Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis.

BACKGROUND: Metabolic divergence of macrophages polarized into different phenotypes represents a mechanistically relevant target for non-invasive characterization of atherosclerotic plaques using positron emission tomography (PET). Carbon-11 (11C)-labeled acetate is a clinically available tracer which accumulates in atherosclerotic plaques, but its biological and clinical correlates in atherosclerosis are undefined. METHODS AND RESULTS: Histological correlates of 14C-acetate uptake were determined in brachiocephalic arteries of western diet-fed apoE-/- mice. The effect of polarizing stimuli on 14C-acetate uptake was determined by proinflammatory (interferon-γ + lipopolysaccharide) vs inflammation-resolving (interleukin-4) stimulation of murine macrophages and human carotid endarterectomy specimens over 2 days. 14C-acetate accumulated in atherosclerotic regions of arteries. CD68-positive monocytes/macrophages vs smooth muscle actin-positive smooth muscle cells were the dominant cells in regions with high vs low 14C-acetate uptake. 14C-acetate uptake progressively decreased in proinflammatory macrophages to 25.9 ± 4.5% of baseline (P < .001). A delayed increase in 14C-acetate uptake was induced in inflammation-resolving macrophages, reaching to 164.1 ± 21.4% (P < .01) of baseline. Consistently, stimulation of endarterectomy specimens with interferon-γ + lipopolysaccharide decreased 14C-acetate uptake to 66.5 ± 14.5%, while interleukin-4 increased 14C-acetate uptake to 151.5 ± 25.8% compared to non-stimulated plaques (P < .05). CONCLUSIONS: Acetate uptake by macrophages diverges upon proinflammatory and inflammation-resolving stimulation, which may be exploited for immunometabolic characterization of atherosclerosis.

Optimization of duplex velocity criteria for diagnosis of internal carotid artery (ICA) stenosis: A report of the Intersocietal Accreditation Commission (IAC) Vascular Testing Division Carotid Diagnostic Criteria Committee.

Diagnostic criteria to classify severity of internal carotid artery (ICA) stenosis vary across vascular laboratories. Consensus-based criteria, proposed by the Society of Radiologists in Ultrasound in 2003 (SRUCC), have been broadly implemented but have not been adequately validated. We conducted a multicentered, retrospective correlative imaging study of duplex ultrasound versus catheter angiography for evaluation of severity of ICA stenosis. Velocity data were abstracted from bilateral duplex studies performed between 1/1/2009 and 12/31/2015 and studies were interpreted using SRUCC. Percentage ICA stenosis was determined using North American Symptomatic Carotid Endarterectomy Trial (NASCET) methodology. Receiver operating characteristic analysis evaluated the performance of SRUCC parameters compared with angiography. Of 448 ICA sides (from 224 patients), 299 ICA sides (from 167 patients) were included. Agreement between duplex ultrasound and angiography was moderate (κ = 0.42), with overestimation of degree of stenosis for both moderate (50-69%) and severe (⩾ 70%) ICA lesions. The primary SRUCC parameter for ⩾ 50% ICA stenosis of peak-systolic velocity (PSV) of ⩾ 125 cm/sec did not meet prespecified thresholds for adequate sensitivity, specificity, and accuracy (sensitivity 97.8%, specificity 64.2%, accuracy 74.5%). Test performance was improved by raising the PSV threshold to ⩾ 180 cm/sec (sensitivity 93.3%, specificity 81.6%, accuracy 85.2%) or by adding the additional parameter of ICA/common carotid artery (CCA) PSV ratio ⩾ 2.0 (sensitivity 94.3%, specificity 84.3%, accuracy 87.4%). For ⩾ 70% ICA stenosis, analysis was limited by a low number of cases with angiographically severe disease. Interpretation of carotid duplex examinations using SRUCC resulted in significant overestimation of severity of ICA stenosis when compared with angiography; raising the PSV threshold for ⩾ 50% ICA stenosis to ⩾ 180 cm/sec as a single parameter or requiring the ICA/CCA PSV ratio ⩾ 2.0 in addition to PSV of ⩾ 125 cm/sec for laboratories using the SRUCC is recommended to improve the accuracy of carotid duplex examinations.

Editor's Choice - Comparison of Outcomes After Open Surgical and Endovascular Lower Extremity Revascularisation Among End Stage Renal Disease Patients on Dialysis.

OBJECTIVES: End stage renal disease (ESRD) patients with peripheral arterial disease (PAD) are at high risk of complications following open surgical revascularisation (OSR). Endovascular revascularisation (ER) is an option, but its role is unclear. This study sought to characterise the outcomes of ER and OSR in ESRD patients treated for claudication or critical limb ischaemia (CLI). METHODS: The United States Renal Data System was used to investigate outcomes after lower extremity ER and OSR from 2005 to 2011. Primary outcomes were mortality, amputation, and peri-procedural myocardial infarction (MI). Kaplan-Meier (K-M) estimates were generated for mortality and amputation, logistic regression models for 30 day predictors, and proportional hazards models for long-term predictors. RESULTS: A total of 20,347 patients underwent OSR and ER (20.3% OSR, 79.7% ER). CLI was the indication in 80.8% of ER and 88.4% of OSR. The unadjusted major amputation rate at 30 days was higher after ER compared with OSR (8.8% vs. 6.4%, p < .001). Conversely, the unadjusted mortality rate at 30 days was lower after ER compared with OSR (8.0% vs. 10.5%, p < .001). Multivariable logistic regression models adjusting for medical covariables and CLI versus claudication status demonstrated increased 30 day mortality risk with OSR compared with ER (OR 2.00, 95% CI 1.43-1.79, p < .001), MI (OR 1.38, 1.23-1.54, p < .001), and the combined endpoint of mortality and major amputation (OR 1.57, 1.16-2.12, p = .004), but lower odds of 30 day major amputation alone (OR 0.67, 0.58-0.77, p < .001). Proportional hazards models demonstrated increased long-term mortality risk with OSR compared with ER (HR 1.05, 1.00-1.09, p = .037), without a difference in major amputation (HR 0.99, 0.93-1.05, p = NS). CONCLUSIONS: In this retrospective analysis of an administrative database, ESRD patients suffer from high mortality and amputation rates following lower extremity revascularisation. Compared with ER, OSR is associated with higher mortality. OSR has better 30 day limb salvage, although long-term outcomes are similar.

Bypass versus endovascular intervention for healing ischemic foot wounds secondary to tibial arterial disease.

OBJECTIVE: Pedal (inframalleolar) bypass is a long-standing therapy for tibial arterial disease in patients with ischemic tissue loss. Endovascular tibial intervention is an appealing alternative with lower risks of perioperative mortality or complications. Our objective was to compare the effectiveness of these two treatment modalities with respect to patency and limb-related clinical outcomes. METHODS: We performed a retrospective chart review of patients presenting between 2006 and 2013 with ischemic foot wounds and infrapopliteal arterial disease who underwent a revascularization procedure (either open surgical bypass to an inframalleolar target or endovascular tibial intervention). Data were collected on baseline demographics and comorbidities, procedural details, and postprocedure outcomes. The primary outcome was successful healing of the index wound, with mortality, major amputation, and patency assessed as secondary outcomes. RESULTS: We identified 417 patients who met our eligibility criteria; 105 underwent surgical bypass and 312 underwent endovascular intervention, with mean follow-up of 25.0 and 20.2 months, respectively (P = .08). The endovascular patients were older at baseline (P = .009), with higher rates of hyperlipidemia (P = .02), prior cerebrovascular accidents (P = .04), and smoking history (P = .04). Within 30 days postoperatively, there was no difference in mortality (P = .31), but bypass patients had longer hospital length of stay (P < .0001), higher rate of discharge to nursing facility (P < .001), and higher rates of myocardial infarctions (P = .03) and wound complications (P < .001). At 6 months, the rate of wound healing was 22.4% in the bypass group compared with 29.0% in the endovascular group (P = .02). At 1 year, survival was higher after bypass (86.2% vs 70.4%; P < .0001), but freedom from major amputation was similar (84.9% vs 82.8%; P = .42). Primary patency (53.1% vs 38.2%; P = .002) and primary assisted patency (76.6% vs 51.7%; P < .0001) were higher in the bypass group, but there was no difference in secondary patency (77.3% vs 73.8%; P = .13). CONCLUSIONS: Endovascular tibial intervention is associated with poorer primary patency but similar secondary patency and wound healing rates compared with the "gold standard" of surgical bypass to a pedal target. In patients with tibial arterial disease, endovascular intervention should be considered a lower risk alternative to pedal bypass that provides similar clinical outcomes.

Prior Endovascular Intervention Is Not Detrimental to Pedal Bypasses for Ischemic Wounds.

BACKGROUND: Endovascular strategies are often preferred for revascularization of ischemic foot wounds secondary to infrapopliteal disease because of the less invasive technique and faster recovery. Bypass is typically reserved for failures or lesions not amenable to balloon angioplasty. However, the effects of an endovascular-first approach on subsequent bypass grafts are largely unknown. This study evaluates the effects of prior endovascular tibial interventions (PTIs) on successive bypasses to pedal targets. METHODS: Patients who presented with ischemic tissue loss and tibial arterial occlusive disease to University of Pittsburgh Medical Center between 2006 and 2013 and underwent a surgical bypass to pedal arteries were included in this study. A retrospective chart review was conducted to obtain patient demographics, past medical history, extent of disease, prior tibial endovascular interventions, the treatment intervention, subsequent interventions, wound healing status, limb salvage, and patient survival. The primary outcome was primary patency of the pedal bypass graft. RESULTS: From 122 eligible patients, 27 had a PTI, whereas 95 had no prior endovascular tibial intervention (nPTI) in the treatment of ischemic pedal wounds with mean follow-up of 24.5 and 20.5 months, respectively (P = 0.36). The 2 groups were largely similar in terms of demographics, comorbidities, wound size, and degree of ischemia. Runoff scores between the 2 groups were also comparable (5.0 ± 1.6 for PTI and 4.8 ± 1.9 for nPTI, P = 0.59). The plantar artery was a more common target vessel in the PTI group, whereas the posterior tibial artery was targeted more often in the nPTI group (P = 0.04). At 12 months, those with a PTI exhibited a shorter primary patency (34.8% vs. 60.2%, P = 0.04). In a multivariate model, PTI was a significant risk factor for primary patency loss (hazard ratio 2.51, P = 0.004). Primary assisted patency and secondary patency were similar between the 2 groups. Wound healing was improved in those patients who had a prior endovascular intervention with 63.8% healed at 1 year compared with only 34.8% of those without intervention (P = 0.01). Amputation-free survival was similar (P = 0.68), as was survival alone (P = 0.50). CONCLUSIONS: Despite a decrease in primary patency, pedal bypass was not otherwise negatively affected by a PTI. Similar primary assisted patency, secondary patency, wound healing, and survival between the 2 patient populations indicate that an endovascular-first approach is a feasible treatment strategy to achieve similar clinical outcomes in the management of ischemic foot wounds.

Heel Wounds Predict Mortality but Not Amputation after Infrapopliteal Revascularization.

BACKGROUND: Ischemic heel ulcerations are generally thought to carry a poor prognosis for limb salvage. We hypothesized that patients undergoing infrapopliteal revascularization for heel wounds, either bypass or endovascular intervention, would have lower wound healing rates and amputation-free survival (AFS) than patients with forefoot wounds. METHODS: A retrospective chart review was performed on patients who presented between 2006 and 2013 to our institution with ischemic foot wounds and infrapopliteal arterial disease and underwent either pedal bypass or endovascular tibial artery intervention. Data were collected on patient demographics, comorbidities, wound characteristics, procedural details, and postoperative outcomes then analyzed by initial wound classification. The primary outcome was major amputation or death. RESULTS: Three hundred ninety-eight limbs underwent treatment for foot wounds; accurate wound data were available in 380 cases. There were 101 bypasses and 279 endovascular interventions, with mean follow-up of 24.6 and 19.9 months, respectively (P = 0.02). Heel wounds comprised 12.1% of the total with the remainder being forefoot wounds; there was no difference in treatment modality by wound type (P = 0.94). Of 46 heel wounds, 5 (10.9%) had clinical or radiographic evidence of calcaneal osteomyelitis. Patients with heel wounds were more likely to have diabetes mellitus (DM) (P = 0.03) and renal insufficiency (P = 0.004). 43.1% of wounds healed within 1 year, with no difference by wound location (P = 0.30). Major amputation rate at 1 year was 17.8%, with no difference by wound location (P = 0.81) or treatment type (P = 0.33). One- and 3-year AFS was 66.2% and 44.0% for forefoot wounds and 45.7% and 17.6% for heel wounds, respectively (P = 0.001). In a multivariate analysis, heel wounds and endovascular intervention were both predictors of death; however, there was significant interaction such that endovascular intervention was associated with higher mortality in patients with forefoot wounds (hazard ratio 2.25, P < 0.001) but not those with heel wounds (hazard ratio 0.67, P = 0.31). CONCLUSIONS: Patients presenting with heel ulceration who undergo infrapopliteal revascularization are prone to higher mortality despite equivalent rates of amputation and wound healing and regardless of treatment modality. These patients may benefit from an endovascular-first strategy.

Comparative effectiveness of anticoagulation on midterm infrainguinal bypass graft patency.

OBJECTIVE: Therapeutic anticoagulation (AC) is used clinically for prolongation of infrainguinal bypass patency, but evidence for the efficacy of this practice is conflicting. The objective of our study was to determine the association of AC with bypass graft primary patency. METHODS: Clinical and comorbid data of patients undergoing infrainguinal bypass grafts to a below-knee target with at least 1 year of follow-up performed from 2003 to 2015 were obtained from the Society for Vascular Surgery Vascular Quality Initiative. Inverse propensity of treatment-weighted Cox regression was used to assess the effect of AC on patency in the total cohort while adjusting for clinical, operative, and comorbid differences between treatment groups. Subgroup analyses of distal targets and conduit type were performed. Perioperative complications were analyzed using propensity-weighted logistic regression. RESULTS: We identified 7612 bypass grafts with intact 1-year follow-up information from 2003 to 2015. The mean age was 67.5 ± 11.2 years; 30.5% (n = 2320) were female, and 28.6% (n = 2165) were discharged on therapeutic AC. The anticoagulated group had a higher rate of tibial, ankle, and pedal targets (52.1% [n = 1127] vs 47.6% [n = 2269]; P < .001), had a greater use of non-single-segment vein conduits (44.3% [n = 951] vs 26.5% [n = 1426]; P < .001), and was more likely to have had a previous ipsilateral bypass (27.2% [n = 589] vs 14.7% [n = 794]; P < .001) or stent (25.4% [n = 550] vs 20.9% [n = 1130]; P < .001). Estimated unadjusted primary patency was 70.8% ± 0.6% at 1 year and lower for anticoagulated bypasses (66.9% ± 1.2% vs 72.4% ± 0.7%; P < .001). Propensity-weighted analysis showed no significant association of AC with primary patency in the overall cohort (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.86-1.11; P = .8) but demonstrated a trend toward improvement of primary patency in those with a non-single-segment vein conduit to a below-knee popliteal target (HR, 0.85; 95% CI, 0.80-1.02; P = .09). AC was associated with significantly improved secondary patency in those with prosthetic bypass grafts (HR, 0.77; 95% CI, 0.62-0.96; P = .02) or prosthetic bypasses to an infrapopliteal target (HR, 0.72; 95% CI, 0.54-0.97; P = .02). Odds of postoperative wound complications were significantly higher in those receiving AC (odds ratio, 1.33; 95% CI, 1.11-1.61; P = .002). CONCLUSIONS: This study does not demonstrate a significant impact of therapeutic AC on primary patency for infrainguinal bypass grafts. Treatment with AC may benefit secondary patency in those with a prosthetic bypass, especially to an infrapopliteal target, but at an increased risk of postoperative wound complications.

Intersocietal Accreditation Commission Accreditation Status of Outpatient Cerebrovascular Testing Facilities Among Medicare Beneficiaries: The VALUE Study.

OBJECTIVES: Accreditation of cerebrovascular ultrasound laboratories by the Intersocietal Accreditation Commission (IAC) and equivalent organizations is supported by the Joint Commission certification of stroke centers. Limited information exists on the accreditation status and geographic distribution of cerebrovascular testing facilities in the United States. Our study objectives were to identify the proportion of IAC-accredited outpatient cerebrovascular testing facilities used by Medicare beneficiaries, describe their geographic distribution, and identify variations in cerebrovascular testing procedure types and volumes by accreditation status. METHODS: As part of the VALUE (Vascular Accreditation, Location, and Utilization Evaluation) Study, we examined the proportion of IAC-accredited facilities that conducted cerebrovascular testing in a 5% Centers for Medicare and Medicaid Services random Outpatient Limited Data Set in 2011 and investigated their geographic distribution using geocoding. RESULTS: Among 7327 outpatient facilities billing Medicare for cerebrovascular testing, only 22% (1640) were IAC accredited. The proportion of IAC-accredited cerebrovascular testing facilities varied by region (χ(2)[3] = 177.1; P < .0001), with 29%, 15%, 13%, and 10% located in the Northeast, South, Midwest, and West, respectively. However, of the total number of cerebrovascular outpatient procedures conducted in 2011 (38,555), 40% (15,410) were conducted in IAC-accredited facilities. Most cerebrovascular testing procedures were carotid duplex, with 40% of them conducted in IAC-accredited facilities. CONCLUSIONS: The proportion of facilities conducting outpatient cerebrovascular testing accredited by the IAC is low and varies by region. The growing number of certified stroke centers should be accompanied by more accredited outpatient vascular testing facilities, which could potentially improve the quality of stroke care.

Patients started on hemodialysis with tunneled dialysis catheter have similar survival after arteriovenous fistula and arteriovenous graft creation.

OBJECTIVE: Current guidelines suggest that arteriovenous fistula (AVF) is associated with survival advantage over arteriovenous graft (AVG). However, AVFs often require months to become functional, increasing tunneled dialysis catheter (TDC) use, which can erode the benefit of an AVF. We sought to compare survival in patients with end-stage renal disease after creation of an AVF or AVG in patients starting hemodialysis (HD) with a TDC and to identify patient populations that may benefit from preferential use of AVG over AVF. METHODS: Using U.S. Renal Data System databases, we identified incident HD patients in 2005 through 2008 and observed them through 2008. Initial access type and clinical variables including albumin levels were assessed using U.S. Renal Data System data collection forms. Attempts at AVF and AVG creation in patients who started HD through a TDC were identified by Current Procedural Terminology codes. We accounted for the effect of changes in access type by truncating follow-up when an additional AVF or AVG was performed. Survival curves were then constructed, and log-rank tests were used for pairwise survival comparisons, stratified by age. Multivariate analysis was performed with Cox proportional hazards regressions; variables were chosen using stepwise elimination. An interaction of access type and albumin level was detected, and Cox models using differing thresholds for albumin level were constructed. The primary outcome was survival. RESULTS: Among the 138,245 patients who started with a TDC and had complete records amenable for analysis, 22.8% underwent AVF creation (mean age ± standard deviation, 68.9 ± 12.5 years; 27.8% mortality at 1 year) and 7.6% underwent AVG placement (70.2 ± 12.0 years; 28.2% mortality) within 3 months of HD initiation; 69.6% remained with a TDC (63.2 ± 15.4 years; 33.8% mortality). In adjusted Cox proportional hazards regression, AVF creation is equivalent to AVG placement in terms of survival (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.93-1.02; P = .349). AVG placement is superior to continued TDC use (HR, 1.54; 95% CI, 1.48-1.61; P < .001). In patients older than 80 years with albumin levels >4.0 g/dL, AVF creation is associated with higher mortality hazard compared with AVG creation (HR, 1.22; 95% CI, 1.04-1.43; P = .013). CONCLUSIONS: For patients who start HD through a TDC, placement of an AVF and AVG is associated with similar mortality hazard. Further study is necessary to determine the ideal access for patients in whom the survival advantage of an AVF over an AVG is uncertain.

Management and outcomes of dialysis access-associated steal syndrome.

OBJECTIVE: Dialysis access-associated steal syndrome (DASS) complicates arteriovenous access surgery. We describe a 10-year experience with the surgical management of DASS. METHODS: DASS operations were retrospectively reviewed from July 2003 to July 2013 from a single academic institution. Demographics, symptoms, surgical details, and outcomes were collected. RESULTS: A total of 201 patients had 218 episodes of DASS. Mean age was 65 years, and 62% were women. DASS was caused by 175 arteriovenous fistulas (80%), 41 upper extremity prosthetic grafts (19%), and two thigh grafts (1%); 87% were brachial artery based. A portion (22%) were referred for DASS from outside practices. All patients had grade 2 (48%) or grade 3 (52%) DASS; 92% (185) were available for follow-up, with a median time to first follow-up of 23 days. Surgical procedures included ligation (73), distal revascularization with interval ligation (DRIL) (59), revision using distal inflow (RUDI) (21), banding (38), proximalization of arterial inflow (12), and distal radial artery ligation (13). There were no differences in preoperative comorbidities between treatment groups. The 30-day complications included continued steal, thrombosis, bleeding, infection, and mortality. Ligation and DRIL were performed most often for grade 3 steal. Ligation and banding were performed most acutely (median time to intervention after access creation of 39 and 24 days vs DRIL and RUDI at 97 and 100 days). Fistula preservation was 0% for ligation, 100% for DRIL, 95% for RUDI, and 89% for banding (P < .01). Improvement of symptoms ranged from 75% (banding) to 98% (DRIL) (P = .005). Women were less likely to have DRIL but more likely to have ligation (P = .001). Complications were highest in the banding (49%) and RUDI (37%) groups. Average mortality was 3.5%, with no significant differences among groups. During the study period, 3287 access procedures were performed, and access volume steadily increased (2003-2008, 1312 access creations; 2008-2013, 1975). Percentage of fistulas (79% vs 86%), incidence of steal (4% vs 6%), and percentage of DRILs (25% vs 28%) were consistent across the two study periods. CONCLUSIONS: DRIL and ligation were performed in patients with the most severe symptoms. Compared with ligation, DRIL has equal symptom resolution, no increase in complications, and fistula preservation. Compared with banding, DRIL resulted in superior fistula preservation and fewer complications. DRIL should be considered the preferred procedure for management of DASS in patients with a functioning autologous fistula who can tolerate a major operation.

Autologous alternative veins may not provide better outcomes than prosthetic conduits for below-knee bypass when great saphenous vein is unavailable.

BACKGROUND: There is a need to better define the role of alternative autologous vein (AAV) segments over contemporary prosthetic conduits in patients with critical limb ischemia when great saphenous vein (GSV) is not available for use as the bypass conduit. METHODS: Consecutive patients who underwent bypass to infrageniculate targets between 2007 and 2011 were categorized in three groups: GSV, AAV, and prosthetic. The primary outcome was graft patency. The secondary outcome was limb salvage. Cox proportional hazards regression was used to adjust for baseline confounding variables. RESULTS: A total of 407 infrainguinal bypasses to below-knee targets were analyzed; 255 patients (63%) received a single-segment GSV, 106 patients (26%) received an AAV, and 46 patients (11%) received a prosthetic conduit. Baseline characteristics were similar among groups, with the exception of popliteal targets and anticoagulation use being more frequent in the prosthetic group. Primary patency at 2 and 5 years was estimated at 47% and 32%, respectively, for the GSV group; 24% and 23% for the AAV group; and 43% and 38% for the prosthetic group. Primary assisted patency at 2 and 5 years was estimated at 71% and 55%, respectively, for the GSV group; 53% and 51% for the AAV group; and 45% and 40% for the prosthetic group. Secondary patency at 2 and 5 years was estimated at 75% and 60%, respectively, for the GSV group; 57% and 55% for the AAV group; and 46% and 41% for the prosthetic group. In Cox analysis, primary patency (hazard ratio [HR], 0.55; P < .001; 95% confidence interval [CI], 0.404-0.758), primary assisted patency (HR, 0.57; P = .004; 95% CI, 0.388-0.831), and secondary patency (HR, 0.56; P = .005; 95% CI, 0.372-0.840) were predicted by GSV compared with AAV, but there was no difference between AAV and prosthetic grafts except for the primary patency, for which prosthetic was protective (HR, 0.38; P < .001; 95% CI, 0.224-0.629). Limb salvage was similar among groups. CONCLUSIONS: AAV conduits may not offer a significant patency advantage in midterm follow-up over prosthetic bypasses.

Arteriovenous grafts are associated with earlier catheter removal and fewer catheter days in the United States Renal Data System population.

OBJECTIVE: Arteriovenous fistulas (AVFs) are associated with improved long-term outcomes but longer maturation times and higher primary failure rates compared with arteriovenous grafts (AVGs). The Fistula First Breakthrough Initiative has recently emphasized tunneled dialysis catheter (TDC) avoidance. We sought to characterize the relationship of AVFs and AVGs to the use of TDCs as well as secondary procedures. METHODS: Using the United States Renal Data System (USRDS) database, we identified incident hemodialysis (HD) patients in 2005 that started HD with a TDC and survived at least 1 year. We then monitored them through 2008. Access creation, TDC removal, TDC placement, and secondary procedures were identified by Current Procedural Terminology codes (American Medical Association, Chicago, Ill). Multivariate logistic regression was used to identify risk factors for the primary end points. RESULTS: In 2005, HD was initiated in 56,495 patients, 74% with a TDC. Of these, 6286 had an access procedure ≤3 months and 1 year of follow-up (AVF, 4634; AVG, 1652). Mean age was 67.7 years (AVF, 67.3; AVG, 68.7 years; P < .001), 53.3% were men (AVF, 58.1%; AVG, 40.5%; P < .001), and 33.8% were obese (AVF, 33.6%; AVG, 34.4%; P = not significant). AVG placement was associated with a higher TDC removal at 1 (7.9% vs 3.1%; P < .001), 3 (47.8% vs 17.8%; P < .001), and 6 (60.6% vs 47.2%; P < .001) months. There was no difference at 9 months (AVG, 64.9% vs AVF, 62.3%; P = .06). The median time to TDC removal was lower in the AVG group (70 days vs 155 days; P < .001). Multivariable model found AVFs were associated with decreased odds of TDC removal at 3 (odds ratio, 0.22; P < .001) and 6 months (odds ratio, 0.54; P < .001). AVGs required more secondary procedures than AVFs at all time points up to 1 year and specifically had increased thrombectomy procedures (39.8% vs 11.5%; P < .001). CONCLUSIONS: In patients starting dialysis with a TDC, AVGs are associated with increased TDC removal and fewer catheter days compared with AVFs at up to 6 months. However, AVGs require more secondary procedures at all time points up to 1 year.

Endovascular strategies for treatment of embolizing thoracoabdominal aortic lesions.

OBJECTIVE: Aortic sources of peripheral and visceral embolization remain challenging to treat. The safety of stent graft coverage continues to be debated. This study reports the outcomes of stent coverage of these complex lesions. METHODS: Hospital records were retrospectively reviewed for patients undergoing aortic stenting between 2006 and 2013 for visceral and peripheral embolic disease. Renal function, method of coverage, and mortality after stent grafting were reviewed. RESULTS: Twenty-five cases of embolizing aortic lesions treated with an endovascular approach were identified. The mean age was 65 ± 13 years (range, 45-87 years), and 64% were female. Sixteen (64%) patients presented with peripheral embolic events, six with concomitant renal embolization. Five patients presented with abdominal or flank pain, and two were discovered incidentally. Three patients had undergone an endovascular procedure for other indications within the preceding 6 months of presentation. Nineteen patients had existing chronic kidney disease (stage II or higher), but only three had stage IV disease. Of the eight patients tested, four had a diagnosed hypercoagulable state. Eight of the patients had lesions identified in multiple aortic segments, and aortic aneurysm disease was present in 24%. Coverage of both abdominal and thoracic sources occurred in eight patients, whereas 17 had only one segment covered. Minimal intraluminal catheter and wire manipulation was paired with the use of intravascular ultrasound in an effort to reduce embolization and contrast use. Intravascular ultrasound was used in the majority of cases and transesophageal echo in 28% of patients. Two patients with stage IV kidney disease became dialysis-dependent within 3 months of the procedure. No other patients had an increase in their postoperative or predischarge serum creatinine levels. No embolic events were precipitated during the procedure, nor were there any recurrent embolic events detected on follow-up. The 1-year mortality rate was 25%. CONCLUSIONS: Endovascular coverage of atheroembolic sources in the aorta is feasible and is safe and effective in properly selected patients. It does not appear to worsen renal function when performed with the use of specific technical strategies.

Endoscopic versus open saphenous vein graft harvest for lower extremity bypass in critical limb ischemia.

OBJECTIVE: Endoscopic vein harvest (EVH) has been demonstrated to improve early morbidity when compared with conventional open vein harvest (OVH) technique for infrainguinal bypass surgery. However, recent literature suggests conflicting results regarding mid- and long-term patency with EVH. The purpose of this study is to compare graft patency between harvest techniques specifically in patients with critical limb ischemia. METHODS: This retrospective study compared two groups of patients (EVH = 39 and OVH = 49) undergoing lower extremity revascularization from January 2009 to December 2011. Outcome measures included patency rates, postoperative complications, and wound infection. Graft patency was assessed using Kaplan-Meier curves. RESULTS: Both groups were matched for demographics and indications for bypass (critical limb ischemia). Median follow-up was 22 months. There was a significant reduction in the incidence of wound infection at the vein harvest site in the EVH group (OVH = 20%; EVH = 0%; P < .001), nevertheless, the difference was not significant when only the anastomotic sites were included (OVH = 12.2%; EVH = 15.4%; P = .43). The hospital length of stay was comparable between the two groups (EVH = 8.73 ± 9.69; OVH = 6.35 ± 3.28; P = .26) with no significant difference in the recovery time. Primary graft patency rate was 43.2% in the EVH group and 69.4% in the OVH group (P = .007) at 3 years. The most common reason for loss of primary patency was graft occlusion (61.5%) in the OVH group and vein graft stenosis (54.5%) in the EVH group. The average number of vascular reinterventions per bypass graft was significantly lower in the OVH group compared with the EVH group (OVH = 0.37; EVH = 1.28; P < .001). CONCLUSIONS: Our findings demonstrate inferior primary patency when using the technique of EVH. Additionally, we identified a significantly higher rate of reintervention in the EVH cohort as well as a higher rate of vein graft body stenosis. However, EVH was associated with a decreased rate of wound complications with similar limb salvage and secondary patency rates when compared to OVH. EVH should therefore be selectively utilized in patients at high risk for wound complications.

