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Objetivo: Descrever um relato de caso sobre anemia perniciosa como provável etiologia para paraplegia em paciente adulto internado em hospital terciário para investigação de bicitopenia. Introdução: Anemia perniciosa refere-se à deficiência de vitamina (Vit) B12 causada por autoanticorpos que interferem na absorção de Vit. B12 ao atingir o fator intrínseco, células parietais gástricas ou ambos. Achados neurológicos são comuns na deficiência crônica de Vit. B12, podendo se manifestar como parestesias, fraqueza progressiva e ataxia; se não tratado poderá progredir para paraplegia. Materiais e métodos: Trata-se de relato de caso elaborado através de revisão de prontuário e consulta à literatura específica. Relato de caso: Homem, 30 anos, internado hospital terciário devido a quadro de bicitopenia. Relato de perda progressiva de força em membros inferiores (MMII) evoluindo com paraplegia, incontinência urinária e constipação. Também referiu perda ponderal de aproximadamente 7 kg em 2 meses. Negava febre, sangramentos ou perda de força em membros superiores. Possuía antecedente de transfusões anteriores de concentrados de hemácias e de plaquetas devido a episódios recorrentes de anemia. Ao exame físico apresentava-se com regular estado geral, emagrecido, descorado ++/4+, sem linfonodomegalias. Força grau 4 em membros superiores, força grau 0 e hipoestesia em MMII. Exames realizados ambulatorialmente em outra instituição evidenciavam: hemoglobina: 6,3 g/dL; hematócrito: 17,4%, volume corpuscular médio: 86 μm3; hemoglobina corpuscular média: 31 pg; leucócitos totais: 3.900 mm3 (segmentados: 47%, linfócitos: 48%, eosinófilos: 4%); plaquetas: 72.000/mm3. Foram solicitados os seguintes exames: ressonância nuclear magnética (RNM) de coluna lombossacra com contraste, sorologias, eletrólitos e novo hemograma. Foi avaliado pela hematologia que solicitou adicionalmente: sorologia para HTLV e RK-39; cinética de ferro, LDH, vit. B12 e ácido fólico. Foi inicado empiricamente reposição de cianocobalamina com a suspeita de anemia por deficiência de vit. B12 e foram solicitados endoscopia digestiva alta, FAN e pesquisa de sangue oculto nas fezes, negativos. Nos dias que se sucederam evoluiu com melhora progressiva de pancitopenia e vit. B12 teve resultado < 50 pg/mL. Endoscopia realizada demonstrou gastrite atrófica moderada de corpo com pesquisa de H Pylorii +. Laudo de RNM de coluna lombossacra apresentou alteração difusa do sinal da medula óssea, podendo estar relacionado a desordens hematopoiéticas, sem lesões compressivas. Recebeu alta com recuperação de seus parâmetros hematimétricos e com recuperação parcial da força. Após alta repetiu exame de endoscopia, o qual confirmou erradicação de H. pylori, após tratamento. Também fez pesquisa de anticorpo anti-fator intrínseco, sendo resultado positivo. Resultados: Finalizado relato de caso após consulta à literatura específica e revisão de prontuário. Discussão: Paciente do sexo masculino com bicitopenia e sintomas neurológicos. Tais sintomas devem chamar atenção para deficiência de Vit. B12 e/ou também de ácido fólico, sendo a anemia perniciosa uma importante causa a ser investigada. Conclusão: É necessário suspeitar de deficiência de Vit. B12 e/ou também de ácido fólico em pacientes com alterações de hemograma e sintomas neurológicos. A anemia perniciosa se torna um importante diagnóstico nesse cenário e caso não seja tratada poderá evoluir para bicitopenia, pancitopenia e até paraplegia.

Objetivo: Avaliar a acurácia dos alertas da presença de blastos e linfócitos atípicos, obtidos através da análise automatizada de amostras de medula óssea, utilizando o equipamento Sysmex® XN-10. Material e métodos: Foram avaliados retrospectivamente os resultados de 40 amostras de medula óssea, selecionadas de forma aleatória, dentre as analisadas no laboratório clínico do Hospital Israelita Albert Einstein para mielograma e imunofenotipagem. O processamento das amostras no equipamento XN-10 foi efetuado de rotina após a realização da imunofenotipagem, com uma alíquota de material excedente filtrada, diluída e submetida à análise no aparelho. Os alertas avaliados foram “Blasts/Abn Lympho?” e “Atypical Lympho?”, os quais foram correlacionados com presença acima de 1% de blastos e 1% de plasmócitos, respectivamente, nos resultados de mielograma e imunofenotipagem. Os resultados obtidos foram registrados em planilha no excel e analisados utilizando o coeficiente “Kappa”. Resultados: Em comparação com o resultado do mielograma, o alerta “Blasts/Abn Lympho?” apresentou concordância adequada em apenas 20 de 40 amostras, evidenciando-se uma pobre concordância “Kappa”, 0,059. Utilizando a Imunofenotipagem como parâmetro de comparação, a concordância do alerta aumentou para 24 amostras, sendo 15 com presença do alerta e 9 sem o alerta, elevando o coeficiente “Kappa” para 0,19. Avaliando-se a detecção da presença de plasmócitos através do alerta “Atypical Lympho?”, observou-se que 16 de 40 amostras tiveram resultados concordantes com mielograma, sendo 12 com e 4 sem a presença do alerta. O coeficiente “Kappa” desta comparação foi de -0,221. Devido ao baixo número de amostras com quantificação de células plasmocitárias através de imunofenotipagem, não foi possível comparar a performance do alerta com os resultados obtidos por este método. Discussão: Embora o equipamento Sysmex® XN-10 apresente boa acurácia, reprodutibilidade e sensibilidade em seus alertas para detecção de blastos e plasmócitos em amostras de sangue periférico, os resultados desta análise demonstram que essa performance não se reproduz em amostras de medula óssea, conforme evidenciado pelas baixas correlações entre a presença dos alertas e os resultados de mielograma e imunofenotipagem das amostras. Esta observação indica que os analisadores hematológicos podem apresentar diferenças de acurácia em análise de amostras diferentes do sangue periférico para estes parâmetros. Conclusão: O estudo demonstrou que a eficácia dos alertas do equipamento Sysmex® XN-10 na detecção de blastos e plasmócitos é substancialmente reduzida quando utilizadas amostras de medula óssea.

Introdução/Objetivos: O ácido etilenodiamino tetra-acético potássico (EDTA K3) é a substância mais utilizada como anticoagulante de amostras para hemogramas. O EDTA sulfato de magnésio (EDTA MgSO4) surgiu como uma alternativa para mitigar interferentes analíticos associados ao EDTA K3, em especial a pseudoplaquetopenia. Há poucos dados quanto à acurácia dos índices hematimétricos e avaliação morfológica em EDTA MgSO4. Este estudo objetiva avaliar os índices hematimétricos e morfologia celular de hemograma em amostras de EDTA MgSO4 em comparação a EDTA K3. Material e métodos: Foram avaliadas 29 amostras de sangue periférico, com coleta síncrona em EDTA K3 e MgSO4, processadas no equipamento Sysmex® XN-10. Registrou-se os parâmetros das séries eritrocitária (HB, HT, VCM, CHCM, NRBC, RET, IRF e RET-HE), leucocitária (WBC, seu diferencial e IG) e plaquetária (PLT-I, MPV, PLT-F, IPF), sendo os mesmos submetidos à avaliação de normalidade pelo teste de Shapiro Wilk. Para analisar a correlação, foi utilizado teste de Pearson e Spearman, para o teste de associação, o teste T de student e teste de Mann Whitney seguindo os critérios de normalidade de cada variável. Por fim, foi avaliado a morfologia do esfregaço destas amostras. Resultados: Houve correlação positiva significativa de acordo com os parâmetros do serviço para todas as variáveis, exceto para NRBC, IRF, IG e IPF. Do ponto de vista da associação, não houve diferença entre os parâmetros avaliados, com exceção do CHCM (p < 0,05) e MPV (p < 0,05). Por fim, à avaliação morfológica não foi identificado prejuízo para análise dos esfregaços. Discussão: Nosso estudo sugere que os parâmetros eritrocitários e leucocitários são equivalentes entre amostras de EDTA K3 e EDTA MgSO4, exceto CHCM e MPV. Quanto à série plaquetária, a divergência dos valores de MPV dentre os anticoagulantes avaliados já havia sido descrita. Teoriza-se que as plaquetas em amostra de EDTA K3 não estão totalmente estabilizadas e, dessa forma, sofrem maiores alterações conformacionais. Embora haja controvérsia em literatura quanto à avaliação morfológica em amostras proveniente de EDTA MgSO4, nosso estudo sugere que sua realização é factível. Conclusão: Os resultados demonstram a plausibilidade do uso do EDTA MgSO4 para avaliação hematimétrica, com aparente equivalência qualitativa e quantitativa. Faz-se necessário, contudo, maiores estudos para seu uso na prática médica.

