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Previous studies have demonstrated that circulating microRNA (miR)-210 levels are elevated in peripheral artery disease (PAD) patients. MiR-210 is known to be a negative regulator of mitochondrial respiration; however, the relationship between miR-210 and mitochondrial function has yet to be studied in PAD. We aimed to compare skeletal muscle miR-210 expression of PAD patients to non-PAD controls (CON) and to examine the relationship between miR-210 expression and mitochondrial function. Skeletal muscle biopsies from CON (n = 20), intermittent claudication (IC) patients (n = 20), and critical limb ischemia (CLI) patients (n = 20) were analyzed by high-resolution respirometry to measure mitochondrial respiration of permeabilized fibers. Samples were also analyzed for miR-210 expression by real-time PCR. MiR-210 expression was significantly elevated in IC and CLI muscle compared to CON (P = 0.008 and P0.001, respectively). Mitochondrial respiration of electron transport chain (ETC) Complexes II (P = 0.001) and IV (P0.001) were significantly reduced in IC patients. Further, CLI patients demonstrated significant reductions in respiration during Complexes I (state 2: P = 0.04, state 3: P = 0.003), combined I and II (P0.001), II (P0.001), and IV (P0.001). The expression of the miR-210 targets, cytochrome c oxidase assembly factor heme A: farnesyltransferase (COX10), and iron-sulfur cluster assembly enzyme (ISCU) were down-regulated in PAD muscle. MiR-210 may play a role in the cellular adaptation to hypoxia and may be involved in the metabolic myopathy associated with PAD.

Traumatic brain injury (TBI) and blunt thoracic aortic injury (BTAI) are the top two leading causes of death after blunt force trauma. Patients presenting with concomitant BTAI and TBI pose a specific challenge with respect to management strategy, because the optimal hemodynamic parameters are conflicting between the two pathologies. Early thoracic endovascular aortic repair (TEVAR) is often performed, even for minimal aortic injuries, to allow for the higher blood pressure parameters required for TBI management. However, the optimal timing of TEVAR for the treatment of BTAI in patients with concomitant TBI remains an active matter of controversy.The Aortic Trauma Foundation international prospective multicenter registry was used to identify all patients who had undergone TEVAR for BTAI in the setting of TBI from 2015 to 2020. The primary outcomes included delayed ischemic or hemorrhagic stroke, in-hospital mortality, and aortic-related mortality. The outcomes were examined among patients who had undergone TEVAR at emergent (6 vs ≥6 hours) or urgent (24 vs ≥24 hours) intervals.A total of 100 patients (median age, 43 years; 79% men; median injury severity score, 41) with BTAI (Society for Vascular Surgery BTAI grade 1, 3%; grade 2, 10%; grade 3, 78%; grade 4, 9%) and concomitant TBI who had undergone TEVAR were identified. Emergent repair was performed for 51 patients (51%). Comparing emergent repair (6 hours) to urgent repair (≥6 hours), no difference was found in delayed cerebral ischemic events (2.0% vs 4.1%; P = .614), in-hospital mortality (15.7% vs 22.4%; P = .389), or aortic-related mortality (2.0% vs 2.0%; P = .996) and no patient had experienced delayed hemorrhagic stroke. Likewise, repairs conducted in an urgent (24 hours) setting showed no differences compared with those completed in an emergent (≥24 hours) setting regarding delayed ischemic stroke (2.6% vs 4.3%; P = .548), in-hospital mortality (18.2% vs 21.7%; P = .764), or aortic-related mortality (1.3% vs 4.3%; P = .654), and no patient had experienced delayed hemorrhagic stroke.In contrast to prior retrospective efforts, results from the Aortic Trauma Foundation international prospective multicenter registry have demonstrated that neither emergent nor urgent TEVAR for patients with concomitant BTAI and TBI was associated with delayed stroke, in-hospital mortality, or aortic-related mortality. In these patients, the timing of TEVAR did not have an effect on the outcomes. Therefore, the decision to intervene should be guided by individual patient factors rather than surgical timing.

The Impella is a percutaneously placed intra-arterial flow pump positioned across the aortic valve for circulatory support. A limitation of the Impella is that it lacks a central wire channel, to maintain intra-arterial wire access when removing the device. Open surgical arterial cutdown is needed for the removal of the Impella CP placed emergently, without the use of preclose sutures. This case review describes an alternative removal method for the aforementioned occasions.

