As cidades e o aquecimento global: desafios para o planejamento urbano, as engenharias e as ciências sociais e básicas

This article aims to present a transdisciplinary approach to the relationship between climate change and cities. Part of the recognition that the current form of urbanization in large metropolitan regions is a strong agent that promotes global warming, at the same time that it is the locus of the harmful manifestation of the effects of these changes. The change in rainfall patterns, with greater frequency and intensity, in the distribution of rainfall and the phenomenon of heat islands, particularly affects the most precarious settlement areas, where high social vulnerability exposes gigantic contingents of people to constant flood risks, landslides, lack of drinking water and basic sanitation, and diseases caused by excessive heat. The search for environmental sustainability involves this social dimension, requiring from sciences and techniques a transdisciplinary effort for integrated actions that can face the ethical challenge of social inequality among those affected by the harmful effects of climate change.Este artigo tem como objetivo apresentar uma abordagem transdisciplinar para a relação entre as mudanças climáticas e as cidades. Parte do reconhecimento de que a atual forma da urbanização das grandes regiões metropolitanas é forte agente promotor do aquecimento global, ao mesmo tempo que constitui lócus da manifestação nociva dos efeitos dessas mudanças. A alteração dos regimes de chuva, com maior frequência e intensidade, da distribuição das precipitações e do fenômeno das ilhas de calor afetam em especial as áreas de assentamentos mais precários, onde a elevada vulnerabilidade social expõe gigantescos contingentes de pessoas a riscos constantes de inundação, deslizamentos, falta de água potável e saneamento básico, e doenças geradas pelo calor excessivo. A busca por sustentabilidade ambiental envolve essa dimensão social, exigindo das ciências e das técnicas um esforço transdisciplinar para ações integradas que possa fazer frente ao desafio ético da desigualdade social entre os afetados pelos efeitos nocivos das mudanças climáticas

Molecular complexity of diffuse large B-cell lymphoma: Can it be a roadmap for precision medicine?

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma; it features extreme molecular heterogeneity regardless of the classical cell-of-origin (COO) classification. Despite this, the standard therapeutic approach is still immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone—R-CHOP), which allows a 60% overall survival (OS) rate, but up to 40% of patients experience relapse or refractory (R/R) disease. With the purpose of searching for new clinical parameters and biomarkers helping to make a better DLBCL patient characterization and stratification, in the last years a series of large discovery genomic and transcriptomic studies has been conducted, generating a wealth of information that needs to be put in order. We reviewed these researches, trying ultimately to understand if there are bases offering a roadmap toward personalized and precision medicine also for DLBCL

Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain

Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care ), and Group B (n=47 -- treated with systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks) in Group A and 55 weeks (range 7.4 -- 213 weeks) in Group B (p=0.0018). In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.O câncer de pulmão de células não pequenas em estádio IV é uma doença fatal, com uma sobrevida mediana de seis meses. Quimioterapia é a abordagem mais freqüente, apresentando um impacto na sobrevida controverso e questionável alteração na qualidade de vida. OBJETIVOS: Comparar o impacto na sobrevida global e na qualidade de vida em pacientes portadores de câncer de pulmão de células não pequenas, estádio IV, tratados com suporte clínico ou quimioterapia. PACIENTES: Entre fevereiro de 1990 e dezembro de 1995, 78 pacientes (pts) portadores de câncer de pulmão de células não pequenas estádio IV foram admitidos. Os pacientes foram divididos em dois grupos: grupo A (n=31 -- tratados com suporte clínico) e grupo B (n=47, tratados com quimioterapia). RESULTADOS: A sobrevida mediana no grupo tratado com suporte clínico foi de 23 semanas (variando de 5-153 semanas) e de 55 semanas no grupo tratado com quimioterapia (variando de 7,4 a 213 semanas), p= 0,0018 -- Qui-quadrada. Em ambos grupos, a incidência de internações hospitalares para a administração intravenosa de antibióticos e hemoderivados foi similar. Pacientes recebendo quimioterapia, foram estratificados entre àqueles que receberam mitomicina, vinblastina e cisplatina, n=25 e àqueles recebendo outros regimes (derivados de platina, associados à outras drogas, n= 22). Pacientes recebendo mitomicina, vinblastina e cisplatina, n=25 apresentaram uma incidência mais alta de neutropenia febril e tiveram atrasos mais longos entre os ciclos de quimioterapia, quando comparados aos pacientes do outro grupo. Pacientes recebendo mitomicina, vinblastina e cisplatina, n=25, também apresentaram uma pior sobrevida mediana (51 versus 66 semanas, p= 0,005 -- Qui-quadrado). CONCLUSÕES: Em pacientes com câncer de pulmão de células não pequenas, estádio IV, não metastático para os pulmões, o uso de quimioterapia aumenta a sobrevida de maneira estatisticamente significativa, quando comparado aos cuidados de suporte

