Thioridazine protects against disturbed flow-induced atherosclerosis by inhibiting RhoA/YAP-mediated endothelial inflammation.

Atherosclerotic diseases remain the leading cause of adult mortality and impose heavy burdens on health systems globally. Our previous study found that disturbed flow enhanced YAP activity to provoke endothelial activation and atherosclerosis, and targeting YAP alleviated endothelial inflammation and atherogenesis. Therefore, we established a luciferase reporter assay-based drug screening platform to seek out new YAP inhibitors for anti-atherosclerotic treatment. By screening the FDA-approved drug library, we identified that an anti-psychotic drug thioridazine markedly suppressed YAP activity in human endothelial cells. Thioridazine inhibited disturbed flow-induced endothelial inflammatory response in vivo and in vitro. We verified that the anti-inflammatory effects of thioridazine were mediated by inhibition of YAP. Thioridazine regulated YAP activity via restraining RhoA. Moreover, administration of thioridazine attenuated partial carotid ligation- and western diet-induced atherosclerosis in two mouse models. Overall, this work opens up the possibility of repurposing thioridazine for intervention of atherosclerotic diseases. This study also shed light on the underlying mechanisms that thioridazine inhibited endothelial activation and atherogenesis via repression of RhoA-YAP axis. As a new YAP inhibitor, thioridazine might need further investigation and development for the treatment of atherosclerotic diseases in clinical practice.

Association between platelet counts and morbidity and mortality after endovascular repair for type B aortic dissection.

This study aimed to assess the association of postoperative platelet counts with early and late outcomes after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). We retrospectively evaluated 892 patients with TBAD who underwent TEVAR from a prospectively maintained database. Postoperative nadir platelet counts were evaluated as a continuous variable, and a categorical variable (thrombocytopenia), which was defined as platelet count≤ the lowest 10% percentile (108 × 109/l). Multivariable logistic regression analyses were conducted to assess the impact of postoperative thrombocytopenia on early outcomes, and multivariable cox regression analyses on long-term mortality. Patients with postoperative thrombocytopenia experienced significantly higher rates of postoperative mortality, prolonged intensive care unit stay, death, stroke, limb ischemia, mesenteric ischemia, acute kidney injury (AKI), and puncture-related hematoma (P< .05 for each), but similar rates of immediate type I endoleak and spinal cord ischemia. Multivariable logistic analyses showed that postoperative thrombocytopenia was independently associated with postoperative stroke, limb ischemia, and AKI. Similar results were observed when postoperative nadir platelet count was modeled as a continuous predictor (P< .05 for each). By multivariable Cox analyses, postoperative thrombocytopenia was an independent predictor for long-term all-cause mortality (hazard ratio 2.72, 95% CI, 1.72-4.29, P< .001). For every 30 × 109/L decrease in postoperative platelet count, the risk of long-term all-cause mortality increased by 15% (HR 1.15; 95% CI 1.07-1.25; P< .001). Therefore, postoperative thrombocytopenia might be a useful tool for risk stratification after TEVAR.

Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells.

AIM: The current study aimed to examine miR-145's contribution to thoracic aortic dissection (AD) development by modulating the biological functions of vascular smooth muscle cells (VSMCs). METHODS: The concentration of circulating miR-145 was determined in patients with AD and healthy controls using quantitative polymerase chain reaction (qPCR). Aortic specimens were obtained from both individuals with Stanford type A AD undergoing surgical treatment and deceased organ donors (serving as controls) whose causes of death were nonvascular diseases. Then, qPCR and fluorescence in situ hybridization were applied to assess miR-145 amounts and location, respectively. Furthermore, qPCR and immunoblot were employed to determine SMAD3 (the target gene of miR-145, involved in the TGF-ß pathway) amounts at the gene and protein levels, respectively. Moreover, in vitro transfection of VSMCs with miR-145 mimics or inhibitors was conducted. Finally, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Transwell assay and flow cytometry were employed for detecting VSMC proliferation, migration, and apoptosis, respectively. RESULTS: The amounts of miR-145 in plasma and aortic specimens were markedly reduced in the AD group in comparison with control values (P < .05). miR-145 was mostly located in VSMCs. Proliferation and apoptosis of VSMCs were significantly induced in vitro by the downregulation of miR-145. Also, miR-145 modulated SMAD3 expression. CONCLUSIONS: miR-145 was found to be downregulated in patients with AD, which induced the proliferation, migration, and apoptosis of VSMCs by targeting SMAD3. This suggested the involvement of miR-145 in the pathogenesis of AD.