Heavy alcohol use can induce skeletal muscle dysfunction referred to as alcoholic myopathy. Likewise, peripheral artery disease (PAD) is characterized by an acquired skeletal muscle metabolic myopathy in ischemic muscles of the lower extremity. Although epidemiological studies have shown that heavy alcohol consumption is associated with a greater risk of PAD, data are lacking on the contribution of alcohol-related myopathy on PAD-associated skeletal muscle pathology. We compared myofiber morphometrics, mitochondrial respiration, and oxidative stress measures in gastrocnemius biopsies from PAD patients with heavy alcohol use (>7 or >14 drinks per week, for females and males, respectively) (n=13) to PAD patients (n=13) and non-PAD controls (n=17) consuming moderate to low/no alcohol. Myofiber area and diameter were lower in heavy-drinking PAD patients compared to low/moderate drinkers (p=0.03 and p=0.04, respectively) and non-PAD controls (p=0.02 and p

Muscle samples are commonly chemically fixed or frozen immediately upon collection for biochemical and morphological analysis. Certain fixatives such as glutaraldehyde and osmium tetroxide are widely used for transmission electron microscopy (TEM) and lead to adequate preservation of muscle ultrastructure, but do not preserve the molecular features of samples. Methacarn is suggested to be a preferable chemical fixative for light microscopy because it maintains immunohistological features of samples. However, the efficacy of methacarn to preserve ultrastructural features as a primary chemical fixative for TEM is currently unclear. Additionally, cryo-preservation of samples for TEM analysis involves freezing processes such as plunge freezing, slam freezing, or high pressure freezing. High pressure freezing is the considered the gold standard but requires costly equipment and may not be a viable option for many labs collecting tissue samples from remote locations. Dimethyl sulfoxide (DMSO) is a commonly used cryoprotectant that may allow for better structural preservation of samples by impairing ice damage that occurs during plunge/snap freezing. We aimed to assess the effectiveness of methacarn as a primary chemical fixative and determine the effect of pre-coating samples with DMSO before plunge/snap freezing tissues to be prepared for TEM. The micrographs of the methcarn-fixed samples indicate a loss of Z-disk integrity, intermyofibrillar space, mitochondria structure, and lipids. Ultimately, methacarn is not a viable primary fixative for tissue sample preparation for TEM. Similarly, liquid nitrogen freezing of samples wrapped in aluminum foil produced non-uniform Z-disk alignments that appeared smeared with swollen mitochondria. DMSO coating before freezing appears to lessen the alterations to contractile and mitochondrial morphological structures. DMSO appears to be useful for preserving the ultrastructure of sarcomeres if samples are covered before freezing.

Objective: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. Methods: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. Results: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. Conclusions: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Background The vascular pathology of peripheral artery disease (PAD) encompasses abnormal microvascular architecture and fibrosis in response to ischemia-reperfusion (I/R) cycles. We aimed to investigate the mechanisms by which pathological changes in the microvasculature direct fibrosis in the context of I/R. Methods Primary human aortic endothelial cells (ECs) were cultured under cycles of normoxia-hypoxia (NH) or normoxia-hypoxia-hyperoxia (NHH) to mimic I/R. Primary human aortic smooth muscle cells (SMCs) were cultured and treated with media from the ECs. Findings The mRNA and protein expression of the pro-fibrotic factors platelet derived growth factor (PDGF)-BB and connective tissue growth factor (CTGF) were significantly upregulated in ECs undergoing NH or NHH cycles. Treatment of SMCs with media from ECs undergoing NH or NHH cycles led to significant increases in TGF-β1, TGF-β pathway signaling intermediates, and collagen expression. Addition of neutralizing antibodies against PDGF-BB and CTGF to the media blunted the increases in TGF-β1 and collagen expression. Treatment of SMCs with PAD patient-derived serum also led to increased TGF-β1 levels. Interpretation In an in-vitro model of I/R, which recapitulates the pathophysiology of PAD, increased secretion of PDGF-BB and CTGF by ECs was shown to be predominantly driving TGF-β1-mediated expression by SMCs. These cell culture experiments help elucidate the mechanism and interaction between ECs and SMCs in microvascular fibrosis associated with I/R. Thus, targeting these pro-fibrotic factors may be an effective strategy to combat fibrosis in response to cycles of I/R. Funding National Institute on Aging at the National Institutes of Health grant number R01AG064420. Research in context Evidence before this study: Previous studies in gastrocnemius biopsies from peripheral artery disease (PAD) patients showed that transforming growth factor beta 1 (TGF-β1), the most potent inducer of pathological fibrosis, is increased in the vasculature of PAD patients and correlated with collagen deposition. However, the exact cellular source of TGF-β1 remained unclear. Added value of this study: Exposing cells to cycles of normoxia-hypoxia-hyperoxia (NHH) resulted in pathological changes that are consistent with human PAD. This supports the idea that the use of NHH may be a reliable, novel in vitro model of PAD useful for studying associated pathophysiological mechanisms. Furthermore, pro-fibrotic factors (PDGF-BB and CTGF) released from endothelial cells were shown to induce a fibrotic phenotype in smooth muscle cells. This suggests a potential interaction between these cell types in the microvasculature that drives increased TGF-β1 expression and collagen deposition. Thus, targeting these pro-fibrotic factors may be an effective strategy to combat fibrosis in response to cycles of ischemia-reperfusion.

