Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling.

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a 'normal' AVF (nAVF) group and an 'outliers' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.

Subacute Limb Ischemia Suspected from COVID-19-Related Arterial Thrombosis Presenting with Local Occlusion Site Tenderness.

A 59-year-old man was admitted to our hospital with severe popliteal fossa pain and mild left calf claudication. He had had an episode of pyrexia and dyspnea approximately 3 weeks prior. Contrast-enhanced computed tomography revealed acute occlusion of the left popliteal artery and multiple infiltration shadows with bilateral multifocal parenchymal consolidation of the lungs, suggesting post-coronavirus disease 2019 (COVID-19) pneumonia. As he had no comorbid risk of cardiogenic embolism or atherosclerosis, we diagnosed him with COVID-19-related arterial thrombosis. COVID-19-related arterial thrombosis should be considered a possible cause of acute limb ischemia, even when ischemic symptoms occur several weeks post infection.

Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan　- Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

BACKGROUND: The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease.Methods and Results: This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. CONCLUSIONS: Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

Saccular and Fusiform Abdominal Aortic Aneurysms Treated With Endovascular Repair Differ in Presentation and Treatment Threshold: Analyses Using a National Clinical Database in Japan.

BACKGROUND: Saccular abdominal aortic aneurysms (AAAs) are considered to be at higher risk of rupture than fusiform AAAs, but not much is known about the extent of this risk. Therefore, this study aimed to compare the rupture presentation between fusiform and saccular AAAs. METHODS AND RESULTS: This is a retrospective cohort study on 27 290 patients who underwent primary endovascular repair for a degenerative AAA between 2016 and 2019, and who were registered in the National Clinical Database in Japan. At operation for nonruptured case, the aneurysm diameter was significantly smaller in saccular AAAs than in fusiform AAAs (median, 44.0 versus 51.0 mm; P<0.001). Similarly, aneurysm diameter at rupture was significantly smaller in saccular AAAs than in fusiform AAAs (median, 55.6 versus 68.0 mm; P<0.001). The likelihood of repair for rupture was significantly higher in saccular AAAs than in fusiform AAAs in the 40- to 54-mm diameter range, in which saccular morphology was found to be an independent risk factor for rupture against fusiform morphology by adjusting for sex and aneurysm diameter (odds ratio, 2.54 [95% CI, 1.75-3.69]). In addition, receiver-operating characteristic curve analysis revealed that the cutoff diameter to predict rupture was smaller in saccular AAAs than in fusiform AAAs (50.5 and 59.5 mm, respectively) based on the Youden index. CONCLUSIONS: Saccular AAAs presented at smaller diameters than fusiform AAAs in patients with ruptured AAAs treated with endovascular aortic repair, which supports the idea that saccular AAAs should be treated at smaller diameters.

A case of endovascular treatment for iatrogenic left vertebral artery injury due to central line catheter placement.

We describe a case of endovascular treatment for an iatrogenic left vertebral artery injury after central line catheter placement in a 68-year-old male patient. The patient had a massive pulmonary embolism, and a Swan-Ganz catheter was required to monitor the patient's circulatory condition. However, the catheter was inserted into the left vertebral artery and passed through the left internal jugular vein. Endovascular treatment was indicated due to the patient's poor general health. Complete hemostasis was achieved, and the postoperative course was uneventful without neurologic deficits.

Poor Limb Prognosis of Patients with Chronic Limb-Threatening Ischemia on Hemodialysis: A Retrospective Observational Study Based on the Global Limb Anatomic Staging System.

BACKGROUND: The Global Limb Anatomic Staging System (GLASS) has been widely used to evaluate patients with chronic limb-threatening ischemia (CLTI). As end-stage kidney disease (ESKD) is a well-known CLTI risk factor, we aimed to determine whether patients on hemodialysis (HD) have a worse limb prognosis than those without ESKD, considering the same GLASS background. METHODS: The data of 445 patients who underwent surgical and/or endovascular revascularization procedures for lower extremity ischemia were retrospectively collected in our division between 2005 and 2018. The major amputation rate and amputation-free survival (AFS) were compared between HD and non-HD patients. RESULTS: Among the 215 (48%) patients receiving HD, 58 limbs required major amputation (27% limb loss rate). Among the non-HD group, the limb loss rate was 13% (P < 0.0001). The overall AFS was significantly worse in patients receiving HD than those not (P < 0.0001). The AFS was significantly worse in HD patients when comparing GLASS-standardized subgroups. CONCLUSIONS: Patients with CLTI who were receiving HD had a worse limb prognosis than those not receiving, even when considering the same GLASS classification. Furthermore, there is a need for an ideal guideline focused on ESKD-directed peripheral artery disease.

