Reduced Muscle Mass and Muscle Quality in Patients with Intermittent Claudication due to Peripheral Artery Disease.

BACKGROUND: Peripheral arterial disease (PAD) is associated with reduced muscle mass and quality, but the effects of leg ischemia caused by PAD on muscle quality remain poorly understood. The purpose of this study was to evaluate leg muscle mass and muscle quality in patients with intermittent claudication due to PAD using bioelectrical impedance analysis (BIA). METHODS: One hundred forty-one patients with intermittent claudication due to PAD who visited Tokyo Medical University Hospital from April 2019 to April 2020 were retrospectively analyzed. Leg ischemia was assessed using ankle-brachial pressure index (ABI). The skeletal muscle mass (SMM) assessed leg muscle mass, while the phase angle (PhA) assessed leg muscle quality using BIA. RESULTS: A total of 282 legs in 141 patients were included in the analysis. Leg PhA and SMM showed a decreasing trend according to the severity of leg ischemia (borderline/no ischemia: 2.80 ± 0.50 kg/m2, 4.38 ± 0.94°; mild ischemia: 2.83 ± 0.49 kg/m2, 4.33 ± 1.03°; moderate/severe ischemia: 2.50 ± 0.40 kg/m2, 3.89 ± 0. 88°; P < 0.001 and P = 0.020, respectively). The ABI was moderately correlated with leg SMM (B = 0.347, ß = 0.134, P < 0.001) and leg PhA (B = 0.577, ß = 0.111, P = 0.013) after adjustment for all significant covariates. Leg PhA was moderately correlated with leg SMM (r = 0.318, P < 0.001). CONCLUSIONS: Leg ischemia, especially when moderate or severe, has an adverse effect on both muscle mass and quality in the lower extremities and is associated with skeletal muscle myopathy.

Association of lower limb ischemia with loss of skeletal muscle mass in patients with peripheral artery disease.

PURPOSE: The influence of lower limb ischemia on the loss of skeletal muscle mass, which is a prerequisite for sarcopenia, remains poorly studied in patients with peripheral artery disease (PAD). We determined whether or not lower limb ischemia correlates with a loss of skeletal muscle mass in patients with PAD. METHODS: The data of 101 patients (202 legs) with PAD were retrospectively analyzed. Body composition was measured using a bioelectrical impedance analysis. Based on the Asian Working Group for Sarcopenia, low muscle mass (LMM) was defined as skeletal muscle mass index (SMI) < 7.00 kg/m2 (male) and < 5.70 kg/m2 (female). Both univariable and multivariable analyses of the risk factors for LMM were performed. RESULTS: There were significant differences in age, ankle-brachial pressure index (ABI) per patient, and the geriatric nutritional risk index (GNRI), between patients with and without LMM. Multivariable logistic regression analysis showed age (odds ratio [OR], 1.09; p = 0.009), GNRI (OR, 0.93; p = 0.003), and ABI per patient (OR, 0.02; p = 0.027) as independent risk factors for LMM. CONCLUSION: These data show a detrimental effect of lower limb ischemia on skeletal muscle mass loss, suggesting that PAD may affect the development of secondary sarcopenia.

Comparison of direct effects of clinically available vasodilators; nitroglycerin, nifedipine, cilnidipine and diltiazem, on human skeletonized internal mammary harvested with ultrasonic scalpel.

Direct vasodilator effects of nitroglycerin, nifedipine, cilnidipine and diltiazem on human skeletonized internal mammary artery graft harvested with ultrasonic scalpel were assessed in the presence of 0.1 or 0.2 µM of noradrenaline. Ring preparations were made of distal end section of the bypass grafts, and those dilated by acetylcholine were used for assessment. Each drug dilated the artery in a concentration-related manner (0.01-10 µM, n = 6 for each drug) with a potency of nitroglycerin > nifedipine = cilnidipine > diltiazem. These results indicate that nitroglycerin can be useful for treating internal mammary artery spasm, that clinical utility of diltiazem may not depend on its vasodilator effect on the bypass graft, and that cilnidipine as well as nifedipine will have anti-spastic action which is in the middle between those of nitroglycerine and diltiazem.

Autologous angiogenic therapy with cultured mesenchymal stromal cells in platelet-rich plasma for critical limb ischemia.

