Koichi Morisaki

Sarcopenia is a prognostic factor for overall survival in patients with critical limb ischemia

BACKGROUND Sarcopenia has been proposed as a prognostic factor for various diseases. Patients with critical limb ischemia (CLI) have a very poor prognosis, but sarcopenia has not been reported as a prognostic factor for CLI patients. If sarcopenia is associated with the prognosis of CLI patients, it could help select the treatment plan. Therefore, we examined whether sarcopenia is a prognostic factor for CLI patients. METHODS We performed a retrospective study of CLI patients diagnosed with Fontaine III or IV peripheral artery disease who underwent preoperative computed tomography imaging and revascularization between January 2002 and December 2009. The presence of sarcopenia was defined as skeletal muscle area of <114.0 cm(2) for men or <89.8 cm(2) for women using transverse computed tomography scans at the third lumbar vertebra. We compared the 5-year survival rate and clinical characteristics between patients with or without sarcopenia. We also screened possible prognostic factors for overall survival using hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS Of 64 eligible patients, 28 patients had sarcopenia and 36 did not. There were significant differences in age, skeletal muscle area, body mass index, and the presence of smoking, cerebrovascular disease, and hemodialysis between patients with and without sarcopenia (all P < .05). The 5-year survival rate was significantly lower in patients with sarcopenia (23.5% vs 77.5%, P = .001). Prognostic factors for overall survival were the presence of sarcopenia (HR, 3.22; 95% CI, 1.24-9.11; P = .02), requirement for hemodialysis (HR, 4.30; 95% CI, 1.60-12.2; P = .004), and postoperative complications (HR, 5.02; 95% CI, 1.90-13.7; P = .001). CONCLUSIONS Our results suggest that sarcopenia is a prognostic factor for CLI patients. Exercise and nutritional interventions focusing on improving sarcopenia might be useful treatment options for CLI patients.

Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism

OBJECTIVES Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis. DESIGN This was an experimental study. MATERIALS AND METHODS Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide synthase (eNOS) was assessed by immunoblotting. RESULTS WT mice treated with cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic surgery on post-operative day 14 based upon laser Doppler measurements of blood flow (cilostazol-treated group, 0.54 ± 0.13 vs. control group, 0.38 ± 0.11; P-<-0.05). The capillary density in the ischaemic hindlimb was also significantly greater in WT mice treated with cilostazol than in non-treated WT mice (cilostazol-treated group, 1.63 ± 0.10 vs. control group, 1.15 ± 0.12; P-<-0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb perfusion. CONCLUSIONS Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases.

Ultrasound-Guided Percutaneous Thrombin Injection for Post-Catheterization Pseudoaneurysm

BACKGROUND The efficacy and safety of ultrasound-guided thrombin injection (UGTI) for the treatment of post-catheterization femoral and brachial artery pseudoaneurysms (PSA) is unclear in Japan. METHODS AND RESULTS A retrospective study of 32 consecutive patients undergoing percutaneous UGTI of post-catheterization PSA between February 2011 and February 2014 was performed. There were 23 femoral PSA and 9 brachial PSA treated with UGTI. The prevalence of CAD and smoking history were higher in the brachial PSA patients, but there were no statistically significant differences in other patient demographic factors or in the preprocedural antiplatelet therapy between the femoral and brachial PSA patients. The median dose of thrombin injected was 200 U (range, 100-600 U). The initial success rate, early recurrence rate and surgical conversion rate were 91%, 0% and 4% in the femoral PSA, and 89%, 11% and 11% in the brachial PSA, respectively. There were 2 cases of medial nerve compression in the brachial PSA group, but there were no complications in the femoral PSA group (P=0.0198). On outpatient clinical follow-up in the successfully treated patients, there were no recurrences after an average follow-up of 16 months. CONCLUSIONS UGTI is a feasible, safe and effective less-invasive treatment for post-catheterization PSA. Brachial PSA, however, might require additional attention because of their tendency toward higher recurrence and complications.

