Chronic Limb-Threatening Ischemia

A severe form of peripheral artery disease in which a hypoperfusion of the BLOOD through an organ or tissue is caused by occlusion of peripheral arterial vessels. It is associated with the presence of chronic ischemic rest pain, ulceration or GANGRENE.

Also Known As:

Networked: 2169 relevant articles (193 outcomes, 347 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Pain (Aches)
2.	Wounds and Injuries (Trauma)
3.	Peripheral Arterial Disease
4.	Thromboangiitis Obliterans (Buerger's Disease)
5.	Ischemia

Experts

1.	Iida, Osamu: 56 articles (03/2022 - 05/2010)
2.	Takahara, Mitsuyoshi: 36 articles (03/2022 - 12/2010)
3.	Soga, Yoshimitsu: 36 articles (01/2022 - 10/2011)
4.	Hirano, Keisuke: 34 articles (10/2021 - 07/2010)
5.	Conte, Michael S: 26 articles (01/2022 - 01/2005)
6.	Katsanos, Konstantinos: 23 articles (12/2020 - 12/2005)
7.	Goodney, Philip P: 21 articles (12/2021 - 10/2009)
8.	Suzuki, Kenji: 21 articles (11/2017 - 10/2011)
9.	Kawasaki, Daizo: 20 articles (01/2022 - 12/2011)
10.	Yamaoka, Terutoshi: 19 articles (01/2022 - 01/2013)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Chronic Limb-Threatening Ischemia:

1.	Hepatocyte Growth Factor (Growth Factor, Hepatocyte)IBA 10/01/2015 - "Clinical Safety and Preliminary Efficacy of Plasmid pUDK-HGF Expressing Human Hepatocyte Growth Factor (HGF) in Patients with Critical Limb Ischemia." 12/01/2022 - "Rationale and design for the study of recombinant human hepatocyte growth factor plasmid in the treatment of patients with chronic limb-threatening ischemia (HOPE CLTI): Randomized, placebo-controlled, double-blind, phase III clinical trials." 12/04/2019 - "A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia." 11/16/2016 - "The demand of a plasmid encoding human hepatocyte growth factor gene (pUDK-HGF) in large quantities at high purity and concentration has increased for gene therapy of critical limb ischemia (CLI) in clinical trials. " 02/10/2022 - "Angiographic Change After Injection of Beperminogene Perplasmid, a Hepatocyte Growth Factor Gene Therapy Product for the Treatment of Critical Limb Ischemia."
2.	DNA (Deoxyribonucleic Acid)IBA 03/01/2014 - "In vivo EP-mediated delivery of HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia and is a potentially suitable nonviral, noninvasive intervention to facilitate therapeutic angiogenesis in critical limb ischemia." 04/01/2011 - "Transfection of human HGF plasmid DNA improves limb salvage in Buerger's disease patients with critical limb ischemia." 05/01/2005 - "Intramuscular injection of naked plasmid DNA was performed in the ischemic limbs of six patients with critical limb ischemia with arteriosclerosis obliterans (n = 3) or Buerger disease (n = 3) graded as Fontaine III or IV. In the efficacy evaluation, a reduction of pain scale of more than 1 cm on a visual analog pain scale was observed in five out of six patients. " 08/19/2012 - "Based on the potent angiogenic effects of hepatocyte growth factor (HGF), therapeutic angiogenesis using human HGF plasmid DNA increased tissue perfusion and reduced symptoms in patients with critical limb ischemia (CLI) in randomized placebo-controlled clinical trials. " 01/01/2020 - "The objective of this combined analysis of data from clinical trials in Japan, using naked plasmid DNA encoding hepatocyte growth factor (HGF), was to document the safety and efficacy of intramuscular HGF gene therapy in patients with critical limb ischemia (CLI). "
3.	Paclitaxel (Taxol)FDA LinkGeneric 08/06/2013 - "Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloons versus conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia undergoing endovascular intervention of below-the-knee arteries. " 10/01/2023 - "Five-Year Outcomes after Paclitaxel Drug-Coated Balloon Treatment of Femoropopliteal Lesions in Diabetic and Chronic Limb-Threatening Ischemia Cohorts: IN.PACT Global Study Post Hoc Analysis." 02/01/2020 - "A formal systematic review and study-level meta-analysis of randomized controlled trials investigating treatment of the infrapopliteal arteries with paclitaxel-coated balloons compared with conventional balloon angioplasty for critical limb ischemia (CLI) was conducted. " 01/01/2020 - "Mortality After Paclitaxel-Coated Device Use in Patients With Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." 10/24/2016 - "Local Ultrasound to Enhance Paclitaxel Delivery After Femoral-Popliteal Treatment in Critical Limb Ischemia: The PACUS Trial."
4.	Vascular Endothelial Growth Factor A (Vascular Endothelial Growth Factor)IBA 03/01/2006 - "Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limb ischemia--a case report." 01/01/2003 - "Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia: safety results from a phase I trial." 01/01/2017 - "Adipose-derived mesenchymal stem cells (ASCs) have been shown to produce vascular endothelial growth factor (VEGF) and can increase perfusion in patients with critical limb ischemia. " 01/01/2016 - "Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia." 01/01/2015 - "These results indicate that modifying ASCs to overexpress VEGF does not enhance the protective effect of ASCs, and that arteriolar proliferation plays a pivotal role in limiting the irreversible tissue damage of critical limb ischemia."
5.	Polytetrafluoroethylene (Teflon)FDA Link 01/01/2004 - "In critical limb ischemia surgeries with PTFE grafts are most effective - in 5 years 77.1% of extremities were saved compared with 69.6% after autovenous reconstructions. " 10/01/2020 - "We report an innovative technique in an 82-year-old patient with a patent but infected right axillobifemoral (AxBF) bypass performed 7 years ago owingto critical limb ischemia who underwent a semielective de novo left-sided composite AxBF bypass consisting of a central prosthetic polytetrafluoroethylene segment and distal autologous limbs to the femoral regions (femoral crossover bypass vein to the right limb using the femoral vein and jump graft to the left femoral limb using the great saphenous vein.) Although AxBF bypass is not considered the "gold standard" surgical composite revascularization procedure in the suprainguinal region, it can constitute an acceptable intervention in selected cases." 08/01/2012 - "The aim of this paper was to study the effect on patency rate of different types of vein collar (Miller's original or St Mary's boot), different length/height shapes of vein collar, and different vein collar volumes at the distal anastomosis of PTFE-bypass grafts to below-knee arteries in patients with critical limb ischemia. " 05/01/2005 - "The objectives of this study were to evaluate the results of polytetrafluoroethylene infragenicular bypass grafts with a distal interposition vein cuff in patients with critical limb ischemia in the absence of ipsilateral greater saphenous vein. " 09/01/2022 - "A below-the-knee distal bypass using the Biotube as a composite with expanded polytetrafluoroethylene grafts was performed to treat a patient with chronic limb-threatening ischemia without a venous graft available. "
6.	Intercellular Signaling Peptides and Proteins (Growth Factors)IBA 11/01/2006 - "Therapeutic angiogenesis using angiogenic growth factor is expected to be a new treatment for patients with critical limb ischemia. " 03/01/2005 - "Therapeutic angiogenesis using angiogenic growth factor is expected to be a new treatment for with patients with critical limb ischemia. " 08/01/2004 - "Therapeutic angiogenesis using angiogenic growth factors is expected to be a new treatment for patients with critical limb ischemia (CLI). " 11/15/2002 - "In the present study, we report that angiogenic growth factors, including HGF, were upregulated in a murine model of critical limb ischemia in vivo, a finding that was in conflict with previous in vitro data. " 01/01/2022 - "With critical limb ischemia (CLI) being a multi-factorial disease, it is becoming evident that gene therapy with a multiple bio-functional growth factor could achieve better therapeutic outcomes. "
7.	Alprostadil (Muse)FDA LinkGeneric 02/01/2003 - "In conclusion, treatment with PGE1 determines a significant improvement in endothelial function in patients with critical limb ischemia." 06/01/2019 - "A retrospective cross-sectional study was conducted in patients diagnosed with critical limb ischemia who received alprostadil in five hospitals in Colombia between September 2011 and July 2017. " 02/01/2003 - "Prostaglandin E1 improves endothelial function in critical limb ischemia." 10/01/1998 - "In patients with critical limb ischemia morbidity decreased from 28.6% in the reference group to 23.2% in PGE1 alpha-ciclodestrina-group and to 19.4% in the PGE1 alpha-ciclodestrina + SCH group. " 03/01/1996 - "We treated 14 patients suffering from critical limb ischemia (CLI) as defined by the Consensus Document, and in whom possibilities of surgical or percutaneous arterial reconstruction were excluded, by PGE1 60 micrograms i.v. daily during 3 weeks. "
8.	Iloprost (Ventavis)FDA Link 03/01/2002 - "Iloprost given in a standard dose regimen (0.5-2 ng/kg/min for 6 hours daily over 21-28 days) has proven to be effective and safe in hospitalized patients with critical limb ischemia. " 09/01/2006 - "Recently, iloprost has been shown to be safe and effective in critical limb ischemia patients when administered per 7 days. " 12/01/2019 - "The aim of this study was to evaluate the impact of intra-arterial administration of iloprost (Endoprost®, Italfarmaco S.p.A., Milan, Italy) on early elastic recoil after balloon angioplasty of below-the-knee (BTK) vessels in patients with critical limb ischemia (CLI). " 09/01/2006 - "Twenty-four critical limb ischemia patients (16 men and 8 women, mean age 76+/-9.7 years) were included in the study and treated with intravenous iloprost (titrated from 0.5 up to 1.5 ng/kg/min) for 16 h a day for seven consecutive days. " 11/07/2023 - "Real-world effect of iloprost in patients with chronic limb-threatening ischemia (CLTI): A cohort study."
9.	Cilostazol (Pletal)FDA LinkGeneric 08/06/2023 - "We conducted the present study to investigate whether cilostazol improved the mid-term outcomes after infrainguinal autologous vein bypass for chronic limb-threatening ischemia (CLTI). " 12/01/2011 - "However, the efficacy of cilostazol in patients with critical limb ischemia (CLI) is unclear. " 12/01/2012 - "Impact of cilostazol on angiographic restenosis after balloon angioplasty for infrapopliteal artery disease in patients with critical limb ischemia." 03/01/2012 - "Regarding "Impact of cilostazol after endovascular treatment for infrainguinal disease in patients with critical limb ischemia"." 12/01/2011 - "Impact of cilostazol after endovascular treatment for infrainguinal disease in patients with critical limb ischemia."
10.	Protein Isoforms (Isoforms)IBA 01/01/2014 - "We aimed to unravel the effect of specific PHD2 isoform silencing in cell-based strategies designed to promote therapeutic revascularization in patients with critical limb ischemia (CLI). " 11/01/2011 - "The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients. " 08/01/2011 - "Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study." 04/01/2016 - "Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia." 03/01/2016 - "Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia."

Therapies and Procedures

1.	Therapeutics 12/26/2016 - "The most effective first-line treatment between endovascular therapy and bypass surgery for patients with critical limb ischemia (CLI) is still not well defined. " 01/01/2018 - "Revascularisation therapy is the current gold standard of care for critical limb ischemia (CLI), although a significant proportion of patients with CLI either are not fit for or do not respond well to this procedure. " 06/01/2016 - "Although endovascular therapy for treatment of patients with critical limb ischemia has undergone significant advances with improved outcomes over the past decade, these patients often have multilevel disease, and it may take weeks or months for ulceration healing. " 04/01/2021 - "Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. " 09/01/2020 - "Despite the increasing age and complexity of patients our data show improvement of outcomes throughout 15 years, probably due to better surgical techniques, more aggressive medical therapy and more effective treatment of critical limb ischemia."
2.	Surgical Amputation (Amputations) 01/01/2001 - "Duplex scan surveillance is highly effective for patients treated for critical limb ischemia, leading to a reduction of major amputations and consequently to a reduction in costs compared with other surveillance programs. " 06/01/2022 - "Patients with chronic limb-threatening ischemia (CLTI) are medically complex and continue to experience high rates of amputation, despite improved diagnosis and treatment. " 01/01/2022 - "Taken together, these data demonstrate that although both muscle- and endothelium-specific expression of PFKFB3 enhanced ischemic revascularization, only muscle-specific PFKFB3 expression improved muscle function.NEW & NOTEWORTHY Critical limb ischemia (CLI) carries a significant risk for limb amputation, and treatment options remain limited. " 01/01/2022 - "Despite improved surgical approaches for chronic limb-threatening ischemia (CLTI), amputation rates remain high and contributing tissue-level factors remain unknown. " 10/01/2021 - "Both DR and IRc offer significantly improved wound healing rates and major amputation rates compared with IR when used to treat critical limb ischemia. "
3.	Limb Salvage 03/01/2003 - "Is revascularization and limb salvage always the best treatment for critical limb ischemia?" 11/01/2022 - "Implantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia. " 02/01/2019 - "Patients with critical limb ischemia, tissue loss, and concomitant CIID can be successfully treated with lower extremity revascularization with similar limb salvage and need for reintervention. " 03/01/2013 - "TAEIs can be used successfully to treat patients with critical limb ischemia with acceptable limb salvage rates. " 02/01/2015 - "Although limb salvage rate has improved in critical limb ischemia (CLI), an improvement in CLI prognosis has been scarcely reported. "
4.	Stents 12/01/2023 - "The optimization framework contributes to the advancement of innovative bioresorbable braided stents for the effective treatment of critical limb ischemia." 11/01/2023 - "Both bypass and endovascular treatment provided safe and effective restoration of patency for femoro-popliteal in-stent occlusion in patients with chronic limb-threatening ischemia. " 01/01/2017 - "The prospective, single-arm, multicenter PES-BTK-70 trial ( ClinicalTrials.gov identifier NCT01630070) evaluated the safety and efficacy of the coronary Stentys Stent System in the treatment of a stenotic or occlusive lesion ≤50 mm long in the tibioperoneal arteries of patients with critical limb ischemia (CLI). " 12/21/2004 - "The objective of this study was an investigation of the safety and efficacy of primary below-knee stent-supported angioplasty (BKSSA) for restoring straight inline arterial flow in patients with critical limb ischemia (CLI) or lifestyle-limiting claudication (LLC). " 04/01/2015 - "Durability and efficacy of tibial arterial stent placement for critical limb ischemia."
5.	Cell- and Tissue-Based Therapy (Cell Therapy) 01/01/2018 - "Therapeutic efficacy of CD34+ cell-involved mononuclear cell therapy for no-option critical limb ischemia: A meta-analysis of randomized controlled clinical trials." 05/01/2016 - "Early-phase trials showed the feasibility and potential efficacy of cell therapy in patients with critical limb ischemia (CLI). " 10/01/2021 - "Autologous cell therapy (ACT) is a new treatment for patients with no-option critical limb ischemia (NO-CLI). " 01/01/2018 - "Early-phase clinical trials in patients with critical limb ischemia (CLI) have shown positive results of mononuclear cell therapy. " 11/01/2023 - "This current opinion article critically evaluates the efficacy of autologous cell therapy (ACT) for chronic limb-threatening ischemia (CLTI), especially in people with diabetes who are not candidates for standard revascularization. "