Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.

A Case of Bilateral Aortoiliac Aneurysm with Persistent Aneurysmal Sciatic Artery Treated by Endovascular Aneurysm Repair.

The femoral artery is the conventional access for endovascular abdominal aortic aneurysm repair (EVAR). Patients with an anomalous persistent sciatic artery (PSA) is usually at the expense of an atrophied femoral artery. Therefore, EVAR for patients with PSA anomalies is exceptionally challenging. We report the case of a 69-year-old man with an aortoiliac aneurysm and right PSA. Preoperative computed tomography angiography (CTA) revealed a tortuous infrarenal abdominal aortic aneurysm, bilateral common-internal iliac aneurysms, and a right aneurysmal PSA with an ipsilateral atrophic femoral and superficial femoral artery. The aortoiliac aneurysm was successfully repaired through an endovascular approach with access through the right persistent sciatic artery, bilateral femoral artery, and left brachial artery. One-month postoperation, CTA revealed a type 1 endoleak originating from the proximal end of the aorta graft. The second and third operations were performed to close the endoleak through extended proximal cuff with chimney bilateral renal stents and sac embolization with coils and fibrin glue at 1 and 14 months, respectively, after the first operation. CTA performed three months after the third operation did not show any endoleaks. A persistent sciatic artery can be used as an access for endovascular repair of a complicated infrarenal aortoiliac aneurysm combined with an anomalous persistent sciatic artery and an atrophied femoral artery.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

Systematic review and meta-analysis of association of prophylactic cerebrospinal fluid drainage in preventing spinal cord ischemia after thoracic endovascular aortic repair.

OBJECTIVE: We conducted a systemic review and meta-analysis to compare the association between prophylactic cerebrospinal fluid drainage (CSFD) vs non-CSFD in preventing spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for aneurysm and dissection. METHODS: The MEDLINE, Embase, and Cochrane databases were systematically searched to identify all relevant studies reported before April 1, 2020. A systematic review and meta-analysis were performed. We assessed the association between CSFD strategies, including routine CSFD vs selective CSFD or no CSFD, and the SCI rates after TEVAR for patients with aortic dissection (AD), solitary thoracic aortic aneurysm (TAA), or thoracoabdominal aortic aneurysm (TAAA). Subgroup analyses were conducted to assess the association between different aortic pathologies, including AD and thoracic aneurysms, and SCI rates after TEVAR with and without prophylactic CSFD. The data are presented as the pooled event rates (ERs) and 95% confidence intervals (CIs). RESULTS: A total of 34 studies of 3561 patients (2671 with TAA or TAAA and 890 with type B AD) were included in the present analysis. The data are presented as the pooled ERs and 95% CIs. The overall SCI rate for patients who had undergone TEVAR with prophylactic CSFD for AD (ER, 1.80%; 95% CI, 0.88%-2.72%) was significantly lower than that for the aortic aneurysm group (ER, 5.73%; 95% CI, 4.20%-7.27%; P < .0001). The SCI rate after TEVAR with prophylactic CSFD was not significantly different from that without CSFD for AD (P = .51). No association was found between the rates of SCI after TEVAR with routine prophylactic CSFD vs selective prophylactic CSFD for aortic aneurysms (P = .76) and AD (P = .70). The SCI rate after TEVAR without CSFD for aortic aneurysms, including isolated TAA and TAAA (ER, 3.49%; 95% CI, 0.23%-6.76%) was not significantly different from that for AD (ER, 3.20%; 95% CI, 0.00%-7.20%; P = .91). For the patients with TAAAs, the rate of SCI after TEVAR with routine prophylactic CSFD was significantly lower than that with selective prophylactic CSFD (P = .04). CONCLUSIONS: Our systematic review and meta-analysis has shown that SCI occurs more often after TEVAR for aortic aneurysms than for AD. Routine prophylactic CSFD, compared with selective CSFD, was associated with a lower rate of postoperative SCI after TEVAR for TAAAs. No significant association was found between the SCI rate and routine prophylactic CSFD for patients undergoing TEVAR for isolated TAA or AD.

Comparative Effectiveness of Endovascular Treatment Modalities for De Novo Femoropopliteal Lesions: A Network Meta-analysis of Randomized Controlled Trials.

