Improvement in adenoma detection using a novel artificial intelligence-aided polyp detection device.

Background and study aims Detecting colorectal neoplasia is the goal of high-quality screening and surveillance colonoscopy, as reflected by high adenoma detection rate (ADR) and adenomas per colonoscopy (APC). The aim of our study was to evaluate the performance of a novel artificial intelligence (AI)-aided polyp detection device, Skout, with the primary endpoints of ADR and APC in routine colonoscopy. Patients and methods We compared ADR and APC in a cohort of outpatients undergoing routine high-resolution colonoscopy with and without the use of a real-time, AI-aided polyp detection device. Patients undergoing colonoscopy with Skout were enrolled in a single-arm, unblinded, prospective trial and the results were compared with a historical cohort. All resected polyps were examined histologically. Results Eighty-three patients undergoing screening and surveillance colonoscopy at an outpatient endoscopy center were enrolled and outcomes compared with 283 historical control patients. Overall, ADR with and without Skout was 54.2 % and 40.6 % respectively ( P  = 0.028) and 53.6 % and 30.8 %, respectively, in screening exams ( P  = 0.024). Overall, APC rate with and without Skout was 1.46 and 1.01, respectively, ( P  = 0.104) and 1.18 and 0.50, respectively, in screening exams ( P  = 0.002). Overall, true histology rate (THR) with and without Skout was 73.8 % and 78.4 %, respectively, ( P  = 0.463) and 75.0 % and 71.0 %, respectively, in screening exams ( P  = 0.731). Conclusion We have demonstrated that our novel AI-aided polyp detection device increased the ADR in a cohort of patients undergoing screening and surveillance colonoscopy without a significant concomitant increase in hyperplastic polyp resection. AI-aided colonoscopy has the potential for improving the outcomes of patients undergoing colonoscopy.

Impact of dosing regimen of custirsen, an antisense oligonucleotide, on safety, tolerability and cardiac repolarization in healthy subjects.

AIMS: Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects. METHODS: Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated. RESULTS: AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration-effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience. CONCLUSION: Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen.