Role of graft oversizing in the fixation strength of barbed endovascular grafts

PurposeThe role of endovascular graft oversizing on risk of distal graft migration following endovascular aneurysm repair for abdominal aortic aneurysm is poorly understood. A controlled in vitro investigation of the role of oversizing in graft-aorta attachment strength for endovascular grafts (EVGs) with barbs was performed.MethodsBarbed stent grafts (N = 20) with controlled graft oversizing varying from 4-45% were fabricated while maintaining other design variables unchanged. A flow loop with physiological flow characteristics and a biosynthetic aortic aneurysm phantom (synthetic aneurysm model with a bovine aortic neck) were developed. The stent grafts were deployed into the aortic neck of the bio-synthetic aortic aneurysm phantom under realistic flow conditions. Computed tomography imaging of the graft-aorta complex was used to document attachment characteristics such as graft apposition, number of barbs penetrated, and penetration depth and angle. The strength of graft attachment to the aortic neck was assessed using mechanical pullout testing. Stent grafts were categorized into four groups based on oversizing: 4-10%; 11-20%; 21-30%; and greater than 30% oversizing.ResultsPullout force, a measure of post-deployment fixation strength was not different between 4-10% (6.23 ± 1.90 N), 11-20% (6.25 ± 1.84 N) and 20-30% (5.85 ± 1.89 N) groups, but significantly lower for the group with greater than 30% oversizing (3.67 ± 1.41 N). Increasing oversizing caused a proportional decrease in the number of barbs penetrating the aortic wall (correlation = −0.83). Of the 14 barbs available in the stent graft, 89% of the barbs (12.5 of 14 on average) penetrated the aortic wall in the 4-10% oversizing group while only 38% (5.25 of 14) did for the greater than 30% group (P < .001). Also, the stent grafts with greater than 30% oversizing showed significantly poorer apposition characteristics such as eccentric compression or folding of the graft perimeter. The number and depth of barb penetration were found to be positively correlated to pullout force.ConclusionGreater than 30% graft oversizing affects both barb penetration and graft apposition adversely resulting in a low pullout force in this in vitro model. Barbed stent grafts with excessive oversizing are likely to result in poor fixation and increased risk of migration.Clinical RelevanceMigration of the endovascular grafts in abdominal aortic aneurysm (AAA) patients continues to be a cause of long-term complication in patients. This study is an assessment of the role of graft oversizing, a key variable chosen by the physician, on the fixation strength of these implants to the parent aorta. The findings suggest caution when choosing stent grafts that are excessively oversized

Stratification of a population of intracranial aneurysms using blood flow metrics.

Indices of the intra-aneurysm hemodynamic environment have been proposed as potentially indicative of their longitudinal outcome. To be useful, the indices need to be used to stratify large study populations and tested against known outcomes. The first objective was to compile the diverse hemodynamic indices reported in the literature. Furthermore, as morphology is often the only patient-specific information available in large population studies, the second objective was to assess how the ranking of aneurysms in a population is affected by the use of steady flow simulation as an approximation to pulsatile flow simulation, even though the former is clearly non-physiological. Sixteen indices of aneurysmal hemodynamics reported in the literature were compiled and refined where needed. It was noted that, in the literature, these global indices of flow were always time-averaged over the cardiac cycle. Steady and pulsatile flow simulations were performed on a population of 198 patient-specific and 30 idealised aneurysm models. All proposed hemodynamic indices were estimated and compared between the two simulations. It was found that steady and pulsatile flow simulations had a strong linear dependence (r ≥ 0.99 for 14 indices; r ≥ 0.97 for 2 others) and rank the aneurysms in an almost identical fashion (ρ ≥ 0.99 for 14 indices; ρ ≥ 0.96 for other 2). When geometry is the only measured piece of information available, stratification of aneurysms based on hemodynamic indices reduces to being a physically grounded substitute for stratification of aneurysms based on morphology. Under such circumstances, steady flow simulations may be just as effective as pulsatile flow simulation for estimating most key indices currently reported in the literature

The Function of Cortactin in the Clustering of Acetylcholine Receptors at the Vertebrate Neuromuscular Junction

