Search

Introduction: Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Innovation: Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Clinical Problem Addressed: Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. Materials and Methods: We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Results: Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Discussion: Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.

Chronic wounds affect ~2% of the U.S. population and increase risks of amputation and mortality. Unfortunately, treatments for such wounds are often expensive, complex, and only moderately effective. Electrotherapy represents a cost-effective treatment; however, its reliance on bulky equipment limits its clinical use. Here, we introduce water-powered, electronics-free dressings (WPEDs) that offer a unique solution to this issue. The WPED performs even under harsh conditions-situations wherein many present treatments fail. It uses a flexible, biocompatible magnesium-silver/silver chloride battery and a pair of stimulation electrodes; upon the addition of water, the battery creates a radial electric field. Experiments in diabetic mice confirm the WPED's ability to accelerate wound closure and promote healing by increasing epidermal thickness, modulating inflammation, and promoting angiogenesis. Across preclinical wound models, the WPED-treated group heals faster than the control with wound closure rates comparable to treatments requiring expensive biologics and/or complex electronics. The results demonstrate the WPED's potential as an effective and more practical wound treatment dressing.

Background: With increasing regionalization of complex aortic surgery within fewer US centers, patients may face increased travel burden when accessing aortic surgery. Longer travel distances have been associated with inferior outcomes after major surgery; however, the impacts of distance on reinterventions and costs have not been described. This study aims to assess the association between patient travel distance and longer-term outcomes including costs and reinterventions after complex aortic surgery., Methods: A retrospective review was conducted of all patients in the Vascular Implant Surveillance and Interventional Outcomes Network database undergoing complex endovascular aortic repair including internal iliac or visceral vessel involvement, complex thoracic endovascular aortic repair including Zone 0-2 proximal extent or branched devices, and complex open abdominal aortic aneurysm repair including suprarenal or higher clamp sites. Travel distance was stratified by Rural-Urban Commuting Area population-density category. Multinomial logistic regression models, negative-binomial models, and zero-inflated Poisson models were used to assess the association between travel distance and index procedural and comprehensive first-year costs, long-term imaging, and long-term reinterventions, respectively., Results: Between 2011 and 2018, 8,782 patients underwent complex aortic surgery in the Vascular Implant Surveillance and Interventional Outcomes Network database, including 4,822 complex endovascular aortic repairs, 2,672 complex thoracic endovascular aortic repairs, and 1,288 complex open abdominal aortic aneurysm repairs. Median travel distance was 22.8 miles (interquartile range 8.6-54.8 miles, range 0-2,688.9 miles). Median age was 75 years for all distance quintiles. Patients traveling farther were more likely to be female (26.8% in quintile 5 [Q5] vs. 19.9% in Q1, P < 0.001) and to have had a prior aortic surgery (20.8% for Q5 vs. 5.9% for Q1, P < 0.001). Patients traveling farther had higher index procedural costs, with adjusted odds ratio (OR) 2.34 (95% confidence interval [CI] 1.86-2.94, P < 0.0001) of being in the highest cost tertile versus lowest for patients in Q5 vs. Q1. For patients with ≥ 1-year follow-up, those traveling farther had higher imaging costs, with adjusted Q5 OR 1.55 (95% CI 1.22-1.95, P = 0.0002), and comprehensive first-year costs, with adjusted Q5 OR 2.06 (95% CI 1.57-2.70, P < 0.0001). In contrast, patients traveling farther had similar numbers of reinterventions and imaging studies postoperatively., Conclusions: Patients traveling farther for complex aortic surgery have higher procedural costs, postoperative imaging costs, and comprehensive first-year costs. These patients should be targeted for increased care coordination for improved outcomes and healthcare system burden., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Median arcuate ligament syndrome (MALS) is a clinical syndrome caused by compression of the celiac artery by the median arcuate ligament that often manifests with nonspecific abdominal pain. Identification of this syndrome is often dependent on imaging of compression and upward bending of the celiac artery by lateral computed tomography angiography, the so-called "hook sign." The purpose of this study was to assess the relationship of radiologic characteristics of the celiac artery to clinically relevant MALS., Methods: An institutional review board-approved retrospective chart review from 2,000 to 2,021 of 293 patients at a tertiary academic center diagnosed with celiac artery compression (CAC) was performed. Patient demographics and symptoms of 69 patients who were diagnosed with symptomatic MALS were compared to 224 patients without MALS (but with CAC) per electronic medical record review. Computed tomography angiography images were reviewed and the fold angle (FA) was measured. The presence of a hook sign (defined as a visual FA < 135°), as well as stenosis (defined as >50% of luminal narrowing on imaging) were recorded. Wilcoxon rank-sum test and Chi-squared test were used for comparative analysis. Logistic model was run to relate the presence of MALS with comorbidities and radiographic findings., Results: Imaging was available in 59 patients (25 males, 34 females) and 157 patients (60 males, 97 females) with and without MALS, respectively. Patients with MALS were more likely to have a more severe FA (120.7 ± 33.6 vs. 134.8 ± 27.9, P = 0.002). Males with MALS were also more likely to have a more severe FA compared with males without MALS (111.1 ± 33.7 vs. 130.4 ± 30.4, P = 0.015). In patients with body mass index (BMI) >25, MALS patients also had narrower FA compared with patients without MALS (112.6 ± 30.5 vs. 131.7 ± 30.3, P = 0.001). The FA was negatively correlated with BMI in patients with CAC. The hook sign and stenosis were associated with diagnosis of MALS (59.3% vs. 28.7%, P < 0.001, and 75.7% vs. 45.2%, P < 0.001, respectively). In logistic regression, pain, stenosis, and a narrow FA were statistically significant predictors of the presence of MALS., Conclusions: The upward deflection of the celiac artery in patients with MALS is more severe compared with patients without MALS. Consistent with prior literature, this bending of the celiac artery is negatively correlated with BMI in patients with and without MALS. When demographic variables and comorbidities are considered, a narrow FA is a statistically significant predictor of MALS. Regardless of MALS diagnosis, a hook sign was associated with narrower FA. While demographics and imaging findings may inform MALS diagnosis, clinicians should not rely on a visual assessment of a hook sign but should quantitatively measure the anatomic bending angle of the celiac artery to assist with the diagnosis and understand the outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Recently evolving practice patterns in complex aortic surgery have led to regionalization of care within fewer centers in the United States, and thus patients may have to travel farther for complex aortic care. Travel distance has been associated with inferior outcomes after non-vascular surgery, particularly non-index