UCSF Benioff Children's Hospital

Mucopolysaccharidoses (MPSs) are characterized by deficient activity of lysosomal hydrolase enzymes, leading to progressive accumulation of glycosaminoglycans. These glycosaminoglycans can be assayed in biofluids as potential markers of disease severity and response to disease-modifying therapies. This study sought to calculate control reference intervals in a largely pediatric population for key MPS biomarkers: heparan sulfate (HS) and dermatan sulfate (DS) in cerebrospinal fluid (CSF) and urine, and CSF monosialic gangliosides GM2 and GM3. We also explored the effect of age on biomarker levels. Biomarker levels were measured using liquid chromatography-tandem mass spectrometry in CSF and urine samples from pediatric and young adult donors and were compared with baseline CSF and urine biomarker levels from an ongoing Phase 1/2 study of children with MPS II. Age-specific reference intervals were estimated for CSF HS, DS, and GM2, and for urine HS, DS, and the sum of HS and DS, after observing that levels of these markers decreased with age. CSF GM3 levels were not found to be age dependent, therefore a single reference interval was estimated for the reference population. In patients with MPS II, levels of HS and DS, respectively, were 6- and 7-fold higher in CSF, and 13- and 30-fold higher in urine than the upper reference interval limits. Establishing age-specific reference intervals will help to optimize biomarker use in clinical studies.

Introduction: Bronchiolitis is one of the most common reasons for pediatric intensive care unit (PICU) admission in the U.S., yet it has significant disparities in treatment based on social determinants of health. The purpose of this study was to assess for associations between the Child Opportunity Index (COI) and PICU outcomes in children with bronchiolitis. Methods: Secondary analysis of a multicenter retrospective cohort study including data from 15 PICUs from 1/1/2019-12/31/2020. The dataset was queried for patients 0-2 years of age with bronchiolitis as the primary diagnosis for PICU admission. Patient addresses were mapped to COI 2.0 and assigned to a quintile (very low, low, moderate, high, very high). Demographics and clinical features were compared by COI quintile. Primary outcomes were severity of illness on presentation via PRISM III score and use of invasive mechanical ventilation (IMV) and noninvasive ventilation (NIV). Secondary outcomes were PICU length of stay (LOS) and mortality. Results: Of 3,671 total admissions, the very low COI group had the highest proportion of admissions (28.1%) and history of prematurity (33%). There was no difference in PRISM III scores across all groups. Paired comparisons of COI groups revealed significantly higher use of NIV in the very high COI group compared to the lowest 3 COI groups (p ≤ 0.008). Both the very high and very low groups had lower rates of intubation compared to low and moderate groups (p ≤ 0.04). Neither PICU LOS nor mortality differed significantly across all groups. Multivariate analysis showed PRISM III score (aOR 2.77, 95% CI 2.34-3.27) and prematurity (aOR 1.32, 95% CI 1.05-1.66) as independent risk factors for any positive pressure ventilation (PPV [both IMV and NIV]), but no difference for COI group. Conclusions: In this study, children admitted to the PICU with bronchiolitis are more often from very low COI neighborhoods. Patients from very high COI neighborhoods are more likely to receive NIV support and less likely to require intubation. Interestingly, patients from the very low COI group are also less likely to need intubation compared to the low and moderate COI groups. Higher PRISM III scores and prematurity were risk factors for PPV use, but COI group was not.

Limited data inform the outcomes of patients with high-risk neuroblastoma (HR-NBL) who relapse after high-dose chemotherapy, autologous stem cell transplantation (ASCT), and external beam radiotherapy (EBRT). This is a multi-institutional retrospective study of 84 patients with HR-NBL diagnosed between 1997-2021 with a first recurrence after definitive upfront treatment, including ≥1 ASCT and EBRT. Site(s) of first relapse were defined with relation to a patient's primary tumor location. Progression-free survival (PFS) and overall survival (OS) outcomes were analyzed using Kaplan-Meier curves and log-rank tests. Cox proportional hazard models were used for univariate and multivariable analyses. Twenty-four patients had local recurrences with or without distant relapses (LR) and 60 had distant relapses only. The LR cohort had higher rates of MYCN amplification (70% vs. 36%, p = 0.016). At relapse, the LR cohort had lower rates of additional radiotherapy (32% vs. 61%, p = 0.029) and higher rates of additional surgery (29% vs. 5%, p = 0.005), with similar rates of chemotherapy for both cohorts. With a median follow-up after first relapse of 1.53 years (range: 0.03-15.82), there were no significant differences in interval PFS and OS between the cohorts. After controlling for age at diagnosis and pattern of recurrence, time to interval relapse ≥ 2 years was a significant predictor of improved OS (HR: 0.50, 95% CI: 0.29-0.85, p = 0.011). Patients with relapsed HR-NBL have poor outcomes with median OS < 2 years. Time to relapse was a significant predictor of OS.

