Abdominal Aortic Aneurysm Rupture Research Articles

Simultaneous Transcatheter Aortic Valve Implantation and Endovascular Aneurysm Repair for Severe Aortic Stenosis and Symptomatic Abdominal Aortic Aneurysm: Mini Review.

Background: The treatment of patients with severe aortic stenosis (SAS) who concomitantly present with abdominal aortic aneurysm (AAA) is not defined. Aortic valve replacement surgery, performed alone, increases the risk of AAA rupture. Transcatheter aortic valve replacement (TAVR) and endovascular abdominal aortic aneurysm repair (EVAR) in the same intervention, especially in high-risk patients, is a safe alternative. Purpose: We report a case of simultaneous endovascular treatment of SAS and AAA and a mini literature review of nineteen cases with similar characteristics. Research design: Case report and literature review. Data Collection: An electronic search of PubMed and Scopus was performed from inception to December 2023. Results: Nineteen case reports of simultaneous transcatheter aortic valve repair and endovascular aneurysm repair for SAS and symptomatic AAA were identified published in the literature. Conclusions: We regard the simultaneous endovascular approach to both pathologies as a promising treatment alternative for selected patients with severe aortic stenosis and abdominal aortic aneurysm. We highlight the need to conduct randomized clinical trials in this patient population.

Endovascular Aneurysm Repair (EVAR) in Rupture of the Infrarenal Abdominal Aortic Aneurysm (AAA) with Severe Neck Angulation in Conscience of National Health Coverage in Tertiary Referral Hospital in Indonesian: Case Report

AbstractAn aortic aneurysm is a condition with focal dilation of 50% or more over the normal aortic diameter. The most frequent form of aortic aneurysms is infrarenal. Endovascular aortic aneurysm repair is a valid treatment for treating patients with abdominal aortic aneurysm. Abdominal aortic aneurysms (AAAs) are electively repaired to prevent rupture. We present a case of an elderly man with an impending rupture of intraluminal infrarenal AAA with bilateral common iliac arteries aneurysms. Overall, the patient had completed the procedure and made a good postoperative recovery with fully coverage of Indonesian national health insurance.

Construction of ferroptosis-related prediction model for pathogenesis, diagnosis and treatment of ruptured abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a dangerous cardiovascular disease, which often brings great psychological burden and economic pressure to patients. If AAA rupture occurs, it is a serious threat to patients' lives. Therefore, it is of clinical value to actively explore the pathogenesis of ruptured AAA and prevent its occurrence. Ferroptosis is a new type of cell death dependent on lipid peroxidation, which plays an important role in many cardiovascular diseases. In this study, we used online data and analysis of ferroptosis-related genes to uncover the formation of ruptured AAA and potential therapeutic targets. We obtained ferroptosis-related differentially expressed genes (Fe-DEGs) from GSE98278 dataset and 259 known ferroptosis-related genes from FerrDb website. Enrichment analysis of differentially expressed genes (DEGs) was performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). Receiver Operating characteristic (ROC) curve was employed to evaluate the diagnostic abilities of Fe-DEGs. Transcription factors and miRNAs of Fe-DEGs were identified through PASTAA and miRDB, miRWalk, TargetScan respectively. Single-sample gene set enrichment analysis (ssGSEA) was used to observe immune infiltration between the stable group and the rupture group. DGIdb database was performed to find potential targeted drugs of DEGs. GO and KEGG enrichment analysis found that DEGs mainly enriched in "cellular divalent inorganic cation homeostasis," "cellular zinc ion homeostasis," "divalent inorganic cation homeostasis," "Mineral absorption," "Cytokine - cytokine receptor interaction," "Coronavirus disease - COVID-19." Two up-regulated Fe-DEGs MT1G and DDIT4 were found to further analysis. Both single and combined applications of MT1G and DDIT4 showed good diagnostic efficacy (AUC = 0.8254, 0.8548, 0.8577, respectively). Transcription factors STAT1 and PU1 of MT1G and ARNT and MAX of DDIT4 were identified. Meanwhile, has_miR-548p-MT1G pairs, has_miR-53-3p/has_miR-181b-5p/ has_miR-664a-3p-DDIT4 pairs were found. B cells, NK cells, Th2 cells were high expression in the rupture group compared with the stable group, while DCs, Th1 cells were low expression in the rupture group. Targeted drugs against immunity, GEMCITABINE and INDOMETHACIN were discovered. We preliminarily explored the clinical significance of Fe-DEGs MT1G and DDIT4 in the diagnosis of ruptured AAA, and proposed possible upstream regulatory transcription factors and miRNAs. In addition, we also analyzed the immune infiltration of stable and rupture groups, and found possible targeted drugs for immunotherapy.

