Co-prevalence of arterial aneurysm location - a correlation analysis based on a retrospective cross-sectional observational study.

Background: The aim of this retrospective single-centre cross-sectional observational study was to investigate co-prevalence of arterial aneurysm location systematically. Patients and methods: Patients with the diagnosis of any arterial aneurysm from January 2006 to January 2016 were investigated in a single centre. Patients with hereditary disorders of connective tissue, systemic inflammatory disease, or arterial pathologies other than true aneurysms were excluded. Aneurysm locations were assessed for every patient included. For patients with at least two co-existing aneurysms, co-prevalence of aneurysm location was investigated by calculating correlation coefficients and applying Fisher's exact test. This study report is prepared according to the STROBE statement. Results: Of 3107 identified patients with arterial aneurysms, 918 were excluded. Of the remaining 2189 patients, 951 patients with at least two aneurysms were included in the study. Bilateral aneurysm combinations of paired iliac, femoral and popliteal arteries showed the highest correlation (ϕ=0.35 to 0.67), followed by bilateral combinations of subclavian (ϕ=0.36) and internal carotid (ϕ=0.38) arteries. Abdominal aortic aneurysms in combination with visceral artery aneurysms (ϕ=-0.24 to -0.12), popliteal arteries (ϕ=-0.22) and the ascending aorta (ϕ=-0.19) showed the lowest correlation, followed by the descending aorta in combination with the common iliac arteries (ϕ=-0.12 to -0.13). Conclusions: In our study sample, aneurysm co-prevalence was highly non-random. This should be considered in the context of aneurysm screening programs.

Characteristics of patients with multiple arterial aneurysms.

Background: The aim of this retrospective cross-sectional observational study was to determine differences of patients with multiple arterial aneurysms to patients with single arterial aneurysms. Patients and methods: Patients with the diagnosis of an arterial aneurysm from January 2006 to January 2016 in the department of vascular surgery Heidelberg were investigated. Excluded were patients with hereditary disorders of connective tissue or systemic inflammatory disease, as well as other arterial pathologies than true aneurysms. Patients with multiple aneurysms (defined by at least four aneurysms) were compared to patients with single aneurysms concerning age at initial diagnosis, sex and affected arterial site. To verify the findings, a replication of the study was performed at a comparable institution. Results: Of 3107 patients with arterial aneurysms, 918 were excluded. Of the resulting 2189 patients, 1238 (56.6%) patients had a single, 808 (36.9%) two or three, and 143 (6.5%) at least four aneurysms (group mult-AA). Nine hundred seventy-two patients (44.4%) had a single abdominal aortic aneurysm (group sing-AAA). Age at initial diagnosis differed between mult-AA (66.7±9.5 y) and sing-AAA (69.1±8.6 y) (p=0.0338). Within mult-AA, 138 patients (96.5%) were male, compared with 865 patients (89.0%) in sing-AAA (p=0.0041). The most frequent aneurysm localization shifted from the abdominal aorta and its branches in patients with a single aneurysm (n=1029; 83.1%) to pelvic and leg arteries in patients with at least four aneurysms (n=318; 63.2%). The replication of the study at the department of vascular surgery Frankfurt confirmed the younger age at initial diagnosis in mult-AA (67.3±12.5 y) compared to sing-AAA (70.9±9.6 y) (p=0.0259) and the distribution shift toward the arteries below the aortic bifurcation in mult-AA. Conclusions: Patients with multiple aneurysms are younger at initial diagnosis and differ concerning aneurysm localization compared to patients with a single aneurysm.

Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke.

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.

Gene Expression Profiling in Abdominal Aortic Aneurysms After Finite Element Rupture Risk Assessment.

PURPOSE: To investigate the association between local biomechanical rupture risk calculations from finite element analysis (FEA) and whole-genome profiling of the abdominal aortic aneurysm (AAA) wall to determine if AAA wall regions with highest and lowest estimated rupture risk show different gene expression patterns. METHODS: Six patients (mean age 74 years; all men) scheduled for open surgery to treat asymptomatic AAAs (mean diameter 55.2±3.5 mm) were recruited for the study. Rupture risk profiles were estimated by FEA from preoperative computed tomography angiography data. During surgery, AAA wall samples of ~10 mm2 were extracted from the lowest and highest rupture risk locations identified by the FEA. Twelve samples were processed for RNA extraction and subsequent whole genome expression profiling. Expression of single genes and of predefined gene groups were compared between vessel wall areas with highest and lowest predicted rupture risk. RESULTS: Normalized datasets comprised 15,079 gene transcripts with expression above background. In biopsies with high rupture risk, upregulation of 18 and downregulation of 18 genes was detected when compared to the low-risk counterpart. Global analysis of predefined gene groups revealed expression differences in genes associated with extracellular matrix (ECM) degradation (p<0.001), matrix metalloproteinase activity (p<0.001), and chemokine signaling (p<0.001). CONCLUSION: Increased expression of genes involved in degrading ECM components was present in AAA wall regions with highest biomechanical stress, supporting the thesis of mechanotransduction. More experimental studies with cooperation of multicenter vascular biobanks are necessary to understand AAA etiologies and identify further parameters of FEA model complementation.

Erythropoietin preconditioning improves clinical and histologic outcome in an acute spinal cord ischemia and reperfusion rabbit model.

OBJECTIVE: This study examined effects and functional outcome of recombinant human erythropoietin (rhEPO) and carbamylated erythropoietin fusion protein (cEPO-FC) preconditioning in a rabbit model for spinal cord ischemia and resulting paraplegia. This model was chosen because only a small surgical effect is needed to cause paraplegia in rabbits, which facilitates postoperative observation of animals. METHODS: Anesthetized but spontaneously breathing New Zealand White rabbits randomly received cEPO-FC (50 µg/kg; n = 8), rhEPO (5000 IU/kg; n = 10), or vehicle (control; n = 10) 30 minutes before and after infrarenal aortic clamping. Ideal clamping time of 22 minutes was identified from preceding clamping tests (15-25 minutes). Postoperative observation time was 96 hours. Spinal cord function was assessed by neurologic evaluation of hind limb motor function every 12 hours using a modified Tarlov score. Spinal cord tissue damage was evaluated after 96 hours using hematoxylin and eosin, elastica van Gieson, Nissl, Masson-Goldner, and hemosiderin staining. Plasma levels of cell senescence markers stathmin, chitinase 1/3, elongation factor 1-α were determined. RESULTS: Rabbits that received rhEPO showed significant improvement of spontaneous lower limb movements until 36 hours of reperfusion and improved histologic scores upon examination of the lumbar spinal cord compared with the control group. In contrast, cEPO-FC treatment showed comparable outcome to the control group concerning movements of the lower limbs and histology. Senescence markers were elevated in the control group, but not in the treatment groups, except for chitinase 3 in the rhEPO group. Only stathmin showed no significant effect. Markers for senescence might increase after acute ischemic injury. Attenuation of senescence markers might not come alone from improvement of the spinal cord. CONCLUSIONS: Preconditioning with rhEPO attenuates ischemia/reperfusion injury of the spinal cord, whereas the carbamylated derivative (cEPO-FC) showed no positive effect on spinal cord function.

Prediction of Rupture Sites in Abdominal Aortic Aneurysms After Finite Element Analysis.

