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Daniel Freund, Silke Brilloff, Tamer Ghazy, Stephan Kirschner, Gabor Gäbel, Irene Hinterseher, Norbert Weiss, Adrian Mahlmann
BACKGROUND: Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia (CLI) and non-ischaemic control subjects. PATIENTS AND METHODS: Biopsy of gastrocnemius muscle was obtained from six patients with unreconstructed CLI referred for surgical major amputation. As control, biopsies of six patients undergoing elective knee arthroplasty without evidence of peripheral arterial occlusive disease were taken...
March 20, 2018: VASA. Zeitschrift Für Gefässkrankheiten
Marina Dias-Neto, Manuela Matschuck, Yvonne Bausback, Ursula Banning-Eichenseher, Sabine Steiner, Daniela Branzan, Holger Staab, Ramon L Varcoe, Dierk Scheinert, Andrej Schmidt
PURPOSE: To report midterm results of the "pave-and-crack" technique to facilitate safe and effective scaffolding of heavily calcified femoropopliteal lesions in preparation for delivery of a Supera interwoven stent. METHODS: Data were collected retrospectively on 67 consecutive patients (mean age 71±8 years; 54 men) treated with this technique between November 2011 and February 2017 at a single center. A third (22/64, 34%) of the patients had critical limb ischemia (CLI)...
March 1, 2018: Journal of Endovascular Therapy
Fadilah S Abdul Wahid, Nor Azimah Ismail, Wan Fariza Wan Jamaluddin, Nor Asiah Muhamad, Mohamad Mohamad Azim Mohamad Idris, Nai Ming Lai
BACKGROUND: Revascularisation therapy is the curent gold standard of care for critical limb ischaemia (CLI), although a significant proportion of patients with CLI either are not fit for or do not respond well to this procedure. Recently, novel angiogeneic therapies such as the use of autologous cell-based therapy (CBT) have been examined, but the results of individual trials were inconsistent. OBJECTIVE: To pool all published studies that compared the safety and efficacy of autologous CBT derived from different sources and phenotypes with non cell-based therapy (NCT) in CLI patients...
March 13, 2018: Current Stem Cell Research & Therapy
Chakradhari Inampudi, Emmanuel Akintoye, Tomo Ando, Alexandros Briasoulis
Peripheral arterial disease (PAD) refers to narrowing of the peripheral arteries and atherosclerosis is the most important cause. In patients with PAD, revascularization is the preferred therapeutic strategy; nonetheless several patients are not deemed candidates for it due to advanced disease or several comorbidities. The main target of therapeutic angiogenesis is to promote development of new arterial vessels and improve perfusion of ischemic tissue. Angiogenic growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), administered intramuscularly or intra-arterially, have been shown to promote angiogenesis and development of collateral vasculature in preclinical studies...
March 9, 2018: Current Opinion in Pharmacology
Romeo Martini
In this review 14 studies were identified reporting the treatment strategy in 4891 patients with Critical Limb Ischemia (CLI) with the aim to investigate if the strategy of treatment of the first episode of CLI has changed during the last 15-20 years. A computer research has been performed on PubMed and Scopus databases on November 2016. The used terms for the investigation about studies evaluating the strategy of treatment of CLI at the first-time presentation, have been "critical leg ischemia", "critical limb ischemia", "critical lower limb ischemia" along with the terms "placebo", "medical treatment" and/or "conservative" revascularisation, surgical revascularisation, endovascular revascularisation, hybrid revascularisation and primary amputation...
March 1, 2018: Clinical Hemorheology and Microcirculation
Michael Creane, Mary Mc Elroy, Aoife Duffy, Chaansha Shaik Dawood, Timothy O'Brien
Critical limb ischemia (CLI) represents the severest manifestation of peripheral arterial disease and is a major unmet medical need. This disease occurs when the arterial blood supply within the limb fails to meet the metabolic demands of the resting muscle or tissue, resulting in chronic ischemic rest pain and/or tissue necrosis. Human mesenchymal stromal cells, termed hMSCs, represent an exciting therapeutic modality for the treatment of this disease due to their immunomodulatory and tissue reparative functions...
January 1, 2018: Toxicologic Pathology
S Keisin Wang, Linden A Green, Ashley R Gutwein, Natalie A Drucker, Clifford M Babbey, Alok K Gupta, Andres Fajardo, Raghu L Motaganahalli, Michael G Wilson, Michael P Murphy
OBJECTIVE: Ethnic minorities (nonwhites) with critical limb ischemia (CLI) have historically performed worse compared with whites with regard to major amputation risk reduction and amputation-free survival (AFS) after peripheral vascular intervention. This post hoc analysis was completed to determine whether this precedent also extended to treatment of CLI without a suitable revascularization option with intramuscular injections of concentrated bone marrow aspirate (cBMA). METHODS: The treatment arm of the randomized, double-blind, multicenter MarrowStim PAD Kit for the Treatment of Critical Limb Ischemia in Subjects with Severe Peripheral Arterial Disease (MOBILE) trial was stratified by ethnicity and evaluated for demographics, comorbidities, and outcomes...