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

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

Abstract 1010: Novel Murine Model For Infrarenal Abdominal Aortic Aneurysm Development And Rupture

Introduction: Abdominal Aortic Aneurysm (AAA) rupture is linked with increased mortality. Multiple rodent models attempt to capitulate AAA pathology to investigate a preventative cure. However, there are currently no murine models that reliably mimic AAA rupture. Compounds such as porcine pancreatic elastase (PPE), papain, β-aminopropionitrile (BAPN) and angiotensin II (ANG II) can independently promote AAA formation in rodents. We hypothesize that combining these agents can lead to reliable infrarenal AAA rupture model in mice. Methods: 28 male C57BL/6 mice underwent aortic topical exposure to 50μL of either saline (sham), PPE, papain or both PPE+papain (20 &amp; 10.3mg/mL respectively) for 20 minutes with a cotton ball to induce AAA degeneration. A group of 10 mice were also exposed to BAPN at 0.3% via drinking water (Fig 1A). After 3 days, another group of 5 mice was further exposed to ANG II subcutaneous pump. Weight and in vivo aortic size were measured longitudinally. Mice that died spontaneously were promptly assessed to evaluate for AAA rupture (Fig 1B). All remaining mice were sacrificed at week 4. Results: Compared to sham, mice exposed to papain or PPE+papain, but no BAPN or ANG II, demonstrated no change in weight gain, but significantly increased aortic diameter at week 4 (p&lt;0.01) while administration of 0.3% BAPN demonstrated further increase in AAA diameter in both groups (p=0.002 and p&lt;0.001, respectively; Fig 1C). All mice that received PPE+papain+0.3% BAPN as well as ANG II pump developed infrarenal AAAs and 80% developed a free rupture by day 9 (Fig 1D). Conclusion: We present a novel murine model that provides a high rate of infrarenal AAA development and rupture. The model not only combines matrix degradation, but also impulse risk factors known to enhance AAA rupture in humans. The feasibility and reliability of the model facilitates its use in future murine genetic and pharmacological studies that aim to understand AAA pathophysiology and methods of prevention.

Abstract 3015: Matrix Metalloproteinase Inhibition In Rat Abdominal Aortic Aneurysm

Background: Matrix metalloproteinases (MMPs) have a robust proteolytic activity and play a fundamental role in degradation of extracellular matrix proteins. This degradation is a hallmark of the initiation, progression, and rupture of abdominal aortic aneurysms (AAAs). Hypothesis: We hypothesized that broad inhibition of MMPs with a 3 rd generation MMP inhibitor (GM6001) can reduce AAA inflammation and rupture using an established rat model. Aims: Our study aimed to investigate the potential of GM6001 in reducing AAA-related inflammation using a rat model, filling a critical gap in AAA research. Methods: Male Sprague-Dawley rats underwent intraluminal infrarenal perfusion of abdominal aorta using porcine pancreatic elastase (PPE), and daily β-aminopropionitrile (BAPN) to promote AAA rupture. Starting on postoperative day 3 (POD3) rats were treated daily either with or without GM6001 via intraperitoneal injections. On POD6, treated and untreated groups, underwent PET/CT imaging using a pan-MMP radiotracer 64Cu-RYM2 and in vivo aortic diameter measurement using ultrasound. Rate of rupture of treated and untreated groups was observed until POD14 (Fig 1A). Results: Treated rats demonstrated no evidence of toxicity or weight loss. Compared to untreated rats, treated rats had lower AAA rupture rates (P&lt;0.01; Fig 1B), smaller AAA diameters (P&lt;0.05; Fig 1C), and lower AAA MMP radiotracer uptake (P&lt;0.05; Fig 1D,1G). Total and active MMP-9 were significantly lower in treated rats (Fig 1E-F). In addition, IL-1B, IL-17A, IL-18, IFN-y, and RANTAS were significantly lower in treated rats, but TNF-a was higher (Fig 1H-M). VVG staining demonstrated a higher content of preserved elastin in treated rats (Fig 1N). Conclusion: Inhibition of MMPs with a 3 rd generation MMP inhibitor appears to be a promising therapeutic approach to impede the progression, inflammation, and rupture of AAAs in rats. This may represent a renewed pathway for MMP inhibition in human subjects with AAAs.