readmission. This study aims to assess the impact of patient travel distance on perioperative outcomes and readmissions after complex aortic surgery., Methods: A retrospective review was conducted of all patients in the Vascular Quality Initiative and Vascular Implant Surveillance and Interventional Outcomes Network databases undergoing complex endovascular aortic repair (EVAR) including internal iliac or visceral vessel involvement, complex thoracic endovascular aortic repair (TEVAR) including zone 0 to 2 proximal extent or branched devices, and complex open abdominal aortic aneurysm (AAA) repair including suprarenal or higher clamp sites. Travel distance was stratified by rural/urban commuting area (RUCA) population-density category. Wilcoxon and χ 2 tests were used to assess relationships between travel distance quintiles and baseline characteristics, mortality, and readmission. Travel distance and other factors were included in multivariable Cox models for survival and Fine-Gray competing risk models for freedom from readmission., Results: Between 2011 and 2018, 8782 patients underwent complex aortic surgery in the Vascular Quality Initiative and Vascular Implant Surveillance and Interventional Outcomes Network databases, including 4822 complex EVARs, 2672 complex TEVARs, and 1288 complex open AAA repairs. Median travel distance was 22.8 miles (interquartile range [IQR], 8.6-54.8 miles). Median age was 75 years for all distance quintiles, but patients traveling longer distances were more likely female (26.8% in quintile 5 [Q5] vs 19.9% in Q1; P < .001), white (93.8% of Q5 vs 83.8% of Q1; P < .001), to have larger-diameter AAAs (median 59 mm for Q5 vs 55 mm for Q1; P < .001), and to have had prior aortic surgery (20.8% for Q5 vs 5.9% for Q1; P < .001). Overall 30-day readmission was more common at farther distances (18.1% for Q5 vs 14.8% for Q1; P = .003), with higher non-index readmission (11.2% for Q5 vs 2.7% for Q1; P < .001) and conversely lower index readmission (6.9% for Q5 vs 12.0% for Q1; P < .001). Multivariable-adjusted Fine-Gray models confirmed greater hazard of non-index readmission with farther distance, with a Q5 hazard ratio of 3.02 (95% confidence interval, 2.12-4.30; P < .001). Multivariable-adjusted Cox models demonstrated no association between travel distance and long-term survival but found that non-index readmission was associated with increased long-term mortality (hazard ratio, 1.46; 95% confidence interval, 1.20-1.78; P = .0001)., Conclusions: Patients traveling farther for complex aortic surgery demonstrate higher non-index readmission, which, in turn, is associated with increased long-term mortality risk. Aortic centers of excellence should consider targeting these patients for more comprehensive follow-up and care coordination to improve outcomes., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Median arcuate ligament syndrome (MALS) is a frequent differential diagnosis in patients with postprandial abdominal symptoms, but diagnosis remains challenging. The aim of this study was to identify characteristics of patients who had MALS compared with non-MALS patients among a cohort of patients diagnosed with celiac artery compression (CAC)., Study Design: An IRB-approved retrospective chart review (2000 to 2021) of patients at our institution with a discharge diagnosis of CAC was performed. Medical record review for clinical symptoms and findings consistent with MALS was performed., Results: Two hundred ninety-three patients with a diagnosis of CAC were identified; 59.7% were women, and average age was 63.9 ± 20.2 years. Sixty-nine (23.5%) patients with CAC had MALS. There were no significant differences in sex or race between MALS and non-MALS patients, but MALS patients were younger (55.7 vs 68.1, p < 0.001). There was no significant difference in gastrointestinal comorbidities between the 2 groups. Patients with MALS were less likely to have diabetes (12.5% vs 26.9%), renal disease (4.6% vs 8.2%), hypertension (41.5% vs 70.3%), mesenteric atherosclerotic disease (14% vs 61.9%), and peripheral artery disease (15.0% vs 39.7%)., Conclusions: We demonstrate a novel observation that MALS patients tend to have fewer atherosclerotic characteristics than non-MALS patients with CAC. Patients in our study with MALS were more likely to be younger, women, and presenting with epigastric pain. MALS patients had a significantly lower incidence of diabetes, hypertension, renal disease, mesenteric artery disease, and peripheral arterial disease compared with the non-MALS group. An important clinically relevant feature of MALS patients may be their lack of atherosclerotic phenotype compared with non- MALS patients with CAC., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine if routine completion angiography for lower extremity bypasses using vein conduit results in lower rates of postoperative bypass occlusion., Summary of Background Data: With the increasing availability of on-table angiography and significant advancements in endovascular techniques, some operators routinely perform completion angiograms. The effect of this surgical paradigm has yet to be rigorously compared to the more widespread selective use of completion imaging in the modern era., Methods: This retrospective cohort study included infrainguinal arterial bypass procedures utilizing vein conduit completed at a single hospital system from 2001 to 2018 and compared postoperative outcomes between bypasses that underwent routine completion angiography versus selective completion angiography. Notably, any bypasses that underwent completion angiography due to intraoperative concerns were excluded from this analysis., Results: 666 bypasses that were performed in 589 patients met inclusion criteria. 126 (16.9%) bypasses were classified into the routine completion angiogram group compared to 540 (81.0%) into the selective completion angiogram group. Patients who underwent routine completion angiograms had a rate of intraoperative reintervention of 22.2%. The routine angiogram group had lower rates of reintervention (3.9% vs 10.0%, P = 0.03) and graft occlusion (2.3% vs 9.2%, P = 0.01) at 1-month postoperatively., Conclusion: Lower extremity bypasses using vein conduit that undergo routine completion angiography are associated with lower rates of graft occlusion at 30-days postoperatively. Completion angiography should thus be routinely performed in infrainguinal bypasses that utilize venous conduit., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Diabetes affects 400 million people globally and patients and causes nephropathy, neuropathy, and vascular disease. Amongst these complications, diabetic foot ulcers remain a substantial problem for patients and clinicians. Aggressive wound care and antibiotics remain important for the healing of these chronic wounds, but even when treated these chronic ulcers can lead to infection and amputations., Areas Covered: This paper reviews the pathophysiology of diabetic foot ulcers and the current management strategies. Then, it discusses novel therapeutics such as topical oxygen therapy as well as autologous patches and macrophage creams., Expert Opinion: Diabetic foot ulcers are a substantial problem for patients and clinicians. Early identification, aggressive wound care, and normoglycemia remain the standard of care, however when these fail it is important to adapt. Since each patient and wound vary drastically we believe they should be treated as such. For patient with intact perfusion, topical ON101 and sucrose octasulfate creams can help. While patient with peripheral arterial disease should consider topical oxygen therapy as an adjunct. However, as scientists gain a better understanding of the pathophysiology behind DFUs, the hope is that this new wave of therapeutics will emerge.