Outcomes of Evolut R Versus CoreValve After Transcatheter Aortic Valve Implantation: A Meta-Analysis.

BACKGROUND: Superiority of the new-generation, self-expanding Evolut R compared with the first-generation CoreValve on outcomes after transcatheter aortic valve implantation (TAVI) is unclear. This meta-analysis sought to investigate the outcomes of Evolut R vs CoreValve after TAVI. METHODS: A systematic review of studies comparing outcomes of Evolut R and CoreValve after TAVI was performed through PubMed, EMBASE and Cochrane Library. Crude risk ratios (RRs) were calculated with 95% confidence intervals using a random effects model. Outcomes of interest were mortality, myocardial infarction (MI), stroke or transient ischaemic attack (TIA), severe bleeding, acute kidney injury (AKI), major vascular complications (MVC), permanent pacemaker implantation (PPI), moderate or severe paravalvular regurgitation (PVR), and device failure. RESULTS: Six studies involving 11,530 patients (4,597 receiving Evolut R and 6,933 receiving CoreValve) were included. There was no significant difference in 30-day all-cause mortality between Evolut R and CoreValve (3.4% vs 5.0%, p = 0.10). The incidence of MI (0.2% vs 0.5%, p = 0.02), AKI (6.0% vs 9.2%, p = 0.001), moderate or severe PVR (6.4% vs 8.0%, p = 0.04), and device failure (3.5% vs 5.2%, p = 0.04) were significantly lower in Evolut R than CoreValve. There were trends toward less severe bleeding (7.2% vs 8.8%, p = 0.05) and PPI (18.6% vs 20.8%, p = 0.05) in Evolut R. The rates of stroke or TIA and MVC were similar between the two prostheses. CONCLUSIONS: Compared with CoreValve, Evolut R did not reduce 30-day all-cause mortality, but significantly improved periprocedural complications after TAVI.

Management of type B aortic dissection with an isolated left vertebral artery.

OBJECTIVE: The objective of this study was to report our single-center experience of thoracic endovascular aortic repair (TEVAR) and concomitant procedures in patients with type B aortic dissection (TBAD) with an isolated left vertebral artery (ILVA) and the early to midterm outcomes in these patients. METHODS: Between March 2011 and June 2018, there were 31 patients (27 men; median age, 55 years; range, 31-66 years) with TBAD and an ILVA who received TEVAR and concomitant procedures in our center. Demographics, coexisting medical conditions, imaging features, operation details, and follow-up outcomes in these patients were retrospectively collected and analyzed. RESULTS: All patients received aortic stent grafts; nine patients also received chimney stents, and 10 patients received aortic arch bypasses. The technical success rate was 96.8% (30/31), with only one patient (3.2%) showing immediate type IA endoleak. One patient experienced transient neurologic deficit, and a puncture-related femoral artery pseudoaneurysm was observed in one patient; both recovered completely before their hospital discharge. There was no death in the early term. The median duration of follow-up was 33 months (range, 2-90 months). Reintervention for a type II endoleak by using coils to seal the origin of the left subclavian artery was performed in one (3.1%) case 72 months postoperatively. One (3.2%) death occurred 42 months after operation as a result of rectal cancer. No neurologic deficits, chimney stent occlusions, or bypass occlusions were observed during the follow-up period. CONCLUSIONS: Our limited experience reveals that TEVAR and concomitant procedures are relatively safe and viable for treatment of TBAD with an ILVA. Further studies with larger samples of patients and longer follow-ups are needed to confirm these findings.

Outcomes of Chimney Technique for Preservation of the Left Subclavian Artery in Type B Aortic Dissection.

OBJECTIVE: To report outcomes of the chimney technique for preservation of the left subclavian artery (LSA) in patients with type B aortic dissection (TBAD). METHODS: A retrospective analysis was performed of a prospectively maintained database from August 2012 to October 2017. Primary endpoints were 30 day and overall mortality. Secondary endpoints were technical success, type Ia endoleak, chimney stent occlusion, aortic rupture, stroke, spinal cord ischaemia, and re-intervention rate. RESULTS: A total of 159 patients (mean age 54 ± 11 years; 141 men) with TBAD were treated using the chimney technique for LSA revascularisation. Acute, subacute, and chronic TBAD accounted for 64%, 28%, and 8% of cases, respectively. One hundred and six cases (67%) were complicated TBAD. One hundred and fifty-six patients (98%) were treated electively, while three (2%) were treated urgently because of intestinal or lower extremity ischaemia. The 30 day mortality and morbidity rates were 2% (3/159) and 4% (7/159), respectively. The technical success rate was 81% (129/159) and immediate type Ia endoleak occurred in 30 (19%) patients. Three major strokes, two spinal cord ischaemia and one aortic rupture, occurred early on. During a mean follow up of 23 ± 16 months (range 1-65 months), three more patients died: from aortic rupture, cerebral haemorrhage, and rectal cancer, respectively. Chimney stent occlusions were observed in four patients and all these chimney stents were self expanding. During follow up, two major strokes, one late type Ia endoleak and one re-intervention, occurred. According to the Kaplan-Meier curve, the estimated one and three year survival rates were 98.1 ± 1.1% and 94.4 ± 2.4%, respectively. CONCLUSION: Short and mid-term outcomes in the present study demonstrate that the chimney technique is safe and feasible for preservation of the LSA in patients with TBAD, but the durability of chimney stent needs to be evaluated carefully and immediate type Ia endoleak is a concern.

Upregulation of miR-146a-5p is associated with increased proliferation and migration of vascular smooth muscle cells in aortic dissection.

BACKGROUND: This study aimed to investigate whether miR-146a-5p was involved in the pathogenesis of thoracic aortic dissection (AD) via regulating the biological function of vascular smooth muscle cells (VSMCs). METHODS: Circulating miR-146a-5p level was measured by quantitative polymerase chain reaction (qPCR) in AD patients and healthy controls. Human dissected aortic samples were obtained from patients with thoracic AD Stanford type A undergoing surgical repair, and normal control samples were from organ donors who died from nonvascular diseases. The expression level of miR-146a-5p was detected using qPCR in each sample. The expression of SMAD4, which is involved in the TGF-ß pathway and indicated as the target gene of miR-146a-5p, was measured by qPCR and Western blot analysis at the mRNA level and protein level, respectively. Subsequently, VSMCs were transfected with miR-146a-5p mimics or inhibitors in vitro. VSMC proliferation and migration were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay, respectively. Flow cytometry was used to identify apoptosis. The expression of SMAD4 in VSMCs was determined using qPCR and Western blot analysis. RESULTS: Plasma level of miR-146a-5p is significantly higher in the AD group as compared with the control group. The expression of miR-146a-5p was significantly upregulated in dissected aorta compared with controls (P < 0.05). The overexpression of miR-146a-5p significantly induced VSMC proliferation and migration in vitro. CONCLUSIONS: The expression of SMAD4 was modulated by miR-146a-5p. miR-146a-5p induced VSMC proliferation and migration through targeting SMAD4 and hence might be potentially involved in the development of AD.

Preoperative risk factors for haemodynamic instability during pheochromocytoma surgery in Chinese patients.

