First-in-Human Clinical Trial of the WeFlow-JAAA Endograft System in Patients With Juxtarenal Abdominal Aortic Aneurysms.

OBJECTIVE: To preliminarily evaluate the safety and efficacy of the WeFlow-JAAA endograft, a novel off-the-shelf device designed for the repair of juxtarenal abdominal aortic aneurysms (JRAAAs) and pararenal abdominal aortic aneurysms (PRAAAs). METHODS: This prospective single-arm first-in-human clinical trial included patients with JRAAAs (infrarenal necks ≤10 mm) or PRAAAs with at least a 5 mm sealing zone below the superior mesenteric artery (SMA) who underwent endovascular repair using the WeFlow-JAAA endograft system. With this system, the celiac artery was addressed with a wide scallop, the renal arteries (RAs) were addressed with 2 standard inner branches, and the SMA was addressed with a "mini-inner-cuff" reinforced fenestration. The primary efficacy endpoint was the clinical success at 12 months. The primary safety endpoint was the freedom from major adverse events (MAEs) in the first 30 days after surgery. RESULTS: Fifteen patients (all men; mean age 68.5±6.0 years) were enrolled between October 2019 and August 2021. The median infrarenal neck length was 0 mm (IQR, 0-4 mm). Technical success was achieved in all patients. No MAEs occurred in the first 30 days. The mean fluoroscopy time was 73.1±27.8 minutes, and the mean volume of contrast media was 130.7±29.4 mL. Clinical success was maintained in all patients at 12 months. No aortic-related deaths, aneurysm rupture, type I or type III endoleak, or open surgery conversion occurred during the follow-up period. The secondary intervention was required only in 1 patient who developed an occluded right RA stent 14 months after the procedure. CONCLUSION: The WeFlow-JAAA endograft device appears to be safe and efficacious in selected patients with JRAAAs or PRAAAs with more than 5 mm sealing zone below SMA. Large-scale, multicenter, and prospective studies with long-term follow-ups are ongoing to validate our findings in China. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04745546 (URL: Guo's Visceral Arteries Reconstruction: The First in Man Study of WeFlow-JAAA Stent Graft System-Full-Text View-ClinicalTrials.gov). CLINICAL IMPACT: The first-in-human clinical trial of the WeFlow-JAAA endograft system demonstrates promising safety and efficacy in treating juxtarenal abdominal aortic aneurysms (JRAAAs) and partial pararenal abdominal aortic aneurysms (PRAAAs). This innovative off-the-shelf device offers a potential alternative to traditional endovascular aortic repair. The successful outcomes, including technical success in all patients, freedom from major adverse events, and maintenance of clinical success at 12 months, suggest a potential shift in clinical practice towards using the WeFlow-JAAA endograft system for selected patients. This study paves the way for larger-scale, multicenter, prospective studies to further validate its long-term safety and efficacy, offering clinicians a new option for managing complex abdominal aortic aneurysms.

A prospective, multicenter, single-arm clinical trial cohort to evaluate the safety and effectiveness of a novel stent graft system (WeFlow-JAAA) for the treatment of juxtarenal abdominal aortic aneurysm: A study protocol.

Introduction: Juxtarenal abdominal aortic aneurysms (JRAAAs) are challenging to cure by traditional endovascular aortic repair (EVAR). Due to the inherent disadvantages of the customized fenestrated and/or branched aortic endografts (such as delayed cycles with a risk of aneurysm rupture, unavailable in emergency or confine operations), several off-the-shelf devices have been developed for the treatment of JRAAA. However, these devices being used in clinical trials have been proven to have a non-negligible risk of reintervention and inadequate anatomic applicability. We have developed a new off-the-shelf aortic endograft system (WeFlow-JAAA) with a mixed design of inner branches and modified fenestrations. The purpose of this cohort study is to assess the safety and effectiveness of the innovative aortic endograft system. Methods and analysis: This is a prospective, multicenter, single-armed clinical trial cohort study. The enrolment will take place in 29 centers in China, and 106 adult patients with JRAAA will be enrolled in total. Clinical information and CT angiography (CTA) images will be collected and recorded. Patients will be followed up for 5 years. The primary safety endpoint is the rate of no major adverse event within 30 days after index EVAR. The primary efficacy endpoint is the rate of immediate technical success and no JRAAA-related reintervention within 12 months after the procedure.

Effect of microRNA-26a on vascular endothelial cell injury caused by lower extremity ischemia-reperfusion injury through the AMPK pathway by targeting PFKFB3.

Vascular endothelial cell (VEC) dysfunction plays an important role in the ischemia-reperfusion injury (IRI)-related diseases, and microRNAs (miRNAs) are key factors during this process. We conducted this study to investigate whether miRNA-26a (miR-26a) has effect on the IRI-induced VEC injury via the AMPK pathway by targeting 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3). IRI rat models were successfully constructed by an abdominal incision. Additionally, the cultured VECs were further treated with miR-26a mimic or inhibitor, and si-PFKFB3. Both the reverse-transcription quantitative polymerase chain reaction and the western blot assay method were carried out to examine the expressions of PFKFB3, endothelial nitric oxide synthase (eNOS), and 5'-adenosine monophosphate-activated protein kinase (AMPK) α1, as well as the extent of the AMPK α1 phosphorylation levels in vascular tissues. Circulating endothelial cell (CEC), von Willebrand factor (VWF), thrombomodulin (TM), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin (ET) were all measured. In the rat model of an IRI, a poorly expressed miR-26a and contrarily highly expressed PFKFB3 were identified in vascular tissues. In response to an overexpression of miR-26a or to the PFKFB3 gene silencing, decreased CEC number, TM, VWF, MDA, and ET contents, increased AMPK α1, and eNOS levels, as well as the extent of AMPK α1 phosphorylation coordinate with both increased SOD and NO contents based on the restoration of the AMPK pathway. Overexpression of the miR-26a or si-PFKFB3 provides an elevation in cell proliferation. Our study suggests that the miR-26a RNA alleviates lower extremity IRI-induced VEC injury in rats through the activation of the AMPK pathway by inhibiting PFKFB3.

MicroRNA-19 restores vascular endothelial cell function in lower limb ischemia-reperfusion injury through the KLF10-dependent TGF-ß1/Smad signaling pathway in rats.

Ischemia-reperfusion injury (IRI) is a severe problem patients diagnosed with acute limb ischemia. Recently, microRNAs (miR) have emerged as regulators of IRI as well as ischemic preconditioning and ischemic postconditioning. Therefore, using rat models, this study aims to explore all of the possible mechanisms that miR-19 exhibits with its relation to the transforming growth factor beta (TGF-ß1)/Smad signaling pathway in the lower limb IRI. An immunofluorescence staining method was used to identify the Krueppel-like factor 10 (KLF10) positive expression and the location of KLF10 expression. The targeting relationship that miR-19 has with KLF10 was verified by the dual-luciferase reporter gene assay. Vascular endothelial cells (VECs) were treated with elevated or suppressed miR-19 or KLF10 knockdown. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to test cell proliferation, and flow cytometry was employed to detect both cell cycle and apoptosis. The KLF10-positive expression in the VECs (both in cytoplasm and nucleus) was found to be elevated in the IRI rats. We found that miR-19 was downregulated, KLF10 upregulated, and the TGF-ß1/Smad signaling pathway activated in the vascular epithelial tissues of IRI rats. KLF10 is a target gene of miR-19. Overexpression of miR-19 decreased the expression of KLF10, TGF-ß1, and Smad2/3. Decreased miR-19 inhibited VEC proliferation, arrested VECs at the G1 phase, and promoted the apoptosis of VECs following their lower limb I/R injury. These results indicate miR-19 as being an inhibitor in the VEC injury of IRI via the TGF-ß1/Smad signaling pathway by suppression of KLF10.

[Relationship of sperm morphology with the outcomes of in vitro fertilization and embryo transfer].

OBJECTIVE: To study the application value of normal sperm morphology on the outcomes of classic in vitro fertilization and embryo transfer (IVF-ET). METHODS: This study included 659 infertile couples admitted to our center for IVF-ET. Based on the percentage of morphologically normal sperm (MNS), we divided the patients into groups A (n = 112, MNS < 2%), B (n = 180, MNS > or = 2 - < 4%), C (n = 74, MNS > or = 4 - < 5%), and D (n = 293, MNS > or = 5%), and compared the rates of fertilization, normal fertilization, embryos obtained, biochemical pregnancy, clinical pregnancy, implantation, and live birth among different groups. RESULTS: The mean fertilization rate was significantly higher in groups C (71.90%) and D (72.89%) than in A (57.97%) and B (63.29%) (P < 0.05), with no remarkable differences either between A and B (P > 0.05) or between C and D (P > 0.05). The normal fertilization rate was also significantly higher in group D (57.16%) than in A (46.52%) and B (50.89%) (both P < 0.05) as well as in C (54.67%) than in A (P < 0.05). The rate of embryos obtained, too, was markedly higher in group D (55.62%) than in B (45.75%) (P < 0.05), but none with remarkable difference from other groups (all P > 0.05). There were no statistically significant differences among the four groups in the rates of biochemical pregnancy, clinical pregnancy, implantation, abortion, and live birth (all P > 0.05). CONCLUSION: The rate of MNS had some influence on IVF-ET, and 5% MNS exhibited a higher value than 4% MNS in predicting the outcomes of IVF.

[Acute Stanford B aortic intramural hematoma: early and midterm follow-ups and morphological changes of computed tomography].

OBJECTIVE: To summarize the clinical performances and analyze the morphological characters of acute Stanford B aortic intramural hematoma (IMH) on computed tomography (CT). METHODS: From January 2010 to June 2012, a total of 28 IMH patients at General Hospital of People's Liberation Army were retrospectively reviewed. Among them, 18 patients were followed up with CT. The data of vessel wall maximum thickness (MT), aortic maximum outside diameter (OD) and aortic inner diameter (ID) at onset and 1 week, 1, 3, 6, 12 months post-onset. Statistical analysis was performed with paired t-test. RESULTS: No mortality occurred. Two patients received endovascular repair. According to the follow-ups of 18 IMH patients, MT was (12.1 ± 2.6) mm on CT. Hematoma disappeared in 44.4% patients at 6 months post-onset. Hematoma disappeared more in the patients with MT ≤ 10 mm than those with > 10 mm (85.7% vs 18.2%, P < 0.01). Hematoma disappeared in 13/15 patients (86.7%) at 12 months post-onset. OD decreased (7.3 ± 2.4) mm per year and (6.7 ± 3.5) and (0.6 ± 1.7) mm within the first 6 months and 6 months later respectively. OD increased (0.9 ± 0.5) mm after the disappearance of hematoma. ID increased (6.1 ± 2.3) mm per year and (4.7 ± 1.8) and (1.2 ± 1.0) mm within the first 6 months and 6 months later respectively. CONCLUSION: The early and midterm outcomes of IHM are satisfactory most of hematoma disappear 12 months after onset. Hematoma disappears more rapidly in the patients with MT ≤ 10 mm than those with > 10 mm. OD reduces and ID increases before the disappearance of hematoma, and both increase afterward. Aortic cavity has a trend of dilating continually.

[Endovascular management of iatrogenic vascular injuries: a retrospective study of 21 cases].

OBJECTIVE: To evaluate the early outcome of endovascular management of iatrogenic vascular injury (IVI). METHODS: From July 2002 to July 2010, 21 cases of IVI undergoing endovascular therapy were studied retrospectively. There were aorta injury (n = 2), peripheral artery injury (n = 11), visceral artery injury (n = 5), arteriovenous injury (n = 1) and venous injury (n = 2). And the procedures included endograft implantation (n = 15), intravascular embolization with coil (n = 4), combination of endovascular balloon intervention and percutaneous thrombin injection (n = 1) and balloon compression for hemostasis (n = 1). RESULTS: Technical success was achieved in all patients. And clinical success, defined as arrested hemorrhage and hemodynamic stabilization, was obtained in 20 (95.2%) patients. There was one case of intra-operative mortality. After the procedure, there were cerebral infarction (n = 2) and partial renal infarction (n = 1). Among them, 19 patients received a median follow-up period of 23.9 months (range: 4 - 84 months). Only 1 patient with iliofemoral vein stent implantation developed stent collapse and thrombosis at Week 3. There were no other complications. CONCLUSION: Endovascular therapy is an effective procedure in the management of different types of IVI. Despite its encouraging early results, the long-term outcomes require further follow-ups and observations.

[Efficacy of anticoagulation on patency post-permanent inferior vena caval filter placements].

OBJECTIVE: To discuss the efficacy of anticoagulation on patency post-permanent inferior vena caval filter (IVCF) placements. METHODS: The patients with deep vein thrombosis (DVT) of the lower extremity who were accepted permanent IVCF placement from December 2001 to December 2007 were reviewed retrospectively. Data on vital status, filter thromboembolism, anticoagulation time, and so on were obtained through follow-up. One hundred and thirty eight patients (75 male and 63 female) with a mean age of 65 years were enrolled in the study. All the patients were divided into non-anticoagulation group, anticoagulation group A with taking warfarin less than 6 months, or anticoagulation group B with taking warfarin more than 6 months. chi(2) test, t test, Kaplan-Meier survival curve, Log-rank test were used for statistics analysis. RESULTS: Sixteen patients died, and 1 of them died of pulmonary embolism. Including the 1 patient mentioned before, there were 19 patients (13.8%) suffered from filter thromboembolism. Upon chi(2) test, there were no significant differences (P = 0.288) on the patency rates between non-anticoagulation, anticoagulation group A and anticoagulation group B (87.8%, 75.0%, and 88.3% respectively). Upon Kaplan-Meier survival analysis, there were still no significant differences (P = 0.227) on the mean patency time and the cumulate rates of patency at the 1st or 3rd year between the 3 groups (87.1%, 80.0%, 94.8% and 87.1%, 74.3%, 85.4% respectively). CONCLUSION: Anticoagulation has no efficacy on patency post-permanent IVCF placements.