Background/purpose: Lack of robust, feasible, and quantitative outcomes impedes Raynaud phenomenon (RP) clinical trials in systemic sclerosis (SSc) patients. Hyperspectral imaging (HSI) non-invasively measures oxygenated and deoxygenated hemoglobin (oxyHb and deoxyHb) concentrations and oxygen saturation (O 2 sat) in the skin and depicts data as oxygenation heatmaps. This study explored the potential role of HSI in quantifying SSc-RP disease severity and activity., Methods: Patients with SSc-RP (n = 13) and healthy control participants (HC; n = 12) were prospectively recruited in the clinic setting. Using a hand-held camera, bilateral hand HSI (HyperMed™, Waltham, MA) was performed in a temperature-controlled room (22 °C). OxyHb, deoxyHb, and O 2 sat values were calculated for 78-mm 2 regions of interest for the ventral fingertips and palm (for normalization). Subjects underwent a cold provocation challenge (gloved hand submersion in 15 °C water bath for 1 min), and repeated HSI was performed at 0, 10, and 20 min. Patients completed two patient-reported outcome (PRO) instruments: the Raynaud Condition Score (RCS) and the Cochin Hand Function Scale (CHFS) for symptom burden assessment. Statistical analyses were performed using the Mann-Whitney U test and a mixed effects model (Stata, College Station, TX)., Results: Ninety-two percent of participants were women in their 40s. For SSc-RP patients, 69% had limited cutaneous SSc, the mean ± SD SSc duration was 11 ± 5 years, and 38% had prior digital ulcers-none currently. Baseline deoxyHb was higher, and O 2 sat was lower, in SSc patients versus HC (p < 0.05). SSc patients had a greater decline in oxyHb and O 2 sat from baseline to time 0 (after cold challenge) with distinct rewarming oxyHb, O 2 sat, and deoxyHb trajectories versus HCs (p < 0.01). There were no significant correlations between oxyHb, deoxyHb, and O 2 sat level changes following cold challenge and RCS or CHFS scores., Conclusion: Hyperspectral imaging is a feasible approach for SSc-RP quantification in the clinic setting. The RCS and CHFS values did not correlate with HSI parameters. Our data suggest that HSI technology for the assessment of SSc-RP at baseline and in response to cold provocation is a potential quantitative measure for SSc-RP severity and activity, though longitudinal studies that assess sensitivity to change are needed., (© 2023. The Author(s).)

Objective: Despite the progressive advancement of devices for endovascular aortic repair (EVAR), endografts continue to fail, requiring explant. We present a single-institutional experience of EVAR explants, characterizing modern failure modes, presentation, and outcomes for partial and complete EVAR explantation., Methods: A retrospective analysis was performed of all EVARs explanted at an urban quaternary center from 2001 to 2020, with one infected endograft excluded. Patient and graft characteristics, indications, and perioperative and long-term outcomes were analyzed. Partial versus complete explants were performed per surgeon discretion without a predefined protocol. This process was informed by patient risk factors; asymptomatic, symptomatic, or ruptured aneurysm presentation; and anatomical or intraoperative factors, including endoleak type., Results: From 2001 to 2020, 52 explants met the inclusion and exclusion criteria. More than one-half (57.7%) were explants of EVAR devices placed at outside institutions, designated nonindex explants. Most patients were male (86.5%), the median age was 74 years (interquartile range, 70-78 years). More than one-half (61.5%) were performed in the second decade of the study period. The most commonly explanted grafts were Gore Excluder (n = 9 grafts), Cook Zenith (n = 8), Endologix AFX (n = 7), Medtronic Endurant (n = 5), and Medtronic Talent (n = 5). Most grafts (78.8%) were explanted for neck degeneration or sac expansion. Five were explanted for initial seal failure, five for symptomatic expansion, and seven for rupture. The median implant duration was 4.2 years, although ranging widely (interquartile range, 2.6-5.1 years), but similar between index and nonindex explants (4.2 years vs 4.1 years). Partial explantation was performed in 61.5%, with implant duration slightly lower, 3.2 years versus 4.4 years for complete explants. Partial explantation was more frequent in index explants (68.2% vs 56.7%). The median length of stay was 8 days. The median intensive care unit length of stay was 3 days, without significant differences in nonindex explants (4 days vs 3 days) and partial explants (4 days vs 3 days). Thirty-day mortality occurred in two nonindex explants (one partial and one complete explant). Thirty-day readmission was similar between partial and complete explants (9.7% vs 5.0%), without accounting for nonindex readmissions. Long-term survival was comparable between partial and complete explants in Cox regression (hazard ratio, 2.45; 95% confidence interval, 0.79-7.56; P = .12)., Conclusions: Explants of EVAR devices have increased over time at our institution. Partial explant was performed in more than one-half of cases, per operating surgeon discretion, demonstrating higher blood loss, more frequent acute kidney injury, and longer intensive care unit stays, however with comparable short-term mortality and long-term survival., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Diabetic foot ulcers are a health crisis that affect millions of individuals worldwide. Current standard of care involves diligent wound care with adjunctive antibiotics and surgical debridement. However, despite this, the majority will still become infected and fail to heal. Recent efforts using bioengineered skin initially appeared promising, but randomized clinical trials have disappointed. Scientists have now begun to understand that the normal wound healing physiology does not apply to diabetic foot ulcers as they maintain a chronic state of inflammation and fail to progress in a linear pathway. Using transcriptomics, research over the past decade has started identifying master genes and protein pathways that are dysregulated in patients with diabetes. This review paper discusses those genes involved and how novel advancements are using this information to create new biologically based compounds to accelerate wound healing in patients with diabetic foot ulcers., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