OBJECTIVE: Pheochromocytoma surgery carries a high risk of haemodynamic instability (HI). However, there are few studies investigating the risk factors for HI for pheochromocytoma surgery in a Chinese population. Therefore, our objective was to identify preoperative risk factors for HI during surgery in a Chinese population with pheochromocytoma. PATIENTS AND METHODS: In this retrospective study, 134 patients undergoing surgery for pheochromocytoma at a single university-affiliated hospital between November 2002 and July 2017 were enrolled. Demographics, comorbidities, preoperative medical preparation, operation details and perioperative haemodynamics of these patients were retrospectively collected and analysed. Multivariable logistic regression analysis was performed to identify the preoperative risk factors for intraoperative HI. RESULTS: 32.8% (44/134) patients suffered from intraoperative HI. According to the result of multivariate analysis, tumour diameter >50 mm (odds ratio [OR] 2.526; 95% confidence interval [CI] 1.163-5.485; P = .019), diabetes/prediabetes (OR 2.251; 95% CI 1.039-4.876; P = .040) and preoperative systolic blood pressure fluctuation >50 mm Hg (OR 3.163; 95% CI 1.051-9.522, P = .041) were independent predictors for intraoperative HI. The observed incidence of HI was 8.9%, 42.6%, 47.8% and 60% when zero, one, two or three risk factors were present, respectively. CONCLUSIONS: HI is common among Chinese patients undergoing surgery for pheochromocytoma. Our study identified three predictive factors for intraoperative HI: a large tumour diameter, diabetes/prediabetes and a great preoperative systolic blood pressure fluctuation. Furthermore, patients are more likely to suffer from HI when they have more predictive risk factors. Identification of these risk factors can help to improve perioperative management.

Outcomes of hybrid procedure for type B aortic dissection with an aberrant right subclavian artery.

OBJECTIVE: To report our single-center experience of the hybrid procedure for type B aortic dissection (TBAD) with an aberrant right subclavian artery (ARSA) and the early to midterm outcomes in these patients. METHODS: From December 2011 to February 2016, 16 patients (12 males; median age, 51 years; range, 40-66 years) underwent thoracic endovascular aortic repair and extraanatomic bypass hybrid procedure for TBAD with an ARSA in our center. Demographics, coexisting medical conditions, imaging features, operation details, and follow-up outcomes of these patients were collected retrospectively and analyzed. RESULTS: Duration from onset to hybrid procedure ranged from 5 to 57 days, with a median duration of 17 days. The median duration of stay in the intensive care unit and duration of in-hospital stay was 126 hours (range, 14-450 hours) and 21 days (range, 11-31 days), respectively. The overall technique success rate was 100%. No perioperative death, major stroke, or spinal cord ischemia was registered. Immediate type Ia endoleak was detected in three patients (18.8%) and immediate type II endoleak was detected in one patient (6.3%). One access-related complication occurred, which was a femoral artery pseudoaneurysm requiring compression bandage. Brachial plexus injury was observed in two patients (12.5%) with weakness of the upper extremity. The median follow-up was 33 months (range, 11-59 months). During follow-up, a retrograde type A aortic dissection was found in one patient (6.3%) 3 months after procedure. The occlusion of left common carotid artery to left subclavian artery bypasses were confirmed by computed tomography angiography in two patients (12.5%). They were left untreated for no symptoms. Reintervention was required in one patient (6.3%) for persistent type II endoleak by using Amplatzer plugs to seal the origin of the ARSA 20 months after the operation. There was no recorded death or stroke during the study period. CONCLUSIONS: Our limited experience demonstrates that a hybrid procedure is a viable and relatively safe treatment strategy for patients with TBAD and an ARSA. A larger series of cases with a longer follow-up is needed to substantiate these results.

Targeting the tyrosine kinase Src in endothelium attenuates inflammation and atherogenesis induced by disturbed flow.

BACKGROUND AND PURPOSE: Previous studies have shown that Src can regulate inflammation and tumour progression. However, the mechanisms by which Src regulates the inflammatory response of vascular endothelium and atherogenesis are currently poorly understood. This study aimed to investigate the role of Src in endothelial inflammation and atherogenesis, as well as the underlying mechanisms. EXPERIMENTAL APPROACH: Real-time quantitative PCR was used to measure the mRNA levels of inflammatory genes. The phosphorylation and localization of proteins were examined using western blotting and immunofluorescence, respectively. The level of p-Src Y416 in mouse endothelium was directly determined using en face staining. Endothelial-specific knockdown of Src was achieved by tail vein injection of AAV-sgSrc in ApoE-/-; Cas9LSL/LSL; Cdh5-cre mice. Atherosclerosis was induced by partial ligation of the carotid artery. KEY RESULTS: Oscillatory shear stress (OSS) promotes the phosphorylation of Src at Y416 in endothelial cells, and Piezo1 is required for this regulatory process. Overexpression of constitutively active Src promotes endothelial inflammation, as well as phosphorylation of Stat3 (at Y705) and its nuclear translocation. Endothelial inflammation induced by OSS was abolished by the Src inhibitor dasatinib or si-Src. Dasatinib, when administered orally, reduced endothelial inflammation and plaque formation in ApoE-/- mice induced by partial carotid artery ligation. Additionally, plaque formation was decreased in the ligated left carotid artery of mice with endothelial-specific Src knockdown. CONCLUSION AND IMPLICATIONS: Disturbed flow promotes endothelial inflammation and atherogenesis through the Piezo1-Src-Stat3 pathway. Therefore, inhibiting Src in endothelial cells could be a promising therapeutic strategy to treat atherogenesis.

Curaxin CBL0137 inhibits endothelial inflammation and atherogenesis via suppression of the Src-YAP signalling axis.

BACKGROUND AND PURPOSE: Atherosclerotic vascular disease is the leading cause of mortality and morbidity worldwide. Our previous study uncovered that endothelium-specific knockdown of YAP suppresses atherogenesis, suggesting that YAP is a promising therapeutic target against atherosclerotic vascular disease. We established a drug screening platform, which aimed to identify new YAP inhibitors for anti-atherosclerotic treatment. EXPERIMENTAL APPROACH: Drug screening was performed by a luciferase reporter gene assay. RNA sequencing was performed to acquire the transcriptomic profile of CBL0137-treated endothelial cells. We assessed and validated the inhibitory effect of CBL0137 on YAP activity and inflammatory response in HUVECs and HAECs. We evaluated the vasoprotective effect of CBL0137 in vivo against plaque formation in ApoE-/- mice, using both disturbed flow-induced and chronic western diet-induced atherosclerotic models. KEY RESULTS: We identified CBL0137 as a novel YAP inhibitor from an FDA drug library. CBL0137 inhibited YAP activity by restraining its phosphorylation at Y357. CBL0137 inhibited YAP activity to repress endothelial inflammation. Mechanistically, CBL0137 suppressed YAP phosphorylation at Y357 via the tyrosine-protein kinase Src. Furthermore, administration of CBL0137 ameliorated endothelial inflammation and the atherogenesis induced by disturbed flow and consumption of an atherogenic diet in ApoE-/- mice. CONCLUSION AND IMPLICATIONS: To our knowledge, this is the first study to identify CBL0137 as a novel YAP inhibitor. We have demonstrated that pharmacologically targeting YAP by CBL0137 inhibits atherogenesis. The present results suggest that CBL0137 holds promise as a new drug for the treatment of atherosclerotic vascular disease.

Perivascular adipose tissue: Fine-tuner of vascular redox status and inflammation.

Perivascular adipose tissue (PVAT) refers to the aggregate of adipose tissue surrounding the vasculature, exhibiting the phenotypes of white, beige and brown adipocytes. PVAT has emerged as an active modulator of vascular homeostasis and pathogenesis of cardiovascular diseases in addition to its structural role to provide mechanical support to blood vessels. More specifically, PVAT is closely involved in the regulation of reactive oxygen species (ROS) homeostasis and inflammation along the vascular tree, through the tight interaction between PVAT and cellular components of the vascular wall. Furthermore, the phenotype-genotype of PVAT at different regions of vasculature varies corresponding to different cardiovascular risks. During ageing and obesity, the cellular proportions and signaling pathways of PVAT vary in favor of cardiovascular pathogenesis by promoting ROS generation and inflammation. Physiological means and drugs that alter PVAT mass, components and signaling may provide new therapeutic insights in the treatment of cardiovascular diseases. In this review, we aim to provide an updated understanding towards PVAT in the context of redox regulation, and to highlight the therapeutic potential of targeting PVAT against cardiovascular complications.