Objetivos: a refratariedade plaquetária trata-se de uma resposta inadequada à transfusão de plaquetas, sendo, portanto, um desafio enfrentado pelos bancos de sangue. Ela pode ser avaliada pelo Cálculo de Incremento Corrigido (CCI), onde consideramos que ocorreu um incremento plaquetário satisfatório se obtivermos um valor ≥5.000 plaquetas após 1hora da transfusão ou ≥2.500 após 24 horas. Os métodos para prevenção desta ocorrência são diversos incluindo testes de imunocompatibilidade até leucorredução no preparo dos concentrados de plaquetas. No entanto, pouco foi estudado com relação a possíveis interferências dos índices plaquetários das bolsas de concentrados a fim de se obter um maior incremento plaquetário. Destacando-se dentre eles a Fração de Plaquetas Imaturas (IPF), índice que se baseia no tamanho da plaqueta e em sua quantidade de RNA. Diante deste cenário o objetivo do presente estudo é estabelecer a relação do IPF com o incremento plaquetário pós transfusão de concentrado de plaquetas. Material e métodos: foram monitoradas 10 bolsas de concentrados de plaquetas desde sua produção a transfusão. Considerando-se sua validade de cinco dias após produção. Obteve-se fragmentos das bolsas nos dias 1, 2, 3, 4, 5 após produção. Em seguida, as amostras foram submetidas a análise automatizada no Sysmex®XN-10 nos dias consecutivos. Foram analisados contagem global do número de plaquetas por impedância e fluorescência, IPF, contagem plaquetária da bolsa pelo banco de sangue, tipagem sanguínea da bolsa, volume da bolsa e data da transfusão. Em relação aos pacientes transfundidos foram analisados tipagem sanguínea, diagnóstico, quantidade plaquetas pré e pós transfusão, bem como hora da coleta do hemograma pós transfusão se, após 1h ou 24h. Coletou-se, ainda, peso, altura e superfície corpórea para cálculo do incremento plaquetário corrigido. Por fim, os dados foram planilhados e submetidos a estatística descritiva, utilizando-se os testes paramétricos t-Student e anova. Resultados: Não houve diferença estatística entre os índices de IPF e os dias até a transfusão da bolsa, obtendo-se um p-valor de 0,77. A contagem média do número de plaquetas presentes nas bolsas foi equivalente a 4,09×1011, com um volume aproximado de 225,1 mL e intervalo médio entre a produção e transfusão da bolsa de 2,7 dias. Discussão: Em nosso espaço amostral apenas uma bolsa não apresentava compatibilidade ABO, mas foi transfundida devido ao título de isohemaglutinina permissivo resultando em incremento plaquetário considerável. Das transfusões apresentadas, apenas uma não apresentou incremento plaquetário satisfatório, este mesmo paciente apresentava um IPF dentro da média esperada no dia da transfusão. Conclusão: Muito provável que, devido limitação apresentada em relação ao tamanho amostral e influência multifatorial para melhor incremento plaquetário, o presente estudo não demonstrou possível relação dos níveis de IPF com incremento plaquetário após transfusão. Fazendo-se necessário, portanto, estudos complementares com maior espaço amostral para melhor estabelecimento de tal relação.

