RESUMO
BACKGROUND: A circulating tumor cell (CTC) count is an established prognostic factor in metastatic breast cancer (MBC). Besides enumeration, CTC characterization promises to improve outcome prediction and treatment guidance. Having shown the feasibility of quantifying clinically relevant mRNA transcripts in CTCs, we determined the prognostic value of CTC gene expression in MBC. PATIENTS AND METHODS: CTCs were isolated and enumerated from blood of 197 MBC patients who were about to start first-line systemic therapy. Of these, 180 were assessable for quantification of mRNA expression by RT-qPCR in relation to time-to-treatment failure (TTF). A prognostic CTC gene profile was generated by leave-one-out cross validation in a 103 patient discovery set and validated in 77 patients. Additionally, all 180 patients were randomly divided into two equal sets to discover and validate a second prognostic profile. RESULTS: CTC count predicted for TTF at baseline {≥5 versus <5 CTCs/7.5 ml blood, hazard ratio (HR) 2.92 [95% confidence interval (CI) 1.71-4.95] P < 0.0001}. A 16-gene CTC profile was generated in the first discovery set, which identified patients with death or TTF <9 months versus those with a better outcome. In multivariate analysis, the 16-gene profile was the only factor associated with TTF [HR 3.15 (95% CI 1.35-7.33) P 0.008]. Validation of this profile in the independent patient set pointed into the same direction, but was not statistically significant. A newly generated 8-gene profile showed similarly favorable test characteristics as the 16-gene profile, but did not significantly pass validation either. CONCLUSION: A 16-gene CTC profile was identified, which provided prognostic value on top of CTC count in MBC patients. However, validation of this profile in an independent cohort, nor of a second profile, reached statistical significance, underscoring the need to further fine-tune the still promising approach of CTC characterization.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Células Neoplásicas Circulantes , Adulto , Bélgica/epidemiologia , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estudos ProspectivosRESUMO
A retrospective cohort study was conducted to evaluate the utility of self-reported tobacco use for developing a clinical prediction rule for poor outcomes of Clostridium difficile infection. Patients with any history of smoking were significantly less likely than never smokers to be cured of their infection within two weeks. Disease recurrence, readmission within 30 days, death before treatment completion, and the severity of Clostridium difficile infection were not associated with smoking status.
Assuntos
Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Técnicas de Apoio para a Decisão , Uso de Tabaco , Idoso , Infecções por Clostridium/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
The significance of Aeromonas spp. as potential water-borne enteric pathogens in Tasmania, Australia, an area with a mild climate and comparatively low year-round water temperatures, was investigated in view of the reported marked peak of Aeromonas-associated gastroenteritis in the summer and the apparent influence of temperature on levels of potentially pathogenic species in water supplies. Biochemical characteristics and virulence-associated properties--exotoxin production (hemolysin, enterotoxin), ability to grow at 43 degrees C, and possession of pili--were determined for 105 Tasmanian isolates of Aeromonas spp.; 43 isolates were from clinical specimens (greater than 75% diarrhea associated) and 62 were from water. Current classification schemes were evaluated for these isolates. A. sobria comprised 35% of the clinical isolates and 16% of the water isolates, A. hydrophila comprised 56 and 79%, and A. caviae comprised 9 and 5%. A total of 42% of the clinical isolates and 15% of the environmental isolates were enterotoxigenic (by the suckling mouse assay); these levels were significantly lower than those found in warmer environments. The majority (74%) of enterotoxigenic isolates were A. sobria. Enterotoxin-producing isolates possessed three or more of the following properties. They were Voges-Proskauer positive, did not hydrolyze arabinose, were positive for lysine decarboxylase, were able to grow at 43 degrees C, and produced large amounts of hemolysin (titer, greater than 128). Thus, the biochemical scheme proposed by Burke et al. (V. Burke, J. Robinson, H.M. Atkinson, and M. Gracey, J. Clin. Microbiol. 15:48-52, 1982) for identifying enterotoxigenic isolates appears to have widespread applicability. Environmental enterotoxigenic isolates possessed numerous pili, but these appeared to be lost once infection was established, as a similar isolates from patients with diarrhea were poorly piliated.