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Background The purpose of this study was to evaluate the factors associated with asymptomatic splenic artery aneurysm (SAA) dilatation. Methods Among patients with SAA admitted to our department from 2001 to 2018, 70 lesions in 59 patients were selected and analyzed retrospectively. There were no cases of rupture or pregnancy in the follow-up period. We defined egg-shell appearance as SAA with >75% calcification of the outer shell. We measured the dilatation rate (mm/year) and evaluated the comorbidity and anatomical factors using univariate and multiple linear regression models. Post-hoc multiple linear regression models were fitted to evaluate the possible interactions. Results The mean age was 61.4 years (range 35–85 years), and the initial aneurysm diameter was 15.1 mm (range 3–47 mm). The mean dilatation rate was 0.26 mm/year (range 0–3.2 mm/year) during the follow-up period (average 4.6 years). Univariate analysis revealed that, portal hypertension (PHT) (P = 0.0003), egg-shell appearance (P = 0.007), and aneurysm diameter > 20 mm (P = 0.05) were significantly associated with the dilatation rate. Multivariate analysis revealed that egg-shell appearance was found to be an independent inverse risk factor of dilatation rate (P = 0.006). The multivariate analysis, including interaction terms, revealed a stronger effect of PHT and diameter >20 mm in cases with no egg-shell appearance (P = 0.08 and P = 0.05 for interactions, respectively). Conclusions The egg-shell appearance of SAA was an independent inverse risk factor affecting the SAA dilatation rate. The dilatation rates in the case of PHT and diameter >20 mm were restricted in the presence of the egg-shell appearance.

Phlegmasia cerulea dolens (PCD) is caused by obstruction of limb venous return that may result in venous gangrene and limb loss. We present a case of a fistula between a ruptured right common iliac artery aneurysm and the left common iliac vein (ilioiliac arteriovenous fistula [AVF]), which initially manifested as left PCD and acute renal failure. Resection of the aneurysm and repair of the AVF immediately improved the PCD and acute renal failure. We should be aware that an iliac AVF might present as PCD and should keep this in mind. Keywords: Phlegmasia cerulea dolens, Arteriovenous fistula, Acute renal failure

BACKGROUND Specialized proresolving mediators from ω-3 polyunsaturated fatty acid may control resolution of inflammation. We evaluated the influence of two specialized proresolving mediators, resolvin D1 (RvD1) and protectin D1 isomer (PD1 iso) on neointimal hyperplasia after balloon injury. MATERIALS AND METHODS Sprague Dawley male rats at 12-14 wk of age were injured as a model of balloon angioplasty. Then, 1 μg/rat of RvD1 or PD1 iso was administered intravenously via the tail vein immediately and 2 d after angioplasty. The proliferation of injured artery and the infiltration of leukocytes, monocytes, and macrophages at 3 d after injury were evaluated by immunostaining. The activity of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) in the injured artery at 3 d after injury was evaluated using an enzyme-linked immuno sorbent assay kit. The proliferation of the neointima was evaluated by calculating the ratio of the neointimal and medial areas using specimens at 14 d after injury. RESULTS RvD1 and PD1 iso attenuated proliferation of medial cells (P

Background Systemic scleroderma (SSc) involves multiple organs including the skin, the lung, the kidney, and the esophagus. Nowadays, patient life prognosis has substantially improved due to more appropriate management of lung complications, including lung transplantation. However, the extension of their survival may increase SSc patients with chronic kidney diseases and requiring renal replacement therapy (RRT). Case presentation A 51-year-old female with SSc who underwent unilateral deceased-donor lung transplantation was referred because of progressive renal dysfunction. Despite no episodes of scleroderma renal crisis, her renal function gradually deteriorated for 2 years with her serum creatinine level increasing from 0.5 mg/dL at transplantation to 4.3 mg/dL. Although we reinforced antihypertensive treatment and reduced calcineurin inhibitor dose, she thereafter developed symptomatic uremia. Due to impaired manual dexterity with contracture of the interphalangeal joints, no caregivers at home, and kidney transplantation donor unavailability, maintenance hemodialysis was chosen as RRT modality. Further, due to the narrowing of superficial vessels in the sclerotic forearm skin and post-transplant immunocompromised status, the native left brachiocephalic arteriovenous fistula was created. Post-operative course was uneventful while any sign of cutaneous infection and pulmonary hypertension was closely monitored. Our literature review also indicates several difficulties with initiating and maintaining RRT in patients with SSc although case reports of kidney failure after lung transplanation in SSc were not accumulated. Conclusions With respect to initiating RRT for post-lung transplant patients with SSc, the clinical course of our case exemplifies recent complex trends of renal management. The optimal modality with secured initiation of RRT should be carefully determined based on the severity and risk for the cardiopulmonary, peripheral vascular, cutaneous, and systemic or local infectious complications.

In this study, we demonstrate the EEG activation patterns during the performance of different difficulty and duration of mental tasks in normal subjects. The EEG was recorded when the subjects performing mental tasks, and the power spectrum was calculated in alpha (8~13Hz) and beta (14~40Hz) frequency band. Maze tasks with different difficulty (size) and duration (execution time) were utilized to control the variability of mental workload. Statistical analysis showed that the decrease in alpha-band activity and the increase in betaband activity were marked between resting condition and performing mental tasks. Here no significant difference was found in the EEG activate pattern between task difficulty and task duration. In conclusion, these results imply that the fact of performing mental tasks is the main player in changing the activation pattern of alpha- and beta-band activity under the combined mental stress.