This paper presents a design optimization framework based on Branch and Bound Algorithm for novel networked electromagnetic soft actuators. The soft actuators work based on the operating principle of solenoids but are made of intrinsically soft materials. We confirmed that by scaling down the size of the soft actuators, their force to volume ratio increases. This suggests that by miniaturizing the actuators size and attaching them as a network based on the arrangement of actin and myosin filaments in skeletal muscles, the output force can be enhanced. In order to achieve the maximum output force, design parameters of a single soft actuator as well as those of a network are considered as design variables. The maximum available volume (thickness, width and length) and deflection range of the network are considered design constraints. The cost function, i.e. the output force is a non-linear mixed-integer function. A Branch and Bound optimization algorithm based on interval analysis is then proposed to solve the optimization problem. Numerical simulations are presented for a representative example of an active soft brace for the human elbow joint. The results suggest that an electromagnetic soft actuator network can provide sufficient torque to be used as a drive train for an active elbow brace for both flexion and extension over a range of around 93 degrees.

Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walking performance in PAD patients. Phytochemicals produced by plants have been widely studied for their potential health effects and role in various diseases including cardiovascular disease and cancer. In this review, we focus on PAD and discuss the evidence related to the clinical utility of different phytochemicals. We discuss phytochemical research in preclinical models of PAD, and we highlight the results of the available clinical trials that have assessed the effects of these compounds on PAD patient functional outcomes.

Blunt thoracic aortic injury (BTAI) is the second leading cause of death from blunt trauma. In the present study, we aimed to determine the outcomes of medical management (MM) for BTAI. We hypothesized from the results of several previously reported studies, that patients with a minimal aortic injury (BTAI grades 1 and 2) could safely be treated with definitive MM alone.The Aortic Trauma Foundation international prospective multicenter registry was used to examine the demographics, injury characteristics, management, and outcomes of patients with BTAI. We analyzed a subset of patients for whom MM was initiated as definitive therapy.From November 2016 to April 2020, 432 patients (median age, 41 years; 76% male; median injury severity score, 34) with BTAI (Society for Vascular Surgery grade 1, 23.6%; grade 2, 14.4%; grade 3, 51.2%; grade 4, 10.9%) were evaluated. Of the 432 patients, 245 (57%) had received MM in the initial period and 114 (26.4%) had received MM as the planned definitive therapy (grade 1, 59.6%; grade 2, 23.7%; grade 3, 15.8%; grade 4, 0.9%). The most common mechanism of BTAI was a motor vehicle collision (60.4%). Hypotension was present on arrival in 74 patients (17.2%). Continuous titratable infusion of antihypertensive medication was used for 49.1%, followed by intermittent bolus administration (29.8%), with beta-blockers (74.6%) the most common agent used. Treatments were targeted to a goal systolic blood pressure for 83.3%, most often to a target goal systolic blood pressure120 mm Hg (66.3%). The MM goals based on blood pressure control were attained in 64.0% (73 of 114). Twelve patients (10.5%; grade 1, 1; grade 2, 0; grade 3, 10; grade 4, 1) had required subsequent intervention after MM. Eleven patients (9.6%) had undergone thoracic endovascular aortic repair and one (0.9%) had required open repair for a grade 4 injury. The overall in-hospital mortality for patients selected for definitive MM was 7.9%. No aortic-related deaths had occurred in the patients receiving definitive MM.Approximately one in four patients with BTAI will receive MM as definitive therapy. The variation in the pharmacologic therapies used is considerable. MM for patients with minimal aortic injury (BTAI grades 1 and 2) is safe and effective, with a low overall intervention rate and no aortic-related deaths. These findings support the use of definitive MM for grade 2 BTAI.

Endovascular operations are not only critical for the life of the patients but also very challenging for the surgeons. Such operations, require extensive surgical training, operative accuracy, and they are time consuming. Vascular robotics is identified as a solution that may facilitate vascular operations. This paper frames itself in the field of invasive robotics used for endovascular operations and proposes a new system for robot navigation. In particular, a fuzzy logic system is proposed that implements endovascular autonomous navigation of a robot in a patient. The fuzzy navigation system is tested on 3-dimensional simulations of the human aorta. The testing case demonstrates the ability of the fuzzy navigation to be an autonomous – i.e. no human intervention is required for navigation-and completes the navigation in the aorta with accuracy and speed.

