Background:The Therapeutic Angiogenesis by Cell Transplantation (TACT) trial demonstrated the efficacy and safety of autologous bone marrow-derived mononuclear cells (BM-MNCs) in patients with critical limb ischemia (CLI). The present study aimed to assess the long-term clinical outcomes of therapeutic angiogenesis using autologous BM-MNC implantation under advanced medical treatment in Japan. Methods and Results:The study was retrospective, observational, and non-controlled. We assessed no-option CLI patients who had BM-MNC implantation performed in 10 institutes. Overall survival (OS), major amputation-free (MAF), and amputation-free survival (AFS) rates were primary endpoints of this study. The median follow-up duration was 31.7 months. The 10-year OS rate was 46.6% in patients with arteriosclerosis obliterans (ASO) (n=168), 90.5% in patients with thromboangiitis obliterans (TAO) (n=108), and 67.6% in patients with collagen disease-associated vasculitis (CDV) (n=69). The 10-year MAF rate was 70.1%, 87.9%, and 90.9%, respectively. The 10-year AFS rate was 37.8%, 80.9%, and 61.2%, respectively. Major adverse cardiovascular events occurred in 6.0% of patients with ASO, 1.9% of patients with TAO, and no patients with CDV.Conclusions: Therapeutic angiogenesis using autologous BM-MNC implantation may be feasible and safe in patients with no-option CLI, particularly those with CLI caused by TAO or CDV.Key Words: Bone marrow-derived mononuclear cells; Critical limb ischemia; Therapeutic angiogenesis ORIGINAL ARTICLE Peripheral Vascular DiseaseAdvance Publication by-J-STAGE KONDO K et al.previous (5 years) or current history of neoplasms, diabetes with untreated retinopathy, age >80 years, the possibility of pregnancy, or the lack of informed consent. 6 We obtained written informed consent from all patients, and the ethics committees of the participating hospitals approved the protocol. Data CollectionWe developed a web-based database using FileMaker Pro (FileMaker, Inc., Santa Clara, CA, USA) and an electronic clinical record form (eCRF) to collect information about patient characteristics, previous medical history, adverse events, and outcomes on the last day on which the physician confirmed the patient's status. All patient data were stored and analyzed independently at the Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan. In 2015, 14 Japanese hospitals participated in this part of the TACT trial. Data were collected with the permission of the Ministry of Health, Labour, and Welfare.This study was retrospective, observational, and noncontrolled. The primary endpoints were the rates of overall survival (OS), major amputation-free (MAF), and amputation-free survival (AFS). AFS in this study included OS and major amputation. The safety of the therapy was assessed in the context of major adverse cardiovascular events (MACE; death, non-fatal myocardial infarctions, decompensated heart failure, and stroke) and all-cause adverse events during the 6-month follow-up period after ...

7, and the declaration was extended nationwide on April 16, 2020. A total of 11,919 cases and 287 deaths have been confirmed in Japan as of April 23, 2020 [4]. Exhaustion of healthcare resources, including medical personnel, medical equipment, and personal protective equipment (PPE), is occurring in many regions while dealing with patients with COVID-19. Recent studies showed that cardiovascular comorbidities are common in patients with COVID-19 and such patients are at a higher risk of morbidity and mortality [5,6]. In addition, various cardiac manifestations, such as myocarditis, venous thrombosis, arrhythmia, and heart failure were reported in patients with

BackgroundMany mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice.Methods and FindingsWe developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/μL, <10 g/dL, >1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened in-hospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the in-hospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II substudy; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01).ConclusionsThis laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index.

CD, particularly with systemic sclerosis (SSc, scleroderma) have experienced Raynaud's phenomenon or digital ulcers (DU) because of inadequate peripheral blood supply. Intractable ischemic ulcers negatively affect patients' quality of life (QOL), and may lead to limb amputation. 2 The European League against Rheumatism (EULAR) recommends intravenous (IV) iloprost, PDE-5 inhibitors, and C ritical limb ischemia (CLI) is caused by chronic arterial obstruction, mainly caused by arteriosclerosis obliterans (ASO), thromboangiitis obliterans (TAO), and collagen disease (CD). Patients with CLI often require limb amputation when conventional revascularization methods such as bypass surgery or endovascular treatment (EVT) fail or are not indicated. 1 Patients with

Recently, the limb salvage rate of patients with critical limb ischemia (CLI) has been improved due to the development of revascularization and wound care treatment. However, many patients with CLI are refractory to standard treatments, including revascularization such as endovascular treatment or surgical bypass. Establishment of a new cell therapy is required to improve the limb salvage rate and prognosis in patients with CLI. In 1997, endothelial progenitor cells were found to be derived from the bone marrow to circulate as CD34 surface antigen positive cells in peripheral blood and to affect therapeutic angiogenesis in ischemic tissues. Later, therapeutic angiogenesis using autologous bone marrow-derived mononuclear cell (BM-MNC) implantation was performed for patients with no-option CLI in clinical practice. Several reports showed the safety and efficacy of the BM-MNC implantation in patients with CLI caused by arteriosclerosis obliterans, thromboangiitis obliterans (TAO), and collagen diseases. In particular, in patients with CLI caused by TAO, limb salvage rate was significantly improved compared with standard treatments. The BM-MNC implantation may be feasible and safe in patients with no-option CLI. Here, we review the efficacy of BM-MNC implantation in no-option CLI, with a focus on therapeutic angiogenesis.