Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) can often be traced to a pre-leukemic clone carrying a prenatal genetic lesion. Postnatally acquired mutations then drive clonal evolution toward overt leukemia. The enzymes RAG1-RAG2 and AID, which diversify immunoglobulin-encoding genes, are strictly segregated in developing cells during B lymphopoiesis and peripheral mature B cells, respectively. Here we identified small pre-BII cells as a natural subset with increased genetic vulnerability owing to concurrent activation of these enzymes. Consistent with epidemiological findings on childhood ALL etiology, susceptibility to genetic lesions during B lymphopoiesis at the transition from the large pre-BII cell stage to the small pre-BII cell stage was exacerbated by abnormal cytokine signaling and repetitive inflammatory stimuli. We demonstrated that AID and RAG1-RAG2 drove leukemic clonal evolution with repeated exposure to inflammatory stimuli, paralleling chronic infections in childhood.

Individual- and Neighborhood-Level Disparities in Audio-Only Telemedicine Utilization Across a Large Academic Health System.

Introduction: The objective of this study was to understand whether use of audio-only telemedicine visits differed by individual- and neighborhood-level patient characteristics during the COVID-19 pandemic. Methods: We conducted a retrospective cross-sectional study of telemedicine encounter data from a large academic health system. The primary outcome was rate of audio-only versus video visits. The exposures of interest were individual- (age, race, insurance, preferred language) and neighborhood-level (Social Deprivation Index [SDI]) patient characteristics. Results: Our study included 1,054,465 patient encounters from January 1, 2020 to December 31, 2021, of which 18.33% were completed via audio-only. Encounters among adults 75 years or older, Black patients, Spanish-speakers, and those with public insurance were more frequently conducted by audio-only (p < 0.001). Overall, populations showed decreasing rates of audio-only visits over time. We also observed an increase in the rate of audio-only encounters as SDI scores increased. Discussion: We found that audio-only disparities exist in telemedicine utilization by individual and zip code level characteristics. Though these disparities have improved over time as seen by our temporal analysis, marginalized and minority groups still showed the lowest rates of video utilization. In conclusion, access to audio-only care is a critical component to ensure that telemedicine is accessible to all populations. State and federal policy should support continued reimbursement of audio-only care to ensure equitable access to care while the implications of different care modalities are further studied.

Provider Perspectives Regarding Ambulatory Telemedicine at a Large Academic Health System During the COVID-19 Pandemic.

Purpose: To understand provider preferences regarding telemedicine across clinical departments and provider demographic groups. Methods: A cross-sectional online survey was distributed to providers at Johns Hopkins Medicine who had completed at least one outpatient telemedicine encounter. The survey included questions about clinical appropriateness and preferred use of telemedicine. Demographic data were obtained from institutional records. Descriptive statistics provided a profile of provider responses. Wilcoxon rank sum tests evaluated departmental and demographic differences. Results: A total of 1,342 of 3,576 providers responded (37.5%). Providers indicated that telemedicine was clinically appropriate for new patients a median of 31.5% of the time (Range: 20% in pediatrics, 80% in psychiatry/behavioral sciences). For existing patients, providers indicated that telemedicine was clinically appropriate a median of 70% of the time (Range: 50% in physical medicine, 90% in psychiatry/behavioral sciences). Providers desired a median of 30% of their schedule template be dedicated to telemedicine (Range: 20% in family medicine, 70% in psychiatry/behavioral sciences). Providers who were female, had fewer than 15 years in practice, or were psychiatrists/psychologists tended to find telemedicine more clinically appropriate (p < 0.05). Conclusions: A majority of providers across clinical departments felt that high-quality care could be delivered through telemedicine, although the amount of care varied widely based on department and patient type. Preferences for future telemedicine similarly showed wide variety across and within departments. These findings indicate that in this early adoption phase of widespread telemedicine integration, there is lack of consensus among providers about the amount of telemedicine appropriate for everyday practice.