The prevalence of arteriosclerosis obliterans (ASO) and critical limb ischemia (CLI) is currently increasing, and arterial reconstruction is often attempted to salvage the limb. Some patients cannot undergo attempted revascularization because of contraindications, and they only receive conservative treatment. In this study, we investigate the comorbidities and survival rates of patients with CLI who receive conservative treatment. Thirty-five patients with CLI due to ASO, who had not undergone revascularization surgery (C group), were enrolled. As controls, 136 patients with CLI due to ASO who did undergo revascularization (R group), mainly via bypass surgery, were enrolled. Coronary artery disease, heart failure, and respiratory dysfunction were factors indicating conservative treatment. Limb salvage rates and survival rates were not significantly different between the two groups. Patients who had survived for less than two years after surgery had a higher prevalence of chronic heart failure, cardiovascular disease, and end-stage renal disease compared to patients who had survived for more than two years. The use of statins, dual antiplatelets, aspirin, or warfarin did not influence whether a patient survived for longer than two years. 77% of patients survived for more than two years after receiving only conservative therapies. Surgical revascularization did not improve the prognosis of patients with CLI as compared with the conservative therapy. Clinicians might start with conservative treatment while considering other treatment options for patients with CLI.

The main objective is to examine whether the severity of peripheral arterial disease (PAD) affects the expenses and hospital stay of the patients who undergo bypass surgery below the inguinal ligament for PAD. Eighty consecutive patients who underwent infrainguinal bypass surgery for PAD between January 2012 and December 2014 were included in the study. Patients were divided into groups according to their critical limb ischemia (CLI) symptoms and the Wound, Ischemia, and Foot Infection (WIfI) classification. As endpoints, we assessed the duration of postoperative hospital stay and expenses during hospitalization. CLI was a significant factor for longer hospital stay and increased medical expenses (p = 0.009 and p = 0.001). In the patients with CLI, significant factors for longer hospital stay and increased medical expenses were (1) history of distal bypass (p = 0.33 and p = 0.003, respectively) and stage 4 local lower limb status in WIfI classification (p = 0.0007 and p = 0.053). PAD severity was associated with prolonged postoperative hospital stay and increased medical expenses. The presence or absence of CLI and its severity according to the WIfI classification correlated with medical expenses and hospital stay duration between the milder and severe groups.

Objective: To elucidate the outcomes of open surgery for popliteal artery aneurysm (PAA) in a single Japanese institution. Materials and Methods: Between 1999 and 2016, 35 patients (44 PAAs) underwent open surgery in our department. The first-line surgical strategy involved the medial approach, with excision of the aneurysm sac and autologous vein bypass grafting. Associations between the outcomes and 1) the surgical management of the aneurysmal sac (aneurysmectomy vs. ligation with bypass) and 2) the preoperative clinical symptoms were evaluated. Results: There were no aneurysm-related deaths during the follow-up period (mean, 4 years; range, 1 - 17.6 years). The 5-year primary, primary-assisted, and secondary patency rates were 67.9%, 72.7%, and 94.5%, respectively. Re-intervention was required for 19 PAAs (14 patients), including two PAAs in patients with suspected Behcet’s disease. Patency rates did not differ between the aneurysmectomy and ligation groups. Remnant sac enlargement occurred in 3 cases. Among asymptomatic patients, clinical symptoms did not deteriorate; however, the ankle brachial pressure index decreased ≥0.15 in patients with artery-graft mismatching. Conclusion: Patency rates were good, and our modified ligation with bypass procedure, which involves excising the sac as much as possible, exhibited less risk in terms of remnant sac enlargement compared to that in previous studies.

A malignant tumor can cause hypercoagulation and it also often coexists with thrombosis. Cisplatin-based chemotherapy can also induce adverse vascular effects, including arterial thrombosis. We herein report a case of acute arterial thrombosis in a patient undergoing postoperative adjuvant cisplatin-based chemotherapy for completely resected lung cancer. The patient complained of acute leg pain after chemotherapy, and computed tomography revealed multiple thrombi from the thoracic to popliteal arteries. Arterial thrombosis during adjuvant chemotherapy is extremely rare; however, careful clinical observation of patients receiving cisplatin-based chemotherapy is important, because arterial thrombosis, even in the absence of the primary malignant tumor, is possible.

Low rates of arteriovenous fistula (AVF) maturation prevent optimal fistula use for hemodialysis; however, the mechanism of venous remodeling in the fistula environment is not well understood. We hypothesized that the embryonic venous determinant Eph-B4 mediates AVF maturation. In human AVF and a mouse aortocaval fistula model, Eph-B4 protein expression increased in the fistula vein; expression of the arterial determinant Ephrin-B2 also increased. Stimulation of Eph-B-mediated signaling with Ephrin-B2/Fc showed improved fistula patency with less wall thickness. Mutagenesis studies showed that tyrosine-774 is critical for Eph-B4 signaling and administration of inactive Eph-B4-Y774F increased fistula wall thickness. Akt1 expression also increased in AVF; Akt1 knockout mice showed reduced fistula diameter and wall thickness. In Akt1 knockout mice, stimulation of Eph-B signaling with Ephrin-B2/Fc showed no effect on remodeling. These results show that AVF maturation is associated with acquisition of dual arteriovenous identity; increased Eph-B activity improves AVF patency. Inhibition of Akt1 function abolishes Eph-B-mediated venous remodeling suggesting that Eph-B4 regulates AVF venous adaptation through an Akt1-mediated mechanism.

