scholarly journals European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ingrid M. B. H. van de Laar ◽  
Eloisa Arbustini ◽  
Bart Loeys ◽  
Erik Björck ◽  
Lise Murphy ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Health Care Professionals ◽  
Consensus Statement ◽  
Vascular Diseases ◽  
Aortic Disease ◽  
Current Data ◽  
Reference Network ◽  
Multicenter Studies ◽  
Pathogenic Variants ◽  
European Reference Network

AbstractThe ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is the main clinical manifestation, a variety of occlusive vascular disease and extravascular manifestations occur in ACTA2-related vasculopathy. Current data suggest possible mutation-specific manifestations of vascular and extra-aortic traits.Despite its relatively high prevalence, comprehensive recommendations on the care of patients and families with pathogenic variants in ACTA2 have not yet been established. We aimed to develop a consensus document to provide medical guidance for health care professionals involved in the diagnosis and treatment of patients and relatives with pathogenic variants in ACTA2.The HTAD Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN) convened to review current literature and discuss expert opinions on clinical management of ACTA2 related vasculopathy. This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy. However, there is a clear need for additional prospective multicenter studies to further define proper guidelines.

scholarly journals eHealth for patients with rare diseases: the eHealth Working Group of the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alessia Paglialonga ◽  
Raffaella Gaetano ◽  
Leema Robert ◽  
Marine Hurard ◽  
Luisa Maria Botella ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Working Group ◽  
Vascular Diseases ◽  
Mobile App ◽  
Reference Network ◽  
Training And Education ◽  
Digital Platforms ◽  
Patient Organizations ◽  
European Reference Network ◽  
Strategic Assets

Abstract Background The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) was launched in 2017 and involves, to date, 35 highly specialised multidisciplinary expert centres (from the 30 full Healthcare Provider members) coming from 11 countries and more than 70 patient organizations from 16 countries. The eHealth Working Group (WG) of VASCERN was set up to develop practical, patient-centred solutions and strategies for effective use of eHealth tools to answer the needs of patients with multisystemic vascular rare diseases. The eHealth WG Following the identified patients’ needs and following the guiding principles of collaboration and patient-centredness, the eHealth WG was created with the following aims: to develop a mobile app to help patients find expert centres and patient organizations, and to develop resources (Pills of Knowledge, PoK) for training and education via digital platforms (eLearning). The mobile app includes, to date, functionalities that allow users to find expert centres and patient organizations across Europe in the area of rare multisystemic vascular diseases. Discussed app developments include personalized digital patient passports, educational material, emergency management guidelines and remote consultations. Regarding training and education, a variety of PoK have been developed. The PoK cover several topics, target several user groups, and are delivered in various formats so that they are easy-to-use, easy-to-understand, informative, and viable for delivery and sharing through digital platforms (eLearning) including, e.g., the VASCERN YouTube™ channel. Conclusion Overall, the work carried out by the eHealth WG of VASCERN can be seen as a pilot experience that may serve as a basis to for collaborative development of patient-centred eHealth tools that answer the needs of patients with various rare diseases, not limited to rare multisystemic vascular diseases. By expanding the multidisciplinary approach here described, clinical and research networks can take advantage of eHealth services and use them as strategic assets in achieving the ultimate goal of ensuring equity of access to prevention programs, timely and accurate diagnosis and specialized care for patients with rare diseases throughout Europe.

scholarly journals Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet–ESPN inherited glomerulopathy working group

2020 ◽  
Vol 28 (10) ◽  
pp. 1368-1378 ◽  
Author(s):  
Beata Stefania Lipska-Ziętkiewicz ◽  
Fatih Ozaltin ◽  
Tuula Hölttä ◽  
Detlef Bockenhauer ◽  
Sandra Bérody ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Consensus Statement ◽  
Kidney Diseases ◽  
Work Group ◽  
Pediatric Nephrology ◽  
Congenital Nephrotic Syndrome ◽  
Genetic Diagnostics ◽  
Reference Network ◽  
European Reference Network ◽  
End Stage

Abstract Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders presenting with massive proteinuria within the first 3 months of life almost inevitably leading to end-stage kidney disease. The Work Group for the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Pediatric Nephrology (ESPN) has developed consensus statement on genetic aspects of CNS diagnosis and management. The presented expert opinion recommends genetic diagnostics as the key diagnostic test to be ordered already during the initial evaluation of the patient, discusses which phenotyping workup should be performed and presents known genotype–phenotype correlations.

scholarly journals A retrospective cohort study on European Reference Network for Rare Vascular Diseases 5 outcome measures for Hereditary Haemorrhagic Telangiectasia in Denmark

2021 ◽  
Author(s):  
Troels Hvelplund ◽  
Bibi Lange ◽  
Susanne Djernes Bird ◽  
Malene Korsholm ◽  
Anette Kjeldsen
Keyword(s):  
Iron Deficiency ◽  
Outcome Measures ◽  
Health Care Providers ◽  
Clinical Symptoms ◽  
Vascular Diseases ◽  
Reference Network ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Care Providers ◽  
Autosomal Dominant Disorder ◽  
European Reference Network

Abstract Background Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by several clinical symptoms including epistaxis, arteriovenous malformations (AVM), and telangiectasia. In 2018, European Reference Network for Rare Vascular Diseases (VASCERN) recommended five outcome measures for HHT-patients to guide health care providers, some with limited experience in treating HHT, and thereby maximizing the number of HHT-patients receiving good care. The outcome measures cover the following aspects: 1) 90% of the patients should receive a pulmonary AVM (PAVM) screening; 2) 90% of the patients should receive written advice on nosebleed; 3) 70% should be assessed for iron deficiency; 4) 100% of the patients should receive written advice on antibiotic (AB) prophylaxis prior to dental and surgical procedures, and; 5) 100% of relevant patients should receive written advice on pregnancy. We have introduced the outcome measures as Benchmarks in our HHT-centre and wanted to evaluate the extend of implementation we have achieved. We constantly struggle to secure the best possible treatment of our HHT-patients.Methods The study was a non-interventional retrospective study. All data was collected from medical journals and from the Danish HHT-database. Results A total of 180 HHT-patients were included, all diagnosed in the period from January 1st 2016 to December 31st 2020. All patients were screened for PAVM. We could confirm that 66% of patients who had epistaxis received thoroughly advice. Assessment for iron deficiency was performed in 80 % of the adult patients. Thoroughly advice on antibiotic prophylaxis was documented in 75%. Thoroughly advice on pregnancy was documented in 80% of female patients 15-45 years of age. There were no significant differences over time for any of the outcome measures. Conclusions The Danish HHT-centre reached the target threshold for outcome measures 1 and 3. We could not document reaching the target thresholds for outcome measures 2, 4, and 5. As information and education is a very important part of HHT care, we will focus on and document that all patients receive the relevant advice and as part of our care, we will in the near future implement an electronic solution with advice for HHT patients.

scholarly journals A retrospective cohort study on European Reference Network for Rare Vascular Diseases 5 outcome measures for Hereditary Haemorrhagic Telangiectasia in Denmark

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Troels Hvelplund ◽  
Bibi Lange ◽  
Susanne Djernes Bird ◽  
Malene Korsholm ◽  
Anette Drøhse Kjeldsen
Keyword(s):  
Iron Deficiency ◽  
Outcome Measures ◽  
Health Care Providers ◽  
Clinical Symptoms ◽  
Vascular Diseases ◽  
Reference Network ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Care Providers ◽  
Autosomal Dominant Disorder ◽  
European Reference Network

Abstract Background Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by several clinical symptoms including epistaxis, arteriovenous malformations (AVM), and telangiectasia. In 2018, European Reference Network for Rare Vascular Diseases (VASCERN) recommended five outcome measures for HHT-patients to guide health care providers, some with limited experience in treating HHT, and thereby maximizing the number of HHT-patients receiving good care. The outcome measures cover the following aspects: (1) 90% of the patients should receive a pulmonary AVM (PAVM) screening; (2) 90% of the patients should receive written advice on nosebleed; (3) 70% should be assessed for iron deficiency; (4) 100% of the patients should receive written advice on antibiotic (AB) prophylaxis prior to dental and surgical procedures, and (5) 100% of relevant patients should receive written advice on pregnancy. We have introduced the outcome measures as Benchmarks in our HHT-centre and wanted to evaluate the extend of implementation we have achieved. We constantly struggle to secure the best possible treatment of our HHT-patients. Methods The study was a non-interventional retrospective study. Data was collected manually from patient records and from the Danish HHT-database. Results A total of 180 HHT-patients were included, all diagnosed in the period from January 1st, 2016, to December 31st, 2020. All patients were screened for PAVM. We could confirm that 66% of patients who had epistaxis received thoroughly advice. Assessment for iron deficiency was performed in 80% of the adult patients. Thoroughly advice on AB prophylaxis was documented in 75%. Thoroughly advice on pregnancy was documented in 80% of female patients 15–45 years of age. There were no significant differences over time for any of the outcome measures. Conclusions The Danish HHT-centre reached the target threshold for outcome measures 1 and 3. It could not be documented that the target thresholds for outcome measures 2, 4, and 5 were achieved. As information and education are a very important part of HHT care, focus on and documentation that all patients receive the relevant advice must be a priority in order to ensure best care.

Abstract 637: Role of Nuclear Smooth Muscle Alpha-Actin in the Differentiation of Vascular Smooth Muscle Cells

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Shuangtao Ma ◽  
Dianna M Milewicz
Keyword(s):  
Smooth Muscle ◽  
Chromatin Remodeling ◽  
Vascular Diseases ◽  
Aortic Disease ◽  
Serum Starvation ◽  
Nuclear Fraction ◽  
Missense Mutations ◽  
Differentiation Markers ◽  
Two Dimensional Gel Electrophoresis ◽  
Protein Levels

Although the function of the cytoplasmic smooth muscle (SM) α-actin in contractile units has been well characterized in vascular SMCs, whether the SM α-actin is present in the nucleus and its nuclear function are yet to be determined. Our previous study discovered the mutations in ACTA2 , which encodes SM α-actin, predispose to both thoracic aortic disease and occlusive vascular diseases (stroke and coronary artery disease). We hypothesize that nuclear SM α-actin is critical for differentiation of SMCs. The cytoplasmic and nuclear fractions of mouse SMCs were isolated and the SM α-actin was detected in both cytosol and nucleus by immunoblotting. Moreover, both cytoplasmic and nuclear SM α-actin were dramatically upregulated during the differentiation of SMCs stimulated with TGF-β. Two-dimensional gel electrophoresis, which can separate actin isoforms based on distinct isoelectric points, was used to show that the ratio of SM α-actin to β-actin was increased in nuclear fraction when compared to cytoplasmic fraction with differentiation of SMCs, driven by serum starvation and TGF-β treatment. Furthermore, differentiation was associated with a significantly higher nuclear to cytoplasmic ratio of SM α-actin, indicating SM α-actin accumulates in the nucleus during differentiation. Co-immunoprecipitation experiments identified that nuclear SM α-actin is a component of the chromatin remodeling complex, Ino80, and the immunofluorescence confirmed co-localization of SM α-actin and Ino80 in the nucleus. To investigate the transcriptional function of nuclear SM α-actin, we performed the chromatin immunoprecipitation quantitative PCR, which revealed that the SM α-actin, but not β-actin, accumulated to the promoter region of SMC differentiation markers, including Myh11 , Cnn1 , and Tagln , during the differentiation of SMC. As expected, the Acta2 mutant SMCs (pArg149Cys) disrupt the differentiation of SMCs based on decreased contractile protein levels and increased proliferation. Furthermore, specific Acta2 missense mutations disrupt the ability for SM α-actin to localize to the nucleus. Taken together, our study found the SM α-actin concentrates into the nucleus of SMCs and may play a role in chromatin remodeling required for differentiation of SMCs.

Statins in Aortic Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7109-7120
Author(s):  
Vasiliki Tsigkou ◽  
Gerasimos Siasos ◽  
Evanthia Bletsa ◽  
Maria-Paraskevi Panoilia ◽  
Angeliki Papastavrou ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Genetic Disorders ◽  
Aortic Disease ◽  
Current Data ◽  
Valve Regurgitation ◽  
Aortic Diseases ◽  
Cochrane Database ◽  
Effect Of Treatment ◽  
Pleiotropic Actions ◽  
Optimal Type

Background: Numerous studies indicate that statins have multiple beneficial actions (known as ‘pleiotropic actions&#39;) on cardiovascular system through the improvement of endothelial dysfunction, inflammation, oxidative stress, excessive arterial thrombosis, and stabilization of the atherosclerotic plaque. Aortic disease primarily consists of aortic valve stenosis, aortic valve regurgitation, aneurysm disease, and genetic disorders such as Marfan syndrome, bicuspid aortic valve and aortic coarctation. Many studies have revealed the cardioprotective actions of statins in aortic disease. </P><P> Objective: Our aim was to present current data concerning the value of treatment with statins in aortic diseases. </P><P> Methods: A thorough search of PubMed and the Cochrane Database was conducted to identify the studies and novel articles related to the use of statins in aortic disease. </P><P> Results: Numerous studies in animals and humans indicate a beneficial effect of treatment with statins in the previous conditions apart from a few conflicting data. </P><P> Conclusion: There is a need of further investigation in this field, especially for the estimation of the optimal type and dose of statins required in each clinical condition of aortic disease.

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