Abdominal Aortic Aneurysm Rupture Research Articles

Induction of CD73 prevents death after emergency open aortic surgery for a ruptured abdominal aortic aneurysm: a randomized, double-blind, placebo-controlled study

Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10 μg) or matching placebo for 6 days after surgery. Major exclusion criteria included fatal hemorrhagic shock, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 min. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. The study was pre-maturely stopped due to a reported drug-drug interaction and was left under-powered. Out of 40 randomized patients 38 were included in the outcome analyses (27 IFN beta-1a and 11 placebo). There was no statistically significant difference between treatment groups at baseline except more open-abdomen and intestinal ischemia was present in the IFN beta-1a arm. D30 all-cause mortality was 22.2% (6/27) in the IFN beta-1a arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI 0.21–8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the IFN beta-1a arm vs. 9.1% in the placebo arm). Patients with high level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids and the presence of IFN beta-1a neutralizing antibodies associated with a poor CD73 response and survival. The initial aim of the trial, if postoperative INF beta-1a treatment results on better RAAA survival, could not be demonstrated. Nonetheless the anticipated target mechanism up-regulation of CD73 was associated with 100% survival. According to present results the INF beta-1a induced up-regulation of serum CD73 was blocked with both use of glucocorticoids and serum IFN beta-1a neutralizing antibodies. The study was pre-maturely stopped due to interim analysis after a study concerning the use if IV IFN beta-1a in ARDS suggested that the concomitant use of glucocorticoids and IFN beta-1a block the CD73 induction.Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered).

Abdominal Aortic Aneurysm Rupture Risk Assessment Using Machine Learning to Integrate Biomechanical, Geometrical, and Patient Characteristics

Introduction: The correlation between maximum diameter and rupture in abdominal aortic aneurysm (AAA) has been studied extensively, and a maximum AAA diameter of 55 mm in men or a diameter growth of more than 10 mm per year are accepted to indicate AAA repair. However, the maximum diameter criterion fails to describe AAA rupture risk in a patient specific manner and should therefore not directly be applied to individual patients. The poor sensitivity of diameter has been known for a long time and has stimulated the search for more patient specific risk indicators.

Patient-Tailored Approach for Diagnostics and Treatment of Mycotic Abdominal Aortic Aneurysm

The existing literature on mycotic aortic aneurysm is scarce and focuses on treatment. This study evaluates the clinical characteristics, diagnostics, treatment and outcome of patients with a mycotic abdominal aortic aneurysm treated in a tertiary referral center. A retrospective cohort study was conducted including all patients with a proven mycotic abdominal aortic aneurysm admitted between May 2010 and July 2020. Primary outcome was mortality and secondary outcome included complications such as vascular graft/endograft infection. Twenty-four patients with a mycotic abdominal aortic aneurysm were included. Patients had a mean age of 68 ± 9 years and 20 (83%) were male. Thirteen patients (57%) had positive preoperative blood cultures. Streptococcus pneumoniae was most frequently isolated by blood culturing, pus, and vascular, or perivascular tissue cultures (17%). In 19 (83%) patients the mycotic abdominal aortic aneurysm was located infrarenally, in three (13%) patients suprarenally, and in one (4%) patient juxtarenally. Median follow-up was 20 (7-42) months. In 8 patients (33%) vascular graft and or endograft infection was diagnosed after surgical repair. Ten (42%) patients died during the follow-up period. The main causes of death were vascular graft/endograft infection-related (n=4) and rupture of the mycotic abdominal aortic aneurysm (n=3). No patient characteristics could be identified as predictive for mortality. This study shows a large variation in presentation, diagnostic approaches, and surgical and antibiotic treatment of mycotic abdominal aortic aneurysm. The detailed information about the diagnostic approaches to this rare disease and its antibiotic and/or other treatment contributes to existing knowledge of mycotic abdominal aortic aneurysm. Because of the individual variation patients should be discussed in a multidisciplinary team with a vascular surgeon, infectious disease specialist, and clinical microbiologist.

The Role of Epigenetic Modifications in Abdominal Aortic Aneurysm Pathogenesis.

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high morbidity and mortality in the setting of acute rupture. Recently, advances in surgical and endovascular repair of AAA have been achieved; however, pharmaceutical therapies to prevent AAA expansion and rupture remain lacking. This highlights an ongoing need to improve the understanding the pathological mechanisms that initiate formation, maintain growth, and promote rupture of AAA. Over the past decade, epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and non-coding RNA, have emerged as important regulators of cellular function. Accumulating studies reveal the importance of epigenetic enzymes in the dynamic regulation of key signaling pathways that alter cellular phenotypes and have emerged as major intracellular players in a wide range of biological processes. In this review, we discuss the roles and implications of epigenetic modifications in AAA animal models and their relevance to human AAA pathology.

Chronic Ruptured Abdominal Aortic Aneurysm

Chronic rupture of Abdominal Aortic Aneurysm is a rare presentation although AAA and its frank rupture is well known phenomenon. Chronic rupture of AAA can be misdiagnosed due to non-specific presentation and absence of haemorrhagic shock. This case report discusses the presentation scenarios as well radiologic findings which may help diagnose a Chronic Ruptured AAA (CR-AAA) and will be helpful in prompt recognition and early management of the situation.

Abdominal Aortic Screening Is a Priority for Health in Smoker Males: A Study on Central Italian Population.

Abdominal aortic aneurysm (AAA) is a major public health problem. In the last decade, in some European countries, abdominal aortic screening (AAS) is emerging as a potential prevention for the rupture of AAA. The goals of our study were to estimate AAA prevalence and risk factors in males and females in a central Italian population, also defining the cost-effectiveness of AAS programs. A pilot study screening was conducted between 1 January 2015 and 31 December 2019 in the municipality of Teramo (Abruzzo Region, Italy) in a group of men and women, ranging from the age of 65 to 79, who were not previously operated on for AAA. The ultrasound was performed by means of Acuson sequoia 512 Simens with a Convex probe. The anterior posterior of the infra-renal aorta was evaluated. The odds ratio values (ORs) were used to evaluate the risk of AAA, and the following determinants were taken into consideration: gender, smoke use, hypertension, and ischemic heart disease. We also estimated the direct costs coming from aneurysmectomy (surgical repair or endovascular aneurysms repair—EVAR). A total of 62 AAA (2.7%, mean age 73.8 ± 4.0) were diagnosed, of which 57 were in men (3.7%, mean age 73.6 ± 4.0) and 5 were in women (0.7%, mean age 74.3 ± 4.1). Male gender and smoke use are more important risk factors for AAA ≥ 3 cm, respectively: OR = 5.94 (2.37–14.99, p < 0.001) and OR = 5.21 (2.63–10.30, p < 0.000). A significant increase in OR was noted for AAA ≥ 3 cm and cardiac arrhythmia and ischemic heart disease, respectively: OR = 2.81 (1.53–5.15, p < 0.000) and OR = 2.76 (1.40–5.43, p = 0.006). Regarding the cost analysis, it appears that screening has contributed to the reduction in costs related to urgency. In fact, the synthetic indicator given by the ratio between the DRGs (disease related group) relating to the emergency and those of the elective activity went from 1.69 in the year prior to the activation of the screening to a median of 0.39 for the five-year period of activation of the screening. It is important to underline that the results of our work confirm that the screening activated in our territory has led to a reduction in the expenditure for AAA emergency interventions, having increased the planned interventions. This must be a warning for local stakeholders, especially in the post-pandemic period, in order to strengthen prevention.

Chronic abdominal aortic rupture mimicking femoral neuropathy

Chronic-contained rupture of an aortic aneurysm is a rare subset of ruptured aneurysms. The presentation is unusual, and the diagnosis is frequently delayed. Here, we describe a case of contained rupture of abdominal aortic aneurysm that presented with signs and symptoms of femoral neuropathy. Clinical and radiological findings were initially misinterpreted. The correct diagnosis was formulated belatedly, causing a progressively increased risk of fatal events. Surgical aortic repair was performed and the postoperative course was uneventful. In conclusion, in the presence of a retroperitoneal mass, a diagnosis of chronic-contained rupture of an abdominal aortic aneurysm should be considered.

Open surgical conversion and management of patients with ruptured abdominal aortic aneurysm after previous endovascular aneurysm repair

Introduction/Objective. The objective was to present the results and technical considerations from high-volume center when performing late open surgical conversion (LOSC) after endovascular aneurysm repair (EVAR) in ruptured abdominal aortic aneurysm (RAAA) patients. Methods. This was a single center retrospective study. LOSC was performed whenever eventual endovascular reintervention failed, was not feasible due to hostile anatomy and unavailability of specific endograft materials, or when patient was hemodynamically unstable necessitating emergent surgery. Results. All previously implanted EVARs had bimodular configuration with suprarenal fixation. Total endograft explantation was performed in 40% of patients. Hospital mortality was 20%. Both patients who died had total endograft explantation with supraceliac clamp lasting more than 30 minutes. 30-day mortality was 30%, with one more patient who died from pulmonary embolism after hospital discharge and two hospital deaths were due to myocardial infarction. Conclusion. LOSC due to RAAA after previous EVAR carries greater mortality for the patient, suggesting multifactorial impacts on the outcome. The appropriate choice of surgical method and technical success are of ultimate importance, with total graft explantation having negative impact on patient?s survival.

A Case of Acute Type B Aortic Dissection with Visceral Malperfusion and Impending Rupture of Abdominal Aortic Aneurysm

A Case of Acute Type B Aortic Dissection with Visceral Malperfusion and Impending Rupture of Abdominal Aortic Aneurysm

Neobične prezentacije urgentnog torakoabdominalnog bola

Introduction: Vascular emergencies in the abdomen are not common, but they are significant due to high mortality, the need for urgent diagnosis and immediate, most often operative treatment. Thromboembolic disorders lead to ischemia and infarction of the affected intra-abdominal organs, while abdominal aortic aneurysm rupture and aortic dissection, as one of the most urgent conditions in medicine, lead to hypovolemic shock and death, if not recognized in time. The aim: of this work is to point out patients with unusual clinical pictures and unexpected circumstances. With them, how not to be late with a timely diagnosis and decision on further treatment? Presentation of case 1 - female patient, aged 57, who was brought by SHMP to the Reception and Triage Clinic of the Emergency Center twice during the night: the first time due to alleged alcoholism and impaired state of consciousness, after which she was referred to the VMA, and the second time she was returned from the aforementioned institution suspected aortic dissection, when, after regaining consciousness, she complained of chest pain. After a CT aortography and a confirmed dissection of the ascending aorta, she underwent urgent surgery. The slow postoperative period with complications ended with a positive outcome, she was discharged from the hospital after 15 days. Presentation of case 2 - patient, 35 years old, who comes to the Emergency Center with severe pain in the epigastrium, which started 1 hour ago. After a suspicious ultrasound finding, elevated D-dimer and pain resistant to analgesia, a good decision was made to perform CT aortography, which indicates thrombosis of the superior mesenteric artery. He was operated on urgently, then re-operated on, and was observed by the consilium all the time, but he died on the 15th day of hospitalization. Conclusion: Unusual presentations of thoracoabdominal pain should be kept in mind, due to timely diagnosis and treatment.

Abdominal Aortic Aneurysm with Persistent and Rebound Coagulopathy Despite Aggressive Corrective Treatment: A Case Report

Abdominal aortic aneurysm (AAA) is not uncommon to cause coagulopathy. Warfarin use in patients presented with ruptured AAA can further complicate the preparation for surgical intervention and affect prognosis. We reported a case of impending rupture AAA that progressed to contained leak AAA in a warfarin user, with persistent elevated and rebound international normalized ratio (INR) despite aggressive correction with fresh frozen plasma (FFP) and three-factor prothrombin complex concentrate (3F-PCC). Persistent and rebound coagulopathy is possible in AAA. Corrective treatment with FFP or 3F-PCC alone does not always guarantee the successful reversal of coagulopathy in AAA. Some cases, especially those that failed the initial corrective treatment, require more aggressive reversal with co-administration of vitamin K. This case described coagulopathy in AAA, anticoagulation reversal agents used and emphasized the importance of rigorous coagulation profile monitoring in managing AAA.

Ketosis Prevents Abdominal Aortic Aneurysm Progression and Rupture in Male Rats

Ketosis Prevents Abdominal Aortic Aneurysm Progression and Rupture in Male Rats

Studies Related to Ruptured Abdominal Aortic Aneurysms in the Past 10 Years (2011-2020): A Bibliometric Analysis.

BackgroundRuptured abdominal aortic aneurysms have been a topic of common global interest for the past 20 years, with a steadily increasing number of publications. The purpose of this study was to explore the research themes and the current status of the last 10 years through a bibliometric analysis of the publications in this field.Material/MethodsWe performed a literature search for ruptured abdominal aortic aneurysms using the Web of Science Core Collection on November 14, 2021 and performed a bibliometric analysis and visualization of the results of the publications using the R-Bibliometrix package and VOSviewer software.ResultsFrom 2011 to 2020, 2381 publications were retrieved, including 2073 articles and 308 reviews. The United States had the highest number of publications and has made a large contribution to the field. Jonathan Golledge is an important researcher with the highest number of publications. Journal of Vascular Surgery is ranked first in terms of the number of publications and local citations. Mortality and outcomes, repair treatment, and risk factors are the 3 main focuses in the field, followed by intraluminal thrombus and molecular expression.ConclusionsOur bibliometric analysis suggests mainstream research is focused on clinical studies related to the surgical approach and its prognosis and on pathological mechanisms and hemodynamic studies related to risk factors for abdominal aortic aneurysms rupture. There are many other opportunities for future research in the clinical joint basis of abdominal aortic aneurysms rupture.

A Case Report on a Successful Treatment of Late Abdominal Aortic Aneurysm Rupture after Endovascular Repair

A Case Report on a Successful Treatment of Late Abdominal Aortic Aneurysm Rupture after Endovascular Repair

Spontaneous Lumbar Artery Injury Resulting in Retroperitoneal Hematoma Mimicking Abdominal Aortic Aneurysm Rupture.

A 73-year-old woman, who had previously undergone endovascular aortic repair (EVAR), developed severe back pain while shoveling snow. Preoperative computed tomography (CT) revealed marked retroperitoneal hematoma around the abdominal aortic aneurysm (AAA) with extravasation of contrast media. Intraoperative angiography demonstrated spontaneous lumbar artery injury (SLI). The bleeding lumbar artery was embolized using lipiodol, and deteriorated hemodynamics were stabilized. SLI is rare and can mimic the clinical symptoms and CT findings of AAA rupture. Vascular surgeons should focus on the status of the aneurysmal sac and the possibility of another retroperitoneal disease to determine appropriate treatment options, despite successful EVAR for AAA.

MiR-424/322 protects against abdominal aortic aneurysm formation by modulating the Smad2/3/runt-related transcription factor 2 axis

Rupture of abdominal aortic aneurysms (AAAs) is one of the leading causes of sudden death in the elderly population. The osteogenic transcription factor runt-related gene (RUNX) encodes multifunctional mediators of intracellular signal transduction pathways in vascular remodeling and inflammation. We aimed to evaluate the roles of RUNX2 and its putative downstream target miR-424/322 in the modulation of several AAA progression-related key molecules, such as matrix metalloproteinases and vascular endothelial growth factor. In the GEO database, we found that male patients with AAAs had higher RUNX2 expression than did control patients. Several risk factors for aneurysm induced the overexpression of MMPs through RUNX2 transactivation, and this was dependent on Smad2/3 upregulation in human aortic smooth muscle cells. miR-424 was overexpressed through RUNX2 after angiotensin II (AngII) challenge. The administration of siRUNX2 and miR-424 mimics attenuated the activation of the Smad/RUNX2 axis and the overexpression of several AAA progression-related molecules in vitro. Compared to their littermates, miR-322 KO mice were susceptible to AngII-induced AAA, whereas the silencing of RUNX2 and the administration of exogenous miR-322 mimics ameliorated the AngII-induced AAA in ApoE KO mice. Overall, we established the roles of the Smad/RUNX2/miR-424/322 axis in AAA pathogenesis. We demonstrated the therapeutic potentials of miR-424/322 mimics and RUNX2 inhibitor for AAA progression.

Local aortic aneurysm wall expansion measured with automated image analysis

BackgroundAssessment of regional aortic wall deformation (RAWD) might better predict for abdominal aortic aneurysm (AAA) rupture than the maximal aortic diameter or growth rate. Using sequential computed tomography angiograms (CTAs), we developed a streamlined, semiautomated method of computing RAWD using deformable image registration (dirRAWD). MethodsPaired sequential CTAs performed 1 to 2 years apart of 15 patients with AAAs of various shapes and sizes were selected. Using each patient’s initial CTA, the luminal and aortic wall surfaces were segmented both manually and semiautomatically. Next, the same patient’s follow-up CTA was aligned with the first using automated rigid image registration. Deformable image registration was then used to calculate the local aneurysm wall expansion between the sequential scans (dirRAWD). To measure technique accuracy, the deformable registration results were compared with the local displacement of anatomic landmarks (fiducial markers), such as the origin of the inferior mesenteric artery and/or aortic wall calcifications. Additionally, for each patient, the maximal RAWD was manually measured for each aneurysm and was compared with the dirRAWD at the same location. ResultsThe technique was successful in all patients. The mean landmark displacement error was 0.59 ± 0.93 mm with no difference between true landmark displacement and deformable registration landmark displacement by Wilcoxon rank sum test (P = .39). The absolute difference between the manually measured maximal RAWD and dirRAWD was 0.27 ± 0.23 mm, with a relative difference of 7.9% and no difference using the Wilcoxon rank sum test (P = .69). No differences were found in the maximal dirRAWD when derived using a purely manual AAA segmentation compared with using semiautomated AAA segmentation (P = .55). ConclusionsWe found accurate and automated RAWD measurements were feasible with clinically insignificant errors. Using semiautomated AAA segmentations for deformable image registration methods did not alter maximal dirRAWD accuracy compared with using manual AAA segmentations. Future work will compare dirRAWD with finite element analysis–derived regional wall stress and determine whether dirRAWD might serve as an independent predictor of rupture risk.

Endovascular Aneurysm Repair for Large Abdominal Aortic Aneurysms is Associated With Higher Late Re-Intervention, Rupture, and Mortality Rates: Abdominal Aortic Aneurysms

Introduction: The risk of abdominal aortic aneurysm (AAA) rupture increases with increasing aneurysm diameter. However, the impact of AAA diameter on late outcomes after aneurysm repair is unclear. Therefore, we assessed the association of large AAA diameter with late outcomes in patients undergoing open and endovascular AAA repair.

A reduction in the vascular smooth muscle cell focal adhesion component syndecan-4 is associated with abdominal aortic aneurysm formation.

BackgroundAbdominal aortic aneurysm (AAA) is a serious vascular disease for which there is no effective drug treatment. The incidence of AAA increases significantly as a subject ages, and the molecular mechanism of AAA formation remains elusive. In the present study, we investigated the role of syndecan‐4 (SDC4), an important component of focal adhesions, in AAA formation and its association with phenotypic changes in vascular smooth muscle cells (VSMCs).Methods and resultsThe protein expression levels of SDC4 were significantly decreased in human AAA tissue and those of an AAA mouse model. Moreover, SDC4 knockout (KO) in mice accelerated the formation and rupture of AAAs induced by angiotensin II (Ang II) and calcium chloride (CaCl2)Mechanistically, the decrease in SDC4 led to the transformation of cultured VSMCs from a contractile to a secretory phenotype. The RhoA‐F/G‐actin‐myocardin‐related transcription factor‐A (MRTF‐A) signalling pathway was shown to be involved in SDC4‐dependent VSMC alteration. Sphingosine‐1‐phosphate (S1P), a G‐protein‐coupled receptor, attenuated the AAA formation in SDC4‐KO and wild‐type (WT) mice in response to Ang II and CaCl2 stimulation.ConclusionWe herein demonstrated that silencing SDC4 was associated with increased AAA formation and phenotypic changes in VSMCs via the RhoA‐F/G‐actin‐MRTF‐A pathway. These findings indicated that a reduction in SDC4 expression was an important pathological alteration and potential therapeutic target for AAA formation.

Identification of crucial genes involved in pathogenesis of regional weakening of the aortic wall

BackgroundThe diameter of the abdominal aortic aneurysm (AAA) is the most commonly used parameter for the prediction of occurrence of AAA rupture. However, the most vulnerable region of the aortic wall may be different from the most dilated region of AAA under pressure. The present study is the first to use weighted gene coexpression network analysis (WGCNA) to detect the coexpressed genes that result in regional weakening of the aortic wall.MethodsThe GSE165470 raw microarray dataset was used in the present study. Differentially expressed genes (DEGs) were filtered using the “limma” R package. DEGs were assessed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. WGCNA was used to construct the coexpression networks in the samples with regional weakening of the AAA wall and in the control group to detect the gene modules. The hub genes were defined in the significant functional modules, and a hub differentially expressed gene (hDEG) coexpression network was constructed with the highest confidence based on protein–protein interactions (PPIs). Molecular compound detection (MCODE) was used to identify crucial genes in the hDEG coexpression network. Crucial genes in the hDEG coexpression network were validated using the GSE7084 and GSE57691 microarray gene expression datasets.ResultA total of 350 DEGs were identified, including 62 upregulated and 288 downregulated DEGs. The pathways were involved in immune responses, vascular smooth muscle contraction and cell–matrix adhesion of DEGs in the samples with regional weakening in AAA. Antiquewhite3 was the most significant module and was used to identify downregulated hDEGs based on the result of the most significant modules negatively related to the trait of weakened aneurysm walls. Seven crucial genes were identified and validated: ACTG2, CALD1, LMOD1, MYH11, MYL9, MYLK, and TPM2. These crucial genes were associated with the mechanisms of AAA progression.ConclusionWe identified crucial genes that may play a significant role in weakening of the AAA wall and may be potential targets for medical therapies and diagnostic biomarkers. Further studies are required to more comprehensively elucidate the functions of crucial genes in the pathogenesis of regional weakening in AAA.