Small AAA Research Articles

Improving cardiovascular health in patients with an abdominal aortic aneurysm: development of the cardiovascular risk reduction in patients with aneurysms (CRISP) behaviour change intervention

BackgroundAbdominal aortic aneurysm (AAA) is an important cardiovascular health problem. Ultrasound screening is proven to reduce AAA mortality and programmes have been implemented in some healthcare systems. Those who are identified as having a small AAA in screening enter into a surveillance programme to monitor AAA size. Individuals in AAA surveillance are at elevated risk of cardiovascular events, which is not currently addressed sufficiently. We aimed to develop a simple intervention to reduce cardiovascular risk, which could be embedded in AAA surveillance pathways.MethodsIntervention mapping methods were used to co-develop the intervention with individuals with AAA, families/carers, and healthcare staff. We identified “targets for change” by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We conducted a series of workshops to identify barriers to and facilitators of change and used taxonomies of behaviour change theories and techniques to match intervention strategies to each target. Further stakeholder involvement work helped refine the intervention.ResultsThe developed intervention focusses on assessment and individually tailored discussion of risk factors, exchanging information, building motivation and action planning, followed by review of progress and problem-solving. Workbooks covering physical activity, diet, stress management, alcohol, smoking, blood pressure and mental health are provided to support behaviour change. The intervention is facilitated by trained healthcare professionals during the patient’s AAA screening appointment for the duration that they are in surveillance.DiscussionThe developed intervention will now be tested to assess whether it can be integrated with the current AAA screening programme. The developed intervention is a novel approach to reducing cardiovascular disease in the AAA population, it is also the first intervention which tries to do this in this population.Trial registrationInternational Clinical Trial Registration: ISRCTN93993995.

Revealing PPP1R12B and COL1A1 as piRNA pathway genes contributing to abdominal aortic aneurysm through integrated analysis and experimental validation

BackgroundAbdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta, with a high mortality rate when rupturing. Although lots of piRNA pathway genes (piRPGs) have recently been linked to both neoplastic and non-neoplastic illnesses, their role in AAA is still unknown. Utilizing integrative bioinformatics methods, this research discovered piRPGs as biomarkers for AAA and explore possible molecular mechanisms. MethodsThe datasets were obtained from the Gene Expression Omnibus and piRPGs were identified from the Genecards database. The “limma” and “clusterProfiler” R-packages were used to discover differentially expressed genes and perform enrichment analysis, respectively. Hub piRPGs were further filtered using least absolute shrinkage and selection operator regression, random forests, as well as receiver operating characteristic curve. Additionally, multi-factor logistic regression (MLR), extreme gradient boosting (XGboost), and artificial neural network (ANN) were employed to construct prediction models. The relationship between hub piRPGs and immune infiltrating cells and sgGSEA were further studied. The expression of hub piRPGs was verified by qRT-PCR, immunohistochemistry, and western blotting in AAA and normal vascular tissues and analyzed by scRNA-seq in mouse AAA model. SRAMP and cMAP database were utilized for the prediction of N6-methyladenosine (m6A) targets therapeutic drug. Results34 differentially expressed piRPGs were identified in AAA and enriched in pathways of immune regulation and gene silence. Three piRPGs (PPP1R12B, LRP10, and COL1A1) were further screened as diagnostic genes and used to construct prediction model. Compared with MLR and ANN, Xgboost showed better predictive ability, and PPP1R12B might have the ability to distinguish small and large AAA. Furthermore, the expression levels of PPP1R12B and COL1A1 were consistent with the results of bioinformatics analysis, and PPP1R12B showed a downward trend that may be related to m6A. ConclusionThe results suggest that piRPGs might serve a significant role in AAA. PPP1R12B, COL1A1, and LRP10 had potential as diagnostic-specific biomarkers for AAA and performed better in XGboost model. The expression and localization of PPP1R12B and COL1A1 were experimentally verified. Besides, downregulation of PPP1R12B caused by m6A might contribute to the formation of AAA.