The inferior mesenteric artery (IMA) has often been overlooked in favor of the celiac or superior mesenteric artery in arterial mesenteric ischemia, owing to the typically robust visceral collateral networks. In the present report, we have described a case series of patients in whom "salvage" revascularization of the IMA was performed after attempted celiac or superior mesenteric artery revascularization had been unsuccessful. The restored IMA inflow had resolved the symptoms for three patients. However, sole IMA revascularization was insufficient to reverse the course for two other patients with severe acute-on-chronic mesenteric ischemia. The IMA should be considered for salvage revascularization in the appropriate clinical scenario., (© 2022 Published by Elsevier Inc. on behalf of Society for Vascular Surgery.)

Objective: Penetrating atherosclerotic ulcers (PAUs) in aortic branch vessels are rare. There is a paucity of data regarding their long-term natural history and associated management. This study aimed to determine the prevalence and natural history of aortic branch PAUs., Methods: Institutional data on all patients with an aortic branch PAU from 2005 to 2020 were retrospectively reviewed. Branch PAUs were defined as any PAU in the iliac, mesenteric, or arch vessels. End points included symptoms, end-organ events, and interventions. All computed tomography angiographies (CTAs) for each patient were reviewed, and total diameter, ulcer width, and ulcer depth were recorded on each computed tomography scan for the branch PAUs. Rate of change was compared between groups (iliac vs arch and visceral vessels) using a linear mixed-effects model., Results: Among 58,800 patients who underwent a CTA, 367 patients had an aortic PAU (prevalence: 0.6%) and 58 patients had a branch PAU (prevalence: 0.1%). Among those 58 patients, there were 66 ulcerated branches. There were 50 iliac (42 common iliac, 7 internal, and 1 external), 11 arch (8 left subclavian, 3 innominate), and 5 visceral ulcers (3 superior mesenteric artery, 1 celiac, and 1 renal). Mean age was 74.0 ± 8.8 years, and 86% of patients were male; 74% had hypertension, 79% had hyperlipidemia, and 59% had a concomitant aortic aneurysm. There were 45 PAU vessels with >1 CTA (total of 167 CTAs) with a median follow-up of 4.0 years (interquartile range: 2.0-6.2 years). Total vessel diameter increased in size by 0.27 mm/y but did not differ between groups (iliac vs visceral/arch vessels). PAU width and depth also did not significantly change over time, nor did it differ between groups. No branch PAUs caused symptoms, end-organ events, or rupture, nor required intervention due to symptoms and/or progression. Four PAUs spontaneously resolved (2 iliac, 2 other), and 1 iliac PAU progressed to a saccular aneurysm., Conclusions: This is one of the largest studies evaluating the natural history of branched PAUs objectively via CTA. Branch PAUs are rare-the prevalence was one-sixth that of aortic PAUs. There was minimal growth noted in a median follow-up of 4 years, and no PAUs required intervention for symptoms or progression. Asymptomatic branch PAUs may be safely observed., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Venous mesenteric ischemia (VMI) presents with variable severity resulting in a spectrum of outcomes. This study sought to characterize the natural history of VMI and identify drivers of intervention and adverse outcomes., Methods: All patients who presented to our institution with acute and subacute VMI between 1993 and 2016 were identified. Images were reviewed to determine thrombosis location and charts were reviewed to identify clinical factors and outcomes. Univariate analysis was performed for demographics, comorbidities, and presenting characteristics, with primary outcomes of intervention, readmission, and 30-day mortality. A survival analysis was performed with log-rank difference testing for demographics, comorbidities, and presenting characteristics., Results: We identified 103 patients with acute and subacute VMI. The locations of the thrombosis included the superior mesenteric vein (SMV) (31.1%); SMV and portal vein (35.9%); SMV, portal, and splenic veins (15.5%); and other combinations of portomesenteric veins (17.4%), without correlation between the location and outcomes. Most patients were male (60.6%), 22.3% were actively smoking, and the median Charlson comorbidity score was 4 (interquartile range, 2-7). The mean patient age was 61.3 years. More than one-half had a known hypercoagulability (52.4%), 22.3% had prior bowel resection, and 8.7% had prior mesenteric venous intervention, including transjugular intrahepatic portosystemic shunt procedures. Thirty-five patients underwent 83 procedures during their hospitalization, and 23 patients underwent surgical intervention specifically. Prior mesenteric venous procedure, abdominal tenderness, and lactatemia of more than 1.5 mmol/L were associated with an increased need for surgical intervention (P < .05). Patients with leukocytosis of greater than 10K/μL had increased surgical intervention (P = .10), although without statistical significance. However, symptoms for less than 2 weeks (P < .05) were associated with decreased surgical intervention. The 30-day mortality was low in this cohort (6.8%), but was increased in patients requiring intervention (11.4%). For those undergoing procedures, a shorter time to intervention was associated with an improved 30-day mortality (8.7% for procedures on hospital days 0-1 vs 16.7% for hospital day 2 or later; P = .01). Abdominal tenderness and lactatemia were associated with increased 30-day mortality (6.8% vs 3.6% [P < .01] and 16.0% vs 3.8% [P = .03], respectively). A Kaplan-Meier survival analysis revealed a median survival of 7.1 years, with a 1-year survival rate of 74.9%, a 3-year survival rate of 67.1%, and a 5-year survival rate of 57.9%. Negative predictors of survival included a higher Charlson comorbidity index (hazard ratio, 3.7; P < .01) and malignancy (hazard ratio, 3.1; P < .01)., Conclusions: The 30-day mortality of VMT is low, but more than one-third of patients required an intervention beyond anticoagulation. Comorbidity, a prior mesenteric vessel or intestinal operation, and presentation with tenderness or relevant laboratory abnormalities portend worse outcomes. Early intervention is associated with improved outcomes., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Duplex ultrasonography is the reference standard for diagnosing chronic venous insufficiency. Bilateral venous reflux ultrasound studies are among the most time-consuming and physically demanding tests for vascular ultrasound technologists to perform. Furthermore, if a venous procedure is required, many insurance policies require that a diagnostic venous ultrasound scan for reflux must be performed within 1 year of the procedure. If the intervention is scheduled for >1 year after the ultrasound scan, the insurance company might require a repeat venous ultrasound scan before granting insurance authorization. Hence, ordering bilateral venous duplex ultrasound scans to evaluate for reflux when an intervention might only be performed on one limb within the year could be a waste of time and resources. The aim of the present study was to determine the utility of ordering bilateral vs unilateral studies to evaluate for reflux in patients with suspected chronic venous insufficiency and to determine whether a resource-saving potential exists for vascular laboratories through optimization of the process of ordering venous duplex ultrasound studies., Methods: A retrospective review of all patients who had undergone bilateral lower extremity ultrasound scanning to evaluate for reflux from January 1, 2016 to December 31, 2016 at the Massachusetts General Hospital vascular laboratory was performed. The demographics, indications for ultrasound scanning, comorbidities, time required to perform the ultrasound study, and interval to intervention were documented. The data were analyzed using SPSS statistical software (IBM Corp, Armonk, NY)., Results: During the study period, 13,854 ultrasound studies had been performed in our vascular laboratory, of which 606 (4.4%) had been bilateral ultrasound scans for venous insufficiency. The time allotted for a bilateral study was 2 hours. Of the 606 studies evaluated, 152 (25.1%) showed no evidence of reflux, 284 (46.9%) showed bilateral lower extremity reflux, and 170 (28.1%) showed only venous insufficiency in one leg. Venous ablation, phlebectomy, and/or sclerotherapy were performed for 28.7% of the patients. However only 6.2% of patients had undergone venous procedures on both legs within 1 year after the ultrasound studies. Ablation was the most common procedure performed (54.6%), followed by phlebectomy (27.