Lee, Jungwha

Distortion product otoacoustic emissions (DPOAEs) offer an outcome measure to consider for clinical detection and monitoring outer hair cell dysfunction as a result of noise exposure. This investigation detailed DPOAE characteristics and behavioral hearing thresholds up to 20 kHz to identify promising metrics for early detection of cochlear dysfunction. In a sample of normal-hearing individuals with and without self-reported noise exposure, the DPOAE and hearing threshold measures, as assessed by two questions, were examined. The effects on various auditory measures in individuals aged 10–65 years old with clinically normal/near-normal hearing through 4 kHz were evaluated. Individuals reporting occupational noise exposures (n = 84) and recreational noise exposures (n = 46) were compared to age-matched nonexposed individuals. The hearing thresholds and DPOAE level, fine structure, and component characteristics for the full frequency bandwidth were examined. The data suggest that the DPOAE levels measured using a range of stimulus levels hold clinical utility while fine structure characteristics offer limited use. Under carefully calibrated conditions, the extension to frequencies beyond 8 kHz in combination with various stimulus levels holds clinical utility. Moreover, this work supports the potential utility of the distortion product place component level for revealing differences in cochlear function due to self-reported, casual noise exposure that are not observable in behavioral hearing thresholds.

Introduction: There is debate over whether Apolipoprotein L1 (APOL1) gene risk variants contribute to African American (AA) live donors’ (LD) increased risk of kidney failure. Little is known about factors influencing physicians’ integration of APOL1 genetic testing of AA LDs into donor evaluation. Design: We conducted a cross-sectional survey, informed by Roger’s Diffusion of Innovations theory, among nephrology and surgeon members of the American Society of Nephrology, American Society of Transplantation, and American Society of Transplant Surgeons about their practices of and attitudes about APOL1 genetic testing of AA potential LDs. Descriptive statistics and bivariate analyses were performed. Results: Of 383 completed surveys, most physicians believed that APOL1 testing can help AA LDs make more informed donation decisions (87%), and the addition of APOL1 testing offers better clinical information about AA LD’s eligibility for donation than existing evaluation approaches (74%). Among respondents who evaluate LDs (n = 345), 63% would definitely or probably begin or continue using APOL1 testing in the next year, however, few use APOL1 testing routinely (4%) or on a case-by-case basis (14%). Most did not know the right clinical scenario to order APOL1 testing (59%), but would use educational materials to counsel AA LDs about APOL1 testing (97%). Discussion: Although physicians were highly supportive of APOL1 genetic testing for AA LDs, few physicians use APOL1 testing. As more physicians intend to use APOL1 testing, an ethical framework and clinical decision support are needed presently to assist clinicians in clarifying the proper indication of APOL1 genetic testing.

ObjectiveCurrently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high‐throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine‐based approach for patients with RA.MethodsRheumatologists at 6 US academic sites were trained in minimally invasive ultrasound‐guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis (OA) were subjected to histologic analysis, fluorescence‐activated cell sorting, and RNA sequencing (RNA‐seq). An optimized protocol for digesting synovial tissue was developed to generate high‐quality RNA‐seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients.ResultsPatients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy.ConclusionPerformance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high‐quality samples for research. Through the use of cutting‐edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine–based approach for patients with RA is attainable.