Rivaroxaban in patients with abdominal aortic aneurysm and high-sensitivity C-reactive protein elevation (BANBOO): study protocol for a randomized, controlled trial

BackgroundAbdominal aortic aneurysm (AAA) is a fatal disease due to the tendency to rupture. The drug treatment for small AAA without surgical indications has been controversial. Previous studies showed that high-sensitivity C-reactive protein (hs-CRP) had become a potential biomarker of the disease, and the anti-inflammatory effect of rivaroxaban for AAA had been well established. Thus, we hypothesized that rivaroxaban could control the progression of AAA in patients with hs-CRP elevation.MethodsThe study is a prospective, open-label, randomized, controlled clinical trial. Sixty subjects are recruited from the General Hospital of Northern Theatre Command of China. Subjects are randomly assigned (1:1) to the intervention arm (rivaroxaban) or control arm (aspirin). The primary efficacy outcome is the level of serum hs-CRP at 6 months. The secondary outcomes include imaging examination (the maximal diameter of AAA, the maximal thickness of mural thrombus, and the length of aneurysm), major adverse cardiovascular and cerebrovascular events (MACCE, including AAA transformation, non-fatal myocardial infarction, acute congestive heart failure, stent thrombosis, ischemia-driven target vessel revascularization, vascular amputation, stroke, cardiovascular death, and all-cause death), and other laboratory tests (troponin T, interleukin 6, D-dimer, and coagulation function).DiscussionThe BANBOO trial tested the effect of rivaroxaban on the progression of AAA in patients with elevated Hs-CRP for the first time.Trial registrationChiCTR2100051990, ClinicalTrials.gov, registered on 12 October 2021.

The effect of diabetes on abdominal aortic aneurysm growth over 2 years

ObjectiveAbdominal aortic aneurysm (AAA) is a common progressive disease and a significant cause of morbidity and mortality. Prior investigations have shown that diabetes mellitus (DM) may be relatively protective of AAA incidence and growth. The Non-invasive Treatment of Aortic Aneurysm Clinical Trial (N-TA3CT) is a contemporary study of small AAA growth that provides a unique opportunity to validate and explore the effect of DM on AAA. Confirming the effect of DM on AAA growth in this study may present opportunities to explore for clues to potential biologic mechanisms as well as inform current patient management. MethodsThis is a secondary analysis examining the association of diabetes and aneurysm growth within N-TA3CT: a placebo-controlled multicenter trial of doxycycline in 261 patients with AAA maximum transverse diameters (MTDs) between 3.5 and 5 cm. The primary outcome is the change in the MTD from baseline as determined by computed tomography (CT) scans obtained during the trial. Secondary outcome is the growth pattern of the AAA. Baseline characteristics and growth patterns were assessed with t tests (continuous) or χ2 tests (categorical). Unadjusted and adjusted longitudinal analyses were performed with a repeated measures linear mixed model to compare AAA growth rates between patients with and without diabetes. ResultsOf 261 patients, 250 subjects had sufficient imaging and were included in this study. There were 56 patients (22.4%) with diabetes and 194 (77.6%) without. Diabetes was associated with higher body mass index and increased rates of hypercholesterolemia and coronary artery disease (P < .05). Diabetes was also associated with increased frequency of treatment for atherosclerosis and hypertension including treatment with statin, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, anti-platelet, and diuretic therapy (P < .05). Baseline MTD was not significantly different between those with (4.32 cm) and without DM (4.30 cm). Median growth rate for patients with diabetes was 0.12 cm/y (interquartile range, 0.07-0.22 cm/y) and 0.19 cm/y (interquartile range, 0.12-0.27 cm/y) in patients without DM, which was significantly different on unadjusted analysis (P < .0001). Diabetes remained significantly associated with AAA growth after adjustment for other relevant clinical factors (coef, −0.057; P < .0001). ConclusionsPatients with diabetes have more than a 35% reduction in the median growth rates of AAA despite more severe concomitant vascular comorbidities and similar initial sizes of aneurysms. This effect persists and remains robust after adjusted analysis; and slower growth rates may delay the time to reach repair threshold. Rapid growth (>0.5 cm/y) is infrequent in patients with DM.

