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Arteriovenous malformations (AVM) are benign vascular anomalies prone to pain, bleeding, and progressive growth. AVM are mainly caused by mosaic pathogenic variants of the RAS-MAPK pathway. However, a causative variant is not identified in all patients. Using ultra-deep sequencing, we identified novel somatic RIT1 delins variants in lesional tissue of three AVM patients. RIT1 encodes a RAS-like protein that can modulate RAS-MAPK signaling. We expressed RIT1 variants in HEK293T cells, which led to a strong increase in ERK1/2 phosphorylation. Endothelial-specific mosaic overexpression of RIT1 delins in zebrafish embryos induced AVM formation, highlighting their functional importance in vascular development. Both ERK1/2 hyperactivation in vitro and AVM formation in vivo could be suppressed by pharmacological MEK inhibition. Treatment with the MEK inhibitor trametinib led to a significant decrease in bleeding episodes and AVM size in one patient. Our findings implicate RIT1 in AVM formation and provide a rationale for clinical trials with targeted treatments., Competing Interests: Declarations Competing interests Friedrich G. Kapp has received consulting fees from Novartis. Jochen Rössler is currently an employee of Novartis Pharma. All other authors declare no conflicts of interest., (© 2024. The Author(s).)

Tranexamic acid is a commonly used hemostatic agent with broad clinical uses across multiple specialties. Systemic toxicity is due to gamma-aminobutyric acid type A and glycine receptor competitive antagonism and has been reported by multiple routes, but toxicity after pulmonary administration via nebulization and BAL has not yet been described. A 44-year-old man with a history of congenital pulmonary arteriovenous malformations underwent routine bronchoscopy for hemoptysis. He received preprocedure nebulized tranexamic acid 500 mg three times daily for 48 h. An additional 1,000 mg was given via BAL for intraprocedural hemostasis. One hour after the procedure, he developed altered mental status, myoclonus, and hyperthermia, which was ultimately controlled with propofol and vecuronium. As the use of pulmonary tranexamic acid increases, toxicity from this agent should be considered. Dose reductions and alternate treatment modalities should be considered in patients with advanced age, arteriovenous malformations, and renal insufficiency., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Published by Elsevier Inc.)

KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS -driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.)., (Copyright © 2024 Massachusetts Medical Society.)

Depending on impairment, treatment of vascular anomalies is decided on a case-by-case basis in pluridisciplinary consultations. Interventional treatments, especially surgery and sclerotherapy, are usually partially efficient and management of patients with vascular anomalies increasingly involves the use of medical drugs. The most common vascular tumor is infantile hemangioma where first-line medical treatment, when necessary, is propranolol. Kasabach-Merritt phenomenon is now largely treated with sirolimus whereas first-line treatment of coagulation disorders associated with venous malformations is based on low-molecular-weight heparins or direct anticoagulants. Sirolimus is the standard treatment for painful inflammatory manifestations of low-flow vascular malformations such capillary, venous, and lymphatic malformations that can occur singly or in combination but PIK3CA inhibitors, originally developed in oncology, have shown promising results in patients with PIK3CA-related overgrowth spectrum. Currently, medical treatments are poorly developed for high-flow malformations such as arteriovenous malformations. However, new research aimed at delineating the different arteriovenous malformations based on molecular findings has given new hope for future development of targeted therapies., (© 2022 The Author. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

In the postnatal period, extensive peripheral arteriovenous malformations (AVM) are associated with high morbidity, especially when localized in the liver. Their urgent treatment is always a challenging problem in neonates and infants. We analyzed four consecutive children aged three days to three years who underwent eight liquid embolization procedures with ethylene-vinyl alcohol copolymer. The AVM were situated on the thoracic wall, in the liver, and on the lower leg. In three cases, the malformations showed total regression. The tibial AVM degenerated widely. If impaired beforehand, cardiac or hepatic function normalized after the interventions. There were no embolization-associated complications such as nontarget embolization or tissue ischemia. We conclude that application of ethylene-vinyl alcohol copolymer seems to be a safe therapeutic option and can be used in neonates and infants with peripheral AVM in consideration of the agent's characteristics. Nevertheless, there are still hardly any data concerning young children., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jochen Pfeifer et al.)

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor., (© 2022 Wiley Periodicals LLC.)

Abstract: Arteriovenous malformations of the orbit are rare congenital hamartomas defined by a direct connection between the arterial and venous systems without an intervening capillary bed. Treatment can be challenging, as these lesions are anatomically complex, often involve multiple locations, and have a tendency to recur. A multidisciplinary approach is typically required, involving endovascular and surgical teams. The authors present a case of a 33-year-old man with a complex, recurrent orbital arteriovenous malformations in the context of wider head and neck vascular anomaly syndrome involving the paranasal sinuses, deep facial tissues, and intracranial spaces. The complex and evolving clinical manifestations of this disease are presented with emphasis on the interdependence of the anomalies and biologic management strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

A 35-year-old woman (gravida 1, para 0) underwent termination of pregnancy (ToP) at 12 weeks of gestation. One month after ToP, she experienced significant vaginal bleeding and the mass with blood flow was identified on imaging. The presence of a placental polyp with arteriovenous malformation (AVM) was suspected on transvaginal sonography and MRI. Since the bleeding had ceased when she visited our hospital, we decided to treat the placental polyp with AVM with gonadotropin-releasing hormone (GnRH) antagonist therapy instead of surgery. Two months after GnRH antagonist treatment, the mass and blood flow in the uterus disappeared. Menstruation resumed 1 month after the completion of treatment. In our case, we were able to successfully treat placental polyps with AVM using GnRH antagonist therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a class of capillary anomalies that are associated with arteriovenous malformations and arteriovenous fistulas, which carry a risk of hemorrhages. There are no broadly effective pharmacological therapies currently available. Most CM-AVMs are associated with a loss of RASA1, resulting in constitutive activation of RAS signaling. However, protein interaction analysis revealed that RASA1 forms a complex with Rho GTPase-activating protein (RhoGAP), a negative regulator of RhoA signaling. Herein, we propose that loss of RASA1 function results in constitutive activation of RhoA signaling in endothelial cells, resulting in enhanced vascular permeability. Therefore, strategies aimed at curtailing RhoA activity should be tested as an adjunctive therapeutic approach in cell culture studies and animal models of RASA1 deficiency., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Retinal racemose hemangiomas (RRH) are vascular malformations comprising of direct arteriovenous communications in the retina. Exudation and neurosensory detachment are some of the complications which may cause decreased visual acuity. Herein, we describe a case of a 38-year-old male presenting with unilateral Group II RRH complicated with macular edema. Initial treatment with intravitreal bevacizumab yielded a poor therapeutic response. Subsequently, he was treated with a posterior sub-tenon injection of triamcinolone acetonide following which there was a prompt decrease in edema with simultaneous improvement in vision. The visual acuity was maintained and no recurrence was seen even after 6 months of successful treatment., Competing Interests: None

Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Shimano is the study chair for a consortium investigator-initiated trial funded by Novartis; the trial is unrelated to the diagnosis or therapy described in this case report. The other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Introduction: A cesarean scar pregnancy (CSP), when combined with an arteriovenous malformation (AVM), is a rare, but potentially life-threatening condition that may be associated with uncontrolled hemorrhage. Hysterectomy is indicated when conservative treatment fails. Preservation of fertility is challenging., Patient Concerns: We reported a 33-year-old woman with a CSP combined with an AVM who failed methotrexate administration as conservative treatment., Diagnoses: A CSP combined with an AVM was diagnosed via three-dimensional color Doppler angiogram and magnetic resonance imaging., Interventions: Transvaginal removal of the ectopic gestation and repair of the uterine defect was performed without incident., Outcomes: The fertility of the patient was preserved and hysterectomy was avoided., Conclusion: Transvaginal fertility-sparing surgery may be successfully performed to prevent hysterectomy when conservative treatment fails in patients with a CSP combined with an AVM.

This case describes a female patient who presented with an acute on chronic deterioration in respiratory symptoms, on a background of chronic obstructive pulmonary disease and heavy cigarette smoking. Chest radiograph demonstrated long-standing hyperlucency of the right lower lobe, with further imaging later confirming the rare combination of Swyer-James-MacLeod syndrome and multiple pulmonary arteriovenous malformations within the affected lung., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Managing extracranial arteriovenous malformations is challenging. Sirolimus (rapamycin) is increasingly being used when surgery and embolization are not advised. Because of its anti-angiogenic properties here we report all extracranial arteriovenous malformation cases treated with sirolimus in 2 French tertiary centers for vascular anomalies. The outcomes were efficacy (complete, partial, no response) based on arteriovenous malformation volume and necrosis/hemorrhage and side effects. We retrospectively included 10 patients (7 children). The sirolimus dose ranged from 0.6 to 3.5 mg/m2. Median (interquartile range [IQR]) treatment time was 24.5 (4.5; 35) months. Five patients showed no response and 5 showed partial response at a median (IQR) of 3 (1; 5) months followed in 2 cases by therapeutic resistance (i.e., progressive disease after 9 and 24 months of treatment). The most frequent side effect was mouth ulcers. This study shows poor efficacy of sirolimus for treating extracranial arteriovenous malformations.

CLAPO syndrome (Capillary vascular malformation of the lower lip, Lymphatic malformations of the head and neck, Asymmetry and Partial or generalized Overgrowth) is a nonfrequent pathology. This syndrome is characterized by the capillary malformation (CM) of the lower lip, a very important clinical sign when diagnosing CLAPO. The aim of our report is to demonstrate that rapamycin could be a reliable and safe targeted therapy in lymphatic malformations (LMs). This drug is useful in reducing the LM's size before final surgical treatment. The clinical and radiological evolution of a patient with CLAPO syndrome is reported in this article, before and after the treatment with rapamycin., (© 2019 Wiley Periodicals, Inc.)

In diffuse forms of arteriovenous malformation following Fontan procedure, "classical" medical therapy, inhaled nitric oxide and sildenafil, may play a role, until re-direction of hepatic flow to pulmonary circulation cures it. However, in refractory cases, as reported in our 2-year-old patient, unusual medications such as calcium channel blockers can be tried and continued if patients respond adequately.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by vascular dysplasia, including typically systemic telangiectases and arteriovenous malformations (AVMs). Due to its variable clinical manifestations, HHT patients often seek medical care from different medical subspecialties and thus experience delays in diagnosis and treatment.This study is designed to analyze the clinical features and treatment options for patients with HHT.Hospitalized patients with a definitive diagnosis of HHT from November 1973 to July 2016 in Peking Union Medical College Hospital were identified after reviewing medical records and electronic databases. Further follow-up data of these patients were collected from outpatient clinical visits and/or telephone interviews.We identified a total of 20 patients, 7 males and 13 females. The mean age was 42.4 ± 20.3 years. Epistaxis (18/20) was the most common presentation, followed by telangiectases of the oral buccal mucosa, tongue and/or lips (14/20), pulmonary AVMs (12/19), hepatic AVMs (9/17), gastrointestinal telangiectases (9/9), and encephalic AVMs (1/12). The correct diagnosis of HHT was delayed on average by about 26.4 ± 17.0 years from the onset of HHT-related clinical signs and symptoms. Although epistaxis is usually presented in childhood (mean age 11 ± 7.1 years), gastrointestinal telangiectasia was often encountered in late middle age (mean age 55.4 ± 12.8 years). Bleeding and anemia were the most common complications. Molecular analysis was conducted in 4 patients. Only 1 patient was found to have a single-base deletion in ENG gene. The mean duration of follow-up of the patients was 41.8 months. The efficacy of locoregional therapy was of limited value and short-lived. Two patients were treated systemically with thalidomide, and their symptoms of epistaxis, melena, and anemia were notably improved.Patients with HHT have variable clinical characteristics, and their diagnoses were delayed on average by about 26 years. An experienced multidisciplinary team is needed for the early diagnosis and optimal management of patients with HHT. Thalidomide may be an effective choice to alleviate the bleeding symptoms of patients with HHT.

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

A 9-month old castrated male Labradoodle presented to the cardiology service at Purdue University for evaluation of a low-grade murmur. Physical examination, thoracic radiography, and echocardiography were strongly supportive of an extracardiac left-to-right shunt. Subsequent evaluation with nuclear scintigraphy and computed tomography angiography revealed a large, complex arteriovenous malformation within the cranial abdomen. Staged interventional attenuation of the shunt was performed using n-butyl cyanoacrylate that resulted in a reduction in echocardiographic and nuclear scintigraphy derived shunt estimation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The International Society for Study of Vascular Anomalies (ISSVA) broadly categorizes vascular anomalies into vascular tumors and vascular malformations. Vascular malformations are further divided based on their flow properties into slow-flow venous and lymphatic malformations, high-flow arteriovenous malformations (AVMs), and congenital mixed syndromes, which can include combinations thereof. Whether occurring in isolation or as part of a broader syndrome, congenital high-flow AVMs are arguably the most complicated, challenging, and gratifying of all vascular malformations to diagnose and manage. Various configurations exist depending on location and coexisting clinical features. Transcatheter embolization has evolved into the mainstay of treatment for most congenital peripheral AVMs with surgical excision playing a growingly limited role as an adjunctive modality. Successful treatment requires technical precision, creativity, patience, and persistence given the ever-evolving angioarchitecture and hemodynamic profile of these lesions. Despite these challenges, certain fundamental principles have been established as our understanding of the pathogenesis, natural history, hemodynamics, and treatment outcomes has expanded and evolved over the last few decades. These principles are crucial to adhere to in the overall management of these lesions and are highlighted and expanded upon herein., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

A polymer based material was developed to act as an embolic agent and drug reservoir for the treatment of arteriovenous malformations (AVM) and hyper vascularized solid tumors. The aim was to combine the blocking of blood supply to the target region and the inhibition of the embolization-stimulated angiogenesis. The material is composed of an ethanolic solution of a linear acrylate based copolymer and acrylate calibrated microparticles containing nanospheres loaded with sunitinib, an anti-angiogenic agent. The precipitation of the linear copolymer in aqueous environment after injection through microcatheter results in the formation of an in-situ embolization gel whereas the microparticles serve to increase the cohesive properties of the embolization agent and to form a reservoir from which the sunitinib-loaded nanospheres are released post-embolization. The swollen state of the microparticles in contact with aqueous medium results in the release of the nanospheres out of microparticles macromolecular structure. After the synthesis, the formulation and the characterization of the different components of the material, anti-angiogenic activity was evaluated in vitro using endothelial cells and in vivo using corneal neovascularization model in rabbit. The efficiency of the arterial embolization was tested in vivo in a sheep model. Results proved the feasibility of this new system for vascular embolization in association with an in situ delivery of anti-angiogenic drug. This combination is a promising strategy for the management of arteriovenous malformations and solid tumors., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Arteriovenous malformations (AVMs) are high-flow vascular malformations characterised by a complex vessel network directly connecting feeding arteries and draining veins, typically featured by a natural history of progression, while spontaneous regressions are purely anecdotal. AVMs are very aggressive entities that possess a locally infiltrative behaviour like neoplasms. Complete "radical" surgical excision presents the highest chance of cure, but nowadays there is still considerable controversy on how to treat large AVMs that are not amenable of "radical" excision. The aim of this paper is to propose a different approach to treat vast AVMs that cannot be removed radically. The association of an antiangiogenic drug (to be initiated before surgery and to be continued in the post-operative period), could prevent the feared "explosive" growth of the remaining nidus after its partial removal. This could make recontouring and other "aesthetically" focused procedures feasible in these patients, with an obvious leap in their quality of life. The most promising antiangiogenic drug seems to be Thalidomide, but other drugs such as Sirolimus, VEGF pathway inhibitors, Interferon or Matrix Metalloproteinase (MMP) Inhibitors could serve the purpose just as well. Even Propranolol could prove useful in this sense as suggested by some recent researches on retinopathy of prematurity and tumour biology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations. Pulmonary arteriovenous malformations may either rupture or be responsible for a right-to-left shunting leading to paradoxical embolism causing stroke or cerebral abscess. Metformin may harbor a pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress. An animal model could be experimented to show its effects on PAVM formation. Metformin could also be tested in human individuals, particularly in patients presenting a diffuse HHT type with tiny PAVM. Metformin may be indicated as a prophylactic or curative therapy in HHT patients presenting with initial lung involvement. Metformin may be proposed to prevent from pulmonary arteriovenous malformation development and subsequent related complications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Stellate ganglion block is an established intervention used in pain management settings. Its use in the treatment of congenital venous malformations (VM) of the upper limb has never been described. We present a case of ultrasound-guided stellate ganglion block for a patient who derived excellent relief from pain uncontrolled with conservative and pharmacological methods., (© 2015 World Institute of Pain.)

Purpose: The aim of the present study was to evaluate the therapeutic outcome of using electrochemical therapy (ECT) combined with a sclerosing agent, pingyangmycin (bleomycin A5 hydrochloride; PYM), for large (>3 cm in diameter) venous malformations (VMs) in the oral and maxillofacial regions., Patients and Methods: Thirty-five patients (15 male and 20 female; age range, 10 to 69 yr; mean age, 32 yr) with large VMs in the oral and maxillofacial region were treated with a combination of ECT and PYM under general anesthesia in the authors' department from June 2012 through May 2014. The size of the lesions varied from 3 × 3 to 12 × 15 cm. A repeated course of ECT and PYM was administered for larger VMs. The therapeutic interval was 3 months for ECT and 2 to 4 weeks for PYM. The dose of PYM for patients was 8 mg each time, and the injection concentration of PYM was 1.6 mg/mL. Patients were followed for 6 to 36 months. Therapeutic results were evaluated by clinical examination and Doppler ultrasonography before and after treatment., Results: Of the 35 patients, 29 (82.9%) received 1 ECT treatment, 5 (14.3%) received 2 ECT treatments, and 1 (2.8%) received 3 ECT treatments. The number of PYM injection sessions was 1 to 5 (average, 2.5 times). According to the therapeutic criteria, the clinical outcome was excellent in 22 patients (62.9%), good in 10 patients (28.6%), and fair in 3 patients (8.5%). All patients (100%) had local swelling postoperatively that lasted approximately 1 to 2 weeks. Two patients (5.7%) had fever. No skin necrosis or nerve damage was found., Conclusions: Percutaneous treatment using ECT and PYM was a straightforward, safe, and reliable treatment modality for large VMs., (Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

A case of acquired Chiari malformation type I with frontal fistulous arteriovenous malformation (AVM) is presented, and the pathophysiology is discussed. The tonsillar herniation and hydrocephalus both resolved after AVM was excised. This case provides some insight into the complex hemodynamic change exerted by the fistulous AVM and the mechanism of the development of acquired Chiari malformation type I.

Cerebral arteriovenous malformations (AVMs) are vascular anomalies that carry a high risk of stroke and death. To test potential AVM therapies, a reverse genetics approach was used to model AVMs in zebrafish. Antisense morpholino oligonucleotides were used to knockdown activin receptor-like kinase I (alk1), which encodes a transforming growth factor (TGF)-beta family type I receptor implicated in a subset of human AVMs. Knockdown of alk1 caused a spectrum of morphologic, functional, and molecular defects that resemble those seen in humans with AVMs. It was found that losartan, an angiotensin II receptor antagonist, attenuated abnormal blood vessel morphology and systemic manifestations of high-output arteriovenous shunting in vivo. SMAD1 phosphorylation was significantly decreased in alk1 morphants compared with uninjected organisms (0.189±0.0201, 0.429±0.0164, P=0.0002). After treatment, morphant SMAD1 levels approached uninjected levels (0.326±0.0360, P=0.0355) and were significantly higher than those seen in the morphant-control group (P=0.0294). These data suggest that modulating the BMP signaling pathway with losartan, a drug in widespread clinical use in humans as an antihypertensive, may have the potential to be further evaluated as a therapeutic strategy for patients with AVMs.

Gastrointestinal bleeding because of arteriovenous malformations (AVMs) is an increasingly recognized complication of continuous flow left ventricular assist devices (LVADs). Currently, therapeutic options for LVAD-associated AVMs are limited and often require repeated endoscopic procedures and reduction or cessation of anticoagulation. Thalidomide has been utilized in the treatment of refractory bleeding because of gastrointestinal vascular malformations. Here we describe the case of a 66-year-old man with severe ischemic cardiomyopathy implanted with a continuous flow HeartMate II. His postoperative course was complicated by multiple hospital admissions for gastrointestinal bleeding because of LVAD-associated AVMs refractory to repeated argon plasma laser coagulation. Anticoagulation was discontinued with subsequent pump stoppage because of thrombus requiring urgent surgical pump exchange. Following this, thalidomide was initiated and anticoagulation with warfarin was continued. Since initiation of thalidomide, the patient has not had further gastrointestinal bleeding or evidence of pump thrombus in the subsequent 1 year.

Uterine arteriovenous malformation (AVM) can cause sudden massive hemorrhage. We report a case of uterine AVM following curettage in a patient treated conservatively with an intermediate-dose pill. An 18-year-old gravida 2 para 0 underwent curettage at 12 weeks of gestation and was examined for massive genital hemorrhage that occurred in postoperative month 4. Abundant blood flow in a mass within the uterine lumen was observed on color Doppler ultrasonography, and the patient was diagnosed with AVM. Six days after starting oral norgestrel/ethinyl estradiol, the hemorrhage ceased, and computed tomography on day 37 of administration showed disappearance of the abnormal vasculature. After 12 months, the patient's course remains favorable without relapse. Transarterial embolization for AVM can cause ovarian failure and subsequent placental malpositioning. Administration of oral norgestrel/ethinyl estradiol may be an alternative conservative treatment option for patients who wish to maintain fertility., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

The transforming growth factor-β superfamily signaling pathway is thought to be involved in the pathogenesis of pulmonary arteriovenous malformation (PAVM). However, the association between bone morphogenetic protein receptor type 2 (BMPR2) gene mutations and PAVM remains unclear. We present a case of concurrent PAVM and pulmonary arterial hypertension (PAH), with a deletion mutation in exon 6 and exon 7 of the BMPR2 gene. Drug treatment for PAH improved the patient's hemodynamics and exercise capacity, but worsened oxygenation. This case suggests that BMPR2 gene mutation may be associated with the complex presentation of PAVM combined with PAH., (Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Ethanol has been used for embolization of arteriovenous malformations (AVMs) for 3 decades. Cardiovascular collapse (CVC), although a rare complication, has been reported and occurs immediately to a few hours after ethanol embolization. The present report describes a case of CVC and disseminated intravascular coagulation (DIC) after ethanol embolotherapy in a patient with upper lip AVMs. Although resuscitated from asystole, the patient died of DIC 2 days later despite intensive care treatment., (Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: To report engorged vessel occlusion after repeated intravitreal injections of bevacizumab to treat the macular oedema in a case of arteriovenous malformation., Case Presentation: A 37-year-old woman presented with a sudden, painless loss of vision in her left eye. Her visual acuity was 20/200 in the left eye, and 20/20 in the right eye. Ophthalmoscopic examination revealed an abnormal tangle of vessels and enlarged draining veins. A fluorescence angiogram revealed fluorescence leakage at a turn near the fovea. Horizontally oriented optical coherence tomography revealed an increased macular thickness and an accumulation of intraretinal fluid, indicating macular oedema. After three intravitreal injections of 1.25 mg bevacizumab, her vision improved to 20/20. Ophthalmoscopic examination revealed a decreased calibre of the previously engorged draining veins and ghost vessels. Repeated horizontally oriented optical coherence tomography revealed a decreased macular thickness and the absence of an intraretinal cyst. At the 2-year follow-up visit, the vision of the patient was stable., Conclusion: This finding implies that certain middle-size vessels can become occluded during anti-vascular endothelium growth factor (anti-VEGF) therapy, which could induce fatal complications if it occurred in the heart or brain. Clinicians should be cautious of the potential thrombotic effects on systemic blood vessels when administering anti-VEGF treatment.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited mucocutaneous disease characterized by recurrent epistaxis, lesions on skin and oral mucosa, and arteriovenous malformations of the soft tissues. This article describes the treatment of a 64-year-old woman with a bleeding nodule, which was diagnosed as an arteriovenous malformation of the gingival mucosa. She was treated using sclerotherapy. Patients with HHT can be treated in the dental office and vascular malformations of these patients can be successfully managed with sclerotherapy, which eliminates the need for invasive surgical procedures and the possibility of postsurgical complications., (©2012 Special Care Dentistry Association and Wiley Periodicals, Inc.)

Introduction: Although Gamma Knife radiosurgery (GKS) is commonly performed under local anesthesia, general anesthesia is sometimes required. The authors previously reported a remote-controlled patient management system consisting of propofol-based general anesthesia with a target-controlled infusion (TCI) that we designed for pediatric GKS. However, a commercially available propofol TCI system has age and weight limitations (<16 years and <30 kg). We examined a manually controlled regimen of propofol appropriate for pediatric GKS., Methods: A pharmacokinetic model of the TIVA Trainer© with Paedfusor's parameter was used. A manually controlled infusion scheme to achieve a sufficient level of propofol for pediatric GKS was examined in five models ranging from 10 to 30 kg., Results: Following a loading dose of 3.0 mg/kg, the combination of continuous infusion of 14, 12, 10, and 8 mg/kg/h resulted in a target concentration of 3.0-4.0 μg/ml, the required level for pediatric GKS., Conclusion: Propofol titration is a key issue in GKS. Manual infusion is less accurate than TCI, but the combination of a small bolus and continuous infusion might be a substitute. Considering the characteristics of propofol pharmacokinetics in children, co-administration of opioids is recommended.

We present a patient undergoing spinal angiography and suspected of having an AVM. During the first injection of nonionic contrast, a nidal AVM supplied by the great anterior radiculomedullary artery at T9 left was found. The second injection at T9 left no longer showed the contrast filling of the AVM. Follow-up angiography showed persistent AVM obliteration with an intact arterial spinal axis. The patient's symptoms resolved. Interaction between nonionic contrast, blood, and vessel wall most likely induced the obliteration.

Hereditary Haemorrhagic Telangiectasia (HHT) is a genetic disorder responsible for cutaneous or mucosal telangiectasia and arteriovenous malformations (AVMs). The most frequent locations are lung and brain. In contrast, orbital AVMs are very rare. We describe a case of symptomatic orbital arteriovenous malformation due to spontaneous thrombosis. A 65-year-old woman was referred for chronic right eye proptosis associated with dilation of conjunctival vessels with a jellyfish pattern. Right visual acuity was 20/40 and intraocular pressure was 40 mmHg. Personal and familial history of recurrent epistaxis, associated with multiple telangiectasia within lips and palate, led to the diagnosis of HHT. Magnetic resonance imaging (MRI) completed with cerebral angiography found a giant and occluded AVM within the right orbit. Other AVMs were also found in brain and chest, confirming the diagnosis. Antiglaucomatous eyedrops were added to reduce intraocular pressure and a steroid therapy was begun. Two months later, visual acuity decreased in the right eye, due to a central retinal vein thrombosis. In conclusion, Most brain or pulmonary AVM can be treated by embolization. By contrast, this treatment in case of orbital location can lead to central retinal artery and/or central retinal vein occlusion, which may also appear as a spontaneous complication of the orbital AVM. Therapeutic management of orbital AVM is thus not standardized, and the balance between spontaneous and iatrogenic risk of visual loss has to be taken into account.

Bannayan-Riley-Ruvacalba syndrome (BRRS) belongs to the PTEN hamartoma tumor syndromes and is characterized by a high risk of malignancy in early adulthood added to local destructive effects of hamartomas in childhood. There is no standard treatment for this condition and patients are usually offered symptomatic surgical relief. Rapamycin has been reported to be effective in the management of other conditions associated with PTEN mutation. We report here a case of BRRS in a 6-year-old male with progressive loss of function of left hand and forearm associated with pain. He was treated with oral rapamycin and regained pain-free full mobility., (Copyright © 2011 Wiley-Liss, Inc.)

Object: The purpose of this study was to present the authors' clinical experience and long-term angiographic and clinical follow-up results in 350 patients with brain arteriovenous malformations (AVMs) treated using prolonged intranidal Onyx injection with a very slow "staged" reflux technique described by the authors., Methods: Three hundred and fifty consecutive patients with brain AVMs treated using Onyx between 1999 and 2008 and in whom definitive status for endovascular treatment was reached are presented. There were 206 (59%) male and 144 (41%) female patients, with a mean age of 34 years. There were 607 endovascular sessions performed. Onyx was the only agent used for intranidal injections in all patients, but in 42 patients high-concentration N-butyl cyanoacrylate glue was used adjunctively to close high-flow direct arteriovenous intra- or perinidal fistulas, or when a feeding vessel or nidus perforation and/or dissection occurred., Results: Angiographically confirmed obliteration was achieved in 179 patients (51%) with only endovascular treatment; 1 patient died due to intracranial hemorrhage after the treatment. Twenty-two patients underwent resection, and 136 patients were sent to radiosurgery after endovascular treatment. In 4 patients embolization therapy was discontinued, and 5 additional patients refused the suggested complementary surgery. In all 178 surviving patients who had angiographically confirmed AVM obliteration by embolization alone, 1-8 years of control angiography (mean 47 months) confirmed stable obliteration, except for 2 patients in whom a very small recruitment was noted in the 1st year on control angiography studies, despite initial apparent total obliteration (recanalization rate 1.1%). In the entire series, 5 patients died; the mortality rate was 1.4%. The permanent morbidity rate was 7.1%., Conclusions: With the prolonged intranidal injection technique described herein, Onyx allows the practitioner to achieve higher rates of anatomical cures compared with the cure rates obtained previously with other embolic agents. More importantly, due to this technique's much more effective intranidal penetration, it allows high-grade AVMs to be made radiosurgically treatable in a group of patients for whom there has been no treatment alternative.