Failure of maturation of arteriovenous fistulae (AVF) remains an ongoing concern for dialysis access. One etiology is the presence of side branches that divert flow from the main AVF channel. This study aims to evaluate the outcomes of endovascular and open surgical interventions for AVF side branches in the setting of maturation failure.A retrospective review of all patients within a 10-year period with primary radio cephalic and brachiocephalic AVF was undertaken, and 380 cases of maturation failure related to branch diversion were selected for the study. Fifty-four percent and 48% of the AVF in the ENDO and OPEN groups respectively have concomitant stenosis further along in the flow path that required intervention by balloon angioplasty at the same time as a side branch intervention. All patients underwent duplex imaging or a fistulogram before intervention. Indications were low flow (600 mL/min) or failure to increase in size (6 mm diameter) in all cases. Interventions were divided into endovascular (coil embolization; ENDO) and surgical (branch ligation; OPEN) interventions. Outcomes of maturation (successful progression to hemodialysis (HD)), re-intervention, and functional dialysis (continuous HD for three consecutive months) were examined.From January 2008 to December 2018, 187 patients (49^ of all cases with side branches; 65% female, age of 57 ± 18 years; mean ± SD) with poorly maturing radiocephalic (70%) and brachiocephalic AVF (30%) underwent intervention due to the presence of accessory venous branches only. Indications were failure to mature in 54% and low flow in 46%. The average time to intervention due to failure to mature was 5 ± 4 weeks (mean ± SD) after primary access placement. Eighty-one had coil embolization and 106 had open branch ligation. Technical success was 90% in ENDO and 100% in OPEN. Technical ENDO failures had a secondary open branch ligation but were considered failures for analysis. Repeat interventions by balloon-assisted maturation were required in 45% of all the cases with no difference between ENDO and OPEN. Recannulation of the ENDO branches occurred in 10% of the cases requiring repeat intervention. Sixty one percent of isolated endovascular (n = 49) and 64% of isolated open (n = 68) matured to successful cannulation (P = 0.84). Median functional dialysis durations remained equivalent between ENDO (2.6 years) and OPEN (2.8 years) groups (P = 0.12).There is an improved maturation rate following the ENDO group compared to OPEN interventions while both ENDO and OPEN modalities demonstrated similar long-term functionality.

Purpose To describe a patient with acute renal artery occlusion who underwent successful revascularization procedure after experiencing a protracted ischemic period, which resulted in successful retrieval of renal function. Case report A 58-year-old male with a history of left renal artery stenosis and stent graft placement presented with symptoms of chest pain, shortness of breath, and flank pain. The patient was admitted to the Intensive Care Unit with the diagnosis of multiorgan failure and subsequent anuria that led to the initiation of hemodialysis. Computed tomography angiography demonstrated an aortic occlusion along with bilateral proximal renal artery occlusion with reconstitution of the mid to distal renal arteries via collateralization. The patient underwent angioplasty with bilateral renal artery stent-graft placement and successful revascularization of proximal renal arteries. Post-operatively, his renal function and urine output improved, and the patient was able to be weaned off hemodialysis along with the benefit of concurrent amelioration of his renovascular hypertension. Conclusion For select patients with renal artery occlusion, revascularization of the renal arteries may result in dialysis independence and stabilization of renovascular hypertension, despite prolonged time of ischemia.

Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress. Sera from 35 patients with intermittent claudication (IC), 26 patients with critical limb ischemia (CLI), and 35 non-PAD controls were analyzed to determine levels of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), nitrate/nitrite (nitric oxides, or NOx), arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the oxidative stress markers 8-Oxo-2&prime, deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), advanced glycation end products (AGEs), and protein carbonyls. NOx was significantly lower in IC and CLI patients compared to controls in association with elevated oxidative stress, with the greatest NOx reductions observed in CLI. Compared with controls, IC and CLI patients had reduced BH4, elevated BH2, and a reduced BH4/BH2 ratio. SDMA, the arginine/SDMA ratio, and the arginine/ADMA ratio were significantly higher in CLI patients. The NO system and its regulators are significantly compromised in PAD. This dysregulation appears to be driven by increased oxidative stress and worsens as the disease progresses from claudication to CLI.

Background The aim of the present study was to assess the effects of the extent of heel ulceration on the outcomes of limb threatening critical ischemia due to isolated infrapopliteal disease. Methods A retrospective review identified 989 patients with isolated infrapopliteal disease and heel ulceration treated from 2001 to 2018. The heel was defined as the back of the foot, extending from the Achilles tendon to around the plantar surface and covering the apex of the calcaneum bone. Heel ulceration was categorized into three groups by area: 10 cm2. The interventions were endovascular, open bypass, major amputation, and wound care. An intention-to-treat analysis by patient group was performed. The 30-day outcomes and amputation-free survival (AFS; survival without a major amputation) were evaluated. Results Of the 989 patients, 384 (58% male; average age, 65 years; n = 768 vessels) had undergone isolated endovascular tibial intervention, 124 (45% male; average age, 59 years) had undergone popliteal tibial vein bypass for limb threatening critical ischemia, 219 (52% male; average age, 67 years) had undergone major amputation, and 242 (49% male; average age, 66 years) had received wound care. No difference was found in the 30-day major adverse cardiac events in the endovascular and open bypass groups, with significantly more events in the major amputation group (P = .03). The 30-day major adverse limb events and 30-day amputation rates were equivalent between the open bypass and endovascular groups. The 5-year AFS rate was superior in the open bypass group (37% ± 8%; mean ± standard error of the mean) compared with the endovascular group (27% ± 9%; P = .04). The wound care group had a 5-year AFS rate of 20% ± 9%, which was not significantly different from that of the endovascular group. Patients with heel ulcers of 10 cm2 were associated with markedly worse 5-year AFS outcomes (0% ± 0%). The presence of end-stage renal disease, osteomyelitis, uncontrolled diabetes (hemoglobin A1c >10%), and/or frailty combined with a heel ulcer >10 cm2 were predictive of poor AFS. Conclusions An increasing heel ulcer area combined with osteomyelitis and systemic comorbidities was associated with worsening 30-day outcomes and 5-year AFS, irrespective of the therapy chosen.

