Ruptured carotid artery pseudoaneurysm following excision of a carotid body tumor: a rare complication managed successfully with surgery and literature review / Pseudoaneurisma de artéria carótida rompida após excisão de tumor do corpo carotídeo: uma complicação rara tratada com sucesso com cirurgia e revisão da literatura

Abstract A 47-year-old male presented with a right-sided Shamblin type 2 carotid body tumor measuring 5*5 cm. After preoperative embolization, a sub adventitial resection of the tumor was done. He was discharged after postoperative day 5 and presented again to emergency 10 days later with a bleeding pseudoaneurysm at the surgical site causing dysphagia and dyspnea. He was taken for emergency exploration of the surgical wound and, intraoperatively, it was observed that the proximal ends of the internal carotid artery and external carotid artery close to the bifurcation were forming a pseudoaneurysm, 1 cm distal to the common carotid artery. The external carotid artery was ligated and a common carotid to internal carotid artery bypass was done with a reversed saphenous vein graft. He recovered well in the postoperative period and was discharged on day 7. Pseudoaneurysm formation following carotid body tumor resection is extremely rare and has only been reported thrice in the literature.

Resumo Um homem de 47 anos apresentou tumor carotídeo Shamblin tipo 2 no lado direito, medindo 5 x 5 cm. Após embolização pré-operatória, foi realizada ressecção subadventicial do tumor. O paciente teve alta no quinto dia pós-operatório e voltou à emergência 10 dias depois, com pseudoaneurisma hemorrágico no sítio operatório causando disfagia e dispneia. Foi levado para exploração emergencial da ferida cirúrgica, e, no intraoperatório, 1 cm distalmente à artéria carótida comum, as extremidades proximais da artéria carótida interna e da artéria carótida externa próximas à bifurcação formavam um pseudoaneurisma. A artéria carótida externa foi ligada, e foi realizada uma ponte de safena de carótida comum para a artéria carótida interna com a veia safena invertida. O paciente se recuperou bem no pós-operatório e recebeu alta no sétimo dia. A formação de pseudoaneurisma após ressecção de tumor do corpo carotídeo é extremamente rara, tendo sido relatada apenas três vezes na literatura.

Estratégias de Avaliação de Tecnologias em Saúde (ATS) para medicamentos para doenças raras: uma revisão rápida de escopo / Health Technology Assessment (HTA) strategies for drugs in rare diseases: a rapid scope review

A Avaliação de Tecnologias em Saúde (ATS) considera os domínios de benefícios clínicos, perfil epidemiológico, inovação, custo-efetividade, ética e de equidade no processo de decisão dos gestores em saúde. No contexto dos medicamentos para doenças raras, é desafiador o trabalho da ATS, dada a baixa disponibilidade de evidências robustas e o alto custo unitário das tecnologias. O objetivo da revisão foi analisar as estratégias disponíveis de avaliação das demandas de incorporação de medicamentos para o tratamento de doenças raras em sistemas de saúde. Foi realizada uma revisão rápida com busca estruturada na base de dados MEDLINE (via PubMed), Cochrane Library e Health Systems Evidence. Incluíram-se estudos sobre estratégias de avaliação de medicamentos utilizados para tratamento de doenças raras. Adicionalmente, foram realizadas buscas nas Agências de ATS do Brasil, Austrália, Nova Zelândia, Canadá, Reino Unido, França, Estados Unidos e Alemanha. A síntese dos resultados foi qualitativa com o agrupamento dos achados nos seguintes eixos temáticos: Segurança e efetividade, Custo-efetividade, Impacto orçamentário e Perspectiva da sociedade. Foram identificadas 267 publicações, sendo selecionadas 16 das bases de dados indexadas e 7 da literatura cinzenta. Com a análise dos documentos, pode-se concluir que a adoção de critérios específicos harmonizada com o atual modelo de ATS é um possível caminho a ser seguido no contexto dos medicamentos para doenças raras. Concomitante a isso, abordagens no sentido de incentivo a pesquisa e produção de dados de mundo real e a criação de comitês específicos para tratativa do tema nas agências de ATS apresentam-se como alternativa para lidar com as fragilidades no contexto de doenças raras.

The Health Technology Assessment (HTA) considers evidence regarding clinical benefits, epidemiological profile, innovation, cost-effectiveness, ethics and equity in its assessment process to support managers' decisions. In the context of drugs in rare diseases, the work of the ATS is challenging given the low availability of evidence and the high cost of technologies. The objective of the review was to analyze the available strategies for evaluating the demands for incorporating drugs for the treatment of rare diseases in health systems. A rapid review was performed with a structured search in the MEDLINE database (via PubMed), the Cochrane Library and Health Systems Evidence. Studies on strategies for evaluating drugs used to treat rare diseases were included and, additionally, searches were carried out in ATS Agencies in Brazil, Australia, New Zealand, Canada, United Kingdom, France, United States and Germany. The synthesis of the results was qualitative, grouping the major ones into thematic axes: Safety and effectiveness, Cost-effectiveness, Budgetary impact and Society's perspective. 267 publications were identified, 16 selected from indexed databases and 7 from gray literature. With the analysis of the documents, it can be concluded that the adoption of specific criteria harmonized with the current ATS model is a possible path to be followed in the context of drugs for rare diseases. At the same time, approaches to encourage research and the creation of specific committees to deal with the issue in HTA agencies would complement actions towards the consolidation of this work.

