Drug Delivery Angle for Various Atherosclerosis and Aneurysm Percentages of the Carotid Artery.

Stroke is the second cause of mortality among adult males and the first cause of death in adult females all around the world. It is also recognized as one of the most important causes of morbidity and dementia in adults. Stenosis or rupture of the only channels of the blood supply from the heart to the brain (carotid arteries) is among the main causes of stroke. In this regard, treatment of the lesions of carotid arteries, including atherosclerosis and aneurysm, could be a huge step in preventing stroke and improving brain performance. Targeted drug delivery by drug-carrying nanoparticles is the latest method for optimal delivery of drug to the damaged parts of the artery. In this study, a wide range of carotid artery lesions, including different percentages of atherosclerosis and aneurysm, were considered. After analyzing the dynamics of the fluid flow in different damaged regions and selecting the magnetic framework with proper ligand (Fe3O4@MOF) as the drug carrier, the size of the particles and their number per cycle were analyzed. Based on the results, the particle size of 100 nm and the use of 300 particles per injection at each cardiac cycle can result in maximum drug delivery to the target site. Then, the effect of the hospital bed angle on drug delivery was investigated. The results showed a unique optimal drug delivery angle for each extent of atherosclerosis or aneurysm. For example, in a 50% aneurysm, drug delivery at an angle of 30° is about 387% higher than that at an angle of 15°. Finally, simulation of real geometry indicated the effectiveness of simple geometry instead of real geometry for the simulation of carotid arteries, which can remarkably decrease the computational time and costs.

Endothelialization of PTFE-covered stents for aneurysms and arteriovenous fistulas created in canine carotid arteries.

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.

Fibromuscular dysplasia of the coronary arteries: An unusual case of sudden death and review of the literature.

Fibromuscular dysplasia of the coronary is an uncommon coronary defect with a range of pathological alterations and unpredictable clinical description that can cause sudden death. We present an autopsy case of sudden cardiac death due to a rupture of a coronary artery aneurysm in a 59-year-old woman. Postmortem autopsy revealed two huge saccular aneurysms located at the right coronary artery, one of which was ruptured leading to a fatal hemopericardium. Histopathological examination revealed coronary artery fibromuscular dysplasia with fibromyxoid dissociation of the media causing saccular aneurysms. The involvement of coronary arteries in fibromuscular dysplasia with aneurysmal features has been rarely reported in the literature and is most likely an underdiagnosed finding. Due to the little number of published studies, the etiology is not fully understood and data on pathogenesis, risk factors, manifestation, disease course, and mortality are still unclear, which is a gap that needs to be filled in order to avoid under-diagnosis of the disease. Our case report aimed to discuss the mechanisms of sudden death attributed to coronary fibromuscular dysplasia.

Smooth Muscle Cell Klf4 Expression Is Not Required for Phenotype Modulation or Aneurysm Formation in Marfan Syndrome Mice-Brief Report.

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 (Fbn1C1041G/+) mouse strains with an inducible vascular SMC fluorescent reporter (MFSSMC) with or without SMC-specific deletion of Klf4 exons 2 to 3 (MFSSMC-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 (WTSMC) mice regardless of Klf4 genotype (P<0.001), but there was no difference in aneurysm growth in MFSSMC-Klf4Δ versus MFSSMC (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 MFSSMC-Klf4Δmice, 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.

Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

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.

Use of Ultra-Widefield Fluorescein Angiography to Guide the Treatment to Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis-Case Report and Literature Review.

PURPOSE: To review the clinical features, diagnosis, and treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and to report a case with the use of ultra-widefield fluorescein angiography (UWFA) for confirming the precise staging of IRVAN and aid in early treatment. The patient improved after being treated with intravitreal aflibercept injection. RESULTS: A 26-year-old female complained of progressive blurred vision OD for one week. Her BCVA was 0.6 OD and 1.0 OS. Fundus examination showed vitritis, retinal hemorrhage, and vasculitis over bilateral eyes. Fluorescein angiography (FA) with a 55 degree of view revealed aneurysmal dilations of the peripapillary arteriole, peripapillary focal leakage, venous leakage, and capillary nonperfusion area. Stage 2 IRVAN was impressed OU. Oral prednisolone was administered. After four months, she experienced decreased visual acuity OS. Optical coherence tomography (OCT) revealed subretinal and intraretinal fluid with hyperreflective material. One posterior subtenon triamcinolone and one intravitreal aflibercept injection were performed OS, and macular edema subsided. A 105-degree ultra-widefield fluorescein angiography (UWFA) showed multiple peripheral background hypofluorescence areas corresponding to capillary nonperfusion. Retinal neovascularization (NV) was found OS, which had not been revealed by the previous 55-degree FA. Stage 3 IRVAN was made OS and panretinal laser photocoagulation (PRP) was performed. Oral prednisone and cyclosporine were prescribed. Her vision improved to 1.0 OU. CONCLUSION: UWFA provides visualization of peripheral retinal pathology and for precise staging. It also had direct implications in the follow-up and treatment strategy.

Extending the spectrum in aortopathy: stenosis to aneurysm.

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.

Clinical presentation and treatment outcomes of arterial involvement in Behçet's disease: a single-centre experience.

Arterial involvement, although rare, accounts for significant mortality and morbidity in patients of Behçet's disease (BD). There is paucity of data on arterial BD. The objective of this 5-year retrospective cohort study was to examine the clinical presentation, pattern of arterial involvement, and treatment outcome in Indian arterial BD patients. Data on demography, clinical presentation, radiology, instituted therapy, vascular interventions and treatment outcomes were recorded and analyzed. Ten (16.9%) out of 59 patients with BD had arterial involvement in 13 vascular territories [mean age 30 (8) years, 9 (90%) males]. Pulmonary artery was most commonly involved (46%), followed by abdominal aorta (15%), femoral artery (15%), descending thoracic aorta (8%), common iliac (8%), and dorsalis pedis artery (8%). Two patients had multi-territory involvement. The median interval between disease onset and development of arterial aneurysms was 3 years (3 months-12 years). Concomitant deep vein thrombosis was seen in 60% cases. Prednisolone and cyclophosphamide were the most common immunosuppressive therapy used; one patient who relapsed on cyclophosphamide responded to infliximab. Five surgical or endovascular interventions were performed. Four patients (40%) died due to aneurysm rupture-all had a delayed diagnosis, and three had pulmonary artery involvement, with death due to massive hemoptysis. Based on the present study, we concluded that arterial involvement in BD is seen predominantly in males and has a high mortality. Early detection and aggressive treatment with immunosuppression and surgical or endovascular interventions are essential for good outcomes.

Idiopathic Aneurysms of the Ascending Aorta in the Mouse and Rat.

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.

Serum Amyloid A Is Present in Human Saccular Intracranial Aneurysm Walls and Associates With Aneurysm Rupture.

Saccular intracranial aneurysm (sIA) rupture leads to a disabling subarachnoid hemorrhage. Chronic inflammation and lipid accumulation in the sIA wall contribute to wall degenerative remodeling that precedes its rupture. A better understanding of the pathobiological process is essential for improved future treatment of patients carrying sIAs. Serum amyloid A (SAA) is an acute-phase protein produced in response to acute and chronic inflammation and tissue damage. Here, we studied the presence and the potential role of SAA in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), that had previously been studied by histology and immunohistochemistry. SAA was present in all sIAs, but the extent of immunopositivity varied greatly. SAA immunopositivity correlated with wall degeneration (p = 0.028) and rupture (p = 0.004), with numbers of CD163-positive and CD68-positive macrophages and CD3-positive T lymphocytes (all p < 0.001), and with the expression of myeloperoxidase, matrix metalloproteinase-9, prostaglandin E-2 receptor, and cyclo-oxygenase 2 in the sIA wall. Moreover, SAA positivity correlated with the accumulation of apolipoproteins A-1 and B-100. In conclusion, SAA occurs in the sIA wall and, as an inflammation-related factor, may contribute to the development of a rupture-prone sIA.

An epithelioid haemangioma of the ulnar artery masquerading as an aneurysm.

Epithelioid haemangiomas are rare benign vascular tumors that usually present as subcutaneous nodules in the head and neck area. Occasionally these tumors can arise in a peripheral artery. When it does so, it is often confused with an aneurysmal dilatation of the respective vessel. In these circumstances, surgical resection with vascular reconstruction is the preferred treatment option.

Development and validation of an institutional nomogram for aiding aneurysm rupture risk stratification.

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.

All trans retinoic acid alleviates coronary stenosis by regulating smooth muscle cell function in a mouse model of Kawasaki disease.

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.

Isolated brachial artery aneurysm: a rare presentation of paediatric Behçet's disease.

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.

Rare and interesting case of solitary peripheral pulmonary artery aneurysm.

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.

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys).

Activating variants in the platelet-derived growth factor receptor ß gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next-generation sequencing-based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB-activating variants through literature search. The conditions caused by PDGFRB-activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant-related phenotypes are present. Whole-body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6- to 12-month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.

The Role of Immunosuppressive Therapy in Aneurysmal Degeneration of Hemodialysis Fistulas in Renal Transplant Patients.

BACKGROUND: Venous aneurysms are long-term complications of arteriovenous fistula (AVF) for hemodialysis with an estimated incidence rate of around 5-6%. The purpose of our study is to investigate the role of immunosuppressive therapy in the development of AVF aneurysms in renal transplant patients, and to determine whether AVF closure following transplantation is necessary. METHODS: Forty-six patients with symptomatic venous AVF aneurysms underwent ligation and resection of their fistulas between January 2013 and January 2020. Immunohistochemical expression of CD3, CD4, and CD8 was assessed on the surgical specimens to characterize lymphocytic infiltrate in the aneurysm wall. Patients were subdivided into "Group A"-kidney transplant patients undergoing immunosuppressive therapy which was comprised of 39 patients and "Group B"-patients who had not undergone kidney transplant which was comprised of 7 patients. The 2 groups did not significantly differ in age, sex nor risk factors for aneurysms. RESULTS: Group A showed a significantly higher aneurysm diameter (P < 0.0001), mean flow (P < 0.0001) and required a longer duration of surgery (P = 0.0007). A CD3+ lymphocytic infiltrate was significantly more common in Group A than in the Group B (90% vs 29%; P < 0.001). No significant differences in localization (adventitia, media or intima) and type (CD4+ vs CD8+) of lymphocytes were found between the 2 groups. CONCLUSION: AVF venous aneurysms were significantly larger and with a more intense T-lymphocytic infiltrate in patients undergoing immunosuppressive therapy. This finding suggests that immunosuppressive therapy plays a role in aneurysm formation, supporting the need for AVF closure in patients with an estimated low risk of rejection.

Natural History of Unruptured Visceral Artery Aneurysms Due to Segmental Arterial Mediolysis and Efficacy of Transcatheter Arterial Embolization: A Retrospective Multiinstitutional Study in Japan.

OBJECTIVE. The purpose of this study was to clarify the natural history of unruptured visceral artery aneurysms due to segmental arterial mediolysis and the efficacy of transcatheter arterial embolization. MATERIALS AND METHODS. Patients with a pathologic or clinical diagnosis of visceral artery aneurysms due to segmental arterial mediolysis between 2005 and 2015 were enrolled. For patients with clinical diagnoses, images were collected and assessed by central radiologic review. To clarify the natural history of unruptured aneurysms, the morphologic changes were assessed. The efficacy and safety of transcatheter arterial embolization for aneurysms due to segmental arterial mediolysis were evaluated. RESULTS. Forty-five patients with 123 aneurysms due to segmental arterial mediolysis were enrolled. Among the 123 aneurysms, 70 unruptured aneurysms were evaluated for natural history. Forty-five of the 70 (64%) aneurysms had no change in morphology. Among the other 25 aneurysms, nine (13% of the 70) were reduced in size, 13 (19%) disappeared, and three (4%) were newly found at follow-up. Aneurysms of the middle colic artery were ruptured in 10 of 11 (91%) cases. Transcatheter arterial embolization was performed on 45 aneurysms and was successful in all cases but caused slight arterial injury in three cases (6.7%). CONCLUSION. At initial diagnosis, unruptured aneurysms due to segmental arterial mediolysis are likely to be stable or to resolve, but the risk of rupture of aneurysms of the middle colic artery appears high. Transcatheter arterial embolization is a useful treatment, but careful manipulation is necessary.