A novel, nonopiod-based treatment approach to men with urologic chronic pelvic pain syndrome using ultrasound-guided nerve hydrodissection and pelvic floor musculature trigger point injections.

INTRODUCTION: Urological chronic pelvic pain syndrome (UCPPS) represents a group of pain symptoms relating to patients with pelvic pain for which treatment is largely unsatisfactory. The objective of this study is to analyze the effects of a novel treatment strategy in males suffering from UCPPS. METHODS: This retrospective, institutional review board-approved study analyzed eight male patients aged 24 to 61 with UCPPS. All the patients had a trial of antibiotic therapy, NSAIDs, and pelvic floor physical therapy before the study. The Visual Analog scale (VAS) and Functional Pelvic Pain scale (FPPS) were collected pretreatment. While continuing physical therapy, patients underwent weekly ultrasound-guided pelvic floor trigger point injections to the iliococcygeus, pubococcygeus, and puborectalis with lidocaine 1%. Concomitantly, patients received peripheral nerve hydrodissection performed on the pudendal nerve and the posterior femoral cutaneous nerve. The first two injections combined 1% lidocaine with dexamethasone, while the next four injections consisted of 1% lidocaine with traumeel (a homeopathic, plant-derived anti-inflammatory medication). At the 6-week follow-up, each patient retook the VAS and FPPS. RESULTS: The mean age of our patients was 31.8 years and the average duration of symptoms of the UCPPS was 21 months. Pretreatment, the mean VAS was 3.3 (STD 1.7) and the mean VAS posttreatment was 1.8 (STD 1.4); P < .05; 95% CI, 0.73 to 2.27. The mean FPPS pretreatment was 11.0 (STD 8.0) and the mean FPPS posttreatment was 6.3 (STD 5.3); P < .05; 95% CI, 0.03 to 9.22. CONCLUSION: Our results show promise for a novel, nonopioid-based treatment for UCPPS.

Stent exteriorization facilitates surgical repair for large-bore sheath complications.

Endovascular therapy for peripheral vascular and valvular disease has rapidly expanded and yet also produced new challenges for vascular access and closure. Current generation thoracic endograft (TEVAR) outer diameter sheath sizes range from 18 to 25 French, and the options for vascular access closure include off-label use of a closure device versus surgical cutdown. We describe a patient with a complex, post-dissection, descending aortic aneurysm who required TEVAR and had a vascular access complication repaired with stent exteriorization with open repair.

The burden of Chronic Pelvic Pain (CPP): Costs and quality of life of women and men with CPP treated in outpatient referral centers.

INTRODUCTION: Chronic Pelvic Pain (CPP) is a complex, multifaceted condition that affects both women and men. There is limited literature on the cost utilization the healthcare system and CPP patients incur. The purpose of this analysis is to characterize the overall healthcare utilization, cost burden, and quality-of-life restrictions experienced by CPP patients using data from an outpatient pelvic rehabilitation practice. METHODS: Healthcare utilization data was gathered by systematically reviewing and analyzing data from new patient visit progress notes stored in the clinic's electronic health records (EHR). We obtained in-network costs by using the FAIR Health Consumer online database. Overall costs were then calculated as the utilization times the per-unit costs from the FAIR database. Additionally, data on patients' visual analogue scale (VAS), absenteeism, presenteeism emergency room visits, usage of common pain medications, use of diagnostics, and participation in common treatment modalities was gathered. RESULTS: Data from 607 patients was used. The overall cost burden per patient for all surgeries combined was $15,750 for in-network services. The cost burden for diagnostics was $5,264.22 and treatments was $8,937 per patient for in-network treatments. CONCLUSION: Chronic Pelvic Pain was found to have a large cost burden of $29,951 for in-network services which includes treatments, diagnostics, and surgeries. This analysis sets the stage for future investigations involving data on costs of medications that patients have tried prior to presenting to us and costs associated with work hours lost.

Heart failure is associated with reduced patency after endovascular intervention for symptomatic peripheral arterial disease.

