Keiji Yoshiya

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.

BubR1 insufficiency impairs angiogenesis in aging and in experimental critical limb ischemic mice

Objectives: Budding uninhibited by benzimidazole‐related 1 (BubR1), a cell cycle‐related protein, is an essential component of the spindle checkpoint that regulates cell division. Mice in which BubR1 expression is reduced to 10% of the normal level display the phenotypic features of progeria. However, the role of BubR1 in vascular diseases and angiogenesis remains unknown. To investigate the influence of BubR1 on angiogenesis, we generated a low‐null‐BubR1‐expressing (BubR1L/−) mouse strain with reduced BubR1 expression as low as 15% of the normal level without any abnormalities in appearance. Methods: To elucidate the role of BubR1 in angiogenesis, we used a hind limb ischemia model induced in BubR1L/− mice and age‐matched wild‐type (WT) littermates. To evaluate the pathologic influence of BubR1 on angiogenesis, we measured the blood flow before and after hind limb ischemia surgery, and the expression of typical angiogenic factors in vivo and in vitro. Results: In WT mice, blood flow in the ischemic left limb gradually recovered to approximately 80%, 14 days after surgery. Conversely, in the BubR1L/− group, blood flow in the left ischemic limb recovered to at most 30% (14 days after surgery, P < .01; immediately after the operation, and 5 and 9 days after surgery, P < .05). In adductor and calf muscles from BubR1L/− mice, regenerated muscle bundles, granulation tissue, and inflammatory cell invasion were more evident than in calf muscles from WT mice at 14 days after surgery. All WT mice at 14 days after surgery had complete limb salvage, but loss of limbs was observed in approximately 70% of BubR1L/− mice (P < .05). The vascular endothelial growth factor protein increase in ischemic hind limb muscles was lower in BubR1L/− mice compared with WT mice (P < .05), and vascular endothelial growth factor levels in human aortic smooth muscle cells treated with BubR1 knockdown siRNA were lower compared with scramble siRNA under hypoxic conditions (P < .01). HIF1&agr; protein levels in the muscles after hind limb ischemia surgery were also significantly lower in BubR1L/− mice compared with WT mice (P < .05). Conclusions: BubR1 insufficiency impairs angiogenesis and results in limb loss in ischemic hind limbs. BubR1 may be a crucial angiogenic factor and might be beneficial for the treatment of limb ischemia. Clinical Relevance: Aging impairs angiogenesis, mediates endothelial dysfunction, and leads to increased prevalence of both cardiovascular disease and adverse sequelae in the elderly. These pathologies lead to higher mortality and an elevated risk of limb amputation. BubR1, a cell cycle‐related protein, is a crucial factor in aging. This study presents novel findings indicating that BubR1 insufficiency impairs angiogenesis and results in limb amputation in the critical limb ischemic mouse model. We also showed that the decrease in BubR1 expression was associated with a reduction in vascular endothelial growth factor expression and hypoxia inducible factor‐1&agr; instability. Therefore, BubR1 insufficiency delayed angiogenesis, which eventually resulted in limb loss.

Functional prognosis of critical limb ischemia and efficacy of restoration of direct flow below the ankle

Objective Patients with critical limb ischemia have serious systemic comorbidities and are at high risk of impairment of limb function. In this study, we assessed the prognostic factors of limbs after revascularization. Methods In this retrospective single-center cohort study, from April 2008 to December 2012, we treated 154 limbs of 121 patients with critical limb ischemia by the endovascular therapy-first approach based on the patients’ characteristics. The primary end point was amputation-free survival. Secondary end points were patency of a revascularized artery, major adverse limb events, or death. Furthermore, we investigated the ambulatory status one year after revascularization as prognosis of limb function. Results Endovascular therapy was performed in 85 limbs in 65 patients as the initial therapy (endovascular therapy group) and surgical reconstructive procedures (bypass group) were performed in 69 limbs in 56 patients. Early mortality within 30 days was not observed in either group. The primary patency rate was significantly better in the bypass group than in the endovascular therapy group (p < 0.0001). Furthermore, the secondary patency rate was similar between the two groups (p = 0.0096). There were no significant differences in amputation-free survival and major adverse limb event between the two groups. Univariate analysis showed that ulcer healing (p < 0.0001), no hypoalbuminemia (p = 0.0019), restoration of direct flow below the ankle (p = 0.0219), no previous cerebrovascular disease (p = 0.0389), and Rutherford 4 (p = 0.0469) were predictive factors for preservation of ambulatory status one year after revascularization. In multivariate analysis, ulcer healing (p < 0.0001) and restoration of direct flow below the ankle (p = 0.0060) were significant predictors. Conclusions Ulcer healing and restoration of direct flow below the ankle are independently associated with prognosis of limb functions in patients who undergo infrainguinal arterial reconstruction.

