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OBJECTIVE Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm 3 ; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm 3 had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm 3 (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80–0.99; p = 0.036). CONCLUSIONS In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.

Abstract Newer approaches to control alloreactivity may produce similar transplant outcomes using HLA-mismatched donors vs HLA-matched unrelated donors (MUD). However, prospective comparisons are lacking. BMT CTN 1702 used a donor search prognosis score to assign patients to an 8/8 HLA MUD or the center’s preference of haploidentical related donors (HAPLO), mismatched unrelated donors (MMUD), or umbilical cord blood (UCB). Outcomes of MUD were compared to HAPLO, MMUD, and UCB transplantation after adjusting for covariates. Patients (n = 1179 [93% adults]) underwent transplantation with MUD (n = 772), HAPLO (n = 254), MMUD (n = 112), and UCB (n = 41) at a median of 3.7, 3.4, 3.9, and 3.8 months from enrollment. Posttransplant cyclophosphamide (PTCy) was used in 23.9%, 83.9%, 65.2%, and 0% of MUD, HAPLO, MMUD, and UCB. In multivariate analyses, compared to MUD, survival was lower for UCB (hazard ratio [HR], 2.65; P&lt; .001) but not statistically different for HAPLO and MMUD (HRs, 1.08 and 1.18, respectively). Relapse risk was not significantly different by donor, but treatment-related mortality (HR, 3.31; P&lt; .001) and disease-free survival (HR, 1.99; P = .002) were inferior for UCB but not different for HAPLO and MMUD than MUD. In patients who received PTCy, HAPLO and MMUD were associated with increased grade 3 or 4 acute graft-versus-host disease (GVHD; HR, 2.39 [P = .017] and 2.53 [P = .038], respectively) and chronic GVHD (HR, 1.71 for both; P = .028 and .080) than MUD, but other outcomes were not different. HAPLO or MMUD may be used to expedite transplantation when finding MUD is unlikely. This study was registered at www.clinicaltrials.gov as NCT03904134.

Abstract The lung, one the largest branching organs in our body and vital for survival at first breath, is commonly known as the gas-exchange organ. Recent novel findings on lung sensing cells, molecules, and lung-brain crosstalk in the emerging discipline of interoception have highlighted the consideration of the lung as a sensory organ. Acknowledging the central importance of lung sensing to human health and disease, NHLBI convened a workshop to synthesize the past, current, and future of lung sensing research, with in-person presentations by ∼20 interdisciplinary experts and a large virtual audience. Here, we highlight the key topics discussed and summarize a blueprint for the future in this important field.

Abstract Background Point-of-care testing (POCT) has expanded rapidly across healthcare systems, increasing both program scale and operational complexity. However, quantitative benchmarking data describing how POCT programs are structured and supported across institutions remain limited. Methods We conducted a cross-sectional survey to characterize POCT program support, including program scope, staffing, operational practices, governance, and challenges. The survey was distributed electronically through professional networks, and 93 institutional responses were analyzed. Descriptive analyses were performed, and derived metrics, including sites per point-of-care testing coordinator (POCC), were used to evaluate the relationship between program scale and staffing. Results POCT programs demonstrated substantial variability in scale, with wide ranges in the number of testing sites and operator populations. Adoption spanned multiple test categories, and many institutions reported use of multiple platforms for the same assays. Training, competency assessment, and quality management activities were primarily supported by laboratory staff and POCCs, with documentation frequently partially electronic. Median POCC staffing increased with program size; however, sites per POCC also increased significantly across program scale tiers (Kruskal–Wallis P &lt; 0.001). Governance structures and operational responsibilities varied across institutions, and common challenges included staffing limitations, training and compliance burden, multisite coordination, and IT/connectivity constraints. Conclusions POCT programs are expanding in scale and complexity, but workforce capacity and governance structures have not scaled proportionally. This mismatch creates a cumulative and multiplicative operational burden. These findings provide benchmarking data to inform scalable staffing models, governance strategies, and infrastructure development for sustainable POCT program management.

Objectives: The electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD) trial is a multisite study evaluating the effectiveness of ECT for severe agitation in individuals with advanced dementia. Given that participants lack decisional capacity because of advanced cognitive impairment, the trial required a structured and ethically sound approach to obtaining informed consent and assent across jurisdictions with differing legal requirements, including Massachusetts, New York, Georgia, Minnesota, and Michigan. This paper describes the approach used in the study. Methods: We describe the consent framework developed for the ECT-AD trial, including procedures for identifying legally authorized representatives, complying with state-specific laws for ECT consent, obtaining surrogate consent for research participation, and assessing patient assent and dissent using a standardized tool. Conclusions: The approach used in this study may serve as a practical model for future research involving individuals without decision-making capacity and legally complex interventions such as ECT.