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BACKGROUND: Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for organ vascular malformations including arteriovenous malformations (AVMs) in the brain and lungs. North American HHT Centers of Excellence (CoEs) routinely screen for brain and lung AVMs, with the primary goal of detecting AVMs which can be treated before complications arise. Current international HHT guidelines provide recommendations for initial screening for brain and lung AVMs among children and adults with the disease, but rescreening recommendations are not comprehensively addressed and have not been reported. We determined current rescreening practices for brain and lung AVMs for children and adults with HHT among North American HHT CoEs. METHODS: We surveyed North American HHT CoEs regarding rescreening practices for new brain and lung AVMs in children and adults with initial negative screening. RESULTS: All thirty CoEs responded; 28 regarding pediatric (93.3%) and 30 (100%) regarding adult HHT care. The median duration of practice experience in HHT was 11.5 (range 3-30) years for providers of pediatric HHT care and 11.5 (range 3-35) years for providers of adult HHT care. The median number of patients followed at each CoE was 60 for children (range 8-500) and 375 for adults (range 30-1500). 25/28 CoEs (89.3%) reported rescreening children for brain AVMs, most commonly with enhanced MRI (21/25, 84%). 25 CoEs rescreen children for lung AVMs, most commonly every 5 years (15/25). Only 4/30 CoEs (13.3%) rescreen adults for brain AVMs. 26/30 CoEs (86.7%) reported rescreening adults for lung AVMs, most commonly every 5 years (18/26, 69.2%). CONCLUSIONS: Most HHT CoEs routinely rescreen children for brain and lung AVMs and adults for lung AVMs when initial screening is negative, but adults are infrequently rescreened for brain AVMs. Long-term data regarding risk for new brain and lung AVMs are required to establish practice guidelines for rescreening.

Endoglin (ENG) mutation causes type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22αCre leads to AVM development in the brain and other organs. We hypothesized that an increase in Eng- negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon-improved cre (icre), which is more potent in recombination of the floxed alleles than the wild-type (WT) cre. R26RCreER;Engf/f mice that have a Rosa promoter driving and tamoxifen (TM)-inducible WT cre expression globally, and PdgfbiCreER;Engf/f mice that have a Pdgfb promoter driving and TM-inducible icre expression in ECs were treated with three intra-peritoneal injections of TM (2.5 mg/25 g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that icre caused more Eng deletion in the brain, indicated by a lower level of Eng proteins (p < 0.001) and fewer Eng-positive ECs (p = 0.01) than mice with WT cre. Mice with icre-mediated Eng deletion have more abnormal vessels (p = 0.02), CD68+ macrophages (p = 0.002), and hemorrhage (p = 0.04) and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that has not been detected in WT cre mice before. RNA-seq analysis showed that 8 out of the 10 top upregulated pathways identified by gene ontology (GO) analysis are related to inflammation. Therefore, the increase in Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng-negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

The article discusses a rare case of a slow-flow venous malformation (VM) in the vulva of an 8-year-old girl. The girl presented with a bluish swelling in the external genitalia, which was diagnosed as a VM through clinical examination and ultrasound with Doppler study. Sclerotherapy with bleomycin injection was used as a treatment, resulting in a 90% resolution after 3 months and complete resolution after 6 months. The article emphasizes the importance of early diagnosis and management of VMs, highlighting sclerotherapy as an effective treatment option with minimal adverse events. [Extracted from the article]

Background: Lung transplantation is a viable lifesaving option for patients with diffuse pulmonary arteriovenous malformations (AVMs). We present a case of diffuse pulmonary AVMs associated with juvenile polyposis and hereditary hemorrhagic telangiectasia (JP-HHT) that was successfully managed by lung transplantation. Case presentation: A 19-year-old woman developed severe hypoxemia due to pulmonary AVMs diagnosed at 4 years of age. She also had epistaxis, hemangioma of the tongue, and numerous polyps in the gastrointestinal tract, leading to the JP-HHT diagnosis. Although she had undergone transcatheter embolization for pulmonary AVMs four times, all lesions became recanalized, and her hypoxemia never improved. She also had hepatic AVMs that did not result in portal hypertension or required any interventions. She underwent bilateral lung transplantation from a brain-dead donor at 3 years after registration. Given that she had severe hypoxemia caused by intrapulmonary shunting, venoarterial extracorporeal membrane oxygenation (V-A ECMO) support was initiated from the femoral vessels under local anesthesia. Then, she was anesthetized and intubated. Peripheral V-A ECMO was switched to central cardiopulmonary bypass during the transplant procedure to prevent persistent hypoxia of the upper body and thromboembolic event due to severe polycythemia. The total graft ischemic time was > 11 h, which resulted in ischemia–reperfusion injury immediately after transplantation. Furthermore, the patient's postoperative course was complicated by acute cellular rejection and right heart failure due to hepatic AVM progression. She was finally discharged home without oxygen therapy on postoperative day 68. At 1-year post-transplantation, she is currently enjoying college life. However, she still has to undergo periodic endoscopic examinations to monitor her numerous polyps, which are known to carry a risk of cancer development. Conclusions: Lung transplantation can be a viable treatment option for diffuse pulmonary AVMs in patients with JP-HHT. However, meticulous perioperative management is mandatory to prevent the development of multiple organ disorders. [ABSTRACT FROM AUTHOR]

Background: Hereditary hemorrhagic telangiectasia (HHT) is characterized by telangiectasia and larger vascular malformations. Liver malformations are the most frequent visceral involvement including the presence of portosystemic malformations (PSM) that can cause hepatic encephalopathy. Minimal hepatic encephalopathy (mHE) is characterized by alterations of brain function in neuropsychological or neurophysiological tests and decreases quality of life. The evidence of mHE in HHT patients is scarce. The aim of this study is to assess the prevalence and health impact of mHE in patients with and without PSM. Methods: We performed a cross-sectional observational study in a cohort of patients from an HHT referral unit. Adult patients with definite HHT and PSM and age and sex matched HHT controls without PSM (1:1) were included. Baseline clinical, imaging and laboratory tests and different neuropsychological tests for the screening of mHE were compared between both groups. Results: Eighteen patients with PSM and 18 controls out of 430 HHT patients were included. Patients with PSM showed higher prevalence of attention disturbances (50% vs. 11.1%, p = 0.027), falls during last 12 months (22.2% vs. 5.6%, p = 0.338), sleep disorders (50% vs. 16.7%, p = 0.075) and a worst performance in s-ANT1 test (14 vs. 19.5 points score, p = 0.739) than HHT controls. Conclusions: HHT patients with PSM showed higher attention difficulties than HHT controls, though both PSM and HHT controls showed findings of mHE. Specific neuropsychological tests for early detection of mHE should be considered in HHT patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate patients with hereditary hemorrhagic telangiectasia (HHT) for the potential reperfusion of pulmonary arteriovenous malformations (PAVM) treated by catheter embolization using coils or embolization plugs and to analyze causes of possible reperfusion in order to further improve treatment. Methods: This retrospective study analyzed the data of 345 patients who underwent screening for pulmonary arteriovenous malformations in cases of suspected or confirmed HHT (Osler's disease). Of these, 118 patients with PAVM that underwent catheter embolization and had at least one follow-up study were included in our study and evaluated for potential reperfusion. Screening and follow-up for the detection of PAVM was performed by dynamic and high-resolution contrast-enhanced magnetic resonance angiography (MRA). The average follow-up time was 6.2 years. Results: Reperfusion was detected in 43 of 118 patients at follow-up. Thirty-five of these patients showed a recanalization of the treated vessel and in eleven patients the formation of collateral vessels resupplying the PAVM were identified as the cause of reperfusion. The average time between embolization and detected reperfusion was 5.6 years. The recanalization of both coils and plugs was observed. The recanalization of coils could be attributed in most cases to an insufficient packing density of the implanted coils. In addition, an enlarged diameter of the feeding artery was confirmed as a risk factor for reperfusion. Conclusions: As the reperfusion of embolized pulmonary arteriovenous malformations can occur after a long time interval post-treatment, regular lifelong follow-up studies after embolization are essential to detect reperfusion at an early stage and avoid serious complications like a brain abscess or stroke through prompt re-embolization. After coil embolization, attention should be paid to sufficiently dense packing to achieve adequate and permanent occlusion. [ABSTRACT FROM AUTHOR]

Background/Objectives: Angiogenesis is involved in the pathogenesis of hereditary hemorrhagic telangiectasia (HHT). VEGF, ANG2, TGFβ1, and ENG are the most studied angiogenic factors, but their clinical significance in blood samples is still not completely defined. The genetic study of HHT mutations is the test of choice for diagnosing the disease, but this route is expensive, and the causative mutation is not found in up to 10% of cases. Therefore, the use of angiogenic biomarkers could facilitate a cheaper and easier approach to the diagnosis of HHT. To determine the diagnostic and prognostic value of the VEGFA, TGFβ1, ANG2, and ENG plasmatic concentrations in patients with HHT. Methods: All the participants were clinically evaluated and the concentrations of these angiogenic factors were measured using MILLIPLEX®MAP immunoassays in plasma samples collected from 44 patients with HHT and 19 controls. To evaluate the diagnostic validity of these parameters, we estimated the maximum Youden index of the ROC curve and evaluated their diagnostic value using multiple logistic regression. Results: Patients with HHT had increased blood levels of TGFβ1 and decreased ENG compared to the control group. We could not identify any angiogenic markers related to the clinical severity or epistaxis. TGFβ1 and ENG exhibited a higher discriminant capacity for HHT, especially patients with HHT1, and it was possible to develop signatures of these factors with diagnostic value. Conclusions: We identified several angiogenic factors that may be important diagnostic biomarkers for HHT and propose that the combination of TGFβ1 and ENG could represent a signature with diagnostic value for this disease. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic brain micro-arteriovenous malformations (micro-AVMs) are considered to constitute a relatively significant portion of pediatric AVMs, though they are often associated with a low bleeding rate, as seen in hereditary hemorrhagic telangiectasia, which frequently involves multiple micro-AVMs. Case summary: We present a rare case of a 10-year-old girl with multiple hemorrhagic micro-AVMs. Intraoperative findings during the emergency operation for hematoma evacuation and post-operative superselective angiography highlighted the unique angioarchitecture of three micro-AVMs (two lesions in the superficial areas and one lesion in the deep-seated area) and the atypical bleeding source due to the complex congestive venous drainage system. One micro-AVM was successfully occluded by a transarterial emboliozation, and remaining two micro-AVMs underwent gamma knife irradiation as a salvage therapy. Conclusion: Superselective angiography is crucial for detecting micro-AVMs, offering detailed insights into small, localized abnormal vascular drainage systems, and guiding therapeutic strategy. Additionally, micro-AVM-associated unique vascular hypersensitivity, such as vasospasm, requires careful consideration, as invasive procedures may significantly alter the visibility of the entire micro-AVM network. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal blood vessel formation, leading to recurrent epistaxis, cutaneous and mucosal telangiectases, and visceral arteriovenous malformations (AVMs). Hepatic involvement may result in complications such as high-output heart failure, portal hypertension, and biliary ischemia. We report an uncommon case of ischemic cholecystitis in a patient with HHT. Methods: A 57-year-old male with HHT type 1, including gastric telangiectases and hepatic AVMs, presented with anemia, melena, epigastric pain, and a history of recurrent epistaxis. Imaging revealed gastric telangiectases and liver AVMs, consistent with HHT. Following an episode of severe epistaxis and aspiration pneumonia, the patient developed right upper quadrant pain. Results: Abdominal CT and ultrasound identified thickening of the gallbladder wall, segmental enhancement defects, and a perivesicular fluid effusion, suggestive of acalculous cholecystitis. A laparoscopic cholecystectomy was performed, revealing ischemic cholecystitis with necrotic gallbladder walls. Conclusions: This case underscores the potential for ischemic cholecystitis in patients with HHT and liver involvement, particularly under conditions of acute hemodynamic instability. Clinicians should be vigilant in recognizing this rare complication, especially in patients with established HHT and associated hepatic vascular anomalies. [ABSTRACT FROM AUTHOR]

