ROR1 expression in mature B lymphoid neoplasms by flow cytometry.

Immunophenotyping by flow cytometry is an integral part of the diagnosis and classification of leukemias/lymphomas. The expression of ROR1 associated with chronic B lymphocytic leukemia (CLL) is well described in the literature, both in its diagnosis and in the follow-up of minimal residual disease (MRD) research, however, there are few studies regarding the expression pattern of ROR1 in other subtypes of mature B lymphoid neoplasms. With the aim of evaluating the expression of ROR1 and associating it with the expression of other important markers for the differentiation of mature B lymphoid neoplasms (MBLN), 767 samples of cases that entered our laboratory for immunophenotyping with clinical suspicion of MBLN were studied. ROR1 expression is predominant in CD5+/CD10- neoplasms. Overall, positive ROR1 expression was observed in 461 (60.1%) cases. The CD5+/CD10- group had a significantly higher proportion of ROR1 positive samples (89.9%) and more brightly expressed ROR1 than the other groups. Our results highlight the importance of evaluating ROR1 expression in the diagnosis of MBLN to contribute to the differential diagnosis, and possibly therapy of mainly CLL, and indicate that this marker could be considered as a useful addition to immunophenotypic panels, particularly for more challenging cases.

Immunostimulatory nanoparticles delivering cytokines as a novel cancer nanoadjuvant to empower glioblastoma immunotherapy.

Glioblastoma (GBM) stands as a highly aggressive and deadly malignant primary brain tumor with a median survival time of under 15 months upon disease diagnosis. While immunotherapies have shown promising results in solid cancers, brain cancers are still unresponsive to immunotherapy due to immunological dysfunction and the presence of a blood-brain barrier. Interleukin-12 (IL-12) emerges as a potent cytokine in fostering anti-tumor immunity by triggering interferon-gamma production in T and natural killer cells and changing macrophages to a tumoricidal phenotype. However, systemic administration of IL-12 toxicity in clinical trials often leads to significant toxicity, posing a critical hurdle. To overcome this major drawback, we have formulated a novel nanoadjuvant composed of immunostimulatory nanoparticles (ISN) loaded with IL-12 to decrease IL-12 toxicity and enhance the immune response by macrophages and GBM cancer cells. Our in vitro results reveal that ISN substantially increase the production of pro-inflammatory cytokines in GBM cancer cells (e.g. 2.6 × increase in IL-8 expression compared to free IL-12) and macrophages (e.g. 2 × increase in TNF-α expression and 6 × increase in IL-6 expression compared to the free IL-12). These findings suggest a potential modulation of the tumor microenvironment. Additionally, our study demonstrates the effective intracellular delivery of IL-12 by ISN, triggering alterations in the levels of pro-inflammatory cytokines at both transcriptional and protein expression levels. These results highlight the promise of the nanoadjuvant as a prospective platform for resharing the GBM microenvironment and empowering immunotherapy.

Detection of arboviruses in Aedes aegypti through transovarian analysis: A study in Goiânia, Goiás

Abstract Background: Arboviral diseases are a group of infectious diseases caused by viruses transmitted by arthropods, mainly mosquitoes. These diseases, such as those caused by the dengue (DENV), Zika (ZIKV), chikungunya (CHIKV), and yellow fever (YFV) viruses, have a significant impact worldwide. In this context, entomological surveillance plays a crucial role in the control and prevention of arboviruses by providing essential information on the presence, distribution, and activity of vector mosquitoes. Based on entomological surveillance, transovarian transmission provides information regarding the maintenance and dissemination of arboviruses. The objective of this study was to detect these arboviruses in Goiânia, Goiás, and analyze the occurrence of transovarian transmission. Methods: Aedes aegypti eggs were collected from different regions of Goiânia and cultivated under controlled laboratory conditions until the emergence of adult mosquitoes. Adult females were grouped into pools containing their heads and thoraxes. These pools were subsequently evaluated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay. Results: A total of 157 pools (N=1570) were analyzed, with two pools testing positive for CHIKV and one pool testing positive for ZIKV, indicating that the offspring resulting from transovarian transmission are potentially infectious. Conclusions: In summary, the demonstration of the vertical transmission mechanisms of CHIKV and ZIKV in A. aegypti serves as an alert to health authorities, as these diseases are still underreported, and their primary urban vector has likely acquired this capacity, contributing to the dissemination of these infections.

Brain-Targeted Drug Delivery.

