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Abstract Background Hypereosinophilic syndrome (HES) consists of a group of disorders characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues, independent of known secondary causes of eosinophilia. Clinical manifestations of HES are highly variable, ranging from asymptomatic eosinophilia to severe tissue damage and end-organ failure. Case presentation We herein present the case of a 65-year-old female with a 38-year history of hemodialysis who presented with lower leg pain, fever, skin eruption with leg edema, and diarrhea. Two months before admission, she underwent placement of a stent made of nickel and titanium for abdominal aortic stenosis. Lower leg pain occurred during hemodialysis, followed by fever, pedal edema with skin eruption, and diarrhea. Gastrointestinal endoscopy, colonoscopy, and biopsy histopathology revealed colitis with massive infiltration of eosinophils, compatible with eosinophilic gastroenteritis and colitis. The patient was treated with prednisolone at an initial dose of 40 mg daily and later reduced to 10 mg daily, after which her symptoms improved and her laboratory parameters normalized. She has not experienced a relapse after 1 year of follow-up. Conclusions Our case of HES manifested as eosinophilic gastroenteritis and colitis and was successfully treated with corticosteroids. Clinicians should consider the differential diagnosis of HES when faced with similar cases in order to effect timely and appropriate treatment.

Abstract Background Findings describing the relationship between pulmonary function and peripheral vascular function have been inconclusive. We explored this relationship in Guangzhou Biobank Cohort Study-Cardiovascular Subcohort (GBCS-CVD). Methods Brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI) were measured by a waveform analyser, and pulmonary function by turbine flowmeter spirometry. Predicted forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were derived using equations for Chinese. Regression analyses were used to investigate the association. Results Of 1528 older Chinese, 980 (64.1%) had arterial stiffness (baPWV ≥1400 cm/s), but only 29 (1.9%) had peripheral arterial disease (PAD) (ABI

Objectives: To determine risk factors for peripheral arterial disease (PAD) in elderly patients with Type-2 diabetes mellitus. Methods: The elderly patients with Type-2 diabetes treated in the Central Hospital of Cangzhou were enrolled and divided into PAD group and non-PAD group between October 2016 and November 2019, The data of the patients including age, gender, body mass index, blood pressure, hemoglobin A1c, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglyceride, white cell count, lymphocyte count, high-sensitivity C-reactive protein, uric acid as well as living habits and complications of Type-2 diabetes mellitus were recorded to determine the risk factors for PAD. Results: One thousand four hundred seventy six (1476) patients were enrolled, in which 465 patients were included in group of PAD, and 1011 in non-PAD group. The univariate analysis revealed that the two groups significantly differed in age (p=0.003), course of T2DM (p=0.001), hypertension (p=0.006), smoking habits (p<0.001), hyperuricemia (p<0.01), high-sensitivity C-reactive protein (p<0.01), white cell count (p<0.001), lymphocyte count (p<0.001) and diabetic neuropathy (p<0.001). In the multivariate analysis, age (OR: 1.56, 95% CI: 1.21-1.89), smoking habit (OR: 1.37, 95% CI: 1.19-1.68), hypertension (OR: 1.44, 95% CI: 1.15-1.98), diabetic neuropathy (OR: 3.55, 95% CI: 2.14-4.29), high-sensitivity C-reactive protein (OR: 1.74, 95% CI: 1.39-2.61) and hyperuricemia (OR: 2.71, 95% CI: 1.66-3.87) were significant risk factors for PAD. Conclusions: Age, smoking habit, hypertension, diabetic neuropathy, high-sensitivity C-reactive protein and hyperuricemia were independent risk factors for peripheral arterial disease in elderly patients with Type-2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is an important cause of morbidity and mortality with little effective medical treatment currently available. Nitric oxide (NO) is crucially involved in organ perfusion, tissue protection and angiogenesis. We hypothesized that a novel NO-donor, MPC-1011, might elicit vasodilation, angiogenesis and arteriogenesis and in turn improve limb perfusion, in a hindlimb ischemia model. Hindlimb ischemia was induced by femoral artery ligation in Sprague-Dawley rats, which were randomized to receive either placebo, MPC-1011, cilostazol or both, up to 28 days. Limb blood flow was assessed by laser Doppler imaging. After femoral artery occlusion, limb perfusion in rats receiving MPC-1011 alone or in combination with cilostazol was increased throughout the treatment regimen. Capillary density and the number of arterioles was increased only with MPC-1011. MPC-1011 improved vascular remodeling by increasing luminal diameter in the ischemic limb. Moreover, MPC-1011 stimulated the release of proangiogenic cytokines, including VEGF, SDF1α and increased tissue cGMP levels, reduced platelet activation and aggregation, potentiated proliferation and migration of endothelial cells which was blunted in the presence of soluble guanylyl cyclase inhibitor LY83583. In MPC-1011-treated rats, Lin−/CD31+/CXCR4+ cells were increased by 92.0% and Lin−/VEGFR2+/CXCR4+ cells by 76.8% as compared to placebo. Here we show that the NO donor, MPC-1011, is a specific promoter of angiogenesis and arteriogenesis in a hindlimb ischemia model in an NO-cGMP-VEGF- dependent manner. This sets the basis to evaluate and confirm the efficacy of such therapy in a clinical setting in patients with PAD and impaired limb perfusion. Image 1 • PAD is a debilitating disease caused by abnormal narrowing of arteries with little or no medical treatment options existing. • Novel and unique NO donor, MPC-1011, promotes angiogenesis via NO-mediated signaling and proliferation of endothelial cells. • Thus, MPC-1011 might be successfully used in clinical setting in patients with PAD or in those with impaired limb perfusion. [ABSTRACT FROM AUTHOR]

Objective: There is evidence that standard assessment techniques for detecting PAD might be of less diagnostic accuracy in people with type 2 diabetes. The aim of this study was to examine diagnostic performance of Plethysmographic-and-Doppler derived ankle brachial index, toe brachial index, and Pulse volume waveform analysis for detecting PAD in people with T2DM.Methods: In this cross-sectional study 303 patients with T2DM were included in the study. The participants underwent ABI measurement, applying both Plethysmographic and Doppler derived devices, as well as TBI, PVW was also recorded for each patient. Diagnostic performance of each test for detecting PAD, applying ultrasound Doppler scan as the reference standard, was measured. Moreover, the best cut-off point for each method to detect PAD was determined.Results: PVW showed the highest sensitivity (81.8%) for detecting PAD, followed by ABIDOP (72.7%), and ABIPLE (20%). However, all devices showed an excellent specificity for detecting PAD. The optimal cut-off point for diagnosis of PAD was 0.9 for ABIDOP, 1.2 for ABIPLE, and 0.38 for TBI.Conclusion: Within this population of patients with T2DM, TBI less than 0.38 provided the best sensitivity for detection of PAD followed by PVW, ABIDOP≤0.9, and ABIPLE<1.2. [ABSTRACT FROM AUTHOR]

