Hasbro Children's Hospital

Introduction: Pediatric extra-corporeal membrane oxygenation (ECMO) is an advanced therapy offered by few centers. Often, patients with severe cardiopulmonary failure undergo urgent transfer from pediatric intensive care units (PICUs) to an ECMO center for potential cannulation. Given the risks associated with ECMO and transport, it is crucial to identify patients most likely to benefit from transfer and ECMO support. Our objective was to determine the rates of and factors contributing to receipt of ECMO and survival of children urgently transferred to an ECMO center. Methods: We performed a multicenter retrospective cohort study of patients 0-18 years referred by 5 PICUs to a pediatric ECMO center in the U.S. Northeast from 2013-2022. We excluded patients already on ECMO at referral and those referred for procedures needing ECMO back-up (not imminently requiring support). Patients’ records were linked across referring PICUs and the ECMO center. We collected demographic data, referral/transfer characteristics, clinical data at various timepoints, and patient outcomes. Results: Preliminary results from completed reviews of 37 records showed that 36 (97%) referred patients were transferred to the ECMO center. One patient did not transfer due to clinical improvement. Mean referral time from PICU admission was 2.3 (SD 3.2) days and transfer occurred at a median of 6.5 (IQR 4.9, 8.6) hours from initial referral. Eight (22%) patients were cannulated onto ECMO at a median of 8.4 (IQR 4.4, 13.9) hours from ECMO center admission. Six (17%) patients died, all after transfer to the ECMO center, including 4 (50%) patients placed on ECMO. Unadjusted analysis showed that patients who received ECMO support were older (median 1.5 vs. 0.5 years), and at transfer, were more severely ill (median PRISM-III score 19.5 vs. 9) with greater life support needs (median OI 12.1 vs. 8.9 and median VIS 10 vs. 7.5). Conclusions: In a regional pediatric ECMO referral network, 22% of referred patients subsequently received ECMO support, with a 17% mortality rate among all referred patients. Factors associated with ECMO cannulation will be determined using cluster analysis once data for the entire cohort is complete. Findings can potentially inform ECMO referral and transfer practices across a referral network.

Medical illustration has played a crucial role through the history of modern medicine. When, with the advent of asepsis and anesthesia, complex surgery became possible, surgeons needed illustrators to describe their exploits, and hand-drawn figures were far clearer than early photographs. Today's high-definition image capture is often still not as useful as medical illustrations: rather than faithfully representing reality, medical illustration aims to inform and teach - to be didactic. It does not even have to be high art: we "all" draw in our daily practice, and we can all hone our visual communication skills.

This study evaluated the extent to which the sleep is disrupted by nighttime awakenings in urban children with and without asthma and examined racial/ethnic differences in sleep outcomes. Three hundred and seventy-nine urban children aged 7 to 9 years with (n = 250) and without (n = 129) asthma were included. Participants were 45% Latino, 34% black, and 21% non-Latino white (NLW). Nighttime awakenings were assessed via actigraphy. Asthma status was assessed by a clinically and via self-report. Children with asthma had significantly more awakenings than those without. Latino children with asthma had more and longer awakenings compared to Latino children without asthma; these effects were not observed among black or NLW participants. Poor asthma control was associated with more awakenings. Urban children face higher risks for poor sleep and asthma outcomes. Multicomponent interventions addressing asthma management and culturally tailored sleep hygiene strategies are necessary to improve asthma and sleep outcomes in this highly burdened population.

Background: The best treatment for children with KD who fail to respond to the first dose of IVIG (refractory KD) is currently unknown. The purpose of this study was to determine treatment practices of pediatric rheumatologists in North America who manage IVIG-refractory KD. Methods: A 34-item web-based survey was sent to 102 randomly selected members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The anonymous survey addressed the use of primary intensification as well as the treatment of IVIG-refractory KD. Results: The response rate was 82%; 56% (all pediatric rheumatologists) completed the survey. Primary intensification was used for macrophage activation syndrome (MAS), KD shock, and those at high risk for coronary artery aneurysms (CAAs) by 84%, 76% and 52% of responders, respectively, with corticosteroids (CSs) used most frequently. For IVIG-refractory KD without CAA, a second dose of IVIG was used most often (63% alone; 23% plus CS). With non-giant CAAs, only 15% used a second IVIG alone, 40% used IVIG plus CS, and 35% took infliximab, usually with CS/IVIG. With giant CAA, treatments used most frequently were CS, a second IVIG, and infliximab (91%, 69%, and 58%, respectively), usually as combinations of two or more medications. Conclusions: Treatment of IVIG-refractory KD varies significantly among North American pediatric rheumatologists, particularly in the presence of CAAs. Our findings emphasize the need for research to identify the most effective therapy for this KD subgroup. The current use of primary intensification and the presence and size of the CAA will need to be considered as consensus treatment plans are developed.

