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Cardiovascular involvement in Behçet's disease (BD) is considerably related to morbidity and mortality. However, the cardiovascular manifestation is sometimes difficult to distinguish from those of other causes. The suspicion of BD and proper treatment is pivotal in the management of BD. Histology demonstrates perivasculitis. Neutrophil seems to play an important role in the inflammation of BD. It is thought that inflammation causes venous thrombosis and arterial aneurysm. Characteristically, BD involves both arteries and veins of variable size in any region. Venous thrombosis needs immunosuppression, and inferior vena cava thrombosis and Budd-Chiari syndrome require intensive immunosuppressive therapy. Arterial involvement causes aneurysm which usually is treated by surgical or endovascular intervention with immunosuppression. Pulmonary artery aneurysm and cardiac involvement require multimodal managements., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Tatton-Brown-Rahman syndrome (TBRS) is a rare disorder, caused by DNMT3A heterozygous pathogenic variants, and first described in 2014. TBRS is characterised by overgrowth, intellectual disability, facial dysmorphism, hypotonia and musculoskeletal features, as well as neurological and psychiatric features. Cardiac manifestations have also been reported, mainly congenital malformations such as atrial septal defect, ventricular septal defect and cardiac valvular disease. Aortic dilatation has rarely been described., Methods: Here we have undertaken a detailed clinical and molecular description of eight previously unreported individuals, who had TBRS and arterial dilatation and/or dissection, mainly thoracic aortic aneurysm (TAA). We have also reviewed the seven previously published cases of TAA in individuals with TBRS to try to better delineate the vascular phenotype and to determine specific follow-up for this condition., Results: We include eight new patients with TBRS who presented with arterial aneurysms mainly involving aorta. Three of these patients presented with dissection that required critical surgery., Conclusions: Arterial aneurysms and dissections are a potentially lethal, age-dependent manifestation. The prevalence of aortic disease in individuals with TBRS is far in excess of that expected in the general population. This cohort, together with individuals previously published, illustrates the importance to consider dilatation/dissection, mainly in aorta but also in other arteries. Arterial vascular weakness may therefore also be a cardinal feature of TBRS and vascular surveillance is recommended., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increased arterial tortuosity has been associated with various cardiovascular complications. However, the extent and role of arterial tortuosity in non-atherosclerotic vascular diseases remain to be fully elucidated. This study aimed to assess arterial tortuosity index (ATI) in patients with non-atherosclerotic vascular diseases and the associated factors., Methods: This is a retrospective analysis of patients with non-atherosclerotic vascular diseases referred to the Malformation and Rare Vascular Disease Center at the University Hospital in Lausanne (Switzerland). Computed tomography angiography (CTA) images performed between October 2010 and April 2022 were retrieved and the aortic tortuosity index (ATI) was calculated. Patients were classified based on diagnosis into the following groups: arterial dissection & aneurysm, arteritis & autoimmune disease, hereditary connective tissue diseases, and fibromuscular dysplasia (FMD). Univariate and multivariate logistic regression analysis was used to determine potentially relevant predictors of aortic tortuosity., Results: The mean age upon computed tomography angiography (CTA) was 46.8 (standard deviation [SD] 14.6) years and 59.1% of the patients were female. Mean ATI was higher in patients over 60 years old (1.27), in those with arterial aneurysms (mean: 1.11), and in those diagnosed with hypertension (mean: 1.13). When only patients over 60 years old were considered, those diagnosed with connective tissue diseases had the highest ATI. At multivariate regression analysis, increasing age (p < 0.05), presence of arterial aneurysms (p < 0.05), and hypertension (p < 0.05) were independently associated with ATI., Conclusions: The ATI may be a promising tool in diagnostic evaluation, cardiovascular risk stratification, medical or surgical management, and prognostic assessment in several non-atherosclerotic vascular conditions. Further studies with longitudinal design and larger cohorts are needed to validate the role of ATI in the full spectrum of vascular diseases., (© 2024. The Author(s).)

To investigate the endothelialization of covered and bare stents deployed in the canine carotid arteries and subclavian arteries for treating experimental aneurysms and arteriovenous fistulas, twenty aneurysms were created in 10 dogs, and 20 fistulas in another 10 dogs. The Willis balloon-expandable covered stent and a self-expandable covered stent were used to treat these lesions, and a self-expandable bare stent was deployed in the subclavian artery for comparison. Followed up for up to 12 months, the gross observation, pathological staining, and scanning electronic microscopic data were analyzed. Two weeks after creation of animal model, thirty self-expandable covered stents and ten balloon-expandable covered stents were deployed. Fifteen bare stents were deployed within the left subclavian arteries. Twenty days after stenting, the aneurysm significantly shrank. At 6 months, the thrombi within the aneurysm cavity were organized. Three to 12 months later, most covered and bare stents were covered by a thin transparent or white layer of endothelial intima. Layers of intima or pseudomembrane were formed on the stent 20-40 days after stent deployment. Over three months, the pseudomembrane became organized, thinner, and merged into the vascular wall. Under scanning electronic microscopy, the surface of covered and bare stents had only deposition of collagen fibers and rare endothelial cells 20-40 days after stenting. From three to ten months, the endothelial cells on the internal surface of stent became mature, with spindle, stripe-like or quasi round morphology along the blood flow direction. Over time, the endothelial cells became mature. In conclusion, three months after deployment in canines' arteries, the self-expandable bare and covered stents have mostly been covered by endothelial cells which become maturer over time, whereas the balloon-expandable covered stents do not have complete coverage of endothelial cells at three months, especially for protruding stent struts and areas. Over time, the endothelialization will become mature., (© 2024. The Author(s).)

True aneurysm of the radial artery is very rare. Aneurysmal expansion of arteries due to degenerative changes, possibly infections, primarily affects the abdominal and thoracic aorta, intra and extracranial sections of cerebral arteries, popliteal artery, and visceral arteries. Published literature does not address the aneurysm on the distal sections of the arteries of upper or lower limb. Unlike the classic symptoms of aneurysmally altered arteries such as rupture, thrombosis and embolization, we encounter more often vascular compression syndrome in distal peripheral aneurysms. We demonstrate the case management of a patient with over 20 years increasing wrist resistance. A fusiform aneurysm of the distal section of the radial artery was identified by sonography. Under general anesthesia, we performed aneurysm resection and artery reconstruction using an interpositum from the ipsilateral cephalic vein. The histological examination of the resected tissue confirmed the presence of all three layers of the vascular wall, confirming the true aneurysm of the radial artery. No complications developed in the patient in the postoperative period and all problems related to the aneurysm subsided (Fig. 4, Ref. 23). Keywords: aneurysm, arteria radialis, surgical reconstruction.

Background: Smooth muscle cell (SMC) phenotypic reprogramming toward a mixed synthetic-proteolytic state is a central feature of aortic root aneurysm in Marfan syndrome (MFS). Previous work identified Klf4 as a potential mediator of SMC plasticity in MFS., Methods: MFS ( Fbn1 C1041G/+ ) mouse strains with an inducible vascular SMC fluorescent reporter ( MFS SMC ) with or without SMC-specific deletion of Klf4 exons 2 to 3 ( MFS SMC-Klf4Δ ) were generated. Simultaneous SMC tracing and Klf4 loss-of-function ( Klf4Δ mice) was induced at 6 weeks of age. Aneurysm growth was assessed via serial echocardiography (4-24 weeks). Twenty-four-week-old mice were assessed via histology, RNA in situ hybridization, and aortic single-cell RNA sequencing., Results: MFS mice demonstrated progressive aortic root dilatation compared with control (WT SMC ) mice regardless of Klf4 genotype ( P <0.001), but there was no difference in aneurysm growth in MFS SMC-Klf4Δ versus MFS SMC ( P =0.884). Efficient SMC Klf4 deletion was confirmed via lineage-stratified genotyping, RNA in situ hybridization, and immunohistochemistry. Single-cell RNA sequencing of traced SMCs revealed a highly similar pattern of phenotype modulation marked by loss of contractile markers (eg, Myh11, Cnn1 ) and heightened expression of matrix genes (eg, Col1a1, Fn1 ) between Klf4 genotypes. Pseudotemporal quantitation of SMC dedifferentiation confirmed that Klf4 deletion did not alter the global extent of phenotype modulation, but reduced expression of 23 genes during this phenotype transition in MFS SMC-Klf4Δ mice, including multiple chondrogenic genes expressed by only the most severely dedifferentiated SMCs (eg, Cytl1, Tnfrsf11b )., Conclusions: Klf4 is not required to initiate SMC phenotype modulation in MFS aneurysm but may exert regulatory control over chondrogenic genes expressed in highly dedifferentiated SMCs., Competing Interests: Disclosures None.

Hughes-Stovin syndrome is a rare disease characterized by thrombophlebitis and multiple pulmonary and/or bronchial aneurysms. The etiology and pathogenesis of HSS are incompletely known. The current consensus is that vasculitis underlies the pathogenic process, and pulmonary thrombosis follows arterial wall inflammation. As such, Hughes-Stovin syndrome may belong to the vascular cluster with lung involvement of Behçet syndrome, although oral aphtae, arthritis, and uveitis are rarely found. Behçet syndrome is a multifactorial polygenic disease with genetic, epigenetic, environmental, and mostly immunological contributors. The different Behçet syndrome phenotypes are presumably based upon different genetic determinants involving more than one pathogenic pathway. Hughes-Stovin syndrome may have common pathways with fibromuscular dysplasias and other diseases evolving with vascular aneurysms. We describe a Hughes-Stovin syndrome case fulfilling the Behçet syndrome criteria. A MYLK variant of unknown significance was detected, along with other heterozygous mutations in genes that may impact angiogenesis pathways. We discuss the possible involvement of these genetic findings, as well as other potential common determinants of Behçet/Hughes-Stovin syndrome and aneurysms in vascular Behçet syndrome. Recent advances in diagnostic techniques, including genetic testing, could help diagnose a specific Behçet syndrome subtype and other associated conditions to personalize the disease management.

The size of the aorta varies in the healthy population and is influenced by a series of mostly common and lower-impact genomic variants. Rare, high-impact variants driving Mendelian diseases of stenosis and aneurysm extend the limits of aortic size out of the typical range. Pathology at both ends of the spectrum is governed by overlapping pathways and processes, such as those affecting structure, integrity, and function of the aorta. As such, aortopathies across the full spectrum from stenosis to aneurysm are likely modified by a similar constellation of common and rarer genetic variants in a directional, weighted, and context-dependent manner. Here, we discuss the role of modifiers in aortic disease by presenting an example of two opposing rare diseases and highlight the need to consider the influence of background genome variation when considering disease outcomes., (Published by Elsevier Ltd.)

Objectives: Currently, cardiovascular risk associated with COVID-19 has been brought to people's attention, but the mechanism is not clear. The aim of this study is to elucidate the mechanisms based on multiple omics data., Methodology: Weighted gene co-expression network analysis (WGCNA) was used to identify key pathways. Combination analysis with aneurysm and atherosclerosis related pathways, hypoxia induced factor-1 (HIF-1) signaling were identified as key pathways of the increased cardiovascular risk associated with COVID-19. ScMLnet algorithm based on scRNA-seq was used to explore the regulation of HIF-1 pathway by intercellular communication. Proteomic analysis was used to detect the regulatory mechanisms between IL18 and HIF-1 signaling pathway. Pseudo time locus analysis was used to study the regulation of HIF1 signaling pathway in macrophages and vascular smooth muscle cells (VSMC) phenotypic transformation. The Virtual Inference of protein-activity by Enriched Regulon (VIPER) analysis was used to study the activity of regulatory proteins. Epigenetic analysis based on methylation revealed epigenetic changes in PBMC after SARS-CoV-2 infection. Potential therapeutic compounds were explored by using Cmap algorithm., Results: HIF-1 signaling pathway is a common key pathway for aneurysms, atherosclerosis and SARS-CoV-2 infection. Intercellular communication analysis showed that macrophage-derived interleukin-18 (IL-18) activates the HIF-1 signaling pathway through IL18R1. Proteomic analysis showed that IL18/IL18R1 promote NF-κB entry into the nucleus, and activated the HIF-1 signaling pathway. Macrophage-derived IL18 promoted the M1 polarization of macrophages and the syntactic phenotype transformation of VSMCs. MAP2K1 mediates the functional regulation of HIF-1 signaling pathway in various cell types. Epigenetic changes in PBMC after COVID-19 infection are characterized by activation of the type I interferon pathway. MEK inhibitors are the promising compounds for the treatment of HIF-1 overactivation., Conclusions: The IL18/IL18R1/HIF1A axis is expected to be an therapeutic target for cardiovascular protection after SARS-CoV-2 infection. MEK inhibitors may be an choice for cardiovascular protection after SARS-COV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Li, Wang, Sun, Wei, Zhang, Wu and Bai.)

Aneurysms of the ascending aorta, unrelated to xenobiotic administration, are described in 5 rats and 2 mice in nonclinical safety studies conducted at Charles River Laboratories (CRL) sites over the past 10 years. The most prominent microscopic finding was focal dilation with disruption of the wall of the ascending aorta with chronic adventitial inflammation or fibroplasia. The pathogenesis of this finding is unknown. There were no associated macroscopic findings, clinical abnormalities, or vascular lesions elsewhere. The results of a search of historical control data from toxicology studies of 1 day to 72 weeks' duration performed at CRL for aortic findings from 5900 mice and 23,662 rats are also reported. Aortic lesions are uncommon in mice and rats used in nonclinical safety studies, but toxicologic pathologists should be aware that aneurysms of the ascending aorta with fibroplasia and inflammation in the aortic wall and adventitia may occur spontaneously or iatrogenically, as they have the potential to impact interpretation in toxicology studies.

Rupture risk stratification is critical for incidentally detected intracranial aneurysms. Here we developed and validated an institutional nomogram to solve this issue. We reviewed the imaging and clinical databases for aneurysms from January 2015 to September 2018. Aneurysms were reconstructed and morphological features were extracted by the Pyradiomics in python. Multiple logistic regression was performed to develop the nomogram. The consistency of the nomogram predicted rupture risks and PHASES scores was assessed. The performance of the nomogram was evaluated by the discrimination, calibration, and decision curve analysis (DCA). 719 aneurysms were enrolled in this study. For each aneurysm, twelve morphological and nine clinical features were obtained. After logistic regression, seven features were enrolled in the nomogram, which were SurfaceVolumeRatio, Flatness, Age, Hyperlipemia, Smoker, Multiple aneurysms, and Location of the aneurysm. The nomogram had a positive and close correlation with PHASES score in predicting aneurysm rupture risks. AUCs of the nomogram in discriminating aneurysm rupture status was 0.837 in a separate testing set. The calibration curves fitted well and DCA demonstrated positive net benefits of the nomogram in guiding clinical decisions. In conclusion, Pyradiomics derived morphological features based institutional nomogram was useful for aneurysm rupture risk stratification.

Coronary artery (CA) stenosis is a detrimental and often life-threatening sequela in Kawasaki disease (KD) patients with coronary artery aneurysm (CAA). Therapeutic strategies for these patients have not yet been established. All-trans-retinoic acid (atRA) is a modulator of smooth muscle cell functions. The purpose of this study was to investigate the effect of atRA on CA stenosis in a mouse model of KD. Lactobacillus casei cell wall extract (LCWE) was intraperitoneally injected into 5-week-old male C57BL/6 J mice to induce CA stenosis. Two weeks later, the mice were orally administered atRA (30 mg/kg) 5 days per week for 14 weeks (LCWE + atRA group, n = 7). Mice in the untreated group (LCWE group, n = 6) received corn oil alone. Control mice were injected with phosphate-buffered saline (PBS, n = 5). Treatment with atRA significantly suppressed CA inflammation (19.3 ± 2.8 vs 4.4 ± 2.8, p < 0.0001) and reduced the incidence of CA stenosis (100% vs 18.5%, p < 0.05). In addition, atRA suppressed the migration of human coronary artery smooth muscle cells (HCASMCs) induced by platelet-derived growth factor subunit B homodimer (PDGF-BB). In conclusion, atRA dramatically alleviated CA stenosis by suppressing SMC migration. Therefore, it is expected to have clinical applications preventing CA stenosis in KD patients with CAA.

We report a rare case of solitary peripheral pulmonary artery aneurysm in a patient who was evaluated for haemoptysis. Incidentally, his total antibodies were positive for Coronavirus 2019 infection. Patient underwent right lower lobectomy uneventfully. Peripheral pulmonary artery aneurysms arising from segmental or intrapulmonary branches are extremely rare. Untreated, the majority end fatally due to sudden rupture and exsanguination. The purpose of this article is to report our rare case and review the pertinent literature., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Behçet's disease is a rare disease characterised by recurrent oral ulcers, with systemic manifestations including genital ulcers, ocular disease, skin lesions, gastrointestinal disease, neurologic disease, vascular disease and arthritis. Most clinical manifestations of Behçet's disease are believed to be due to vasculitis. The heterogeneous clinical spectrum is influenced by sex, ethnicity and country of residence. Vascular manifestation in the form of isolated large brachial artery aneurysm is rare in children. Treatment involves aneurysmorrhaphy to avoid rupture or ischaemic sequelae in addition to lifelong medical management to control vasculitis.

Objective: Popliteal artery aneurysm (PAA) is the second most common arterial aneurysm. Vascunet is an international collaboration of vascular registries. The aim was to study treatment and outcomes., Methods: This was a retrospective analysis of prospectively registered population based data. Fourteen countries contributed data (Australia, Denmark, Finland, France, Hungary, Iceland, Italy, Malta, New Zealand, Norway, Portugal, Serbia, Sweden, and Switzerland)., Results: During 2012-2018, data from 10 764 PAA repairs were included. Mean values with between countries ranges in parenthesis are given. The incidence was 10.4 cases/million inhabitants/year (2.4-19.3). The mean age was 71.3 years (66.8-75.3). Most patients, 93.3%, were men and 40.0% were active smokers. The operations were elective in 73.2% (60.0%-85.7%). The mean pre-operative PAA diameter was 32.1 mm (27.3-38.3 mm). Open surgery dominated in both elective (79.5%) and acute (83.2%) cases. A medial surgical approach was used in 77.7%, and posterior in 22.3%. Vein grafts were used in 63.8%. Of the emergency procedures, 91% (n = 2 169, 20.2% of all) were for acute thrombosis and 9% for rupture (n = 236, 2.2% of all). Thrombosis patients had larger aneurysms, mean diameter 35.5 mm, and 46.3% were active smokers. Early amputation and death were higher after acute presentation than after elective surgery (5.0% vs. 0.7%; 1.9% vs. 0.5%). This pattern remained one year after surgery (8.5% vs. 1.0%; 6.1% vs. 1.4%). Elective open compared with endovascular surgery had similar one year amputation rates (1.2% vs. 0.2%; p = .095) but superior patency (84.0% vs. 78.4%; p = .005). Veins had higher patency and lower amputation rates, at one year compared with synthetic grafts (86.8% vs. 72.3%; 1.8% vs. 5.2%; both p < .001). The posterior open approach had a lower amputation rate (0.0% vs. 1.6%, p = .009) than the medial approach., Conclusion: Patients presenting with acute ischaemia had high risk of amputation. The frequent use of endovascular repair and prosthetic grafts should be reconsidered based on these results., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

