Introduction and Objective: Regulatory T cells (Tregs) are critical for immune homeostasis. In T1D, inflammation and IL-2 scarcity in the pancreas can result in Treg instability and dysfunction. Autologous expanded polyclonal Tregs have improved c-peptide preservation in some recently diagnosed T1D patients. Antigen-specific Tregs are more effective in preventing T1D onset preclinically. GNTI-122 is an autologous engineered regulatory T (EngTreg) cell therapy designed to prevent progression of recently diagnosed T1D by targeting islet antigens and addressing Treg instability and IL-2 scarcity. Methods: Clinical scale GNTI-122 was produced from bulk CD4+ T cells gene edited at the TRAC and FOXP3 loci, with targeted insertions via two AAV6 donor templates. The resulting cell product was characterized by flow cytometry, cytokine secretion assays, and suppression assays. Results: GNTI-122 purity exceeded 90% dual-edited product, with a monoclonal TCR directed at an islet-specific antigen (IGRP), and cell yields of >3X109 with high viability. The cell product displays characteristic Treg markers: FOXP3, CD25, low CD127, CTLA4, EOS, TNFRII, CD27, and low CD70. Upon stimulation, the cells have elevated LAP and GARP expression, characteristic of an immune suppressive profile, with reduced expression of pro-inflammatory cytokines (IL-2, TNF-α, and IFN-γ). GNTI-122 demonstrates pSTAT5 signaling with IL-2 or through the engineered chemically induced signaling complex (CISC), activated by rapamycin. GNTI-122 demonstrates potent suppression of T conventional cells (Tconv). Conclusion: We have demonstrated a robust clinical scale manufacturing process, Treg phenotype and activity profile. GNTI-122 represents a promising therapeutic to halt progression of recently diagnosed T1D. Finally, GentiBio has designed the Polaris study, a Phase 1 study to test this novel cell therapy in recently diagnosed adult T1D participants starting in the 2H2025. M. Gose: None. P. Sharma: None. A.K. Meiners: None. S.J. Albertson: None. P. Saikumar lakshmi: None. G.I. Uenishi: Employee; GentiBio. C. Patel: None. T.F. Chen: Employee; GentiBio. B.R. Christin: None.
Round about the phantom flow, Infused microbubbles go. With pulses varied and rarefied, In cavitation's course we bide. Double, double toil and trouble; Pressure rise and bubbles rumble. Energy from echoes seen, Mapped in colors, red and green. Rarefaction's peak doth tell, Stable hum or inertial spell. Long or short, the pulse doth play, Cavitation marks the way. Double, double toil and trouble; Pressure rise and bubbles rumble. Metrics dense of dose defined, Energy coursing, fate entwined. Stable charms or collapse to see, Impacting efficacy. For venous flow or clots to break, Future schemes for patients' sake. Double, double toil and trouble; Pressure rise and bubbles rumble. Cavitation with image masks, the spell complete, For healing tasks, the charm is sweet. To delve the depths of knowledge nigh, Seek thou this DOI: https://doi.org/10.1016/j.ultrasmedbio.2023.08.002.
Data on monkeypox in children and adolescents aged <18 years are limited (1,2). During May 17–September 24, 2022, a total of 25,038 monkeypox cases were reported in the United States,† primarily among adult gay, bisexual, and other men who have sex with men (3). During this period, CDC and U.S. jurisdictional health departments identified Monkeypox virus (MPXV) infections in 83 persons aged <18 years, accounting for 0.3% of reported cases. Among 28 children aged 0–12 years with monkeypox, 64% were boys, and most had direct skin-to-skin contact with an adult with monkeypox who was caring for the child in a household setting. Among 55 adolescents aged 13–17 years, most were male (89%), and male-to-male sexual contact was the most common presumed exposure route (66%). Most children and adolescents with monkeypox were non-Hispanic Black or African American (Black) (47%) or Hispanic or Latino (Hispanic) (35%). Most (89%) were not hospitalized, none received intensive care unit (ICU)–level care, and none died. Monkeypox in children and adolescents remains rare in the United States. Ensuring equitable access to monkeypox vaccination, testing, and treatment is a critical public health priority. Vaccination for adolescents with risk factors and provision of prevention information for persons with monkeypox caring for children might prevent additional infections.
Introduction: Timely data entry into patient registries is foundational to learning health systems such as the Cystic Fibrosis Learning Network. The US Cystic Fibrosis Foundation Patient Registry (CFFPR) is an established registry that collects encounter data for clinical and research activities. Coordinators manually enter approximately 1,500 encounters annually at our institution, but there is limited evidence for interventions facilitating timely data entry. Our institution aimed to reduce the number of days between a clinical encounter and data entry into the CFFPR from an average of 43 days (range 0 to 183 days) to less than 30 days in a 3-month interval. Methods: Data coordinators tested interventions to address barriers in four themes: accountability, work burden, communication, and visibility using plan-do-study-act cycles. We used statistical process control charts to assess progress on average time of entry. Coordinators provided feedback about acceptability and satisfaction for process changes. Results: Initial interventions standardized process and reduced average time to data entry from 42.6 to 22.5 days in 3 months, but this process was not stable in the subsequent 6 months. Subsequent changes to increase metric visibility and improve team communication increased stability and decreased the average time to data entry to 23.0 days. Coordinators reported high satisfaction with process changes and have sustained improved time for over 2 years. Conclusions: This quality improvement project reduced and maintained data entry time by addressing significant barriers without additional personnel. Increased access to near real-time data in CFFPR accelerates learning for clinical care, quality improvement, and research.
Introduction: In Snohomish County, WA, the time from obtaining a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and initiating contact tracing is 4-6 days. We tested whether emergency department (ED)-based contact tracing reduces time to initiation and completion of contact tracing investigations. Methods: All eligible coronavirus disease 2019 (COVID-19)-positive patients were offered enrollment in this prospective case-control study. Contact tracers were present in the ED from 7 AM to 2 AM for 60 consecutive days. Tracers conducted interviews using the Washington State Department of Health’s extended COVID-19 reporting form, which is also used by the Snohomish Health District (SHD). Results: Eighty-one eligible SARS-CoV-2 positive patients were identified and 71 (88%) consented for the study. The mean time between positive COVID-19 test result and initiation of contact tracing investigation was 111 minutes with a median of 32 minutes (range: 1-1,203 minutes). The mean time from positive test result and completion of ED-based contact tracing investigation was 244 minutes with a median of 132 minutes (range: 23-1,233 minutes). In 100% of the enrolled cases, contact tracing was completed within 24 hours of a positive COVID-19 test result. For comparison, during this same period, SHD was able to complete contact tracing in 64% of positive cases within 24 hours of notification of a positive test result (P < 0.001). In the ED, each case identified a mean of 2.8 contacts as compared to 1.4 contacts identified by SHD-interviewed cases. There was no statistically significant difference between the percentage of contacts reached through ED contact tracing (82%) when compared to the usual practice (78%) (P = 0.16). Conclusion: When contact tracing investigations occur at the point of diagnoses, the time to initiation and completion are reduced, there is higher enrollment, and more contacts are identified.