Background: Percutaneous transluminal angioplasty is established as the first-line vascular procedure in patients with lower extremity artery disease. Purpose: We aimed to evaluate the technical and clinical effectiveness of percutaneous transluminal angioplasty in the management of ischemic foot ulcers. Material and Methods: All consecutive patients presenting with a foot ulcer at the outpatient vascular surgery clinic of our hospital between June 2009 and June 2015 were evaluated using foot pulse assessment, ankle-brachial index, and duplex scanning. If non-invasive parameters suggested lower extremity artery disease, CT angiography and/or digital subtraction angiography were performed and a percutaneous transluminal angioplasty was carried out when feasible during the same session. All patients were followed until healing, amputation, death, or for at least two years. Short- and long-term clinical success was evaluated based on ulcer size and appearance. Patients with worsening ulcers after percutaneous transluminal angioplasty underwent bypass grafting or amputation. Results: Percutaneous transluminal angioplasty was performed in 161 patients (100%) with stenoses > 50%, including cases lesions > 10 cm and/or multiple/calcified lesions, 144 of which completed the study. In 88 (61.2%) patients, percutaneous transluminal angioplasty was performed in the suprapopliteal axis exclusively, in 10 (6.8%) patients in the infrapopliteal axis only, and in 46 (31.9%) in both levels. Percutaneous transluminal angioplasty was technically successful in 141 (98%) patients. After 3.1 years, the rate of healing was 68%, limb salvage 88%, overall survival 69.5%, and amputation-free survival 64%. Conclusion: Our data suggest that percutaneous transluminal angioplasty for ischemic foot ulceration treatment is in the majority of patients feasible, effective, and safe with high rates of healing and limb salvage. [ABSTRACT FROM AUTHOR]

Background: Foot complications such as ulceration and neuropathy are common complications of diabetes mellitus (DM). Previous reports have demonstrated a possible increased risk of these complications in diabetic patients with low levels of serum vitamin D.Objectctive: The purpose of this study is to compare serum vitamin D levels in diabetic patients with and without Charcot neuroarthropathy (CN), peripheral arterial disease (PAD), infection (DFI), ulceration (DFU), and peripheral neuropathy (DPN). Design: A retrospective chart review of all patients undergoing foot and ankle surgery with a history of DM over a 13 month period was performed. From this cohort, fifty subjects with CN were matched with 50 without CN and preoperative lab values were compared. A secondary evaluation was performed on the subjects' other comorbidities including PAD, DFI, DFU, and DPN. Results: Seventy-eight percent of our patients had vitamin D deficiency or insufficiency. Preoperative serum vitamin D levels were not significantly different between diabetic patients with and without CN (p = 0.55). Diabetic patients with PAD (p = 0.03), DFI (p = 0.0006), and DFU (p = 0.04) were all found to have significantly lower serum vitamin D levels than diabetic patients without these complications. Lower levels of serum albumin and higher serum creatinine were also noted with subjects with PAD, DFI, DPN, and DFU. While seasonal serum vitamin D level fluctuation was noted, this difference did not reach statistical significance with the numbers available. Conclusion: We found various lower extremity complications to be associated with low serum vitamin D including PAD, DFI, and DFU. While other studies have questioned the role of vitamin D and CN, we were unable to identify any significant difference between diabetic patients with and without Charcot neuroarthropathy. Level of evidence: Level 2 [ABSTRACT FROM AUTHOR]

Background: Peripheral Arterial Disease (PAD) is a serious cardiovascular condition that affects millions of people worldwide. It is characterized by the narrowing of arteries that carry blood to the lower limbs, leading to significant pain and discomfort. Following surgical interventions for PAD, patients often experience substantial pain and reduced quality of life. Objective: The purpose of this study is to explore the effectiveness of massage and kinesiotherapy techniques in improving well-being and reducing pain in postoperative PAD patients. We aim to demonstrate that these methods can contribute to faster and more efficient recovery. Material and methods: A clinical study involving a sample of 30 subjects with PAD who have recently undergone surgery is currently underway at the Emergency County Clinical Hospital in Târgu Mureş, from March to June 2024. The subjects are undergoing a six-week program of massage and kinesiotherapy. We regularly monitor their well-being and pain levels through standardized questionnaires and clinical assessments. Results : Our findings indicate a significant improvement in well-being and a reduction in pain among subjects who participated in the massage and kinesiotherapy program. Most subjects reported better quality of life and improved ability to perform daily activities. Conclusions: Massage and kinesiotherapy can play a crucial role in the recovery and rehabilitation of postoperative PAD patients. These non-invasive and cost-effective methods should be considered an integral part of postoperative treatment plans for PAD patients. Our study suggests that these techniques can significantly enhance patients' quality of life and alleviate pain associated with PAD. [ABSTRACT FROM AUTHOR]

Objective: Toll-like receptors (TLRs) are key pattern recognition receptors in the innate immune system. In particular, the TLR4-mediated immune response has been implicated in ischemia-induced tissue injury. Mounting evidence supports a detrimental role of the innate immune system in the pathophysiology of skeletal muscle damage in patients with chronic limb-threatening ischemia (CLTI), in whom patient-oriented functional outcomes are poor. The overall aim of this study was to investigate the potential role of TLR4 in skeletal muscle dysfunction and damage in CLTI., Methods: The role of TLR4 in ischemic muscle was investigated by (1) studying TLR4 expression and distribution in human gastrocnemius muscle biopsies, (2) evaluating the functional consequences of TLR4 inhibition in myotubes derived from human muscle biopsies, and (3) assessing the therapeutic potential of modulating TLR4 signaling in ischemic muscle in a mouse hindlimb ischemia model., Results: TLR4 was found to be expressed in human muscle biopsies, with significant upregulation in samples from patients with CLTI. In vitro studies using cultured human myotubes demonstrated upregulation of TLR4 in ischemia, with activation of the downstream signaling pathway. Inhibition of TLR4 before ischemia was associated with reduced ischemia-induced apoptosis. Upregulation of TLR4 also occurred in ischemia in vivo and TLR4 inhibition was associated with decreased inflammatory cell infiltration and diminished apoptosis in the ischemic limb., Conclusions: TLR4 is upregulated and activated in ischemic skeletal muscle in patients with CLTI. Modulating TLR4 signaling in vitro and in vivo was associated with attenuation of ischemia-induced skeletal muscle damage. This strategy could be explored further for potential clinical application., Competing Interests: None., (© 2024 by the Society for Vascular Surgery. Published by Elsevier Inc.)

Abstract Chronic limb ischaemia presents over time. The most common cause of chronic ischaemia is peripheral arterial disease (PAD). Risk factors for the development of PAD may be modifiable or non-modifiable (age, gender, ethnicity and family history). Intermittent claudication, the most common presenting symptom, may have a relatively benign prognosis in many cases, whereas critical limb ischaemia (CLI) refers to disease progression with threatened limb loss, and requires intervention. In contrast, acute limb ischaemia occurs suddenly, commonly due to thrombosis, embolization or trauma (including iatrogenic causes), and may also be limb threatening, requiring urgent investigation and intervention in order to reduce risks of limb loss. [ABSTRACT FROM AUTHOR]

The transplantation of various immune cell types are promising approaches for the treatment of ischemic cardiovascular disease including myocardial infarction (MI) and peripheral arterial disease (PAD). Major limitation of these so-called Advanced Therapy Medicinal Products (ATMPs) is the ischemic microenvironment affecting cell homeostasis and limiting the demanded effect of the transplanted cell products. Accordingly, different clinical and experimental strategies have been evolved to overcome these obstacles. Here, we give a short review of the different experimental and clinical strategies to solve these issues due to ischemic cardiovascular disease.

