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Introduction and purpose: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and complex vascular disorder characterized by abnormal blood vessel formation. It can present significant challenges in diagnosis and management, as it is currently estimated up to 90% of those affected are never diagnosed. Despite its rarity, HHT can carry substantial implications for patients and their families, at times requiring comprehensive medical care and support. This paper aims to provide an in-depth exploration of HHT, encompassing its epidemiology, genetics, clinical manifestations, diagnostic approaches, and current management strategies. Moreover, we hope to point out possible areas in need of future research. Description of the state knowledge: HHT is an autosomal dominant genetic disorder that affects 1 in 5-10,000 people. Its most prominent symptoms include telangiectasia of skin and mucous membranes, recurrent epistaxis, gastrointestinal bleeding and arteriovenous malformations in vital organs. In the vast majority of cases, it is caused by a mutation in one of the following genes: ENG, ACVRL1, SMAD4; however, mutations in other genes have been described to cause a similar or much the same constellation of symptoms. Treatment options are focused on managing symptoms and improving quality of life, but possible new treatment options are being researched that could change the landscape of HHT management. Summary: HHT is a severely underdiagnosed disease that has seen a surge of researchers’ interest in recent years. We firmly believe that, combined with plummeting costs of genetic testing and possible new treatment options, means that HHT will become increasingly important in physicians’ everyday practice. [ABSTRACT FROM AUTHOR]

Abstract Background Renal arteriovenous malformation (AVM) in Hereditary Hemorrhagic Telangiectasia (HHT) is uncommon and only few cases have been described, mainly with surgical management because of uncontrolled hematuria. Case presentation We managed a 70-year-old patient with HHT who presented with hematuria and left flank pain. Computed Tomography and ultrasound showed left renal AVM of 18 mm with clotting in the urinary tract. An external ureteral catheter was placed during 3 days to allow rinsing and facilitate elimination of clots. Given the patient's hemodynamic stability, a non-surgical management was chosen. Treatment of the AVM was performed by trans-arterial embolization using micro-coils and ethylene–vinyl alcohol copolymer. Conclusions Our case study shows a conservative management by embolization of ruptured left renal AVM revealed by hematuria in a 70-year-old patient with HHT.

Background: Renal arteriovenous malformation (AVM) in Hereditary Hemorrhagic Telangiectasia (HHT) is uncommon and only few cases have been described, mainly with surgical management because of uncontrolled hematuria. Case presentation: We managed a 70-year-old patient with HHT who presented with hematuria and left flank pain. Computed Tomography and ultrasound showed left renal AVM of 18 mm with clotting in the urinary tract. An external ureteral catheter was placed during 3 days to allow rinsing and facilitate elimination of clots. Given the patient's hemodynamic stability, a non-surgical management was chosen. Treatment of the AVM was performed by trans-arterial embolization using micro-coils and ethylene–vinyl alcohol copolymer. Conclusions: Our case study shows a conservative management by embolization of ruptured left renal AVM revealed by hematuria in a 70-year-old patient with HHT. [ABSTRACT FROM AUTHOR]

Clarification of the aetiology of ischemic stroke (IS) in young adults (aged between 18 and 45 years) is an extremely difficult task, as rare causes that are hardly known to neurologists are very common. One of these causes is paradoxical embolism due to pulmonary arteriovenous malformation (AVM), one of the manifestations of hereditary hemorrhagic telangiectasia (HHT). The diagnosis of HHT-associated pulmonary AVMs and IS is a multistep task that requires a personalized multidisciplinary approach using high-tech ultrasound, tomographic and genetic examination methods. This article discusses the clinical case of a young patient with HHT and recurrent IS through the mechanism of paradoxical embolism from pulmonary AVMs; issues of diagnosis, treatment and prevention of both the underlying disease and recurrent vascular events are discussed.

RenduOslerWeber disease or hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease. It is characterized by vascular dysplasia with the formation of telangiectasias on the skin, mucous membranes of the respiratory and digestive tracts, arteriovenous malformations (AVMs) in the internal organs, which is manifested by bleeding. Diagnosis is based on Curacao criteria: recurrent and spontaneous nosebleeds, multiple telangiectases on the characteristic localizations, AVMs in one or more of the internal organs, a family history of HHT (i.e. first-degree relative who meets these same criteria for definite HHT). Therapy is aimed at preventing and stopping gastrointestinal, nosebleeds, correction of iron deficiency anemia. A promising method of therapy is the use of angiogenesis inhibitors, in particular bevacizumab. The article presents a description of a clinical case of HHT in a 49-year-old woman with telangiectisia on the mucous membrane of the tongue, gastrointestinal tract and liver AVMs.