Subclavian Artery Aneurysm in Marfan Syndrome

We present a case of a left subclavian artery aneurysm in a 48-year-old man with Marfan syndrome. Aneurysms of the subclavian artery are rare in patients with Marfan syndrome. Resection of the aneurysm and interposition with a synthetic graft were performed through a supra- and infraclavicular incision, without resecting the clavicle. Histological findings were compatible with Marfan syndrome. In patients with Marfan syndrome, regular follow-up is important because of the occurrence of peripheral aneurysms other than the aorta.

Clinical Outcome of Surgical Endarterectomy for Common Femoral Artery Occlusive Disease

BACKGROUND Although common femoral artery endarterectomy (CFE) is the standard treatment for occlusive disease of the common femoral artery (CFA), several studies have noted encouraging results for endovascular therapy in this anatomical area. METHODSANDRESULTS  A retrospective multi-center study of 118 consecutive limbs from 111 symptomatic patients undergoing CFE between April 1998 and December 2014 was performed. Seventy-five CFE were performed on limbs for intermittent claudication and 43 CFE were performed for critical limb ischemia (CLI). The prevalence of perioperative complications was higher in patients with CLI than in the claudication patients. The technical success rate was 99% in all cases. The 1- and 5-year primary patency rates were 100% and 100% for claudication and 95% and 95% for CLI, respectively. The assisted-primary patency rates were 100% at both time points in both groups. Freedom from major amputation at 1 and 5 years was 100% and 100% in the claudication patients and 93% and 82% in the CLI patients, respectively. The 1- and 5-year overall survival rates were 97% and 89% in the claudication patients and 69% and 33% in the CLI patients, respectively. CONCLUSIONS CFE is a safe, effective and durable procedure for occlusive disease of the CFA. This procedure should remain the standard treatment for this anatomical region.

Risk factors for wound complications and 30-day mortality after major lower limb amputations in patients with peripheral arterial disease

Purpose Risk factors for wound complications or 30-day mortality after major amputation in patients with peripheral arterial disease remain unclear. We investigated the outcomes of major amputation in patients with peripheral arterial disease. Methods Patients who underwent major amputation from 2008 to 2015 were retrospectively analyzed. The main outcome measures were risk factors for wound complications and 30-day mortality after major lower limb amputations. Major amputation was defined as above-knee amputation or below-knee amputation. Wound complications were defined as surgical site infection or wound dehiscence. Results In total, 106 consecutive patients underwent major amputation. The average age was 77.3 ± 11.2 years, 67.9% of patients had diabetes mellitus and 35.8% were undergoing hemodialysis. Patients who underwent primary amputation constituted 61.9% of the cohort, and the proportions of above-knee amputation and below-knee amputation were 66.9% and 33.1%, respectively. The wound complication rate was 13.3% overall, 10.3% in above-knee amputation, and 19.5% in below-knee amputation. Multivariate analysis showed that the risk factors for wound complications were female sex (hazard ratio, 4.66; 95% confidence interval, 1.40–17.3; P = 0.01) and below-knee amputation (hazard ratio, 4.36; 95% confidence interval, 1.20–17.6; P = 0.03). The 30-day mortality rate was 7.6%, pneumonia comprised the most frequent cause of 30-day mortality, followed by sepsis and cardiac death. Multivariate analysis showed that a low serum albumin concentration (hazard ratio, 3.87; 95% confidence interval, 1.12–16.3; P = 0.03) was a risk factor for 30-day mortality. Conclusions Female sex and below-knee amputation were risk factors for wound complications. A low serum albumin concentration was a risk factor for 30-day mortality after major amputation in Japanese patients with peripheral arterial disease.

Efficacy and Safety of DVC1-0101 for Intermittent Claudication Secondary to Peripheral Artery Disease: Study Protocol of a Randomized Phase IIb Trial

1.1. Background: We have developed a new gene transfer vector based on nontransmissible recombinant Sendai virus expressing the human fibroblast growth factor-2 gene (DVC1-0101) to treat peripheral arterial disease. A phase I/IIa open-label four dose-escalation clinical trial for critical limb ischemia was completed. We concluded that DVC1-0101 is safe and well tolerated, and resulted in significant improvement of limb function. We present the protocol of the next phase of our study. 1.2. Methods: We plan to conduct a phase IIb clinical trial, which will be a randomized, placebo-controlled, parallel design, single-dose blinded and single center clinical trial in Japan. This study will enroll 60 patients diagnosed with PAD with intermittent claudication. Subjects who meet eligibility criteria will be randomized to receive a single dose of either placebo, 5 × 109 ciu/limb of DVC1-0101, or 1 × 109 ciu/limb of DVC1-0101 administered by direct intramuscular injection. The participation length in this trial for subjects will be approximately 12 months with nine visits. The primary endpoints are to evaluate the efficacy of DVC1-0101 versus placebo on peak walking time, and to evaluate the safety and tolerability of two dosage levels of DVC1-0101. The secondary endpoints are 1) to evaluate the effect of DVC1-0101 on claudication onset time, measured by a treadmill test and quality of life, measured using the Walking Impairment Questionnaire, 2) to determine the effect of DVC1-0101 on qualifying limb hemodynamics, and 3) to explore the pharmacodynamics of DVC1-0101 by evaluating biomarkers. 1.3. Discussion: The results of this trial will provide insights into the potential of DVC1-0101 for improving walking activities. The results will also help with the design of a possible phase III study.

Elective endovascular vs. open repair for abdominal aortic aneurysm in octogenarians.

Purpose The purpose of this study was to investigate the operative mortality and short-term and midterm outcomes of treatment of abdominal aortic aneurysm in Japanese patients over 80 years of age. Methods Between January 2007 and December 2011, 207 patients underwent elective repair of infrarenal abdominal aortic aneurysms. Comorbidities, operative morbidity and mortality, midterm outcomes were analyzed retrospectively. Results The average age (endovascular aneurysm repair, 84.4 ± 0.3; open, 82.8 ± 0.3, P < 0.01) and the percentage of hostile abdomen (endovascular aneurysm repair, 22.2%; open repair, 11.1%, P < 0.05) were higher in the endovascular aneurysm repair group. Percentage of outside IFU was higher in open repair (endovascular aneurysm repair, 38.5%; open repair, 63.3%, P < 0.01). The cardiac complication (endovascular aneurysm repair, 0%; open repair, 5.6%, P < 0.01) and length of postoperative hospital stay (endovascular aneurysm repair, 10.3 ± 0.8 days; open, 18.6 ± 1.6 days, P < 0.05) were significantly lower in the endovascular aneurysm repair group. There were no differences in operative mortality (endovascular aneurysm repair, 0%; open, 1.1%, P = 0.43) and the aneurysm-related death was not observed. The rate of secondary interventions (EVAR, 5.1%; open repair, 0%, P < 0.01) and midterm mortality rate were much higher in the endovascular aneurysm repair group. Conclusions Endovascular aneurysm repair is less invasive than open repair and useful for treating abdominal aortic aneurysm in octogenarians; however, open repair can be acceptable treatment in the inappropriate case treated by endovascular aneurysm repair.

Radial force measurement of endovascular stents: Influence of stent design and diameter

Background and purpose Angioplasty and endovascular stent placement is used in case to rescue the coverage of main branches to supply blood to brain from aortic arch in thoracic endovascular aortic repair. This study assessed mechanical properties, especially differences in radial force, of different endovascular and thoracic stents. Material and methods We analyzed the radial force of three stent models (Epic™, E-Luminexx® and SMART®) stents using radial force-tester method in single or overlapping conditions. We also analyzed radial force in three thoracic stents using Mylar® film testing method: conformable Gore®-TAG®, Relay®, and Valiant® Thoracic Stent Graft. Results Overlapping SMART stents had greater radial force than overlapping Epic or Luminexx stents (P < 0.01). The radial force of the thoracic stents was greater than that of all three endovascular stents (P < 0.01). Conclusions Differences in radial force depend on types of stents, site of deployment, and layer characteristics. In clinical settings, an understanding of the mechanical characteristics, including radial force, is important in choosing a stent for each patient.

Recurrent brachial artery embolism caused by a crutch-induced axillary artery aneurysm: report of a case

We report a case of axillary artery aneurysm with brachial artery embolism in a 60-year-old man who had walked with the assistance of axillary crutches all of his life since poliomyelitis during infancy had left him with lower limb paralysis. We performed bypass grafting from the axillary to brachial artery with exclusion of the aneurysm. An axillary artery aneurysm is rare, but potentially lethal for the upper extremity; therefore, surgical treatment should be considered.