Prognostic factors of ulcer healing and amputation-free survival in patients with critical limb ischemia

Objective A multidisciplinary approach is required to treat critical limb ischemia. We determined the poor prognostic factors of ischemic ulcer healing after optimal arterial revascularization, and assessed the efficacy of the medication therapy using cilostazol, which is a selective inhibitor of phosphodiesterase 3. Methods In this retrospective, single-center, cohort study, 129 limbs that underwent infrainguinal arterial revascularization for Rutherford class 5 critical limb ischemia were reviewed. The primary end point was the ulcer healing time after arterial revascularization. The secondary end point was the amputation-free survival rate. Results Of the 129 limbs, endovascular therapy was performed in 69 limbs, and surgical reconstructive procedures were performed in 60 limbs for initial therapy. Complete ulcer healing was achieved in 95 limbs (74%). The median ulcer healing time was 90 days. In multivariate analysis, no cilostazol use significantly inhibited ulcer healing (p = 0.0114). A white blood cell count >10,000 (p = 0.0185), a major defect after debridement (p = 0.0215), and endovascular therapy (p = 0.0308) were significant poor prognostic factors for ulcer healing. Additionally, ischemic heart disease (p < 0.0001), albumin levels <3 g/dl (p = 0.0016), no cilostazol use (p = 0.0078), and a major defect after debridement (p = 0.0208) were significant poor prognostic factors for amputation-free survival rate. Conclusions Ulcer healing within 90 days after arterial revascularization is impaired by no cilostazol use, a white blood cell count >10,000, a major defect after debridement, and endovascular therapy. Furthermore, cilostazol improves amputation-free survival rate in patients with critical limb ischemia.

Successful surgical intervention for rectal perforation due to polyarteritis nodosa: report of a case

BackgroundPolyarteritis nodosa (PAN) is a primary systemic necrotizing vasculitis with diffuse organ involvements, resulting in a high mortality rate due to multiple organ failure. Although the small bowel is the frequently targeted organ of PAN-associated vasculitis, rectal involvement is very rare, and only one case of rectal bleeding has been previously reported. The mortality rate of PAN with gastrointestinal (GI) perforation is reportedly much higher than that of without severe GI involvement. We herein report the first case of rectal perforation due to PAN, successfully managed with an adequate surgical intervention.Case presentationA 66-year-old woman with PAN had abdominal pain and melena with guarding. Computed tomography scan showed abdominal free air and bubbles in the rectal hematoma. We diagnosed it acute peritonitis, and emergency surgery was performed. After removing rectal hematoma and necrotic tissue, a huge lack of rectal wall spreading to the pelvirectal space was observed. In order to totally remove the necrotic tissue, abdominoperineal resection was needed. Together with histopathological examinations which showed neutrophils and fibrinous necrosis, we finally diagnosed rectal perforation due to PAN. At 19-month follow-up after surgery, she was still healthy with a stable disease of PAN.ConclusionsWe herein reported the first case of successfully managed rectal perforation due to PAN. Early adequate surgical resection may be important for the case with rectal perforation.

A theoretical model to predict tensile deformation behavior of balloon catheter

In this technical note, a simple theoretical model was proposed to express the tensile deformation and fracture of balloon catheter tested by the ISO standard using piece-wise linear force-displacement relations. The model was then validated by comparing with the tensile force-displacement behaviors of two types of typical balloon catheters clinically used worldwide. It was shown that the proposed model can effectively be used to express the tensile deformation behavior and easily be handled by physicians who are not familiar with mechanics of materials.