Previous studies have shown that chronic heavy alcohol consumption and consumption of a high-fat (HF) diet can independently contribute to skeletal muscle oxidative stress and mitochondrial dysfunction, yet the concurrent effect of these risk factors remains unclear. We aimed to assess the effect of alcohol and different dietary compositions on mitochondrial activity and oxidative stress markers. Male and female mice were randomized to an alcohol (EtOH)-free HF diet, a HF + EtOH diet, or a low-Fat (LF) + EtOH diet for 6 weeks. At the end of the study, electron transport chain complex activity and expression as well as antioxidant activity and expression, were measured in skeletal muscles. Complex I and III activity were diminished in muscles of mice fed a HF + EtOH diet relative to the EtOH-free HF diet. Lipid peroxidation was elevated, and antioxidant activity was diminished, in muscles of mice fed a HF + EtOH diet as well. Consumption of a HF diet may exacerbate the negative effects of alcohol on skeletal muscle mitochondrial health and oxidative stress.

Endovascular tibial interventions for chronic limb-threatening ischemia are frequent, but the implications of early failure (≤30 days) of an isolated tibial intervention are still unclear. The aim of this study was to examine the patient-centered outcomes after early failure of isolated tibial artery intervention.A database of patients undergoing lower extremity endovascular interventions between 2007 and 2017 was retrospectively queried. Patients with chronic limb-threatening ischemia (Rutherford classes 4, 5, and 6) were selected, and failures within 30 days were identified. Lack of technical success at the time of the procedure was an exclusion. Intention-to-treat analysis by patient was performed. Patient-oriented outcomes of clinical efficacy (absence of recurrent symptoms, maintenance of ambulation, and absence of major amputation), amputation-free survival (survival without major amputation), and freedom from major adverse limb events (MALEs; above-ankle amputation of the index limb or major reintervention [new bypass graft, jump or interposition graft revision]) were evaluated.There were 1779 patients (58% male; average age, 65 years; 2898 vessels) who underwent tibial intervention for chronic limb-threatening ischemia; 284 procedures (16%) were early failures. In the early failure group, 124 cases (44%) were considered immediate (24 hours), and 160 cases (56%) failed within the first 30 days after intervention. The two modes of failure were hemodynamic failure (47%) and progression of chronic limb-threatening ischemia (53%). Bypass after early failure was successful in patients with adequate vein, target vessel of ≥3 mm, and good inframalleolar runoff. Progression of symptoms was associated with major amputation in patients with Rutherford class 5 and class 6 disease. Presentation with diabetes and end-stage renal disease were identified as independent clinical predictors for early failure. Lesion calcification, reference vessel diameter 3 mm, lesion length300 mm, and poor inframalleolar runoff were identified as independent anatomic predictors for early failure and increased MALEs. Early failure was predictive of poor long-term clinical efficacy (11% ± 9% vs 39% ± 8% at 5 years, mean ± standard error of the mean, early vs no early failure; P = .01) and amputation-free survival (16% ± 9% vs 47% ± 9% at 5 years, mean ± standard error of the mean, early vs no early failure; P = .02).Both clinical and anatomic factors can predict early failure of endovascular therapy for isolated tibial disease. Early failure significantly increases 30-day major amputation and 30-day MALEs and is associated with poor long-term patient-centered outcomes.

