Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn ...increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases.
To evaluate the technical aspects and early clinical results of stent placement for managing postthrombotic chronic total occlusion (CTO) of the iliofemoral vein through ipsilateral popliteal access.
...A retrospective analysis of 110 patients (44 men; mean age, 51 y; 118 limbs; 102 left limbs) with postthrombotic CTO of the iliofemoral vein treated with stent placement in a single institution from January 2007-December 2011 was conducted. All occlusions were initially accessed via ipsilateral popliteal veins under the guidance of venography or ultrasonography. Technical aspects, quality of life, stent patency, and Villalta scores were recorded at follow-up evaluation. Risk factors of in-stent restenosis and early in-stent thrombosis were evaluated using Cox proportional hazards regression model.
Percutaneous recanalization was successful in 112 of 118 limbs (95%). The mean duration of the procedure was 43 minutes (range, 10-120 min). The quality of life and Villalta scores were significantly improved (P < .01). The 3-year primary, assisted primary, and secondary cumulative stent patency rates were 70%, 90%, and 94%. During a median follow-up period of 25 months (range, 1-52 mo), the relief rates of severe leg pain (visual analog scale > 5) and severe leg swelling (grade 3) were 72% (49 of 68) and 70% (64 of 91), respectively, and the healing of ulcers was successful in 78% (36 of 46) of the cases. After stent placement, the limbs with visible remaining collateral circulation had a higher rate of early in-stent thrombosis (22.5% vs 6.1%; P = .007). The patients with long stents extending below the inguinal ligament had a higher rate of in-stent restenosis (hazard ratio = 1.77-6.5; P = .0146).
Transpopliteal venous stent placement is an effective, safe, and feasible method of managing postthrombotic CTO of the iliofemoral vein. The stent extending below the inguinal ligament is the major risk factor of in-stent restenosis. The visible remaining collateral circulation after stent placement may indicate persistent hemodynamically significant stenosis.
Mesenchymal-epithelial transition factor (c-Met) is the only high affinity receptor for hepatocyte growth factor (HGF), and is frequently activated in many human cancers. However, little is known ...about the role of the HGF/c-Met signaling pathway in the progression of human oral squamous cell carcinoma (OSCC). This study evaluated the role of the HGF/c-Met signaling pathway in the progression of human OSCC. We found that the expression of c-Met was significantly increased in human OSCC tissues than in normal mucosa adjacent to the tumor (P<0.05), but was not correlated with clinicopathological parameters. Additionally, the selective c-Met inhibitor JNJ was found to inhibit cell viability and migration and promote apoptosis in OSCC cell lines, and also blocked the activation AKT, ERK1/2, and NF-κB p65; thus, suggesting that HGF/c-Met signaling may play an important role in the tumorigenic properties of OSCC cells via the AKT, ERK1/2, and NF-κB pathways. Collectively, these results indicated that HGF/c-Met signaling may serve essential roles in the progression of human OSCC, and may thus be a basis for the development of novel therapeutic approaches in the treatment of OSCC.
Reconstruction of the aortic major branches during thoracic endovascular aortic repair is complicated because of the complex anatomic configuration and variation of the aortic arch. In situ laser ...fenestration has shown great potential for the revascularization of aortic branches. This study aims to evaluate the feasibility, effectiveness, and safety of in situ laser fenestration on the three branches of the aortic arch during thoracic endovascular aortic repair.
Before clinical application, the polytetrafluoroethylene and Dacron grafts were fenestrated by an 810-nm laser system ex vivo, which did not damage the bare metal portion of the endografts and created a clean fenestration while maintaining the integrity of the endografts. In vivo
6 anesthetized female swine survived after this operation, including stent-graft implantation in the aortic arches, laser fenestration, and conduit implantation through the innominate arteries and the left carotid arteries. Based on the animal experiments, in situ laser fenestration during thoracic endovascular aortic repair was successively performed on 24 patients (aged 33-86 years) with aortic artery diseases (dissection type A: n=4, type B: n=7, aneurysm: n=2, mural thrombus: n=7). Fenestration of 3 aortic branches was performed in 2 (8.3%) patients. Both the left carotid artery and the left subclavian artery were fenestrated in 6 (25%) patients. Only left subclavian artery fenestration surgery was done in 16 (66.7%) patients. Among these patients, 1 fenestration was abandoned secondary to an acute takeoff of the innominate artery in a type III aortic arch. The average operative time was 137±15 minutes. The technical success rate was 95.8% (n=23). No fenestration-related complications or neurological morbidity occurred after this operation. During a mean postoperative 10-month follow-up (range: 2-17 months), 1 patient died of severe pneumonia, and all the left subclavian artery and carotid artery stents were patent with no fenestration-related endoleaks upon computed tomography angiography images.