Motion capture device reveals a quick learning curve in vascular anastomosis training.

PURPOSE: Surgical procedures are often evaluated subjectively, and an objective evaluation has been considered difficult to make and rarely reported, especially in open surgery, where the range of motion is wide. This study evaluated the effectiveness of surgical suturing training as an educational tool using the Leap Motion Controller (LMC), which can capture hand movements and reproduce them as data comprising parametric elements. METHODS: We developed an off-the-job training system (Off-JT) in our department, mainly using prosthetic grafts and various anastomotic methodologies with graded difficulty levels. We recruited 50 medical students (novice group) and 6 vascular surgeons (expert group) for the study. We evaluated four parameters for intraoperative skills: suturing time, slope of the roll, smoothness, and rate of excess motion. RESULTS: All 4 parameters distinguished the skill of the novice group at 1 and 10 h off-JT. After 10 h of off-JT, all 4 parameters of the novices were comparable to those of the expert group. CONCLUSION: Our education system using the LMC is relatively inexpensive and easy to set up, with a free application for analyses, serving as an effective and ubiquitous educational tool for young surgeons.

Deformed Popliteal Artery Due to Highly Flexed Knee Position Can Cause Kinks, Creating an Unfavorable Hemodynamic State.

BACKGROUND: Endovascular treatment devices of the femoropopliteal artery have evolved, improving clinical results. However, the effects of dynamic changes in the popliteal artery during knee flexion have not been sufficiently investigated. In this study we performed a 3-dimensional analysis to clarify the dynamic changes in the popliteal artery during knee flexion and their effects on hemodynamics.Methods and Results: To analyze dynamic changes in the popliteal artery in the knee flexion position, a computed tomography protocol was developed in the right-angled and maximum flexion knee positions. Thirty patients with lower extremity artery disease were recruited. V-Modeler software was used for anatomical and hemodynamic analyses. Various types of deformations of the popliteal artery were revealed, including hinge points and accessory flexions. Kinks can occur in the maximum flexion position; however, they rarely occur in the right-angled flexion position. In addition, hemodynamic analysis revealed a tendency for lower minimum wall shear stress and a higher maximum oscillatory shear index at the maximum curvature of the popliteal artery. CONCLUSIONS: Kinks in the maximum flexion position suggested that the outcome of endovascular treatment may change in areas such as Japan, where knee flexion is customary. Hemodynamics at the maximum curvature of the popliteal artery indicated that the luminal condition was unfavorable for endovascular treatment.

Giant Coeliac Artery Aneurysm Treated with a Hybrid Approach: A Case Report.

Introduction: Coeliac artery aneurysms are rare and have a high mortality rate when ruptured. Although they are often asymptomatic, treatment is recommended for patients with true coeliac aneurysms >2.5 cm, noted enlargement, or associated symptoms. Less invasive endovascular treatment is predominantly performed for coeliac artery aneurysms, while open surgery is preferred for patients with compression symptoms. Here, a case of symptomatic giant coeliac artery aneurysm that was successfully treated with hybrid surgery is reported. Report: A 73 year old man was referred with continuous epigastric discomfort and loss of appetite for two weeks. Abdominal ultrasound and computed tomography revealed a 12 cm aneurysm of the coeliac artery. The splenic and common hepatic arteries were severely distorted and compressed by the aneurysm, making their origins unclear. Considering the risk of rupture, semi-urgent surgery was performed with interruption of the inflow and outflow arteries using open and endovascular techniques together with aneurysmorrhaphy. Vascular reconstruction was omitted because abundant collateral flow to the liver and spleen was confirmed on angiography. Discussion: With the hybrid approach, aneurysmorrhaphy was performed safely with minimal incision and dissection. Short term outcomes were satisfactory, with complete resolution of compression symptoms and remarkable sac shrinkage at 12 months. Owing to the possibility of the pancreaticoduodenal arcade developing as a collateral pathway, periodic surveillance for de novo aneurysms is warranted.

Risk Factors for Incisional Hernia After Open Abdominal Aortic Aneurysm Repair.

BACKGROUND/AIM: Incisional hernia is among the most prevalent complications associated with open abdominal aortic aneurysm repair. However, risk factors for incisional hernias in patients with abdominal aortic aneurysm are multifactorial. Therefore, this study evaluated the risk factors of incisional hernia after open abdominal aortic aneurysm repair, including surgical factors. PATIENTS AND METHODS: We retrospectively extracted data from patients with incisional hernias after abdominal aortic aneurysm repair between 2012 and 2019 and investigated their perioperative characteristics and wound closure techniques. RESULTS: The mean follow-up periods were 41.5±30.3 months, and 30 of 131 (22.9%) patients suffered an incisional hernia. Regarding the underlying disease, only diabetes mellitus was significantly more common in the incisional hernia group (11 of 30 patients, 36.6%), and no significant differences were found in the patients' perioperative data. Interrupted sutures were used in all 30 patients in the hernia group. Moreover, in 8 of the 101 remaining cases, barbed sutures were used, and no incisional hernia occurred in any of these cases. CONCLUSION: In addition to diabetes mellitus, abdominal aortic aneurysm is a significant risk factor for incisional hernia after abdominal aortic aneurysm repair. Therefore, employing the barbed suture technique may effectively prevent incisional hernias after abdominal aortic aneurysm repair.

Area reduction of perforation with a small-size sheath technique for iatrogenic femoral artery pseudoaneurysm with a large perforation.

Open surgery for femoral artery pseudoaneurysms is invasive, and complications can be detrimental. Several cases of treatment of iatrogenic femoral artery pseudoaneurysms using percutaneous suture-mediated closure devices have been reported. However, it is difficult to properly deploy the foot of the device to the arterial wall when the perforation area is large. We developed a technique using a double guidewire to partially occupy the perforation with a small-size sheath, which reduces the area of the perforation. This AREPAS (area reduction of perforation with a small-sized sheath) technique might allow for minimally invasive closure of perforations even in patients with large perforation areas.

A case of popliteal artery rupture in an 11-year-old patient with vascular Ehlers-Danlos syndrome.

We have described a case of multiple surgeries for a ruptured popliteal artery in an 11-year-old female patient with vascular Ehlers-Danlos syndrome. She underwent emergency hematoma evacuation and ruptured popliteal artery interposition with the great saphenous vein graft, which was notably fragile during surgery and had ruptured on the seventh postoperative day. We performed another emergency hematoma evacuation and popliteal artery interposition with an expanded polytetrafluoroethylene vascular graft. Despite the early occlusion of the expanded polytetrafluoroethylene graft, she recovered with mild intermittent claudication in the left lower extremity and was discharged on postoperative day 20 after the first surgery.

Popliteal artery aneurysm in a 14-year-old boy with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is rarely associated with aneurysms. We have described a patient with a popliteal artery aneurysm that was associated with TSC and occlusion of the right posterior tibial artery. The patient underwent aneurysm resection and vein graft replacement, with an uneventful postoperative course and no recurrence at 11 months of follow-up. Patients with TSC could have aneurysms in areas that will not be recognized on abdominal imaging. Physical examination of the lower extremities should be performed owing to the possibility of a popliteal artery aneurysm, and imaging studies should be performed if an aneurysm is suspected.

Midterm outcomes of AFX2 endografts used in combination with aortic cuffs.

