SEPSE e choque séptico - uso de novos biomarcadores e inteligência artificial para diagnóstico precoce, bem como perspectivas atuais de tratamento com uso de imunomoduladores / SEPSIS and septic shock - use of new biomarkers and artificial intelligence for early diagnosis, as well as current perspectives of treatment with the use of immunomodulators

A sepse é uma disfunção orgânica que decorre de uma resposta inflamatória exacerbada do organismo frente a um processo infeccioso; quando acompanhada de alteração do padrão hemodinâmico e hipoperfusão dos tecidos, caracteriza-se o quadro como choque séptico. Em termos epidemiológicos, a síndrome apresenta uma incidência anual de 19 milhões de casos, dos quais cerca de 5 milhões evoluem para óbito. Em vista de sua gravidade, novos estudos têm sido feitos a fim de melhor elucidar a fisiopatologia da sepse e possibilitar que métodos diagnósticos precoces e tratamentos específicos sejam desenvolvidos. Nesse sentido, alguns avanços têm sido feitos, como a descoberta de novos biomarcadores - como a Proadenomedulina - que podem vir a substituir futuramente os métodos tradicionais de diagnóstico através de escores, como o SOFA. Além disso, o uso de inteligência artificial vêm sendo estudado para implementação não só no manejo da sepse, mas em outras áreas da Medicina, já que possibilita uma análise de dados de saúde do paciente que podem ajudar no diagnóstico e prognóstico de outras doenças. Por fim, avanços têm sido feitos no tratamento de sepse e choque séptico; alguns estudos apontam que a modulação de vias específicas da cascata inflamatória seja mais eficiente para o tratamento e que se obtêm melhores resultados e menos efeitos colaterais através dessa nova proposta terapêutica. Outrossim, um exemplo dessa nova modalidade de tratamento, é a modulação da via da proteína de morte celular programada 1/ligante de morte programada (PD-1/PD-L), a qual é supressora da atividade de linfócitos T e da liberação de citocinas; a ativação anormal dessa via durante esse evento, constitui uma das principais razões da imunoparalisia nos pacientes séptico

Impacto da pandemia de COVID-19 no ensino de medicina veterinária em universidades públicas da região sudeste do Brasil: Impact of the COVID-19 pandemic on veterinary medicine teaching in public universities in the southeast region of Brazil

O ensino remoto tornou-se realidade nas instituições de ensino públicas e privadas do Brasil, como uma das medidas preventivas decorrente do novo cenário pandêmico mundial imposto pelo novo Coronavírus. O presente trabalho teve como objetivo avaliar as dificuldades enfrentadas em cursos de Medicina Veterinária de universidades públicas do Sudeste do Brasil diante desse novo molde educacional, segundo a opinião de discentes e docentes. A obtenção desses dados foi por meio de dois questionários elaborados na plataforma “Google Forms” e compartilhados por plataformas digitais (E-mail, Instagram, Facebook e WhatsApp), sendo que, ao final, foram coletadas 209 respostas (98,5% discentes e 1,5% coordenadores) de 16 universidades públicas. O questionário direcionado aos discentes buscou obter informações sobre identificação e impacto da pandemia na graduação, desempenho acadêmico, acessibilidade e apoio tecnológico, vida pessoal e saúde mental. Já o formulário direcionado aos coordenadores objetivou coletar informações sobre identificação e o impacto da pandemia na graduação, acessibilidade e apoio tecnológico e experiência como profissional. Os resultados demonstram que, na opinião do público-alvo, a pandemia afetou de forma negativa o ensino e vida pessoal, impactando áreas como aproveitamento acadêmico e saúde mental. Consequentemente, mesmo que os entrevistados tenham apontado obter melhores notas e médias ponderadas durante o ensino remoto, os mesmos julgaram que seu conhecimento e aprendizado decaíram e que houve preocupação com o prejuízo social e educacional em sua formação e futuro

Abordagens farmacológicas para a prevenção de recaídas em Depressão

As abordagens farmacológicas para a prevenção de recaídas em depressão desempenham um papel crucial na gestão contínua do transtorno. A personalização do tratamento, monitoramento atento e colaboração entre profissionais de saúde mental são elementos essenciais para otimizar os resultados e melhorar a qualidade de vida dos pacientes que enfrentam esse desafio persistente. Este estudo teve como objetivo avaliar o papel das abordagens farmacológica para a prevenção de recaídas em depressão. Para isso, se realizou uma revisão sistemática da literatura, utilizando as bases de dados Scielo, Lilacs e Medline. Com a análise qualitativa dos resultados, concluiu-se que as intervenções farmacológicas desempenham um papel significativo no cuidado mental, proporcionando benefícios em diversas situações. Contudo, o limite reside na necessidade de abordar cuidadosamente os desafios associados a essas intervenções e reconhecer a diversidade de respostas individuais à terapia farmacológica

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Paradoxical Role of Matrix Metalloproteinases in Liver Injury and Regeneration after Sterile Acute Hepatic Failure

Acetaminophen (APAP) poisoning is one of the leading causes of acute hepatic failure and liver transplantation is often the only lifesaving alternative. During the course of hepatocyte necrosis, an intense accumulation of neutrophils is often observed within the liver microenvironment. Despite the classic idea that neutrophil accumulation in tissues causes collateral tissue damage, there is a growing body of evidence showing that neutrophils can also orchestrate the resolution of inflammation. In this work, drug-induced liver injury was induced by oral administration of APAP and pharmacological intervention was made 12 h after this challenge. Liver injury and repair kinetics were evaluated by a novel combination of enzyme quantifications, ELISA, specific antagonists of neutrophil enzymes and confocal intravital microscopy. We have demonstrated that neutrophil infiltration is not only involved in injury amplification, but also in liver tissue repair after APAP-induced liver injury. In fact, while neutrophil depletion led to reduced hepatic necrosis during APAP poisoning, injury recovery was also delayed in neutropenic mice. The mechanisms underlying the neutrophil reparative role involved rapid degranulation and matrix metalloproteinases (MMPs) activity. Our data highlights the crucial role of neutrophils, in particular for MMPs, in the resolution phase of APAP-induced inflammatory response.status: publishe

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt