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Background: Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation., Methods: AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression., Results: Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive., Conclusions: AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Disparities in health care are well documented for several racial, ethnic, and gender groups. In peripheral arterial disease, differences in prevalence, treatment selection, treatment outcomes, and resulting quality of life have negative effects on some minority groups and women. It may be easy to document disparities, but it is harder to understand their underlying causes. Are there biologic differences between members of racial and ethnic groups that influence disease presentation and outcomes? Or is the socioeconomic environment that surrounds them the true driver of observed differences? This article reviews the evidence for racial and gender disparities in vascular surgery and presents some potential mechanisms that may explain the disparities., (Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Vein bypass surgery is an effective therapy for atherosclerotic occlusive disease in the coronary and peripheral circulations; however, long-term results are limited by progressive attrition of graft patency. Failure of vein bypass grafts in patients with critical limb ischemia results in morbidity, limb loss, and additional resource use. Although technical factors are known to be critical to the success of surgical revascularization, patient-specific risk factors are not well defined. In particular, the relationship of race/ethnicity and gender to the outcomes of peripheral bypass surgery has been controversial., Methods and Results: We analyzed the Project of Ex Vivo Vein Graft Engineering via Transfection III (PREVENT III) randomized trial database, which included 1404 lower extremity vein graft operations performed exclusively for critical limb ischemia at 83 North American centers. Trial design included intensive ultrasound surveillance of the bypass graft and clinical follow-up to 1 year. Multivariable modeling (Cox proportional hazards and propensity score) was used to examine the relationships of demographic variables to clinical end points, including perioperative (30-day) events and 1-year outcomes (vein graft patency, limb salvage, and patient survival). Final propensity score models adjusted for 16 covariates (including type of institution, technical factors, selected comorbidities, and adjunctive medications) to examine the associations between race, gender, and outcomes. Among the 249 black patients enrolled in PREVENT III, 118 were women and 131 were men. Black men were at increased risk for early graft failure (hazard ratio [HR], 2.832 for 30-day failure; 95% confidence interval [CI], 1.393 to 5.759; P=0.0004), even when the analysis was restricted to exclude high-risk venous conduits. Black patients experienced reduced secondary patency (HR, 1.49; 95% CI, 1.08 to 2.06; P=0.016) and limb salvage (HR, 2.02; 95% CI, 1.27 to 3.20; P=0.003) at 1 year. Propensity score models demonstrate that black women were the most disadvantaged, with an increased risk for loss of graft patency (HR, 2.02 for secondary patency; 95% CI, 1.27 to 3.20; P=0.003) and major amputation (HR, 2.38; 95% CI, 1.18 to 4.83; P=0.016) at 1 year. Perioperative mortality and 1-year mortality were similar across race/gender groups., Conclusions: Black race and female gender are risk factors for adverse outcomes after vein bypass surgery for limb salvage. Graft failure and limb loss are more common events in black patients, with black women being a particularly high-risk group. These data suggest the possibility of an altered biological response to vein grafting in this population; however, further studies are needed to determine the mechanisms underlying these observed disparities in outcome.

Peripheral arterial disease (PAD) is a growing health problem for many Americans and often occurs along with other cardiovascular risk factors, including diabetes mellitus (DM), low-grade inflammation, hypertension, and lipid disorders. Intermittent claudication (IC), an early manifestation of PAD, commonly leads to reduced quality of life for patients who are limited in their ambulation. While recent wide adoption of percutaneous peripheral interventional (PPI) techniques has increased the number patients being aggressively treated for IC, the overall effectiveness of PPI for the treatment of IC is not well known, especially for DM patients who have both hemodynamic and functional obstacles to treatment success. This review is designed to illustrate how treatment outcomes for IC can be measured by different modalities and how diabetes and inflammation can influence those outcomes. In the setting of greater concern for health care resources and clinical accountability, better understanding of treatment outcomes and efficacy will help us manage these complex challenges.