GSK3 are involved in different physical and pathological conditions and inflammatory regulated by macrophages contribute to significant mechanism. Infection stimuli may modulate GSK3 activity and influence host cell adaption, immune cells infiltration or cytokine expressions. To further address the role of GSK3 modulation in macrophages, the signal transduction of three major organs challenged by endotoxin, virus and genetic inherited factors are briefly introduced (lung injury, myocarditis and autosomal dominant polycystic kidney disease). As a result of pro-inflammatory and anti-inflammatory functions of GSK3 in different microenvironments and stages of macrophages (M1/M2), the rational resolution should be considered by adequately GSK3., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest and no financial support for this publication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Inferior vena cava (IVC) aneurysms are extremely rare with variable clinical manifestations. Patients are usually asymptomatic or present with complications of thrombosis and rupture. To date, there have been only a few reports of the condition in the literature, and diagnosis of IVC aneurysms may be difficult., Case Presentation: A 33-year-old male patient presented to hospital because of a retroperitoneal mass found by computerized tomography during a health examination. He was asymptomatic, and post medical history and physical examination were unremarkable. Laboratory tests including tests for paraganglioma were all negative. Contrast-enhanced computed tomography scan revealed a stenosis of IVC in the suprarenal segment and two retroperitoneal mass on the right side of IVC. The larger one is about 3 cm in diameter and the smaller one is about 1 cm in diameter, which was considered as a retroperitoneal tumor with an enlarged lymph node. However, two IVC diverticular aneurysms were confirmed during the retroperitoneal laparoscopic exploration. The larger aneurysm was resected from the IVC successfully. Since the smaller aneurysm was about 1 cm in diameter without thrombosis, we did not resect it during surgery. The patient recovered well from surgery and discharged from our department successfully., Conclusions: This is the first report of multiple IVC aneurysms. Because of the extremely low prevalence of IVC diverticular aneurysm, it may be misdiagnosed as other disease. Due to the high rate of thrombosis, surgical treatment especially retroperitoneal laparoscopy is recommended for small diverticular aneurysms.

Competing Interests: Competing interests: None declared.

Rationale: The incidence of pure arterial malformations is relatively low, and few cases have been reported. Only 2 cases with pure arterial malformation have been reported to receive surgery or endovascular treatment., Patient Concerns: We report 3 cases and review the relevant literatures. The head examinations of the patients suggested the presence of high-density shadows in front of the pons and midbrain, the dilation of the supraclinoid segment of the right internal carotid artery, and moyamoya in the left brain with an aneurysm-like expansion located on the left posterior communicating artery respectively. After admission, head digital subtraction angiography (DSA) was performed., Diagnoses: Digital subtraction angiography (DSA) for these 3 patients showed that the left posterior communicating artery, the supraclinoid segment of the right internal carotid artery, and the left posterior communicating artery appeared dilated, tortuous, and spirally elongated. In addition, the lesions in the latter 2 patients were accompanied with local aneurysmal changes., Interventions: Two patients were given conservative treatment, and another patient was given endovascular treatment. A head DSA was reviewed 6 months after therapy., Outcomes: The prognosis status of the 3 patients was good. Two patients in the conservative treatment group showed no changes in the lesions on head DSA examination. The DSA examination of the third patient indicated that the vascular remodeling of the diseased vessels was good, the blood vessels were unobstructed, and the aneurysms had disappeared., Lessons: Pure arterial malformations mostly occur in young women and may involve any blood vessels in the brain. It can be accompanied with local aneurysms and calcification. The patients are often given conservative treatment but need to be reviewed regularly. However, it is beneficial to give endovascular treatment to the patients with local aneurysms.

Background: Matrix metalloproteinases (MMPs) are involved in vascular wall degradation, and drugs able to modulate MMP activity can be used to prevent or treat aneurysmal disease. In this study, we evaluated the effects of statins on MMP-2, MMP-9, and neutrophil gelatinase-associated lipocalin (NGAL) in both plasma and tissue in patients with aneurysmal disease., Methods: We performed a prospective, single-blind, multicenter, control group clinical drug trial on 184 patients of both sexes >18 years old with a diagnosis of arterial aneurysmal disease. Enrolled patients were divided into two groups: Group I under statin treatment and Group II not taking statins. In addition, 122 patients without aneurysmal disease and under statin treatment were enrolled as a control group (Group III). The expression of MMPs and NGAL in plasma was evaluated using ELISA, while their expression in endothelial tissues was evaluated using Western blot., Results: The ELISA test revealed greater plasma levels ( p < 0.01) of MMPs and NGAL in Groups I and II vs. Group III. Western blot analysis showed higher expression ( p < 0.01) of MMPs and NGAL in Group II vs. Group I, and this increase was significantly higher ( p < 0.01) in patients treated with low potency statins compared to high potency ones., Conclusions: MMPs and NGAL seem to play a major role in the development of aneurysms, and their modulation by statins suggests that these drugs could be used to prevent arterial aneurysmal disease.

Background: Splenic artery aneurysm (SAA) is a rare but potentially fatal condition. Rupture results in 25% mortality up to 75% in pregnant women with 95% fetal mortality. Brief reports suggest an increased risk of developing SAA in patients with HHT., Methods: We analyzed enhanced multidetector CT data in 186 HHT patients matched (gender and ± 5 year old) with 186 controls. We screened for SAA and recorded diameter of splenic and hepatic arteries and hepatic, pancreatic and splenic parenchymal involvements. We determined by univariate and multivariate analysis, the relationship with age, sex, genetic status, cardiovascular risk factors (CVRF) and visceral involvement., Results: SAA concerned 24.7% of HHT patients and 5.4% of controls, p<0.001. Factors associated with increased risk of SAA in HHT were female gender (p = 0.04, OR = 2.12, IC 95% = 1.03-4.50), age (p = 0.0003, OR = 1.04, 95% CI = 1.02-1.06) and pancreatic parenchymal involvement (p = 0.04, OR = 2.13, 95% CI = 1.01-4.49), but not type of mutation, hepatic or splenic parenchymal involvements, splenic size or splenic artery diameter or CVRF., Conclusions: We found a 4.57 higher rate of SAA in HHT patients without evidence of splenic high output related disease or increased CVRF. These results suggest the presence of a vascular intrinsic involvement. It should lead to screening all HHT patients for SAA. The vasculopathy hypothesis could require a change in management as screening of all systemic arteries and even the aorta and to further research in the field., Competing Interests: The authors have declared that no competing interests exist.

We describe a case of fusiform aneurysm of the renal artery on a background of dolichoectasia in a kidney recovered from a deceased donor. The donor, a 57-year-old female, had died of an extensive nonsurvivable subarachnoid hemorrhage. Fusiform aneurysms involving the main renal artery and its superior branch had extended into the hilum with insufficient accessible stump for safe reconstruction. Placement of a stent through an intraoperative radiologic intervention was not possible without compromising renal perfusion. Consequently, renal transplant did not proceed. Dolichoectasia is a condition associated with generalized weakness of the arterial vascular wall and may result in aneurysm formation. When the renal artery is involved, a safe reconstruction excising the aneurysmal segment may be considered before transplant of the kidney.

Histological observations in human pulmonary arterial hypertension (PAH) suggest a link between plexiform lesions and pulmonary supernumerary arteries. Pulmonary microvascular endothelial cells are characterized as hyperproliferative and progenitor-like. This study investigates the hypothesis that aneurysm-type plexiform lesions form in pulmonary supernumerary arteries because of their anatomical properties and endothelial characteristics similar to pulmonary microvascular endothelial cells. To induce PAH, rats were injected with Sugen5416, and exposed to hypoxia (10% O 2 ) for 3 days (early stage) or 3 wk (mid-stage), or 3 wk of hypoxia with an additional 10 wk of normoxia (late-stage PAH). We examined morphology of pulmonary vasculature and vascular remodeling in lung serial sections from PAH and normal rats. Aneurysm-type plexiform lesions formed in small side branches of pulmonary arteries with morphological characteristics similar to supernumerary arteries. Over the course of PAH development, the number of Ki67-positive cells increased in small pulmonary arteries, including supernumerary arteries, whereas the number stayed consistently low in large pulmonary arteries. The increase in Ki67-positive cells was delayed in supernumerary arteries compared with small pulmonary arteries. In late-stage PAH, ~90% of small unconventional side branches that were likely to be supernumerary arteries were nearly closed. These results support our hypothesis that supernumerary arteries are the predominant site for aneurysm-type plexiform lesions in Sugen5416/hypoxia/normoxia-exposed PAH rats partly because of the combination of their unique anatomical properties and the hyperproliferative potential of endothelial cells. We propose that the delayed and extensive occlusive lesion formation in supernumerary arteries could be a preventive therapeutic target in patients with PAH.

Upper gastrointestinal bleeding (UGIB) is a common life-threatening presentation in the emergency department. Causes are typically divided into variceal and non-variceal bleeds. Non-variceal pathologies typically include bleeding peptic ulcers, haemorrhagic gastritis and Mallory Weiss Tears. Occassionally, less common pathologies are encountered such as Dieulafoy's lesions, haemosuccus pancreas, haemobilia or aorto-enteric fistula. The following report documents the case of a 49-year-old man who presented with an UGIB. His risk factors included a history of nonsteroidal anti-inflammatory drug, smoking and ethanol abuse. Despite his typical presentation and risk factors, investigation revealed an unusual and rare pathology. He was found to have a giant splenic artery aneurysm, abutting and eroding the gastric mucosa. Diagnosis was made using a combination of gastro-oesophagoscopy and CT scan. Successful treatment consisted of angio-embolisation of the aneurysm., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations., Methods: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared., Results: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years)., Conclusions: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Athletes are generally young, high-functioning individuals. Pathology in this cohort is associated with a decrease in function and consequently has major implications on quality of life. Venous disorders can be attributed to a combination of vascular compression with a high burden of activity., Objective: This article promotes increased awareness of these uncommon conditions specific to the athlete by summarizing pathophysiology, clinical features, investigation, and treatment protocols for use in clinical practice. Prognostic outcomes of these management regimens are also discussed, allowing for clinicians to counsel these high-functioning individuals appropriately. With the aim of providing an overview of sport-related venous pathology, a literature review was undertaken identifying articles that were independently reviewed by the authors., Results: Lower limb venous thrombosis has been identified in young, high-functioning athletes attributed to both compression-related venous trauma, associated with repetitive movements resulting in intimal damage, and blunt trauma. The diagnosis and treatment follow the same protocols as for the general population. Of note, early ambulation is advocated, with an aim to return to premorbid (noncontact) function within 6 weeks. Athletes performing high-intensity repetitive upper limb movement, such as baseball players, are predisposed to upper limb deep venous thrombosis (DVT). Diagnosis follows the same protocols as for lower extremity DVT; however, the optimal treatment strategy remains debated. Current guidelines advocate the use of anticoagulation alone. A specific subset of primary upper limb DVT is effort thrombosis, where there is compression at the level of the thoracic outlet. Thrombolysis with first rib resection is indicated in the acute setting within 14 days. In cases of complete occlusion, surgical decompression with venous reconstruction may be required. Popliteal vein entrapment syndrome is also discussed. This entity has been identified as an overuse injury associated with popliteal vein compression. Duplex ultrasound examination is indicated as a first-line investigation, with conservative noninvasive options considered as an initial management strategy. Chronic venous insufficiency or persistent symptoms may require subsequent surgical decompression., Conclusions: Key conditions including upper extremity and lower extremity venous thrombosis, venous aneurysms, Paget-Schroetter syndrome (effort thrombosis), and popliteal vein entrapment syndrome are discussed. Further studies evaluating long-term outcomes on morbidity for current treatment regimens in upper extremity DVT, effort thrombosis, venous thoracic outlet syndrome, and popliteal venous entrapment syndrome are required., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Wall shear stress, the frictional force of blood flow tangential to an artery lumen, has been demonstrated in multiple studies to influence aneurysm formation and risk of rupture. In this article, the authors review the ways in which shear stress may influence aneurysm growth and rupture through changes in the vessel wall endothelial cells, smooth-muscle cells, and surrounding adventitia, and they discuss shear stress-induced pathways through which these changes occur.

Competing Interests: Competing interests: None declared.

The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor β gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher's exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent auto-phosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors., (Published by Elsevier Inc.)

Background: Missense variants in SMAD2 , encoding a key transcriptional regulator of transforming growth factor beta signalling, were recently reported to cause arterial aneurysmal disease., Objectives: The aims of the study were to identify the genetic disease cause in families with aortic/arterial aneurysmal disease and to further define SMAD2 genotype-phenotype correlations., Methods and Results: Using gene panel sequencing, we identified a SMAD2 nonsense variant and four SMAD2 missense variants, all affecting highly conserved amino acids in the MH2 domain. The premature stop codon (c.612dup; p.(Asn205*)) was identified in a marfanoid patient with aortic root dilatation and in his affected father. A p.(Asn318Lys) missense variant was found in a Marfan syndrome (MFS)-like case who presented with aortic root aneurysm and in her affected daughter with marfanoid features and mild aortic dilatation. In a man clinically diagnosed with Loeys-Dietz syndrome (LDS) that presents with aortic root dilatation and marked tortuosity of the neck vessels, another missense variant, p.(Ser397Tyr), was identified. This variant was also found in his affected daughter with hypertelorism and arterial tortuosity, as well as his affected mother. The third missense variant, p.(Asn361Thr), was discovered in a man presenting with coronary artery dissection. Variant genotyping in three unaffected family members confirmed its absence. The last missense variant, p.(Ser467Leu), was identified in a man with significant cardiovascular and connective tissue involvement., Conclusion: Taken together, our data suggest that heterozygous loss-of-function SMAD2 variants can cause a wide spectrum of autosomal dominant aortic and arterial aneurysmal disease, combined with connective tissue findings reminiscent of MFS and LDS., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A 60-year-old man, presented with a 3-month history of a painless, non-pulsatile firm mass in the left groin. He was referred to sarcoma clinic for a biopsy following MRI and B mode ultrasound (US). This was abandoned when colour flow US imaging revealed the mass more in keeping with a pseudoaneurysm rather than malignancy. He was then referred to the vascular team for further investigation, where CT angiography revealed a large and thrombosed true aneurysm of his left femoral circumflex artery. This was treated with open surgical repair. Technical challenges included an adherent femoral nerve, which was carefully dissected off the aneurysm before the aneurysm was ligated and resected. An uneventful recovery followed with discharge within 48 hours. Follow-up duplex US scan revealed patent arteries with no further abnormalities., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

A spermatic vessel aneurysm is a rare entity, described only a few times in the literature. In most cases, it is caused by trauma or inflammation and appears as a painful mass in the scrotum or the inguinal area. We present a case of a 22-year-old man who came to our Surgical Department with a painful, palpable mass in the right inguinal area. A spermatic vein aneurysm was diagnosed with the use of ultrasonography and it was surgically excised. The findings were confirmed by pathological examination. The patient is well, four months after surgery. A spermatic vessel aneurysm, though rare, should always be included in the differential diagnosis of a scrotal or inguinal mass. The lesion can be cured by surgical resection.

Purpose: Determining the presence of aneurysms, thrombosis, and stenosis is very important for the diagnosis of atypical Kawasaki disease (AKD) and in the follow-up of AKD patients with aneurysms. We aimed to demonstrate high-pitch low-dose dual-source computed tomography (CT) angiography findings in pediatric patients with AKD., Methods: Over a 5-year period, high-pitch low-dose CT angiography was performed to determine vascular aneurysms or occlusions in 17 patients who had suspected AKD. The patients ranged from 2 months of age to 11.3 years, with a mean age of 3 years. The American Heart Association's criteria were used to diagnose AKD., Results: We did not detect any vascular problems in 6 of the patients, and they were not included in our study. Arterial aneurysms were present in 11 patients (aged 2 months to 11.3 years; mean age, 4.2 years; 7 males). In one patient, there was also a thrombus at an arterial aneurysm. Coronary artery aneurysms were detected in 7 patients and systemic artery aneurysms were detected in 7 patients. Three patients had both systemic and coronary aneurysms., Conclusion: Our results suggest that high-pitch low-dose dual-source CT can detect all types of aneurysms, stenosis and occlusions of vessels in patients with AKD who were not previously diagnosed. This useful, easy, robust and fast technique may be preferred to diagnose AKD.

Endovascular biopsy can increase understanding of vascular disease by granting access to epigenetic data that are not normally attainable. This study compares biopsy yields among multiple devices used, examining differences in cell counts according to species, device type, sampling location and disease state. Chi-square analysis compared means of cells harvested with respect to these variables. Assessment of samples in 38 rabbits and 32 humans found no differences for species, location or pathology. Phenox clot retriever devices and retrievable stents yielded more cells (LR 64.2; p < 0.001) than other devices. Phenox clot retrievers and retrievable stents yield more cells than other device types. Further study of these devices for endovascular sampling is warranted to refine its use for this purpose.

An asymptomatic 71-year-old woman was admitted to the hospital due to aneurysm of visceral artery. CT angiography revealed that she possessed a hepatosplenic artery aneurysm with hepatosplenomesenteric trunk anomaly. The aneurysm was big with diameter about 28 mm, and is very adjacent to the superior mensenteric artery. The neck of the aneurysm is wide (the diameter of the neck was 5.5-6.0 mm) and short (length of the proximal landing zone was about 2.0 mm). The patient received endovascular reconstruction of the hepatosplenic artery and coil embolization of the aneurysm, and got satisfactory result.