OBJECTIVE: Congestive heart failure (CHF) is a highly prevalent comorbidity among patients with symptomatic peripheral arterial disease. The effect of CHF on the procedural success of endovascular treatment, however, remains unknown. Theoretically, poor inflow secondary to systolic dysfunction and peripheral vascular alterations may predispose endovascular interventions to failure. METHODS: A retrospective review of a prospectively maintained database was performed to identify CHF patients undergoing endovascular peripheral arterial intervention from 2004 to 2009. Demographics, comorbidities, procedural details, and outcomes were analyzed. Patients underwent duplex ultrasound imaging and clinical follow-up at scheduled intervals. Kaplan-Meier and Cox proportional hazards models were used to evaluate risk factors for loss of primary patency, secondary patency, and limb salvage. RESULTS: Of 1220 patients undergoing intervention, 271 (22%) with documented congestive heart failure (CHF) underwent an intervention for claudication (22.5%) or critical limb ischemia (77.5%). Primary patency at 1 year was 51.9% ± 2.5% among those with CHF vs 64.6% ± 1.3% in those without CHF (P < .001); this disparity continued throughout follow-up (P < .001). Patients with CHF also had reduced secondary patency throughout follow-up. Multivariate analysis showed CHF was an independent predictor of reduced primary patency (hazard ratio [HR], 1.2; 95% confidence interval [CI] 1.0-1.4; P = .038) and secondary patency (HR, 1.5; 95% CI, 1.2-1.8; P < .001). In the setting of CHF, 1-year patency was 56.6% ± 4.1% if the ejection fraction (EF) was >40% (n = 147) vs 43.2% ± 3.5% if the EF was <40% (n = 124; P < .001). Secondary patency was also significantly reduced in patients with EF <40% throughout follow-up compared with patients without CHF (n = 949) as well as those with CHF and EF >40% (P < .001). CHF with EF <40% was an independent predictor of reduced primary patency (HR, 1.4; 95% CI, 1.2-1.8; P < .01) and secondary patency (HR, 1.8; 95% CI, 1.3-2.3; P < .001). Limb salvage was also worse in patients with EF <40% (P = .038). CONCLUSIONS: CHF is associated with reduced patency after peripheral endovascular intervention and is an independent risk factor for patency loss. Specifically, CHF and reduced EF (<40%) is a strong independent risk factor for patency loss.

Midterm outcomes after treatment of type II endoleaks associated with aneurysm sac expansion.

PURPOSE: To examine the outcomes following interventions for type II endoleaks in patients with aneurysm sac expansion after endovascular aneurysm repair (EVAR). METHODS: A retrospective review was conducted of all patients who underwent treatment for type II endoleak from July 2001 to September 2010 in a single center. In this time period, 29 (4.7%) patients (22 men; mean age 78.6 years, range 54-87) were identified as having a type II endoleak and enlargement of the aneurysm sac, meeting the criterion for treatment. All patients had at least one attempted percutaneous intervention. Patients were followed both clinically and radiographically, with computed tomographic angiography every 3 to 12 months, over a follow-up period that ranged from 1 to 10 years (mean 3.5). RESULTS: Forty-eight interventions were performed on the 29 patients. Of these, 15 (56%) patients underwent multiple (2-4) procedures. Of the 11 endoleaks with an isolated inferior mesenteric artery identified as the source, initial success for transarterial embolization at 2 years was 72%, with 2 of the failures having successful secondary interventions. For the 18 endoleaks with a lumbar source, the success of the initial intervention was 17% at 2 years; repeated embolization attempts produced a 40% secondary success rate. Seven (24%) patients had continued endoleak despite multiple treatment attempts; 3 ultimately required elective aortic graft explantation. There were no ruptures or deaths during the study period. In a comparison of type II endoleak patients who had stable aneurysm sacs and those who had persistent sac expansion, the only significant differences in preoperative anatomical characteristics were a lower prevalence of mural thrombus (p = 0.036) and longer right iliac arteries (p = 0.012) in the group with sac expansion. Independent predictors of type II endoleak were mural thrombus (p<0.001), patent lumbar arteries (p = 0.004), aneurysm length (p = 0.011), and iliac artery length (p = 0.004). CONCLUSION: This study demonstrates that most patients require multiple reinterventions to treat type II endoleaks; specifically, lumbar artery embolization carries a low midterm success rate.

Endovascular management of superior mesenteric artery pseudoaneurysm.

A 31-year-old man underwent a Whipple procedure for a pancreatic neuroendocrine tumor, which consists of a pancreaticoduodenectomy and reconstruction to restore intestinal continuity. Six weeks after the operation, he presented with severe mid-epigastric pain radiating to his back. Imaging studies revealed a large pseudoaneurysm arising from the superior mesenteric artery. Selective superior mesenteric angiography confirmed the presence of the pseudoaneurysm. A 6 mm × 2.5 cm stent graft (Viabhan; W.L. Gore, Flagstaff, Ariz) was deployed across the pseudoaneurysm origin with preservation of the mesenteric branches. The patient had immediate resolution of symptoms and follow-up imaging showed patency of the stent graft and exclusion of the pseudoaneurysm.

Lesion types and device characteristics that predict distal embolization during percutaneous lower extremity interventions.

OBJECTIVE: Distal embolization (DE) during percutaneous lower extremity revascularization (LER) may cause severe clinical sequelae. To better define DE, we investigated which lesion types and treatment modalities increase the risk for embolization. METHODS: A prospective registry of LER from 2004 to 2009 was reviewed. All cases with runoff evaluated before and after intervention were included. Angiograms and operative reports were reviewed for evidence of DE. Interventions included percutaneous transluminal angioplasty (PTA), with or without stent placement, and atherectomy with four different devices. Chi-square analysis and Fisher's exact test were used to assess significance. Patency rates were calculated using Kaplan-Meier analysis and compared using log-rank analysis. RESULTS: There were 2137 lesions treated in 1029 patients. The embolization rate was 1.6% (34 events). Jetstream (Pathway, Kirkland, Wash) and DiamondBack 360 (Cardiovascular Systems Inc, St Paul Minn) devices had a combined embolization rate of 22% (8 of 36), 4 of 18 (22%) in each group, which was significantly higher than with PTA alone (5 of 570, 0.9%), PTA and stent (5 of 740, 0.7%), SilverHawk (ev3, Plymouth, Minn) atherectomy (14 of 736, 1.9%), and laser atherectomy (2 of 55, 3.6%; P < .001). There was a significantly higher rate of embolization for in-stent restenosis (6 of 188, 3.2%) and chronic total occlusions (15 of 615, 2.4%) compared with stenotic lesions (13 of 1334, 0.9%; P = .01). The embolization rate was significantly higher in Transatlantic Inter-Society Consensus (TASC) II C and D lesions compared with TASC A and B lesions (P = .018). DE rates were not affected by preoperative runoff status (P = .152). Patency was restored at the completion of the procedure in 32 of 34 cases of DE. The 24-month primary patency, assisted primary patency, and secondary patency in the DE group was 54.0% ± 11.9%, 70.0% ± 10.3%, and 73.2% ± 10.3%, respectively, and was 44.4% ± 1.7%, 61.5% ± 1.7%, and 68.2% ± 1.6%, respectively, when embolization did not occur (P > .05). Limb salvage was 72.6% ± 3.1% in lesions in which no DE occurred vs 83.3% ± 15.2% in lesions in which DE occurred (P = .699). CONCLUSIONS: DE is a rare event that occurs more often with the Jetstream and DiamondBack 360 devices. In-stent and complex native lesions are at higher risk for DE. DE is typically reversible with endovascular techniques and has no effect on patency rates and limb salvage.

Endovascular management as first therapy for chronic total occlusion of the lower extremity arteries: comparison of balloon angioplasty, stenting, and directional atherectomy.

PURPOSE: To evaluate the role of endovascular therapy in the management of infrainguinal arterial chronic total occlusions (CTOs). METHODS: Data on all patients with CTOs treated at a single center from 2004 to 2010 were extracted from a prospectively maintained database for retrospective analysis. Patient demographics, angiographic studies, noninvasive vascular test results, and clinical outcomes were evaluated. In this time frame, 481 patients (283 men; mean age 71.7±11.5 years, range 52-85) with claudication (n = 177) or critical limb ischemia (CLI, n = 304) were treated for 688 CTOs. Lesions were segregated according to location [SFA (n = 193), popliteal (n = 67), tibial (n = 217), and multilevel (n = 211)] and analyzed based on treatment mode (angioplasty, angioplasty with stenting, or atherectomy) and clinical indication. Primary patency, assisted primary patency, and secondary patency, as well as limb salvage rates for CLI patients, were calculated. RESULTS: At 2 years in claudicants with CTOs confined to the SFA, primary patency ranged from 44% to 58% and secondary patency to 92% depending on treatment type; there were no significant differences among the treatments. However, in CLI patients with SFA CTOs, atherectomy produced better outcomes at 2 years (p = 0.002 for primary and p = 0.012 for secondary patency) than angioplasty alone. The limb salvage rates ranged from 73% to 91% (no differences among treatment types). In diabetics, CTOs treated with angioplasty and stent had improved secondary patency rates over angioplasty alone. CONCLUSION: The endovascular management of CTO results in reasonable primary patency; moreover, secondary patency at 2 years is excellent. Endovascular therapy should be the first-line option for many patients with peripheral artery disease, including those with CLI, claudicants with poor bypass conduit, or patients at high medical risk for surgery. The presence of CTOs does not appear to change these recommendations. Although multiple reinterventions may be required, endovascular therapies can be considered a primary therapy for many patients with CTO.

Endovascular management of type B aortic dissection after attempted central venous catheterization.

A 41-year-old woman, status postmastectomy for breast cancer had an attempted 8-F left subclavian vein chemotherapy port placed in her. She developed severe upper back pain radiating to the left shoulder. A computed tomographic scan and angiography revealed catheter placement in the left subclavian artery and a type B aortic dissection. A thoracic stent-graft was used to treat the aortic dissection. While removing the catheter, a covered stent was deployed to seal the arterial puncture and a balloon-expandable stent was placed over a persistent subclavian dissection. This case illustrates an example of the feasibility of endovascular management to treat serious iatrogenic access complications.

Determining criteria for predicting stenosis with ultrasound duplex after endovascular intervention in infrainguinal lesions.

BACKGROUND: Studies examining duplex surveillance of lower extremity bypass grafts have defined a role for guiding graft re-intervention. The goal of this study is to determine the utility of duplex scanning to detect angiographic restenosis after endovascular therapy in patients with infrainguinal arterial disease. METHODS: A prospective registry including all patients treated for lower extremity atherosclerotic disease between February 2004 and September 2008 was established. Patients were followed up with duplex ultrasound at 1, 3, 6, 12 months, and then annually. Patients receiving repeat angiograms were identified and angiogram and duplex data were abstracted. Velocity ratios (Vr) were calculated for each lesion by dividing the peak velocity within the lesion by the peak velocity proximal to the lesion. Logarithmic regression and receiver operator characteristic (ROC) curve analyses were used. RESULTS: Repeat angiograms were performed on 345 lesions in 143 patients, and 254 lesions in 103 patients had a corresponding duplex ultrasound. Indications for the initial intervention were claudication (n = 62, 43.4%), rest pain (n = 23, 16.1%), and tissue loss (n = 58, 40.5%). A total of 178 superficial femoral artery (SFA) lesions, 59 popliteal lesions, and 17 tibial lesions were identified by surveillance duplex in 103 patients. In all, 70.5% of the intervened vessels that were studied were nonstented and the remaining 29.5% were stented. A total of 65% of the patients had diabetes. On determining correlations for peak systolic velocity (PSV) as measured by duplex ultrasound with degree of angiographic stenosis, strong correlation coefficients for SFA disease (R² = 0.84) and popliteal disease (R² = 0.88) were found. However, poor correlation was found in patients with tibial disease. When analyzing the lesions on the basis of Vr < 2.0, 11 of 86 (12.8%) had >70% angiographic stenosis. In lesions with ratios from 2 to 2.5, 12 of 13 (92.3%) had >70% angiographic stenosis and in lesions with ratios >2.5, 69 of 75 (92.0%) had >70% angiographic stenosis. ROC curve analysis showed that to detect ≥ 70% stenosis in the SFA, a PSV ≥ 204 cm/sec had a sensitivity of 97.6% and specificity of 94.7%. To detect ≥ 70% stenosis in the overall femoropopliteal region, a PSV ≥ 223 cm/sec had a sensitivity of 94.1% and specificity of 95.2%. CONCLUSIONS: Duplex ultrasound surveillance correlates to the degree of angiographic stenosis on the basis of PSV in the SFA and popliteal region. Correlation in the tibial vessels is poor. Vr > 2.0 appear to correlate to angiographic stenosis of > 70%. ROC analysis shows that PSV can have sufficiently high sensitivity and specificity to predict angiographic stenosis in the femoropopliteal region.