%) and sclerotherapy (17.9%). Overall, 94.7% of patients had not undergone a venous procedure on both legs within 1 year after the ultrasound studies and, hence, would have required a repeat duplex ultrasound scan to ensure insurance coverage for future procedures., Conclusions: Most bilateral ultrasound scans for venous insufficiency will not result in an intervention. Thus, most patients (95%) could have undergone a unilateral scan before the initial intervention instead of bilateral duplex ultrasound scanning., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The presence of cancer increases arterial thromboembolic events, specifically myocardial infarction and stroke, before a formal diagnosis of cancer. To the best of our knowledge, this increase in thrombotic risk has not been studied in patients with lower extremity bypass grafts. In the present study, we aimed to determine the effect of occult cancer on femoropopliteal bypass patency., Methods: A retrospective review of femoropopliteal bypass procedures completed from 2001 to 2018 was performed. International Classification of Diseases, 9th and 10th revision, codes corresponding to breast, lung, prostate, colorectal, skin, brain, and hematologic cancer were used to identify patients who had had occult cancer. Occult cancer was defined as cancer diagnosed within ≤1 year after the bypass procedure. The demographics, comorbidities, bypass configuration and conduit, 1-month, 3-month, 6-month, and 1-year occlusion rates, major adverse limb events, and mortality rates were analyzed. Statistical analysis included t tests, χ 2 tests, and Cox regression analysis., Results: A total of 621 procedures in 517 patients met the inclusion criteria. Of the 621 procedures, 36 (5.8%) were classified as procedures in patients with occult cancer. The patients with occult cancer had had higher occlusion rates at 3 months (27.8% vs 8.0%; P < .001), 6 months (30.5% vs 15.1%; P < .01), and 1 year (44.4% vs 19.8%; P < .001). In Cox regression analysis for bypass thrombosis at 1 year, the only significant predictors were occult cancer (hazard ratio [HR], 2.03; P = .01), below-the-knee distal target (HR, 1.88; P < .01), and a compromised conduit (HR, 2.14; P < .001)., Conclusions: We found an increase in bypass graft thrombosis rates in patients who had undergone femoropopliteal bypass who had had occult cancer. Thrombosis of the graft within 1 year postoperatively might be a sign of occult cancer., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Chronic venous insufficiency (CVI) affects more than 25 million adults in the United States alone, and more 6 million with advanced stages of venous disease. The high incidence of CVI and the increasing costs of care, place a heavy financial burden on the US health care system. Recent studies estimate the total cost of care at more than $3 billion per year. These staggering numbers highlight the importance of timely diagnosis, treatment, and prevention of CVI. In this article, we review the epidemiology and prevalence of CVI, and its financial impact on national health care budget. Racial disparities in CVI and the impact of socioeconomic status on access to care are also discussed. Finally, we discuss CVI-related screening programs and the importance of preventative measures in venous disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sex-related differences in outcomes have been identified in patients with peripheral artery disease (PAD). We hypothesized that women with PAD would have equivalent inpatient mortality with men after vascular intervention., Methods: Patients with a primary diagnosis of critical limb ischemia (CLI) or lifestyle-limiting claudication (LLC) receiving endovascular (EV) or open surgical repair from 2003-2012 were identified from the Nationwide Inpatient Sample. Demographics, comorbidities, and inpatient mortality were analyzed by chi-squared tests of independence and independent-samples t-tests. Logistic regression analysis was performed to identify predictors of inpatient mortality. SPSS 24 software was used with P < 0.05 considered statistically significant., Results: We identified 139,435 (59,432 women and 80,003 men) individuals meeting the aforementioned criteria. Women were older than men (71.5 years vs. 68.2, P < 0.001). There were no differences in racial distribution but women had lower rates of diabetes (38.6% vs. 39.7%, P < 0.001), chronic obstructive pulmonary disease (17.9% vs. 19.5%, P < 0.001), and coronary artery disease (38.6% vs. 47.4%, P < 0.001), while having a higher rate of hypertension (60.0% vs. 56.1%, P < 0.001). There was no sex-related difference in the rate of chronic renal failure. Women had higher inpatient mortality than men after vascular intervention (1.3% vs. 1.1%, P < 0.001). When stratified by surgical technique, women also had higher inpatient mortality after EV repair (1.0% vs. 0.8%, P < 0.05) and open repair (1.9% vs 1.3%, P < 0.001). When separated by admitting diagnosis, women with CLI had higher inpatient mortality than men after open surgery (2.3% vs. 1.9%, P < 0.05) but not after EV intervention. Women with LLC had higher inpatient mortality after both open (0.6% vs. 0.3%, P < 0.05) and EV surgery (0.3% vs. 0.1%, P < 0.05). Regression analysis revealed female sex as an independent predictor of inpatient mortality in patients with LLC (OR, 1.74; 95% CI 1.30-2.32, P < 0.001) but not CLI., Conclusions: Women had higher inpatient mortality than men after vascular intervention for PAD. Women were also older and more likely to have EV intervention than men. Subgroup analysis suggests that these sex-related differences in inpatient mortality are more pronounced in patients with LLC than with CLI. Furthermore, regression analysis shows that sex is a significant predictor for patients diagnosed with LLC but not with CLI. Treatment guidelines should include consideration of sex in their indications for revascularization, particularly for patients diagnosed with LLC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: A commonly used treatment for open wounds, negative pressure wound therapy (NPWT) has recently been used to optimize wound healing in the setting of surgically closed wounds; however, the specific mechanisms of action by which NPWT may benefit patients after surgery remain unknown. Using a swine wound healing model, the current study investigates angiogenesis as a candidate mechanism., Methods: Multiple excisional wounds were created on the dorsa of 10 male Yorkshire pigs and closed by primary suture. The closed wounds underwent treatment with either NPWT dressing or control dressings in the absence of negative pressure. Dressings were maintained for 8 days followed by euthanasia of the animal. Scar evaluation of the wounds by photographic analysis was performed, and wounds were analyzed for angiogenesis markers by enzyme-linked immunosorbent assay and immunohistochemistry., Results: Scar evaluation scores were observed to be significantly higher for the NPWT-treated sites compared with the control sites (P < 0.05). The enzyme-linked immunosorbent assay results demonstrated increases for vascular endothelial growth factor (VEGF) staining at the incision site treated with NPWT compared with other treatment groups (P < 0.05). In addition, an approximately 3-fold elevation in VEGF expression was observed at the NPWT-treated sites (2.8% vs. 1%, respectively; P < 0.0001).). However, there was no significant difference in immunohistochemistry staining., Conclusions: The use of NPWT improves the appearance of wounds and appears to increase VEGF expression after 8 days in the setting of a closed excisional wound model, suggesting that improved angiogenesis is one mechanism by which NPWT optimizes wound healing when applied to closed surgical wound sites.

