Small AAAs: Recommendations for Rodent Model Research for the Identification of Novel Therapeutics.

CLINICAL PROBLEM: Most abdominal aortic aneurysms (AAAs) are small with low rupture risk (<1%/y) when diagnosed but slowly expand to ≥55 mm and undergo surgical repair. Patients and clinicians require medications to limit AAA growth and rupture, but drugs effective in animal models have not translated to patients. RECOMMENDATIONS FOR INCREASING TRANSLATION FROM MOUSE MODELS: Use models that simulate human AAA tissue pathology, growth patterns, and rupture; focus on the clinically relevant outcomes of growth and rupture; design studies with the rigor required of human clinical trials; monitor AAA growth using reproducible ultrasound; and perform studies in both males and females. SUMMARY OF STRENGTHS AND WEAKNESSES OF MOUSE MODELS: The aortic adventitial elastase oral ß-aminopropionitrile model has many strengths including simulating human AAA pathology and modeling prolonged aneurysm growth. The Ang II (angiotensin II) model performed less well as it better simulates acute aortic syndrome than AAA. The elastase plus TGFß (transforming growth factor-ß) blocking antibody model displays a high rupture rate, making prolonged monitoring of AAA growth not feasible. The elastase perfusion and calcium chloride models both display limited AAA growth.

ß-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice.

BACKGROUND: ß-aminopropionitrile (BAPN) is a pharmacological inhibitor of LOX (lysyl oxidase) and LOXLs (LOX-like proteins). Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice. METHODS: BAPN was administered in drinking water for a period ranging from 1 to 12 weeks. The impacts of BAPN were first assessed with regard to BAPN dose, and mouse strain, age, and sex. BAPN-induced aortic pathological characterization was conducted using histology and immunostaining. To investigate the mechanistic basis of regional heterogeneity, the ascending and descending thoracic aortas were harvested after 1 week of BAPN administration before the appearance of overt pathology. RESULTS: BAPN-induced aortic rupture predominantly occurred or originated in the descending thoracic aorta in young C57BL/6J or N mice. No apparent differences were found between male and female mice. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while there were more heterogeneous changes in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissections with false lumen formation, collagen deposition, and remodeling of the wall surrounding the false lumen. Cells surrounding the false lumen were predominantly positive for α-SMA (α-smooth muscle actin). One week of BAPN administration compromised contractile properties in both regions equivalently, and RNA sequencing did not show obvious differences between the 2 aortic regions in smooth muscle cell markers, cell proliferation markers, and extracellular components. CONCLUSIONS: BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in mice.

A sudden death, an aortic rupture, and an unexpected cause: a report about suspected child abuse.

All unexpected deaths of children require an autopsy to determine the cause of death. In cases of aortic rupture, the immediate cause of death is easily identified at autopsy. Although the majority of aortic ruptures are caused by high-energy trauma, other causes should not be missed.We present and discuss the case of a 29-month-old child who died suddenly at home. Her recent medical history and the ecchymotic lesions observed on external examination of the body appeared potentially suspicious of physical abuse. The autopsy concluded that death was due to complete rupture of the abdominal aorta with associated vertebral disjunction. At first glance, the overall forensic picture could suggest a traumatic death. However, careful inspection of the retroperitoneum revealed a discrete atypical mass of infiltrative tissue within the hematoma. Histopathological examinations confirmed tumor proliferation of the soft tissues, triggering vascular and spinal injuries. Other paraneoplastic elements or metastases were ultimately revealed (orbital and subcutaneous). Overall, this was a rare and fatal case of abdominal aortic rupture induced by tumors. Due to the mechanisms and the forces needed to cause vertebral dislocations and aortic rupture, the combination of the two is highly suggestive of child abuse when an accidental traumatic history is absent or inconsistent with the injuries. Nevertheless, this case illustrates the importance of a systematic and rigorous forensic examination, rather than ignoring other possible diagnoses.

Sudden Death Due to Rupture of Aneurysm of Sinus Valsalva: An Autopsy Case.