At present, brain diseases affect one in six people worldwide, and they include a wide range of neurological diseases from Alzheimer's and Parkinson's diseases to epilepsy, brain injuries, brain cancer, neuroinfections and strokes [...].

Polymeric nanoparticles targeting Sialyl-Tn in gastric cancer: A live tracking under flow conditions.

Drug delivery using nanoparticles (NPs) represents a potential approach for therapy in cancer, such gastric cancer (GC) due to their targeting ability and controlled release properties. The use of advanced nanosystems that deliver anti-cancer drugs specifically to tumor cells may strongly rely on the expression of cancer-associated targets. Glycans aberrantly expressed by cancer cells are attractive targets for such delivery strategy. Sialylated glycans, such as Sialyl-Tn (STn) are aberrantly expressed in several epithelial tumors, including GC, being a potential target for a delivery nanosystem. The aim of this study was the development of NPs surface-functionalized with a specific antibody targeting the STn glycan and further evaluate this nanosystem effectiveness regarding its specificity and recognition capacity. Our results showed that the NPs surface-functionalized with anti-STn antibody efficiently are recognized by cells displaying the cancer-associated STn antigen under static and live cell monitoring flow conditions. This uncovers the potential use of such NPs for drug delivery in cancer. However, flow exposure was disclosed as an important biomechanical parameter to be taken into consideration. Here we presented an innovative and successful methodology to live track the NPs targeting STn antigen under shear stress, simulating the physiological flow. We demonstrate that unspecific binding of NPs agglomerates did not occur under flow conditions, in contrast with static assays. This robust approach can be applied for in vitro drug studies, giving valuable insights for in vivo studies.

Conhecimento da equipe multiprofissional sobre segurança do paciente em Unidade de Terapia Intensiva / Knowledge of the multidisciplinary team on patient safety in an Intensive Care Unit

Analisar os fatores que interferem na segurança do paciente em Unidades de Terapia Intensiva (UTI) mediante o conhecimento da equipe multiprofissional. Tratou-se de um estudo descritivo com abordagem quantiqualitativa realizado com 40 profissionais de saúde, que compõe a equipe multiprofissional da UTI de um hospital estadual, referência regional. A coleta de dados foi realizada entre os meses de maio a dezembro de 2020. Deu-se por meio de entrevista semiestruturada, direcionada por um roteiro temático e questionário sociodemográfico. Os dados foram processados no software IRAMUTEQ, através da Classificação Hierárquica Descendente e analisados por meio da técnica do discurso do sujeito coletivo. Foi evidenciado que a fragilidade no conhecimento sobre o conceito de segurança do paciente, a falta de protocolos assistências, os problemas interpessoais, a ocorrência de eventos adversos, a subnotificação e dimensionamento inadequado são alguns dos fatores que interferem na segurança do paciente na UTI. Nota-se a necessidade de resolução das falhas existentes, sobretudo ao que refere ao dimensionamento de pessoal, as questões relacionadas à interação da equipe multiprofissional e a implementação de protocolos institucionais, que são norteadores do cuidado. Com o fortalecimento da cultura de segurança, onde os profissionais sintam-se empoderados a realizar a notificação, não apenas dos EA, como também das circunstâncias notificáveis.

The aim of this study was to analyze the factors that interfere with patient safety in Intensive Care Units (ICU) through the knowledge of the multidisciplinary team. This was a descriptive study with a quantitative and qualitative approach, carried out with 40 health professionals, who make up the multidisciplinary team of the ICU of a regional reference hospital of the state. Data collection was carried out between the months of May and December 2020. It took place through a semi-structured interview, guided by a thematic script and a sociodemographic questionnaire. Data were processed using IRAMUTEQ software, through Descending Hierarchical Classification, and were analyzed using the collective subject discourse technique. It was demonstrated that the lack of knowledge about the concept of patient safety, the lack of care protocols, interpersonal problems, the occurrence of adverse events, underreporting, and inadequate estimations are some of the factors that interfere with patient safety in the ICU. There is a need to resolve existing flaws, especially regarding personnel size, issues related to the interaction of the multidisciplinary team, and the implementation of institutional protocols, which guide care. By strengthening the safety culture, professionals feel empowered to report not only AEs, but also reportable circumstances.

