78 results on '"Brewster LP"'
Search Results
2. Ecthyma gangrenosum following toxic epidermal necrolysis syndrome in a 3-year-old boy-a survivable series of events.
- Author
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Gresik CM, Brewster LP, Abood G, Supple KG, Silver GM, Gamelli RL, Nickoloff BJ, Gresik, Christine M, Brewster, Luke P, Abood, Gerard, Supple, Kathy G, Silver, Geoffrey M, Gamelli, Richard L, and Nickoloff, Brian J
- Published
- 2008
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3. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
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Gornik HL, Aronow HD, Goodney PP, Arya S, Brewster LP, Byrd L, Chandra V, Drachman DE, Eaves JM, Ehrman JK, Evans JN, Getchius TSD, Gutiérrez JA, Hawkins BM, Hess CN, Ho KJ, Jones WS, Kim ESH, Kinlay S, Kirksey L, Kohlman-Trigoboff D, Long CA, Pollak AW, Sabri SS, Sadwin LB, Secemsky EA, Serhal M, Shishehbor MH, Treat-Jacobson D, and Wilkins LR
- Subjects
- Humans, United States, Cardiology standards, Societies, Medical standards, Peripheral Arterial Disease therapy, Peripheral Arterial Disease diagnosis, Lower Extremity blood supply, American Heart Association
- Abstract
Aim: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia)., Methods: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate., Structure: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed., (Copyright © 2024 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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4. Hyperoxia impairs induced pluripotent stem cell-derived endothelial cells and drives an atherosclerosis-like transcriptional phenotype.
- Author
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Carr SM, Owsiany K, Scrivner O, McLaughlin D, Jo H, Brewster LP, and Hekman KE
- Abstract
Background: Induced pluripotent stem cells (iPSCs) directed to endothelial identity (iPSC-ECs) are emerging as a potent tool for regenerative medicine in vascular disease. However, iPSC-ECs lose expression of key identity markers under standard in vitro conditions, limiting their clinical applications., Methods: To model physiological in vivo conditions, we examined the bioenergetics, presence of key cell markers, and proliferative and angiogenic capacity in iPSC-ECs at late and early passage under hyperoxic (21%) and physiological (4%) oxygen concentrations., Results: Physoxia resulted in relative preservation of mitochondrial bioenergetic activity, as well as CD144 expression in late passage iPSC-ECs, but not proliferative capacity or tube formation. Single cell RNA sequencing (scRNA-seq) revealed that late passage hyperoxic iPSC-ECs develop an endothelial-to-mesenchymal phenotype. Comparing scRNA-seq data from iPSC-ECs and from atherosclerotic ECs revealed overlap of their transcriptional phenotypes., Conclusions: Taken together, our studies demonstrate that physiological 4% oxygen culture conditions were sufficient to improve mitochondrial function in high passage cells, but alone was insufficient to preserve angiogenic capacity. Furthermore, late passage cells under typical conditions take on an endothelial-to-mesenchymal phenotype with similarities to ECs found in atherosclerosis., Competing Interests: None.
- Published
- 2024
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5. Search Engines to Capture Missing Deaths From Institutional Data Warehouse.
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Dayal YS, Foster DG, Hao Y, Bennett SG, and Brewster LP
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- Humans, Databases, Factual, Data Warehousing, Search Engine
- Abstract
Introduction: Clinical publications use mortality as a hard end point. It is unknown how many patient deaths are under-reported in institutional databases. The objective of this study was to query mortality in our patient cohort from our data warehouse and compare these deaths to those identified in different databases., Methods: We passed the first/last name and date of birth of 134 patients through online mortality search engines (Find a Grave Index, US Cemetery and Funeral Home Collection, etc.) to assess their ability to capture patient deaths and compared that to deaths recorded from our institutional data warehouse., Results: Our institutional data warehouse found approximately one-third of the total patient mortalities. After the Social Security Death Index, we found that the Find a Grave Index captured the most mortalities missed by the institutional data warehouse. These results highlight the advantages of incorporating readily available search engines into institutional data warehouses for the accurate collection of patient mortalities, particularly those that occur outside of index operative admission., Conclusions: The incorporation of the mortality search engines significantly augmented the capture of patient deaths. Our approach may be useful for tailored patient outreach and reporting mortalities with institutional data., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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6. Single-Cell RNA sequencing investigation of female-male differences under PAD conditions.
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Sánchez Marrero G, Villa-Roel N, Li F, Park C, Kang DW, Hekman KE, Jo H, and Brewster LP
- Abstract
Peripheral arterial disease (PAD) is an age-related medical condition affecting mostly muscular arteries of the limb. It is the 3
rd leading cause of atherosclerotic morbidity. The mechanical environment of endothelial cells (ECs) in PAD is characterized by disturbed blood flow (d-flow) and stiff extracellular matrices. In PAD, the stiffness of arteries is due to decreased elastin function and increased collagen content. These flow and stiffness parameters are largely missing from current models of PAD. It has been previously proven that ECs exposed to d-flow or stiff substrates lead to proatherogenic pathways, but the effect of both, d-flow and stiffness, on EC phenotype has not been fully investigated. In this study, we sought to explore the effect of sex on proatherogenic pathways that could result from exposing endothelial cells to a d-flow and stiff environment. We utilized the scRNA-seq tool to analyze the gene expression of ECs exposed to the different mechanical conditions both in vitro and in vivo . We found that male ECs exposed to different mechanical stimuli presented higher expression of genes related to fibrosis and d-flow in vitro . We validated our findings in vivo by exposing murine carotid arteries to d-flow via partial carotid artery ligation. Since women have delayed onset of arterial stiffening and subsequent PAD, this work may provide a framework for some of the pathways in which biological sex interacts with sex-based differences in PAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sánchez Marrero, Villa-Roel, Li, Park, Kang, Hekman, Jo and Brewster.)- Published
- 2023
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7. Comparison of arterial storage conditions for delayed arterial ring testing.
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McLaughlin DK, Hoffmann C, Sasaki M, Li F, Ma J, Cui X, Sutliff RL, and Brewster LP
- Abstract
Objective: Arterial ring testing is the gold standard for measuring arterial function. Increased arterial tone through arterial contraction and impaired endothelial relaxation (endothelial dysfunction) are key metrics of impaired arterial health in peripheral arterial disease (PAD). To allow for comparative testing of arteries during standard laboratory hours, storage buffers and conditions have been used to extend the functional life of arteries. Various storage conditions have been compared, but there has not been a robust comparison or validation in human arteries. The objective of this work is to optimize storage of arterial segments for endothelial cell (EC) testing in a murine model and to test EC function in human PAD arteries. We hypothesized that certain storage conditions would be superior to others., Methods: Healthy murine aortas were harvested from 10- to 14-week-old C57/Bl6J male and female mice and compared under different storage protocols (24 hours) to immediate arterial testing. The storage conditions tested were: Opti-MEM (37°C or 4°C), Krebs-HEPES with 1.8 mmol/L or 2.5 mmol/L calcium (4°C), or Wisconsin (WI) solution at 4°C. Vascular function was evaluated by isometric force testing. Endothelium-dependent and -independent relaxation were measured after precontraction with addition of methacholine or sodium nitroprusside, respectively. Arterial contraction was stimulated with potassium chloride or phenylephrine. Analysis of variance was used to determine significance compared with immediate testing with P < .05. Under institutional review board approval, 28 PAD arteries were collected at amputation and underwent vascular function testing as described. Disturbed flow conditions were determined by indirect (upstream occlusion) flow to the harvested tibial arteries. Stable flow arteries had in-line flow. Arterial calcification was quantified manually as present or not present., Results: We found that 4°C WI and 37°C Opti-MEM best preserved endothelium-dependent relaxation and performed similarly to immediately testing aortas (termed fresh for freshly tested) ( P > .95). Other storage conditions were inferior to freshly tested aortas ( P < .05). Vascular smooth muscle function was tested by endothelial-independent relaxation and contractility. All storage conditions preserved endothelial-independent relaxation and contractility similar to freshly tested arteries. However, 4°C WI and 37°C Opti-MEM storage conditions most closely approximated the maximum force of contraction of freshly tested arteries in response to potassium chloride ( P > .39). For human arterial testing, 28 tibial arteries were tested for relaxation and contraction with 16 arteries with peripheral artery occlusive disease (PAD with disturbed flow) and 12 without peripheral artery occlusive disease (PAD with stable flow), of which 14 were calcified and 14 were noncalcified. Endothelial-dependent relaxation data was measurable in 9 arteries and arterial contraction data was measurable in 14 arteries. When comparing flow conditions, arteries exposed to disturbed flow (n = 4) had significantly less relaxation (2% vs 59%; P = .03) compared with stable flow conditions (n = 5). In contrast, presence the (n = 6) or absence of calcification (n = 3) did not impact arterial relaxation. Arterial contraction was not different between groups in either comparison by flow (n = 9 disturbed; n = 5 stable) or calcification (n = 6 present; n = 8 absent)., Conclusions: In healthy murine aortas, arterial storage for 24 hours in 4°C WI or 37°C Opti-MEM both preserved endothelium-dependent relaxation and maximum force of contraction. In human PAD arteries stored in 4° WI, flow conditions before arterial harvest, but not arterial calcification, led to differences in arterial relaxation in human PAD arteries. Arterial contractility was more robust (11/28 arteries) compared with arterial relaxation (7/28 arteries), but was not significantly different under flow or calcification parameters. This work defines ideal storage conditions for arterial ring testing and identifies that EC dysfunction from disturbed flow may persist in delayed ex vivo arterial testing.
- Published
- 2023
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8. Effect of Aging, Sex, and Gene (Fbln5) on Arterial Stiffness of Mice: 20 Weeks Adult Fbln5-knockout Mice Have Older Arteries than 100 Weeks Wild-Type Mice.
- Author
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Dong H, Ferruzzi J, Liu M, Brewster LP, Leshnower BG, and Gleason RL
- Abstract
The arterial stiffening is a strong independent predictor of cardiovascular risk and has been used to characterize the biological age of arteries ('arterial age'). Here we revealed that the Fbln5 gene knockout (Fbln5
-/- ) significantly increases the arterial stiffening for both male and female mice. We also showed that the arterial stiffening increases with natural aging, but the stiffening effect of Fbln5-/- is much more severe than aging. The arterial stiffening of 20 weeks old mice with Fbln5-/- is much higher than that at 100 weeks in wild-type (Fbln5+/+ ) mice, which indicates that 20 weeks mice (equivalent to ∼26 years old humans) with Fbln5-/- have older arteries than 100 weeks wild-type mice (equivalent to ∼77 years humans). Histological microstructure changes of elastic fibers in the arterial tissue elucidate the underlying mechanism of the increase of arterial stiffening due to Fbln5-knockout and aging. These findings provide new insights to reverse 'arterial age' due to abnormal mutations of Fbln5 gene and natural aging. This work is based on a total of 128 biaxial testing samples of mouse arteries and our recently developed unified-fiber-distribution (UFD) model. The UFD model considers the fibers in the arterial tissue as a unified distribution, which is more physically consistent with the real fiber distribution of arterial tissues than the popular fiber-family-based models (e.g., the well-know Gasser-Ogden-Holzapfel [GOH] model) that separate the fiber distribution into several fiber families. Thus, the UFD model achieves better accuracies with less material parameters. To our best knowledge, the UFD model is the only existing accurate model that could capture the property/stiffness differences between different groups of the experimental data discussed here.- Published
- 2023
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9. Myoglobinemia, Peripheral Arterial Disease, and Patient Mortality.
