Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR.

Standard noninvasive methods for detecting renal allograft rejection and injury have poor sensitivity and specificity. Plasma donor-derived cell-free DNA (dd-cfDNA) has been reported to accurately detect allograft rejection and injury in transplant recipients and shown to discriminate rejection from stable organ function in kidney transplant recipients. This study used a novel single nucleotide polymorphism (SNP)-based massively multiplexed PCR (mmPCR) methodology to measure dd-cfDNA in various types of renal transplant recipients for the detection of allograft rejection/injury without prior knowledge of donor genotypes.

Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

This corrects the article DOI: 10.1038/nature22364.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study.

Incidence of X and Y Chromosomal Aneuploidy in a Large Child Bearing Population.

Background: X&Y chromosomal aneuploidies are among the most common human whole-chromosomal copy number changes, but the population-based incidence and prevalence in the child-bearing population is unclear.

Methods: This retrospective analysis of prospectively collected data leveraged a routine non-invasive prenatal test (NIPT) using parental genotyping to estimate the population-based incidence of X&Y chromosome variations in this population referred for NIPT (generally due to advanced maternal age).

Results: From 141,916 women and 29,336 men, 119 X&Y chromosomal abnormalities (prevalence: 1 in 1,439) were identified.

Detection of Clonal and Subclonal Copy-Number Variants in Cell-Free DNA from Patients with Breast Cancer Using a Massively Multiplexed PCR Methodology.

We demonstrate proof-of-concept for the use of massively multiplexed PCR and next-generation sequencing (mmPCR-NGS) to identify both clonal and subclonal copy-number variants (CNVs) in circulating tumor DNA. This is the first report of a targeted methodology for detection of CNVs in plasma. Using an in vitro model of cell-free DNA, we show that mmPCR-NGS can accurately detect CNVs with average allelic imbalances as low as 0.

Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test.

Objective: We sought to determine the ability of single-nucleotide polymorphism-based noninvasive prenatal testing (NIPT) to identify triploid, unrecognized twin, and vanishing twin pregnancies.

Study Design: The study included 30,795 consecutive reported clinical cases received for NIPT for fetal whole-chromosome aneuploidies; known multiple gestations were excluded. Cell-free DNA was isolated from maternal blood samples, amplified via 19,488-plex polymerase chain reaction, and sequenced.

Evaluation of telemedicine for screening of diabetic retinopathy in the Veterans Health Administration.

Objective: To explore the cost-effectiveness of telemedicine for the screening of diabetic retinopathy (DR) and identify changes within the demographics of a patient population after telemedicine implementation.

Design: A retrospective medical chart review (cohort study) was conducted.

Participants: A total of 900 type 1 and type 2 diabetic patients enrolled in a medical system with a telemedicine screening program for DR.

Timing of testing and treatment for asymptomatic diseases.

Many papers in the medical literature analyze the cost-effectiveness of screening for diseases by comparing a limited number of a priori testing policies under estimated problem parameters. However, this may be insufficient to determine the best timing of the tests or incorporate changes over time. In this paper, we develop and solve a Markov Decision Process (MDP) model for a simple class of asymptomatic diseases in order to provide the building blocks for analysis of a more general class of diseases.