No abstract

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports (https://gtrx.radygenomiclab.com). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.

Background and ObjectivesThere are limited data on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer. We aimed to assess the efficacy and safety of NOACs in AF patients with cancer in this study.MethodsIn 2,568 consecutive non-valvular AF patients with newly diagnosed cancer, we analyzed ischemic stroke/systemic embolism (SE), major bleeding, and all-cause death. Based on propensity score matching, 388 matched pairs were included in the NOAC and warfarin groups.ResultsPatient baseline characteristics were comparable between the matched groups. During median follow-up of 1.8 years, the NOAC group had significantly lower incidences of ischemic stroke/SE (p<0.001), major bleeding (p<0.001), and all-cause death (p<0.001) than the warfarin group. Moreover, the incidence of major bleeding was significantly lower in the NOAC group than in the warfarin group with optimal international normalized ratio control (p=0.03). Especially, within 1 year after cancer diagnosis, the incidences of all clinical events were significantly lower in the NOAC group than in the warfarin group.ConclusionsIn AF patients with newly diagnosed cancer, NOACs showed lower incidences of ischemic stroke/SE, major bleeding, and all-cause death than warfarin, especially within 1 year after cancer diagnosis.