Purpose: To summarize a single-center experience using the single/double chimney technique in association with thoracic endovascular aortic repairs (TEVAR) for aortic arch pathologies. Methods: From November 2007 to March 2016, 122 patients (mean age 50.4±12.7 years, range 29-80; 92 men) with aortic arch pathologies underwent TEVAR combined with single (n=101) or double (n=21) chimney grafts to reconstruct the supra-aortic branches: 21 innominate arteries, 114 left common carotid arteries, and 8 left subclavian arteries (LSA). Pathologies included type B aortic dissection (n=47), aortic arch dissection (n=49), retrograde type A aortic dissection (n=8), thoracic aortic aneurysm (n=7), penetrating aortic arch ulcer (n=9), and post-TEVAR type I endoleak (n=2). Follow-up examinations included computed tomography at 0.5, 3, 6, and 12 months and yearly thereafter. Results: The aortic stent-grafts were deployed in zone 0 (n=21), zone 1 (n=93), and zone 2 (n=8). One (0.8%) of the 122 patients died at 4 days due to a perforated peptic ulcer. Type Ia endoleaks were found intraoperatively in 13 (10.7%) patients, including 3 with the double chimney technique. Type II endoleaks occurred in 6 (4.9%) patients; 3 were treated with duct occluders in the LSA. Postoperative chimney graft migration occurred in 1 (0.8%) patient with double chimneys; additional stent-grafts were deployed in both chimneys. Median follow-up was 32.3 months, during which 1 (0.8%) patient died after a stroke at 3 months. Chimney stent-graft patency was observed in the remaining 120 patients. Two (1.7%) secondary TEVARs were performed for distal aortic dissection. Nine asymptomatic type Ia endoleaks and 1 type II endoleak persisted in follow-up; a type II endoleak in 1 patient with Marfan syndrome sealed in 52 months. Conclusion: TEVAR with the chimney technique provides a safe, minimally invasive alternative with good chimney graft patency and low postoperative mortality during midterm follow-up. The double chimney technique should be used judiciously owing to its potential complications.

Cardiotoxicity is an aggravating side effect of many clinical antineoplastic agents such as arsenic trioxide (As2O3), which is the first-line treatment for acute promyelocytic leukemia (APL). Clinically, drug combination strategies are widely applied for complex disease management. Here, an optimized, cardiac-friendly therapeutic strategy for APL was investigated using a combination of As2O3 and genistein or resveratrol. Potential combinations were explored with respect to their effects on mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity, autophagy, and apoptosis in both NB4 cells and neonatal rat left ventricular myocytes. All experiments consistently suggested that 5 µM resveratrol remarkably alleviates As2O3-induced cardiotoxicity. To achieve an equivalent effect, a 10-fold dosage of genistein was required, thus highlighting the dose advantage of resveratrol, as poor bioavailability is a common concern for its clinical application. Co-administration of resveratrol substantially amplified the anticancer effect of As2O3 in NB4 cells. Furthermore, resveratrol exacerbated oxidative stress, mitochondrial damage, and apoptosis, thereby reflecting its full range of synergism with As2O3. Addition of 5 µM resveratrol to the single drug formula of As2O3 also further increased the expression of LC3, a marker of cellular autophagy activity, indicating an involvement of autophagy-mediated tumor cell death in the synergistic action. Our results suggest a possible application of an As2O3 and resveratrol combination to treat APL in order to achieve superior therapeutics effects and prevent cardiotoxicity.

Background/Objectives: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs). Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT) was identified by confocal microscopy. Right ventricular systolic pressure (RVSP) was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH) was determined by weighing the cardiac muscle. Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH. Conclusion: Rev produced a beneficial effect partially by enhancing the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel future strategy for the treatment of PAH.

