Stage Of Peripheral Arterial Disease Research Articles

Efficacy of retrograde revascularization in diabetic patients with chronic limb-threatening ischemia after a failed antegrade approach.

Chronic limb-threatening ischemia is the end stage of peripheral arterial disease. The revascularization of patients suffering from diabetes mellitus who present chronic total occlusions of below-the-knee vessels can be technically very difficult and sometimes impossible to achieve by performing only an antegrade approach. As regards retrograde recanalization, several studies have investigated the efficacy and safety of this technique in the femoropopliteal axis or in the infrageniculate arterial vessels in patients with advanced atherosclerotic disease. Currently in the literature there are still few studies analyzing the effectiveness of the retrograde approach in the treatment of occlusions of below-the-knee vessels in patients suffering from diabetes mellitus. The purpose of the study was to retrospectively evaluate safety, technical success, and clinical outcome of retrograde transpedal/transtibial recanalization in patients suffering from diabetes mellitus. This is a retrospective observational monocentric study. We retrospectively analyzed data over a three-year period (August 2019-September 2022) of patients that underwent revascularization of one or more below-the-knee vessels for chronic limb-threatening ischemia and had a retrograde transpedal/transtibial approach after a failed antegrade transfemoral revascularization. We identified and included in the study 28 out of 352 patients. We evaluated clinical comorbidities, Rutherford-Becker classification, Texas classification, and the occluded vessels (only below-the-knee or multi-level occlusions); we then analyzed technical, procedural and clinical success, survival rate, and procedural complications. All patients included in the study underwent a 6 months follow-up. Patients belonged to Rutherford-Becker stage V (18) or VI (10), Texas wound classification IIC: 7 IID: 8 IIIC: 4 IIID: 9, all suffering from diabetes, and five were on dialysis. Treatment of a femoropopliteal lesion was performed during the same procedure in 6 of 28 patients (28.6%). Technical success was obtained in 25 out of 28 patients (89.3%), and procedural success was achieved in 23 of 28 patients (82.1%). No complications occurred at the pedal/tibial access. One minor complication at the femoral access was observed. The cure rate 6 months after the procedure was 57.1% (16/28 patients), and the 6-month survival rate was 96.4%. Three major amputations (10.7%) and four minor amputations (14.2%) were performed after revascularization procedures. Two patients were readmitted for vascular causes (7.1%). Retrograde approach for revascularization of below-the-knee vessels in diabetic patients is safe and effective with high procedural and clinical success rates in the absence of significant complications. It should be considered when revascularization cannot be achieved with an antegrade transfemoral approach.

Pedal Acceleration Time An Alternative Tool To Ankle-Brachial Index In Peripheral Arterial Disease.

Ankle-Brachial Index (ABI) is a well-established diagnostic tool for evaluating peripheral arterial disease (PAD). Limitations in its application led to the development of alternative diagnostic methods, including Toe-Brachial Index (TBI) and Transcutaneous Pressure of Oxygen (TcPO2), yet these are not as widely available as ABI. Recently, Pedal Acceleration Time (PAT), has gained popularity as a new tool to assess PAD, requiring only an ultrasound. This study seeks to further establish the correlation between ABI and PAT, determining whether PAT can be a reliable alternative for diagnosing and assessing the severity of PAD. ABI and PAT were measured in patients attending our consult with no history of vascular or endovascular surgery. Limbs with unmeasurable ABI were excluded. Patients were categorized into groups based on their PAD stage according to the Fontaine classification. Patient demographics, comorbidities and respective ABI and PAT were analysed. Sixty-nine patients (114 limbs) were included in the study. Mean age 68 ± 11.7 years, 78.3% male and 33.3% diabetic patients. Fifty-three claudicant limbs (46.5%) and 26 limbs (22.8%) with chronic limb threatening ischemia. Pearson correlation coefficient between ABI and PAT, showed a strong negative correlation (r= -0.78; p<0.01). Mean ABI and PAT for limbs in Fontaine stage I were 0.94 ± 0.17 and 82.0 ± 27.4 ms; Fontaine stage IIa 0.69 ± 0.21 and 141.3 ± 57.8 ms; Fontaine stage IIb 0.54 ± 0.14 and 173.4 ± 65.1 ms; Fontaine stage III 0.43 ± 0.15 and 216 ± 33.2 ms; Fontaine stage IV 0.49 ± 0.17 and 206.7 ± 78.1 ms, respectively. Our study suggests an inverse correlation between ABI and PAT, in accordance with the findings published in the literature, thus supporting the use of PAT as an easily reproducible and efficient alternative to ABI for evaluating the severity of PAD.