Procedimentos para vinculação de dados da saúde: aplicações na vigilância em saúde / Procedimientos para la vinculación de datos sanitarios: aplicaciones en la vigilancia en la salud / Procedures for health data linkage: applications in health surveillance

Objetivo: Apresentar metodologia padronizada para vinculação de diferentes bancos de dados em saúde pública. Métodos: Artigo de revisão metodológica, com descrição específica de processos de tratamento de dados para vinculação (linkage) determinística entre bancos de dados estruturados. Instruiu-se como tratar os dados, selecionar chaves de vinculação e vincular os bancos, utilizando-se dois bancos de dados simulados no software R. Resultados: Foram apresentados os comandos utilizados para a vinculação determinística, do tipo inner_join. O processo de vinculação resultou em um banco de dados com 40.108 pares ao se utilizar apenas a chave "Nome". Com a adição da segunda chave, "Nome da mãe", o resultado caiu para 112 pares. Ao adicionar a terceira chave, "Data de nascimento", apenas dois pares foram identificados. Conclusão: A vinculação de bancos de dados e suas análises são ferramentas válidas e úteis para os serviços de saúde, no apoio a ações de vigilância em saúde.

Objetivo: Presentar metodología estandarizada para vincular diferentes bases de datos de salud pública. Métodos: Artículo de revisión metodológica y descripción de los procesos de tratamiento de datos para la vinculación determinista entre bases de datos. Se dieron instrucciones sobre como manejar los datos, seleccionar claves de vinculación y vincular las bases de datos empleando dos bases de datos simuladas en el software R. Resultados: Se presentaron los comandos utilizados para la vinculación determinista, del tipo inner-join. El proceso resultó en una base de datos con 40.108 pares utilizando únicamente la clave "Nombre". Con la adición de la segunda clave, "Nombre de la madre", el resultado se redujo a 112 pares. Al agregar la tercera clave, "Fecha de nacimiento", solo se identificaron dos pares. Conclusión: La vinculación de bases de datos y sus análisis son herramientas válidas y útiles para que los servicios de salud las utilicen para apoyar las acciones de vigilancia en la salud.

Objective: To present a standardized methodology for linking different public health databases. Methods: This was a methodological review article specifically describing data processing procedures for deterministic linkage between structured databases. It instructs on how to: treat data, select linkage keys, and link databases using two databases simulated in R software. Results: The commands used for the deterministic linkage of the inner_join type were presented. The linkage process resulted in a database with 40,108 pairs using only the "Name" key. Adding the second key, "Name of mother", the resulted dropped to 112 pairs. By adding the third key, "Date of birth", only two pairs were identified. Conclusion: Database linkage and its analysis are valid and valuable tools for health services in supporting health surveillance actions.

Intratumoral VEGF nanotrapper reduces gliobastoma vascularization and tumor cell mass.

Glioblastoma multiforme (GBM) is the most aggressive and invasive malignant brain cancer. GBM is characterized by a dramatic metabolic imbalance leading to increased secretion of the pro-angiogenic factor VEGF and subsequent abnormal tumor vascularization. In 2009, FDA approved the intravenous administration of bevacizumab, an anti-VEGF monoclonal antibody, as a therapeutic agent for patients with GBM. However, the number of systemic side effects and reduced accessibility of bevacizumab to the central nervous system and consequently to the GBM tumor mass limited its effectiveness in improving patient survival. In this study, we combined experimental and computational modelling to quantitatively characterize the dynamics of VEGF secretion and turnover in GBM and in normal brain cells and simultaneous monitoring of vessel growth. We showed that sequestration of VEGF inside GBM cells, can be used as a novel target for improved bevacizumab-based therapy. We have engineered the VEGF nanotrapper, a cargo system that allows cellular uptake of bevacizumab and inhibits VEGF secretion required for angiogenesis activation and development. Here, we show the therapeutic efficacy of this nanocargo in reducing vascularization and tumor cell mass of GBM in vitro and in vivo cancer models.

Host-specific gene expression as a tool for introduction success in Naupactus parthenogenetic weevils.