Background: Revascularization of the supra-aortic major branches in thoracic endovascular aortic repair (TEVAR) is challenging owing to the complex anatomic configuration of aortic arch pathologies. This study aims to evaluate the feasibility, effectiveness, and safety of three major techniques-chimney, fenestrated, and in-situ fenestration-for patients with aortic arch pathologies. Methods: A retrospective analysis was performed involving 234 patients with aortic arch lesions, who underwent TEVAR with adaptations in technique (chimney, fenestrated, or in-situ fenestration) between January 2016 and December 2017. Results: One hundred and twenty-six patients underwent the chimney technique (98 single chimneys, 24 double chimneys, and four triple chimneys); one hundred and two patients (102/234) were treated with on-the-table fenestration technique (92 single fenestrations, nine double fenestrations, and one double fenestration plus innominate artery chimney); and the remaining six patients underwent in-situ needle fenestration technique. Overall, indications included aortic dissections (99/234), aortic arch aneurysms (60/234), penetrating aortic ulcers (72/234), and re-interventions (3/234). The technical success rates were 99.6%. There were five cases of early all-cause mortality. The patency rates of overall branches were 99.6%.There were 15 cases with type Ia endoleak-14 in the chimney group (11.1%) and one in the on-the-table fenestration group (1%). Five patients underwent re-interventions. The median follow-up time for all patients was 28 (range, 16-41) months. Conclusions: Our experience suggests that chimney, on-the-table fenestration, and in-situ needle fenestration techniques are feasible, effective, and safe treatment options for aortic arch pathologies with encouraging mid-term results. Long-term durability concerns require further evaluation.

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Background: Deep venous thrombosis (DVT) is a common complication after stroke. It is easy to identify the patients with symptomatic DVT; however, the tool for asymptomatic high-risk population needs to be further explored. Our aim was to explore the risk factors of acute stroke patients with asymptomatic DVT. Methods: We performed a prospective observation study among 452 patients with acute stroke who had a stroke within 14 days. Ultrasound examination of deep veins was repeatedly performed in each patient for DVT every 7 days during his admission. The dynamic rate of DVT in acute stroke was analyzed. Then risk factors were compared between DVT patients and non-DVT patients. The predictive model was explored based on thr cox proportion model. Results: Asymptomatic DVT was detected in 52 (11.5%) patients with stroke and 85.9% of thrombi were identified in their distal veins. Patients with longer length of stay ( P = .004), more severe stroke ( P = 0.001), higher level of D-dimer ( P = .003), and higher blood glucose level were associated with higher risk of DVT, while patients with higher triglyceride level ( P = .003) were less likely to have DVT, after adjusting age and sex. With the median of D-dimer (0.38 FEU mg/L) as cutoff value. Patients with higher level of D-dimer might have a higher risk of DVT with a significant statistical difference. Also, the severity of stroke differed DVT risk in Kaplan-Meier model. Using cox-proportion hazard regression model, asymptomatic DVT could be predicted (area under the curve 0.852). Conclusion: Our data showed that asymptomatic DVT was common in patients with acute stroke and most of thrombosis occurred in distal veins. Combination of clinical manifestation and laboratory results might be helpful predict DVT. DVT prophylaxis should be condisdered in high risk.

BackgroundStroke is one of the major causes of morbidity and mortality. Its recovery and treatment depends on close clinical monitoring by a clinician especially during the first few hours after the onset of stroke. Patients who do not exhibit early motor recovery post thrombolysis may benefit from more aggressive treatment.MethodA novel approach for monitoring stroke during the first few hours after the onset of stroke using a wireless accelerometer based motor activity monitoring system is developed. It monitors the motor activity by measuring the acceleration of the arms in three axes. In the presented proof of concept study, the measured acceleration data is transferred wirelessly using iMote2 platform to the base station that is equipped with an online algorithm capable of calculating an index equivalent to the National Institute of Health Stroke Score (NIHSS) motor index. The system is developed by collecting data from 15 patients.ResultsWe have successfully demonstrated an end-to-end stroke monitoring system reporting an accuracy of calculating stroke index of more than 80%, highest Cohen’s overall agreement of 0.91 (with excellent κ coefficient of 0.76).ConclusionA wireless accelerometer based ‘hot stroke’ monitoring system is developed to monitor the motor recovery in acute-stroke patients. It has been shown to monitor stroke patients continuously, which has not been possible so far with high reliability.

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