OBJECTIVE: Type III endoleaks after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) with the Endologix unibody endograft remain a major concern, despite fabric, system, and instructional updates. The purpose of this study was to examine real-world outcomes of repairing AAAs using the current version of the AFX2 main body in combination with an aortic cuff, specifically focusing on type III endoleaks and morphological changes of the endograft. METHODS: We recruited facilities in Japan that used AFX2 combined with an aortic cuff for at least five cases between April 2017 and March 2018. A total of 175 cases in 24 facilities were analyzed. Patients' background information, including anatomic factors, operative findings, device component variations, and midterm outcomes at 3 years after the EVAR were collected. The data on computed tomography scans from cases registered as types I and III endoleaks and migration from each institute were sent to our department for verification. RESULTS: The mean patient age was 74.6 ± 8.1 years, and 48 cases (27%) were saccular aneurysms. The mean fusiform and saccular AAA diameters were 50.5 ± 5.8 mm and 43.5 ± 8.9 mm, respectively. No in-hospital deaths occurred. Data at 3 years, including computed tomography images, of 128 cases were analyzed. Overall survival, freedom from aneurysm-related mortality, and freedom from reintervention rates at 3 years were 85.8%, 99.3%, and 87.3%, respectively. There were three, one, and three cases of types I, IIIa, and IIIb endoleaks without sac dilatations, respectively. Among five migration cases, one case of aortic cuff migration presented as a type Ia endoleak, and four cases demonstrated sideways displacement, one of which presented as a type IIIa endoleak. The sac regression and enlargement rates at 3 years were 41.4% and 20.5% in the fusiform group and 44.2% and 16.7% in the saccular group, respectively. The proximal neck diameter slightly increased from 20.8 ± 2.7 mm before the EVAR to 22.2 ± 4.6 mm after the repair. CONCLUSIONS: Midterm outcomes of the AFX2 used in combination with an aortic cuff were acceptable, considering the rates of types I and III endoleaks. However, there were cases of sideways displacement that could cause future type IIIa endoleaks. When the AFX2 is used in combination with an aortic cuff, close surveillance for endograft deformations and subsequent adverse events, including type III endoleaks, is needed.

Systemic single administration of anti-inflammatory microRNA 146a-5p loaded in polymeric nanomedicines with active targetability attenuates neointimal hyperplasia by controlling inflammation in injured arteries in a rat model.

Neointimal hyperplasia (NIH) after revascularization is a key unsolved clinical problem. Various studies have shown that attenuation of the acute inflammatory response on the vascular wall can prevent NIH. MicroRNA146a-5p (miR146a-5p) has been reported to show anti-inflammatory effects by inhibiting the NF-κB pathway, a well-known key player of inflammation of the vascular wall. Here, a nanomedicine, which can reach the vascular injury site, based on polymeric micelles was applied to deliver miR146a-5p in a rat carotid artery balloon injury model. In vitro studies using inflammation-induced vascular smooth muscle cell (VSMC) was performed. Results showed anti-inflammatory response as an inhibitor of the NF-κB pathway and VSMC migration, suppression of reactive oxygen species production, and proinflammatory cytokine gene expression in VSMCs. A single systemic administration of miR146a-5p attenuated NIH and vessel remodeling in a carotid artery balloon injury model in both male and female rats in vivo. MiR146a-5p reduced proinflammatory cytokine gene expression in injured arteries and monocyte/macrophage infiltration into the vascular wall. Therefore, miR146a-5p delivery to the injury site demonstrated therapeutic potential against NIH after revascularization.

