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2.
Arq. Asma, Alerg. Imunol ; 6(2): 151-169, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400194

ABSTRACT

O angioedema hereditário é uma doença autossômica dominante caracterizada por crises recorrentes de edema que acometem o tecido subcutâneo e o submucoso, com envolvimento de diversos órgãos. Os principais locais afetados são face, membros superiores e inferiores, as alças intestinais e as vias respiratórias superiores. Em decorrência da falta de conhecimento dessa condição por profissionais de saúde, ocorre atraso importante no seu diagnóstico, comprometendo a qualidade de vida dos indivíduos afetados. Além disso, o retardo no diagnóstico pode resultar em aumento da mortalidade por asfixia devido ao edema de laringe. A natureza errática das crises com variação do quadro clínico e gravidade dos sintomas entre diferentes pacientes, e no mesmo paciente ao longo da vida, se constitui em desafio no cuidado dos doentes que têm angioedema hereditário. O principal tipo de angioedema hereditário é resultante de mais de 700 variantes patogênicas do gene SERPING1 com deficiência funcional ou quantitativa da proteína inibidor de C1, porém nos últimos anos outras mutações foram descritas em seis outros genes. Ocorreram avanços importantes na fisiopatologia da doença e novas drogas para o tratamento do angioedema hereditário foram desenvolvidas. Nesse contexto, o Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) em conjunto com a Associação Brasileira de Alergia e Imunologia (ASBAI) atualizou as diretrizes brasileiras do angioedema hereditário. O maior conhecimento dos diversos aspectos resultou na divisão das diretrizes em duas partes, sendo nessa primeira parte abordados a definição, a classificação e o diagnóstico.


Hereditary angioedema is an autosomal dominant disease characterized by recurrent attacks of edema that affect the subcutaneous tissue and the submucosa, involving several organs. The main affected sites are the face, upper and lower limbs, gastrointestinal tract, and upper airways. Because health professionals lack knowledge about this condition, there is a significant delay in diagnosis, compromising the quality of life of affected individuals. Furthermore, delayed diagnosis may result in increased mortality from asphyxia due to laryngeal edema. The erratic nature of the attacks with variations in clinical course and severity of symptoms among different patients and in one patient throughout life constitutes a challenge in the care of patients with hereditary angioedema. The main type of hereditary angioedema results from more than 700 pathogenic variants of the SERPING1 gene with functional or quantitative deficiency of the C1 inhibitor protein, but in recent years other mutations have been described in six other genes. Important advances have been made in the pathophysiology of the disease, and new drugs for the treatment of hereditary angioedema have been developed. In this context, the Brazilian Study Group on Hereditary Angioedema (GEBRAEH) in conjunction with the Brazilian Association of Allergy and Immunology (ASBAI) updated the Brazilian guidelines on hereditary angioedema. Greater knowledge of different aspects resulted in the division of the guidelines into two parts, with definition, classification, and diagnosis being addressed in this first part.


Subject(s)
Humans , Therapeutics , Classification , Diagnosis , Angioedemas, Hereditary , Quality of Life , Asphyxia , Signs and Symptoms , Societies, Medical , Pharmaceutical Preparations , Glycoproteins , Laryngeal Edema , Allergy and Immunology , Mutation
3.
Arq. Asma, Alerg. Imunol ; 6(2): 170-196, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400199

ABSTRACT

O tratamento do angioedema hereditário tem início com a educação dos pacientes e familiares sobre a doença, pois é fundamental o conhecimento da imprevisibilidade das crises, assim como os seus fatores desencadeantes. O tratamento medicamentoso se divide em terapia das crises e profilaxia das manifestações clínicas. As crises devem ser tratadas o mais precocemente possível com o uso do antagonista do receptor de bradicinina, o icatibanto ou o concentrado de C1-inibidor. É necessário estabeler um plano de ação em caso de crises para todos os pacientes. A profilaxia de longo prazo dos sintomas deve ser realizada preferencialmente com medicamentos de primeira linha, como concentrado do C1-inibidor ou o anticorpo monoclonal anti-calicreína, lanadelumabe. Como segunda linha de tratamento temos os andrógenos atenuados. Na profilaxia de curto prazo, antes de procedimentos que podem desencadear crises, o uso do concentrado de C1-inibidor é preconizado. Existem algumas restrições para uso desses tratamentos em crianças e gestantes que devem ser consideradas. Novos medicamentos baseados nos avanços do conhecimento da fisiopatologia do angioedema hereditário estão em desenvolvimento, devendo melhorar a qualidade de vida dos pacientes. O uso de ferramentas padronizadas para monitorização da qualidade de vida, do controle e da atividade da doença são fundamentais no acompanhamento destes pacientes. A criação de associações de pacientes e familiares de pacientes com angioedema hereditário tem desempenhado um papel muito importante no cuidado destes pacientes no nosso país.


The treatment of hereditary angioedema begins with the education of patients and their families about the disease, as it is essential to know the unpredictability of attacks as well as their triggering factors. Drug treatment is divided into attack therapy and prophylaxis of clinical manifestations. Attacks should be treated as early as possible with the bradykinin receptor antagonist icatibant or C1-inhibitor concentrate. An action plan needs to be established for all patients with attacks. Long-term prophylaxis of symptoms should preferably be performed with first-line drugs such as C1-inhibitor concentrate or the anti-kallikrein monoclonal antibody lanadelumab. Attenuated androgens are the second line of treatment. In short-term prophylaxis, before procedures that can trigger attacks, the use of C1-inhibitor concentrate is recommended. There are some restrictions for the use of these treatments in children and pregnant women that should be considered. New drugs based on advances in knowledge of the pathophysiology of hereditary angioedema are under development and are expected to improve patient quality of life. The use of standardized tools for monitoring quality of life and controlling disease activity is essential in the follow-up of these patients. The creation of associations of patients and families of patients with hereditary angioedema has played a very important role in the care of these patients in Brazil.


Subject(s)
Humans , Drug Therapy , Angioedemas, Hereditary , Antibodies, Monoclonal, Humanized , Bradykinin Receptor Antagonists , Patients , Quality of Life , Therapeutics , Bradykinin , Pharmaceutical Preparations , Kallikreins , Reference Drugs
4.
Int Arch Allergy Immunol ; 183(5): 572-577, 2022.
Article in English | MEDLINE | ID: mdl-35325890

ABSTRACT

BACKGROUND: Acquired deficiency of C1 inhibitor (AAE-C1-INH) is a very rare cause of recurrent angioedema, with few cases reported in the literature. We aimed to describe a series of patients with AAE-C1-INH who were diagnosed and received care at angioedema reference centers in Brazil, affiliated to the Brazilian Group of Studies on Hereditary Angioedema. METHODS: Fourteen patients from 8 Brazilian Angioedema Reference Centers, diagnosed with AAE-C1-INH, were included in this study. Clinical data collected included sex, date of birth, date of onset of symptoms, date of diagnosis, plasma levels of antigenic and/or functional C1-INH, levels of C4 and C1q, location and treatment of angioedema attacks, long-term prophylaxis, associated diseases, and definitive treatment. RESULTS: Fourteen patients were identified with AAE-C1-INH. Most patients (10/14; 71.4%) were female. The median age at onset of symptoms was 56.5 years (range, 14-74 years; interquartile range [IQR], 32-64 years), and median age at diagnosis was 58.0 years (range, 20-76 years; IQR, 38-65 years), with a median time until diagnosis of 2 years (range, 0-6 years; IQR, 1-3 years). The most common manifestations were cutaneous (face, eyelids, lips, trunk, hands, feet, and genitals). Most patient had low levels of C4 (13/14; 92.8%) and of antigenic C1-INH (8/14; 57.1%). Four had decreased functional activity of C1-INH (4/7; 57.1%) and C1q levels were low in 5 patients (5/12; 41.6%). Underlying diseases were identified in all 14 patients, with lymphoma of the splenic marginal zone and monoclonal gammopathy of undetermined significance being the most frequent. Nine patients (64.2%) needed long-term prophylactic treatment for recurrent angioedema and 5 patients (46.7%) required treatment for angioedema attacks. Most of them (12/14; 85.7%) had resolution of angioedema. CONCLUSION: Therapy of AAE-C1-INH aims to control symptoms; however, diagnosis and treatment of the underlying disease, when present, should be an important target and may lead to the resolution of angioedema in patients with AAE-C1-INH.