Introduction and purpose: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and complex vascular disorder characterized by abnormal blood vessel formation. It can present significant challenges in diagnosis and management, as it is currently estimated up to 90% of those affected are never diagnosed. Despite its rarity, HHT can carry substantial implications for patients and their families, at times requiring comprehensive medical care and support. This paper aims to provide an in-depth exploration of HHT, encompassing its epidemiology, genetics, clinical manifestations, diagnostic approaches, and current management strategies. Moreover, we hope to point out possible areas in need of future research. Description of the state knowledge: HHT is an autosomal dominant genetic disorder that affects 1 in 5-10,000 people. Its most prominent symptoms include telangiectasia of skin and mucous membranes, recurrent epistaxis, gastrointestinal bleeding and arteriovenous malformations in vital organs. In the vast majority of cases, it is caused by a mutation in one of the following genes: ENG, ACVRL1, SMAD4; however, mutations in other genes have been described to cause a similar or much the same constellation of symptoms. Treatment options are focused on managing symptoms and improving quality of life, but possible new treatment options are being researched that could change the landscape of HHT management. Summary: HHT is a severely underdiagnosed disease that has seen a surge of researchers’ interest in recent years. We firmly believe that, combined with plummeting costs of genetic testing and possible new treatment options, means that HHT will become increasingly important in physicians’ everyday practice.

BackgroundCerebral arteriovenous malformations (AVMs) are common in patients with hereditary hemorrhagic telangiectasia (HHT). However, due to the rarity of HHT and little published evidence of outcomes from management of brain AVMs in this disease, current international HHT guidelines recommend an individualized approach. Specifically, the outcomes for surgical vs nonsurgical management of these lesions have not been reported to date.ObjectiveTo report long-term outcomes of surgical resection of brain AVMs in HHT patients compared to outcomes in nonsurgically treated patients.MethodsFrom the database of the Brain Vascular Malformation Consortium HHT project, 19 patients with 20 resected AVMs (group 1) and 22 patients with 33 AVMs who received nonsurgical treatment (group 2) were studied. The groups were retrospectively reviewed for changes in functional status (modified Rankin Scale score) during the follow-up period.ResultsDuring the follow-up period, 9% of patients in group 1 suffered from worsening of functional status, whereas this figure was 16% for group 2 (P > .05). Functional outcomes were not statistically different between the 2 groups at the latest follow-up (P > .05).ConclusionHHT patients treated surgically for brain AVMs appear to have long-term functional outcomes comparable to nonsurgical (including observational) therapy with fewer unfavorable outcomes. It is therefore reasonable to consider surgical resection as a management option in the multidisciplinary team's individualized treatment strategy for HHT patients with brain AVMs.

Objectives: To evaluate short- and long-term safety and efficacy of embolization with Onyx® for recurrent pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia (HHT). Methods: In total, 45 consecutive patients (51% women, mean (SD) age 53 (18) years) with HHT referred to a reference center for treatment of recurrent PAVM were retrospectively included from April 2014 to July 2021. Inclusion criteria included evidence of PAVM recurrence on CT or angiography, embolization using Onyx® and a minimal 1-year-follow-up CT or angiography. Success was defined based on the standard of reference criteria on unenhanced CT or pulmonary angiography if a recurrence was suspected. PAVMs were analyzed in consensus by two radiologists. The absence of safety distance, as defined by a too-short distance for coil/plug deployment, i.e., between 0.5 and 1 cm, between the proximal extremity of the primary embolic material used and a healthy upstream artery branch, was reported. Results: In total, 70 PAVM were analyzed. Mean (SD) follow-up was 3 (1.3) years. Safety distance criteria were missing in 33 (47%) PAVMs. All procedures were technically successful, with a short-term occlusion rate of 100% using a mean (SD) of 0.6 (0.5) mL of Onyx®. The long-term occlusion rate was 60%. No immediate complication directly related to embolization was reported, nor was any severe long-term complication such as strokes or cerebral abscesses. Conclusions: In HHT, treatment of recurrent PAVM with Onyx® showed satisfactory safety and efficacy, with an immediate occlusion rate of 100% and a long-term rate of 60%. [ABSTRACT FROM AUTHOR]

ObjectiveTo study the genotypes and phenotypes of cerebral arteriovenous fistulas that drain or do not drain through the vein of Galen, and true vein of Galen aneurysmal malformations, in order to determine whether genotyping could help improve classification of these malformations and their management.MethodsWe carried out a retrospective review of genetic and phenotypic data in databases of four centers. All children with cerebral arteriovenous fistula or vein of Galen aneurysmal malformations aged below 18 years at onset were included. We recorded the nature of the genetic variant or absence of variant, age at onset, type of malformation, symptoms at onset (hemorrhage, neurological deficit, hydrocephalus, incidental, and heart failure), type of venous drainage and the long-term outcome.ResultsOne hundred and fifteen children were included. Autosomal dominant variants were identified in 39% of patients. The most frequent variant affected was the RASA1 gene (25%) followed by EPHB4 (8%) and the HHT-associated genes (5%). HHT gene variants were only observed in pial arteriovenous fistula not draining into the vein of Galen; on the contrary, EPHB4 variants were only seen in genuine vein of Galen aneurysmal malformation. RASA1 variants were identified in all types of shunts.ConclusionsEPHB4 variants seem specific to the vein of Galen aneurysmal malformation, RASA1 variants are associated with either pial arteriovenous fistulas or with genuine VGAM and HHT gene variants seem specific to pial arteriovenous fistulas. The genetic data helps to classify these malformations and to guide treatment toward lowest risk of post-operative cerebral ischemic-hemorrhagic complications.

In October 2021, a 51-year-old woman developed a skin rash. Abdominal computed tomography revealed a large splenic artery aneurysm and an intrahepatic portovenous shunt. As her splenic artery aneurysm was at risk of rupture, she was referred to the Kindai University Hospital and underwent coiling surgery. In October 2023, approximately two years after she had been initially referred, contrast-enhanced ultrasound revealed findings suggestive of focal nodular hyperplasia. No reports have confirmed the occurrence of liver masses in patients with hereditary hemorrhagic telangiectasia, which is considered to be an interesting finding when investigating the mechanism of tumor development.

The publication presents a clinical case of hereditary hemorrhagic telangiectasia in a woman of 75 years. In the first part of the article, literature data on the incidence and features of Rundu-Osler-Weber disease are presented, modern diagnostic principles based on the Curaçao criteria(1999) are reviewed, which allow to define the diagnosis as “reliable”, with three criteria, “probable” — with Two criteria (most often the family nature of the disease and spontaneous nasal bleeding) and “doubtful”, with one criterion of the above. Methods of treating hereditaryhemorrhagic telangiectasia are considered, the authors draw attention to the fact that the choice of the method of therapy depends on the degree of damage to the target organ. Symptomatic methods of treatment suggest slight relief for patients, but hereditary hemorrhagic telangiectasiaremains a progressive, severe and potentially life-threatening pathology. The second part of the article presents a clinical observation with late verification of the patient’s P., 75 years of age. The data of medical history, including anamnesis, catamnesis, photographs of macro- andmicro-preparations are given. The presented observation illustrates the severe course of hereditary hemorrhagic telangiectasia, manifested by severe hemorrhagic syndrome, due to vascular malformations, the gradual involvement of internal organs in the pathological process with the formation of arteriovenous shunts, aneurysms. The manifestation of hereditary hemorrhagic telangiectasia in the described clinical case was manifested as abundant nasal, uterine bleeding, skin telangiectasias, followed by involvement in the pathological process of the lungs, organs of the gastrointestinal tract. The authors were able to observe a variant of the course and manifestation of visceral vascular anomalies. This clinical case illustrates the need to take into account the totality of all the symptoms of the disease in hereditary hemorrhagic telangiectasia for early detection of the disease, dynamic observation of the patient and the timely administration of therapy

Rendu–Osler–Weber syndrome or hereditary hemorrhagic telangiectasia (HHT) is a rare systemic disease. Its primary pathogenic expression is multiple arteriovenous malformations (AVM) and severe hypoxia. A case of suspected pulmonary embolism in a 49-year-old male with intestinal, cardiac, and pulmonary HHT affection is reported. Pulmonary AVM could create an apparent mismatch perfusion defect evident upon ventilation and perfusion scan (V/Q scan), leading to misinterpretation. It reinforces the importance between clinics, anatomy, and functional evaluation. Care must be taken when interpreting V/Q scan and the reporting physician must be alert to the possible sources of errors. [ABSTRACT FROM AUTHOR]

Background: Rendu-Osler-Weber disease (Osler's disease) is the most common cause of pulmonary arteriovenous fistula. We report a case of pulmonary arteriovenous fistula associated with Osler's disease that was treated by lobectomy., Case Report: A 44-year-old man with Osler's disease presented with respiratory distress. Computed tomography showed a pulmonary arteriovenous fistula, which had a 26-mm-long diameter in S6 of the left lung. Transcatheter treatment had a high risk of recurrence, and surgery was indicated. The pulmonary arteriovenous fistula was found at the beginning of A6. A6 and the basilar artery were cut together with a stapler. The postoperative course was uneventful, and respiratory distress symptoms improved with no recurrence., Conclusion: We report a case of pulmonary arteriovenous fistula caused by Osler's disease treated by lobectomy. Although transcatheter treatment is the mainstream treatment for pulmonary arteriovenous fistulas, surgical resection may be effective depending on the size of the lesion., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

• Hypophosphatemic osteomalacia may be induced by recurrent ferric infusions. • Increased levels of FGF-23 leading to hypophosphatemia might be involved. • Phosphate levels and bone symptoms should be monitored if recurrent iron infusions. • Discontinuing or switching the iron therapy is the most effective treatment. Osteomalacia is an uncommon, overlooked and debilitating metabolic bone disease with numerous aetiologies. Herein, we report an atypical cause of osteomalacia – intravenous iron therapy. Description of a case report of hypophophatemic osteomalacia induced by ferric carboxymaltose infusions. A 70-year-old male with Rendu-Osler-Weber syndrome requiring repeated infusions of ferric carboxymaltose was admitted for disabling lower limb pain associated with persistent hypophosphatemia (1.6 mg/dL) and increased urinary fractional excretion of phosphate (43%, UP04 = 118.3 mg/dL), serum fibroblast growth factor 23 (324 UA/mL), intact parathyroid hormone (110 pg/mL) and bone alkaline phosphatase (40.1 mcg/L). X-ray and CT of the feet showed severe diffuse bone demineralization. Feet MRI displayed a subchondral fracture of the cuneiform-navicular joints. Spine X-ray revealed dorsolumbar vertebral flattening. Somatostatin receptor PET scan excluded an occult tumor. Bone biopsy with histomorphometry confirmed the presence of osteomalacia. After excluding other causes, a diagnosis of hypophosphatemic osteomalacia induced by frequent ferric carboxymaltose infusions was made. The iron formulation was replaced by saccharated ferric oxide infusions and progressive titration of calcitriol up to 1.5 mg/day and oral disodium phosphate up to 5740 mg/day was started. After 6 months, there was a clear clinical and analytical improvement. Osteomalacia may be a consequence of prolonged hypophosphatemia induced by recurrent ferric infusions, which is an uncommon and neglected bone adverse event of this therapy. Phosphate levels and bone symptoms should be monitored during repetitive iron infusions, maintaining a high level of suspicion for osteomalacia as it is important to identify and treat it in a timely manner, minimizing its severe morbidity. [ABSTRACT FROM AUTHOR]

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events.

Background Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that results in mucocutaneous telangiectasias and arteriovenous visceral malformations. Nasal telangiectasias lead to recurrent epistaxis, which affects up to 96% of patients. Different morphologic classifications and methods of visualization of nasal lesions have been described in the literature. We developed a new method of intraoperative endoscopy based on the intravenous administration of fluorescein. Preliminary data of this technique are reported. Methods After the intravenous administration of sodium fluorescein, an intraoperative fluorescein-guided endoscopy was carried out using photographic customized yellow filters on top of a 0-degree, 4-mm endoscope. Results In 2015, 65 HHT patients underwent surgery for their epistaxis in our institution, and in 7 patients (3 males, 4 females; mean age, 54 years) an intraoperative fluorescein-guided intraoperative nasal endoscopy was performed. No adverse events or complications were observed. Conclusion First impressions regarding the usage of this technique in HHT patients seem to be promising and positive in terms of efficacy and safety. However, further studies with larger cohorts of patients should be performed in order to better investigate the use of this method for diagnostic and surgical purposes in HHT. [ABSTRACT FROM AUTHOR]

Objectives The authors present the guidelines of the French Oto-Rhino-Laryngology – Head and Neck Surgery Society ( Société Française d’Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou : SFORL) concerning specific treatment of epistaxis in Rendu-Osler-Weber disease. Methods A multidisciplinary work-group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members’ individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. Results Rendu-Osler-Weber disease is diagnosed from the presence of at least three of Curaçao's four criteria. In acute epistaxis, bidigital compression is recommended. Embolization is reserved for resistant epistaxis. Non-resorbable nasal packing and cauterization are contraindicated. Patient education is essential. Telangiectasia of the nasal mucosa can be treated by various local means. In the event of insufficient control, systemic administration of tranexamic acid is recommended. [ABSTRACT FROM AUTHOR]

Hereditary haemorrhagic telangiectasia is a rare systemic autosomal dominantly inherited disorder of the fibrovascular tissue with a wide variety of clinical manifestations. Diagnosis is based on the clinical Curaçao criteria or molecular genetic testing. Dilated vessels can develop into telangiectases or larger vascular malformations in various organs, calling for an interdisciplinary approach. Epistaxis and gastrointestinal bleeding can result from these vascular defects. Various conservative and interventional treatments have been described for these conditions. However, no optimal therapy exists. Treatment can become especially difficult due to progressive anaemia or when anticoagulant or anti-thrombotic therapy becomes necessary. Screening for pulmonary arteriovenous malformations (PAVM) should be performed in all confirmed and suspected patients. Treatment by percutaneous transcatheter embolotherapy and antibiotic prophylaxis is normally effective for PAVM. Cerebral or hepatic vascular malformations and rare manifestations need to be evaluated on a case-by-case basis to determine the best course of action for treatment. [ABSTRACT FROM AUTHOR]

The case report of a 20 years young patient is presented, with the diagnosis of moderate hemoptysis who was admitted in the Intensive Care Unit from "Dr. Juan Bruno Zayas Alfonso" Teaching General Hospital in Santiago de Cuba, where multiple tests were carried out whose results allowed to arrive to the definitive diagnosis of Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia. After the indication of other procedures, the patient had a satisfactory clinical course and he was discharged from the institution. [ABSTRACT FROM AUTHOR]

