Yutaka Matsubara

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.

Sarcopenia is a risk factor for cardiovascular events experienced by patients with critical limb ischemia

Background: Prognosis is poor for patients with critical limb ischemia (CLI), and the most frequent cause of death is cardiovascular disease. Low grip strength is a risk factor for cardiovascular events, and sarcopenia may be associated as well. Thus, we hypothesized that sarcopenia is a risk factor for cardiovascular events experienced by patients with CLI. If this is true and appropriate therapy becomes available, the prognosis of patients with CLI will improve with appropriate risk management strategies to prevent cardiovascular events. Therefore, the aim of this study was to verify this hypothesis. Methods: We studied 114 patients who underwent revascularization and computed tomography between January 2002 and December 2012 in the Department of Surgery and Sciences at Kyushu University in Japan. Sarcopenia was defined as skeletal muscle area measured by L3‐level computed tomography scan <114.0 cm2 and <89.8 cm2 for men and women, respectively. Clinical characteristics, cardiovascular event‐free survival, <2‐year death, causes of death, and effective treatments for sarcopenia were investigated. Results: We identified 53 (46.5%) patients with sarcopenia. Three‐year cardiovascular event‐free survival rates were 43.1% and 91.2% for patients with and without sarcopenia, respectively (P < .01). During follow‐up, cardiovascular disease caused the deaths of 4 and 15 patients without and with sarcopenia (P < .01), respectively, and in particular, ischemic heart disease caused the deaths of 0 and 5 patients without or with sarcopenia (P < .05), respectively. Single antiplatelet therapy (SAPT; hazard ratio, 0.46; 95% confidence interval, 0.24‐0.82; P < .01) and statin therapy (hazard ratio, 0.38; 95% confidence interval, 0.16‐0.78; P < .01) were independent factors associated with improved cardiovascular event‐free survival. Three‐year cardiovascular event‐free survival rates for patients with sarcopenia who received SAPT, dual antiplatelet therapies, and no antiplatelet therapy were 75.3%, 21.1%, and 29.5%, respectively (P < .01). Conclusions: Sarcopenia is a risk factor for worse cardiovascular event‐free survival, and SAPT and statin therapy reduced this risk for patients with CLI. Furthermore, SAPT but not dual antiplatelet therapy increased cardiovascular event‐free survival in patients with sarcopenia.

Improved quality of life in patients with no-option critical limb ischemia undergoing gene therapy with DVC1-0101.

Critical limb ischemia (CLI) has a poor prognosis and adversely affects patients’ quality of life (QOL). Therapeutic angiogenesis may improve mobility, mortality, and QOL in CLI patients. However, the effectiveness of gene therapy on such patients’ QOL is unknown. DVC1-0101, a non-transmissible recombinant Sendai virus vector expressing human fibroblast growth factor-2 gene, demonstrated safety and efficacy in a phase I/II study of CLI patients. We investigated the effects of DVC1-0101 on QOL in this cohort. QOL was assessed using the Short Form-36 health survey version 2 (SF-36) in 12 patients at pre-administration, 28 days, and 3, 6, and 12 months post-treatment. We examined differences between pre and post-administration QOL scores and correlations between QOL scores and vascular parameters. Patients demonstrated low baselines scores on every SF-36 dimension. Post-treatment scores showed significant improvements in physical functioning at 3 and 6 months (P < 0.05), role-physical at 3, 6, and 12 months (P < 0.05), bodily pain at 1, 3, 6, and 12 months (P < 0.05), vitality at 1, 6, and 12 months (P < 0.05), and physical component summary at 6 and 12 months (P < 0.05). DVC1-0101-based gene therapy may improve QOL in CLI patients over a 6-month period.

Radial forces of stents used in thoracic endovascular aortic repair and bare self-expanding nitinol stents measured ex vivo – Rapid rescue for obstruction of the innominate artery using bare self-expanding nitinol stents

Purpose Our objective was to compare the radial forces of several stents ex vivo to identify stents suitable for rescue of the unexpected coverage of aortic arch branches in thoracic endovascular aortic repair. Methods We measured the radial forces of two types of self-expanding bare nitinol stents (E-luminexx and Epic) used singly or as double-walled pairs, and of three endoprostheses used in thoracic endovascular aortic repair (TEVAR, Gore c-TAG, Relay, and Valiant) by compressing the stent using an MTS Instron universal testing machine (model #5582). We also examined the compressive effects of the TEVAR endoprostheses and the bare nitinol stents on each other. Results The radial force was greater in the center than at the edge of each stent. In all stents tested, the radial force decreased incrementally with increasing stent diameter. The radial force at the center was two times greater when using two stents than with a single stent. In the compression test, only E-luminexx used as a pair was not compressed after compressing a Relay endoprosthesis by 12 mm. Conclusion Two E-luminexx stents are appropriate to restore the blood flow if a TEVAR endoprosthesis covers the innominate artery following innominate–carotid–left subclavian arterial bypass.

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.

Late Type III Endoleak of a Powerlink Stent Graft : Report of a Case

We herein report a case of a late type III endoleak caused by disconnection of the aorta extension and main body of a Powerlink four years after implantation. Migration of the main body caused a disconnection of the main body and extension despite the fact that the size of the aneurysm had been decreasing. The endoleak was successfully repaired using the interpolation of an Endurant aortic extender. In case of necessity of implantation of the extension, first implantation of extension before deploying the main body may help to prevent type III endoleaks caused by disconnection of the stentgraft in patients treated with the Powerlink system. To our knowledge, this is the first reported case of a late type III endoleak caused by a Powerlink device.

Prognostic factor of the two-year mortality after revascularization in patients with critical limb ischemia:

Purposes The aim of this study was to evaluate the risk factors for the two-year survival after revascularization of critical limb ischemia. Methods Between 2008 and 2012, 142 patients underwent revascularization. A retrospective analysis was performed to measure the risk factor. Results A total 85 patients underwent surgical revascularization, 31 patients underwent endovascular therapy while 26 patients underwent hybrid therapy. By multivariate analysis, the following variables were considered to be risk factors: ejection fraction <50 % (HR, 3.14; 95% CI, 1.22–7.95; P = 0.02), serum albumin level <2.5 g/dL (HR, 3.45; 95% CI, 1.01–11.7; P = 0.04) and nonambulatory status (HR, 4.11; 95% CI, 1.79–9.70; P < 0.01). The two-year survival rate of the patients with no risk factors was 85.5%, while the patients with at least one risk factor had an unfavorable prognosis (one; 56.7%, two; 45.4%). Conclusions The nonambulatory status, serum albumin level <2.5 g/dL and ejection fraction <50% were the risk factors for the two-year mortality after revascularization in critical limb ischemia patients. These risk factors may be useful for the treatment strategy of critical limb ischemia patients.

BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality

A delay in liver regeneration after partial hepatectomy (PHx) leads to acute liver injury, and such delays are frequently observed in aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, and BubR1 down-regulation promotes aging-associated phenotypes. In this study we investigated the effects of BubR1 insufficiency on liver regeneration in mice. Low-BubR1-expressing mutant (BubR1L/L) mice had a delayed recovery of the liver weight-to-body weight ratio and increased liver deviation enzyme levels after PHx. Microscopic observation of BubR1L/L mouse liver showed an increased number of necrotic hepatocytes and intercalated disc anomalies, resulting in widened inter-hepatocyte and perisinusoidal spaces, smaller hepatocytes and early-stage microvilli atrophy. Up-regulation of desmocollin-1 (DSC1) was observed in wild-type, but not BubR1L/L, mice after PHx. In addition, knockdown of BubR1 expression caused down-regulation of DSC1 in a human keratinocyte cell line. BubR1 insufficiency results in the impaired liver regeneration through weakened microstructural adaptation against PHx, enhanced transient liver failure and delayed hepatocyte proliferation. Thus, our data suggest that a reduction in BubR1 levels causes failure of liver regeneration through the DSC1 abnormality.

BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E‐Deficient Mice

Background Budding uninhibited by benzimidazole‐related 1 (BubR1), a cell cycle–related protein, is an essential component of the spindle checkpoint that regulates cell division. BubR1 insufficiency causes early aging‐associated vascular phenotypes. We generated low‐BubR1‐expressing mutant (BubR1 L/L) and apolipoprotein E‐deficient (ApoE −/−) mice (BubR1 L/L ‐ApoE −/− mice) to investigate the effects of BubR1 on atherosclerosis. Methods and Results Eight‐week‐old male BubR1 L/L ‐ApoE −/− mice and age‐matched ApoE −/− mice were used in this study. Atherosclerotic lesion development after being fed a high‐cholesterol diet for 12 weeks was inhibited in BubR1 L/L ‐ApoE −/− mice compared with ApoE −/− mice, and was accompanied by decreased accumulation of macrophages. To address the relative contribution of BubR1 on bone marrow–derived cells compared with non‐bone marrow–derived cells, we performed bone marrow transplantation in ApoE −/− and BubR1 L/L ‐ApoE −/− mice. Decreased BubR1 in bone marrow cells and non‐bone marrow–derived cells decreased the atherosclerotic burden. In vitro assays indicated that decreased BubR1 expression impaired proliferation, but not migration, of bone marrow–derived macrophages. Conclusions BubR1 may represent a promising new target for regulating atherosclerosis.