BACKGROUND:Thoracic aortic dissection (TAD) is a lethal vascular emergency lacking targeted therapies. Fibroblast activation protein (FAP), a protease implicated in tissue remodeling, exhibits unknown roles in TAD pathogenesis. METHODS:Human TAD specimens and β-aminopropionitrile-induced TAD models were used to assess FAP expression. Global and fibroblast-specific Fap knockout mice were generated to evaluate biological effects of FAP. Bulk and single-cell RNA sequencing were used to map cellular crosstalk and dysregulated signaling pathways. A combination of pharmacological inhibition (Ac-Gly-BoroPro), surface plasmon resonance (SPR), co-immunoprecipitation (co-IP), and functional rescue experiments was utilized to dissect the enzymatic versus nonenzymatic functions of FAP and its interaction with PLAUR/ITGB1 signaling. RESULTS:Fibroblast-derived FAP was significantly upregulated in TAD lesions. Fap deletion markedly attenuated inflammatory infiltration, extracellular matrix degradation, and TAD incidence. Surprisingly, pharmacological inhibition of FAP's enzymatic activity failed to protect against TAD. SPR, co-IP, and functional assays revealed that FAP binds directly to macrophage PLAUR via nonenzymatic sites. This interaction triggers ITGB1/FAK signaling, promoting a pro-inflammatory macrophage phenotype that drives TAD progression. CONCLUSION:This study demonstrates that FAP promotes TAD through a nonenzymatic mechanism involving fibroblast-macrophage crosstalk via the FAP/PLAUR/ITGB1/FAK axis. Targeting this pathway might offer a promising therapeutic strategy for TAD.
Background: Few studies have investigated the characteristics and long-term outcomes of type B aortic dissection (BAD) patients with simple renal cysts (SRC) after thoracic endovascular aortic repair (TEVAR). Methods: A multi-center retrospective cohort study was performed, including 718 BAD patients undergoing TEVAR from 2003 to 2016. The prevalence of SRC was 34.5% (n = 248). After propensity score matching, 214 matched pairs were selected for further analysis. Primary outcomes were long-term aortic-related adverse events (ARAEs). The effects of SRC in each subgroup of interest and their interactions were analyzed. Results: BAD patients with SRC were older and had a greater prevalence of comorbidities, including hypertension, coronary artery disease and chronic occlusive pulmonary disease. In addition, the SRC group presented a greater proportion of pleural effusion and aortic calcification. Compared with the non-SRC group, a significantly higher maximal diameter of ascending aorta was observed in the SRC group. Apart from the timing of the operation, no differences were found in the medication regime or intra-operative parameters. In the matched population, patients with SRC were at a higher risk of ARAEs in the long term. The multivariable Cox model indicated that SRC was an independent predictor of long-term ARAEs (hazard ratio: 1.84, 95% confidence interval: 1.13–3.00). The interaction between SRC and hypertension on rupture after TEVAR was statistically significant (p = 0.023). Conclusions: Compared with the non-SRC group, BAD patients with SRC experienced a higher risk of long-term ARAEs after TEVAR. Among the SRC subgroup, hypertensive patients had the highest risk of rupture after TEVAR.
Background Stent-graft-induced inflammation is an independent risk factor for adverse aortic remodeling in aortic dissection. In this context, we asked that whether a methylprednisolone-loaded stent-graft could reduce inflammation and degradation. Methods First, a coaxial electrospinning technique was used to create a core-shell film with methylprednisolone encapsulated in the inner of poly (L-lactide-co-caprolactone) nanofibers for controllable drug release. Second, an in vitro study was conducted to evaluate the biocompatibility of the nanofiber meshes. Third, the porcine aortic dissection model was developed to investigate the therapeutic effects of the methylprednisolone-loaded stent-graft. Results The results demonstrated that the nanofiber-coated film with a methylprednisolone-poly-caprolactone core layer and a poly (L-lactide-co-caprolactone) shell layer could effectively sustain drug release in vitro. In vivo study showed that the methylprednisolone-loaded stent-graft could reduce degradtion of aortic dissection by regulating inflammation. Conclusions Overall, the controllable drug release by coaxial nanofiber is a promising approach to alleviate aortic inflammation and promote aortic remodeling after stent-graft implantation.