ABSTRACT: Aneurysm of sinus Valsalva is a defined as dilatation of the sinuses located between the aortic valve annulus and the sinotubular junction and mostly found in the right coronary sinus. It can be either congenital or acquired. This condition is usually asymptomatic unless it can cause intracardiac rupture or aortic valve insufficiency. Extracardiac rupture and associated fatal cases of cardiac tamponade are extremely rare. Our case is one of the rare cases in the literature that was diagnosed during autopsy. Our case is 65-year-old male patient with a history of hypertension suddenly fell ill after swimming in the sea. On gross examination of heart, there was an aneurysmatic enlargement of the right sinus Valsalva measuring 4.5 × 4 cm with a hemorrhagic appearance on the outer surface and a 0.3 cm rupture area. Histopathological examination revealed hemorrhage in and around the aneurysm wall.

Characterizing Tissue Remodeling and Mechanical Heterogeneity in Cerebral Aneurysms.

Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression - blood flow dynamics, immune infiltration, and extracellular matrix remodeling - all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA's fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture.

Early Detection of Aortic Degeneration in a Mouse Model of Sporadic Aortic Aneurysm and Dissection Using Nanoparticle Contrast-Enhanced Computed Tomography.

[Figure: see text].

Modern diagnostic approach to patients with abdominal aortic aneurysm.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relatively frequent and serious condition in vascular surgery. The diagnostic and indication process and its treatment are driven by the guidelines which dictate an intervention when the maximum AAA diameter is more than 55 mm. Nevertheless, this approach is not fully sufficient in all AAA cases and thus we have been seeking to develop a modern diagnostic tool using computer modeling and vascular wall stress analysis. METHODS: The project has been ongoing in cooperation with engineers from VUT Brno (Brno University of Technology) and VŠB Ostrava (Technical University of Ostrava) for ten years. The design of the analytical tool was created during the first, experimental period of the project; this tool is able to assess vascular wall stress from regular CT scans using the finite element method. This primary model was gradually altered and its precision was increased considerably in the course of the years using data from mechanical and histological tests of AAA wall specimens harvested during open repairs. Additionally, other patient specific data are included in the analysis such as blood pressure, gender and material characteristics. RESULTS: The effectiveness of the method was evaluated in a pseudo-prospective study, showing clear superiority of the vascular wall stress analysis over the maximum diameter approach. The method was used in clinical practice for the first time during restrictions due to the COVID-19 pandemic; based on the analysis we were able to assess which AAA cases can be postponed and which had a high risk of rupture and an intervention was required despite the restrictions. The method achieved 100% sensitivity, and its specificity was also much better compared to the maximum diameter approach. CONCLUSION: The vascular wall stress analysis of AAA seems to be much more precise than the classic indication approach based only on the maximum diameter, and it can be used to determine the therapy based on patient specific parameters.

Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture.

BACKGROUND: Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal condition. Identifying mechanisms that drive aortic degeneration is a crucial step in developing an effective pharmacologic treatment to prevent disease progression. Recent evidence has indicated that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical role in vascular inflammation and destruction. Here, we examined the involvement of this mechanism in aortic degeneration and sporadic AAD formation. METHODS: The presence of cytosolic DNA in aortic cells and activation of the STING pathway were examined in aortic tissues from patients with sporadic ascending thoracic AAD. The role of STING in AAD development was evaluated in Sting-deficient (Stinggt/gt) mice in a sporadic AAD model induced by challenging mice with a combination of a high-fat diet and angiotensin II. We also examined the direct effects of STING on SMC death and macrophage activation in vitro. RESULTS: In human sporadic AAD tissues, we observed the presence of cytosolic DNA in SMCs and macrophages and significant activation of the STING pathway. In the sporadic AAD model, Stinggt/gt mice showed significant reductions in challenge-induced aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions. Single-cell transcriptome analysis revealed that aortic challenge in wild-type mice induced the DNA damage response, the inflammatory response, dedifferentiation and cell death in SMCs, and matrix metalloproteinase expression in macrophages. These changes were attenuated in challenged Stinggt/gt mice. Mechanistically, nuclear and mitochondrial DNA damage in SMCs and the subsequent leak of DNA to the cytosol activated STING signaling, which induced cell death through apoptosis and necroptosis. In addition, DNA from damaged SMCs was engulfed by macrophages in which it activated STING and its target interferon regulatory factor 3, which directly induced matrix metalloproteinase-9 expression. We also found that pharmacologically inhibiting STING activation partially prevented AAD development. CONCLUSIONS: Our findings indicate that the presence of cytosolic DNA and subsequent activation of cytosolic DNA sensing adaptor STING signaling represent a key mechanism in aortic degeneration and that targeting STING may prevent sporadic AAD development.

Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm.

Thoracic aortic aneurysm and dissection (TAAD) is a deadly disease characterized by intimal disruption induced by hemodynamic forces of the circulation. The effect of exercise in patients with TAAD is largely unknown. ß-Aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase that induces TAAD in mice. The objective of this study was to investigate the effect of aerobic exercise on BAPN-induced TAAD. Upon weaning, mice were given either BAPN-containing water or standard drinking water and subjected to either conventional cage activity (BAPN-CONV) or forced treadmill exercise (BAPN-EX) for up to 26 wk. Mortality was 23.5% (20/85) for BAPN-CONV mice versus 0% (0/22) for BAPN-EX mice (hazard ratio 3.8; P = 0.01). BAPN induced significant elastic lamina fragmentation and intimal-medial thickening compared with BAPN-untreated controls, and aneurysms were identified in 50% (5/10) of mice that underwent contrast-enhanced CT scanning. Exercise significantly decreased BAPN-induced wall thickening, calculated circumferential wall tension, and lumen diameter, with 0% (0/5) of BAPN-EX demonstrating chronic aortic aneurysm formation on CT scan. Expression of selected genes relevant to vascular diseases was analyzed by qRT-PCR. Notably, exercise normalized BAPN-induced increases in TGF-ß pathway-related genes Cd109, Smad4, and Tgfßr1; inflammation-related genes Vcam1, Bcl2a1, Ccr2, Pparg, Il1r1, Il1r1, Itgb2, and Itgax; and vascular injury- and response-related genes Mmp3, Fn1, and Vwf. Additionally, exercise significantly increased elastin expression in BAPN-treated animals compared with controls. This study suggests that moderate aerobic exercise may be safe and effective in preventing the most devastating outcomes in TAAD.NEW & NOTEWORTHY Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-ß, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise.

Comparison of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms.

BACKGROUND: Previous studies have suggested that finite element analysis (FEA) can estimate the rupture risk of an abdominal aortic aneurysm (AAA); however, the value of biomechanical estimates over measurement of AAA diameter alone remains unclear. This study aimed to compare peak wall stress (PWS) and peak wall rupture index (PWRI) in participants with ruptured and asymptomatic intact AAAs. METHODS: The reproducibility of semiautomated methods for estimating aortic PWS and PWRI from CT images was assessed. PWS and PWRI were estimated in people with ruptured AAAs and those with asymptomatic intact AAAs matched by orthogonal diameter on a 1 : 2 basis. Spearman's correlation coefficient was used to assess the association between PWS or PWRI and AAA diameter. Independent associations between PWS or PWRI and AAA rupture were identified by means of logistic regression analyses. RESULTS: Twenty individuals were included in the analysis of reproducibility. The main analysis included 50 patients with an intact AAA and 25 with a ruptured AAA. Median orthogonal diameter was similar in ruptured and intact AAAs (82·3 (i.q.r. 73·5-92·0) versus 81·0 (73·2-92·4) mm respectively; P = 0·906). Median PWS values were 286·8 (220·2-329·6) and 245·8 (215·2-302·3) kPa respectively (P = 0·192). There was no significant difference in PWRI between the two groups (P = 0·982). PWS and PWRI correlated positively with orthogonal diameter (both P < 0·001). Participants with high PWS, but not PWRI, were more likely to have a ruptured AAA after adjusting for potential confounders (odds ratio 5·84, 95 per cent c.i. 1·22 to 27·95; P = 0·027). This association was not maintained in all sensitivity analyses. CONCLUSION: High aortic PWS had an inconsistent association with greater odds of aneurysm rupture in patients with a large AAA.

The hepatoprotective potential of resveratrol in an experimental model of ruptured abdominal aortic aneurysm via oxidative stress and apoptosis.