Shear Stress and Metabolic Disorders-Two Sides of the Same Plaque.

Significance: Shear stress and metabolic disorder are the two sides of the same atherosclerotic coin. Atherosclerotic lesions are prone to develop at branches and curvatures of arteries, which are exposed to oscillatory and low shear stress exerted by blood flow. Meanwhile, metabolic disorders are pivotal contributors to the formation and advancement of atherosclerotic plaques. Recent Advances: Accumulated evidence has provided insight into the impact and mechanisms of biomechanical forces and metabolic disorder on atherogenesis, in association with mechanotransduction, epigenetic regulation, and so on. Moreover, recent studies have shed light on the cross talk between the two drivers of atherosclerosis. Critical Issues: There are extensive cross talk and interactions between shear stress and metabolic disorder during the pathogenesis of atherosclerosis. The communications may amplify the proatherogenic effects through increasing oxidative stress and inflammation. Nonetheless, the precise mechanisms underlying such interactions remain to be fully elucidated as the cross talk network is considerably complex. Future Directions: A better understanding of the cross talk network may confer benefits for a more comprehensive clinical management of atherosclerosis. Critical mediators of the cross talk may serve as promising therapeutic targets for atherosclerotic vascular diseases, as they can inhibit effects from both sides of the plaque. Hence, further in-depth investigations with advanced omics approaches are required to develop novel and effective therapeutic strategies against atherosclerosis. Antioxid. Redox Signal. 37, 820-841.

The impact of machine-learning-derived lean psoas muscle area on prognosis of type B aortic dissection patients undergoing endovascular treatment.

OBJECTIVES: The aim of this work was to investigate the impact of machine-learning-derived baseline lean psoas muscle area (LPMA) for patients undergoing thoracic endovascular aortic repair. METHODS: A retrospective study was undertaken of acute and subacute complicated type B aortic dissection patients who underwent endovascular treatment from 2010 to 2017. LPMA (a marker of frailty) was calculated by multiplying psoas muscle area and density measured at L3 level from the computed tomography. The optimal cut-off value of LPMA was determined by the Cox hazard model with restricted cubic spline. RESULTS: A total of 428 patients who met the inclusion criteria were included in this study. Patients were classified into low LPMA group (n = 218) and high LPMA group (n = 210) using the cut-off value of 395 cm2 Hounsfield unit. An automatic muscle segmentation algorithm was developed based on U-Net architecture. There was high correlation between machine-learning method and manual measurement for psoas muscle area (r = 0.91, P < 0.001) and density (r = 0.90, P < 0.001). Multivariable regression analyses revealed that baseline low LPMA (<395 cm2 Hounsfield unit) was an independent positive predictor for 30-day (odds ratio 5.62, 95% confidence interval 1.20-26.23, P = 0.028) and follow-up (hazard ratio 5.62, 95% confidence interval 2.68-11.79, P < 0.001) mortality. Propensity score matching and subgroup analysis based on age (<65 vs ≥65 years) confirmed the independent association between baseline LPMA and follow-up mortality. CONCLUSIONS: Baseline LPMA could profoundly affect the prognosis of patients undergoing thoracic endovascular aortic repair. It was feasible to integrate the automatic muscle measurements into clinical routine.

Influence of Sex on Outcomes After Thoracic Endovascular Repair for Type B Aortic Dissection.

We aimed to investigate whether sex differences influence the clinical outcomes of patients who undergo thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). We retrospectively analyzed a prospectively maintained single-center cohort of patients with TBAD who underwent TEVAR between January 2010 and June 2017. We evaluated the in-hospital and long-term mortality and composite end point. Of the 913 patients, 793 (86.8%) were male and 120 (13.1%) were female. Compared to male patients, the female patients were older, more likely to have diabetes mellitus, but less likely to smoke or have hypertension. The proximal landing zone in 0 and 1 was higher in male patients (P = .023), who were more likely to require an aortic arch bypass. Endoleak, delirium, and ICU stay after stent-graft implantation were also more frequent in men. Sex factor was not associated with in-hospital or long-term mortality or the composite end point in the multivariable regression analyses and Cox regression model. The mean estimated survival time was similar between males and females (2462.9 ± 141.2 vs 2804.1 ± 117.4 days, P = .167) in the propensity score-matched cohort. Despite distinct characteristics between sex, there was no sex-related difference in long-term clinical outcomes after TEVAR for TBAD.

