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INTRODUCTION: Hemophilia A is an inherited bleeding disorder caused by pathogenic variants in the factor VIII gene (F8), which leads to factor VIII (FVIII) deficiency. Immune tolerance induction (ITI) is a therapeutic approach to eradicate alloantibodies (inhibitors) against exogenous FVIII in people with inherited hemophilia A. Few studies have evaluated the role of F8 variants on ITI outcome. MATERIAL AND METHODS: We included people with severe hemophilia A (FVIII Ë 1 international units/dL) and high-responding inhibitors (≥ 5 Bethesda units/mL lifelong) who underwent a first course of ITI. Socio-demographic, clinical and laboratory data were collected. ITI outcomes were defined as total, partial successes, and failure. Detection of intron 1 and 22 inversions was performed by polymerase-chain reaction, followed by F8 sequencing. RESULTS: We included 168 people with inherited hemophilia A and high-responding inhibitors, median age 6 years at ITI start. Intron 22 inversion was the most prevalent variant (53.6 %), followed by nonsense (16.1 %), small insertion/deletion (11.3 %), and large deletion (10.7 %). In comparison with intron 22 inversion, the odds of ITI failure were 15.5 times higher (odds ratio [OR] 15.50; 95 % confidence interval [95 % CI] 4.59-71.30) and 4.25 times higher (95 % CI, 1.53-12.3) among carriers of F8 large deletions and small insertions and deletions, respectively. CONCLUSION: F8 large deletions and small insertions/deletions predicted ITI failure after a first course of ITI in patients with severe hemophilia A and high-responding inhibitors. This is the first study to show F8 large deletions and small insertions/deletions as predictors of ITI failure.
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Background: Immune tolerance induction (ITI) is the treatment of choice to eradicate neutralizing anti-factor (F)VIII alloantibodies (inhibitors) in people with inherited hemophilia A. However, it is not successful in 10% to 40% of the cases. The biological mechanisms and biomarkers associated with ITI outcome are largely unknown. Objectives: The aim of this study was to investigate the association of plasma cytokines (interferon-γ, tumor necrosis factor, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-10, and IL-17A), chemokines (IL-8/CXCL8, RANTES/CCL5, MIG/CXCL9, MCP-1/CCL2, and IP-10/CXCL10), and anti-FVIII immunoglobulin (Ig) G total, IgG1, and IgG4 with ITI outcome. Methods: In this cross-sectional analysis of the Brazilian Immune Tolerance Study, we assessed plasma levels of anti-FVIII IgGs using an enzyme-linked immunosorbent assay with plasma-derived FVIII and recombinant FVIII as target antigens, immobilized in microplates. Results: We assayed 98 plasma samples of moderately severe and severe (FVIII activity, <2%) people with hemophilia A after completion of a first ITI course. Levels of anti-recombinant FVIII IgG total and IgG4 were higher in people with hemophilia A who failed ITI (IgG total optical density [OD], 0.37; IQR, 0.15-0.73; IgG4 OD, 2.19; IQR, 0.80-2.52) than in those who had partial (IgG total OD, 0.03; IQR, 0.00-0.14; IgG4 OD, 0.39; IQR, 0.09-1.11; P < .0001 for both) or complete success (IgG total OD, 0.04; IQR, 0.00-0.07; IgG4 OD, 0.07; IQR, 0.06-0.40; P < .0001 for both). Plasma cytokines, chemokines, and anti-FVIII IgG1 were not associated with ITI outcome. Conclusion: Our results show that high levels of plasma anti-FVIII IgG4 and IgG total are associated with ITI failure.
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BACKGROUND: Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results. OBJECTIVES: We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis. DESIGN AND SETTING: Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil. METHODS: The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds. RESULTS: Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: -1.58; 95% confidence interval -2.50, -0.66, P = 0.0008; I2 = 68.4%, P = 0.0031). CONCLUSION: Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results. SYSTEMATIC REVIEW REGISTRATION: CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.
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Anticorpos Biespecíficos , Anticorpos Monoclonais Humanizados , Hemofilia A , Hemorragia , Humanos , Hemofilia A/tratamento farmacológico , Hemofilia A/complicações , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controleRESUMO
ABSTRACT BACKGROUND: Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results. OBJECTIVES: We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis. DESIGN AND SETTING: Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil. METHODS: The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds. RESULTS: Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: −1.58; 95% confidence interval −2.50, −0.66, P = 0.0008; I2 = 68.4%, P = 0.0031). CONCLUSION: Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results. SYSTEMATIC REVIEW REGISTRATION: CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.
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Abstract Introduction As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates. Method We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender. Results In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies. Conclusion These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Infecções por Coronavirus , Teste Sorológico para COVID-19 , COVID-19 , Plasma , Doadores de Sangue , SARS-CoV-2RESUMO
INTRODUCTION: As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates. METHOD: We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender. RESULTS: In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies. CONCLUSION: These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms.
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Resumo: Introdução: A Faculdade de Medicina da Universidade Federal de Goiás (FM-UFG) iniciou um novo processo de mudança curricular em 2014. As disciplinas de Semiologia I e II passaram a adotar metodologias ativas de ensino para adequação às necessidades da reforma curricular. O objetivo deste artigo foi avaliar a percepção dos discentes do primeiro ano da FM-UFG sobre o ambiente educacional das disciplinas de Semiologia I e II. Método: Trata-se de um estudo descritivo, do tipo corte transversal, envolvendo 86 alunos. O instrumento de coleta de dados foi o questionário Dundee Ready Education Environment Measure (Dreem), versão em português. Os resultados foram considerados em três níveis: questões individuais, cinco dimensões e Dreem global. Calcularam-se a média, o desvio padrão e os respectivos intervalos de confiança de 95%. Obteve-se a confiabilidade interna do Dreem pelo cálculo do alfa de Cronbach, avaliou-se a distribuição dos dados da amostra pelo teste de Shapiro-Wilk e realizou-se a comparação entre os percentuais da média dos escores dos domínios e do DRREM global pela ANOVA, seguida do teste de Tukey. Resultados: A média do Dreem global foi de 134,83/200 ± 17,42, uma percepção mais positiva que negativa. As cinco dimensões tiveram os seguintes resultados: percepção da aprendizagem (32,74 / 48 ± 5,59 / uma visão mais positiva); percepção dos docentes (32,71 / 44 ± 6,23 / na direção certa); percepção dos resultados acadêmicos (20,22 / 32 ± 4,09 / sentimento positivo); percepção do ambiente geral (31,74 / 48 ± 5,69 / atitude positiva); percepção das relações sociais (17,42 / 28 ± 3,83 / não é tão ruim). Foram encontrados alguns pontos problemáticos em relação a fatos memorizáveis, metodologia de ensino prévio e cansaço para cursarem a disciplina. A dimensão com mais áreas fortes foi a percepção dos docentes. Houve significância estatística quando os percentuais da média dos escores dos domínios e do Dreem global foram comparados. Conclusão: O ambiente educacional das disciplinas de Semiologia I e II da Faculdade de Medicina da UFG criado pelas inovações metodológicas foi avaliado positivamente pelos discentes participantes, com destaque para o domínio percepção dos docentes.
Abstract: Introduction: In 2014, the Medical School of the Federal University of Goias (FM-UFG) started its curricular changing process. The disciplines of Semiology I and II started to use active teaching methodologies to fit the curricular reform needs. The objective of this article was to evaluate the FM-UFG students' perception of the Educational Environment in the disciplines of Semiology I and II. Method: This is a descriptive, cross-sectional study encompassing 86 students. The data collection tool was the Dundee Ready Education Environment Measure (DREEM) questionnaire, in its Portuguese version. Results were considered at three levels: individual questions, five domains and global DREEM. Mean values, standard deviation and respective 95% confidence intervals were calculated. The internal reliability of the DREEM was determined using Cronbach's alpha; the sample normality was determined using the Shapiro-Wilk test; and the comparison between the mean score percentages of the domains and of the global DREEM was performed by ANOVA ,followed by Tukey's test. Results: The global DREEM mean was 134.83 / 200 ± 17.42, a more positive than negative perception. The five domains showed the following results: Students' Perception of Learning - SPL (32.74 / 48 ± 5.59 / a more positive approach); Students' Perception of Teachers - SPT (32.71 / 44 ± 6.23 / going in the right direction); Students' Academic Self-Perception - SASP: (20.22 / 32 ± 4.09 / feeling more on the positive side); Students' Perception of the Atmosphere - SPA (31.74 / 48 ± 5.69 / a more positive attitude); Students' Social Self-Perception - SSSP: (17.42 / 28 ± 3.83 / not too bad). Some issues were found in relation to: memorizable facts; previous teaching methodology; and, fatigue to attend the discipline. The SPT was the domain with the largest number of strong areas. Statistical significance was found when comparing the mean score percentages of the domains and the global DREEM. Conclusion: Students positively evaluated the educational environment in the subjects Semiology I and II created by the new active teaching methodologies adopted by the institution, with the SPT domain being highlighted.
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ABSTRACT Introduction: Hemophilia is well known in males, but poorly recognized in hemophilia carriers, who may have a hemorrhagic tendency, and the symptoms may be frequent and severe. Few studies have been done evidencing this bleeding in female carriers of the hemophilia gene. Objectives: To verify the prevalence of hemorrhagic symptoms in HC, compared to women in the general population. Material and method: The articles published between October 1996 and November 2016 were searched in the PubMed, Scielo, Lilacs, Web of Science, Scopus and Cochrane Central databases. Results and discussion: Seventy-five articles were found in electronic databases and 2 additional articles, through manual search in journal summaries and bibliographical references of other review articles. There is a limitation as to the number of studies that explore the association between the risk of hemorrhagic events and HC A or B. Among the few existing studies, there is a methodological difference, evidenced by control groups with distinct recruitments, divergent questionnaires and non-standardized concepts. Conclusion: This review verified the existence of a higher prevalence of hemorrhagic symptoms in the HC in some outcomes, however, due to the limitations of the few studies found, there is still insufficient evidence to state that the HC has a greater hemorrhagic tendency in relation to the general population.
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Período Pós-Parto , Hemofilia A , Hemorragia , Heterozigoto , MenorragiaRESUMO
INTRODUCTION: Hemophilia is well known in males, but poorly recognized in hemophilia carriers, who may have a hemorrhagic tendency, and the symptoms may be frequent and severe. Few studies have been done evidencing this bleeding in female carriers of the hemophilia gene. OBJECTIVES: To verify the prevalence of hemorrhagic symptoms in HC, compared to women in the general population. MATERIAL AND METHOD: The articles published between October 1996 and November 2016 were searched in the PubMed, Scielo, Lilacs, Web of Science, Scopus and Cochrane Central databases. RESULTS AND DISCUSSION: Seventy-five articles were found in electronic databases and 2 additional articles, through manual search in journal summaries and bibliographical references of other review articles. There is a limitation as to the number of studies that explore the association between the risk of hemorrhagic events and HC A or B. Among the few existing studies, there is a methodological difference, evidenced by control groups with distinct recruitments, divergent questionnaires and non-standardized concepts. CONCLUSION: This review verified the existence of a higher prevalence of hemorrhagic symptoms in the HC in some outcomes, however, due to the limitations of the few studies found, there is still insufficient evidence to state that the HC has a greater hemorrhagic tendency in relation to the general population.
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CONTEXT AND OBJECTIVE: Routine use of the script concordance test (SCT) is not common in Brazilian universities. This study aimed to analyze application of the SCT in the medical school of a Brazilian university. DESIGN AND SETTING: Quantitative, analytical and descriptive study in the medical school of a Brazilian university. METHODS: A total of 159/550 students participated. The test comprised ten clinical cases within internal medicine, with five items per case, rated on a five-point Likert scale. The test was scored in accordance with a marking key that had been validated by a reference panel. RESULTS: In the pre-clinical and clinical phases, the mean scores were 51.6% and 63.4% of the maximum possible scores, respectively. Comparison of the means of the responses among all the years showed that there were significant differences in 40% of the items. The panel marked all the possible answers in five items, while in one item, all the panelists marked a single answer. Cronbach's alpha was 0.64. The results indicated that the more senior students performed better. Construction of an SCT with discriminative questions was not easy. The low reliability index may have occurred due to: a) problems with the construction of the questions; b) limitations of the reference panel; and/or c) the scoring key. CONCLUSION: This instrument is very difficult to construct, apply and correct. These difficulties may make application of an SCT as an assessment method unfeasible in units with limited resources.
RESUMO CONTEXTO E OBJETIVO: O uso rotineiro do teste de concordância de script (SCT) não é comum nas universidades brasileiras. Este estudo objetiva analisar a aplicação do SCT na graduação em medicina de uma universidade brasileira. TIPO DE ESTUDO E LOCAL: Estudo quantitativo, analítico e descritivo na faculdade de medicina de uma universidade brasileira. MÉTODOS: Participaram 159/550 acadêmicos. O teste possuía dez casos clínicos em Medicina Interna, cada caso com cinco itens, classificados em uma escala de Likert de cinco pontos. O teste foi corrigido conforme gabarito validado por um painel de referência. RESULTADOS: Na fase pré-clínica, a média foi 51,6% e, na fase clínica, 63,4% da nota máxima. Comparando a média das respostas entre todos os anos, obteve-se diferença significante em 40% dos itens. O painel demarcou todas as possiblidades em cinco itens e em um item todos marcaram uma resposta. O índice alfa de Cronbach foi de 0,64. Demonstramos que os mais graduados obtiveram desempenho melhor. A construção de um SCT com questões discriminativas não foi fácil. O índice de confiabilidade baixo pode ter acontecido por: a) problemas na construção das questões; b) limitações do painel de referência; c) sistema de pontuação. CONCLUSÕES: O instrumento é de grande dificuldade de construção, aplicação e correção. Essas dificuldades podem inviabilizar a sua aplicação como método de avaliação em unidades com recursos limitados.
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Humanos , Adolescente , Adulto , Adulto Jovem , Faculdades de Medicina , Estudantes de Medicina/psicologia , Competência Clínica/normas , Educação de Graduação em Medicina , Avaliação Educacional/métodos , Brasil , Aprendizagem Baseada em Problemas , Tomada de DecisõesRESUMO
ABSTRACT CONTEXT AND OBJECTIVE The cognitive processes relating to the development of clinical reasoning are only partially understood, which explains the difficulties in teaching this skill in medical courses. This study aimed to understand how clinical reasoning develops among undergraduate medical students. DESIGN AND SETTING Quantitative and qualitative exploratory descriptive study conducted at the medical school of Universidade Federal de Goiás. METHODS The focus group technique was used among 40 students who participated in five focus groups, with eight students from each year, from the first to fifth year of the medical school program. The material was subjected to content analysis in categories, and was subsequently quantified and subjected to descriptive statistical analysis and chi-square test for inferential statistics. RESULTS The content of the students' statements was divided into two categories: clinical reasoning - in the preclinical phase, clinical reasoning was based on knowledge of basic medical science and in the clinical phase, there was a change to pattern recognition; knowledge of basic medical science - 80.6% of the students recognized its use, but they stated that they only used it in difficult cases. CONCLUSION In the preclinical phase, in a medical school with a traditional curriculum, clinical reasoning depends on the knowledge acquired from basic medical science, while in the clinical phase, it becomes based on pattern recognition.
RESUMO CONTEXTO E OBJETIVO Tem-se compreensão parcial dos processos cognitivos relacionados ao desenvolvimento do raciocínio clínico, o que justifica as dificuldades no ensino dessa competência nos cursos de medicina. Este estudo tem como objetivo compreender como se desenvolve o raciocínio clínico em acadêmicos de medicina. TIPO DE ESTUDO E LOCAL Pesquisa descritiva exploratória quantitativa e qualitativa, realizada na Faculdade de Medicina da Universidade Federal de Goiás. MÉTODOS A técnica de grupos focais foi utilizada entre 40 acadêmicos, que participaram de cinco grupos focais, com oito acadêmicos de cada ano, do primeiro ao quinto ano do curso médico. O material foi submetido a análise de conteúdo por categorias, posteriormente quantificado e submetido a análise estatística descritiva e teste de qui-quadrado para estatística inferencial. RESULTADOS O conteúdo das falas dos participantes foi dividido em duas categorias: raciocínio clínico - na fase pré-clínica, o raciocínio clínico é baseado no conhecimento das disciplinas básicas e, na fase clínica, há uma mudança para o reconhecimento de padrões; conhecimento das disciplinas básicas - 80,6% percebem sua utilização, porém assinalam que o usam apenas em casos difíceis. CONCLUSÃO Na fase pré-clínica, em uma escola médica com currículo tradicional, o raciocínio clínico é dependente dos conhecimentos adquiridos nas disciplinas básicas e, na fase clínica, passa para o reconhecimento de padrões.
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Humanos , Competência Clínica/normas , Cognição , Educação de Graduação em Medicina/organização & administração , Avaliação Educacional , Tomada de Decisão Clínica/métodos , Faculdades de Medicina , Estudantes de Medicina , Brasil , Educação Baseada em Competências , CurrículoRESUMO
CONTEXT AND OBJECTIVE: Routine use of the script concordance test (SCT) is not common in Brazilian universities. This study aimed to analyze application of the SCT in the medical school of a Brazilian university. DESIGN AND SETTING: Quantitative, analytical and descriptive study in the medical school of a Brazilian university. METHODS: A total of 159/550 students participated. The test comprised ten clinical cases within internal medicine, with five items per case, rated on a five-point Likert scale. The test was scored in accordance with a marking key that had been validated by a reference panel. RESULTS: In the pre-clinical and clinical phases, the mean scores were 51.6% and 63.4% of the maximum possible scores, respectively. Comparison of the means of the responses among all the years showed that there were significant differences in 40% of the items. The panel marked all the possible answers in five items, while in one item, all the panelists marked a single answer. Cronbach's alpha was 0.64. The results indicated that the more senior students performed better. Construction of an SCT with discriminative questions was not easy. The low reliability index may have occurred due to: a) problems with the construction of the questions; b) limitations of the reference panel; and/or c) the scoring key. CONCLUSION: This instrument is very difficult to construct, apply and correct. These difficulties may make application of an SCT as an assessment method unfeasible in units with limited resources.
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Competência Clínica/normas , Educação de Graduação em Medicina , Avaliação Educacional/métodos , Faculdades de Medicina , Estudantes de Medicina , Adolescente , Adulto , Brasil , Tomada de Decisões , Humanos , Aprendizagem Baseada em Problemas , Estudantes de Medicina/psicologia , Adulto JovemRESUMO
CONTEXT AND OBJECTIVE The cognitive processes relating to the development of clinical reasoning are only partially understood, which explains the difficulties in teaching this skill in medical courses. This study aimed to understand how clinical reasoning develops among undergraduate medical students. DESIGN AND SETTING Quantitative and qualitative exploratory descriptive study conducted at the medical school of Universidade Federal de Goiás. METHODS The focus group technique was used among 40 students who participated in five focus groups, with eight students from each year, from the first to fifth year of the medical school program. The material was subjected to content analysis in categories, and was subsequently quantified and subjected to descriptive statistical analysis and chi-square test for inferential statistics. RESULTS The content of the students' statements was divided into two categories: clinical reasoning - in the preclinical phase, clinical reasoning was based on knowledge of basic medical science and in the clinical phase, there was a change to pattern recognition; knowledge of basic medical science - 80.6% of the students recognized its use, but they stated that they only used it in difficult cases. CONCLUSION In the preclinical phase, in a medical school with a traditional curriculum, clinical reasoning depends on the knowledge acquired from basic medical science, while in the clinical phase, it becomes based on pattern recognition.
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Competência Clínica/normas , Tomada de Decisão Clínica/métodos , Cognição , Educação de Graduação em Medicina/organização & administração , Avaliação Educacional , Brasil , Educação Baseada em Competências , Currículo , Humanos , Faculdades de Medicina , Estudantes de MedicinaRESUMO
Haemolytic uraemic syndrome is a disfunction known as thrombotic microangiopathy. When it is not caused by Shiga toxin, produced by Escherichia coli, the disease is called atypical, which is classified in primary and secondary. This paper aims to study two case reports diagnosed as atypical haemolytic uraemic syndrome secondary to calcineurin inhibitors. Both are patients that had undergone kidney transplantation, but lost their graft due to atypical haemolytic uraemic syndrome. Their presentations were pancytopenia for one and anaemia of difficult management for the other, the first one was taking the medication called tacrolimus and the second one was taking cyclosporine. Nephrotoxicity related to the usage of calcineurin inhibitors was already known since it was introduced in the medical practice, however its efficacy in the control of graft rejection may exceed the problems regarding side effects. Nevertheless, it was observed that in long terms, the morbidity related to these side effects are indeed relevant. Therefore, new medicines and therapeutic schemes capable of lowering exposure to calcineurin inhibitors are being studied. There are two options of treatment established to atypical haemolytic uraemic syndrome and both of them were used in the case reports presented in this paper: plasmapheresis or plasma infusion and eculizumab, an antibody that blocks the complement system pro inflammation, pro thrombotic and lytic functions. There is great discussion regarding which one of these treatments are the most suitable for atypical haemolytic uraemic syndrome. However, the choice of the therapy depends of each patient, individually, as was seen in the cases presented in this article.
