15th Annual Pediatrics Research Retreat

The Neuroscience of Pediatric Brain Cancer
Michelle Monje-Deisseroth, MD, PhD - Milan Gambhir Professor of Pediatric Neuro-Oncology and Professor, by courtesy, of Neurosurgery, of Pediatrics, of Pathology and of Psychiatry and Behavioral Sciences

In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Concordantly, neuronal activity robustly promotes progression of both high-grade and low-grade glioma subtypes in preclinical models. Crucial mechanisms mediating activity-regulated glioma growth include paracrine secretion of BDNF and the synaptic protein neuroligin-3 (NLGN3). NLGN3 induces multiple oncogenic signaling pathways in the cancer cell, and also promotes glutamatergic synapse formation between neurons and glioma cells. Glioma cells integrate into neural circuits through neuron-to-glioma synapses that exhibit mechanisms of malignant synaptic plasticity. This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. Thus, both paracrine and synaptic neuron-glioma interactions play important roles in the pathogenesis of glial cancers, highlighting a number of potential therapeutic opportunities. The subversion of mechanisms of neurodevelopment and plasticity by malignant gliomas underscores the importance of understanding the neuroscience of brain cancer. Similar mechanisms of neuron-cancer interactions are increasingly appreciated in brain metastases and in cancers outside of the CNS; nervous system-cancer interactions are now emerging a new hallmark of cancer.

Improving the Launch: Kangaroo Care for Children Born Very Preterm
Heidi Feldman, MD, PhD - Professor, Developmental and Behavioral Pediatrics
Approximately 50% of survivors of preterm birth experience mild to severe neurodevelopmental disorders. Improving outcomes of prematurity is thus a public health imperative. In a series of retrospective studies of survivors of prematurity from the LPCH NICU, we asked whether a developmental care practice--skin-to-skin holding, also known as Kangaroo care--would be associated with indices of neurodevelopment: (1) features of the white matter circuits in the brain from near-term diffusion MRI scans and (2) the infant's developmental test scores at age 12 months. We found convincing evidence that the amount of skin-to-skin holding related to long-term neurodevelopment outcomes after very preterm birth.

The Current State of School-Based Sexual Education in California - Perspectives of Parents & Educators
Lauren Rivkin, MD - Resident, Stanford Pediatrics Residency Program
California has been heralded as a leader in the realm of school-based sexual education since the enactment of the California Healthy Youth Act (CHYA) in 2016, a policy that mandates comprehensive sexual education (CSE) in the state’s public and charter schools. Through community-based participatory research, we elicited parent and educator perceptions of current school-based CSE, ranging from stigmatization of certain teaching topics to inconsistencies in the curriculum structure. The findings provide important insight into how the pediatric community can better support effective implementation of CSE.

Organoid Model of Neonatal Brain Hypoxic Injury Uncovers Circadian Regulation of Synapse Pruning in Astrocytes
Li Li, MD, PhD - Postdoctoral Scholar, Neonatal & Developmental Medicine
During perinatal and early postnatal stage, primitive cortical network forms and neural circuits start assembling. Hypoxia exposure during this period is a common environmental factor that confers susceptibility to neuropsychiatric disorders such as Autism Spectrum Disorders (ASD). Using a cellular model of hypoxia brain injury based on human stem cell-derived brain organoids, we identified that astrocytes, a critical cell type for shaping neuronal network through phagocytosing synapses, are impacted by hypoxia through disrupting their cellular circadian clock.

Neonatal Intubation:  Lost Art or Missing Science?
Lou Halamek, MD - Professor, Neonatal & Developmental Medicine
Intubation is both a lifesaving and a life-threatening technical intervention in the neonate. Numerous publications in the past two decades have documented declining success rates among healthcare professionals performing this procedure and associated adverse sequelae in patients. Historically, intubation has been described and assessed by highly subjective (“feel”) and relatively crude objective (“in” or “out”) criteria. This reliance on subjective rather than sophisticated objective performance markers severely impairs both the initial acquisition and the maintenance of this critically important skill. Dr. Halamek and the team at CAPE have created a highly standardized simulated clinical environment that minimizes confounding variables and facilitates the acquisition quantitative data via:

1. Four-angle high-resolution video documentation of variations in manual technique
2. Measurement of force and torque used
3. Motion tracking of fingers and hands in relationship to the simulated patient
4. Vision tracking to determination of the point(s) of visual fixation. We hypothesize that subjects will display differences in overall technique, force and torque, motion paths, and visual fixation, and that these differences will a) correlate with the success rates of intubation and b) discriminate between different levels of experience and expertise with intubation.

Investigating Novel Determinants of Pancreatic Beta Cell Development Using a Novel Genetic Mouse Model of Neonatal Diabetes
Aimee Bastidas Ponce, PhD - Postdoctoral Scholar, Pediatric Endocrinology
Neonatal diabetes (NDM) represents a rare form of diabetes, which is characterized by the onset of severe hyperglycemic condition during the first 6 months of life. Diabetes can result from defects in pancreas and beta-cell development, beta-cell loss or defects in the machinery coupling glucose metabolism to insulin secretion. In a mouse model of NDM have identified a novel homozygous mutation in regulatory sequence at the Gins4 locus which results in a failure of pancreatic beta-cell development. We are investigating how this mutation affects gene regulation and RNA splicing of genes at the locus and alters pancreatic beta-cell development. The identification and understanding of genetic variations related to disease risk, influences treatment and prognosis and has informed our understanding of pancreas development in humans.

Development of Innovative Therapies for Fanconi Anemia
Agnieszka Czechowicz, MD, PhD - Assistant Professor, Pediatrics Stem Cell Transplantation
Dr. Czechowicz will discuss innovative therapies in development based upon her research efforts including antibody-based conditioned transplantation, in utero transplantation and gene-editing approaches.

Preschool Impulse Oscillometry Predicts Active Asthma and Impaired Lung Function at School Age
Hanna Knihtila, MD, PhD - Resident, Stanford Pediatric Residency Program
Most patients with asthma develop symptoms during early childhood. However, identifying preschool children who go on to develop asthma is challenging, because spirometry is generally not feasible in this age group. We investigated the clinical utility of impulse oscillometry (IOS) in a multiethnic birth cohort. We found that increased respiratory resistance in preschool IOS was associated with frequent respiratory symptoms and short-acting beta-agonist use. Furthermore, increased respiratory resistance in preschool IOS was associated with active asthma and impaired lung function at school age. Our findings highlight the potential of IOS as an objective measure for identifying children at increased risk of future respiratory morbidity.

Protecting Adolescent Confidentiality with NLP
Keith Morse, MD, MBA - Clinical Associate Professor, Pediatric Hospital Medicine
Federally-mandated EHR information sharing rules risk violating teen's right to privacy when receiving care for certain confidential topics. Tools to identify these topics automatically are needed to protect teen confidentiality and support a robust physician-patient relationship. This presentation outlines the development and implementation of such an NLP-based tool to enable retrospective note audits and educational feedback at Stanford Children's.

PedsQL, Exercise Capacity, And Endothelial Function In Pediatric Fontan Patients
Jerin Jose, MD - Fellow, Pediatric Cardiology
The Pediatric Quality of Life Inventory (PedsQL) is a widely used tool to assess health-related quality of life in pediatric patients. In Fontan patients, who have undergone a palliative surgical procedure for single-ventricle congenital heart disease, exercise capacity is a crucial aspect of their overall well-being. We present the baseline PedsQL and exercise capacity data on pediatric Fontan patients who are enrolled in the RE-ENERGIZE FONTAN Study at Stanford. This is a randomized control study to evaluate whether a live-video-supervised exercise intervention will improve the cardiac and physical capacity, as well as quality of life, in pediatric Fontan patients.

Macrophage Functional Diversity During Persistent Bacterial Infection
Trung Pham, MD, PhD - Assistant Professor, Pediatric Infectious Diseases
Intracellular bacteria such as Salmonella enterica and Mycobacterium tuberculosis infect hundreds of millions of people and disproportionally burden children. These pathogens can establish persistent infection and survive in host tissues for months to years. Macrophages direct key antimicrobial immune responses to eradicate pathogens during infection and execute critical physiologic functions to maintain tissue homeostasis. Yet they can also act as a permissive cellular niche for intracellular bacteria to persist in infected tissues. Using a persistent murine Salmonella infection model, we aim to uncover the molecular and cellular mechanisms underlying macrophage heterogeneity and functional diversity during persistent bacterial infection. A greater understanding of these mechanisms will inform new therapeutic strategies to limit infection and restore health following an infectious attack.

Antibiotic Prescribing Patterns in Outpatient Clinics in Western and Coastal Kenya
Melanie Kiener, MD - Postdoctoral Scholar, Pediatric Infectious Diseases
We analyzed outpatient sick visits at several clinics in Western and Coastal Kenya from 2019 to 2022 to understand factors associated with antibiotic prescriptions. Our results highlight high rates of antibiotic prescriptions without clear bacterial diagnoses, particularly among children.