One Year Outcomes of Zilver PTX Versus Eluvia for Femoropopliteal Disease in Real-World Practice: REALDES Study.

PURPOSE: This multicenter, prospective, observational study aimed to compare Zilver PTX and Eluvia stents in real-world settings for treating femoropopliteal lesions as the differences in the 1-year outcomes of these stents have not been elucidated. MATERIALS AND METHODS: Overall, 200 limbs with native femoropopliteal artery disease were treated with Zilver PTX (96 limbs) or Eluvia (104 limbs) at 8 Japanese hospitals between February 2019 and September 2020. The primary outcome measure of this study was primary patency at 12 months, defined as a peak systolic velocity ratio of ≤2.4, without clinically-driven target lesion revascularization (TLR) or stenosis ≤50% based on angiographic findings. RESULTS: The baseline clinical and lesion characteristics of Zilver PTX and Eluvia groups were roughly comparable (of all limbs analyzed, approximately 30% presented with critical limb-threatening ischemia, approximately 60% presented with Trans-Atlantic Inter-Society Consensus II C-D, and approximately half had total occlusion), except for the longer lesion lengths in the Zilver PTX group (185.7±92.0 mm vs 160.0±98.5 mm, p=0.030). The Kaplan-Meier estimates of primary patency at 12 months were 84.9% and 88.1% for Zilver PTX and Eluvia, respectively (log-rank p=0.417). Freedom from clinically-driven TLR rates were 88.8% and 90.9% for Zilver PTX and Eluvia, respectively (log-rank p=0.812). CONCLUSIONS: The results of the Zilver PTX and Eluvia stents were not different regarding primary patency and freedom from clinically-driven TLR at 12 months after treating patients with femoropopliteal peripheral artery disease in real-world settings. CLINICAL IMPACT: This is the first study to reveal that the Zilver PTX and Eluvia have similar results in real-world practice when the proper vessel preparation is performed. However, the type of restenosis in the Eluvia stent may differ from that in the Zilver PTX stent. Therefore, the results of this study may influence the selection of DES for femoropopliteal lesions in routine clinical practice.

Endovascular Aneurysm Repair With Inferior Mesenteric Artery Embolization for Preventing Type II Endoleak: A Prospective Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of inferior mesenteric artery (IMA) embolization during endovascular aneurysm repair (EVAR) in patients at high risk of type II endoleak (T2EL) in randomized controlled trial (RCT). SUMMARY BACKGROUND DATA: Several studies have demonstrated a reduction of T2EL by IMA embolization before EVAR. However, there have been no RCT confirming the efficacy of IMA embolization. METHODS: Patients scheduled for elective EVAR between April 2014 and March 2018 were eligible. Patients at high risk of T2EL (IMA patency with IMA ≥3 mm, LAs ≥2 mm, or an aortoiliac-type aneurysm) were prospectively randomized to receive EVAR with or without IMA embolization. The primary endpoint was occurrence of T2EL during follow-up. Secondary endpoints included aneurysmal sac changes, adverse events from IMA embolization, and reintervention rate due to T2EL. This trial is registered with the University Hospital Medical Information Network, number UMIN000022147. RESULTS: One hundred thirteen patients had high risk and 106 were randomized. In the intention-to-treat analysis, the incidence of T2EL was significantly lower in the embolization group [24.5% vs 49.1%; P = 0.009, absolute risk reduction = 24.5%; 95% confidence interval (CI), 6.2-40.5, number needed to treat = 4.1; 95% CI, 2.5-16.1]. The aneurysmal sac shrunk significantly more in the embolization group (-5.7 ±â€Š7.3 mm vs -2.8 ±â€Š6.6 mm; P = 0.037), and the incidence of aneurysmal sac growth related to T2EL was significantly lower in the embolization group (3.8% vs 17.0%; P = 0.030). There were no complications related to IMA embolization or reinterventions associated with T2EL. CONCLUSIONS: Our results demonstrated the effectiveness of IMA embolization during EVAR in high-risk patients for the prevention of T2EL, which is suggested for avoiding aneurysmal sac enlargement related to T2EL.