The role of therapeutic MicroRNA in arteriogenesis process in limb ischemia: A systematic review

Background Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease (PAD) and has poor clinical outcomes. Recently, stimulating arteriogenesis has been proposed to improve clinical outcomes. Several studies have shown that miRNAs have beneficial effects on limb ischemia related to arteriogenesis. This study aimed to review the roles of therapeutic miRNAs in the arteriogenesis of limb ischemia. Methods A systematic search was conducted through July 2021 using the PubMed, Scopus, and ScienceDirect databases. Two authors independently assessed studies that investigated the role of miRNAs in the arteriogenesis of limb ischemia, both in vivo and in clinical studies. Results All selected studies were in vivo studies, with a total of 36 articles and 28 types of miRNAs. miRNAs potentially regulate arteriogenesis by targeting different targets. The following miRNAs were upregulated to enhance arteriogenesis: miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. Meanwhile, microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. MiRNA-126 was the most studied miRNA, and SPRED1 was the most common target of microRNA. However, the included studies showed high heterogeneity in terms of inducing hindlimb ischemia, the timing of administration, and the method used for evaluating arteriogenesis. Moreover, most studies presented unclear or high-risk bias. Conclusion MicroRNA application in a preclinical model of hindlimb ischemia has beneficial effects on arteriogenesis. This result indicates that miRNAs might be potentially beneficial in patients with CLTI. Registration The review protocol was registered with PROSPERO under registration number CRD42024484988.

Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia.

Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

Establishing a Critical Limb Ischemia Outpatient Center: Separating Facts from Myth

Critical Limb Ischemia or chronic limb-threatening ischemia represents the end stage of peripheral artery disease where arterial flow is compromised to the lower extremities and risk of limb loss may become imminent. Revascularization of lower extremities is one of the cornerstones of limb salvage and amputation prevention. Establishing centers of high quality CLI therapy requires creating different foundational pillars in order to be successful. This article discusses critical limb ischemia center creation from the perspective of critical limb ischemia therapists working in an outpatient setting.

Mitochondrial respiration in peripheral arterial disease depends on stage severity.

Peripheral arterial disease (PAD) is an increasing cause of morbidity and its severity is graded based on clinical manifestation. To investigate the influence of the different stages on myopathy of ischemic muscle we analysed severity-dependent effects of mitochondrial respiration in PAD. Eighteen patients with severe PAD, defined as chronic limb-threatening ischemia, 47 patients with intermittent claudication (IC) and 22 non-ischemic controls were analysed. High-resolution respirometry (HRR) was performed on muscle biopsies of gastrocnemius and vastus lateralis muscle of patients in different PAD stages to investigate different respiratory states. Results from HRR are given as median and interquartile range and were normalized to citrate synthase activity (CSA), a marker for mitochondrial content. In order to account for inter-individual differences between patients and controls, we calculated the ratio of O₂-flux in gastrocnemius muscle over vastus muscle ('GV ratio'). CSA of the gastrocnemius muscle as a proxy for mitochondrial content was significantly lower in critical ischemia compared to controls. Mitochondrial respiration normalized to CSA was higher in IC compared to controls. Likewise, the GV ratio was significantly higher in IC compared to control. Mitochondrial respiration and CSA of PAD patients showed stage-dependent modifications with greater changes in the mild PAD stage group (IC).

The Clinical Utility of Lower Extremity Dual-Energy CT Angiography in the Detection of Bone Marrow Edema in Diabetic Patients with Peripheral Artery Disease.