Drugs for diabetes are required to demonstrate cardiovascular safety through CV outcome trials (CVOT). The pre-defined end-points for cardiovascular outcome studies may not be sufficient to capture all clinically relevant atherosclerotic cardio vascular disease (ASCVD) events particularly peripheral arterial disease (PAD). We planned a scoping review and searched database to identify CVOT conducted in population with diabetes measuring lower limb events due to PAD as the primary outcome measure. We also searched CVOT for reported differential cardiovascular outcomes in population with PAD. We identified that CV outcomes are measured as 3 point major adverse cardiovascular outcomes (3P-MACE) that includes nonfatal MI and nonfatal stroke or 4P-MACE that included additional unstable angina which is further expanded to 5P-MACE by the inclusion of hospitalization for heart failure (HHF). These CV end points are captured as surrogate for CV mortality based on the biological plausibility of relation between the surrogate and final outcome from pathophysiological studies. We found the prevalence of PAD is no lesser than other CV events in people with diabetes. Moreover, PAD contributes to the significant morbidity associated with diabetes as a surrogate for mortality. However, none of the CVOT with anti-diabetic drugs include PAD events as primary outcome measure despite the inclusion of 6–25 % participants with PAD in major CVOT. PAD outcomes are objectively measurable with tibial arterial waveforms and clinical end-point as lower extremity amputation. PAD outcomes do improve with treatment including intensive glycemic control and novel oral anticoagulants. We suggest the inclusion of PAD to MACE as a pre-specified outcome for a comprehensive capture of major adverse vascular event in future studies for people with diabetes. MACE should be expanded to include PAD event as major adverse vascular event in cardiovascular outcome studies since PAD is clinically relevant and objectively measurable in diabetes. • Major adverse cardiovascular event do not capture all events as surrogate for cardiovascular mortality in outcome trials. • Peripheral arterial disease significantly contribute to morbidity and cardiovascular mortality as broad definition of atherosclerotic cardiovascular disease. • Peripheral arterial disease should be objectively assessed by tibial arterial waveforms Cinical events captured as lower limb tissue loss and limb amputation to be included as primary outcome measure in cardiovascular outcome studies in diabetes. [ABSTRACT FROM AUTHOR]

Background: In the management of Peripheral Arterial Disease (PAD), the administration of anticoagulant or antiplatelet agents is imperative. The use of Dual Antiplatelet Therapy (DAPT) in conjunction with rivaroxaban has shown potential in mitigating adverse outcomes. Given the heterogeneity in the pathology of lower limb arteries, there is a compelling case for individualized treatment strategies., Methods: In a single-center retrospective study on pharmacotherapy for peripheral artery disease, patients were treated with either aspirin combined with rivaroxaban or aspirin coupled with clopidogrel. The primary efficacy outcome encompassed a composite of increases in the Rutherford classification, acute limb ischemia, amputations due to vascular causes, target lesion revascularization, myocardial infarction, ischemic stroke, and cardiovascular death. The primary safety outcome was major bleeding, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria; meanwhile, major bleeding as categorized by the International Society on Thrombosis and Haemostasis (ISTH) served as a secondary safety outcome. The study differentiated between two subgroups: patients with only above-the-knee and below-the-knee arterial lesions., Results: From January 2016 to December 2021, 455 patients received either clopidogrel plus aspirin or rivaroxaban plus aspirin following endovascular treatment (EVT). The rivaroxaban group ( n  = 220) exhibited a lower incidence of primary efficacy outcomes [49.1% vs. 60.4%, hazard ratio (HR) 0.77, P  = 0.006] but had more TIMI major bleeding events (5.9% vs. 2.1%, HR 2.6, P  = 0.04). ISTH major bleeding events did not show a significant difference, though a higher percentage of rivaroxaban patients discontinued medication due to bleeding (10% vs. 4.7%, HR 2.2, P  = 0.03). In the above-the-knee arterial disease subgroup, the rivaroxaban group demonstrated a lower incidence of primary efficacy outcomes (28.2% vs. 45.2%, HR 0.55, P  = 0.02). In the below-the-knee arterial disease subgroup, no significant difference was observed in the occurrence of primary efficacy events between the two groups (58.7% vs. 64.8%, HR 0.76, P  = 0.14)., Conclusion: Rivaroxaban plus aspirin improved outcomes compared to DAPT in patients with lower extremity artery disease. Similar findings were observed in the above-the-knee artery lesion-only group. However, in the below-the-knee artery lesion-only group, rivaroxaban plus aspirin did not surpass DAPT in efficacy. Regarding safety, rivaroxaban plus aspirin exhibited higher bleeding risks and more frequent treatment discontinuation than aspirin combined with clopidogrel., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Huo and Cheng.)

Background: Specialized pro-resolving lipid mediators (SPM) such as resolvin D1 (RvD1) attenuate inflammation and exhibit vasculo-protective properties., Methods: We investigated poly-lactic-co-glycolic acid (PLGA)-based nanoparticles (NP), containing a peptide targeted to tissue factor (TF) for delivery of 17R-RvD1 and a synthetic analog 17-R/S-benzo-RvD1 (benzo-RvD1) using in vitro and in vivo models of acute vascular injury. NPs were characterized in vitro by size, drug loading, drug release, TF binding, and vascular smooth muscle cell migration assays. NPs were also characterized in a rat model of carotid angioplasty., Results: PLGA NPs based on a 75/25 lactic to glycolic acid ratio demonstrated optimal loading (507.3 pg 17R-RvD1/mg NP; P  = ns) and release of RvD1 (153.1 pg 17R-RvD1/mg NP; P  < .05). NPs incorporating the targeting peptide adhered to immobilized TF with greater avidity than NPs with scrambled peptide (50 nM: 41.6 ± 0.52 vs 32.66 ± 0.34; 100 nM: 35.67 ± 0.95 vs 23.5 ± 0.39; P  < .05). NPs loaded with 17R-RvD1 resulted in a trend toward blunted vascular smooth muscle cell migration in a scratch assay. In a rat model of carotid angioplasty, 16-fold more NPs were present after treatment with TF-targeted NPs compared with scrambled NPs ( P  < .01), with a corresponding trend toward higher tissue levels of 17R-RvD1 ( P  = .06). Benzo-RvD1 was also detectable in arteries treated with targeted NP delivery and accumulated at 10 times higher levels than NP loaded with 17R-RvD1. There was a trend toward decreased CD45 immunostaining in vessels treated with NP containing benzo-RvD1 (0.76 ± 0.38 cells/mm 2 vs 122.1 ± 22.26 cells/mm 2 ; P  = .06). There were no significant differences in early arterial inflammatory and cytokine gene expression by reverse transcription-polymerase chain reaction., Conclusions: TF-targeting peptides enhanced NP-mediated delivery of SPM to injured artery. TF-targeted delivery of SPMs may be a promising therapeutic approach to attenuate the vascular injury response., Competing Interests: M.S.C. and T.D. are co-inventors on US Patents Nos. 9,463,177 and 10,111,847 assigned to the University of California and Brigham and Womens Hospital. M.S.C. and T.D. are co-founders of VasaRx., (© 2023 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery.)

Objectives To study international differences in incidence and practice patterns as well as time trends in lower limb amputations related to peripheral arterial disease and/or diabetes mellitus. Methods Data on lower limb amputations during 2010–2014 were collected from population based administrative data from countries in Europe and Australasia participating in the VASCUNET collaboration. Amputation rates, time trends, in hospital or 30 day mortality and reimbursement systems were analysed. Results Data from 12 countries covering 259 million inhabitants in 2014 were included. Individuals aged ≥ 65 years ranged from 12.9% (Slovakia) to 20.7% (Germany) and diabetes prevalence among amputees from 25.7% (Finland) to 74.3% (Slovakia). The mean incidence of major amputation varied between 7.2/100,000 (New Zealand) and 41.4/100,000 (Hungary), with an overall declining time trend with the exception of Slovakia, while minor amputations increased over time. The older age group (≥65 years) was up to 4.9 times more likely to be amputated compared with those younger than 65 years. Reported mortality rates were lowest in Finland (6.3%) and highest in Hungary (20.3%). Countries with a fee for service reimbursement system had a lower incidence of major amputation compared with countries with a population based reimbursement system (14.3/100,000 versus 18.4/100,000, respectively, p <.001). Conclusions This international audit showed large geographical differences in major amputation rates, by a factor of almost six, and an overall declining time trend during the 4 year observation of this study. Diabetes prevalence, age distribution, and mortality rates were also found to vary between countries. Despite limitations attributable to registry data, these findings are important, and warrant further research on how to improve limb salvage in different demographic settings. [ABSTRACT FROM AUTHOR]

In this review 14 studies were identified reporting the treatment strategy in 4891 patients with Critical Limb Ischemia (CLI) with the aim to investigate if the strategy of treatment of the first episode of CLI has changed during the last 15–20 years. A computer research has been performed on PubMed and Scopus databases on November 2016. The used terms for the investigation about studies evaluating the strategy of treatment of CLI at the first-time presentation, have been “critical leg ischemia”, “critical limb ischemia”, “critical lower limb ischemia” along with the terms “placebo”, “medical treatment” and/or “conservative” revascularisation, surgical revascularisation, endovascular revascularisation, hybrid revascularisation and primary amputation. Studies were included if they were either retrospective or prospective and reporting the rate of patients who underwent to any form of revascularization, conservative treatment and primary amputation. The one-year limb and life survival rates have been reported as major outcomes. The pooled rate of revascularization was 72.5% (95% CI 80-64.96) of which 54.5%, surgical, 38.3% endovascular and 7.1% hybrid. The bivariate regression of revascularisation procedures has been with not significant increase, from 68% in 1993 to 88% in 2015. The endovascular procedures have shown a significant increase of the trend, from 2% to more the 50% (p 0.007), while surgical and hybrid procedures have not. The pooled rate of conservative treatment was 18% (95% CI 11.6–24.5%) with a not significant increasing trend and primary amputation pooled rate was 8.7% (95% CI 12.0-5,4) with a significant decreasing trend (p 0.009). The one-year limb survival rate was 75,4% (95% CI 81.5-69.3%) and the life survival was 76%. (95% CI 85.4-66.1%) both with a not significant increasing trend. In conclusion, this review highlights how the treatment strategy of the first CLI manifestation has changed over the last 15–20 years. It has shown an increase of the rate of revascularization procedures, particularly for endovascular and a significant reduction of the rate of primary amputations. The rate of patients treated conservatively appears to be unchanged and maybe influencing the rate of limb and life survival, that have remained unchanged. [ABSTRACT FROM AUTHOR]

Previous studies have reported that light-to-moderate drinkers have a lower risk of peripheral arterial disease (PAD) than abstainers, and that heavy drinking increases the risk of PAD. However, reports of the effects of severe alcohol drinking on PAD are lacking within a population-based cohort. Alcohol intoxication is typically considered a medical emergency at clinics in Taiwan and is commonly attributed to excessive alcohol use. The present study aimed to investigate the association between alcohol intoxication and PAD risk. We conducted a retrospective, population-based, health insurance cohort study consisting of 56,544 adult patients with alcohol intoxication between January 1, 2000 and December 31, 2009, using claims data from the National Health Insurance Research Database (NHIRD) of Taiwan. This database included a control cohort of 226,176 residents without alcohol intoxication. The patients were age- and gender-matched. The incidence rate of PAD, after data regarding alcohol intoxication were obtained, was 12.8 per 10,000 person-years, and the adjusted hazard ratio (aHR) of PAD was 3.80 (95% confidence interval [CI] = 3.35-4.32, p < 0.05). The log-rank test showed that patients with alcohol intoxication had a considerably higher PAD cumulative incidence rate than those without alcohol intoxication. Alcohol intoxication was significantly associated with an increased risk of PAD in men (hazard ratio [HR] = 3.77, 95% CI = 3.30-4.31) and women (HR = 4.26, 95% CI = 2.60-6.97). The aHRs of PAD risk were 7.64 (95% CI = 4.39-13.3), 4.51 (95% CI = 3.83-5.29), and 2.16 (95% CI = 1.69-2.77) for patients with alcohol intoxication compared to participants of the control group aged <35 years, 35-64 years, and ≥65 years, respectively. The individuals with alcohol intoxication and without any comorbidities had a 3.77-fold increased risk of PAD in comparison to that of the control cohorts (HR = 3.77, 95% CI = 3.30-4.30). The aHR of PAD in patients with alcohol intoxication was 4.53 (95% CI = 2.51-8.16) in comparison to the control cohort, which consisted of patients with at least one existing comorbidity. Alcohol intoxication, along with the severe complications of excessive alcohol use, should be considered as major risk factors of PAD in the setting of a medical emergency. Further research needs to be performed to evaluate the quantitative effect of alcohol use on PAD. [ABSTRACT FROM AUTHOR]

The clinical features of patients with critical limb ischemia (CLI) who responded to angiogenesis using autologous peripheral blood mononuclear cell transplantation (PB-MNC) have not yet been fully characterized, and there are no useful predictors to judge the curative effect in the early period after PB-MNC. This study sought to clarify the clinical features and predictors in patients with CLI who were successfully treated using PB-MNC. 30 consecutive patients [arteriosclerosis obliterans: 24 patients, thromboangiitis obliterans: 6 patients] who were diagnosed with major amputation despite maximal medical therapy were enrolled in this study. The study endpoint was major amputation within 3 months after PB-MNC. The collected data were evaluated for correlation between patients with and without major amputation within 3 months after PB-MNC. Six patients underwent major amputation and 1 patient underwent minor amputation. In the patients with major amputation, transcutaneous oxygen tension before PB-MNC and transplanted CD34-positive cells were lower than those of patients without major amputation. In the patients with amputation, interleukin-6 (IL-6) continued to increase after the first PB-MNC, and basic fibroblast growth factor (bFGF) decreased within 3 days after the first PB-MNC. PB-MNC was useful for the patients who were managed for inflammation and who had revascularization of the upper-popliteal arteries and two of the infra-popliteal arteries by endovascular and/or surgical revascularization. Variation in IL-6 and bFGF in the early period after PB-MNC could be useful predictors for the requirement of amputation within 3 months after PB-MNC. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) complicated with diabetes mellitus (DM) still remains a thorny issue due to lack of effective strategies. Our previous study has demonstrated that inhibition of mTORC1 protected adipose-derived stromal cells from hindlimb ischemic injury in PAD mice. However, whether inhibition of mTORC1 could protect against PAD in diabetes mellitus and the underlying mechanisms remained elusive. In this study, we employed endothelial-specific raptor (an essential component of the mTORC1 signaling complex) knockout (KO) mice (Tie2-mTORC1 ko ) to investigate whether and how mTORC1 downregulation could alleviate hindlimb ischemic injury in diabetic mice. Tie2-mTORC1 ko mice and their wild-type littermates were intraperitoneally injected with streptozocin to induce type 1 diabetic model, after which the hyperglycemic mice were randomly allocated to sham operation or PAD operation (femoral artery ligation). The restoration of hindlimb blood perfusion and recovery of limb functions were improved in diabetic Tie2-mTORC1 ko PAD mice with significant improvements of autophagy, angiogenesis and vascular integrity as well as attenuation of apoptosis, inflammation and oxidative stress. In vitro , high glucose combining with hypoxia/serum deprivation treatment (HG+H/SD) significantly triggered apoptosis, reactive oxygen species generation and inflammation while inhibited autophagy and tube formation in HUVECs. The effect could be accentuated and attenuated by mTORC1 over-expression ( TSC2 siRNA) and mTORC1 silencing ( raptor siRNA), respectively. Moreover, autophagy inhibitor 3-MA could simulate the effects of TSC2 siRNA while autophagy inducer rapamycin could mimic the effects of raptor siRNA, suggesting that the beneficial effects of mTORC1 deletion were associated with autophagy induction. In conclusion, our present study demonstrates that endothelial mTORC1 deletion protects against hindlimb ischemic injury in diabetic mice possibly via activation of autophagy, attenuation of oxidative stress and alleviation of inflammation. Therapeutics targeting mTORC1 may therefore represents a promising strategy to rescue limb ischemia in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle--brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68-4.58), p<0.001), secondary end points (HR, 1.39 (95% CI, 0.97-1.99), p<0.076), and death (HR, 1.84 (95% CI, 1.26-2.68), p=0.002). PAD was common in this population: of 819 kidney transplant recipients, 46% had PAD. Low ABI was associated with a threefold greater risk of graft failure, a twofold greater risk of death after transplant, and a threefold greater risk of secondary end points. Screening for PAD is important in this patient population because of the potential impact on long-term outcomes. [ABSTRACT FROM AUTHOR]

Objectives/Background The objective was to validate the diagnoses of peripheral arterial disease (PAD) in the legs, obtained from national registers in Denmark. Methods In total, 1435 registered cases of PAD were identified in the Danish National Patient Registry among 57,053 middle aged participants from the Danish Diet, Cancer and Health cohort study. Validation was performed by reviewing all medical records using pre-specified criteria for a diagnosis of PAD. Results The overall positive predictive value (PPV) of PAD diagnoses was 69.4% [95% confidence interval (CI) 67.0–71.7]. The PPV of diagnoses given in departments of vascular surgery was significantly higher than diagnoses given in other departments: 71.9% (95% CI 69.2–74.4) versus 58.3% (95% CI 52.2–64.2), respectively. In a sub-study, 141 potential cases of PAD also registered in the Danish National Vascular Registry were evaluated, and a PPV of 87.9% (95% CI 81.4–92.4) was found for these diagnoses. Conclusion More than 30% of the diagnoses of PAD notified in the Danish National Patient Registry were not valid, stressing the importance of validation when using register information for research purposes. In contrast, diagnoses obtained from the Danish National Vascular Registry had a high validity ready for use without further validation. [ABSTRACT FROM AUTHOR]

AIM: The purpose of this study was the application of a second derivative near infrared spectrophotometric (NIRS) technique to the human calf muscle in order to see if peripheral arterial disease (PAD) patients can be discriminated from control subjects, before, during and after a standard treadmill exercise test. METHODS: Three groups of human subjects were studied: group A consisted of 10 control subjects and groups B and C were formed by PADpatients classified as Fontaine's stage 2a (5 patients) and 2b (10 patients), respectively. The measurement protocol for all groups was 9.75 minutes of standing up (phase 1), 1 minute of exercise (phase 2) and 1 minute of rest (phase 3). Seven variables were defined at different times from the onset of the measurement protocol. RESULTS: All variables were significantly higher (p < 0.05) in group A in comparison to groups B and C. The level of significance was ten times higher (p < 0.005) at the onset (15 seconds) of the experiment and during phases 2 and 3. However, none of the variables in group B was significantly different from those in group C. CONCLUSIONS: It is shown for the first time that a second derivative NIRS technique can discriminate (p = 0.003) healthy subjects from PAD patients, in just 15 seconds of standing, with no exercise requirement. More experiments are required in order to uncover the full potential of the technique in the diagnosis of the PAD. [ABSTRACT FROM AUTHOR]

Muscle injury resulting from ischemia-reperfusion largely aggravates patient prognosis but whether and how muscle phenotype modulates ischemia-reperfusion-induced mitochondrial dysfunction remains to be investigated. We challenged the hypothesis that glycolytic muscles are more prone to ischemia-reperfusion-induced injury than oxidative skeletal muscles. We therefore determined simultaneously the effect of 3 h of ischemia induced by aortic clamping followed by 2 h of reperfusion (IR, n = 11) on both gastrocnemius and soleus muscles, as compared to control animals (C, n = 11). Further, we investigated whether tempol, an antioxidant mimicking superoxide dismutase, might compensate a reduced defense system, likely characterizing glycolytic muscles (IR-Tempol, n = 7). In the glycolytic gastrocnemius muscle, as compared to control, ischemia-reperfusion significantly decreased mitochondrial respiration (-30.28 ±6.16%, p = 0.003), increased reactive oxygen species production (+79.15 ± 28.72%, p = 0.04), and decreased reduced glutathione (-28.19 ± 6.80%, p = 0.011). Less deleterious effects were observed in the oxidative soleus muscle (-6.44 ± 6.30%, +4.32 ± 16.84%, and -8.07 ± 10.84%, respectively), characterized by enhanced antioxidant defenses (0.63 ± 0.05 in gastrocnemius vs. 1.24 ± 0.08 μmol L-1 - g-1 in soleus). Further, when previously treated with tempol, glycolytic muscle was largely protected against the deleterious effects of ischemia-reperfusion. Thus, oxidative skeletal muscles are more protected than glycolytic ones against ischemia-reperfusion, thanks to their antioxidant pool. Such pivotal data support that susceptibility to ischemia-reperfusion-induced injury differs between organs, depending on their metabolic phenotypes. This suggests a need to adapt therapeutic strategies to the specific antioxidant power of the target organ to be protected. [ABSTRACT FROM AUTHOR]