PURPOSE: To associate regions of highest local rupture risk from finite element analysis (FEA) to subsequent rupture sites in abdominal aortic aneurysms (AAA). METHODS: This retrospective multicenter study analyzed computed tomography angiography (CTA) data from 13 asymptomatic AAA patients (mean age 76 years; 8 men) experiencing rupture at a later point in time between 2005 and 2011. All patients had CTA scans before and during the rupture event. FEA was performed to calculate peak wall stress (PWS), peak wall rupture risk (PWRR), rupture risk equivalent diameters (RRED), and the intraluminal thrombus volume (ILTV). PWS and PWRR locations in the prerupture state were compared with subsequent CTA rupture findings. Visible contrast extravasation was considered a definite (n=5) rupture sign, while a periaortic hematoma was an indefinite (n=8) sign. A statistical comparison was performed between the 13-patient asymptomatic AAA group before and during rupture and a 23-patient diameter-matched asymptomatic AAA control group that underwent elective surgery. RESULTS: The asymptomatic AAAs before rupture showed significantly higher PWRR and RRED values compared to the matched asymptomatic AAA control group (median values 0.74 vs 0.52 and 77 vs 59 mm, respectively; p<0.0001 for both). No statistical differences could be found for PWS and ILTV. Ruptured AAAs showed the highest maximum diameters, PWRR, and RRED values. In 7 of the ruptured AAAs (2 definite and 5 indefinite rupture signs), CTA rupture sites correlated with prerupture PWRR locations. CONCLUSION: The location of the PWRR in unruptured AAAs predicted future rupture sites in several cases. Asymptomatic AAA patients with high PWRR and RRED values have an increased rupture risk.

Current treatment strategies for ruptured abdominal aortic aneurysm.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) represents one of the most challenging emergencies in surgery. Open repair (OR) is associated with relevant morbidity and mortality and has not been reduced significantly over the last decade. The introduction of endovascular aneurysm repair (EVAR) and its meanwhile common use in the treatment of rAAA has raised the demand for randomised controlled trials (RCTs) in order to resolve a potential superiority of either OR or EVAR. PURPOSE: This review discusses the current treatment strategies in rAAA repair including diagnostics, peri-operative management and results of OR and EVAR, focussing on RCTs comparing both modalities. RESULTS: Thirty-day mortality after OR and EVAR shows no significant difference in published RCTs. In particular with respect to OR, 30-day mortality was much lower than anticipated throughout all RCTs ranging from 18 to 37 %. EVAR for rAAA resulted in reduced in-hospital stay. Limitations of all except one RCT are low patient recruitment and exclusion of haemodynamically unstable patients. CONCLUSIONS: OR and EVAR need to be provided for rAAA. Despite lacking evidence, EVAR is the first choice treatment in experienced high-volume vascular centres. Low mortality rates in all RCTs raise the question if aortic surgery should be centralised.

Increased expression and activation of absent in melanoma 2 inflammasome components in lymphocytic infiltrates of abdominal aortic aneurysms.

Chronic vascular inflammation is a key hallmark in the pathogenesis of abdominal aortic aneurysm (AAA). Recent investigations have suggested that the inflammasome, a cytosolic multiprotein complex that recognizes pathogen-associated molecular patterns, plays a role in atherosclerosis. However, its role in AAA inflammation has not yet been investigated. This pilot study analyzed inflammasome activation and its intramural localization in 24 biopsy samples from 11 patients with asymptomatic AAA versus 12 aortic samples from apparently healthy controls. Using a histological inflammation scale, we identified grade 2/3 inflammatory changes with lymphoid aggregates/tertiary lymphoid organs in 21 out of 24 AAA samples, whereas only 7 of the 12 control samples exhibited local grade 1 inflammatory changes. Strong expression levels of "apoptosis-associated speck-like protein with a caspase recruitment domain" (ASC), caspase-1, caspase-5 and "absent in melanoma 2" (AIM2) were detected by immunohistochemistry in both sporadic infiltrating lymphoid cells and lymphoid aggregates located in the outer media and adventitia of AAA samples. In contrast, inflammasome-positive cells were restricted to cholesterol plaque-associated areas and to single infiltrating cells in control aortas. Analysis of gene expression using real-time polymerase chain reaction (PCR) revealed significantly increased median mRNA levels of the inflammasome core components PYCARD (ASC), CASP1 (Caspase-1) and IL1B (IL-1ß) in AAA tissue compared with normal aorta. Moreover, significantly increased median amounts of AIM2 protein and mature caspase-5 (p20) were found in samples associated with high rupture risk compared with paired low rupture risk samples of the same AAA patient. We conclude from our data that AAA-associated lymphoid cells are capable of inflammasome signaling, suggesting that inflammasome activation is involved in the chronic inflammatory process driving AAA progression.

