Five-year follow-up of randomized clinical trial for pre-emptive inferior mesenteric artery embolization during endovascular aneurysm repair.

INTRODUCTION: Type II endoleak (T2EL) is the most common type of endoleak after endovascular aneurysm repair (EVAR) and a common indication for reintervention due to late sac enlargement. Although pre-emptive embolization of the inferior mesenteric artery (IMA) has been proposed to prevent this, no studies have prospectively demonstrated its efficacy. This study aimed to prove the validity of IMA embolization during EVAR in selective cases by analyzing the mid-term outcomes of a randomized clinical trial (RCT). METHODS: This single-center, parallel-group, non-blinded RCT included participants at high risk of T2EL, characterized by a patent IMA in conjunction with one or more following risk factors: a patent IMA ≥3 mm in diameter, lumbar arteries ≥2 mm in diameter, or an aortoiliac-type aneurysm. The participants were randomly assigned to two groups in a 1:1 ratio: one undergoing EVAR with IMA embolization and the other without. The primary endpoint was T2EL occurrence. The secondary endpoints included aneurysm sac changes and reintervention. In addition to RCT participants, outcomes of patients with low-risk of T2EL were also analyzed. RESULTS: The embolization and non-embolization groups each contained 53 patients. Five-year follow-up after the last patient enrolment revealed that T2ELs occurred in 28.3% and 54.7% of patients in the IMA embolization and non-embolization groups, respectively (P=.006). Both freedom from T2EL-related sac enlargement ≥5 mm and cumulative incidence of sac shrinkage ≥5 mm were significantly higher in the IMA embolization group than in the non-embolization group (95.5% vs. 73.6% at 5 years; P=.021, 54.2% vs. 33.6% at 5 years; P=.039). The freedom from T2EL-related sac enlargement ≥10 mm, an alternative indicator for T2EL-related reintervention, showed similar results (100% vs. 90.4% at 5 years; P=.019). Outcomes in the low-risk group were preferable than those in the non-embolization group and comparable to those in the IMA embolization group. CONCLUSION: A lower threshold for pre-emptive IMA embolization when implementing EVAR would be more appropriate if limited to patients at high risk of T2ELs.

miR-709 exerts an angiogenic effect through a FGF2 upregulation induced by a GSK3B downregulation.

The aim of this study was to identify angiogenic microRNAs (miRNAs) that could be used in the treatment of hindlimb ischemic tissues. miRNAs contained in extracellular vesicles (EVs) deriving from the plasma were analyzed in C57BL/6 mice, which have ischemia tolerance, and in BALB/c mice without ischemia tolerance as part of a hindlimb ischemia model; as a result 43 angiogenic miRNA candidates were identified. An aortic ring assay was employed by using femoral arteries isolated from BALC/c mice and EVs containing miRNA; as a result, the angiogenic miRNA candidates were limited to 14. The blood flow recovery was assessed after injecting EVs containing miRNA into BALB/c mice with hindlimb ischemia, and miR-709 was identified as a promising angiogenic miRNA. miR-709-encapsulating EVs were found to increase the expression levels of the fibroblast growth factor 2 (FGF2) mRNA in the thigh tissues of hindlimb ischemia model BALB/c mice. miR-709 was also found to bind to the 3'UTR of glycogen synthase kinase 3 beta (GSK3B) in three places. GSK3B-knockdown human artery-derived endothelial cells were found to express high levels of FGF2, and were characterized by increased cell proliferation. These findings indicate that miR-709 induces an upregulation of FGF2 through the downregulation of GSK3B.

Early Clinical Results From the Japanese Prospective Multicenter Study to Evaluate Zenith Alpha Abdominal Stent Graft for Abdominal Aortic Aneurysm (JUSTICE) Registry Demonstrate Acceptable Limb Patency at 12 Months.

PURPOSE: Recent reports of the Zenith Alpha abdominal endovascular graft (Zenith Alpha AAA, Cook, Inc., Bloomington, Indiana) have demonstrated an unexpectedly high incidence of limb graft occlusion (LGO). The purpose of this study was to prospectively evaluate the performance of the Zenith AAA in Japan, with a specific focus on LGO. MATERIALS AND METHODS: All endovascular aneurysm repairs (EVARs) for abdominal aortic aneurysms performed using the Zenith Alpha AAA from July 2020 to October 2021 in 23 Japanese hospitals were prospectively evaluated. All computed tomographic images were analyzed in the core laboratory. Late complications were defined as any aneurysm-related events occurring >30 days after EVAR, including aneurysm sac enlargement of >5 mm and any reinterventions performed. Endoleaks without sac enlargement or reintervention were excluded as late complications. RESULTS: During the study period, 147 EVARs were performed using the Zenith Alpha AAA. The mean patient age was 76.5±7.7 years, 84.4% of patients were male, and the mean aneurysm diameter was 52.4±9.2 mm. Instruction-for-use violations were observed in 76 patients (51.7%), primarily associated with a severely angulated proximal neck (>60°). There were six intraoperative complications and 62 additional intraoperative treatments reported, most of which involved preemptive coil embolization of the inferior mesenteric artery (37 cases). Technical success, defined as the absence of type 1 or 3 endoleaks on final angiography, was achieved in 99.3% of patients. At 12 months, there was only one case of type 1/3 endoleak (0.8%) and one aneurysm sac enlargement exceeding 5 mm (0.8%); however, a high incidence of type 2 endoleaks was observed in 35.2% of patients, and aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients. Nine late complications were observed, and the rate of freedom from late complications at 12 months was 93.5%, encompassing four LGOs and one limb graft stenosis (3.4%). CONCLUSIONS: In contrast to recent reports, our Japanese multicenter prospective study demonstrated satisfactory early clinical results, including an acceptable LGO rate, for the low-profile Zenith Alpha AAA. Long-term follow-ups will be performed to confirm the persistence of these outcomes. CLINICAL IMPACT: This study prospectively evaluated the performance of 147 Zenith Alpha AAAs used for endovascular aneurysm repair with core-lab adjudication focusing especially on limb graft occlusion (LGO). At 12 months, aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients, and there was only one type 1/3 endoleak, one aneurysm sac enlargement (>5 mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg." 5mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg.

Time-Dependent Changes of Extremity Volume and Tissue Alterations in Swollen Arms Caused by Taxanes.

Background: We aimed to determine the course of arm swelling caused by the use of taxanes and to identify valid predictors of persistent swelling. Methods and Results: A total of 15 patients with unilateral arm swelling that developed during the course, or within 3 months after termination, of postoperative taxane-based chemotherapy were included in the present study. The patients attended follow-up appointments every 3-6 months for 24 months after their initial visit. Their arm circumference was measured at each follow-up appointment, while ultrasonography of the skin and subcutaneous tissues was performed at the 0-, 6-, 12-, and 24-month follow-ups. Of the 15 patients, 12 (80%) saw their taxane-induced arm swelling resolved within a median of 12 months (range, 3-29 months) after their final taxane administration. Of the 12 patients whose swelling resolved, 9 did not use compression sleeves; however, their course of resolution did not differ from the other 3 patients who regularly used compression sleeves. In the three patients with persistent swelling, the excess subcutaneous thickness in the medial upper arm (median, 283%) was significantly greater than that in the patients whose swelling resolved (120%; p < 0.05) during their initial visits. Conclusions: Of the 15 patients included in the present study, 80% saw their taxane-induced arm swelling resolve within a median of 12 months after their final taxane administration, independent of the use of compression therapy. Persistent swelling may be predicted during the initial visit based on subcutaneous thickening of the medial upper arm.

Efficacy of Airbo·Wave in Nighttime Compression for Leg Lymphedema.

