| Part 1:Impact of unsuccessful aortic remodeling after frozen elephant trunk on early outcomes in patients undergoing two-stage thoracoabdominal aortic repairObjective:Patients who underwent previous frozen elephant trunk(FET)implantation for Stanford type A aortic dissection(AAD)remain at risk for secondary intervention due to unsuccessful distal aortic remodeling.We aimed to investigate the impact of distal aortic remodeling on early outcomes in patients who underwent two-stage thoracoabdominal aortic repair(TAAR).Methods:Fifty-eight patients who previously underwent FET implantation and TAAR between October 2012 and December 2018 were enrolled in this study.The extent of distal aortic remodeling was evaluated,including aortic diameter,area ratio of the false lumen/aortic lumen and patency of the FL at three levels of the aorta.Logistic regression analyses were performed to investigate the risk factors for early outcomes.Results:The overall mean age was 41.19±10.21 years,and most patients in the sample were male(82.76%).From level of distal end of the FET to level of the infrarenal aorta,the mean aortic diameter decreased in all patients,with values of 50.28±23.25 mm at distal end of the FET,41.85±8.84 mm at proximal to the celiac artery and 39.89±17.55 mm at the infrarenal aorta.The aortic diameter at distal end of the FET was significantly higher in the early death group than in the survivor group(87.85±26.21 mm vs.45.96±18.75 mm,P<0.01).The optimal cutoff value for the aortic diameter at the distal FET was 65 mm.Patients with an aortic diameter<65 mm at distal end of the FET had a better early outcome,including a lower blood loss during operation(1432.79 ± 867.60 ml vs.2413.33±1422.71 ml,P=0.003),a shorter intubation time(30.51 ± 23.02 h vs.70.13±127.72 h,P=0.05),a shorter postoperative hospital stay(17.21 ± 7.53 d vs.11.07±10.28 d,P=0.02),a lower volume of drainage on the first day postoperatively(646.74±449.98 ml vs.1615.33±2112.33 ml,P=0.01),lower incidences of early death(0 vs.40%,P<0.001),adverse events(12.3%vs.26.7%,P=0.02)and pulmonary infection(23.3%vs.60%,P=0.02),and re-exploration for hemorrhage(2.3%vs.26.7%,P=0.02).The aortic diameter at the distal FET was identified as a significant risk factor for early death in patients undergoing TAAR.Conclusion:Patients undergoing TAAR with an aortic diameter≥65 mm at the distal FET have worse early outcomes.Moreover,an aortic diameter at the distal FET is a significant risk factor for early death in patients undergoing TAAR.Two-stage TAAR should be performed as soon as possible for patients with indications for surgery to reduce the risks due to the enlarged aorta.Part 2:Application and comparison of partial cardiopulmonary bypass and normothermic autologous bypass in thoracoabdominal aortic repairObjective:The aim of this study was to investigate the differences in early outcomes between normothermic autologous bypass and partial cardiopulmonary bypass techniques in thoracoabdominal aortic repair(TAAR),and to analyze the advantages and disadvantages of both techniques to guide the development of surgical strategies in the different patients.Methods:Patients who underwent TAAR at our center from October 2012 to December 2018 were included in this study.Inclusion criteria included patients with TAAR for chronic aortic dissection and TAAR extent including Crawford Ⅱ and Ⅲ.Exclusion criteria included TAAR with deep hypothermic cardiac arrest(DHCA),emergency surgery and patients with true aneurysms.The primary endpoint event for this study was early death,including patient death during hospitalization or within 30 days from all causes.Secondary endpoints were adverse events,including permanent stroke,permanent paraplegia,and permanent renal failure requiring dialysis.A propensity score matching approach was used for analysis,and a subgroup analysis was performed for patients with a proximal aortic diameter≥65 mm,based on the results of the part I of the study.Results:A total of 121 patients,89 males and 32 females,were included in this study.19 patients were treated with the partial cardiopulmonary bypass technique and 102 patients with the normothermic autologous bypass technique.The early mortality rate was significantly higher in the partial cardiopulmonary bypass group than in the normothermic autologous bypass(26.3%vs 4.9%;P=0.01).In addition,the incidence of adverse events was 14%in total cohort,and no significant difference was seen in the incidence of adverse events between the two groups.After performing propensity score matching analysis,no significant difference was showed in early mortality between the two groups(16.7%vs 27.8%;P=0.69).In a subgroup analysis of patients with proximal aortic diameters≥65 mm,no statistically significant differences were seen in intraoperative details and postoperative outcomes between the two groups.However,the incidence of adverse events was lower in the partial cardiopulmonary bypass group than in the normothermic autologous bypass group,with a trend toward a significant difference(P=0.06).Interaction analysis showed a significant interaction between proximal aortic diameter and different surgical strategies on adverse events(interaction test,P<0.001).Conclusions:Both partial cardiopulmonary bypass technique and normothermic autologous bypass technique are safe and feasible strategies in TAAR.However,the partial cardiopulmonary bypass technique has potential advantages in patients with larger proximal aortic diameters.Due to the small sample size,further validation in a large sample,multicenter,prospective clinical trial is needed.Part 3:Bioinformatics analysis for immune microenvironment and inflammation-related hub genes of abdominal aortic aneurysmsObjective:Abdominal aortic aneurysm(AAA)is potentially life threatening and characterized by immune-inflammatory cell infiltration and extracellular matrix degradation.Currently,pharmacotherapy mainly aims to control risk factors without reversion of the dilated aorta.This study analyzed the immune-inflammatory response and identified the immune-related hub genes of AAA.Method:Gene Expression Omnibus datasets(GSE57691,GSE47472 and GSE7084)were downloaded.After identification of GSE57691 differentially expressed genes(DEGs),weighted gene co-expression network(WGCNA)analysis of the DEGs was performed.Through enrichment analysis of each module and screening in Immunology Database and Analysis Portal,immune-related hub genes were identified via protein-protein interaction(PPI)network construction and lasso regression.CIBERSORT was utilized to analyze AAA immune infiltration.The correlations between the immune-related hub genes and infiltrating immune cells were investigated.Receiver operating characteristic(ROC)curve analysis was performed to determine immune-related hub gene cutoff values,which were validated in GSE47472 and GSE7084.In addition,clinical samples were collected for further quantitative real-time polymerase chain reaction(qRT-PCR)analysis of the hub genes,and the results were validated by in vitro experiments.Result:In GSE57691,1,018 DEGs were identified.Five modules were identified in the co-expression network.The blue and green modules were found to be related to immuneinflammatory responses,and 61 immune-related genes were identified.PPI and lasso regression analyses identified FOS,IL6 and IL2RB as AAA immune-related hub genes.CIBERSORT analysis indicated significantly increased infiltration of naive B cells,memory activated CD4 T cells,follicular helper T cells,monocytes and M1 macrophages and significantly decreased infiltration of M2 macrophages in AAA compared with normal samples.IL2RB was more strongly associated with immune infiltration in AAA than were FOS and IL6.The IL2RB area under the ROC curve(AUC)value was>0.9 in both the training and validation set,demonstrating its strong,stable diagnostic value in AAA.In addition,a total of 9 diseased aortic wall tissues from patients with aortic aneurysms(test group)and 7 normal aortic wall tissues from patients without aortic lesions(control group)were collected in this study.The results of qRT-PCR showed that the expression of FOS,IL2RB,and IL6 was significantly higher in the test group than in the control group.Conclusion:AAA and normal samples had different immune infiltration statuses.IL2RB,FOS and IL6 were identified as hub genes related to AAA immune response,among which IL2RB is involved in the immune inflammatory response of AAA through regulating the JAK/STAT pathway,which provide a new research direction for molecular targeting therapy of AAA. |
PDF Full Text Request