(1) Background: Type 2 diabetes is a major cause of incidences and the progression of peripheral artery disease (PAD). Bone marrow edema (BME) is an important finding suggestive of underlying bone inflammation in non-traumatic diabetic patients with PAD. Our aim was to evaluate the presence, severity, and clinical implications of BME detected by virtual non-calcium application (VNCa) of dual-energy CT angiography (DE-CTA). (2) Methods: A consecutive series of 76 diabetic patients (55 men; mean age 71.6 ± 11.2 yrs) submitted to lower limb DE-CTA for PAD evaluation and revascularization planning, which were retrospectively analyzed. VNCa images were independently and blindly revised for the presence, location, and severity of BME by two radiologists with 10 years of experience. BME and non-BME groups were evaluated in terms of PAD clinical severity and 6-month secondary major amputation rate. (3) Results: BME was present in 17 (22%) cases, while 59 (78%) patients were non-BME. The BME group showed a significantly higher incidence of major amputation (p < 0.001) and a significantly higher number of patients with advanced clinical stages of PAD compared to the non-BME group (p = 0.024). (4) Conclusions: Lower limb DE-CTA with VNCa application is a useful tool in the detection of BME in diabetic patients with PAD, simultaneously enabling the evaluation of the severity and location of the arterial disease for revascularization planning. BME presence could be a marker of clinically severe PAD and a possible risk factor for revascularization failure.

The prevalent causes of death in patients with peripheral artery disease undergoing revascularisation or amputation.

Preventing untimely death in patients with peripheral artery disease (PAD) requires a detailed understanding of the predominant causes of death (COD). This literature review aims to describe how short- and long-term COD are reported in patients who had surgery for PAD. A literature review was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for articles reporting specific causes of mortality in patients who had surgery for all stages of PAD. Articles were included if they reported COD after open surgical or endovascular revascularisation, or major or minor amputation for PAD. Critical appraisals were conducted according to included study types, using the Joanna Briggs Institute tools. Cause of death was reported in 21 publications. Twenty were observational and one was a randomised control trial. Study size ranged from 25 to 10,505 patients. Cardiovascular disease was the most prevalent COD in perioperative periods (42.5% from 13 studies). Long-term follow-up ranged from 1month and 7years with 15 studies reporting cardiac related mortality as the most frequent cause of death. However, mortality from neoplasia, respiratory disease (including pneumonia and pulmonary emboli), stroke and sepsis were prevalent. Many studies were low-average quality, with few population-based observational studies. Whilst cardiovascular COD are the most prevalent reasons for mortality in patients with PAD, the proportion of patients dying from neoplasia and respiratory disease is high. Improved reporting standards for COD in studies examining PAD are needed.

Successful wound healing by autologous peripheral blood mononuclear cell therapy in a diabetic patient on hemodialysis with no-option critical limb ischemia: a case report.

Peripheral artery disease is a common condition in patients on chronic dialysis treatment, end-stage kidney failure itself being a risk factor. The most severe stage of peripheral artery disease, critical limb ischemia, causes marked chronic pain and is associated with risk of limb loss. Despite improvements in revascularization procedures, the results of limb salvage proceduresamong dialysis patients remains poor, and lower extremity amputation is associated with high mortality and grimsocio-economic implications. We report on alimb salvage approach that was successfully employed in a 74-year-old woman on hemodialysis suffering from no-option critical limb ischemia complicated by diabetic foot infection, i.e. otherwise a candidate for major amputation. The approach consists in implanting in the wound bed of the affected limb a concentrate of autologous peripheral blood mononuclear cells collected from the peripheral blood of the patient using a selective filtration separation system. The procedure, performed by a vascular surgeon in an outpatient setting and sterile conditions, was repeated three times at intervals of 15days, and was well tolerated; no adverse safety signals were observed. Complete wound healing was obtained, with successful limb rescue.

Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Promote Muscle Regeneration in a Diabetic Mouse Model of Critical Limb Threatening Ischemia

Critical limb threatening ischemia (CLTI), the end stage of peripheral arterial disease (PAD), is diagnosed in 500,000 patients each year, often results in amputation, and has a ~50% 5-year mortality rate. Diabetic CLTI patients experience especially high morbidity and mortality, and no effective non-surgical therapy exists for this population. Our Phase II MOBILE trial demonstrated that autologous bone marrow nucleated cells were unable to prevent amputations in diabetic patients; however, data from a Phase I trial shows that allogeneic bone marrow-derived mesenchymal stromal cells (BMD-MSC) stimulated angiogenesis in ischemic muscle, including diabetics. While allogeneic MSC may be an effective cell preparation to treat diabetic CLTI, passaging-related cell senescence prevents generation of sufficient cell numbers for therapeutic use. The development of induced pluripotent stem cell (iPSC)-derived MSC overcomes cell senescence issues and offers the possibility of genetic modifications to enhance cell function. The current study was designed to determine potential mechanisms by which iPSC-MSC stimulate muscle regeneration in a rodent CLTI model.&#x0D; The CLTI mouse model was created by ligation/excision of the femoral artery in male polygenic diabetic TallyHo mice. Mice with intramuscular administration of iPSC-MSC displayed positive indicators of muscle regeneration compared to vehicle control mice. Real-time PCR performed with gastrocnemius muscle obtained 7- or 30-days post iPSC-MSC injection showed an increase in mRNA expression for MyH3, MyoD1, Mrc1, FoxP3, and VEGF-A vs. vehicle treated muscle, indicating promotion of muscle regeneration, M2-biased macrophage expression, T regulatory cell (Treg) expansion, and vascular proliferation. Downregulation of the NADPHoxidase subunit p47phox indicated a decrease in oxidative stress in the treated mice. The results are consistent with iPSC-MSC promotion of muscle regeneration via a Treg mediated stimulation of the M1-M2 macrophage phenotypic shift. Thus, human iPSC-MSC could be an effective treatment to stimulate muscle regeneration and ameliorate CLTI in diabetic patients.

The impact of Covid-19 on mortality and clinical characteristics in hospitalized patients with peripheral artery disease in the year 2020

Abstract Background The Covid-19 pandemic developed its full destructive capacity and caused over 6.6 million confirmed deaths worldwide in the year 2020. This retrospective study aimed to examine the effects of Covid-19 on the mortality and clinical characteristics of peripheral artery disease (PAD) patients because these chronically ill patients are at risk for arterial embolic vascular complications and a fatal outcome. Methods and results From a German nationwide registry of 2020 all patients hospitalized with PAD (n=173.075) were compared in four different groups. The first group had no additional diabetes mellitus type 2 or Covid-19 (n=110.531), the second diabetes mellitus but no Covid-19 (n=59.991), the third diabetes mellitus and Covid-19 (n=1497) and the fourth no diabetes mellitus but Covid-19 (n=1056). Mortality rates in all PAD patients without Covid-19 were low and ranging between 1.1-3.6%, depending on PAD classification. However, PAD patients with Covid-19 had significantly higher mortality rates of 11.1-12.6%. Clinical characteristics and the Charlson- comorbidity index surprisingly revealed that PAD patients with Covid-19 but without diabetes mellitus presented more complications such as higher rates of stroke (1.4%), cardiogenic shock (3.3%), chronic kidney failure with GFR &amp;lt; 15 ml/min (10.5%) and prolonged ventilation time &amp;gt;48 hours (4.4%). Conclusion Covid-19 massively increased death rates in PAD patients in the year 2020. Neither disease severity of different stages of PAD nor additional diabetes mellitus had an effect on in-hospital mortality. One explanation of this finding might be that the risk for arterial embolism increases after a Covid-19 infection and thus leads to higher mortality rates in PAD patients, who are in danger for vascular/embolic complications. Our study reveals the importance of preventing the spread of Covid-19 disease, especially in the case of patients with atherosclerotic diseases.