Outcomes Of Chimney Technique For Aortic Arch Diseases: A Single-Center Experience With 226 Cases.

PURPOSE: The goal of present study is to document our single-center experience with chimney technique for aortic arch diseases. PATIENTS AND METHODS: From August 2012 to October 2017, 226 patients (mean age 54±12 years; 197 men) with aortic arch diseases underwent thoracic endovascular aortic repair combined with chimney stents. The aortic stent-grafts were deployed in zone 0 (n=22), zone 1 (n=13), or zone 2 (n=191). RESULTS: The technical success rate was 84% (189/226) and immediate type Ia endoleak (ELIa) happened in 37 (16%) patients. The 30-day mortality and morbidity rates were 2% (4/226) and 4% (8/226), respectively. Major adverse events include four major strokes, three spinal cord ischemia and one aortic rupture in the early-term. The clinical and imaging follow-up rates were 98% (218/222) and 78% (173/222), respectively. The average lengths of clinical and imaging follow-up were 22±16 months and 20±15 months, respectively. Chimney stent obstructions in left subclavian arteries were recorded in six (3%) patients. During follow-up, five patients died (2%) and two major strokes occurred (1%). One patient (0.5%) underwent reintervention. CONCLUSION: The current study documented that the chimney technique is effective and safe for treating aortic arch diseases in different aortic zones. Cautions are needed to assess the permanency of chimney stent and to reduce the immediate ELIa rate.

Predictors associated with an increased prevalence of postimplantation syndrome after thoracic endovascular aortic repair for type B aortic dissection†.

OBJECTIVES: The aim of this study was to identify patients who are at high risk of developing postimplantation syndrome (PIS) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection. METHODS: This retrospective study included 646 patients who underwent TEVAR for type B aortic dissection between January 2010 and December 2015 at the Guangdong General Hospital. PIS was defined as fever (>38°C) and leucocytosis (>12 000 µl-1) without evidence of infection. The PIS rate was calculated, and a multivariable logistic regression model was used to investigate the factors related to PIS. RESULTS: A total of 646 patients (58.8 ± 11.0 years, 87.9% men) were included in the analysis. PIS was diagnosed in 204 (31.6%) patients. Age <60 years [odds ratio (OR) 1.828, 95% confidence interval (CI) 1.277-2.619; P < 0.001), hypertension (OR 12.125, 95% CI 4.310-34.111; P < 0.001), >1 stent graft placed (OR 1.862, 95% CI 1.109-3.124; P = 0.011), arch vessel bypass (OR 2.107, 95% CI 1.397-3.176; P = 0.001) and Ankura stent graft placement (OR 1.951, 95% CI 1.298-2.933; P = 0.001) were positively associated with PIS, whereas statin use (OR 0.659, 95% CI 0.460-0.944; P = 0.023) was negatively associated with PIS in the multivariable logistic regression analysis based on a stepwise regression model. CONCLUSIONS: Age <60 years, comorbid hypertension, >1 stent graft placed, arch vessel bypass and Ankura stent graft placement emerged as independent predictors of PIS. Stepwise increases in the prevalence of PIS were found to depend on the number of independent predictors.

Molecular Mechanism of Loading Sulfur Hexafluoride in γ-Cyclodextrin Metal-Organic Framework.