BackgroundThere is a lack of evidence about the predictive role of serum cardiac troponin I (cTnI) on the long-term adverse outcomes of acute type B aortic dissection (aTBAD) patients after thoracic endovascular aortic repair (TEVAR). In this study, we identified whether cTnI was an independent risk factor of 5-year adverse outcomes for aTBAD patients after TEVAR.MethodsWe reviewed consecutive aTBAD patients without previous heart disease who were admitted for TEVAR. The total study population was divided into the cTnI(+) group (≥0.03 ng/mL) and the cTnI(−) group (<0.03 ng/mL) according to the time-dependent receiver operating characteristic curve analysis. The differences in clinical characteristics, operative details and clinical outcomes were compared between the two groups.ResultsThere was no difference in age and male prevalence between the two groups. Compared with the cTnI(−) group, the incidence of chronic kidney disease was higher in patients with cTnI ≥0.03 ng/mL. In addition, the cTnI(+) group presented with more frequent premature beats and non-myocardial-infarction ST-T segment changes. In terms of laboratory examinations, white blood cell counts, neutrophil counts, serum D-dimer and serum fibrin degradation products showed an increase in the cTnI(+) group, while lymphocyte and platelet counts showed a decrease in these patients. Patients with elevated cTnI suffered from increased risks of 5-year aortic-related adverse events (hazard ratio, HR = 1.822, 95% confidence interval, CI: 1.094–3.035; p = 0.021) and all-cause mortality (HR = 4.009, 95% CI: 2.175–7.388; p < 0.001).ConclusionAmong aTBAD patients without previous heart disease, preoperative elevated cTnI identified patients at an increased risk of long-term adverse outcomes after TEVAR.
Thoracic aortic aneurysms and dissections are precarious conditions that often cannot be diagnosed with fatal outcomes. Over the last few years, pathogenic variants in numerous genes have been identified that predispose to heritable presentations of TAAD. An evidence-based strategy for the selection of genes to test in familial TAAD helps inform family screening and intervention to prevent life-threatening events. Using whole-exome sequencing, four members of three unrelated families clinically diagnosed with TAAD were used to identify the genetic origin of the disorder. Variant evaluation was carried out to detect the pathogenic mutation. Our studies suggest that mutations of COL3A1 and ACTA2 are responsible for familial TAAD. In addition, we highlight FBLN5, FBN1, SLC2A10, FBN2, and NOTCH1 as candidate genes. Future studies of crosstalk among the pathways may provide us a step toward understanding the pathogenic mechanism. This finding indicates the necessity of obtaining family medical history and screening of extended relatives of patients with TAAD for the early identification and treatment of TAAD.
Objective: To examine the feasibility, integrity, efficacy, and safety of endovascular repair of the aortic arch pathologies with the mini-cross prefenestration (MCPF) on stent grafts. Methods: First, to prove the feasibility of the MCPF, an in-vitro prefenestration experiment was conducted. Second, to examine the integrity of the MCPF stent grafts, a fatigue test was conducted. Then, the membranes and metal structures of stent grafts were examined by light microscopy and scanning electron microscopy (SEM). Third, a clinical experiment was conducted to investigate the efficacy and safety of this novel technique ( ClinicalTrials.gov Identifier: NCT04544579). Results: All the 12 branch stents were successfully implanted and flared in vitro . After the fatigue test stimulating a 5-year cardiac cycle, no obvious disintegration or fracture was found in light microscopy or SEM. From December 2017 to February 2020, 26 patients with left subclavian arteries and/or left common carotid arteries involved received the novel technique. The endovascular repair with the MCPF was successfully performed on all the 26 (100%) patients. Eighteen (69.2%) patients underwent the reconstruction of the left subclavian artery (LSCA) only. The fenestrations of both the LSCA and left common carotid artery (LCCA) were conducted in 8 (30.8%) patients. Median operative time was 120 [interquartile range (IQR), 95–137.5] min and median revascularization time of the LSCA and LCCA was 30.5 (IQR, 22.8–42.0) s and 20.0 (IQR, 18.0–32.0) s separately. During the median follow-up duration of 38.9 (range, 18.8–44.2) months, one case needed an open surgery because of retrograde type A aortic dissection 3 months after implantation and no other complications or mortality occurred. The maximum aortic diameters were significantly decreased in patients with thoracic aortic dissection and thoracic aortic aneurysm ( p < 0.05). Conclusion: The existing evidence demonstrated the safety, rapid branch artery revascularization, and positive aortic remodeling of the novel technique. Long-term observation is warranted to prove the durability.
急性胰腺炎是内镜逆行胰胆管造影术(ERCP)治疗最常见的并发症,但进展为重症急性胰腺炎(SAP)者少见。SAP病程复杂,后期可能会合并感染性胰腺坏死、腹腔出血、多器官功能障碍等,十分凶险。现报道1例ERCP后SAP合并腹腔出血,又因出血量大引起失血性休克和多器官功能障碍患者的多学科诊治过程。该患者胰腺坏死伴感染,又先后3次发生腹腔出血,伴失血性休克、急性肝损伤、急性肾损伤,经过多学科诊治最终抢救成功。
Background Acute type B aortic dissection is a life-threatening medical emergency, and hypertension is believed to be an important predictor of aortic dissection; the impact of blood pressure variability on the onset and development of aortic dissection has attracted increasing attention. Methods A total of 120 acute type B aortic dissection patients and 57 hypertensive patients without aortic dissection were consecutively enrolled and retrospectively reviewed between January 2013 and November 2015. There were 60 acute type B aortic dissection patients in both high and low blood pressure variability groups. Results Blood pressure variability showed higher diagnostic value than hypertension in aortic dissection, and the best threshold of blood pressure variability is 5.71 mmHg. By performing multivariable logistic regression, we found that the history of hypertension was likely to be a risk factor of blood pressure variability (95% CI: 1.155–6.422, P = 0.022). Nine patients from high blood pressure variability group and two from low blood pressure variability group ( χ2 = 4.90, P = 0.027) received emergency surgery within 24 hours after admission. The presence of multiple tears (>2, 55.0% vs. 45.0%, P = 0.001), configuration of the false lumen (spiral false lumen) (50.0% vs. 21.7%, P = 0.001), the diameter of the false lumen (49.6 ± 15.0 mm vs. 37.6 ± 10.8 mm, P < 0.001), the false/true lumen ratio (1.53 ± 1.02 vs. 0.929 ± 0.733, P < 0.001), and the number of visceral arteries involved (1.75 ± 0.942 vs. 0.800 ± 0.927, P < 0.001) showed significant differences between high and low blood pressure variability groups. Nine (30%) patients from the high blood pressure variability group showed a maximum diameter of false lumen over 60 mm, while none was found in the low blood pressure variability group. Conclusions High blood pressure variability, the presence of multiple tears (>2), the configuration of false lumen, the diameter of the false lumen, false/true lumen ratio, and the number of visceral arteries involved were independent risk factors for acute type B aortic dissection.
