Tromboelastometria rotacional como biomarcador de formas graves de Covid-19 e sua possível aplicabilidade em algoritmo de decisão para intervenções terapêuticas

Tese (doutorado) — Universidade de Brasília, Faculdade de Ciências Médicas, Programa de Pós-Graduação em Ciências Médicas, 2022.Fundamentos: Desde o início da pandemia da Doença pelo Corona Vírus de 2019 (COVID19), observou-se aumento da incidência de fenômenos tromboembólicos em todos os territórios vasculares, com alta prevalência de tromboembolismo pulmonar. Apesar da evidente alteração da hemostasia, os exames de avaliação da coagulação rotineiramente utilizados (D-dímeros, Tempo de Atividade da Protrombina e Tempo de Tromboplastina Parcial Ativada) não são capazes de diferenciar as distintas fases de formação e dissolução do coágulo, nem de quantificar o excesso ou deficiência dos participantes desse complexo sistema biológico. A tromboelastometria como método de avaliação da coagulação, tem potencial para suprir muitas dessas lacunas e parâmetros tromboelastométricos poderiam possivelmente ser utilizados como ferramentas para tomada de decisões clínicas terapêuticas. Objetivo: Nosso objetivo foi descrever o perfil tromboelastométrico de pacientes diagnosticados com COVID-19, tanto na forma grave quanto na forma não-grave e avaliar a possibilidade de utilização de parâmetros tromboelastométricos como biomarcadores de formas graves. Pacientes e Métodos: Foi realizado um estudo transversal, com a inclusão sucessiva de pacientes que procuraram assistência hospitalar com confirmação de COVID-19 por reação em cadeia de polimerase (PCR). Todos os pacientes e os controles normais tiveram sangue venoso coletado para avaliação pela tromboelastometria rotacional (ROTEM). Foram avaliados os testes da via extrínseca da coagulação (EXTEM), da via intrínseca (INTEM), avaliação funcional do fibrinogênio (FIBTEM) e estudo sem ativadores (NATEM). Resultados: Foram incluídos 41 pacientes com diagnóstico de COVID-19, sendo 21 graves, 20 não-graves, além de 09 controles normais. Os pacientes graves mostraram perfil tromboelastométrico hipercoagulável, caracterizado pelo aumento da amplitude máxima do coágulo (MCF), do ângulo alfa (ALPHA) e do Índice do Potencial Trombodinâmico (TPI). O marcador de fibrinólise, a lise máxima (ML), não foi diferente entre os grupos. Pacientes nãograves apresentaram comportamento mais parecido com os controles normais, exceto para o teste sem ativadores (NATEM) que, assim como nos graves, mostrou valores do Tempo de Coagulação (CT) estatisticamente reduzidos em relação aos controles normais, demonstrando a presença de ativadores endógenos da hemostasia. Construímos Árvores de Decisão com parâmetros tromboelastométricos para separar pacientes graves de não-graves, graves de controles normais, não-graves de controles normais e controles normais de pacientes COVID-19. O parâmetro que melhor mostrou capacidade de diferenciação foi o MCF da avaliação funcional do fibrinogênio (FIBTEM). Conclusão: Pacientes COVID-19 graves apresentaram nítido padrão hipercoagulável no ROTEM. Pacientes não-graves, assim como os graves, mostraram ativação endógena da hemostasia no teste NATEM. Nossa amostra não mostrou diferenças quanto à ocorrência de fibrinólise. Foi possível a utilização de parâmetros tromboelastométricos para gerar Árvores de Decisão com intuito de tomada de decisões terapêuticas, diferenciando pacientes graves de não-graves.Background: Since the beginning of the 2019 Corona Virus Disease (COVID-19) pandemic, increased incidences of thromboembolic phenomena have been observed in all vascular territories with a high prevalence of pulmonary thromboembolism. Despite the evident alteration of hemostasis, the tests routinely used to evaluate the coagulation (D-dimers, Prothrombin Activity Time and Activated Partial Thromboplastin Time) are not capable of differentiating the different stages of clot formation and dissolution, nor of quantifying the excess or deficiency of the participants of this complex biological system. Thromboelastometry as a coagulation assessment method has the potential to fill many of these gaps and thromboelastometric parameters could possibly be used as tools for therapeutic clinical decisions. Objective: Our objective was to describe the thromboelastometric profile of patients with severe and non-severe forms of COVID-19 and to evaluate the possibility of using thromboelastometric parameters as biomarkers of severe forms. Patients and Methods: A cross-sectional study was carried out with successive inclusion of patients seeking hospital care with confirmation of COVID-19 by polymerase chain reaction (PCR). All patients and normal controls had venous blood drawn for evaluation of rotational thromboelastometry (ROTEM). The tests of the extrinsic pathway of coagulation (EXTEM), the intrinsic pathway (INTEM), functional assessment of fibrinogen (FIBTEM) and study without activators (NATEM) were evaluated. Results: 41 patients were included, classified as 21 critically ill and 20 non-severe, besides 9 normal controls. Severe patients were characterized by a hypercoagulable profile, with increased Maximum Clot Firmness (MCF), alfa angle (ALPHA), and Thrombodynamic Potential Index (TPI). The fibrinolysis marker, maximum lysis (ML), was not different between groups. Non-severe patients behave more similarly to normal controls, except for the Clotting Time (CT) in the non-activated test (NATEM), which was statistically reduced as was observed for severe patients, demonstrating the presence of endogenous activators of hemostasis. We constructed Decision Trees with thromboelastometric parameters to separate severe from nonsevere patients, severe from normal controls, non-severe from normal controls and controls from COVID-19 patients. The parameter that best showed the ability to differentiate both forms of the disease was the MCF of FIBTEM. Conclusion: Severe COVID-19 patients have a clear hypercoagulable pattern in ROTEM. Severe and non-severe patients showed endogenous activation of coagulation. Our sample did not show differences regarding the occurrence of fibrinolysis. It was possible to use thromboelastometric parameters to generate Decision Trees for therapeutic decision-making differentiating critically ill patients from non-serious patients

Pre-operative anesthetic assessment of patients with rheumatoid arthritis

O manejo e as intervenções cirúrgicas de problemas decorrentes direta ou indiretamente da artrite reumatoide variam drasticamente. O anestesiologista e o reumatologista devem estar atentos às peculiaridades da avaliação anestésica pré-operatória desses pacientes, incluindo a avaliação de possíveis distúrbios das vias aéreas, além do manejo intraoperatório e da análise dos parâmetros farmacológicos pertinentes. É essencial que o médico anestesiologista esteja familiarizado com as peculiaridades da doença e com as características específicas dos medicamentos usados no seu tratamento, pois, assim, ele poderá planejar da melhor forma possível a técnica anestésica para o ato cirúrgico em questão, oferecendo segurança e conforto ao paciente. Ao reumatologista, cabe conhecer o procedimento a que o paciente será submetido e ter noção da técnica anestésica mais indicada em cada caso. Isso permitirá melhor interação entre o reumatologista e o anestesiologista na avaliação pré-anestésica, através do compartilhamento de informações relevantes sobre o acometimento articular e sistêmico pela doença que possam interferir com o manejo pré e intraoperatório. Além disso, as informações sobre a avaliação pré-anestésica e a escolha da técnica de anestesia contribuirão para que o reumatologista possa esclarecer dúvidas que o paciente e seus familiares porventura apresentem, bem como orientá-los quanto à manutenção ou não das medicações em uso e, eventualmente, da necessidade de suplementação da dose do corticosteroide. O objetivo desta revisão é familiarizar o reumatologista com os principais conceitos relacionados à avaliação anestésica pré-operatória de pacientes com diagnóstico de AR, incluindo, principalmente, as noções gerais que ditam a escolha da técnica anestésica.The management and surgical interventions of problems directly or indirectly arising from rheumatoid arthritis vary drastically. Anesthesiologists and rheumatologists should be aware of the peculiarities of the anesthetic preoperative assessment of these patients, including the assessment of possible disorders of the airways, in addition to the intra-operative management and analysis of relevant pharmacological parameters. It is critical that the anesthetist is familiar with the peculiarities of the disease and the specific characteristics of drugs used in its treatment: thus, he/she will be able to plan the best possible anesthetic technique for the surgery in question, offering safety and comfort to his/her patient. It is up to the rheumatologist to know the procedure to which the patient will be submitted to and be aware of the most appropriate anesthetic technique in each case. This will allow a better interaction between the rheumatologist and the anesthesiologist in the pre-anesthetic evaluation, through the sharing of relevant information on the articular and systemic involvement by the disease that might interfere with preoperative and intraoperative management. Furthermore, the information on the pre-anesthetic assessment and the choice of anesthetic technique will enable the rheumatologist to clarify any doubts that his/her patient and family may have, as well as to guide them as to whether or not the medications in use should be maintained, and eventually about the need for a supplemental dose of corticosteroid. The objective of this review is to acquaint the rheumatologist with key concepts related to the anesthetic preoperative assessment of patients diagnosed with RA, mainly including general notions that dictate the choice of the anesthetic technique

Treatment of chronic Hepatitis C with daclatasvir, sofosbuvir and simeprevir in patients from the reference hospital of infectology in central Brazil/ Tratamento da Hepatite C crônica com daclatasvir, sofosbuvir e simeprevir em pacientes do hospital de referência de infectologia do centro do Brasil

The drug treatment of hepatitis C represents a great therapeutic advance in favor of the elimination of the virus. The present study assessed the efficacy of treatment regimens involving direct action antivirals (DAAs), given to patients with chronic hepatitis C, attended at a referral hospital of infectology, central Brazil. This is a descriptive and cross - sectional study, based on the electronic database of the outpatient pharmacy, that evaluated the characteristics of patients and drug regimens involving DAA, from November 2015 to June 2017. Among 717 patients enrolled in this study, most of them had advanced liver fibrosis, were treatment naïve and HCV genotype 1 infected almost 80% of participants. A high efficacy of HCV treatment was achieved with 97% (95% CI: 94.9-98.2%) of SVR among the 431 patients who presented the results of viral load tests (HCV-RNA) at 12 weeks post-treatment. Patients infected with genotype 3 and who were cirrhotic had a lower SVR rate (87%). Treatment efficacy was not associated with age or sex among participants. The results of this study corroborate the findings in literature that showed a high efficacy of DAAs in the treatment of chronic hepatitis C, implemented through the clinical protocol and therapeutic guidelines for hepatitis C of the Ministry of Health in 2015. Many challenges must be overcome in order to combating viral hepatitis. In this context, the efficacy of HCV treatment it is an important issue to achieve the HCV elimination as a public health threa

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era : severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy

Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines

Amazon hydrology from space : scientific advances and future challenges

As the largest river basin on Earth, the Amazon is of major importance to the world's climate and water resources. Over the past decades, advances in satellite-based remote sensing (RS) have brought our understanding of its terrestrial water cycle and the associated hydrological processes to a new era. Here, we review major studies and the various techniques using satellite RS in the Amazon. We show how RS played a major role in supporting new research and key findings regarding the Amazon water cycle, and how the region became a laboratory for groundbreaking investigations of new satellite retrievals and analyses. At the basin-scale, the understanding of several hydrological processes was only possible with the advent of RS observations, such as the characterization of "rainfall hotspots" in the Andes-Amazon transition, evapotranspiration rates, and variations of surface waters and groundwater storage. These results strongly contribute to the recent advances of hydrological models and to our new understanding of the Amazon water budget and aquatic environments. In the context of upcoming hydrology-oriented satellite missions, which will offer the opportunity for new synergies and new observations with finer space-time resolution, this review aims to guide future research agenda toward integrated monitoring and understanding of the Amazon water from space. Integrated multidisciplinary studies, fostered by international collaborations, set up future directions to tackle the great challenges the Amazon is currently facing, from climate change to increased anthropogenic pressure

Molecular and cellular biomarkers of COVID-19 prognosis : protocol for the prospective cohort TARGET study

Background: Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. Objective: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. Methods: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction–confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. Results: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase

Evidence confirms an anthropic origin of Amazonian Dark Earths.

Arising from: Silva et al. Nature Communications https://doi.org/10.1038/s41467-020-20184-2 (2021

Avaliação anestésica pré-operatória de pacientes com artrite reumatoide

O manejo e as intervenções cirúrgicas de problemas decorrentes direta ou indiretamente da artrite reumatoide variam drasticamente. O anestesiologista e o reumatologista devem estar atentos às peculiaridades da avaliação anestésica pré-operatória desses pacientes, incluindo a avaliação de possíveis distúrbios das vias aéreas, além do manejo intraoperatório e da análise dos parâmetros farmacológicos pertinentes. É essencial que o médico anestesiologista esteja familiarizado com as peculiaridades da doença e com as características específicas dos medicamentos usados no seu tratamento, pois, assim, ele poderá planejar da melhor forma possível a técnica anestésica para o ato cirúrgico em questão, oferecendo segurança e conforto ao paciente. Ao reumatologista, cabe conhecer o procedimento a que o paciente será submetido e ter noção da técnica anestésica mais indicada em cada caso. Isso permitirá melhor interação entre o reumatologista e o anestesiologista na avaliação pré-anestésica, através do compartilhamento de informações relevantes sobre o acometimento articular e sistêmico pela doença que possam interferir com o manejo pré e intraoperatório. Além disso, as informações sobre a avaliação pré-anestésica e a escolha da técnica de anestesia contribuirão para que o reumatologista possa esclarecer dúvidas que o paciente e seus familiares porventura apresentem, bem como orientá-los quanto à manutenção ou não das medicações em uso e, eventualmente, da necessidade de suplementação da dose do corticosteroide. O objetivo desta revisão é familiarizar o reumatologista com os principais conceitos relacionados à avaliação anestésica pré-operatória de pacientes com diagnóstico de AR, incluindo, principalmente, as noções gerais que ditam a escolha da técnica anestésica