Objectives: This study aimed to clarify the efficacy of Airbo·Wave EV1 in nighttime compression therapy as part of complex decongestive therapy (CDT) for leg lymphedema. Patients and Methods: We retrospectively reviewed 33 patients with leg lymphedema who used Airbo·Wave EV1 between April 2021 and September 2022. In these patients, the changes in leg volume and skin hardness were assessed using a scale ranging from 1 (softest) to 7 (hardest), and dermal thickness before and after the use of Airbo·Wave EV1 was evaluated. Results: Twenty-two patients used Airbo·Wave EV1 for nighttime compression in CDT. Their skin hardness in the lower calf decreased mildly (mean scale: before, 3.9; after, 3.6 [p <0.05]), but the leg volume and skin thickness were unchanged. Eleven patients who were nonadherent could restart compression therapy by using Airbo·Wave EV1. Their skin hardness in the medial lower calf (before, 5.1; after, 4.3 [p <0.05]), leg volume (before, 8412 mL; after, 8191 mL [p <0.01]), and skin thickness in the medial and lateral lower leg were reduced. Conclusion: Airbo·Wave EV1 could improve skin hardness in the calf area. Moreover, it is a safe procedure for the nonadherent while reducing leg volume reasonably.

Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

BACKGROUND: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version.Methods and Results: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. CONCLUSIONS: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Dependent Leg Edema in Older Patients with or without Skin Lesion.

Objective: This study aimed to clarify the features and causes of dependent edema (DE) in the legs of patients in geriatrics. Patients and Methods: We retrospectively reviewed 224 patients with DE, aged ≥65 years, who visited our clinic from April 2009-March 2022. DE was defined as bilateral leg edema in patients without known systemic edemagenic conditions, venous insufficiency confirmed by duplex venous scanning, or a cancer treatment history in the pelvic/inguinal lesions. Results: The median patient age was 77 years (range: 65-94 years), where 74% were female. Overall, 198 patients (88%) had gait disturbances caused mainly by musculoskeletal disorders, but 58 (26%) walked without aid. Compared with patients with DE only (N=129), patients with DE and venous stasis-related skin lesions (N=95) included a larger number of those with obesity than did those with DE only (26% vs. 14%, p=0.02). Conclusion: The primary cause of DE in older patients was the sedentary lifestyle secondary to aging and gait disturbance, not solely because of reduced leg function. The complications of obesity are associated with increased venous stasis-related skin lesions.

Burkholderia cepacia-contaminated dentures possibly cause pneumonia.

We report a case in which a patient was suspected of developing pneumonia due to wearing dentures that were immersed in a storage solution contaminated with 3.0 × 108 colony-forming units (cfu)/mL of Burkholderia cepacia. It is highly possible that the contaminated denture solution entered the trachea and caused the pneumonia, possibly due to the prolonged supine positioning of the patient. We demonstrated that B. cepacia isolated from the sputum and B. cepacia isolated from the denture storage solution had the same DNA fingerprint, and that the patient recovered from pneumonia after stopping the use of dentures. These findings suggest the storage solution as the main source of infection.

Leg volume reduction during tiptoe movement is caused by venous ejection and calf muscle contraction.

OBJECTIVES: To clarify the cause of leg volume reduction during tiptoe movement in the standing position. METHODS: The right legs of 20 participants were assessed. The participants performed tiptoe movement in the supine position, and then stood up and performed the tiptoe movement and ankle dorsiflexion. Leg volume changes were recorded continuously using air plethysmography. RESULTS: Differences between leg volume changes due to tiptoe movement and the refilling volumes were not significantly different between the supine (59 mL) and standing (49 mL) positions, indicating that this amount of motion artifact was included in the downward trace recorded by tiptoe movement in the standing position. CONCLUSIONS: Leg volume reduction during tiptoe movement in the standing position included a significant amount of motion artifacts. Therefore, it may be difficult to accurately measure the ejection volume using tiptoe movement in the standing position.

Post-treatment course of acute lipodermatosclerosis.

OBJECTIVES: We aimed to clarify whether acute lipodermatosclerosis (LDS) progress to chronic LDS without continued compression therapy. METHODS: Between April 2015 and November 2021, 30 patients with acute/subacute LDS, which was diagnosed clinically by presence of isolated, poorly demarcated, tender erythema, and induration limited to the lower leg(s), visited our clinic and were able to be followed up for longer than a year. We reviewed their treatment results and the post-treatment courses. RESULTS: In all cases, the symptoms in the acute phase subsided with compression bandages. After the discontinuation of compression therapy, 18 legs (56%) progressed to chronic LDS, and 14 legs (44%) did not. In the legs without progression, subcutaneous tissue in the affected leg was thicker compared with that in the contralateral leg (median 19.1 mm vs. 13.4 mm, p < 0.05) on the initial visit. In the legs with progression, the difference in subcutaneous tissue thickness between the affected and unaffected legs was not significant (10.0 mm vs. 7.6 mm). CONCLUSIONS: Our findings suggest that in legs which later progress to chronic LDS, subcutaneous tissue contraction due to panniculitis is already present during the acute phase; therefore, long-term compression therapy is unlikely to improve the prognosis.

Outcomes of the Gore Excluder Iliac Branch Endoprosthesis for Japanese Patients With Aortoiliac Aneurysms: A Study Based on J-Preserve Registry.

PURPOSE: To evaluate the clinical utility of the Gore Excluder iliac branch endoprosthesis (IBE) for Japanese patients with aortoiliac aneurysms. MATERIALS AND METHODS: This was a multicenter retrospective cohort study (J-Preserve Registry). Patients undergoing endovascular aortic repair using the Gore Excluder IBE for aortoiliac aneurysms between August 2017 and June 2020 were enrolled. Data pertaining to the baseline and anatomical characteristics, technical details, and clinical outcomes were collected from each institution. The primary endpoints were technical success, IBE-related complications, and reinterventions. Secondary endpoints were mortality, aneurysm size change, and reintervention during follow-up. Technical success was defined as accurate deployment of the IBE without type Ib, Ic, or III endoleaks on the IBE sides on completion angiography. A change in aneurysm size of 5 mm or more was taken to be a significant change. RESULTS: We included 141 patients with 151 IBE implantations. Sixty-five IBE implantations (43.0%) had at least one instruction for use violation. Twenty-two patients (15.6%) required internal iliac artery (IIA) embolization for external iliac artery extension on the contralateral side. Of 151 IBE implantations, 19 exhibited IIA branch landing zones due to IIA aneurysms. Mean maximum and proximal common iliac artery (CIA) diameters were 32.9±9.9 mm and 20.5±6.9 mm, respectively. The mean CIA length was 59.1±17.1 mm. The IIA landing diameter and length were 9.0±2.3 mm and 33.8±14.6 mm. The overall technical success rate was 96.7%. There were no significant differences in IBE-related complications (2.3% vs 5.3%, p=0.86) or IBE-related reinterventions (1.5% vs 5.3%, p=0.33) between the IIA trunk and IIA branch landing groups. The mean follow-up period was 635±341 days. The all-cause mortality rate was 5.0%. There were no aneurysm-related deaths or ruptures during the follow-up. Most patients (95.7%) had sac stability or shrinkage. CONCLUSION: The Gore Excluder IBE was safe and effective for Japanese patients in the midterm. Extending the IIA device into the distal branches of the IIA was acceptable, which may permit extending indications for endovascular aortic aneurysm repair of aortoiliac aneurysms to more complex lesions. CLINICAL IMPACT: This study suggests clinical benefits of the Gore Excluder IBE for Japanese patients, despite 43% of the IBE implantations having at least one IFU violation.

Cryopreserved allogenic fibroblast sheets: development of a promising treatment for refractory skin ulcers.

The purpose of this study was to investigate the therapeutic effect of cryopreserved allogenic fibroblast cell sheets in a mouse model of skin ulcers. It is necessary to reduce the cost of regenerative medicine for it to be widely used. We consider that cell sheets could be applied to various diseases if cryopreservation of allogenic cell sheets was possible. In this study, fibroblasts were frozen using a three-dimensional freezer. Freeze-thawed fibroblasts had ~80% cell viability, secreted ≥ 50% vascular endothelial growth factor, hepatocyte growth factor, and stromal derived factor-1α compared with non-frozen fibroblast sheets, and secreted approximately the same amount of transforming growth factor-ß1. There was no difference in wound-healing rates in the skin ulcer model between non-frozen and freeze-thawed fibroblast sheets regardless of autologous and allogenic cells. The degree of angiogenesis was comparable between autologous and allogenic cells. The number of CD3-positive cells in healed tissues was larger for allogenic fibroblast sheets compared with autologous fibroblast sheets. However, histopathological images showed that the fibrosis, microvascular density, and healing phase of the wound in allogenic freeze-thawed fibroblast sheets were more similar to autologous freeze-thawed fibroblast sheets than to allogenic non-frozen fibroblast sheets. These results suggest that allogenic freeze-thawed fibroblast sheets may be a promising therapeutic option for refractory skin ulcers.

Effects of leg compression and calf muscle contraction by active ankle motion on venous hemodynamics in sitting individuals.

OBJECTIVES: To clarify the effects of compression and active ankle motion on venous hemodynamics in healthy sitting individuals. METHODS: In the sitting position, 14 participants performed plantar flexion and dorsiflexion of the ankle for 3 s each without compression. Changes in the calf volume were recorded using air plethysmography. Subsequently, the process was repeated with the application of tubular elastic bandage (TEB), followed by anti-thrombotic stocking (ATS). RESULTS: The median interface pressure at the calf was 16 mmHg with TEB and 21 mmHg with ATS. Without compression (N), the median venous volume was 76 mL. This was reduced to 58 mL with TEB and 56 mL with ATS (p < .01 vs. N for both). On the other hand, ejection volume by plantar flexion in N (27 mL) was not significantly changed with TEB (31 mL) or ATS (31 mL). Also, ejection volume by dorsiflexion in N (53 mL, p < .001 vs. plantar flexion) was not significantly changed with TEB (53 mL, p < .01 vs. plantar flexion) or ATS (41 mL, p < .05 vs. plantar flexion). CONCLUSIONS: The venous volume, which is defined as the change in enclosed calf volume from elevation to dependency, in the sitting position reduced similarly with TEB and ATS; however, the ejection volumes did not change significantly. Dorsiflexion exerted a larger ejection volume than plantar flexion in the sitting position.

Perivascular Adipose Tissue Is a Major Source of Nitric Oxide in Saphenous Vein Grafts Harvested via the No-Touch Technique.

Background Saphenous vein grafts (SVGs) are broadly used in coronary artery bypass grafting despite their inferior patency compared with arterial grafts. Recently, the no-touch technique (NT), in which an SVG is harvested with a pedicle of perivascular adipose tissue (PVAT) without conduit distension, was shown to improve long-term patency compared with conventional preparation (CV), wherein outer tissue is removed with distension. The NT was also reportedly associated with reduced atherosclerosis. Although endothelial damage provoked by conventional distension may underlie poor patency when CV is performed, the precise mechanisms underlying the salutary effects of the NT have been unclear. Methods and Results Residual SVGs prepared with CV (CV-SVGs) or NT (NT-SVGs) were obtained during coronary artery bypass grafting. Nitric oxide (NO2-/NO3- (NOx)) levels after 24 hours of tissue culture were quantified. The protein expression and localization were analyzed. The isometric force of SVG strips was measured. NT-SVGs showed superior NOx production to CV-SVGs. PVAT generated the majority of NOx in NT-SVGs. PVAT highly expressed arginosuccinate synthase 1, a rate-limiting enzyme in the molecular circuit for NO synthesis, thereby continuously providing the substrate for NO. A substantial level of endothelial NO synthase was also expressed in PVAT. Pharmacological inhibition of arginosuccinate synthase 1 or endothelial NO synthase significantly suppressed the NOx production in NT-SVGs. PVAT induced vasorelaxation through NO production, even in the endothelium-denuded SVG strips. Conclusions Preserving PVAT was predominantly involved in the superior NOx production in NT-SVGs. Since NO plays crucial roles in suppressing atherosclerosis, this mechanism may greatly contribute to the excellent patency in NT-SVGs.

Comparison of Outcomes and Complications Among Patients with Different Indications of Acute/Subacute Complicated Stanford Type B Aortic Dissection Treated by TEVAR: Data from the JaPanese REtrospective multicenter stuDy of ThoracIc Endovascular Aortic Repair for Complicated Type B Aortic Dissection (J-Predictive Study).

PURPOSE: To investigate the relationships between indications for thoracic endovascular aortic repair for acute/subacute complicated Stanford type B aortic dissection and clinical outcomes, and complications specific to thoracic endovascular aortic repair. MATERIAL AND METHODS: The J-predictive study retrospectively collected data of patients treated with thoracic endovascular aortic repair for complicated Stanford type B aortic dissection at 20 institutions from January 2012 to March 2017. From the database, those treated for acute/subacute complicated Stanford type B aortic dissection were extracted (n = 118; 96 men; average age, 66.1 years; standard deviation, ± 13) and classified into groups 1, 2, and 3 according to thoracic endovascular aortic repair indications (rupture, superior mesenteric artery malperfusion, and renal or lower extremity malperfusion, respectively). Primary and secondary measures were mortality (overall and aortic-related) and complications related to thoracic endovascular aortic repair, respectively. For each outcome, the risks of being in groups 1 and 2 were statistically compared with that of being in group 3 as a control using Fisher's exact test. RESULTS: Mortality rate (odds ratio, 5.22; 95% confidence interval [CI], 1.33-20.53) and prevalence of paraparesis/paraplegia (odds ratio, 30.46; confidence interval, 1.71-541.77) were higher in group 1 than in group 3. Compared to group 3, group 2 showed no statistically significant differences in mortality or complications related to thoracic endovascular aortic repair. CONCLUSIONS: Rupture as an indication for thoracic endovascular aortic repair for type B aortic dissection was more likely to result in worse mortality and high prevalence of spinal cord ischemia. LEVEL OF EVIDENCE: Level 4, Case series.

Hardness Sensed by Skin Palpation in Legs with Lymphedema Is Predominantly Correlated with Dermal Thickening.

Background: We aimed to clarify whether pathological changes in skin and subcutaneous tissue with lymphedema affected the skin hardness sensed by palpation. Methods and Results: In 50 patients with unilateral legs with lymphedema (LE), the skin hardness of the lower inner thigh and lower inner calf was determined using a scale ranging from 1 (softest) to 7 (hardest) based on palpation. Then, the skin hardness was correlated with the measurements of skin/subcutaneous tissue ultrasonography images obtained from the palpated parts. Multivariate logistic regression analysis demonstrated that dermal thickness was a significant factor that affected the difference in skin hardness between the LE and the contralateral asymptomatic leg for both thigh (p < 0.05) and calf (p < 0.01). When the thigh and calf in the LE were individually studied, subcutaneous echogenicity (p < 0.05), indicating subcutaneous inflammation/fibrosis, and subcutaneous thickness (p < 0.01) also seemed to affect skin hardness, respectively. Conclusions: The skin hardness sensed in the LE seemed to be affected predominantly by dermal thickening. In addition, the pathological changes in the subcutaneous tissue caused by LE seemed to have an impact on skin hardness. Clinical Trial Registration number 2020-150.

Hyperbaric Oxygen Therapy Is an Effective Adjunctive Therapy to Manage Treatment-Resistant Venous Leg Ulcers.

We report five cases of venous leg ulcers (VLU) that were resistant to conservative therapy for 22-119 months and were eventually healed via hyperbaric oxygen therapy (HBOT). In one patient, VLU recurred four times and was managed using HBOT, each time. The VLU sizes ranged from 18 to 68 cm2 before HBOT. HBOT was administered at 2.0 atmospheres absolute with 100% oxygen for 60 min per session, five sessions a week during hospitalization. All VLUs healed after 17-66 sessions of HBOT.

A pilot study using cell-mixed sheets of autologous fibroblast cells and peripheral blood mononuclear cells to treat refractory cutaneous ulcers.

BACKGROUND/AIMS: We invented a cell-mixed sheet consisting of autologous fibroblast cells and peripheral blood mononuclear cells (PBMNCs) to treat refractory cutaneous ulcers. These sheets secrete the growth factors needed throughout the wound healing process in animal models. METHODS: We performed this study as a pilot phase I clinical trial (UMIN-CTR: UMIN000031645). Fibroblast cells were isolated and cultured from the oral tissue, and PBMNCs were collected by apheresis. A cell-mixed sheet was prepared by co-culturing these collected cells for 3 days. The primary observation index was safety, including all adverse events. Additional observation indices were wound healing over 1, 3, and 6 months; wound healing rate at 7 days and 1, 3, and 6 months. RESULTS: Six patients with venous leg ulcers (VLUs) were enrolled in the study, including three patients who were treated with the cell-mixed sheet transplantation. One patient was excluded because no fibroblast cells grew from the oral tissue culture, and other two were excluded because the growth factor secreted from mixed-cell sheets did not reach the reference value. The VLUs of two patients who received the cell-mixed sheet transplantation healed, and the VLU in one patient decreased in size. CONCLUSIONS: This pilot study demonstrated that cell-mixed sheets might be a new topical intervention to treat VLUs. However, it was also suggested that this treatment might be limited when using autologous cells collected from patients with VLUs. Therefore, it may be necessary to use high-quality allogeneic cells instead of autologous cells to improve the feasibility of this treatment.

Treatment Results of Endovascular Aneurysm Repair Using the Parallel Stent-Graft Double D Technique for Distal Saccular Abdominal Aortic Aneurysms and Common Iliac Aneurysms.

BACKGROUND: Endovascular aneurysm repair (EVAR) using a bifurcated stent graft may involve technical challenges when aortic disease (aneurysm or dissection) consists of a length <70 mm between the inferior renal artery and aortic bifurcation or narrow aortic bifurcation that is common in asymmetric distal abdominal aortic aneurysms (AAAs) or iliac artery aneurysms (IAAs). We use EVAR with the double D technique (DDT-EVAR) for such cases, which involves straight type of stent grafts with same diameter in left and right that are deployed parallel to an aortic cuff that has been previously placed. In addition, DDT-EVAR can preserve the inferior mesenteric artery (IMA) for IAA. METHODS: DDT-EVAR was performed for 21 of 910 (2%) cases from April 2007 to April 2019 at our institution. The median patient age was 74 years (range, 52-85). Nineteen patients (90%) were men. Six patients (all saccular; 1 rupture) had AAAs, 12 had IAAs, and 3 had chronic type B aortic dissociation (TBAD) for re-entry closure. AAA and IAA had diameters of 45 mm (range, 34-71) and 34 mm (range, 25-58), respectively. An aortic cuff was used for 19 (90%) cases. Endurant II (Medtronic, Santa Rosa, CA) was used for 12 cases. The Excluder (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used for 7 cases. Endurant II was used for 20 cases, and the VBX (W.L. Gore & Associates, Inc) was used for 1 case as stent-graft limbs. RESULTS: The procedural success rate was 100%. The median operative time was 146 min (range, 88-324). IMA planned for preservation was successful for all 12 cases. Type I and type III endoleaks were not observed. With TBAD, flow to the false lumen decreased or disappeared, and no complications during the hospital stay were associated with the procedure. For 2 patients whose procedure involved Endurant II stent-graft limb, limb occlusions were observed postoperatively, and reintervention was required. No other patients required additional treatment at a median follow-up of 18 months (range, 4-50). CONCLUSIONS: DDT-EVAR is a safe and straightforward technique for the treatment of distal AAA, common iliac artery aneurysm, and TBAD. It may help preserve the IMA and internal iliac artery, even when it is impossible to preserve them with a bifurcated stent graft.

Extracellular Fluid Content in the Legs of Patients with Chronic Venous Disease.

BACKGROUND: This study aimed to determine the factors that affect the extracellular fluid (ECF) content in the legs of patients with chronic venous disease (CVD). METHODS: Bioimpedance analysis and air plethysmography (APG) were performed in 79 patients with CVD who visited our clinic between September 2016 and March 2019. The normal right legs (N) of 14 healthy volunteers were also reviewed for comparison. The ratio of ECF resistance (Re) of the leg to that of the arm (ReL/ReA) was used to express the ECF content in the tested leg. The severity of CVD was expressed using the clinical, etiological, anatomical, and pathophysiological (CEAP) classification. RESULTS: The ReL/ReA decreased as the CEAP class increased (N: median; 0.81 [range 0.66-0.95], C0-1: 0.79 [0.60-0.98], C2: 0.77 [0.56-1.08], C3: 0.67 [0.57-0.85], C4: 0.64 [0.44-0.89]). Older age, female sex, and CEAP class affected the ReL/ReA, but body mass index did not. The ReL/ReA did not correlate with the parameters that were derived from APG, including the venous filling index. CONCLUSIONS: We found that the ECF content in legs of patients with CVD might be primarily affected by patient-related factors and CEAP class, as opposed to venous hemodynamics.