Abdominal Aortic Aneurysm Rupture Research Articles

Abstract 4137693: CC-Chemokine Receptor 2 Inhibition Prevents Monocyte/Macrophages Recruitment in Abdominal Aortic Aneurysms

Intro: Abdominal aortic aneurysm (AAA) is a prevalent condition in the elderly, with a significant risk of mortality if it ruptures. Despite this, there is currently no effective medical therapy to prevent AAA growth and rupture. The monocyte chemoattractant protein (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis appears to play a role in AAA development. We demonstrated the potential of CCR2 as a theranostic marker for predicting AAA rupture, along with the effectiveness of a CCR2 inhibitor (RS-504393) in mitigating rupture. We further hypothesized that CCR2 inhibition can impact monocytes/macrophages trafficking in aortic tissue. Mehtods: Sprague-Dawley rats (N=54) underwent intraluminal aortic exposure to porcine pancreatic elastase (PPE) to induce aneurysmal degeneration. To stimulate AAA rupture, rats also recieved β-aminopropionitrile (BAPN). After 3 days of PPE exposure, a group of rats with AAA were administered a CCR2 inhibitor (CCR2i) either daily until the end of the study (CCR2i Full), or discontinued at day 5 (CCR2i Short), while the remaining rats proceeded without intervention (Fig1A). Ultrasound (12MHz) was performed at 7&14 days to assess diameter, while another cohort of animals were euthanized at 6 days, prior to rupture, for single-cell RNA sequencing analysis. The relative content of inflammatory cells within the aortic tissue was analyzed. Results: Both CCR2i Short and CCR2i Full treated, exhibited a significant reduction in AAA diameter at day 7 and 14 compared to controls (p<0.05; Fig1B&C). Notably, rats treated with CCR2i Full did not experience any AAA ruptures, while controls had a 56% risk of rupture. In contrast, CCR2i Short delayed the occurrence of ruptures without reducing the rupture rate (p<0.01; Fig1D). Single-cell RNA seq analysis of aortic tissue revealed that CCR2 inhibition led to a decrease in the number of recruited monocytes/macrophages. Cell recruitment was also relative to the duration of CCR2i treatment (Fig1E-G). Conclusions: Our study findings highlight the impact of CCR2-targeting in reducing AAA growth and the risk of rupture. Interestingly, length of CCR2i was a crucial variable for AAA rupture prevention. Furthermore, treatment length impacted the relative recruitment of monocytes/macrophages to AAA tissue, highlighting the role these cells in AAA disease pathology. Future analysis of CCR2+ inflammatory cell subgroups may help elucidate how CCR2 mechanistically modulates AAA progression and rupture risk.

Impact of Geometric Attributes on Abdominal Aortic Aneurysm Rupture Risk: An InVivo FSI-Based Study.

Reported in this paper is a cutting-edge computational investigation into the influence of geometric characteristics on abdominal aortic aneurysm (AAA) rupture risk, beyond the traditional measure of maximum aneurysm diameter. A Comprehensive fluid-structure interaction (FSI) analysis was employed to assess risk factors in a range of patient scenarios, with the use of three-dimensional (3D) AAA models reconstructed from patient-specific aortic data and finite element method. Wall shear stress (WSS), and its derivatives such as time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT) and transverse WSS (transWSS) offer insights into the force dynamics acting on the AAA wall. Emphasis is placed on these WSS-based metrics and seven key geometric indices. By correlating these geometric discrepancies with biomechanical phenomena, this study highlights the novel and profound impact of geometry on risk prediction. This study demonstrates the necessity of a multidimensional assessment approach, future efforts should complement these findings with experimental validations for an applicable approach for clinical use.

Local Morphologic and Hemodynamic Analyses for the Prediction of Abdominal Aortic Aneurysm Rupture Based on Patient-Specific CTA and Computational Modeling.

