Dual color chromogenic in situ hybridization for determination of HER2 status in breast cancer: a large comparative study to current state of the art fluorescence in situ hybridization

<p>Abstract</p> <p>Background</p> <p>Chromogenic in situ hybridization (CISH) is fast becoming a well established technique for easy and sensitive determination of HER2 gene status in breast cancer. However, for the chromogenic method to achieve status as a safe and reliable technique, the method needs to be validated against already known and validated FISH techniques.</p> <p>Methods</p> <p>Here it is reported from a comparative study where HER2 gene status obtained by <it>HER2 </it>CISH pharmDx™ Kit was compared to HER2 gene status obtained by the FDA approved <it>HER2 </it>FISH pharmDx™ Kit and the PathVysion HER-2 DNA probe Kit. The study included 365 formalin fixed and paraffin-embedded invasive breast cancer tissue specimens collected consecutively at a US reference laboratory.</p> <p>Results</p> <p>The data obtained revealed an overall HER2 status concordance of approximately 98% for comparisons of <it>HER2 </it>CISH pharmDx™ Kit to both <it>HER2 </it>FISH pharmDx™ Kit and PathVysion HER-2 DNA Probe Kit.</p> <p>Conclusions</p> <p>The concordance between results obtained using the recently FDA approved <it>HER2 </it>CISH pharmDx™ Kit with previously FDA approved FISH techniques for HER2 gene status determination indicate that the <it>HER2 </it>CISH pharmDx™ Kit is a reliable chromogenic alternative to fluorescence-based methods.</p

Pharmacokinetics and Safety of Prolonged Paracetamol Treatment in Neonates: An Interventional Cohort Study

Aims To investigate the pharmacokinetics and safety of prolonged paracetamol use (\u3e72 h) for neonatal pain. Methods Neonates were included if they received paracetamol orally or intravenously for pain treatment. A total of 126 samples were collected. Alanine aminotransferase and bilirubin were measured as surrogate liver safety markers. Paracetamol and metabolites were measured in plasma. Pharmacokinetic parameters for the parent compound were estimated with a nonlinear mixed-effects model. Results Forty-eight neonates were enrolled (38 received paracetamol for \u3e72 h). Median gestational age was 38 weeks (range 25–42), and bodyweight at inclusion was 2954 g (range 713–4750). Neonates received 16 doses (range 4–55) over 4.1 days (range 1–13.8). The median (range) dose was 10.1 mg/kg (2.9–20.3). The median oxidative metabolite concentration was 14.6 μmol/L (range 0.12–113.5) and measurable \u3e30 h after dose. There was no significant difference (P \u3e .05) between alanine aminotransferase and bilirubin measures at \u3c72 h or \u3e72 h of paracetamol treatment or the start and end of the study. Volume of distribution and paracetamol clearance for a 2.81-kg neonate were 2.99 L (% residual standard error = 8, 95% confidence interval 2.44–3.55) and 0.497 L/h (% residual standard error = 7, 95% confidence interval 0.425–0.570), respectively. Median steady-state concentration from the parent model was 50.3 μmol/L (range 30.6–92.5), and the half-life was 3.55 h (range 2.41–5.65). Conclusion Our study did not provide evidence of paracetamol-induced liver injury nor changes in metabolism in prolonged paracetamol administration in neonates