The article from the Indian Dermatology Online Journal provides a comprehensive review of the cutaneous manifestations associated with cerebrovascular accidents (CVA). Various skin conditions such as Anti Phospholipid Antibody Syndrome, Sneddon syndrome, vasculitis, Scleromyxedema, and others are discussed in relation to their direct or indirect association with CVA. Additionally, the article highlights the impact of certain drugs used in CVA treatment on the skin, such as heparin-induced thrombocytopenia and warfarin necrosis. The review aims to fill the gap in literature regarding the dermatological features of stroke. [Extracted from the article]

This document is an editorial announcing the new Journal Impact Factor (IF) for Seminars in Thrombosis and Hemostasis (STH) for the year 2023. The 2023 IF for STH is 3.6, which is a decrease from previous years. The decrease in IF is attributed to changes in calculation methods, the inclusion of additional journals, and the impact of the COVID-19 pandemic. The document also highlights the impact of COVID-19 on research and publishing, with STH publishing four issues focused on COVID-19. It emphasizes that the IF is just one measure of journal quality and provides rankings of STH in relevant categories. The document lists the most highly cited papers contributing to the 2023 IF, many of which are related to COVID-19. The inclusion of Young Investigator winners and original studies on the list is noted. The article also discusses the success of select original studies published in STH and the support provided for the Young Investigator Awards. It provides information on submission and acceptance rates for unsolicited manuscripts, as well as data on the number of issues, pages, and cumulative count of papers published in STH. The article concludes by celebrating the 50th anniversary of STH and expressing hopes for its continued success. [Extracted from the article]

The article announces the winners of the Eberhard F. Mammen Young Investigator Awards, which recognize outstanding presentations or meeting abstracts in the fields of thrombosis and hemostasis. The winners receive a cash prize and are selected by the Senior Editors of Seminars in Thrombosis & Hemostasis. The article also provides a list of previous award winners and their resulting publications. Additionally, the article lists various articles published in the journal Seminars in Thrombosis and Hemostasis, covering topics such as primary immune thrombocytopenia, heparin-induced thrombocytopenia, hemophilia, von Willebrand disease, platelet function, and anticoagulant therapy. The articles offer insights into the causes, diagnosis, and treatment of these conditions. [Extracted from the article]

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is characterized by telangiectasia and larger vascular malformations. Liver malformations are the most frequent visceral involvement including the presence of portosystemic malformations (PSM) that can cause hepatic encephalopathy. Minimal hepatic encephalopathy (mHE) is characterized by alterations of brain function in neuropsychological or neurophysiological tests and decreases quality of life. The evidence of mHE in HHT patients is scarce. The aim of this study is to assess the prevalence and health impact of mHE in patients with and without PSM. Methods We performed a cross-sectional observational study in a cohort of patients from an HHT referral unit. Adult patients with definite HHT and PSM and age and sex matched HHT controls without PSM (1:1) were included. Baseline clinical, imaging and laboratory tests and different neuropsychological tests for the screening of mHE were compared between both groups. Results Eighteen patients with PSM and 18 controls out of 430 HHT patients were included. Patients with PSM showed higher prevalence of attention disturbances (50% vs. 11.1%, p = 0.027), falls during last 12 months (22.2% vs. 5.6%, p = 0.338), sleep disorders (50% vs. 16.7%, p = 0.075) and a worst performance in s-ANT1 test (14 vs. 19.5 points score, p = 0.739) than HHT controls. Conclusions HHT patients with PSM showed higher attention difficulties than HHT controls, though both PSM and HHT controls showed findings of mHE. Specific neuropsychological tests for early detection of mHE should be considered in HHT patients.

Background Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disorder that primarily affects the vasculature and exhibits a broad spectrum of clinical manifestations. There is a paucity of detailed literature on its clinical characteristics. Objective This study aims to deepen the understanding of HHT's clinical aspects by documenting the presentations, management, and outcomes of 30 patients diagnosed with the condition, thereby improving recognition and treatment approaches among healthcare professionals. Methods A retrospective review was conducted on 30 HHT cases treated at Peking Union Medical College Hospital from December 2012 to September 2023, focusing on analyzing their clinical features, therapeutic interventions, and follow-up outcomes. Results The study included 8 males and 22 females, with a mean onset age of 20.0 years (range 10.5-34.0 years) and an average disease duration of 19.5 years (range 7.8-26.0 years). Epistaxis was universally present (100.0%), skin and mucosal telangiectasia were noted in 27 patients (90.0%), and 28 (93.3%) exhibited involvement of internal organs, including liver in 24 (80.0%), lungs in 15 (50.0%), gastrointestinal tract in 5 (16.7%), and brain in 3 (10.0%). Additionally, pulmonary hypertension was observed in 17 (56.7%) and iron deficiency anemia in 15 (50.0%). Genetic analysis in 15 patients identified ACVRL1 mutations in 12, ENG mutations in 2, and one patient with both. Beyond routine symptomatic care, some patients underwent targeted medical or interventional treatments, with the majority showing clinical improvement. Conclusion HHT is a systemic disorder affecting multiple organs, with frequent liver and occasional brain involvement. It commonly leads to serious complications such as pulmonary hypertension and iron deficiency anemia. Detailed patient history, thorough examinations, targeted screening of visceral vessels, and genetic testing are essential for early diagnosis and effective management in suspected cases.