March 1, 2018: Journal of Vascular Surgery
Mengchao Xiao, Wenjian Chen, Chao Wang, Yingfu Wu, Shiwei Zhu, Chuyang Zeng, Yongchao Cai, Changcheng Liu, Zhiying He
Chronic liver injury (CLI) is a complex pathological process typically characterized by progressive destruction and regeneration of liver parenchymal cells due to diverse risk factors such as alcohol abuse, drug toxicity, viral infection, and genetic metabolic disorders. When the damage to hepatocytes is mild, the liver can regenerate itself and restore to the normal state; when the damage is irreparable, hepatocytes would undergo senescence or various forms of death including apoptosis, necrosis and necroptosis...
February 2, 2018: Oncotarget
Simon Vergnaud, Valéry-Pierre Riche, Philippe Tessier, Nicolas Mauduit, Adrien Kaladji, Yann Gouëffic
OBJECTIVES: To evaluate the budget impact of progressive replacement of standard polytetrafluoroethylene (PTFE) grafts by heparin-bound PTFE (Propaten) for below-the-knee (BTK) bypass in patients with critical limb ischaemia (CLI). DESIGN: From a review of the scientific literature, we calculated a theoretical BTK primary patency for Propaten grafts. Using the French hospital expenditure database (PMSI), we retrospectively estimated a rehospitalisation rate for standard PTFE grafts...
February 28, 2018: BMJ Open
Toshio Takayama, Jon S Matsumura
BACKGROUND: Complete revascularization, achieving inline flow to the foot through at least 1 patent tibioperoneal artery, is considered to be desirable for treating critical limb ischemia (CLI). Hybrid procedure, combined femoral endarterectomy and endovascular treatment, is commonly performed on patients with CLI because they often present with complicated lower extremity lesions involving the common femoral artery. This study aimed to investigate the efficacy of complete revascularization (CR) achieved by hybrid procedure on limb salvage in patients with CLI...
January 1, 2018: Vascular and Endovascular Surgery
Li Cong, Shuting Yang, Yong Zhang, Jianguo Cao, Xiaohua Fu
7‑difluoromethoxy‑5,4'‑dimethoxy‑genistein (DFMG) is a novel active chemical entity, which modulates the function and signal transduction of endothelial cells and macrophages (MPs), and is essential in the prevention of atherosclerosis. In the present study, the activity and molecular mechanism of DFMG on MPs was investigated using a Transwell assay to construct a non‑contact co‑culture model. Human umbilical vein endothelial cells (HUVE‑12), which were incubated with lysophosphatidylcholine (LPC), were seeded in the upper chambers, whereas PMA‑induced MPs were grown in the lower chambers...
February 23, 2018: International Journal of Molecular Medicine
Tenna Klit, Marie Dahl, Kim Christian Houlind, Hans Ravn
BACKGROUND: In patients with critical leg ischemia (CLI), the standard operative choice is an in situ bypass to the lower extremity to improve the patients´ prognosis and quality of life. Postoperative complications after surgery occur in 18 % of the patients, prolonging hospitalization and convalescence. The main operative complication is edema. This can be prevented by early mobilization or stimulation of the natural venous pump in the leg. OBJECTIVE: To investigate whether compression therapy with foot pump reduces postoperative edema, facilitates wound healing of the operation wounds, promotes healing of ischemic ulcers, and shortens hospitalization, increasing and improving the patient's subjective quality of life faster...
February 20, 2018: JMIR Research Protocols
Tianyue Pan, Zheng Wei, Yuan Fang, Zhihui Dong, Weiguo Fu
Early-phase clinical trials in patients with critical limb ischemia (CLI) have shown positive results of mononuclear cell therapy. The current meta-analysis investigated whether cluster of differentiation (CD) 34+ mononuclear cell therapy (CD34+ MCT) is effective for no-option CLI. Ten randomized controlled clinical studies of CD34+ MCT for no-option CLI with 479 patients were identified and analyzed for pooled results. Compared to control groups, the CD34+ MCT was associated with lower total amputation (odds ratio (OR): 0...
February 1, 2018: Vascular Medicine
Dominic Simm, Martin Kollmar
Stable single-alpha helices (SAH-domains) function as rigid connectors and constant force springs between structural domains, and can provide contact surfaces for protein-protein and protein-RNA interactions. SAH-domains mainly consist of charged amino acids and are monomeric and stable in polar solutions, characteristics which distinguish them from coiled-coil domains and intrinsically disordered regions. Although the number of reported SAH-domains is steadily increasing, genome-wide analyses of SAH-domains in eukaryotic genomes are still missing...
2018: PloS One
Fredrik Ghosh, Hodan Abdshill, Karin Arnér, Ulrikke Voss, Linnéa Taylor
The purpose of this study was to explore retina-intrinsic neuroinflammatory reactions, effects on neuronal survival, relationship with classic gliosis, and possible role of the toll-like receptor 4 (TLR4). To isolate the adult retina from the systemic immune system, a previously described large animal explant culture model was used in which full-thickness porcine retinal sheets can be kept in vitro for extended time periods. Explants were kept for 5 days in vitro (DIV) and were treated with either; lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) inhibitor (CLI-095), LPS + CLI-095, or solvent vehicle throughout the culture period after which retinal sections were examined with hematoxylin and eosin staining and extensive immunohistochemistry...
February 7, 2018: Experimental Eye Research
Naveed Afzal, Vishnu Priya Mallipeddi, Sunghwan Sohn, Hongfang Liu, Rajeev Chaudhry, Christopher G Scott, Iftikhar J Kullo, Adelaide M Arruda-Olson
BACKGROUND: Critical limb ischemia (CLI) is a complication of advanced peripheral artery disease (PAD) with diagnosis based on the presence of clinical signs and symptoms. However, automated identification of cases from electronic health records (EHRs) is challenging due to absence of a single definitive International Classification of Diseases (ICD-9 or ICD-10) code for CLI. METHODS AND RESULTS: In this study, we extend a previously validated natural language processing (NLP) algorithm for PAD identification to develop and validate a subphenotyping NLP algorithm (CLI-NLP) for identification of CLI cases from clinical notes...
March 2018: International Journal of Medical Informatics
Mehdi Oualha, Christophe Chardot, Dominique Debray, Fabrice Lesage, Annie Harroche, Sylvain Renolleau, Jean-Marc Treluyer, Saïk Urien
AIM: Preventing post liver transplantation (LT) hepatic artery and portal vein thrombosis includes enoxaparin administration. Enoxaparin pharmacokinetics (PK) has not been investigated in children following LT. We described an enoxaparin PK model in 22 children the first week following the LT. METHODS: Anti-Xa activity time-courses were analyzed using a nonlinear mixed effects approach with Monolix version 2016R. RESULTS: Anti-Xa activity time-courses were well described by a one-compartment model with first order absorption and elimination...
February 8, 2018: British Journal of Clinical Pharmacology
S Keisin Wang, Ashley R Gutwein, Natalie A Drucker, Michael P Murphy, Andres Fajardo, Michael C Dalsing, Raghu L Motaganahalli, Gary W Lemmon
OBJECTIVE: Single-length saphenous vein continues to be the conduit of choice in infected-field critical limb ischemia (CLI). However, half of these individuals have inadequate vein secondary to previous use or chronic venous disease. We reviewed our outcomes of infected-field infrainguinal bypasses performed with cryopreserved homografts (CH), a widely-accepted alternative to autogenous vein in this setting. METHODS: This is a retrospective, institutional descriptive analysis of infected-field infrainguinal revascularizations between 2012-2015...
February 5, 2018: Annals of Vascular Surgery
Bahare Fazeli, Maliheh Dadgar Moghadam, Shabnam Niroumand
To date, there is still no treatment protocol for patients with thromboangiitis obliterans (TAO) who are also afflicted with critical limb ischemia (CLI). Smoking cessation on its own cannot be considered a treatment for the purposes of salvaging a limb of a TAO patient with CLI. The aim of this review was to evaluate different studies of various treatment protocols for avoiding amputation in TAO patients. A systematic search for relevant studies dating from 1990 to the end of 2016 was performed on the PubMed, SCOPUS, and Science Direct databases...
February 5, 2018: Annals of Vascular Surgery
Lisheng Wang, Hua Wang, QingLin Zhang, Zhijian Yang, Fanxuan Kong, Chu-Tse Wu
Stem cells and gene therapy have become promising strategies for treating ischemia diseases and regenerating tissue. Hepatocyte growth factor (HGF) is an angiogenic growth factor with multiple functions including promoting angiogenesis, regulating inflammation, inhibiting fibrosis and activating tissue regeneration. Numerous preclinical experiments and clinical trials have demonstrated the feasibility and efficacy of HGF gene therapy in treatment of ischemia diseases and tissue regeneration. This review summarized the current advances of therapeutic angiogenesis using HGF gene transfer and modified stem cells...
February 6, 2018: Human Gene Therapy
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