Telangiectasias, recurrent epistaxis and a strong family history-a case of Osler- Weber-Rendu Syndrome in Pakistan.

Osler-Weber-Rendu syndrome or Hereditary Haemorrhagic Telangiectasia (HHT) is a rare condition, with very few reported cases, especially in Pakistan. As healthcare workers, we encounter multiple cases of recurrent epistaxis in the emergency as well as outpatient departments. However, patients are usually treated symptomatically without a thorough workup. HHT should be considered among the differentials for recurrent epistaxis, as a clinical diagnosis can be made with detailed family history and physical examination. Here is the case of a 58-year-old male who presented to the Gastroenterology OPD, Combined Military Hospital, Lahore, in November 2021, with complaints of generalised weakness and blood in stools. He had a history of recurrent epistaxis and telangiectasias, and further inquiry revealed a strong family history of similar symptoms. He was diagnosed as a case of Osler-Weber- Rendu Syndrome. Informed consent was taken from the patient prior to the writing of the manuscript.

Prevalence of hereditary hemorrhagic telangiectasia in a medical care program organization in Buenos Aires, Argentina.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia that might affect 1/5000-10 000 individuals worldwide. It is a rare and underdiagnosed condition. Population-based epidemiological studies are crucial for comprehending and quantifying the impact of this disease. We aim to estimate the prevalence in a Prepaid Health Care System of Buenos Aires, Argentina. METHODS: A descriptive cross-sectional study was designed, which included all patients over 18 years of age affiliated with the Hospital Italiano Medical Care Program (IHMCP), a prepaid health maintenance organization (HMO) of Buenos Aires. For case inclusion, individuals were required to have a clinical diagnosis of HHT. Case detection included the search in our Institutional Registry. The prevalence was calculated by dividing the number of cases of HHT by the total number of all active affiliates at January 2023. Age and gender specific prevalence rates were estimated. RESULTS: 48 cases were reported. The prevalence was 3.2 in 10 000 (IC 95% 2.4-4.2). Specific prevalence in women was 3.9 in 10 000 (IC 95% 2.8-5.5) and in men 2.1 in 10 000 (IC 95% 1.2-3.6). The average age was 54.8 (19), 35 patients were women (72.9%) with an average age of 55 (19.9), and 55 (17.2) for men. The most common referrals were physicians (60.4%) followed by family history (18.7%). The 48 patients corresponded to 39 families. DISCUSSION: The prevalence identified in our study is higher than the one documented in other studies.

Introducción: La telangiectasia hemorrágica hereditaria (HHT) es una displasia vascular que puede afectar a 1 de 5000 a 10 000 personas en el mundo. Es una afección rara y subdiagnosticada. Los estudios epidemiológicos son fundamentales para comprender y cuantificar el impacto de esta enfermedad. Nuestro objetivo fue estimar la prevalencia en un Sistema Prepago de Atención de la Salud, en Buenos Aires, Argentina. Métodos: Estudio descriptivo transversal en pacientes mayores de 18 años afiliados al Programa de Atención Médica del Hospital Italiano en Buenos Aires (Plan de Salud). Para la inclusión de casos, se requería el diagnóstico de HHT. La detección de casos incluyó su búsqueda en nuestro Registro Institucional. La prevalencia se calculó dividiendo el número de casos por el número total de afiliados activos en enero de 2023. Se estimaron tasas específicas por edad y género. Resultados: Se reportaron 48 casos. La prevalencia fue de 3.2 por 10 000 personas (IC 95% 2.4-4.2). La específica en mujeres fue de 3.9 (IC 95% 2.8-5.5) y en hombres de 2.1 por 10 000 (IC 95% 1.2-3.6). La edad promedio fue de 55 años (19), con 35 pacientes mujeres (72.9%) con una edad promedio de 55 años (19.9) y 55 (17.2) para hombres. La derivación más común fue de médicos (60.4%), seguidas por antecedentes familiares (18.7%). Los 48 pacientes correspondían a 39 familias. Discusión: La prevalencia identificada en nuestro estudio es más alta que la documentada en otros estudios.

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. We aimed to confirm whether brain VMs can form de novo in patients with HHT. METHODS: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review. RESULTS: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation. CONCLUSIONS: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted.

Personalised stroke evaluation and management: tailoring individualised patient care for hereditary haemorrhagic telangiectasia.

SummaryHereditary haemorrhagic telangiectasia (HHT) has an estimated prevalence of 1 in 5000-8000 individuals globally with pulmonary arteriovenous malformations (PAVMs) affecting approximately 15%-50% of HHT patients. Ischaemic stroke is a known complication of PAVMs that affects ≤30% of patients with PAVMs. Studies have shown that patients with PAVMs have ischaemic stroke a decade earlier than routine stroke. The predominant mechanism of ischaemic stroke in HHT patients is paradoxical embolism due to PAVMs, but most HHT-related PAVMs are asymptomatic. Additionally, HHT is often underdiagnosed in patients and poses a challenge to physicians due to its rarity. We present a case of a patient with ischaemic stroke who was subsequently diagnosed with HHT and found to have a PAVM on further evaluation. This case highlights the importance of using an individualised patient-centred stroke evaluation and screening for PAVMs in patients who had a stroke with possible or suspected HHT and definite HHT.

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family.

Hereditary hemorrhagic telangiectasia (HHT), also called Rendu-Osler syndrome, is a group of rare genetic diseases characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The correlations between the phenotype and genotype for HHT are not clear. An HHT Chinese pedigree was recruited. Whole exome sequencing (WES) analysis, Sanger verification, and co-segregation were conducted. Western blotting was performed for monitoring ENG/VEGFα signaling. As a result, a nonsense, heterozygous variant for ENG/CD105: c.G1169A:p. Trp390Ter of the proband with hereditary hemorrhagic telangiectasia type 1 (HHT1) was identified, which co-segregated with the disease in the M666 pedigree. Western blotting found that, compared with the normal levels associated with non-carrier family members, the ENG protein levels in the proband showed approximately a one-half decrease (47.4% decrease), while levels of the VEGFα protein, in the proband, showed approximately a one-quarter decrease (25.6% decrease), implying that ENG haploinsufficiency, displayed in the carrier of this variant, may affect VEGFα expression downregulation. Pearson and Spearman correlation analyses further supported TGFß/ENG/VEGFα signaling, implying ENG regulation in the blood vessels. Thus, next-generation sequencing including WES should provide an accurate strategy for gene diagnosis, therapy, genetic counseling, and clinical management for rare genetic diseases including that in HHT1 patients.

Usefulness of endoscopic endonasal underwater surgery using a combination of coblation and a lens-cleaning system for hemostasis in hereditary hemorrhagic telangiectasia.

Hemostatic procedures for controlling nasal bleeding in refractory diseases such as hereditary hemorrhagic telangiectasia (HHT) can be challenging. In this report, we present a novel technique for underwater endoscopic endonasal hemostatic surgery, which was performed on a 69-year-old man with HHT. The patient had been experiencing frequent episodes of nasal bleeding and had many telangiectasias in the nasal cavity, which were the cause of the bleeding. These telangiectasias were effectively treated using a coblation device in combination with an endoscope lens-cleaning system that supplied saline to create stable underwater conditions. There are several advantages to this technique, including provision of a stable and clear endoscopic field of view, allowing for better visualization of the surgical site. This makes it easier to identify bleeding points and ensure accurate hemostasis. Additionally, the hydrostatic pressure created by the underwater environment helps to reduce bleeding during the procedure. However, it is important to take careful precautions to prevent water from entering the lower airway. With this precautionary measure, this technique is particularly useful in managing bleeding in patients with HHT.

Hereditary hemorrhagic telangiectasia with hepatic arteriovenous shunt diagnosed due to liver damage.

A 53-year-old woman was diagnosed with liver dysfunction in August 20XX. Computed tomography (CT) revealed multiple hepatic AV shunts, and she was placed under observation. In March 20XX + 3, she developed back pain, and CT performed during an emergency hospital visit showed evidence of intrahepatic bile duct dilatation. She was referred to our gastroenterology department in May 20XX + 3. We conducted investigations on suspicion of hereditary hemorrhagic telangiectasia (HHT) with hepatic AV shunting based on contrast-enhanced CT performed at another hospital. HHT is generally discovered due to epistaxis, but there are also cases where it is diagnosed during examination of liver damage.

Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation / Tratamiento comparativo de lesiones mucocutáneas en pacientes con telangiectasia hemorrágica hereditaria con láser dual secuencial de colorante pulsado y neodimio: itrio-aluminio-granate versus neodimio: itrio-aluminio-granate solo: un estudio controlado aleatorizado doble ciego con evaluación de la calidad de vida

Background: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. Objective: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. Methods A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. Results: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2–4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2–3; mean 2.61) vs 2 (IQR 2–3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. Conclusions DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments. (AU)

Antecedentes: La telangiectasia hemorrágica hereditaria (THH) se caracteriza por la presencia de telangiectasias y malformaciones arteriovenosas de mayor tamaño en diferentes órganos. Las telangiectasias a nivel mucocutáneo pueden sangrar y convertirse en un problema estético, afectando la calidad de vida (CdV). Sin embargo, aún no se ha definido su mejor enfoque terapéutico. Objetivo: Evaluar la eficacia y la seguridad del láser dual secuencial de longitud de onda de 595/1064nm (DWSL) en comparación con el láser de 1064nm (Nd:YAG) solo. Por otro lado, evaluar el deterioro de la calidad de vida en los pacientes con THH y su mejora tras la terapia con láser. Métodos: Estudio prospectivo, doble ciego, aleatorizado, comparativo, de cuerpo dividido (DWSL vs. Nd:YAG). Se registraron las características demográficas, clínicas y del tratamiento. La gravedad y el grado de mejora fueron evaluados por tres examinadores ciegos que calificaron las imágenes previas al tratamiento y posteriores al tratamiento en una escala de 5 puntos. Los pacientes cumplimentaron las pruebas Skindex-29 y FACE-Q® y se evaluó el dolor asociado al procedimiento y la satisfacción del paciente. Resultados: Se analizaron 111 áreas de tratamiento (55 tratadas con DWSL y 56 con Nd:YAG) de 26 pacientes. La mediana del número de sesiones de láser fue de 2 (rango intercuartílico [RIC] 2-4; media 2,90 vs. 2,88, respectivamente). La mediana de la puntuación de mejora, independientemente de la ubicación, fue significativamente mayor para Nd:YAG en comparación con DWSL: 3 (IQR 2-3; media 2,61) frente a 2 (IQR 2-3; media 2,32), p=0,031. Tanto el índice FACE-Q como los resultados de la prueba Skindex-29 mejoraron significativamente (p<0,001), y el 92,4% de los pacientes informaron un alto grado de satisfacción (≥8). No se informaron eventos adversos graves... (AU)

[Artículo traducido] Tratamiento comparativo de lesiones mucocutáneas en pacientes con telangiectasia hemorrágica hereditaria con láser dual secuencial de colorante pulsado y neodimio: itrio-aluminio-granate versus neodimio: itrio-aluminio-granate solo: un estudio controlado aleatorizado doble ciego con evaluación de la calidad de vida / Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation

Antecedentes: La telangiectasia hemorrágica hereditaria (THH) se caracteriza por la presencia de telangiectasias y malformaciones arteriovenosas de mayor tamaño en diferentes órganos. Las telangiectasias a nivel mucocutáneo pueden sangrar y convertirse en un problema estético, afectando la calidad de vida (CdV). Sin embargo, aún no se ha definido su mejor enfoque terapéutico. Objetivo: Evaluar la eficacia y la seguridad del láser dual secuencial de longitud de onda de 595/1064nm (DWSL) en comparación con el láser de 1064nm (Nd:YAG) solo. Por otro lado, evaluar el deterioro de la calidad de vida en los pacientes con THH y su mejora tras la terapia con láser. Métodos: Estudio prospectivo, doble ciego, aleatorizado, comparativo, de cuerpo dividido (DWSL vs. Nd:YAG). Se registraron las características demográficas, clínicas y del tratamiento. La gravedad y el grado de mejora fueron evaluados por tres examinadores ciegos que calificaron las imágenes previas al tratamiento y posteriores al tratamiento en una escala de 5 puntos. Los pacientes cumplimentaron las pruebas Skindex-29 y FACE-Q® y se evaluó el dolor asociado al procedimiento y la satisfacción del paciente. Resultados: Se analizaron 111 áreas de tratamiento (55 tratadas con DWSL y 56 con Nd:YAG) de 26 pacientes. La mediana del número de sesiones de láser fue de 2 (rango intercuartílico [RIC] 2-4; media 2,90 vs. 2,88, respectivamente). La mediana de la puntuación de mejora, independientemente de la ubicación, fue significativamente mayor para Nd:YAG en comparación con DWSL: 3 (IQR 2-3; media 2,61) frente a 2 (IQR 2-3; media 2,32), p=0,031. Tanto el índice FACE-Q como los resultados de la prueba Skindex-29 mejoraron significativamente (p<0,001), y el 92,4% de los pacientes informaron un alto grado de satisfacción (≥8). No se informaron eventos adversos graves... (AU)

Background: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. Objective: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. Methods: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. Results: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2–4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2–3; mean 2.61) vs 2 (IQR 2–3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. Conclusions: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments. (AU)

Pulmonary vascular phenotype identified in patients with GDF2 (BMP9) or BMP10 variants: an international multicentre study.

BACKGROUND: Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by GDF2 and BMP10, respectively, play a pivotal role in pulmonary vascular regulation. GDF2 variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of GDF2 and BMP10 carriers remains largely unexplored. METHODS: We report the characteristics and outcomes of PAH patients in GDF2 and BMP10 carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients. RESULTS: 26 PAH patients were identified: 20 harbouring heterozygous GDF2 variants, one homozygous GDF2 variant, four heterozygous BMP10 variants, and one with both GDF2 and BMP10 variants. The prevalence of GDF2 and BMP10 variants was 1.3% and 0.4%, respectively. Median age at PAH diagnosis was 30 years, with a female/male ratio of 1.9. Congenital heart disease (CHD) was present in 15.4% of the patients. At diagnosis, most of the patients (61.5%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise (median (range) pulmonary vascular resistance 9.0 (3.3-40.6) WU). Haemoptysis was reported in four patients; none met the HHT criteria. Two patients carrying BMP10 variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of GDF2 carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in BMP10 carriers. CONCLUSIONS: GDF2 and BMP10 pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among GDF2 carriers are limited according to the literature. BMP10 full phenotypic ramifications warrant further investigation.

Genome sequencing identify chromosome 9 inversions disrupting ENG in 2 unrelated HHT families.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a dominant inherited vascular disorder. The clinical diagnosis is based on the Curaçao criteria and pathogenic variants in the ENG and ACVRL1 genes are responsible for most cases of HHT. Four families with a negative targeted gene panel and selected by a multidisciplinary team were selected and whole-genome sequencing was performed according to the recommendations of the French National Plan for Genomic Medicine. Structural variations were confirmed by standard molecular cytogenetic analysis (FISH). In two families with a definite diagnosis of HHT, we identified two different paracentric inversions of chromosome 9, both disrupting the ENG gene. These inversions are considered as pathogenic and causative for the HHT phenotype of the patients. This is the first time structural variations are reported to cause HHT. As such balanced events are often missed by exon-based sequencing (panel, exome), structural variations may be an under-recognized cause of HHT. Genome sequencing for the detection of these events could be suggested for patients with a definite diagnosis of HHT and in whom no causative pathogenic variant was identified.

Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances.

Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. However, despite the substantial benefits of these new treatments in terms of alleviating symptom severity, this not-so-uncommon bleeding disorder still currently lacks any FDA- or European Medicines Agency-approved (EMA-approved) therapies.

[Liver failure caused by recurrent biliary bleeding associated with Osler's disease: a case report].

A 34-year-old female patient with epigastric pain was admitted to our hospital. She reported an underlying condition of Rendu-Osler-Weber disease and a history of coil embolization for pulmonary arteriovenous fistula. A blood test revealed high hepatobiliary enzyme levels. An abdominal contrast-enhanced computed tomography revealed numerous arterioportal and arteriovenous shunts in the liver and a high-density area in the bile duct, which was diagnosed as biliary bleeding. She underwent transpapillary biliary drainage by endoscopic retrograde cholangiopancreatography, but recurrent biliary bleeding caused cholangitis, which was complicated by multiple liver abscesses. She was awaiting her turn for liver transplantation from brain-dead donors, but the liver abscesses were difficult to improve. Further, liver failure, septic pulmonary embolism, and disseminated intravascular coagulation were complicated. Thus, recurrent further biliary bleeding resulted in hemorrhagic shock, which required frequent blood transfusions. Furthermore, the continuous abscess to the intrahepatic bile duct in the anterior superior segment penetrated her diaphragm, causing hemothorax and eventually, death. Establishing progressive treatment, including liver transplantation, is considered necessary for this intractable disease.

Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells.