Background: Postsynaptic enrichment of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (NMJ) depends on the activation of the muscle receptor tyrosine MuSK by neural agrin. Agrin-stimulation of MuSK is known to initiate an intracellular signaling cascade that leads to the clustering of AChRs in an actin polymerization-dependent manner, but the molecular steps which link MuSK activation to AChR aggregation remain incompletely defined. Methodology/Principal Findings: In this study we used biochemical, cell biological and molecular assays to investigate a possible role in AChR clustering of cortactin, a protein which is a tyrosine kinase substrate and a regulator of F-actin assembly and which has also been previously localized at AChR clustering sites. We report that cortactin was co-enriched at AChR clusters in situ with its target the Arp2/3 complex, which is a key stimulator of actin polymerization in cells. Cortactin was further preferentially tyrosine phosphorylated at AChR clustering sites and treatment of myotubes with agrin significantly enhanced the tyrosine phosphorylation of cortactin. Importantly, forced expression in myotubes of a tyrosine phosphorylation-defective cortactin mutant (but not wild-type cortactin) suppressed agrin-dependent AChR clustering, as did the reduction of endogenous cortactin levels using RNA interference, and introduction of the mutant cortactin into muscle cells potently inhibited synaptic AChR aggregation in response to innervation. Conclusion: Our results suggest a novel function of phosphorylation-dependent cortactin signaling downstream fro

Keratitis caused by the recently described new species Aspergillus brasiliensis: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Human infections caused by <it>Aspergillus brasiliensis </it>have not yet been reported. We describe the first two known cases of fungal keratitis caused by <it>Aspergillus brasiliensis</it>.</p> <p>Case presentations</p> <p>A 49-year-old Indian Tamil woman agricultural worker came with pain and defective vision in the right eye for one month. Meanwhile, a 35-year-old Indian Tamil woman presented with a history of a corneal ulcer involving the left eye for 15 days. The fungal strains isolated from these two cases were originally suspected to belong to <it>Aspergillus </it>section <it>Nigri </it>based on macro- and micromorphological characteristics. Molecular identification revealed that both isolates represent <it>A. brasiliensis</it>.</p> <p>Conclusion</p> <p>The two <it>A. brasiliensis </it>strains examined in this study were part of six keratitis isolates from <it>Aspergillus </it>section <it>Nigri</it>, suggesting that this recently described species may be responsible for a significant proportion of corneal infections caused by black Aspergilli. The presented cases also indicate that significant differences may occur between the severities of keratitis caused by individual isolates of <it>A. brasiliensis</it>.</p

Traumatic physical health consequences of intimate partner violence against women: what is the role of community-level factors?

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) against women is a serious public health issue with recognizable direct health consequences. This study assessed the association between IPV and traumatic physical health consequences on women in Nigeria, given that communities exert significant influence on the individuals that are embedded within them, with the nature of influence varying between communities.</p> <p>Methods</p> <p>Cross-sectional nationally-representative data of women aged 15 - 49 years in the 2008 Nigeria Demographic and Health Survey was used in this study. Multilevel logistic regression analysis was used to assess the association between IPV and several forms of physical health consequences.</p> <p>Results</p> <p>Bruises were the most common form of traumatic physical health consequences. In the adjusted models, the likelihood of sustaining bruises (OR = 1.91, 95% CI = 1.05 - 3.46), wounds (OR = 2.54, 95% CI = 1.31 - 4.95), and severe burns (OR = 3.20, 95% CI = 1.63 - 6.28) was significantly higher for women exposed to IPV compared to those not exposed to IPV. However, after adjusting for individual- and community-level factors, women with husbands/partners with controlling behavior, those with primary or no education, and those resident in communities with high tolerance for wife beating had a higher likelihood of experiencing IPV, whilst mean community-level education and women 24 years or younger were at lower likelihood of experiencing IPV.</p> <p>Conclusions</p> <p>Evidence from this study shows that exposure to IPV is associated with increased likelihood of traumatic physical consequences for women in Nigeria. Education and justification of wife beating were significant community-level factors associated with traumatic physical consequences, suggesting the importance of increasing women's levels of education and changing community norms that justify controlling behavior and IPV.</p

Comparison of the Association of Sac Growth and Coil Compaction with Recurrence in Coil Embolized Cerebral Aneurysms - Fig 4

<p><b>(A) Coil mass center translation, δ, in the recurrence (N = 9) and control cohorts (N = 9)</b>. The box and whisker plots show quartiles and the p-values are from one-tail Mann-Whitney U test for hypothesizing that δ will be higher in the recurrence cohort than in control (null hypothesis, <i>H</i>₀: δ_<b>RECR</b> ≤ δ_<b>CTRL</b>; alternative hypothesis, <i>H</i>_<b>A</b>: δ_<b>RECR</b> > δ_<b>CTRL</b>). The triangles indicate raw data values. <b>(B) Receiver operator curve showing the predictability of δ in recurrence (N = 9) and control (N = 9) aneurysms.</b> δ is a better predictor of recurrence than clinically measured sac size, as it has a larger area under the curve or AUC (AUC = 0.74). Optimal sensitivity and specificity in differentiating recurrence aneurysms from control was found at δ = 1.1 mm.</p

Aneurysm sac growth (<i>V</i>_SG) and Coil mass growth (<i>V</i>_CG) in the recurrence and control cohorts.

<p>The box and whisker plots show quartiles and the p-values are from paired one-tail Wilcoxon tests for hypothesizing that the aneurysm sac will grow (null hypothesis, <i>H</i>₀: <i>V</i>_<b>SG</b> ≤ 0; alternative hypothesis, <i>H</i>_<b>A</b>: <i>V</i>_<b>SG</b> > 0) and the coil mass will compact (<i>H</i>₀: <i>V</i>_<b>CG</b> ≥ 0; <i>H</i>_<b>A</b>: <i>V</i>_<b>CG</b> < 0).</p

Study subject procedural and demographic information

<p>*RE indicates recurrence; C, control; F, female; M, male; L, left; R, right; MCA, middle cerebral artery; Acom, anterior communicating artery; Pcom, posterior communicating artery; ICA, internal carotid artery</p><p>Study subject procedural and demographic information</p

Schematic illustration of the image processing protocol.

<p>‘1- ‘ indicates the pre-first coiling treatment time point; ‘1+’, post-first coiling treatment time point; ‘2-’, pre-second coiling treatment time point; ‘2+’, post-second coiling treatment time point; 3DRA, 3D rotational angiogram. The first column depicts the image processing protocol for the 1- time point, beginning with generation of the aneurysm and vessel model from the subtracted 3DRA scan. The aneurysm sac is then automatically isolated from the vasculature. A representative 1- aneurysm sac model is shown at the bottom of column 1. The adjacent column details the workflow for analyzing the data from the 1+ time point. At this time point the coil mass model is generated from the baseline (or bone) 3DRA scan, while the vessel and residual blood model is generated from the subtracted angiographic scan. The coil mass, vessel and residual blood models are then added together by Boolean union. The aneurysm sac is the combination of the coil mass and any outlying residual blood, of which the aneurysm neck surface is automatically determined. A representative 1+ aneurysm sac model is shown at the bottom of column 2. The remaining two columns outline a similar workflow for analyzing data from the 2- and 2+ time points respectively.</p

Methodology for estimation of annual risk of rupture for abdominal aortic aneurysm

Background and Objective: Estimating patient specific annual risk of rupture of abdominal aortic aneurysm (AAA) is currently based only on population. More accurate knowledge based on patient specific data would allow surgical treatment of only those AAAs with significant risk of rupture. This would be beneficial for both patients and health care system. Methods: A methodology for estimating annual risk of rupture (EARR) of abdominal aortic aneurysms (AAA) that utilizes Bayesian statistics, mechanics and patient-specific blood pressure monitoring data is proposed. EARR estimation takes into consideration, peak wall stress in AAA computed by patient-specific finite element modeling, the probability distributions of wall thickness, wall strength, systolic blood pressure and the period of time that the patient is known to have already survived with the intact AAA. Initial testing of proposed approach was performed on fifteen patients with intact AAA (mean maximal diameter 51mm +/- 8mm). They were equipped with a pressure holter and their blood pressure was recorded over 24 hours. Then, we calculated EARR values for four possible scenarios - without considering any days of survival prior identification of AAA at computed tomography scans (EARR_0), considering past survival of 30 (EARR_30), 90 (EARR_90) and 180 days (EARR_180). Finally, effect of patient-specific blood pressure variability was analyzed. Results: Consideration of past survival does indeed significantly improve predictions of future risk: EARR_30 (1.04% +/- 0.87%), EARR_90 (0.67% +/- 0.56%) and EARR_180 (0.47% +/- 0.39%) which are unrealistically high otherwise (EARR_0 5.02% +/- 5.24%). Finally, EARR values were observed to vary by an order as a consequence of blood pressure variability and by factor of two as a consequence of neglected growth. Conclusions: Methodology for computing annual risk of rupture of AAA was developed for the first time. Sensitivity analyses showed respecting patient specific blood pressure is important factor and should be included in the AAA rupture risk assessment. Obtained EARR values were generally low and in good agreement with confirmed survival time of investigated patients so proposed method should be further clinically validated.Web of Science200art. no. 10591