Brain and lung arteriovenous malformation rescreening practices for children and adults with hereditary hemorrhagic telangiectasia.

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.

CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia.

Increased endothelial cell proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). Here, we report a cyclin-dependent kinase 6 (CDK6)-driven mechanism of cell cycle deregulation involved in endothelial cell proliferation and HHT pathology. Specifically, endothelial cells from the livers of HHT mice bypassed the G1/S checkpoint and progressed through the cell cycle at an accelerated pace.

Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse.

Study Design And Methods: Retrospective chart review was conducted at St.

Barriers and facilitators to designing, maintaining, and utilizing rare disease patient registries: a scoping review protocol.

Objective: The objectives of this review are to identify barriers/facilitators to designing, maintaining, and utilizing rare disease patient registries (RDPRs); determine whether and how these differ among patient partners, other knowledge users (KUs), and researchers; and chart definitions of rare diseases and RDPRs.

Introduction: RDPRs are vital to improving the understanding of the natural histories and predictors of outcomes for rare diseases, assessing interventions, and identifying potential participants for clinical trials. Currently, however, the functionality of RDPRs is not fully optimized.

De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia.

Background: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening.

Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia.

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.

Reply to Eker et al. Comment on "Kilian et al. Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT. 2023, , 2704".

We are grateful to Eker et al. for their thoughtful analysis and response to our publication titled Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT [..

Transarterial Embolization of Simple Pulmonary Arteriovenous Malformations: Long-Term Outcomes of 0.018-Inch Coils versus Vascular Plugs.

Purpose: To compare the safety, effectiveness, and persistence rates of 0.018-inch coils with those of Amplatzer vascular plugs (AVPs; Abbott Vascular, Abbott Park, Illinois) for the treatment of pulmonary arteriovenous malformations (PAVMs) in response to a growing concern that 0.018-inch coil embolization would increase the long-term persistence rate.

Pre-operative embolization of a complex systemic to pulmonary vascular malformation.

A 38-year-old male patient presenting with mild exertional dyspnea was noted to have a lingular opacity on chest radiograph. CT of the chest demonstrated an unusual complex inferior lingular vascular malformation with branches arising from the left internal thoracic artery and the left inferior diaphragmatic artery via the celiac artery. There was suspected communication with both pulmonary arterial and venous branches.

CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia.

Increased endothelial cell (EC) proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). The underlying mechanism and disease relevance of this abnormal cell proliferative state of the ECs remain unknown. Here, we report the identification of a CDK6-driven mechanism of cell cycle progression deregulation directly involved in EC proliferation and HHT vascular pathology.

An analysis of sex differences in pulmonary arteriovenous malformation presentation, complications and management in a large, multinational registry of patients with hereditary haemorrhagic telangiectasia.

https://bit.ly/3TNLA6v.

Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterized by the development of vascular malformations (VMs) in organs such as the brain and lungs, as well as telangiectases on mucosal surfaces. Prophylactic treatment of organ VMs may prevent potential complications, such as hemorrhage. However, brain VM treatment-surgical resection, embolization, and/or radiosurgery-is not recommended for all patients due to the associated risks.

Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia.

Background: Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given its associated morbidity and impact on quality of life. We aimed to measure the effectiveness of oral doxycycline for the treatment of epistaxis and explore mechanisms of action on angiogenic, inflammatory and pathway markers in HHT using a randomized controlled trial.

MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant genetic disorder characterized by life-threatening vascular dysplasia. Myeloid angiogenic cells (MACs), alternatively called early endothelial progenitor cells or circulating angiogenic cells, do not directly incorporate into developing blood vessels, but augment angiogenesis in a paracrine manner. MAC dysfunction has been reported in HHT.

Quantification metrics for telangiectasia using optical coherence tomography.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments.

Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial.

Background: The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes.

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia.

Background: Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors.

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations.

Background: Vascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifying patients at risk for complications or with certain disease phenotypes.

Methods: A validated multiplex protein array consisting of 26 angiogenic and inflammatory biomarkers (Angiome) was assessed in plasma isolated from healthy controls and patients with either sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformation (CCM), or hereditary hemorrhagic telangiectasia (HHT).

Weekly epistaxis duration as an indicator of epistaxis severity in hereditary hemorrhagic telangiectasia-Preliminary results from a randomized controlled trial.

Objectives: There is great interest in developing and studying novel therapies for epistaxis in hereditary hemorrhagic telangiectasia (HHT) given its associated morbidity and impact on patients' quality of life. Several recent randomized controlled trials (RCTs) have been negative, likely attributed to poorly characterized outcome measures. This study reported on and evaluated an epistaxis outcome measure, weekly epistaxis duration (WED) in an ongoing RCT, with the aim of better characterizing the measurement of epistaxis for clinical trials.

Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation.

Background: Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of non-steroidal anti-inflammatory drugs. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions.

Endoglin deficiency impairs VEGFR2 but not FGFR1 or TIE2 activation and alters VEGF-mediated cellular responses in human primary endothelial cells.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by vascular dysplasia. Mutations of the endoglin (ENG) gene that encodes a co-receptor of the transforming growth factor β1 signaling pathway cause type I HHT. ENG is primarily expressed in endothelial cells (ECs), but its interaction with other key angiogenic pathways to control angiogenesis has not been well addressed.