Delayed permanent paraplegia after endovascular repair of abdominal aortic aneurysm.

Spinal cord ischemia is a rare complication after abdominal aortic surgery and has been attributed to surgical devascularization of the spinal cord, atheroembolization of the cord circulation, or hypoperfusion of cord structures secondary to hypotension or cord edema. We present a diabetic, hypertensive 75-year-old male with endstage renal disease who presented with a 5.5 cm asymptomatic infrarenal abdominal aortic aneurysm, and concomitant 3.5 cm right common iliac artery aneurysm. After undergoing successful endovascular repair with an aorto-uni-iliac device, unilateral hypogastric artery embolization, and femoral-femoral bypass, he was discharged to a rehabilitation facility neurologically intact with a stage 2 decubitus ulcer. He returned on postoperative day 21 with a large stage 4 septic decubitus ulcer, fever, leukocytosis, hypotension, and paraplegia. We hypothesize that the compromised blood flow from the initial reconstruction, combined with the delayed hypotension imposed by sepsis, resulted in spinal cord infarction. He was eventually discharged to a nursing facility with no improvement in his neurologic status. We report the first case of significantly delayed permanent paraplegia after endovascular abdominal aortic aneurysmorrhaphy.

MARCKS silencing differentially affects human vascular smooth muscle and endothelial cell phenotypes to inhibit neointimal hyperplasia in saphenous vein.

Intimal hyperplasia (IH) limits the patency of all cardiovascular vein bypass grafts. We previously found the myristoylated alanine-rich C kinase substrate (MARCKS), a key protein kinase C (PKC) substrate, to be up-regulated in canine models of IH. Here, we further characterize the role of MARCKS in IH and examine the phenotypic consequences of MARCKS silencing by small interfering RNA (siRNA) transfection in human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) in vitro and use a rapid 10-min nonviral siRNA transfection technique to determine the effects of MARCKS silencing in human saphenous vein cultured ex vivo. We demonstrate MARCKS silencing attenuates VSMC migration and arrests VSMC proliferation in part through the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1). Conversely, MARCKS silencing had little or no effect on EC migration or proliferation. These phenotypic changes culminated in reduced neointimal formation in cultured human saphenous vein. These data identify MARCKS as a pathogenic contributor to IH and indicate therapeutic MARCKS silencing could selectively suppress the "atherogenic," proliferative phenotype of VSMCs without collateral harm to the endothelium. This approach could be readily translated to the clinic to silence MARCKS in vein bypass grafts prior to implantation.

Significance of initial aortic aneurysm pressure sensor readings varies with aortic endograft design.

BACKGROUND: The differences in implantable pressure sensor aneurysm sac readings were compared following endovascular aneurysm repair (EVAR) among three different stent grafts. METHODS: From January 2006 to March 2009, 51 aortic stent grafts were implanted along with the Endosure sensor. Grafts used were Zenith, Talent, and Excluder. In the present retrospective study, pulse ratios were measured intraoperatively before and after aneurysm sac exclusion and in follow-up (within 30 days). Analysis of variance was used to determine significance. RESULTS: The average aneurysm size that was repaired was 5.75 cm (range: 4-8.5 cm); 41 patients (80.4%) being male with an average age of 76.3 years (range: 58-90 years). Thirty-four grafts were Zenith, 9 were Talent, and 8 were Excluder. The average pre-aneurysm exclusion pulse ratios for the Zenith, Talent, and Excluder were 1.00, 1.08, and 0.95 (p = 0.18), respectively. The average post-aneurysm exclusion pulse ratios were 0.34, 0.67, and 0.35, respectively (p = 0.003). Pulse ratios at the time of follow-up (within 30 days) were 0.17, 0.22, and 0.11, respectively (p = 0.44). Nine of 51 (17.6%) patients had a reduction of pulse ratio of less than 30% after endograft implantation. Five of those 9 patients (55.5%) had the Talent endograft, although there was no angiographic evidence of endoleak. CONCLUSIONS: The Talent graft has significantly higher pulse ratios following endograft implantation despite having no angiographic evidence of endoleak when compared to the Zenith and Excluder grafts. However, the pulse ratios decreased to levels similar to Zenith and Excluder within 30 days of endograft implantation. This suggests that the Talent endograft may have increased porosity initially. If pulse ratios do not appropriately decrease immediately after device implantation, further angiographic imaging may not be necessary if no obvious endoleak is seen.

