Children's Hospital of Pittsburgh

OBJECTIVE:To assess the 2022 American College of Rheumatology (ACR)/EULAR classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in children with chronic small-to-medium vessel vasculitis. METHODS:A cohort of 574 patients, identified by physician's diagnosis (MD-diagnosis) in A Registry of Childhood Vasculitis, was classified by computation of registry data as having granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic GPA after applying (1) ACR/EULAR AAV criteria and (2) pediatric-adapted European Medicines Agency (Ped-EMA) classification algorithm (incorporating Ankara GPA criteria). Venn diagrams compared the resulting GPA and MPA cohorts with MD-diagnosis. Sensitivity and specificity of criteria for GPA were evaluated against MD-diagnosis. Fisher exact test evaluated differences in the frequencies of individual clinical features in GPA versus MPA. RESULTS:Comparing ACR/EULAR criteria against the Ped-EMA algorithm for classifying AAV, more patients were classified as GPA or MPA (n = 396 vs 360, respectively), fewer had GPA (n = 261 vs 288, respectively), more had MPA (n = 135 vs 72, respectively), and fewer GPA cases coclassified as MPA (12% vs 28%, respectively); there were more differences between GPA and MPA in Pediatric Vasculitis Activity Score-defined clinical features (n = 14 vs 10, respectively). When classifying GPA by ACR/EULAR or Ankara criteria, sensitivity (74.5% vs 72.1%, respectively) was comparable, and specificity for ACR/EULAR criteria (93.9% vs 79.9%, respectively) was improved. CONCLUSION:The 2022 ACR/EULAR classification criteria for AAV perform at least as well as previous pediatric criteria and provide categorical MPA criteria where none existed previously; the criteria for GPA and MPA now specifically differentiate each other, with more differences between them in the frequencies of clinical features. Our findings support the preferential use of ACR/EULAR over Ankara criteria for GPA in pediatrics.

Children, adolescents, and young adults with congenital heart disease (CHD) frequently experience disruptions in neurodevelopment affecting their executive functioning and other cognitive abilities, which in turn can impact academic performance, psychosocial adjustment, and overall quality of life. This exploratory study aims to investigate the impact of CHD on functional brain network connectivity and cognitive function, with a particular focus on executive functioning. Rather than relying on a single network construction method or arbitrary thresholds, our study methodically employed both weighted networks and binarized networks generated using absolute and proportional thresholding. This cross-method approach enables us to identify functional connectivity features that persist across heuristically and arbitrarily defined parameters, and to evaluate their association with neurocognition. Using resting-state fMRI data, we examined several network metrics across brain regions using three network construction types: weighted networks, absolute-threshold binarized networks, and proportional-threshold binarized networks. Regression models were then fit to neuropsychological test scores using metrics obtained from each network construction approach. Our results identified differences in network connectivity with a predilection for temporal, occipital, and subcortical regions, across both weighted and binarized networks. Furthermore, we identified distinct correlations between network metrics and cognitive performance, suggesting potential compensatory mechanisms within specific brain regions. These results provide an initial, methodologically transparent characterization of altered network organization in CHD and offer directions for future hypothesis-driven investigations.

BACKGROUND:Despite advances in treatments, children with type 1 diabetes struggle to achieve glycemic targets. Though school-based programs may help support families to achieve targets, challenges remain with coordinating care between health systems and schools, where students spend much of their day. Monthly, virtual meetings between a parent, school nurse, and a diabetes specialist may bridge this gap by using a shared treatment plan to meet goals. METHODS:This is a pilot cluster-randomized trial to test a school-partnered collaborative care model (SPACE for T1D) for children aged 5-12 years with type 1 diabetes for ≥6 months. School districts were randomized in a 2:1 allocation ratio to the intervention (SPACE for T1D) or enhanced usual care. Participants complete the study over four consecutive months. Parents and school nurses evaluate the feasibility, acceptability, appropriateness, and usability of SPACE using valid questionnaires. The study team monitors retention, fidelity, and practicality. Exploratory outcomes assess change in glycemia, care utilization, type 1 diabetes-related quality of life, self-efficacy skills, and missed class time due to diabetes interventions. RESULTS:Twelve school districts were randomized. One dropped out due to no eligible students, leaving 11 participating districts. We approached 46 students; 30 provided consent for a recruitment rate of 65%. CONCLUSIONS:This study will evaluate the feasibility and acceptability of the SPACE for T1D intervention in varied school districts. Findings will facilitate a fully-powered trial to evaluate the impact on health and academic outcomes, adding to the evidence base of school-based interventions to support youth with chronic disease. NCT: NCT06420661.

BACKGROUND:Sentinel lymph node (SLN) biopsy is a critical staging tool in skin and soft tissue cancers. Although technetium lymphoscintigraphy is the most common adjunct, indocyanine green (ICG) demonstrates a promising alternative in pediatric, adolescent, and young adult (AYA) skin and soft tissue cancers. METHODS AND OBJECTIVES:Evaluate the safety and efficacy of ICG in SLN biopsy (SLNB) in diverse pediatric and AYA solid cancers in a multi-institutional environment. This is a prospective, observational study conducted at 13 member institutions in the Pediatric Surgical Oncology Research Collaborative between 2019 and 2023. Eligible patients underwent SLNB for primary or recurrent solid skin and soft tissue tumors. Peritumoral ICG was administered intraoperatively. Outcomes included SLN detection rates, histopathology of excised specimens, and surgeon-reported assessment of utility. Safety was assessed through adverse event reporting. RESULTS:Forty SLNB procedures yielded 84 specimens: 13 melanoma (32.5%), 12 squamous cell carcinoma (30%), 11 non-rhabdomyosarcoma soft tissue sarcoma (27.5%), two rhabdomyosarcoma (5%), one Ewing sarcoma (2.5%), and one malignant peripheral nerve sheath tumor (2.5%). Histologic evaluation identified 81 lymph nodes, 75 benign (89.3%) and six malignant (7.1%); three specimens were adipose tissue (3.6%). Of 81 lymph nodes, 76% were ICG-positive. ICG had a sensitivity of 79.5%, a specificity of 33%, and a positive predictive value of 96%. All malignant nodes were ICG-avid. There were no adverse reactions to ICG at 30 days. CONCLUSIONS:ICG is a safe and effective adjunct for SLNB in pediatric and AYA soft tissue and skin malignancies.

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to impact overall survival (OS). The influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium (PIDTC) from 1990-2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced intensity regimens were associated with lower T cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hotspot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS following HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This study was registered at www.clinicaltrials.gov as #NCT02064933.