Introduction: The prevalence of diabetes mellitus is increasing globally, including in Japan. Patients with diabetes often experience microangiopathy and macroangiopathy, which lead to difficult-to-treat foot ulcers and diabetic gangrene. Conventional cellular therapies have limited safety and are invasive. In this study, we investigated the use of cultured autologous mesenchymal stromal cells derived from the bone marrow and grown in platelet-rich plasma as a potential treatment for diabetic complications. Methods: A prospective clinical trial was conducted to assess safety as the primary endpoint and efficacy as the secondary endpoint of the aforementioned therapy in five patients with critical limb ischemia, with or without hemodialysis. Results: Five patients with critical limb ischemia were enrolled between 2016 and 2019, three of whom underwent hemodialysis. Platelet-rich plasma was obtained from 288 ± 39.6 mL of blood/patient, yielding 31.6 ± 1.67 mL of platelet-rich plasma. Bone marrow aspiration yielded 18.4 ± 4.77 mL/patient, and 4.64 ± 1.51 × 107 cells were incubated for 16 ± 2.8 days to obtain 3.26 ± 0.33 × 107 mesenchymal stromal cells. Although several adverse events were observed, none were directly attributed to cell therapy. Clinical severity, as assessed by both the Fontaine stage and Rutherford category, improved significantly following therapy. This improvement was accompanied by enhancements in the 6-min walking distance, dorsal skin perfusion pressure, ankle transcutaneous partial oxygen pressure, and ankle brachial pressure index. Conclusion: Autologous angiogenic therapy with cultured mesenchymal stromal cells derived from the bone marrow and grown in platelet-rich plasma is a safe and feasible, and was expected as a potential treatment for critical limb ischemia.

Complete Resection of a Cavoatrial Metastatic Liposarcoma under Hypothermic Circulatory Arrest.

A patient underwent surgical resection twice for primary and metastatic dedifferentiated liposarcomas. Computed tomography revealed a tumor mass at the cavoatrial junction. Prompt surgical resection of the tumor with thrombectomy was successfully performed using cardiopulmonary bypass with hypothermic circulatory arrest. Despite the poor prognosis of metastatic or recurrent liposarcoma, the patient has survived for 8 years since the first tumor resection.

Dual functional catalysis of [Nb6O19]8--modified Au/Al2O3.

A catalyst prepared by modifying the surface of Au nanoparticles (NPs) on Al2O3 with [Nb6O19]8- clusters had specific base and reduction abilities, and the reduction of p-nitrophenol to p-aminophenol using H2 as a reductant proceeded efficiently with the dual functional catalyst. At the interface between Au NPs and basic [Nb6O19]8-, heterolytically cleaved hydrogen species are generated, which can efficiently react with nitrophenolate ions generated by base catalysis. Moreover, this surface modification strategy was applicable to the reduction of other nitro compounds.

Evaluation of pharmacogenetic algorithm for warfarin dose requirements in Japanese patients.

BACKGROUND: Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation. METHODS AND RESULTS: The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking). CONCLUSIONS: The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation.

Emergency thromboembolectomy for impending paradoxical embolism through a patent foramen ovale owing to venous thromboembolism in a severely obese patient.

A severely obese patient with dyspnea and weighing 197 kg presented to us. He experienced an impending paradoxical embolism in the left ventricle caused by a deep vein thrombosis passing through a patent foramen ovale, as well as an acute massive pulmonary thromboembolism. Emergency thromboembolectomy from the right atrium and the bilateral pulmonary arteries was successfully performed. This is an extremely rare case of a severely obese patient with a body mass index of 66.6 kg/m2 who required emergency cardiac surgery by a cardiopulmonary bypass.

Circulating odd-chain saturated fatty acids were associated with arteriosclerosis among patients with diabetes, dyslipidemia, or hypertension in Sri Lanka but not Japan.

The differences in the morbidity and mortality of cardiovascular diseases between Sri Lankan and Japanese populations might be explained by the differences in their diet, especially fat. To test the hypothesis that the fatty acid (FA) compositions differ between Sri Lankan and Japanese populations and that high concentrations of n-3 polyunsaturated FAs and linoleic acid are associated with a low level of arteriosclerosis, the authors compared the circulating FA compositions between Sri Lankan and Japanese populations and examined the association of the circulating FA composition with arterial stiffness in each population. The study participants were patients with diabetes, dyslipidemia, or hypertension in Sri Lanka (n = 100) or Japan (n = 236). Serum FA compositions were measured by gas chromatography. Arterial stiffness was measured using the cardio-ankle vascular index (CAVI). Analysis of covariance was used to compare the FA compositions between the populations. Multiple regression was used to assess the association between each FA and CAVI levels. The concentrations of myristic, γ-linolenic, dihomo-γ-linolenic, and arachidonic acids were higher in the Sri Lankan patients than in the Japanese patients. In contrast, the concentrations of linoleic, α-linolenic, and eicosapentaenoic acids were higher in the Japanese patients than in the Sri Lankan patients. Although no associations of n-3 polyunsaturated FAs and linoleic acid with CAVI were observed in both patient populations, odd-chain saturated FAs (pentadecanoic and heptadecanoic acids) were significantly inversely associated with CAVI levels in the Sri Lankan (P for trend = .03) but not the Japanese patients. The odd-chain saturated FAs might be inversely associated with atherosclerosis in this Sri Lankan population.

