RESUMO
BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.
Assuntos
Injúria Renal Aguda , COVID-19 , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Adulto , Idoso , COVID-19/terapia , Dextranos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina , Curva ROC , Terapia de Substituição Renal/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
This article proposes a study of the SARS-CoV-2 virus spread and the efficacy of public policies in Brazil. Using both aggregated (from large Internet companies) and fine-grained (from Departments of Motor Vehicles) mobility data sources, our work sheds light on the effect of mobility on the pandemic situation in the Brazilian territory. Our main contribution is to show how mobility data, particularly fine-grained ones, can offer valuable insights into virus propagation. For this, we propose a modification in the SENUR model to add mobility information, evaluating different data availability scenarios (different information granularities), and finally, we carry out simulations to evaluate possible public policies. In particular, we conduct a case study that shows, through simulations of hypothetical scenarios, that the contagion curve in several Brazilian cities could have been milder if the government had imposed mobility restrictions soon after reporting the first case. Our results also show that if the government had not taken any action and the only safety measure taken was the population's voluntary isolation (out of fear), the time until the contagion peak for the first wave would have been postponed, but its value would more than double.
Assuntos
COVID-19/transmissão , Movimento , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Bases de Dados Factuais , Humanos , Modelos Teóricos , Pandemias , Política Pública , Quarentena , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: Several species of Aspidosperma plants are referred to as remedies for the treatment of malaria, especially Aspidosperma nitidum. Aspidosperma pyrifolium, also a medicinal plant, is used as a natural anti-inflammatory. Its fractionated extracts were assayed in vitro for activity against malaria parasites and for cytotoxicity. METHODS: Aspidosperma pyrifolium activity was evaluated against Plasmodium falciparum using extracts in vitro. Toxicity towards human hepatoma cells, monkey kidney cells or human monocytes freshly isolated from peripheral blood was also assessed. Anti-malarial activity of selected extracts and fractions that presented in vitro activity were tested in mice with a Plasmodium berghei blood-induced infection. RESULTS: The crude stem bark extract and the alkaloid-rich and ethyl acetate fractions from stem extract showed in vitro activity. None of the crude extracts or fractions was cytotoxic to normal monkey kidney and to a human hepatoma cell lines, or human peripheral blood mononuclear cells; the MDL50 values of all the crude bark extracts and fractions were similar or better when tested on normal cells, with the exception of organic and alkaloidic-rich fractions from stem extract. Two extracts and two fractions tested in vivo caused a significant reduction of P. berghei parasitaemia in experimentally infected mice. CONCLUSION: Considering the high therapeutic index of the alkaloidic-rich fraction from stem extract of A. pyrifolium, it makes the species a candidate for further investigation aiming to produce a new anti-malarial, especially considering that the active extract has no toxicity, i.e., no mutagenic effects in the genototoxicity assays, and that it has an in vivo anti-malarial effect. In its UPLC-HRMS analysis this fraction was shown to have two major components compatible with the bisindole alkaloid Leucoridine B, and a novel compound, which is likely to be responsible for the activity against malaria parasites demonstrated in in vitro tests.
Assuntos
Antimaláricos/farmacologia , Aspidosperma/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Brasil , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Haplorrinos , Humanos , Malária/terapia , Camundongos , Carga Parasitária , Parasitemia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plasmodium berghei/isolamento & purificação , Resultado do TratamentoRESUMO
Euterpe oleracea (Açaí) fruit are widely consumed at the Brazilian Amazon region, and biological potentials such as immunomodulatory and antioxidant have been described for its extracts. However, its antimicrobial properties remain poorly investigated. Here, the antimicrobial and antibiofilm activities of the methanolic extract of an artisanally-manufactured açaí pulp (MEAP) were evaluated against clinical isolates of Staphylococcus aureus. Besides, MEAP interference on the activity of antimicrobial drugs of clinical relevance was explored, and its cytotoxicity against hepatocellular carcinoma cells (HepG2) was investigated. Biochemical and physicochemical properties of the pulp were investigated, and the presence of polyphenols on the extract was confirmed. For the first time, we report that the methanolic extract of açaí pulp is effective against planktonic cells and biofilms of S. aureus, and also decreased the proliferation of HepG2 cells. Statistically significant synergism was observed when the extract was combined to the tested antimicrobials except for erythromycin, and all biochemical and physicochemical parameters ranged within the accepted values established by the Brazilian legislation. Our data open doors for more studies on the antimicrobial activity of phytomolecules isolated from Euterpe oleracea extracts, and also for its combined use with antimicrobial drugs.
Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Euterpe/química , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antioxidantes/farmacologia , Brasil , Combinação de Medicamentos , Sinergismo Farmacológico , Eritromicina/farmacologia , Frutas/química , Células Hep G2/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificação , Polifenóis/químicaRESUMO
BACKGROUND: Primaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. RESULTS: All primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro. Sera from mice pretreated with the test compounds thus assumed to have drug metabolites, caused no in vitro haemolysis of human erythrocytes, whereas sera from mice pretreated with primaquine did cause haemolysis. The ability of the PQ-TZs to block malaria transmission was evaluated based on the oocyst production and percentage of mosquitoes infected after a blood meal in drug pre-treated animals with experimental malaria caused by either Plasmodium gallinaceum or Plasmodium berghei; four and five PQ-TZs significantly inhibited sporogony in avian and in rodent malaria, respectively. Selected PQ-TZs were tested for their inhibitory activity on P. berghei liver stage development, in mice and in vitro, one compound (4m) caused a 3-day delay in the malaria pre-patent period. CONCLUSIONS: The compound 4m was the most promising, blocking malaria transmissions and reducing the number of exoerythrocytic forms of P. berghei (EEFs) in hepatoma cells in vitro and in mice in vivo. The same compound also caused a 3-day delay in the malaria pre-patent period.
