O FUTURO DA IMUNOTERAPIA: CAR-T UMA INOVADORA TERAPIA NA ONCO-HEMATOLOGIA E SUAS LIMITAÇÕES PARA TUMORES SÓLIDOS

With the increasing development of the use of immunotherapy of oncological diseases, the treatment with CAR-T cells (T lymphocytes with Chimeric Antigen Receptors), strategies are being used to take advantage of the immune system itself to fight cancers. The innovative technique of cell therapy, has been obtaining impressive results in cases that no longer had therapeutic options left whose prognoses were weak and practically unlikely, studies presented expose both limitations for solid tumors and side effects from the release of cytokines, as advances in the reprogramming of T lymphocytes in their production, benefiting hematological patients. Advances have been presented in the creations of the generations of CAR-T cells, we know that there are four generations, based on the development of the first generation. They showed limited efficacy in terms of persisting the antitumor response. It is important to note that these generations represent major advances in the reformulation of CAR-T cells and in intracellular activation and signaling strategies, with the aim of improving therapeutic efficacy. The present study is justified by the interest in exposing data and details of CAR-T cell therapy, which represents an advance in science and in the treatment of patients suffering from hematological neoplasms. Concept, technology and process for advanced therapies are presented, where the clinical application is addressed, being presented products already approved as: Kymriah, Yescarta.Con el creciente desarrollo del uso de la inmunoterapia de enfermedades oncológicas, el tratamiento con células CAR-T (linfocitos T con receptores de antígenos quiméricos), se están utilizando estrategias para aprovechar el propio sistema inmunológico para combatir los cánceres. La innovadora técnica de terapia celular, ha ido obteniendo resultados impresionantes en casos que ya no tenían opciones terapéuticas cuyos pronósticos eran débiles y prácticamente improbables, estudios presentados exponen tanto limitaciones para tumores sólidos y efectos secundarios por la liberación de citoquinas, como avances en la reprogramación de linfocitos T en su producción, beneficiando a pacientes hematológicos. Se han presentado avances en las creaciones de las generaciones de células CAR-T, sabemos que son cuatro generaciones, basadas en el desarrollo de la primera generación. Mostraron una eficacia limitada en términos de persistencia de la respuesta antitumoral. Es importante destacar que estas generaciones representan grandes avances en la reformulación de células CAR-T y en estrategias de activación y señalización intracelular, con el objetivo de mejorar la eficacia terapéutica. El presente estudio se justifica por el interés en exponer datos y detalles de la terapia de células CAR-T, lo que representa un avance en la ciencia y en el tratamiento de pacientes con neoplasias hematológicas. Se presenta concepto, tecnología y proceso para terapias avanzadas, donde se aborda la aplicación clínica, presentándose productos ya aprobados como: Kymriah, Yescarta.Com o desenvolvimento crescente da utilização da imunoterapia de doenças oncológicas, o tratamento com células CAR-T (linfócitos T com Receptores Antígenos Quiméricos), estão sendo utilizadas estratégias para aproveitar o próprio sistema imunológico para combater os canceres. A inovadora técnica de terapia celular, vem obtendo resultados impressionantes em casos que não restavam mais opções terapêuticas, cujo prognósticos eram fracos e praticamente improváveis. Estudos apresentados expõe tanto limitações para tumores sólidos e efeitos colaterais provenientes da liberação de citocinas, como avanços na reprogramação dos linfócitos T em sua produção, beneficiando pacientes hematológicos. Foram apresentados avanços na criação das gerações das células CAR-T, sabemos que existem quatro gerações, tendo como base de desenvolvimento a primeira geração. Elas mostraram uma eficácia limitada em termos de persistência a resposta antitumoral. É importante observar que essas gerações representam grandes avanços na reformulação das células CAR-T e nas estratégias de ativação e sinalização intracelular, com o objetivo de melhorar a eficácia terapêutica. O presente estudo justifica-se pelo interesse em expor dados e detalhes da terapia CAR-T cell, que representa um avanço na ciência e no tratamento de pacientes vítimas de neoplasias hematológicas. São apresentados conceitos, tecnologias e processo para terapias avançadas, onde é abordada a aplicação clínica, sendo apresentados produtos já aprovados como: Kymriah, Yescarta.Com o desenvolvimento crescente da utilização da imunoterapia de doenças oncológicas, o tratamento com células CAR-T (linfócitos T com Receptores Antígenos Quiméricos), estão sendo utilizadas estratégias para aproveitar o próprio sistema imunológico para combater os canceres. A inovadora técnica de terapia celular, vem obtendo resultados impressionantes em casos que não restavam mais opções terapêuticas, cujo prognósticos eram fracos e praticamente improváveis. Estudos apresentados expõe tanto limitações para tumores sólidos e efeitos colaterais provenientes da liberação de citocinas, como avanços na reprogramação dos linfócitos T em sua produção, beneficiando pacientes hematológicos. Foram apresentados avanços na criação das gerações das células CAR-T, sabemos que existem quatro gerações, tendo como base de desenvolvimento a primeira geração. Elas mostraram uma eficácia limitada em termos de persistência a resposta antitumoral. É importante observar que essas gerações representam grandes avanços na reformulação das células CAR-T e nas estratégias de ativação e sinalização intracelular, com o objetivo de melhorar a eficácia terapêutica. O presente estudo justifica-se pelo interesse em expor dados e detalhes da terapia CAR-T cell, que representa um avanço na ciência e no tratamento de pacientes vítimas de neoplasias hematológicas. São apresentados conceitos, tecnologias e processo para terapias avançadas, onde é abordada a aplicação clínica, sendo apresentados produtos já aprovados como: Kymriah, Yescarta