The mortality rate in ruptured abdominal aortic aneurysms can today be reduced through cardiovascular surgery. However, ischemia and reperfusion-induced tissue damage develop due to aortic cross-clamping applied during surgery. The present study aimed to reduce oxidative stress-induced hepatic damage resulting from ischemia and reperfusion due to aortic cross-clamping during surgery by means of resveratrol administration. Forty male Sprague-Dawley rats were randomly assigned into four groups: control (healthy), glycerol+ischemia/reperfusion (I/R) (sham), I/R, and I/R + Resveratrol. In all groups scheduled for I/R, 60 min of shock was followed by 60 min of ischemia. In the I/R + Resveratrol group, 10 mg/kg of resveratrol was administered 15 min before ischemia and immediately before reperfusion via the intraperitoneal route. In addition, 120 min of reperfusion was applied under anesthesia after ischemia in all groups. Intralobar and interlobar necrosis, vascular congestion, and edematous fields resulting from aortic occlusion were present. Liver tissue malondialdehyde (MDA) levels and cleaved caspase-3 positivity increased, while glutathione (GSH) levels decreased. However, resveratrol administration reduced intralobular and interlobar necrosis, vascular congestion and edematous fields, cleaved caspase-3 positivity, and MDA levels, and increased GSH levels. Our findings suggest that resveratrol is effective against aortic occlusion-induced liver injury by reducing oxidative stress and apoptosis.

Biomechanical Analysis of Cadaveric Thoracic Aorta Zones: The Isthmus is the Weakest Region.

BACKGROUND: The thoracic aorta is a site of multiple pathological processes, such as aneurysms and dissections. When considering the development of endovascular devices, this vessel has been extensively manipulated because of aortic diseases, as well as to serve as a route for procedures involving the head and neck vessels. Therefore, the aim of the present study was to obtain biomechanical experimental information about the strength and deformability of this vessel. MATERIALS AND METHODS: Thirty-one thoracic aorta specimens were harvested during the autopsy procedure. They were carefully dissected and transversally sectioned according to Criado's aortic arch map landing zones (0 to 4). The supra-aortic trunks were removed, and the aortic rings were opened in their convexity, which resulted in flat tissue segments. Four millimeter-wide strips were prepared from each zone after which they were attached to a clip system connected to the INSTRON SPEC 2200 device, which was responsible for pulling the fragment up to its rupture during the uniaxial tension test. The INSPEC software was used to coordinate the test, and data management was conducted via the SERIES IX software. The biomechanical variables that were measured included failure stress, failure tension, and failure strain. RESULTS: When comparing the five segments from all 31 aortas, three different strength levels were observed. Zones 0 and 1 exhibited the highest failure stress and failure tension values, followed by Zones 2 and 4. Zone 3 (aortic isthmus) was the weakest segment that was tested when compared to the stress and tension of Zones 0 and 1 (P < 0.001), the stress and tension of Zone 2 (P = 0.005 and P = 0.002, respectively) and the stress and tension of Zone 4 (P = 0.023 and P = 0.006, respectively). Among donors > 65 years-old, women presented significantly weaker descending aortas than men in regards to stress (P = 0.049) and tension (P = 0.014). Among male donors, the elderly donors presented significantly stiffer aortic walls and weaker ascending (P = 0.029 for stress) and descending (P = 0.004 for stress; P = 0.031 for tension) aortas than younger men. CONCLUSIONS: Uniaxial tensile strength tests revealed that the thoracic aorta is a very heterogeneous vessel. Isthmus frailty may add to the understanding of the pathophysiology of some aortic diseases that commonly compromise this region. The lower strength that was verifiedin some aortic segments from elderly donors may contribute to the genesis of some thoracic aorta diseases among that group of donors. These data can contribute to the development of new endovascular devices that are specifically designed for this vessel.

Experimental Study of Rupture Pressure and Elasticity of Abdominal Aortic Aneurysms Found at Autopsy.

BACKGROUND: Resistance and elasticity of normal and aneurysmal aorta walls are directly associated with this vessel's growth and rupture. This study aims to experimentally analyze the biomechanical behavior of aneurysmal specimens found at autopsy, comparing them with normal diameter aortas removed from age-matched donors. METHODS: Thirty-eight human aortas (30 normal aortas; 8 infrarenal abdominal aortic aneurysms) were harvested during autopsy. An apparatus was built with a digital gauge, plastic tray, connections, and hoses that conducted fluid (air) from a pump through the system. Specimens were dissected, and a flexible balloon was introduced in each of them to avoid leakage. The specimens were fastened on the test tray, and activation of the air pump enhanced system pressure up to their rupture. RESULTS: All 8 aneurysms and all 30 normal aortas specimens evolved to rupture under inflation pressures above 590 mm Hg (mean ± standard deviation = 1,035 ± 375 mm Hg) and 840 mm Hg (mean ± SD = 1,405 ± 342 mm Hg), respectively. In the aneurysm group, 25% of specimens did not rupture in their most dilated region. Percentage of increment in diameter was higher in normal aortas (mean ± SD = 0.2106 ± 0.144) than in aneurysms (mean ± SD = 0.093 ± 0.070). CONCLUSIONS: In the present experiment, unruptured infrarenal abdominal aortic aneurysms could support high pressures nearly as much as nonaneurysmal abdominal aortas. In some specimens, the most dilated part of the aneurysm was not the most vulnerable under pressure. Normal aortas presented higher elasticity than aneurysms.

Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental?

Abdominal aortic aneurysm (AAA) is a degenerative vascular pathology resulting in significant morbidity and mortality in older adults due to rupture and sudden death. Despite 150 000 new cases and nearly 15 000 deaths annually, the only approved treatment of AAA is surgical or endovascular intervention when the risk for aortic rupture is increased. The goal of the scientific community is to develop novel pharmaceutical treatment strategies to reduce the need for surgical intervention. Because most clinically relevant AAAs contain a complex structure of fibrin, inflammatory cells, platelets, and red blood cells in the aneurysmal sac known as an intraluminal thrombus (ILT), antithrombotic therapies have emerged as potential pharmaceutical agents for the treatment of AAA progression. However, the efficacy of these treatments has not been shown, and the effects of shrinking the ILT may be as detrimental as they are beneficial. This review discusses the prospect of anticoagulant and antiplatelet (termed collectively as antithrombotic) therapies in AAA. Herein, we discuss the role of the coagulation cascade and platelet activation in human and animal models of AAA, the composition of ILT in AAA, a possible role of the ILT in aneurysm stabilization, and the implications of antithrombotic drugs in AAA treatment.

The Role of Animal Models in Elucidating the Etiology and Pathology of Abdominal Aortic Aneurysms: Development of a Novel Rupture Mechanism Model.

Existing animal models do not replicate all aspects of abdominal aortic aneurysms (AAAs), including the rupture mechanisms. From histopathological analyses conducted in humans, it has been found that the vasa vasorum of the AAA wall is the starting point of circulatory failure and that bulging and dilatation of the abdominal aorta occurs through inflammation and tissue degeneration. We created a new animal model (the hypoperfusion-induced model) of AAAs. In this study, we describe the current animal models of AAAs and present the utility of our new model of AAAs.

A Modified Murine Abdominal Aortic Aneurysm Rupture Model Using Elastase Perfusion and Angiotensin II Infusion.

BACKGROUND: The perfused elastase AAA model and subcutaneous Angiotensin II infusion AAA model are widely used murine AAA models. We modified these two current models and developed a new murine model to study aneurysm formation and rupture. METHODS: The murine abdominal aorta was treated with elastase. Angiotensin II was infused at a dose of 1,000 ng/kg/min via an osmotic pump placed subcutaneously. A saline osmotic pump was used as the control. The aortas were harvested from the mice 4 weeks later, or earlier if mice died. The abdominal aorta was inspected using ultrasound and microscopy for aneurysm formation and/or signs of rupture. The aneurysm outcome was measured using aortic expansion and proinflammatory cytokine expression. It was also compared with the established conventional elastase perfusion and angiotensin II infusion abdominal aortic aneurysm models. RESULTS: By day 28 after surgery, all abdominal aortas of mice treated in the modified group had dilated and progressed to abdominal aortic aneurysms with 60% ruptured aneurysms, whereas none of the control aortas treated with saline became aneurysmal. In mice treated with elastase solution alone, 100% developed aneurysms and only one had a ruptured aneurysm. In mice given angiotensin II infusion alone, 37.5% developed aneurysms and none had a ruptured aneurysm. Histological examination of the modified murine abdominal aortic aneurysm rupture model was identical to that observed in the conventional elastase model. Quantitative polymerase chain reaction analysis revealed similarly increased levels of proinflammatory cytokines. CONCLUSIONS: We modified two current murine abdominal aortic aneurysm models to develop a murine abdominal aortic aneurysm model with consistent aneurysm formation and high rupture incidence, which can be used for studying abdominal aortic aneurysm rupture and treatment.

Successful emergency endovascular aortic repair for intratumoral hemorrhage in extensive retroperitoneal mass of testicular origin.

BACKGROUND: Metastatic germ cell cancer of the testis is characterized by favorable prognosis since effective treatment methods are available even in cases of extensive disease. Retroperitoneal masses frequently encroach major blood vessels requiring a vascular intervention usually performed in association with the post-chemotherapy retroperitoneal lymph node dissection (RPLND). Reported clinical case describes a successful pre-treatment endovascular surgery for abdominal aortic rupture allowing for full-dose systemic chemotherapy administration, and subsequent radical surgical intervention at primary tumor site as well as metastatic retroperitoneal lymph node dissection including the reconstruction of inferior caval vein. CASE PRESENTATION: Patient presented with left-sided testicular tumor and voluminous retroperitoneal mass with vascular involvement. Soon after the patient had been admitted for the first cycle of cisplatin-based chemotherapy, computed tomographic angiography (CTA) revealed a dorsal aortic wall rupture with active extravasation and irregular pseudoaneurysmatic dilatation of the aorta below the leak area. Retroperitoneal intratumoral hemorrhage associated with the bilateral iliac venous thrombosis required an endovascular repair procedure of infrarenal abdominal aorta. CONCLUSIONS: Following the successful endovascular aortic repair 3 cycles of BEP (bleomycin, etoposide, cisplatin) regimen were administered with subsequent delayed left radical orchiectomy and RPLND associated with vena cava inferior (VCI) resection. Reconstruction of VCI was originally not deemed necessary as collateral blood flow appeared sufficient, however, intraoperative complications resulted in the need for unilateral VCI reconstruction, using the interposed bypass between right common iliac vein and infrarenal segment of VCI. Histopathologic examination of the attained specimen detected no vital cancer structures. The patient remains disease-free 18 months after the RPLND.

Patients at Risk for Aortic Rupture Often Exposed to Fluoroquinolones during Hospitalization.

Several studies have indicated that fluoroquinolone use may be associated with an increased risk of aortic aneurysm or dissection (AAD). Because patients with AAD or Marfan syndrome are at increased risk for aortic rupture, we performed a retrospective cohort study to determine the prevalence of systemic fluoroquinolone exposure and predictors of fluoroquinolone use in these patients. Data were obtained from the advisory board billing and administrative database, which contained information on 22 million adult hospitalizations in the United States for the study period (2009 to 2015). International Classification of Diseases (9/10) and Current Procedural Terminology codes were used to identify patients who had AAD or Marfan syndrome or underwent aortic repair. We identified 136,789 admissions for AAD, which involved 99,818 unique patients, 20% of whom received fluoroquinolone during a hospital admission. Of the 7,045 patients with dissection, 18% were exposed to fluoroquinolone. Of the 27,876 AAD patients who underwent aortic repair, 19% received fluoroquinolone during a hospitalization before the repair. In the AAD patients, having a diagnosis of pneumonia or urinary tract infection increased the likelihood of receiving fluoroquinolone during admission by 46% and 40%, respectively (P < 0.001). Additionally, we identified 2,871 admissions for Marfan syndrome, which involved 1,872 patients, 14% of whom received fluoroquinolone during an admission. In these patients, pneumonia and urinary tract infections also increased the risk of fluoroquinolone exposure. If the deleterious effects of fluoroquinolone on aortic integrity are substantiated, reducing fluoroquinolone use in hospitalized patients with aortic disorders will become an urgent safety issue for antibiotic stewardship programs.

Mas receptor deficiency augments angiotensin II-induced atherosclerosis and aortic aneurysm ruptures in hypercholesterolemic male mice.

OBJECTIVE: Previous studies demonstrated that deficiency of angiotensin-converting enzyme 2 (ACE2) augmented angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysm (AAA) formation in hypercholesterolemic mice. Effects of ACE2 deficiency could arise from increased concentrations of its substrate, AngII, or decreased concentrations of its product, angiotensin-(1-7) [Ang-(1-7)]. Infusion of Ang-(1-7), a Mas receptor (MasR) ligand, to hypercholesterolemic male mice reduced AngII-induced atherosclerosis, suggesting a protective role of the Ang-(1-7)/MasR axis. However, it is unclear whether endogenous Ang-(1-7) acts at MasR to influence AngII-induced vascular diseases. The purpose of this study was to define the role of MasR deficiency in AngII-induced atherosclerosis and AAA formation and severity in hypercholesterolemic male mice. METHODS: MasR+/+ and MasR-/- male mice on a low-density lipoprotein receptor-deficient (Ldlr-/-) or apolipoprotein E-deficient (Apoe-/-) background were infused with AngII at either 600 or 1000 ng/kg/min by osmotic minipump for 28 days. Atherosclerosis was quantified at study end point as percentage lesion surface area of the aortic arch in Ldlr-/- mice. Abdominal aortic internal diameters were quantified by ultrasound, and maximal external AAA diameters were quantified at study end point. Blood pressure was quantified by radiotelemetry and a tail cuff-based technique. Serum cholesterol concentrations and vascular tissue characterization were examined at study end point. RESULTS: MasR deficiency did not influence body weight, systolic blood pressure at baseline and during AngII infusion, or serum cholesterol concentrations in either Apoe-/- or Ldlr-/- mice. MasR deficiency increased AngII-induced atherosclerosis in aortic arches of Ldlr-/- mice (P < .05), associated with increased oxidative stress and apoptosis in aortic root sections (P < .05). MasR deficiency also augmented internal and external AAA diameters and increased aortic ruptures of both Ldlr-/- and Apoe-/- mice (P < .05). These effects were associated with increased elastin breaks and T-lymphocyte and macrophage accumulation into abdominal aortas of AngII-infused MasR-deficient mice (P < .05). CONCLUSIONS: These results demonstrate that MasR deficiency augmented AngII-induced atherosclerosis and AAA rupture through mechanisms involving increased oxidative stress, inflammation, and apoptosis, suggesting that MasR activation may provide therapeutic efficacy against vascular diseases.

Aortic neck dilation is not associated with adverse outcomes after fenestrated endovascular aneurysm repair.

OBJECTIVE: Long-term outcomes after endovascular aneurysm repair (EVAR) are threatened by aortic neck dilation (AND), graft migration, and subsequent endoleak development. The aim of this study was to determine the rate of AND and the occurrence of endoleaks after fenestrated EVAR of juxtarenal aneurysms with physician-modified endovascular grafts (PMEGs). METHODS: The study included 77 patients presenting with asymptomatic and ruptured juxtarenal abdominal aortic aneurysms treated with PMEGs who received radiologic follow-up. Analysis of computed tomography images took place on a three-dimensional workstation (TeraRecon, San Mateo, Calif). Aortic neck diameter was measured before and after EVAR at the lowest patent renal artery outer wall to outer wall. Significant AND was defined as >3-mm increase between baseline and follow-up, and sac regression >5 mm was considered significant. The patient's 1-month initial postoperative computed tomography measurement was considered baseline. The rate of AND was measured by comparing the baseline measurement with measurements at 6 months, 12 months, and annually thereafter up to 4 years. RESULTS: In this cohort of patients, 75% were men with a mean age of 74 ± 7.9 years. Median preoperative aneurysm size was 62 (57-73) mm, and median follow-up was 12 (3.5-30) months. Mean endograft oversizing was 17% ± 12.5%, and mean seal zone length was 41 ± 11 mm. At 1-year follow-up, the median aortic neck increase was 1.7 (0-3) mm. Maximum aneurysm size decreased dramatically during the first postoperative year, with significant sac regression in 65% of the patients. Aortic neck diameter at 1 year did correlate positively with the percentage of device oversizing. No other correlations were found. During the 4-year follow-up, there were no cases of type IA endoleaks. CONCLUSIONS: AND does not influence outcome after endovascular repair of juxtarenal aneurysms using PMEGs. These midterm results support the applicability of PMEGs in juxtarenal aneurysm repair.