Prediction Models for Two Year Overall Survival and Amputation Free Survival After Revascularisation for Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to create prediction models for two year overall survival (OS) and amputation free survival (AFS) after revascularisation in patients with chronic limb threatening ischaemia (CLTI). METHODS: This was a retrospective analysis of prospectively collected multicentre registry data (JAPAN Critical Limb Ischaemia Database; JCLIMB). Data from 3 505 unique patients with CLTI who had undergone revascularisation from 2013 to 2017 were extracted from the JCLIMB for the analysis. The cohort was randomly divided into development (2 861 patients) and validation cohorts (644 patients). In the development cohort, multivariable risk models were constructed to predict two year OS and AFS using Cox proportional hazard regression analysis. These models were applied to the validation cohort and their performances were evaluated using Harrell's C index and calibration plots. RESULTS: Kaplan-Meier estimates of two year OS and AFS post-revascularisation in the whole cohort were 69% and 62%, respectively. Strong predictors for OS consisted of age, activity, malignant neoplasm, chronic kidney disease (CKD), congestive heart failure (CHF), geriatric nutritional risk index (GNRI), and sex. Strong predictors for AFS included age, activity, malignant neoplasm, CKD, CHF, GNRI, body temperature, white blood cells, urgent revascularisation procedure, and sex. Prediction models for two year OS and AFS showed good discrimination with Harrell's C indexes of 0.73 (95% confidence interval [CI] 0.69 - 0.77) and 0.72 (95% CI 0.68 - 0.76), respectively CONCLUSION: Prediction models for two year OS and AFS post-revascularisation in patients with CLTI were created. They can assist in determining treatment strategies and serve as risk adjustment modalities for quality benchmarking for revascularisation in patients with CLTI at each facility.

Volumetric computed tomography analysis for gastroduodenal and pancreaticoduodenal artery aneurysm formation: A retrospective single-center study.

ABSTRACT: Gastroduodenal artery aneurysms (GDAA) and pancreaticoduodenal artery aneurysms (PDAA) are rare, have high rupture risks, and are located in the arcade between the celiac artery and the superior mesenteric artery. Pancreaticoduodenal artery aneurysms are associated with celiac artery stenosis, and it is hypothesized that these celiac lesions might contribute to the formation of aneurysms. In contrast, a few studies have reported an association between a gastroduodenal artery aneurysm and celiac lesions. This study aimed to investigate the potential differences between patients with gastroduodenal and pancreaticoduodenal artery aneurysms and better understand their pathogenesis.We selected patients with GDAA and PDAA who were admitted to our department between January 2010 and December 2020. Aortic wall volume, aortic wall calcification, and pancreaticoduodenal arcade volume of computed tomography images were calculated semi-manually using Horos 3.3.5.Eight GDAAs and 11 PDAAs were analyzed. Celiac lesions were found in all PDAA patients, with none in GDAA cases. Volumetry demonstrated that aortic wall volume and calcification were more prominent in the GDAA group than in the PDAA group (P = .026 and P = .049, respectively). The pancreaticoduodenal arcade volume was larger in the PDAA group (P = .002).In our study, celiac artery lesions were strongly correlated with PDAA. The volume of the pancreaticoduodenal arcade was larger in the PDAA group, and aortic wall volume and calcification were larger in the GDAA group.

Endothelial Cell TGF-ß (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency.

BACKGROUND: Arteriovenous fistulae (AVF) are the gold standard for vascular access for hemodialysis. Although the vein must thicken and dilate for successful hemodialysis, excessive wall thickness leads to stenosis causing AVF failure. Since TGF-ß (transforming growth factor-beta) regulates ECM (extracellular matrix) deposition and smooth muscle cell (SMC) proliferation-critical components of wall thickness-we hypothesized that disruption of TGF-ß signaling prevents excessive wall thickening during venous remodeling. METHODS: A mouse aortocaval fistula model was used. SB431542-an inhibitor of TGF-ß receptor I-was encapsulated in nanoparticles and applied to the AVF adventitia in C57BL/6J mice. Alternatively, AVFs were created in mice with conditional disruption of TGF-ß receptors in either SMCs or endothelial cells. Doppler ultrasound was performed serially to confirm patency and to measure vessel diameters. AVFs were harvested at predetermined time points for histological and immunofluorescence analyses. RESULTS: Inhibition of TGF-ß signaling with SB431542-containing nanoparticles significantly reduced p-Smad2-positive cells in the AVF wall during the early maturation phase (days 7-21) and was associated with decreased AVF wall thickness that showed both decreased collagen density and decreased SMC proliferation. SMC-specific TGF-ß signaling disruption decreased collagen density but not SMC proliferation or wall thickness. Endothelial cell-specific TGF-ß signaling disruption decreased both collagen density and SMC proliferation in the AVF wall and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. CONCLUSIONS: Endothelial cell-targeted TGF-ß inhibition may be a translational strategy to improve AVF patency.