Subject(s)
Angioedema , Angioedemas, Hereditary , Adolescent , Adult , Aged , Angioedema/diagnosis , Angioedema/etiology , Angioedemas, Hereditary/therapy , Brazil/epidemiology , Complement C1 Inhibitor Protein/genetics , Complement C1q/therapeutic use , Female , Humans , Male , Middle Aged , Young Adult
5.
Arq. Asma, Alerg. Imunol ; 6(1): 141-143, jan.mar.2022.
Article in English | LILACS | ID: biblio-1400124

ABSTRACT

Hereditary angioedema (HAE) is a rare autosomal dominant disorder, Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease involving hypersensitivity to the fungi Aspergillus fumigatus which occur in susceptible patient with asthma or cystic fibrosis, also considered a rare disease. We report a case of HAE and ABPA in a single patient. HAE diagnosis was confirmed: C4 = 3 mg/dL, C1INH < 2.8 mg/dL - nephelometry. Former lung function showed elevation RV and RV/FVC, suggesting small airways lung disease. Positive skin prick test to Aspergillus fumigatus (03 mm); total serum IgE level 3,100 IU/mL (nephelometry - BNII Siemens), eosinophilia 11% (528/mm3) and specific A. fumigatus IgG antibodies 6,8 mgA/L (FEIA - fluorenzymeimmunoassay - ThermoFisher) and Chest CT showed mucoid impaction of the bronchi, consistent to current ABPA. Controlling ABPA could prevent and reduce angioedema attacks, and lung structural damage. Early diagnosis and treatment of both diseases should be emphasized to reduce mortality and morbidity


Angioedema hereditário (AEH) é uma doença autossômica dominante; aspergilose broncopulmonar alérgica (ABPA) é uma doença de hipersensibilidade pulmonar relacionada ao esporo de Aspergillus fumigatus, mais suscetível em pacientes com asma e fibrose cística, ambas são consideradas doenças raras. Apresentamos um caso de AEH e ABPA em um paciente. O diagnóstico de AEH foi confirmado com exames laboratoriais: C4 = 3 mg/dL, C1INH < 2,8 mg/dL - nefelometria. Prova de função pulmonar evidenciou aumento de VR e VR/CVF, sugerindo doenças de pequenas vias aéreas. Teste de puntura positivo para A. fumigatus (03 mm); IgE total = 3.100 IU/mL (nefelometria - BNII Siemens), eosinofilia 11% (528/mm3) e IgG específica para A. fumigatus 6,8 mgA/L (FEIA - ThermoFisher), TC de tórax evidenciou impactação mucoide, consistente com ABPA. Controlar ABPA pode prevenir e reduzir as crises de angioedema e os danos ao tecido pulmonar. O diagnóstico precoce de ambas as doenças deve ser enfatizado para reduzir a morbimortalidade.


Subject(s)
Humans , Male , Child , Aspergillosis, Allergic Bronchopulmonary , Angioedemas, Hereditary , Patients , Association , Asthma , Therapeutics , Immunoglobulin E , Rare Diseases , Early Diagnosis , Diagnosis , Eosinophilia
6.
J Clin Immunol ; 41(7): 1479-1489, 2021 10.
Article in English | MEDLINE | ID: mdl-34164762

ABSTRACT

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).


Subject(s)
COVID-19/diagnosis , Primary Immunodeficiency Diseases/diagnosis , SARS-CoV-2/physiology , Systemic Inflammatory Response Syndrome/diagnosis , Adult , Asymptomatic Diseases , Brazil , COVID-19/mortality , Cross-Sectional Studies , Disease Progression , Female , Humans , Male , Middle Aged , Primary Immunodeficiency Diseases/mortality , Severity of Illness Index , Survival Analysis , Systemic Inflammatory Response Syndrome/mortality , Young Adult
7.
Clin Rev Allergy Immunol ; 61(1): 60-65, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33755867

