Assuntos
Teste para COVID-19 , COVID-19/diagnóstico , Procedimentos Cirúrgicos Eletivos , Cuidados Pré-Operatórios , Infecções Assintomáticas , COVID-19/epidemiologia , COVID-19/transmissão , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , SARS-CoV-2 , Texas/epidemiologia , Precauções UniversaisRESUMO
BACKGROUND: Examine effects of hospital transfer into a quaternary care center on surgical outcomes of intestinal atresia. METHODS: Children <1 yo principally diagnosed with intestinal atresia were identified using the Kids' Inpatient Database (2012). Exposure variable was patient transfer status. Outcomes measured were inpatient mortality, hospital length of stay (LOS) and discharge status. Linearized standard errors, design-based F tests, and multivariable logistic regression were performed. RESULTS: 1672 weighted discharges represented a national cohort. The highest income group and those with private insurance had significantly lower odds of transfer (OR:0.53 and 0.74, p < 0.05). Rural patients had significantly higher transfer rates (OR: 2.73, p < 0.05). Multivariate analysis revealed no difference in mortality (OR:0.71, p = 0.464) or non-home discharge (OR: 0.79, p = 0.166), but showed prolonged LOS (OR:1.79, p < 0.05) amongst transferred patients. CONCLUSIONS: Significant differences in hospital LOS and treatment access reveal a potential healthcare gap. Post-acute care resources should be improved for transferred patients.
Assuntos
Atresia Intestinal/mortalidade , Atresia Intestinal/cirurgia , Transferência de Pacientes , Feminino , Mortalidade Hospitalar , Humanos , Renda , Lactente , Seguro Saúde , Tempo de Internação/estatística & dados numéricos , Masculino , Análise Multivariada , Setor Privado , População Rural , Estados Unidos/epidemiologiaRESUMO
Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of hepatic injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found in high concentrations in green tea, downregulates OPN expression through OPN mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease OPN mRNA levels, and other studies have shown that EGCG modulates the expression of multiple microRNAs. In our study, we first demonstrated that OPN induces hepatic stellate cells to transform into an activated state. We then identified three microRNAs which target OPN mRNA: miR-181a, miR-10b, and miR-221. In vitro results show that EGCG upregulates all three microRNAs, and all three microRNAs are capable of down regulating OPN mRNA when administered alone. Interestingly, only miR-221 is necessary for EGCG-mediated OPN mRNA degradation and miR-221 inhibition reduces the effects of EGCG on cell function. In vivo experiments show that thioacetamide (TAA)-induced cell cytotoxicity upregulates OPN expression; treatment with EGCG blocks the effects of TAA. Furthermore, chronic treatment of EGCG in vivo upregulates all three microRNAs equally, suggesting that in more chronic treatment all three microRNAs are involved in modulating OPN expression. We conclude that in in vitro and in vivo models of TAA-induced hepatic fibrosis, EGCG inhibits OPN-dependent injury and fibrosis. EGCG works primarily by upregulating miR-221 to accelerate OPN degradation. EGCG may therefore have utility as a protective agent in settings of liver injury.
Assuntos
Antioxidantes/uso terapêutico , Catequina/análogos & derivados , Cirrose Hepática/tratamento farmacológico , MicroRNAs/genética , Regulação para Cima/efeitos dos fármacos , Animais , Antioxidantes/química , Catequina/química , Catequina/uso terapêutico , Linhagem Celular , Células Hep G2 , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Osteopontina/metabolismo , Ratos Sprague-Dawley , Chá/químicaRESUMO
Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-ß (TGF-ß) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN-) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-ß1 to mediate adoption of the CAF phenotype. This OPN-TGF-ß1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-ß1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN-MZF1-TGF-ß1 pathway.