Extensive research has focused on the evaluation of rupture risks in abdominal aortic aneurysms (AAAs) through comprehensive morphologic and hemodynamic analyses, primarily considering the AAA as a whole entity. This study tried to identify the high-risk rupture sites of AAAs more precisely before the fatal process based on morphologic and hemodynamic analyses at the local segment. Computed tomography angiography of a specific AAA patient was conducted at the follow-up 4 months before rupture, 1 day before rupture, the day of the rupture, and 15 days after endovascular aortic repair. The evolution of local morphology and the hemodynamic characteristics at these critical timepoints were investigated based on patient-specific reconstructions and computational fluid dynamics. The morphologic and hemodynamic parameters of the rupture region vary continuously in the process of AAA development and rupture. The surface area and volume of the rupture segment were gradually enlarged at the follow-up 4 months before rupture (47.33 cm2; 67.35 mL), 1 day before rupture (57.23 cm2; 85.24 mL), and on the day of the rupture (62.41cm2; 104.73ml). A prominent decrease in time-averaged wall shear stress and velocity for the rupture segment is observed. The percentages of the lowest time-averaged wall shear stress (<0.1 Pa) area are increased in the AAA region (20.42%, 33.85%, and 53.00%, separately). The results based on precisely rebuilt geometries for the complete follow-ups of patient-specific computed tomography angiography demonstrate that notable morphologic and hemodynamic evolutions have occurred in the local segment of the AAA, which was further proved at the rupture site. The significant changes occurring at the local segment may provide valuable information for the evaluation of aneurysm rupture risk and locate the most probable site of rupture. Capturing the entire process of AAA rupture through CTA imaging is a rare occurrence in clinical practice. The evolution of morphology and hemodynamic characteristics observed in the illustrated results provides valuable insights for clinicians to monitor the state of AAA from a different perspective. These findings suggest that variations in morphology and hemodynamics within the local segment of the AAA might serve as an alternative approach for predicting the rupture risk of AAA.

Systematic review of clinical effectiveness and safety of abdominal aortic aneurysm screening in men

Abstract Background Abdominal aortic aneurysm (AAA) is characterised by a bulging in the aortic wall. AAA is typically asymptomatic until aneurysm rupture, which is associated with a very high mortality rate (approximately 80%). In the context of an ageing population and increasing life expectancy, innovative approaches to early detection and intervention are needed. The aim of this review was to assess the clinical effectiveness and safety of one-time ultrasound screening for AAA in men. Methods Systematic searches were conducted in electronic databases and grey literature sources. The primary outcomes of interest were AAA-related mortality, AAA rupture, all-cause mortality, rate of surgical repair and safety. The following study designs were included: systematic reviews, randomised controlled trials (RCTs), comparative observational studies and population-based non-comparative observational studies. Results Results from a systematic review by the US Preventive Services Task Force analysed 4 population-based RCTs, showing that one-time population-based screening for AAA in men (≥ 65 years) led to significant reductions in AAA-related mortality (OR = 0.65, 95% CI: 0.57 to 0.74), AAA rupture (OR = 0.61, 95% CI: 0.54 to 0.69) and emergency surgeries (OR = 0.53, 95% CI: 95% CI: 0.44 to 0.64) at 13-15 years follow-up, relative to no screening. Separate to this systematic review an additional 24 studies reported on clinical effectiveness, safety and psychosocial harms of AAA screening. Limited evidence from these studies suggest screening was associated with a reduction in AAA-related mortality and rupture but also transient psychological distress in some cases. Conclusions One-time ultrasound screening in men ≥65 years appears to offer benefits in terms of reducing AAA ruptures and AAA-related mortality, though the balance of benefits and harms requires careful consideration. In an ageing population, AAA screening could be transformative, by reducing mortality and rupture risks. Key messages • One-time ultrasound screening for AAA in older men (≥ 65 years) can reduce AAA-related mortality and rupture. • In the context of an ageing population in Europe, AAA screening could be transformative, but benefits must be weighed against potential risks.

Toward assessment of rupture risk predictors in abdominal aortic aneurysms including intraluminal thrombus based on 3D+t ultrasound images.