Vascular groin wound and median sternotomy infections are challenging complications that may lead to serious sequela. Traditional gauze dressings have poor bacteria barrier properties, and so there has been a recent enthusiasm for the use of closed-incision negative-pressure therapy as an effective closed environment, which controls exudate and helps hold the incision edges together. Studies suggest that it may reduce surgical site infection in cardiothoracic and vascular surgery.

Background: The cells lining the endothelium of blood vessels are recognized as playing critical roles in vascular health and disease. The mechanisms that regulate endothelial cells (ECs) proliferation and release of mediators remain poorly understood but represent a potential source of disease modulation. Actin-cytoskeleton remodeling and cell shape have been suggested as key regulators of phosphorylation of yes-associated protein (YAP) which controls cellular growth and proliferation. Because different types of flow have been shown to affect cell shape and cytoskeleton differently, we hypothesized that the level of phosphorylated yes-associated protein (pYAP; serine 127) decreases in EC exposed to pulsatile uniform flow or steady laminar flow, whereas exposure to pulsatile disturbed flow causes an increase or no change., Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to pulsatile uniform flow, pulsatile disturbed flow, or steady laminar flow and analyzed by immunoblotting., Results: Exposure of HUVECs to steady laminar flow caused a significant decrease in the levels of pYAP (69.7 + 2.6%, P < 0.05), whereas total YAP levels remained nearly unchanged. Conversely, exposure to either pulsatile uniform or disturbed flow caused a significant decrease in the levels of both pYAP (63.2 + 10.9% and 69.8 + 11.9%, respectively; P < 0.05) and total YAP (57.1 + 17.8% and 58.4 + 16.3%, respectively; P < 0.05). Addition of MG132, a ubiquitin-proteasome system inhibitor, failed to significantly inhibit the decrease in the levels of total YAP in HUVECs exposed to either pulsatile uniform or disturbed flow., Conclusions: Flow causes a decrease in pYAP. The observed decrease in total YAP levels with pulsatile flow is due to degradation via a proteasome-independent mechanism. This may be a potential target for intervention for disease states such as atherosclerosis and intimal hyperplasia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Acute mesenteric ischemia (AMI) continues to be one of the most devastating diagnoses requiring emergent vascular intervention. There is a national trend toward increased use of endovascular procedures, with improved survival for the treatment of these patients. Our aim was to evaluate whether this trend has changed the treatment of AMI and the subsequent impact on length of hospitalization and hospitalization costs., Methods: We identified all patients admitted for AMI from the National Inpatient Sample from 2004 to 2014 who received open surgical revascularization (OPEN) or an endovascular intervention (ENDO). Primary end points included length of hospital stay and cost of hospitalization. Our secondary end points included acute kidney injury (AKI), in-hospital mortality, and routine discharge., Results: Among 10,381 discharges identified in the data set, 3833 (37%; 97.5% confidence interval [CI], 35%-39%) were male patients with a mean age of 69 years (range, 18-98 years); 4543 (44%; 97.5% CI, 41%-47%) patients were treated ENDO, and 5839 (56%; 97.5% CI, 53%-59%) patients were treated OPEN. Although a higher proportion of patients in the ENDO group (28%; 97.5% CI, 24%-31%) vs the OPEN group (14%; 97.5% CI, 11%-16%) had a moderate to severe Charlson Comorbidity Index (P < .0001), ENDO was associated with a lower mortality rate (12.3% [97.5% CI, 9.8%-14.8%] vs 33.1% [97.5% CI, 29.9%-36.2%]; P < .0001) and a lower mean hospitalization cost ($41,615 [97.5% CI, $38,663-$44,567] vs $60,286 [97.5% CI, $56,736-$63,836]; P < .0001). After propensity-adjusted logistic regression analysis, OPEN retained a significant association with higher mortality than ENDO (odds ratio, 3.0; 97.5% CI, 2.2-4.1) and with higher costs (mean, $9196; 97.5% CI, $3797-$14,595). Patients in the OPEN group had higher risk for AKI (P < .0001) and discharge to a skilled nursing facility (P < .0001) rather than home., Conclusions: Although the rate of ENDO continues to rise nationally, it still has not surpassed OPEN revascularization in the face of AMI. Patients treated endovascularly demonstrated one-third the rate of in-hospital mortality (odds ratio, 3.0; 97.5% CI, 2.2-4.1), an increased hazard ratio for discharge alive (hazard ratio, 2.27; 97.5% CI, 2.00-2.58), and a cost saving of $9196 (97.5% CI, $3797-$14,595) per hospitalization. Furthermore, they were less likely to develop AKI and to be discharged home after hospitalization., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