Outcomes of Extended Endovascular Aortic Repair for Aorto-Iliac Aneurysm with Internal Iliac Artery Occlusion.

Objective: Patients of aorto-iliac aneurysms who undergo endovascular aortic repair (EVAR) require internal iliac artery (IIA) occlusion with coil embolization and its coverage with the stent graft to prevent type II endoleak after extending the endograft into the external iliac artery. However, it has become well recognized that IIA occlusion cause buttock claudication and other various sequelae due to pelvic ischemia. We retrospectively analyzed IIA occlusion outcomes. Methods: From October 2008 to February 2015, 71 patients with aorto-iliac aneurysms underwent IIA occlusion prior to EVAR. The relationship between pelvic circulation and symptom of pelvic ischemia was studied. Results: Buttock claudication occurred in 17 patients (22.9%) of all. Eight patients (14.8%) in unilateral IIA occlusion group (54 patients) and nine patients (52.9%) in bilateral IIA group (17 patients) had sequelae of claudication. The sacrifice of the communication of superior gluteal artery (SGA) and inferior gluteal artery (IGA) led to buttock claudication in 18 (64.3%) of 28 limbs. Instead, only 4 of 60 limbs had buttock claudication, when we preserved the communication between SGA and IGA. In all patients, staged treatment of aorto-iliac aneurysms with IIA occlusion and EVAR were done successfully without pelvic ischemic complications except for buttock claudication, and postoperative CT scanning showed no endoleakage. Conclusion: IIA occlusion prior to EVAR is recognized as a safe and reasonable strategy. It is emphasized that preservation of the communication of SGA and IGA is important to prevent buttock claudication. (This is a translation of Jpn J Vasc Surg 2016; 25: 240-245.).

Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1.

In our study, resveratrol (polyphenol) has been identified as a very important stimulus/agent for the induction of new vessel growth. Occlusion of a main coronary depletes the blood supply to the myocardium and subsequently reduces cardiac function, which ultimately leads to heart failure. Progressive, chronic coronary artery occlusion has been shown to induce development of collateral arteries to re-establish and maintain blood flow to the myocardium at risk via the growth of new capillary vessels or angiogenesis. Studies from our laboratory, as well as from others, have already confirmed the protective role of collaterals against myocardial ischemia and cell death. We have successfully demonstrated in rat myocardial infarction (MI) model an effect of resveratrol on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI. Pretreatment with resveratrol also increased nitric-oxide synthase (inducible NOS and endothelial NOS) along with increased antiapoptotic and proangiogenic factors nuclear factor (NF)-kappaB and specificity protein (SP)-1. We also were able to demonstrate increased capillary density as well as improved left ventricular function by pharmacological preconditioning with resveratrol 3 wk after MI.

Abdominal aortic grafting for renal and lower extremity hypoperfusion due to aortic dissection with progressive thrombosis of a false channel.

We present the case of a 53-year-old man with renal and bilateral limb ischemia due to Stanford B aortic dissection. The thrombosis of the false lumen had progressed and compressed the true lumen, developing renal and leg ischemia. Urgent graft replacement of the infrarenal abdominal aorta with proximal fenestration was successfully performed and the patient was discharged without complications.

Aortic operation after previous coronary artery bypass grafting: management of patent grafts for myocardial protection.

