Brinjikji, Waleed

Preclinical studies are important in helping practitioners and device developers improve techniques and tools for endovascular treatment of intracranial aneurysms. Thus an understanding of the major animal models used in such studies is important. The New Zealand rabbit elastase induced arterial aneurysm of the common carotid artery is one of the most commonly used models in testing the safety and efficacy of new endovascular devices. In this review we discuss: (1) the various techniques used to create the aneurysm, (2) complications of aneurysm creation, (3) natural history of the arterial aneurysm, (4) histopathologic and hemodynamic features of the aneurysm, (5) devices tested using this model, and (6) weaknesses of the model. We demonstrate how preclinical studies using this model are applied in the treatment of intracranial aneurysms in humans. The model has similar hemodynamic, morphological, and histologic characteristics to human aneurysms, and demonstrates similar healing responses to coiling as human aneurysms. Despite these strengths, however, the model does have many weaknesses, including the fact that the model does not emulate the complex inflammatory processes affecting growing and ruptured aneurysms. Furthermore, the extracranial location of the model affects its ability to be used in preclinical safety assessments of new devices. We conclude that the rabbit elastase model has characteristics that make it a simple and effective model for preclinical studies on the endovascular treatment of intracranial aneurysms, but further work is needed to develop aneurysm models that simulate the histopathologic and morphologic characteristics of growing and ruptured aneurysms.

OBJECT Tobacco smoking is one of the most important risk factors for the formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhages. Smoking has also been suggested to contribute to the recurrence of aneurysms after endovascular coiling. To improve the understanding of the impact of smoking on long-term outcomes after coil embolization of intracranial aneurysms, the authors studied a consecutive contemporary series of patients treated at their institution. The aims of this study were to determine whether smoking is an independent risk factor for aneurysm recurrence and retreatment after endovascular coiling. METHODS All patients who had received an intrasaccular coil embolization of an intracranial aneurysm, who had undergone a follow-up imaging exam at least 6 months later, and whose smoking history had been recorded from January 2005 through December 2012 were included in this study. Patients were stratified according to smoking status into 3 groups: 1) never a smoker, 2) current smoker (smoked at the time of treatment), and 3) former smoker (quit smoking before treatment). The 2 primary outcomes studied were aneurysm recurrence and aneurysm retreatment after treatment for endovascular aneurysms. Kruskal-Wallis and chi-square tests were used to test statistical significance of differences in the rates of aneurysm recurrence, retreatment, or of both among the 3 groups. A multivariate logistic regression analysis controlling for smoking status and for several characteristics of the aneurysm was also performed. RESULTS In total, 384 patients with a combined total of 411 aneurysms were included in this study. The aneurysm recurrence rate was not significantly associated with smoking: both former smokers (OR 1.00, 95% CI 0.61–1.65; p = 0.99) and current smokers (OR 0.58, 95% CI 0.31–1.09; p = 0.09) had odds of recurrence that were similar to those who were never smokers. Former smokers (OR 0.78, 95% CI 0.46–1.35; p = 0.38) had odds of retreatment similar to those of never smokers, and current smokers had a lower odds of undergoing retreatment (OR 0.44, 95% CI 0.21–0.91; p = 0.03) than never smokers. Moreover, an analysis adjusting for aneurysm rupture, diameter, and initial occlusion showed that former smokers (OR 0.65, 95% CI 0.33–1.28; p = 0.21) and current smokers (OR 1.04, 95% CI 0.60–1.81; p = 0.88) had odds of aneurysm recurrence similar to those who were never smokers. Adjusting the analysis for aneurysm rupture, diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23–1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46–1.46; p = 0.50) had odds of retreatment similar to those of patients who were never smokers. CONCLUSIONS The results show that smoking was not an independent risk factor for aneurysm recurrence and aneurysm retreatment among patients receiving endovascular treatment for intracranial aneurysms at the authors' institution. Nonetheless, patients with intracranial aneurysms should continue to be counseled about the risks of tobacco smoking.

ABSTRACTBackgroundAcute coronary syndromes account for half of all deaths secondary to cardiovascular disease and represent a significant economic burden in the United States. Therefore, assessing hospitalization costs relative to Medicare reimbursement for these patients is important in understanding the impact of these patients on hospitals. We hypothesized that hospitalization costs for acute myocardial infarction patients treated with percutaneous coronary intervention (PCI) were higher than their associated Medicare payments.MethodsUsing the Nationwide Inpatient Sample, we evaluated hospitalization costs for patients treated with PCI from 2001 through 2009 by multiplying hospital charges by the group average cost‐to‐charge ratio for each patient's hospitalization. Primary end points examined were total hospital costs and trends over time, which were correlated with clinical outcomes and insurance payments. Costs were inflation adjusted with 2009 as the reference year.ResultsMedian hospitalization costs of PCI increased from $15 889 (interquartile range [IQR] = $12 057–$21 204) in 2001 to $19 349 (IQR = $14 660–$26 282) in 2009. From 2004 to 2009, inflation‐adjusted costs for PCI decreased at a rate of 0.3% per year. In 2009, a total of 265,531 patients received PCI for acute myocardial infarction. Of these, 143 654 were <65 years old, and 121 876 were ≥65 years old. Average 2009 Medicare payments ranged from $9303 to $17 500 depending on the Medicare Severity‐Diagnosis Related Groups (MS‐DRG) billed, leaving hospitals at a loss of anywhere from $4493 to $7940 per patient when comparing costs and reimbursements across all included MS‐DRG codes.ConclusionsHospitalization costs for patients treated with PCI have been stabilizing over the last few years; however, there still remains a significant disparity between Medicare reimbursements and hospitalization costs, which has potential implications on patient outcomes, quality of care, and hospital sustainability.

Background Expansion of the endovascular and surgical workforce in the USA might lead to carotid revascularization procedures being carried out at low volume centers. Objective To evaluate trends in the treatment of carotid stenosis at high volume centers in the USA and compare outcomes by hospital volume. Methods Using the Nationwide Inpatient Sample, we evaluated trends in the proportion of carotid revascularization procedures performed at high volume centers in the USA from 2005 to 2011. High volume was defined as combined endarterectomy/stenting volume ≥130 patients/year, carotid endarterectomy volume ≥117 cases/year and carotid stenting volume ≥38 cases/year. In-hospital mortality, discharge to a long-term facility, intracranial hemorrhage, and postoperative stroke rates were compared between high and low volume centers. Results A total of 181 972 patients were included in this study. Overall, 63 442 patients (34.9%) were treated at high volume centers. The proportion of patients treated at high volume carotid revascularization centers decreased from 38.3% in 2005–2006 to 30.2% in 2010–2011. The proportion of patients treated at high volume centers decreased from 35.7% to 30.0% for carotid endarterectomy (p<0.0001) and 45.2% to 35.1% for carotid stenting. Patients treated at low volume centers had significantly higher rates of discharge to a long-term facility than high volume center patients (6.3% vs 5.0%, p<0.0001). The same was true for endarterectomy patients (6.0% vs 4.7%, p<0.0001) and stenting patients (8.3% vs 6.5%, p<0.0001). Conclusions A trend toward a lower proportion of patients with carotid stenosis being treated in high volume centers from 2005 to 2011 is concerning as these high volume centers had lower complication rates.

Background and purpose A recent expansion of the neurointerventional workforce in the USA could lead to a trend toward cerebral aneurysms being increasingly treated at low volume centers. Such a trend could have a negative impact on patient care as higher volume centers are known to have better outcomes. Methods Using the Nationwide Inpatient Sample, we evaluated trends in aneurysm treatment in the USA from 2001 to 2010. Annual volumes of both ruptured and unruptured aneurysms were counted, as well as annual percentages of cases treated at high volume centers (≥50 aneurysms/year clipped or coiled). Results The number of ruptured aneurysms treated per year has fluctuated between 9000 and 12 000 from 2003 to 2010. In 2001–2002, 27.4% of intracranial aneurysm patients were treated with clipping or coiling at high volume centers, with a peak of 70.1% in 2007–2008. This proportion dropped to 61.8% in 2009–2010. The proportion of patients clipped at high volume centers was 23.3% in 2001–2002 and peaked at 65.0% in 2007–2008. In 2009–2010, the proportion dropped to 58.6%. For coiling patients, 46.4% were treated at high volume centers in 2001–2002, with a peak of 70.1% in 2007–2008, and a drop to 61.8% in 2009–2010. Conclusion A trend toward less cerebral aneurysms being treated in high volume centers in 2009 and 2010 is worrisome because high volume centers are known to tend to have better outcomes. This trend is likely due to recent expansion of the neurointerventional workforce.

Background and Purpose— Use of endovascular coiling for treatment of ruptured and unruptured intracranial aneurysms (IAs) in the elderly is increasing. We performed a meta-analysis of the literature examining clinical and angiographic outcomes for treatment of IAs in the elderly. Methods— We performed a comprehensive review of the literature from 1995 to 2012, reporting series of patients ≥65 years of age with ruptured or unruptured IAs treated with endovascular approach. Event rates were pooled across studies using random effects meta-analysis. Results— A total of 21 studies reporting on 1511 patients were included. Long-term aneurysm occlusion rates were 79% (95% confidence interval [CI], 70%–85%). Perioperative stroke occurred in 4% (95% CI, 3%–6%), with similar rates between patients with ruptured (5%; 95% CI, 3%–7%) and unruptured aneurysms (4%; 95% CI, 1%–14%; P =0.68). Intraprocedural rupture occurred in 1% (95% CI, 0%–3%) and 4% (95% CI, 2–6%; P =0.04) of patients with unruptured and ruptured aneurysms, respectively. Perioperative mortality rate for patients with ruptured aneurysms was 23% (95% CI, 17%–30%) and 1% (95% CI, 0%–6%) for patients with unruptured aneurysms ( P <0.01). Rates of good clinical outcome at 1 year were 93% (95% CI, 88%–96%) and 66% (95% CI, 59%–72%) in patients with unruptured and ruptured aneurysms, respectively. Conclusions— This study suggests that endovascular treatment of IAs in the elderly is associated with high long-term occlusion rates. Given the morbidity and mortality associated with endovascular treatment of IAs in the elderly, careful patient selection, especially in the case of patients with unruptured aneurysm, is recommended.

Background and Purpose— Acute intraprocedural thrombus formation complicating endovascular cerebral aneurysm treatment is often treated with intra-arterial or intravenous administration of thrombolytic agents or glycoprotein IIb/IIIa (GpIIb/IIIa) inhibitors. We sought to evaluate the morbidity and mortality associated with such treatments using a large multihospital database. Methods— Using the Premier Perspective Database, we examined outcomes for patients receiving endovascular coiling for ruptured and unruptured aneurysms requiring rescue therapy, defined as treatment with GpIIb/IIIa inhibitors and fibrinolytic therapy. We compared discharge status, length of stay, and complication rates across 3 groups: (1) patients receiving GpIIb/IIIa inhibitors only, (2) patients receiving fibrinolytic therapy only, and (3) patients receiving both GpIIb/IIIa inhibitors and fibrinolytics. Student t test was used to compare continuous variables, and Fisher exact test was used to compare categorical variables. Results— Seven-percent (254/3627) of patients treated for unruptured aneurysms received rescue therapy. When compared with patients receiving GpIIb/IIIa inhibitors alone, patients receiving only fibrinolytics had significantly higher rates of discharge to institutions other than home (37.5% [9/24] versus 7.4% [15/201]; P <0.0001). Eight-percent of patients (338/4204) treated for ruptured aneurysms received rescue therapy. When compared with patients receiving GpIIb/IIIa inhibitors alone, patients receiving only fibrinolytics had significantly higher rates of mortality (26.0% [18/69] versus 14.5% [35/241]; P =0.02) and discharge to institutions other than home (59.4% [41/69] versus 36.5% [88/241]; P <0.0001). Conclusions— Pharmacological rescue therapy occurred in 7% to 8% of endovascular coiling patients with unruptured and ruptured intracranial aneurysms. Rescue therapy with thrombolytic agents resulted in significantly more morbidity and mortality than rescue therapy with GpIIb/IIIa inhibitors.