γ-Cyclodextrin metal-organic framework (γ-CD-MOF) is a new type of highly porous carrier for potential loading of therapeutic or diagnostic gas like sulfur hexafluoride (SF6). Here, loading of SF6 into γ-CD-MOF was investigated for its mechanism by molecular simulation and quantitative determination of SF6 using quantitative nuclear magnetic resonance (qNMR). For the SF6 loading, γ-CD-MOF was first degassed to remove the air without thermal decomposition or loss of framework crystallinity, then placed in the copper tube, and sealed to adsorb SF6 under 1.2 MPa and 25 °C for 12 h. The qNMR was employed for the determination of SF6 loaded in γ-CD-MOF using Span 80 as suspending agent and trifluoroacetic acid as internal standard. Then, the thermodynamic parameters had been estimated. Finally, molecular modeling combining with 19F NMR spectra was conducted to reveal the status of SF6 molecules in γ-CD-MOF. The results demonstrated that the content of SF6 loaded in γ-CD-MOF was 2.67 ± 0.46 wt %. After exposing to the environment of free SF6 at 0.1 MPa for 10 days, the relative content was 74.7%. It was confirmed that SF6 preferred to stay in the cavity of γ-CD-MOF cubes rather than in the γ-CD molecular pairs, which was a nonchemical adsorptive process. In conclusion, this research has established qNMR method and molecular simulation to demonstrate SF6 molecules in γ-CD-MOF and its loading mechanism.

Risk of spinal cord ischemia after thoracic endovascular aortic repair.

BACKGROUND: Spinal cord ischemia (SCI) is a recognized grave complication after thoracic endovascular aortic repair (TEVAR). The present study aimed to evaluate the incidence and investigate risk of SCI after TEVAR based on current prophylactic strategies designed against established risk factors. METHODS: The study retrospectively reviewed a prospectively maintained database to investigate patients who underwent TEVAR successfully between January 2009 and December 2012 in a single cardiovascular center. Detailed assessment of SCI risk was routinely performed for all patients before TEVAR was carried out. Prophylactic measures, including left subclavian artery (LSA) revascularization, blood pressure augmentation and cerebrospinal fluid (CSF) pressure control after TEVAR, were employed in high-risk patients and physical neurological examinations were regularly done to evaluate SCI after TEVAR. Patients were further divided into SCI group and non-SCI group. RESULTS: A total of 650 patients were enrolled in the study. Eleven patients (1.69%) developed SCI after TEVAR. Baseline level of hemoglobin was significantly lower in the SCI group (113.00 vs. 128.50, P=0.023). More patients in the SCI patients in the SCI group underwent TEVAR under general anesthesia (45.5% vs. 17.7%, P=0.033). A significantly higher incidence of post TEVAR hypotension was found in the SCI group (2.7% vs. 27.3%, P=0.004). Logistic regression analysis revealed that post-TEVAR hypotension (OR, 8.379; 95% CI, 1.833-38.304; P=0.006) was strongly associated with development of SCI and high normal baseline hemoglobin was a protective factor (OR, 0.969; CI, 0.942-0.998; P=0.037). The mortality in hospital and mortality at 1 year were not significant different between the SCI and the non-SCI group (0% vs. 1.6% P=1.000; 9.1% vs. 3.0%, P=0.294, respectively). While length of post-TEVAR stay (13.00 vs. 7.00 days, P=0.000) and length of hospital stay (20.00 vs. 13.00 days, P=0.001) were significantly greater in the SCI group. CONCLUSIONS: Our study revealed that, based on current prophylactic measures to curtail SCI, including LSA revascularization, blood pressure augmentation and CSF pressure control after TEVAR, post-TEVAR hypotension remains a major and independent risk factor for SCI and high normal baseline hemoglobin level is protective. SCI results in longer post-TEVAR stay and hospital stay, but not associated with increased mortality. Robust precautions should be taken against underlying causes for post-TEVAR hypotension and low level of hemoglobin should be avoided.

Surgical resection of adrenocortical carcinoma with invasion into the inferior vena cava: a case report and literature review.

Adrenocortical carcinoma (ACC) is a malignant endocrine tumor. Moreover, ACC with invasion into the inferior vena cava is rare. Early diagnosis and treatment are crucial for such cases. Radical surgical resection is the key therapeutic option in ACC.