Purpose: To report the results of a network meta-analysis of randomized controlled trials (RCTs) comparing multiple endovascular treatments for de novo femoropopliteal lesions. Materials and Methods: The MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched on June 1, 2019, for prospective RCTs comparing 14 treatments [ie, atherectomy, brachytherapy, cryoplasty, cutting balloons, drug-coated balloons, bare nitinol stents, drug-eluting stents (DES), covered stents (CS), and combinations] in the treatment of de novo femoropopliteal lesions. Outcomes were technical success; binary restenosis and target lesion revascularization (TLR) at 6, 12, and/or 24 months; and all-cause mortality at 12 months. Ultimately, 53 articles reporting on 45 studies (91 study arms; 5565 patients) were selected. For the technical success outcome, all types of stents, all balloons, and all atherectomy devices were aggregated in stent, balloon, and atherectomy technology groups, respectively. Results: In terms of technical success for aggregated treatment types, stent technology was the most effective treatment and was better than balloon and atherectomy technologies. In terms of binary restenosis, DES was the most effective single treatment at the 6- and 12-month follow-up and CS at the 24-month follow-up. Both DES and CS were better than the majority of other single treatments, including balloon angioplasty, cutting balloon, cryoplasty, directional atherectomy, and bare nitinol stent during all follow-up periods. In terms of TLR, DES was the second most effective single treatment and the most effective single treatment at the 6- and 12-month follow-up intervals; CS was the most effective single treatment at the 24-month follow-up. Both DES and CS were better than the majority of other single treatments. The 12-month all-cause mortality of both DES and CS were similar to other treatments, whereas cryoplasty seemed to be the least effective treatment with regard to binary restenosis and TLR. Conclusion: Both DES and CS had substantial advantages in terms of restenosis and TLR in femoropopliteal lesions and were similar to aggregate stent technology in terms of technical success. DES performed better within 12 months after operation and CS at ~24 months, but neither had much advantage in terms of mortality. In contrast, cryoplasty seemed to be a less effective treatment.

Comparative Efficacy and Safety of Endovascular Treatment Modalities for Femoropopliteal Artery Lesions: A Network Meta-analysis of Randomized Controlled Trials.

PURPOSE: We conducted a network meta-analysis of randomized controlled trials comparing the efficacy and safety of multiple endovascular treatments for femoropopliteal lesions. METHODS: Nine treatments for femoropopliteal lesions were identified. We compared major amputation and all-cause mortality at 12-month follow-ups and primary patency at 6-, 12- and 24-month follow-ups of the treatments. RESULTS: Altogether, 26 studies (52 study arms; 4102 patients) were considered eligible. In terms of primary patency, drug-eluting stent (DES) placement was the most effective treatment at 6- and 12-month follow-ups and covered stent (CS) placement at 24-month follow-ups, whereas directional atherectomy (DA) was the least effective treatment during all follow-up periods; both DES and CS placements were better than the majority of other single treatments, including balloon angioplasty, DA, nitinol stent (NS) placement and drug-coated balloon use, during all follow-up periods. In terms of 12-month major amputation and all-cause mortality, DA was the most safe treatment, whereas NS placement was the least safe single treatment. CONCLUSIONS: DES and CS placements have shown encouraging results in terms of primary patency for femoropopliteal lesions, DES placement performs better within 12 months after operation and CS placement at approximately 24 months, while DA seems to be less effective. DA may be better than other treatments in terms of major amputation and all-cause mortality, while NS seems to be less safe.

A Network Meta-analysis of Randomized Controlled Trials Comparing Treatment Modalities for Infrapopliteal Lesions in Critical Limb Ischemia.

BACKGROUND: We aimed to conduct a network meta-analysis of randomized controlled trials comparing treatment modalities for infrapopliteal lesions in critical limb ischemia. METHODS: Five treatments for infrapopliteal lesions in critical limb ischemia were recognized. We compared primary patency, target lesion revascularization (TLR), major amputation at the 12-month follow-up, and technical success rate of the treatment modalities. RESULTS: Altogether, 11 studies (22 study arms; 1,330 patients) were considered eligible. The drug-eluting balloon (DEB) significantly increased primary patency compared with balloon angioplasty (BA; odds ratio [OR] 9.02, 95% confidence interval [CI] 3.18-25.55), the bare metal stent (BMS; OR 14.39, 95% CI 4.33-47.87), and the drug-eluting stent (DES; OR 3.70, 95% CI 1.20-11.11). The DES significantly increased primary patency compared with BA (OR 2.42, 95% CI 1.57-3.74) and BMS (OR 3.86, 95% CI 2.24-6.65). DES significantly increased the technical success rate compared with BA (OR 11.78, 95% CI 1.42-97.59). According to the value of the surface under the cumulative ranking curve (SUCRA), DEB was considered the best treatment in terms of primary patency (SUCRA = 99.7) and TLR (SUCRA = 70.7), and DES was considered the best treatment in terms of technical success rate (SUCRA = 90.6) and major amputation (SUCRA = 85.9). CONCLUSIONS: DEB has shown encouraging results in terms of primary patency for infrapopliteal lesions in critical limb ischemia; furthermore, DEB may be better than other treatments in terms of TLR. DES may be better than other treatments in terms of technical success and major amputation. In contrast, BA and BMS seem to be less effective treatment options.

R-Smad signaling-mediated VEGF expression coordinately regulates endothelial cell differentiation of rat mesenchymal stem cells.