Patients living farther from a tertiary care center are more likely to undergo peripheral arterial bypass for acute and chronic limb-threatening ischemia

ObjectiveThe aim of this study was to assess the association between the proximity to the tertiary care hospital and the severity of peripheral arterial disease (PAD) at the time of lower extremity bypass (LEB) in a rural-urban mix region. MethodsPatients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on a median distance from hospital (ie, Group I: ≥34 miles and Group II: <34 miles). Patients’ demographic features, preoperative data including comorbidities, and medications were analyzed. A univariate analysis for the patient characteristics between the two study groups, along with evaluation of postoperative outcomes, and a multivariate predictive modeling to study the PAD stage as the indication of LEB was performed. A P-value of < .05 was set as a significant difference between the groups for all the analyses. ResultsThere were 175 patients (49.9%) in Group I and 176 patients (50.1%) in Group II with a mean age of 65 ± 11.92 years (median, 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between study groups. It was observed that patients in Group I were more likely to be overweight or obese (71.3% vs 57%; P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%; P = .036) in comparison to Group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in Group I had 56% higher likelihood of LEB for chronic limb-threatening ischemia (adjusted odds ratio, 1.56; 95% confidence interval, 0.92-2.62; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (adjusted odds ratio, 5.07; 95% confidence interval, 1.42-18.13; P = .012) as compared with those in the Group II. ConclusionsPatients’ proximity to a major tertiary hospital may have implications on the disease progression for patients with PAD and could also be related to inadequate vascular services in primary and secondary hospitals. Lack of preventive care and disease management in regions afar from a tertiary hospital could be other implicating factors and highlights the need for outreach programs, along with distribution of vascular specialists, to reduce geographical disparities and ensure equity in access to care.

Rare Case of Chronic Limb-Threatening Ischemia in a 32-Year-Old Patient with Nephrotic Syndrome: A Case Report

AbstractChronic limb-threatening ischemia represents the end stage of peripheral artery disease (PAD), primarily affecting individuals over 60 years old. While quite rare, nephrotic syndrome (NS) is recognized for increasing the susceptibility to arterial thromboembolism (ATE). A 32-year-old male complained of resting pain in his left leg and pain after walking 50 meters with his right leg. He had a 9-year history of NS confirmed through biopsy and was on a daily regimen of 2 × 360 mg mycophenolic acid and 1 × 8 mg methylprednisolone. He had no history of hypertension, diabetes, or smoking. Atrophy and ulcers were observed on his left leg. Laboratory tests revealed elevated D-dimer and borderline high cholesterol levels. The right ankle-brachial index was 0.5, and for the left, it was 0.33. Computed tomography angiography identified occlusion in the left external iliac artery and right superficial femoral artery (SFA). The patient underwent percutaneous transluminal angioplasty with a plain balloon on both legs and an additional drug-eluting stent on the left SFA. He was discharged on rivaroxaban, clopidogrel, aspirin, simvastatin, mycophenolic acid, and methylprednisolone, with no complaints. The mechanism behind NS-caused ATE remains unclear, although it is associated with the loss of anticoagulants in urine, increased procoagulant activity, altered fibrinolytic systems, thrombocytosis, and enhanced platelet activation. Prolonged corticosteroid therapy in NS management also amplifies the risk of thromboembolism by promoting a hypercoagulable state. We suspected NS and the prolonged use of corticosteroids as risk factors for ATE, manifested as PAD in our patient. While optimal NS therapy may reduce the risk of PAD, prolonged corticosteroid use should be closely monitored.

Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function.

(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (p = 0.0359), age (p = 0.0488), body mass index (p = 0.0110), and plasma sE-selectin levels (p = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (p = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD.

A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells

BackgroundChronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and death. Thus, an effective therapeutic strategy is urgently needed. In this context, autologous bone marrow mononuclear cell (auto-BM-MNC) and allogeneic mesenchymal stem cells represent a promising therapeutic approach for treating CLTI. In this study, we compared the safety and beneficial therapeutic effect of auto-BM-MNC versus allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI.MethodsWe performed a randomized, prospective, double-blind and controlled pilot study. Twenty-four diabetic patients in the advanced stage of CLTI (4 or 5 in Rutherford’s classification) and a transcutaneous oxygen pressure (TcPO2) below 30 mmHg were randomized to receive 15 injections of (i) auto-BM-MNC (7.197 × 106 ± 2.984 × 106 cells/mL) (n = 7), (ii) allo-WJ-MSCs (1.333 × 106 cells/mL) (n = 7) or (iii) placebo solution (1 mL) (n = 10), which were administered into the periadventitial layer of the arterial walls under eco-Doppler guidance. The follow-up visits were at months 1, 3, 6, and 12 to evaluate the following parameters: (i) Rutherford’s classification, (ii) TcPO2, (iii) percentage of wound closure, (iv) pain, (v) pain-free walking distance, (vi) revascularization and limb-survival proportion, and (vii) life quality (EQ-5D questionnaire).ResultsNo adverse events were reported. Patients with CLTI who received auto-BM-MNC and allo-WJ-MSCs presented an improvement in Rutherford’s classification, a significant increase in TcPO2 values‬, a reduction in the lesion size in a shorter time, a decrease in the pain score and an increase in the pain-free walking distance, in comparison with the placebo group. In addition, the participants treated with auto-BM-MNC and allo-WJ-MSCs kept their limbs during the follow-up period, unlike the placebo group, which had a marked increase in amputation.ConclusionsOur results showed that patients with CLTI treated with auto-BM-MNC and allo-WJ-MSCs conserved 100% of their limb during 12 months of the follow-up compared to the placebo group, where 60% of participants underwent limb amputation in different times. Furthermore, we observed a faster improvement in the allo-WJ-MSC group, unlike the auto-BM-MNC group.Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT05631444).

Patients Residing Afar From Tertiary Care Center Are More Likely to Receive Lower Extremity Revascularization for Chronic Limb-Threatening Ischemia: A Relationship Between the Distance From Hospital and Clinical Severity of Peripheral Arterial Disease

This study aimed to assess the association between the proximity to the hospital and the severity of peripheral arterial disease at the time of infrainguinal lower extremity bypass (LEB) in a rural-urban mixed region. Medical records of patients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on the median distance of their residence from the hospital (group I: ≥34 miles and group II: <34 miles). Patients’ demographic features, preoperative data including comorbidities, the severity of peripheral arterial disease (PAD), and medications were analyzed. Univariate analysis for the patient characteristics between the two study groups, evaluation of postoperative outcomes, and multivariate predictive modeling to study the PAD stage as the indication of LEB were performed. A P value of <.05 was set as a significant difference between the groups for all the analyses. A total of 351 patients met the inclusion criteria for this study. There were 175 (49.9%) patients in group I and 176 (50.1%) patients in group II, with a mean age of 65 ± 11.92 years (median: 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between the study groups. It was observed that patients in group I were more overweight or obese (71.3% vs 57%, P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%, P = .036) compared with those in group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in group I were less likely to be treated for life-limiting claudication (adjusted odds ratio [AOR]: 0.36 [0.20-0.65]; P = .001) and had a 56% higher likelihood of LEB for chronic limb-threatening ischemia (AOR: 1.56 [0.92-2.62]; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (AOR: 5.07 [1.42-18.13]; P = .012). The Fig shows the distribution of patients by indication of LEB and patient’s residence in a zip code. Patient proximity to a major tertiary hospital may have implications for the disease progression of patients with PAD. It could be related to inadequate vascular services in primary and secondary hospitals. The lack of preventive care and disease management in regions afar from a tertiary hospital could be other factors. This highlights the need for vascular surgery outreach programs and the distribution of vascular specialists to reduce geographical disparities and ensure equity in access to care.