Food resource access can mediate establishment success in invasive species, and generalist herbivorous insects are thought to rely on mechanisms of transcriptional plasticity to respond to dietary variation. While asexually reproducing invasives typically have low genetic variation, the twofold reproductive capacity of asexual organisms is a marked advantage for colonization. We studied host-related transcriptional acclimation in parthenogenetic, invasive, and polyphagous weevils: Naupactus cervinus and N. leucoloma. We analyzed patterns of gene expression in three gene categories that can mediate weevil-host plant interactions through identification of suitable host plants, short-term acclimation to host plant defenses, and long-term adaptation to host plant defenses and their pathogens. This approach employed comparative transcriptomic methods to investigate differentially expressed host detection, detoxification, immune defense genes, and pathway-level gene set enrichment. Our results show that weevil gene expression responses can be host plant-specific, and that elements of that response can be maintained in the offspring. Some host plant groups, such as legumes, appear to be more taxing as they elicit a complex gene expression response which is both strong in intensity and specific in identity. However, the weevil response to taxing host plants shares many differentially expressed genes with other stressful situations, such as host plant cultivation conditions and transition to novel host, suggesting that there is an evolutionarily favorable shared gene expression regime for responding to different types of stressful situations. Modulating gene expression in the absence of other avenues for phenotypic adaptation may be an important mechanism of successful colonization for these introduced insects.

How I investigate minimal residual disease in acute lymphoblastic leukemia.

Minimal Residual Disease (MRD) is the most important independent prognostic factor in acute lymphoblastic leukemia (ALL) and refers to the deep level of measurable disease in cases with complete remission by conventional pathologic analysis, especially by cytomorphology. MRD can be detected by multiparametric flow cytometry, molecular approaches such as quantitative polymerase chain reaction for immunoglobulin and T-cell receptor (IG/TR) gene rearrangements or fusion genes transcript, and high-throughput sequencing for IG/TR. Despite the proven clinical usefulness in detecting MRD, these methods have differences in sensitivity, specificity, applicability, turnaround time and cost. Knowing and understanding these differences, as well as the principles and limitations of each technology, is essential to laboratory standardization and correct interpretation of MRD results in line with treatment time points, therapeutic settings, and clinical trials. Here, we review the methodological approaches to measure MRD in ALL and discuss the advantages and limitations of the most commonly used techniques.

Effective intracellular delivery of bevacizumab via PEGylated polymeric nanoparticles targeting the CD44v6 receptor in colon cancer cells.

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world, mainly due to its metastatic and metabolic ability. The CD44 receptor isoform containing exon 6 (CD44v6) is a transmembrane protein that plays an important role in the establishment of tumors and metastasis, which make this molecule a potential target for therapy and diagnosis of tumors. Aiming at a targeted therapy, the anti-VEGF monoclonal antibody (mAb) bevacizumab was loaded into poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) functionalized with an antibody fragment (Fab) specific for CD44v6-expressing human cancer cells. The sizes of NPs were in the range of 150-250 nm and they had a negative charge between -5 and -10 mV, with an association efficiency (AE) of bevacizumab of 86%. v6 Fab-PLGA-PEG NPs containing bevacizumab specifically bonded to the CD44v6 cell surface receptor and exhibited higher internalization into CD44v6+ epithelial cells than bare and (-) Fab-PLGA-PEG NPs. To understand the biological effect of NP targeting, the intracellular levels of bevacizumab and VEGF were evaluated after the incubation of targeted and untargeted NPs. The intracellular levels of bevacizumab were significantly higher in cells incubated with v6 Fab-PLGA-PEG NPs and these NPs resulted in a significant decrease in the intracellular VEGF compared to untargeted NPs and free bevacizumab. PLGA-PEG NPs, surface-functionalized with a v6-specific Fab, have the potential to intracellularly deliver bevacizumab into CD44v6 expressing cancer cells.

Performance of eight-color dry antibody reagent in the detection of minimal residual disease in chronic lymphocytic leukemia samples.

BACKGROUND: Minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) has prognostic and predictive significance. One of the approaches to detect MRD by flow cytometry (FC) is the use of dry antibody reagents such as DuraClone® RE CLB (Beckman Coulter-BC). The aim of this study was to evaluate the performance of the DuraClone® RE CLB in detecting MRD in CLL compared to liquid reagents. METHODS: DuraClone® RE CLB is composed by CD81FITC, ROR1PE, CD79bPC5.5, CD19PC7, CD5APC, CD43APCA750, CD20PB, and CD45KrO. For the liquid reagent assay, we used CD43FITC, ROR1PE, CD3ECD, CD5PC5.5, CD20PC7, CD79bAPC, CD19APC750, CD81 APCH7, and CD45KrO. The liquid and dry tubes were used to detect 20 MRD-positive CLL samples. The samples were analyzed using Radar Plots Kaluza Software (BC). RESULTS: The statistical correlation between the liquid and dry reagents was acceptable (R2 = .9583) and no discrepancy was observed in MRD percentages. The average of the total number of acquired events in DuraClone® RE CLB was 758.583 (362.632-2.290.387), which allowed accurate sensitivity for the FC assay. The lowest MRD frequency detected by DuraClone® RE CLB was 0.01%, corresponding to a cluster with 106 events in a total of 737.030. The radar plots allowed the discrimination between normal B-cell population and CLL cells. CONCLUSION: The DuraClone® RE CLB method allowed the accurate detection of MRD in clinical and interlaboratorial CLL samples, thereby supporting the use of this method to potentially increase productivity, reduce pipetting-associated errors and cost, and allow better standardization.

The solid progress of nanomedicine.

This commentary article conveys the views of the board of the Nanomedicine and Nanoscale Delivery Focus Group of the Controlled Release Society regarding the decision of the United States National Cancer Institute (NCI) in halting funding for the Centers of Cancer Nanotechnology Excellence (CCNEs), and the subsequent editorial articles that broadened this discussion. Graphical abstract.

Myelodysplastic syndrome: validation of flow cytometry multilineage score system.

OBJECTIVE: To validate multilineage score system correlating results of flow cytometry, cytogenetics, cytomorphology and histology from samples of patients with suspected myelodysplastic syndrome or cytopenia of unknown origin. METHODS: A retrospective study analyzing laboratory data of 49 patients with suspected myelodysplastic syndrome or cytopenia of unknown origin, carried out between May and September 2017. The inclusion criteria were availability of flow cytometry results, and at least one more method, such as morphology, histology or cytogenetics. Thirty-eight patients were classified as diagnosis of myelodysplastic syndromes, whereas 11 were classified as normal. Patients were evaluated based on score systems, Ogata score and flow cytometry multilineage score. RESULTS: Comparing the scores obtained in the Ogata score and the multilineage score, it was observed that in four cases the Ogata score was zero or 1 point, while the multilineage score was higher than 3 points. In addition, in 12 cases with Ogata score of 2, the multilineage score was greater than 3. CONCLUSION: The flow cytometry multilineage score system demonstrated to be more effective in dysplasia analysis, by assessing the erythroid, monocytic, granulocytic and precursor cell lineages, apart from the parameters evaluated by the Ogata score.

Myelodysplastic syndrome: validation of flow cytometry multilineage score system / Síndrome mielodisplásica: validação de ficha de escore multilinhagem por citometria de fluxo

ABSTRACT Objective To validate multilineage score system correlating results of flow cytometry, cytogenetics, cytomorphology and histology from samples of patients with suspected myelodysplastic syndrome or cytopenia of unknown origin. Methods A retrospective study analyzing laboratory data of 49 patients with suspected myelodysplastic syndrome or cytopenia of unknown origin, carried out between May and September 2017. The inclusion criteria were availability of flow cytometry results, and at least one more method, such as morphology, histology or cytogenetics. Thirty-eight patients were classified as diagnosis of myelodysplastic syndromes, whereas 11 were classified as normal. Patients were evaluated based on score systems, Ogata score and flow cytometry multilineage score. Results Comparing the scores obtained in the Ogata score and the multilineage score, it was observed that in four cases the Ogata score was zero or 1 point, while the multilineage score was higher than 3 points. In addition, in 12 cases with Ogata score of 2, the multilineage score was greater than 3. Conclusion The flow cytometry multilineage score system demonstrated to be more effective in dysplasia analysis, by assessing the erythroid, monocytic, granulocytic and precursor cell lineages, apart from the parameters evaluated by the Ogata score.

RESUMO Objetivo Validar ficha de escore multilinhagem correlacionando resultados obtidos de citometria de fluxo, citogenética, citomorfologia e histologia de amostras de pacientes com suspeita de síndrome mielodisplásica ou citopenias a esclarecer. Métodos Estudo retrospectivo de análise de dados laboratoriais de 49 pacientes com suspeita clínica de síndrome mielodisplásica ou citopenias a esclarecer realizado entre maio e setembro de 2017. Os critérios de inclusão foram a disponibilidade de resultados de citometria de fluxo e de, pelo menos, outra metodologia, entre morfologia, histologia, ou citogenética. Trinta e oito pacientes foram classificados como diagnosticados com síndromes mielodisplásicas enquanto 11 foram classificados como normais. Os pacientes foram avaliados utilizando sistemas de escore, escore de Ogata e ficha multilinhagem. Resultados Comparando as pontuações obtidas no escore de Ogata e na ficha multilinhagem, observou-se que, em quatro casos, o score de Ogata foi zero ou 1 ponto, enquanto, pela ficha multilinhagem, a pontuação foi superior a 3 pontos. Além disso, em 12 casos com escore de Ogata 2, a pontuação pela ficha multilinhagem foi superior a 3. Conclusão A ficha multilinhagem demonstrou ser mais eficaz na análise de displasia por avaliar as linhagens eritroide, monocítica, granulocítica e células precursoras, além dos parâmetros avaliados no escore de Ogata.