ABSTRACT

Hereditary angioedema (HAE) is an autosomal dominant disease mostly due to the deficiency of C1 inhibitor (C1-INH). HAE with normal C1-INH was first described in 2000 and associated with mutations in the coagulation factor XII in 2006. Both diseases are associated with high bradykinin production, resulting in increased vascular permeability. Gastrointestinal edema due to HAE can be misdiagnosed as acute abdomen and unnecessary surgical procedures may be performed. The present study evaluates the prevalence of surgical procedures and/or acute abdomen in HAE patients with the coagulation factor XII mutation. It is a retrospective study where patients were diagnosed with recurrent angioedema without urticaria, normal C1-INH levels, and positive family history of angioedema. All patients were evaluated for the known mutations located at exon 9 of the F12 gene. Medical records were evaluated and questionnaires were applied to 52 patients with normal C1-INH levels (age range 13-76 years; 47/52, 90.38% women; 5/52, 9.61% men). F12 mutation was present in 32/52 patients (61.5%). Acute abdominal pain was diagnosed in 16/52 (30.76%) patients, appendicitis in 9/16 (56.2%), and undetermined diagnosis in 7/16 (43.7%). Among patients diagnosed with acute abdominal pain, 13/16 (81.2%) underwent surgery and 3/16 (18.7%) improved without surgical intervention. We conclude that many HAE patients with coagulation factor XII mutation were misdiagnosed with acute abdomen and subjected to unnecessary invasive procedures. It is critical to disseminate information about this rare mutation in patients with otherwise normal C1-INH activity, in order to speed up diagnosis and avoid misconduct.


Subject(s)
Abdomen, Acute , Angioedema , Angioedemas, Hereditary , Abdominal Pain , Adolescent , Adult , Aged , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/genetics , Complement C1 Inhibitor Protein , Factor XII/genetics , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
8.
Int Arch Allergy Immunol ; 182(7): 585-591, 2021.
Article in English | MEDLINE | ID: mdl-33508850

ABSTRACT

INTRODUCTION: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. METHODS: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. RESULTS: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. CONCLUSIONS: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.


Subject(s)
Angioedemas, Hereditary/epidemiology , Adolescent , Anaphylaxis/etiology , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/therapy , Brazil/epidemiology , Child , Child, Preschool , Delayed Diagnosis , Disease Management , Female , Follow-Up Studies , Humans , Male , Public Health Surveillance , Quality of Life
10.
Article in English | MEDLINE | ID: mdl-33012673

ABSTRACT

OBJECTIVE: The aim of this study was to report on clinical experience in Brazil in the dental treatment and the oral conditions of a group of patients with hereditary angioedema (HAE). STUDY DESIGN: The study analyzed demographic data, type of HAE, intensity of attacks, long-term and short-term prophylaxis, dental procedures, and occurrence of crises after the procedures were performed. Radiographic evaluation of the number of teeth and bone loss was also performed. RESULTS: Data from 12 patients were collected; most were women, presenting with C1-INH-HAE type I and a history of severe attacks. All patients reported use of regular medications (long-term prophylaxis), mostly attenuated androgens, to prevent/attenuate HAE attacks. These patients had several missing teeth and alveolar bone loss. Tooth extraction was the most common procedure. In half the patients, the procedures had been performed without modification in long-term prophylaxis. The others were treated with an additional prophylaxis protocol (short-term prophylaxis), particularly those who underwent tooth extraction. None of the study patients developed HAE attacks after dental procedures. CONCLUSION: The occurrence and intensity of a possible HAE attack after dental procedures are unpredictable, but with careful preliminary screening by dental and immunology teams and the use of therapeutic prophylaxis, the risk could be minimized.


Subject(s)
Angioedemas, Hereditary , Brazil , Complement C1 Inhibitor Protein , Dental Care , Female , Humans , Tooth Extraction
11.
Arq. Asma, Alerg. Imunol ; 3(4): 406-420, out.dez.2019. ilus
Article in Portuguese | LILACS | ID: biblio-1381355

ABSTRACT

A microbiota intestinal humana influencia diversos sistemas orgânicos e há evidências de sua ação sobre o sistema imunológico. O objetivo desta revisão foi verificar a influência da microbiota intestinal humana e sua interface com o sistema imunológico. A partir das palavras-chaves gut (intestino) e microbiota (microbiota), e utilizando o operador boleano AND para correlacionar a palavra-chave com os diversos temas propostos para o artigo de revisão, como por exemplo, gut microbiota AND delivery ou gut microbiota AND mode of delivery, foram selecionados artigos obtidos da busca na base PubMed, sobretudo nos últimos 10 anos (2009-2019). Há evidências de que a janela de oportunidade para intervenção e prevenção primária das doenças alérgicas começa antes do nascimento e provavelmente dentro do período fetal, estendendo-se ao tipo de parto, alimentação nos primeiros meses de vida, fatores ambientais e uso de antibióticos. Compreender esta complexa interface que envolve, por um lado a microbiota (microrganismos e seus subprodutos) e, por outro, receptores e células especializadas, é fundamental para o entendimento dos mecanismos de tolerância ou desequilíbrio imunológico, os quais estão respectivamente ligados ao estado fisiológico de saúde ou aos processos patofisiológicos de diversas doenças, sobretudo aquelas de contexto imunomediado.