Background Major lower extremity amputations remain among the most common procedures performed by vascular surgeons in patients with diabetes and its associated peripheral vascular disease. After major amputation, this population commonly suffers from high readmission rates, increased wound complications, and conversion to more proximal major amputations. These events impact quality in terms of cost, resources, and subjective quality of life. The aim of this study is to compare outcomes between primary lower extremity above-ankle amputations (primary amputation [PA]) and staged ankle guillotine amputations followed by interval formalization to an above-ankle amputation (staged amputation [SA]) for nonsalvageable infected diabetic foot disease. Methods A retrospective review of all de novo major lower extremity amputations performed by the vascular surgery service at a single institution between January 2014 and March 2017 was performed. Inclusion criteria were diabetic patients with foot gangrene who underwent a major de novo above- or below-knee amputation. Amputations for trauma, acute limb ischemia, or malignancy were excluded. Per institutional practice, SA was performed for uncontrolled infection and/or infection with uncontrolled diabetes, and PA was performed in the absence of active infection and in stable diabetes. The primary outcome measure was 30-day freedom from conversion to a higher level amputation. Secondary outcome measures were 30-day stump complications, 30-day readmissions, 30-day major adverse cardiovascular events, and 30-day mortality. Results One hundred sixteen patients met the inclusion criteria. Sixty-eight percent were male, 18% were active smokers, 30% had end-stage renal disease, and 22% had congestive heart failure. Sixty-one patients underwent SA, and 55 patients underwent PA. The two cohorts were well-matched by demographics and comorbidities. Consistent with the institutional practice, 57% of SA patients met two or more systemic inflammatory response syndrome criteria at presentation compared with 24% of PA patients (P = .0003). There were no 30-day mortalities. There was no significant difference in major adverse cardiovascular events between the groups (2% vs 4%; SA vs PA, respectively; P = .6). The average length of stay did not significantly differ between SA and PA (mean of 14 ± 8 days vs 11 ± 11 days; P = .1). SA patients had a lower rate of 30-day readmission (7% vs 27%; P = .005) and 30-day unplanned conversion to higher level amputation (2% vs 13%; P = .026) compared with PA patients. Conclusions In the setting of infected diabetic foot disease, a staged lower extremity amputation achieves quality outcomes superior to a one-stage amputation, despite the former cohort's greater illness acuity level. SA should be considered in all diabetic patients presenting with active foot infection.

Widespread adoption of endovascular aneurysm repair has led to increased incidence of late complications, such as endograft migration. Treatment options have to be tailored to the patient's health, quality of proximal aorta, and extent of migration. Complete or partial endograft removal is associated with significant morbidity and mortality. We describe a case in which open repair with endograft preservation was employed, with the additional benefit of a sutured proximal anastomosis. Keywords: Endovascular aneurysm repair (EVAR), Abdominal aortic aneurysm, Endograft migration, Type I endoleak, Reintervention

Background Detailed knowledge of the dimensions and shape of the main arteries of the body and how they change with age and disease is important for understanding arterial pathophysiology and improving minimally invasive devices to treat arterial diseases. Our goal was to describe and compare geometric remodeling of the aorta and peripheral arteries in the context of patient demographics and cardiovascular risk factors. Methods Three-dimensional reconstructions of computed tomography angiography scans were performed in 122 subjects 5–93 years of age (mean 47 ± 24 years, 64 M/58 F). Best-fit arterial diameters, lengths, and tortuosity for the principle named arteries in the chest, abdomen, pelvis, and upper thigh were measured, and multiple linear regression analysis was performed to examine how these morphologic parameters associate with patient demographics and risk factors. Results Large elastic arteries increased their diameter, length, and tortuosity with age, whereas muscular arteries primarily became more tortuous. Demographics and risk factors explained >70% of the variation in diameters of the abdominal aorta, paravisceral aorta, and the aortic arch; and >75% of variation in tortuosity from the profunda femoris to the brachiocephalic artery. Male sex, larger body mass index, and hypertension contributed to larger diameters, whereas the presence of diabetes was associated with somewhat-straighter arteries. Overall, the effects of cardiovascular risk factors on geometric remodeling were small compared with those of demographics. Conclusion The geometry of the vascular tree is greatly affected by aging, demographics, and some risk factors. Elastic and muscular arteries remodel differently, possibly as the result of differences in their microstructure.

Peripheral artery disease (PAD), which affects an estimated 27 million people in Europe and North America, is caused by atherosclerotic plaques that limit blood flow to the legs. Chronic, repeated ischemia in the lower leg muscles of PAD patients is associated with loss of normal myofiber morphology and myofiber degradation. In this study, we tested the hypothesis that myofiber morphometrics of PAD calf muscle are significantly different from normal calf muscle and correlate with reduced calf muscle strength and walking performance.Gastrocnemius biopsies were collected from 154 PAD patients (Fontaine stage II) and 85 control subjects. Morphometric parameters of gastrocnemius fibers were determined and evaluated for associations with walking distances and calf muscle strength.Compared with control myofibers, PAD myofiber cross-sectional area, major and minor axes, equivalent diameter, perimeter, solidity, and density were significantly decreased (P0.005), whereas roundness was significantly increased (P0.005). Myofiber morphometric parameters correlated with walking distances and calf muscle strength. Multiple regression analyses demonstrated myofiber cross-sectional area, roundness, and solidity as the best predictors of calf muscle strength and 6-min walking distance, whereas cross-sectional area was the main predictor of maximum walking distance.Myofiber morphometrics of PAD gastrocnemius differ significantly from those of control muscle and predict calf muscle strength and walking distances of the PAD patients. Morphometric parameters of gastrocnemius myofibers may serve as objective criteria for diagnosis, staging, and treatment of PAD.