Covid-19: Por que a proteção de trabalhadores e trabalhadoras da saúde é prioritária no combate à pandemia? / COVID-19: why the protection of health workers is a priority in the fight against the pandemic? / COVID-19: ¿por qué la protección de los trabajadores de la salud es prioridad en la lucha contra la pandemia?

Resumo A pandemia causada pelo novo coronavírus (SARS-CoV-2) configura quadro de emergência de saúde pública mundial. Algumas categorias ocupacionais têm risco elevado de exposição à infecção, como os(as) trabalhadores(as) da saúde. Neste artigo, objetiva-se sumarizar e sistematizar aspectos relativos às condições de trabalho e de saúde dos(as) trabalhadores(as) da saúde nessa pandemia, enfatizando a situação no Brasil, experiências exitosas na proteção do trabalho em saúde em outros países e recomendações para o contexto brasileiro. Iniciativas imediatas de proteção e combate à pandemia em outros países incluíram como pontos estratégicos: adequação das condições de trabalho; testagem sistemática e ações específicas de assistência aos(às) trabalhadores(as). Para o enfrentamento da Covid-19 no Brasil, destacam-se como recomendações: revisão de fluxos de atendimento e definição de características e condições para cada etapa de atendimento; estabelecimento da Covid-19 como doença relacionada ao trabalho para os grupos expostos; registro efetivo da 'ocupação' nos sistemas de informação; estabelecimento de condições especiais para execução do trabalho na situação de epidemia; atenção às jornadas laborais e ações para redução de estressores ocupacionais. A atuação desses(as) trabalhadores(as) é elemento central no enfrentamento da pandemia, portanto, o plano de combate ao Covid-19 deve incluir proteção e preservação de sua saúde física e mental.

Abstract The pandemic caused by the new coronavirus (SARS-CoV-2) is a worldwide public health emergency. Some occupational categories, such as health workers, are at high risk of exposure to the infection. This article aims to summarize and systematize aspects related to the health and working conditions of health workers in this pandemic, especially in Brazil, successful experiences in the protection of healthcare work in other countries and recommendations for the Brazilian context. Immediate initiatives to protect and combat the pandemic in other countries included as strategic points: adequacy of working conditions; systematic testing and specific assistance actions for healthcare workers. In order to face COVID-19 in Brazil, the following recommendations stand out: review of service flows and definition of characteristics and conditions for each stage of service; establishment of COVID-19 as a work-related disease for exposed groups; effective registration of 'occupation' in information systems; establishment of special conditions for carrying out work in the event of an epidemic; attention to working hours and actions to reduce occupational stressors. The performance of these workers is a central element in facing the pandemic, therefore, the plan to combat COVID-19 must include protection and preservation of their physical and mental health.

Resumen La pandemia causada por el nuevo coronavirus (SARS-CoV-2) constituye una emergencia mundial de la salud pública. Algunas categorías profesionales corren un alto riesgo de exposición a la infección, como lo son los trabajadores de la salud. Este artículo tiene como objetivo resumir y sistematizar aspectos relacionados a las condiciones laborales y de salud de los trabajadores de salud en esta pandemia, enfatizando la situación en Brasil, experiencias que dieron resultado para la protección del trabajo de salud en otros países y recomendaciones para el contexto brasileño. Iniciativas inmediatas de protección y combate de la pandemia en otros países incluyen como puntos estratégicos: adecuación de las condiciones de trabajo; pruebas sistemáticas y acciones puntuales de asistencia para los trabajadores. Para enfrentar el COVID-19 en Brasil, se destacan las siguientes recomendaciones: revisión de los flujos de atendimiento y definición de características y condiciones para cada etapa del atendimiento; establecimiento de COVID-19 como enfermedad relacionada al trabajo para grupos expuestos; registro efectivo de "ocupación" en los sistemas de información; establecimiento de condiciones especiales para realizar trabajos en caso de epidemia; control de las horas de trabajo y acciones para reducir los motivadores de estrés laboral. El desempeño de estos trabajadores es un elemento central para enfrentar la pandemia, por lo tanto, el plan para combatir COVID-19 debe incluir protección y preservación de su salud física y mental.

Inalação/perfusão pulmonar por SPECT-CT e ANGIO-TC de tórax no diagnóstico do tromboembolismo pulmonar em centro oncológico / Pulmonary inhalation/perfusion by SPECT-CT and ANGIO-TC of thorax in the diagnosis of pulmonary thromboembolism in oncologic center

Introdução: O Tromboembolismo Pulmonar (TEP) é uma entidade clínica e patológica caracterizada pela obstrução de coágulos sanguíneos na circulação pulmonar. Estes coágulos geralmente são oriundos da circulação venosa sistêmica estando intrinsecamente ligada à trombose venosa profunda (TVP), com redução ou escassez do fluxo sanguíneo para a área afetada, podendo levar o paciente rapidamente a morte. O TEP é evento muito comum em pacientes hospitalizados e com câncer. Hoje seu diagnóstico é definido pelas técnicas de ANGIO-TC de tórax (padrão ouro) e I/P por SPECT-CT. A técnica de I/P por SPECT-CT vem demonstrando alta acurácia para o diagnóstico de TEP, e por ser uma técnica de baixa dose de radiação e com definição tomográfica é de grande valia considera-la para o diagnóstico de TEP em pacientes oncológicos que frequentemente estão sendo submetidos a procedimentos de radiação e quimioterápicos. Objetivos: O objetivo do presente estudo é analisar o desempenho diagnóstico e a concordância entre os exames realizados pelas técnicas de Inalação/Perfusão Pulmonar por SPECT-CT e da ANGIO-TC de Tórax no diagnóstico do TEP em um Centro Oncológico. Avaliar o perfil dos pacientes e o Impacto na conduta médica. Métodos: Estudo de coorte descritivo, retrospectivo, quantitativo, qualitativo e unicêntrico; realizado através da análise de exames de Tomografia Computadorizada de Tórax-Protocolo para Pesquisa de TEP com contraste venoso iodado, realizados no Setor da Tomografia. E da análise dos exames de I/P por SPECT-CT com a inalação do DTPA99m e administração endovenosa do Macro-Agregado de Albumina99m ou MAA99m no Serviço de Medicina Nuclear do Departamento de Imagem do A.C.Camargo Câncer Center de Janeiro de 2015 a Maio de 2018. Resultados: Foi analisado um total de 410 exames e 363 pacientes. Duzentos e noventa e nove pacientes foram diagnosticados como negativos pra TEP e 64 pacientes como positivos pra TEP. Trezentos e trinta e cinco pacientes realizaram o exame de ANGIO-TC de tórax, 75 realizaram o exame de I/P pulmonar por SPECT-CT e 47 pacientes realizaram os dois exames. Oitenta por cento dos pacientes oncológicos apresentaram mais de uma das comorbidades além do câncer, sendo as mais prevalentes e que demonstraram associação com o diagnóstico de TEP o histórico de TEP/TVP, o Uso de anticoagulantes, Doenças pulmonares pré-existentes e HAS. Os tipos de câncer que demonstraram associação com o diagnóstico de TEP foram Câncer de pulmão, pâncreas e cérebro. Sendo mais prevalente o Câncer de pulmão nos pacientes com suspeita e diagnóstico de TEP. Os métodos de I/P pulmonar por SPECT-CT e ANGIO-TC de tórax obtiveram uma boa concordância nos resultados, e não houve impacto na conduta médica mediante o diagnóstico e tratamento nos dois Grupos analisados. Conclusão: Os métodos de I/P pulmonar por SPECT-CT e ANGIO-TC de tórax demonstraram ser ambos confiáveis e com alta acurácia para o diagnóstico do TEP em pacientes oncológicos. O SPECT-CT demonstrou ótima acurácia para o diagnóstico de TEP negativo podendo ser preferível e mais indicado para afastar TEP em pacientes oncológicos dada a sua menor radiação, porém para o diagnóstico de TEP positivo a ANGIO-TC de tórax ainda é mais indicada (AU)

Introduction: Pulmonary thromboembolism (PTE) is a clinical and pathological entity characterized by obstruction of blood clots in the pulmonary circulation. These clots usually come from the systemic venous circulation and are intrinsically linked to deep vein thrombosis (DVT), with reduced or scarce blood flow to the affected area, which can lead the patient quickly to death. PTE is a very common event in hospitalized patients with cancer. Today its diagnosis is defined by the techniques of ANGIO-TC of thorax (gold standard) and I/P by SPECT-CT. The technique of I/P by SPECT-CT has demonstrated high accuracy for the diagnosis of PTE, and because it is a technique of low radiation dose and with tomographic definition is of great value to consider it for the diagnosis of PTE in oncologic patients who are often undergoing radiation and chemotherapy procedures. Objectives: The objective of this study is to analyze the diagnostic performance and agreement between the tests performed by the inhalation/perfusion Pulmonary SPECT-CT and the ANGIO-TC Chest techniques in the diagnosis of PTE in an Oncologic Center. To evaluate the profile of patients and the impact on medical conduct. Methods: Descriptive, retrospective, quantitative, qualitative and unicentric cohort study; performed through the analysis of Thoracic Computed Tomography-Protocol for PTE Research with iodinated venous contrast, performed in the Tomography Sector. And the analysis of SPECT-CT I/P exams with inhalation of DTPA99m and intravenous administration of Macro-Agregado de Albumina99m or MAA99m at the Nuclear Medicine Service of the Imaging Department of the A.C.Camargo Cancer Center from January 2015 to May 2018. Results: A total of 410 tests and 363 patients were analyzed. Two hundred and ninety-nine patients were diagnosed as negative for TEP and 64 patients as positive for TEP. Three hundred and thirty-five patients underwent ANGIO-TC chest exam, 75 underwent SPECT-CT lung I/P exam and 47 patients underwent both exams. Eighty percent of oncologic patients presented more than one of the comorbidities besides cancer, being the most prevalent and that showed association with the diagnosis of PTE the history of PTE/TVP, the use of anticoagulants, pre-existing lung diseases and SAH. The types of cancer that demonstrated association with the diagnosis of PTE were Lung, pancreas and brain cancer. Lung cancer is more prevalent in patients with suspected and diagnosed PTE. The lung I/P methods by SPECT-CT and ANGIO-TC of thorax obtained a good agreement in the results, and there was no impact in the medical conduct through diagnosis and treatment in the two Groups analyzed. Conclusion: The methods of pulmonary I/P by SPECT-CT and ANGIO-TC of thorax demonstrated to be both reliable and with high accuracy for the diagnosis of PTE in oncologic patients. The SPECT-CT showed excellent accuracy for the diagnosis of negative PTE and may be preferable and more indicated to rule out PTE in oncologic patients due to its lower radiation, but for the diagnosis of positive PTE the chest ANGIO-TC is even more indicated (AU)

Enhanced anti-angiogenic effects of bevacizumab in glioblastoma treatment upon intranasal administration in polymeric nanoparticles.

Glioblastoma multiforme (GBM) is one of the most aggressive cancers, where the aggressiveness of tumor has been associated to its high vascularization rate. Bevacizumab (Avastin®), an anti-angiogenic monoclonal antibody, has been used to decrease the angiogenic profile. To circumvent the blood-brain barrier (BBB) and decrease off-target organ toxicity, bevacizumab-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) were developed and intranasally administrated in CD-1 mice to study their pharmacokinetic and pharmacodynamic profile. After 7 days of administration, PLGA NP showed a higher brain bioavailability of bevacizumab when compared to intranasally administrated free bevacizumab. On the other hand, bevacizumab-loaded PLGA NP were able to increase the penetration (higher Cmáx) and the residence time of bevacizumab into the brain (higher Clast). Furthermore, PLGA NP formulation totally prevented bevacizumab systemic exposure. The efficacy of this nanosystem was next evaluated in a validated orthotopic GBM nude mice model, studying the tumor growth over time by bioluminescence and the anti-angiogenic effects. After 14 days, bevacizumab-loaded PLGA NP demonstrated a reduction in the tumor growth accompanied by a higher anti-angiogenic effect compared to the free bevacizumab. These results can be explained by the fact that bevacizumab was found in the brain just for bevacizumab-loaded PLGA NP group, after 14 days of formulation administration. Therefore, we believe that our strategy would be an efficient alternative to improve GBM treatment with high impact for patient life quality and survival.