Effect of Abdominal Aortic Aneurysm Size on Mid-Term Mortality After Endovascular Repair

BackgroundPrevious studies have suggested that large preoperative AAA size may impact late survival after elective EVAR. It is unclear, however, whether this association applies to patients with smaller AAA between 5.0-5.5 cm, who constitute a substantial portion of patients undergoing elective EVAR. The purpose of this study was to delineate the effect of AAA size between 5.0 and 5.5 cm on mid-term mortality after EVAR by analyzing a large national cohort, the Vascular Quality Initiative (VQI) database. MethodsUsing the Vascular Quality Initiative (VQI) national database, patients who underwent EVAR for intact AAA between 2003 and 2018 were identified and stratified based on maximal AAA diameter into 3 groups: Group 1 (4.0 cm ≤ AAA <5.0 cm); Group 2 (5.0 cm ≤ AAA < 5.5 cm); and Group 3 (AAA ≥ 5.5 cm). Cox proportional hazard model and propensity score matching method were used to estimate AAA size effect on all-cause mortality at 1, 3, and 5 years after EVAR while adjusting for potential confounders. ResultsThe study included 32,398 patients, of whom 81% were men with a mean age of 74. The most common group who underwent EVAR was Group 2 (5.0 cm ≤ AAA < 5.5 cm). Larger AAA size was associated with male sex (75% versus 79% versus 84%, for Groups 1, 2, and 3 respectively; P < 0.0001) and with coronary artery disease (27% versus 29% versus 31%, for Groups 1, 2, and 3 respectively, P< 0.0001); but was negatively associated with active smoking (33% versus 31% versus 30%, for Groups 1, 2, and 3, respectively, P< 0.001). While 10% of the largest and smallest AAA groups (Groups 3 and 1, respectively) were symptomatic, only 5% of patients in Group 2 were symptomatic (P < 0.01). Adjusted Cox proportional hazard modeling revealed that patients in Group 2 were at significantly lower risk of 5-year mortality when compared to patients in Group 3 (HR 0.66, 95% CI 0.61-0.72, P< 0.01), while similar in risk when compared to patients in Group 1 (HR 1.11, 95% CI 0.93-1.32, P= 0.26). ConclusionOur analysis found that over 40% of EVAR in the national VQI cohort were performed for AAA < 5.5 cm, with the greatest number of patients undergoing EVAR at AAA size 5.0-5.5cm. Patients with AAA size 5.0-5.5 cm had better 5-year survival outcomes than patients with AAA ≥ 5.5 cm, and similar survival to patients with small AAA between 4.0-5.0 cm.

Voltaic Cells: The Good (Faraday), the Bad (Volta), and the Ugly (Galvani)

Although the phrase “seat of EMF” in describing chemical cells has fallen into disuse, by distinguishing the distinct but incorrect conceptions both of Galvani and of Volta, in favor of the correct view of Faraday, “seat of EMF” it becomes possible (among other things) to understand:why internal resistance really is internal;why small AAA cells have the same 1.5-V EMF as much larger D cells;why AAA cells provide a given current for much less time than D cells; andwhy there is a difference between a slow (and fast) charge and discharge of an automobile battery.

Top 10 candidate aortic disease trials.

Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.

Hexameric structure of the ATPase motor subunit of magnesium chelatase in chlorophyll biosynthesis.

Magnesium chelatase (MgCh) is a heterotrimeric enzyme complex, composed of two AAA+ family subunits that can assembly into a double ring structure and a large catalytic subunit. The small AAA+ subunit has ATPase activity and can self-oligomerize into a ring structure, while the other AAA+ subunit lacks independent ATPase activity. Previous structural studies of the ATPase motor subunit of MgCh from a bacteriochlorophyll-synthesizing bacterium have identified a unique ATPase clade, but the model of oligomeric assembly is unclear. Here we present the hexameric structure of the MgCh ATPase motor subunit from the chlorophyll-synthesizing cyanobacterium Synechocystis sp. PCC 6803. This structure reveals details of how the hexameric ring is assembled, and thus provides a basis for further studying the heterotrimeric complex.

The Hsp70 chaperone network.

