Worth an Arm and a Leg: The Critical Importance of Limb Ischemia.
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ABSTRACT:
SUBMITTER: Valle JA
PROVIDER: S-EPMC6201406 | biostudies-literature | 2018 Aug
REPOSITORIES: biostudies-literature
Publications
Worth an Arm and a Leg: The Critical Importance of Limb Ischemia.
Valle Javier A JA Waldo Stephen W SW
Journal of the American Heart Association 20180801 16
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Project description: Not available
| S-EPMC5856450 | biostudies-literature
Project description:Peripheral artery disease, caused by chronic arterial occlusion of the lower extremities, affects over 200 million people worldwide. Peripheral artery disease can progress into critical limb ischemia (CLI), its more severe manifestation, which is associated with higher risk of limb amputation and cardiovascular death. Aiming to improve tissue perfusion, therapeutic angiogenesis held promise to improve ischemic limbs using delivery of growth factors but has not successfully translated into benefits for patients. Moreover, accumulating studies suggest that impaired downstream signaling of these growth factors (or angiogenic resistance) may significantly contribute to CLI, particularly under harsh environments, such as diabetes mellitus. Noncoding RNAs are essential regulators of gene expression that control a range of pathophysiologies relevant to CLI, including angiogenesis/arteriogenesis, hypoxia, inflammation, stem/progenitor cells, and diabetes mellitus. In this review, we summarize the role of noncoding RNAs, including microRNAs and long noncoding RNAs, as functional mediators or biomarkers in the pathophysiology of CLI. A better understanding of these ncRNAs in CLI may provide opportunities for new targets in the prevention, diagnosis, and therapeutic management of this disabling disease state.
| S-EPMC7047615 | biostudies-literature
Project description:Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis.
| S-EPMC3761355 | biostudies-literature
Project description:This is a TMT-labeled proteomics analysis of human skeletal muscle specimens obtained from the following groups: older adult controls, critical limb ischemia patients undergoing surgical intervention, and critical limb ischemia patients undergoing limb amputation.
2021-10-06 | PXD021849 | JPOST Repository
Project description:ObjectivesHeavy cannabis use has been associated with the development of acute myocardial infarction and stroke. The objective of this study was to determine if heavy, chronic cannabis use is associated with the development of acute limb ischemia (ALI) or critical limb ischemia (CLI).MethodsWe conducted a retrospective cohort study within the National Inpatient Sample (2006-2015). Patients without cannabis use disorder (CUD) were matched to patients with CUD in a 2:1 ratio using propensity scores. Our primary outcomes were incidence of ALI and CLI. Secondary outcomes included incidence of acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), frequency of open or endovascular interventions, length of stay, and total costs. Sensitivity analyses were performed with alternative models, including in the entire unmatched cohort with regression models utilizing survey weights to account for sampling methodology.ResultsWe identified a cohort of 46,297 857 unmatched patients. Patients with CUD in the unmatched cohort were younger, with less cardiovascular risk factors, but higher rates of smoking and substance abuse. The matched cohort included 824,856 patients with CUD and 1,610,497 controls. Those with CUD had a higher incidence of ALI (OR 1.20 95% CI: 1.04-1.38 P=.016). Following multiple sensitivity analyses, there was no robust association between CLI and CUD. We observed no robust association of CUD with AMI, CMI, procedures performed, frequency of amputation, costs, or total length of stay.ConclusionsCannabis use disorder was associated with a significantly higher incidence of admission for acute limb ischemia. CUD was not associated with an increased risk of critical limb ischemia following sensitivity analysis. Given CUD is often seen in younger, less co-morbid patients it provides an important target for intervention in this population.
| S-EPMC9163779 | biostudies-literature
Project description: Not available
| S-EPMC4802465 | biostudies-literature
Project description:Critical limb ischemia (CLI) represents the most advanced stage of peripheral arterial obstructive disease (PAOD) with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life.
| S-EPMC4537766 | biostudies-literature
Project description:BackgroundCritical limb ischemia (CLI) is a feared complication of peripheral vascular disease that often requires surgical management and may require amputation of the affected limb. We developed a decision model to inform clinical management for a 63-year-old woman with CLI and multiple medical comorbidities, including advanced heart failure and diabetes.MethodsWe developed a Markov decision model to evaluate 4 strategies: amputation, surgical bypass, endovascular therapy (e.g. stent or revascularization), and medical management. We measured the impact of parameter uncertainty using 1-way, 2-way, and multiway sensitivity analyses.ResultsIn the base case, endovascular therapy yielded similar discounted quality-adjusted life months (26.50 QALMs) compared with surgical bypass (26.34 QALMs). Both endovascular and surgical therapies were superior to amputation (18.83 QALMs) and medical management (11.08 QALMs). This finding was robust to a wide range of periprocedural mortality weights and was most sensitive to long-term mortality associated with endovascular and surgical therapies. Utility weights were not stratified by patient comorbidities; nonetheless, our conclusion was robust to a range of utility weight values.ConclusionsFor a patient with CLI, endovascular therapy and surgical bypass provided comparable clinical outcomes. However, this finding was sensitive to long-term mortality rates associated with each procedure. Both endovascular and surgical therapies were superior to amputation or medical management in a range of scenarios.
| S-EPMC5643229 | biostudies-literature
Project description:Mutant MetRS in MSCs allows efficient and specific identification of dynamic cell proteomics in situ, which reflect the functions and adaptive changes of MSCs that may be leveraged to understand and improve stem cell therapy in critical limb ischemia
2021-09-07 | PXD026954 | Pride
Project description:Critical limb ischemia (CLI) is the most severe clinical presentation of peripheral arterial disease and manifests as chronic limb pain at rest and/or tissue necrosis. Current clinical interventions are largely ineffective and therapeutic angiogenesis based trials have shown little efficacy, highlighting the dire need for new ideas and novel therapeutic approaches. Despite a decade of research related to skeletal muscle as a determinant of morbidity and mortality outcomes in CLI, very little progress has been made toward an effective therapy aimed directly at the muscle myopathies of this disease. Within the muscle cell, mitochondria are well positioned to modulate the ischemic cellular response, as they are the principal sites of cellular energy production and the major regulators of cellular redox charge and cell death. In this mini review, we update the crucial importance of skeletal muscle to CLI pathology and examine the evolving influence of muscle and endothelial cell mitochondria in the complex ischemic microenvironment. Finally, we discuss the novelty of muscle mitochondria as a therapeutic target for ischemic pathology in the context of the complex co-morbidities often associated with CLI.
| S-EPMC4649016 | biostudies-literature