[Surgery in Elderly Patient for Coronary Arteriovenous Fistula and Giant Coronary Artery Aneurysm Associated with Cardiac Failure;Report of a Case].

An 82-year-old woman visited the hospital with the chief complaint of dyspnea on light exertion. Computed tomography (CT) showed a coronary artery aneurysm and coronary arteriovenous fistulas. The pulmouary flow/systemic flow (Qp/Qs) ratio was 1.4, and the left-to-right shunt rate was 31%.Two anomalous vessels were identified. One arose from the right coronary artery, formed an aneurysm, and drained into the coronary sinus, while the other originated from the distal circumflex branch and drained directly into the coronary sinus. The aneurysm measured 50×45 mm. The anomalous vessel from the right coronary artery was ligated at the sites of flow from the right coronary artery and at the site of drainage into the coronary sinus. The circumflex artery was ligated at the last branch and at the site of drainage into the coronary sinus. The aneurysm was incised and the vessel flowing into the aneurysm was sutured closed. Postoperative CT showed no anomalous blood vessel and the circumflex artery was visualized up to the last branch.

Focal Adhesion Kinase Promotes the Progression of Aortic Aneurysm by Modulating Macrophage Behavior.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear. APPROACH AND RESULTS: We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-α-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages. FAK also promotes macrophage chemotaxis. In mice, the administration of a FAK inhibitor that tempers local macrophage accumulation markedly suppresses the development and progression of chemically induced AAA. CONCLUSIONS: FAK plays a key role in macrophage behavior, which underlies the chronic progression of AAA. These findings provide insights into AAA progression and identify FAK as a novel therapeutic target.

Identification of Anatomical Risk Factors for Type II Endoleak to Guide Selective Inferior Mesenteric Artery Embolization.

BACKGROUND: It is unclear which patients are the best candidates for inferior mesenteric artery (IMA) embolization to reduce type II endoleak (ELII). Therefore, this study aimed to identify the anatomical risk factors for ELII after endovascular aneurysm repair (EVAR) and to determine the best candidates for preventative, preoperative IMA embolization. MATERIALS AND METHODS: Between April 2007 and September 2014, 196 patients underwent standard EVAR. Anatomical risk factors of postoperative, persistent ELII were detected using logistic regression analysis. Preoperative treatment of the IMA occlusion in patients with anatomical risk factors was performed to reduce ELII. RESULTS: ELII was detected in 48 patients (24.5%). Overall, patency of the IMA (odds ratio [OR], 4.13; P = 0.004) and lumbar artery (LA) diameter ≥2.0 mm (OR, 3.30; P = 0.008) were significant risk factors for ELII, whereas an Endurant stent graft protected against ELII (OR, 0.22; P = 0.023). However, in patients with patent IMA, IMA diameter ≥3.0 mm (OR, 4.09; P = 0.011), LA diameter ≥2.0 mm (OR, 3.16; P = 0.043), and aortoiliac aneurysm (OR, 6.36; P = 0.026) were significant risk factors for ELII. Incidence rates of ELII in patients with and without these factors were 37.8% and 11.2%, respectively. ELII did not occur in patients with risk factors who underwent treatment of preoperative IMA occlusion. CONCLUSIONS: Patients with these risk factors are the candidates for undergoing treatment of preoperative IMA occlusion to reduce ELII.

[One-stage Surgery for a Non-Marfan Elderly Patient with Aortic Regurgitation and Pectus Excavatum].

We describe a case of 1-stage surgery comprising aortic valve replacement and thoracoplasty that was performed on an elderly patient with a good result. An 85 -year-old man visited our hospital with the chief complaint of chest discomfort. Examination revealed aortic regurgitation and pectus excavatum. Respiratory dysfunction, pulmonary hypertension, and cardiac failure were observed. We considered that pectus excavatum could affect breathing and circulation after surgery;therefore, we decided to perform a 1-stage surgery comprising aortic valve replacement and thoracoplasty. The costal cartilage and xiphoid process were resected, and median sternotomy was performed. The internal thoracic artery and vein were preserved. Aortic valve replacement was performed per the usual method. The resected costal cartilage was placed back at its site and the periosteum was sutured. The medially resected sternum was fixed and lifted with Kirschner wire. The patient recovered without any complication.

Treatment Options for Celiac Stenosis and Pancreaticoduodenal Artery Aneurysms.

Celiac stenosis may result in a pancreaticoduodenal artery aneurysm (PDAA). Celiac stenosis with a PDAA is rare and treatment guidelines are absent. Here, we report 4 cases of celiac stenosis treated using different methods. Of these, 3 involved PDAAs. The PDAAs were successfully treated with coil embolization. For celiac stenosis, we performed open surgery for decompression in 1 patient, stenting in 2 patients, and bypass grafting in 1 patient. In the patients who underwent stenting, stent-associated thrombosis occurred. PDAAs can be treated with coil embolization; however, treatment of celiac stenosis with the endovascular approach might be difficult.

Innovative Procedure for Inferior Mesenteric Artery Embolization Using the Amplatzer Vascular Plug 4 during Endovascular Aneurysm Repair.

PURPOSE: The aim of this study is to present an easy and quick technique for embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm repair (EVAR). TECHNIQUE: We performed IMA embolization using a conventional EVAR device alone with the femoral artery approach during EVAR, which has not been reported previously. First, a 16F or 18F DrySeal Sheath is inserted from the femoral artery into the site around the IMA. Second, cannulation is performed in the IMA with an angiography catheter having a 0.038-inch inner lumen that is used for gate cannulation during EVAR. Third, IMA embolization is performed using the Amplatzer Vascular Plug 4 (AVP4). The use of the DrySeal Sheath facilitates cannulation of the IMA, and its combination with a stent-graft balloon allows the AVP4 to be placed at the root of the IMA without deviation of the catheter. The success rate of the procedure was 90.9% (30/33 cases). The median procedure time was 11.6 min. No complications due to IMA embolization were noted. CONCLUSION: This procedure enables safe and quick placement of the AVP4 in the IMA using the catheter insertion approach from the femoral artery, which has been conventionally regarded as difficult.

A study of leg edema in immobile patients.

BACKGROUND: Our objectives were to elucidate the pathophysiology of leg edema in immobile patients and to discuss reasonable management of this condition. METHODS AND RESULTS: The 30 patients with leg edema had visited our clinic between April 2009 and March 2013; they suffered from severe gait disturbance, had no significant venous abnormalities detected using duplex ultrasound, and did not have any systemic diseases that could cause leg edema. Here, we review their symptoms, examinations, and treatments. Among 59 edematous legs of the 30 patients, 30 legs (51%) had symptoms that indicated advanced chronic venous insufficiency. The ankle range of motion and calf : ankle circumference ratio were abnormal in only 3 (5%) and 10 (17%) of the legs, respectively. The severity of edema and subcutaneous inflammation, which was confirmed using ultrasonography, was significantly influenced by gravity. Air plethysmography and lymphangioscintigraphy were completed in 15 and 10 patients, respectively, neither of which revealed any significant abnormalities. Reasonable success for all patients was achieved by compression therapy and physical therapy without medications. CONCLUSIONS: It was assumed that leg edema in these immobile patients was mainly caused by venous stasis because of the immobility itself, not because of anatomical problems. The patients were successfully managed by compression and physical therapy alone.

Fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography for diagnosis of infected aortic aneurysms.

BACKGROUND: Infected aortic aneurysms are diagnosed on the basis of a positive bacterial blood culture, clinical evidence of inflammation, and morphologic findings on computed tomography (CT). However, preoperative diagnosis is often difficult because blood cultures are frequently negative and patients can be asymptomatic. Because therapeutic approaches differ significantly, it is vital to determine whether an aortic aneurysm is infected prior to surgery. METHODS: From June 2007 to July 2012, we investigated 11 cases of suspected infected aortic aneurysm using fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET/CT). In addition to contrast-enhanced CT examination, blood culture and histologic examinations were performed to aid diagnosis. RESULTS: Patients with a final diagnosis of infected aortic aneurysms showed a maximum standard uptake value (SUVmax) of >4.46, whereas infection-free cases had an SUVmax of <2.59 (mean 6.5 ± 1.8 vs. 1.9 ± 0.5; P < 0.001). CONCLUSION: FDG-PET/CT examination is useful in the diagnosis of infected aortic aneurysms.

Re-evaluation of qualitative lymphangioscintigraphic findings in secondary lower extremity lymphedema.

PURPOSE: To re-evaluate whether qualitative lymphangioscintigraphy (LAS) findings are sensitive enough to diagnose or classify the clinical severity of lower extremity lymphedema. METHODS: LAS was performed in 78 extremities with lymphedema and 24 extremities without lymphedema between April, 2009 and March, 2012. We assessed the proportion of extremities in which there was no visual evidence of the ilioinguinal lymph nodes (LN-60) or the lymphatic trunk (Tr-60) 60 min after tracer injection, the number of visualized ilioinguinal lymph nodes (#LN), and the proportion of extremities with dermal backflow (pDBF) and lymph stasis (pLS). These were associated with the International Society of Lymphology (ISL) clinical stage. RESULTS: LN-60, Tr-60, #LN, pDBF, and pLS, especially when extending into both the thigh and lower leg, were significantly associated with the ISL stage. The sensitivity of LN-60, Tr-60, and #LN <2 for diagnosing lymphedema was 49, 47, and 59 %, respectively, with no significant difference among these parameters for consecutive ISL stages. CONCLUSIONS: None of the above measures was sufficiently sensitive to diagnose lymphedema or classify the severity of the disease; however, each of these criteria can aid in diagnosis, by excluding other diseases and assessing disease pathophysiology.

Important role of the angiotensin II pathway in producing matrix metalloproteinase-9 in human thoracic aortic aneurysms.

BACKGROUND: The precise pathologic mechanisms underlying human thoracic aortic aneurysms (TAAs) remain uncertain, except that matrix metalloproteinase-9 (MMP-9) is considered a key enzyme for the degradation of extracellular matrix in aneurysm walls. The aim of this study was to elucidate the significance of the angiotensin II (AngII) pathway to MMP-9 production in human TAA walls. METHODS AND RESULTS: We examined the activation of Smad2, a common downstream molecule of AngII and transforming growth factor ß (TGF-ß) pathways, and the expression of MMP-9 in human nonsyndromic TAA walls. We observed significant increases in Smad2 activation and MMP-9 expression, associated with disruption of elastic lamellae. Using human TAA walls in ex vivo culture, we investigated whether AngII and/or TGF-ß pathways are essential for MMP-9 production. Unexpectedly, TGF-ß receptor inhibitor had no effect on MMP-9 production. We used PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) activation, and demonstrated that PD98059 dramatically reduced MMP-9 production with attenuation of Smad2 activation. Moreover, exogenous AngII resulted in increases in Smad2 activation and MMP-9 production, in an ERK-dependent manner. CONCLUSION: Our findings indicate that the AngII/ERK pathway has an important role in the production of MMP-9 in human nonsyndromic TAA walls.

[Technical Report: Quality Assurance for 125I Seed Sources in Permanent Prostate Brachytherapy].

This technical report provides useful information on the current status and issues of quality control in 125I seed source strength measurement for Permanent Prostate Brachytherapy in Japan.With the spread of 125I seed brachytherapy, the traceability of source strength measurements with the single-seed assay was established in Japan. This allows medical facilities to measure reference air kerma rate of 125I seeds with their own well-type of ionization chamber. However, it is difficult to maintain the traceability chain because the 125I reference air kerma rate standards have been hardly utilized by medical facilities so far. Meanwhile, some serious incidents of contamination of the different source strengths and dead seeds were reported in Japan.To address the specific issues in Japan, JASTRO Brachytherapy Subcommittee established a working group (WG) in 2021. The goal of this WG is to investigate the management methods of source strength measurement used in medical facilities, and to discuss the ideal and practicable methods of source management such as verifying the number of seeds and source strength. Initially, a questionnaire survey was conducted to facilities offering 125I seed brachytherapy in Japan. Sixty-seven out of 95 facilities responded (response rate 70.5%). This survey revealed that 41% of facilities did not perform either confirmation of the number of seeds or measurement of source strength. There are several reasons why the source strength was not measured in those facilities. For example, 125I seeds are provided under the sterilized conditions; quality assurance by source suppliers is reliable; and there is not sufficient staff.The single-seed assay is regarded as an internationally standardized and the most reliable measurement method. Therefore, it is an essential measurement technique to ensure traceability of source strength measurements. However, our survey found that most Japanese facilities do not perform single-seed assays. Meanwhile, some facilities have performed batch assay as an alternative method, in which all of the multiple sources in a batch are measured while loaded into sterilized cartridges. Although the measurement by the batch assay is less accurate than the one by the single-seeded assay, the batch assay does not require re-sterilization of the source and can be performed quickly. It might be useful to detect unexpected errors such as differences in the number of sources and abnormalities in source strength.In this report, we will introduce several methods of source strength measurement that have been implemented in medical facilities. The quality assurance of 125I seed sources in prostate interstitial brachytherapy should be provided not only by the source suppliers but also by the medical facilities that use sources to treat patients. We hope that medical facilities will refer to this technical report and use it as an aid to quality assurance in their own facilities.

Primary lymphedema complicated by weeping chylous vesicles in the leg and scrotum: report of a case.

We report a case of primary lymphedema complicated by leaking chylous vesicles in the toe and scrotum, caused by lymphangiectasia, which was eventually managed with lymphaticovenular anastomoses after conservative treatments proved ineffective. The patient was a 25-year-old man with a 5-year history of massive swelling with chylous weeping of his right leg and scrotum. Lymphangioscintigraphy (LAS) showed dilated iliac lymph trunks causing lymph reflux. Although he was instructed in standard methods of complex therapy, it did not alleviate his symptoms. Because of the increasing frequency of cellulitis, lymphatic surgery was finally indicated. The operation consisted of lymphaticovenous anastomoses (LVA) in the ankle and groin, using a super-micro-surgical technique. After surgery, his symptoms resolved and have been controlled by self-care. Thus, early LAS to confirm the dilated iliac lymph trunks causing lymph reflux, followed by LVA might be beneficial for the management of this disease.

Lymphocyte antigen 6 complex locus G6D downregulation is a novel parameter for functional impairment of neutrophils in aged mice.

Immunological aging is a critical event that causes serious functional impairment in the innate immune system. However, the identification markers and parameters are still poorly understood in immunological aging of myeloid lineage cells. Here, we show that a downregulation of lymphocyte antigen 6 complex locus G6D (Ly-6G) observed in aged mouse neutrophils could serve as a novel marker for the prediction of age-associated functional impairment in the neutrophils. Ly-6G expression was significantly downregulated in the bone marrow (BM) neutrophils of aged mice compared to young mice confirmed by flow cytometry analysis. In vitro experiments using BM-isolated neutrophils showed significant downregulations in their activities, such as phagocytosis, reactive oxygen species (ROS) production, interleukin (IL)-1ß production, neutrophil extracellular trap (NET) formation, and migration as well as bacterial clearance, in the aged mouse neutrophils compared to those of young mice counterparts. Interestingly, the magnitudes of functional parameters were strongly correlated with the Ly-6G expression in the neutrophils. Thus, our results suggest that downregulation of Ly-6G reflects the age-associated functional attenuation of the neutrophils.

Correlation Between the Severity of Subcutaneous Echo-Free Space and the Amount of Extracellular Fluid Determined by Bioelectrical Impedance Analysis of Leg Edema.

BACKGROUND: Both subcutaneous echo-free space (SEFS) observed by ultrasonography and the ratio of intracellular fluid resistance to extracellular fluid resistance (Ri/Re) calculated from bioelectrical impedance analysis (BIA) represent extracellular edema status in the extremities. We tried to correlate these parameters. METHODS AND RESULTS: In 70 legs with venous edema (VE) and 68 legs with lymphedema (LE), subcutaneous tissue ultrasonography to determine SEFS severity (range, 0-2) and BIA to calculate Ri/Re were performed. In the calf, SEFS severity showed good linear correlation with Ri/Re, particularly in the lower lateral calf where the mean Ri/Re for LE (SEFS grade 0: 3.2 ± 0.8; SEFS grade 1: 4.0 ± 0.9; SEFS grade 2: 6.3 ± 3.6) and VE (SEFS grade 0: 3.6 ± 0.6; SEFS grade 1: 4.4 ± 1.6; SEFS grade 2: 5.3 ± 2.0) was similar. In the thigh, a mild correlation was confirmed only in LE. CONCLUSIONS: It may be concluded that SEFS in the lower calf area well represents the local fluid status regardless of the type of edema, but not so in the thigh.

Differentiation of functional venous insufficiency and leg lymphedema complicated by functional venous insufficiency using subcutaneous tissue ultrasonography.

OBJECTIVE: To use subcutaneous ultrasonography to differentiate legs with edema because of obesity-related functional venous insufficiency (FVIob), immobility-related FVI (FVIim), secondary lymphedema (LE), LE complicated by obesity (LEob), and LE complicated by immobility (LEim). METHODS: Ninety-nine legs with edema (16 FVIob, 32 FVIim, 22 LE, 9 LEob, and 20 LEim), and 10 normal legs were examined. Subcutaneous tissue ultrasonography was performed at eight points (medial, lateral, upper, lower, thigh, and calf) in each leg. Subcutaneous echogenicity (SEG) and subcutaneous echo-free space (SEFS) were assessed, and each graded as 0, 1, and 2 according to their severity. RESULTS: In normal legs, SEG and SEFS were graded 0 in almost all parts of the leg. SEG was diffusely increased in FVIob, whereas SEG was increased in accordance with gravity in FVIim (upper medial thigh, 0.6 ± 0.5 vs lower medial calf, 1.2 ± 0.4; P < .001). In LE, SEG was increased in the medial side, particularly evident in upper thigh (upper medial thigh, 1.1 ± 0.4 vs upper lateral thigh, 0.6 ± 0.6; P < .01). SEFS was increased in accordance with gravity in all of these legs (FVIob: upper medial thigh, 0.2 ± 0.4 vs lower medial calf, 0.7 ± 0.8; P = .05; FVIim: upper medial thigh, 0.1 ± 0.2 vs lower medial calf, 1.3 ± 0.7; P < .0001; LE: upper medial thigh, 0.4 ± 0.7 vs lower medial calf, 0.9 ± 0.9; P < .05). The increases of SEG and SEFS in legs with LEob or LEim were diffuse and similar. As determined via stepwise logistic regression analyses, the increases in SEG in the upper medial thigh and SEFS in the lower medial thigh in LE cases, the increases in SEG in the upper lateral thigh and SEFS in the lower lateral thigh in cases with obesity-related leg edema (ie, FVIob and LEob), and the increase in SEFS in the lower lateral calf in cases with immobility-related leg edema (ie, FVIim and LEim) were determined to be significant factors to characterize each leg edema. CONCLUSIONS: Differences in the extent and distribution of SEG and SEFS might help in differentiating LE from FVIob and FVIim, although assessment of LE complicated by obesity vs immobility remains difficult.

Risk Factors in Patients with Venous Stasis-Related Skin Lesions without Major Abnormalities on Duplex Ultrasonography.

Purpose: To clarify the risk factors for venous stasis-related skin lesions in the legs in patients without major abnormalities on duplex ultrasonography (DUS). Methods: Fifty patients (nine males and 41 females, age 27-93 years) with symptoms of C4 or greater according to the Clinical, Etiological, Anatomical, Pathological (CEAP) classification, but having no abnormalities on DUS were reviewed for known risk factors for chronic venous insufficiency (CVI) such as older age (>70 years), obesity (body mass index [BMI] >30 kg/m2), short walking distance (<200 m/day), reduced ankle range of motion (<20°), and occupation requiring prolonged standing (>8h per day). Results: The risk factor was different between male and female patients; although all patients had at least one of the above risk factors, the most commonly found risk factor in male patients was occupation requiring prolonged standing (63%), while advanced age (78%) and limited walking distance (83%) were risk factors in female patients. Conclusions: Although male and female patients had different risk factors, insufficient walking seemed to be closely related to the development of venous stasis-related skin lesions.