Minimum information to report about a flow cytometry experiment on extracellular vesicles: Communication from the ISTH SSC subcommittee on vascular biology

The Extracellular Vesicle Flow Cytometry Working Group ( http://www.evflowcytometry.org ) is formed by members of the International Society for Extracellular Vesicles (ISEV), the International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH). This working group of flow cytometry experts develops guidelines for best practices regarding flow cytometry detection of extracellular vesicles. To improve rigor and standardization, this working group published a framework outlining the minimal information to report about a flow cytometry experiment on extracellular vesicles (MIFlowCyt-EV) in the Journal of Extracellular Vesicles, the ISEV journal, in 2020. In parallel, an article explaining MIFlowCyt-EV was published in Cytometry Part A, one of the ISAC journals, and now will be introduced to the ISTH as an SSC Communication in the Journal of Thrombosis and Haemostasis. The goal of this SSC Communication is to explain why flow cytometry is becoming the instrument of choice to characterize single extracellular vesicles, the obstacles that have been identified and (mostly) overcome by developing procedures to calibrate flow cytometers, and the relevance of reporting minimal information to improve reliability and reproducibility of experiments in which flow cytometers are used for characterization of extracellular vesicles.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Two-year results after combined phacoemulsification and iris-fixated phakic intraocular lens removal

Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and present results after a technique for cataract surgery combined with explantation of an iris-fixated phakic...