Assuntos
Actinomicose/etiologia , Esofagite Eosinofílica/complicações , Actinomicose/tratamento farmacológico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Asma/complicações , Asma/tratamento farmacológico , Transtornos de Deglutição/etiologia , Quimioterapia Combinada , Esofagite Eosinofílica/dietoterapia , Esofagite Eosinofílica/tratamento farmacológico , Hérnia Hiatal/complicações , Humanos , Imunocompetência , Masculino , Fumar/efeitos adversosRESUMO
Transbronchial lung cryobiopsy (TBLC) is an emerging technique for the diagnosis of interstitial lung disease (ILD), but its risk benefit ratio has been questioned. The objectives of this research were to describe any adverse events that occur within 90 days following TBLC and to identify clinical predictors that could help to detect the population at risk. METHODS: We conducted an ambispective study including all patients with suspected ILD who underwent TBLC. Data were collected concerning the safety profile of this procedure and compared to various clinical variables. RESULTS: Overall, 257 TBLCs were analysed. Complications were observed in 15.2% of patients; nonetheless, only 5.4% of all patients required hospital admission on the day of the procedure. In the 30 and 90 days following the TBLC, rates of readmission were 1.3% and 3.5% and of mortality were 0.38%, and 0.78% respectively. Two models were built to predict early admission (AUC 0.72; 95% CI 0.59-0.84) and overall admission (AUC 0.76; 95% CI 0.67-0.85). CONCLUSIONS: Within 90 days after TBLC, 8.9% of patients suffered a complication serious enough to warrant hospital admission. Modified MRC dyspnoea score ≥2, FVC<50%, and a Charlson Comorbidity Index score ≥2 were factors that predicted early and overall admission.
Assuntos
Biópsia/efeitos adversos , Biópsia/métodos , Congelamento/efeitos adversos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Idoso , Biópsia/mortalidade , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Fatores de TempoRESUMO
Development of resistance to therapy continues to be a serious clinical problem in breast cancer management. Cancer stem/progenitor cells have been shown to play roles in resistance to chemo and radiotherapy. Here, we examined their role in the development of resistance to the oestrogen receptor antagonist tamoxifen. Tamoxifenresistant cells were enriched for stem/progenitors and expressed high levels of the stem cell marker Sox2. Silencing of the SOX2 gene reduced the size of the stem/progenitor cell population and restored sensitivity to tamoxifen. Conversely, ectopic expression of Sox2 reduced tamoxifen sensitivity in vitro and in vivo. Gene expression profiling revealed activation of the Wnt signalling pathway in Sox2expressing cells, and inhibition of Wnt signalling sensitized resistant cells to tamoxifen. Examination of patient tumours indicated that Sox2 levels are higher in patients after endocrine therapy failure, and also in the primary tumours of these patients, compared to those of responders. Together, these results suggest that development of tamoxifen resistance is driven by Sox2dependent activation of Wnt signalling in cancer stem/progenitor cells.