The 70-kDa heat shock proteins (Hsp70s) are ubiquitous molecular chaperones that act in a large variety of cellular protein folding and remodelling processes. They function virtually at all stages of the life of proteins from synthesis to degradation and are thus crucial for maintaining protein homeostasis, with direct implications for human health. A large set of co-chaperones comprising J-domain proteins and nucleotide exchange factors regulate the ATPase cycle of Hsp70s, which is allosterically coupled to substrate binding and release. Moreover, Hsp70s cooperate with other cellular chaperone systems including Hsp90, Hsp60 chaperonins, small heatshock proteins and Hsp100 AAA+ disaggregases, together constituting a dynamic and functionally versatile network for protein folding, unfolding, regulation, targeting, aggregation and disaggregation, as well as degradation. In this Review we describe recent advances that have increased our understanding of the molecular mechanisms and working principles of the Hsp70 network. This knowledge showcases how the Hsp70 chaperone system controls diverse cellular functions, and offers new opportunities for the development of chemical compounds that modulate disease-related Hsp70 activities.

Hinge-Linker Elements in the AAA+ Protein Unfoldase ClpX Mediate Intersubunit Communication, Assembly, and Mechanical Activity.

The ClpXP protease plays important roles in protein homeostasis and quality control. ClpX is a ring-shaped AAA+ homohexamer that unfolds target proteins and translocates them into the ClpP peptidase for degradation. AAA+ modules in each ClpX subunit-consisting of a large AAA+ domain, a short hinge-linker element, and a small AAA+ domain-mediate the mechanical activities of the ring hexamer. Here, we investigate the roles of these hinge-linker elements in ClpX function. Deleting one hinge-linker element in a single-chain ClpX pseudohexamer dramatically decreases unfolding and degradation activity, in part by compromising the formation of closed rings, protein-substrate binding, and ClpP binding. Covalently reclosing the broken hinge-linker interface rescues activity. Deleting one hinge-linker element from a single-chain dimer or trimer prevents assembly of stable hexamers. Mutationally disrupting a hinge-linker element preserves closed-ring assembly but reduces ATP-hydrolysis cooperativity and degradation activity. These results indicate that hinge-linker length and flexibility are optimized for efficient substrate unfolding and support a model in which the hinge-linker elements of ClpX facilitate efficient degradation both by maintaining proper ring geometry and facilitating subunit-subunit communication. This model informs our understanding of ClpX as well as the larger AAA+ family of motor proteins, which play diverse roles in converting chemical into mechanical energy in all cells.

Abdominal aortic aneurysm: screening and management

AbstractAbdominal aortic aneurysm (AAA) is a frequent cause of death. Management of AAA includes different strategies: open surgery repair, endovascular repair and, for small AAA, medical therapy and careful follow‐up. Endovascular repair is a valid alternative to surgical repair, especially in patients whit high procedural risk.

Cardiovascular risk in patients with small abdominal aortic aneurysms

BackgroundAbdominal aortic aneurysm (AAA) is a cardiovascular health problem. Ultrasound screening has been shown to reduce the risk of AAA-related, but not all-cause, mortality. The recent introduction of screening in several countries has meant that thousands of patients with a small AAA (<5·5cm) that does not require immediate treatment are diagnosed annually. We sought to investigate the cardiovascular profiles of patients with ectatic aortas and assess whether participation in screening reduces cardiovascular risk. MethodsWe used three sets of data: from the National Health Service AAA Screening Programme (NAAASP) during the 2013–14 round that were linked with Health Episode Statistics (HES) (235 409 individuals); a subset of the Framingham Study population who had an abdominal CT scan in 2004–05 and were followed up for 10 years (1383 individuals); and data for patients with a small AAA who had been in surveillance for at least 1 year in the UK Aneurysm Growth Study (UKAGS) (384 individuals) or from a national UK audit (1538 individuals), to assess cardiovascular risk and events. FindingsIn the linked NAAASP–HES cohort, cardiovascular mortality was 0·30% (95% CI 0·28–0·32) for individuals with an abdominal aortic diameter of less than 2·5 cm; 0·81% (0·51–1·11) for those between 2·5 and 2·9 cm; and 1·30% (0·90–1·71) for those less than 3·0 cm. Death from a cardiovascular event was more likely for individuals with a small AAA than for those without AAA (risk ratio 4·33, 95% CI 3·15–5·97). In the Framingham cohort, abdominal aortic diameter was independently associated with cardiovascular events (hazard ratio [HR] 1·1, 95% CI 1·02–1·18; p<0·0001). An abdominal aortic diameter of more than 2·5 cm was also associated with cardiovascular events (HR 7·6, 95% CI 5·1–11·3; p<0·0001). In the UKAGS and audit populations, patients were not more likely to take antiplatelet agents or statins after entering screening surveillance; cholesterol concentrations and blood pressure also increased. InterpretationIn these contemporary large cohorts of patients with small AAA, cardiovascular events and death were common and were the leading cause of death. The implication is that patients are not more likely to receive cardiovascular protection if they enter screening or surveillance with existing protocols. Cardiovascular risk reduction interventions should be implemented in screening programmes in the future. FundingAcademy of Medical Sciences, National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, NIHR.

