Peak wall rupture index is associated with risk of rupture of abdominal aortic aneurysms, independent of size and sex.

BACKGROUND: Information on the predictive determinants of abdominal aortic aneurysm rupture from CT angiography are scarce. The aim of this study was to investigate biomechanical parameters in abdominal aortic aneurysms and their association with risk of subsequent rupture. METHODS: In this retrospective study, the digital radiological archive was searched for 363 patients with ruptured abdominal aortic aneurysms. All patients who underwent at least one CT angiography examination before aneurysm rupture were included. CT angiography results were analysed to determine maximum aneurysm diameter, aneurysm volume, and biomechanical parameters (peak wall stress and peak wall rupture index). In the primary survival analysis, patients with abdominal aortic aneurysms less than 70 mm were considered. Sensitivity analyses including control patients and abdominal aortic aneurysms of all sizes were performed. RESULTS: A total of 67 patients who underwent 109 CT angiography examinations before aneurysm rupture were identified. The majority were men (47, 70%) and the median age at the time of CTA examination was 77 (71-83) years. The median maximum aneurysm diameter was 56 (interquartile range 46-65) mm and the median time to rupture was 2.13 (interquartile range 0.64-4.72) years. In univariable analysis, maximum aneurysm diameter, aneurysm volume, peak wall stress, and peak wall rupture index were all associated with risk of rupture. Women had an increased HR for rupture when adjusted for maximum aneurysm diameter or aneurysm volume (HR 2.16, 95% c.i. 1.23 to 3.78 (P = 0.007) and HR 1.92, 95% c.i. 1.06 to 3.50 (P = 0.033) respectively). In multivariable analysis, the peak wall rupture index was associated with risk of rupture. The HR for peak wall rupture index was 1.05 (95% c.i. 1.03 to 1.08) per % (P < 0.001) when adjusted for maximum aneurysm diameter and 1.05 (95% c.i. 1.02 to 1.08) per % (P < 0.001) when adjusted for aneurysm volume. CONCLUSION: Biomechanical factors appear to be important in the prediction of abdominal aortic aneurysm rupture. Women are at increased risk of rupture when adjustments are made for maximum aneurysm diameter alone.

Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm-related events.

OBJECTIVE: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. METHODS: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. RESULTS: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p < 0.001) were associated with significantly higher risks of AAA events. In the CART analysis, PWRI was identified as the best single predictor of AAA events at a cut-off value of > 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. CONCLUSION: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. KEY POINTS: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone.

Virtual Transcriptomics: Noninvasive Phenotyping of Atherosclerosis by Decoding Plaque Biology From Computed Tomography Angiography Imaging.

[Figure: see text].

Effect of Telmisartan on the Peak Wall Stress and Peak Wall Rupture Index of Small Abdominal Aortic Aneurysms: An Exploratory Analysis of the TEDY Trial.

OBJECTIVE: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among individuals with small AAAs. METHODS: Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p < .100) or systolic blood pressure (SBP) at one year. RESULTS: Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19; 95% CI -8.24, -0.14 kPa/year; p = .043) and PWRI (-0.014; 95% CI -0.026, -0.001; p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. CONCLUSION: The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.

Comparison of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms.