Image-based patient-specific rupture risk analysis for abdominal aortic aneurysms (AAAs) has shown considerable promise. However, clinical translation has been hampered by the use of invasive and costly imaging modalities. Despite being a promising alternative, ultrasound (US) makes a full analysis, including intraluminal thrombus (ILT), not trivial. This study explored the feasibility of assessing AAA rupture risk parameters, e.g., peak wall stress (PWS) and peak wall rupture index (PWRI), using US-based models of the AAA wall, finally including ILT. Three-dimensional US data were segmented from a group of AAA patients whose CT data were available within 30 days. The segmented vessel wall and ILT boundaries were converted into a mesh including and excluding ILT to evaluate the effect of adding ILT on the model output. US-based rupture risk parameters (PWS and PWRI) were compared to CT-based results. The US-based PWS and PWRI, including ILT, showed good agreement with CT-based results, and the model excluding ILT showed no significant bias in wall stress or rupture index. When including ILT, a lower US-based wall stress and rupture index of 7.2% and 3.8% were found, respectively. The intraclass correlation coefficient (ICC) of PWS was 0.60. The highest ICC was found for the PWRI (ICC = 0.86), indicating good absolute agreement. This study showed that PWRI can be estimated with US when including the ILT, yielding comparable results to CT, and good absolute agreement. Future work should focus on improving the contrast of ILT in US, since this will be essential to performing large-scale studies in AAA cohorts.

Early and Midterm Outcomes of Chimney Endovascular Aortic Repair for Ruptured Abdominal Aortic Aneurysms.

To compare the outcomes of endovascular aortic aneurysm repair using a chimney technique (ch-EVAR) with those of the standard EVAR (st-EVAR) for ruptured abdominal aortic aneurysms (RAAA). We implemented ch-EVAR for juxtarenal RAAA based on obvious anatomical indications after converting the strategy for RAAA from open repair to EVAR. A retrospective, cohort-based study was conducted on patients with RAAA who were treated using EVAR in our hospital between July 2011 and March 2022. EVAR cases were extracted, and outcomes were compared between ch-EVAR and st-EVAR. Patient clinical status, anatomical variables, treatment, and follow-up data were evaluated. A total of 56 (82%) and 12 (18%) patients were treated by st-EVAR and ch-EVAR, respectively. Thirty-day mortality rates were comparable between the 2 groups [8.9% in st-EVAR vs 8.3% in ch-EVAR (p= 0.95)]. Short-term outcomes showed that no type Ia endoleak occurred in either group. Midterm outcomes, including sac enlargement [7.5% in st-EVAR vs 0% in ch-EVAR (p= 0.37)], shrinkage [77.5% in st-EVAR vs 80.0% in ch-EVAR (p= 0.86)], and overall survival and freedom from aneurysm-related reintervention at 3 years [64.7% and 96.4% in the EVAR group vs 91.7% and 100% in the ch-EVAR group, respectively (p= 0.30 and 0.52)], were not significantly different between the 2 groups. Ch-EVAR for RAAA showed remarkably excellent outcomes, comparable to those of st-EVAR. Ch-EVAR is considered technically feasible in experienced centers. The indications for EVAR for RAAA may be further expanded using the chimney technique, resulting in overall improved outcomes for RAAA. This is a retrospective, single-center analysis of 68 patients with ruptured abdominal aortic aneurysms (RAAAs) treated by endovascular repair (EVAR) to investigate the efficacy of the chimney technique for juxtarenal RAAA. Thirty-day mortality rate was 8.3% for the chimney EVAR group, which was equivalent to that in the standard EVAR group. Mid-term outcomes including sac enlargement/shrinkage, overall survival, and freedom from aneurysm-related reintervention were comparable between the two groups. This report suggests the possibility of broadening the selection criteria of the current endovascular strategy using the chimney technique.

Optimising Abdominal Aortic Aneurysm Screening of 65 Year Old Men by Exploring Risk Factor Based Targeted Screening Strategies in Light of Declining Prevalence of the Disease

A decline in abdominal aortic aneurysm (AAA) prevalence calls into question the credibility of general population screening of 65 year old men. Selectively targeting high risk individuals among this group could be more effective in preventing death from AAA rupture. This cross sectional study analysed risk factor data in a cohort of 65 year old men screened in the Swedish general population based AAA screening program, with the aim of exploring the effectiveness of hypothetical targeted screening strategies. All men attending AAA screening in four neighbouring counties in Sweden between 2006 and 2010 completed a health questionnaire on smoking habits and medical history. Abdominal aortic aneurysm was defined as measuring ≥ 30 mm. The sensitivity and specificity of different targeted screening strategies, with targeted subpopulations defined by duration of smoking with and without additional risk factors, were explored using receiver operating characteristic (ROC) curves. A total of 16 232 men were screened, with 236 (1.5%) screening detected AAAs. A strategy combining smoking, presence of coronary artery disease (CAD), or both was associated with the mathematically optimal balance between sensitivity and specificity (optimal threshold) in the ROC analysis. The optimal threshold corresponded to targeting men having smoked for thirty years or more, a history of CAD, or both, where 74.0% of all AAAs could be detected by screening 33.0% of the population, compared with general screening. Targeting men that have smoked for ten years or more indicated that 84.0% of all AAAs could be detected by screening 55.0% of the population. A simplified strategy of targeting ever smokers resulted in detecting 85.0% of all AAAs by screening 61.0% of the population. Targeted screening of men at high risk of AAA, focusing on smoking history for inclusion, may be a safe and effective alternative to general population screening.