Rendu-Osler-Weber disease (hereditary hemorrhagic teleangiectasia, HHT) is a dominant disorder that leads to multiorgan vascular dysplasia, involving teleangiectasias and arteriovenous malformations of the skin, the nose, lungs, the alimentary tract and the central nervous system. Thromboembolic incidents in patients with HHT occur rarely, however present serious therapeutic challenge. We present a case of 57-year old male patient with HHT and lower extremity deep vein thrombosis, complicated with pulmonary embolism in whom administration of antithrombotic drugs in therapeutic dose resulted in uncontrollable epistaxis. Eventually, embolization of bleeding vessels enabled the therapy with accurate dosage of anticoagulant drug. [ABSTRACT FROM AUTHOR]

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-yearold 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. [ABSTRACT FROM AUTHOR]

Background: Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an autosomal dominant vascular disorder characterized by severe and recurrent nosebleeds, muco-cutaneous telangiectasias, and, in some cases, life-threatening visceral arteriovenous malformations. Ocular abnormalities include conjunctival telangiectasia, arteriovenous fistula, angiectasia, phlebectasia, and angioma. Material and Methods: We describe the ocular abnormalities in 8 patients from a pedigree with hereditary hemorrhagic telangiectasia. This article also reviews and discusses the relevant literature. Results: Five patients (62.5%) had conjunctival telangiectasias and 3 (37.5%) retinal abnormalities, consisting mainly of choriocapillaris atrophy. Conclusions: To the best of our knowledge, this is the first report describing the occurrence of choriocapillaris atrophy in patients affected by hereditary hemorrhagic telangiectasia and belonging to the same pedigree. [ABSTRACT FROM AUTHOR]

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Background Mutations in endoglin (ENG) and activin receptor-like kinase 1 (ALK-1 or ACVRL1) genes are the underlying basis of hereditary haemorrhagic telangiectasia (HHT) types 1 and 2, respectively. Both genes belong to the transforming growth factor-β (TGF-β) receptors superfamily and are expressed in endothelial cells. The current model for HHT is that ENG or ALK-1 haplo-insufficiency affects angiogenesis and predisposes to vascular dysplasia and arteriovenous malformations. Materials and methods Using microarray technology, we compared human umbilical vein endothelial cells (HUVEC) from newborns with ENG or ALK-1 mutations to control cells to search for gene profiles associated with early stages of the disease. Real-time polymerase chain reaction and Western blot analysis were used to validate a subset of the modulated genes and functionally related genes. Results Our results indicate that HHT endothelial cells in vitro display several gene expression disturbances, including genes associated with the activation phase of angiogenesis, with cell guidance and intercellular connections, and also with the TGF-β pathway. Hierarchical clustering using modulated genes enables discrimination between affected and non-affected samples. Conclusion HHT HUVECs display gene modulations which can suggest that ENG and ALK-1 haplo-insufficiency induces compensatory regulatory mechanisms at the expression levels. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic disorder with autosomal dominance and variable penetrance, characterized by epistaxis, telangiectasia and visceral manifestations of the disease. The estimated minimal prevalence is 1/10,000 inhabitants. The diagnosis is established on clinical criteria, and may be further confirmed by the identification of causative mutations in either the ENG or the ACVRL1 gene coding for endoglin and ALK1, respectively. Pulmonary vascular manifestations of HHT include pulmonary arteriovenous malforma- tions (PAVMs; especially in patients with ENG mutations) and less frequently pulmonary hypertension (especially in patients with ACVRL1 mutations). In 15–33% of patients with HHT, PAVMs consist of abnormal communications between pulmonary arteries and pulmonary veins, causing right-to-left shunting, and thus, frequently hypoxemia and dyspnea on exertion, although PAVMs may remain asymptomatic and frequently undiagnosed unless complications occur. PAVMs result in severe and frequent complications often at a young age, which may reveal the diagnosis, e.g. transient ischemic attack and cerebral stroke (10–19% of patients), systemic severe infections and abscesses (including cerebral abscess in 5–19% of patients), and rarely massive hemoptysis or hemothorax. Infections in HHT are related to the right-to-left shunting that bypasses the pulmonary capillaries and facilitates the passage of septic or aseptic emboli into the systemic and especially cerebral circulation, and potentially to minor defects in innate immunity. Treatment of PAVMs based on transcatheter coil vaso-occlusion of the feeding artery significantly decreases right-to-left shunting, hypoxemia and dyspnea on exertion, and reduces the risk of systemic complications. Long-term follow-up is warranted after transcatheter vaso-occlusion of PAVMs due to frequent recanalization of treated PAVMs and development or growth of untreated PAVMs. Patients with HHT should be informed of the risk of PAVM and potentially severe complications occurring in heretofore asymptomatic subjects. All adult patients with HHT should be proposed systematic screening for PAVM, by contrast echocardiography (preceded by anteroposterior chest radiograph) or computed tomography of the chest. Pulmonary hypertension is rare in HHT, and may be due either to systemic arteriovenous shunting in the liver increasing cardiac output or be clinically and histologically indistinguishable from idiopathic pulmonary arterial hypertension. Pulmonary hypertension is detected by systematic examination of right cardiac cavities and tricuspid regurgitation flow at echocardiography, and the diagnosis is established by right heart catheterization. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations. Cutaneous telangiectases are the most obvious sign of this disorder and are not a merely cosmetic problem owing to their risk for bleeding, which may constitute an authentic matter of concern to these patients. Methods: Three patients with type-II HHT disease who presented cutaneous and labial lesions were treated with an intense pulsed light (IPL) system associated with a long-pulsed Nd:YAG laser (Photoderm-Vasculight, Lumenis). Labial lesions were treated with the IPL system and cutaneous lesions were treated with the IPL system and the long-pulsed Nd:YAG laser. All treatments were accomplished on an outpatient basis, without anesthesia. Results: All three patients experienced a reduction in the frequency and severity of bleeding episodes and a great cosmetic improvement, with total lesion clearance. Side effects, such as purpura, hypopigmentation, hyperpigmentation or textural changes, were not observed. Recurrences were not detected after a maximum period of 24 months of follow-up. Conclusion: The combination of an IPL system and a long-pulsed Nd:YAG laser is efficient and safe for the treatment of cutaneous and labial telangiectases in patients with HHT disease and constitutes an important tool in improving their quality of life. [ABSTRACT FROM AUTHOR]