Abstract 126: Reduction Of Abdominal Aortic Aneurysm Rupture By Modulating Smooth Muscle Cell Phenotype Switching

Background: Vascular smooth muscle cell (SMC) loss and phenotype switch promote abdominal aortic aneurysm (AAA) development, yet whether strategically enhancing positive aortic wall remodeling can reduce AAA rupture is unknown. We hypothesize inhibiting necroptosis signaling in SMCs may drive differentiation into resilient and regenerative phenotypes, thus reinforcing AAA wall integrity and rupture resistance. Methods: We developed Cre-loxP transgenic mice with SMC-specific loss-of-function mutation of the necroptosis regulatory gene, Ripk3 ( Ripk3 Δ). AAAs were induced using the topical elastase plus β-aminopropionitrile murine model. Results: Rupture-free survival at 56-days post-AAA induction was drastically improved with both homozygous and heterozygous loss of SMC RIPK3 function ( Ripk3 Δ HO : 100%, Ripk3 Δ Het : 92.3% versus Ripk3 Δ WT : 47.1%). Ripk3 mutant aortas demonstrated rupture-resistance despite substantial aneurysmal dilations ranging 127-527%, and morphologically displayed significant medial thickening with SMC expansion. Bulk RNA-sequencing revealed stark transcriptional changes between 14-day Ripk3 Δ HO and Ripk3 Δ WT aortas. Both genotypes showed typical aneurysmal processes, however, Ripk3 depletion greatly reduced aneurysm-induced inflammatory responses. We identified 54 uniquely altered transcripts in mutant tissues, coding for cell cycle regulators and extracellular matrix proteins. Ongoing tissue analysis will determine whether regenerative, matrix-producing SMCs vary among human AAAs and healthy aortas. Conclusions: AAA rupture is significantly reduced by inhibiting RIPK3 in SMCs, likely by promoting positive structural adaptations and down-regulating classic pathways of aneurysmal degeneration. We postulate pharmacologically inhibiting RIPK3-mediated SMC modulation could be a novel approach in AAA patient management, to reduce rupture risk from diagnosis to optimal timing of surgical repair.

Abstract 149: The Protective Effect Of Vamp8 Deficiency In Aortopathies: Potential Impact Of Impaired Platelet Cargo Release

Introduction and Objective: Platelet activation and subsequent cargo secretion play a critical role in thrombus formation and aortic remodeling, factors potentially influencing the growth and rupture of abdominal aortic aneurysms (AAA). Despite the compelling data that platelet activation is associated with AAA and rupture, the underlying mechanisms remain poorly understood. This study hypothesizes that VAMP8, a key element of platelets’ secretory machinery, significantly contributes to AAA formation. Approach and Results: A retrospective, single-center multiple comparisons study of adult aneurysmal patients admitted to UKHealthCare between 2004 and 2023 revealed a significantly lower platelet count in AAA patients (n=3131, 213.76 ± 3.46) vs. healthy individuals (n= 6309, 243.18 ± 4.09) suggesting an increase in platelets consumption, potentially in the aneurysmal sack. Thoracic aortic aneurysm and aortic dissection patients also indicated lower platelet count. In vivo , platelets were shown to accumulate at elastin break sites and false lumens of abdominal aortas from 28-day AngII-infused hypercholesteremic mice. To assess the role of platelets, specifically platelet secretion, we utilized VAMP8 null mice. We first validated the platelet secretion defect in these mice and then used RNASeq and proteomics array to define the role of VAMP8 in platelet cargo packaging. Next, VAMP8 -/- or WT hypercholesterolemic male mice fed a Western diet were infused with AngII (1,000 ng/kg/min) for 4 weeks. Our results revealed that VAMP8 -/- mice are protected against AngII-driven aortic rupture. Additionally, aortic ex vivo analysis indicated that the VAMP8 deficiency (n=15, aortic diameter: 0.9 mm ± 0.03) profoundly attenuated AngII-induced AAA compared to control (n=9, aortic diameter: 2.0 mm ± 0.2). Further analysis also indicated a marked reduction in thoracic aortic aneurysm and atherosclerosis development in VAMP8 -\- vs. Control group. Conclusion: Our results elucidate that a deficiency in VAMP8 results in the profound attenuation of aortic aneurysms and atherosclerosis development, introducing a novel paradigm for understanding the impact of platelet cargo secretion in the development of aortopathies.

Divergent Effects of IL-18- and IL-18R-deficiency on Angiotensin II-induced Abdominal Aortic Aneurysm Formation

Currently, there are no pharmacological treatments for abdominal aortic aneurysms (AAA), and AAA rupture is fatal in ~90% of patients. Aortic inflammation is strongly correlated with the expansion of AAA and recently the NLRP3 inflammasome has been implicated in thedevelopment of AAA. Interleukin (IL)-18, an inflammasome-derived cytokine, exerts pro-inflammatory responses when bound to its cognate IL-18 receptor (IL-18Rα). The current project aimed to determine the effect of IL-18- and IL-18Rα-deficiency on the incidence of angiotensin (Ang) II-induced AAA. Ten-week-old male C57BL/6 (WT), IL-18-deficient ( Il18−/−) and IL-18Rα-deficient ( Il18r1−/−) mice were infused with Ang II (1.44 mg/kg/day, s.c.) for 28 days via osmotic minipump. Ang II-induced AAA incidence differed in all strains. While 52% of WT mice developed AAA (including premature deaths due to rupture), no AAAs were detected in Il18−/− mice (p&lt;0.05, n=20-23). Strikingly, Il18r1−/− mice exhibited a higher incidence of AAA and associated mortality compared to WT mice(88%; p&lt;0.05, n=23-25). Consistent with this finding, in vivo ultrasound imaging confirmed advanced dilation of the abdominal aorta at d7 after Ang II-treatment in Il18r1−/− mice cf. WT mice (1.49 ± 0.13 vs 1.15 ± 0.05 mm; p&lt;0.05; n=23-25). Single cell RNA-sequencing of Ang II-infused mouse aorta revealed Il18r1 gene expression was limited to gamma-delta T cells, suggesting these cells may be driving IL-18 mediated AAA formation. In summary, IL-18-deficiency affords protection from AAA formation, while AAA incidence and severity were augmented in Il18r1−/− mice. Neutralisation of IL-18, but not IL-18Rα inhibition, may represent a novel therapeutic strategy to treat AAA. NHMRC (GNT1143674). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 1001: Interleukin-33 Deficiency Exacerbated Angiotensin II-induced Abdominal Aortic Aneurysms

Objective: Chronic infusion of angiotensin II (AngII) promotes development of abdominal aortic aneurysms (AAAs) in Apolipoprotein E-deficient (ApoE-/-) mice. Interleukin 33 (IL-33), known as one of IL-1 family, is rapidly released from damaged endothelial and epithelial cells. IL-33 binds to its receptor, ST2, and exerts various physiological functions through its downstream signaling. Previous studies have shown that exogenous IL-33 attenuates development of AAAs through wound healing resolution. The purpose of this study was to evaluate whether IL-33 deficiency exacerbated development of AAAs by using IL-33xApoE double deficient (IL-33-/-xApoE-/-) mice. Methods and Results: Male ApoE-/- and IL-33-/-xApoE-/- (8-12 weeks old) mice were assigned into saline infused group (ApoE-/- n=5, IL-33-/-xApoE-/- n=7) and AngII infused group (ApoE-/- n=19, IL-33-/-xApoE-/- n=19). Mice were infused subcutaneously with either saline or AngII by osmotic minipumps for 4 weeks. During 4-week AngII infusion, 3 mice died by AAA rupture in each AngII-infused group. There was no significant difference in ex vivo abdominal aortic width between saline infused groups (ApoE-/- 0.87±0.17 mm vs IL-33-/-xApoE-/- 0.87±0.14 mm, n.s.) nor body weight (ApoE-/- 27.3±0.9 g vs IL-33-/-xApoE-/- 27.9±0.9 g, n.s.) but serum total cholesterol concentrations in IL-33-/-xApoE-/- was higher than in ApoE-/- (522±85 mg/dL vs 427±108 mg/dL, p=0.026). AngII equally elevated systolic blood pressure (ApoE-/- 151±15 mmHg, IL-33-/-xApoE-/- 155±17 mmHg, n.s.). AngII increased ex vivo maximum abdominal aortic width in AngII infused groups, but AAAs were further exacerbated in the group of IL-33-/-xApoE-/- mice (ApoE-/- 1.31±0.09 mm vs IL-33-/-xApoE-/- 1.76±0.09 mm, p=0.001). In addition, the severity of AAAs in AngII infused groups was significantly worse in IL-33-/-xApoE-/- than in ApoE-/- (p=0.037). Conclusion: Our study demonstrated IL-33 deficiency exacerbated AngII-induced AAAs in male ApoE-/- mice.

Abstract 3013: Indoleamine 2,3-dioxygenase-mediated Tryptophan Catabolism Limits Experimental Abdominal Aortic Aneurysms

Background: Indoleamine 2,3-dioxygenase (IDO) promotes immunosuppression. Genetic IDO deficiency limits angiotensin II-induced abdominal aortic aneurysms (AAAs) in hyperlipidemic mice. We investigated the influence of IDO inhibition or IDO-catabolized tryptophan catabolite on elastase-induced AAAs in normolipidemic mice. Methods: AAAs were induced in male C57B/6J mice via intra-aortic porcine pancreatic elastase (PPE) infusion. Mice were treated with IDO inhibitor 1-methyl-DL-tryptophan (MT, 2 mg/ml in drinking water), tryptophan metabolite 3-hydroxyanthranilic acid (HAA, 200 mg/kg, oral gavage), or vehicle, starting 3 days prior to PPE infusion for 17 days. AAAs were assessed via ultrasonography and histopathology at sacrifice. Results: The Figure summarizes aortic diameters and histopathology in differentially treated PPE-infused mice. Rapid aortic enlargement was noted in MT-, as compared to vehicle-treated mice following PPE infusion. AAA rupture, unusual for this model, was noted in MT-treated AAA mice. No difference was noted between groups in medial elastin degradation, smooth muscle cell depletion, or macrophage accumulation. However, mural neoangiogenesis and lymphocyte accumulation were remarkably augmented in MT-treated mice. HAA Treatment attenuated aortic enlargement in conjunction with improved medial elastin and smooth muscle cell retention and reduced aortic leukocyte accumulation and neovessels. Conclusion: IDO activity and its tryptophan metabolite HAA limit experimental AAA progression in the PPE model. These results provide further support for investigating tryptophan metabolites in clinical AAA disease suppression.

Abstract 2008: Characterizing Changes In Abdominal Aortic Aneurysm Principal Wall Strain Using Ultrasound Elastography

Pressure-normalized aortic principal wall strain (ep+/pp, %/mmHg) is a biomechanical parameter for abdominal aortic aneurysm (AAA) stability correlated with aneurysm growth rate. We hypothesized that ep+/pp decreases as AAAs degenerate. This study aimed to characterize ep+/pp change over time using ultrasound elastography (USE). Axial ultrasound images of patient AAAs were collected at two consecutive clinic visits. The USE algorithm applied a finite element mesh over the aneurysm wall at the point of maximum diameter. A custom image-registration protocol tracked frame-to-frame displacement fields of the images over one cardiac cycle to calculate maximum ep+/pp (Fig 1). Clinical data were collected from patient records. The cohort was separated by index ep+/pp terciles. Thirty-one patients with a mean age of 71.7 ± 10.1 at index visit were included, with follow-up imaging at an interval of 7.1 ± 3.4 months. For the cohort, maximum ep+/pp decreased from 2.3 ± 1.0 %/mmHg to 2.0 ± 0.9 %/mmHg (p=0.08), and average AAA diameter increased from 4.4 ± 0.6 cm to 4.5 ± 0.7 cm (p=0.04). The “high-strain” tercile was associated with a strain reduction of -1.7 ± 0.8 %/mmHg, compared to “low” (0.1 ± 1.0 %/mmHg, p&lt;0.01) and “intermediate” (-0.4 ± 0.5 %/mmHg, p=0.04) terciles (Fig 2). There was no difference in AAA growth or rupture between terciles. The present findings indicate that AAA ep+/pp at baseline predicts the degree of ep+/pp decrease over time. These data suggest that biomechanical changes in the aortic wall related to aneurysmal degeneration can be quantized by a novel ultrasound technique. Research correlating these results with histopathologic AAA remodeling may inform monitoring.

Abstract 1015: Knockout Of P27 Kip1 Accelerates Topical Elastase/3-aminopropionitrile Fumarate Salt-induced Abdominal Aortic Aneurysm Rupture In Mice

Background: Abdominal aortic aneurysms (AAAs) are multifactorial diseases, and unknown genetic factors could contribute to aneurysms. The cell cycle inhibitor CDKN1B gene, also known as p27 Kip1 (p27), affects the arterial response to injury. Previous studies have shown that the loss of p27 exacerbates atherosclerosis progression by increasing vascular smooth muscle cells and macrophages. To assess the role of p27 in AAA development, another form of arterial response to inflammatory injury, we conducted experiments on the AAA model using p27 knockout (p27 -/- ) and wild-type (WT) mice. Methods: AAAs were induced in male and female p27 -/- and WT (C57BL/6J) mice by topically applying porcine pancreatic elastase and administrating 0.2% 3-aminopropionitrile fumarate salt (BAPN) in the drinking water. Topical elastase application was divided into active and heat-inactivated elastase groups. The aortic diameter was evaluated by ultrasound examination preoperatively and every 7 days postoperatively ( Fig. A ). Surviving mice were sacrificed after the final ultrasound evaluation, and aortic samples were collected for histological analysis. Results: Fig. B shows the aortic diameter change evaluated by ultrasound examination. AAA rupture occurred in one male p27-/- mice (33%, 1 of 3) and two female p27-/- mice (40%, 2 of 5), but in no WT mice of either gender. Macrophages were assessed using anti-F4/80 antibody. In the elastase-active group, both male and female p27 -/- mice had a significantly higher accumulation of macrophage than WT mice (P&lt;0.01 and P&lt;0.01, respectively), but there was no significant staining of F4/80 in the elastase-inactive group ( Fig. C and D ). Conclusions: Knockout of p27 exacerbated aneurysm rupture in a topical elastase/BAPN-induced AAA model and was associated with increased macrophage infiltration.

Editor's Choice – A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair

Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets (COS) has been developed. COS, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents) 15 questions were eliminated, and 11 further questions were eliminated after round 2 (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: death at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, five year survival, and continued sac growth. Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and to define instruments for cognitive functioning is needed.

Effect of EVAR on International Ruptured AAA Mortality-Sex and Geographic Disparities.

Background: We sought to investigate the differential impact of EVAR (endovascular aneurysm repair) vis-à-vis OSR (open surgical repair) on ruptured AAA (abdominal aortic aneurysm) mortality by sex and geographically. Methods: We performed a retrospective study of administrative data on EVAR from state statistical agencies, vascular registries, and academic publications, as well as ruptured AAA mortality rates from the World Health Organization for 14 14 states across Australasia, East Asia, Europe, and North America. Results: Between 2011-2016, the proportion of treatment of ruptured AAAs by EVAR increased from 26.1 to 43.8 percent among females, and from 25.7 to 41.2 percent among males, and age-adjusted ruptured AAA mortality rates fell from 12.62 to 9.50 per million among females, and from 34.14 to 26.54 per million among males. The association of EVAR with reduced mortality was more than three times larger (2.2 vis-à-vis 0.6 percent of prevalence per 10 percentage point increase in EVAR) among females than males. The association of EVAR with reduced mortality was substantially larger (1.7 vis-à-vis 1.1 percent of prevalence per 10 percentage point increase in EVAR) among East Asian states than European+ states. Conclusions: The increasing adoption of EVAR coincided with a decrease in ruptured AAA mortality. The relationship between EVAR and mortality was more pronounced among females than males, and in East Asian than European+ states. Sex and ethnic heterogeneity should be further investigated.