Autogenous vein grafts remain the gold standard conduit for arterial bypass, particularly for the treatment of critical limb ischemia. Vein graft adaptation to the arterial environment, i.e., adequate dilation and wall thickening, contributes to the superior performance of vein grafts. However, abnormal venous wall remodeling with excessive neointimal hyperplasia commonly causes vein graft failure. Since the PREVENT trials failed to improve vein graft outcomes, new strategies focus on the adaptive response of the venous endothelial cells to the post-surgical arterial environment. Eph-B4, the determinant of venous endothelium during embryonic development, remains expressed and functional in adult venous tissue. After surgery, vein grafts lose their venous identity, with loss of Eph-B4 expression; however, arterial identity is not gained, consistent with loss of all vessel identity. In mouse vein grafts, stimulation of venous Eph-B4 signaling promotes retention of venous identity in endothelial cells and is associated with vein graft walls that are not thickened. Eph-B4 regulates downstream signaling pathways of relevance to vascular biology, including caveolin-1, Akt, and endothelial nitric oxide synthase (eNOS). Regulation of the Eph-B4 signaling pathway may be a novel therapeutic target to prevent vein graft failure.

Background The use of drug-coated balloons (DCBs) with anti-proliferative agents in treating femoropopliteal lesions was approved in Japan in 2017. A better limb salvage rate or amputation-free rate of DCBs relative to plain old balloon angioplasty (POBA) has been reported; however, there is little evidence of the direct effect on intimal hyperplasia (IH). Case presentation A 70-year-old man with chronic limb-threatening ischemia and foot gangrene had undergone bypass surgery from the left common femoral artery to the dorsalis pedis artery 2 years earlier. We evaluated the bypass graft using ultrasonography and found stenosis around the proximal anastomotic site, presumably due to IH. POBA was performed every 3 months due to the repeated re-stenosis of the lesion. Since using the DCB, no restenosis has been detected to date (10 months). Conclusion DCB might be an effective tool for treating re-stenosis due to IH or vein grafts that do not respond to POBA.

Central venous stenosis is an important entity contributing to arteriovenous fistula (AVF) failure. A murine AVF model was modified to create a partial ligation of the inferior vena cava (IVC) in the outflow of the fistula, mimicking central venous stenosis. Technical aspects of this model are introduced. The aorta and IVC are exposed, following an abdominal incision. The infra-renal aorta and IVC are dissected for proximal clamping, and the distal aorta is exposed for puncture. The IVC at the midpoint between the left renal vein and the aortic bifurcation is carefully dissected to place an 8-0 suture beneath the IVC. After clamping the aorta and IVC, an AVF is created by puncturing the infra-renal aorta through both walls into the IVC with a 25 G needle, followed by ligating a 22 G intra-venous (IV) catheter and IVC together. The catheter is then removed, creating a reproducible venous stenosis without occlusion. The aorta and IVC are unclamped after confirming primary hemostasis. This novel model of central vein stenosis is easy to perform, reproducible, and will facilitate studies on AVF failure.

BACKGROUND Wound healing is one of the most important endpoints after revascularization for critical limb ischemia. The purpose of this study was to evaluate the risk factors for wound healing after revascularization for critical limb ischemia (CLI). METHODS A retrospective study was conducted at a single university hospital, and data were collected retrospectively between January 2005 and September 2016. All admitted patients who were diagnosed with CLI and underwent revascularization for the first time were enrolled. The risk factors for wound healing were analyzed. RESULTS The risk factors for wound healing were analyzed in 153 patients. The cumulative rate of wound healing at 12 months after revascularization was 79%. The independent risk factors for wound healing were non-ambulatory status (hazard ratio, 1.95; 95% CI [1.22-3.21], P=0.004), and wound, ischemia and foot infection (WIfI) stage 4 (hazard ratio, 1.89; 95% CI [1.25-2.91], P=0.002). CONCLUSIONS In our study, non-ambulatory status and WIfI stage 4 were independent risk factors for wound healing after revascularization. WIfI criteria well reflected the prognosis of patients with CLI in wound healing, as well as limb salvage.

Objective— Arteriovenous fistulae (AVF) are the most common access created for hemodialysis; however, many AVF fail to mature and require repeated intervention, suggesting a need to improve AVF maturation. Eph-B4 (ephrin type-B receptor 4) is the embryonic venous determinant that is functional in adult veins and can regulate AVF maturation. Cav-1 (caveolin-1) is the major scaffolding protein of caveolae—a distinct microdomain that serves as a mechanosensor at the endothelial cell membrane. We hypothesized that Cav-1 function is critical for Eph-B4–mediated AVF maturation. Approach and Results— In a mouse aortocaval fistula model, both Cav-1 mRNA and protein were increased in the AVF compared with control veins. Cav-1 KO (knockout) mice showed increased fistula wall thickening ( P =0.0005) and outward remodeling ( P P =0.0001; Cav-1 KO, P =0.7552; Cav-1 RC, P =0.0002). Cavtratin—a Cav-1 scaffolding domain peptide—decreased AVF wall thickness in WT mice and in Eph-B4 het mice compared with vehicle alone (WT, P =0.0235; Eph-B4 het, P =0.0431); cavtratin also increased AVF patency (day 42) in WT mice ( P =0.0275). Conclusions— Endothelial Cav-1 mediates Eph-B4–mediated AVF maturation. The Eph-B4-Cav-1 axis regulates adaptive remodeling during venous adaptation to the fistula environment. Manipulation of Cav-1 function may be a translational strategy to enhance AVF patency.

