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Frontiers in Cardiovascular Medicine 2024Peripheral artery disease (PAD) continues to increase in prevalence worldwide due to risk factors such as advanced age, diabetes mellitus, and obesity. Critical limb... (Review)
Review
Peripheral artery disease (PAD) continues to increase in prevalence worldwide due to risk factors such as advanced age, diabetes mellitus, and obesity. Critical limb ischemia (CLTI) is the advanced form of PAD that can result in a lack of healing and limb loss as the most devastating consequence. Patients with PAD, especially CLTI, benefit from multidisciplinary care to optimize outcomes by reducing cardiovascular morbidity and mortality and preventing lower extremity amputation. Collaboration between various specialties allows a focus on problems involved in treating the patient with PAD including prevention, screening, medical care, wound care, infection, and revascularization when needed. Although there is no clear definition or consensus on the structure of the PAD team, certain guidelines are applicable to most clinical scenarios emphasizing "provider champions" in leading a clinical program. A vascular specialist (vascular surgery, interventional radiology, interventional cardiology) and a soft tissue specialist (podiatry, plastic surgery) are the typical "champions," often involving orthopedics, general surgery, vascular medicine, diabetology/endocrinology, infectious disease, nephrology, and rehabilitation medicine. The team should also include wound nurses, nutritionists, occupational therapists, orthotists, pharmacists, physical therapists, prosthetists, and social workers. This paper presents a brief overview of the structure of the multidisciplinary team with key components and functions of such a team to optimize treatment outcomes for PAD and CLTI.
PubMed: 38751662
DOI: 10.3389/fcvm.2024.1368655 -
Frontiers in Endocrinology 2024Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning.
Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.
BACKGROUND
Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning.
MATERIALS AND METHODS
A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification.
RESULTS
Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687-0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001).
CONCLUSION
Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.
Topics: Humans; Male; Female; Machine Learning; Aged; Diabetes Mellitus, Type 2; Retrospective Studies; Risk Assessment; Physical Functional Performance; Longitudinal Studies; Aged, 80 and over; Geriatric Assessment; Prognosis; Italy; Follow-Up Studies; Risk Factors; Mortality
PubMed: 38745954
DOI: 10.3389/fendo.2024.1359482 -
Circulation Jun 2024The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide... (Review)
Review
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
AIM
The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia).
METHODS
A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate.
STRUCTURE
Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.
Topics: Humans; Peripheral Arterial Disease; Lower Extremity; American Heart Association; United States; Cardiology
PubMed: 38743805
DOI: 10.1161/CIR.0000000000001251 -
Cureus Apr 2024Symmetrical peripheral gangrene (SPG) is a rare yet severe condition characterized by peripheral ischemic lesions without significant vascular occlusion. Its clinical... (Review)
Review
Symmetrical peripheral gangrene (SPG) is a rare yet severe condition characterized by peripheral ischemic lesions without significant vascular occlusion. Its clinical presentation includes peripheral cyanosis, mottling, and symmetrical ischemia of distal limbs, often progressing to gangrene. Recent years have seen a rise in SPG cases, with mortality rates ranging from 40% to 90%. The condition is associated with systemic diseases, such as sepsis, vasculitis, and coagulopathy. DIC frequently complicates SPG, reflecting a disturbed procoagulant-anticoagulant balance and depletion of natural anticoagulants. While vasopressor therapy, particularly high-dose administration, has been implicated in SPG pathogenesis due to sustained vasoconstriction or idiosyncratic responses, recent evidence suggests it may not be the underlying cause. Studies indicate a low incidence of ischemic limb necrosis associated with high-dose vasopressors, with DIC and shock liver potentially explaining limb ischemia instead. The characteristic temporal interval between the onset of shock liver and limb ischemic necrosis suggests a more complex pathophysiology. The role of infectious agents, such as bacteria and viruses, in SPG pathogenesis is under investigation, with both direct vascular invasion and immune-mediated mechanisms proposed. Diagnosis involves ruling out other causes of acral gangrene through clinical examination, laboratory tests, imaging studies, and biopsy. Treatment strategies aim to halt disease progression, eliminate causative factors, and prevent complications. While anticoagulants, vasodilators, and adjunctive therapies like hyperbaric oxygen show promise, the efficacy of interventions varies, emphasizing the need for individualized management. Notably, hemoadsorption has emerged as a promising treatment, demonstrating significant improvement in SPG cases. Amputation remains a last resort option in irreversible cases. Early recognition and multidisciplinary management are crucial for improving outcomes. Further research is needed to better understand SPG's etiology and develop effective treatments through collaborative efforts.