Impacto de la caracterización genómica en pacientes con atrofia muscular espinal no 5q / Impact of Genomic Characterization in Patients with Non-5q Spinal Muscular Atrophy / Impacto da caracterização genômica em pacientes com atrofia muscular espinhal não 5q

Resumen: La atrofia muscular espinal (AME) se define como un conjunto de trastornos neurodegenerativos hereditarios causantes de una variabilidad fenotípica y genotípica que genera un impacto sobre la calidad de vida, desarrollo psicosocial, emocional y funcional de quien la padece. En Colombia se considera una enfermedad huérfana con relación a su baja prevalencia, cronicidad y alta complejidad. El objetivo de este reporte de caso es describir, caracterizar y correlacionar fenotípica y genotípicamente un paciente con sospecha clínica de enfermedad neurodegenerativa. Se trata de una paciente femenina de 32 años de edad, con cuadro clínico consistente en equinismo, varismo, supinación del retropié, aducción del antepié derecho y limitación en muñecas con posterior debilidad y atrofia muscular predominantemente en miembros inferiores, arreflexia generalizada y signo de Gowers positivo. Ante sospecha de enfermedad neuromuscular progresiva degenerativa se solicitan estudios endocrinos, neuromusculares, cardiovasculares, biopsia de nervio sural y estudio genético. Los resultados arrojan biopsia de nervio sural con pérdida de axones con poca desmielinización, y estudio genómico secuenciación de exoma clínico trío realizado utilizando la tecnología Illumina con identificación de variantes con significado clínico patogénico en el gen NOD2 con cigosidad heterocigota y DYNC2H1 homocigota. Finalmente se realiza red de interacción génica mediante programa GeneMania determinando asociaciones génicas. Conclusión: el diagnóstico de AME representa un desafío debido a su amplia variabilidad fenotípica-genotípica, aunque en la mayoría de los pacientes se deben a variantes en el gen SMN1 existen otros genes no 5q asociados a esta patología, un diagnóstico específico impacta en el tratamiento, pronóstico y morbimortalidad atribuida, estableciendo riesgo de heredabilidad y consejería genética en aras de medicina preventiva, predictiva, personalizada y participativa.

Abstract: Spinal Muscular Atrophy (SMA) is defined as a set of hereditary neurodegenerative disorders that cause phenotypic and genotypic variability, impacting the quality of life, psychosocial, emotional, and functional development of those affected. In Colombia, it is considered a rare disease due to its low prevalence, chronicity, and high complexity. The objective of this case report is to describe, characterize, and correlate phenotypically and genotypically a patient with clinical suspicion of neurodegenerative disease. The patient is a 32-year-old female with a clinical picture of equinus, varus, supination of the hindfoot, adduction of the right forefoot, and limitation in wrists with subsequent weakness and predominantly lower limb muscle atrophy, generalized areflexia, and positive Gowers sign. Given the suspicion of progressive degenerative neuromuscular disease, endocrine, neuromuscular, cardiovascular studies, sural nerve biopsy, and genetic testing are requested. The results show sural nerve biopsy with axonal loss with little demyelination, and genomic study using trio clinical exome sequencing performed using Illumina technology with identification of pathogenic clinically significant variants in the Nod2 gene with heterozygous and DYNC2H1 gene with homozygous status. Finally, a gene interaction network is created using the GeneMania program, determining gene associations. The conclusion of this study was the diagnosis of Sma represents a challenge due to its wide phenotypic-genotypic variability. Although most patients are due to variants in the SmN1 gene, there are other non-5q genes associated with this pathology. A specific diagnosis impacts treatment, prognosis, and attributed morbidity and mortality, establishing heritability risk and genetic counseling for the sake of preventive, predictive, personalized, and participatory medicine.

Resumo: A atrofia muscular espinhal (AME) é definida como um conjunto de transtornos neurodegenerativos hereditários causadores de uma variabilidade fenotípica e genotípica que tem um impacto na qualidade de vida, desenvolvimento psicossocial, emocional e funcional daqueles que a têm. Na Colômbia, ela é considerada uma doença rara devido à sua baixa prevalência, cronicidade e alta complexidade. O objetivo deste relatório de caso é descrever, caracterizar e correlacionar fenotípica e genotipicamente um paciente com suspeita clínica de doença neurodegenerativa. Trata-se de uma paciente do sexo feminino, com 32 anos de idade, com quadro clínico consistente em equinismo, varismo, supinação do retropé, adução do antepé direito e limitação nos pulsos, com subsequente fraqueza e atrofia muscular predominantemente nos membros inferiores, arreflexia generalizada e sinal de Gowers positivo. Diante da suspeita de doença neuromuscular progressiva degenerativa, foram solicitados estudos endócrinos, neuromusculares, cardiovasculares, biópsia do nervo sural e estudo genético. Os resultados mostraram biópsia do nervo sural com perda de axônios com pouca desmielinização e estudo genômico de sequenciamento do exoma clínico trio realizado com tecnologia Illumina, identificando variantes com significado clínico patogênico no gene Nod2 com zigosidade heterozigota e DYNC2H1 homozigota. Finalmente, realizou-se uma rede de interação gênica mediante o programa GeneMania, determinando associações genéticas. Conclusão: O diagnóstico de AME representa um desafio devido à sua ampla variabilidade fenotípica-genotípica. Embora a maioria dos pacientes devem-se a variantes no gene SmN1, existem outros genes não 5q associados a essa patologia. Um diagnóstico específico impacta no tratamento, prognóstico e morbimortalidade atribuída, estabelecendo risco de hereditariedade e aconselhamento genético em prol da medicina preventiva, preditiva, personalizada e participativa.

Coincidencia de Rhupus y embarazo. Reporte de caso / Coincidence of Rhupus and pregnancy. Case report

Resumen ANTECEDENTES: Si bien el lupus eritematoso sistémico y la artritis reumatoide son enfermedades suficientemente descritas, no lo es la asociación de estas, que se denomina rhupus, que hace referencia a la manifestación clínica resultante de ambas enfermedades enmascaradas que dificulta el diagnóstico y tratamiento. CASO CLÍNICO: Paciente de 37 años que inició con un cuadro con características de lupus eritematoso sistémico y artritis reumatoide hacía 16 años. Se encontró con alteraciones en los estudios de laboratorio y con hallazgos radiológicos que apoyaron el cuadro de rhupus. Por lo anterior se documenta la evolución de este padecimiento, que coincide con su embarazo y después de éste. CONCLUSIONES: La aparición simultánea de lupus eritematoso sistémico y artritis reumatoide, aun cuando fue reportada desde hace décadas, es una enfermedad rara en frecuencia, por lo que hay escasa información del rhupus solo y más aún en coincidencia con el embarazo.