Derivation of functional vascular smooth muscle cells (VSMCs) from human induced pluripotent stem cells (hiPSCs) to generate tissue-engineered blood vessels (TEBVs) holds great potential in treating patients with vascular diseases. Herein, hiPSCs were differentiated into alpha-smooth muscle actin (α-SMA) and calponin-positive VSMCs, which were seeded onto polymer scaffolds in bioreactors for vascular tissue growth. A functional TEBV with abundant collagenous matrix and sound mechanics resulted, which contained cells largely positive for α-SMA and smooth muscle myosin heavy chain (SM-MHC). Moreover, when hiPSC-derived TEBV segments were implanted into nude rats as abdominal aorta interposition grafts, they remained unruptured and patent with active vascular remodeling, and showed no evidence of teratoma formation during a 2-week proof-of-principle study. Our studies represent the development of the first implantable TEBVs based on hiPSCs, and pave the way for developing autologous or allogeneic grafts for clinical use in patients with vascular disease.

Background Ankle brachial index can be falsely elevated in cases of medial arterial calcification, and its clinical use should be limited, especially in patients with diabetes. The aim of this study was to evaluate the potential role of pulse volume recording in detecting falsely elevated ankle brachial index. Methods Two parameters of the pulse waveform were automatically calculated: upstroke time and percentage mean artery pressure. Pulse volume recordings were retrospectively evaluated in 171 consecutive patients (342 limbs); 73 (43%) had a diagnosis of diabetes. Results On multivariate analysis, diabetes (hazard ratio = 1.7), ankle brachial index ≤ 0.90 (hazard ratio = 4.4), upstroke time ≥ 180 ms (hazard ratio = 2.1), and percentage mean artery pressure ≥ 45% (hazard ratio = 2.8) were significantly related to toe brachial index 0.90. The difference between ankle brachial index and toe brachial index differentiated the limbs of diabetic patients, with percentage mean artery pressure ≥ 45%, from controls (0.45 ± 0.17 vs. 0.35 ± 0.16, p = 0.03); upstroke time was not found to be a discriminating factor. Conclusions Although measurement of ankle brachial index remains the gold standard for diagnosing peripheral arterial disease, percentage mean artery pressure, automatically obtained in ankle brachial index measurement, may be useful to detect falsely elevated ankle brachial index, especially in patients with diabetes.

Background Carotid endarterectomy is the established treatment for carotid artery stenosis, and remains the primary surgical option due to its superior outcomes compared to carotid arterial stenting. However, Japanese patients are known to have unfavorable anatomical conditions for carotid endarterectomy, with a relatively higher level of the carotid artery bifurcation than in the Western population. We investigated the outcomes of carotid endarterectomy in our institute and evaluated the procedural quality by comparing patients based on higher or lower lesion levels. Methods The clinical data of 65 patients who underwent carotid endarterectomy were collected retrospectively. The outcomes reviewed included stroke-free survival and stroke-free rate. The patients were divided into a higher group ( n = 25) and a lower group ( n = 40), based on lesion location in respect of the 2nd cervical vertebral level. Results There was no perioperative death and only one case of stroke in the higher group within 30 days after carotid endarterectomy. At 5 years after carotid endarterectomy, the stroke-free survival rates were 83.4% in the higher group and 87.8% in the lower group, while the stroke-free rates were 96.0% and 94.0%, respectively; there were no significant differences between groups. Conclusions Stenotic lesion level did not affect the outcome or procedural quality of carotid endarterectomy.

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases, veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared with the venous environment. Successful venous adaptation to the arterial environment is critical for long-term success of the vein graft or AVF and, in both cases, is generally characterized by venous dilation and wall thickening. However, AVF are exposed to a high flow, high shear stress, low-pressure arterial environment and adapt mainly via outward dilation with less intimal thickening. Vein grafts are exposed to a moderate flow, moderate shear stress, high-pressure arterial environment and adapt mainly via increased wall thickening with less outward dilation. We review the data that describe these differences, as well as the underlying molecular mechanisms that mediate these processes. Despite extensive research, there are few differences in the molecular pathways that regulate cell proliferation and migration or matrix synthesis, secretion, or degradation currently identified between vein graft adaptation and AVF maturation that account for the different types of venous adaptation to arterial environments.

Several models of arteriovenous fistula (AVF) have excellent patency and help in understanding the mechanisms of venous adaptation to the arterial environment. However, these models fail to exhibit either maturation failure or fail to develop stenoses, both of which are critical modes of AVF failure in human patients. We used high-resolution Doppler ultrasound to serially follow mice with AVFs created by direct 25-gauge needle puncture. By day 21, 75% of AVFs dilate, thicken, and increase flow, i.e., mature, and 25% fail due to immediate thrombosis or maturation failure. Mature AVF thicken due to increased amounts of smooth muscle cells. By day 42, 67% of mature AVFs remain patent, but 33% of AVFs fail due to perianastomotic thickening. These results show that the mouse aortocaval model has an easily detectable maturation phase in the first 21 days followed by a potential failure phase in the subsequent 21 days. This model is the first animal model of AVF to show a course that recapitulates aspects of human AVF maturation.