Objective: PGC-1 alpha achieves the protective effect of TNF-alpha-induced injury to human umbilical vein endothelial cells by inhibiting the Ca2+/NFAT pathway.Methods: Human umbilical vein endothelial cells were treated with 20, 40, and 80 ng/mL TNF-alpha to create three models with different degrees of cell injury. The human umbilical vein endothelial cells were cultured in vitro and transfected by interfering with the PGC-1 alpha RNA lentivirus. The silencing of the PGC-1 alpha gene was divided into two groups: the control group and the down-regulation of the PGC-1 alpha gene group. The effects of different concentrations of TNF-alpha on apoptosis of human umbilical vein endothelial cells were determined by flow cytometry. The expression of intracellular genes was detected by real-time quantitative PCR, and the expression of intracellular protein was measured by western blot assay. The concentrations of mtROS and Ca2+ were measured.Results: After human vein endothelial cells were treated for 24 h with different concentrations of TNF-alpha, the apoptosis rate gradually increased with the increase of TNF-alpha concentration, and the difference was statistically significant compared with the control group (P<0.05). The expression of PGC-1 alpha mRNA in each group was significantly lower than that of the control group after human venous endothelial cells were treated for 24 h of with different concentrations of TNF-alpha (P<0.05). After treatment with different concentrations of TNF-alpha, the relative expression rate of PGC-1 alpha protein in each group was remarkably lower than that in the control group (P<0.05). The expression of NFAT1 mRNA in the TNF-alpha 40 and 80 ng/mL treatment groups was significantly higher than that in the control group (P<0.05), and the expression of NFAT2 mRNA in different concentrations of the TNF-alpha treatment groups was markedly higher than that in the control group (P<0.05). The expression of NFAT1 protein in the TNF-alpha 40 and 80 ng/mL treatment groups was significantly higher than that in the control group (P<0.05), and the expression level of NFAT2 protein in different concentrations of TNF-alpha treatment group was clearly higher than that in the control group (P<0.05). The intracellular mROS and Ca2+ concentrations were significantly higher than that in the control group after the down-regulation of the PGC-1 alpha gene expression (P<0.05). After down-regulating the expression of the PGC-1 alpha gene, the levels of NFAT1, NFAT2, mRNA, and protein in the cells were significantly higher than those in the control group (P<0.05).Conclusion: 20, 40, and 80 ng/mL of TNF-alpha can induce different degrees of human umbilical vein endothelial cell injury. PGC-1 alpha has a protective effect on this kind of cell injury, and its related mechanism may be to inhibit the Ca2+/NFAT signalling pathway by reducing the intracellular mtROS concentration, and thus to protect damaged cells.
随着生活水平的提高和人口结构老龄化,血管系统疾病的发病率呈明显上升趋势,主动脉夹层是其中最凶险的一种.其起病急骤,病情凶险,很多病人在开始治疗前甚至在明确诊断前即因主动脉破裂而死亡,或引起重要脏器缺血(心梗、脑梗、内脏或下肢缺血)等严重并发症,往往需急诊治疗,且花费巨大.我们对主动脉夹层的治疗现状作一综述,并重点阐述主动脉弓部夹层的治疗现状与未来.
目的 探讨AngioJet血栓抽吸技术在急性下肢深静脉血栓形成中"一站式"治疗的意义.方法 2013年10月至2015年2月上海第二军医大学附属长海医院收治的急性下肢深静脉血栓28例,予以AngioJet机械血栓抽吸术联合左髂静脉PTA术(9例术中造影见左髂静脉狭窄)完成"一站式"治疗.结果 全部28例病人,手术技术成功率为100%,病人在术中可见静脉血流恢复通畅.2例出现穿刺点周围皮下淤血,13例出现血红蛋白尿,术后无肺栓塞和死亡病例,住院日(3.9±1.1)d.结论 AngioJet血栓抽吸术在急性下肢深静脉血栓形成中"一站式"治疗中是安全、有效的,且具有卧床时间短、住院时间少、术后并发症少等优点.
Objectives Visceral arterial aneurysms may be treated using open surgery or endovascular repair, but the best approach remains controversial. This was a retrospective study aiming to compare open surgery and endovascular treatment strategies for visceral arterial aneurysms. Methods The study included all 93 patients who were admitted with visceral artery aneurysms between January 2001 and January 2011 at the Department of Vascular Surgery, Changhai Hospital, Shanghai, China. All cases underwent either open or endovascular procedures. Overall survival and adverse events were compared between the groups. Success rate, blood loss, length of surgery, and length of hospital stay were also compared. The patients were followed up at three, six, and 12 months then every year until April 2014. Results Open surgery was performed on 34 patients and endovascular procedures on 59. There were no differences in characteristics of the patients between the open surgery and endovascular groups. The perioperative complication rate was 52.9 and 13.6% in the open surgery and endovascular groups, respectively. Mean follow-up was 36.8 months (range: 11 months to 10 years). The one- and five-year survival rates were 100 and 60.6%, respectively, in the open surgery group, compared to 100 and 84.5% in the endovascular group. Multivariate analysis for factors related to overall survival showed that there was a significant relationship with the treatment approach (HR = 0.479, 95%CI: 0.278–0.825; P = 0.008) and the presence of false aneurysm (HR = 2.929, 95%CI: 1.388–6.180, P = 0.005). Conclusions Endovascular repair could be considered as an effective method for visceral artery aneurysm. Endovascular repair showed lower perioperative complication rates and better long-term survival.