Finite element analysis of abdominal aortic aneurysms: predicted rupture risk correlates with aortic wall histology in individual patients.

PURPOSE: To evaluate a finite element analysis (FEA) model as a predictive tool for abdominal aortic aneurysm (AAA) rupture risk assessment. METHODS: FEA of asymptomatic infrarenal AAAs in 15 men (mean age 72 years) was performed preoperatively using semiautomatic finite element analysis software (A4clinics) to calculate peak wall stress (PWS) and regions of highest and lowest rupture risk index (RRI). The areas of high and low RRI identified on the preoperative FEA were sampled during open surgery; aortic wall specimens were prepared for histological analysis. A semiquantitative score compared the histological findings from high and low rupture risk samples. RESULTS: Significant correlation was found between histological AAA wall integrity and RRI in individual patients. AAA wall regions with highest RRI showed advanced histological disintegrity compared to regions with lower RRI within the same AAA: mean smooth muscle cells: 0.43 vs. 1.21, respectively (p=0.031); elastic fibers: 0.57 vs. 1.29, respectively (p=0.008); cholesterol plaque: 2.60 vs. 2.20, respectively (p=0.034); and calcified plaque: 2.27 vs. 1.40, respectively (p=0.017). The amount of calcified plaque was significantly correlated with PWS (r=0.528, p=0.043) by univariate regression analysis. However, there was no correlation between PWS or RRI and the histological findings between patients. CONCLUSION: These preliminary results show that high rupture risk regions estimated by FEA contain increased histopathological degeneration compared to low rupture risk samples within the same AAA. Until now, the role of FEA in predicting individual AAA rupture risk has not been established as a validated diagnostic tool. However, these data provide promising results for FEA model verification.

Correlation of four-dimensional ultrasound strain analysis with computed tomography angiography wall stress simulations in abdominal aortic aneurysms.

Objective: Biomechanical modeling of infrarenal aortic aneurysms seeks to predict ruptures in advance, thereby reducing aneurysm-related deaths. As individual methods focusing on strain and stress analysis lack adequate discretization power, this study aims to explore multifactorial characterization for progressive aneurysmal degeneration. The study's objective is to compare stress- and strain-related parameters in infrarenal aortic aneurysms. Methods: Twenty-two patients with abdominal aortic aneurysms (AAAs) (mean maximum diameter, 53.2 ± 7.2 mm) were included in the exploratory study, examined by computed tomography angiography (CTA) and three-dimensional real-time speckle tracking ultrasound (4D-US). The conformity of aneurysm anatomy in 4D-US and CTA was determined with the mean point-to-point distance (MPPD). CTA was employed for each AAA to characterize stress-related indices using the semi-automated A4-clinics RE software. Five segmentations from one 4D-US examination were fused into one averaged model for strain analysis using MATLAB and the Abaqus solver. Results: The mean MPPD between the adjacent points of the 4D-US and CTA-derived geometry was 1.8 ± 0.4 mm. The interclass correlation coefficients for all raters and all measurements for the maximum AAA diameter in 2D, 4D ultrasound, and CTA indicate moderate to good reliability (interclass correlation coefficient1 0.69 with 95% confidence interval [CI], 0.49-0.84; P < .001). The peak wall stress (PWS) correlates fairly with the maximum AAA diameter in 2D-US (r = 0.54; P < .01) and 4D-US (r = 0.53; P < .05) and moderately strongly with the maximum exterior AAA diameter (r = 0.63; P < .01). The peak wall rupture risk index shows a strong correlation with the PWS (ρ > 0.9; P < .001) and is influenced by anatomical parameters with equal strength. Isolated observation of the intraluminal thrombus does not provide significant information in the determination of PWS. The maximum AAA diameter in 2D-US shows a fair negative correlation with the mean circumferential, longitudinal and in-plane shear strain (ρ = -0.46; r = -0.45; ρ = -0.47; P < .05 for all). The circumferential strain ratio as an indicator of wall motion heterogeneity increases with the aneurysm diameter (r = 0.47; P < .05). The direct comparison of wall strain and wall stress indices shows no quantitative correlation. Conclusions: The strain and stress analyses provide independent biomechanical information of AAAs. At the current stage of development, the two methods are considered complementary and may optimize a more patient-specific rupture risk prediction in the future.

