RESUMO
BACKGROUND: Endoscopic percutaneous tracheostomy (PT) is a safe technique that is performed frequently by otolaryngologists and intensivists. New challenges have been identified in order to maintain the safety of this procedure during the COVID-19 pandemic. A novel approach, using a modified demistifier canopy, was developed during the first wave of the pandemic and implemented for 17 consecutive percutaneous tracheostomies in order to enhance procedural safety. METHODS: A protocol was developed after performing a literature review of tracheostomy in COVID-19 patients. A multidisciplinary tracheostomy team was established, including the departments of otolaryngology, critical care, and respiratory therapy. Simulation was performed prior to each PT, and postoperative debriefings were done. RESULTS: A protocol and technical description of PT using a modified demistifier canopy covering was written and video documented. Data were collected on 17 patients who underwent this procedure safely in our tertiary care hospital. There were no procedure-related complications, and no evidence of COVID-19 transmission to any member of the health care team during the study period. CONCLUSION: As patients continue to recover from COVID-19, their need for tracheostomy will increase. The technique described provides a safe, multidisciplinary method of performing PT in COVID-19 patients.
Assuntos
COVID-19 , Humanos , Traqueostomia/métodos , Pandemias , Unidades de Terapia Intensiva , Cuidados CríticosRESUMO
BACKGROUND: Epidemiological and laboratory evidences led to the hypothesis that molecular mimicry between viruses and self-proteins could be linked to the onset of autoimmune hepatitis (AIH). Hepatotropic viruses could be good candidates, as a pro-inflammatory environment may facilitate the development of AIH. AIMS: The aims of this study were to test a virus ability to induce an AIH through molecular mimicry and the influence of hepatic inflammation in this process. METHODS: C57BL/6 mice were injected i.v. or i.m. with recombinant adenoviral vectors (RecAdV) encoding for human type 2 AIH antigens to target xenoantigens expression in the liver and to create a transient hepatitis (i.v.) or for 'peripheral' xenoantigens expression (i.m.). Liver injury and B-cell response were evaluated. RESULTS: Late-onset hepatitis was observed 8 months after i.v. or i.m. RecAdV injections, despite presence or absence of an initial transient hepatitis. Intensity of B-cell response was similar for both type of injections, but the Ig isotypes produced were different. B-cell autoimmune response spread to several liver proteins. CONCLUSIONS: Liver autoimmune response can be initiated using molecular mimicry over a long period of time, validating the hit-and-run hypothesis. Initial liver inflammatory injury is neither necessary, nor detrimental to the development of AIH. These results highlight the significance of initial events on the pathogenesis of autoimmune liver injury.
Assuntos
Antígenos Heterófilos/imunologia , Hepatite Autoimune/imunologia , Fígado/imunologia , Mimetismo Molecular , Adenoviridae/genética , Amônia-Liases/genética , Amônia-Liases/imunologia , Animais , Antígenos Heterófilos/biossíntese , Antígenos Heterófilos/genética , Linfócitos B/imunologia , Linfócitos B/virologia , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/imunologia , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Glutamato Formimidoiltransferase/genética , Glutamato Formimidoiltransferase/imunologia , Hepatite Autoimune/patologia , Hepatite Autoimune/virologia , Humanos , Injeções Intramusculares , Injeções Intravenosas , Fígado/patologia , Fígado/virologia , Camundongos , Camundongos Endogâmicos C57BL , Enzimas Multifuncionais , Células Th1/imunologia , Células Th1/virologia , Células Th2/imunologia , Células Th2/virologia , Fatores de TempoRESUMO
The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. The guanine nucleotide exchange factor (GEF) linking netrin-1/DCC to Rac1 activation has not yet been identified. Here, we show that the RhoGEF Trio mediates Rac1 activation in netrin-1 signaling. We found that Trio interacts with the netrin-1 receptor DCC in mouse embryonic brains and that netrin-1-induced Rac1 activation in brain is impaired in the absence of Trio. Trio(-/-) cortical neurons fail to extend neurites in response to netrin-1, while they are able to respond to glutamate. Accordingly, netrin-1-induced commissural axon outgrowth is reduced in Trio(-/-) spinal cord explants, and the guidance of commissural axons toward the floor plate is affected by the absence of Trio. The anterior commissure is absent in Trio-null embryos, and netrin-1/DCC-dependent axonal projections that form the internal capsule and the corpus callosum are defective in the mutants. Taken together, these findings establish Trio as a GEF that mediates netrin-1 signaling in axon outgrowth and guidance through its ability to activate Rac1.