Objective: To evaluate the quality of information on gestational syphilis (GS) and congenital syphilis (CS) on the Sistema de Informação de Agravos de Notificação (SINAN-Syphilis Brazil - Notifiable Diseases Information System) by compiling and validating completeness indicators between 2007 and 2018., Methods: Overall, care, and socioeconomic completeness scores were compiled based on selected variables, by using ad hoc weights assigned by experts. The completeness scores were analysed, considering the region and area of residence, the pregnant woman's race/colour, and the year of case notification. Pearson's correlation coefficients were used to validate the scores obtained by the weighted average method, compared with the values obtained by principal component analysis (PCA)., Results: Most selected variables presented a good or excellent degree of completeness for GS and CS, except for clinical classification, pregnant woman's level of education, partner's treatment, and child's race/colour, which were classified as poor or very poor. The overall (89.93% versus 89.69%) and socioeconomic (88.71% versus 88.24%) completeness scores for GS and CS, respectively, were classified as regular, whereas the care score (GS-90.88%, and CS-90.72%) was good, despite improvements over time. Differences in the overall, care and socioeconomic completeness scores according to region, area of residence, and ethnic-racial groups were reported for syphilis notifications. The completeness scores estimated by the weighted average method and PCA showed a strong linear correlation (> 0.90)., Conclusion: The completeness of GS and CS notifications has been improving in recent years, highlighting the variables that form the care score, compared with the socioeconomic scores, despite differences between regions, area of residence, and ethnic-racial groups. The weighted average was a viable methodological alternative easily operationalised to estimate data completeness scores, allowing routine monitoring of the completeness of gestational and congenital syphilis records.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH., Objective: To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital., Methods: This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy., Results: Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p = 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%., Conclusions: The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

COVID-19 is spreading worldwide at disturbing rates, overwhelming global healthcare. Mounting death cases due to disease complications highlight the necessity of describing efficient drug therapy strategies for severe patients. COVID-19 severity associates with hypercoagulation and exacerbated inflammation, both influenced by ACE2 downregulation and cytokine storm occurrence. In this review, we discuss the applicability of the anticoagulant heparin and the anti-inflammatory corticosteroid dexamethasone for managing severe COVID-19 patients. The upregulated inflammation and blood clotting may be mitigated by administrating heparin and its derivatives. Heparin enhances the anticoagulant property of anti-thrombin (AT) and may be useful in conjunction with fibrinolytic drugs for severe COVID-19 patients. Besides, heparin can also modulate immune responses, alleviating TNF-α-mediated inflammation, impairing IL-6 production and secretion, and binding to complement proteins and leukotriene B 4 (LTB 4 ). Moreover, heparin may present anti-SARS-CoV-2 potential once it can impact viral infectivity and alter SARS-CoV-2 Spike protein architecture. Another feasible approach is the administration of the glucocorticoid dexamethasone. Although glucocorticoid's administration for viral infection managing is controversial, there is increasing evidence demonstrating that dexamethasone treatment is capable of drastically diminishing the death rate of patients presenting with Acute Respiratory Distress Syndrome (ARDS) that required invasive mechanical ventilation. Importantly, dexamethasone may be detrimental by impairing viral clearance and inducing hyperglycemia and sodium retention, hence possibly being deleterious for diabetics and hypertensive patients, two major COVID-19 risk groups. Therefore, while heparin's multitarget capacity shows to be strongly beneficial for severe COVID-19 patients, dexamethasone should be carefully administered taking into consideration underlying medical conditions and COVID-19 disease severity. Therefore, we suggest that the multitarget impact of heparin as an anti-viral, antithrombotic and anti-inflammatory drug in the early stage of the COVID-19 could significantly reduce the need for dexamethasone treatment in the initial phase of this disease. If the standard treatment of heparins fails on protecting against severe illness, dexamethasone must be applied as a potent anti-inflammatory shutting-down the uncontrolled and exacerbated inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Braz-de-Melo, Faria, Pasquarelli-do-Nascimento, Santos, Kobinger and Magalhães.)

COVID-19, caused by SARS-CoV-2, is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Several reports from around the world have identified obesity and severe obesity as one of the strongest risk factors for COVID-19 hospitalization and mechanical ventilation. Moreover, countries with greater obesity prevalence have a higher morbidity and mortality risk of developing serious outcomes from COVID-19. The understanding of how this increased susceptibility of the people with obesity to develop severe forms of the SARS-CoV-2 infection occurs is crucial for implementing appropriate public health and therapeutic strategies to avoid COVID-19 severe symptoms and complications in people living with obesity. We hypothesize here that increased ACE2 expression in adipose tissue displayed by people with obesity may increase SARS-CoV-2 infection and accessibility to this tissue. Individuals with obesity have increased white adipose tissue, which may act as a reservoir for a more extensive viral spread with increased shedding, immune activation and pro-inflammatory cytokine amplification. Here we discuss how obesity is related to a pro-inflammatory and metabolic dysregulation, increased SARS-CoV-2 host cell entry in adipose tissue and induction of hypercoagulopathy, leading people with obesity to develop severe forms of COVID-19 and also death. Taken together, it may be crucial to better explore the role of visceral adipose tissue in the inflammatory response to SARS-CoV-2 infection and investigate the potential therapeutic effect of using specific target anti-inflammatories (canakinumab or anakinra for IL-1β inhibition; anti-IL-6 antibodies for IL-6 inhibition), anticoagulant or anti-diabetic drugs in COVID-19 treatment of people with obesity. Defining the immunopathological changes in COVID-19 patients with obesity can provide prominent targets for drug discovery and clinical management improvement., (Copyright © 2020 Pasquarelli-do-Nascimento, Braz-de-Melo, Faria, Santos, Kobinger and Magalhães.)

Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.

Foam cells are specialized lipid-loaded macrophages derived from monocytes and are a key pathological feature of atherosclerotic lesions. Lysophosphatidylcholine (LPC) is a major lipid component of the plasma membrane with a broad spectrum of proinflammatory activities and plays a key role in atherosclerosis. However, the role of LPC in lipid droplet (LD) biogenesis and the modulation of inflammasome activation is still poorly understood. In the present study, we investigated whether LPC can induce foam cell formation through an analysis of LD biogenesis and determined whether the cell signaling involved in this process is mediated by the inflammasome activation pathway in human endothelial cells and monocytes. Our results showed that LPC induced foam cell formation in both types of cells by increasing LD biogenesis via a NLRP3 inflammasome-dependent pathway. Furthermore, LPC induced pyroptosis in both cells and the activation of the inflammasome with IL-1β secretion, which was dependent on potassium efflux and lysosomal damage in human monocytes. The present study described the IL-1β secretion and foam cell formation triggered by LPC via an inflammasome-mediated pathway in human monocytes and endothelial cells. Our results will help improve our understanding of the relationships among LPC, LD biogenesis, and NLRP3 inflammasome activation in the pathogenesis of atherosclerosis., (Copyright © 2020 Corrêa, Silva, Ribeiro, Almeida, Santos, Corrêa, Sant'Ana, Assunção, Bozza and Magalhães.)

Background and Objectives: Low back pain is a prevalent disease in the adult population, whose quality of life is considerably affected. In order to solve this problem, several therapies have been developed, of which ozone therapy is an example. Our objective in this study was to determine the effectiveness of ozone therapy for lumbar pain relief in adult patients compared to other therapies (steroid and placebo)., Method: We used randomized clinical trials to compare the effectiveness of ozone and other therapies for lumbar pain relief in adults (Prospero: CRD42018090807). Two independent reviewers searched the Medline (1966-April/2018), Scopus (2011-May/2018), Lilacs (1982-May/2018), and Embase (1974-March/2018) databases. We use the terms ozone and pain as descriptors. The primary variable was pain relief and the secondary ones were complication, degree of satisfaction, quality of life, and recurrence of pain., Results: Of the 779 identified articles, six selected clinical trials show that ozone therapy is more effective for lumbar pain relief; however, they were mostly classified as having a high or uncertain risk of bias (Cochrane Handbook). The meta-analysis regarding the effectiveness of pain relief did not show a significant difference between groups in the three-month period (RR = 1.98, 95% CI: 0.46-8.42, p = 0.36; 366 participants). It also showed greater effectiveness of the ozone therapy at six months compared to other therapies (steroid and placebo) (RR = 2.2, 95% CI: 1.87-2.60, p < 0.00001; 717 participants)., Conclusions: The systematic review has shown that ozone therapy used for six months for lumbar pain relief is more effective than other therapies; however, this result is not definitive as data from studies with moderate to high risk of bias were used., (Copyright © 2019 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: Since implant placement on diabetic patients still is a controversial topic and systematic reviews are at the top of scientific evidence hierarchy, a thorough assessment of the methodological quality of these reviews must be performed to inform clinicians if their conclusions and recommendations can be followed on clinical practice. An overview of systematic reviews was performed with the purpose to assess the methodological quality of systematic reviews regarding dental implant placement on diabetic patients. In addition, we presented a synthesis of clinical outcomes about the focused theme., Material and Methods: An online search was performed on MEDLINE via PubMed, EMBASE, DARE-Cochrane, Scopus, Web of Science, LILACS, and SIGLE via Open Grey. Searches were conducted from database inception to May 2018. Systematic review articles with or without meta-analysis about the placement of dental implants on diabetic patients were included. Exclusion criteria were: articles whose primary outcome was not the survival/success rate of dental implants on diabetic patients; studies that do not relate the survival/success rate of dental implants with diabetes; duplicated papers. Methodological quality assessment was performed with AMSTAR. A descriptive synthesis of clinical outcomes was performed., Results: We identified 1.661 initial hits and eight articles were selected for overview (kappa=0.83; strong agreement). Six studies presented moderate methodological quality and two showed high methodological quality. Implant survival rate ranged from 31.8% to 100% and data from four meta-analysis showed that diabetes does not affect implant survival rate. On the other hand, data from two meta-analysis for marginal bone loss showed that diabetes statistically affects this outcome., Conclusions: Two of the eight included studies presented high methodological quality and their meta-analysis showed that implant placement on diabetic patients does not affect implant survival rate and statistically affects marginal bone loss. However, clinicians must be aware that marginal bone loss values were not clinically relevant and may not be safe to follow the conclusions and recommendations of these studies.