Both open surgery and endovascular peripheral interventions have been shown to effectively improve outcomes in patients with peripheral artery disease, but minimal data exist comparing outcomes performed at and below the knee. The purpose of this study was to compare outcomes following infrageniculate lower extremity open bypass (LEB) versus peripheral vascular intervention (PVI) in patients with critical limb ischemia. Using data from the 2008–2014 Vascular Quality Initiative, 1-year primary patency, major amputation, and mortality were compared among all patients undergoing LEB versus PVI at or below the knee for rest pain or tissue loss. Overall, 2566 patients were included (LEB=500, PVI=2066). One-year primary patency was significantly worse following LEB (73% vs 81%; p<0.001). One-year major amputation (14% vs 12%; p=0.18) and mortality (4% vs 6%; p=0.15) were similar regardless of revascularization approach. Multivariable analysis adjusting for baseline differences between groups confirmed inferior primary patency following LEB versus PVI (HR 0.74; 95% CI, 0.60–0.90; p=0.004), but no significant differences in 1-year major amputation (HR 1.06; 95% CI, 0.80–1.40; p=0.67) or mortality (HR 0.71; 95% CI, 0.44–1.14; p=0.16). Based on these data, we conclude that endovascular revascularization is a viable treatment approach for critical limb ischemia resulting from infrageniculate arterial occlusive disease. [ABSTRACT FROM AUTHOR]

Some believe that certain patients with intermittent claudication may be unsuitable for supervised exercise therapy (SET), based on the presence of comorbidities and the possibly increased risks. We conducted a systematic review (MEDLINE, EMBASE and CENTRAL) to summarize evidence on the potential influence of diabetes mellitus (DM) on the response to SET. Randomized and nonrandomized studies that investigated the effect of DM on walking distance after SET in patients with IC were included. Considered outcome measures were maximal, pain-free and functional walking distance (MWD, PFWD and FWD). Three articles met the inclusion criteria (n = 845). In one study, MWD was 111 meters (128%) longer in the non-DM group compared to the DM group after 3 months of follow-up (p = 0.056). In a second study, the non-DM group demonstrated a significant increase in PFWD (114 meters, p ⩽ 0.05) after 3 months of follow-up, whereas there was no statistically significant increase for the DM group (54 meters). On the contrary, the largest study of this review did not demonstrate any adverse effect of DM on MWD and FWD after SET. In conclusion, the data evaluating the effects of DM on SET were inadequate to determine if DM impairs the exercise response. While trends in the data do not suggest an impairment, they are not conclusive. Practitioners should consider this limitation when making clinical decisions. [ABSTRACT FROM AUTHOR]

Prospective studies supporting a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident peripheral arterial disease (PAD) are limited. We evaluated the association of Lp-PLA2 with incident PAD in a multi-ethnic cohort without clinical cardiovascular disease. A total of 4622 participants with measurement of Lp-PLA2 mass and Lp-PLA2 activity and an ankle–brachial index (ABI) between 0.9 and 1.4 were followed for the development of PAD (median follow-up = 9.3 years), defined as an ABI ⩽0.9 and decline from baseline ⩾0.15. There were 158 incident PAD events during follow-up. In adjusted logistic regression models, each higher standard deviation of both Lp-PLA2 activity and mass did not confer an increased risk of developing PAD [odds ratios, (95% confidence intervals)]: 0.92 (0.66–1.27) for Lp-PLA2 activity and 1.06 (0.85–1.34) for mass. Additionally, no significant interaction was found according to ethnicity: p=0.43 for Lp-PLA2 activity and p=0.55 for Lp-PLA2 mass. We found no evidence of an association between Lp-PLA2 and incident PAD. [ABSTRACT FROM AUTHOR]

Background: Literatures reported that poor sleep complaints were associated with a great deal of health outcomes. However, there are few studies on the association of poor sleep complaints with diabetic vascular complications. Methods: Aiming on the association, a cross-sectional survey was conducted among 1220 diabetic patients in this study. Poor sleep complaints were composed of difficulty falling asleep, early final awakening, short sleep and long sleep. The diabetic vascular complications involved in the study were diagnosed according to the Standards of Medical Care in Diabetes (ADA 2016). Results: Our findings indicated that short sleep remained independently associated with diabetic kidney disease (DKD) (OR > 1, P < 0.05) after the adjustments; long sleep independently associated with diabetic retinopathy (DR) (OR > 1, P < 0.05); early final awakening and short sleep independently associated with cardiovascular disease (OR > 1, P < 0.05); short sleep independently associated with peripheral arterial disease (OR > 1, P < 0.05); there was no association between poor sleep complaints and neuropathy (P > 0.05). Conclusions: The study suggests that the poor sleep complaints were distinguishably associated with diabetic vascular complications. Clinicians should take poor sleep complaints into account in diabetes treatment. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic capabilities of orbital synchronized helical scanning at lower extremity computed tomography angiography between the Add/Sub software and the deformable image registration., Methods: From March 2015 to December 2016, 100 dialysis patients underwent orbital synchronized lower limb CT subtraction angiography and lower limb endovascular treatment within 4 months. For the visual evaluation of blood vessels in the lower extremities, a stenosis rate of 50% or more was considered to be stenosis. It was classified into two areas: above-knee (AK) region (superficial femoral artery and popliteal artery) and below-knee (BK) region (anterior tibial artery, posterior tibial artery, and fibula artery). Considering angiography for the lower limb endovascular treatment as the golden standard, we calculated the sensitivity, specificity, positive-predictive value, negative-predictive value, and diagnostic capabilities. Receiver operating characteristic curve (ROC) analysis was performed to calculate the area under curve (AUC)., Results: Calcification subtraction failure was observed to be 11% in the AK region and 2% in the BK region using the Add/Sub software. The specificity, positive-predictive value, diagnostic capabilities, and AUC of the deformable image registration were lower than those of the Add/Sub software., Conclusions: Add/Sub software and deformable image registration have high diagnostic capability to remove calcification. On the other hand, the specificity and AUC of the deformable image registration were lower than those of the Add/Sub software. Also, even if the same deformable image registration is used, caution is required because the diagnostic performance varies depending on the site.