Abstract Background Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for organ vascular malformations including arteriovenous malformations (AVMs) in the brain and lungs. North American HHT Centers of Excellence (CoEs) routinely screen for brain and lung AVMs, with the primary goal of detecting AVMs which can be treated before complications arise. Current international HHT guidelines provide recommendations for initial screening for brain and lung AVMs among children and adults with the disease, but rescreening recommendations are not comprehensively addressed and have not been reported. We determined current rescreening practices for brain and lung AVMs for children and adults with HHT among North American HHT CoEs. Methods We surveyed North American HHT CoEs regarding rescreening practices for new brain and lung AVMs in children and adults with initial negative screening. Results All thirty CoEs responded; 28 regarding pediatric (93.3%) and 30 (100%) regarding adult HHT care. The median duration of practice experience in HHT was 11.5 (range 3–30) years for providers of pediatric HHT care and 11.5 (range 3–35) years for providers of adult HHT care. The median number of patients followed at each CoE was 60 for children (range 8–500) and 375 for adults (range 30–1500). 25/28 CoEs (89.3%) reported rescreening children for brain AVMs, most commonly with enhanced MRI (21/25, 84%). 25 CoEs rescreen children for lung AVMs, most commonly every 5 years (15/25). Only 4/30 CoEs (13.3%) rescreen adults for brain AVMs. 26/30 CoEs (86.7%) reported rescreening adults for lung AVMs, most commonly every 5 years (18/26, 69.2%). Conclusions Most HHT CoEs routinely rescreen children for brain and lung AVMs and adults for lung AVMs when initial screening is negative, but adults are infrequently rescreened for brain AVMs. Long-term data regarding risk for new brain and lung AVMs are required to establish practice guidelines for rescreening.

Epistaxis greatly affects patients with hereditary hemorrhagic telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis. This multicenter phase 2 randomized, placebo-controlled, double-blind trial was conducted between June 2020 and February 2023. Inclusion criteria were being over 18 years old and having a confirmed HHT diagnosis with an epistaxis severity score greater than 4. Sixty patients were randomized to receive either nintedanib or placebo for 12 weeks with a 12 week follow-up. The primary endpoint was the proportion of patients achieving a reduction of at least 50% in mean monthly epistaxis duration comparing the 8 weeks before treatment to the last 8 weeks of treatment. Main secondary outcomes included monthly duration and frequency of epistaxis and hemoglobin levels. Of the 60 randomized patients, 56 completed the trial. Thirteen patients (43%) in the nintedanib group vs 8 (27%) in the placebo group met the primary endpoint (p = 0.28). We observed a significant decrease in median epistaxis (57% vs 27%, p = 0.013) and a significant increase in median hemoglobin levels (+ 18 vs − 1 g/L, p = 0.02) in the nintedanib vs the placebo group. Although we did not achieve our primary outcome, we observed a significant reduction in epistaxis duration and a significant increase in hemoglobin levels in patients treated with nintedanib. This supports the efficacy of nintedanib, and further studies are needed. [ABSTRACT FROM AUTHOR]

Hemodynamic cues are thought to control blood vessel hierarchy through a shear stress set point, where flow increases lead to blood vessel diameter expansion, while decreases in blood flow cause blood vessel narrowing. Aberrations in blood vessel diameter control can cause congenital arteriovenous malformations (AVMs). We show in zebrafish embryos that while arteries behave according to the shear stress set point model, veins do not. This behavior is dependent on distinct arterial and venous endothelial cell (EC) shapes and sizes. We show that arterial ECs enlarge more strongly when experiencing higher flow, as compared to vein cells. Through the generation of chimeric embryos, we discover that this behavior of vein cells depends on the bone morphogenetic protein (BMP) pathway components Endoglin and Alk1. Endoglin (eng) or alk1 (acvrl1) mutant vein cells enlarge when in normal hemodynamic environments, while we do not observe a phenotype in either acvrl1 or eng mutant ECs in arteries. We further show that an increase in vein diameters initiates AVMs in eng mutants, secondarily leading to higher flow to arteries. These enlarge in response to higher flow through increasing arterial EC sizes, fueling the AVM. This study thus reveals a mechanism through which BMP signaling limits vein EC size increases in response to flow and provides a framework for our understanding of how a small number of mutant vein cells via flow-mediated secondary effects on wildtype arterial ECs can precipitate larger AVMs in disease conditions, such as hereditary hemorrhagic telangiectasia (HHT). [ABSTRACT FROM AUTHOR]

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal vascular dysplasia characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in solid organs. The Curaçao criteria and/or detection of ALK1, ENG, and SMAD4 gene mutations are used for diagnosis. Juvenile Polyposis Syndrome (JPS) is diagnosed according to the number and localization of juvenile polyps, and family history of JPS. Both entities have a low prevalence. Mutation of SMAD4 leads to a combined syndrome of these two conditions called HHT-JPS Overlap Syndrome. We aim to describe the clinical characteristics associated with this condition focusing on long term follow up and review of the literature. A cross-sectional descriptive study of HHT-JPS cases from an HHT Institutional Registry was designed. Patients were eligible for this case series if they fulfilled both HHT and JPS diagnostic criteria and/or mutation on SMAD4. A comprehensive review was conducted on the clinical phenotype associated with HHT and its gastrointestinal involvement. Fourteen patients from eleven families in 788 previously HHT-diagnosed patients met the inclusion criteria. The ages ranged between 25 and 70 years old and 12 were females. In addition to the typical signs/symptoms of HHT, two distinct phenotypes were observed. Nine patients predominantly exhibited initially upper, while five showed predominantly initially lower gastrointestinal involvement. Numerous musculoskeletal and cardiovascular anomalies were also identified. The observed phenotypic diversity, particularly in gastrointestinal involvement, underscores the need for tailored clinical approaches. Comprehensive assessments identified associated musculoskeletal and cardiovascular anomalies, emphasizing the systemic nature of HHT-JPS. [ABSTRACT FROM AUTHOR]

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members. Case presentation We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism. Conclusions When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn’t be missed in the evaluation of embolic sources.