PubMed: 38741803
DOI: 10.7759/cureus.58117 -
EXCLI Journal 2024Peripheral artery disease (PAD) is an atherosclerotic disease impacting over 200 million individuals and the prevalence increases with age. PAD occurs when plaque builds... (Review)
Review
Peripheral artery disease (PAD) is an atherosclerotic disease impacting over 200 million individuals and the prevalence increases with age. PAD occurs when plaque builds up within the peripheral arteries, leading to reduced blood flow and oxygen supply to the outer extremities. Individuals who experience PAD suffer from ischemia, which is typically accompanied by significant damage to skeletal muscles. Additionally, this tissue damage affects mitochondria, causing them to become dysregulated and dysfunctional, resulting in decreased metabolic rates. As there is no known cure for PAD, researchers are exploring potential therapeutic targets by examining coexisting cardiovascular conditions and metabolic risk factors, such as the aging process. Among these comorbidities, type-two diabetes mellitus and obesity are particularly common in PAD cases. These conditions, along with aging itself, are associated with an elevated accumulation of ectopic lipids within skeletal muscles, similar to what is observed in PAD. Researchers have attempted to reduce excess lipid accumulation by increasing the rate of fatty acid beta oxidation. Manipulating acetyl coenzyme A carboxylase 2, a key regulatory protein of fatty acid beta oxidation, has been the primary focus of such research. When acetyl coenzyme A carboxylase 2 is inhibited, it interrupts the conversion of acetyl-CoA into malonyl-CoA, resulting in an increase in the rate of fatty acid beta oxidation. By utilizing samples from PAD patients and applying the pharmacological strategies developed for acetyl coenzyme A carboxylase 2 in diabetes and obesity to PAD, a potential new therapeutic avenue may emerge, offering hope for improved quality of life for individuals suffering from PAD.
PubMed: 38741727
DOI: 10.17179/excli2024-7004 -
Stem Cell Research & Therapy May 2024Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host...
BACKGROUND
Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival.
METHODS
In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection.
RESULTS
At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats.
CONCLUSIONS
The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.
Topics: Animals; Autoantibodies; Receptor, Angiotensin, Type 1; Rats; Dopaminergic Neurons; Parkinson Disease; Disease Models, Animal; Benzimidazoles; Male; Biphenyl Compounds; Tetrazoles; Angiotensin II Type 1 Receptor Blockers; Oxidopamine; Humans; Rats, Sprague-Dawley
PubMed: 38735991
DOI: 10.1186/s13287-024-03751-y -
International Journal of Molecular... May 2024Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation... (Review)
Review
Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics. Various pathological conditions, such as ischemia, hypoxia, toxic substances, and increased protein production, may disturb protein folding, causing an increase in misfolding proteins in the ER. Such an overload of the folding process leads to ER stress and causes the unfolded protein response (UPR), which increases folding capacity in the ER. Uncompensated ER stress impairs intracellular signaling and cell function, resulting in various diseases, such as diabetes and degenerative neurological diseases. ER stress may be a critical universal mechanism underlying human diseases. Pain sensations involve the central as well as peripheral nervous systems. Several preclinical studies indicate that ER stress in the nervous system is enhanced in various painful states, especially in neuropathic pain conditions. The purpose of this narrative review is to uncover the intricate relationship between ER stress and pain, exploring molecular pathways, implications for various pain conditions, and potential therapeutic strategies.
Topics: Humans; Endoplasmic Reticulum Stress; Animals; Unfolded Protein Response; Pain; Endoplasmic Reticulum; Signal Transduction; Neuralgia; Protein Folding
PubMed: 38732214
DOI: 10.3390/ijms25094995 -
International Journal of Molecular... Apr 2024The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat...
