Multisystem inflammatory syndrome drug treatment in countries with different income profiles: a scoping review

Objective: The purpose of this study was to map and describe the studies that have investigated therapeutic alternatives for the management of paediatric multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Considering the origin of the studies performed (low-, middle- and high-income countries), a systematic scoping review was conducted with primary studies that reported the use of medications for the treatment of patients with MIS-C.Sources: The searches were performed in MEDLINE, Embase, Lilacs, Epistemonikos, CINAHL, and CENTRAL, in the grey literature (theses and dissertations from CAPES, ProQuest, and PROSPERO) and in clinical trial databases until May 2022. The selection and extraction of studies were performed independently by two reviewers.Summary of the findings: A total of 173 studies were included, most of which were published as case reports or series. No randomized controlled clinical trials (RCTs) were identified. The investigated drugs were immunoglobulins, glucocorticoids, monoclonal antibodies, anticoagulants, and antiplatelet agents.Conclusion: The dosages, when reported, were heterogeneous among the studies. The ethnicity and comorbidity of the participants were poorly reported. Monoclonal antibodies, drugs with higher costs, were mostly described in studies of high-income countries

Flow cytometry immunophenotyping for diagnostic orientation and classification of pediatric cancer based on the euroflow solid tumor orientation tube (Stot)

© 2021 by the authors.Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination—solid tumor orientation tube, STOT—for diagnostic screening of pediatric cancer by MFC. A total of 476 samples (139 tumor mass, 138 bone marrow, 86 lymph node, 58 peripheral blood, and 55 other body fluid samples) from 296 patients with diagnostic suspicion of pediatric cancer were analyzed by MFC vs. conventional diagnostic procedures. STOT was designed after several design–test–evaluate–redesign cycles based on a large panel of monoclonal antibody combinations tested on 301 samples. In its final version, STOT consists of a single 8-color/12-marker antibody combination (CD99-CD8/numyogenin/CD4-EpCAM/CD56/GD2/smCD3-CD19/cyCD3-CD271/CD45). Prospective validation of STOT in 149 samples showed concordant results with the patient WHO/ICCC-3 diagnosis in 138/149 cases (92.6%). These included: 63/63 (100%) reactive/disease-free samples, 43/44 (98%) malignant and 4/4 (100%) benign non-hematopoietic tumors together with 28/38 (74%) leukemia/lymphoma cases; the only exception was Hodgkin lymphoma that required additional markers to be stained. In addition, STOT allowed accurate discrimination among the four most common subtypes of malignant CD45− CD56++ non-hematopoietic solid tumors: 13/13 (GD2++ numyogenin− CD271−/+ nuMyoD1− CD99− EpCAM−) neuroblastoma samples, 5/5 (GD2− numyogenin++ CD271++ nuMyoD1++ CD99−/+ EpCAM−) rhabdomyosarcomas, 2/2 (GD2−/+ numyogenin− CD271+ nuMyoD1− CD99+ EpCAM−) Ewing sarcoma family of tumors, and 7/7 (GD2− numyogenin− CD271+ nuMyoD1− CD99− EpCAM+) Wilms tumors. In summary, here we designed and validated a new standardized antibody combination and MFC assay for diagnostic screening of pediatric solid tumors that might contribute to fast and accurate diagnostic orientation and classification of pediatric cancer in routine clinical practice.This research was funded by the EuroFlow Consortium; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Brazil (FAPERJ), numbers: E26/110.105/2014, E-26/010.101259/2018, and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, Brazil (CNPQ), Brasília, Brazil, numbers: 303765/2018-6, 409440/2016-7, and 400194/2014-7; and Instituto Desiderata/Chevron, Rio de Janeiro, Brazil, grant “Actions to improve pediatric cancer assistance in RJ”; the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15

CHILDREN WITH MULTIPLE CONGENITAL DEFECTS: WHAT ARE THE LIMITS BETWEEN THERAPEUTIC OBSTINACY AND THE TREATMENT OF UNCERTAIN BENEFIT? Crianças com múltiplas malformações congênitas: quais são os limites entre obstinação terapêutica e tratamento de benefíci

Objective: Therapeutic approach of children with multiple malformations poses many dilemmas, making it difficult to build a line between the treatment of uncertain benefit and therapeutic obstinacy. The aim of this paper was to highlight possible sources of uncertainty in the decision-making process, for this group of children. Case description: An 11-month-old boy, born with multiple birth defects and abandoned by his parents, has never been discharged home. He has complex congenital heart disease, main left bronchus stenosis and imperforate anus. He is under technological support and has gone through many surgical procedures. The complete correction of the cardiac defect seems unlikely, and every attempt to wean the ventilator has failed. Comments: The first two main sources of uncertainty in the management of children with multiple birth defects are related to an uncertain prognosis. There is a lack of empirical data, due to the multiple possibilities of anatomic or functional organ involvement, with few similar cases described. Prognosis is also unpredictable for neuro-developmental evolution, as well as the capacity for the development and regeneration of other ABSTRACT RESUM

A perspectiva da ética das virtudes para o processo de tomada de decisão médica

Resumo A bioética é vista por muitos médicos como disciplina que deve substanciar decisões e condutas em situações dilemáticas, indicando regras de ação racionais e universais. Nesse cenário, a perspectiva da ética das virtudes propõe substituição da pergunta de “como agir” para “como se constituir”; e, formando o próprio caráter, permitir que a pessoa seja capaz de tomar as decisões da vida, inclusive profissionais, de forma sábia e prudente. Neste ensaio, apresentar-se-á a perspectiva da ética aristotélica, seus autores contemporâneos e as respostas às principais críticas, explicitando vantagens que esse referencial oferece à deliberação médica – suas características valorativa, particularista e teleológica. Mais do que proclamar um paciente autônomo e um profissional que busca regras externamente estabelecidas, a ética das virtudes reconhece que paciente e profissional estão inseridos em comunidades, tradições e culturas, respeitando valores e virtudes, em busca do fim determinado de suas práticas e vidas

VALIAÇÃO DA ATIVIDADE ANTILEUCÊMICA DE L-ASPARAGINASE RECOMBINANTE DE ZYMOMONAS MOBILIS

A Leucemia Linfoblástica Aguda (LLA) é o câncer pediátrico mais comum e no Brasil. A enzima L-Asparaginase (L-Asp) é um componente essencial para o tratamento de LLA da infância. Pacientes que não completam o tratamento com L-Asp tem o risco de recidiva aumentado. A principal limitação do uso de L-Asp é a hipersensibilidade e a produção de anticorpos que a inativam, o que ocorre com frequência similar em todas as L-Asparaginases disponíveis na sua forma nativa. Nestes casos é possível a substituição por uma L-Asp de outra fonte terapeuticamente eficaz. Porém, no Brasil os medicamentos à base de L-Asparaginase empregados são importados e apenas uma das formas disponíveis tem seu uso aprovado pela Agência Nacional de Vigilância Sanitária (ANVISA). Com base em trabalhos que demonstraram que a bactéria Zymomonas mobilis produz L-Asparaginase, o objetivo deste estudo foi avaliar o potencial antileucêmico de uma L-Asparaginase recombinante de Zymomonas mobilis. Foram realizados ensaios para avaliar aspectos citotóxicos e citostáticos desta enzima sobre as células leucêmicas das linhagens Jurkat e Reh, e amostras primárias de pacientes com diagnóstico de LLA. Foi possível verificar in vitro o efeito desta enzima e sua eficácia sobre as linhagens utilizadas e amostras primárias que apresentaram responsividade a L-Asparaginase.Palavras-chave: Leucemia Linfoblástica Aguda. L-asparaginase. Cultura de Células

Abandonment of Treatment for Latent Tuberculosis Infection and Socioeconomic Factors in Children and Adolescents: Rio De Janeiro, Brazil

<div><p>Background</p><p>Routine data on the use of isoniazid preventive therapy (IPT) in children and adolescents are scarce in high tuberculosis (TB) burden countries.</p><p>Objective</p><p>To describe the factors related to abandonment of IPT in children and adolescents with latent tuberculosis infection (LTBI) receiving routine care.</p><p>Methods</p><p>Retrospective (2005–2009) descriptive study of 286 LTBI cases with indication of IPT and serviced at a pediatric hospital in the State of Rio de Janeiro, Brazil. Survival analysis of the risk of abandonment of IPT over six months was performed, including multivariate analysis using the Cox proportional hazards model.</p><p>Results</p><p>Out of the 245 cases of LTBI included, 62 abandoned IPT (25.3%; 95% CI: 20%-31%). On multivariate analysis, the variables related to the IPT abandonment hazard ratio were the Human Development Index (HDI) (hazard ratio—HR: 0.004; 0.000–0.569) of the place of residence and the contact with adults that were not undergoing anti-TB treatment (HR: 7.30; 1.00–53.3).</p><p>Conclusion</p><p>This study reveals the relevance of the relation of abandonment of IPT to the socioeconomic conditions at the place of residence and poor adherence to the active TB treatment. Educational measures to stimulate preventive treatment of child contacts and curative treatment of index cases should target the full familial setting.</p></div