Background/Objectives: To propose criteria for retreating previously embolized PAVMs and determining the effectiveness of the criteria to prevent paradoxical embolization. Methods: A retrospective review of patients with PAVMs treated at a single HHT center of excellence between 1 January 2013, and 10 September 2023, was performed. Patients with PAVM recurrence were either retreated or observed based on the following criteria for PAVM reintervention: 1. Embolic device(s) not creating a sufficiently dense matrix, such that a channel through them may be >/ 2 mm; 2. Accessory feeding artery or pulmonary collateral >/ 2 mm; 3. Hemoptysis in a patient with no other explanation. Results: A total of 438 PAVMs were treated in 151 patients, including 106 patients with definite, 14 possible, and 31 doubtful HHT. Post-embolization PAVM recurrence occurred in 36 patients (36/151, 23.8%), including 15 patients (15/151, 9.9%) with 22 PAVMs (22/438, 5.0%) meeting criteria for reintervention. A total of 21 patients (21/151, 13.9%) with recurrence did not meet reintervention criteria and were therefore observed. Pre-treatment paradoxical embolization occurred in 36 patients (36/151) for a lifetime prevalence rate of 23.7%. Post-treatment paradoxical embolization did not occur in any patients following PAVM embolization (0/151). There was one case of iatrogenic paradoxical embolization in a patient being treated for systemic collateral reperfusion and hemoptysis. However, this was not included given that it was not a spontaneous event. Conclusions: Utilizing modern embolization techniques and devices, the proposed reintervention criteria, and screening intervals, paradoxical embolizations can be effectively prevented in patients with PAVMs. [ABSTRACT FROM AUTHOR]

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members. Case presentation: We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism. Conclusions: When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn't be missed in the evaluation of embolic sources. [ABSTRACT FROM AUTHOR]

This document contains summaries of various research studies in the field of neurosurgery and endovascular treatment. The studies cover a range of topics, including stroke treatment, aneurysm treatment, and other neurovascular conditions. The summaries provide insights into different treatment approaches, outcomes, and potential advancements in the field. They offer an overview of current research in neurosurgery and neurointerventional procedures. [Extracted from the article]

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs) in internal organs. HHT is caused by inheritance of a loss of function mutation in one of three genes. Although individuals with HHT are haploinsufficient for one of these genes throughout their entire body, rather than exhibiting a systemic vascular phenotype, vascular malformations occur as focal lesions in discrete anatomic locations. The inconsistency between genotype and phenotype has provoked debate over whether haploinsufficiency or a different mechanism gives rise to the vascular malformations. We previously showed that HHT-associated skin telangiectases develop by a two-hit mutation mechanism in an HHT gene. However, somatic mutations were identified in only half of the telangiectases, raising the question whether a second-hit somatic mutation is a necessary (required) event in HHT pathogenesis. Here, we show that another mechanism for the second hit is loss of heterozygosity across the chromosome bearing the germline mutation. Secondly, we investigate the two-hit mutation mechanism for internal organ AVMs, the source of much of the morbidity of HHT. Here, we identified somatic molecular genetic events in eight liver telangiectases, including point mutations and a loss of heterozygosity event. We also identified somatic mutations in one pulmonary AVM and two brain AVMs, confirming that mucocutaneous and internal organ vascular malformations undergo the same molecular mechanisms. Together, these data argue that bi-allelic loss of function in an HHT gene is a required event in the pathogenesis of HHT-associated vascular malformations. Hereditary hemorrhagic telangiectasia is an autosomal-dominant disorder consisting of focal vascular malformations. We show that some malformations acquire a somatic mutation in trans with the germline mutation, leading to bi-allelic gene loss. Others exhibit loss of heterozygosity across the chromosome bearing the germline mutation, supporting a two-hit mutation mechanism of pathogenesis. [ABSTRACT FROM AUTHOR]

A 40-year-old man presented with erythematous changes on his lower legs, diagnosed as telangiectasia macularis eruptiva perstans (TMEP). Despite initial concerns of systemic mastocytosis due to mast cell increase, further investigations ruled out this diagnosis. The final diagnosis was cutaneous collagenous vasculopathy (CCV), a rare microangiopathy primarily affecting middle-aged and older White individuals, characterized by widespread cutaneous telangiectasias. The article highlights the importance of histological confirmation for diagnosing CCV and discusses potential treatment options for cosmesis. [Extracted from the article]

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular malformations, including Pulmonary Arteriovenous Malformations (PAVMs), which can lead to serious complications such as dyspnea and hemorrhage. This report features a 37-year-old woman with HHT and multiple PAVMs. The diagnosis was established through physical examination, laboratory tests, and thoracic multislice computed tomography (MSCT). A hybrid management approach was applied, including embolization and thoracotomy. The patient underwent successful embolization of the inferior segment, followed by thoracotomy to overcome procedural difficulties. After the intervention, the patient's symptoms improved significantly, with no recurrence. Management of complex PAVMs may require a combination of methods, including embolization and surgery. The importance of early detection and adaptive management in HHT patients is expressed, given the high risk of complications. Embolization is the primary treatment for PAVMs, but in complex cases, surgical intervention is required. This study emphasizes the importance of a hybrid management approach and early detection in preventing serious complications in HHT patients, as well as the need for the development of better clinical guidelines for the management of PAVMs. [ABSTRACT FROM AUTHOR]

BACKGROUND Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life. METHODS We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations). RESULTS The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P=0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash. CONCLUSIONS Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. [ABSTRACT FROM AUTHOR]