We conducted the PediQUEST Response to the Pediatric Oncology Symptom Experience (PQ Response) randomized controlled trial (RCT) to assess whether combining feedback from an electronic patient-reported outcome (ePRO) system with specialized pediatric palliative care (SPPC) consultation improved health-related quality of life (HRQOL) in children with advanced cancer. This multicenter open-label RCT enrolled children 2 years and older with advanced cancer. The study was conducted between April 2018 and December 2021 at five US tertiary-level pediatric cancer centers. All parents and children 5 years and older answered weekly child HRQOL and symptom surveys over 18 weeks (2-week run-in). Child-parent dyads were assigned (1:1) to PQ Response (n = 74) or usual care (n = 80) for 16 weeks. Primary outcomes were the difference between average 16-week and baseline Pediatric Quality of Life Inventory (PedsQL-4.0) total scores reported by parents and children (range, 0-100; higher = better HRQOL; minimal clinically important difference [MCID], 4.5). Secondary outcomes were PedsQL subscales and symptom scores. Analyses followed an intention-to-treat approach. Of 154 participants randomly assigned, 50% were girls, 78% were White, 17% were Hispanic, and 45% had brain tumors. The mean age was 11 years (standard deviation, 6.1). Parents assigned to PQ Response reported greater improvements in child HRQOL (PedsQL total mean difference 3.45 points [{95% CI, 0.48 to 6.43}; P = .023]; PedsQL physical 4.61 [{95% CI, 0.40 to 8.82}; P = .032]). Children reported similar improvements. Effects did not exceed MCIDs. No improvements were observed in PedsQL-psychosocial or symptom scores. Sensitivity analyses showed consistent effects, with most physical HRQOL scores and several child-reported symptom scores exceeding MCIDs. We observed site-specific variability. At the site with the largest adherence, all effects exceeded MCIDs. No adverse events reported. Findings suggest benefits of integrating electronic patient-reported outcome feedback and SPPC into pediatric advanced cancer care. Enhanced implementation strategies are needed to optimize clinical impact.

Prolonged pediatric fever is most often due to a self-limiting infectious illness, but can sometimes be a sign of much more serious disease. The care of children with prolonged fever can be challenging, since there is significant variation in the definition of prolonged pediatric fever, and evidence-based decision support tools to guide evaluation and management of children with prolonged fever are limited. This issue constructs a framework for initial emergency department evaluation and management of children with fever lasting ≥5 days and fever of unknown origin lasting ≥8 days.

Racial inequities in hospital-based care for Black adults are well-documented, yet the mechanisms by which interpersonal and institutional racism contribute to these inequities remain poorly understood. Non-clinician hospital staff, such as patient care assistants, spend significant time with patients and are often members of minoritized communities, yet their perspectives on racism in the hospital are rarely studied. To investigate non-clinician staff members' perspectives on how interpersonal and institutional racism affect hospital-based care for Black adult patients. Qualitative study using in-depth, semi-structured interviews and community-based participatory research principles. Fifteen hospital staff members (patient care assistants, custodians, transporters, and ward clerks) from a large, urban, academic medical center on the West Coast. Participants self-identified as Black (27%), Hispanic (20%), and/or Asian (53%). Semi-structured interviews explored respondents' perspectives on racism in the hospital. Interviews were analyzed using thematic analysis. A Community Advisory Board of eight Black individuals provided feedback and member checking. Five themes emerged from the data: (1) staff members experienced workplace racism; (2) racial stereotypes appeared to contribute to inequitable care for Black patients; (3) institutional factors, such as inadequate staffing, were felt to contribute to inequitable care; (4) individual factors, such as going "above-and-beyond" job responsibilities, helped mitigate inequitable care; and (5) institutional diversity, equity, and inclusion (DEI) interventions received mixed appraisals, with staff often excluded from initiatives. Inequities in hospital-based care for Black patients may have roots in complex interactions between individual biases, workplace discrimination, institutional factors, and systemic underinvestment in non-clinician staff. Respondents perceived that institutional factors, such as inadequate staffing and demanding workloads, amplified racist beliefs, resulting in inequitable care for Black patients. Hospitals should invest in non-clinician hospital staff and address structural factors impeding staff members' ability to provide equitable care to all patients.