Assuntos
Eritrócitos/parasitologia , Glucosefosfato Desidrogenase/metabolismo , Malária/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium gallinaceum/efeitos dos fármacos , Primaquina/análogos & derivados , Primaquina/farmacologia , Animais , Linhagem Celular Tumoral , Galinhas , Chlorocebus aethiops , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Células Hep G2 , Humanos , Malária/transmissão , Malária Aviária/tratamento farmacológico , Malária Aviária/transmissão , Camundongos , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium gallinaceum/crescimento & desenvolvimentoRESUMO
Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation.
Assuntos
Aminoquinolinas/farmacologia , Antimaláricos/farmacologia , Malária/tratamento farmacológico , Modelos Moleculares , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Aminoquinolinas/química , Animais , Antimaláricos/química , Linhagem Celular Tumoral , Cloroquina , Relação Dose-Resposta a Droga , Resistência a Medicamentos/fisiologia , Ensaio de Imunoadsorção Enzimática , Hemeproteínas/antagonistas & inibidores , Humanos , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Camundongos , Estrutura Molecular , Plasmodium berghei/metabolismo , Plasmodium falciparum/enzimologia , Plasmodium falciparum/metabolismo , Ligação Proteica , Conformação Proteica , Sais de Tetrazólio , TiazóisRESUMO
Os distúrbios respiratórios que acometem os idosos são condições que possuem alta taxa de morbidade e mortalidade e resultam em impactos sociais, econômicos e pessoais. Objetivo: Este estudo tem por objetivos determinar e comparar o perfil das internações hospitalares e óbitos por distúrbios respiratórios em idosos na macrorregião Leste de Saúde e na região metropolitana do Vale do Aço, numa perspectiva temporal. Métodos: Analisaram-se os dados do Ministério da Saúde referentes às internações e aos óbitos por doenças respiratórias em idosos entre 1998 a 2006. Resultados: O coeficiente de internação por doenças do aparelho respiratório em idosos na Macrorregião Leste de Saúde variou entre 2,7 a 4,3 / 100 idosos, apresentando uma redução ao longo dos anos. No entanto, na região metropolitana do Vale do Aço, a taxa de internação foi maior, apresentando uma variação entre 4,3 a 5,9 / 100 idosos. As duas principais causas de internação e óbitos em ambas as regiões correspondem às doenças obstrutivas crônicas e à pneumonia, que vêm aumentado nos últimos anos. Observou-se um efeito sazonal sobre as internações que apresentaram aumentadas nos meses de maio, junho, julho e agosto. Conclusões: Os resultados sugerem que estudos devem ser realizados de forma local, identificando as particularidades das variações dos coeficientes de morbidade e mortalidade em idosos, a fim de subsidiar políticas de saúde e determinar ações preventivas adicionais.
Assuntos
Idoso , Humanos , Pessoa de Meia-Idade , Doenças Respiratórias/mortalidade , Saúde do Idoso , Hospitalização/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Brasil/epidemiologia , Causas de Morte , Morbidade , Periodicidade , Características de Residência , Estudos de Séries Temporais , População UrbanaRESUMO
A pericadite constritiva, causada por espessamento, inflamação ou calcificação pericárdica, é condição limitante ao enchimento diastólico do coração. Seu diagnóstico clínico nem sempre é fácil e suas manifestações clínicas, frequentemente, mimetizam outras patologias, principalmente as causas de congestão venosa sistêmica e de ascite refratária. Existem critérios ecocardiográficos, já bem estabelecidos, que auxiliam nesse diagnóstico diferencial, e a acurácia da ecocardiográfia nessa condição tem tido incrementos importantes, sobretudo com a descrição de novos critérios do Doppler tecidual. Essas técnicas de análise agregam dados inclusive para a diferenciação entre a pericardite constritiva e a miocardiopatia restritiva, o que usualmente representava um desafio. Esse relato demonstra um caso de pericardite constritiva, manifestando-se como ascite refratária que mimetizava hepatopatia, cujo diagnóstico diferencial, confirmado por cirurgia, consistiu em desafio, com participação definitiva da ecocardiografia nas tomadas de decisão.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Ascite/complicações , Ascite/diagnóstico , Pericardiectomia/métodos , Pericardiectomia , Pericardite Constritiva/complicações , Pericardite Constritiva/diagnósticoRESUMO
Cardioversão de flutter atrial, em pacientes sem anticoagulação, constitui risco de tromboembolismo. Anticoagulação prolongada com warfarina, antes da cardioversão, produz evidente redução do risco de tromboembolismo relacionado à cardioversão. Acredita-se que o benefício da terapia anticoagulante seja a organização do trombo atrial. Entretanto, a evolução natural dos trombos não está bem definida. O caso a seguir descreve a presença de grande trombo em apêndice atrial esquerdo (AAE), em paciente com flutter atrial, que desapareceu completamente, após quatro semanas de anticoagulação, sem ocorrência de evento tromboembólico.