OBJECTIVES: Aortic surgery for progressive aortic valve disease or aortic aneurysm after previous coronary artery bypass grafting (CABG) is a challenging procedure. We report the outcome of aortic reoperation after previous CABG and evaluate our management of patent grafts and our methods for obtaining myocardial protection. METHODS: From February 2001 to July 2003, 6 patients with progressive aortic valve disease and aneurysm of the thoracic aorta were operated on. The group comprised 3 men and 3 women with a mean age of 67.6 years. There were 4 patients with an aneurysm of the aortic arch, 1 with chronic ascending aortic dissection, and 1 with progressive aortic valve stenosis. The interval between previous CABG and aortic surgery was 74.0 +/- 44.2 months. All reoperations were performed via median resternotomy. Myocardial protection was obtained by hypothermic perfusion of patent in-situ arterial grafts following cold-blood cardioplegia administration via the aortic root under aortic cross clamping. RESULTS: The operative procedure was aortic arch replacement in 4 patients, ascending aortic replacement with double CABG in 1, and aortic valve replacement in 1. All patients survived the reoperation. Postoperative maximum creatine kinase-MB was 49.2 +/- 29.8 and no new Q-waves occurred in the electrocardiogram nor were any new wall motion abnormalities recognized on echocardiography. There were no late deaths during a follow-up of 30.7 months. CONCLUSION: Reoperative aortic procedures after CABG can be performed safely with myocardial protection via hypothermic perfusion of a patent in-situ arterial graft.

Topical spraying of cefazolin and gentamicin reduces deep sternal wound infections after heart surgery: a multicenter, large volume, retrospective study.

OBJECTIVE: The use of topical antimicrobials applied to the sternum during cardiac procedures in combination with intravenous agents to prevent mediastinitis has been reported to yield good results. The objective of this study is to provide optimal method of topical antimicrobials for the prevention of sternal wound infection after cardiac surgery. METHODS: We retrospectively evaluated the patients undergoing adult cardiac surgery at five institutions between January 1994 and August 2013 for the incidence of deep sternal wound infection (DSWI). The patients were sprayed with a solution of cefazolin and gentamicin into the surgical site several times during surgery. The incidence of DSWI was evaluated. Four major risk factors [diabetes mellitus (DM), emergency operation, dialysis and prolonged operation] were also evaluated for their implications in the outcome with the antimicrobial spraying. RESULTS: Totally, 6960 patients were analyzed. The incidence of DSWI was 0.46% in the spraying group versus 1.7% in control group (p < 0.0001). There is no significant difference of the incidence of DSWI between DM and non-DM groups (p = 1.00), emergency and elective operation groups (p = 0.25) under usage of antimicrobial spraying. However, there is significant difference of the incidence of DSWI between dialysis and non-dialysis groups (p = 0.0222), longer than six-hour duration and lesser than six-hour duration operation groups (p = 0.0269). CONCLUSION: Topical spraying of cefazolin and gentamicin reduces deep sternal wound infections after cardiac surgery. DM and emergency operation were not the risk factors of DSWI when antimicrobial spraying is administered. Considering the benefits, antimicrobial spraying could be used intermittently during such procedures.

Safety assessment of bone marrow derived MSC grown in platelet-rich plasma.

The injection of endothelial progenitor cells and mononuclear cells derived from bone marrow at the ischemic region of peripheral artery disease patients is reported to be effective for therapeutic angiogenesis; however, these cell therapies require large amounts of bone marrow to obtain sufficient numbers of cells. To solve this problem, we attempted to culture bone-marrow-derived mesenchymal stem cells (BM-MSC), which are supposed to secrete several cytokines that promote angiogenesis. We also focused on using platelet-rich plasma (PRP) as a supplement for cell culture instead of fetal bovine serum. Human BM-MSC obtained from healthy volunteers expanded rapidly when cultured with 10% PRP prepared from their own blood. FACS analysis revealed that these cultured human MSC were homogeneous populations, and chromosomal analysis showed a normal karyotype. Moreover, the angiogenetic effect was apparent two weeks after human BM-MSC were injected into the ischemic muscle in SCID mice. Tumor formation was not detected three months after injection into SCID mice either subcutaneously or intramuscularly. To simulate clinical settings, canine BM-MSC were grown with canine PRP and injected into their ischemic muscles. We confirmed that donor cells existed in situ two and six weeks after operation without any side effects. These results suggest that cultured human BM-MSC can be a promising cell source for therapeutic angiogenesis.

A morphological study of the scaphoid using a mathematical technique and comparative study of the three-dimensional measurements of the scaphoid.

To guide reconstruction of scaphoid non-union, we attempted to create full-scale models of the scaphoid by three-dimensional computed tomography (3D CT) of the healthy side. In this study, we obtained 3D scans of 51 cadaveric hands and studied the difference in morphology between genders and between the left and right sides. The major axis length on a fixed plane and Fourier transformation curve were examined. Ten scaphoid images were also obtained with 3D CT before and after removal from the cadaveric hands. Our findings suggest good correlation between models produced using 3D CT images of the scaphoid alone, and this could serve as an accurate model if the magnification is corrected using the regression line. However, the model using 3D CT images of the intact wrist joint has a large margin of error and its use will not be practical.