Epitranscriptomics in normal and malignant hematopoiesis

Epitranscriptomics analyze the biochemical modifications borne by RNA and their downstream influence. From this point of view, epitranscriptomics represent a new layer for the control of genetic information and can affect a variety of molecular processes including the cell cycle and the differentiation. In physiological conditions, hematopoiesis is a tightly regulated process that produces differentiated blood cells starting from hematopoietic stem cells. Alteration of this process can occur at different levels in the pathway that leads from the genetic information to the phenotypic manifestation producing malignant hematopoiesis. This review focuses on the role of epitranscriptomic events that are known to be implicated in normal and malignant hematopoiesis, opening a new pathophysiological and therapeutic scenario. Moreover, an evolutionary vision of this mechanism will be provided

Can the new and old drugs exert an immunomodulatory effect in acute myeloid leukemia?

Acute myeloid leukemia (AML) is considered an immune-suppressive neoplasm capable of evading immune surveillance through cellular and environmental players. Increasing knowledge of the immune system (IS) status at diagnosis seems to suggest ever more attention of the crosstalk between the leukemic clone and its immunologic counterpart. During the last years, the advent of novel immunotherapeutic strategies has revealed the importance of immune dysregulation and suppression for leukemia fitness. Considering all these premises, we reviewed the “off-target” effects on the IS of different drugs used in the treatment of AML, focusing on the main advantages of this interaction. The data reported support the idea that a successful therapeutic strategy should consider tailored approaches for performing leukemia eradication by both direct blasts killing and the engagement of the IS

Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, distinct subtype of T-ALL characterized by genomic instability, a dismal prognosis and refractoriness to standard chemotherapy. Since its first description in 2009, the expanding knowledge of its intricate biology has led to the definition of a stem cell leukemia with a combined lymphoid-myeloid potential: the perfect trick. Several studies in the last decade aimed to better characterize this new disease, but it was recognized as a distinct entity only in 2016. We review current insights into the biology of ETP-ALL and discuss the pathogenesis, genomic features and their impact on the clinical course in the precision medicine era today

FLT3 mutational analysis in acute myeloid leukemia: Advantages and pitfalls with different approaches

FMS-like tyrosine kinase 3 (FLT3) is one of the most closely studied genes in blood diseases. Numerous methods have been adopted for analyses, mainly in acute myeloid leukemia (AML) diagnostic work-up. According to international recommendations, the current gold standard approach allows FLT3 canonical mutations to be investigated, providing the main information for risk assessment and treatment choice. However, the technological improvements of the last decade have permitted “black side” gene exploration, revealing numerous hidden aspects of its role in leukemogenesis. The advent of the next-generation sequencing era emphasizes lights and shadows of FLT3 conventional mutational analysis, highlighting the need for a more comprehensive study of the gene. However, more extensive analysis is opening new, unexplored questions whose impact on clinical outcomes is still unknown. The present work is focused on the main topics regarding FLT3 mutational analysis in AML, debating the strengths and weaknesses of the current gold standard approach. The rights and wrongs of NGS introduction in clinical practice will be discussed, showing that a more extensive knowledge of FLT3 mutational status could lead to reconsidering its role in AML management

Nanopore Sequencing in Blood Diseases: A Wide Range of Opportunities

The molecular pathogenesis of hematological diseases is often driven by genetic and epigenetic alterations. Next-generation sequencing has considerably increased our genomic knowledge of these disorders becoming ever more widespread in clinical practice. In 2012 Oxford Nanopore Technologies (ONT) released the MinION, the first long-read nanopore-based sequencer, overcoming the main limits of short-reads sequences generation. In the last years, several nanopore sequencing approaches have been performed in various “-omic” sciences; this review focuses on the challenge to introduce ONT devices in the hematological field, showing advantages, disadvantages and future perspectives of this technology in the precision medicine era

Terapia de reposição hormonal e o risco de câncer de mama: avaliação de atitudes em pacientes previamente tratadas por câncer de mama

INTRODUCTION: In the postmenopausal period, an average of 25% of women will present symptomatic ovarian failure requiring hormonal replacement therapy. Estrogen can relieve vasomotor symptoms. Hormonal replacement therapy is generally not recommended for breast cancer patients due to the potential risk of tumor recurrence. To answer the questions about the safety of hormonal replacement therapy in this subgroup of women, it is necessary to establish the acceptance of treatment. METHODS: Between September 1998 and February 2001, a cohort of 216 breast cancer patients were asked to complete a questionnaire. All patients had completed their treatment and were informed about survival rates after breast cancer and hormonal replacement therapy. RESULTS: Among the 216 patients, 134 (62%) would refuse hormonal replacement therapy. A hundred patients were afraid of relapse (74.6%). Adjuvant tamoxifen therapy was the only statistically significant variable (70.3% versus 29.7% p=0.003). Understanding clinical stage (p= 0.045) and type of medical assistance (private versus public , p=0.033) also seemed to influence the decision. Early stage disease (p= 0.22), type of surgical procedure (radical versus conservative, p=0.67), adjuvant chemotherapy (p=0.082) or marital status (p=0.98 ) were not statistically significant in decision making. Several patients submitted to adjuvant chemotherapy (41.6%) would accept hormonal replacement therapy under medical supervision, as did most of advanced clinical stage patients (58.3%; p=0.022). CONCLUSION: There is a high level of rejection for hormonal replacement therapy among breast cancer patients when current data on tumor cure rates, and potential risks of estrogen use is available. Adverse effects of tamoxifen in the adjuvant setting may be the reason for refusal of hormonal replacement therapy .INTRODUÇÃO: Cerca de 25% das mulheres apresentarão deficiência estrogênica sintomática necessitando terapia de reposição hormonal. A utilização de terapia de reposição hormonal diminui os sintomas vasomotores e outras morbimortalidades. A terapia de reposição hormonal geralmente não é recomendada para as pacientes com câncer de mama, devido o possível aumento no risco de recorrência. Para responder às questões sobre a segurança da terapia de reposição hormonal neste subgrupo de mulheres, é necessário estabelecer a aceitação do tratamento. MÉTODO: Entre setembro de 1998 e fevereiro de 2001, 216 pacientes foram submetidas a um questionário auto-aplicável. As pacientes haviam encerrado o tratamento antineoplásico e, receberam informações sobre as taxas de sobrevida após câncer de mama e terapia de reposição hormonal. RESULTADOS: Entre as 216 pacientes, 134(62%) não fariam terapia de reposição hormonal. Cem pacientes receavam uma recorrência (74,6%). Tamoxifeno adjuvante foi a única variável estatisticamente significativa (70,3% versus 29,7% p=0,003). Conhecimento do estádio clínico (p= 0,045) e tipo de assistência médica (privada versus pública , p=0,033) parecem influenciar a decisão. Estádio inicial (p= 0,22), tipo de cirurgia (radical versus conservadora, p=0,67), quimioterapia adjuvante (p=0,082) ou estado civil (p=0,98) não foram estatisticamente significativos. Várias pacientes submetidas à quimioterapia adjuvante (41,6%) aceitariam terapia de reposição hormonal sob supervisão médica, assim como a maioria das pacientes com doença avançada (58,3%; p=0,022). DISCUSSÃO: Foi observada uma alta taxa de rejeição à terapia de reposição hormonal entre as pacientes quando informações atualizadas sobre taxas de cura, e potenciais riscos do uso de estrógeno estão disponíveis. Efeitos adversos associados ao tamoxifeno adjuvante poderiam estar relacionados à maior recusa