BACKGROUND: Previous studies have suggested that finite element analysis (FEA) can estimate the rupture risk of an abdominal aortic aneurysm (AAA); however, the value of biomechanical estimates over measurement of AAA diameter alone remains unclear. This study aimed to compare peak wall stress (PWS) and peak wall rupture index (PWRI) in participants with ruptured and asymptomatic intact AAAs. METHODS: The reproducibility of semiautomated methods for estimating aortic PWS and PWRI from CT images was assessed. PWS and PWRI were estimated in people with ruptured AAAs and those with asymptomatic intact AAAs matched by orthogonal diameter on a 1 : 2 basis. Spearman's correlation coefficient was used to assess the association between PWS or PWRI and AAA diameter. Independent associations between PWS or PWRI and AAA rupture were identified by means of logistic regression analyses. RESULTS: Twenty individuals were included in the analysis of reproducibility. The main analysis included 50 patients with an intact AAA and 25 with a ruptured AAA. Median orthogonal diameter was similar in ruptured and intact AAAs (82·3 (i.q.r. 73·5-92·0) versus 81·0 (73·2-92·4) mm respectively; P = 0·906). Median PWS values were 286·8 (220·2-329·6) and 245·8 (215·2-302·3) kPa respectively (P = 0·192). There was no significant difference in PWRI between the two groups (P = 0·982). PWS and PWRI correlated positively with orthogonal diameter (both P < 0·001). Participants with high PWS, but not PWRI, were more likely to have a ruptured AAA after adjusting for potential confounders (odds ratio 5·84, 95 per cent c.i. 1·22 to 27·95; P = 0·027). This association was not maintained in all sensitivity analyses. CONCLUSION: High aortic PWS had an inconsistent association with greater odds of aneurysm rupture in patients with a large AAA.

Biomechanical indices are more sensitive than diameter in predicting rupture of asymptomatic abdominal aortic aneurysms.

OBJECTIVE: Several studies of biomechanical rupture risk assessment (BRRA) showed its advantage over the diameter criterion in rupture risk assessment of abdominal aortic aneurysm (AAA). However, BRRA studies have not investigated the predictability of biomechanical risk indices at different time points ahead of rupture, nor have they been performed blinded for biomechanical analysts. The objective of this study was to test the predictability of the BRRA method against diameter-based risk indices in a quasi-prospective patient cohort study. METHODS: In total, 12 women and 31 men with intact AAAs at baseline have been selected retrospectively at two medical centers. Within 56 months, 19 cases ruptured, whereas 24 cases remained intact within 2 to 56 months. This outcome was kept confidential until all biomechanical activities in this study were finished. The biomechanical AAA rupture risk was calculated at baseline using high-fidelity and low-fidelity finite element method models. The capability of biomechanics-based and diameter-based risk indices to predict the known outcomes at 1 month, 3 months, 6 months, 9 months, and 12 months after baseline was validated. Besides common cohort statistics, the area under the curve (AUC) of receiver operating characteristic curves has been used to grade the different rupture risk indices. RESULTS: Up to 9 months ahead of rupture, the receiver operating characteristic analysis of biomechanics-based risk indices showed a higher AUC than diameter-based indices. Six months ahead of rupture, the largest difference was observed with an AUC of 0.878 for the high-fidelity biomechanical risk index, 0.859 for the low-fidelity biomechanical risk index, 0.789 for the diameter, and 0.821 for the sex-adjusted diameter. In predictions beyond 9 months, none of the risk indices proved to be superior. CONCLUSIONS: High-fidelity biomechanical modeling improves the predictability of AAA rupture. Asymptomatic AAA patients with high biomechanical AAA rupture risk indices have an increased risk of rupture. Integrating biomechanics-based diagnostic indices may significantly decrease the false-positive rate in AAA treatment. CLINICAL RELEVANCE: Rupture of abdominal aortic aneurysm (AAA) is the tenth leading cause of death in men older than 60 years; however, the currently used maximal diameter criterion has a high false-positive rate. In this study, we have compared this criterion with biomechanical rupture risk assessment on the unique data set of 43 asymptomatic AAAs, of which 19 ruptured later. Moreover, the AAA outcome was blinded to the operator for the first time. Our data demonstrated that the biomechanical rupture risk assessment is superior to maximal diameter in predicting AAA rupture up to 9 months ahead and significantly decreases the false-positive rate.

Systematic review and meta-analysis of the association between intraluminal thrombus volume and abdominal aortic aneurysm rupture.

BACKGROUND: Intraluminal thrombus (ILT) is present in most abdominal aortic aneurysms (AAAs), although its role in AAA progression is controversial. METHODS: A literature search was performed to identify studies that investigated the association between ILT volume and AAA rupture. A study assessment tool was developed to assess the methodologic quality of included studies. A meta-analysis was conducted using an inverse variance-weighted random-effects model to compare the ILT volume in ruptured and asymptomatic intact AAAs. Leave-one-out sensitivity analyses were conducted to assess the robustness of the findings. A subanalysis was performed including studies in which patients with asymptomatic intact and ruptured AAAs were matched for aortic diameter. Interstudy heterogeneity was assessed using the I2 statistic. RESULTS: Eight studies involving 672 patients were included in this systematic review. Meta-analysis of all studies found a greater ILT volume in patients with ruptured AAAs than in patients with asymptomatic intact AAAs (standardized mean difference, 0.56; 95% confidence interval, 0.17-0.96; P = .005; I2 = 79.8%). Sensitivity analyses suggested that the findings were robust; however, aortic diameter was significantly larger in ruptured than in asymptomatic intact AAAs (mean ± standard deviation, 78 ± 18 and 64 ± 15 mm, respectively; P < .001). In the subanalysis of studies that matched for diameter, no significant difference in ILT volume between groups was found (standardized mean difference, 0.03; 95% confidence interval, -0.27 to 0.33; P = .824; I2 = 0%). CONCLUSIONS: This meta-analysis suggests that ILT volume is greater in patients with ruptured AAAs than in patients with asymptomatic intact AAAs, although this is most likely due to the larger diameter of ruptured AAAs.

Amorphous and crystalline ices studied by dielectric spectroscopy.

This work reports on frequency dependent ambient-pressure dielectric measurements of hyperquenched glassy water, ice IV, ice VI, as well as a CO2-filled clathrate hydrate, the latter featuring a chiral water network. The dipolar time scales and the spectral shapes of the loss spectra of these specimens are mapped out and compared with literature data on low-density and high-density amorphous ices as well as on amorphous solid water. There is a trend that the responses of the more highly dense amorphous ices are slightly more dynamically heterogeneous than those of the lower-density amorphous ices. Furthermore, practically all of the amorphous ices, for which broadband dielectric spectra are available, display a curved high-frequency wing. Conversely, the high-frequency flanks of the nominally pure ice crystals including ice V and ice XII can be characterized by an approximate power-law behavior. While the spectral shapes of the nominally pure ices thus yield some hints regarding their amorphicity or crystallinity, a comparison of their time scale appears less distinctive in this respect. In the accessible temperature range, the relaxation times of the crystalline ices are between those of low-density and high-density amorphous ice. Hence, with reference also to previous work, the application of suitable doping currently seems to be the best dielectric spectroscopy approach to distinguish amorphous from crystalline ices.

Aortic Lumen Area Is Increased in Ruptured Abdominal Aortic Aneurysms and Correlates to Biomechanical Rupture Risk.

PURPOSE: To investigate how 2-dimensional geometric parameters differ between ruptured and asymptomatic abdominal aortic aneurysms (AAAs) and provide a biomechanical explanation for the findings. METHODS: The computed tomography angiography (CTA) scans of 30 patients (mean age 77±10 years; 23 men) with ruptured AAAs and 60 patients (mean age 76±8 years; 46 men) with asymptomatic AAAs were used to measure maximum sac diameter along the center lumen line, the cross-sectional lumen area, the total vessel area, the intraluminal thrombus (ILT) area, and corresponding volumes. The CTA data were segmented to create 3-dimensional patient-specific models for finite element analysis to compute peak wall stress (PWS) and the peak wall rupture index (PWRI). To reduce confounding from the maximum diameter, 2 diameter-matched groups were selected from the initial patient cohorts: 28 ruptured AAAs and another with 15 intact AAAs (diameters 74±12 vs 73±11, p=0.67). A multivariate model including the maximum diameter, the lumen area, and the ILT area of the 60 intact aneurysms was employed to predict biomechanical rupture risk parameters. RESULTS: In the diameter-matched subgroup comparison, ruptured AAAs had a significantly larger cross-sectional lumen area (1954±1254 vs 1120±623 mm2, p=0.023) and lower ILT area ratio (55±24 vs 68±24, p=0.037). The ILT area (2836±1462 vs 2385±1364 mm2, p=0.282) and the total vessel area (3956±1170 vs 4338±1388 mm2, p=0.384) did not differ statistically between ruptured and intact aneurysms. The PWRI was increased in ruptured AAAs (0.80 vs 0.48, p<0.001), but the PWS was similar (249 vs 284 kPa, p=0.194). In multivariate regression analysis, lumen area was significantly positively associated with both PWS (p<0.001) and PWRI (p<0.01). The ILT area was also significantly positively associated with PWS (p<0.001) but only weakly with PWRI (p<0.01). The lumen area conferred a higher risk increase in both PWS and PWRI when compared with the ILT area. CONCLUSION: The lumen area is increased in ruptured AAAs compared to diameter-matched asymptomatic AAAs. Furthermore, this finding may in part be explained by a relationship with biomechanical rupture risk parameters, in which lumen area, irrespective of maximum diameter, increases PWS and PWRI. These observations thus suggest a possible method to improve prediction of rupture risk in AAAs by measuring the lumen area without the use of computational modeling.

Gender, smoking, body size, and aneurysm geometry influence the biomechanical rupture risk of abdominal aortic aneurysms as estimated by finite element analysis.

OBJECTIVE: Finite element analysis (FEA) has been suggested to be superior to maximal diameter measurements in predicting rupture of abdominal aortic aneurysms (AAAs). Our objective was to investigate to what extent previously described rupture risk factors were associated with FEA-estimated rupture risk. METHODS: One hundred forty-six patients with an asymptomatic AAA of a 40- to 60-mm diameter were retrospectively identified and consecutively included. The patients' computed tomography angiograms were analyzed by FEA without (neutral) and with (specific) input of patient-specific mean arterial pressure (MAP), gender, family history, and age. The maximal wall stress/wall strength ratio was described as a rupture risk equivalent diameter (RRED), which translated this ratio into an average aneurysm diameter of corresponding rupture risk. RESULTS: In multivariate linear regression, RREDneutral increased with female gender (3.7 mm; 95% confidence interval [CI], 0.13-7.3) and correlated with patient height (0.27 mm/cm; 95% CI, 0.11-0.43) and body surface area (BSA, 16 mm/m2; 95% CI, 8.3-24) and inversely with body mass index (BMI, -0.40 mm/kg m-2; 95% CI, -0.75 to -0.054) in a wall stress-dependent manner. Wall stress-adjusted RREDneutral was raised if the patient was currently smoking (1.1 mm; 95% CI, 0.21-1.9). Age, MAP, family history, and patient weight were unrelated to RREDneutral. In specific FEA, RREDspecific increased with female gender, MAP, family history positive for AAA, height, and BSA, whereas it was inversely related to BMI. All results were independent of aneurysm diameter. Peak wall stress and RRED correlated with aneurysm diameter and lumen volume. CONCLUSIONS: Female gender, current smoking, increased patient height and BSA, and low BMI were found to increase the mechanical rupture risk of AAAs. Previously described rupture risk factors may in part be explained by patient characteristic-dependent variations in aneurysm biomechanics.

Inflammatory profile discriminates clinical subtypes in LRRK2-associated Parkinson's disease.

BACKGROUND AND PURPOSE: The presentation of Parkinson's disease patients with mutations in the LRRK2 gene (PDLRRK2 ) is highly variable, suggesting a strong influence of modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes. METHODS: An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PDLRRK2 patients from the MJFF LRRK2 Consortium, stratified by three different subtypes as recently proposed for idiopathic Parkinson's disease: diffuse/malignant, intermediate and mainly pure motor. RESULTS: Patients classified as diffuse/malignant presented with the highest levels of the pro-inflammatory proteins interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 1-ß (MIP-1-ß) paralleled by high levels of the neurotrophic protein brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their inflammatory profile by using discriminant and area under the receiver operating characteristic curve analysis. CONCLUSIONS: Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-ß as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PDLRRK2 and predict progression.

[Stereotactic laser thermocoagulation in epilepsy surgery]. / Stereotaktische Laserthermokoagulation in der Epilepsiechirurgie.

In common with other stereotactic procedures, stereotactic laser thermocoagulation (SLT) promises gentle destruction of pathological tissue, which might become especially relevant for epilepsy surgery in the future. Compared to standard resection, no large craniotomy is necessary, cortical damage during access to deep-seated lesions can be avoided and interventions close to eloquent brain areas become possible. We describe the history and rationale of laser neurosurgery as well as the two available SLT systems (Visualase® and NeuroBlate®; CE marks pending). Both systems are coupled with magnetic resonance imaging (MRI) and MR thermometry, thereby increasing patient safety. We report the published clinical experiences with SLT in epilepsy surgery (altogether approximately 200 cases) with respect to complications, brain structural alterations, seizure outcome, neuropsychological findings and treatment costs. The rate of seizure-free patients seems to be slightly lower than for resection surgery. Due to the inadequate quality of studies, the neuropsychological superiority of SLT has not yet been unambiguously demonstrated.

Volume growth of abdominal aortic aneurysms correlates with baseline volume and increasing finite element analysis-derived rupture risk.

BACKGROUND: The diagnosis and management of abdominal aortic aneurysms (AAAs) currently relies on the aortic maximal diameter, which grows in an unpredictable manner. Infrarenal aortic volume has recently become clinically feasible to measure, and an estimate of biomechanical rupture risk derived from finite element analysis, the peak wall rupture index (PWRI), has been shown to predict AAA rupture. Our objective was to ascertain how well volume growth correlates with baseline volume and increasing PWRI, compared with the maximal diameter. METHODS: We retrospectively identified 41 AAA patients (nine women, 32 men) at our institution who had undergone two computed tomography angiographies with an interval of 8 to 17 months. Digital three-dimensional reproductions of the aneurysms were segmented from the 82 computed tomography angiographies. AAA diameter, volume, and PWRI were measured and calculated with finite element analysis software. Growth rates of diameter and volume were related to baseline diameter and volume as well as to change rates of PWRI. Significant growth was defined as growth exceeding our interobserver 95% limits of agreement. RESULTS: Diameter growth rate did not correlate with baseline diameter (r = 0.15, 95% confidence interval [CI], -0.17 to 0.45), but volume growth rate correlated with baseline volume (r = 0.56; 95% CI, 0.30-0.75). The correlation between baseline volume and volume growth rate was stronger than the correlation between baseline diameter and diameter growth rate (95% CI, 0.086-0.71). Increasing PWRI correlated with volume growth rate (r = 0.70; 95% CI, 0.40-0.87) but not with diameter growth rate (r = 0.044; 95% CI, -0.44 to 0.51), and the difference between the correlation coefficients was significant (95% CI, 0.11-1.16). CONCLUSIONS: Volume better predicts aneurysm growth rate and correlates stronger with increasing estimated biomechanical rupture risk compared with diameter. Our results support the notion of monitoring all three dimensions of an AAA.

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

GBA-associated parkinsonism and dementia: beyond α-synucleinopathies?

BACKGROUND AND PURPOSE: To date the role of GBA mutations beyond α-synucleinopathies in the parkinsonism-dementia spectrum is still unclear. The aim of the study was to screen for GBA mutations in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and the behavioural variant of frontotemporal dementia (bvFTD). METHODS: In all, 303 patients with a clinical diagnosis of PSP (n = 157), CBS (n = 39), PPA (n = 35) and bvFTD (n = 72) and 587 neurologically healthy controls were screened for the most common GBA mutations. RESULTS: GBA mutations were detected in one healthy control and four patients with a clinical diagnosis of PSP (n = 1), probable CBS (n = 2) and PPA (n = 1, with concomitant C9orf72 expansion). Overall the prevalence of GBA mutations was low in non-α-synucleinopathies but significantly higher in the CBS subgroup compared to controls. CONCLUSION: Although numbers are small, our findings indicate that the clinical phenotype of GBA-associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying α-synucleinopathies. This may be of relevance, once causal therapeutic strategies for GBA-associated neurodegenerative disease are developed.

