This report describes outbreaks of legionellosis in two nursing homes, representing the first reported outbreaks of infection caused by Legionella sainthelensi. The association with illness of dietary characteristics indicative of swallowing disorders suggests that aspiration was the most likely mode of infection. The diagnosis of legionellosis should be considered during outbreaks of respiratory infection in nursing homes.
561 Background: Breast Cancer Index (BCI), a continuous risk index, combines the ratio of HOXB13 to IL17BR (H/I) and the molecular grade index (MGI) (Jerevall et al., British J Cancer, 2011). Here, the prognostic and predictive performance of BCI for BC relapse in MA.14 trial was examined. Methods: MA.14 randomly assigned 667 hormone receptor positive (HR+) women to 5 years of tamoxifen (TAM) +/- 2 years of octreotide LAR (TAM-OCT). A representative subgroup of 299 patients was profiled by RT-PCR for BCI. The primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS) with median 9.8 years follow-up. Association of BCI was assessed with step-wise forward stratified Cox regression. Pre-defined categories of low (L), intermediate (I) and high (H) BCI risk groups were used to provide adjusted 5- and 10-year RFS. Results: 292 of 299 patient samples passed internal analytical quality control. The 292 patients contained 49% LN+ patients and had 19.9% BC relapses. Both continuous and pre-specified BCI risk groups were significant multivariate factors (p<0.0001; p=0.007) with higher BCI associated with shorter RFS. Adjusted univariate hazard ratios and 95% CI were 2.53 (1.36 – 4.71) for BCI-H vs -L and 1.28 (0.65 – 2.52) for BCI-I vs -L. With both LN- and LN+ included, BCI-L had 5- and 10-year RFS of 94.0% and 87.5%; -I, 91.8% and 83.9%; and -H, 81.5% and 74.7%. No significant difference in BCI’s ability to stratify patients into 3 risk groups was observed between LN-/no chemotherapy subgroup vs balance of MA.14 patients (p=0.26). Higher pathologic T-stage was multivariately associated with shorter RFS (p=0.01). Interactions between trial therapy and BCI was not significant (p=0.40). Conclusions: This study confirmed the strong prognostic effect of BCI on breast cancer recurrence. BCI was prognostic in both LN- and LN+ patients. The lower 10-year RFS in the BCI-L group than in our previous studies reflected the mixed LN-/LN+ population examined. Like the parent MA.14 trial, BCI did not predict benefit of adding OCT to TAM therapy (Pritchard et al., J Clin Oncol, 2011). This retrospective study is an independent validation of the prognostic performance of BCI within a prospective trial.
Background Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. Aims To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. Methods Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. Results Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1β, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. Conclusions When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.
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