Histopathological Characterization of Abdominal Aortic Aneurysms from Patients with Multiple Aneurysms Compared to Patients with a Single Abdominal Aortic Aneurysm.

The aim of this study was to investigate histopathological differences in abdominal aortic aneurysms (AAAs) between patients with multiple and single arterial aneurysms, as we suspect that there are different underlying mechanisms in aneurysm formation. Analysis was based on a previous retrospective study on patients with multiple arterial aneurysms (mult-AA; defined as at least four, n = 143) and a single AAA (sing-AAA, n = 972) who were admitted to our hospital for treatment between 2006 and 2016. Available paraffin-embedded AAA wall specimens were derived from the Vascular Biomaterial Bank Heidelberg (mult-AA, n = 12 vs. sing-AAA, n = 19). Sections were analyzed regarding structural damage of the fibrous connective tissue and inflammatory cell infiltration. Alterations to the collagen and elastin constitution were assessed by Masson-Goldner trichrome and Elastica van Gieson staining. Inflammatory cell infiltration, response and transformation were assessed by CD45 and IL-1ß immunohistochemistry and von Kossa staining. The extent of aneurysmal wall alterations was assessed by semiquantitative gradings and was compared between the groups using Fisher's exact test. IL-1ß was significantly more present in the tunica media in mult-AA compared to sing-AAA (p = 0.022). The increased expression of IL-1ß in mult-AA compared to sing-AAA indicates inflammatory processes play a role in aneurysm formation in patients with multiple arterial aneurysms.

Association of Tumor Volumetry with Postoperative Outcomes for Cervical Paraganglioma.

Objectives: To analyze the association of tumor volume with outcome after surgery for cervical paraganglioma. Materials and Methods: This retrospective study included consecutive patients undergoing surgery for cervical paraganglioma from 2009-2020. Outcomes were 30-day morbidity, mortality, cranial nerve injury, and stroke. Preoperative CT/MRI was used for tumor volumetry. An association between the volume and the outcomes was explored in univariate and multivariable analyses. A receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) was calculated. The study was conducted and reported according to the STROBE statement. Results: Volumetry was successful in 37/47 (78.8%) of included patients. A 30-day morbidity occurred in 13/47 (27.6%) patients with no mortality. Fifteen cranial nerve lesions occurred in eleven patients. The mean tumor volume was 6.92 cm3 in patients without and 15.89 cm3 in patients with complications (p = 0.035) and 7.64 cm3 in patients without and 16.28 cm3 in patients with cranial nerve injury (p = 0.05). Neither the volume nor Shamblin grade was significantly associated with complications on multivariable analysis. The AUC was 0.691, indicating a poor to fair performance of volumetry in predicting postoperative complications. Conclusions: Surgery for cervical paraganglioma bears a relevant morbidity with a particular risk of cranial nerve lesions. Tumor volume is associated with morbidity, and MRI/CT volumetry can be used for risk stratification.

Case report: Resuscitative endovascular balloon occlusion after iatrogenic injury of the common iliac artery during neurosurgical dorsal lumbar microdiscectomy.

Introduction and importance: This case report describes resuscitative endovascular balloon occlusion (REBOA) of the aorta in a patient with life-threatening iatrogenic bleeding of the right common iliac artery during elective dorsal lumbar spine surgery. REBOA is an emergency procedure for temporary intra-aortic balloon occlusion being increasingly reported and published since its inauguration in 1954. The interdisciplinary management of hemorrhage and technical notes for a successful REBOA procedure will be presented. Case presentation: A 53-year-old female patient was admitted to the neurosurgery clinic suffering from left-sided L5 radiculopathy. During surgery, the anterior longitudinal ligament was perforated and an arterial vessel was lacerated. The patient became hemodynamically unstable demanding prompt supine repositioning and cardiopulmonary resuscitation (CPR). REBOA enabled cardiovascular stabilization after 90 min of CPR and laparotomy with vascular reconstruction and contributed to the survival of the patient without major clinical deficits. The patient was discharged from the ICU after 7 days. Clinical discussion: Resuscitative endovascular balloon occlusion of the aorta is an emergency procedure to control life-threatening hemorrhage. REBOA should be available on-scene and applied by well-trained vascular surgery personnel to control vascular complications or extend to emergency laparotomy and thoracotomy with aortic cross-clamping in case of in-hospital non-controllable hemorrhages. In case of ongoing CPR, we recommend surgical groin incision, open puncture of the pulseless common femoral artery, and aortic balloon inflation in REBOA zone I. Hereby, fast access and CPR optimization for heart and brain perfusion are maintained. Conclusion: Training for REBOA is the decisive factor to control selected cases of in-house and outpatient massive arterial abdominal bleeding complications.

A novel scatterplot-based method to detect copy number variation (CNV).

Objective: Most methods to detect copy number variation (CNV) have high false positive rates, especially for small CNVs and in real-life samples from clinical studies. In this study, we explored a novel scatterplot-based method to detect CNVs in microarray samples. Methods: Illumina SNP microarray data from 13,254 individuals were analyzed with scatterplots and by PennCNV. The data were analyzed without the prior exclusion of low-quality samples. For CNV scatterplot visualization, the median signal intensity of all SNPs located within a CNV region was plotted against the median signal intensity of the flanking genomic region. Since CNV causes loss or gain of signal intensities, carriers of different CNV alleles pop up in clusters. Moreover, SNPs within a deletion are not heterozygous, whereas heterozygous SNPs within a duplication show typical 1:2 signal distribution between the alleles. Scatterplot-based CNV calls were compared with standard results of PennCNV analysis. All discordant calls as well as a random selection of 100 concordant calls were individually analyzed by visual inspection after noise-reduction. Results: An algorithm for the automated scatterplot visualization of CNVs was developed and used to analyze six known CNV regions. Use of scatterplots and PennCNV yielded 1019 concordant and 108 discordant CNV calls. All concordant calls were evaluated as true CNV-findings. Among the 108 discordant calls, 7 were false positive findings by the scatterplot method, 80 were PennCNV false positives, and 21 were true CNVs detected by the scatterplot method, but missed by PennCNV (i.e., false negative findings). Conclusion: CNV visualization by scatterplots allows for a reliable and rapid detection of CNVs in large studies. This novel method may thus be used both to confirm the results of genome-wide CNV detection software and to identify known CNVs in hitherto untyped samples.

Arterial Aneurysm Localization Is Sex-Dependent.

The aim of this study was to investigate sex-dependent aneurysm distributions. A total of 3107 patients with arterial aneurysms were diagnosed from 2006 to 2016. Patients with anything other than true aneurysms, hereditary connective tissue disorders or vasculitides (n = 918) were excluded. Affected arterial sites and age at first aneurysm diagnosis were compared between women and men by an unpaired two-tailed t-test and Fisher's exact test. The study sample consisted of 2189 patients, of whom 1873 were men (85.6%) and 316 women (14.4%) (ratio m:w = 5.9:1). Men had considerably more aneurysms in the abdominal aorta (83.4% vs. 71.1%; p < 0.001), common iliac artery (28.7% vs. 8.9%; p < 0.001), internal iliac artery (6.6% vs. 1.3%; p < 0.001) and popliteal artery (11.1% vs. 2.5%; p < 0.001). In contrast, women had a higher proportion of aneurysms in the ascending aorta (4.4% vs. 10.8%; p < 0.001), descending aorta (11.1% vs. 36.4%; p < 0.001), splenic artery (0.9% vs. 5.1%; p < 0.001) and renal artery (0.8% vs. 6.0%; p < 0.001). Age at disease onset and further aneurysm distribution showed no considerable difference. The infrarenal segment might be considered a natural border for aneurysm formation in men and women suspected to have distinct genetic, pathophysiologic and ontogenetic factors. Screening modalities for women at risk might need further adjustment, particularly thoracic cross-sectional imaging complementation.

Gene Expression Profiling in Abdominal Aortic Aneurysms.

Gene expression profiling of abdominal aortic aneurysms (AAA) indicates that chronic inflammatory responses, active matrix metalloproteinases, and degradation of the extracellular matrix components are involved in disease development and progression. This study investigates intra- and interpersonal RNA genome-wide expression profiling differences (Illumina HumanHT-12, BeadCHIP expression) of 24 AAA biopsies from 12 patients using a single gene and pathway (GeneOntology, GO enrichment) analysis. Biopsies were collected during open surgical AAA repair and according to prior finite element analysis (FEA) from regions with the highest and lowest wall stress. Single gene analysis revealed a strong heterogeneity of RNA expression parameters within the same and different AAA biopsies. The pathway analysis of all samples showed significant enrichment of genes from three different signaling pathways (integrin signaling pathway: fold change FC 1.63, p = 0.001; cholecystokinin receptor pathway: FC 1.60, p = 0.011; inflammation mediated by chemokine signaling pathway: FC 1.45, p = 0.028). These results indicate heterogeneous gene expression patterns within the AAA vascular wall. Single biopsy investigations do not permit a comprehensive characterization of activated molecular processes in AAA disease.

Genetic Variation in LRP1 Associates with Stanford Type B Aortic Dissection Risk and Clinical Outcome.

Genetic variation in LRP1 (low-density lipoprotein receptor-related protein 1) was reported to be associated with thoracic aortic dissections and aneurysms. The aims of this study were to confirm this association in a prospective single-center patient cohort of patients with acute Stanford type B aortic dissections (STBAD) and to assess the impact of LRP1 variation on clinical outcome. The single nucleotide variation (SNV) rs11172113 within the LRP1 gene was genotyped in 113 STBAD patients and 768 healthy control subjects from the same population. The T-allele of rs11172113 was more common in STBAD patients as compared to the reference group (72.6% vs. 59.6%) and confirmed to be an independent risk factor for STBAD (p = 0.002) after sex and age adjustment in a logistic regression model analyzing diabetes, smoking and hypertension as additional risk factors. Analysis of clinical follow-up (median follow-up 2.0 years) revealed that patients with the T-allele were more likely to suffer aorta-related complications (T-allele 75.6% vs. 63.8%; p = 0.022). In this study sample of STBAD patients, variation in LRP1 was an independent risk factor for STBAD and affected clinical outcome.

Multiple Arterial Dissections and Connective Tissue Abnormalities.

BACKGROUND: Although patients with multiple arterial dissections in distinct arterial regions rarely present with known connective tissue syndromes, we hypothesized that mild connective tissue abnormalities are common findings in these patients. METHODS: From a consecutive register of 322 patients with cervical artery dissection (CeAD), we identified and analyzed 4 patients with a history of additional dissections in other vascular beds. In three patients, dermal connective tissue was examined by electron microscopy. DNA from all four patients was studied by whole-exome sequencing and copy number variation (CNV) analysis. RESULTS: The collagen fibers of dermal biopsies were pathologic in all three analyzed patients. One patient carried a CNV disrupting the COL3A1 and COL5A2 genes (vascular or hypermobility type of Ehlers-Danlos syndrome), and another patient a CNV in MYH11 (familial thoracic aortic aneurysms and dissections). The third patient carried a missense substitution in COL5A2. CONCLUSION: Three patients showed morphologic alterations of the dermal connective tissue, and two patients carried pathogenic variants in genes associated with arterial connective tissue dysfunction. The findings suggest that genetic testing should be recommended after recurrent arterial dissections, independently of apparent phenotypical signs of connective tissue disorders.