Investigation of Strategies to Block Downstream Effectors of AT1R-Mediated Signalling to Prevent Aneurysm Formation in Marfan Syndrome.

Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent aortic dissection. Angiotensin II receptor blockers (ARBs) prevent aneurysm formation in MFS mouse models. In patients, ARBs only slow down aortic dilation. Downstream signalling from the angiotensin II type 1 receptor (AT1R) is mediated by G proteins and ß-arrestin recruitment. AT1R also interacts with the monocyte chemoattractant protein-1 (MCP-1) receptor, resulting in inflammation. In this study, we explore the targeting of ß-arrestin signalling in MFS mice by administering TRV027. Furthermore, because high doses of the ARB losartan, which has been proven beneficial in MFS, cannot be achieved in humans, we investigate a potential additive effect by combining lower concentrations of losartan (25 mg/kg/day and 5 mg/kg/day) with barbadin, a ß-arrestin blocker, and DMX20, a C-C chemokine receptor type 2 (CCR2) blocker. A high dose of losartan (50 mg/kg/day) slowed down aneurysm progression compared to untreated MFS mice (1.73 ± 0.12 vs. 1.96 ± 0.08 mm, p = 0.0033). TRV027, the combination of barbadin with losartan (25 mg/kg/day), and DMX-200 (90 mg/kg/day) with a low dose of losartan (5 mg/kg/day) did not show a significant beneficial effect. Our results confirm that while losartan effectively halts aneurysm formation in Fbn1C1041G/+ MFS mice, neither TRV027 alone nor any of the other compounds combined with lower doses of losartan demonstrate a notable impact on aneurysm advancement. It appears that complete blockade of AT1R function, achieved by administrating a high dosage of losartan, may be necessary for inhibiting aneurysm progression in MFS.

Histone deacetylase 9-mediated phenotypic transformation of vascular smooth muscle cells is a potential target for treating aortic aneurysm/dissection.

Aortic aneurysm/dissection (AAD) is a serious cardiovascular condition characterized by rapid onset and high mortality rates. Currently, no effective drug treatment options are known for AAD. AAD pathogenesis is associated with the phenotypic transformation and abnormal proliferation of vascular smooth muscle cells (VSMCs). However, endogenous factors that contribute to AAD progression remain unclear. We aimed to investigate the role of histone deacetylase 9 (HDAC9) in AAD pathogenesis. HDAC9 expression was considerably increased in human thoracic aortic dissection specimens. Using RNA-sequencing (RNA-seq) and chromatin immunoprecipitation, we demonstrated that HDAC9 transcriptionally inhibited the expression of superoxide dismutase 2 and insulin-like growth factor-binding protein-3, which are critically involved in various signaling pathways. Furthermore, HDAC9 triggered the transformation of VSMCs from a systolic to synthetic phenotype, increasing their proliferation and migration abilities and suppressing their apoptosis. Consistent with these results, in vivo experiments revealed that TMP195, a pharmacological inhibitor of HDAC9, suppressed the formation of the ß-aminopropionitrile-induced AAD phenotype in mice. Our findings indicate that HDAC9 may be a novel endogenous risk factor that promotes the onset of AAD by mediating the phenotypic transformation of VSMCs. Therefore, HDAC9 may serve as a potential therapeutic target for drug-based AAD treatment. Furthermore, TMP195 holds potential as a therapeutic agent for AAD treatment.

Fluoroquinolone-associated adverse events of interest among hospitalized veterans affairs patients with community-acquired pneumonia who were treated with a fluoroquinolone: A focus on tendonitis, Clostridioides difficile infection, and aortic aneurysm.

STUDY OBJECTIVE: The objectives of this study were to (i) quantify the incidence of three concerning fluoroquinolone adverse events of interest (FQAEI, i.e., adverse tendon event (TE), clostridioides difficile infection (CDI), and aortic aneurysm/dissection (AAD)), (ii) identify the patient-level factors that predict these events, and (iii) develop clinical risk scores to estimate the predicted probabilities of each FQAEI based on patient-level covariates available on clinical presentation. DESIGN: Retrospective cohort study. SETTING: Upstate New York Veterans' Healthcare Administration from 2011 to 2016. PATIENTS: Hospitalized patients with community-acquired pneumonia receiving care in the Upstate New York Veterans' Healthcare Administration from 2011 to 2016. INTERVENTION: N/A. MEASUREMENTS: The outcomes of interest for this study were the occurrence of TE, CDI, and AAD. We also evaluated a composite of these three outcomes, FQAEI. MAIN RESULTS: The study population consisted of 1071 patients. The overall incidence of FQAEI, TE, AAD, and CDI was 6.5%, 1.8%, 4.5%, and 0.3%, respectively. For each outcome evaluated, the probability of the event of interest was predicted by the presence of certain comorbidities, previous healthcare exposure, choice of specific FQ antibiotic, or therapy duration. Concomitant steroids, pneumonia in preceding 180 days, and creatinine clearance <30 mL/min predicted FQAEI. CONCLUSIONS: Individual frequencies of three important FQAEIs were quantified, and risk scores were developed to estimate the probabilities of experiencing these events to help clinicians individualize treatment decisions for patients and reduce the potential risks of select FQAEIs.

Intravenous thrombolysis in a patient with acute ischemic stroke associated with a ruptured sinus Valsalva aneurysm: The first case report.

Sinus Valsalva aneurysms (SVA) are rare asymptomatic cardiac anomalies, which can rupture and cause heart failure, myocardial infarction and also, they can be a potential source for embolic strokes. We report the first case of a patient with acute ischemic stroke associated with a ruptured SVA, who was treated with intravenous thrombolysis (tPA) without further complications.

Administration of anti-inflammatory M2 macrophages suppresses progression of angiotensin II-induced aortic aneurysm in mice.

Aortic aneurysm (AA) is a vascular disorder characterized pathologically by inflammatory cell invasion and extracellular matrix (ECM) degradation. It is known that regulation of the balance between pro-inflammatory M1 macrophages (M1Ms) and anti-inflammatory M2 macrophages (M2Ms) plays a pivotal role in AA stabilization. We investigated the effects of M2M administration in an apolipoprotein E-deficient (apoE-/-) mouse model in which AA was induced by angiotensin II (ATII) infusion. Mice received intraperitoneal administration of 1 million M2Ms 4 weeks after ATII infusion. Compared with a control group that was administered saline, the M2M group exhibited reduced AA expansion; decreased expression levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1); and a lower M1M/M2M ratio. Moreover, the M2M group exhibited upregulation of anti-inflammatory factors, including IL-4 and IL-10. PKH26-labeled M2Ms accounted for 6.5% of cells in the aneurysmal site and co-expressed CD206. Taken together, intraperitoneal administration of M2Ms inhibited AA expansion by reducing the inflammatory reaction via regulating the M1M/M2M ratio. This study shows that M2M administration might be useful for the treatment of AA.

Infectious native aortic aneurysm with negative blood cultures: do not forget the pneumococcal urinary antigen test!

Infectious native aortic aneurysm (INAA) are rare but life-threatening infections. Early microbiological identification is crucial to initiate adequate therapy and decrease the peri-operative risk, but can be challenging when blood cultures remain negative. We describe two cases of pneumococcal INAA with negative blood cultures, diagnosed in the with the pneumococcal urinary antigen test.

Intravenous tocilizumab for Takayasu arteritis with aortic aneurysms, bilateral renal artery stenosis, and atypical aortic coarctation in a 2-year-old girl.

Takayasu arteritis (TAK) is classified as large vessel vasculitis, and continuous inflammation of the vessel results in aneurysm or stenosis, which leads to various serious complications. Recently, a TAKT [TAK treated with tocilizumab (TCZ)] study showed that subcutaneous TCZ, a humanised anti-interleukin-6 receptor monoclonal antibody, is an effective treatment in patients with TAK above 12 years of age; however, the effectiveness of TCZ for juvenile TAK under 12 years old remains unclear. Here, we described the case of a 2-year-old girl with TAK, which was successfully treated with intravenous TCZ. She was diagnosed with TAK type V (Numano's angiographic classification system) with aortic aneurysms, bilateral renal arteries stenosis, and atypical descending aortic coarctation based on contrast-enhanced computed tomography findings. Treatment was started with 2 mg/kg/day prednisolone (PSL) and methotrexate instead of methylprednisolone pulse due to renovascular hypertension. She was immediately afebrile and her C-reactive protein level decreased, although it was elevated 4 weeks after starting PSL. Intravenous TCZ of 8 mg/kg/2 weeks was added because the progression of aneurysms or stenosis might lead to a poor prognosis. PSL was steadily reduced under intravenous TCZ. Magnetic resonance imaging showed that aortic aneurysms, renal arteries stenosis, and aortic coarctation ameliorated 4 months after starting TCZ, with the amelioration maintained at 1 year after starting TCZ. Aneurysms and stenosis improved; therefore, TCZ may be effective for the treatment of inflammation of vessels, aneurysms, and stenosis. It is desirable to examine the effect of TCZ on TAK patients under 12 years of age.

Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication.

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H4B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers.

Fluoroquinolones: old drugs, putative new toxicities.

INTRODUCTION: Fluoroquinolone (FQ) antibiotics were approved in 1986 for treatment of urinary tract infections, sinusitis, and bronchitis. Numerous putative FQ-associated adverse events have been recently reported. AREAS COVERED: We review international regulatory agency experience with these FQ-associated toxicities. A 2015 FDA Advisory Committee meeting led regulatory agencies in Canada, Australia, the European Union, New Zealand, and Japan between 2017 and 2021 to evaluate FQ-associated long-term disability and aortic aneurysm/dissections. Regulatory agency guidance in the United States in 2016 warn that FQs should not be used as first-line therapies for urinary tract infections, sinusitis, and bronchitis if other antibiotics are available because of potential long-term and disabling toxicity. Regulatory agencies in European Union countries warn that FQs should not be used to treat mild infections. Product labels in Australia, New Zealand, Japan, and Canada do not have warnings related to FQ-associated disability. Revised product labels and public health advisories in the United States, the European Union, and Japan warn against FQ administration to persons at aortic aneurysm/dissection risks, while product labels and regulatory agency notifications from Canada, Australia, and New Zealand do not include these warnings. EXPERT OPINION: Harmonization of warnings related to FQ-associated disability in particular should be considered.

Allopurinol blocks aortic aneurysm in a mouse model of Marfan syndrome via reducing aortic oxidative stress.

BACKGROUND: Increasing evidence indicates that redox stress participates in MFS aortopathy, though its mechanistic contribution is little known. We reported elevated reactive oxygen species (ROS) formation and NADPH oxidase NOX4 upregulation in MFS patients and mouse aortae. Here we address the contribution of xanthine oxidoreductase (XOR), which catabolizes purines into uric acid and ROS in MFS aortopathy. METHODS AND RESULTS: In aortic samples from MFS patients, XOR protein expression, revealed by immunohistochemistry, increased in both the tunicae intima and media of the dilated zone. In MFS mice (Fbn1C1041G/+), aortic XOR mRNA transcripts and enzymatic activity of the oxidase form (XO) were augmented in the aorta of 3-month-old mice but not in older animals. The administration of the XOR inhibitor allopurinol (ALO) halted the progression of aortic root aneurysm in MFS mice. ALO administrated before the onset of the aneurysm prevented its subsequent development. ALO also inhibited MFS-associated endothelial dysfunction as well as elastic fiber fragmentation, nuclear translocation of pNRF2 and increased 3'-nitrotyrosine levels, and collagen maturation remodeling, all occurring in the tunica media. ALO reduced the MFS-associated large aortic production of H2O2, and NOX4 and MMP2 transcriptional overexpression. CONCLUSIONS: Allopurinol interferes in aortic aneurysm progression acting as a potent antioxidant. This study strengthens the concept that redox stress is an important determinant of aortic aneurysm formation and progression in MFS and warrants the evaluation of ALO therapy in MFS patients.

Short-term rapamycin treatment increases life span and attenuates aortic aneurysm in a murine model of Marfan-Syndrome.

BACKGROUND: Marfan syndrome (MFS) is a genetic disorder leading to medial aortic degeneration and life-limiting dissections. To date, there is no causal prevention or therapy. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, regulating cell growth and metabolism. The mgR/mgR mice represent an accepted MFS model for studying aortic pathologies to understand the underlying molecular pathomechanisms. This study investigated whether rapamycin inhibits the development of thoracic aortic aneurysms and dissections in mgR/mgR mice. METHODS: Isolated primary aortic smooth muscle cells (mAoSMCs) from mgR/mgR mice were used for in vitro studies. Two mg kg/BW rapamycin was injected intraperitoneally daily for two weeks, beginning at 7-8 weeks of age. Mice were sacrificed 30 days post-treatment. Histopathological and immunofluorescence analyses were performed using adequate tissue specimens and techniques. Animal survival was evaluated accompanied by periodic echocardiographic examinations of the aorta. RESULTS: The protein level of the phosphorylated ribosomal protein S6 (p-RPS6), a downstream target of mTOR, was significantly increased in the aortic tissue of mgR/mgR mice. In mAoSMCs isolated from these animals, expression of mTOR, p-RPS6, tumour necrosis factor α, matrix metalloproteinase-2 and -9 was significantly suppressed by rapamycin, demonstrating its anti-inflammatory capacity. Short-term rapamycin treatment of Marfan mice was associated with delayed aneurysm formation, medial aortic elastolysis and improved survival. CONCLUSIONS: Short-term rapamycin-mediated mTOR inhibition significantly reduces aortic aneurysm formation and thus increases survival in mgR/mgR mice. Our results may offer the first causal treatment option to prevent aortic complications in MFS patients.

Targeting autophagy in aortic aneurysm and dissection.

Autophagy is a well-conserved biological process that maintains homeostasis. Accumulating evidence has revealed that autophagy plays an important role in various cardiovascular diseases, such as aneurysm, aortic dissection, atherosclerosis, and myocardial ischemia-reperfusion injury. Here, we summarize the current experimental evidence on the function of autophagy and autophagy proteins in aortic aneurysm and dissection (AAD). AAD is a very serious aortic disease, and there are currently no effective drug treatment options. Studies have shown that autophagy is activated during AAD. However, the role of autophagy in AAD is still controversial. For example, knocking out autophagy related 5 (ATG5) or ATG7 to inhibit autophagy and excessive autophagy activation can promote the occurrence of AAD. Recently, multiple studies have demonstrated that rapamycin and metformin, which are autophagy activators, can delay the progression of AAD. Thus, targeting autophagy has the potential to become a new therapeutic strategy for AAD. In addition, we discuss the recent research progress on AAD from the perspective of single-cell RNA sequencing. Moreover, we offer our perspective on current challenges and barriers in this research field.

Rosmarinic Acid Suppresses Abdominal Aortic Aneurysm Progression in Apolipoprotein E-deficient Mice.

An abdominal aortic aneurysm is a life-threatening cardiovascular disorder caused by dissection and rupture. No effective medicine is currently available for the > 90% of patients whose aneurysms are below the surgical threshold. The present study investigated the impact of rosmarinic acid, salvianolic acid C, or salvianolic acid B on experimental abdominal aortic aneurysms. Abdominal aortic aneurysms were induced in apolipoprotein E-deficient mice via infusion of angiotensin II for 4 wks. Rosmarinic acid, salvianolic acid C, salvianolic acid B, or doxycycline as a positive control was provided daily through intraperitoneal injection. Administration of rosmarinic acid was found to decrease the thickness of the aortic wall, as determined by histopathological assay. Rosmarinic acid also exhibited protection against elastin fragmentation in aortic media and down-regulated cell apoptosis and proliferation in the aortic adventitia. Infiltration of macrophages, T lymphocytes, and neutrophils in aortic aneurysms was found, especially at the aortic adventitia. Rosmarinic acid, salvianolic acid C, or salvianolic acid B inhibited the infiltration on macrophages specifically, but these compounds did not influence T lymphocytes and neutrophils. Expression of matrix metalloproteinase 9 and macrophage migration inhibitory factor significantly increased in aortic aneurysms. Rosmarinic acid and salvianolic acid C decreased the expression of matrix metalloproteinase-9 in media, and rosmarinic acid also tended to reduce migration inhibitory factor expression. Further then, partial least squares-discriminate analysis was used to classify metabolic changes among different treatments. Rosmarinic acid affected most of the metabolites in the biosynthesis of the citrate cycle, fatty acid pathway significantly. Our present study on mice demonstrated that rosmarinic acid inhibited multiple pathological processes, which were the key features important in abdominal aortic aneurysm formation. Further study on rosmarinic acid, the novel candidate for aneurysmal therapy, should be undertaken to determine its potential for clinical use.

Aneurisma infeccioso primário da aorta: série de casos e revisão da literatura / Primary infectious aortic aneurysm: a case series and review of the literature

Resumo Aneurismas infecciosos, anteriormente chamados de aneurismas micóticos, são raros; acometem com maior frequência a aorta de pacientes jovens e apresentam maior tendência à rotura do que aneurismas de outras etiologias. O formato sacular é o mais característico, e os agentes etiológicos mais comuns são Staphylococcus sp e Salmonella sp. A literatura fornece informações limitadas e imprecisas sobre a correta nomenclatura, diagnóstico e tratamento da doença. Os autores reuniram três casos cujos procedimentos diagnósticos e terapêuticos foram documentados. Além de relatar essa série de casos, realiza-se uma revisão sobre o tema, a fim de estabelecer estratégias diagnósticas e terapêuticas pertinentes.

Abstract Infectious aneurysms, formerly known as mycotic aneurysms, are rare, most often involve the aorta in young patients, and have a greater tendency to rupture than aneurysms of other etiologies. The most characteristic shape is saccular and the most common etiologic agents are Staphylococcus sp. and Salmonella sp. There is scant and imprecise information in the literature about correct nomenclature, diagnosis, and treatment. The authors present three cases in which diagnostic and therapeutic procedures were documented. In addition to reporting this case series, the authors also present a review of the subject, outlining pertinent diagnostic and therapeutic strategies.

Myocardial dissection complicating left sinus of Valsalva aneurysm in silent takayasu arteritis.

BACKGROUND: Myocardial dissection (MD) in a left sinus of Valsalva aneurysm (LSVA) is a rare condition that may lead to a fatal complication. Determining the MD etiology is challenging because of various possibilities ranging from congenital to acquired diseases. Here, we discuss an approach for determining the etiology of MD complicating LSVA in Takayasu arteritis (TA) and its treatment. CASE PRESENTATION: A 41-year-old man presented with dyspnea on heavy activities and a history of consciousness loss at the age of 24 years. He was diagnosed with dilated cardiomyopathy and MD complicating LSVA in TA based on combined clinical and pathognomonic diagnostic criteria of TA evaluated using vascular Doppler and computed tomography angiography of the aorta. The patient refused to undergo surgery and received an optimal dose of chronic heart failure therapy, a high-dose steroid, and azathioprine. The patient experienced some improvements in clinical condition, functional outcome, and inflammatory markers at 1-year follow-up. CONCLUSIONS: Clinical criteria and various imaging modalities may be used to determine the etiology of MD complicating LSVA in silent TA. As an alternative to surgery, the optimal medical treatment might result in a satisfactory outcome.

Tratamiento del aneurisma de aorta infrarrenal roto: cirugía abierta versus tratamiento endovascular / Treatment of ruptured abdominal aortic aneurysm: open surgical repair versus endovascular repair

Introducción: el aneurisma de aorta abdominal roto (AAAr) es una patología que asocia una elevada morbimortalidad. El objetivo es analizar los resultados del tratamiento del AAAr en nuestro centro, comparando cirugía abierta (CA) y endovascular (EVAR). Material y métodos:estudio de cohortes retrospectivo de pacientes intervenidos por AAAr con cuello infrarrenal entre enero de 2006 y diciembre de 2017, dividido en grupo CA y grupo EVAR. Análisis comparativo de comorbilidad, características anatómicas, técnica y resultados.Resultados:54 pacientes fueron incluidos, 26 (48,1 %) en el grupo CA y 28 (51,9 %) en el EVAR. Sin diferencias en cuanto a edad (70,7 ± 7,8 años vs. 72,5 ± 9,5, p = 0,45) ni comorbilidades, salvo la dislipemia (26,9 % vs. 67,9 % p = 0,003). Los aneurismas eran mayores en el grupo CA (88,1 ± 17,9 mm vs. 72,4 ± 16 mm, p = 0,02), con un mayor porcentaje de aneurisma iliaco asociado (34,6 % vs. 17,8 %, p = 0,07). Un 65,4 % del grupo CA presentó inestabilidad hemodinámica preoperatoria, frente al 60,7 % del EVAR (p = 0,72). Se empleó anestesia local en el 50 % del grupo EVAR. Las necesidades transfusionales intraoperatorias medianas para el grupo CA y EVAR fueron 11 ± 6 y 4 ± 3 concentrados de hematíes respectivamente (p = 0,001). La mortalidad hospitalaria fue mayor en el grupo CA (46,2 % vs. 28,6 %) (p = 0,18). En dicho grupo hubo 4 éxitus intraoperatorios. Un 54,5 % de pacientes del grupo CA y un 64,3 % del EVAR (p = 0,48) presentaron complicaciones mayores, siendo las más frecuentes la intubación prolongada y el fracaso renal que requirió terapia de reemplazo renal. La tasa de reintervención hospitalaria fue 18,2 % en el grupo CA y 25 % en el EVAR (p = 0,56), siendo en este grupo todas las reintervenciones en el subgrupo de endoprótesis aortouniiliaca. La supervivencia a 2 años fue del 51,7 % en el grupo CA y del 65,2 % en el EVAR (p = 0,28).(AU)

Background: the ruptured abdominal aortic aneurysm (rAAA) is associated with high morbimortality. The purpose of this study was to compare results of open surgical repair (OSR) and EVAR in our institution in the management of rAAA. Material and methods:retrospective observational cohort study was conducted on rAAA patients with infrarenal neck between January 2006 and December 2017. Sample was divided according to intervention: OSR vs. EVAR. Comorbidities, anatomical features, intervention and results were analyzed by repair method. Results:fifty-four patients were included, 26 (48,1 %) using OSR and 28 (51,9 %) using EVAR. Age (70,7 ± 7,8 years vs. 72,5 ± 9,5; p = 0,45) and comorbidities showed no statistical significance, except for dyslipidemia (26,9 % vs. 67,9 %; p = 0,003). Aneurysms were larger in OSR group (88,1 ± 17,9 mm vs. 72,4 ± 16 mm; p = 0,02), with a higher rate of associated iliac aneurysm (34,6 % vs. 17,8 %, p = 0,07). 65,4 % of patients in OSR group showed preoperative hemodynamic instability, compared to 60,7 % in EVAR group (p = 0,72). 50 % of EVAR procedures were performed under local anesthesia. Median intraoperative transfusion requirements for OSR group and EVAR group were, respectively, 11 ± 6 and 4 ± 3 red blood cell concentrates (p = 0.001). Hospital mortality was higher in OSR group (46.2 % vs. 28.6 %) (p = 0.18). There were four intraoperative deaths in this group. 54.5 % of OSR patients and 64.3 % of EVAR presented major complications. The most common ones were longtime intubation and acute renal failure requiring renal replacement therapy. Reintervention rate was 18.2 % in CA group and 25 % in EVAR group (p = 0.56), all reinterventions in EVAR group performed in rAAAs repaired by an aortouniiliac device. Two-year survival rate was 51.7 % in CA group and 65.2 % in EVAR group (p = 0.28).(AU)

Fluoroquinolone Prescribing for Diabetic Foot Infections following an FDA Drug Safety Communication for Aortic Aneurysm Risk.

In 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding fluoroquinolone-associated aortic aneurysm. This quasi-experimental study assessed antibiotic prescribing for 198 patients hospitalized with diabetic foot infection. Following the warning, median inpatient fluoroquinolone days of therapy (DOT) decreased from 3 to 0 days (P < 0.001), corresponding to increased beta-lactam DOT and outpatient parenteral antimicrobial therapy enrollment. FDA communications may influence antibiotic selection and transitions of care, representing opportunities for antimicrobial stewardship.

Current Pharmacological Management of Aortic Aneurysm.

ABSTRACT: Aortic aneurysm (AA) remains one of the primary causes of death worldwide. Of the major treatments, prophylactic operative repair is used for AA to avoid potential aortic dissection or rupture. To halt the development of AA and alleviate its progression into aortic dissection, pharmacological treatment has been investigated for years. Currently, ß-adrenergic blocking agents, losartan, irbesartan, angiotensin-converting-enzyme inhibitors, statins, antiplatelet agents, doxycycline, and metformin have been investigated as potential candidates for preventing AA progression. However, the paradox between preclinical successes and clinical failures still exists, with no medical therapy currently available for ideally negating the disease progression. This review describes the current drugs used for pharmacological management of AA and their individual potential mechanisms. Preclinical models for drug screening and evaluation are also discussed to gain a better understanding of the underlying pathophysiology and ultimately find new therapeutic targets for AA.

PET/CT in therapy control of infective native aortic aneurysms.

Infective native aortic aneurysms (INAA) are aneurysms arising from infection of the aortic wall. Treatment is demanding with 5-year survival rates between 53 and 55%. The aim of our study was to evaluate the usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the long-term monitoring of patients with proven INAA. Fifty-three PET/CT were performed in 15 patients with INAA in this single-center retrospective cohort study and retrospective analysis of prospectively collected Vascular Graft Cohort Study (VASGRA) data. Median metabolic activity (as measured by maximum standardized uptake value, SUVmax) of the aneurysms at the initial PET/CT was high (6.8 (IQR 5.7-21.8)), and lower at the last PET/CT prior to the end of antimicrobial therapy (3.9 (IQR 2.7-6.8); n = 11) as well as in the first PET/CT after the end of the treatment (3.9 (IQR 3.0-4.4);n = 6). Compared to the course of C-reactive protein alone, PET/CT provided different (> 20% difference in trend) or altering (opposed trend) information on the course of disease in at least 14 comparisons (56%) in 11 patients (73%). The one-year and five-year freedom from all-cause lethality was 92% (95% confidence interval 57%-99%). As compared to the course of C-reactive protein, PET/CT provides different and occasionally altering information in therapy control of INAA.