Endothelial cells (ECs) respond to concurrent stimulation by biochemical factors and wall shear stress (SS) exerted by blood flow. Disruptions in flow-induced responses can result in remodeling issues and cardiovascular diseases, but the detailed mechanisms linking flow-mechanical cues and biochemical signaling remain unclear. Activin receptor-like kinase 1 (ALK1) integrates SS and ALK1-ligand cues in ECs; ALK1 mutations cause hereditary hemorrhagic telangiectasia (HHT), marked by arteriovenous malformation (AVM) development. However, the mechanistic underpinnings of ALK1 signaling modulation by fluid flow and the link to AVMs remain uncertain. We recorded EC responses under varying SS magnitudes and ALK1 ligand concentrations by assaying pSMAD1/5/9 nuclear localization using a custom multi-SS microfluidic device and a custom image analysis pipeline. We extended the previously reported synergy between SS and BMP9 to include BMP10 and BMP9/10. Moreover, we demonstrated that this synergy is effective even at extremely low SS magnitudes (0.4 dyn/cm2) and ALK1 ligand range (femtogram/mL). The synergistic response to ALK1 ligands and SS requires the kinase activity of ALK1. Moreover, ALK1's basal activity and response to minimal ligand levels depend on endocytosis, distinct from cell-cell junctions, cytoskeleton-mediated mechanosensing, or cholesterol-enriched microdomains. However, an in-depth analysis of ALK1 receptor trafficking's molecular mechanisms requires further investigation.

Use of Polyurethane-Covered Stents for Exclusion of Pulmonary Arteriovenous Malformations.

PURPOSE: To evaluate the safety, technical success and short-term effectiveness of polyurethane-covered stent (PK Papyrus, BioTronik, Berlin) in the treatment of pulmonary arteriovenous malformations (PAVMs) that are not amenable to embolotherapy. MATERIALS AND METHODS: In this IRB-approved, retrospective study, data from patients who received polyurethane-covered stents for exclusion of PAVMs were analyzed. The study included 5 patients (all women) with a median age of 40 years (range 25-60). Patients presented with hypoxemia, TIAs, and/or epistaxis; 4 were confirmed to have HHT. All had multiple PAVMs diagnosed on chest CT and underwent embolization with other devices in addition to the polyurethane-covered stent. The indication for stent placement in all cases was a short and/or tortuous feeding artery. Safety was assessed by immediate or short-term complications, e.g., migration, stent thrombosis, and fracture. Technical success was defined as the ability to accurately place the stent at the intended location. Effectiveness was defined as successful exclusion of PAVM with no perfusion across the AVM. RESULTS: Technical success of stent placement was 100%. AVM exclusion rate was 80% after single stent deployment; in the case of incomplete exclusion, success was achieved using an overlapping stent to completely cover a second feeding artery. During the median follow-up period of 5 months (range 2-10), all stents remained patent, and AVMs were excluded without other complications. CONCLUSION: Exclusion of PAVMs with polyurethane-covered stents is technically feasible, safe, and shows short-term effectiveness for PAVMs with a short/tortuous feeding artery when traditional embolization techniques are not possible.

Stereotactic radiosurgery for brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.

OBJECTIVE: Brain arteriovenous malformations (AVMs) in patients with hereditary hemorrhagic telangiectasia (HHT) present different characteristics from sporadic AVMs, and they have lower initial bleeding rates. Conservative management is usually preferred for the treatment of these lesions. In this case study, we present the largest series of HHT patients treated with stereotactic radiosurgery to date. METHODS: We identified eight patients with HHT and 14 AVMs. We retrospectively collected clinical, radiographic, and treatment characteristics of the patients and each AVM. RESULTS: Most patients in our sample presented with small AVMs. The median volume of these AVMs was 0.22 cm3 (IQR 0.08-0.59). Three out of eight patients presented with initial intracerebral hemorrhage (ICH). The majority of lesions had low (12/14) Spetzler-Martin grades (I-II). Median maximum and margin doses used for treatment were 36.2 (IQR 35.25-44.4) and 20 (IQR 18-22.5) Gy, respectively. The overall obliteration rate after SRS was 11/14, and the median time to obliteration across all 11 obliterated AVMs was 35.83 months (IQR, 17-39.99). Neurological status was favorable with all patients having a mRS of 0 or 1 at the last follow-up. Symptomatic radiation-induced changes (RIC) after SRS were low (7.1%), and there were no permanent RIC. CONCLUSIONS: Patients with HHT who present with multiple brain AVMs are generally well served by SRS. Obliteration can be achieved in the majority of HHT patients and with a low complication rate. In the current study, initial hemorrhage rates prior to SRS were noticeable which supports the decision to treat these AVMs. Future studies are needed to better address the role of SRS for HHT patients harboring ruptured and unruptured AVMs.

Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation. / [Artículo traducido] Tratamiento comparativo de lesiones mucocutáneas en pacientes con telangiectasia hemorrágica hereditaria con láser dual secuencial de colorante pulsado y neodimio: itrio-aluminio-granate versus neodimio: itrio-aluminio-granate solo: un estudio controlado aleatorizado doble ciego con evaluación de la calidad de vida.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.