Abstract BACKGROUND: Although systemic lupus erythematosus and rheumatoid arthritis are sufficiently described diseases, the association of these is not, and is called rhupus, which refers to the clinical manifestation resulting from both diseases masked, making diagnosis and treatment difficult. CLINICAL CASE: 37-year-old patient who started with a clinical picture with features of systemic lupus erythematosus and rheumatoid arthritis 16 years ago. She was found to have alterations in laboratory studies and radiological findings that supported the diagnosis of rheupus. Therefore, the evolution of this condition is documented, which coincides with and after her pregnancy. CONCLUSIONS: The simultaneous occurrence of systemic lupus erythematosus and rheumatoid arthritis, even though it was reported decades ago, is a rare disease in frequency, so there is scarce information on rhupus alone and even more so in coincidence with pregnancy.

Tumor neuroectodérmico primitivo periférico de riñón, reporte de caso

Introducción: El tumor neuroectodérmico primitivo periférico de riñón (PNETk) es una enfermedad rara muy agresivo que afecta mayormente a varones jóvenes. Reporte de caso: paciente varón de 19 años con cuadro clínico dolor abdominal, hematuria y masa palpable, en la tomografía se evidencia una enorme tumoración renal izquierda, Se le realiza nefrectomía radical convencional y se envía a estudio patológico más histoquímica resultando de PNETk. Luego paciente siguió su manejo por oncología para quimiterapia inicialmente. Conclusión: El PNETk que describimos representa el primer caso reportado en nuestro país, constituye una entidad clínica única por su rareza siendo un reto hacer diagnóstico y su comportamiento y manejo se sigue basando a reportes de casos debido a su poca frecuencia.

Introduction: Peripheral primitive neuroectodermal tumor of the kidney (PNETk) is a very aggressive rare disease that mainly affects young men. Case report: A 19-year-old male patient with symptoms of abdominal pain, hematuria and a palpable mass, the tomography shows a large left renal tumor. Conventional radical nephrectomy was performed and sent for pathology study plus histochemistry, resulting in PNETk. The patient then continued his oncology management for chemotherapy initially. Conclusion: The PNETk that we describe represents the first case reported in our country, it constitutes a unique clinical entity due to its rarity, being a challenge to make a diagnosis and its behavior and management is still based on case reports due to its infrequency.

Cutis verticis gyrata. Presentación de un caso y revisión de la literatura

RESUMEN La cutis verticis gyrata es una patología poco frecuente del cuero cabelludo caracterizada por la proliferación del tejido celular subcutáneo e hipertrofia que produce pliegues y surcos que le dan aspecto cerebriforme. Aunque su etiología es aún desconocida, la condición no es exclusivamente congénita, se ha propuesto como teoría la presencia de mutaciones autosómicas dominantes en el receptor de factor de crecimiento de fibroblastos 2. Esta patología es extremadamente rara en pediatría. Se divide en primaria y secundaria. Se presenta el caso de un adolescente de 15 años, de sexo masculino con presencia de cutis verticis gyrata primaria esencial, donde la principal preocupación fue el prurito y la presencia de fetidez. Teniendo en cuenta el carácter benigno de esta condición, se decidió solo manejo sintomático. El caso que se presenta es el primero reportado en la provincia Cienfuegos en edad pediátrica, lo que reafirma la importancia de reconocer esta entidad y su abordaje adecuado para distinguir las formas clínicas de presentación para su mejor tratamiento terapéutico. Dada la rareza de la entidad en edad pediátrica se decide presentar este caso, además de una revisión de la literatura.

ABSTRACT Cutis verticis gyrata is a rare pathology of the scalp characterized by the proliferation of subcutaneous cellular tissue and hypertrophy that produces folds and furrows that give it a cerebriform appearance. Although its etiology is still unknown, the condition is not exclusively congenital, the presence of autosomal dominant mutations in the fibroblast growth factor receptor 2 has been proposed as a theory. This pathology is extremely rare in pediatrics. It is divided into primary and secondary. The case of a 15-year-old male adolescent with the presence of essential primary cutis verticis gyrata, where the main concern was pruritus and the presence of fetidity is presented. Taking into account the benign nature of this condition, only symptomatic management was decided. The case presented is the first reported in Cienfuegos province in pediatric age, which reaffirms the importance of recognizing this entity and its adequate approach to distinguish the clinical forms of presentation for its best therapeutic treatment. Once the oddity of the entity in pediatric age was given this case, in addition to a revision of literature decides to show up.

MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia / 生物医学与环境科学（英文）

Objective@#Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.@*Methods@#Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.@*Results@#MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.@*Conclusion@#This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

Mastitis granulomatosa: una simuladora de cáncer, un gran reto diagnóstico y terapéutico / Granulomatous mastitis: a cancer simulator, a great diagnostic and therapeutic challenge

Resumen ANTECEDENTES: La mastitis granulomatosa idiopática es un padecimiento benigno de la glándula mamaria sumamente raro, simulador de cáncer de mama. Las manifestaciones clínicas más significativas son: nódulo palpable, cambios en la coloración de la piel y mastalgia. Para integrar su diagnóstico se requiere el apoyo de estudios auxiliares de imagen, sin que por ello deje de ser imprescindible la toma de biopsia para establecer el diagnóstico definitivo. No existen pautas de tratamiento debidamente establecidas, pero sí de tratamiento farmacológico y quirúrgico, ésta última se reserva para casos de recidivas, que son frecuentes. CASO CLÍNICO: Paciente de 35 años, nuligesta; acudió a consulta debido a la aparición de un tumor palpable en la glándula mamaria derecha, de siete meses de evolución, con cambios en la coloración y retracción del pezón. La mastografía y ecografía catalogaron el tumor en BI-RADS 5. La biopsia con aguja de corte y citología integraron el diagnóstico de mastitis granulomatosa idiopática. Se indicó tratamiento farmacológico y el tumor desapareció espontáneamente. CONCLUSIONES: La mastitis granulomatosa es una enfermedad rara y de diagnóstico complejo. Para cada paciente habrá un protocolo diferente para evitar el sobretratamiento. Su pronóstico es bueno, a pesar de ser un simulador de cáncer de mama. El tratamiento aún es ambiguo, pero en primera instancia se recomiendan los corticosteroides o inmunosupresores y la cirugía se reserva para casos de recidivas.