Background and Objective: The systematic review of randomized clinical trials is crucial to assess the safety and effectiveness of intermediate procedures. The objective of this article is to present a tutorial for the planning and execution of systematic review and meta-analysis of randomized clinical trial studies., Content: The systematic literature review is the type of research that organizes, criticizes, and integrates available evidence published in the health field. Systematization leads to less bias, however, the quality of systematic reviews may not always be perceived due to the way it is described in the articles. The information disclosed in the articles is not always free of bias. The steps for carrying out a systematic review include design, protocol registration, implementation, mathematical analysis of results, and dissemination. PRISMA statement has improved the quality of systematic review reports by providing a list of items to be described, and this article emphasizes the key steps for performing a systematic review of interventions., Conclusion: The evidence generated through a systematic review can provide the clinician with greater confidence in decision making at the moment of clinical practice and optimize the benefits to his patients, serving as a tool to assist managers in making decisions regarding the implementation of new strategies in favor of the public health., (Copyright © 2018. Publicado por Elsevier Editora Ltda.)

Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Naphthoquinones (NQ) are considered privileged structures in medicinal chemistry due to their plethora of biological activities, including antimicrobial and anticancer effects. Nitrogen-containing heterocycles such as 1,2,3-1H-triazoles have been identified as general scaffolds for generating glycosidase inhibitors. In the present study, the NQ and 1,2,3-1H-triazole cores have been combined to chemically synthesize 18 new 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles (1,2-FNQT). Their cytotoxicities were evaluated against four different leukemia cell lines, including MOLT-4 and CEM (lymphoid cell lines) and K562 and KG1 (myeloid cell lines), as well as normal human peripheral blood mononucleated cells (PBMCs). The new 1,2-FNQT series showed high cytotoxic potential against all leukemia cell lines tested, and some compounds (12o and 12p) showed even better results than the classical therapeutic compounds such as doxorubicin or cisplatin. Others compounds, such as 12b, are promising because of their high selectivity against lymphoblastic leukemia and their low activity against normal hematopoietic cells. The cells of lymphoid origin (MOLT and CEM) were generally more sensitive than the myeloid cell lines to this series of compounds, and most of the compounds that showed the highest cytotoxicity were similarly active against both cell lines., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Naphtoquinones have been used as promising scaffolds for drug design studies against protozoan parasites. Considering the highly toxic and limited therapeutic arsenal, the global negligence with tropical diseases and the elevated prevalence of co-morbidities especially in developing countries, the parasitic diseases caused by various Leishmania species (leishmaniasis) became a significant public health threat in 98 countries. The aim of this work was the evaluation of antileishmanial in vitro potential of thirty-six 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones obtained by a three component reaction of lawsone, the appropriate aldehyde and thiols adequately substituted, exploiting the in situ generation of o-quinonemethides (o-QM) via the Knoevenagel condensation. The antileishmanial activity of the naphthoquinone derivatives was evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum and their cytotoxicity was verified in mammalian cells. Among the thirty-six compounds, twenty-seven were effective against promastigotes, with IC50 values ranging from 8 to 189 µM; fourteen compounds eliminated the intracellular amastigotes, with IC50 values ranging from 12 to 65 µM. The compounds containing the phenyl groups at R1 and R2 and with the fluorine substituent at the phenyl ring at R2, rendered the most promising activity, demonstrating a selectivity index higher than 15 against amastigotes. A QSAR (quantitative structure activity relationship) analysis yielded insights into general structural requirements for activity of most compounds in the series. Considering the in vitro antileishmanial potential of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones and their structure-activity relationships, novel lead candidates could be exploited in future drug design studies for leishmaniasis.

