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Trends in Cardiovascular Medicine Apr 2020Lower extremity critical limb ischemia (CLI) represents symptoms related to end-stage atherosclerotic peripheral arterial disease manifested by rest pain and tissue... (Review)
Review
Lower extremity critical limb ischemia (CLI) represents symptoms related to end-stage atherosclerotic peripheral arterial disease manifested by rest pain and tissue loss. It is associated with increased risk of limb amputation and cardiovascular-related mortality. The prevalence and cost of CLI are expected to increase with both the aging of the U.S. population and continued influence of smoking and diabetes. Treatments encompass measures to reduce cardiovascular risk and preserve limb viability. Despite increasing popularity of endovascular modalities, revascularization with either surgical bypass or endovascular intervention is the cornerstone of therapy. Adequate Level I data to guide decisions regarding optimal strategies to treat CLI, particularly in patients who are candidates for both open and percutaneous approaches, are currently lacking. Ongoing randomized controlled trials aim to resolve the clinical equipoise.
Topics: Amputation, Surgical; Chronic Disease; Clinical Decision-Making; Critical Illness; Decision Support Techniques; Endovascular Procedures; Humans; Ischemia; Limb Salvage; Lower Extremity; Patient Selection; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Treatment Outcome; Vascular Grafting
PubMed: 31005554
DOI: 10.1016/j.tcm.2019.04.002 -
Vascular Medicine (London, England) Apr 2021
Topics: Amputation, Surgical; Chronic Limb-Threatening Ischemia; Critical Illness; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Risk Factors; Treatment Outcome
PubMed: 33825576
DOI: 10.1177/1358863X211000425 -
Stem Cell Research & Therapy Aug 2023Peripheral artery disease is an ischemic vascular disease caused by the blockage of blood vessels supplying blood to the lower extremities. Mesenchymal stem cells (MSCs)...
BACKGROUND
Peripheral artery disease is an ischemic vascular disease caused by the blockage of blood vessels supplying blood to the lower extremities. Mesenchymal stem cells (MSCs) and endothelial colony-forming cells (ECFCs) have been reported to alleviate peripheral artery disease by forming new blood vessels. However, the clinical application of MSCs and ECFCs has been impeded by their poor in vivo engraftment after cell transplantation. To augment in vivo engraftment of transplanted MSCs and ECFCs, we investigated the effects of hybrid cell spheroids, which mimic a tissue-like environment, on the therapeutic efficacy and survival of transplanted cells.
METHODS
The in vivo survival and angiogenic activities of the spheroids or cell suspension composed of MSCs and ECFCs were measured in a murine hindlimb ischemia model and Matrigel plug assay. In the hindlimb ischemia model, the hybrid spheroids showed enhanced therapeutic effects compared with the control groups, such as adherent cultured cells or spheroids containing either MSCs or ECFCs.
RESULTS
Spheroids from MSCs, but not from ECFCs, exhibited prolonged in vivo survival compared with adherent cultured cells, whereas hybrid spheroids composed of MSCs and ECFCs substantially increased the survival of ECFCs. Moreover, single spheroids of either MSCs or ECFCs secreted greater levels of pro-angiogenic factors than adherent cultured cells, and the hybrid spheroids of MSCs and ECFCs promoted the secretion of several pro-angiogenic factors, such as angiopoietin-2 and platelet-derived growth factor.
CONCLUSION
These results suggest that hybrid spheroids containing MSCs can serve as carriers for cell transplantation of ECFCs which have poor in vivo engraftment efficiency.
Topics: Humans; Animals; Mice; Neovascularization, Physiologic; Endothelial Cells; Mesenchymal Stem Cells; Cells, Cultured; Ischemia; Peripheral Arterial Disease
PubMed: 37533021
DOI: 10.1186/s13287-023-03435-z -
Advanced Science (Weinheim,... Apr 2021Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood... (Review)
Review
Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non-healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so-called "no option patients" which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro-angiogenic nucleic acid, protein, and stem cell-based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.
Topics: Biocompatible Materials; Chronic Disease; Humans; Ischemia; Limb Salvage; Lower Extremity; Peripheral Arterial Disease
PubMed: 33854887
DOI: 10.1002/advs.202003119 -
Vascular Feb 2022Revascularization according to the angiosome concept is of proven importance for limb salvage in chronic limb threatening ischaemia but it is not always practicable....
OBJECTIVES
Revascularization according to the angiosome concept is of proven importance for limb salvage in chronic limb threatening ischaemia but it is not always practicable. Bifurcated bypasses could be considered as an option when an endovascular approach is not feasible or has already failed and a single bypass would not allow direct revascularization of the ischaemic area. Bifurcated bypasses are characterized by landing on two different arteries, the main artery (in direct continuity with the foot vessels) and the secondary one (perfusing the angiosome district). The aim of this study is to evaluate the safety and effectiveness of bifurcated bypass in chronic limb threatening ischaemia.
