Incorporation of Donor-derived Cell-free DNA Into Clinical Practice for Renal Allograft Management.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)-based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients. METHODS: To assess the clinical utility of a clinically available SNP-based massively multiplexed polymerase chain reaction dd-cfDNA assay, we analyzed biopsy data contemporaneous to dd-cfDNA results at 33 participating clinics and calculated the rate of rejection in dd-cfDNA-matched biopsy results. RESULTS: A total of 1347 dd-cfDNA test samples from 879 patients were accessioned from October 3, 2019, to November 2, 2020. The dd-cfDNA testing classified 25.2% (340/1347) of samples as high-risk (dd-cfDNA fraction ≥ 1%). Clinical follow-up was available for 32.1% (109/340) of the high-risk results, which included samples from 28 patients with definitive biopsy results within 2 weeks of dd-cfDNA testing. Pathology reports indicated a 64% (18/28) rate of active rejection in biopsy result-matched samples. Total cfDNA measurements indicated a skewed distribution and a correlation with dd-cfDNA-derived patient risk classification. CONCLUSIONS: This is the first report showing the impact of dd-cfDNA on patient management in a multicenter real-world clinical cohort. The data indicate that incorporating dd-cfDNA testing into practice may improve physician decision making regarding renal allograft recipients.

National Association of Medical Examiners Position Paper: Recommendations for the Definition, Investigation, Postmortem Examination, and Reporting of Deaths in Custody.

The National Association of Medical Examiners commissioned an ad hoc committee to provide recommendations for the investigation, examination, and reporting of deaths in custody. Deaths in custody, whether occuring in jail/prison or during an altercation with law enforcement, is a complex issue and requires the forensic pathologist to be knowledgable and deliberative about his/her diagnosis. This paper provides recommendations for the forensic pathologist as it relates to 1) categorization of deaths in custody, 2) critical information required during investigation, 3) enhanced autopsy procedures, 4) guidance on death certification, 5) parameters for statistical reporting, and 6) release of information to the public. A uniform approach by medical examiners and coroners to the investigation and evaluation of deaths in custody is critical. The establishment of recommendations has the potential to ensure consistency and reliability to the definition, investigation, and certification of these cases. Such uniformity and consistency will instill confidence in the independence of the medical examiner/forensic pathologist/coroner by the criminal justice system, public health system, and community at large.