Iron Overload and Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a chronic vascular degenerative disease characterized by progressive segmental dilation of the abdominal aorta. The rupture of an AAA represents a leading cause of death in cardiovascular diseases. Despite numerous experimental and clinical studies examining potential drug targets and therapies, currently there are no pharmaceutical treatment to prevent AAA growth and rupture. Iron is an essential element in almost all living organisms and has important biological functions. Epidemiological studies have indicated that both iron deficiency and overload are associated with adverse clinical outcomes, particularly an increased risk of cardiovascular events. Recent evidence indicates that iron overload is involved in the pathogenesis of abdominal aortic aneurysms. In this review, we provide an overview of the role of iron overload in AAA progression and explore its potential pathological mechanisms. Although the exact molecular mechanisms of iron overload in the development of AAA remain to be elucidated, the inhibition of iron deposition may offer a promising strategy for preventing these aneurysms.

The effect of aortic morphology on perioperative rupture of abdominal aortic aneurysm-a retrospective cohort study.

The high mortality from ruptured abdominal aortic aneurysm (AAA) is well-documented. However, the perioperative rupture risk is often underestimated. Aortic morphology is a key unresolved factor influencing this risk. This study aims to assess the impact of aortic morphology on the risk of perioperative rupture of AAAs. A multicenter retrospective cohort study was conducted among patients undergoing perioperative endovascular aneurysm repair (EVAR) for AAAs between September 2017 and October 2021. All measurements were obtained using dedicated hospital reconstruction software. The primary endpoints were mortality and AAAs rupture. Univariate and multivariate logistic regression were used to analyze the association of risk factors with rupture. Piecewise linear regression was used to analyze the threshold effect of proximal neck angulation on rupture of AAAs. The clinical correlation between proximal aneurysm neck angulation and rupture was retrospectively studied after adjusting for potential confounders. A total of 160 patients were included. The incidence of AAAs rupture in patients with severe proximal aneurysm neck angulation was significantly higher than in patients without proximal aneurysm neck angulation (15.9% vs. 7.8%, P=0.001). After adjusting for gender, max aneurysm diameter and symptom, severe proximal aneurysm neck angulation was independently associated with AAAs rupture [odds ratio (OR) =8.159, 95% confidence interval (CI): 2.202-30.236; P=0.001]. After adjusting for gender, proximal aneurysm neck angulation and symptom, max aneurysm diameter was independently associated with AAAs rupture (OR =1.093, 95% CI: 1.046-1.143; P<0.001). The female seemed to have severe proximal neck angulation. When the angulation was greater than 41°, the risk of rupture increased linearly. EVAR remains the preferred surgical approach for managing AAAs, guided by morphological and anatomical considerations. We have established a significant correlation between the extent of proximal neck angulation and the risk of perioperative rupture in aneurysms. Proximal neck angulation differs significantly between genders, with females exhibiting greater angulation than males. Clinicians should meticulously assess proximal neck angulation in patients undergoing EVAR and consider early intervention for those with severe angulation to mitigate the risk of rupture.

Reduction of Abdominal Aortic Aneurysm Rupture By Modulating Smooth Muscle Cell Phenotype Switching

Reduction of Abdominal Aortic Aneurysm Rupture By Modulating Smooth Muscle Cell Phenotype Switching

Initial signs in patients with ruptured abdominal aortic aneurysms: time for an expanded triad?

Background and objectiveMisdiagnosis of ruptured abdominal aortic aneurysms (rAAA) contributes to delayed treatment and potentially higher mortality. The symptomatology in patients with rAAA is complex and challenging, 25–50% presumably fulfill the criteria of the standard triad of signs (STS). The objective was to determine the initial signs registered for patients with verified rAAAs, and to investigate if an expanded diagnostic triad could increase the diagnostic accuracy.MethodsA population-based study was conducted among all patients presenting with verified rAAAs in Stockholm County, Sweden, from January 2010 to October 2021. Patients were identified with ICD code 171.3 (rAAA). The STS was defined as (1) abdominal pain, (2) syncope and (3) the finding of a pulsatile abdominal mass, the prevalence of STS was investigated. An expanded triad included similar and related signs commonly registered for patients with rAAA, and was referred to as the modified abdominal aortic aneurysm rupture signs (MARS). The MARS-signs encompassed (1) the registered pain-associated symptoms or signs, (2) all hypovolemic associated signs, and (3) pulsatile abdominal mass and/or ultrasound finding, and the prevalence was similarly investigated. Finally, the STS and MARS were compared to evaluate the usefulness and performance of the MARS-score.ResultsA total of 216 patients were identified. The majority were men (77%) with a median age of 78 years. The dominating symptom was abdominal pain (84%), followed by dizziness (50%). Few patients presented with three STS (13%), two STS were found in 37% and one STS in almost half of the patients (41%). By contrast, when applying MARS 35% presented with the complete expanded triad, 47% with two and 17% with one. Comparison of accuracy favored MARS (13 vs. 35% with 3 signs, P < 0.001 for STS vs. MARS) (2 or 3 signs, 48 vs. 82% STS vs. MARS, P < 0.001).ConclusionsThe expanded MARS-signs could aid in easier and faster identification of rAAA patients, thus facilitating the first step with accurate diagnosis into the lifesaving rAAA care chain. Supportive diagnostic mnemonics and tools are especially important when targeting fatal diagnoses such as rAAA. Further studies are needed to investigate the implementation of the MARS-signs in various clinical settings.

Tension-based abdominal aortic aneurysm rupture risk assessment improves its accuracy and reduces the time of analysis

The biomechanical rupture risk assessment (BRRA) of abdominal aortic aneurysms (AAA) has higher sensitivity than maximal diameter criterion (DSEX) but its estimation is time-consuming and relies on an uncertain estimation of wall thickness. The aim of this study is to test tension-based criterion in the BRRA of AAA which removes the necessity of wall thickness measurement and should be faster. For that, we retrospectively analyzed 99 patients with intact AAA (25 females). Nineteen of them experienced a rupture later. BRRA was performed with wall tension PRRIT as a primary criterion. The ability of criterion to separate intact and ruptured AAAs at 1,3,6,9 and 12 months was estimated. Next, the receiver operating characteristics and the percentage of true negative cases for a different time to an outcome were estimated. Finally, the computational time was recorded. The results were compared to stress-based criterion PRRI and DSEX which served as a reference. All three criterions were able to discriminate between intact and ruptured AAAs up to 9 months (p < 0.05) while none of them could do for a 12 month prediction. PRRIT exhibited a significantly higher percentage of true negatives for 12 and 9 month predictions (45 % and 20 % respectively) and similar to other criteria for other prediction times. The mean computational time for estimating PRRIT was 19 h per patient compared to 67 h for PRRI. The tension- based BRRA of AAA leads to better outcomes for a 9 and 12 month prediction while the computational time drops by more than 70 % compared to PRRI.

A case of chronic contained rupture of abdominal aortic aneurysm mimicking a retroperitoneal tumor.

Chronic contained rupture of abdominal aortic aneurysm (CCR-AAA) is a rare subtype of abdominal aortic rupturethat can mimic other retroperitoneal lesions. We report a case of CCR-AAA in a man in his sixties who presented witha 10-month history of right low back pain and weight loss. Contrast-enhanced computed tomography (CT) revealed alobulated retroperitoneal mass around the abdominal aorta, initially misdiagnosed as a possible hemorrhagicretroperitoneal tumor. Despite multiple imaging studies including CT, magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucosepositron emission tomography (FDG-PET)/CT, as well as a CT-guided biopsy, the correct diagnosisremained elusive for 34 months. Key findings included subtle aortic wall irregularity on CT, high signal intensity onT1-weighted MRI suggesting hematoma, peripheral FDG uptake on PET/CT, and histological findings of biopsy tissueconsistent with organizing hematoma. Surgery confirmed the diagnosis, revealing an organized hematoma with adefect in the right wall of the abdominal aortic aneurysm. This case demonstrates that CCR-AAA can present withatypical radiological features, potentially leading to misdiagnosis. When encountering a para-aortic mass with ahemorrhagic component, careful observation of the AAA morphology and aortic wall contour is crucial for anaccurate diagnosis of CCR-AAA.

Establishment of Mouse Models of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a chronic vascular disease that commonly affects elderly individuals but has recently increased in younger populations. As the aneurysm grows, it can cause compression symptoms such as abdominal pain, rupture, and bleeding, which are absent in the early stages. Once an AAA ruptures and causes bleeding, the mortality rate is alarmingly high. Currently, the pathogenesis for AAA is unknown, and therapeutic options are limited, necessitating improvement in treatment efficacy. An essential research method for studying the processes and potential treatment of AAA is establishing animal models using mice. The present study provides a detailed overview of the widely used AAA mouse animal models and their construction strategies, advantages, disadvantages, scope of applications, and prospects.

Aorto caval fistulas.

The purpose of this paper is to examine and assess the outcomes following open repair in 39 patients who experienced aorto-caval fistula (ACF) resulting from the spontaneous rupture of an abdominal aortic aneurysm (AAA). We reviewed the clinical records of all patients surgically treated with open repair for ACF at the Clinic for Vascular and Endovascular Surgery of the Serbian Clinical Center in Belgrade, Serbia, from January 2012 to February 2023. All of the patients in this series were consecutive and had aorto-caval fistula from AAA. No patients were excluded from the procedure due to the life-threatening nature of the state. A follow-up assessment was performed during the follow-up examination or by telephone interview with the patient or a family member. All patients were male, with mean age 67.4±8.3 years (range: 52-83 years). The 30-day mortality rate in our cohort was 35.9%, with three (7.7%) intraoperative deaths, and 11 deaths in the postoperative period (28.2%). A total of 25 patients out of 39 (64.1%) in the original cohort have survived the surgery and the postoperative period and were followed-up for a total of 67.1 person-years. The mean follow-up was 3.7±2.2 years (range 0.25-8.4 years). Two patients (8.0%) died during the follow-up, 16 patients (64.0%) survived, and seven (28.0%) were lost to follow-up. The long-term mortality rate in the cohort that survived the postoperative period was 3.0/100 person-years. ACF caused by spontaneous AAA rupture into the inferior caval vein or iliac veins is a relatively rare, life-threatening condition which requires prompt treatment. An exact preoperative diagnosis is essential for perioperative strategy. As the comparison of our results with the results from contemporary literature indicates, wherever possible endovascular repair should be considered since it results might be superior to open repair.

Exploration of small molecule compounds targeting abdominal aortic aneurysm based on CMap database and molecular dynamics simulation.

The mitigation of abdominal aortic aneurysm (AAA) growth through pharmaceutical intervention offers the potential to avert the perils associated with AAA rupture and the subsequent need for surgical intervention. Nevertheless, the existing effective drugs for AAA treatment are limited, necessitating a pressing exploration for novel therapeutic medications. AAA-related transcriptome data were downloaded from GEO, and differentially expressed genes (DEGs) in AAA tissue were screened for GO and KEGG enrichment analyses. Small molecule compounds and their target proteins with negative connectivity to the AAA expression profile were predicted in the Connectivity Map (CMap) database. Molecular docking and molecular dynamics simulation were performed to predict the binding of the target protein to the small molecule compound, and the MM/GBSA method was used to calculate the binding free energy. Cluster analysis was performed using the cluster tool in the GROMACS package. An AAA cell-free model was built, and CETSA experiments were used to demonstrate the binding ability of small molecules to the target protein in cells. A total of 2244 DEGs in AAA were obtained through differential analysis, and the DEGs were mainly enriched in the tubulin binding biological function and cell cycle pathway. The CMap results showed that Apicidin had a potential therapeutic effect on AAA with a connectivity score of -97.74, and HDAC4 was the target protein of Apicidin. Based on literature, HDAC4-Apicidin was selected as the subsequent research object. The lowest affinity of Apicidin-HDAC4 molecular docking was -8.218kcal/mol. Molecular dynamics simulation results indicated that Apicidin-HDAC4 could form a stable complex. MM/GBSA analysis showed a total binding free energy of -55.40 ± 0.79kcal/mol, and cluster analysis showed that there were two main conformational clusters during the binding process, accounting for 22.4% and 57.8%, respectively. Apicidin could form hydrogen bonds with surrounding residues for stable binding. CETSA experiment proved the stable binding ability of Apicidin and HDAC4. Apicidin inhibited HDAC4 in AAA and exhibited favorable protein-ligand interactions and stability, making it a potential candidate drug for treating AAA.

Prevalence of abdominal aortic aneurysm in patients with hidradenitis suppurativa in the Veterans Affairs Health Care System.

Our study investigated the relationship between abdominal aortic aneurysm (AAA) and hidradenitis suppurativa (HS) in patients within the Veterans Affair Health Care System. Overall, we found that patients with HS had a higher prevalence of AAA compared to those without HS, with women and men with HS having higher odds of AAA. Further research should consider clinical outcomes such as AAA rupture and associated mortality.

Right-to-left shunt due to iatrogenic atrial septal defect manifested by aorto-caval fistula: a case report

BackgroundAn aorto-caval fistula is a rare but critical complication of abdominal aortic aneurysm (AAA) rupture, leading to high-output heart failure and increased venous pressure. The anesthetic management of such cases, particularly when complicated by an intraoperative right-to-left shunt, is seldom reported.Case presentationA 71-year-old man with a history of atrial fibrillation and catheter ablation presented with heart failure and abdominal pain, leading to cardiac arrest. Imaging revealed an AAA rupture into the inferior vena cava. During emergency surgery, severe venous bleeding was managed using intra-aortic balloon occlusion (IABO). Transesophageal echocardiography (TEE) identified a right-to-left shunt due to an iatrogenic atrial septal defect.ConclusionEarly TEE recognition and timely IABO intervention were crucial in managing this complex case, underscoring the importance of these techniques in similar emergency scenarios.

Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights from Genetic and Experimental Models.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medications. This study integrated genetic, proteomic, and metabolomic data to identify causation between increased triglyceride (TG)-rich lipoproteins and AAA risk. Three hypertriglyceridemia mouse models were employed to test the hypothesis that increased plasma TG concentrations accelerate AAA development and rupture. In the angiotensin II-infusion AAA model, most Lpl -deficient mice with severely high plasma TG concentrations died of aortic rupture. Consistently, Apoa5 -deficient mice with moderately increased TG concentrations had accelerated AAA development, while human APOC3 transgenic mice with dramatically increased TG concentrations exhibited aortic dissection and rupture. Increased TG concentrations and palmitate inhibited lysyl oxidase maturation. Administration of antisense oligonucleotide targeting Angptl3 profoundly inhibited AAA progression in human APOC3 transgenic mice and Apoe -deficient mice. These results indicate that hypertriglyceridemia is a key contributor to AAA pathogenesis, highlighting the importance of triglyceride-rich lipoprotein management in treating AAA.

Effect of differences in proximal neck angles on biomechanics of abdominal aortic aneurysm based on fluid dynamics.

This study aimed to analyze the effect of proximal neck angulation on the biomechanical indices of abdominal aortic aneurysms (AAA) and to investigate its impact on the risk of AAA rupture. CT angiography (CTA) data of patients with AAA from January 2015 to January 2022 were collected. Patients were divided into three groups based on the angle of the proximal neck: Group A (∠β ≤ 30°), Group B (30°<∠β ≤ 60°), and Group C (∠β > 60°). Biomechanical indices related to the rupture risk of AAA were analyzed using computational fluid dynamics modeling (CFD-Post) based on the collected data. Group A showed slight turbulence in the AAA lumen with a mixed laminar flow pattern. Group B had a regular low-speed eddy line characterized by cross-flow dominated by lumen blood flow and turbulence. In Group C, a few turbulent lines appeared at the proximal neck, accompanied by eddy currents in the lumen expansion area following the AAA shape. Significant differences were found in peak wall stress, shear stress, and the maximum blood flow velocity impact among the three groups. The maximum blood flow velocity at the angle of the proximal neck impact indicated the influence of the proximal neck angle on the blood flow state in the lumen. As the angle of the proximal neck increased, it caused stronger eddy currents and turbulent blood flow due to a high-speed area near the neck. The region with the largest diameter in the abdominal aortic aneurysm was prone to the highest stress, indicating a higher risk of rupture. The corner of the proximal neck experienced the greatest shear stress, potentially leading to endothelial injury and further enlargement of the aneurysm.