Objective: To systematically review the vascular effects of glibenclamide. Background: Infusion of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener (KCO) levcromakalim dilates cranial arteries and induces headache and migraine attacks. Recent data show that levcromakalim-induced vasodilation is associated with headache. Glibenclamide is a KATP channel blocker that may alter the vascular tone and thus has an impact on headache or migraine prevention. Methods: A search through PubMed was undertaken for studies investigating the vascular effects of glibenclamide in vitro as well as in vivo published until July 2019. Results: We identified 58 articles; 31 in vitro studies, 24 in vivo studies and 3 studies with both. The main findings were that glibenclamide inhibited levcromakalim-induced and other KCOs-induced vasodilation, while the basal vascular tone remained unchanged. Conclusion: Glibenclamide could inhibit vasodilation by KCOs, and further studies are needed to clarify the vascular effect of glibenclamide on human cranial arteries.

Digital image analysis and assisted reading of the HER2 score display reduced concordance: pitfalls in the categorisation of HER2-low breast cancer Aims: Digital image analysis (DIA) is used increasingly as an assisting tool to evaluate biomarkers, including human epidermal growth factor receptor 2 (HER2) in invasive breast cancer (BC). DIA can assist pathologists in HER2 evaluation by presenting quantitative information about the HER2 staining in APP assisted reading (AR). Concurrently, the HER2-low category (HER2-1+/2+ without HER2 gene amplification) has gained prominence due to newly developed antibody-drug conjugates. However, major inter-and intraobserver variability have been observed for the entity. The present quality assurance study investigated the concordance between DIA and AR in clinical use, especially concerning the HER2-low category. Methods and results: HER2 immunohistochemistry (IHC) in 761 tumours from 727 patients was evaluated in tissue microarray (TMA) cores by DIA (Visiopharm HER2-CONNECT) and AR. Overall concordance between HER2-scores were 73% (n = 552, weighted-j: 0.66), and 88% (n = 669, weighted-j: 0.70), when combining HER2-0/1+. A total of 205 scores were discordant by one category, while four were discordant by two categories. A heterogeneous HER2 pattern was relatively common in the discordant cases and a pitfall in the categorisation of HER2-low BC. AR more commonly reassigned a lower HER2 score (from HER2-1+ to HER2-0) within the HER2-low subgroup (n = 624) compared with DIA. Conclusion: DIA and AR display moderate agreement with heterogeneous and aberrant staining, representing a source of discordance and a pitfall in the evaluation of HER2.