Use and abuse of atherectomy: where should it be used?

Surgical bypass has long been considered the "gold standard" for treatment of peripheral arterial disease. Endovascular therapy with percutaneous transluminal angioplasty and adjunctive stenting has recently become a primary treatment of lower extremity peripheral arterial disease. However, there has been concern regarding the long-term patency of percutaneous interventions and the increased need for reintervention. An alternative to standard percutaneous transluminal angioplasty and stent is the excision of the obstructing arterial plaque using atherectomy devices. There are several different types of atherectomy devices including directional atherectomy devices, such as the SilverHawk Atherectomy (EV3, Minneapolis, MN) device, orbital atherectomy devices, such as the CSI DiamondBack 360 (CSI, Minneapolis, MN) rotational atherectomy device, such as the Pathway Jetstream (Pathway Medical Technologies, Inc., Kirkland, WA), the Rotablator device (Boston Scientific, Natick, MA), and laser atherectomy devices, including the Spectranetics Excimer Laser (Spectranetics, Colorado Springs, CO). All of these devices will be reviewed. Multiple series, including our experience with atherectomy devices, will be discussed. Overall, atherectomy devices have an important emerging role for complex lesions, especially those extending into tibial vessels. Atherectomy devices have the distinct advantage of removing the obstructing atherosclerotic or intimal hyperplastic lesions without the disadvantage of a foreign body such as a stent in the artery. If reintervention is required after atherectomy, this can be generally accomplished at the same site with low risk of complications or discomfort to the patient. Finally, atherectomy also does not preclude use of bypass for the treatment of peripheral arterial disease nor, in most cases, change the anastomotic sites if surgical bypass is required, in contrast to stenting.

A20, a modulator of smooth muscle cell proliferation and apoptosis, prevents and induces regression of neointimal hyperplasia.

A20 is a NF-kappaB-dependent gene that has dual anti-inflammatory and antiapoptotic functions in endothelial cells (EC). The function of A20 in smooth muscle cells (SMC) is unknown. We demonstrate that A20 is induced in SMC in response to inflammatory stimuli and serves an anti-inflammatory function via blockade of NF-kappaB and NF-kappaB-dependent proteins ICAM-1 and MCP-1. A20 inhibits SMC proliferation via increased expression of cyclin-dependent kinase inhibitors p21waf1 and p27kip1. Surprisingly, A20 sensitizes SMC to cytokine- and Fas-mediated apoptosis through a novel NO-dependent mechanism. In vivo, adenoviral delivery of A20 to medial rat carotid artery SMC after balloon angioplasty prevents neointimal hyperplasia by blocking SMC proliferation and accelerating re-endothelialization, without causing apoptosis. However, expression of A20 in established neointimal lesions leads to their regression through increased apoptosis. This is the first demonstration that A20 exerts two levels of control of vascular remodeling and healing. A20 prevents neointimal hyperplasia through combined anti-inflammatory and antiproliferative functions in medial SMC. If SMC evade this first barrier and neointima is formed, A20 has a therapeutic potential by uniquely sensitizing neointimal SMC to apoptosis. A20-based therapies hold promise for the prevention and treatment of neointimal disease.

Clinical significance of the clopidogrel-proton pump inhibitor interaction after peripheral endovascular intervention for claudication.

OBJECTIVE: Despite numerous studies in the cardiology literature, the clinical impact of proton pump inhibitor (PPI) administration on the antiplatelet effect of clopidogrel remains controversial. The objective of this study is to evaluate the effects of concurrent PPI and clopidogrel administration on outcomes after percutaneous transluminal angioplasty and stenting (PTA&S) of the superficial femoral artery (SFA) for claudication. METHODS: Retrospective review of a prospectively maintained database (2004-2010) identified patients undergoing PTA&S of the SFA for lifestyle-limiting claudication (Rutherford Class III). Statistical analysis included univariate comparison (Wilcoxon, chi-square) of demographics, lesion characteristics, complication rates, and outcome measures. Patency comparisons were made with Cox-PH multivariable models and Kaplan-Meier survival analysis. RESULTS: Totally, 109 limbs were treated in 103 patients. All were prescribed clopidogrel for 1 month; concurrent PPI use (+PPI) was identified after 42 (38.5%) interventions. There were no statistically significant differences in demographics, comorbidity prevalence, lesion length, degree of stenosis, or runoff associated with PPI use. There were no cases of early thrombosis in either group. There were more instances of patency loss (28 [50%] vs 21 [42%]; P = .40) in patients with +PPI, and a trend toward reduced primary patency that did not achieve statistical significance (P = .5). By multivariate analysis only TransAtlantic Inter-Society Consensus (TASC) D lesions were independent predictors of primary (hazards ratio [HR] = 4.366; [95% confidence interval (CI): 1.291-14.764; P = .018) and assisted patency loss (HR = 6.815 [1.181-39.327]; P = .032). CONCLUSIONS: The clinical significance of the clopidogrel-PPI interaction is a controversial topic that has been the subject of numerous studies in the cardiology literature. This is the first report to examine this medication interaction after peripheral intervention. While there is no apparent association between PPI coadministration with clopidogrel in this series, the high prevalence of PPI use among patients prescribed clopidogrel following peripheral intervention warrants ongoing attention to this purported medication interaction.

Dynamic diffuse optical tomography imaging of peripheral arterial disease.

Peripheral arterial disease (PAD) is the narrowing of arteries due to plaque accumulation in the vascular walls. This leads to insufficient blood supply to the extremities and can ultimately cause cell death. Currently available methods are ineffective in diagnosing PAD in patients with calcified arteries, such as those with diabetes. In this paper we investigate the potential of dynamic diffuse optical tomography (DDOT) as an alternative way to assess PAD in the lower extremities. DDOT is a non-invasive, non-ionizing imaging modality that uses near-infrared light to create spatio-temporal maps of oxy- and deoxy-hemoglobin in tissue. We present three case studies in which we used DDOT to visualize vascular perfusion of a healthy volunteer, a PAD patient and a diabetic PAD patient with calcified arteries. These preliminary results show significant differences in DDOT time-traces and images between all three cases, underscoring the potential of DDOT as a new diagnostic tool.

Choosing the appropriate intervention for symptomatic and asymptomatic carotid disease in the era of multiple therapies: integration of risk profile and technical data.

With rapid evolution of endovascular techniques, carotid artery stenting has emerged as an alternative to carotid endarterectomy. Several investigations have been performed that examine the roles of carotid endarterectomy and carotid artery stenting and some trials have sought to compare the two treatment modalities. There have also been advances in the understanding of optimal medical management of carotid artery stenosis. The obvious question that arises is what is the most appropriate treatment option for patients with symptomatic and asymptomatic carotid artery stenosis? The answer is not straightforward and requires an understanding of differential outcomes in select subgroups. A review of the major studies, including some of the most recent trials, will help to elucidate the optimal therapy.

Gender differences in outcomes of endovascular treatment of infrainguinal peripheral artery disease.

OBJECTIVE: Our goal was to assess the outcomes of females compared to males treated with endovascular lower extremity interventions in order to determine optimal therapy based on gender. METHODS: We performed a retrospective review evaluating the outcomes of primary transluminal angioplasty (PTA) and PTA + stenting (PTA + S) for peripheral arterial disease (PAD). Patency rates and limb salvage were the primary end points. RESULTS: A total of 1017 lesions were analyzed in 537 patients (229 male and 308 female) between 2004 and 2009. There were no differences between genders in lesion characteristics. Women were more likely to have interventions for critical limb ischemia (CLI). In CLI patients with superficial femoral artery (SFA) and tibial lesions, women had better patency rates (P < .005). CONCLUSIONS: Women have better patency rates compared with men following treatment of some CLI lesions. Interestingly, women are treated more frequently for CLI when compared to men. For some lesion types in women, PTA alone was equivalent to PTA + S. Our results suggest that outcomes may be optimized by tailoring interventions to gender.

A20 modulates lipid metabolism and energy production to promote liver regeneration.

BACKGROUND: Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. METHODOLOGY AND PRINCIPAL FINDINGS: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.ßgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. CONCLUSION: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation.