Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.

RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

Value of delayed duplex ultrasound assessment after endothermal ablation of the great saphenous vein.

OBJECTIVE: Endothermal ablation (ETA) of the great saphenous vein (GSV) is associated with a small but definite risk of endothermal heat-induced thrombosis (EHIT) extending into the common femoral vein. Follow-up duplex ultrasound imaging to detect EHIT after ETA is considered standard of care, although the exact timing of duplex ultrasound imaging to detect EHIT after ETA remains unclear. We hypothesized that an additional duplex ultrasound assessment 1 week after ETA would not identify a significant number of patients with EHIT and would significantly increase health care costs. METHODS: This was a retrospective review of consecutive ETA GSV procedures from 2007 to 2014. All patients were evaluated with duplex ultrasound imaging on postprocedure day 1, and 79% of patients underwent a second ultrasound assessment 1 week postprocedure. EHIT was considered present when proximal GSV closure progressed to level ≥4, based on a six-tier classification system. RESULTS: From January 1, 2007, until December 31, 2014, 842 patients underwent GSV ETA. Patients with EHIT were more likely to have had a prior deep venous thrombosis (DVT; P = .002) and a larger GSV (P = .006). Forty-three procedures (5.1%) were classified as having EHIT requiring anticoagulation, based on a level ≥4 proximal closure level. Of the 43 patients with EHIT, 20 (47%) were found on the initial ultrasound assessment performed 24 hours postprocedure, but 19 patients (44%) with EHIT would not have been identified with a single postoperative ultrasound scan performed 24 hours after intervention. These 19 patients had a level ≤3 closure level at the duplex ultrasound scan performed 24 hours postprocedure and progressed to EHIT on the delayed duplex ultrasound scan. Lastly, thrombotic complications in four patients (9%), representing three late DVT and one DVT/pulmonary embolism presenting to another hospital, would not have been identified regardless of the postoperative surveillance strategy. Maximum GSV diameter was the only significant predictor of progression to EHIT on multivariate analysis (P = .007). Based on 2014 United States dollars, the two-ultrasound surveillance paradigm is associated with health care charges of $31,109 per identified delayed venous thromboembolism event. CONCLUSIONS: Delayed duplex ultrasound assessment after ETA of the GSV comes with associated health care costs but does yield a significant number of patients with progression to EHIT. Better understanding of the timing, risk factors, and significance of EHIT is needed to cost-effectively care for patients after ETA for varicose veins.

Patients with familial abdominal aortic aneurysms are at increased risk for endoleak and secondary intervention following elective endovascular aneurysm repair.

OBJECTIVE: A recent investigation has documented an increased risk of aneurysm-related complications after endovascular aneurysm repair (EVAR) of familial abdominal aortic aneurysms (fAAAs). We hypothesized that fAAA patients are not at increased risk for complications following open AAA repair or EVAR when compared with sporadic abdominal aortic aneurysm (spAAA) patients. To this end, we performed a single institution retrospective review. METHODS: Epidemiologic data were collected through the electronic medical record. Family history data were obtained from a questionnaire administered at the initial vascular surgery consultation. Major adverse events were defined as myocardial infarction, respiratory failure, renal failure, bowel ischemia, limb ischemia, multisystem organ failure, intracranial hemorrhage, paraplegia, hemorrhage, or death. Endoleaks were classified in accordance with the standardized reporting practices of the Society for Vascular Surgery. AAA-related complications were defined as the need for a secondary intervention due to endoleak, limb ischemia, or postimplantation rupture. RESULTS: A total of 392 patients with complete clinical data underwent elective AAA repair from 2004 to 2014. Of these 392 patients, 89 (23%) were classified as fAAA patients and 303 (77%) were classified as spAAA patients. With the exception of increased rates of chronic obstructive pulmonary disease (P = .0009) and pack-years smoked (P = .03) in spAAA patients, demographics did not differ. Sixty-two percent (n = 55) of fAAA patients and 68% (n = 205) of spAAA patients underwent EVAR (P = .30). fAAA patients did not incur any significant difference in major adverse events following open AAA repair (fAAA, 9% vs spAAA, 11%; P = .75). Additionally, fAAA patients did not incur any significant difference in major adverse events following EVAR (fAAA, 4% vs spAAA, 5%; P = .70). Patients with fAAA did have a significantly increased rate of endoleak (fAAA, 24% vs spAAA, 12%; P = .03) and secondary intervention following EVAR (fAAA, 21% vs spAAA, 12%; P = .04). CONCLUSIONS: The current study shows that patients with fAAA do not have increased perioperative morbidity following open or endovascular AAA repair. However, patients with fAAA do have an increased risk of endoleak and secondary intervention following EVAR. These findings suggest that EVAR and open AAA repair are both safe and effective for fAAA patients. The increased rate of endoleak and secondary intervention in patients with fAAA suggests that this subpopulation may benefit from closer post-EVAR surveillance or open surgical repair in good risk patients.

The potential role of DNA methylation in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology.

ePhenotyping for Abdominal Aortic Aneurysm in the Electronic Medical Records and Genomics (eMERGE) Network: Algorithm Development and Konstanz Information Miner Workflow.

BACKGROUND AND OBJECTIVE: We designed an algorithm to identify abdominal aortic aneurysm cases and controls from electronic health records to be shared and executed within the "electronic Medical Records and Genomics" (eMERGE) Network. MATERIALS AND METHODS: Structured Query Language, was used to script the algorithm utilizing "Current Procedural Terminology" and "International Classification of Diseases" codes, with demographic and encounter data to classify individuals as case, control, or excluded. The algorithm was validated using blinded manual chart review at three eMERGE Network sites and one non-eMERGE Network site. Validation comprised evaluation of an equal number of predicted cases and controls selected at random from the algorithm predictions. After validation at the three eMERGE Network sites, the remaining eMERGE Network sites performed verification only. Finally, the algorithm was implemented as a workflow in the Konstanz Information Miner, which represented the logic graphically while retaining intermediate data for inspection at each node. The algorithm was configured to be independent of specific access to data and was exportable (without data) to other sites. RESULTS: The algorithm demonstrated positive predictive values (PPV) of 92.8% (CI: 86.8-96.7) and 100% (CI: 97.0-100) for cases and controls, respectively. It performed well also outside the eMERGE Network. Implementation of the transportable executable algorithm as a Konstanz Information Miner workflow required much less effort than implementation from pseudo code, and ensured that the logic was as intended. DISCUSSION AND CONCLUSION: This ePhenotyping algorithm identifies abdominal aortic aneurysm cases and controls from the electronic health record with high case and control PPV necessary for research purposes, can be disseminated easily, and applied to high-throughput genetic and other studies.

Proinflammatory role of stem cells in abdominal aortic aneurysms.

OBJECTIVE: The pathogenesis of abdominal aortic aneurysm (AAA) formation includes inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. That multipotent stem cells have an important role in cardiovascular health and disease has been well established, but the role of stem cells in aortic structural deterioration is poorly defined. We sought to describe the presence of stem cells in human AAA tissue and also investigated the differentiation of stem cells within the aneurysmal aorta. METHODS: Infrarenal aortic wall specimens were collected from patients (n = 7) undergoing open AAA surgical repair. Nonaneurysmal infrarenal aortic control samples (n = 4) were collected at autopsies. Using immunohistochemistry, we compared the abundance of Stro1-positive ((+)), c-kit(+), and CD34(+) cells in aortic tissue. Using double-immunofluorescence staining, we evaluated stem cell differentiation into smooth muscle cells (SM22), fibroblasts (FSP1), and macrophages (CD68). We then investigated the colocalization of CD68(+) cells with the cellular marker of proliferation Ki67. RESULTS: The media and adventitia of infrarenal AAA samples both demonstrated a significantly greater number of c-kit(+) and CD34(+) cells compared with matched control nonaneurysmal aortic tissues; however, the abundance of Stro1(+) cells was not significantly different between the groups. Using double-immunofluorescence staining, we identified that AAA stem cells express the macrophage marker CD68 but not the smooth muscle cell marker SM22 or the fibroblast marker FSP1. CD68(+) cells within the aortic wall colocalized with the cellular marker of proliferation Ki67. CONCLUSIONS: Stem cells are significantly elevated in infrarenal AAA tissue compared with matched control aortic tissue. Our data also demonstrate that AAA stem cells express macrophage surface antigens but not smooth muscle cell or fibroblast markers. Furthermore, CD68(+) cells within the aortic wall colocalized with the cellular marker of proliferation Ki67. These finding suggest an inflammatory/immune role of stem cells during AAA pathogenesis and raise the possibility of localized replenishment therapy within the aneurysm wall.

Population risk factor estimates for abdominal aortic aneurysm from electronic medical records: a case control study.

BACKGROUND: Using abdominal aortic aneurysm (AAA) as a model, this case-control study used electronic medical record (EMR) data to assess known risk factors and identify new associations. METHODS: The study population consisted of cases with AAA (n =888) and controls (n =10,523) from the Geisinger Health System EMR in Central and Northeastern Pennsylvania. We extracted all clinical and diagnostic data for these patients from January 2004 to December 2009 from the EMR. From this sample set, bootstrap replication procedures were used to randomly generate 2,500 iterations of data sets, each with 500 cases and 2000 controls. Estimates of risk factor effect sizes were obtained by stepwise logistic regression followed by bootstrap aggregation. Variables were ranked using the number of inclusions in iterations and P values. RESULTS: The benign neoplasm diagnosis was negatively associated with AAA, a novel finding. Similarly, type 2 diabetes, diastolic blood pressure, weight and myelogenous neoplasms were negatively associated with AAA. Peripheral artery disease, smoking, age, coronary stenosis, systolic blood pressure, age, height, male sex, pulmonary disease and hypertension were associated with an increased risk for AAA. CONCLUSIONS: This study utilized EMR data, retrospectively, for risk factor assessment of a complex disease. Known risk factors for AAA were replicated in magnitude and direction. A novel negative association of benign neoplasms was identified. EMRs allow researchers to rapidly and inexpensively use clinical data to expand cohort size and derive better risk estimates for AAA as well as other complex diseases.

Ultrasound-guided percutaneous thrombin injection of iatrogenic upper extremity pseudoaneurysms.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of ultrasound-guided thrombin injection (TI) for the treatment of upper extremity iatrogenic pseudoaneurysms (PAs) after percutaneous upper extremity arterial access. METHODS: This is a retrospective single-institution study from January 2009 to December 2012. All patients with clinical suspicion of an upper extremity PA after arterial puncture underwent duplex examination. Patients with and without PAs were compared to identify risk factors for development of PAs. Outcomes were analyzed in those patients with PAs that were treated with TI. RESULTS: Between January 1, 2009, and December 31, 2012, there were 61 upper extremity arterial duplex examinations performed for a clinical suspicion of an upper extremity PA. Eighteen ultrasound examinations (29.5%) demonstrated an iatrogenic upper extremity PA (13 brachial and five radial). Those patients with an upper extremity PA were more likely to have a history of hypertension, atrial fibrillation, and chronic kidney disease. Sheath size, preprocedural antiplatelet therapy, periprocedural anticoagulation regimen, service specialty performing the procedure, and procedure type did not influence the development of PA. Of 18 patients with PA, 14 were treated with TI with an overall success rate of 86%. There was one PA that failed to thrombose with TI, and there was one native brachial artery thrombosis requiring emergent surgical intervention. Outpatient clinical follow-up in the successfully treated patients demonstrated no recurrences at an average follow-up of 8 months. CONCLUSIONS: Ultrasound-guided percutaneous TI appears safe and effective for the treatment of iatrogenic brachial and radial artery PAs.

Endoleak visualized with carbon dioxide angiography during endovascular aneurysm repair using the Endurant stent-graft.

PURPOSE: To make interventionists aware of the potential for type IV endoleak on completion carbon dioxide (CO2) angiography during endovascular aneurysm repair (EVAR) using the Endurant stent-graft. CASE REPORT: A 74-year-old man with chronic kidney disease underwent EVAR with an Endurant stent-graft using CO2 angiography to guide graft placement. Completion CO2 angiography demonstrated immediate accumulation of CO2 in the aneurysm sac suggestive of an endoleak, but confirmatory angiography with conventional iodinated contrast showed no evidence of an endoleak. We speculate that this is a type IV endoleak, and graft porosity may be responsible. CONCLUSION: Interventionists should be alerted to the possibility of visualizing these endoleaks through Endurant stent-grafts under CO2 angiography. Further work should be done to elucidate the exact mechanism of the endoleak.

Novel pathways in the pathobiology of human abdominal aortic aneurysms.

OBJECTIVES: Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs. METHODS: A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes. RESULTS: Altogether 38 of the 43 genes on the 'AAA-chip' showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings. CONCLUSION: The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.

Intravascular lipoma of the internal jugular vein.

Benign primary venous tumors are rare. While venous lipomas have been reported in the vena cava, their incidence in the remainder of the venous circulation is less well known. We present what we believe to be the first reported case of an intravascular lipoma arising from the internal jugular vein. The clinical presentation, imaging characteristics, and histologic features are presented. We also performed a review of the current literature.

MicroRNA expression signature in human abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a dilatation of the aorta affecting most frequently elderly men. Histologically AAAs are characterized by inflammation, vascular smooth muscle cell apoptosis, and extracellular matrix degradation. The mechanisms of AAA formation, progression, and rupture are currently poorly understood. A previous mRNA expression study revealed a large number of differentially expressed genes between AAA and non-aneurysmal control aortas. MicroRNAs (miRNAs), small non-coding RNAs that are post-transcriptional regulators of gene expression, could provide a mechanism for the differential expression of genes in AAA. METHODS: To determine differences in miRNA levels between AAA (n = 5) and control (n = 5) infrarenal aortic tissues, a microarray study was carried out. Results were adjusted using Benjamini-Hochberg correction (adjusted p < 0.05). Real-time quantitative RT-PCR (qRT-PCR) assays with an independent set of 36 AAA and seven control tissues were used for validation. Potential gene targets were retrieved from miRNA target prediction databases Pictar, TargetScan, and MiRTarget2. Networks from the target gene set were generated and examined using the network analysis programs, CytoScape® and Ingenuity Pathway Core Analysis®. RESULTS: A microarray study identified eight miRNAs with significantly different expression levels between AAA and controls (adjusted p < 0.05). Real-time qRT-PCR assays validated the findings for five of the eight miRNAs. A total of 222 predicted miRNA target genes known to be differentially expressed in AAA based on a prior mRNA microarray study were identified. Bioinformatic analyses revealed that several target genes are involved in apoptosis and activation of T cells. CONCLUSIONS: Our genome-wide approach revealed several differentially expressed miRNAs in human AAA tissue suggesting that miRNAs play a role in AAA pathogenesis.

Comparison of outcomes with coils versus vascular plug embolization of the internal iliac artery for endovascular aortoiliac aneurysm repair.

OBJECTIVE: To compare the safety and efficacy of coil embolization (COIL) to Amplatzer vascular plug embolization (PLUG) to achieve internal iliac artery (IIA) occlusion prior to endovascular aortiliac aneurysm repair (EVAR). METHODS: Data from consecutive patients who underwent IIA embolization prior to EVAR over a 6-year period (2004-2010) were retrospectively reviewed. Patient demographics, treatment modalities, and outcomes were compared. RESULTS: From January 1, 2004 to December 31, 2010, a total of 53 patients underwent percutaneous embolization of 57 IIAs prior to EVAR. Twenty-nine IIAs underwent COIL and 28 IIAs underwent PLUG embolization. Patient demographics and risk factors were similar between the two groups. Patients underwent repair for aneurysmal dilation of the infrarenal aorta in conjunction with the common or internal iliac arteries (n = 35, 62%) or isolated iliac artery aneurysms (n = 19, 38%). A significantly greater number of embolization devices were used in the COIL group (5.8 ± 3.8 vs 1.1 ± 0.4; P < .0001). Patients undergoing PLUG embolization demonstrated significantly shorter procedure times (118.4 ± 64.7 minutes vs 72.6 ± 22.4 minutes; P = .008) and fluoroscopy times (32.6 ± 14.6 vs 14.4 ± 8.6 minutes; P = .002). However, radiation dose between the groups did not differ (COIL: 470,192.7 ± 190,606.6 vs PLUG: 300,972.2 ± 191,815.7 mGycm(2); P = .10). Overall periprocedural morbidity did not differ between the groups (COIL: 11% vs PLUG: 6%; P = 1.0), and there were no perioperative mortalities or severe complications. Nontarget embolization occurred in two COIL and no PLUG cases (COIL: 6.9% vs PLUG: 0%; P = .49). Patient-reported buttock claudication at 1 month was 17.2% for COIL and 39.3% for PLUG patients (P = .08). At last follow-up, persistent buttock claudication was reported in 13.8% of COIL and in 14.3% of PLUG embolizations (P = 1.0). There was no significant difference in charges for the embolization material, operating room, or overall hospital charges (COIL: 44,720 ± 19,153 vs 37,367 ± 10,915; P = .22). Lastly, zero endoleaks in the COIL group and three in the PLUG group (P = .40) were detected on the most recent follow-up computed tomography imaging. No endoleak was related to the site of IIA embolization. CONCLUSIONS: COIL and PLUG embolization both provide effective IIA embolization with low complication rates when used for EVAR. Buttock claudication did occur in approximately one-third of patients but resolved in half of those affected. PLUG embolization took significantly less time to perform and required decreased fluoroscopy times. Based on outcomes and cost-analysis, COIL and PLUG embolization are equivalent methods to achieve IIA occlusion during EVAR.

Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.

BACKGROUND: The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression. RESULTS: We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007). CONCLUSIONS: Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.

Role of complement cascade in abdominal aortic aneurysms.

OBJECTIVE: The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues. CONCLUSIONS: These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.

Small Bowel Volvulus in a Quadriplegic: A Rare Complication of the Simon Nitinol Inferior Vena Cava Filter.

The advent and use of inferior vena cava (IVC) filters have reduced the overall incidence of pulmonary embolism in hospitalized patients, but are not without potential complications. With the exponential increase in the utilization of IVC filters over the past two decades, it is important to consider the use of retrievable filters, where indicated, in order to potentially reduce long-term IVC filter-related complications. We report a rare case of small bowel volvulus due to IVC perforation by a Simon Nitinol filter strut in a quadriplegic patient 4 years after IVC filter insertion.

Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.

OBJECTIVE: The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs). METHODS: A genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with AAA was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set. RESULTS: A genome wide association study of AAA cases and controls identified a candidate AAA-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with AAA in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with AAA was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for AAA. The AAA-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site. CONCLUSION: This study identifies a region on chromosome 3 that is significantly associated with AAA in 2 distinct study populations.

Optional filters in trauma patients: can retrieval rates be improved?

Prophylactic inferior vena cava interruption may be appropriate in trauma patients at risk for pulmonary embolism for whom anticoagulation is contraindicated. The Recovery filter is approved for removal up to 180 days from insertion. High retrieval rates need to be achieved before we can lower the threshold for inserting these filters prophylactically. The objective of this study was to evaluate the retrieval rate of the Recovery filter in this patient population and how it has influenced our practice. This is a retrospective study in which the records of 122 consecutive trauma patients in whom the Recovery filters were inserted between October 2003 and October 2005 were reviewed. Patients who had the new generation of this filter were excluded. All these filters were inserted with the intention of retrieval. We attempted to contact all these patients at 3 months. The technical factors associated with failure to retrieve these filters were reviewed. There were no complications related to filter insertion. Excluding six patients (4.9%) who expired from causes unrelated to the insertion procedure, 20 patients could not be reached (17.3%) and 21 patients declined retrieval (18.1%). The filters were considered permanent in 18 patients (15.5%) if they were not ambulatory or if they developed inferior vena cava occlusion. Inferior vena cava occlusion was diagnosed in four patients (5.5%). Seventy-three (62.9%) patients presented for follow-up and were evaluated by color venous duplex ultrasound. We attempted to retrieve the filters in 52 patients and were successful in 45 (86.5%). However, the total retrieval rate was 40.5%. All failures of retrieval were related to tilting of the filters or bending of the limbs. There were no complications related to the retrieval procedure. Insertion and retrieval of the Recovery inferior vena cava filter are safe. In spite of the thorough follow-up and the good success rate in retrieving the filters, the overall retrieval rate in this patient population is still low. This should be strongly considered at the time of insertion. Multiple factors were found to contribute. Attention to details in patient selection and follow-up as well as modifications in technique may improve the retrieval rate.

Treatment of spontaneous lumbar artery pseudoaneurysm by computed tomography--guided thrombin injection.

A case of spontaneous pseudoaneurysm of a lumbar artery that was treated with computed tomography- guided thrombin injection is reported in this study. To the authors' knowledge, pseudoaneurysm of lumbar artery without any predisposing factors has been reported only twice in the literature previously. The aims of this case report are to discuss the differential diagnosis and management of this difficult problem.