Objective: This study evaluated the hypothesis that protein concentration and mitochondrial content in gastrocnemius biopsies from patients with peripheral arterial disease (PAD) predict mortality rates. Background: PAD patients experience advancing myopathy characterized by mitochondrial dysfunction, myofiber degradation, and fibrosis in their ischemic legs, along with increased mortality rates. Methods: Samples from the gastrocnemius of PAD patients were used for all analyses. Protein concentration was normalized to muscle wet weight, and citrate synthase activity (standard measure of mitochondrial content in cells) was normalized to muscle wet weight and protein concentration. Protein and citrate synthase data were grouped into tertiles and 5-year, all-cause mortality for each tertile was determined with Kaplan-Meier curves and compared by the modified Peto-Peto test. A Cox-regression model for each variable controlled for the effects of clinical characteristics. Results: Of the 187 study participants, 46 died during a mean follow-up of 23.0 months. Five-year mortality rate was highest for patients in the lowest tertile of protein concentration. Mortality was lowest for patients in the middle tertile of citrate synthase activity when normalized to either muscle wet weight or protein concentration. The mortality hazard ratios (HRs) from the Cox analysis were statistically significant for protein concentration normalized to muscle wet weight (lowest vs middle tertile; HR = 2.93; P = 0.008) and citrate synthase normalized to protein concentration (lowest vs middle tertile; HR = 4.68; P = 0.003; and lowest vs highest tertile; HR = 2.36; P = 0.027). Conclusions: Survival analysis of a contemporaneous population of PAD patients identifies protein and mitochondrial content of their gastrocnemius as predictors of mortality rate.

Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic lower extremities, which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired limb function. Desmin, a protein of the cytoskeleton, is central to maintenance of the structure, shape and function of the myofiber and its organelles, especially the mitochondria, and to translation of sarcomere contraction into muscle contraction. In this study, we investigated the hypothesis that disruption of the desmin network occurs in gastrocnemius myofibers of PAD patients and correlates with altered myofiber morphology, mitochondrial dysfunction, and impaired limb function. Using fluorescence microscopy, we evaluated desmin organization and quantified myofiber content in the gastrocnemius of PAD and control patients. Desmin was highly disorganized in PAD but not control muscles and myofiber content was increased significantly in PAD compared to control muscles. By qPCR, we found that desmin gene transcripts were increased in the gastrocnemius of PAD patients as compared with control patients. Increased desmin and desmin gene transcripts in PAD muscles correlated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. In conclusion, our studies identified disruption of the desmin system in gastrocnemius myofibers as an index of the myopathy and limitation of muscle function in patients with PAD.

Renal arteriovenous fistulas (AVFs) are an uncommon complication of nephrectomy. In this report, we present the case of a 66-year-old female presenting with progressive dyspnea on exertion and exercise intolerance. She was diagnosed and treated for adult onset reactive airway disease. The patient underwent nephrectomy at age 18 secondary to recurrent pyelonephritis from vesicoureteral reflux. She underwent a surveillance computed tomography (CT) scan to evaluate a small ascending aneurysm that was initially detected on cardiac echocardiogram. A large left renal AVF was detected incidentally on the CT scan. The fistula was successfully treated by ligation of the renal artery with resolution of pulmonary symptoms.

Introduction Work on human and mouse skeletal muscle by our group and others has demonstrated that aging and age-related degenerative diseases are associated with mitochondrial dysfunction, which may be more prevalent in males. There have been, however, no studies that specifically examine the influence of male or female sex on human skeletal muscle mitochondrial respiration. The purpose of this study was to compare mitochondrial respiration in the gastrocnemius of adult men and women. Methods Gastrocnemius muscle was obtained from male (n = 19) and female (n = 11) human subjects with healthy lower-extremity musculoskeletal and arterial systems and normal ambulatory function. All patients were undergoing operations for the treatment of varicose veins in their legs. Mitochondrial respiration was determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Complex I-, II-, III-, and IV-dependent respiration was measured individually and normalized to muscle weight, total protein content, and citrate synthase (CS, index of mitochondrial content). Results Male and female patients had no evidence of musculoskeletal or arterial disease and did not differ with regard to age, race, body mass index, or other clinical characteristics. Complex I-, II-, III-, and IV-dependent respiration normalized to muscle weight, total protein content, and CS did not statistically differ for males compared with females. Conclusions Our study evaluates, for the first time, gastrocnemius mitochondrial respiration of adult men and women who have healthy musculoskeletal and arterial systems and normal ambulatory function. Our data demonstrate there are no differences in the respiration of gastrocnemius mitochondria between men and women.

