Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.

BACKGROUND: Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS: We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS: In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). CONCLUSIONS: Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877 .).

In-situ characterization of the bacterial biofilm associated with Xeroform™ and Kaltostat™ dressings and evaluation of their effectiveness on thin skin engraftment donor sites in burn patients.

Biofilm forms when bacteria surrounded by an extracellular matrix aggregate on a surface. It can develop on many surfaces, including wound dressings; this can be particularly nefarious for burn patients undergoing skin grafting (autograft) for burn wound coverage as they often suffer from compromised immune system function. Autograft donor sites are particularly vulnerable to biofilm formation; as such, timely healing of these sites is essential. Our aim was to apply scanning electron microscopy to compare the efficacy of two types of wound dressings in preventing the formation of bacterial biofilm on burn patient skin graft donor sites. One dressing contained bismuth tribromophenate at a concentration of 3% which confers it bacteriostatic properties (Xeroform™). The other was an absorptive alginate calcium sodium dressing (Kaltostat™). Samples of each wound dressing, which were in contact with the skin graft donor site, were prepared for analysis under the scanning electron microscope (SEM) using an original method developed by our research group that aims to maintain the integrity of the biofilm microstructure. Samples prepared by this method were then analyzed using SEM, which allowed the characterization of biofilm and the evaluation of bacterial density on the studied dressing samples. To this day, this imaging technique has been rarely employed for dressing analysis and this is the first time that it is employed for in situ biofilm visualization for this particular application.

SK channel blockade promotes burst firing in dorsal raphe serotonergic neurons.

Previous in vivo studies have shown that blockade of small-conductance Ca(2+)-activated potassium (SK) channels enhances burst firing in dopaminergic neurons. As bursting has been found to be physiologically relevant for the synaptic release of serotonin (5-HT), we investigated the possible role of SK channels in the control of this firing pattern in 5-HT neurons of the dorsal raphe nucleus. In these cells, bursts are usually composed of doublets consisting of action potentials separated by a small interval (< 20 ms). Both in vivo and in vitro extracellular recordings were performed, using anesthetized rats and rat brain slices, respectively. In vivo, the specific SK blocker UCL 1684 (200 microm) iontophoresed onto presumed 5-HT neurons significantly increased the production of bursts in 13 out of 25 cells. Furthermore, the effect of UCL 1684 persisted in the presence of both the GABA(A) antagonist SR 95531 (10 mm) and the GABA(B) antagonist CGP 35348 (10 mm), whereas these agents by themselves did not significantly influence the neuronal firing pattern. In vitro, bath superfusion of the SK channel blocker apamin (300 nm) induced bursting in only three out of 18 neurons, although it increased the coefficient of variation of the interspike intervals in all the other cells. Our results suggest that SK channel blockade promotes bursting activity in 5-HT neurons via a direct action. An input which is present only in vivo seems to be important for the induction of this firing pattern in these cells.