Treatment of asymptomatic carotid artery disease: Similar early outcomes after carotid stenting for high-risk patients and endarterectomy for standard-risk patients

BackgroundThe role of carotid angioplasty and stenting (CAS) in the treatment of asymptomatic patients with carotid disease remains controversial. The purpose of this report is to compare outcomes in asymptomatic patients treated with CAS and carotid endarterectomy (CEA). This was the initial experience performing CAS for most of the surgeons. For comparison, we also report our outcomes in standard-risk patients treated concurrently with CEA during the same period of time.MethodsA retrospective, nonrandomized review of asymptomatic patients undergoing CEA or CAS at Washington University Medical Center in St. Louis was done. Patients with >70% asymptomatic carotid stenosis treated between September 2003 and April 2005 were identified. CEA was the first therapeutic consideration in all patients. CAS was reserved for high-risk patients. Thirty-day outcomes of stroke or death were recorded. During this time interval, 248 patients were treated including with 93 CAS and with 145 CEA. Symptomatic or clinically detected adverse outcomes such as myocardial infarction (MI), arrhythmia, renal failure, or pulmonary complications were noted but were not the primary end points of this review. This study addresses only the periprocedural outcomes of CEA and CAS in asymptomatic patients. No data >30-day follow-up are included.ResultsDuring this period, 93 CAS and 145 CEA procedures were done in asymptomatic patients. Patient characteristics in both groups were similar. Carotid protection devices were used in 91.4% of CAS patients. The results in the CAS group showed one death (1.1%) and one stroke (1.1%). In the CEA group, three strokes occurred (2.1%, P = 0.9999), one associated with death (0.7%, P = 0.9999). The CAS group had 1.34 ± 0.83 risk factors vs 0.39 ± 0.58 in the CEA group (P < .0001). Median CAS and CEA length of stay was 1 day.ConclusionsCAS for asymptomatic carotid stenosis demonstrated equivalent outcomes compared with CEA, despite CAS being reserved for use in a disadvantaged subset of high-risk patients owing to anatomic risk factors or medical comorbidities. These results suggest CAS should be considered a reasonable treatment option in the high-risk but asymptomatic patient. Enthusiasm for CAS should be tempered by the recognition that long-term outcomes in CAS-treated asymptomatic patients remain unknown

The effect of food on tramadol and celecoxib bioavailability following oral administration of Co-Crystal of Tramadol-Celecoxib (CTC): a randomised, open label, single-dose, crossover study in healthy volunteers

ackground and Objective Co-Crystal of Tramadol-Celecoxib (CTC), in development for the treatment of moderate to severe acute pain, is a first-in-class co-crystal containing a 1:1 molecular ratio of two active pharmaceutical ingredients; rac- tramadol·HCl and celecoxib. This randomised, open-label, crossover study compared the bioavailability of both components after CTC administration under fed and fasting conditions. Methods Healthy adults received single doses of 200 mg CTC under both fed and fasting conditions (separated by a 7-day washout). Each dose of CTC was administered orally as two 100 mg tablets, each containing 44 mg tramadol·HCl and 56 mg celecoxib. In the fed condition, a high-fat, high-calorie meal [in line with recommendations by the US Food and Drug Administration (FDA)] was served 30 min before CTC administration. Tramadol, O-desmethyltramadol and celecoxib plasma concentrations were measured pre- and post-dose up to 48 h. Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety was also assessed. Results Thirty-six subjects (18 female/18 male) received one or both doses of CTC; 33 provided evaluable pharmacokinetic data under fed and fasting conditions. For tramadol and O-desmethyltramadol, fed-to-fasting ratios of geometric least-squares means and corresponding 90% confidence interval (CI) values for maximum plasma concentration (Cmax) and extrapolated area under the plasma concentration-time curve to infinity (AUC∞) were within the pre-defined range for comparative bio- availability (80-125%). For celecoxib, Cmax and AUC∞ fed-to-fasting ratios (90% CIs) were outside this range, at 130.91% (116.98-146.49) and 129.34% (121.78-137.38), respectively. The safety profile of CTC was similar in fed and fasting conditions. Conclusions As reported for standard-formulation celecoxib, food increased the bioavailability of celecoxib from single-dose CTC. Food had no effect on tramadol or O-desmethyltramadol bioavailability

Overt ischemic colitis after endovascular repair of aortoiliac aneurysms

AbstractObjectiveControversy exists as to the cause of ischemic colitis complicating endovascular aneurysm repair. Occlusion of the hypogastric arteries (HAs) during endovascular repair of aortoiliac aneurysms (AIAs) results in a significant incidence of buttock claudication, and has been suggested as a causative factor in the development of postprocedural colonic ischemia, in addition to factors such as systemic hypotension, embolization of atheromatous debris, and interruption of inferior mesenteric artery inflow. To analyze the relationship between perioperative HA occlusion and postoperative ischemic colitis, we reviewed our experience over 2 years with Food and Drug Administration–approved endovascular graft devices for treatment of AIAs.MethodsElective repair of AIAs with bifurcated endovascular grafts was performed in 233 patients over a 2-year period. These included 184 AneuRx grafts, 17 Ancure grafts, and 32 Excluder grafts. During the experience, 44 patients (18.9%) underwent unilateral perioperative HA occlusion (28 right, 16 left) during the course of endovascular AIA repair, and 1 patient (0.4%) underwent bilateral HA occlusion.ResultsIn 4 patients (1.7%) signs and symptoms of ischemic colitis developed 2.0 ± 1.4 days postoperatively. In all patients the diagnosis was confirmed at sigmoidoscopy, and initial treatment included bowel rest, hydration, and intravenous antibiotic agents. Three patients with bilateral patent HAs required colonic resection 14.7 ± 9.7 days after the initial diagnosis, and 2 of these 3 patients died in the postoperative period. Pathologic findings confirmed the presence of atheroemboli in the colonic vasculature in all 3 patients who underwent colonic resection. The fourth patient had undergone multiple manipulations of the left HA in an unsuccessful attempt to preserve patency of this vessel during AIA repair. This patient recovered completely with nonoperative management. Perioperative unilateral HA occlusion was not associated with a significantly higher incidence of postoperative ischemic colitis.ConclusionPerioperative HA occlusion during aortoiliac open or endovascular surgery may contribute to development of the rare but potentially lethal complication of ischemic colitis. However, our extensive experience suggests that embolization of atheromatous debris to the HA tissue beds during endovascular manipulations, rather than proximal HA occlusion, is the primary cause of clinically significant ischemic colitis after endovascular aneurysm repair

Effect of challenging neck anatomy on mid-term migration rates in AneuRx endografts

Objective: To establish the effect of challenging neck anatomy on the mid- and long-term incidence of migration with the AneuRx bifurcated device in patients treated after Food and Drug Administration approval and to identify the predictive factors for device migration. Methods: Prospectively maintained databases at the University of North Carolina (UNC) and Washington University (WU) were used to identify 595 patients (UNC, n = 230; WU, n = 365) who underwent endovascular repair of an infrarenal abdominal aortic aneurysm with the AneuRx bifurcated stent graft. Those patients with at least 30 months of follow-up were identified and underwent further assessment of migration (UNC, n = 25; WU, n = 59) by use of multiplanar reconstructed computed tomographic scans. Results: Eighty-four patients with a mean follow-up time of 40.3 months (range, 30-55 months) were studied. Seventy percent of the patients (n = 59) met all inclusion criteria for neck anatomy (length, angle, diameter, and quality) as defined by the revised instructions for use guidelines and are referred to as those with favorable neck anatomy (FNA). The remaining 25 patients retrospectively fell outside of the revised instructions for use guidelines and are referred to as those with unfavorable neck anatomy (UFNA). Life-table analysis for FNA patients at 2 and 4 years revealed a migration rate of 0% and 6.1%, respectively. For UFNA patients, it was 24.0% and 42.1% at 2 and 4 years, respectively (P < .0001). The overall (FNA and UFNA) migration rate was 7.1% and 17.1% at 2 and 4 years, respectively. Overall, late graft-related complications occurred in 38% of patients (FNA, 27%; UFNA, 64%; P = .003; relative risk, 1.7). There was no incidence of late rupture or open conversion. The relative risk of migration for UFNA patients was 2.5 compared with FNA patients (P = .0003). A larger neck angle and a longer initial graft to renal artery distance were predictors of migration, whereas shorter neck length approached but did not reach statistical significance. Conclusions: Patients who have unfavorable aneurysm neck anatomy experience significantly higher migration, devicerelated complication, and secondary intervention rates. However, there was no incidence of open conversion, rupture, or abdominal aortic aneurysm–related death, thereby supporting the AneuRx device as a feasible alternative to open repair even in patients with challenging neck characteristics. Enhanced surveillance should be used in these high-risk patients. ( J Vasc Surg 2006;44:932-7.

Quantifying the Evolution of Vascular Barrier Disruption in Advanced Atherosclerosis with Semipermeant Nanoparticle Contrast Agents

Acute atherothrombotic occlusion in heart attack and stroke implies disruption of the vascular endothelial barrier that exposes a highly procoagulant intimal milieu. However, the evolution, severity, and pathophysiological consequences of vascular barrier damage in atherosclerotic plaque remain unknown, in part because quantifiable methods and experimental models are lacking for its in vivo assessment.To develop quantitative nondestructive methodologies and models for detecting vascular barrier disruption in advanced plaques.Sustained hypercholesterolemia in New Zealand White (NZW) rabbits for >7-14 months engendered endothelial barrier disruption that was evident from massive and rapid passive penetration and intimal trapping of perfluorocarbon-core nanoparticles (PFC-NP: ∼250 nm diameter) after in vivo circulation for as little as 1 hour. Only older plaques (>7 mo), but not younger plaques (<3 mo) demonstrated the marked enhancement of endothelial permeability to these particles. Electron microscopy revealed a complex of subintimal spongiform channels associated with endothelial apoptosis, superficial erosions, and surface-penetrating cholesterol crystals. Fluorine ((19)F) magnetic resonance imaging and spectroscopy (MRI/MRS) enabled absolute quantification (in nanoMolar) of the passive permeation of PFC-NP into the disrupted vascular lesions by sensing the unique spectral signatures from the fluorine core of plaque-bound PFC-NP.The application of semipermeant nanoparticles reveals the presence of profound barrier disruption in later stage plaques and focuses attention on the disrupted endothelium as a potential contributor to plaque vulnerability. The response to sustained high cholesterol levels yields a progressive deterioration of the vascular barrier that can be quantified with fluorine MRI/MRS of passively permeable nanostructures. The possibility of plaque classification based on the metric of endothelial permeability to nanoparticles is suggested