METHODS
Thirty-five patients were consecutively treated with a bifurcated bypass for chronic limb threatening ischaemia from January 2014 to December 2019 in a single vascular surgery centre. Data from clinical records and operative registers were collected prospectively in an electronic database and retrospectively analysed. Primary and primary assisted bypass patency, amputation-free survival, morbidity and mortality rates at 12 and 24 months were analysed.
RESULTS
Mean follow-up period was 25.1 months (range 2-72 months). Thirty-six bifurcated bypasses were performed on 35 patients (age 75.3 ± 7.2 years; 69.4% were male). According to Wound, Ischemia, foot Infection classification 22.2% belonged to stage 3 and 77.8% to stage 4 and the mean Rutherford's class was 5.1 ± 0.7. Immediate technical success was 100%. Early mortality and morbidity rates were respectively 5.5%, and 33.3%; foot surgery was performed in 50% of cases with wound healing in all patients. Primary patency and primary assisted bypass patency were 96.7% and 100% at 6 months; 85.2% and 92% at 12 months, 59.9% and 73.4% at 24 months, respectively. Amputation-free survival at 12 and 24 months was, respectively, 95.6% and 78.8%. Overall survival rates at 12 and 24 months were respectively 94.4% and 91.6%.
CONCLUSIONS
Bifurcates bypass can provide good results in patients with chronic limb threatening ischaemia without endovascular option, especially in diabetic ones. Bifurcated bypass is a complex surgical solution, both to be planned and performed, and it is quite invasive for frail patients that should be accurately selected.
Topics: Aged; Aged, 80 and over; Amputation, Surgical; Chronic Limb-Threatening Ischemia; Humans; Ischemia; Limb Salvage; Male; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Treatment Outcome; Vascular Patency
PubMed: 33691547
DOI: 10.1177/1708538121999856 -
Journal of Vascular Surgery Jun 2020Deep venous arterialization (DVA) is a technique aimed at providing an option for chronic limb-threatening ischemia patients with no options except amputation. In... (Review)
Review
OBJECTIVE
Deep venous arterialization (DVA) is a technique aimed at providing an option for chronic limb-threatening ischemia patients with no options except amputation. In patients with no outflow distal targets permitting bypass, DVA involves creating a connection between a proximal arterial inflow and a distal venous outflow in conjunction with disruption of the vein valves in the foot. This permits blood flow to reach the foot and potentially to resolve rest pain or to assist in healing of a chronic wound. We aimed to provide an up-to-date review of DVA indications; to describe the open, percutaneous, and hybrid technique; to detail outcomes of each of the available techniques; and to relay the postoperative considerations for the DVA approach.
METHODS
A literature review of relevant articles containing all permutations of the terms "deep venous arterialization" and "distal venous arterialization" was undertaken with the MEDLINE, Cochrane, and PubMed databases to find cases of open, percutaneous, and hybrid DVA in the peer-reviewed literature. The free text and Medical Subject Headings search terms included were "ischemia," "lower extremity," "venous arterialization," "arteriovenous reversal," and "lower limb salvage." Studies were primarily retrospective case series but did include two studies with matched controls. Recorded primary outcomes were patency, limb salvage, wound healing, amputation, and resolution of rest pain, with secondary outcomes of complication and overall mortality. Studies were excluded if there was insufficient discussion of technical details (graft type, target vein) or lack of reported outcome measure.
RESULTS
Studies that met inclusion criteria (12 open, 3 percutaneous, 2 hybrid) were identified, reviewed, and summarized to compare technique, patient selection, and outcomes between open, percutaneous, and hybrid DVA. For open procedures, 1-year primary patency ranged from 44.4% to 87.5%; secondary patency was less reported but ranged from 55.6% at 1 year to 72% at 25-month follow-up. Limb salvage rates ranged from 25% to 100%, wound healing occurred in 28.6% to 100% of cases, and rest pain resolved in 11.9% to 100% across cohorts. For the endovascular approach, primary patency ranged from 28.6% to 40% at 6-month and 10-month follow-up. Limb salvage rates ranged from 60% to 71%, with rates of major amputation ranging from 20% to 28.5%.
CONCLUSIONS
This review provides an up-to-date review of DVA indications, description of various DVA techniques, patient selection associated with each approach, and outcomes for each technique.
Topics: Amputation, Surgical; Chronic Disease; Foot; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Recovery of Function; Risk Factors; Time Factors; Treatment Outcome; Vascular Grafting; Vascular Patency; Wound Healing
PubMed: 31901360
DOI: 10.1016/j.jvs.2019.10.085 -
Interventional Cardiology Clinics Apr 2020Chronic limb-threatening ischemia represents end-stage peripheral artery disease. It is underdiagnosed; it relies on clinical symptoms and traditional noninvasive tests,... (Review)
Review
Chronic limb-threatening ischemia represents end-stage peripheral artery disease. It is underdiagnosed; it relies on clinical symptoms and traditional noninvasive tests, which significantly underestimate the severity of disease. Innovative techniques, approaches, technologies, and risk-assessment tools have significantly improved our ability to treat these patients and to better understand their complex disease process. For patients with chronic limb-threatening ischemia considered without options, the reengineering of deep venous arterialization procedures has shown promising results. Finally, the creation of interactive and multidisciplinary teams in centers of excellence is of paramount importance to significantly improve the care and outcomes of these patients.
Topics: Angiography; Endovascular Procedures; Humans; Ischemia; Leg; Peripheral Arterial Disease; Popliteal Artery; Risk Factors
PubMed: 32147121
DOI: 10.1016/j.iccl.2019.12.006 -
Practical Neurology Feb 2023A 57-year-old man was diagnosed with acute myocardial infarction and Stanford type A aortic dissection that had spread to the common iliac arteries. He underwent a...
A 57-year-old man was diagnosed with acute myocardial infarction and Stanford type A aortic dissection that had spread to the common iliac arteries. He underwent a Bentall procedure for vascular repair. Immediately after surgery, he developed numbness and severe weakness in his left leg. On examination, he had hypotonia, absent deep tendon reflexes, weakness in the left leg (Medical Research Council (MRC) scale for muscle strength - 0/5 distal, 3/5 proximal) and reduced sensation in the left leg. Electromyography confirmed subacute involvement of the left lumbar and lumbosacral plexus. MR scan of the lumbar plexus showed diffuse muscle oedema involving the left gluteus maximus. We diagnosed ischaemic lumbosacral plexopathy secondary to extensive aorta dissection and internal iliac artery occlusion. We discuss the clinical features of ischaemic plexopathy and the diagnostic approach and review the vascular anatomy of the lumbosacral plexus.
Topics: Male; Humans; Middle Aged; Ischemia; Iliac Artery; Muscle, Skeletal; Electromyography; Aortic Dissection
PubMed: 35995555
DOI: 10.1136/pn-2022-003462 -
Vascular Medicine (London, England) Apr 2021Critical limb ischemia (CLI) constitutes the most advanced form of peripheral artery disease (PAD) and is characterized by ischemic rest pain, tissue loss and/or... (Review)
Review
Critical limb ischemia (CLI) constitutes the most advanced form of peripheral artery disease (PAD) and is characterized by ischemic rest pain, tissue loss and/or gangrene. Optimized medical care and risk factor modification in addition to revascularization could reduce the incidence of cardiovascular events and major adverse limb events, improving patients' quality of life and promising higher survival rates. Adequate adherence to cardioprotective medications, including antithrombotic therapy (e.g., antiplatelets, anticoagulants), cholesterol-lowering agents (e.g., statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors), angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and smoking cessation should be strongly encouraged for patients with CLI. This review examines these guideline-recommended therapies in terms of cardiovascular and limb-related risk reduction in patients with CLI.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Limb-Threatening Ischemia; Humans; Ischemia; Peripheral Arterial Disease; Proprotein Convertase 9; Quality of Life; Risk Factors; Risk Reduction Behavior
PubMed: 33587692
DOI: 10.1177/1358863X20987612 -
Biomarkers in Medicine Aug 2019During periods of ischemia and hypoxia, intracellular adenosine triphosphate stores are rapidly depleted. Its metabolism results in release of purine nucleosides into... (Review)
Review
During periods of ischemia and hypoxia, intracellular adenosine triphosphate stores are rapidly depleted. Its metabolism results in release of purine nucleosides into the systemic circulation. While the potential of purine nucleosides as a biomarker of ischemia has long been recognized, this has been limited by their complex physiological role and inherent instability leading to problematic sampling and prolonged, complex analysis procedures. Purine release has been demonstrated from cerebral tissue in patients undergoing carotid endarterectomy and patients presenting to hospital with stroke and transient ischemic attack. Rises in purine nucleosides have also been demonstrated in patients with angina and myocardial infarction, during systemic hypoxia, exercise, in patients with peripheral arterial disease and during surgery. This article reviews purine nucleoside production in ischemia, the development of purine analysis technology and details results of the studies investigating purine nucleosides as a biomarker of ischemia with suggestions for areas of future research.
Topics: Biomarkers; Humans; Hypoxia; Ischemia; Purine Nucleosides
PubMed: 31321992
DOI: 10.2217/bmm-2019-0049