IntroductionThe rise of antibiotic-resistant infections worldwide has created a need to enhance the efficacy of existing antibiotics. Modification of metabolism has been shown to potentiate antibiotic lethality. In this study, we employed a novel ex vivo microbiome culture approach to study the effects of different forms of iron on amoxicillin susceptibility.MethodsSynthetic and human stool-derived microbiota were cultured and treated with amoxicillin, with growth monitored by optical density. These samples were sequenced using an Oxford nanopore long-read 16S rRNA V4–V9 approach and computationally defined using the Emu algorithm. The validity of this pipeline was confirmed with consortia, murine cecal content, and a human stool sample. The stool-derived community was then cultured for 24 h with ranging concentrations of either hemin, FeSO4, or FeCl3 and concurrent amoxicillin dosage, then profiled to identify the effects of different forms of iron on amoxicillin susceptibility.ResultsAlpha diversity, beta diversity, and normalized relative abundances confirmed the efficacy of the selected ex vivo pipeline, allowing for ~77% species retention over 24 h. Treatment of communities with hemin protected Bacteroides, Escherichia-Shigella, Parabacteroides, and Parasutterella against amoxicillin, while two forms of free iron did not.DiscussionThis ex vivo pipeline enables reproducible assessment of how metabolic modulators like hemin alter amoxicillin susceptibility, highlighting a link between iron-sequestering genera and antibiotic-protection. Future mechanistic insights may support hemin-based strategies to boost antibiotic efficacy.

e22007 Background: CBFA2T3::GLIS2 (CBF/GLIS2) rearranged AML is a highly refractory AML subtype arising in infants and young children. The CBF/GLIS2 fusion is associated with overexpression of FRα. Luveltamab tazevibulin (luvelta) is an anti–FRα-targeting antibody-drug conjugate with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR = 4), which induces cytotoxic and immunologic cell death. Since 2021, luvelta was used alone or in combination with AML therapy to treat children with CBF/GLIS2 AML in the context of a compassionate use program. Data from the first 25 children were reported in December 2023 Blood 142 (Supplement 1): 4295. These children represent a heterogenic group with varying prior treatments and disease burden. They included 17 children who started luvelta with ≥5% bone marrow (BM) blasts and 8 children who had < 5% BM blast with persistent MRD positivity. Luvelta was mostly given at doses of 4.3 or 5.2 mg/kg every 2-4 weeks (4 received fractionated doses on days 1, 3, 5 per cycle). Out of 25 children, 21 received ≥ 1 dose of monotherapy initially, while 4 received combination with AML chemotherapy. All participants were followed for long-term survival. Objectives: Determine long-term overall survival (OS) in the first 25 children who received luvelta for CBF/GLIS2 AML. Methods: All clinical data was reported by compassionate use Investigators. OS was calculated from the date of the first dose of luvelta. Results: As of July 15, 2024, 7 of 25 children were alive, with a median OS of 8.8 months (95% confidence interval [CI] 5.3 -20.4). Among the 7 surviving children, 2 received luvelta as monotherapy while 5 received luvelta in combo either from the beginning of treatment or after failing monotherapy. Most of the deaths occurred in children who did not respond (N = 11) or recurred after luvelta (N = 5); two occurred post-transplant, 1 from progression and 1 from infection. Median OS was 9.7 months (95% CI 5.7-29.8) in the 21 children who received non-fractionated doses every 2 to 4 weeks. Overall, MRD negativity was achieved in 10 of the 25 children: the median OS was 29.8 months (95% CI 6.2-Not Reached [NR]) in those who became MRD negative and 5.3 months (95% CI 1.5-8.6) in those who did not. Nine children received hematopoietic stem cell transplants after morphologic and/or molecular response to luvelta. Post transplant median OS was 22.1 months (95% CI 1.8-NR). Five children received post-transplant maintenance. Conclusions: Luvelta alone or in combination with AML chemotherapy could achieve MRD negativity in more than one third of CBF/GLIS2 AML patients, allowing transplant and resulting survival of more than 2 years. Additional children have received luvelta through compassionate use since 2023 and the pivotal phase 1/2 trial for these patients is now open and enrolling (clinicaltrials.gov NCT06679582).

Background: Both tibial spine fractures (TSFs) and anterior cruciate ligament (ACL) tears result in functional loss of knee stability. Nonetheless, it remains unclear why some patients sustain ACL tears, whereas others have TSFs. Purpose: To identify the common morphological risk factors for pediatric ACL tears and TSFs and to determine the morphological differences between them using multiplanar reconstruction of magnetic resonance imaging (MRI). Study Design: Cohort study; Level of evidence, 3. Methods: Age- and sex-matched participants (159 total [53 ACL tears, 53 TSFs, and 53 controls]) aged <18 years who visited a pediatric tertiary-care center for ACL tears, TSFs, or anterior knee pain from March 2009 to April 2023 were included. Each group comprised 41 male and 12 female participants. Data on demographic characteristics and estimated bone age based on the knee MRI atlas were retrospectively collected, and various knee morphological parameters were evaluated using multiplanar reconstruction of MRI. Parameters showing significant differences among the 3 groups were selected as independent variables for multivariable multinomial logistic regression analysis, with the groups as dependent variables. Results: The mean chronological age at the time of MRI was 13.2 ± 2.3 years. Height, weight, body mass index, bone age, articular medial tibial slope, and bony medial tibial slope did not differ among the groups. Articular lateral tibial slope was independently associated with the occurrence of both ACL tears (relative risk ratio [RRR], 1.42 [95% confidence interval (CI), 1.16-1.74]; P = .001) and TSFs (RRR, 1.33 [95% CI, 1.10-1.62]; P = .004). A high notch width index was a protective factor against ACL tears (RRR, 0.86 [95% CI, 0.77-0.96]; P = .006) but not against TSFs (RRR, 1.01 [95% CI, 0.91-1.12]; P = .848). Conclusion: A high articular lateral tibial slope was a common risk factor for ACL tears and TSFs. Patients with ACL tears had a narrower intercondylar notch than those with TSFs and controls.