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder leading to frequent bleeding in several organs. As HHT diagnosis is demanding and depends on clinical criteria, liquid biopsy would be beneficial. Exosomes from biofluids are nano-sized vesicles for intercellular communication. Their cargo and characteristics represent biomarkers for many diseases. Here, exosomes of HHT patients were examined regarding their biosignature. Methods: Exosomes were isolated from the plasma of 20 HHT patients and 17 healthy donors (HDs). The total exosomal protein was quantified, and specific proteins were analyzed using Western blot and antibody arrays. Human umbilical vein endothelial cells (HUVECs) co-incubated with exosomes were functionally examined via immunofluorescence, proliferation, and scratch assay. Results: The levels of the angiogenesis-regulating protein Thrombospondin-1 were significantly higher in HHT compared to HD exosomes. Among HHT, but not HD exosomes, a negative correlation between total exosomal protein and soluble Endoglin (sENG) levels was found. Other exosomal proteins (ALK1, ALK5) and the particle concentration significantly correlated with disease severity parameters (total consultations/interventions, epistaxis severity score) in HHT patients. Functionally, HUVECs were able to internalize both HD and HHT exosomes, inducing a similar change in the F-Actin structure and a reduction in migration and proliferation. Conclusions: This study provided first insights into the protein cargo and function of HHT-derived exosomes. The data indicate changes in sENG secretion via exosomes and reveal exosomal Thrombospondin-1 as a potential biomarker for HHT. Several exosomal characteristics were pointed out as potential liquid biomarkers for disease severity, revealing a possible new way of diagnosis and prognosis of HHT. [ABSTRACT FROM AUTHOR]

Background: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations and telangiectases, in which the endothelium and immune system play a role in the pathophysiology. Therefore, treatments with antiangiogenic properties which are also regarded as immunomodulators were demonstrated to play an important role in treatment. This systematic review aimed to gather the accumulated information of the use of thalidomide and its analogs in the treatment of HHT. Methods: In this systematic review, publications that were published up to March 2024 and met the inclusion criteria were compiled using the keywords 'thalidomide', 'lenalidomide', 'pomalidomide', 'immunomodulatory drugs' and 'HHT' in Medline and Scholars databases. Results: A total of 53 articles were evaluated and 15 were included in the study. Thalidomide was the predominant used agent and was observed to be used in patients with ages ranging from 37 to 77 years, with doses ranging from 50 to 200 mg daily, and the mean follow-up period was observed to be 6–60 months. Assessments regarding efficacy were based on the epistaxis severity score (ESS), hemoglobin level, and transfusion independence. While thalidomide showed significant efficacy, it also had an adverse event rate of any severity of up to 85% of patients. Use of lenalidomide to control bleeding in HHT was reported in a single case report, while the use of pomalidomide was observed to be investigated in Phase 1 and Phase 2 studies in patients aged 48 to 70 years, with doses ranging from 1 to 5 mg daily for 6–24 months. This treatment was reported to provide significant improvement in hemoglobin levels and ESS. Adverse events of any severity were observed at a frequency of 60–66%. Conclusions: Antiangiogenic agents such as thalidomide, lenalidomide, and pomalidomide may be effective in managing HHT. However, further studies are needed to optimize the timing, dose, and sequence. [ABSTRACT FROM AUTHOR]

Background: Hereditary hemorrhagic telangiectasia (HHT, Rendu-Osler-Weber disease, or Osler's disease for short) is a systemic disease that can severely impair the quality of life and that requires interdisciplinary treatment. Among rare diseases, it is relatively common, with a prevalence of approximately 1/5000. Methods: This review is based on publications retrieved by a selective literature search, including the two international guidelines on clinically relevant aspects of HHT. Results: On average, about two decades elapse between the initial symptoms and the diagnosis of HHT. 95% of patients have nosebleeds; these usually begin before age 20 but can occur at any time, from infancy to old age. The diagnosis is usually made on clinical grounds on the basis of the characteristic telangiectases, a positive family history, and possible involvement of the gastrointestinal tract, lungs, liver, and brain. Nosebleeds can sometimes be reduced by outpatient measures including counseling on keeping the nose moist (expert consensus), self-application of a nasal packing (which improves the quality of life, according to an online survey), and the prescription of tranexamic acid (reduction of nosebleeds from 17.3% [5.5; 27.6] to 54%). In particular, screening (expert consensus) for pulmonary vascular malformations (frequency 10-50%) can prevent many adverse outcomes. If pulmonary vascular malformations cannot be ruled out, antibiotic prophylaxis is recommended before medical procedures that can cause bacteremia (expert consensus). Conclusion: Broad awareness of the condition, early diagnosis, and interdisciplinary treatment improve the quality of life and ultimate outcome of persons with HHT. Nevertheless, there are few options supported by good evidence for the appropriate treatment of this rare, often serious disease.. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of the blood vessels that leads to the formation of telangiectasias and arteriovenous malformations (AVMs). HHT affects ∼1/5,000 people, but this varies significantly by geography and ancestry. The Curaçao criteria for HHT consist of four diagnostic criteria: spontaneous epistaxis, first-degree relative with HHT, AVMs in characteristic location (liver, lung, brain), and telangiectasias. Sequelae and major symptomology include recurrent epistaxis, dyspnea, heart failure, and stroke from paradoxical emboli among others. HHT patients are best cared for by a multidisciplinary team, ideally all with HHT-specific experience, but in this review, we will discuss the major aspects of the disease including etiology, diagnosis, and treatment recommendations. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformations (AVMs) in several organs. This report is the first to document and image a thyroid AVM complication in HHT. A 72-year-old woman with HHT was referred for thyroid nodule evaluation. Ultrasonography showed a hypervascularized nodule in the right thyroid lobe which was initially suspected to be malignant. However, 3-dimensional computed tomography angiography demonstrated a thyroid AVM with abnormal anastomosis of the superior thyroid artery and the inferior thyroid vein. In the formation of thyroid AVM, here, chronic thyroiditis and hypothyroidism complications may have been a second hit, due to the predisposing first-hit germline mutation. This report sheds light on overlooked thyroid lesions in HHT and advocates a noninvasive imaging approach in diagnosing thyroid AVMs. Furthermore, this case suggests a potential mechanism of AVM formation in human HHT, possibly supporting the second-hit hypothesis. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the development of arteriovenous malformations (AVMs) that can result in significant morbidity and mortality. HHT is caused primarily by mutations in bone morphogenetic protein receptors ACVRL1/ALK1, a signaling receptor, or endoglin (ENG), an accessory receptor. Because overexpression of Acvrl1 prevents AVM development in both Acvrl1 and Eng null mice, enhancing ACVRL1 expression may be a promising approach to development of targeted therapies for HHT. Therefore, we sought to understand the molecular mechanism of ACVRL1 regulation. We previously demonstrated in zebrafish embryos that acvrl1 is predominantly expressed in arterial endothelial cells and that expression requires blood flow. Here, we document that flow dependence exhibits regional heterogeneity and that acvrl1 expression is rapidly restored after reinitiation of flow. Furthermore, we find that acvrl1 expression is significantly decreased in mutants that lack the circulating Alk1 ligand, Bmp10, and that, in the absence of flow, intravascular injection of BMP10 or the related ligand, BMP9, restores acvrl1 expression in an Alk1-dependent manner. Using a transgenic acvrl1:egfp reporter line, we find that flow and Bmp10 regulate acvrl1 at the level of transcription. Finally, we observe similar ALK1 ligand-dependent increases in ACVRL1 in human endothelial cells subjected to shear stress. These data suggest that ligand-dependent Alk1 activity acts downstream of blood flow to maintain or enhance acvrl1 expression via a positive feedback mechanism, and that ALK1 activating therapeutics may have dual functionality by increasing both ALK1 signaling flux and ACVRL1 expression. [ABSTRACT FROM AUTHOR]