We report the case of an 8-year-old patient with a history of nephrotic syndrome, who presented to the emergency department with right foot pain. The patient's mother described intermittent pain that woke her son from sleep and was accompanied by the foot turning purple and becoming cold to touch. Physical examination revealed capillary refill of over 10 seconds in the right and less than 2 seconds in the left foot. Ankle-brachial indices (ABIs) were 0.0 on the right and 0.96 on the left. The patient was admitted and started on therapeutic intravenous heparin. After consultation with his parents, right lower extremity angiography and thrombolysis was performed over 2 days. He subsequently underwent fasciotomy and amputation of the tip of all 5 toes. Eighteen months later, there is no leg length discrepancy, he is walking with foot inserts and has normal ABIs bilaterally., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Treatment for lifestyle limiting claudication (LLC) that is due to infra-inguinal peripheral artery disease relies on either bypass, angioplasty, and/or stenting. Given the enthusiasm and shift toward more endovascular therapy for treatment of LLC, we sought to analyze whether octogenarians benefit from infra-inguinal interventions in the same manner as their younger counterparts., Methods: We identified all patients admitted for elective treatment of LLC from the Nationwide Inpatient Sample from 2003 to 2012, who received open surgical or endovascular intervention for infra-inguinal peripheral arterial disease. These patients were divided into two groups including those between the ages 60-80 years (younger cohort) and those older than 80 years (octogenarians). Primary end-points included morbidity and mortality and the secondary end-points were length of hospital stay (LOS) and disposition after dismissal., Results: Among 59,323 discharges identified in the dataset, 34,658 (58%) were males. There were 50,323 (85%) patients in the younger cohort and 9,000 (15%) octogenarians. The mean age was 69.9 ± 5.7 years and 84.2 ± 3.0 years for the younger cohort and octogenarians, respectively. The mean Charlson comorbidity index (CCI) was higher in our younger cohort (2.1 ± 1.1, P < 0.001). Octogenarians mainly treated with open surgery prior to 2004 are now treated endovascularly and this trend has remained stable. The younger cohort's treatment modality has fluctuated through the study period and most recently is treated mainly with open surgery. The rate of acute kidney injury, exacerbation of congestive heart failure and mortality was higher in octogenarians (P < 0.001). The rate of infectious wound complications was higher in the younger cohort (P < 0.05). Octogenarians have longer LOS and are dismissed in higher percentage to a skilled nursing facility (P < 0.001). On binary logistic regression analysis, age over 80 years, female sex, higher CCI and having an open as opposed to an endovascular procedure are independent predictors of in-hospital mortality., Conclusions: Although endovascular techniques seem to dominate the care for octogenarians with LLC, the overall morbidity and mortality rates are significantly higher in this patient population. Other options such as medical management and/or supervised exercise therapy should be explored in this patient group., (© 2018 Wiley Periodicals, Inc.)

Objective: Chronic mesenteric ischemia (CMI) continues to be a devastating diagnosis. There is a national trend toward increased use of endovascular procedures with improved survival for the treatment of these patients. Our aim was to evaluate whether this trend has changed CMI patients' length of hospitalization and health care cost., Methods: We identified all patients admitted for CMI from the National Inpatient Sample (NIS) from 2000 to 2014. Our primary end points included length of hospital stay (LOS) and cost of hospitalization (COH). Our secondary end points included mortality assessment of the CMI hospitalization., Results: There were 15,475 patients admitted for CMI. The mean age of patients was 71 years, and 4022 (26.0%) were male. There were 10,920 (70.6%) patients treated endovascularly (ENDO) and 4555 (29.4%) patients treated in an open fashion (OPEN). Although a higher proportion of patients in the ENDO (43.3%) group vs OPEN (33.1%) had a Charlson Comorbidity Index score of ≥2 (P < .0001), they had a lower mortality rate (2.4% vs 8.7%; P < .0001), lower mean LOS (6.3 vs 14.0 days; P < .0001), and lower COH ($21,686 vs $42,974; P < .0001). After adjusting for clinical and hospital factors, OPEN continued to demonstrate higher mortality than ENDO (odds ratio, 7.2; 95% confidence interval, 4.9-10.6; P < .0001), longer LOS (mean, +9.7 days; P < .0001), and higher COH (mean, +$25,834; P < .0001)., Conclusions: The rate of ENDO continues to rise nationally in the treatment of CMI patients. After adjusting for clinical and hospital factors, patients in the ENDO group tend to have lower in-hospital mortality of 2.4% and lower LOS by 10 days, and they incur a cost saving of >$25,000 compared with patients in the OPEN group. ENDO should be considered first line of therapy for patients with CMI., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum-starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to-and-fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber. At the end of experimentation, cell lysates were immunoblotted with antibodies to phospho-ERK5 and total ERK5. ERK5 activation was assessed by the levels of phosphorylated ERK5. The densitometric mean ± SEM is calculated and analyzed by ANOVA. p  < 0.05 is considered significant. Levels of ERK5 decreased with all flow conditions with the largest decrease in TFF flow condition. TFF and CLF exhibited sustained ERK5 phosphorylation in HUVECs stimulated for up to 4 hours. PFF had transient phosphorylation of ERK5 at 2 hours, which then became undetectable at 4 hours of exposure to flow. Also, TFF and CLF both showed decreased levels at 4 hours, suggesting a decrease in activation for these flow conditions. Exposure of HUVEC to different types of shear stress results in varying patterns of activation of ERK5. Activation of ERK5 with TFF suggests a role in the pathogenesis of atherosclerosis and vascular remodeling under disturbed flow conditions.