A potential contribution of dipeptidyl peptidase-4 by the mediation of monocyte differentiation in the development and progression of abdominal aortic aneurysms

ObjectiveAbdominal aortic aneurysms (AAAs) are characterized by the destruction of elastin and collagen in the media and adventitia. Dipeptidyl peptidase-4 (DPP-4, an adipokine known as CD26) influences cell signaling, cell-matrix interactions, and the regulation of the functional activity of incretins in metabolic and inflammatory disorders. Although the role of DPP-4 in AAA evolution has been demonstrated, the underlying mechanisms of DPP-4-regulated AAA development remains unknown. MethodsPatients with AAA (n = 93) and healthy controls (CTL, n = 20) were recruited. Based on computed tomography image analyses, 93 patients were divided into two groups: those with a small AAA (SAA, aortic diameter <5 cm, n = 16) and those with a large AAA (LAA, aortic diameter ≥5 cm, n = 77). Plasma DPP-4, glucagon-like peptide-1 levels, and expression of CD26 on mononuclear cells were analyzed. In addition, phorbol 12-myristate 13-acetate (PMA)-induced THP-1 cells and angiotensin II-infused apolipoprotein EtmlUnc mice were used to explore the underlying mechanisms. ResultsThe levels of DPP-4 (μU/μg) increased while active glucagon-like peptide-1 (pM) decreased in patients with AAA in a diameter-dependent manner [CTL: 2.3 ± 1.5 and 3.7 ± 2.4, respectively; SAA: 10.0 ± 10.9 and 2.1 ± 0.9, respectively; LAA: 32.2 ± 15.0 and 1.8 ± 1.1, respectively]. A significant decline in monocyte CD26 expression in patients with AAAs was observed relative to the CTL group. In vitro studies demonstrated that the inhibition of DPP-4 promoted PMA-induced monocytic cells differentiation, with increased CD68 and p21 expression, regulated by extracellular signal-regulated protein kinase 1/2 activation. Furthermore, inhibition of DPP-4 significantly increased the phosphorylation of PYK2 and paxillin in PMA-induced THP-1 cell differentiation. Finally, the animal study was used to confirm the in vitro results that LAA mice showed marked macrophage infiltration in the adventitia with a decreased expression of DPP-4 as compared with SAA mice. ConclusionsIncreased plasma DPP-4 activity may correlate with aneurysmal development. CD26 on monocytes plays a critical role in cell differentiation, possibly mediated by extracellular signal-regulated protein kinase 1/2-p21 axis signaling pathways and cytoskeletal proteins reassembly. Exploring the role of DPP-4 further may yield potential therapeutic insights.

Abstract 26: Low Plasma Mir-155 Levels and RhoA Activation Correlates with Small AAA Expansion

Introduction: Given increased abdominal imaging studies, the incidental diagnosis and treatment of small AAAs is problematic. Presently, no specific recommendations for medical management can be made other than serial observation. The ras homolog member A (RhoA) signaling cascade is implicated in vascular diseases due to its ability to modulate monocyte endothelial invasion. We sought to investigate the RhoA signaling pathway in AAA expansion, along with an endogenous inhibitor of RhoA, microRNA-155 (miR-155). Hypothesis: We hypothesize that RhoA is activated to enable AAA expansion, but once expanded, miR-155 is called on to inhibit RhoA activation so that the expanded AAA can be stabilized. Methods: Peripheral blood was collected for monocyte and plasma isolation from stable AAA (&lt; 0.1 cm/year) (n=9) and expanding AAA (≥ 0.1 cm/year) (n=10) patients. Rhotekin-RBD assay and western blots were used to assess relative Rho-GTP expression and quantitative PCR for miR-155 detection in blood plasma. T-test and χ2 analysis were used to determine statistical significance. Results: Given limited monocytes, 6 stable and 10 expanding AAA patients were identified for RhoA analysis. Monocytes from expanding AAA patients contained higher active Rho-GTP protein levels compared to stable AAA monocytes (Figure 1a: 1.60±.075 vs 1.20±.088, ρ=.0004). Plasma concentrations of miR-155 were significantly lower in expanding AAA plasma compared to stable AAAs (Figure 1b: -2.17±.95, P=.005). Conclusions: Expanding AAA patients have greater monocyte activation of RhoA and decreased plasma expression of miR-155, when compared to stable AAA patients. The RhoA signaling pathway has altered activation in AAA disease and its regulation may reduce expansion rates and inflammation.