Identification and Evaluation of Blood-Based Biomarkers for Abdominal Aortic Aneurysm.

Blood-based biomarkers for abdominal aortic aneurysm (AAA) have been studied individually; however, we considered a panel of proteins to investigate AAA prognosis and its potential to improve predictive accuracy. Using a prospectively recruited cohort of patients with/without AAA (n = 452), we conducted a prognostic study to develop a model that accurately predicts AAA outcomes using clinical features and circulating biomarker levels. Serum concentrations of 9 biomarkers were measured at baseline, and the cohort was followed for 2 years. The primary outcome was major adverse aortic event (MAAE; composite of rapid AAA expansion [>0.5 cm/6 months or >1 cm/12 months], AAA intervention, or AAA rupture). Using 10-fold cross-validation, we trained a random forest model to predict 2 year MAAE using (1) clinical characteristics, (2) biomarkers, and (3) clinical characteristics and biomarkers. Two-year MAAE occurred in 114 (25%) patients. Two proteins were significantly elevated in patients with AAA compared with those without AAA (angiopoietin-2 and aggrecan), composing the protein panel. For predicting 2 year MAAE, our random forest model achieved area under the receiver operating characteristic curve (AUROC) 0.74 using clinical features alone, and the addition of the 2-protein panel improved performance to AUROC 0.86. Using a combination of clinical/biomarker data, we developed a model that accurately predicts 2 year MAAE.

The role of diabetes on the development of abdominal aortic aneurysms (AAA)

An abdominal aortic aneurysm (AAA) is a pathological local dilatation of the abdominal aorta that may develop from a variety of causes. With a 80% mortality rate, it is mainly linked to male gender, age above 65 years, smoking, and a family history of AAA. Ultrasonography is an effective method for screening males who are 65 or older for AAA. Endovascular aneurysm repair (EVAR) procedure reduces 30-day operative mortality and hospital stay, becoming a global standard. Both open and endovascular surgery aim to cut off the aneurysm's circulation, preventing it from rupturing. Diabetes mellitus (DM) may provide protection against regrowth and the need for additional intervention after endovascular AAA repair, thereby limiting the enlargement and rupture of AAAs. Hyperglycemia thickens the aortic walls and reduces wall stress in diabetic patients' abdominal aortas. It stabilizes collagen structure and promotes the synthesis of collagen type IV. Anti-diabetic drugs like metformin, thiazolidinedione, and dipeptidyl peptidase 4 inhibitors (DPP-4i) have been shown in both animal and human studies to protect against aortic aneurysms. In a dose-response pattern, these antidiabetic drugs may lower the prevalence, incidence, and enlargement rate of AAA.

Anesthetic Management for Abdominal Aortic Aneurysm Rupture

Background: Aortic aneurysm is the thirteenth leading cause of death in the united states. Around 15.000 people died each year because of aortic aneurysm rupture. The mortality rate for this case are still high at around 90%. Patient diagnosed with acute aortic rupture will need an urgent surgery.Case: A 36-year-old man came with complaints of pain in the waist to back area since 1 week before entering the hospital and worsening 2 days before entering the hospital. Pain is felt intermittent. The pain is sharp and severe when the patient strains. On physical examination found high blood pressure (160/104 mmHg), chest X-ray showed widening of the mediastinum suspected descending aortic aneurysm, CT angiography showed a fusiform type descending aortic aneurysm pars thoracoles, ruptured abdominal aortic aneurysm of juxtarenal fusiform type to the terminal abdominal aorta and hemoperitoneum. The patient underwent repair of an abdominal aortic aneurysm under general anesthesia. After surgery the patient was admitted to the ICU for clinical and hemodynamic monitoring, but the patient's condition in the ICU worsened. The patient experienced acute kidney failure and liver failure, then the patient died on the 10th day after surgery.Discussion: Surgery for ruptured abdominal aortic aneurysm is associated with high mortality. Even patients who survive the initial procedure are at high risk of complications (such as renal, cardiac, respiratory, haematological, or gastrointestinal failure). The main goal of anesthesia is to maintain anesthesia with cardiovascular stability and normothermia for as long as possible. Minimum standards of monitoring for surgery include electrocardiogram, CVP, arterial line, temperature, and urine output. This operation uses a cell saver machine which functions to collect lost blood, clean the blood and return it to the patient.Conclusion: Surgery for patients with acute aortic rupture requires complicated and complex anesthetic techniques. This operation requires collaboration and good communication between the surgeon and the anesthesiologist.

Protective effect of clotrimazole on lung injury in an experimental model of ruptured abdominal aortic aneurysm.

Lungs are the target organs most affected by ischemia/reperfusion (I/R) injury, which is exacerbated when hemorrhagic shock occurs. Suppressing various proinflammatory cytokines, inflammation and oxidation that initiate and aggravate lung damage with various drugs or methods provides significant benefits in preventing lung damage. This study aims to evaluate the protective effect of clotrimazole (CLT), an antimycotic drug, on lung injury and systemic inflammatory response in rats by creating an experimental model of a ruptured abdominal aortic aneurysm (RAAA). Thirty-six male Sprague Dawley rats were randomly divided into 5 groups: sham, sham+CLT, sham+polyethylene glycol (PEG), shock+ischemia/reperfusion (SIR), and SIR+CLT. Saline, CLT and PEG were administered in the sham groups without shock and I/R. The hemorrhagic shock was developed in SIR groups by drawing blood for 1 h to keep the mean arterial pressure at 50 mm Hg. After 60 min, the SIR+CLT group was given 20 mg/kg CLT; then, the aortic clamps were opened, and rats were left for 120 min of reperfusion. The blood taken to create hemorrhagic shock was returned in a controlled manner during this time. At the end of the reperfusion procedure, samples were taken for cytokine levels in serum and lung tissue and for other biochemical analyses. Blood gas, histopathological examination and wet/dry weight measurements were performed to assess lung injury. An increase was observed in all parameters in the SIR group compared to the sham group. In the SIR+CLT group, the serum myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), lung MPO values, histologically lung injury scores, and lung tissue wet/dry ratio were decreased significantly when compared to the SIR group (p < 0.05). These results indicate that CLT may reduce the systemic inflammatory response and lung injury due to shock and I/R in an experimental model of RAAA.

The Role of Integrated Air Transport System in Managing Patients with Abdominal Aortic Aneurysm Rupture

Ruptured abdominal aortic aneurysms (rAAAs) are highly morbid emergencies. Not all hospitals are equipped to repair them, and an air ambulance network may aid in regionalising specialty care to quaternary referral centres. The association between travel distance by air ambulance and rAAA mortality in patients transferred as an emergency for repair was examined. A retrospective review of institutional data. Adults with rAAA (2002 - 2019) transferred from an outside hospital (OSH) to a single quaternary referral centre for repair via air ambulance were identified. Patients who arrived via ground transport or post-repair at an OSH for continued critical care were excluded. Patients were divided into near and far groups based on the 75th percentile of the straight line travel distance (> 72 miles) between hospitals. The primary outcome was 30 day mortality. Multivariable logistic regression was used to assess the association between distance and mortality after adjusting for age, sex, ethnicity, cardiovascular comorbidities, and repair type. A total of 290 patients with rAAA were transported a median distance of 40.4 miles (interquartile range 25.5, 72.7) with 215 (74.1%) near and 75 (25.9%) far patients. Both the near and far groups had similar ages, sex, and ethnicity. There was no difference in pre-operative loss of consciousness, intubation, or cardiac arrest between groups. Endovascular aneurysm repair utilisation and intra-operative aortic occlusion balloon use were also similar. Neither the observed (26.8% vs. 23.9%, p= .61) nor the adjusted odds ratio (0.70, 95% confidence interval 0.36 - 1.39, p= .32) 30 day mortality rate differed significantly between the near and far groups. Increasing distance travelled during transfer by air ambulance was not associated with worse outcomes in patients with rAAA. The findings support the regionalisation of rAAA repair to large quaternary centres via an integrated and robust air ambulance network.