Background: Hyperspectral imaging (HSI) is a technology that with limited training can noninvasively measure oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin concentrations in the skin to create an oxygenation map. This pilot study determined whether HSI could be used to demonstrate vascular dysfunction in the upper extremity of patients with peripheral artery disease (PAD) and coronary artery disease (CAD)., Methods: This prospective study included 93 consecutive, consented patients presenting to the vascular clinic, with and without diagnosed arterial disease, and healthy volunteers. Patients underwent HSI at the upper arm, forearm, and palm before and after cuff occlusion (50 mm Hg above systolic) for 5 minutes. Medical records of enrolled patients were reviewed for demographic data, medications, surgical history, and other pertinent information., Results: Significant changes occurred with oxyHb, with minimal to no effects on deoxygenated hemoglobin. The highest values of oxyHb were detected in the upper arm, followed by the forearm and hand. The absolute and percentage change in oxyHb measured in the upper arm and forearm was significantly reduced in controls aged >40 years compared with controls aged <40 years. Significant differences were noted in the upper arm oxyHb absolute change in response to cuff occlusion comparing PAD or CAD (n = 47) vs the older control cohort (P = .028). When the 23 patients with PAD only were separated out, the upper arm oxyHb response to cuff occlusion is even more significantly impaired (P < .01) compared with controls., Conclusions: Our study suggests the ability of HSI to assess the presence of PAD or CAD based on systemic vascular dysfunction at sites remote from the clinically diseased vascular bed. This could enable early screening and tracking of arterial disease patients before the development of clinically advanced disease., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm(2) SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm(2), a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.

Yes-associated protein (YAP) is a mechanosignaling protein that relays mechanical information to the nucleus by changing its level of phosphorylation. We hypothesize that different flow patterns show differential effect on phosphorylated YAP (pYAP) (S127) and total YAP and could be responsible for flow dependent localization of atherosclerosis. Confluent human umbilical vein endothelial cells (HUVECs) seeded on fibronectin-coated glass slides were exposed to continuous forward flow (CFF) and pulsatile forward flow (PFF) using a parallel plate flow chamber system for 30 minutes. Cell lysates were prepared and immunoblotted to detect the levels of phosphorylated YAP and total YAP. HUVECs exposed to both PFF and CFF showed a mild decrease in the levels of both pYAP (S127) and total YAP. While the levels of pYAP (S127) decreased to 87.85 and 85.21% of static control with PFF and CFF, respectively, the levels of total YAP significantly decreased to 91.31 and 92.27% of static control. No significant difference was seen between CFF and PFF on their effect on pYAP (S127), but both conditions resulted in a significant decrease in total YAP at 30 minutes. The results of this experiment show that the possible effect of different types of flow on YAP is not induced before 30 minutes. Experiments exposing endothelial cells to various types of flow for longer duration of time could help to elucidate the role of YAP in the pathogenesis of atherosclerosis.

Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial cell integrity and protect from vascular dysfunction under continuous laminar flow. However, the effect of flow on ERK5 levels has not been determined. Confluent human umbilical vein endothelial cells (HUVECs) were seeded on fibronectin coated glass slides and serum starved for 2 hours with 1% fetal bovine serum (FBS). HUVECs were then exposed to to and fro flow (TFF), pulsatile forward flow (PFF), or continuous laminar flow (CLF) in a parallel plate flow chamber for up to 2 hours. At the end of experiment, cell lysates were prepared and immunoblotted with antibodies to total ERK5. Both CLF and TFF exhibited a decrease in ERK5 after levels after 2-hour exposure. However, the level of ERK5 for PFF remained the same. Disturbed, but not uniform pulsatile, flow decreases ERK5 levels in HUVECs.

Significant progress in limb salvage for patients with peripheral arterial disease and critical limb ischemia has occurred in the past 2 decades. Improved patient outcomes have resulted from increased knowledge and understanding of the disease processes, as well as efforts to improve revascularization techniques and enhance patient care after open and endovascular procedures. An imaging modality that is noninvasive, fast, and safe would be a useful tool for clinicians in assessing lower-extremity perfusion when planning interventions. Among the current and emerging regional perfusion imaging modalities are transcutaneous oxygen monitoring, hyperspectral imaging, indocyanine green dye-based fluorescent angiography, nuclear diagnostic imaging, and laser Doppler. These tests endeavor to delineate regional foot perfusion to guide directed revascularization therapy in patients with critical limb ischemia and foot ulceration., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Although the rate of lower limb amputation in patients with diabetes is decreasing, amputation still remains a major complication of diabetes. Prosthetics have been long used to help amputees ambulate. The last decade has seen many advances in prostheses with the enhanced understanding of the mechanics of ambulation and improved use of technology. This review describes the different types of prosthetic options available for below knee, ankle, and foot amputees, emphasizing the latest advances in prosthetic design., (Copyright © 2014 Elsevier Inc. All rights reserved.)