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Co-creating sustainability indicators for the local water-energy-food nexus

Sustainability indicators have become essential tools to deal with compartmentalized resources planning and management in cities. The development of water, energy, and food nexus (WEF nexus) indicators is a prominent goal of current research, but the focus is mainly on economic issues and material flows. Attention to the local scale and context, social aspects, and the inclusion of non-academic actors is mostly lacking. To address these gaps, this paper reports and reflects on the co-creation of sustainability indicators related to the WEF nexus in the city of Sao Paulo, Brazil. With a transdisciplinary approach, non-academic actors were included in the different stages of the process using the Urban Living Lab methodology, to improve the usability of the produced indicators' set. The case of Sao Paulo concerned on-going actions in the peri-urban and rural areas of the city which seek to improve environmental protection by stimulating more sustainable forms of agriculture. Thirty-four indicators were developed through a sequence of interactive activities, such as workshops, meetings, and field trips. The presented process aims to strongly enhance usability by actively involving users from the start, connecting the nexus approach to previous knowledge and familiar frameworks, paying attention to the local scale and context, and to social aspects, and by anticipating future use in various ways

Co-creating sustainability indicators for the local water-energy-food nexus

Sustainability indicators have become essential tools to deal with compartmentalized resources planning and management in cities. The development of water, energy, and food nexus (WEF nexus) indicators is a prominent goal of current research, but the focus is mainly on economic issues and material flows. Attention to the local scale and context, social aspects, and the inclusion of non-academic actors is mostly lacking. To address these gaps, this paper reports and reflects on the co-creation of sustainability indicators related to the WEF nexus in the city of Sao Paulo, Brazil. With a transdisciplinary approach, non-academic actors were included in the different stages of the process using the Urban Living Lab methodology, to improve the usability of the produced indicators' set. The case of Sao Paulo concerned on-going actions in the peri-urban and rural areas of the city which seek to improve environmental protection by stimulating more sustainable forms of agriculture. Thirty-four indicators were developed through a sequence of interactive activities, such as workshops, meetings, and field trips. The presented process aims to strongly enhance usability by actively involving users from the start, connecting the nexus approach to previous knowledge and familiar frameworks, paying attention to the local scale and context, and to social aspects, and by anticipating future use in various ways

Endividamento: um estudo do pré e pós da crise empresarial brasileira na pandemia do COVID-19

A economia brasileira, desde antes da pandemia, vinha passando por um processo de desaceleração, enfrentando dificuldades para o seu crescimento. Com o cenário pandêmico da Covid-19, as empresas sofreram ainda mais com esse momento de crise, devido a paralisação das atividades presenciais. Dessa forma, para a obtenção dos resultados da pesquisa, teve-se como objetivo geral do presente estudo, analisar e comparar o estado econômico das empresas brasileiras, listadas na B3. Neste estudo, foram aplicados sete indicadores financeiros, os quais são ferramentas utilizadas pelos gestores na compreensão dos números das suas empresas. Quanto à metodologia, decorreu de uma pesquisa descritiva e quantitativa utilizado o teste T de Student e o teste F de Levene. A partir das informações extraídas dos testes estatísticos há indícios de que houve um aumento significativo, do ponto de vista estatístico, do endividamento geral da empresa contribuindo para o aumento do risco dos negócios

Relações entre profissionais de saúde e usuários durante as práticas em saúde Relationships between health professionals and users throughout health care practices

Apresenta-se uma revisão integrativa sobre estudos que abordam as relações entre profissionais de saúde e usuários durante as práticas em saúde. Objetivou-se identificar os aspectos pesquisados no cotidiano dos serviços acerca dessas relações. A coleta foi realizada nas bases Lilacs e Pubmed segundo os descritores: acolhimento; relações profissional-família; relações profissional-paciente; humanização da assistência; e a palavra 'vínculo' associada ao descritor Sistema Único de Saúde. Selecionaram-se 290 estudos publicados entre 1990 e 2010. Por meio da análise temática, foram criados cinco núcleos de sentido: a relevância da confiança na relação profissional-usuário; sentimentos e sentidos na prática do cuidado; a importância da comunicação nos serviços de saúde; modo de organização das práticas em saúde; e (des)colonialismo. Identificou-se que as relações estabelecidas nas práticas de saúde têm uma dimensão transformadora. No entanto, permanece o desafio de humanizar os serviços de saúde. A enfermagem se destaca na produção do conhecimento nessa temática.<br>This article presents an integrative review about studies that address the relationships between health professionals and users in health care practices. It aimed to identify aspects that were researched on the daily life of the services concerning such relationships. Data were collected from the Lilacs and Pubmed databases based on these descriptors: user embracement; professionalfamily relations; professionalpatient relations; humanization of the care; and the bonding word associated to the Single Health System descriptor. Two hundred and ninety studies, published from 1990 to 2010, were selected. Through thematic analyses, five meaning cores were created: the relevance of the confidence in the professionaluser relationship; feelings and senses in the health care practice; the importance of communications in health care services; ways to organize health care practices and (de)colonialism. It was found that relationships established in health care practices have a transformative dimension. However, the challenge to humanize health care services remains. Nursing stands out in the production of knowledge on such theme

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5-19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school-aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity. Funding: UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union