Abstract BACKGROUND: Idiopathic granulomatous mastitis is an extremely rare benign entity of the mammary gland, simulating breast cancer. The most significant clinical manifestations are: palpable nodule, skin discoloration changes and mastalgia. The diagnosis requires the support of auxiliary imaging studies, although a biopsy is essential to establish the definitive diagnosis. There are no well-established treatment guidelines, but there are guidelines for pharmacological and surgical treatment, the latter is reserved for cases of recurrence, which are frequent. CLINICAL CASE: A 35-year-old nulligesta patient came for consultation due to the appearance of a palpable tumor in the right mammary gland, of 7 months of evolution, with changes in color and nipple retraction. The mastography and ultrasound catalogued the tumor in BI-RADS 5. The biopsy with cutting needle and cytology integrated the diagnosis of idiopathic granulomatous mastitis. Pharmacological treatment was indicated, and the tumor disappeared spontaneously. CONCLUSIONS: Granulomatous mastitis is a rare disease with a complex diagnosis. For each patient there will be a different protocol to avoid overtreatment. Its prognosis is good, despite being a breast cancer simulator. Treatment is still ambiguous but, in the first instance, corticosteroids or immunosuppressants are recommended and surgical treatment is reserved for cases of recurrence.

CLINICOPATHOLOGICAL STUDY OF ACUTE PROMYELOCYTIC LEUKEMIA: AN EXPERIENCE FROM A TEACHING HOSPITAL IN INDIA

Data on the clinicopathological features of acute promyelocytic leukemia (APL) patients from India is limited. Present study was a cross sectional study which included 18 patients of APL. Medical records of these 18 patients were reviewed to collect their clinical details and laboratory results. High risk patients (total leucocyte count >10,000/cmm) were treated with modified APML 4 protocol.Low risk patients (total leucocyte count <10,000/cmm) were treated with protocol APL- 0406-Intergroup Study AL WP GIMEMA-DSIL protocol. Outcomes in terms of complete remission were assessed in both these groups. Mean haemoglobin levels was 7.03gm%, mean total leucocyte count was 30,462per cmm, mean platelet count was 27,222/cmm. Bone marrow was reported as suggestive of APL in 17 cases while in 1 case, BM aspirate was inadequate. Average percentage of abnormal promyelocytes in bone marrow was 84.25%. PT was prolonged in 15 cases, while APTT was prolonged in 3 cases. Flow cytometry analysis was done in 12 patients. All patients were CD45, MPO, CD13, CD33 and CD64 positive. Chromosomal analysis was possible in 11 cases. t(15;17)(q22;21) was identified in 6 cases (54.62%). 3 cases (27.27%) showed normal karyotype. 2 (18.18%) cases had additional cytogenetic abnormalities. All patients under high risk category attained CR. 1 patient under low risk category with additional cytogenetic abnormality died 6 days after induction therapy was started. 10 (55.55%) patients developed complications such as neutropenic sepsis, intracranial hemorrhage, differentiation syndrome, cerebral venous sinus thrombosis, pseudotumorcerebri, QTc interval prolongation, and pneumonia.

La enfermedad de Huntington: una difícil relación entre los enfermos y el derecho a la salud en Colombia / Huntington's Disease: A Difficult Relationship between Patients and the Right to Health in Colombia / A doença de Huntington: uma difícil relação entre os doentes e o direito à saúde na Colômbia

Resumen Introducción: el derecho a la salud está consagrado en la Constitución Política y en la Ley Estatutaria de Salud 1751 de 2015. Las personas con enfermedad de Huntington requieren atención especializada e interdisciplinaria, por ser un complejo trastorno genético neurodegenerativo, que comienza en mitad de la vida adulta y no es curable. Materiales y métodos: estudio cualitativo, en diferentes regiones, mediante entrevistas en visita familiar, observación participante y revisión documental. Los resultados son fruto del análisis, realizado según postulados de la teoría fundamentada con origen en la sociología. Resultados: se encontró una difícil relación de las personas con el sistema de salud: los que buscan atención, encuentran múltiples barreras que tratan de superar a través de la tutela, viven en ciudades principales o intermedias con alguna atención que los favorezca. Otros, en regiones distantes como Chocó y Juan de Acosta (Atlántico) emprenden pocas acciones en una suerte de "desesperanza aprendida", como propone Seligman: "no hacer nada porque nada va a funcionar". Conclusión: ellos presentan la enfermedad en estado genuino, no reciben atención y sus condiciones son precarias hasta estados de desnutrición y abandono. La mayoría no tuvo acceso al trabajo formal; por lo tanto, no tendrán posibilidad de la pensión de invalidez o vejez, otros se debaten en el proceso de lograrla, y se encuentran en condiciones de pobreza y precariedad.

Abstract Introduction: The right to health is enshrined in the Political Constitution of Colombia as well as in the Statutory Health Legislation 1751 of 2015. Patients with Huntington's disease require specialized and interdisciplinary care because of the complex genetic neurodegenerative nature of the disorder, which usually affects the middle-aged individuals and is incurable. Materials and methods: This qualitative study was conducted in different regions, followed by data collection through interviews during family visits, participant observation, and documentary review. The results are a part of the analysis, which was conducted according to the grounded theory postulates with an origin in sociology. Results: A difficult relationship was noticed between the individuals and health system, indicating that those seeking care encounter multiple barriers and then attempt to overcome them through tutelage and live in principal or intermediate cities with favorable care availabilities. Others living in remote regions, such as Chocó and Juan de Acosta on the Atlantic, undertake only a few actions as a sort of "learned helplessness," better summarized by Seligman as "doing nothing because nothing will work." Conclusion: The results of the present study indicate that Huntington's disease in the genuine state receives no care and that the conditions of these patients are precarious to the states of malnutrition and abandonment. The majority of these patients have no access to formal employment; thus, they see no possibility for disability pension or retirement, while others debate about the process of achieving it and suffering from poverty and precariousness.

Resumo Introdução: o direito à saúde está consagrado na Constituição Política e na Lei Sanitária Estatutária 1751 de 2015. Pessoas com doença de Huntington requerem atendimento especializado e interdisciplinar por se tratar de uma doença genética neurodegenerativa complexa, que se inicia na metade da vida adulta e não é curável. Materiais e métodos: estudo qualitativo, realizado em diferentes regiões. A coleta foi realizada por meio de entrevistas em visitas familiares, observação participante e revisão documental. Os resultados são fruto de análises, realizadas de acordo com os postulados da teoria fundamentada com origem na sociologia. Resultados: constatou-se a difícil relação entre as pessoas e o sistema de saúde: quem busca atendimento encontra múltiplas barreiras que tentam superar por meio de processo judicial, moram em cidades principais ou intermediárias com algum atendimento que os favorece. Outros, vivem em regiões distantes como Chocó e Juan de Acosta no Atlântico, empreendem poucas tentativas de processo judicial como uma espécie de "desesperança aprendida" como propõe Seligman: "não faça nada porque nada vai funcionar". Conclusão: os pacientes apresentam a doença de forma genuína, não recebem atenção médica e vivem em condições precárias com certo grau de desnutrição e em estado de abandono. A maioria não teve acesso ao trabalho formal, portanto, não terá a possibilidade de receber aposentadoria por invalidez ou idade, outros estão lutando para obtê-lo, e se encontram em condições de pobreza e precariedade.

Síndrome de Prader-Willi. A propósito de un caso / Prader-Willi Syndrome. About a Case

RESUMEN El síndrome de Prader-Willi es una enfermedad genética rara, caracterizada por anomalías del eje hipotálamo-hipofisario, que cursa con hipotonía grave durante el período neonatal y los dos primeros años de vida, con hiperfagia con alto riesgo de desarrollar obesidad mórbida en la infancia y la edad adulta; así como dificultades de aprendizaje y graves problemas de conducta y/o psiquiátricos. Se presenta el caso de una paciente de 17 años de edad, de color de piel blanca. La paciente mostró entre sus principales manifestaciones: desviación de la fisura palpebral y alteraciones del diámetro, manos y pies pequeños, obesidad, hipogenitalismo, diabetes mellitus, disfunción muscular, deficiencia mental, estatura baja, entre otras. Los criterios clínicos y resultados de estudios complementarios fueron compatibles con el diagnóstico de síndrome de Prader-Willi. Se presenta este caso por lo necesario que resulta describir las características clínicas y genéticas de pacientes con síndrome de Prader-Willi debido a que es una enfermedad genética rara con compromiso importante para la vida futura de quienes la padecen.

ABSTRACT Prader-Willi syndrome is a rare genetic disease, characterized by hypothalamic-pituitary anomalies, which presents with severe hypotonia during the neonatal period and the first two years of life, with hyperphagia with a high risk of developing morbid obesity in childhood and adulthood; as well as learning difficulties and serious behavioral and / or psychiatric problems. A 17-years-old patient with white skin color is presented. The main manifestations of the patient showed: deviation of the palpebral fissure and alterations in the diameter, small hands and feet, obesity, hypogenitalism, diabetes mellitus, muscular dysfunction, mental deficiency, short stature, among others. The clinical criteria and results of complementary studies were compatible with the diagnosis of Prader-Willi syndrome. This case is presented because it is necessary to describe the clinical and genetic characteristics of patients with Prader-Willi syndrome, since it is a rare genetic disease with important compromise for the future life of those who suffer from it.

Epidermólisis ampollosa o bullosa congénita. Actualización clínica / Congenital Bullous Epidermolysis. Clinical Update

RESUMEN La epidermólisis ampollosa o bullosa es una enfermedad hereditaria, crónica, incurable y de baja prevalencia. Se caracteriza por la aparición de ampollas luego de traumatismos mínimos, de manifestación predominantemente cutánea y de difícil manejo. Es causada por mutaciones en diversos genes que codifican para las proteínas de la unión dermoepidérmica, lo cual conlleva a la formación de ampollas y erosiones, además de otras múltiples alteraciones sistémicas. Existen tres grandes grupos dependiendo de la mutación genética. Para su diagnóstico se realiza la biopsia de piel. No existe ningún tratamiento efectivo, siendo los tratamientos más utilizados los sintomáticos y paliativos. La epidermólisis bullosa o ampollosa congénita es una enfermedad que se observa rara vez, por esta razón es un desafío médico pasar del diagnóstico sindrómico al específico. En tal sentido el objetivo de este trabajo es describir las principales características de la epidermólisis ampollosa. Para ello se revisaron un total de 15 bibliografías.

ABSTRACT Bullous epidermolysis is an inherited, chronic, incurable and low prevalence disease. It is characterized by the appearance of blisters after minimal trauma, predominantly cutaneous and difficult to manage. It is caused by mutations in various genes that code for dermoepidermal junction proteins, which leads to the formation of blisters and erosions, in addition to multiple other systemic alterations. There are three large groups depending on the genetic mutation. For its diagnosis, a skin biopsy is performed. There is no effective treatment, the most commonly used treatments being symptomatic and palliative. Congenital bullous epidermolysis is a rarely observed disease, for this reason it is a medical challenge to go from syndromic to specific diagnosis. In this sense, the objective of this work is to describe the main characteristics of bullous epidermolysis. A total of 15 bibliographies were reviewed.

Rare Presentation of Schwannoma in the Ankle: A Case Report / Apresentação rara de schwannoma no tornozelo: Um relato de caso

Abstract Schwannomas are benign slow-growing tumors that constitute 8% of all soft-tissue tumors. The clinical signs and symptoms are often misinterpreted because of the low incidence, and these tumors are often misdiagnosed. A 39-year-old male patient presented with non-traumatic solitary swelling in the posteromedial aspect of the right ankle that gradually increased in size and was associated with pain. Clinically, the swelling was firm, non-fluctuant, and was not associated with sensorimotor impairment. Surgical excision of the swelling was performed without damaging the surrounding vessels and nerves. The histopathological examination of the excised tumor revealed a schwannoma.

Resumo Schwannomas são tumores benignos de crescimento lento, e constituem 8% de todos os tumores de tecido mole. Os sinais clínicos e sintomas são muitas vezes mal interpretados por causa da baixa incidência, e, muitas vezes, esses tumores são mal diagnosticados. Um paciente do sexo masculino de 39 anos apresentou um inchaço solitário não traumático sobre o aspecto posteromedial do tornozelo direito, que aumentou gradualmente de tamanho e estava associado a dor. O inchaço era clinicamente firme, não flutuante, e não associado a qualquer comprometimento sensório-motor. A excisão cirúrgica do inchaço foi feita sem danificar os vasos e os nervos circundantes. O exame histopatológico do tumor excisado revelou schwannoma.

Angioedema hereditario tipo III en una embarazada: a propósito de un caso / Hereditary angioedema type III in pregnant women: case report and literature review

Resumen ANTECEDENTES: El angioedema hereditario es una enfermedad rara, caracterizada por episodios recurrentes de edema en cualquier parte del cuerpo, sobre todo en las extremidades, la cara y las vías respiratorias. Existen tres tipos de enfermedad en función de su causa, el menos frecuente es el III con un nivel y función del inhibidor de C1 normales. Su fisiopatología es poco conocida; por lo tanto, su diagnóstico es difícil. Su tratamiento ha avanzado en los últimos años, aunque queda mucho por definir, sobre todo durante el embarazo. OBJETIVO: Evaluar la bibliografía disponible relacionada con el angioedema hereditario y su atención médica en mujeres embarazadas. CASO CLÍNICO: Paciente de 30 años, en curso de su primer embarazo. El único antecedente personal destacable fue haber padecido angioedema hereditario tipo III, diagnosticado 10 años antes después de varios episodios de angioedema orofacial. A lo largo del embarazo sobrevinieron varias crisis de la enfermedad que requirieron tratamiento de los episodios agudos y de mantenimiento en el tercer trimestre. Por último, ocurrió un parto instrumentado mediante vaccum, por riesgo de pérdida de bienestar fetal con buen desenlace materno y fetal en el posparto inmediato. CONCLUSIONES: El angioedema hereditario tipo III es una enfermedad muy rara y poco conocida en la Ginecoobstetricia que requiere establecer un protocolo y estandarización de la atención clínica, sobre todo en las embarazadas, lo que ayudará a proporcionar una información y asistencia de calidad a estas pacientes.

Abstract BACKGROUND: Hereditary angioedema is a rare disease characterized by recurrent episodes of edema anywhere in the body, especially in the extremities, face and airways. There are three types of the disease depending on its cause, the most infrequent being III with normal C1 inhibitor level and function. Its pathophysiology is poorly understood; therefore, its diagnosis is difficult. Its treatment has advanced in recent years, although much remains to be defined, especially during pregnancy. OBJECTIVE: To evaluate the available literature related to hereditary angioedema and its medical care in pregnant women. CLINICAL CASE: 30-year-old female patient, during her first pregnancy. The only personal history of note was hereditary angioedema type III, diagnosed 10 years earlier after several episodes of orofacial angioedema. Throughout the pregnancy, several crises of the disease occurred, requiring treatment in acute episodes and maintenance treatment in the third trimester. Finally, one delivery was instrumented by vaccum, due to risk of loss of fetal well-being with good maternal and fetal outcome in the immediate postpartum period. CONCLUSIONS: Hereditary angioedema type III is a very rare and little-known disease that requires establishing a protocol and standardization of clinical care, especially in pregnant women, which will help to provide quality information and assistance to these patients.

Perfil farmacoeconômico do tratamento da fibrose pulmonar idiopática demandado por idosos no estado do Pará / Pharmacoeconomic profile of the treatment of idiopathic pulmonary fibrosis demanded by the elderly in the state of Pará

Objetivo: O objetivo deste estudo foi realizar o levantamento de custo dos medicamentos antifibróticos para o tratamento da fibrose pulmonar idiopática no estado do Pará. Métodos: Trata-se de uma pesquisa documental do tipo descritiva, retrospectiva e quantitativa, referente às tecnologias pirfenidona e nintedanibe, demandadas entre os meses de junho de 2016 a junho de 2019. Para a obtenção dos dados, acessaram-se os relatórios de dispensação por paciente, notas fiscais relacionadas à aquisição dos medicamentos, além de planilha Excel de cadastro e acompanhamento de processos dos anos correspondentes, disponibilizados pela Secretaria de Estado de Saúde. Resultados: Foram atendidos 81 processos destinados à aquisição dos medicamentos (2 em 2016, 13 em 2017, 31 em 2018 e 35 em 2019); dos quais 29 solicitando nintedanibe e 52, pirfenidona. Quanto aos gastos, identificou-se que, em 2016, se pagou R$ 38.673,32 para a aquisição nintedanibe. Em 2017, foi R$ 158.881,27 para a aquisição de pirfenidona e R$ 322.277,67 para o atendimento de nintedanibe. Para 2018, percebeu-se o aumento impactante de pirfenidona (R$ 627.959,33), se comparada aos anos anteriores, enquanto o nintedanibe totalizou R$ 670.337,55. Já para o primeiro semestre de 2019 foram investidos R$ 620.393,55 para a pirfenidona e R$ 464.079,84 para nintedanibe. Conclusões: Identificou-se que a demanda de tecnologias em saúde destinadas aos portadores de fibrose pulmonar idiopática no Pará segue em constante crescente, por ser uma tecnologia inovadora que ainda não está incorporada no Sistema Único de Saúde, fazendo-se necessários critérios que regulamentem a sustentabilidade do acesso ao tratamento dessa doença rara

Objective: The objective of this study was to perform the cost survey of antifibrotic drugs for the treatment of idiopathic pulmonary fibrosis in the state of Pará. Methods: This is a descriptive, retrospective and quantitative documentary research on Pirfenidone and Nintedanibe technologies, demanded from June 2016 to June 2019. To obtain the data were accessed dispensing reports per patient, Invoices related to the purchase of medicines, in addition to Excel spreadsheet for registration and monitoring of processes of the corresponding years, available from the Secretary of State for Health. Results: 81 cases were received for the purchase of medicines (2 in 2016, 13 in 2017, 31 in 2018 and 35 in 2019); of which 29 requesting nintedanibe and 52, pirfenidone. Regarding expenses, it was identified that in 2016, R$ 38,673.32 was paid for the acquisition of nintedanibe. In 2017, it was R$ 158,881.27 for the acquisition of pirfenidone and R$ 322,277.67 for the service of nintedanibe. For 2018, there was a significant increase in pirfenidone (R$ 627,959.33) compared to the previous year, while nintedanibe totaled R $ 670,337.55. For the first half of 2019, R$ 620,393.55 was invested for pirfenidone and R$ 464,079.84 for nintedanibe. Conclusions: It was identified that the demand for health technologies for patients with idiopathic pulmonary fibrosis in Pará continues to grow, as it is an innovative technology that is not yet incorporated into the Unified Health System. sustainability of access to treatment for this rare disease

Tetraploid/near-tetraploid acute promyelocytic leukaemia with double (15;17) translocation

@#A 57-year-old man presented with intermittent fever and bleeding following dental surgery. Peripheral smear and bone marrow aspirate exhibited unusually large and bizarre-looking abnormal cells which were found to be myeloblasts with aberrant CD56 and CD2 expression on immunophenotyping. Fluorescence in situ hybridization analysis revealed an extra RARA gene rearrangement. This finding correlated well with a near-tetraploid karyotype with double t(15;17)(q22;q21). Bcr-3 type PML/ RARA copies were identified in reverse transcriptase-polymerase chain reaction. The diagnosis of near-tetraploid acute promyelocytic leukaemia (APML) was established. The patient was treated with all-trans retinoic acid and idarubicin and six weeks later achieved complete remission. Tetraploid/ near-tetraploid APML is exceedingly rare. It is a distinct cytogenetic subgroup with unique clinical and biological features as highlighted by atypical morphology, frequent CD2 expression and association with the bcr-3 type PML/RARA fusion transcripts. Early recognition of this rare entity is essential for timely and appropriate treatment.

A Century after! Rediscovery of the ancient catfish Diplomystes Bleeker 1858 (Siluriformes: Diplomystidae) in coastal river basins of Chile and its implications for conservation

The ancient catfish family Diplomystidae, with seven species endemic to rivers of southern South America, represents one of the oldest branches of the diverse order Siluriformes. With most species endangered, new reports of these species become extremely valuable for conservation. Currently, it is assumed that Diplomystes species inhabit only Andean (large) basins, and that they are extinct from coastal (small) basins from which their presence have not been recorded since 1919. Here, we document new records of the family Diplomystidae in the Laraquete and Carampangue basins, two coastal basins from the Nahuelbuta Coast Range, Chile, with no previous reports. This finding represents the rediscovery of the genus in coastal basins in more than a Century. Based on analysis of mitochondrial DNA sequences, the collected specimens were found to be closely related to Diplomystes nahuelbutaensis from the Andean Biobío Basin, but sufficiently differentiated to suggest that coastal basin populations are a different management unit. These populations are important because, contrary to previous thoughts, they prove these catfish can survive in small river networks, providing unique opportunities for research and conservation. The conservation category of Critically Endangered (CE) is recommended for the populations from the Laraquete and Carampangue basins.(AU)

La familia de bagres Diplomystidae, con siete especies endémicas de ríos del sur de Sudamérica, es uno de los linajes mas antiguos del diverso orden Siluriformes. Al estar la mayoría de las especies amenazadas, nuevos registros de éstas son extremadamente valiosos para su conservación. Actualmente, se ha asumido que los Diplomystidos se distribuyen solo en cuencas Andinas (más grandes), y que sus especies estarían extintas en cuencas de menor tamaño como las costeras, sin registros desde 1919. En este trabajo documentamos la familia Diplomistidae en las cuencas de Carampangue y Laraquete, dos cuencas costeras de la Cordillera de Nahuelbuta, Chile, lo que representa el primer registro de esta familia en estas cuencas costeras. Además, este hallazgo representa el re-descubrimiento de la familia en cuencas costeras después de un siglo. Sobre la base de análisis de ADN mitocondrial, los especímenes colectados se relacionaron más cercanamente con poblaciones de la especie Diplomystes nahuelbutaensis presente en la cuenca del Biobío. Sin embargo, existen diferencias genéticas suficientes entre las poblaciones costeras y las del Biobío para justificar su separación como unidad de manejo distinta. Estas poblaciones costeras son importantes porque demuestran que los Diplomístidos pueden sobrevivir en cuencas de pequeño tamaño, ofreciendo oportunidades únicas para su investigación y conservación. Se recomienda la categoría de conservación En Peligro Critico de Extinción (CR) para las poblaciones de las cuencas Laraquete y Carampangue.(AU)

