RESUMO
OBJECTIVE: There are limited data on which patients not treated with intravenous (IV) tissue-type plasminogen activator (tPA) due to mild and rapidly improving stroke symptoms (MaRISS) have unfavorable outcomes. MATERIALS AND METHODS: Acute ischemic stroke (AIS) patients not treated with IV tPA due to MaRISS from January 1, 2009 to December 31, 2013 were identified as part of the Georgia Coverdell Acute Stroke Registry. Multivariable regression analysis was used to identify factors associated with a lower likelihood of favorable outcome, defined as discharge to home. RESULTS: There were 1614 AIS patients who did not receive IV tPA due to MaRISS (median National Institutes of Health stroke scale [NIHSS] 1], of which 305 (19%) did not have a favorable outcome. Factors associated with lower likelihood of favorable outcome included Medicare insurance status (odds ratio [OR]: .53, 95% confidence interval [CI]: .34-.84), arrival by emergency medical services (OR: .46, 95% CI: .29-.73), increasing NIHSS score (per unit OR: .89, 95% CI: .84-.93), weakness as the presenting symptom (OR: .50, 95% CI: .30-.84), and a failed dysphagia screen (OR: .43, 95% CI: .23-.80). During the study period, <1% of patients presenting to participating hospitals with MaRISS within the eligible time window received IV tPA. CONCLUSIONS: Baseline characteristics, presenting symptoms, and response to dysphagia screen identify a subgroup of patients who are more likely to have an unfavorable outcome. Whether IV tPA treatment can improve the outcome in this subgroup of patients needs to be evaluated in a randomized placebo-controlled trial.
Assuntos
Isquemia Encefálica/complicações , Transtornos de Deglutição/etiologia , Deglutição , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/terapia , Avaliação da Deficiência , Feminino , Georgia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Alta do Paciente , Valor Preditivo dos Testes , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Resultado do TratamentoAssuntos
Anti-Infecciosos/efeitos adversos , Ansiedade/induzido quimicamente , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Cianose/induzido quimicamente , Dapsona/efeitos adversos , Edema/induzido quimicamente , Glioblastoma/terapia , Infecções Oportunistas/prevenção & controle , Pneumonia por Pneumocystis/prevenção & controle , Ansiedade/diagnóstico , Ansiedade/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Quimiorradioterapia/efeitos adversos , Cianose/diagnóstico , Cianose/terapia , Edema/diagnóstico , Edema/terapia , Feminino , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/microbiologia , Resultado do TratamentoRESUMO
Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.