A pulmonary arteriovenous fistula (PAVF) is a rare vascular malformation commonly treated by embolization with coils or balloons to prevent the risk of several serious complications such as cerebral embolism and brain abscess. A 32-year-old female with two PAVFs and neurological ischemic manifestations has been successfully treated by transcatheter embolization of both fistulas using a new device (Amplatzer Vascular Plug). This self-expanding cylindrical nitinol mesh cage with high radial strength allows a chance of relocation until properly positioned. It is preferred to coils or balloons because a large caliber of feeding artery implied high risk of uncontrollable distal embolization. There appear to be no reports in the literature concerning use of this device, which could represent a useful innovative tool in embolotherapies, especially in large vascular areas. [ABSTRACT FROM AUTHOR]

Background and Aim: A new argon plasma coagulation (APC) system was developed to improve the conduction characteristics of existing systems and to achieve a true non-contact procedure. We evaluated the new system in an ex vivo experiment and in two different clinical cases. Methods: Swine gastric walls were cauterized at various current settings and time intervals. The diameter and penetration depth of the cauterized areas were measured. We also describe the use of this method to treat patients with gastric hemorrhagic hereditary telangiectasias and a mucosal gastric cancer. Results: The ex vivo study revealed an improved maintenance of current conduction and greater control of the extent and penetration depth of the cauterization effects on tissue using the new APC system. In the clinical cases, hemorrhagic telangiectasias and an early stage gastric cancer were treated successfully without relapse using the new system. Conclusions: Improved current conduction and controllability of cauterization corresponding to emission time were demonstrated for the new APC. The new system allows expeditious superficial cauterization of a wide area without any contact with tissue. The therapeutic effect appeared favorable compared with previous APC devices for gastrointestinal applications. [ABSTRACT FROM AUTHOR]

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The medical literature provides little information on manifestations of hereditary hemorrhagic telangiectasia (HHT) in children. The presented investigation was initiated to analyze early presenting symptoms in HHT, which should help to make the diagnosis at a young age and thus prevent potential complications from occult visceral arteriovenous malformations (AVM), which have commonly been described in HHT. A series of 15 children and adolescents with a suspicious diagnosis of HHT were examined clinically for typical signs and symptoms of the disorder. If the diagnosis of HHT seemed to be likely, recommendations for non-invasive screening procedures were given. Screening was directed at the detection of occult visceral AVMs. Main outcome measures were the definition of principal signs of HHT in children and adolescents. Family history was positive for HHT in 13 persons. The principal sign of recurrent epistaxis was present in 10/15 individuals and the earliest age of onset with regard to epistaxis was 4 years. Cutaneous vascular lesions were present in 5/15 patients. Screening for AVMs was performed in six individuals and revealed vascular lesions of the brain in two patients and vascular lesions of the lung in two patients. Gastrointestinal hemorrhages were present in one infant. Based on these findings, diagnosis of HHT seemed likely in ten individuals and unlikely in five individuals. Signs and symptoms of HHT in children and adolescents may be discrete, but are detectable at an earlier age than previously thought. Clinical examinations in children from HHT families may help identify candidates who will benefit from molecular genetic testing or screening imaging studies. [ABSTRACT FROM AUTHOR]

Background. Hereditary hemorrhagic telangiectasia is characterized by angiodysplastic lesions. So far, knowledge is limited on the vascular architecture and rate of occult manifestation of telangiectases. Contact endoscopy has not been used for this task before. Methods. Eleven patients with hereditary hemorrhagic telangiectasia were examined with contact endoscopy to identify occult telangiectases. Sixty enoral telangiectases were studied in detail to characterize their architecture. Results. No occult telangiectases could be detected. In most cases, telangiectases consisting of a simple dilated loop were small. In contrast, most of the complex telangiectases were larger. Conclusions. Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not seem to have abnormal vascularization. Simple dilated capillary loops might be precursors of telangiectases with a more complex structure. Contact endoscopy seems to be a promising tool for the in vivo monitoring of therapies and the natural course of vascular disorders in humans and in animal models. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) is a heterogeneous disease that can present with a variety of clinical manifestations. The neurovascular complications of this disease, especially in children, may be potentially devastating. The purpose of this article was to review the therapeutic results of endovascular treatment of neurovascular malformations in children. A total of 31 patients under the age of 16 were included in this retrospective analysis. All children were treated in a single center. Twenty children presented with 28 arteriovenous (AV) fistulae, including seven children with spinal AV fistulae and 14 children with cerebral AV fistulae (one child had both a spinal and cerebral fistulae). Eleven children had small nidus-type AV malformations. All embolizations were performed employing superselective glue injection. Follow-up ranged between 3 and 168 months (mean 66 months). A total of 115 feeding vessels were embolized in 81 single sessions, resulting in a mean overall occlusion rate of the malformation of 77.4% (ranging from 30 to 100%). Two of 31 patients (6.5%) died as a direct complication of the embolization procedure; two patients (6.5%) had a persistent new neurological deficit; eight patients (26.7%) were clinically unchanged following the procedure; in 13 patients (41.9%) an amelioration of symptoms but no cure could be achieved; and six patients (19.4%) were completely asymptomatic following the endovascular procedure. In the surviving patients morphological complete occlusion was possible in twelve patients (38.7%); therapy is still not completed in six patients. Since the natural history of neurovascular manifestations of HHT in children is associated with high morbidity and mortality, therapeutic intervention is mandatory. In most instances a morphological target can be identified; therefore, even partial and staged treatment can be performed. Our results demonstrate that in 27/31 patients these targeted interventions resulted in stabilizing the disease, ameliorating the symptoms or even complete resolution. The endovascular approach employing glue as the embolizing agent represents a safe and efficient way to control the neurovascular phenotypes of HHT. [ABSTRACT FROM AUTHOR]

In this report we described a case of a cerebral abscess that developed in presence of asymptomatic pulmonary arteriovenous malformations (PAVMs) in a 53-year-old woman with hereditary hemorrhagic telangiectasia (HHT). The brain abscess was aspirated with good clinical result and the arterio venous fistulae qualified for transcatheter embolo therapy. Each patient suspected to suffer from HHT should be diagnosed for the presence of viscera! vascular malformations. Most of them are found in the lungs, liver and brain. Early diagnosis and treatment of PAVM prevent the occurrence of severe neurological complications such as brain stroke or brain abscess. Cases of a cerebral abscess in adults of unexplained etiology should raise the suspicion of an asymptomatic PAVM. [ABSTRACT FROM AUTHOR]

: BackgroundIntracranial varices are rare and most are associated with vein of Galen arteriovenous malformations (AVM) or fistulas (AVF).: DescriptionA 43-year-old left-handed man presented with right hemihypesthesia and spastic gait. Neuroradiological examination revealed a spinal AVF and a giant intracerebral varix associated with a high-flow pial AVF. He had recurrent episodes of nasal bleeding, which were also confirmed in his mother''s medical history, and telangiectases in the tip of his tongue and fingers. He was diagnosed with Rendu-Osler-Weber disease. After resection of the spinal AVF that produced his symptoms, we surgically exposed and obliterated the giant varix and AVF under intra- and postoperative hypotension and mild barbiturate therapy. The arteriovenous shunt was completely obliterated without hyperperfusion of the surrounding brain.: ConclusionThis is an extremely rare case of Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF that did not involve the vein of Galen. [Copyright &y& Elsevier]

This study describes the imaging features of the intrahepatic portohepatic venous (PHV) shunt, which is a potential cause of portosystemic encephalopathy in Rendu-Osler-Weber disease. Six patients with Rendu-Osler-Weber disease (two men, four women; age range 42-73 years) were retrospectively studied. There were two from one family and three from another family. Of these patients, one was diagnosed with definitive portosystemic encephalopathy because of a psychiatric disorder. We retrospectively reviewed the radiological examinations, including abdominal angiography (n=6), three-phase dynamic helical computed tomography (CT; n=3), and conventional enhanced CT (n=1). In one patient, CT during angiography and CT angioportography were also performed. Evaluation was placed on the imaging features of intrahepatic PHV shunts. On angiography, intrahepatic PHV shunts showing multiple and small shunts <5 mm in diameter in an apparent network were detected in all patents. In two patients, a large shunt with a size of either 7 or 10 mm was associated. These intrahepatic PHV shunts were predominantly distributed in the peripheral parenchyma. Intrahepatic PHV shunts would be characterized by small and multiple shunts in an apparent network on the periphery with or without a large shunt. [ABSTRACT FROM AUTHOR]

Hepatic involvement in hereditary hemorrhagic telangiectasia is infrequent and poorly studied. We describe a 62-year-old woman with Rendu-Osler-Weber (ROW) disease and recurrent gastrointestinal bleeding episodes. Blood chemistry was consistent with the presence of cholestasis. Imaging studies revealed prominent vascular abnormalities in the liver and focal intrahepatic bile duct dilatations. The intimate anatomic relationship of the vascular abnormalities to the dilated bile ducts suggests that external vascular compression could have caused their dilatation. To our knowledge, this mechanism has not been proposed in the literature as a possible explanation of biliary dilatation in patients with ROW. [ABSTRACT FROM AUTHOR]

To date much of the recent work on pathological angiogenesis has focused on inflammatory diseases, diabetes and cancer in particular. Hereditary hemorrhagic telangiectasia or Rendu-Osler-Weber disease provides an example of the genetic disorder of angiogenesis in which a multisystemic angiodysplasia is responsible for severe hemorrhage. The disease pathogenesis is partially explained by a defect in the TGF-β signaling system, although in more recent works a possible role of other vascular growth factors has been proposed. This paper provides a model of an aberrant angiogenesis in which multiple vascular growth factors could be involved in a diffuse angiodysplasia.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Hepatic encephalopathy is suspected in non-cirrhotic cases of encephalopathy because the symptoms are accompanied by hyperammonaemia. However, the cause of the large portal-systemic shunt formation observed in these cases is not clear, as cirrhosis and portal hypertension are absent. The frequency of such cases reported in the literature is increasing with progress and spread of abdominal imaging diagnostic techniques. Some cases have been misdiagnosed as psychiatric diseases (dementia, depression and others) and consequently patients have been hospitalized in psychiatric institutions or geriatric facilities. Some paediatric cases have also been misdiagnosed. Therefore, the importance of accurate diagnosis of this disease should be strongly emphasized. Some paediatric cases have also been misdiagnosed. When psychoneurological symptoms are suggestive of hepatic encephalopathy but objective and subjective symptoms or abnormal values of liver function tests are not sufficiently indicative of liver cirrhosis, portal-systemic encephalopathy should be suspected. Abnormal angiograms of the portal vein, superior mesenteric vein or splenic vein are conclusive evidence of portal-systemic encephalopathy. Transrectal portal scintigraphy also provides information useful for detection of shunts and a quantitative estimation of shunt index. We classified the disease into five types based on whether the shunt is formed inside or outside the liver. Type I (intrahepatic type) designates cases in which shunts are located between the portal and systemic veins. Type II designates a type of intra/extrahepatic shunt that originates from the umbilical part of the portal vein and serpentines in the liver, then leaves the liver. Type III (extrahepatic type) occurs most frequently. Type IV (extrahepatic) is accompanied by shunts similar to those in type III, but hepatic pathology presents as idiopathic portal hypertension. Type V (extrahepatic) represents the congenital absence of the portal vein, where the superior mesenteric vein joins the intrahepatic inferior vena cava or the left renal vein. The prevalence of each type in our country was examined by a nationwide investigation. In addition to the conventional diet or drug treatments, obliteration by less invasive interventional radiology using a metallic coil and ethanol has recently been used more frequently than surgical occlusion of shunts. Shunt-preserving disconnection of portal and systemic circulation and partial splenic artery embolization are also performed. International investigation of the disease status and establishment of diagnostic and therapeutic methods for the disease are awaited and investigation of long-term prognosis after therapy is also necessary. [ABSTRACT FROM AUTHOR]

A 55-year-old woman with Rendu-Osler-Weber disease underwent surgical resection of a pulmonary arteriovenous fistula deriving from right middle lobe vessels. The fistula was 10 × 6 × 5 cm, to our knowledge, the largest ever reported. Although the major part of the fistula was well exposed through median sternotomy, extensive bleeding during dissection of feeding and drainage vessels precluded safe dissection. Total cardiopulmonary bypass was therefore used to divert the pulmonary blood flow. Anatomy was clearly delineated and connecting vessels were safely suture-closed from within the fistula without sacrificing the right middle lobe vein, which might have been damaged without cardiopulmonary bypass. The postoperative course was uneventful, and no complications associated with cardiopulmonary bypass occurred. [ABSTRACT FROM AUTHOR]

A patient with hereditary hemorrhagic telangiectasia and diffuse intrahepatic arteriovenous fistulas developed secondary high-output ventricular failure and pulmonary hypertension. A serial staged hepatic arterial coil embolization was performed with long-term resultant haemodynamic and clinical improvement. The methods of this procedure and related complications are discussed. [ABSTRACT FROM AUTHOR]