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PURPOSE On the basis of the results of the ZUMA-3 trial, brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, gained US Food and Drug Administration approval in October 2021 for adults with relapsed/refractory (R/R) B-cell ALL (B-ALL). We report outcomes of patients treated with brexu-cel as a standard therapy. METHODS We developed a collaboration across 31 US centers to study adults with B-ALL who received brexu-cel outside the context of a clinical trial. Data were collected retrospectively from October 2021 to October 2023. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). RESULTS At the time of data lock, 204 patients had undergone apheresis and 189 were infused. Median follow-up time was 11.4 months. Forty-two percent of patients received brexu-cel in morphologic remission and would have been ineligible for participation in ZUMA-3. After brexu-cel, 151 achieved complete remission (CR), of which 79% were measurable residual disease (MRD) negative remissions. Median progression-free survival (PFS) was 9.5 months and median overall survival was not reached. Grade 3-4 CRS or ICANS occurred in 11% and 31%, respectively. In multivariable analysis, patients receiving consolidative hematopoietic cell transplantation (HCT; hazard ratio, 0.34 [95% CI, 0.14 to 0.85]) after brexu-cel had superior PFS compared with those who did not receive any consolidation or maintenance therapy. CONCLUSION Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation after brexu-cel resulted in improved PFS.

BACKGROUND: Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function. METHODS: We investigated 1053 study participants in PVDOMICS (Redefining Pulmonary Hypertension Through the PVD Phenomics Program) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance severity. Right heart chamber size and function were qualitatively assessed using a percentile-based approach above the median values to create a clinical grading system for right heart adaptation. The relationship between echocardiographic categories and all-cause mortality was examined using survival analyses adjusted for potential confounders. RESULTS: A stepwise increase in adverse right heart remodeling was observed with a concomitant decrease in functional parameters by pulmonary vascular resistance strata ( P <0.001 for all). Mild, moderate, and severe categories of right heart chamber size and dysfunction were defined using a percentile-based approach across the spectrum of PVD. During a median follow-up of 2.07 years (interquartile range, 1.23–3.01 years), 130 participants died (11.4%). Progressive pulmonary vascular resistance increase and 2DE evidence of right heart dysfunction inclusive of fractional area change, and right ventricular global longitudinal strain were independently associated with increased all-cause mortality risk in multivariate analysis adjusted for age, disease duration, and male sex. CONCLUSIONS: In this well-characterized sample of adults with diverse etiologies and varying PVD severity, we define categories of abnormal right heart chamber size and function. Further, we demonstrate a stepwise relationship between these categories of abnormal morphology and function and all-cause mortality. Defining grades of right ventricular dysfunction in individuals with known PVD has important clinical implications for monitoring disease progression and response to therapies.

AbstractINTRODUCTIONRecent technological advances have increased the risk that de‐identified brain images could be re‐identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de‐identified brain imaging, who quickly acted to protect participants’ privacy.METHODSAn independent expert committee evaluated 11 face‐deidentification (“de‐facing”) methods and selected four for formal testing.RESULTSEffects of de‐facing on brain measurements were comparable across methods and sufficiently small to recommend de‐facing in ADNI. The committee ultimately recommended mri_reface for advantages in reliability, and for some practical considerations. ADNI leadership approved the committee's recommendation, beginning in ADNI4.DISCUSSIONADNI4 de‐faces all applicable brain images before subsequent pre‐processing, analyses, and public release. Trained analysts inspect de‐faced images to confirm complete face removal and complete non‐modification of brain. This paper details the history of the algorithm selection process and extensive validation, then describes the production workflows for de‐facing in ADNI.Highlights ADNI is implementing “de‐facing” of MRI and PET beginning in ADNI4. “De‐facing” alters face imagery in brain images to help protect privacy. Four algorithms were extensively compared for ADNI and mri_reface was chosen. Validation confirms mri_reface is robust and effective for ADNI sequences. Validation confirms mri_reface negligibly affects ADNI brain measurements.

Goals: To determine long-term efficacy and safety of tCS for treatment of EoE. Background: Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed. Study: This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS. Results: Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence; P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy). Conclusions: Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE.

Purpose: The goal of this study was to develop a lot release assay for iPSC residuals following directed differentiation of iPSCs to retinal pigment epithelial (RPE) cells. Methods: RNA Sequencing (RNA Seq) of iPSCs and RPE derived from them was used to identify pluripotency markers downregulated in RPE cells. Quantitative real time PCR (qPCR) was then applied to assess iPSC residuals in iPSC-derived RPE. The limit of detection (LOD) of the assay was determined by performing spike-in assays with known quantities of iPSCs serially diluted into an RPE suspension. Results: ZSCAN10 and LIN28A were among 8 pluripotency markers identified by RNA Seq as downregulated in RPE. Based on copy number and expression of pseudogenes and lncRNAs ZSCAN10 and LIN28A were chosen for use in qPCR assays for residual iPSCs. Reverse transcription PCR indicated generally uniform expression of ZSCAN10 and LIN28A in 21 clones derived from 8 iPSC donors with no expression of either in RPE cells derived from 5 donor lines. Based on qPCR, ZSCAN10 , and LIN28A expression in iPSCs was generally uniform. The LOD for ZSCAN10 and LIN28A in qPCR assays was determined using spike in assays of RPE derived from 2 iPSC lines. Analysis of ΔΔC t found the limit of detection to be <0.01% of cells, equivalent to <1 iPSC/10,000 RPE cells in both iPSC lines. Conclusions: qPCR for ZSCAN10 and LIN28A detects <1 in 10,000 residual iPSCs in a population of iPSC-derived RPE providing an adequate LOD of iPSC residuals for lot release testing.

Summary Cannabis use is becoming increasingly common, both for recreational and medical purposes. However, there is a paucity of data regarding cannabis use in the context of eosinophilic esophagitis (EoE). We aimed to determine the impact of cannabis use on presentation and treatment response in EoE. To this end, we conducted a retrospective cohort study at a large academic medical center of newly diagnosed EoE patients age ≥ 12 years. Self-reported cannabis use status, baseline characteristics, and treatment response to topical corticosteroids and dietary therapy data were extracted. Bivariate and multivariable analyses were used to compare cannabis users and non-users at time of EoE diagnosis and to assess treatment response. Of 983 EoE patients, 80 reported using cannabis, with the majority reporting daily use and administration by inhalation. Baseline symptoms and peak eosinophil count were similar between cannabis users and non-users; cannabis users were less likely to have baseline endoscopic findings of exudates, edema, and stricture, and lower total Endoscopic Reference Score. On multivariable analysis, younger age, male sex, non-White race, and psychiatric diagnosis were independently associated with history of cannabis use at EoE presentation and stricture was independently associated with cannabis non-use. Post-treatment symptom and histologic responses were similar between cannabis users and non-users though there was a higher odds of post-treatment endoscopic inflammatory features with cannabis use. In conclusion, despite presenting with milder initial endoscopic findings, cannabis users exhibited greater inflammatory findings after treatment, highlighting a potential negative influence of cannabis use on EoE management.