Exploration of tumour-infiltrating lymphocytes as a predictive biomarker for adjuvant endocrine therapy in early breast cancer.

PURPOSE:Tumour-infiltrating lymphocytes (TILs) have been shown to be prognostic for disease-free survival and predictive for the benefit of chemotherapy in patients with early breast cancer, but have not been studied for endocrine therapy. EXPERIMENTAL DESIGN:The number of CD8-positive TILs was assessed in a subcohort of 236 patients in the Intergroup Exemestane Study. AQ After 2-3 years of adjuvant tamoxifen, AQpatients were randomized between the schemes of continuation for 5 years on tamoxifen and switching to exemestane. The numbers of CD8-positive TILs were analysed for correlations with disease-free survival (DFS) and overall survival (OS). A similar analysis was performed on 2596 patients in the TEAM trial who were randomized between the sequential scheme and the exemestane monotherapy. RESULTS:In the first cohort, patients with low (below median) numbers of CD8-positive TILs had a univariate hazard ratio (HR) for DFS of 0.27 (95% CI 0.13-0.55) in favour of treatment with exemestane, whereas this benefit was not observed in patients with high numbers of CD8-positive TILs (HR 1.34, 95% CI 0.71-2.50, HR for interaction 5.02, p = 0.001). In the second cohort, patients with low numbers of CD8-positive TILs showed a benefit of exemestane treatment on recurrence-free survival (RFS HR 0.67, 95% CI 0.45-0.99), and not with above-median numbers of CD8-positive TILs (HR 0.86, 95% CI 0.59-1.26, HR for interaction 1.29, p = 0.36). CONCLUSIONS:This study is the first to propose the number of CD8-positive TILs as potential predictive markers for endocrine therapy, with the low presence of CD8-positive TILs associated to benefit for exemestane-inclusive therapy. However, treatment-by-marker interactions were only significant in one cohort, indicating the need for further validation

Effect of Sanitation on Soil-Transmitted Helminth Infection: Systematic Review and Meta-Analysis

A systematic review and meta-analysis by Kathrin Ziegelbauer and colleagues finds that sanitation is associated with a reduced risk of transmission of helminthiases to humans

Bioavailability of pivampicillin and ampicillin trihydrate administered as an oral paste in horses

Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses, Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only, The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg, Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin, Ampicillin concentrations in plasma were determined up to 24 hours after administration, After administration of pivampicillin to starved and fed horses the mean areas under the plasma concentration-time curve (AUCs) were 23.0 and 19.3 mu g.h.ml(-1), respectively, After administration of ampicillintrihydrate to fed horses the mean AUC was 0.7 mu g.h.ml(-1). The peak plasma concentrations were 4.8, 6.7, and 0.1 mu g/ml, after administration of pivampicillin to starved and fed horses and of ampicillin trihydrate to fed horses, respectively, There was no statistically significant difference in peak plasma concentration or AUC between pivampicillin administered to starved or fed horses, It is concluded that pivampicillin administered as an oral paste at a dose of 19.9 mg/kg gives satisfactory plasma concentrations in both starved and fed horses, whereas ampicillin trihydrate produces negligible plasma concentrations, Pivampicillin binds to feedstuffs at the pH found in the horse's stomach and small intestine. After incubation for 6h at pH 6, approximately 15% remains in solution, and after incubation for 3h at pH 1.9, approximately 40% remains in solution, Ampicillin, which binds to feedstuffs to a lesser extent, has a lower bioavailability than pivampicillin, Therefore, binding to feedstuffs does not seem to be a critical factor in the absorption of aminopenicillins