Commentary on ‘Rupture of Abdominal Aortic Aneurysms in Patients under Screening Age and Elective Repair Threshold’

patients and larger aneurysms, respectively. 3 Interestingly, 18.3% of all patients were younger than the universally accepted screening age of 65 years, demonstrating also a gender specific difference (21.4% of men and 3.0% of women were younger than 65 years). This proportion was even larger for smokers, who were more likely to present with an early RAAA than non-smokers, with 28.4% of smokers being under the screening age. These results come as no surprise. Our guidelines acknowledge the fact that a significant number of ruptures occur in individuals younger than 65 years, with the reported proportion varying from 5% to 18%. 2 In agreement with the authors’ findings (18.3% of all patients being below the generally accepted screening age of 65 years), in our personal unpublished series of RAAA, 17% of all patients were younger than 65 years (17.5% and 9.1% for the subgroup of men and women, respectively). In the landmark ADAM study, the mean unadjusted prevalence of AAA 4 cm in male smokers in the two age groups of 55e64 years and 65e79 years was 1.2% and 2.4%, respectively, 1 indicating that restricting AAA screening to the latter group of patients will miss 33% of all AAAs in this population; these observations fit perfectly with the 28.4% frequency of ruptured AAAs in smokers younger than 65 reported by the authors. According to the guidelines, screening should be considered at an earlier age for those at higher risk of AAA, 2,4 such as male smokers, males and also females with a family history of a AAA, or in the presence of any atherosclerotic vascular disease or other risk factors. Obviously a second screening scan would be required at a later stage. According to the authors’ study, 6% of men and 12% of women had a RAAA below the suggested repair diameter threshold of 55 mm and 52 mm, respectively. Since the mean AAA diameter was significantly lower in women than in men, females had an odds ratio of 3.2 compared with men for experiencing rupture of a small (O < 55 mm) AAA in a logistic regression analysis. In the UKSAT study, death was attributable to a ruptured AAA in 5% of men and 14% of women who died, 5 indicating firstly the need to lower the repair threshold for women, secondly the necessity for vigorous follow up of real world patients with a small AAA, and thirdly a commitment to more research on identifying markers predicting future rupture of small AAAs.

Incidence of small abdominal aortic aneurysms rupture, impact of comorbidities and our experience with rupture risk prediction based on wall stress assessment

AimAbdominal aortic aneurysm rupture (AAA) threatens a patient's life, requiring an urgent open repair or endovascular surgery. If an asymptomatic AAA is found before a rupture the next steps are directed by its diameter – if it is less than 55mm the patient is dispensarized, and if it is more a repair is indicated. According to literary sources 10–24% of ruptured AAA are less than 55mm in diameter, thus a significant portion of dispensarized patients are threatened by a rupture. The objective of our study was to determine a portion of small ruptured AAA repaired in our center in the last four years and try to identify potential risk factor. The secondary goal was to show our experience with a modern method of rupture prediction, using CT scans to compute the wall stress of AAA and thus predict its rupture risk. MethodsA retrospective study of documentation of patients with ruptured AAA in last four years. CT findings were used to measure maximal diameter of ruptured AAA and portion of small AAA was determined. Some other important information from patient's medical history were also compared in both groups and statistically evaluated. Results41 patients underwent an open repair of ruptured AAA. Out of this number 7 ruptured AAA were small, which is equivalent to 17.1%. ConclusionThis finding shows us the shortages of the present indication criteria based on an AAA diameter. In accordance to these criteria patients with small AAA are dispensarized and thus a significant part of them are in risk of rupture.

SU-E-T-533: Evaluation of Dose Calculation Accuracy for Small Elongated Targets On the Edge Linac

Purpose: To evaluate output factors and dose calculation accuracy on a novel SRS linear accelerator, the Edge (Varian), for treatments of small, elongated targets using flattening filter free (FFF) beam. Methods: Total scatter/output factors (OF’s) for 24 elongated, small, high definition multi-leaf collimator (HDMLC)-defined fields were measured on the Edge machine using 6X FFF beam. 3 detectors were used in water tank: CC01 ion chamber (active volume 10cc), stereotactic photon diode (SFD) (active diameter 0.6mm, active thickness 0.06mm), Edge detector (active volume 0.0019cc). The 24 MLC apertures have widths ranging from 5 to 20mm and length/width ratio from 0.25 to 5. Readings were cross calibrated with CC04 at field size 3×3 cm. A beam model was developed using commissioning measurements for treatment planning in Eclipse (AAA, version 11). One representative patient case (IMRT, target volume 0.2cc, 4×4×14mm) was calculated using AAA 11 and delivered on the Edge. Results: Due to volume averaging effects, CC01 readings were 11.2±0.9% lower than SFD readings for 5mm field sizes. The Edge diode showed a uniform over-response of 2.6±0.7% compared to SFD. Calculation using AAA v11 showed the best agreement with SFD measurements (2.4±1.7% lower than SFD). The largest difference between AAA v11 and SFD occurs at 5mm field sizes. For the patient plan, dose delivered on Edge was measured to be 2.2% higher than AAA v11 calculation. Conclusion: Cross-calibrated SFD output measurements presented the best agreement with commissioned AAA v11 beam model. Field sizes smaller than 1cm posed challenges to both the detectors and the calculation algorithm. For the representative patient with small elongated target, AAA v11 and measurements agreed within ~2% on the Edge linac. Although encouraging, a more comprehensive study is required to validate the overall algorithmic accuracy.

Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness

Small abdominal aortic aneurysms (AAAs; 3.0-5.4 cm in diameter) are usually asymptomatic and managed by regular ultrasound surveillance until they grow to a diameter threshold (commonly 5.5 cm) at which surgical intervention is considered. The choice of appropriate surveillance intervals is governed by the growth and rupture rates of small AAAs, as well as their relative cost-effectiveness. The aim of this series of studies was to inform the evidence base for small AAA surveillance strategies. This was achieved by literature review, collation and analysis of individual patient data, a focus group and health economic modelling. We undertook systematic literature reviews of growth rates and rupture rates of small AAAs. The databases MEDLINE, EMBASE on OvidSP, Cochrane Central Register of Controlled Trials 2009 Issue 4, ClinicalTrials.gov, and controlled-trials.com were searched from inception up until the end of 2009. We also obtained individual data on 15,475 patients from 18 surveillance studies. Systematic reviews of publications identified 15 studies providing small AAA growth rates, and 14 studies with small AAA rupture rates, up to December 2009 (later updated to September 2012). We developed statistical methods to analyse individual surveillance data, including the effects of patient characteristics, to inform the choice of surveillance intervals and provide inputs for health economic modelling. We updated an existing health economic model of AAA screening to address the cost-effectiveness of different surveillance intervals. In the literature reviews, the mean growth rate was 2.3 mm/year and the reported rupture rates varied between 0 and 1.6 ruptures per 100 person-years. Growth rates increased markedly with aneurysm diameter, but insufficient detail was available to guide surveillance intervals. Based on individual surveillance data, for each 0.5-cm increase in AAA diameter, growth rates increased by about 0.5 mm/year and rupture rates doubled. To control the risk of exceeding 5.5 cm to below 10% in men, on average a 7-year surveillance interval is sufficient for a 3.0-cm aneurysm, whereas an 8-month interval is necessary for a 5.0-cm aneurysm. To control the risk of rupture to below 1%, the corresponding estimated surveillance intervals are 9 years and 17 months. Average growth rates were higher in smokers (by 0.35 mm/year) and lower in patients with diabetes (by 0.51 mm/year). Rupture rates were almost fourfold higher in women than men, doubled in current smokers and increased with higher blood pressure. Increasing the surveillance interval from 1 to 2 years for the smallest aneurysms (3.0-4.4 cm) decreased costs and led to a positive net benefit. For the larger aneurysms (4.5-5.4 cm), increasing surveillance intervals from 3 to 6 months led to equivalent cost-effectiveness. There were no clear reasons why the growth rates varied substantially between studies. Uniform diagnostic criteria for rupture were not available. The long-term cost-effectiveness results may be susceptible to the modelling assumptions made. Surveillance intervals of several years are clinically acceptable for men with AAAs in the range 3.0-4.0 cm. Intervals of around 1 year are suitable for 4.0-4.9-cm AAAs, whereas intervals of 6 months would be acceptable for 5.0-5.4-cm AAAs. These intervals are longer than those currently employed in the UK AAA screening programmes. Lengthening surveillance intervals for the smallest aneurysms was also shown to be cost-effective. Future work should focus on optimising surveillance intervals for women, studying whether or not the threshold for surgery should depend on patient characteristics, evaluating the usefulness of surveillance for those with aortic diameters of 2.5-2.9 cm, and developing interventions that may reduce the growth or rupture rates of small AAAs. The National Institute for Health Research Health Technology Assessment programme.

Surveillance Intervals for Small Abdominal Aortic Aneurysms

Small abdominal aortic aneurysms (AAAs [3.0 cm-5.4 cm in diameter]) are monitored by ultrasound surveillance. The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture. To limit risk of aneurysm rupture or excessive growth by optimizing ultrasound surveillance intervals. Individual patient data from studies of small AAA growth and rupture were assessed. Studies were identified for inclusion through a systematic literature search through December 2010. Study authors were contacted, which yielded 18 data sets providing repeated ultrasound measurements of AAA diameter over time in 15,471 patients. AAA diameters were analyzed using a random-effects model that allowed for between-patient variability in size and growth rate. Rupture rates were analyzed by proportional hazards regression using the modeled AAA diameter as a time-varying covariate. Predictions of the risks of exceeding 5.5-cm diameter and of rupture within given time intervals were estimated and pooled across studies by random effects meta-analysis. AAA growth and rupture rates varied considerably across studies. For each 0.5-cm increase in AAA diameter, growth rates increased on average by 0.59 mm per year (95% CI, 0.51-0.66) and rupture rates increased by a factor of 1.91 (95% CI, 1.61-2.25). For example, to control the AAA growth risk in men of exceeding 5.5 cm to below 10%, on average, a 7.4-year surveillance interval (95% CI, 6.7-8.1) is sufficient for a 3.0-cm AAA, while an 8-month interval (95% CI, 7-10) is necessary for a 5.0-cm AAA. To control the risk of rupture in men to below 1%, the corresponding estimated surveillance intervals are 8.5 years (95% CI, 7.0-10.5) and 17 months (95% CI, 14-22). In contrast to the commonly adopted surveillance intervals in current AAA screening programs, surveillance intervals of several years may be clinically acceptable for the majority of patients with small AAA.

Effects of duration of type 2 diabetes mellitus on lengthening and enlargement of small abdominal aortic aneursym

Objective: The purpose of our study aimed at evaluating the relationship of type 2 diabetes with longitudinal extension of AAA. Methods: All of 460 AAA patients aged from 41 to 92 years were retrospected in our study, and they were at least twice admitted into our hospital from January 2000 to April 2010. All patients received ultrasound measurement of aorta during each admission. Results: Our results indicated that changes of length of AAA were significantly greater in patients with diabetes than those in patients without diabetes. Type 2 diabetes was associated with length extension of AAA. In subgroup analysis, type 2 diabetes was only related to length change of small AAA rather than large AAA. Diabetes was not an independent risk factor for length extension of small AAA. There was no significant difference of glycosy-lated hemoglobin between diabetes patients and nondiabetes patients. Conclusions: Type 2 diabetes mellitus is closely related to length growth of small AAA, whereas diabetes is not an independent risk factor for length extension of small AAA, and serum glucose under better control could not bring about better result in limiting length extension of small AAA.