下肢静脉曲张是血管外科常见病,传统的高位结扎+剥脱术虽然疗效确切,但该术式具有创伤大、术中出血量多、恢复慢等缺陷[1].随着外科手术技术的不断发展更新,创伤更小的手术方式如泡沫硬化剂、激光等[2],使大隐静脉曲张的治疗不断趋向微创化.近年来采用硬化剂注射治疗下肢静脉曲张,逐渐成为静脉曲张主要手术方式之一,硬化剂注射治疗具有经济、微创、恢复快、疗效较好、并发症发生率低等优点,但在临床实际工作中仍会遇到相关并发症的发生,现将长海医院血管科收治的1例硬化剂注射治疗致下肢动脉栓塞的病例报告如下.
Objective To summarize the experience of AngioJet mechanical thrombectomy for the treatment of acute arterial embolism (AE). Methods Clinical data of 39 patients with acute AE treated by AngioJet mechanical thrombectomy during December 2013 and April 2015 were analyzed retrospectively. Clinical symptom was graded based on pre- and post-treatment angiography.Follow-up was performed by Doppler ultrasound and clinical evaluation. Results All the patients received mechanical thrombectomy with AngioJet. The average length of hospitalization was (4.3 ±1.5) days. The average operation time was (1.3±0.4) hours. Thirty three patients were treated with AngioJet thrombolysis, which failed in 6 patients who subsequently received catheter-directed thrombolysis (CDT). Immediate technique success rate was 79.5%. However, after percataneoustransluminal angioplasty and bare stents implantation to treat arterial stenosis, a technique success rate of 94.9% was achieved. The average reduction of hemoglobin was (7.6± 2.7)g/L. Fifteen patients had myoglobinuria to different extent. During follow-up of more than one year , the treated lesions remained patent in 32 patients. Three patients had reoccurence of limb ischemia. Conclusion AngioJet is safe and effective for treating acute AE with or without angioplasty. The short-term follow-up is satisfactory, when long-term follow-up is needed.
Teaching methods directly affect the teaching effect and quality. This paper analyzes the advantages and disadvantages of the current mainstream of medical teaching methods, and combined with my own experience, report of the application of mixed teaching method based on concept of MOOC used by Second Military Medical University Changhai Hospital. Practice has proved that satisfactory results, is worthy to be popularized.
Objective To compare the treatment outcomes in patients with lower extremity deep venous thrombosis (DVT) who underwent either catheter-directed thrombolysis (CDT) or percutaneous mechanical thrombectomy (PMT) intervention.Methods A retrospective analysis of clinical records of all patients with lower extremity DVT (n=48) in our center from December 2013 to December 2015 was undertook.All patients underwent PMT treatment with AngioJet (PMT group,n=24) or CDT treatment (CDT group,n=24).Results In PMT group,complete thrombolysis was found in 20 cases (83.3%) with grade Ⅲ,3withgradelⅡ (12.5%) and l with grade Ⅰ (4.2%),respectively.And in CDT group,itwasl9 (79.1%),4 (16.7%) and 1 (4.2%),respectively.There were no significant differences of the thrombolysis outcomes between two groups (P=0.919).No significant differences of the clinical symptomatic improvement were found between two groups (21 vs.18,P=0.461).The procedural time was shorter in the PMT group (0.25±0.11 h) compared with CDT group [(45.68±8.25) h,P<0.001].Urokinase dose was lower in the PMT group than CDT group [(16.7±3.20) million units vs.(144±20.37) million units,P<0.001].There were no major complications in the both groups.Subcutaneous congestion around puncture site,catheter infection and blood platelet reduction occurred in 3,1 and 1 patient,respectively.The thigh and calf circumferences of CDT group decreased more than PMT group,but with no significant statistical differences [(4.98±3.38)cm vs.(4.11±1.71) cm,P=0.424;(4.52±2.14) cm vs.(3.72±1.25) cm,P=0.272].Conclusion PMT with the AngioJet device for lower extremity DVT requires shorter procedure time and lower urokinase doses than conventional CDT,while providing the same results.
BACKGROUND Stent grafting is a therapeutic option for patients who are unable to undergo urgent surgical repair of ascending aortic dissections. However, follow-up regarding outcomes is limited.OBJECTIVES This study reports mid-term outcomes with endovascular repair for ascending aortic dissections in patients deemed high risk for open repair. METHODS Between May 1, 2009 and January 31, 2011, 15 ascending aortic dissection patients (ages 45 to 78 years) ineligible for direct surgical repair underwent endovascular repair (1 acute dissection, 7 subacute dissections, and 7 chronic dissections) and were closely followed up for a median of 72 months (range 61 to 81 months).RESULTS The mean interval between aortic dissection onset and treatment was 25.5 (range 6 to 353) days. Technical success was achieved in all patients. No major morbidity or deaths occurred perioperatively. During the follow-up period, there were no deaths, 8 complications occurred, and there were 4 reinterventions. A new dissection in the aortic arch was treated with a branched endograft. One patient developed retrograde aortic dissection and a left ventricular pseudoaneurysm was successfully treated with open surgery. One cardiovascular ischemia was treated with stenting and 1 supraventricular tachycardia was treated with radiofrequency ablation. Other morbidities included perigraft endoleak, a bird-beak sign, a temporary pericardial effusion, and a left kidney atrophy. Significant enlargements of true lumens and shrinkage of false lumens and overall thoracic aorta were observed at 12 months. No significant changes were detected subsequently. Minimal impact on aortic valve function was recorded over time.CONCLUSIONS Our results with the novel endovascular procedure appear acceptable. Additional evidence and studies with larger sample size and longer follow-up are needed to support the durability of this new technique. (C) 2016 by the American College of Cardiology Foundation.
OBJECTIVE:The aim of the current study was to evaluate the early experience of the application of transcatheter aortic valve implantation with the balloon-expandable system in China. The transcatheter aortic valve implantation technology has been widely used for patients with inoperable severe aortic stenosis in the developed world. The application of transcatheter aortic valve implantation is still in the early stages of testing in China, particularly for the balloon-expandable valve procedure.METHODS:This was a retrospective study. All patients undergoing transcatheter aortic valve implantation with balloon-expandable system in our hospital between 2011 and 2014 were included. Edwards SAPIEN XT Transcatheter Heart Valve was used. The improvement of valve and heart function was evaluated as well as 30-day mortality and major complications according to the VARC-2 definition.RESULTS:A total of 10 transcatheter aortic valve implantation procedures with the balloon-expandable system were performed in our hospital, of which 9 were transfemoral and 1 was transapical. The median age was 76 years, and the median STS score and Logistic EuroSCORE (%) were 8.9 and 16.2. The implantation was successfully conducted in all patients, only 2 patients had mild paravalvular leak. There was no second valve implantation. Moreover, no 30-day mortality or complications was reported. Following the transcatheter aortic valve implantation procedure, the heart and valve functions had improved significantly. During the follow-up period of 3-34 months, one patient died of lung cancer 13 months after the operation.CONCLUSION:This early experience has provided preliminary evidence for the safety and efficacy of transcatheter aortic valve implantation procedure with the balloon-expandable system in the developing world with an increasing aging population.
Objective To discuss the feasibility about the using of transcatheter aortic valve implantation(TAVI)in severe aortic valve stenosis Chinese patients,then to make more exploration and accumulate enough experience.Methods We selected 10 out-patients with severe aortic valve stenosis and calcified with 9 males and 1 females at age of76.4(65-81) years in our hospital from January 2011 to March 2014.All the patients can't tolerate traditional open surgery through preoperative evaluation.So we chose the Sepian TX system,balloon dilated transcatheter aortic valve,to treat them via transfemoral approach.Results Ten patients accomplished TAVI successfully.One patient was assisted by the left-ventricular puncture.No complication occurred.The function of aortic valve after TAVI improved significantly.The hospital stay time was 3-5 days.The patients were followed up for 3-34 months.One patient died of pulmonary cancer during the following-up.Conclusions Transcatheter balloon dilated aortic valve replacement can be used in Chinese severe aortic valve stenosis patient,but more accurate preoperative preparation,evaluation,and operation are needed.