Barrett\'s esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett\'s metaplasia and low-grade dysplasia. This was a retrospective matched case-control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett\'s metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett\'s metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett\'s metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett\'s metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd\'s ratio 6.7, 95% CI 1.8-24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case-control study, p53 expression associated with a high risk of malignant progression in Barrett\'s low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.

Intentional aerosolization of Yersinia pestis may result in pneumonic plague which is highly fatal if not treated early.
We conducted a phase 1 randomized, double blind (within each group), placebo controlled, dose escalation trial to evaluate a plague vaccine, Flagellin/F1/V, in healthy adults aged 8 through 45years. Vaccine was administered intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10mcg. Subjects were observed for 4h after vaccination for cytokine release syndrome. Reactogenicity and adverse events (AE) were collected for 14 and 28days, respectively, after each vaccination. Serious AE were collected for the entire study. ELISA antibody and cytokines were measured at multiple time points. Subject\'s participation lasted 13months.
Sixty healthy subjects were enrolled; 52% males, 100% non-Hispanic, 91.7% white and mean age 30.8years. No severe reactogenicity events occurred; most AE were mild. No serious AE related to vaccine occurred. A dose response effect was observed to F1, V and flagellin. The peak ELISA IgG antibody titers (95% CI) after two 10mcg doses of vaccine were 260.0 (102.6-659.0) and 983.6 (317.3-3048.8), respectively, against F1 and V antigens. The 6mcg dose group provided similar titers. Titers were low for the placebo, 1mcg and 3mcg recipients. A positive antibody dose response was observed to F1, V and flagellin. Vaccine antigen specific serum IgE was not detected. There were no significant rises in serum or cellular cytokine responses and no significant IgG increase to flagellin after the second dose.
The Flagellin/F1/V vaccine exhibited a dose dependent increase in immunogenicity and was well tolerated at all doses. Antibody specific responses to F1, V and flagellin increased as dose increased. Given the results from this trial, testing higher doses of the vaccine may be merited.