Morphology of neuromuscular junction in patients with peripheral artery disease

Peripheral artery disease (PAD) is primarily caused by occlusion of arteries that supply blood to the lower limbs and presents significantly pathological changes of calf muscles, include degenerating and regenerating fibers, reduction of the skeletal muscle area, connective tissue proliferation and fibrosis, fat accumulation, and abnormal mitochondria, all of which are predictors of muscle functional decline. Additionally, skeletal muscles also require the motor nerve innervation for the signal transmission through the neuromuscular junction (NMJ) to induce skeletal muscle contraction. To observe whether the NMJ is changed in the PAD patients, gastrocnemius muscles were collected from 2 health subjects and 6 PAD stage III/IV patients. The motor nerve terminals were labeled with anti-neurofilament 200 and anti-synaptophysin antibodies, the nicotinic acetylcholine receptors (nAChRs) were labeled with α-Bungarotoxin. Labeled NMJs were imaged using a laser scanning confocal microscope with Z-stack. The image was captured in 65 NMJs from health subjects and 140 NMJs from PAD patients, respectively. The total nAChR area and the number of discrete fragments of each nAChR cluster, the area per fragment, the percentage of fragmented nAChR clusters, the nerve innervation and the nerve terminal occupancy were calculated. The results were represented with mean ± standard error (SE). The nAChR area was 354.9 ± 12.7 and 209.4 ± 8.2, the average number of fragment/ nAChR cluster was 2.6 ± 0.2 and 3.1 ± 0.2, 6.2% and 19.3% of the nAChR clusters were fragmented, and the nerve terminal occupancy was 61.5 ± 1.4 % and 52.0 61.5 ± 1.8 in the health subjects and PAD patients, respectively. All nAChR clusters were innervated by the motor nerve terminal in the health subjects, whereas 8.6% of nAChR clusters were denervated in PAD Patients. These data indicate that the total nAChR area per nAChR cluster and the area of each discrete fragment are reduced and fragmented nAChR clusters are increased in PAD patients. Additionally, the denervation of nAChR clusters is increased in PAD patients. These results suggest that the neuromuscular transmission is compromised in PAD patients, which limits patients’ physical activities. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Peripheral Arterial Disease Treatment in the Non-Hospital Setting.

Treatment of peripheral artery disease (PAD) has undergone a progressive shift toward less invasive, endovascular options within the last three decades. For PAD patients, the benefits of this shift are numerous and include less periprocedural pain, decreased blood loss, shorter recovery times, and fewer missed workdays. Commonly, patient-reported outcomes are very positive with this "endovascular first" strategy and the number of open surgical procedures for various stages of PAD has declined steadily over the last 20 years. Coincident with this trend is the move toward "ambulatory" lower extremity arterial intervention (LEAI) in the hospital outpatient "same-day" department. The next logical extension was then performing LEAI in a true physician office-based lab (OBL), ambulatory surgical center (ASC), or "non-hospital setting." This article examines these trends and the concept that the OBL/ASC provides a safe, alternative site of service for PAD patients requiring LEAI.

Coronary Artery Disease in Patients Hospitalized for Peripheral Artery Disease: A Nationwide Analysis of 1.8 Million Patients.

Coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent in society. This nationwide analysis aimed to evaluate the trends of in-hospital treatment of patients admitted due to PAD with and without concomitant CAD, to determine the prevalence and risk factors of concomitant CAD in patients with PAD. Using data from the German Federal Statistical Office, we included all admissions for PAD (with and without concomitant CAD) in Germany between 2009 and 2018. Baseline patient characteristics, outcomes and comorbidities were analyzed. Elixhauser comorbidity groups and the linear van Walraven comorbidity score (vWs) were calculated to assess the comorbidity burden. Of all 1,793,517 patients hospitalized for PAD, a total of 21.8% (390,259) had concomitant CAD, increasing from 18.6% in 2009 to 24.4% in 2018. Patients with accompanying CAD showed higher in-hospital mortality (3.7 vs. 2.6%), more major amputations (9.0 vs. 7.7%) and more comorbidities (Elixhauser score: 4.2 vs. 3.2 and vWs: 9.1 vs. 6.1), resulting in higher costs (median: EUR 4541 vs. EUR 4268 per case). More advanced stages of PAD were associated with multi-vessel CAD (10% of all patients with PAD Fontaine IV showed 3-vessel CAD) and the prevalence of multi-vessel CAD increased predominantly in patients with advanced PAD. One in four patients hospitalized for PAD had concomitant CAD, showing an increase over time with an additional medical and economic burden for hospitals compared with patients without CAD.

CRITICAL LIMB ISCHEMIA. A LITERATURE REVIEW (PART 2)

Critical lower limb ischemia (CLI) is the final stage of peripheral arterial disease and occurs with chronic pain at rest, loss of tissue and limb. Despite the active development of new technologies, including endovascular and open surgical methods of treatment, and the development of various guidelines, CLI still remains an unresolved burden of vascular surgery around the world. The second part of the review describes large randomized trials, open and endovascular methods of lower limb revascularization in CLI. Also, the use of deep vein arterialization technology in No-option cases for conventional methods of revascularization.