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]

Purpose: The purpose of this study was to describe the molecular diagnosis and atypical ocular presentation of a patient who suffered for a Rendu–Osler–Weber syndrome associated with juvenile polyposis syndrome. Methods: This is a case report of a patient who underwent fundus examination, brain MRI, and arteriography. Genetic testing was performed by next-generation sequencing. Results: A 35-year-old woman presented with right hemiplegia with right homonymous lateral hemianopia and homolateral complete sensory deficit. She also had Roth spots in her left fundus. Genetic testing revealed a pathogenic variation in the heterozygous state in the SMAD-4 gene (c.1245_1248del). Conclusion: Hereditary hemorrhagic telangiectasia also known as Rendu–Osler–Weber syndrome is a rare autosomal dominant disease, which reveals mostly with epistaxis and cutaneous telangiectasias. Our clinical case reports Roth spots in the context of hereditary hemorrhagic telangiectasia associated with juvenile polyposis syndrome. SMAD-4 mutation may explain the presence of a carotid-ophthalmic aneurysm, which is not a lesion usually found in hereditary hemorrhagic telangiectasia. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 28-year-old pregnant woman diagnosed with pulmonary arteriovenous malformations (PAVMs) after presenting with hypoxemia. Topics include the initial diagnostic process involving imaging that revealed bilateral lung abnormalities, management strategies such as cesarean delivery and postpartum oxygen support, and the subsequent coil embolization procedure that successfully improved oxygen saturation levels.

Abstract Background In vitro disease modeling enables translational research by providing insight into disease pathophysiology and molecular mechanisms, leading to the development of novel therapeutics. Nevertheless, in vitro systems have limitations for recapitulating the complexity of tissues, and a single model system is insufficient to gain a comprehensive understanding of a disease. Results Here we explored the potential of using several models in combination to provide mechanistic insight into hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder. Genome editing was performed to establish hPSCs (H9) with ENG haploinsufficiency and several in vitro models were used to recapitulate the functional aspects of the cells that constitute blood vessels. In a 2D culture system, endothelial cells showed early senescence, reduced viability, and heightened susceptibility to apoptotic insults, and smooth muscle cells (SMCs) exhibited similar behavior to their wild-type counterparts. Features of HHT were evident in 3D blood-vessel organoid systems, including thickening of capillary structures, decreased interaction between ECs and surrounding SMCs, and reduced cell viability. Features of ENG haploinsufficiency were observed in arterial and venous EC subtypes, with arterial ECs showing significant impairments. Molecular biological approaches confirmed the significant downregulation of Notch signaling in HHT-ECs. Conclusions Overall, we demonstrated refined research strategies to enhance our comprehension of HHT, providing valuable insights for pathogenic analysis and the exploration of innovative therapeutic interventions. Additionally, these results underscore the importance of employing diverse in vitro systems to assess multiple aspects of disease, which is challenging using a single in vitro system.

Telangiectases and arteriovenous malformations (AVMs) are the characteristic lesions of Hereditary Hemorrhagic Telangiectasia (HHT). Somatic second-hit loss-of-function variations in the HHT causative genes, ENG and ACVRL1, have been described in dermal telangiectasias. It is unclear if somatic second-hit mutations also cause the formation of AVMs and nasal telangiectasias in HHT. To investigate the genetic mechanism of AVM formation in HHT, we evaluated multiple affected tissues from fourteen individuals. DNA was extracted from fresh/frozen tissue of 15 nasal telangiectasia, 4 dermal telangiectasia, and 9 normal control tissue biopsies, from nine unrelated individuals with HHT. DNA from six formalin-fixed paraffin-embedded (FFPE) AVM tissues (brain, lung, liver, and gallbladder) from five individuals was evaluated. A 736 vascular malformation and cancer gene next-generation sequencing (NGS) panel was used to evaluate these tissues down to 1% somatic mosaicism. Somatic second-hit mutations were identified in three in four AVM biopsies (75%) or half of the FFPE (50%) samples, including the loss of heterozygosity in ENG in one brain AVM sample, in which the germline mutation occurred in a different allele than a nearby somatic mutation (both are loss-of-function mutations). Eight of nine (88.9%) patients in whom telangiectasia tissues were evaluated had a somatic mutation ranging from 0.68 to 1.96% in the same gene with the germline mutation. Six of fifteen (40%) nasal and two of four (50%) dermal telangiectasia had a detectable somatic second hit. Additional low-level somatic mutations in other genes were identified in several telangiectasias. This is the first report that nasal telangiectasias and solid organ AVMs in HHT are caused by very-low-level somatic biallelic second-hit mutations. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia. Case presentation: We present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins—features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70–80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%. Conclusion: Diffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient's family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Osler Weber Rendu disease is a rare genetic disorder characterized by multiple telangiectasias and arteriovenous malformations involving parenchymatous organs, leading to hemorrhagic, sometimes life-threatening vascular complications. The most often involved regions are the central nervous system and lungs, but the disease can also manifest at hepatic, intestinal, splenic or urinary level. The objective of this article is to raise the awareness over an extremely severe complication of Osler Weber Rendu and the importance of an early diagnosis. Materials and methods: We present the case of a 65 years old woman with Osler Weber Rendu with many complications, who was hospitalized and surgically treated for massive hemothorax and hemorrhagic shock by rupture of a pulmonary vascular malformation. The patient presented for latero-thoracic and anterior chest pain with a sudden onset in the last 24 hours, which was followed by progressive dyspnea, being further diagnosed with massive right hemothorax. Results: After the emergency surgical treatment which consisted of inferior bi-lobectomy, the evolution was a difficult one, the recovery of the patient being slowed down by her altered neurological status and the presence of a persistent bronchial stump fistula. Her disease was complicated by a post transfusion syndrome which aggravated the respiratory failure and necessitated the initiation of cortico-therapy and also by the colonization and subsequent infection of the respiratory tract with multi resistant microorganisms. The patient died on the 32nd postoperative day. Conclusions: Our patient had in her personal medical history few complications of Osler Weber Rendu disease, but these manifested as non-specific symptoms which were not further investigated in order to early establish the diagnosis of the disease. Therefore, the importance of the disease was overridden as time passed and the diagnosis was delayed, which prevented any therapeutic measures of the associated life-threatening complications, as is in this case the massive hemothorax. [ABSTRACT FROM AUTHOR]

Objective: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. Methods: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. Results: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. Conclusions: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment. [ABSTRACT FROM AUTHOR]

Interstitial Lung Disease (ILD) in diffuse cutaneous Systemic Sclerosis (SSc) patients is present in about 53% of cases and 35% in cases with limited cutaneous SSc. Even though there are only a few case reports of ILD associated with Hereditary Haemorrhagic Telangiectasia (HHT), a direct association of SSc and HHT has not been reported. Hence, little is known about the pathogenetic link between the two diseases. In this case report, a 24 years old married female patient presented with progressive breathlessness for one year. Initial evaluation of the patient suggested the diagnosis of SSc based on clinical findings like sclerodactyly along with telangiectasia. High Resolution Computed Tomography (HRCT) of the chest revealed the presence of pulmonary arteriovenous malformation along with ILD. Past medical history and family history of epistaxis for three generations suggested the diagnosis of HHT. This case reports a rare association of Connective Tissue Disease (CTD) and an autosomal disorder of vascular dysplasia with overlapping features of telangiectasia. This case is presented to highlight the possible association of HHT with CTDs. With the currently available literature, an attempt is made to find a plausible pathogenetic link between HHT and SSc. Transforming Growth Factor-β (TGF-β) is a pleiotropic growth factor that regulates the growth and differentiation of various cell types, and immune regulation has been implicated in the pathogenesis of both HHT and SSc. The other pathogenetic mechanism common to both diseases is impaired nitric oxide-mediated vasodilation. This case report emphasises the need for further research for a better understanding of the pathogenesis of both diseases. [ABSTRACT FROM AUTHOR]

Key points: Severe epistaxis occurs in 2% of PNN ablation cases, independent of method or device type.Major epistaxis requiring intervention after PNN ablation can occur on average 20 days post‐procedure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) can cause acute ischemic strokes (AISs) through paradoxical embolism. The clinical and imaging features of AIS due to PAVMs have not been studied. We report a case and perform a systematic review of the clinical and imaging characteristics of patients with AIS due to PAVMs. This may provide clues to screen patients with AIS for PAVMs and treat them appropriately to prevent further strokes. MATERIALS AND METHODS: MEDLINE, EMBASE, and Web of Science databases were searched from inception to October 2023. We included patients of any age with AIS attributed to PAVM. Studies without clinical data were excluded. Demographics, AIS characteristics (location and arterial territories), and PAVM characteristics (location, size, and treatment) were recorded. RESULTS: A 47-year-old female presented with acute vertigo and gait imbalance. Magnetic resonance imaging showed AIS in the right cerebellum. CT chest confirmed a PAVM in the right lower lobe. Endovascular coil closure was performed. We identified 102 patients from 96 records. The mean age was 47.4 ± 17 years (67% female). Seventy percent had single AIS and 30% had multiple. The location was anterior circulation in 50%, posterior in 37%, and both in 13%. The most common arterial territory was middle-cerebral (51%), followed by posterior-cerebral (25%). PAVMs were mostly single (78%) and in the lower lobes (66%). Thirty-three had hereditary hemorrhagic telangiectasia (HHT) (33%). CONCLUSIONS: PAVM-related strokes occur at a young age and may have a high propensity for multifocality and posterior circulation location. Patients with PAVMs and AIS should be screened for HHT and venous thromboses. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic condition, which is diagnosed based on strict criteria. The main symptoms include recurrent epistaxis episodes, multiple mucocutaneus telangiectasia, the presence of organ arteriovenous malformations (AVMs) and a family history of the disease. Up to 98% of patients present with epistaxis episodes, some of which could potentially be life threatening. Different approaches have been used in historical perspective to gain control over the site of bleeding, with hemodynamically unstable patients requiring urgent medical supportive care. Endovascular therapy is a still relatively unexplored treatment option for such cases. Purpose: To establish the safety and efficacy of endovascular embolization as a treatment option of malignant refractory epistaxis in patients with HHT. Materials and methods: We present a case series of endovascular embolizations of the maxillary artery and/or its branches, supplying bleeding lesions in patients, refractory to other conventional means of treatment. Between the period of February 2022 and March 2024, nine patients with HHT underwent such an endovascular procedure. Results: Satisfactory results were achieved in all cases, with no added neurological complications being observed. Only one of the patients had a recurrence of the condition and required an additional embolization procedure. Conclusion: Endovascular embolization of the maxillary artery and its branches for malignant recurrent epistaxis in patients with HHT is a safe and effective way to control the site of bleeding. [ABSTRACT FROM AUTHOR]