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Scrivner O, Fletcher E, Hoffmann C, Li F, Wilkinson T, Miserlis D, Smith RS, Bohannon WT, Sutliff R, Jordan WD, Koutakis P, and Brewster LP
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- Animals, Mice, Swine, Nitric Oxide, Myoglobin, Biomarkers, Endothelial Cells metabolism, Peripheral Arterial Disease
- Abstract
Background: Peripheral arterial disease (PAD) causes leg muscle damage due to inadequate perfusion and increases cardiovascular events and mortality 2- to 3-fold. It is unclear if PAD is a biomarker for high-risk cardiovascular disease or if skeletal muscle injury harms arterial health. The objective of this work is to test if serum myoglobin levels (myoglobinemia) are a marker of PAD, and if so, whether myoglobin impairs vascular health., Study Design: Patient blood samples were collected from PAD and control (no PAD) patients and interrogated for myoglobin concentrations and nitric oxide bioavailability. Patient mortality over time was captured from the medical record. Myoglobin activity was tested on endothelial cells and arterial function., Results: Myoglobin is a biomarker for symptomatic PAD and was inversely related to nitric oxide bioavailability; 200 ng/mL myoglobin in vitro increased endothelial cell permeability in vitro and decreased nitrate bioavailability. Ex vivo, 100 ng/mL myoglobin increased vascular tone in naive murine aortas approximately 1.5 times, impairing absolute vessel relaxation. In vivo, we demonstrated that myoglobinemia caused impaired flow-mediated dilation in a porcine model. Patients presenting with myoglobin levels of 100 ng/mL or greater had significantly more deaths than those with myoglobin levels of less than 100 ng/mL., Conclusions: Using a combination of patient data, in vitro, ex vivo, and in vivo testing, we found that myoglobin is a biomarker for symptomatic PAD and a potent regulator of arterial health that can increase vascular tone, increase vascular permeability, and cause endothelial dysfunction, all of which may contribute to the vulnerability of PAD patients to cardiovascular events and death.
- Published
- 2023
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10. Effect of a Decision Aid on Agreement Between Patient Preferences and Repair Type for Abdominal Aortic Aneurysm: A Randomized Clinical Trial.
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Eid MA, Barry MJ, Tang GL, Henke PK, Johanning JM, Tzeng E, Scali ST, Stone DH, Suckow BD, Lee ES, Arya S, Brooke BS, Nelson PR, Spangler EL, Murebee L, Dosluoglu HH, Raffetto JD, Kougais P, Brewster LP, Alabi O, Dardik A, Halpern VJ, O'Connell JB, Ihnat DM, Zhou W, Sirovich BE, Metha K, Moore KO, Voorhees A, and Goodney PP
- Subjects
- Aged, Decision Support Techniques, Female, Humans, Male, Patient Preference, Aortic Aneurysm, Abdominal surgery, Endovascular Procedures methods
- Abstract
Importance: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair., Objective: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive., Design, Setting, and Participants: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021., Interventions: Presurgical consultation using a decision aid vs usual care., Main Outcomes and Measures: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios., Results: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70)., Conclusions and Relevance: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures., Trial Registration: ClinicalTrials.gov Identifier: NCT03115346.
- Published
- 2022
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11. COVID-19-associated venous thromboembolism portends worse survival.
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Meena RA, Sharifpour M, Gaddh M, Cui X, Xie Y, Di M, Brewster LP, Duwayri Y, and Alabi O
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- Hospitalization, Humans, Retrospective Studies, Risk Factors, SARS-CoV-2, COVID-19, Venous Thromboembolism diagnosis, Venous Thromboembolism epidemiology
- Abstract
Patients with coronavirus disease 2019 (COVID-19) seem to be at high risk for venous thromboembolism (VTE) development, but there is a paucity of data exploring both the natural history of COVID-19-associated VTE and the risk for poor outcomes after VTE development. This investigation aims to explore the relationship between COVID-19-associated VTE development and mortality. A prospectively maintained registry of patients older than 18 years admitted for COVID-19-related illnesses within an academic health care network between March and September 2020 was reviewed. Codes from the tenth revision of the International Classification of Diseases for VTE were collected. The charts of those patients with a code for VTE were manually reviewed to confirm VTE diagnosis. There were 2,552 patients admitted with COVID-19-related illnesses. One hundred and twenty-six patients (4.9%) developed a VTE. A disproportionate percentage of patients of Black race developed a VTE (70.9% VTE v 57.8% non-VTE; P = .012). A higher proportion of patients with VTE expired during their index hospitalization (22.8% VTE v 8.4% non-VTE; P < .001). On multivariable logistic regression analysis, VTE was independently associated with mortality (odds ratio = 3.17; 95% confidence interval, 1.9-5.2; P < .001). Hispanic/Latinx ethnicity was associated with decreased mortality (odds ratio = 0.45; 95% confidence interval, 0.21-1.00; P = .049). Hospitalized patients of Black race with COVID-19 were more prone to VTE development, and patients with COVID-19 who developed in-hospital VTE had roughly nearly threefold higher odds of mortality. Further emphasis should be placed on optimizing COVID-19 anticoagulation protocols to reduce mortality in this high-risk cohort., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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12. Vascular calcification: a left-handed compliment for aging.
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Brewster LP
- Subjects
- Aging, Humans, Vascular Calcification diagnostic imaging
- Published
- 2021
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13. The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins.
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Ismaeel A, Papoutsi E, Miserlis D, Lavado R, Haynatzki G, Casale GP, Bohannon WT, Smith RS, Eidson JL, Brumberg R, Hayson A, Kirk JS, Castro C, Sawicki I, Konstantinou C, Brewster LP, Pipinos II, and Koutakis P
- Abstract
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'-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.
- Published
- 2020
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14. Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study.
- Author
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Mehta A, Mavromatis K, Ko YA, Rogers SC, Dhindsa DS, Goodwin C, Patel R, Martini MA, Prasad M, Mokhtari A, Hesaroieh IG, Frohwein SC, Kutner MH, Harzand A, Wells BJ, Duwayri Y, Alabi O, Rajani RR, Brewster LP, Waller EK, and Quyyumi AA
- Subjects
- Female, Humans, Male, Ankle Brachial Index, Diabetes Mellitus epidemiology, Double-Blind Method, Exercise Test, Injections, Subcutaneous, Walking physiology, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor adverse effects, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Lower Extremity, Peripheral Arterial Disease epidemiology, Peripheral Arterial Disease therapy
- Abstract
Background: Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD., Methods: We plan to recruit 176 patients in this ongoing randomized, double-blind, placebo-controlled Phase IIB trial. After screening for inclusion and exclusion criteria, eligible subjects undergo a 4-week screening phase where they perform subcutaneous placebo injections thrice weekly and walk at least three times a day until they develop claudication. After the screening phase, eligible subjects undergo baseline testing and are randomized 2:1 to receive 500 μg/day of GM-CSF subcutaneously thrice weekly for three weeks or placebo injections. After 3 months, follow-up endpoint testing is performed and subjects in the GM-CSF group receive the second administration of the drug for three weeks while subjects in placebo group receive matching placebo injections. All participants undergo endpoint testing at six-month and nine-month follow-up. The primary endpoint is change in 6-min walk distance between baseline and 6-month follow-up., Conclusion: GPAD-3 explores a novel approach to address the need for alternative therapies that can alleviate symptoms among patients with lower extremity PAD. If successful, this study will pave the way for a pivotal Phase III trial., Competing Interests: Declaration of Competing Interest No authors have any competing interests., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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15. Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association.
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Misra S, Shishehbor MH, Takahashi EA, Aronow HD, Brewster LP, Bunte MC, Kim ESH, Lindner JR, and Rich K
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- American Heart Association, Ankle Brachial Index, Equipment and Supplies, Ethnicity, Evidence-Based Medicine, Extremities blood supply, Healthcare Disparities, Humans, Ischemia epidemiology, Peripheral Arterial Disease epidemiology, Regional Blood Flow, United States epidemiology, Extremities pathology, Ischemia diagnosis, Peripheral Arterial Disease diagnosis
- Abstract
There are >12 million patients with peripheral artery disease in the United States. The most severe form of peripheral artery disease is critical limb ischemia (CLI). The diagnosis and management of CLI is often challenging. Ethnic differences in comorbidities and presentation of CLI exist. Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain. A thorough evaluation of limb perfusion is important in the diagnosis of CLI because it can not only enable timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with other causes for ulcers, including venous, neuropathic, or pressure changes. This scientific statement discusses the current tests and technologies for noninvasive assessment of limb perfusion, including the ankle-brachial index, toe-brachial index, and other perfusion technologies. In addition, limitations of the current technologies along with opportunities for improvement, research, and reducing disparities in health care for patients with CLI are discussed.
- Published
- 2019
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16. Poor glycemic control is a strong predictor of postoperative morbidity and mortality in patients undergoing vascular surgery.
- Author
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Long CA, Fang ZB, Hu FY, Arya S, Brewster LP, Duggan E, and Duwayri Y
- Subjects
- Aged, Biomarkers blood, Blood Glucose drug effects, Databases, Factual, Female, Humans, Hyperglycemia blood, Hyperglycemia drug therapy, Hyperglycemia mortality, Hypoglycemic Agents therapeutic use, Male, Middle Aged, Patient Readmission, Reoperation, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Vascular Surgical Procedures mortality, Blood Glucose metabolism, Hyperglycemia etiology, Vascular Surgical Procedures adverse effects
- Abstract
Objective: Hyperglycemia is a common occurrence in patients undergoing cardiovascular surgery. It has been identified in several surgical cohorts that improved perioperative glycemic control reduced postoperative morbidity and mortality. A significant portion of the population with peripheral arterial disease suffers from the sequelae of diabetes or metabolic syndrome. A paucity of data exists regarding the relationship between perioperative glycemic control and postoperative outcomes in vascular surgery patients. The objective of this study was to better understand this relationship and to determine which negative perioperative outcomes could be abated with improved glycemic control., Methods: This is a retrospective review of a vascular patient database at a large academic center from 2009 to 2013. Eligible procedures included carotid endarterectomy and stenting, endovascular and open aortic aneurysm repair, and all open bypass revascularization procedures. Data collected included standard demographics, outcome parameters, and glucose levels in the perioperative period. Perioperative hyperglycemia was defined as at least one glucose value >180 mg/dL within 72 hours of surgery. The primary outcome was 30-day mortality, with secondary outcomes of complications, need to return to the operating room, and readmission., Results: Of the total 1051 patients reviewed, 366 (34.8%) were found to have perioperative hyperglycemia. Hyperglycemic patients had a higher 30-day mortality (5.7% vs 0.7%; P < .01) and increased rates of acute renal failure (4.9% vs 0.9%; P < .01), postoperative stroke (3.0% vs 0.7%; P < .01), and surgical site infections (5.7% vs 2.6%; P = .01). In addition, these patients were also more likely to undergo readmission (12.3% vs 7.9%; P = .02) and reoperation (6.3% vs 1.8%; P < .01). Furthermore, multivariable logistic regression demonstrated that perioperative hyperglycemia had a strong association with increased 30-day mortality and multiple negative postoperative outcomes, including myocardial infarction, stroke, renal failure, and wound complications., Conclusions: This study demonstrates a strong association between perioperative glucose control and 30-day mortality in addition to multiple other postoperative outcomes after vascular surgery., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2019
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17. Reversible secretome and signaling defects in diabetic mesenchymal stem cells from peripheral arterial disease patients.
- Author
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Chadid T, Morris A, Surowiec A, Robinson S, Sasaki M, Galipeau J, Pollack BP, and Brewster LP
- Subjects
- Aged, Amputation, Surgical, Blood Platelets metabolism, Bone Marrow Cells drug effects, Bone Marrow Cells pathology, Cell Extracts pharmacology, Cell Movement, Cell Proliferation, Cell Survival, Cells, Cultured, Diabetic Angiopathies pathology, Diabetic Angiopathies surgery, Epidermal Growth Factor pharmacology, Female, Fibroblast Growth Factor 2 pharmacology, Human Umbilical Vein Endothelial Cells metabolism, Humans, Male, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells pathology, Middle Aged, Peripheral Arterial Disease pathology, Peripheral Arterial Disease surgery, Phenotype, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, Secretory Pathway, Adipose Tissue cytology, Bone Marrow Cells metabolism, Diabetic Angiopathies metabolism, Mesenchymal Stem Cells metabolism, Neovascularization, Physiologic, Peripheral Arterial Disease metabolism, Signal Transduction
- Abstract
Objective: Regenerative medicine seeks to stall or to reverse the pathologic consequences of chronic diseases. Many people with diabetes have peripheral arterial disease (PAD), which increases their already high risk of major amputation. Cellular therapies are a promising regenerative medicine approach to PAD that can be used to focally inject regenerative cells to endangered tissue beds. Mesenchymal stem cells (MSCs) are known to promote tissue regeneration through stromal support and paracrine stimulation of new blood vessels (angiogenesis). Whereas little is known about human diabetic MSCs (dMSCs), particularly those from patients with PAD, dMSCs have a limited expansion capacity but can be improved with human platelet lysate (PL) supplementation. PL is rich in many growth factors, including epidermal growth factor (EGF), which is known to be important to cell proliferation and survival signaling pathways. We hypothesize that dMSCs have a reversible defect in EGF receptor pathways. The objective of this work was to test this hypothesis using dMSCs from PAD patients., Methods: The secretome expression of EGF and prominent angiogens was characterized from bone marrow (BM)-derived and adipose tissue-derived (ATD) dMSCs from five patients (six limbs) undergoing major amputation. Western blot was used to characterize the AKT and extracellular signal-regulated protein kinases 1 and 2 expression in dMSCs under standard culture (5% fetal bovine serum plus fibroblast growth factor 2 [FGF2]), 5% human PL, or 5% fetal bovine serum plus EGF. Healthy donor MSCs were control cells. The angiogenic activity of BM- and ATD-dMSCs was tested on human umbilical vein endothelial cells (ECs). Paired t-test, analysis of variance, and Kruskal-Wallis tests were used as appropriate., Results: Both BM- and ATD-dMSCs had typical MSC surface marker expression and similar expansion profiles, and they did not express EGF in their secretome. PL supplementation of dMSCs improved AKT signaling, but they were resistant to FGF2 activation of extracellular signal-regulated protein kinases 1 and 2. EGF supplementation led to similar AKT expression as with PL, but PL had greater phosphorylation of AKT at 30 and 60 minutes. The conditioned media from both BM- and ATD-dMSCs had robust levels of prominent angiogens (vascular endothelial growth factor, monocyte chemoattractant protein 1, hepatocyte growth factor), which stimulated EC proliferation and migration, and the co-culture of dMSCs with ECs led to significantly longer EC sprouts in three-dimensional gel than EC-alone pellets., Conclusions: PL and EGF supplementation improves AKT expression in dMSCs over that of FGF2, but PL improved pAKT over that of EGF. Thus, PL supplementation strategies may improve AKT signaling, which could be important to MSC survival in cellular therapies. Furthermore, BM- and ATD-dMSCs have similar secretomes and robust in vitro angiogenic activity, which supports pursuing dMSCs from both reservoirs in regenerative medicine strategies., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2018
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18. The small heat shock protein HSPB1 protects mice from sepsis.
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Breed ER, Hilliard CA, Yoseph B, Mittal R, Liang Z, Chen CW, Burd EM, Brewster LP, Hansen LM, Gleason RL Jr, Pandita TK, Ford ML, Hunt CR, and Coopersmith CM
- Subjects
- Animals, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Disease Models, Animal, Gene Knockout Techniques, Male, Mice, Mice, Inbred C57BL, Molecular Chaperones, Mortality, Peritoneum immunology, Sepsis genetics, Sepsis immunology, Heat-Shock Proteins genetics, Interferon-gamma metabolism, Interleukin-6 metabolism, Neoplasm Proteins genetics, Sepsis mortality
- Abstract
In vitro studies have implicated the small heat shock protein HSPB1 in a range of physiological functions. However, its in vivo relevance is unclear as the phenotype of unstressed HSPB1
-/- mice is unremarkable. To determine the impact of HSPB1 in injury, HSPB1-/- and wild type (WT) mice were subjected to cecal ligation and puncture, a model of polymicrobial sepsis. Ten-day mortality was significantly higher in HSPB1-/- mice following the onset of sepsis (65% vs. 35%). Ex vivo mechanical testing revealed that common carotid arteries from HSPB1-/- mice were more compliant than those in WT mice over pressures of 50-120 mm Hg. Septic HSPB1-/- mice also had increased peritoneal levels of IFN-γ and decreased systemic levels of IL-6 and KC. There were no differences in frequency of either splenic CD4+ or CD8+ T cells, nor were there differences in apoptosis in either cell type. However, splenic CD4+ T cells and CD8+ T cells from HSPB1-/- mice produced significantly less TNF and IL-2 following ex vivo stimulation. Systemic and local bacterial burden was similar in HSPB1-/- and WT mice. Thus while HSPB1-/- mice are uncompromised under basal conditions, HSPB1 has a critical function in vivo in sepsis, potentially mediated through alterations in arterial compliance and the immune response.- Published
- 2018
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19. Invited commentary.
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Brewster LP
- Published
- 2018
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20. Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease.
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Arya S, Khakharia A, Binney ZO, DeMartino RR, Brewster LP, Goodney PP, and Wilson PWF
- Subjects
- Aged, Comorbidity, Dose-Response Relationship, Drug, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Peripheral Arterial Disease complications, Peripheral Arterial Disease mortality, Platelet Aggregation Inhibitors therapeutic use, Propensity Score, Proportional Hazards Models, Risk Factors, Treatment Outcome, Amputation, Surgical statistics & numerical data, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Peripheral Arterial Disease drug therapy
- Abstract
Background: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality., Methods: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding., Results: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins ( P <0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses., Conclusions: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well., (© 2018 American Heart Association, Inc.)
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- 2018
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21. Human diabetic mesenchymal stem cells from peripheral arterial disease patients promote angiogenesis through unique secretome signatures.
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Morris AD, Dalal S, Li H, and Brewster LP
- Subjects
- Biomarkers metabolism, Case-Control Studies, Cell Movement, Cell Proliferation, Enzyme-Linked Immunosorbent Assay, Humans, Mesenchymal Stem Cell Transplantation, Diabetes Mellitus metabolism, Endothelial Cells physiology, Mesenchymal Stem Cells metabolism, Neovascularization, Physiologic physiology, Peripheral Arterial Disease metabolism
- Abstract
Background: Diabetic patients are at increased risk of complications from severe peripheral arterial disease. Mesenchymal stem cells (MSC) may be useful in limiting these complications. Our objective is to test the angiogenic potential of diabetic versus healthy MSCs., Methods: MSCs' angiogenic potential was tested by endothelial cell (EC) proliferation, migration, and 3-dimensional sprouting. Diabetic conditions were simulated with 5.5, 20, or 40 mM glucose. MSC secretome was quantified by enzyme-linked immunosorbent assay., Results: Human aortic ECs were most sensitive to glucose conditions and were used for all MSC experiments. Diabetic MSCs had greater 3-dimensional invasion than healthy MSCs (P<.05), but EC sprouting was decreased in high glucose conditions in both diabetic and healthy MSCs. Secretome analysis demonstrated that 20mM glucose stimulated epidermal growth factor (EGF) expression in diabetic and healthy MSCs, but that diabetic MSCs had a unique secretome with increased levels of chemokine (C-X-C motif) ligand 1 (CXCL-1), interleukin six (IL-6), and monocyte chemoattractant protein 1 (MCP-1) (P<.05)., Conclusion: Despite having similar in vitro angiogenic activity, diabetic MSCs secrete a unique and inflammatory angiogenic signature that may influence MSC survival and function after transplantation in cell therapy applications. Strategies that normalize secretome in diabetic patients may improve the utility of autologous MSCs in this population of patients., (Published by Elsevier Inc.)
- Published
- 2018
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22. Race and Socioeconomic Status Independently Affect Risk of Major Amputation in Peripheral Artery Disease.
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Arya S, Binney Z, Khakharia A, Brewster LP, Goodney P, Patzer R, Hockenberry J, and Wilson PWF
- Subjects
- Aged, Comorbidity, Data Warehousing, Diabetes Mellitus economics, Diabetes Mellitus ethnology, Female, Humans, Incidence, Male, Middle Aged, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease economics, Peripheral Arterial Disease ethnology, Prevalence, Renal Insufficiency, Chronic economics, Renal Insufficiency, Chronic ethnology, Retrospective Studies, Risk Assessment, Risk Factors, United States epidemiology, United States Department of Veterans Affairs, Black or African American, Amputation, Surgical economics, Healthcare Disparities economics, Healthcare Disparities ethnology, Income, Peripheral Arterial Disease surgery, Social Class, Veterans Health economics, Veterans Health ethnology, White People
- Abstract
Background: Black race has been shown to be a risk factor for amputation in peripheral artery disease (PAD); however, race has been argued to be a marker for socioeconomic status (SES) rather than true disparity. The aim of this study is to study the impact of race and SES on amputation risk in PAD patients., Methods and Results: Patients with incident PAD in the national Veterans Affairs Corporate Data Warehouse were identified from 2003 to 2014 (N=155 647). The exposures were race and SES (measured by median income in residential ZIP codes). The outcome was incident major amputation. Black veterans were significantly more likely to live in low-SES neighborhoods and to present with advanced PAD. Black patients had a higher amputation risk in each SES stratum compared with white patients. In Cox models (adjusting for covariates), black race was associated with a 37% higher amputation risk compared with white race (hazard ratio: 1.37; 95% confidence interval, 1.30-1.45), whereas low SES was independently predictive of increased risk of amputation (hazard ratio: 1.12; 95% confidence interval, 1.06-1.17) and showed no evidence of interaction with race. In predicted amputation risk analysis, black race and low SES continued to be significant risk factors for amputation regardless of PAD presentation., Conclusions: Black race significantly increases the risk of amputation within the same SES stratum compared with white race and has an independent effect on limb loss after controlling for comorbidities, severity of PAD at presentation, and use of medications., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)
- Published
- 2018
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23. High hemoglobin A 1c associated with increased adverse limb events in peripheral arterial disease patients undergoing revascularization.
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Arya S, Binney ZO, Khakharia A, Long CA, Brewster LP, Wilson PW, Jordan WD Jr, and Duwayri Y
- Subjects
- Aged, Blood Glucose drug effects, Comorbidity, Diabetes Mellitus drug therapy, Diabetes Mellitus epidemiology, Disease-Free Survival, Endovascular Procedures methods, Female, Follow-Up Studies, Humans, Hypoglycemic Agents therapeutic use, Ischemia blood, Ischemia mortality, Ischemia surgery, Kaplan-Meier Estimate, Limb Salvage adverse effects, Lower Extremity surgery, Male, Middle Aged, Perioperative Care methods, Peripheral Arterial Disease epidemiology, Peripheral Arterial Disease surgery, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Amputation, Surgical statistics & numerical data, Diabetes Mellitus blood, Endovascular Procedures adverse effects, Glycated Hemoglobin analysis, Limb Salvage methods, Lower Extremity blood supply, Peripheral Arterial Disease blood
- Abstract
Objective: Diabetes and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has not been studied. We examined the effects of poor glycemic control (high hemoglobin A
1c level) on the risk of amputation and modified major adverse limb events (mMALEs) after lower extremity revascularization., Methods: Patients undergoing PAD revascularization who had hemoglobin A1c (HbA1c ) levels available within 6 months were identified in the Veterans Affairs database of 2003 to 2014 (N = 26,799). The diagnosis of preoperative diabetes mellitus (PreopDM) was defined using diabetes diagnosis codes and evidence of treatment. Amputation and mMALE risk was compared for HbA1c levels using Kaplan-Meier analysis. Cox proportional hazards models were created to assess the effect of high HbA1c levels on amputation and mMALE (adjusted for age, gender, race, socioeconomic status, comorbidities, cholesterol levels, creatinine concentration, suprainguinal or infrainguinal procedure, open or endovascular procedure, severity of PAD, year of cohort entry, and medications) for all patients and stratified by PreopDM., Results: High HbA1c levels were present in 33.2% of the cohort, whereas 59.9% had PreopDM. Amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had mMALE. Kaplan-Meier curves showed the worst outcomes in patient with PreopDM and high HbA1c levels. In the Cox model, incremental HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8% were associated with 26% (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.39), 53% (HR, 1.53; 95% CI, 1.37-1.7), and 105% (HR, 2.05; 95% CI, 1.87-2.26) higher risk of amputation, respectively. Similarly, the risk of mMALE also increased by 5% (HR, 1.05; 95% CI, 0.99-1.11), 21% (HR, 1.21; 95% CI, 1.13-1.29), and 33% (HR, 1.33, 95% CI, 1.25-1.42) with worsening HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8%, respectively (vs HbA1c ≤6.0%). In stratified analysis by established PreopDM, the relative risk of amputation or mMALE was much higher with poor glycemic control (HbA1c >7.0%) in patients without PreopDM., Conclusions: PAD patients with worse perioperative glycemic control have a significantly higher risk of amputation and mMALE. Incremental increases in HbA1c levels are associated with higher hazards of adverse limb outcomes independent of PreopDM status. Poor glycemic control (HbA1c >7.0%) in patients without a PreopDM diagnosis carries twice the relative risk of amputation and mMALE than in those with good glycemic control. These results suggest that screening of diabetic status and better management of glycemic control could be a target for improvement of perioperative and long-term outcomes in PAD patients., (Published by Elsevier Inc.)- Published
- 2018
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24. Disturbed Flow Promotes Arterial Stiffening Through Thrombospondin-1.
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Kim CW, Pokutta-Paskaleva A, Kumar S, Timmins LH, Morris AD, Kang DW, Dalal S, Chadid T, Kuo KM, Raykin J, Li H, Yanagisawa H, Gleason RL Jr, Jo H, and Brewster LP
- Subjects
- Aging, Animals, Atrial Remodeling, Carotid Arteries metabolism, Carotid Arteries physiopathology, Cell Line, Collagen genetics, Collagen metabolism, Disease Models, Animal, Down-Regulation, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Female, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, RNA, Ribosomal, 18S metabolism, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta genetics, Receptors, Transforming Growth Factor beta metabolism, Shear Strength, Thrombospondin 1 deficiency, Thrombospondin 1 genetics, Transforming Growth Factor beta metabolism, Thrombospondin 1 metabolism, Vascular Stiffness physiology
- Abstract
Background: Arterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial stiffness is not well understood. The objective of this study was to define the role of d-flow on arterial stiffening and discover the relevant signaling pathways by which d-flow stiffens arteries., Methods: D-flow was induced in the carotid arteries of young and old mice of both sexes. Arterial stiffness was quantified ex vivo with cylindrical biaxial mechanical testing and in vivo from duplex ultrasound and compared with unmanipulated carotid arteries from 80-week-old mice. Gene expression and pathway analysis was performed on endothelial cell-enriched RNA and validated by immunohistochemistry. In vitro testing of signaling pathways was performed under oscillatory and laminar wall shear stress conditions. Human arteries from regions of d-flow and stable flow were tested ex vivo to validate critical results from the animal model., Results: D-flow induced arterial stiffening through collagen deposition after partial carotid ligation, and the degree of stiffening was similar to that of unmanipulated carotid arteries from 80-week-old mice. Intimal gene pathway analyses identified transforming growth factor-β pathways as having a prominent role in this stiffened arterial response, but this was attributable to thrombospondin-1 (TSP-1) stimulation of profibrotic genes and not changes to transforming growth factor-β. In vitro and in vivo testing under d-flow conditions identified a possible role for TSP-1 activation of transforming growth factor-β in the upregulation of these genes. TSP-1 knockout animals had significantly less arterial stiffening in response to d-flow than wild-type carotid arteries. Human arteries exposed to d-flow had similar increases TSP-1 and collagen gene expression as seen in our model., Conclusions: TSP-1 has a critical role in shear-mediated arterial stiffening that is mediated in part through TSP-1's activation of the profibrotic signaling pathways of transforming growth factor-β. Molecular targets in this pathway may lead to novel therapies to limit arterial stiffening and the progression of disease in arteries exposed to d-flow., (© 2017 American Heart Association, Inc.)
- Published
- 2017
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25. An endovascular model of ischemic myopathy from peripheral arterial disease.
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Long CA, Timmins LH, Koutakis P, Goodchild TT, Lefer DJ, Pipinos II, Casale GP, and Brewster LP
- Subjects
- Angiography, Animals, Blood Flow Velocity, Constriction, Pathologic, Disease Models, Animal, Female, Femoral Artery diagnostic imaging, Femoral Artery pathology, Gait, Hindlimb, Humans, Iliac Artery diagnostic imaging, Iliac Artery pathology, Ischemia diagnostic imaging, Ischemia pathology, Ischemia physiopathology, Muscle, Skeletal pathology, Muscle, Skeletal physiopathology, Peripheral Arterial Disease diagnostic imaging, Peripheral Arterial Disease pathology, Peripheral Arterial Disease physiopathology, Regional Blood Flow, Severity of Illness Index, Stents, Sus scrofa, Time Factors, Ultrasonography, Doppler, Duplex, Vascular Remodeling, Endovascular Procedures instrumentation, Femoral Artery physiopathology, Hemodynamics, Iliac Artery physiopathology, Ischemia etiology, Muscle, Skeletal blood supply, Peripheral Arterial Disease etiology
- Abstract
Objective: Peripheral arterial disease (PAD) is a significant age-related medical condition with limited pharmacologic options. Severe PAD, termed critical limb ischemia, can lead to amputation. Skeletal muscle is the end organ most affected by PAD, leading to ischemic myopathy and debility of the patient. Currently, there are not any therapeutics to treat ischemic myopathy, and proposed biologic agents have not been optimized owing to a lack of preclinical models of PAD. Because a large animal model of ischemic myopathy may be useful in defining the optimal dosing and delivery regimens, the objective was to create and to characterize a swine model of ischemic myopathy that mimics patients with severe PAD., Methods: Yorkshire swine (N = 8) underwent acute right hindlimb ischemia by endovascular occlusion of the external iliac artery. The effect of ischemia on limb function, perfusion, and degree of ischemic myopathy was quantified by weekly gait analysis, arteriography, hindlimb blood pressures, femoral artery duplex ultrasound scans, and histologic examination. Animals were terminated at 5 (n = 5) and 6 (n = 3) weeks postoperatively. Ossabaw swine (N = 8) fed a high-fat diet were used as a model of metabolic syndrome for comparison of arteriogenic recovery and validation of ischemic myopathy., Results: There was persistent ischemia in the right hindlimb, and occlusion pressures were significantly depressed compared with the untreated left hindlimb out to 6 weeks (systolic blood pressure, 31 ± 21 vs 83 ± 15 mm Hg, respectively; P = .0007). The blood pressure reduction resulted in a significant increase of ischemic myopathy in the gastrocnemius muscle in the treated limb. Gait analysis revealed a functional deficit of the right hindlimb immediately after occlusion that improved rapidly during the first 2 weeks. Peak systolic velocity values in the right common femoral artery were severely diminished throughout the entire study (P < .001), and the hemodynamic environment after occlusion was characterized by low and oscillatory wall shear stress. Finally, the internal iliac artery on the side of the ischemic limb underwent significant arteriogenic remodeling (1.8× baseline) in the Yorkshire but not in the Ossabaw swine model., Conclusions: This model uses endovascular technology to produce the first durable large animal model of ischemic myopathy. Acutely (first 2 weeks), this model is associated with impaired gait but no tissue loss. Chronically (2-6 weeks), this model delivers persistent ischemia, resulting in ischemic myopathy similar to that seen in PAD patients. This model may be of use for testing novel therapeutics including biologic therapies for promoting neovascularization and arteriogenesis., (Published by Elsevier Inc.)
- Published
- 2017
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26. Longer Patient Travel Times Associated with Decreased Follow-Up after Endovascular Aortic Aneurysm Repair (EVAR).
- Author
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Morris AD, Preiss JE, Ogbuchi S, Arya S, Duwayri Y, Dodson TF, Jordan WD, and Brewster LP
- Subjects
- Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Abdominal mortality, Blood Vessel Prosthesis Implantation mortality, Cohort Studies, Continuity of Patient Care, Female, Follow-Up Studies, Hospitals, University, Humans, Male, Prognosis, Retrospective Studies, Risk Assessment, Survival Rate, Time Factors, Aortic Aneurysm, Abdominal surgery, Blood Vessel Prosthesis Implantation methods, Endovascular Procedures methods, Patient Compliance statistics & numerical data, Transportation of Patients trends
- Published
- 2017
27. Promoting Limb Salvage through Multi-Disciplinary Care of the Diabetic Patient.
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Salvo NL, Walsh MD, and Brewster LP
- Abstract
Opinion Statement: Despite an explosion in the number of options available for helping diabetic patients heal wounds, major amputation remains a critical issue for these persons. Since diabetes prematurely ages tissues and no organ system is immune to its presence, it makes inherent sense that multi-disciplinary team approaches to these patients is necessary to make significant strides forward. Here, we present literature from the fields of podiatric surgery/medicine, vascular and plastic surgery and introduce the successes that a multi-disciplinary limb salvage center can have on the lives and limbs of patients with diabetes.
- Published
- 2017
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28. Advances, Pauses, and Future Opportunity for the Prevention of Venous Thromboembolism in the Trauma Population.
- Author
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Ramos CR and Brewster LP
- Subjects
- Humans, Risk Factors, Venous Thromboembolism
- Published
- 2017
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29. A Novel Approach to Assess the In Situ Versus Ex Vivo Mechanical Behaviors of the Coronary Artery.
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Wang R, Raykin J, Brewster LP, and Gleason RL Jr
- Subjects
- Animals, Blood Flow Velocity physiology, Blood Pressure physiology, Computer Simulation, Coronary Vessels anatomy & histology, Elastic Modulus physiology, Materials Testing instrumentation, Reproducibility of Results, Sensitivity and Specificity, Swine, Tensile Strength physiology, Vascular Resistance physiology, Coronary Vessels diagnostic imaging, Coronary Vessels physiology, Image Interpretation, Computer-Assisted methods, Materials Testing methods, Models, Cardiovascular, Ultrasonography, Interventional methods
- Abstract
Ex vivo mechanical testing has provided tremendous insight toward prediction of the in vivo mechanical behavior and local mechanical environment of the arterial wall; however, the role of perivascular support on the local mechanical behavior of arteries is not well understood. Here, we present a novel approach for quantifying the impact of the perivascular support on arterial mechanics using intravascular ultrasound (IVUS) on cadaveric porcine hearts. We performed pressure-diameter tests (n = 5) on the left anterior descending coronary arteries (LADCAs) in situ while embedded in their native perivascular environment using IVUS imaging and after removal of the perivascular support of the artery. We then performed standard cylindrical biaxial testing on these vessels ex vivo and compared the results. Removal of the perivascular support resulted in an upward shift of the pressure-diameter curve. Ex vivo testing, however, showed significantly lower circumferential compliance compared to the in situ configuration. On a second set of arteries, local axial stretch ratios were quantified (n = 5) along the length of the arteries. The average in situ axial stretch ratio was 1.28 ± 0.16; however, local axial stretch ratios showed significant variability, ranging from 1.01 to 1.70. Taken together, the data suggest that both the perivascular loading and the axial tethering have an important role in arterial mechanics. Combining nondestructive testing using IVUS with traditional ex vivo cylindrical biaxial testing yields a more comprehensive assessment of the mechanical behavior of arteries.
- Published
- 2017
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30. The Readmission Event after Vascular Surgery: Causes and Costs.