The purpose of this study was to examine the contextual interference effect modulated by skill level in the throwing of different ball types by pitchers. College and high school baseball pitchers were asked to throw straight balls and breaking balls to the outside half and lower half of the home plate. Twenty pitchers were divided into 4 groups, determined by a combination of practice order (random or blocked) and skill level (high or low). A pretest comprised 10 trials (5 straight balls and 5 breaking balls in random order); 40 trials in a practice session were divided into 4 blocks, 10 trials each; and a posttest and retention test (after one day) involved 10 trials, similar to the pretest. The main finding of interest was an interaction effect of skill level with practice order in the retention test. For the low level pitchers there was no difference of practice order groups. However, for the high level pitchers, those in the random practice order group showed better control than the blocked practice order group. The result suggests that the contextual interference e?ect is modulated by skill level of pitchers.

Background In this study, we aimed to clarify both systemic and local prognosis after surgical interventions for critical limb ischemia (CLI) due to vasculitis or connective tissue related disease, and to search for any risk factors that can worsen the prognosis. Methods One hundred and ninety three patients that underwent surgical interventions for CLI between 2005 and 2014 were followed up for a median of 2.7 years. The patients were grouped into a group with vasculitis or connective tissue related disease (V) or with atherosclerosis (control: C). Two groups were retrospectively reviewed and compared. Results Thirty-one patients were grouped into the V group. At three years after intervention, V group showed significantly higher survival rate compared to C group (89% vs. 73%). On the other hand, limb survival rate after bypass surgery was significantly lower (74% vs. 94%), due to lower patency of the bypassed graft. Within V group, preoperative skin perfusion pressure of lower than 20 mmHg showed significantly worse prognosis of the limb. (HR 1.8; P=0.01) Regarding specific diseases, systemic scleroderma, rheumatoid arthritis and systemic lupus erythematosus tended to show worse prognosis. Conclusions Patients with CLI due to vasculitis or connective tissue related disease have a longer life expectancy with lower limb salvage rate that can lead to low quality of the remaining life.

BACKGROUND Distal bypass is the first-line treatment for patients with critical limb ischemia (CLI). In Japanese high-volume centers, approximately half of these patients are on hemodialysis (HD). We have treated such patients first with bypass using a multidisciplinary perioperative strategy. We reveal the recent characteristics of patients who underwent distal bypass and the surgical outcomes in Japan, especially focusing on the foot conditions by using the wound, ischemia, and foot infection (WIfI) classification.Methods and Results:The 152 patients underwent distal bypass in a tertiary center hospital, and we compared patients on HD (HD group) to those not on HD (non-HD group). There were significant differences between the 2 groups in the overall survival, major adverse cardiac event-free survival and amputation-free survival (AFS) rates (P

Background The poor clinical results that are frequently reported for arteriovenous fistulae (AVF) for hemodialysis are typically due to failure of AVF maturation. We hypothesized that early AVF maturation is associated with generation of reactive oxygen species and activation of the hypoxia-inducible factor-1 (HIF-1) pathway, potentially promoting neointimal hyperplasia. We tested this hypothesis using a previously reported mouse AVF model that recapitulates human AVF maturation. Methods Aortocaval fistulae were created in C57Bl/6 mice and compared with sham-operated mice. AVFs or inferior vena cavas were analyzed using a microarray, Amplex Red for extracellular H2O2, quantitative polymerase chain reaction, immunohistochemistry, and immunoblotting for HIF-1α and immunofluorescence for NOX-2, nitrotyrosine, heme oxygenase-1 (HO-1), and vascular endothelial growth factor (VEGF)-A. Results Oxidative stress was higher in AVF than that in control veins, with more H2O2 (P = 0.007) and enhanced nitrotyrosine immunostaining (P = 0.005). Immunohistochemistry and immunoblot showed increased HIF-1α immunoreactivity in the AVF endothelium; HIF-1 targets NOX-2, HO-1 and VEGF-A were overexpressed in the AVF (P

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.

BACKGROUND Patients with both cardiothoracic lesions and abdominal aortic aneurysm (AAA) are increasing in Japan. The objective of this study was to clarify the effect of 2-staged surgery on complication rates. METHODS AND RESULTS Three hundred and forty-six patients who underwent elective surgery for infrarenal AAA were entered. History of cardiac and thoracic aortic surgery within 1 year before AAA repair was recorded. A retrospective study regarding perioperative complications was performed. Operative mortality and complication rates were 0.6% and 10.7%, respectively. Seventy patients (20.2%) underwent prior cardiac and thoracic aortic surgery before AAA repair. There was no significant difference in preoperative characteristics between the group with prior cardiac and thoracic aortic surgery and the group without prior surgery. Significant risk factors for postoperative morbidity were: (1) prior cardiac and thoracic aortic surgery (odds ratio [OR] 2.5; 95%CI 1.1-5.1); (2) open aneurysm repair (OAR) (OR 2.7; 95%CI 1.3-5.1); and (3) VSG-CRI score ≥6 (OR 2.9; 95%CI 1.2-6.8). Subanalysis revealed that, although prior cardiac and thoracic aortic surgery was still a risk within patients undergoing OAR, it was not a risk factor for patients undergoing endovascular aneurysm repair (EVAR). CONCLUSIONS Prior cardiac and thoracic aortic surgery carries high risk for AAA repair. To lower complication rates, we propose to perform EVAR on these patients if they are anatomically suitable.

Objective: The CHADS2 score is a stroke risk stratification scheme in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to determine whether the CHADS2 score can help to predict the risk of non-cerebral acute arterial embolism. Materials and Methods: One hundred and seventeen patients who underwent surgery for non-cerebral acute arterial embolism with NVAF between 1997 and 2009 were enrolled in the cross sectional study. The CHADS2 score of each patient was calculated at the onset of symptoms. The distribution of the CHADS2 score was compared with that of other studies analyzing patients with stroke. Results: The perioperative mortality was 11.1%. A comparison of patients with stroke revealed that our distribution curves were significantly shifted to the left, showing that the CHADS2 score did better in predicting stroke than non-cerebral embolism. On the other hand, the distribution in our series coincides with that of NVAF patients in general. These results indicated that the risk of non-cerebral embolism occurs at the same rate regardless of the CHADS2 score. Conclusions: The CHADS2 scoring system seems to be an unreliable predictor of non-cerebral embolism, and may not contribute in avoiding potentially life-threatening acute arterial occlusion of the peripheral artery.

Acute occlusion of the digital arteries frequently causes painful infarction requiring digital amputation. We describe a 55-year-old male patient who presented with acute onset of digital ischemia with impending gangrene on the right hand. Because angiography revealed bypass surgery was not feasible, he underwent thoracoscopic sympathectomy (TS) one week after onset of the symptom, which resulted in rapid pain resolution. He was diagnosed, thereafter, with malignant rheumatoid arthritis and methotrexate was administered. Postoperative angiography revealed that the occluded digital artery had become recanalized. Timely TS is therefore a treatment of choice for acute digital ischemia.

症例は77歳の男性で，回盲部を中心とした腸管壊死に対し同部位を緊急切除後も，食後の腹痛があり血管撮影検査で小腸が下腸間膜動脈のみで支配される腹部アンギーナと診断した．待機手術準備中に再度腸管壊死および汎発性腹膜炎を発症．自家静脈がなく，人工血管による血行再建を必要としたが，感染を考慮し腸切除のみとした．腹腔内汚染が落ち着いてから血行再建の方針として中心静脈栄養管理としていたが，腸管壊死が再度認められた．腸切除のみでは今後も腸管壊死を繰り返すおそれがあったため，緊急で虚血回腸切除・人工肛門造設・人工血管による上腸間膜動脈へのバイパスを施行した．術後経過は良好で，人工血管感染や短腸症候群を呈することなく人工肛門も閉鎖できた．腸切除と人工血管を使用する手術は2期的手術が原則であるが，止むを得ず行う場合には厳密な術中操作を施行すれば可能であると考えられた．

To determine the midterm outcomes of distal bypass surgery for very elderly patients, and to determine the ideal candidates for this procedure.Of 268 consecutive patients (328 limbs) with critical limb ischemia who were treated between 2006 and 2013, 106 (126 limbs) underwent distal bypass and were retrospectively reviewed. Nineteen patients (22 limbs) were aged ≥80 years (very elderly group) and 87 patients (104 limbs) were aged80 years (control group).The baseline characteristics differed between the 2 groups in terms of regular hemodialysis rate (very elderly group, 4 [21%] vs control group, 60 [69%]; P = .0002) and the Charlson comorbidity index (very elderly group, 3.2 ± 1.7 vs control group, 5.0 ± 2.0; P = .0005). According to the Rutherford category of limb ischemia (4/5/6), the very elderly and control groups were classified as 5/17/0 and 11/87/6, respectively (P = .18). Before the surgery, 17 patients (77%) and 67 patients (64%) were ambulatory in the very elderly and control groups, respectively. At follow-up at 29 ± 22 months, the rates of primary (P = .33) and secondary patency (P = .14), limb salvage (P = .50), survival (P = .26), amputation-free survival (P = .42), major adverse limb event and also perioperative death (P = .11), and major adverse cardiovascular events (P = .36) did not significantly differ between the groups. In multivariate analysis, a history of coronary artery disease (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.9; P = .005), preoperative nonambulatory status (HR, 4.2; 95% CI, 2.1-8.1; P.0001), and serum albumin levels3 g/dL (HR, 2.7; 95% CI, 1.3-5.4; P = .01) were significantly related to poor amputation-free survival. Thirteen patients (59%) remained ambulatory at the latest follow-up. In 91 patients (110 limbs) with tissue loss, the Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on Wound, Ischemia, and foot Infection classification stages 3 and 4 negatively affected complete wound healing, according to multivariate analysis (HR, 0.34; 95% CI, 0.20-0.61; P = .0005).A very elderly age should not preclude a patient from undergoing distal bypass surgery. A history of coronary artery disease, a nonambulatory status, and hypoalbuminemia, along with the Wound, Ischemia, and foot Infection classification for patients with tissue loss, should be carefully considered to obtain the most benefit from distal bypass surgery.