The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences AFLLKETEEGPPATE for hERG1 and ALQSINEWAAQTT- DGKLPEVTKDVERTD for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.
Topics: Humans; Extracellular Vesicles; Biomarkers; Male; Cardiovascular Diseases; Female; Myocytes, Cardiac; Middle Aged; Animals; HSP47 Heat-Shock Proteins; Rats; ERG1 Potassium Channel; Aged; Adult; Ether-A-Go-Go Potassium Channels; Heart Failure
PubMed: 38732154
DOI: 10.3390/ijms25094913 -
Cureus May 2024The pain associated with lower extremity arterial disease is difficult to treat, even with lower extremity revascularization. We sought to evaluate in-hospital and...
INTRODUCTION
The pain associated with lower extremity arterial disease is difficult to treat, even with lower extremity revascularization. We sought to evaluate in-hospital and post-operative opioid usage in patients with different disease severities and treatments for lower extremity vascular disease.
METHODS
A retrospective review was performed for all hospital encounters for patients with an International Classification of Diseases (ICD) code consistent with lower extremity arterial disease admitted to a single center between January 2018 and March 2023. Cases included patients admitted to the hospital with a primary diagnosis of lower extremity arterial disease. These patients were subdivided based on disease severity, treatment type, and comorbid diagnosis of diabetes mellitus. The analysis focused on in-hospital opioid use frequency and dosage among these patients. The control group (CON) included encounters for patients admitted with a secondary diagnosis of lower extremity atherosclerotic disease. A total of 438 patients represented by all the analyzed encounters were then reviewed for the number and type of vascular procedures performed as well as opioid use in the outpatient setting for one year.
RESULTS
Critical limb ischemia (CLI) encounters were more likely to use opioids as compared to the CON and peripheral arterial disease (PAD) without rest pain, ulcer or gangrene groups (CLI 67.9% (95% CI: 63.6%-71.6%) versus CON 52.1% (95% CI: 48.5%-55.7%), < 0.001 and CLI 67.9% (95% CI: 63.6%-71.6%) versus PAD 50.2% (95% CI: 42.6%-57.4%), < 0.001). Opioid use was also more common in encounters for gangrene and groups treated with revascularization (REVASC) and amputation (AMP) as compared to CON (gangrene 74.5% (95% CI: 68.5%-82.1%) versus CON 52.1% (95% CI: 48.5%-55.7%), < 0.01; REVASC 58.3% (95% CI: 57.3%-66.4%) versus CON 52.1% (95% CI: 48.5%-55.7%), =0.01; and AMP 72.3% (95% CI: 62.1%-74.0%) versus CON 52.1% (95% CI: 48.5%-55.7%), < 0.01). Significantly increased oral opioid doses per day (MME/day) were not noted for any of the investigated groups as compared to the CON. In the outpatient setting, 186 (42.5% (95% CI: 37.2%-46.4%)) patients were using opioids one month after the most recent vascular intervention. By one year, 31 (7.1% (95% CI: 1.30%-7.70%)) patients were still using opioids. No differences in opioid usage were noted for patients undergoing single versus multiple vascular interventions at one year. Patients undergoing certain vascular surgery procedures were more likely to be using opioids at one year.
CONCLUSION
Patients with CLI and gangrene as well as those undergoing vascular treatment have a greater frequency of opioid use during hospital encounters as compared to those patients with less severe disease and undergoing conservative management, respectively. However, these findings do not equate to higher doses of opioids used during hospitalization. Patients undergoing multiple vascular procedures are not more likely to be using opioids long-term (at one year) as compared to those patients treated with single vascular procedures.
PubMed: 38726358
DOI: 10.7759/cureus.59963 -
Farmacia Hospitalaria : Organo Oficial... May 2024To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and... (Review)
Review
PURPOSE
To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety.
METHODS
Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included.
RESULTS
NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA.
CONCLUSIONS
Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.
PubMed: 38724402
DOI: 10.1016/j.farma.2024.04.003