A series of 36 new phenylsulfanylmethyl[1,4]naphthoquinones (7-42) were synthesized by a three-component reaction that involves lawsone, the appropriate aldehyde and thiols with variable substitution patterns. These reactions involve the in situ generation of o-quinone methides (o-QM) via Knoevenagel condensation and 1,4-nucleophilic addition under conventional heating or microwave irradiation. The new naphthoquinones obtained by this methodology were shown to have moderate to good in vitro antimalarial activity against Plasmodium falciparum (3D7)., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: Hantavirus is a genus of ribonucleic acid (RNA) viruses included in the family Bunyaviridae. Hantaviruses are rodent-borne zoonoses that, in the last 18 years, became an emergent public health problem in the Americas, causing a severe cardiopulmonary syndrome. This disease has no specific treatment and has a high case fatality. The transmission of hantavirus to man occurs by inhaling aerosols of rodent excreta. The aim of this study was to determine the prevalence of antibodies to hantavirus in the population of the rural settlement of Tupã in the county of Marcelândia, state of Mato Grosso, Brazil., Methods: The participants of the serologic survey were visited at their homes and selected randomly among the settlement population. Blood samples of the participants were collected by venopuncture. The serum samples were tested by an IgG-ELISA using an N recombinant protein of Araraquara hantavirus as antigen, using the protocol previously established by Figueiredo et al., Results: IgG antibodies to hantavirus were detected in 7 (13%) of the 54 participants. The positivity was higher among men. It was observed that there was an association of seropositivity to hantavirus within the participants born in the south of Brazil., Conclusions: The results suggest that, in this rural area, everyone is exposed to the same risk of becoming infected with hantavirus, and, therefore, there is a need to intensify surveillance activities and education of the local people to prevent this viral infection.

Melanoma biopsies from 22 Brazilian patients were evaluated for estrogen (ER), progesterone (PR) and glucocorticoid receptors (GR) by the dextran-coated charcoal method. Fifty percent (11/22) of the tumors exhibited specific estrogen and progesterone binding activities ranging from 5 to 25 fmol/mg protein for ER and from 18 to 200.75 fmol/mg protein for PR; 20/22 (90%) of the biopsies displayed significant quantities of GR, which ranged from 10.0 to 362.5 fmol/mg protein. The incidence and concentration of positive receptors in melanoma samples from Brazilian patients are similar to those of countries with populations of Caucasian origin.

Thirty patients with unresectable disseminated melanoma (Stage IV) were treated with Bacillus Calmette-Guerin (BCG) (Moreau strain--Rio de Janeiro) by mouth, with weekly doses ranging between 200 mg and 28,000 mg. Five patients died in the first two months of treatment. Of the remaining 25 patients, two (8%) showed complete regression, and one (4%) partial regression. Seven patients (28%) had stabilization of the disease for a six-month period, and 15 (60%) had progression of the disease. Complete and partial regressions were seen only in patients with extravisceral (subcutaneous) metastases, and were associated with a longer survival time. Regression of the subcutaneous metastatic nodules was always accompanied by the following local phenomena: increased temperature; local inflammation; softening, pain and pruritus at the nodule site; and a gradual decrease in size. At the site of the tumor mass, a hypochromic halo appeared. This halo remained permanently and was pathognomonic of the metastatic nodule rejection. When the halo was fully established, the inflammatory infiltrate was minimal and the malignant cells disappeared. If the area contained hairs, they underwent complete albinization. Serial biopsies of the nodules undergoing inflammatory changes and decreased consistency exhibited an intense cellular infiltration of lymphocytes, macrophages, and plasma cells around the malignant cells. This sometimes simulated lymphoid follicle formation involving the melanoma cells associated with necrosis in a centripetal way. Some patients with visceral metastases (particularly pulmonary) had an unexpectedly long survival, apparently associated with interruption of the growth rate of the masses. Eleven out of 20 deaths were due to cerebral metastases. When cerebral disease was diagnosed, BCG was discontinued and the administration of corticoids was usually associated with a disappearance of the inflammatory signs at the nodule sites, but with progression of the disease. Toxicity was minimal.