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Duwayri Y, Goss J, Knechtle W, Veeraswamy RK, Arya S, Rajani RR, Brewster LP, Dodson TF, and Sweeney JF
- Subjects
- Angioplasty adverse effects, Angioplasty economics, Aortic Aneurysm, Abdominal economics, Aortic Aneurysm, Abdominal surgery, Blood Vessel Prosthesis economics, Blood Vessel Prosthesis Implantation adverse effects, Blood Vessel Prosthesis Implantation economics, Carotid Artery Diseases economics, Carotid Artery Diseases surgery, Chi-Square Distribution, Costs and Cost Analysis, Endarterectomy, Carotid adverse effects, Endarterectomy, Carotid economics, Endovascular Procedures instrumentation, Georgia, Humans, Length of Stay economics, Postoperative Complications therapy, Retrospective Studies, Risk Factors, Stents economics, Time Factors, Treatment Outcome, Vascular Surgical Procedures instrumentation, Endovascular Procedures adverse effects, Endovascular Procedures economics, Hospital Costs, Patient Readmission economics, Postoperative Complications economics, Postoperative Complications etiology, Vascular Surgical Procedures adverse effects, Vascular Surgical Procedures economics
- Abstract
Background: The study evaluates the readmission diagnoses after vascular surgical interventions and the associated hospital costs., Methods: Patients readmitted after undergoing carotid artery stenting (CAS), carotid endarterectomy (CEA), infrarenal endovascular abdominal aortic aneurysm repair (EVAR), open abdominal aortic aneurysm repair (OAAA), suprainguinal revascularization (SUPRA), or infrainguinal revascularization (INFRA) between January 1, 2008 and October 20, 2013 at a single academic institution were retrospectively identified. Demographic, preoperative, and postoperative event variables were obtained by chart review. The diagnoses and the costs of the readmission event were obtained by chart review and from hospital financial data. Readmission indications were grouped as unrelated or planned readmissions, procedure-specific complications, wound complications, cardiac causes, and other. Univariate analyses of categorical variables were performed with χ
2 or Fisher exact test where appropriate. Continuous variables were analyzed using the Wilcoxon rank-sum test., Results: A total of 1,170 patient records were identified. Thirty-day readmission occurred in 112 patients (9.6%). The readmission rate was significantly different between groups: 4.5% in CAS (n = 8/177), 8.5% in CEA (21/246), 5.8% in EVAR (18/312), 11.4% in OAAA (4/35), 15.6% in INFRA (33/212), 13.5% in SUPRA (24/178), and 40% in combined SUPRA and INFRA (4/10) (P < 0.0001). Readmissions were unrelated or planned in 19.6% of patients. Wound complications were the most common readmission diagnoses (36.6%, 41/112).There was a difference in the distribution of readmission indications among procedure groups, with wound complications being predominant in INFRA and SUPRA groups (60.6% and 58.3%, respectively), and cardiac events predominantly in EVAR patients (42%) (P < 0.001). In univariable analysis of predictors of readmission, significant preoperative factors were chronic obstructive pulmonary disease, renal insufficiency, and lower hematocrit. Significant postoperative predictors included any postoperative complication, number of complications, increased length of stay, wound complications, postoperative infections, blood transfusion, and reoperation. The median hospital cost for readmission for wound complications was 29,723 USD (interquartile range 23,841-36,878), and for cardiac complications was 39,784 USD (26,305-46,918). The median cost of readmission for bypass graft occlusion was 33,366 USD (20,530-43,170). The median length of stay also differed depending on the readmission diagnosis and was highest for bypass graft occlusion (8.5 days)., Conclusions: Readmissions after vascular procedures are associated with high cost and hospital bed utilization. Wound complications continue to be the dominant readmission etiology. The characterization of these costs and risk factors in this study can allow for resource allocation to minimize preventable related readmissions. A significant proportion of readmissions after vascular interventions are planned or unrelated, which should be taken into consideration in metric benchmarking and performance comparisons., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2016
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31. Preoperative Frailty Increases Risk of Nonhome Discharge after Elective Vascular Surgery in Home-Dwelling Patients.
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Arya S, Long CA, Brahmbhatt R, Shafii S, Brewster LP, Veeraswamy R, Johnson TM 2nd, and Johanning JM
- Subjects
- Age Factors, Aged, Aged, 80 and over, Canada, Chi-Square Distribution, Databases, Factual, Elective Surgical Procedures, Female, Geriatric Assessment, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Patient Transfer, Postoperative Complications diagnosis, Postoperative Complications etiology, Rehabilitation Centers, Retrospective Studies, Risk Factors, Skilled Nursing Facilities, Treatment Outcome, United States, Vascular Diseases diagnosis, Aging, Frail Elderly, Independent Living, Patient Discharge, Postoperative Complications therapy, Vascular Diseases surgery, Vascular Surgical Procedures adverse effects
- Abstract
Background: Patient-centered quality outcomes such as disposition after surgery are increasingly being scrutinized. Preoperative factors predictive of nonhome discharge (DC) may identify at-risk patients for targeted interventions. This study examines the association among preoperative risk factors, frailty, and nonhome DC after elective vascular surgery procedures in patients living at home., Methods: The 2011-2012 National Surgical Quality Improvement Project database was queried to identify all home-dwelling patients who underwent elective vascular procedures (endovascular and open aortic aneurysm repair, suprainguinal and infrainguinal bypasses, peripheral endovascular interventions, carotid endarterectomy, and stent). Preoperative frailty was measured using the modified frailty index (mFI; derived from Canadian Study of Health and Aging). Univariate and multivariate logistic regression analysis was performed to examine the association of frailty and nonhome DC., Results: Of 15,843 home-dwelling patients, 1,177 patients (7.4%) did not return home postoperatively. Frailty (mFI > 0.25) conferred a significantly increased 2-fold risk of nonhome DC disposition for each procedure type. Frailty, female gender, open procedures, increasing age, end-stage renal disease, and occurrence of any postoperative complication were associated with increased risk of nonhome DC. On multivariate logistic regression analysis, frailty increased the odds of nonhome DC by 60% (odds ratio 1.6, 95% confidence interval 1.4-1.8) after adjusting for other covariates. In the presence of complications, the risk of nonhome DC was 27.5% in frail versus 16.5% in nonfrail patients (P < 0.001). In the absence of complications, although absolute risk was lower, frail patients were nearly twice as likely to not return home (frail 5.5% vs. nonfrail 2.75%, P < 0.001)., Conclusions: Frail home-dwelling patients undergoing elective vascular procedures are at high risk of not returning home after surgery. Preoperative frailty assessment appears to hold potential for counseling regarding postsurgery disposition and DC planning., (Published by Elsevier Inc.)
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- 2016
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32. Women undergoing aortic surgery are at higher risk for unplanned readmissions compared with men especially when discharged home.
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Flink BJ, Long CA, Duwayri Y, Brewster LP, Veeraswamy R, Gallagher K, and Arya S
- Subjects
- Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Thoracic diagnostic imaging, Chi-Square Distribution, Databases, Factual, Female, Humans, Length of Stay, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Postoperative Complications diagnosis, Postoperative Complications etiology, Retrospective Studies, Risk Factors, Sex Factors, Time Factors, Treatment Outcome, United States, Aortic Aneurysm, Abdominal surgery, Aortic Aneurysm, Thoracic surgery, Health Status Disparities, Healthcare Disparities, Patient Discharge, Patient Readmission, Postoperative Complications therapy, Vascular Surgical Procedures adverse effects
- Abstract
Objective: Women undergoing vascular surgery have higher morbidity and mortality. Our study explores gender-based differences in patient-centered outcomes such as readmission, length of stay (LOS), and discharge destination (home vs nonhome facility) in aortic aneurysm surgery., Methods: Patients were identified from the American College of Surgeons National Surgical Quality Improvement Project database (2011-2013) undergoing abdominal, thoracic, and thoracoabdominal aortic aneurysms (N = 17,763), who were discharged and survived their index hospitalization. The primary outcome was unplanned readmission, and secondary outcomes were discharge to a nonhome facility, LOS, and reasons for unplanned readmission. Univariate, multivariate, and stratified analyses based on gender and discharge destination were used., Results: Overall, 1541 patients (8.7%) experienced an unplanned readmission, with a significantly higher risk in women vs men (10.8% vs 8%; P < .001) overall (Procedure subtypes: abdominal aortic aneurysm [10.1% vs 7.7%; P < .001], thoracic aortic aneurysm [14.1% vs 13.5%; P = .8], and thoracoabdominal aortic aneurysm [14.8% vs 10%; P = .051]). The higher odds of readmission in women compared with men persisted in multivariate analysis after controlling for covariates (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05-1.4). Similarly, the rate of discharge to a nonhome facility was nearly double in women compared with men (20.6% vs 10.7%; P < .001), but discharge to a nonhome facility was not a significant predictor of unplanned readmission. Upon stratification by discharge destination, the higher odds of readmissions in women compared with men occurred in patients who were discharged home (OR, 1.2; 95% CI, 1.02-1.4) but not in those who were discharged to a nonhome facility (OR, 1.06; 95% CI, 0.8-1.4). Significant differences in LOS were seen in patients who were discharged home. No gender differences were found in reasons for readmission with the three most common reasons being thromboembolic events, wound infections, and pneumonia., Conclusions: Gender disparity exists in the risk of unplanned readmission among aortic aneurysm surgery patients. Women who were discharged home have a higher likelihood of unplanned readmission despite longer LOS than men. These data suggest that further study into the discharge planning processes, social factors, and use of rehabilitation services is needed for women undergoing aortic procedures to decrease readmissions., (Published by Elsevier Inc.)
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- 2016
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33. A novel platelet lysate hydrogel for endothelial cell and mesenchymal stem cell-directed neovascularization.
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Robinson ST, Douglas AM, Chadid T, Kuo K, Rajabalan A, Li H, Copland IB, Barker TH, Galipeau J, and Brewster LP
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- Animals, Cells, Immobilized metabolism, Cells, Immobilized transplantation, Coculture Techniques, Disease Models, Animal, Endothelial Cells transplantation, Female, Heterografts, Hindlimb blood supply, Hindlimb metabolism, Humans, Ischemia therapy, Male, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Mice, Inbred NOD, Mice, SCID, Blood Platelets chemistry, Endothelial Cells metabolism, Hydrogels chemistry, Neovascularization, Physiologic
- Abstract
Unlabelled: Mesenchymal stem cells (MSC) hold promise in promoting vascular regeneration of ischemic tissue in conditions like critical limb ischemia of the leg. However, this approach has been limited in part by poor cell retention and survival after delivery. New biomaterials offer an opportunity to localize cells to the desired tissue after delivery, but also to improve cell survival after delivery. Here we characterize the mechanical and microstructural properties of a novel hydrogel composed of pooled human platelet lysate (PL) and test its ability to promote MSC angiogenic activity using clinically relevant in vitro and in vivo models. This PL hydrogel had comparable storage and loss modulus and behaved as a viscoelastic solid similar to fibrin hydrogels despite having 1/4-1/10th the fibrin content of standard fibrin gels. Additionally, PL hydrogels enabled sustained release of endogenous PDGF-BB for up to 20days and were resistant to protease degradation. PL hydrogel stimulated pro-angiogenic activity by promoting human MSC growth and invasion in a 3D environment, and enhancing endothelial cell sprouting alone and in co-culture with MSCs. When delivered in vivo, the combination of PL and human MSCs improved local tissue perfusion after 8days compared to controls when assessed with laser Doppler perfusion imaging in a murine model of hind limb ischemia. These results support the use of a PL hydrogel as a scaffold for MSC delivery to promote vascular regeneration., Statement of Significance: Innovative strategies for improved retention and viability of mesenchymal stem cells (MSCs) are needed for cellular therapies. Human platelet lysate is a potent serum supplement that improves the expansion of MSCs. Here we characterize our novel PL hydrogel's desirable structural and biologic properties for human MSCs and endothelial cells. PL hydrogel can localize cells for retention in the desired tissue, improves cell viability, and augments MSCs' angiogenic activity. As a result of these unique traits, PL hydrogel is ideally suited to serve as a cell delivery vehicle for MSCs injected into ischemic tissues to promote vascular regeneration, as demonstrated here in a murine model of hindlimb ischemia., (Published by Elsevier Ltd.)
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- 2016
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34. Gender and frailty predict poor outcomes in infrainguinal vascular surgery.
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Brahmbhatt R, Brewster LP, Shafii S, Rajani RR, Veeraswamy R, Salam A, Dodson TF, and Arya S
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- Aged, Aged, 80 and over, Canada epidemiology, Female, Humans, Lower Extremity surgery, Male, Middle Aged, Retrospective Studies, Sex Factors, United States epidemiology, Frail Elderly statistics & numerical data, Lower Extremity blood supply, Postoperative Complications epidemiology, Vascular Surgical Procedures mortality
- Abstract
Background: Women have poorer outcomes after vascular surgery as compared to men as shown by studies recently. Frailty is also an independent risk factor for postoperative morbidity and mortality. This study examines the interplay of gender and frailty on outcomes after infrainguinal vascular procedures., Materials and Methods: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent infrainguinal vascular procedures from 2005-2012. Frailty was measured using a modified frailty index (mFI; derived from the Canadian Study of Health and Aging). Univariate and multivariate analysis were performed to investigate the association of preoperative frailty and gender, on postoperative outcomes., Results: Of 24,645 patients (92% open, 8% endovascular), there were 533 deaths (2.2%) and 6198 (25.1%) major complications within 30 d postoperatively. Women were more frail (mean mFI = 0.269) than men (mean mFI = 0.259; P < 0.001). Women and frail patients (mFI>0.25) were more likely to have a major morbidity (P < 0.001) or mortality (P < 0.001) with the highest risk in frail women. On multivariate logistic regression analysis, female gender and increasing mFI were independently significantly associated with mortality (P < 0.05) as well as major complications. The interaction of gender and frailty in multivariate analysis showed the highest adjusted 30-d mortality and morbidity in frail females at 2.8% and 30.1%, respectively and that was significantly higher (P < 0.001) than nonfrail males, nonfrail females and frail males., Conclusions: Female gender and frailty are both associated with increased risk of complications and death following infrainguinal vascular procedures with the highest risk in frail females. Further studies are needed to explore the mechanisms of interaction of gender and frailty and its effect on long-term outcomes for peripheral vascular disease., (Published by Elsevier Inc.)
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- 2016
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35. Posttraumatic Resuscitation Affects Stent Graft Sizing in Patients with Blunt Thoracic Aortic Injury.
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Hoffman JR, Chowdhury R, Johnson LS, Brewster LP, Duwayri Y, Reeves JG, Veeraswamy RK, Dodson TF, and Rajani RR
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- Adult, Aorta, Thoracic injuries, Aortography methods, Blood Vessel Prosthesis Implantation methods, Cardiopulmonary Resuscitation adverse effects, Cohort Studies, Endovascular Procedures methods, Female, Hospital Mortality, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Assessment, Survival Analysis, Thoracic Injuries diagnostic imaging, Thoracic Injuries mortality, Tomography, X-Ray Computed methods, Trauma Centers, Treatment Outcome, Wounds, Nonpenetrating diagnostic imaging, Wounds, Nonpenetrating mortality, Aorta, Thoracic diagnostic imaging, Cardiopulmonary Resuscitation methods, Stents, Thoracic Injuries surgery, Wounds, Nonpenetrating surgery
- Abstract
Patients with blunt aortic injury often present to the emergency department in a relatively hypovolemic state. These patients undergo extensive inhospital resuscitation. The effect of posttraumatic resuscitation on aortic diameter has implications for stent graft sizing. The potential utility of repeat aortic imaging after resuscitation remains unclear. A retrospective chart review of all adult patients presenting to a Level I trauma center between the years 2007 and 2013 was performed. Fifty-three patients were identified with a diagnosis of traumatic aortic injury. Of those, 10 had 2 CT scans before aortic repair and were selected as the study population for analysis. After resuscitation, there was a significant increase in aortic diameter both proximal and distal to the aortic injury: proximal aortic diameter increase of 1.97 mm and distal aortic diameter increase of 1.48 mm. This retrospective study shows that after resuscitation, there is a significant increase in proximal and distal aortic diameter. Interval reimaging of the thoracic aorta may be beneficial after adequate stabilization of the patient's other injuries. In certain cases, more appropriate sizing may prevent a device-related complication.
- Published
- 2016
36. Late mortality in females after endovascular aneurysm repair.
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Preiss JE, Arya S, Duwayri Y, Shafii SM, Veeraswamy RK, Rajani RR, Dodson TF, and Brewster LP
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- Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal mortality, Female, Georgia epidemiology, Humans, Reoperation statistics & numerical data, Retrospective Studies, Aortic Aneurysm, Abdominal surgery, Endovascular Procedures mortality
- Abstract
Background: Abdominal aortic aneurysm (AAA) rupture is an adverse arterial remodeling event with high mortality risk. Because females have increased rupture risk with smaller AAAs (<5.5 cm), many recommend elective repair before the AAA reaches 5.5 cm. Elective repair improves survival for large AAAs, but long-term benefits of endovascular aneurysm repair (EVAR) for small AAAs in females remain less understood. The objective of this study was to identify if differences in late mortality exist between females undergoing elective EVAR at our institution for small and/or slow-growing AAAs compared with those who meet standard criteria., Methods: We retrospectively analyzed all patients that underwent EVAR for infrarenal AAA from June, 2009-June, 2013. We excluded patients that were male, treated emergently or for iliac artery aneurysm, and that received renal and/or mesenteric artery stenting. Patients did not meet anatomic criteria if preoperative AAA diameter was <5.5 cm or enlarged <0.5 cm over 6 mo. Late mortality was assessed from the social security death index., Results: Thirty-six of 162 elective EVAR patients (22.2%) were female (mean follow-up, 37.2 mo). Twenty patients (55.6%) met AAA size and/or growth criteria, whereas 16 (44.4%) did not meet criteria. Despite comparable demographics, comorbidities, and complications, patients that did not meet criteria had higher late mortality (37.5% versus 5%; P = 0.03) with a trend toward increased reoperation rate (25% versus. 5%; P = 0.48). Meeting size and/or growth criteria decreased odds of late death (odds ratio, 0.09; 95% confidence intervals, 0.01-0.83)., Conclusions: There is increased late mortality in females receiving elective EVAR at our institution for small and/or slow-growing AAAs. This late mortality may limit the benefits of EVAR for this population., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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37. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease.
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Bradley JM, Islam KN, Polhemus DJ, Donnarumma E, Brewster LP, Tao YX, Goodchild TT, and Lefer DJ
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- Animals, Coronary Vessels metabolism, Coronary Vessels physiopathology, Delayed-Action Preparations, Disease Models, Animal, Dose-Response Relationship, Drug, Dyslipidemias drug therapy, Dyslipidemias metabolism, Dyslipidemias physiopathology, Female, Heart Diseases metabolism, Heart Diseases physiopathology, Male, Metabolic Syndrome metabolism, Metabolic Syndrome physiopathology, Nitric Oxide Synthase Type III metabolism, Obesity drug therapy, Obesity metabolism, Obesity physiopathology, Oxidation-Reduction, Peripheral Vascular Diseases metabolism, Peripheral Vascular Diseases physiopathology, Severity of Illness Index, Swine, Coronary Vessels drug effects, Heart Diseases prevention & control, Metabolic Syndrome drug therapy, Myocardium metabolism, Oxidative Stress drug effects, Peripheral Vascular Diseases drug therapy, Sodium Nitrite pharmacology, Vasodilation drug effects
- Abstract
Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.
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- 2015
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38. Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome.
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Polhemus DJ, Bradley JM, Islam KN, Brewster LP, Calvert JW, Tao YX, Chang CC, Pipinos II, Goodchild TT, and Lefer DJ
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- Animals, Delayed-Action Preparations, Disease Models, Animal, Hindlimb blood supply, Hindlimb drug effects, Muscle, Skeletal blood supply, Muscle, Skeletal metabolism, Nitrates metabolism, Nitrites metabolism, S-Nitrosothiols metabolism, Swine, Angiogenesis Inducing Agents pharmacology, Iliac Artery surgery, Ischemia, Metabolic Syndrome, Muscle, Skeletal drug effects, Neovascularization, Physiologic drug effects, Peripheral Arterial Disease, Sodium Nitrite pharmacology
- Abstract
Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine (n = 18) by unilateral external iliac artery deployment of a full cross-sectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post-CLI day 14, pigs were randomized to placebo (n = 9) or SR-nitrite (80 mg, n = 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease.
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- 2015
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39. Hydrogen Sulfide Levels and Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI).
- Author
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Islam KN, Polhemus DJ, Donnarumma E, Brewster LP, and Lefer DJ
- Subjects
- Aged, Biomarkers analysis, Cystathionine beta-Synthase genetics, Cystathionine beta-Synthase metabolism, Cystathionine gamma-Lyase genetics, Cystathionine gamma-Lyase metabolism, Female, Glutathione Peroxidase metabolism, Humans, Leg surgery, Male, Oxidative Stress genetics, RNA, Messenger, Signal Transduction genetics, Sulfides analysis, Sulfurtransferases genetics, Sulfurtransferases metabolism, Superoxide Dismutase metabolism, Amputation, Surgical, Hydrogen Sulfide analysis, Ischemia surgery, Leg blood supply, Muscle, Skeletal metabolism, NF-E2-Related Factor 2 metabolism
- Abstract
Background: Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen sulfide (H2S). Functions of H2S are mediated by several targets including ion channels and signaling proteins. Nuclear factor-erythroid 2-related factor 2 is responsible for the expression of antioxidant response element-regulated genes and is known to be upregulated by H2S. We examined the levels of H2S, H2S-producing enzymes, and nuclear factor-erythroid 2-related factor 2 activation status in skeletal muscle obtained from critical limb ischemia (CLI) patients., Methods and Results: Gastrocnemius tissues were attained postamputation from human CLI and healthy control patients. We found mRNA and protein levels of cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase were significantly decreased in skeletal muscle of CLI patients as compared to control. H2S and sulfane sulfur levels were significantly decreased in skeletal muscle of CLI patients. We also observed significant reductions in nuclear factor-erythroid 2-related factor 2 activation as well as antioxidant proteins, such as Cu, Zn-superoxide dismutase, catalase, and glutathione peroxidase in skeletal muscle of CLI patients. Biomarkers of oxidative stress, such as malondialdehyde and protein carbonyl formation, were significantly increased in skeletal muscle of CLI patients as compared to healthy controls., Conclusions: The data demonstrate that H2S bioavailability and nuclear factor-erythroid 2-related factor 2 activation are both attenuated in CLI tissues concomitant with significantly increased oxidative stress. Reductions in the activity of H2S-producing enzymes may contribute to the pathogenesis of CLI., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
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- 2015
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40. Frailty increases the risk of 30-day mortality, morbidity, and failure to rescue after elective abdominal aortic aneurysm repair independent of age and comorbidities.