In situ laser fenestration is a feasible, effective, rapid, repeatable, and safe option for the reconstruction of aortic arch during thoracic endovascular aortic repair, which might be available to revascularize the 3 branches. However, follow-up periods should be extended to evaluate the robustness of this technique.
To assess the clinical and patency results of stent placement for the management of symptomatic nonthrombotic iliac vein compression lesions (NIVCLs) in chronic venous disease (CVD).
A retrospective ...analysis of patients with CVD was conducted at a single institution from January 2000 to May 2010. In 2,093 patients with CVD, venous computed tomography (CT) angiography or transfemoral venography was selectively performed in patients with severe symptoms and in patients with symptom recurrence after endovenous laser ablation (EVLA) for superficial venous insufficiency in the left lower extremity. NIVCLs were found in 297 patients (41 NIVCLs were found in 74 patients whose symptoms recurred after EVLA for superficial venous insufficiency). In 205 patients, NIVCLs were successfully treated with stent placement. Among these 205 patients, 117 patients (132 limbs) with associated superficial reflux were treated by EVLA for superficial venous insufficiency. Quality of life and the severity of venous disorders were evaluated by questionnaire and clinical examination before and after treatment. Patency was evaluated by duplex Doppler ultrasound.
A total of 227 stents were placed in 205 patients (224 limbs; median age, 50.53 years). The rate of technical success was 100%. Three limbs were treated with two stents because of proximal migration of the incipient stent. Follow-up periods ranged from 1-117 months (mean 50 months ± 36). The primary and assisted-primary cumulative patency rates at a mean of 4 years were 98.7% and 100%. The cumulative edema relief rate was 89.1% (156 of 175), and the healing rate for active ulcers was 82.3% (51 of 62). The pain level (using a visual analogue scale from 0-10) declined from a median level of 4.3 before the procedure to 0.4 after the procedure. Quality of life improved significantly after intervention. Complications were minor and improved quickly.
Venous stent placement is an effective and durable treatment for NIVCL, with long-term high patency and results in significant relief of the major symptoms of CVD. NIVCL is an important reason for symptom recurrence after left lower extremity varicose vein surgery.
To evaluate the technical aspects and early clinical results of combined stent placement for the management of postthrombotic syndrome (PTS) in chronic total occlusions (CTOs) of the iliofemoral ...veins.
A total of 81 consecutive patients (mean age, 57 y; 37 men; 81 limbs; 65 left limbs) with postthrombotic CTO of the iliofemoral veins treated with combined stent placement in a single institution from January 2013 to December 2014 were retrospectively analyzed. Wallstents were used for femoral inflow and E-Luminexx stents for iliac outflow. Technical aspects, quality of life (QOL), stent patency, and Villalta scores were recorded at follow-up. Primary, primary assisted, and secondary patency rates were estimated with Kaplan-Meier methods with the log-rank test.
Percutaneous recanalization was successful in 77 of 81 limbs (95.1%). Stents were deployed in all iliofemoral occlusions, with two stents in 63 lesions (77.8%) lesions and three stents in 18 lesions (22.2%). Venous perforation occurred in 32 patients (37.4%) and was resolved in all cases after stent placement. Back pain occurred during balloon angioplasty (93.8%) and persisted after stent placement in 56.8% of patients. However, the symptoms were self-limiting without further therapy. QOL and Villalta scores were significantly improved during a median follow-up of 19 months (range, 1-38 mo; P < .01). The 2-year primary, primary assisted, and secondary cumulative stent patency rates were 81.5%, 91.4%, and 93.8%, respectively.
Combined stent placement is an effective, safe, and feasible method of management of PTS in iliofemoral CTO until commercial venous stents designed for PTS become available.
Adipose‐derived stem cell (ADSC)‐based therapy is promising for critical limb ischemia (CLI) treatment, especially in patients with diabetes. However, the therapeutic effects of diabetic ADSCs ...(D‐ADSCs) are impaired by the diabetes, possibly through intracellular reactive oxygen species (ROS) accumulation. The objective of the present study was to detect whether overexpression of methylglyoxal‐metabolizing enzyme glyoxalase‐1 (GLO1), which reduces ROS in D‐ADSCs, can restore their proangiogenic function in a streptozotocin‐induced diabetic mice model of CLI. GLO1 overexpression in D‐ADSCs (G‐D‐ADSCs) was achieved using the lentivirus method. G‐D‐ADSCs showed a significant decrease in intracellular ROS accumulation, increase in cell viability, and resistance to apoptosis under high‐glucose conditions compared with D‐ADSCs. G‐D‐ADSCs also performed better in terms of migration, differentiation, and proangiogenic capacity than D‐ADSCs in a high‐glucose environment. Notably, these properties were restored to the same level as that of nondiabetic ADSCs under high‐glucose conditions. G‐D‐ADSC transplantation induced improved reperfusion and an increased limb salvage rate compared D‐ADSCs in a diabetic mice model of CLI. Histological analysis revealed higher microvessel densities and more G‐D‐ADSC‐incorporated microvessels in the G‐D‐ADSC group than in the D‐ADSC group, which was comparable to the nondiabetic ADSC group. Higher expression of vascular endothelial growth factor A and stromal cell‐derived factor‐1α and lower expression of hypoxia‐induced factor‐1α were also detected in the ischemic muscles from the G‐D‐ADSC group than that of the D‐ADSC group. The results of the present study have demonstrated that protection from ROS accumulation by GLO1 overexpression is effective in reversing the impaired biological function of D‐ADSCs in promoting neovascularization of diabetic CLI mice model and warrants the future clinical application of D‐ADSC‐based therapy in diabetic patients. Stem Cells Translational Medicine 2017;6:261–271
Aortic dissection (AD) is one of the most catastrophic aortic diseases associated with a high mortality rate. In contrast to the advances in most cardiovascular diseases, both the incidence and ...in-hospital mortality rate of AD have experienced deviant increases over the past 20 years, highlighting the need for fresh prospects on the prescreening and in-hospital treatment strategies.
Through two cross-sectional studies, we adopt image recognition techniques to identify pre-disease aortic morphology for prior diagnoses; assuming that AD has occurred, we employ functional data analysis to determine the optimal timing for BP and HR interventions to offer the highest possible survival rate.
Compared with the healthy control group, the aortic centerline is significantly more slumped for the AD group. Further, controlling patients' blood pressure and heart rate according to the likelihood of adverse events can offer the highest possible survival probability.
The degree of slumpness is introduced to depict aortic morphological changes comprehensively. The morphology-based prediction model is associated with an improvement in the predictive accuracy of the prescreening of AD. The dynamic model reveals that blood pressure and heart rate variations have a strong predictive power for adverse events, confirming this model's ability to improve AD management.
Background Venous malformations (VMs) are the commonest vascular anomalies. Treatment of extratruncular venous malformations (EVMs) is difficult. Surgery has been the mainstay therapy for EVMs but ...can be hazardous, leading to major blood loss and incomplete resection. Recurrence and cosmetic problems are also common after resection. Endovenous laser ablation (EVLA) has been found to be safe and effective for endovenous ablation of incompetent saphenous veins. We report our experience of diode laser ablation in percutaneous ultrasound (US)-guided treatment of congenital EVMs with respect to effectiveness and safety. Methods A consecutive series of patients (16 males and 22 females; age, 13-46 years) were treated by US-guided EVLA for EVMs at our institution. A questionnaire was used to assess preoperative and postoperative symptoms. Effectiveness was assessed by procedural success and clinical success. Subjective improvement of symptoms was further assessed simultaneously with objective evidence of improved clinical signs. This included reduction of lesion size, general swelling, or improved range of motion of the joint. Duplex US imaging was used to assess blood flow within lesions. Safety was assessed by morbidity and mortality, including laser-related adverse events, postoperative deep vein thrombosis, pulmonary embolism, and hematoma. Results All patients tolerated the procedure and recovered uneventfully. Fifty-six procedures were undertaken in 38 patients. All procedures were successful. Thirty-three patients had resolution of presenting pain symptoms after laser treatment; the remaining patients were able to significantly reduce the number of pain medications from that used before treatment. For complaints related to swelling and cosmetic effect, clinical success was 70% and 67%, respectively. No patients returned with recurrent symptoms after initial successful treatment at a mean follow-up of 12.7 months. Thirty-six (64%) treated lesions areas were classified as “excellent,” 18 (32%) were “good,” and 2 (4%) were “fair” using duplex US imaging at final follow-up. Better results were obtained with localized types of VMs, in which palliation was achieved after only one treatment. Complications were minor and improved quickly. Conclusions Treatment of congenital EVMs with endovenous laser ablation under US guidance achieved palliation in most symptomatic patients; it was safe, with minimal morbidity during short-term follow-up.
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