH patients with MIS were developed for clinical practice.Results: A total of 326 patients were enrolled in this study.49(15.0%)patients died within one month,134(41.1%)patients had unfavorable prognosis at one year.We developed and internally validated the nomogram(Nomogram-1m)and clinical predictive scale(MIS-1m score)for predicting the one-month mortality based on five independent risk factors including age,GCS score,intraventricular hemorrhage,blood creatinine and glucose.The Nomogram-1m and MIS-1m score had an AUC of 0.818(95%CI 0.772-0.859)and 0.815(95%CI 0.769-0.856)respectively.Hosmer-Lemeshow test revealed excellent calibration ability of the Nomogram-1m(P=0.357)and MIS-1m score(P=0.205).DCA indicated that the two prediction models had good clinical practicability.We developed and internally validated the nomogram(Nomogram-1y)and clinical predictive scale(MIS-1y score)for predicting the long-term unfavorable prognosis based on five independent risk factors including age,NIHSS score,hematoma volume,blood glucose and hematoma location.The Nomogram-1y and MIS-1y score had an AUC of 0.795(95%CI 0.747-0.837)and 0.772(95%CI 0.722-0.816)respectively.Hosmer-Lemeshow test revealed excellent calibration ability of Nomogram-1m(P=0.264)and MIS-1m score(P=0.207).DCA indicated that the two prediction models had good clinical practicability.Conclusions: We developed new prediction models to predict one-month mortality and longterm prognosis of ICH patients with MIS,which might predict the risk of unfavorable prognosis of patients with MIS and improve patient counseling.PART II External validation and comparison of prediction models for predicting the prognosis of patients with intracerebral hemorrhage after minimally invasive surgeryObjective:In the first part,we developed prediction models for predicting outcomes of ICH patients after minimally invasive surgery.Internal validation showed that new models had good discrimination,calibration ability and clinical practicability.The existing expert consensus stated that unvalidated models should not be used in clinical practice because derivational studies often overestimated the accuracy of new fitting models and recommended external validation of new models.Therefore,External validation and comparison were performed on new models(Nomogram-1m,Nomogram-1y,MIS-1m score,MIS-1y score)and existing models(ICH score,MIS score,Sw ICH score,max-ICH score)to evaluate the ability of new models.Methods: We collected the clinical data of patients with MIS for ICH evacuation in Tongji Hospital of Wuhan from July 2016 to January 2020.All the predictors of the eight models and the outcomes were collected in the ICH patients with MIS.The external validation of the eight models were quantified by discrimination,calibration ability,and good clinical practicability.Results: Of 204 ICH patients,30(14.7%)died within 30 days,86(42.1%)patients had unfavorable prognosis at 365 days.The Nomogram-1m and the MIS-1m score had areas under the curve of 0.810(95% CI 0.749-0.861)and 0.795(95% CI 0.733-0.848)in predicting one-month mortality.The Nomogram-1m and the MIS-1m score had a significantly better discrimination improvement than ICH score,MIS score and Sw ICH score(P<0.05).Regarding calibration,the Nomogram-1m(P=0.637)and the MIS-1m score(P=0.768)were well calibrated.DCA showed that the Nomogram-1m had stronger clinical practicability compared to other models.DCA showed that the MIS-1m score had good clinical practicability.The Nomogram-1m had AUC of 0.758(95% CI 0.693-0.815)in predicting long-term prognosis of ICH patients with minimally Invasive Surgery.The Nomogram-1y had a significantly better discrimination improvement than ICH score(P=0.045)and had better discrimination than the max-ICH score(P=0.078).Regarding calibration,the Nomogram-1y were well calibrated(P=0.763).DCA showed that Nomogram-1y had significantly better discrimination improvement than ICH score and max-ICH score.The MIS-1y score had AUC of 0.740(95% CI 0.674-0.799)in predicting long-term prognosis of ICH patients with MIS.The MIS-1y score had a better discrimination improvement than ICH score(P=0.279)and(P=0.131).Regarding calibration,the MIS-1y score were well calibrated(P=0.280).DCA showed that had good clinical practicability.Conclusions: External validation showed that Nomogram-1m and MIS-1m score might be significantly superior to other models(ICH score,MIS score,Sw ICH score)for predicting the one-month mortality of ICH patients with minimally invasive surgery.Nomogram-1y and MIS-1y score might be better or not worse than other models(ICH score,max-ICH score)for predicting long-term prognosis of ICH patients with minimally invasive surgery.PART III Association between perioperative blood pressure variability and prognosis in patients with spontaneous intracerebral hemorrhageObjective: As previously mentioned,41% ICH patients had poor prognosis after MIS.It is necessary to take corresponding therapeutic measures to improve the prognosis of these patients.More and more studies suggested that blood pressure variability might be a potential risk factor of prognosis in ICH patients,and stabilizing blood pressure variability might be a potential therapeutic target for ICH.However,the perioperative blood pressure variability of ICH patients with minimally invasive surgery was greater than conservative treatment.It is not clear whether the perioperative blood pressure variability is related to the poor prognosis of ICH patients with minimally invasive surgery.It’s very necessary to further study.The aim of this study is to investigate whether perioperative blood pressure variability is associated with poor prognosis in ICH patients with minimally invasive surgery.Methods: We retrospectively analyzed the clinical data of ICH patients with minimally invasive surgery from Tongji Hospital.Perioperative blood pressure was collected from admission to 24 hours after surgery.Blood pressure variability was measured by standard deviation(SD)and coefficient of variation(CV)of systolic blood pressure(SBP).The SBP variables were analyzed as continuous variables and quintiles.We estimated associations between blood pressure variability and outcomes(postoperative rebleeding,one-month death and long-term poor prognosis)by logistic regression analysis.Results: A total of 264 patients were enrolled,including 182(68.9%)males and 82(31.1%)females with a median age of 53 years(47-62 years).24(9.1%)patients had postoperative rebleeding,38(14.4%)died at one month and 106(40.2%)had unfavorable prognosis at one year.The maximum SBP was associated with postoperative rebleeding in multivariable analysis(P=0.004).The SD(P=0.064),CV(P=0.068),mean(P=0.098)and minimum(P=0.584)of SBP were not associated with postoperative rebleeding.The SD(P=0.017)and CV(P=0.014)of SBP were significantly associated with one-month death in ICH patients with minimally invasive surgery,while the maximum(P=0.072),minimum(P=0.214)and mean(P=0.197)of SBP had no significant correlation with one-month death.The maximum(P=0.003),SD(P=0.002)and CV(P=0.002)of SBP were significantly associated with longterm poor prognosis of ICH patients,while the minimum(P=0.087)and mean(P=0.378)of SBP had no significant correlation.Conclusions: Perioperative blood pressure variability was significantly associated with poor prognosis in patients with spontaneous ICH.The maximum SBP was associated with postoperative rebleeding.Stabilization of blood pressure variability may be a potential perioperative therapeutic target for ICH patients with minimally invasive surgery.Further prospective studies are warranted to understand any cause-effect relationship and whether controlling for blood pressure variability may improve the prognosis of ICH patients.