Objectives: We sought to determine the long-term results of revision procedures performed for repair of stenotic lesions in infrainguinal vein bypass grafts., Methods: A retrospective review of 188 vein grafts, from a total series of 1260 bypasses, undergoing revision of stenotic lesions between January 1, 1987, and December 31, 2002, at Brigham & Women's Hospital was undertaken. Lesions were identified by recurrence of symptoms, change in examination findings, or with routine duplex ultrasound graft surveillance. Demographic and medical risk factors, and surgical variables were analyzed with respect to patency outcomes after the initial graft revision, with descriptive statistics, logistic regression, and life table analysis. Primary and secondary patency rates were determined from the time of graft revision., Results: Patients included 108 men (57%) and 80 women (42%) who underwent revision at a mean age of 67.8 years. One hundred thirty grafts required only a single revision, whereas 58 required subsequent additional revisions. Revision procedures included 99 vein patches (52.7%), 23 jump grafts (12.2%), 23 interposition grafts (12.2%), 8 transpositions to new outflow vessels (4.3%), and 35 balloon angioplasty procedures (18.6%). During a mean follow-up of 1535 days, 5-year primary patency rate was 49.3% +/- 4.5% (SE) and 5-year secondary patency rate was 80.3% +/- 3.6%. There was no difference in patency rate for different revision procedures, type of vein graft, indication for the original procedure, or for patients with diabetes mellitus or renal disease. The overall limb salvage rate was 83.2% +/- 3.5% 5 years after graft revision. With COX proportional hazard analysis of time to failure of the revision procedure, the outflow level of the original bypass and the time of revision proved to be an important predictor of durability of the graft revision. Revision of popliteal bypass grafts resulted in a 60% 5-year primary patency rate, whereas revision of tibial grafts resulted in a 42% 5-year primary patency rate (P = .004; hazard ratio [HR], 2.06). Five-year secondary patency rates were 90% and 76%, respectively (P = .009; HR = 3.43). The timing of the graft revision proved an additional predictor. Grafts revised within 6 months of the index operation had lower primary patency than those with later revisions (42.9% vs 80.7%, respectively; HR = 1.754; P = .0152)., Conclusions: Vein graft revisions offer durable patency and limb salvage rates after repair of stenotic infrainguinal bypass grafts. Vigilant ongoing surveillance is essential, because 30.9% of revised grafts will develop additional lesions that will require repair. Tibial level bypass grafts that require early repeat intervention to treat graft stenosis are at particular risk for development of subsequent lesions.

Objective: Repeat percutaneous endoluminal interventions for femoropopliteal occlusive disease are common, but the outcomes are poorly understood. We sought to determine the results of second-time femoropopliteal percutaneous transluminal angioplasty/stenting (SPTAS) and identify factors associated with success or failure of a continued endoluminal revascularization strategy. Methods: A retrospective review of patients undergoing multiple percutaneous endoluminal lower extremity interventions at a single institution from 2002 and 2009 identified 70 SPTAS in 70 limbs. Patient comorbidities, anatomic severity of disease, and procedural characteristics were analyzed with respect to outcomes with descriptive statistics, Kaplan-Meier curves, and Cox proportional hazards modeling. Patency rates were determined from the time of SPTAS. Results: Patients included 37 men (63%) and 22 women (27%) at a mean age of 70 ± 10 years. Indications for SPTAS included claudication in 54 limbs (77%) and critical limb ischemia (CLI) in 16 (23%). Median time from the initial endoluminal intervention to SPTAS was 330 days. Lesion TransAtlantic InterSociety Consensus II (TASCII) classification was A in 18 (25.7%), B in 18 (25.7%), C in 25 (35.7%), and D in 9 (12.9%). Technical success was achieved in 68 (97%) with low rates of intraprocedural (10%) and postprocedural (4%) complications as well as initial clinical improvement in 61 (87%) patients. Over a median follow-up of 22.9 months following SPTAS, 2-year primary patency, secondary patency, limb salvage (in patients with CLI), and survival were 33% ± 7%, 63% ± 7%, 87% ± 9%, and 88% ± 5%, respectively. Cox proportional hazard modeling showed that SPTAS within 180 days of the initial endovascular intervention was the only significant predictor of failure of primary patency (hazard ratio, 2.65; 95% confidence interval, 1.4-5.2) and secondary patency (hazard ratio, 3.1; 95% confidence interval, 1.4-7.1) of SPTAS. Conclusions: Second-time femoropopliteal angioplasty/stenting has excellent technical success but limited midterm primary and secondary patency. Early failure of the initial endovascular intervention strongly predicts poor outcome following SPTAS and in this cohort was more significant than comorbidities, anatomic factors, or procedural characteristics. These data suggest that after early endovascular failure, alternatives to a continued endoluminal strategy should be adopted. [Copyright &y& Elsevier]

Introduction: Recent evidence suggests disparities exist among racial groups with peripheral arterial disease (PAD). Hispanics (HI) are the fastest growing demographic in the United States, but little outcome data is available for this population. Therefore, we undertook this study to compare the results of autogenous infrainguinal bypass grafting in HI to Caucasians (CA) and African Americans (AA). Methods: This was a comparative cohort study of prospectively collected registry data of infrainguinal bypass performed at a tertiary center. Patient demographics and comorbidities, operative indications, bypass graft characteristics, and postoperative courses were analyzed. Cumulative patency rates, limb salvage, mortality, and factors associated with these outcomes were determined using Kaplan-Meier analysis and Cox proportional hazards models. Results: From January 1, 1985, through December 31, 2007, 1646 consecutive patients (1408 CA, 57 HI, and 181 AA) underwent 1646 autogenous infrainguinal reconstructions. HI and AA were younger and more often diabetic than CA but HI had less chronic renal insufficiency (CRI) and dialysis-dependence than AA. AA, but not HI, more commonly underwent bypass for critical limb ischemia (CLI) in comparison to CA (AA 90% vs CA 80%, P < .0001; HI 86%). HI and AA bypass grafts had inflow and outflow distal to that in CA. Perioperative mortality (2.3%) and morbidity were similar between groups. Five-year primary patency (± standard error [SE]) was significantly lower in HI compared to CA and similar to that in AA (HI 54% ± 7% vs CA 69% ± 1%, P = .02; AA 58% ± 4%). Cox proportional hazard modeling showed high-risk conduit, age <65, CLI, female gender, and AA race were risk factors for failure of primary patency. Secondary patency of HI grafts, unlike AA, was not different than that in CA. Five-year limb salvage (± SE) was significantly lower in HI compared to CA and similar to that in AA (HI 80% ± 6% vs CA 91% ± 1%, P = .004; AA 83% ± 3%). Hispanic ethnicity, CLI, high-risk conduit, age <65, CRI, female gender, and diabetes were significant predictors of limb loss. Conclusion: Autogenous infrainguinal bypass surgery in HI is associated with primary patency and limb salvage inferior to that of CA and similar to that of AA, despite HI rates of CLI equivalent to CA and HI comorbidities less severe than AA. HI ethnicity was an independent predictor of limb loss. Our data provides evidence of outcome disparities in HI treated aggressively for their PAD. Further investigation with regard to biologic and social factors is required to delineate the reasons for these inferior outcomes in HI patients. [Copyright &y& Elsevier]

Occlusion after infra-inguinal bypass surgery for peripheral artery disease is a major complication with potentially devastating consequences. In this descriptive analysis, we sought to describe the natural history and explore factors associated with long-term major amputation-free survival following occlusion of a first-time infra-inguinal bypass. Using a prospective database from a tertiary care vascular center, we conducted a retrospective cohort study of all patients with peripheral artery disease who underwent a first-time infra-inguinal bypass and subsequently suffered a graft occlusion (1997-2021). The primary outcome was longitudinal rate of major amputation-free survival after bypass occlusion. Cox proportional hazard models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to explore predictors of outcomes. Of the 1318 first-time infra-inguinal bypass surgeries performed over the study period, 255 bypasses occluded and were included in our analysis. Mean age was 66.7 (12.6) years, 40.4% were female, and indication for index bypass was chronic limb threatening ischemia (CLTI) in 89.8% (n = 229). 48.2% (n = 123) of index bypass conduits used great saphenous vein, 29.0% (n = 74) prosthetic graft, and 22.8% (n = 58) an alternative conduit. Median (interquartile range) time to bypass occlusion was 6.8 (2.3-19.0) months, and patients were followed for median of 4.3 (1.7-8.1) years after bypass occlusion. Following occlusion, 38.04% underwent no revascularization, 32.94% graft salvage procedure, 25.1% new bypass, and 3.92% native artery recanalization. Major amputation-free survival following occlusion was 56.9% (50.6%-62.8%) at 1 y, 37.1% (31%-43.3%) at 5 y, and 17.2% (11.9%-23.2%) at 10 y. In multivariable analysis, factors associated with lower amputation-free survival were older age, female sex, advanced cardiorenal comorbidities, CLTI at index procedure, CLTI at time of occlusion, and distal index bypass outflow. Initial treatment after occlusion with both a new surgical bypass (HR 0.44, CI: 0.29-0.67) or a graft salvage procedure (HR 0.56, CI: 0.38-0.82) showed improved amputation-free survival. One-year rate of major amputation or death were 59.8% (50.0%-69.6%) for those who underwent no revascularization, 37.9% (28.7%-49.0%) for graft salvage, and 26.7% (17.6%-39.5%) for new bypass. Long-term major amputation-free survival is low after occlusion of a first-time infra-inguinal bypass. While several nonmodifiable risk factors were associated with lower amputation-free survival, treatment after graft occlusion with either a new bypass or a graft salvage procedure may improve longitudinal outcomes. [ABSTRACT FROM AUTHOR]

Critical limb ischemia (CLI) is a frequent and major vascular problem and can lead to amputation and death despite surgical revascularization. Women have been shown to have 3 to 4 per cent lower revascularization rates for CLI compared with men as well as inferior outcomes. We hypothesize that this difference is a result of women being more likely admitted to low-volume hospitals, which in turn perform fewer revascularizations. Prospective cohort study. Data from the Nationwide Inpatient Sample 2007 to 2010 were used to identify admissions with primary International Classification of Diseases-9 codes for CLI (International Classification of Diseases-9 codes: 440.22, 440.23, 440.24, 707.1, 707.10-707.15, or 707.19). Hospitals were grouped in quintiles by annual revascularization procedures. Bivariate analyses were performed and multivariable logistic regression was used to analyze the odds of revascularization, amputation, and mortality while controlling for patient and hospital-level factors. Of 113,631 admissions, 54,370 (47.8%) were women, who were more likely admitted to low-volume hospitals (very low: 49.6% vs very high: 47.1%; P < 0.001). Revascularization rates were lower in women (31.6% vs 35.1%, P < 0.001) across all volume quintiles, whereas the difference was greatest in the use of open surgical revascularization (12.5% vs 16.0%, P < 0.001). In multivariable analysis, female gender [odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83-0.92, P < 0.001] and very-low hospital volume (OR 0.21, 95% CI 0.17-0.26, P < 0.001) were both significantly associated with lower rates of revascularization. Women had lower odds of major amputation compared with men (OR 0.75, 95% CI 0.69-0.82, P < 0.001), whereas treatment in a very high-volume hospital was associated with increased odds for amputation (OR 1.37, 95% CI 1.09-1.73, P = 0.008). Neither gender nor hospital volume were independently associated with in-hospital mortality in the multivariable regression model. Women are more likely to be admitted to low-volume hospitals for treatment of CLI. Because of this, they are less likely to undergo revascularization, although they also had lower rates of major amputation. [ABSTRACT FROM AUTHOR]

BACKGROUND: We hypothesized that human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. We also evaluated the impact of clinical parameters on the adipose phenotype. Our overall goal is to understand. the determinants of adipose biology so that this tissue can be manipulated therapeutically to lessen peripheral vascular disease. METHODS: Perivascular and subcutaneous adipose tissues were collected from patients undergoing lower-extremity amputation (n = 27) and protein assayed for proinflammatory mediators (ie, interleukin 6, interleukin 8, leptin, tumor necrosis factor α, monocyte chemoattractant protein-1 , and resistin), atheroprotective adiponectin, and the fibrinolysis inhibitor plasminogen activator inhibitor-1. RESULTS: Leptin (2.7-fold, P = .015), TNF-α (2.2-fold, P = .013), MCP-1 (1.5-fold, P = .047), and adiponectin (1.8-fold, P = .004) were more abundant in subcutaneous vs perivascular adipose tissue. Age positively correlated with perivascular adipose tissue PAl-I expression (β = .64, P = .042), and hyperlipidemia negatively correlated with perivascular adiponectin (β = -1.18, P = .039). CONCLUSIONS: Human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. In amputation patients, the subcutaneous adipose tissue proinflammatory phenotype was relatively attenuated in perivascular adipose tissue. [ABSTRACT FROM AUTHOR]