Accreditation status and geographic location of outpatient vascular testing facilities among Medicare beneficiaries: the VALUE (Vascular Accreditation, Location & Utilization Evaluation) study.

OBJECTIVE: There is limited information on the accreditation status and geographic distribution of vascular testing facilities in the US. The Centers for Medicare & Medicaid Services (CMS) provide reimbursement to facilities regardless of accreditation status. The aims were to: (1) identify the proportion of Intersocietal Accreditation Commission (IAC) accredited vascular testing facilities in a 5% random national sample of Medicare beneficiaries receiving outpatient vascular testing services; (2) describe the geographic distribution of these facilities. METHODS: The VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study examines the proportion of IAC accredited facilities providing vascular testing procedures nationally, and the geographic distribution and utilization of these facilities. The data set containing all facilities that billed Medicare for outpatient vascular testing services in 2011 (5% CMS Outpatient Limited Data Set (LDS) file) was examined, and locations of outpatient vascular testing facilities were obtained from the 2011 CMS/Medicare Provider of Services (POS) file. RESULTS: Of 13,462 total vascular testing facilities billing Medicare for vascular testing procedures in a 5% random Outpatient LDS for the US in 2011, 13% (n=1730) of facilities were IAC accredited. The percentage of IAC accredited vascular testing facilities in the LDS file varied significantly by US region, p<0.0001: 26%, 12%, 11%, and 7% for the Northeast, South, Midwest, and Western regions, respectively. CONCLUSIONS: Findings suggest that the proportion of outpatient vascular testing facilities that are IAC accredited is low and varies by region. Increasing the number of accredited vascular testing facilities to improve test quality is a hypothesis that should be tested in future research.

SATB2, coordinated with CUX1, regulates IL-1ß-induced senescence-like phenotype in endothelial cells by fine-tuning the atherosclerosis-associated p16INK4a expression.

Genome-wide association studies (GWAS) have validated a strong association of atherosclerosis with the CDKN2A/B locus, a locus harboring three tumor suppressor genes: p14ARF , p15INK4b , and p16INK4a . Post-GWAS functional analysis reveals that CUX is a transcriptional activator of p16INK4a via its specific binding to a functional SNP (fSNP) rs1537371 on the atherosclerosis-associated CDKN2A/B locus, regulating endothelial senescence. In this work, we characterize SATB2, another transcription factor that specifically binds to rs1537371. We demonstrate that even though both CUX1 and SATB2 are the homeodomain transcription factors, unlike CUX1, SATB2 is a transcriptional suppressor of p16INK4a and overexpression of SATB2 competes with CUX1 for its binding to rs1537371, which inhibits p16INK4a and p16INK4a -dependent cellular senescence in human endothelial cells (ECs). Surprisingly, we discovered that SATB2 expression is transcriptionally repressed by CUX1. Therefore, upregulation of CUX1 inhibits SATB2 expression, which enhances the binding of CUX1 to rs1537371 and subsequently fine-tunes p16INK4a expression. Remarkably, we also demonstrate that IL-1ß, a senescence-associated secretory phenotype (SASP) gene itself and a biomarker for atherosclerosis, induces cellular senescence also by upregulating CUX1 and/or downregulating SATB2 in human ECs. A model is proposed to reconcile our findings showing how both primary and secondary senescence are activated via the atherosclerosis-associated p16INK4a expression.

Impact of endovascular options on lower extremity revascularization in young patients.

OBJECTIVE: This study assessed outcomes of revascularization strategies in young patients with premature arterial disease. METHODS: Lower extremity revascularization outcomes from 2000 to 2008 were retrospectively compared among consecutive patients with comparable indications and procedures: age <50 years (group A) at the time of revascularization, 51 to 60 years (group B), and >60 years (control group C). Patency, limb salvage, and survival by limb or patient level were assessed by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: A total of 409 limbs in 298 patients were treated: 44% for claudication and 56% for critical limb ischemia (CLI). Group A patients were more likely to be smokers and have a hypercoagulable state but less likely to have diabetes and renal failure. Treatment indications were comparable among groups, and procedures were equally distributed between open surgical and endovascular interventions. Two perioperative deaths occurred in group C (2%). Mean follow-up was 29 months, and 16% of claudicant patients in group A progressed to CLI (B, 3%; C, 2%; P < .001). Overall, 2-year primary, primary assisted, and secondary patency were significantly lower in group A (50.5%, 65.2%, 68.2%; P = .045) vs B (65.7%, 81.4%, 86.8%; P = .01) and C (57.9%, 78.9%, 83.9%; P < .001). Claudicant patients in group A had an unexpectedly low 2-year freedom from major amputation after intervention of only 90%. Results were more comparable across groups for CLI. The 2-year freedom from reintervention was similar (A, 81.0%; B, 78.9%; C, 83.5%), irrespective of the indication for intervention (P = .60). Younger patients had a significantly higher 3-year survival (A, 89.5%; B, 85.3%) compared with patients aged >60 years (C, 71.4%; P = .005). The 2-year freedom from major amputation rate was significantly lower in claudicant patients in group A vs C undergoing endovascular revascularization (P = .002), but not in patients treated with open revascularization (P = .40). Predictors of loss of primary patency included age <50 years (P = .003), endovascular revascularization (P = .005), and progression from claudication to CLI (P < .001). Age <50 years was also an independent predictor of limb loss vs age >60 years (P = .05). CONCLUSIONS: Endovascular options are commonly being used in young patients, especially those with claudication, but patency rates and outcomes remain very poor.

Treatment strategies of arterial steal after arteriovenous access.

INTRODUCTION: Ischemic steal syndrome (ISS) associated with arteriovenous (AV) access is rare but can result in severe complications. Multiple techniques have been described to treat ISS with varying degrees of success. This study compares the management and success associated with these techniques. METHODS: Patients with ISS between June 2003 and June of 2008 at the University of Pittsburgh Medical Center were retrospectively reviewed. Demographics, type of AV access, management technique, and success of intervention were recorded. Success was defined as resolution of ISS symptoms while preserving access function. One hundred consecutive AV access procedures were reviewed for comparison. Data were analyzed using χ(2) test, Fisher's exact test, and Student's t test. The study was approved by our institutional review board. RESULTS: A total of 114 patients with ISS had a mean age of 65 years (range, 20-90 years), were predominantly female (66%), diabetic (61%), and with a brachial origin fistula (69%). Risk factors for ISS included coronary artery disease (CAD; P < .001), hypertension (P < .001), and tobacco use (P = .048). Women were noted to have a brachial origin access more frequently than men (odds ratio [OR], 3.1; P = .009). Forty-four patients with mild steal were observed. Seventy patients underwent 87 procedures. Procedures performed included ligation (n = 27), banding (n = 22), distal revascularization and interval ligation (DRIL; n = 21), improvement of proximal inflow (n = 9), revision using distal inflow (RUDI; n = 4), and proximalization of arterial inflow (PAI; n = 3). Early procedures (<30 days from the index fistula) were mostly ligation (50%) or banding (38%), while DRIL was the most frequent choice for late interventions (41%). Banding had a high failure rate (62%) and was the most common reason for reintervention (8 of 11, 73%) and DRIL had a better success rate than banding (P ≤ .05). In our current practice, 18% of patients had an AV fistula with the proximal radial artery (PRA) as the inflow source, while this type of fistula accounted for only 2% of all ISS patients. Ligation resolved symptoms in all patients, but the AV access was lost. CONCLUSIONS: Risk factors for development of ISS include CAD, diabetes, female gender, hypertension, and tobacco use. Among various options to treat ISS, banding has a low success rate and high likelihood for reintervention, while DRIL is particularly effective although not uniformly. Less invasive treatment options such as RUDI and PAI may be quite effective in treating ISS. Use of the PRA as the inflow source may decrease the incidence of ISS.

The impact of a systemwide policy for emergent off-hours venous duplex ultrasound studies.

BACKGROUND: We evaluated the impact of an after-hours policy regulating venous duplex ultrasound (VDU) for deep vein thrombosis (DVT) diagnosis on resource utilization and patient care. METHODS: On July 1, 2007, we altered the approach to emergent VDU of patients with potential DVT during off-hours (defined as 5:00 p.m. to 7:00 a.m. weekdays, after 3:30 p.m. Saturdays and Sundays). Instead of 24 hr access, we permitted a venous duplex study in the noninvasive vascular laboratory (NIVL) only after meeting set criteria developed collaboratively across services. In the emergency department (ED), we based all VDU requests on a preset modified Wells score (MWS) as determined by the ED physician. Those patients with MWS 0 or 1 and those above 1 who could receive empiric single-dose low-molecular weight heparin (LMWH) received next-morning imaging unless consultation with a vascular surgeon created an emergent imaging plan. In parallel, inpatient emergent VDU was permitted only after contact with an attending vascular surgeon and where empiric short-term anticoagulation could not occur safely. We tracked NIVL utilization, patient morbidity, sonographer retention, and satisfaction. RESULTS: The number of overall off-hours emergent VDUs decreased from 59 to 19/month after implementation. Testing was deferred in 52 ED patients: 15 stayed in the ED for testing in the morning and 37 were discharged to be tested the following day. Thirty-one of 37 patients returned for testing as outpatient follow-up. Twenty-eight received ED LMWH while awaiting testing. No adverse events were noted with the delay. The mean MWS for ED after-hours studies was 2.9+/-1.6 and that for deferred ER studies was 2.4+/-1.3 (p=0.005). Incidentally, overall off-hours inpatient and ED VDU requests decreased 64% with no clinical adverse events in the first year. The rate of overall positive studies done off-hours increased from 6.7% to 20% (p<0.0001). Sonographer satisfaction was maintained with regulation of call. CONCLUSION: Our collaborative approach allowed off-hour VDU utilization to decrease without any measurable negative care impact.