Relationship between arteriosclerosis obliterans and the ratio of serum eicosapentaenoic acid to arachidonic acid.

PURPOSE: A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) has been associated with coronary artery disease. We retrospectively examined serum concentrations of polyunsaturated fatty acids in patients with arteriosclerosis obliterans (ASO) and in non-atherosclerotic patients. METHODS: From April 2011 to March 2012, serum EPA/AA was retrospectively examined in 33 consecutive outpatients with ASO complicated by intermittent claudication and 21 outpatients with hypercholesterolemia without ASO as controls. The Student's t-test was used for continuous variables and Chi-square test for categorical variables, with analysis of covariance adjusting for age, sex, body mass index, smoking, alcohol, and diabetes. RESULTS: The ASO group were significantly different with regard to mean age (71.5 vs. 63.9 year-old, p = 0.03), body mass index (21.3 vs. 24.1 kg/m(2), p = 0.002) and morbidity of diabetes mellitus (51.5 vs. 4.8%, p = 0.0004). Serum EPA/AA was significantly decreased in ASO (0.36 vs. 0.61, p = 0.03), when adjusted for age, sex, body mass index, smoking status and alcohol drinking, but was not statistically significant when adjusted for diabetes. CONCLUSION: Patients with ASO were more likely to have a low EPA/AA ratio and non- diabetic patients with ASO had a significantly reduced EPA/AA.

Cilostazol improves lymphatic function by inducing proliferation and stabilization of lymphatic endothelial cells.

BACKGROUND: Cilostazol, an inhibitor of phosphodiesterase type III, is an antiplatelet agent and vasodilator. Some clinical reports have suggested that this drug can improve progressive and refractory lymphedema. OBJECTIVE: In this study, we investigated whether cilostazol has the potential to proliferate lymphatic vessels and to improve lymphatic function using human lymphatic endothelial cells (LECs) and mouse lymphedema models. METHODS: Human LECs were counted at several time points while they were cultured in the presence of cilostazol and/or protein kinase A inhibitor. After receiving a diet including 0.1% cilostazol or control diet, skin tissue and lymphatic function of k-cyclin transgenic (kCYC(+/-)) mice, which have pernicious lymphatic dysfunction, was analyzed. A different lymphedema model was generated in wild type mice by excising circumferential tail skin to remove the superficial lymphatics. After oral administration of cilostazol, tail lymphedema was examined in this mouse model. RESULTS: Proliferation of LECs was promoted in a dose-dependent manner, which was partially inhibited by a protein kinase A inhibitor. Lymphatic vessel count increased in the cilostazol-treated kCYC(+/-) mice over that in the non-treated mice. Lymph flow improved in cilostazol-fed kCYC(+/-) mice as assessed by subcutaneous injection of Evans blue dye into the footpad. Oral administration of cilostazol also decreased lymphedema in a tail of wild type mice. CONCLUSION: Cilostazol promoted growth of human LECs and improved lymph flow and lymphedema in two different mouse lymphedema models. These results suggest that cilostazol would be a promising agent for the treatment of lymphedema.

Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: neuropathic, ischemic, and neuro-ischemic type.

AIMS: To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time. METHODS: Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan-Meier method. Healing time among the three types was compared using the log rank test. RESULTS: The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle-brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values. CONCLUSIONS: Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs.

Right Aortic Arch and Kommerell's Diverticulum Repaired without Reconstruction of Aberrant Left Subclavian Artery.

Right aortic arch with Kommerell's diverticulum is a very rare situation. Surgical treatment is recommended for symptomatic patients or asymptomatic patients with a large diverticulum. However planning the strategy of operation is difficult without a 3D imaging. We report a case of a 57-year-old man with right aortic arch, Kommerell's diverticulum, and aberrant left subclavian artery. After a 3D-CT imaging, the patient underwent descending aortic replacement without reconstruction of aberrant left subclavian artery. After operation, there was no signs or symptoms of ischemia of the left arm. If the reconstruction of the aberrant subclavian artery was too difficult, closing its orifice is an acceptable decision. It has been found advantageous because of a decrease blood loss and a shorter cardiopulmonary bypass duration. If an ischemia of the arm is noticed, additional reconstruction will have to be considered. 3D-CT imaging was very useful to have a proper orientation and plan for the operative strategy.