IMUNOGENICIDADE E SEGURANÇA DA VACINA INATIVADA (CORONAVAC) COMPARADA À VACINA BNT162B2 (PFIZER) CONTRA SARS-COV-2 EM CRIANÇAS E ADOLESCENTES (PROJETO CURUMIM)

Introdução/Objetivo: A maioria dos casos pediátricos de COVID-19 é leve, porém casos graves podem ocorrer. No Brasil ocorreram mais de 300 óbitos em em crianças e adolescentes, no ano de 2022, destacando a necessidade da vacinação. Este ensaio clínico avaliou imunogenicidade e segurança da vacinação de crianças e adolescentes, de 3 a 17 anos, com a vacina inativada (Coronavac) contra o SARS-Cov2 com grupo controle que recebeu a vacina BNT162b2 (Pfizer). Métodos: Ensaio clínico de não inferioridade para avaliar imunogenicidade e segurança da vacina inativada (Coronavac/Butantan) em crianças de 3 a 17 anos, com braço randomizado, duplo-cego de comparação com imunizante BNT/Pfizer. Os participantes (5-17 anos) do braço randomizado foram divididos em dois grupos (2:1) e receberam vacina Coronavac/Butantan ou BNT162b2 (Pfizer). Todos receberam duas doses com intervalo de 28 dias. Foram coletadas amostras nos tempos: pré-vacinação, 28 dias, 3 meses, 6 meses e 12 meses após segunda dose. Para determinação quantitativa de anticorpos contra a porção Receptor Binding Domain - RBD da proteína Spike do SARS-CoV-2 foi empregado o ensaio de eletroquimioluminescência do tipo sanduíche-duplo denominado Anti-SARS-CoV-2 S da Abbott. Considerou positivo ≥50 AU/mL ou 7,1 BAU/mL. O tamanho da amostra considerou análise de não inferioridade, taxa de soroconversão, poder de estudo de 80%, erro alfa de 5% e perdas de 30% (160 indivíduos por grupo). Resultados: Foram incluídas 1.125 crianças de 3 a 17 anos, sendo 460 de 5 a 17 anos no braço randomizado (293 no grupo Coronavac e 167 no grupo Pfizer). Não houve eventos adversos moderados ou graves em nenhum grupo. A frequência geral de eventos adversos locais ou sistêmicos foi menor no grupo Coronavac em comparação à Pfizer. Os eventos sistêmicos foram mais comuns em crianças de 3-4 anos. A soroconversão foi 100% em todos os grupos, com títulos médios geométricos significativamente maiores após a vacinação. Coronavac foi não inferior a BNT/Pfizer para induzir soroconversão de anticorpos (anti-RBD IgG-S) mas a BNT/Pfizer induz títulos maiores de IgG-S comparado com Coronavac, na faixa etária de 5-17 anos. Conclusão: A Coronavac foi menos reatogênica e não inferior à BNT/Pfizer na indução de soroconversão de anticorpos anti-RBD IgG-S. Ambas as vacinas foram seguras, sem eventos adversos graves ou moderados. Estudo registrado no ClinicalTrials.gov NCT05225285

Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting

Pilar de Goiás: a vila entre a memória, a história e a materialidade

This article seeks to understand the interface established between historical archeology, history and the national policy of protection of historical, artistic, architectural and archaeological heritage - through the legal instrument of tipping - materialized in the case of the city of Pilar de Goiás, in the state of Goiás. This protection, begun in the 1950s, occurred in a conceptually and technically fragile way, led to a series of problems and challenges in the fields of history and archeology, especially in the preservation of this same national patrimony. The eighteenth-century mining town went through innumerable “gold bullfights” followed by mining abandonment and population decline (every time the metal fountains were exhausted). This process, initiated in the colonial period and still in progress, favored the construction of a series of memories that complicate the more objective interpretation of the profile of this colonial village. In the present work we seek to understand these processes and how the scientific researches - and even the policies for the patrimony - were informed in the memory, creating a somewhat confusing scenario regarding the colonial past of Pilar de Goiás. The historiography, we propose an interpretation about Pilar de Goiás based on a very plastic society, plural and multifaceted economy. This procedure, far from the grandiose and excessively grounded interpretations of the search for what would be a “mining society”, helps us to understand the processes involved in colonial occupation and the construction of networks of commerce, transit, and urbanization of the central portion of the Colony.Este artigo busca compreender a interface estabelecida entre a arqueologia histórica, a história e a política nacional de proteção do patrimônio histórico, artístico, arquitetônico e arqueológico - através do instrumento legal de tombamento - materializada no caso da cidade de Pilar de Goiás, no estado de Goiás. Essa proteção, iniciada na década de 1950, ocorrida de modo conceitual e tecnicamente frágil, acarretou uma série de problemas e desafios para os campos da história e da arqueologia, sobretudo no tocante à preservação desse mesmo patrimônio nacional. A vila mineradora setecentista passou por inúmeras “corridas do ouro” seguidas de abandono das lavras e decréscimo populacional (toda vez que se esgotavam as fontes do metal). Tal processo, iniciado em período colonial e ainda em andamento, favoreceu a construção de uma série de memórias que complicam a interpretação mais objetiva do perfil dessa vila colonial. No presente trabalho buscamos compreender esses processos e como as pesquisas científicas - e mesmo as políticas para o patrimônio - informaram-se na memória, criando um cenário algo confuso a respeito do passado colonial de Pilar de Goiás. Diante disso, e recorrendo aos documentos históricos e à historiografia, propomos uma interpretação a respeito de Pilar de Goiás, fundamentada em uma sociedade muito plástica, plural e de economia multifacetada. Procedimento que, distante das interpretações grandiosas e excessivamente fundamentadas na busca daquilo que seria uma “sociedade mineradora”, auxilia-nos a compreender os processos envolvidos na ocupação colonial e na construção de redes de comércio, de trânsito e de urbanização da parcela central da Colônia

Neotropical freshwater fisheries : A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes