uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays. Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists.

The Cxbladder Monitor test significantly outperforms current Food and Drug Administration-approved urine-based monitoring tests, as well as cytology, in a large representative population undergoing surveillance for recurrent UC. This supports using Cxbladder Monitor as a confirmatory negative adjunct to cystoscopy or to justify postponing cystoscopic investigations in patients with a low risk of recurrence.

Despite a wealth of evidence in vitro that AMPA receptors are inserted into the postsynaptic membrane during long-term potentiation (LTP), it remains unclear whether this occurs in vivo at physiological concentrations of receptors. To address the issue of whether native AMPA or NMDA receptors undergo such trafficking during LTP in the adult brain, we examined the synaptic and surface expression of glutamate receptor subunits during the early induction phase of LTP in the dentate gyrus of awake adult rats. Induction of LTP was accompanied by a rapid NMDA receptor-dependent increase in surface expression of glutamate receptor 1-3 (GluR1-3) subunits. However, in the postsynaptic density fraction only GluR1 accumulated. GluR2/3-containing AMPA receptors, in contrast, were targeted exclusively to extrasynaptic sites in a protein synthesis-dependent manner. NMDA receptor subunits exhibited a delayed accumulation, both at the membrane surface and in postsynaptic densities, that was dependent on protein synthesis. These data suggest that trafficking of native GluR1-containing AMPA receptors to synapses is important for early-phase LTP in awake adult animals, and that this increase is followed homeostatically by a protein synthesis-dependent trafficking of NMDA receptors.

IntroductionThis study aimed to demonstrate the clinical utility of non-invasive multigene Cxbladder urine tests in reducing the overall number of diagnostic tests and invasive procedures used in the clinical evaluation of patients presenting with microhematuria, a key symptom of urothelial carcinoma (UC). There is a belief that using non-invasive molecular diagnostic tests in patients with hematuria may lead to patients undergoing unnecessary and costly invasive procedures that can cause adverse events and decrease patient quality of life. The objective of this study was to determine whether or not this was the case, using Cxbladder.MethodsData from 396 patient-by-urologist interactions generated 792 decision points from a standardized cohort of 33 patients evaluated by 12 urologists. Participant physicians recommended a selection of tests and procedures based on referral data, then reviewed and amended their recommendations in the context of diagnostic information from Cxbladder used in the Triage and Triage and Detect clinical modalities.ResultsAll urologists changed their diagnostic behavior in at least one patient case with the addition of Cxbladder results. The total number of diagnostic procedures was reduced by 5% and 25% following disclosure of results from Cxbladder in the Triage and the Triage and Detect modalities, respectively. The total number of requested invasive procedures was reduced from 425 at referral to 379 (−11%) and 292 (−31%) following disclosure of Cxbladder information in the Triage and Triage and Detect modalities, respectively.ConclusionsUrologists made compelling changes to their clinical decision-making when they were provided with Cxbladder results for patients presenting with hematuria. Cxbladder provides an increase in clinical utility by focusing the use of invasive diagnostic procedures to appropriate patients, reducing both the total number and number of invasive procedures used in the clinical management of patients with hematuria, thereby improving the diagnostic experience and outcomes for patients.FundingPacific Edge Ltd.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0518-7) contains supplementary material, which is available to authorized users.

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