The current literature strongly supports the use of supervised exercise therapy (SET) as the first-line treatment for symptomatic peripheral arterial disease (PAD) such as intermittent claudication (IC). However, this form of treatment remains underutilised in clinical practice. The home-based exercise therapy (HBET), in which patients must conduct themselves unsupervised is generally less effective than SET in terms of improving functional walking capacity. Nevertheless, it may be a useful alternative where SET is unavailable. The objective of this systematic review is to determine the effectiveness of HBET in reducing symptoms of IC in patients with PAD. Studies eligible for inclusion in this systematic review were parallel-group randomised controlled trials (RCTs) published in the English language that compared the effect of HBET to a comparator arm (SET or no exercise/attention control) in adults with PAD and IC. Studies were eligible if outcome measures were available at baseline and at 12 weeks of follow-up or more. The electronic databases PubMed, Google Scholar, and the Cochrane Library were searched from the earliest records up to January 2021. The Cochrane Collaboration risk of bias tool for RCTs (RoB 2) was used to assess the risk of bias in individual studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) classification system was used to appraise the quality of evidence for each outcome across all studies. The primary investigator independently collected, pooled, and analysed the data. The data was then entered into the ReviewManager 5 (RevMan 5) software, and a meta-analysis was performed by using a fixed or random effects model depending on the presence or absence of statistical heterogeneity. The review author identified seven RCTs involving a total of 754 patients which were included in this study. Overall, the risk of bias in the included studies was moderate. Even though the results were variable, this analysis supported the ability of HBET to improve functional walking capacity and self-reported quality of life (QoL) to an extent. This review shows that a home-based exercise intervention with regular professional support and encouragement is beneficial in improving functional walking capacity as well as some aspects of QoL in patients with PAD and IC when compared to no exercise. However, when HBET is compared to hospital-based supervised exercise intervention, SET yields greater benefits., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Twomey et al.)

Background: Type 2 diabetes mellitus (T2DM) is a poorly controlled epidemic worldwide that demands active research into mitigation of the factors that are associated with poor control. Aims: The study was to determine the factors associated with suboptimal glycemic control. Materials and Methods: Electronic medical records of 263 adult patients with T2DM in our suburban internal medicine office were reviewed. Patients were divided into two groups: Group 1 [optimal diabetes control with glycosylated hemoglobin (HbA1c) of 7% or less] and Group 2 (suboptimal diabetes control with HbA1c greater than 7%). The influence of factors such as age, gender, race, social history, comorbid conditions, gestational diabetes, family history of diabetes, diabetes management, statin use, aspirin use, angiotensin convertase enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) use, body mass index (BMI), blood pressures, lipid profile, and urine microalbumin level were analyzed in the two groups. Results: In the suboptimal diabetes control group (N = 119), the majority (86.6%) of the patients were 41-80 years old. Factors associated with the suboptimal control were male gender [odds ratio (OR) 2.6, 95% confidence interval (CI), 1.579-4.321], Asian ethnicity (OR 1.4, 95% CI, 0.683-3.008), history of peripheral arterial disease (PAD; OR 3.9, 95% CI, 1.017-14.543), history of congestive heart failure (CHF; OR 3.9, 95% CI, 1.017-14.543), elevated triglycerides (OR 1.004, 95% CI, 1.000-1.007), and elevated urine microalbumin level of 30 mg/24 h or above (OR 4.5, 95% CI, 2.446-8.380). Patients with suboptimal diabetes control had a 3.8 times greater odds (95% CI, 1.493-6.885) of receiving the insulin and oral hypoglycemic agent together. Conclusions: In adult patients with T2DM, male gender, Asian ethnicity, CHF, PAD, management with insulin along with oral hypoglycemic agents, hypertriglyceridemia, and microalbuminuria were associated with suboptimal control. [ABSTRACT FROM AUTHOR]

Background and Objective: Vascular calcification (VC) and resulting vascular disease is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). CKD itself is increasingly recognized as a risk factor for cardiac and peripheral arterial disease (PAD). This paper examines the atherosclerotic plaque composition and specific endovascular considerations in the end stage renal disease (ESRD) patients. The literature was reviewed regarding the current status of medical and interventional management arteriosclerotic disease in patients with CKD. Lastly, three representative cases displaying typical endovascular treatment options are provided., Methods: A literature search was performed in PubMed covering publications up to September 2021 as well as discussion with experts in the field., Key Content and Findings: The high prevalence of atherosclerotic lesions in patients with chronic renal failure and high (re-)stenosis cause problems in the medium and long term as vascular calcium load represents one of the most widely encountered predictors of failure of endovascular treatment of PAD and future cardiovascular events (e.g., coronary calcium score). Patients with CKD also suffer from a greater risk for major vascular adverse events in general and worse revascularization outcomes following peripheral vascular intervention. A correlation between calcium burden and drug-coated balloon (DCB) performance has been established for PAD necessitating the need for different tools to cope with vascular calcium such as endoprosthesis or braided stents. Patients with CKD are at a higher risk of developing contrast-induced nephropathy (CIN). In addition to recommendations such as the administration of intravenous fluids, carbon dioxide (CO 2 ) angiography is one option to potentially provide an effective and safe alternative both to iodine-based contrast media allergy and to the use of iodine-based contrast media in patients with CKD., Conclusions: Management and endovascular procedures of patients with ESRD are complex. In the course of time, new endovascular therapy methods have been developed such as directional atherectomy (DA) and the so-called "pave-and-crack" technique to deal with high vascular calcium burden. Besides interventional therapy, vascular patients with CKD benefit from aggressive medical management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-53/coif). The series “Endovascular and Surgical Interventions in the End Stage Renal Disease Population” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Introduction Supervised exercise therapy (SET) is the first-line treatment for the peripheral arterial disease (PAD), however, access and compliance are low. An alternative method of delivering this therapy is through mobile health applications, which can be more accessible and convenient for patients. The aim of this study is to evaluate patient, public and healthcare professional (HCP) priorities with regard to a dedicated mobile phone application to deliver remote SET. Methods Bespoke questionnaires were designed for patients and HCPs to assess app functionality and prioritisations for development. These were distributed through social media and the Norfolk and Norwich University Hospital. Results Functionality questionnaires were completed by 62 patients and 44 HCPs. Eighty-four per cent of patients wanted their therapy to be monitored by their vascular team with the majority (78%) interested in measuring walking distances. Most patients (76%) were interested in watching exercise videos. These views were shared by HCPs. A communication platform was prioritised for messaging and pictures by the patient (74% and 68% respectively), but not so by HCPs (40%). Documenting other forms of physical activity and the use of wearable technology was less valuable to patients but favoured by HCPs (50%). The ability to interact with other users was not prioritised by either group. Conclusion Delivery of a mobile phone application to deliver health programmes for SET in patients with PAD is an acceptable method for patients and HCPs. This data will enable the next stages of mobile phone application development to be appropriately prioritised, focusing on building exercise videos, a communication platform and further walking tests., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Sivagangan et al.)

Objectives The aim of this study is to compare values of force–velocity and functional walking capacity in elderly patients with intermittent claudication with respect to the control group. Materials and methods The study involved 135 individuals: 85-peripheral arterial disease (PAD) group diagnosed with stage II chronic lower limb ischemia, according to Fontaine's classification, and 50-control group. The studies included an assessment of walking capacity using a six-minute walk test (6MWT) and measurement of force–velocity parameters (peak torque—PTQ, total work—TW, average power—AVGP) of the lower limbs obtained by means of a functional dynamometry under isokinetic conditions. Results The peripheral arterial disease group is characterized by significantly lower values of force–velocity parameters compared to the control group ( p < 0.005). Walking capacity in this group is significantly reduced due to significant differences in the distance covered ( p < 0.0001), walking speed ( p < 0.01), and its intensity ( p < 0.01). Further, a positive correlation was found between the maximum distance specified in the six-minute walk test and lower limb muscle strength in the isokinetic test. Conclusions Mean values of all force–velocity parameters and walk distance were significantly higher in the control group than in the peripheral arterial disease group. In the PAD group, in both men and women, the value of the agonist/antagonist ratio of both lower limbs are lower in men and women comparing to the control group. A rehabilitation program for patients with intermittent claudication must consider exercises improving strength, exercise capacity, and endurance in patients with PAD. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is a long-term devastating condition characterised by obstruction or narrowing of the arteries, mainly the arteries that supply blood to the lower limbs. PAD involves atherosclerosis of the abdominal aorta, iliac and lower extremity arteries, causing intermittent claudication (IC) (a cramp-like pain in the legs and/or buttocks on exertion which is relieved by resting), ischaemic rest pain, ischaemic ulceration, and limb loss. PAD is associated with significant reduction in quality of life and is a substantial public health problem. Unfortunately, the 10-year mortality of PAD is about 50% and the majority of patients with PAD are asymptomatic until the advanced stage. As a result, PAD is underreported, under-diagnosed and sub-optimally treated. [ABSTRACT FROM AUTHOR]

Purpose: The peripheral arterial disease is a powerful indicator of coexistent generalized atherosclerosis. As plaques in femoral arteries are diffused and can span a length of 30 cm, a large coverage of the arteries is required to assess the full extent of atherosclerosis. Recent development of 3D black-blood magnetic resonance imaging sequences has allowed fast acquisition of images with an extended longitudinal coverage. Vessel wall volume quantification requires the segmentation of the lumen and outer wall boundaries, and conventional manual planimetry would be too time-consuming to be feasible for analyzing images with such a large coverage. To address this challenge in image analysis, this work introduces an efficient 3D algorithm to segment the lumen and outer wall boundaries for plaque and vessel wall quantification in the femoral artery. Methods: To generate the initial lumen surface, a user identified the location of the lumen centers manually on a set of transverse images with a user-specified interslice distance (ISD). A number of geometric operators were introduced to automatically adjust the initial lumen surface based on pixel intensity and gradient along the boundary and at the center of each transverse slice. The adjusted surface was optimized by a 3D deformable model driven by the local stiffness force and external force based on image gradient. The optimized lumen surface was expanded to obtain the initial outer wall surface, which was subsequently optimized by the 3D deformable model. Results: The algorithm was executed with and without adjustment of the initial lumen surface and for three different selections of ISD: 10, 20, and 30 mm. The segmentation accuracy was improved in a statistically significant way with the introduction of initial lumen surface adjustment, but was insensitive to the ISD setting. When compared with the manual segmentation, the settings with adjustment have, on average, mean absolute differences (MADs) of 0.28 and 0.36 mm, respectively, for lumen and outer wall segmentations, which are significantly lower than those obtained when the adjustment operators were not applied (MAD = 0.43 and 0.59 mm for lumen and outer wall segmentations). The algorithm took about 1% of the time required for manual segmentation to complete segmenting the whole 3D femoral artery. Conclusions: The proposed semiautomatic algorithm generated accurate lumen and outer wall boundaries from 3D black-blood MR images with few user interactions, thereby allowing rapid and streamlined assessment of plaque burden in the femoral arteries. [ABSTRACT FROM AUTHOR]

Quiescent-interval single-shot MRA (QISS-MRA) is a promising nonenhanced imaging technique for assessment of peripheral arterial disease (PAD). Previous studies at 3 Tesla included only very limited numbers of patients for correlation of QISS-MRA with digital subtraction angiography (DSA) as standard of reference (SOR). The aim of this prospective institutional review board-approved study was to compare QISS-MRA at 3 Tesla with DSA in a larger patient group. Our study included 32 consecutive patients who underwent QISS-MRA, contrast-enhanced MRA (CE-MRA), and DSA. Two readers independently performed a per-segment evaluation of QISS-MRA and CE-MRA for image quality and identification of non-significant stenosis (<50 %) versus significant stenosis (50-100 %). The final dataset included 1,027 vessel segments. Reader 1 and 2 rated image quality as diagnostic in 96.8 and 98.0 % of the vessel segments on QISS-MRA and in 99.3 and 98.4 % of the vessel segments on CE-MRA, respectively. DSA was available for 922 segments and detected significant stenosis in 133 segments (14.4 %). Consensus reading yielded the following diagnostic parameters for QISS-MRA versus CE-MRA: sensitivity: 83.5 % (111/133) versus 82.7 % (110/133), p = 0.80; specificity: 93.9 % (741/789) versus 95.7 % (755/789), p = 0.25; and diagnostic accuracy: 92.4 % (852/922) versus 93.8 % (865/922), p = 0.35. In conclusion, using DSA as SOR, QISS-MRA and CE-MRA at 3 Tesla showed similar diagnostic accuracy in the assessment of PAD. A limitation of QISS-MRA was the lower rate of assessable vessel segments compared to CE-MRA. [ABSTRACT FROM AUTHOR]

Objective/Background Arterial calcification may render the ankle-brachial index (ABI) unreliable in diabetic patients. Although guidelines recommend the toe-brachial index (TBI) for patients with falsely elevated ABI arbitrarily defined as an ABI > 1.4, arterial calcification is also common among diabetic patients with an ABI ≤ 1.4. This could result in a “falsely normalized” ABI and under-diagnosis of peripheral arterial disease (PAD). We investigated whether diabetes invalidates the ABI as opposed to the TBI, and if the TBI may therefore be more suitable for detecting PAD in diabetic patients. Methods The difference between ABI and TBI was compared between diabetic and non-diabetic patients with an ABI ≤ 1.4 referred to the vascular laboratory. A Bland–Altman plot was constructed to assess whether ABI–TBI differences were dependent on the magnitude of the measurements. Subgroup analyses were performed for patients with a normal ABI, and for patients with critical ischemia. Results The population comprised 161 diabetic (252 limbs) and 160 non-diabetic (253 limbs) patients (mean age 67). Median ABIs (0.79 vs. 0.80) were similar, while median TBI was 0.07 higher in diabetics ( p = 0.024). The ABI–TBI difference in diabetics and non-diabetics was similar (0.32 vs. 0.35; p = .084), and was also similar for patients with a normal ABI. Moreover, ABI–TBI differences in diabetic- and non-diabetic patients overlapped, irrespective of the magnitude of the measurements. Diabetes was not associated with larger differences between ankle and toe pressures (mean difference −0.9 mmHg, 95% confidence interval −15 to 13 mmHg) among patients with critical ischemia. Conclusion No evidence was found that the TBI may overcome the potentially invalidated ABI in diabetic patients with an ABI ≤ 1.4. ABI and TBI are strongly associated, and this relationship is not influenced by diabetes. Therefore, the TBI does not allow for earlier detection of ischemia in diabetes. [ABSTRACT FROM AUTHOR]