A myopathy characterized by myofiber degeneration and impaired limb function is present in the legs of patients with peripheral artery disease (PAD). A characteristic of myofibers in PAD legs is abnormal distribution and accumulation of desmin, a key protein of the myofiber cytoskeleton. Using a mouse model of chronic hindlimb ischemia, we investigated the effects of chronic inflow arterial occlusion on myofiber morphology and desmin expression in the gastrocnemius, in relation to limb function. Hindlimb ischemia was induced by staged ligation/division of the common femoral and iliac arteries of C57BL/6 mice and muscles were harvested 12 weeks later. Desmin expression was analyzed by quantitative fluorescence microscopy of slide-mounted gastrocnemius specimens and by Western Blot analysis of gastrocnemius lysates of 10 ischemic and 10 control mice. Gastrocnemius myofiber morphometrics were determined by fluorescence microscopy and limb muscle endurance was measured with a RotaRod apparatus. Desmin was significantly increased both in myofibers and in lysates of ischemic muscle compared to control muscle (+35%, p

Introduction: Patients with peripheral arterial disease (PAD) develop a myopathy in their ischemic limbs which is characterized by myofiber degeneration, mitochondrial dysfunction and decreased muscle force production. Desmin, a cytoskeletal protein of the myofiber, is central to maintenance of the structure, shape and function of the myofiber and its organelles especially the mitochondria. Hypothesis: We hypothesized that desmin expression in myofibers of the gastrocnemius of PAD patients is abnormal and correlates with decreased mitochondrial respiration and reduced muscle strength. Methods and Results: We quantified desmin protein and gene transcripts in myofibers of gastrocnemius biopsies from 30 PAD patients and 29 controls and determined their association with myofiber morphology, mitochondrial respiration and calf muscle strength. Compared to control, desmin protein and gene transcripts were increased in myofibers of PAD gastrocnemius. Increased expression was associated with a diffuse appearance of the protein, suggesting a loss of its normally filamentous structure. These changes in desmin correlated with altered myofiber morphology, decreased mitochondrial respiration and reduced calf muscle strength. Conclusions: Desmin expression and organization are abnormal in myofibers of the gastrocnemius of patients with PAD and these changes correlate with decreased mitochondrial function and reduced muscle strength.

Background Peripheral arterial disease ( PAD ) is characterized by myofiber degeneration and loss of function in muscles of the lower limbs. Human enterovirus ( HEV ) infection has been implicated in the pathogenesis of a number of muscle diseases. However, its association with PAD has not been studied. In this study, we tested the hypothesis that infectious HEV is present in skeletal muscle of patients with PAD and is associated with severity of disease. Methods and Results Gastrocnemius biopsies from 37 patients with PAD and 14 controls were examined for the presence of HEV RNA , viral capsid protein, viral RNA copy number, and viral infectivity. HEV RNA was detected in 54% of the biopsies from patients with PAD but was not detected in muscle biopsies from control patients. This difference in prevalence among PAD and control patients was significant at P RNA copy numbers were increased significantly at the later stages of disease; Fontaine Stage IV (10 5.50 copies/mg muscle wet weight, at P 4.87 copies/mg, at P 2.50 copies/mg). Viral replication was confirmed by the presence of the negative‐strand of viral RNA in all specimens positive for HEV RNA . Cultures of HeLa and human skeletal muscle cells treated with muscle homogenates showed HEV replication and the presence of HEV capsid protein. Conclusion Our data identified infectious HEV in the gastrocnemius of PAD patients but not in controls. Viral copy number and prevalence of infection were higher in the later stages of disease. Our data point to the need for further studies to determine the contribution of HEV infection to the pathophysiology of PAD .

Peripheral arterial disease (PAD), which affects ∼10 million Americans, is characterized by atherosclerosis of the noncoronary arteries. PAD produces a progressive accumulation of ischemic injury to the legs, manifested as a gradual degradation of gastrocnemius histology. In this study, we evaluated the hypothesis that quantitative morphological parameters of gastrocnemius myofibers change in a consistent manner during the progression of PAD, provide an objective grading of muscle degeneration in the ischemic limb, and correlate to a clinical stage of PAD. Biopsies were collected with a Bergström needle from PAD patients with claudication ( n = 18) and critical limb ischemia (CLI; n = 19) and control patients ( n = 19). Myofiber sarcolemmas and myosin heavy chains were labeled for fluorescence detection and quantitative analysis of morphometric variables, including area, roundness, perimeter, equivalent diameter, major and minor axes, solidity, and fiber density. The muscle specimens were separated into training and validation data sets for development of a discriminant model for categorizing muscle samples on the basis of disease severity. The parameters for this model included standard deviation of roundness, standard deviation of solidity of myofibers, and fiber density. For the validation data set, the discriminant model accurately identified control (80.0% accuracy), claudicating (77.7% accuracy), and CLI (88.8% accuracy) patients, with an overall classification accuracy of 82.1%. Myofiber morphometry provided a discriminant model that establishes a correlation between PAD progression and advancing muscle degeneration. This model effectively separated PAD and control patients and provided a grading of muscle degeneration within clinical stages of PAD.