Osteogénesis imperfecta de tipo III en niño ecuatoriano / Osteogenesis imperfecta type III in an Ecuadorian child

Introducción: la osteogénesis imperfecta es una rara enfermedad genética hereditaria caracterizada por su heterogeneidad causada por defectos del tejido conectivo con el rasgo de fragilidad ósea determinante de múltiples fracturas, incluso prenatales; deformidades de huesos largos y columna vertebral y otros síntomas extra-esqueléticos, como escleróticas de color azul, dentinogénesis imperfecta, trastorno de audición y afectación cardiovascular. Objetivo: Presentar un paciente con las características clínicas e imagenológicas de osteogénesis imperfecta de tipo III. Presentación del caso: Niño ecuatoriano de 4 años de edad de baja talla con antecedente de fracturas múltiples desde los 8 meses de nacido, con deformidad en columna vertebral demostrada por radiología por cifoescoliosis en forma de "S" y fracturas vertebrales, con deformidad progresiva en huesos largos; ha sufrido 16 fracturas, no deambula, sensorio presente, orientado en tiempo y espacio, desarrollo cognitivo normal para la edad. La fragilidad ósea del niño según el fenotipo clasifica al diagnóstico de tipo III de osteogénesis imperfecta, el cual es progresivo e invalidante por las deformidades óseas y múltiples fracturas demostradas en exámenes imagenológicos, sin modificaciones en el color de escleróticas, de herencia presumiblemente dominante. Conclusiones: La descripción clínica y radiológica de osteogénesis imperfecta, afección poco conocida, correspondiente al fenotipo III de la enfermedad, reportada en niño ecuatoriano de 4 años de edad, con talla baja que no deambula, expresión de la severidad de su afección genética, con severas alteraciones óseas por su fragilidad con fracturas múltiples en huesos largos y vértebras(AU)

Introduction: Osteogenesis imperfecta is a rare hereditary genetic disease characterized by its heterogeneity caused by connective tissue defects with the feature of bone fragility determining multiple fractures, even prenatal ones; also deformities of long bones and spine, and other extra-skeletal symptoms, such as blue sclerotic, dentinogenesis imperfecta, hearing disorder and cardiovascular affectations. Objective: To present a patient with clinical and radiological findings of osteogenesis imperfect type III. Case presentation: Ecuadorean male child of 4 years old, with a short height, history of multiple fractures from 8 months of age, with spinal deformity demonstrated by radiology due to "S" shaped kyphoscoliosis and vertebral fractures, with progressive deformity in long bones. The boy has suffered 16 fractures, he does not wander, and he is sensory present, oriented in time and space, with normal cognitive development for his age. The bone fragility of the child according to the phenotype classifies in the type III diagnosis of osteogenesis imperfecta, which is progressive and invalidating due to bone deformities and multiple fractures evidenced in imaging tests, without changes in the color of sclerotics and of presumably dominant inheritance. Conclusions: The clinical and radiological description of osteogenesis imperfecta, which is little-known pathology, corresponding to type III phenotype is reported in a 4-year-old boy who, due to his involvement, has a short height and does not wander as a consequence of the severity of bone affectations with fractures in long bones and vertebrae, mainly produced by the fragility of the bones due to his genetic disease(AU)

Da busca pelo diagnóstico às incertezas do tratamento: desafios do cuidado para as doenças genéticas raras no Brasil / From the search for diagnosis to treatment uncertainties: challenges of care for rare genetic diseases in Brazil

Resumo As doenças genéticas raras constituem um importante problema de saúde pública, mas ainda são pouco estudadas na perspectiva da Saúde Coletiva. Este artigo tem por objetivo analisar os itinerários terapêuticos de pacientes com doenças genéticas raras nas cidades do Rio de Janeiro, Salvador e Porto Alegre, tendo por foco os desafios materiais, emocionais e estruturais enfrentados na busca por diagnóstico e tratamento. Foram realizadas entrevistas semiestruturadas com pacientes/cuidadores e profissionais de saúde em serviços públicos de genética médica. Observou-se que a experiência da doença genética rara, além de ser um desafio em si pelo caráter debilitante e incapacitante, é agravada por problemas de ordem prático-relacionais e burocrático-institucionais que não se resolvem com a chegada a um serviço especializado. A existência de longos itinerários terapêuticos até o diagnóstico, o desconhecimento dos médicos não geneticistas sobre as doenças raras, as dificuldades de transporte e de acesso a especialistas, a exames diagnósticos e complementares e o acesso a medicamentos e insumos alimentares de alto custo foram comuns às narrativas nas três cidades. A adesão aos cuidados oferecidos exigem estratégias de ação que dependem de arranjos envolvendo familiares, médicos, associações de pacientes e o Estado.

Abstract Rare genetic diseases are an important public health problem, but they are still little studied in Collective Health. This article aims to analyze the 'therapeutic itineraries' of patients in search of a diagnosis and treatment for rare genetic diseases in the cities of Rio de Janeiro, Salvador and Porto Alegre. It focuses on the material challenges, emotional and structural problems faced in these trajectories. Semi-structured interviews were conducted with patients/caregivers and health professionals in the context of public health medical genetics. Our findings suggest that the experience of the rare genetic disease is aggravated by practical, inter-relational and bureaucratic/institutional problems. The reality of long and circuitous journeys to obtain a diagnosis, non-geneticists' lack of knowledge about rare diseases, difficulties in transportation and access to specialists, diagnostic and complementary examinations, and access to high-cost medicines and food supplies were common challenges in all the narratives examined in the three Brazilian cities. In addition, adherence to care provided by medical genetics requires action and strategies that depend on arrangements involving family members, physicians, patient associations, and the state.