A low-efficiency yield hinders the use of stem cells as a source of endothelial cells (ECs) for therapeutic vascularization, and the diversity of the transforming growth factor-ß (TGF-ß) superfamily has undermined understanding the effects of its potent vascularization-inducing. Herein, we studied the role of the TGF-ß superfamily in EC differentiation of rat bone marrow mesenchymal stem cells (MSCs) induced by Smad2/3 and Smad1/5/8 signaling. MSCs that had been sorted by flow cytometry as CD31-negative were cultured for 14 days in medium supplemented with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as the control. The Smad2/3 pathway was activated by TGF-ß1 and Smad1/5/8 by bone morphogenetic proteins (BMPs). In the early phase in the Smad2/3-activated group, there were 10% CD31-positive cells, which was significantly higher than in the control group. A low Smad1/5/8 phosphorylation level after BMP4 activation doubled the number of CD31-positive cells, while a higher phosphorylation level after BMP9 activation showed no effect. A Smad2/3 inhibitor initially blocked differentiation but later promoted it, while a Smad1/5/8 inhibitor reversed the induction observed with BMPs. Moreover, the positive effects of R-Smad on differentiation were weakened by the VEGF neutralizing antibody, and a Smad3 inhibitor decreased VEGF expression and blocked differentiation in both the early and late phases. In conclusion, differentiation of ECs from MSCs via Smad2/3 signaling is stage dependent. Activation, particularly by Smad3, significantly promotes differentiation at an early phase but later is suppressive. A low Smad1/5/8 phosphorylation level has a positive effect, and R-Smad effects are partly mediated by VEGF.

Green tea polyphenol epigallocatechin-3-gallate enhances 5-fluorouracil-induced cell growth inhibition of hepatocellular carcinoma cells.

AIM: 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic drugs. Resistance to 5-FU is a major cause of chemotherapy failure in advanced-stage hepatocellular carcinoma (HCC). Green tea polyphenol Epigallocatechin-3-gallate (EGCG) plays a critical role in growth inhibition and apoptotic induction in HCC cell lines. The aim of this study is to investigate whether EGCG can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell growth. Western blotting analysis was performed to detect the proteins expression in Hep3B cells. Small interfering RNA was used to suppress cyclooxygenase-2 (COX-2) expression. Furthermore, enzyme linked immunosorbent assay was used to test the prostaglandin E(2) (PGE(2) ) production in cell cultures. RESULTS: Epigallocatechin-3-gallate augmented the anti-tumor effect of 5-FU in Hep3B cells. Significant difference was observed between the treated groups and the control group (P < 0.05). EGCG (its concentrations at over 5 µmol/L) combined with 5-FU presented a synergic effect. Furthermore, the combination of EGCG and 5-FU abrogated the COX-2 overexpression and PGE(2) secretion induced by 5-FU. The upregulation of COX-2 expression decreased the phosphorylation of Akt (Thr(308) ) expression. These appeared to be followed by the AMPK hyperactivation. CONCLUSION: Epigallocatechin-3-gallate sensitizes HCC cells to 5-FU antitumor activity, and the combination of EGCG and 5-FU exhibits synergism in chemo-resistant cancer cells. The results suggest potential novel therapies for the treatment of advanced-stage liver cancer.

[Experience of endovenous radiofrequency combined with TriVex in treatment of chronic venous insufficiency in lower extremity].

OBJECTIVE: To evaluate therapeutic results of endovenous radiofrequency in combination with TriVex in treatment of venous insufficiency in lower extremities. METHODS: One hundred and fifty patients with chronic venous insufficiency (150 limbs) were randomly assigned to Group A (75 limbs) and Group B (75 limbs). Patients in Group A were treated with long saphenous veins radiofrequency ablation procedures in combination with TriVex. Patients in Group B were treated with long saphenous veins traditional stripping operation in combination with TriVex. The postoperative pain, average hospital stay and short-term results in hospital were compared between the two groups. Self-assessment of the operation 4 weeks after, changes of CEAP classification, venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ) score were compared between the two groups. RESULTS: The operation time in Group A was (67 +/- 11) min, compared with (59 +/- 9) min in Group B (P > 0.05). Postoperative pain and average hospital stay in Group A were significantly lower than those in Group B (P < 0.05). The scores of self-assessment of the operation in Group A was higher than that in Group B 4 weeks after operation (P < 0.05). The change of CEAP classification, VCSS and quality of life were significant after operation in both groups. The VCSS of Group A decreased by 4.6 +/- 2.5 compared with 4.3 +/- 2.7 in Group B (P > 0.05). CONCLUSIONS: Endovenous radiofrequency combined with TriVex for treatment of venous insufficiency in lower extremity is available, effective and with less trauma and faster recovery. CEAP classification, VCSS and CIVIQ are useful tools for assessing outcomes after radiofrequency in these patients.