The human gut microbiota influences various organ systems, and there is evidence of its action on the immune system. The aim of this review was to determine the influence of the human gut microbiota and its interface with the immune system. The PubMed database was searched for articles published from 2009 to 2019 using the keywords "gut" and "microbiota". The Boolean operator AND was used to combine terms in the search, such as "gut microbiota AND delivery" and "gut microbiota AND mode of delivery". There is evidence that the window of opportunity for intervention and primary prevention of allergic diseases begins before birth, probably within the fetal period, and includes mode of delivery, early infant feeding, environmental factors, and antibiotic use. Understanding the complex interface that involves, on the one hand, the microbiota (microorganisms and their by-products) and, on the other hand, specialized receptors and cells is essential for understanding the mechanisms of tolerance and immune imbalance, which are respectively linked to the physiological health status and to the pathophysiological processes of various diseases, especially of immune-mediated diseases.


Subject(s)
Humans , Infant, Newborn , Infant , Breast Feeding , Microbiota , Gastrointestinal Microbiome , Immune System , Health Status , Parturition , PubMed , Infant Formula , Anti-Bacterial Agents
13.
Braz. j. allergy immunol ; 1(5): 253-260, sept.-out. 2013.
Article in Portuguese | LILACS | ID: lil-775972

ABSTRACT

A deficiência específica de anticorpo antipolissacarídeo de pneumococo é o comprometimento da resposta IgG específica aos antígenos polissacarídeos do pneumococo e manifesta-se de maneira semelhante às outras deficiências de imunoglobulinas, com infecções recorrentes do trato respiratório. A prevalência é variável, entre 7 a 19%, representando no Brasil 8,7% dos casos de imunodeficiências. O diagnóstico funcional baseia-se na capacidade do organismo montar uma resposta imune constituída pela produção de anticorpos quando estimulado por antígenos polissacarídeos presentes na vacina pneumocócica polissacarídea pura. No estudo da resposta à vacina pneumocócica polissacarídea pura é necessário testar os sorotipos não comuns à vacina polissacarídea conjugada para determinar a resposta de anticorpos antipolissacarídeos sem a interferência de anticorpos antiproteínas advindos da vacina polissacarídea conjugada. São reconhecidos quatro diferentes fenótipos da doença, denominados memória, leve, moderada e grave. O objetivo do presente trabalho foi realizar revisão da literatura para verificar a epidemiologia, diagnóstico e fenótipos da deficiência específica de anticorpo antipolissacarídeo de pneumococo. Trata-se de revisão narrativa de artigos nos últimos 10 anos sobre a deficiência de anticorpo específica para o pneumococo. Concluímos que a deficiência específica de anticorpo antipolissacarídeo de pneumococo é frequente, com espectro laboratorial variável.


Specific anti-pneumococcal polysaccharide antibody deficiency is characterized by impairment of specific IgG response to pneumococcal polysaccharide antigens. Its clinical manifestation is similar to other immunoglobulin deficiencies, with recurrent infections of the respiratory tract. Prevalence is variable, ranging from 7 to 19%; in Brazil, it accounts for 8.7% of cases of immunodeficiencies. Diagnosis is based on the body’s functional ability to mount an immuneresponse including the production of antibodies after stimulation by polysaccharide antigens present in the pure pneumococcal polysaccharide vaccine. When studying responses to this vaccine, it is necessary to test serotypes other than those present in the pneumococcal conjugate vaccine, in order to determine the response of anti-polysaccharide antibodies not influenced by antiprotein antibodies originating from the conjugate vaccine. Four different phenotypes of the disease are known: memory, mild, moderate, and severe. The objective of the present study was to review the literature on the epidemiology, diagnosis, and phenotypes of specific antipolysaccharide antibody deficiency. This narrative review includes papers published in the past 10 years on specific anti-pneumococcal polysaccharide antibody deficiency. We conclude that the condition is common, with a variable spectrum of laboratory findings.


Subject(s)
Humans , Immunoglobulins , Immunologic Deficiency Syndromes , Pneumococcal Infections , Pneumococcal Vaccines , Polysaccharides, Bacterial , Severe Combined Immunodeficiency , Streptococcus pneumoniae , Diagnostic Techniques and Procedures , Epidemiology , Methods , Prevalence
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