Laminar shear stress (SS) induces an antiproliferative and anti-inflammatory endothelial phenotype and increases Klf2 expression. We altered the diameter of an arteriovenous fistula (AVF) in the mouse model to determine whether increased fistula diameter produces disturbed SS in vivo and if acutely increased disturbed SS results in decreased Klf2 expression. The mouse aortocaval fistula model was performed with 22, 25, or 28 gauge needles to puncture the aorta and the inferior vena cava. Duplex ultrasound was used to examine the AVF and its arterial inflow and venous outflow, and SS was calculated. Arterial samples were examined with western blot, immunohistochemistry, and immunofluorescence analysis for proteins and qPCR for RNA. Mice with larger diameter fistulae had diminished survival but increased AVF patency. Increased SS magnitudes and range of frequencies were directly proportional to the needle diameter in the arterial limb proximal to the fistula but not in the venous limb distal to the fistula, with 22-gauge needles producing the most disturbed SS in vivo. Klf2 mRNA and protein expression was diminished in the artery proximal to the fistula in proportion to increasing SS. Increased fistula diameter produces increased SS magnitude and frequency, consistent with disturbed SS in vivo. Disturbed SS is associated with decreased mRNA and protein expression of Klf2. Disturbed SS and reduced Klf2 expression near the fistula are potential therapeutic targets to improve AVF maturation.

Objective Surgical treatment of arterial lesions associated with Behcet disease (BD) is often complicated by graft occlusion and recurrence of aneurysms. The purpose of this study was to clarify the long-term outcome of surgical intervention for arterial involvement in BD. Methods Ten patients with BD (9 men, 1 woman) who underwent surgical treatment for arterial aneurysms between 1980 and 2004 were included in the study. The age of patients at the first operation ranged from 36 to 69 years (mean, 50.4 ± 9.0 years). The mean period between the onset of BD and that of arterial manifestations was 8.0 ± 5.0 years. We retrospectively reviewed their postoperative courses, including survival, graft occlusion, formation of anastomotic false aneurysms, and the development of aneurysms at different sites. The Kaplan-Meier method was used to calculate the chronologic incidence of complications after surgery. Results The mean follow-up period was 133 ± 92 months, ranging from 5 to 285 months. One patient died of rupture of a dissecting aortic aneurysm after undergoing several surgical interventions for multiple aneurysms. There were five graft occlusions among 21 grafts. The cumulative primary graft patency rate in the infrainguinal region was 83.9% at 3 years. Five anastomotic false aneurysms formed among 49 anastomoses between grafts and host arteries. The overall cumulative incidence of formation of anastomotic pseudoaneurysm was 12.9% at 5 and 10 years. All of them formed within 18 months after surgery. Development of new aneurysms in different arteries was observed in two patients. Conclusions Early occurrence of anastomotic false aneurysm is characteristic of BD. Further investigation is necessary to establish effective postoperative treatment.

Background Pretreatment with antibiotics is commonly performed before surgical implantation of prosthetic materials. We previously showed that pericardial patches are infiltrated by macrophages and arterial stem cells after implantation into an artery. We hypothesized that antibiotic pretreatment would diminish the number of cells infiltrating into the patch, potentially affecting early neointimal formation. Methods Bovine pericardial patches were pretreated with saline, bacitracin (500 U/mL), or cephalexin (10 mg/mL) for 30 minutes before implantation into the Wistar rat infrarenal aorta. Patches were retrieved on day 7 or day 30 and analyzed for histology and cell infiltration. Markers of proliferation, apoptosis, vascular cell identity, and M1 and M2 macrophage subtypes were examined using immunofluorescence and immunohistochemistry. Extracted proteins were analyzed by Western blot. Results At day 7, pericardial patches pretreated with bacitracin or cephalexin showed similar amounts of neointimal thickening ( P = .55) and cellular infiltration ( P = .42) compared with control patches. Patches pretreated with antibiotics showed similar proliferation ( P = .09) and apoptosis ( P = .84) as control patches. The cell composition of the neointima in pretreated patches was similar to control patches, with a thin endothelial layer overlying a thin layer of smooth muscle cells ( P = .45), and containing similar numbers of CD34-positive ( P = .26) and vascular endothelial growth factor receptor 2-positive ( P = .31) cells. Interestingly, within the body of the patch, there were fewer macrophages ( P = .0003) and a trend towards fewer endothelial progenitor cells ( P = .051). No M1 macrophages were found in or around any of the patches. M2 macrophages were present around the patches, and there was no difference in numbers of M2 macrophages surrounding control patches and patches pretreated with antibiotics ( P = .24). There was no difference in neointimal thickness at day 30 between control patches and patches pretreated with antibiotics ( P = .52). Conclusions Pretreatment of bovine pericardial patches with the antibiotics bacitracin or cephalexin has no detrimental effect on early patch healing, with similar neointimal thickness, cellular infiltration, and numbers of M2 macrophages compared with control patches. These results suggest that the host vessel response to patch angioplasty using pericardial patches is adaptive remodeling (eg, arterial healing).

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta and inferior vena cava (IVC) are exposed. The proximal infrarenal aorta and the distal aorta are dissected for clamp placement and needle puncture, respectively. Special attention is paid to avoid dissection between the aorta and the IVC. After clamping the aorta, a 25 G needle is used to puncture both walls of the aorta into the IVC. The surrounding connective tissue is used for hemostatic compression. Successful creation of the AVF will show pulsatile arterial blood flow in the IVC. Further confirmation of successful AVF can be achieved by post-operative Doppler ultrasound.

A 61-year-old woman with multiple splanchnic arterial aneurysms (SAAs) was transferred to our hospital in a state of shock. She underwent coil embolization under the diagnosis of ruptured pancreaticoduodenal artery aneurysm. Follow-up computed tomography performed 2 weeks later showed rapid enlargement of a gastric artery aneurysm, and she underwent an additional embolization. Atherosclerotic, inflammatory or hereditary causes were excluded, and the patient was clinically diagnosed with segmental arterial mediolysis accompanied by multiple SAAs, one of which showed acute remodeling after endovascular treatment.

A 72 year-old man was admitted to the hospital to receive treatment for resting pain and an ulcer, which had developed on an amputation stump, 4 months after he had undergone a thrombectomy, below-the-knee popliteal-dorsal pedis artery bypass of his left leg, and digital amputation of his 2nd toe. Angiography demonstrated diffuse arterial and bypass occlusion in his left leg that did not include a sural artery, which was the main collateral. Therefore, the patient underwent reversed saphenous vein bypass from the common femoral artery to the medial sural artery. His leg pain disappeared, and the ulcer healed promptly.

Objective: To identify the outcome of below knee bypass that focuses on the functional status and to investigate whether preoperative functional status can predict these outcomes. Materials and Methods: One hundred and fifty one limbs in one hundred and thirty two patients that underwent below knee bypass between 2004 and 2008 were retrospectively reviewed. The patients were grouped as “ambulatory,” “non-ambulatory transfer” and “non-ambulatory bedridden,” according to their functional status. Clinical success was defined as the achievement of all of following end points; graft patency to wound healing, limb salvage for 1 year or until death, maintenance of ambulatory status for 1 year, and survival for 6 months. The effect of preoperative ambulatory status was analyzed. Results: The overall primary and secondary graft patency, limb salvage and survival at 1 year were 76.3%, 81.8%, 89.1% and 84.1%, respectively. The overall success rate was 62.0%. Clinical success rates for the ambulatory and non-ambulatory groups were 75.6% and 34.9% (P = 0.0009, OR: 4.4; 95% CI: 1.8–10.6). Conclusions: Bypass surgery is justified for maintaining the independent status of ambulatory patients. On the other hand, the high likelihood of poor outcomes for non-ambulatory patients must be considered before performing bypass surgery.

Objective The aim of this study was to examine whether the plantar flexion test could adequately replace treadmill testing in patients who were unable to exercise. Design Prospective observational study. Patients Twenty-seven patients with intermittent claudication secondary to peripheral arterial disease (PAD). Methods Patients performed two treadmill tests and two plantar flexion tests. Ankle pressure, near infrared spectroscopy (NIRS) data, heart rate and blood pressures were monitored along with pain-free and maximum walking distances for treadmill, pain-free and maximum exercise time for plantar flexion. Results Maximum exercise time and walking distance were well correlated (R=0.74). Eleven patients (41%) developed non-claudicating symptoms during the treadmill test but not during the flexion test. Rate pressure product was significantly higher after the treadmill but not after the plantar flexion. Conclusions Plantar flexion test showed good reliability and correlation. Plantar flexion may serve as an alternative to treadmill testing in evaluating muscle pain in patients with intermittent claudication.

Objective. In Japan, the incidence of both colorectal carcinoma and vascular disease is increasing. We screened preoperative patients with abdominal aortic aneurysm (AAA) or peripheral artery disease (PAD) for colorectal cancer. Design of study. This study was retrospective and cross-sectional. Materials. The subjects were 492 patients admitted for elective surgery of AAA or PAD. Methods. The patients underwent immunochemical faecal occult blood tests (FOBT) before operation, and those with positive results underwent investigations for colorectal neoplasm. We compared the results with that of screening programmes performed on the general population. Results. Of the 408 patients that underwent FOBT, 104 (25.5%) were positive. After colonoscopy, six (1.5%) had colorectal carcinoma and 16 (3.9%) had advanced adenoma. These values were several folds higher than that for the general population in Japan. Conclusions. Patients with AAA or PAD carry a high risk for colorectal neoplasm.

Methods: The 2-hour and 24-hour attachment of Staphylococcus aureus TCH1516 and Pseudomonas aeruginosa PA01-UW was determined on polytetrafluoroethylene, Dacron, nitinol, cobalt chromium, and Viabahn endoprosthesis. Individually and in combination, concentrations at 104, 105, 106, 107, and 108 were tested on 2-mm sections of each graft. After each time interval, the prosthetics were rinsed to remove nonattached bacteria, sonicated to release the attached bacteria, spiral plated, and then analyzed for the attached concentration. Results: After 2 hours, there was a significant difference in the median attachment rates on Dacron (14%) compared with nitinol (2.1%), cobalt (1.4%), and Viabahn (0.73%) across all bacterial combinations (P < .05). Pseudomonas aeruginosa achieved the greatest attachment at most concentrations, regardless of the material. At the 24-hour mark, the median attachment for each concentration was greater than the highest initial concentration (108), with nitinol and cobalt having a statistically significant lower attachment (P < .05). Conclusions: Initial attachment is consistently poor, regardless of inoculation concentration, but greater on the synthetic grafts compared with metal stents. However, after 24 hours in a nutrient-poor environment, Staphylococcus aureus and Pseudomonas aeruginosa are still able to achieve full attachment throughout.