Local Diameter, Wall Stress, and Thrombus Thickness Influence the Local Growth of Abdominal Aortic Aneurysms.

PURPOSE: To investigate the influence of the local diameter, the intraluminal thrombus (ILT) thickness, and wall stress on the local growth rate of abdominal aortic aneurysms. METHODS: The infrarenal aortas of 90 asymptomatic abdominal aortic aneurysm (AAA) patients (mean age 70 years; 77 men) were retrospectively reconstructed from at least 2 computed tomography angiography scans (median follow-up of 1 year) and biomechanically analyzed with the finite element method. Each individual AAA model was automatically sliced orthogonally to the lumen centerline and represented by 100 cross sections with corresponding diameters, ILT thicknesses, and wall stresses. The data were grouped according to these parameters for comparison of differences among the variables. RESULTS: Diameter growth was continuously distributed over the entire aneurysm sac, reaching absolute and relative median peaks of 3.06 mm/y and 7.3%/y, respectively. The local growth rate was dependent on the local baseline diameter, the local ILT thickness, and for wall segments not covered by ILT, also on the local wall stress level (all p<0.001). For wall segments that were covered by a thick ILT layer, wall stress did not affect the growth rate (p=0.08). CONCLUSION: Diameter is not only a strong global predictor but also a local predictor of aneurysm growth. In addition, and independent of the diameter, the ILT thickness and wall stress (for the ILT-free wall) also influence the local growth rate. The high stress sensitivity of nondilated aortic walls suggests that wall stress peaks could initiate AAA formation. In contrast, local diameters and ILT thicknesses determine AAA growth for dilated and ILT-covered aortic walls.

Finite element analysis in asymptomatic, symptomatic, and ruptured abdominal aortic aneurysms: in search of new rupture risk predictors.

OBJECTIVES: To compare biomechanical rupture risk parameters of asymptomatic, symptomatic and ruptured abdominal aortic aneurysms (AAA) using finite element analysis (FEA). STUDY DESIGN: Retrospective biomechanical single center analysis of asymptomatic, symptomatic, and ruptured AAAs. Comparison of biomechanical parameters from FEA. MATERIALS AND METHODS: From 2011 to 2013 computed tomography angiography (CTA) data from 30 asymptomatic, 15 symptomatic, and 15 ruptured AAAs were collected consecutively. FEA was performed according to the successive steps of AAA vessel reconstruction, segmentation and finite element computation. Biomechanical parameters Peak Wall Rupture Risk Index (PWRI), Peak Wall Stress (PWS), and Rupture Risk Equivalent Diameter (RRED) were compared among the three subgroups. RESULTS: PWRI differentiated between asymptomatic and symptomatic AAAs (p < .0004) better than PWS (p < .1453). PWRI-dependent RRED was higher in the symptomatic subgroup compared with the asymptomatic subgroup (p < .0004). Maximum AAA external diameters were comparable between the two groups (p < .1355). Ruptured AAAs showed the highest values for external diameter, total intraluminal thrombus volume, PWS, RRED, and PWRI compared with asymptomatic and symptomatic AAAs. In contrast with symptomatic and ruptured AAAs, none of the asymptomatic patients had a PWRI value >1.0. This threshold value might identify patients at imminent risk of rupture. CONCLUSIONS: From different FEA derived parameters, PWRI distinguishes most precisely between asymptomatic and symptomatic AAAs. If elevated, this value may represent a negative prognostic factor for asymptomatic AAAs.

Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. METHODS: The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. RESULTS: Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2) = 0 per cent). CONCLUSION: This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA.

Genetic assessment of familial and early-onset Parkinson's disease in a Greek population.

BACKGROUND AND PURPOSE: Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population. METHODS: A genetic analysis in 111 familial or sporadic with early-onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene. RESULTS: In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations. CONCLUSIONS: The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.