A síndrome hemolítico-urêmica (SHU) é uma disfunção caracterizada por microangiopatia trombótica (MTA). Quando sua causa não é devido à toxina Shiga, produzida por Escherichia coli, ela é dita atípica, que se classifica em primária e secundária. Este artigo visou relatar dois casos clínicos de síndrome hemolítico-urêmica atípica secundária ao uso de inibidores da calcineurina, para os quais foram feitos os seguintes diagnósticos diferenciais: púrpura trombocitopênica trombótica, síndrome hemolítico-urêmica atípica primária, anemia hemolítica autoimune e hemoglobinúria paroxística noturna. Ambos os casos eram pacientes transplantados renais que sofreram perda do enxerto devido à síndrome hemolítico-urêmica atípica; um estava em uso de tacrolimo, enquanto a outra paciente estava em uso de ciclosporina. A nefrotoxicidade relacionada com o uso de inibidores da calcineurina já era conhecida desde sua introdução na prática clínica, entretanto sua eficácia no controle da rejeição do enxerto superava as preocupações em relação às reações adversas. Porém observou-se que, a longo prazo, a morbidade relacionada a essas reações é significativa e, hoje, os estudos buscam novos medicamentos e esquemas terapêuticos capazes de diminuir a exposição aos inibidores da calcineurina. O tratamento estabelecido para síndrome hemolítico-urêmica atípica era de plasmaferese e/ou infusão de plasma, mas, em 2011, foi aprovado o uso de eculizumabe, um anticorpo que bloqueia as funções pró-inflamatórias, pró-trombóticas e líticas do complemento. O uso de eculizumabe para tratamento dessa enfermidade é ainda recente, mas já demonstra benefícios em relação ao tratamento de plasmaferese e infusão de plasma.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Rim , Tacrolimo , Ciclosporina , Calcineurina , Síndrome Hemolítico-Urêmica/diagnóstico , ImunossupressoresRESUMO
Introdução: A leucemia mieloide crônica é um distúrbio mieloproliferativo clonal com uma anormalidade citogenética específica, resultante da translocação entre os cromossomos 9 e 22 com consequente produção de uma proteína com atividade tirosina quinase alterada. Tratamentos históricos com drogas como bussulfan, hidroxiureia e interferon passaram a ser pouco utilizados devido ao surgimento dos inibidores de tirosina quinase, cujo principal representante é o mesilato de imatinibe. Esse fármaco é a terapia de primeira linha, sendo bem tolerado pelos pacientes e com baixo risco de eventos adversos severos. Entretanto, com cerca de dez anos de uso, ainda há preocupação com efeitos colaterais em longo prazo, tais como o desenvolvimento de segunda neoplasia. Objetivo: Descrever a ocorrência de múltiplas neoplasias em um portador de leucemia mieloide crônica. Método: Relata-se o caso de um paciente com leucemia mieloide crônica há 13 anos, tendo utilizado hidroxiureia e interferon como terapias prévias e em uso de mesilato de imatinibe há nove anos. Resultados: Há dois anos, o paciente apresentou dois nódulos em coxa esquerda que foram totalmente ressecados. Diagnosticou-se lipossarcoma mixoide e o paciente foi submetido à radioterapia. A tomografia computadorizada do abdomên de controle aos seis meses detectou nódulo espiculado na gordura mesenquimal adjacente ao jejuno/íleo. Feita laparotomia exploradora e ressecção, o anatomopatológico demonstrou fibromatose desmoide. Conclusão: O portador de tumor maligno tem risco aumentado de desenvolver uma segunda neoplasia, que pode dessa forma ocorrer nos portadores de leucemia mieloide crônica. Essa associação pode estar relacionada aos fármacos usados no tratamento da mesma.
Assuntos
Humanos , Masculino , Adulto , Hidroxiureia/efeitos adversos , Interferons/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Mesilatos/efeitos adversos , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/terapiaRESUMO
JUSTIFICATIVA E OBJETIVOS: A formação profissional na área da saúde tem um modelo tecnificado e mercantilizado. As frequentes transformações mundiais provocam mudanças em todos os setores da sociedade, exigindo alterações de postura e quebras de paradigmas frente às novas situações. Os profissionais da saúde necessitam constantemente de atualização científica, através de pesquisas. O objetivo deste estudo foi estudar as dificuldades relativas ao ensino, pesquisa e ética médica no Brasil. CONTEÚDO: As pesquisas podem gerar conflitos de interesse entre os setores da sociedade envolvidos. O Brasil se encontra instrumentalizado para as revisões éticas das pesquisas, podendo assim minimizar os efeitos destes conflitos. Porém, a manutenção dos requisitos éticos e científicos no desenvolvimento de pesquisas ultrapassa o processo de revisão dos protocolos éticos. CONCLUSÃO: A capacitação técnica dos pesquisadores é fundamental para manter a integridade das pesquisas, no entanto, a realidade do ensino nas escolas médicas está em descompasso com esta necessidade, a formação ética dos alunos está sendo realizada de maneira deficitária.
BACKGROUND AND OBJECTIVES: Professional training in health has a model technician and commodified. The frequent transformations which the world is causing changes in all sectors of society, requiring modifications in posture and breaks paradigms in the face of new situations. Health professionals need to constantly scientific upgrade through research. The objective of this study is the difficulties related to teaching, research and medical ethics in Brazil. CONTENTS: The researches can create conflicts of interest among various sectors of society involved. The Brazil is capable to the ethical review of research and thereby minimizes the effects of these conflicts. However, the maintenance of ethical and scientific requirements in research exceeds the review of protocols. CONCLUSION: The technical training of researchers is critical to maintaining the integrity of research. Paradoxically, the reality of teaching in medical schools is mismatched with this need; the ethical education of students (future researchers) is being performedin a deficient way.
Assuntos
Ética Médica , Pesquisa , Ensino , BrasilRESUMO
Aplastic anemia is an uncommon complication of thymoma and is extremely infrequent after the surgical removal of a thymic tumor. Aplastic anemia is a result of marrow failure and is characterized by peripheral pancytopenia and severely depressed marrow cellularity; it may be an autoimmune manifestation of thymoma. As thymoma-associated hematological dyscrasias, which include pure red cell aplasia, aplastic anemia and myasthenia gravis, are supposed to be of immunologic origin, two cases of very severe aplastic anemia following the resection of lymphocytic thymomas treated with immunosuppression are herein presented.
Assuntos
Humanos , Masculino , Idoso , Anemia Aplástica , Ciclosporina/uso terapêutico , Tolerância Imunológica , Miastenia Gravis/terapiaRESUMO
Aceruloplasminemia is a rare autosomal recessive disease in which a mutation leads to the absence or dysfunction of ceruloplasmin. Deficiency of this enzyme leads to the accumulation of iron in various organs; aceruloplasminemia is usually characterized by diabetes, retinal degeneration and neurological disorders. Diagnosis is suspected by the presence of elevated levels of ferritin, anemia, decreased serum copper and absence of ceruloplasmin in serum. Treatment of aceruloplasminemia is mainly based on the control of iron overload.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Ceruloplasmina , Ceruloplasmina/uso terapêutico , Distúrbios do Metabolismo do Ferro , Transtornos Cognitivos/etiologiaRESUMO
Aceruloplasminemia is a rare autosomal recessive disease in which a mutation leads to the absence or dysfunction of ceruloplasmin. Deficiency of this enzyme leads to the accumulation of iron in various organs; aceruloplasminemia is usually characterized by diabetes, retinal degeneration and neurological disorders. Diagnosis is suspected by the presence of elevated levels of ferritin, anemia, decreased serum copper and absence of ceruloplasmin in serum. Treatment of aceruloplasminemia is mainly based on the control of iron overload.
RESUMO
Aplastic anemia is an uncommon complication of thymoma and is extremely infrequent after the surgical removal of a thymic tumor. Aplastic anemia is a result of marrow failure and is characterized by peripheral pancytopenia and severely depressed marrow cellularity; it may be an autoimmune manifestation of thymoma. As thymoma-associated hematological dyscrasias, which include pure red cell aplasia, aplastic anemia and myasthenia gravis, are supposed to be of immunologic origin, two cases of very severe aplastic anemia following the resection of lymphocytic thymomas treated with immunosuppression are herein presented.