- Author
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Arya S, Kim SI, Duwayri Y, Brewster LP, Veeraswamy R, Salam A, and Dodson TF
- Subjects
- Age Factors, Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal diagnosis, Aortic Aneurysm, Abdominal mortality, Canada epidemiology, Chi-Square Distribution, Comorbidity, Databases, Factual, Elective Surgical Procedures, Female, Health Status Indicators, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Postoperative Complications diagnosis, Postoperative Complications mortality, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, United States epidemiology, Vascular Surgical Procedures mortality, Aortic Aneurysm, Abdominal surgery, Health Status, Postoperative Complications etiology, Vascular Surgical Procedures adverse effects
- Abstract
Background: Frailty, defined as a biologic syndrome of decreased reserve and resistance to stressors, has been linked to adverse outcomes after surgery. We evaluated the effect of frailty on 30-day mortality, morbidity, and failure to rescue (FTR) in patients undergoing elective abdominal aortic aneurysm (AAA) repair., Methods: Patients undergoing elective endovascular AAA repair (EVAR) or open AAA repair (OAR) were identified in the National Surgical Quality Improvement Program database for the years 2005 to 2012. Frailty was assessed using the modified frailty index (mFI) derived from the Canadian Study of Health and Aging (CSHA). The primary outcome was 30-day mortality, and secondary outcomes included 30-day morbidity and FTR. The effect of frailty on outcomes was assessed by multivariate regression analysis, adjusted for age, American Society of Anesthesiology (ASA) class, and significant comorbidities., Results: Of 23,207 patients, 339 (1.5% overall; 1.0% EVAR and 3.0% OAR) died ≤30 days of repair. One or more complications occurred in 2567 patients (11.2% overall; 7.8% EVAR and 22.1% OAR). Odds ratios (ORs) for mortality adjusted for age, ASA class, and other comorbidities in the group with the highest frailty score were 1.9 (95% confidence interval [CI], 1.2-3.0) after EVAR and 2.3 (95% CI, 1.4-3.7) after OAR. Similarly, compared with the least frail, the most frail patients were significantly more likely to experience severe (Clavien-Dindo class IV) complications after EVAR (OR, 1.7; 95% CI, 1.3-2.1) and OAR (OR, 1.8; 95%, CI, 1.5-2.1). There was also a higher FTR rate among frail patients, with 1.7-fold higher risk odds of mortality (95% CI, 1.2-2.5) in the highest tertile of frailty compared with the lowest when postoperative complications occurred., Conclusions: Higher mFI, independent of other risk factors, is associated with higher mortality and morbidity in patients undergoing elective EVAR and OAR. The mortality in frail patients is further driven by FTR from postoperative complications. Preoperative recognition of frailty may serve as a useful adjunct for risk assessment., (Published by Elsevier Inc.)
- Published
- 2015
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41. Carotid artery stenting has increased risk of external carotid artery occlusion compared with carotid endarterectomy.
- Author
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Brown K, Itum DS, Preiss J, Duwayri Y, Veeraswamy RK, Salam A, Dodson TF, and Brewster LP
- Subjects
- Aged, Carotid Artery, Internal physiopathology, Carotid Stenosis diagnosis, Carotid Stenosis physiopathology, Carotid Stenosis surgery, Cerebrovascular Circulation, Databases, Factual, Georgia, Humans, Recurrence, Regional Blood Flow, Retrospective Studies, Risk Factors, Time Factors, Angioplasty adverse effects, Angioplasty instrumentation, Carotid Artery, External physiopathology, Carotid Artery, Internal surgery, Carotid Stenosis therapy, Endarterectomy, Carotid adverse effects, Stents
- Abstract
Objective: The external carotid artery (ECA) can be an important source of cerebral blood flow in cases of high-grade internal carotid artery stenosis or occlusion. However, the treatment of the ECA is fundamentally different between carotid endarterectomy (CEA) and carotid artery stenting (CAS). CEA is routinely associated with endarterectomy of the ECA, whereas CAS excludes the ECA from direct flow. We hypothesize that these differences make ECA occlusion more common after CAS. Further, the impact of CAS on blood flow into the ECA is interesting because the flow from the stent into the ECA is altered in a way that may promote local inflammation and may influence in-stent restenosis (ISR). Thus, our objective was to use our institutional database to identify whether CAS increased the rate of ECA occlusion and, if it did, whether ECA occlusion was associated with ISR., Methods: Patients undergoing CAS or CEA from February 2007 to February 2012 were identified from our institutional carotid therapy database. Preoperative and postoperative images of patients who followed up in our institution were included in the analysis of ECA occlusion and rates of ISR., Results: There were 210 (67%) CAS patients and 207 (60%) CEA patients included in this analysis. Despite CAS patients being younger (68 vs 70 years), having shorter follow-up (12.5 vs 56.2 months), and being more likely to take clopidogrel (97% vs 35%), they had an increased rate of ECA occlusion (3.8%) compared with CEA patients (0.4%). CAS patients who went on to ECA occlusion had an increased incidence of prior neck irradiation (50% vs 15%; P = .03), but we did not identify an association of ECA occlusion with ISR >50%., Conclusions: Whereas prior publications have identified increased rates of external carotid stenosis, this is the first demonstration of increased ECA occlusion after CAS. However, ECA occlusion is uncommon (∼4%) and did not have an association with ISR >50%. Future work modeling ECA flow patterns before and after CAS will be used to further test this interaction., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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42. Influence of the hostile neck on restenosis after carotid stenting.
- Author
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Brown KA, Itum DS, Duwayri Y, Reeves JG, Rajani R, Veeraswamy RK, Arya S, Salam A, Dodson TF, and Brewster LP
- Subjects
- Aged, Aged, 80 and over, Angioplasty adverse effects, Angioplasty mortality, Cardiovascular Diseases etiology, Carotid Stenosis diagnosis, Carotid Stenosis mortality, Comorbidity, Female, Georgia, Humans, Male, Middle Aged, Prosthesis Failure, Radiotherapy adverse effects, Recurrence, Retreatment, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Angioplasty instrumentation, Carotid Stenosis therapy, Stents
- Abstract
Background: Carotid artery stenting (CAS) for carotid stenosis is favored over carotid endarterectomy (CEA) in patients with a hostile neck from prior CEA or cervical irradiation (XRT). However, the restenosis rate after CAS in patients with hostile necks is variable in the literature. The objective of this study was to quantify differences in the in-stent restenosis (ISR)/occlusion and reintervention rates after CAS in patients with and without a hostile neck. Here we hypothesize that patients with hostile necks have an increased ISR, and that this increase may add morbidity to these patients., Materials and Methods: All patients undergoing CAS from 2007 to 2013 for carotid artery stenosis with follow-up imaging at our institution were queried from our carotid database (n = 236). Patients with hostile necks, including both CAS after prior CEA (n = 65) and prior XRT (n = 37), were compared with patients who underwent CAS for other reasons including both anatomical (n = 46) and medical comorbidities (n = 88). The primary end points were ISR, repeat intervention, and stent occlusion. Secondary end points of the study were stroke/myocardial infarction (MI)/death at 30 days, perioperative cardiovascular accident, transient ischemic attack, MI, groin access complications, hyperperfusion syndrome, and periprocedural hypotension or bradycardia., Results: Despite the hostile neck cohort being younger and having lower incidence of chronic obstructive pulmonary disease, coronary artery disease, and renal insufficiency, they had a greater incidence of ISR (11% vs. 4%; P = .03) and required more reinterventions (8% vs. 2%; P = .04). Stent occlusion and periprocedural morbidity/mortality were not different between groups., Conclusions: Patients with hostile necks have increased risk of restenosis and need for reinterventions after CAS compared with patients without a hostile neck. However, they do not appear to have higher rates of stent occlusion or per-procedural events., (Published by Elsevier Inc.)
- Published
- 2015
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43. Smoking cessation is the least successful outcome of risk factor modification in uninsured patients with symptomatic peripheral arterial disease.
- Author
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Huen KH, Chowdhury R, Shafii SM, Brewster LP, Arya S, Duwayri Y, Veeraswamy RK, Dodson TF, and Rajani RR
- Subjects
- Adult, Black or African American, Age Factors, Aged, Aged, 80 and over, Antihypertensive Agents therapeutic use, Comorbidity, Female, Humans, Hypoglycemic Agents therapeutic use, Hypolipidemic Agents therapeutic use, Male, Medicaid, Medicare, Middle Aged, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease ethnology, Registries, Retrospective Studies, Risk Factors, Smoking adverse effects, Smoking ethnology, Treatment Outcome, United States epidemiology, Health Services Accessibility, Healthcare Disparities ethnology, Medically Uninsured ethnology, Peripheral Arterial Disease therapy, Risk Reduction Behavior, Smoking Cessation, Smoking Prevention
- Abstract
Background: Patients with peripheral arterial disease (PAD) have multiple atherosclerotic risk factors. Risk factor modification can reduce severity of disease at presentation and improve treatment outcomes. The Trans-Atlantic Inter-Society Consensus II (TASC II) has issued several recommendations that are widely adopted by specialists. However, the ability to provide proper services to patients may depend on the specific patient's access to care, which is primarily determined by the presence of health insurance. The purpose of our study was to determine whether insurance status impairs the ability of patients with symptomatic PAD to meet select TASC II recommendations., Methods: A retrospective review of patients with symptomatic PAD from August 2011 to May 2013 was conducted; demographic, preoperative, procedural, and standard outcome variables were collected. Patients were divided into the insured group (private insurance, Medicare, Medicaid) or the uninsured group (self-pay). Insurance status was analyzed for its association to select TASC II recommendations: smoking cessation, referral to smoking cessation program, low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL), low-density lipoprotein cholesterol <1.81 mmol/L (<70 mg/dL), patients with coexisting hyperlipidemia and diabetes, glycated hemoglobin <7%, systolic blood pressure <140 mm Hg, prescription of aspirin, and prescription of a statin., Results: One hundred and forty-four patients with symptomatic PAD were identified. Insured patients were more likely to be African American, older at presentation, or have a diagnosis of congestive heart failure. There was no significant difference between insured and uninsured patients in success rates of low-density lipoprotein cholesterol targets (65.1% vs. 51.1% for <2.59 mmol/L; 24.3% vs. 19.1% for <1.81 mmol/L), glycated hemoglobin targets (61.9% vs. 61.1% for <7%), blood pressure control (51.1% vs. 50.0% for systolic blood pressure <140), aspirin use (72.8% vs. 59.6%), or statin use (77.2% vs. 63.5%). However, insured patients were more likely to quit smoking than uninsured patients (35.1% vs. 17.7%, P = 0.023). Furthermore, there was no difference in patterns of referral to a multidisciplinary smoking cessation program between the 2 groups (31.5% vs. 38.5%)., Conclusions: Insurance status does not impair patients' ability to meet most TASC II guidelines to modify cardiovascular risk factors in patients who have access to health care. Uninsured patients are, however, less likely to cease smoking compared with insured patients, despite no significant difference in referral patterns between the 2 groups for multidisciplinary smoking cessation counseling. Future efforts to assist patients with symptomatic PAD with atherosclerotic risk factor modification should focus on aiding uninsured patients in smoking cessation efforts., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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44. Carotid duplex criteria for patients with contralateral occlusion.
- Author
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Preiss JE, Itum DS, Reeves JG, Duwaryi Y, Rajani R, Veeraswamy R, Salam A, Dodson TF, and Brewster LP
- Subjects
- Aged, Angiography, Carotid Artery, Common physiology, Carotid Artery, Internal physiology, Carotid Stenosis epidemiology, Carotid Stenosis physiopathology, Databases, Factual, Female, Humans, Magnetic Resonance Angiography, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Tomography, X-Ray Computed, Carotid Artery, Common diagnostic imaging, Carotid Artery, Internal diagnostic imaging, Carotid Stenosis diagnostic imaging, Ultrasonography, Doppler, Duplex methods, Ultrasonography, Doppler, Duplex standards
- Abstract
Background: Contralateral occlusion (CLO) occurs in approximately 8% of patients undergoing intervention for carotid artery stenosis. Patients with CLO have increased stroke risk compared with patients without CLO, but standard carotid duplex ultrasonography (CDUS) criteria are not a reliable manner to screen or follow patients with CLO. Because appropriate duplex criteria for these patients are not well understood, this article defines CDUS parameters that accurately predict carotid artery stenosis at our institution., Methods: Sixty-five patients with ipsilateral carotid stenosis and CLO were identified from our institutional database. Fifteen of sixty-five patients had arteriography, computed tomography angiography, or magnetic resonance angiography within 6 mo of CDUS. We determined accuracy of our laboratory's criteria for determining stenosis category compared with three-dimensional imaging. Receiver operating characteristic curves were used to determine optimal peak systolic velocity (PSV), end diastolic velocity (EDV), and systolic ratio (SR) cutoff values for diagnosing ≥50% stenosis in this pilot cohort. Finally, the revised criteria were prospectively applied to a validation cohort (n = 8) from the same institution., Results: Categorization of stenosis by standard PSV, EDV, and SR criteria saw similar accuracy trends in both pilot (46.7, 53.3, and 66.7%) and validation (25, 25, and 62.5%) cohorts. Receiver operating characteristic curve analysis in the pilot cohort identified optimized PSV, EDV, and SR cutoffs (≥250, ≥90, and ≥2.3 cm/s, respectively) for diagnosing ≥50% stenosis. In the pilot cohort, new PSV criteria increased specificity (60%-100%) with minimal decreased sensitivity (90%-80%), whereas new EDV criteria increased specificity (40%-71.4%) and maintained 100% sensitivity. New SR criteria failed to improve sensitivity or specificity above 80%. Similar trends for the new CDUS velocity criteria were observed in the validation cohort., Conclusions: Increasingly stringent ultrasound parameters can provide reliable criteria for determining ≥50% carotid stenosis in patients with CLO. Further prospective validation that includes more patients with high-grade ipsilateral stenosis will help identify the role of SR in segregating high-grade versus moderate stenosis in CLO patients., (Published by Elsevier Inc.)
- Published
- 2015
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45. Differential mechanical response and microstructural organization between non-human primate femoral and carotid arteries.
- Author
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Wang R, Raykin J, Li H, Gleason RL Jr, and Brewster LP
- Subjects
- Animals, Biomechanical Phenomena, Collagen metabolism, Elastin metabolism, Female, Humans, Male, Models, Cardiovascular, Stress, Mechanical, Carotid Arteries anatomy & histology, Carotid Arteries physiology, Femoral Artery anatomy & histology, Femoral Artery physiology, Macaca mulatta physiology
- Abstract
Unique anatomic locations and physiologic functions predispose different arteries to varying mechanical responses and pathologies. However, the underlying causes of these mechanical differences are not well understood. The objective of this study was to first identify structural differences in the arterial matrix that would account for the mechanical differences between healthy femoral and carotid arteries and second to utilize these structural observations to perform a microstructurally motivated constitutive analysis. Femoral and carotid arteries were subjected to cylindrical biaxial loading and their microstructure was quantified using two-photon microscopy. The femoral arteries were found to be less compliant than the carotid arteries at physiologic loads, consistent with previous studies, despite similar extracellular compositions of collagen and elastin ([Formula: see text]). The femoral arteries exhibited significantly less circumferential dispersion of collagen fibers ([Formula: see text]), despite a similar mean fiber alignment direction as the carotid arteries. Elastin transmural distribution, in vivo axial stretch, and opening angles were also found to be distinctly different between the arteries. Lastly, we modeled the arteries' mechanical behaviors using a microstructural-based, distributed collagen fiber constitutive model. With this approach, the material parameters of the model were solved using the experimental microstructural observations. The findings of this study support an important role for microstructural organization in arterial stiffness.
- Published
- 2014
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46. Stent graft therapy for false lumen aneurysmal degeneration in established type B aortic dissection (FADED) results in differential volumetric remodeling of the thoracic versus abdominal aortic segments.
- Author
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Ruddy JM, Reisenman P, Priestley J, Brewster LP, Duwayri Y, and Veeraswamy RK
- Subjects
- Aged, Aortic Dissection diagnostic imaging, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Thoracic diagnostic imaging, Female, Humans, Male, Middle Aged, Radiographic Image Interpretation, Computer-Assisted, Retrospective Studies, Tomography, X-Ray Computed, Treatment Outcome, Aortic Dissection surgery, Aortic Aneurysm, Abdominal surgery, Aortic Aneurysm, Thoracic surgery, Blood Vessel Prosthesis, Blood Vessel Prosthesis Implantation methods, Stents
- Abstract
Background: Despite optimal medical therapy of type B aortic dissections, false lumen aneurysmal degeneration of these established dissections (FADED) occur over long term (>6 months). The efficacy of thoracic stent grafts (thoracic endovascular aortic repair [TEVAR]) in promoting aortic remodeling when placed at late time points remains controversial and was the focus of this investigation., Methods: Utilizing tomographic scans, the volume of 6 distinct aortic compartments were calculated including the stented true lumen and stented false lumen (STL and SFL), below-stent true and false lumens (BSTL and BSFL), and the infrarenal aorta true and false lumens (IRA TL and IRA FL) when applicable. Cross-sectional areas were calculated at 1-cm intervals, collated, and volumetric ratios were derived from preoperative values., Results: From 2004 to 2011, 21 patients met inclusion criteria. Complete false lumen (FL) thrombosis was achieved in 85.7% of SFL and 26.3% of BSFL. Volumetric analysis demonstrated that 71% of patients had increased STL volume and 71% had decreased SFL. In the below-stent region, 75% of patients had increased true lumen (TL) with 59% concurrently decreased FL volume. The IRA TL volume increased in 85% of patients and the IRA FL also expanded in 75% of this cohort. At the latest time point, overall growth was noted in the infrarenal aortic segment., Conclusions: Utilization of TEVAR in patients suffering from FADED can promote TL expansion with concurrent FL regression; however, progressive dilation in the total infrarenal aorta volume may occur and warrants close surveillance., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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47. Designing an ethics curriculum to support global health experiences in surgery.
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Martin BM, Love TP, Srinivasan J, Sharma J, Pettitt B, Sullivan C, Pattaras J, Master VA, and Brewster LP
- Subjects
- Adult, Clinical Clerkship methods, Cross-Sectional Studies, Curriculum, Education, Medical, Undergraduate methods, General Surgery ethics, Humans, Physician-Patient Relations ethics, Students, Medical, Clinical Clerkship ethics, Education, Medical, Undergraduate ethics, Ethics, Medical education, General Surgery education, Global Health education, Global Health ethics
- Abstract
Background: The field of global health is rapidly expanding in many medical centers across the US. As a result, medical students have increasing opportunities to incorporate global health experiences (GHEs) into their medical education. Ethics is a critical component of global health curricula, yet little literature exists to direct the further development of didactic training. Therefore, we sought to define ethical encounters experienced by medical students participating in short-term surgical GHEs and create a framework for the design of ethics curriculum specific to global surgery., Materials and Methods: Emory University Departments of Surgery, Urology, and Anesthesia, in partnership with the non-profit organization Project Medishare, have taken annual humanitarian surgical trips to Hinche, Haiti. All medical students returning from the trips in 2011 and 2012 received a 35-question survey to assess demographic data, extent of prior ethics education, frequency of exposure and situational confidence to ethical subject matter, as well as ethical conflicts involved in surgical GHEs. The same comparative data were also collected for domestic clinical clerkships., Results: Seventeen out of 21 medical students completed the survey. Nearly all (88.3%) students had previous formal ethics training as an undergraduate or in medical school. Ethical issues were commonly encountered during domestic clinical encounters and volunteerism. However, students reported enhanced exposure to the professional obligation of surgeons (P = 0.025) and truth-telling/surgeon-patient relationships (P = 0.044) during surgical volunteerism. Despite increased exposure, situational confidence did not change., Conclusions: Ethical issues are commonly confronted during GHEs in surgery and differ from domestic clinical encounters. Healthcare ethics curriculum should be designed to meet the needs of medical students involved in global health., (Copyright © 2014. Published by Elsevier Inc.)
- Published
- 2014
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48. Anatomic characteristics of aortic transection: centerline analysis to facilitate graft selection.
- Author
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Rajani RR, Johnson LS, Brewer BL, Brewster LP, Duwayri Y, Reeves JG, Veeraswamy RK, and Dodson TF
- Subjects
- Adult, Aorta, Thoracic injuries, Female, Humans, Injury Severity Score, Male, Patient Selection, Predictive Value of Tests, Prosthesis Design, Radiographic Image Interpretation, Computer-Assisted, Registries, Trauma Centers, Aorta, Thoracic diagnostic imaging, Aorta, Thoracic surgery, Aortography methods, Blood Vessel Prosthesis, Blood Vessel Prosthesis Implantation instrumentation, Stents, Tomography, X-Ray Computed, Vascular System Injuries diagnostic imaging, Vascular System Injuries surgery, Wounds, Nonpenetrating diagnostic imaging, Wounds, Nonpenetrating surgery
- Abstract
Background: Traumatic transection of the thoracic aorta is a life-threatening complication that most commonly occurs after high-speed motor vehicle collisions. Although such injuries were previously treated with open surgical reconstruction, they are now more commonly being treated with endovascularly placed stent grafts. Unfortunately, most stent grafts are designed for treating aortic aneurysmal disease instead of traumatic injury. Further refinements in stent graft technology depend on a thorough anatomic understanding of the transection injury process., Methods: All patients with computed tomography (CT) evidence of blunt aortic injury (BAI) between 2006 and 2012 at a Level 1 trauma center were queried. Their initial CT scans were imported into the Intuition (Terarecon, Inc.) viewing program, and off-line centerline reconstruction was performed. Standard demographic data were collected in addition to anatomic characteristics, including aortic diameters and the relationship of the injury to the arch vessels., Results: Thirty-five patients were identified. Three patients were injured proximal to the left subclavian artery. The average length from the left subclavian artery to the proximal site of injury was 16.2 mm (range 2-31 mm). Most patients had >15 mm of landing zone beyond the left subclavian artery. The range of proximal diameters ranged from 17 to 32 mm, with an average aortic diameter of 23.9 mm. The average length of injured aortic segment was 27 mm., Conclusions: In this contemporary series from a large trauma center, 91% of patients are anatomically able to be treated with a stent graft that does not require coverage of the left common carotid artery. Most patients have an aortic diameter that falls between 21 and 26 mm in diameter, as well as a short segment of injured artery. Centers interested in emergently treating aortic transections are able to do so while maintaining a limited stock of stent grafts that can be used to treat the majority of the population., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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49. Femoral and carotid intima media thickness--two different measurements in two different arteries.
- Author
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Beal S and Brewster LP
- Subjects
- Humans, Male, Femoral Artery physiology, Tunica Intima physiology, Tunica Media physiology
- Published
- 2013
- Full Text
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50. In-situ characterization of the uncrimping process of arterial collagen fibers using two-photon confocal microscopy and digital image correlation.
- Author
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Wang R, Brewster LP, and Gleason RL Jr
- Subjects
- Animals, Macaca mulatta, Microscopy, Confocal methods, Blood Pressure physiology, Carotid Artery, Common physiology, Collagen metabolism, Image Processing, Computer-Assisted, Models, Cardiovascular, Vasodilation physiology
- Abstract
Uncrimping of collagen fibers in the arterial wall is an integral process in regulating the macro-level mechanical response of arteries. Uncrimping of collagen fibers leads to a gradual, but significant strain-stiffening response of the artery at physiological pressures and prevents overdistention at elevated pressures. In this study, we imaged adventitial collagen fibers from fresh primate arteries using two-photon excitation microscopy while subjecting the arteries to physiological inflation pressures and axial stretches. The imaging focal plane was fixed at a constant radial location in the adventitial wall by adjusting the focal distance as the arteries inflated, allowing for the continuously monitoring of the uncrimping process of a single region of collagen fibers. Digital image correlation was then applied to the sequential images to assess and correlate the local displacements to manual traces of selected reference fibers and their engagements. We found that the collagen fibers of interest became fully engaged at a luminal pressure of 20mmHg, this was then followed by rotation of these fibers as the bulk artery continued to dilate. This technique helps to further the understanding of the uncrimping process of collagen fibers under physiological loads, which can aid in the development of more accurate microstructural constitutive models., (© 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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