Medicine and Health Sciences Commons^™

A Case Of Dock8 Deficiency Treated With Dupilumab, Melissa Anderson, Brandon D. Newell, Hugo Escobar, Erin Stahl, Nikita Raje

Research Days

Background: Dedicator of cytokinesis 8 gene (DOCK8) deficiency is an immune disorder associated with autosomal recessive hyper-IgE syndrome, characterized by elevated IgE levels, atopic dermatitis, and predisposition to recurrent skin and lung infections.

Objectives/Goal: A 12-year-old male presented to Immunology clinic for DOCK8 deficiency. He was diagnosed in infancy due to diffuse papulopustular eruption positive for candidiasis and known family history. Past medical history included severe eczematous dermatitis, asthma, interstitial lung disease, food allergies, and poor growth, with cutaneous HSV and fungal infections, HSV keratitis, and MRSA bacteremia. Family history was notable for two siblings with DOCK8 deficiency, both deceased. …

Stewardship Opportunities For Cervical Lymphadenitis And Deep Neck Space Abscesses, Aaron Shaw, Brian R. Lee, Lauren Kazmaier, Emily Baker, Tina Dao, Sandra Arnold, Angela Myers

Research Days

Background: Cervical lymphadenitis (LAD) and deep neck space abscesses (DNSA) are common pediatric infections caused by similar bacteria. We sought to determine differences in presentation, diagnosis, and treatment between LAD and DNSA to identify antimicrobial and diagnostic stewardship opportunities.

Methods: Charts were obtained using ICD9/10 codes for retropharyngeal and parapharyngeal abscessed (DNSA), and LAD between 1/1/10-12/31/20 from two pediatric centers. 1981 charts were identified. Charts were excluded if the diagnosis was not a bacterial infection (e.g. Kawasaki disease), if the LAD was not in the neck, or if caused by less common bacteria (e.g. tuberculosis). Data on presenting signs, symptoms, …

Association Between Remote Monitoring And Interstage Morbidity And Mortality In Single Ventricle Patients Across Socioeconomic Groups, Bianca Cherestal

Research Days

Background: Despite improvements in outcomes over time, morbidity and mortality for infants with single ventricle (SV) heart disease remains high. Among other risk factors for mortality, infants of low socioeconomic status (SES) are known to be particularly vulnerable following stage 1 palliation.

Objectives/Goal: We sought to determine whether use of a novel remote monitoring program, CHAMP (Cardiac High Acuity Monitoring Program), mitigates differences in outcomes by SES for infants with SV during the interstage period.

Methods/Design: Using the CHAMP database, we identified 610 infants across 11 institutions enrolled in the program between 2014–2021. All enrolled patients’ families were provided with …

Functional Evaluation Of A Novel Rpl30 Mutation And Its Role In Diamond Blackfan Anemia (Dba), Alexandra Prosser, Alexandria Cockrell, Danny Miller, Chris Seidel, Tamara Potapova, John M. Perry, Midhat Farooqi, Erin M. Guest, Jennifer Gerton

Research Days

Background: Bone marrow failure is life-threatening and requires prompt, intensive treatment, which is dependent upon identification of genetic drivers. Although there has been investigation into associated genetic mutations, especially in Diamond Blackfan anemia (DBA), the relationship between genotype and phenotype remains unclear.DBA has been identified as a ribosomopathy, also known as a disease associated with defects in ribosome biogenesis. We identified a novel heterozygous variant (c.167+769C >T) in the noncoding region of RPL30 in a patient with clinical diagnosis of DBA. Clinical RNA sequencing (RNA-seq) suggests the variant generates a novel splice acceptor site resulting in truncated RPL30 transcripts. Elucidation …

Sepsis-Induced Acute Lung Injury (Ali) And The Development Of Bronchopulmonary Dysplasia (Bpd) In Premature Infants., Jacob S. Ward, Hung-Wen Yeh, Megan Tucker, Venkatesh Sampath

Research Days

Background: Bronchopulmonary dysplasia (BPD) is a significant cause of morbidity and mortality in premature infants with several known risk factors. Recent literature described the harmful effect of inflammation on the developing lung. Recently, we showed that late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) causes acute lung injury (ALI) in preterm infants as measured by increases in pulmonary severity scores (PSS). The aim of this study was to investigate the association between LOS-induced ALI and BPD outcomes. We hypothesized that LOS would increase the likelihood of developing BPD, and the associated LOS-induced ALI will add to the ability to predict development …

Memory T Cell Populations In Human Leukemia, Sara Mcelroy

Research Days

Background: Incorporating the immune system into cancer management is an area of robust research. Treatment modalities aimed at activating cytotoxic T cells against malignancies include immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor (CAR) tumor-specific T cells. Most anti-cancer T cell research is narrowly focused, but knowledge about the nature of diverse sub-populations of T cells in cancer, particularly memory T cells, is vital prior to potential incorporation into therapies. T memory stem cells (Tscm) are of interest due to their longevity and powerful abilities of self-renewal and creating the full spectrum of memory CD8+ T cells, including …

Variation In Laboratory & Radiographic Workup And Outcome In Children Hospitalized With Common Musculoskeletal Infections, Emily Bonanni

Research Days

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Background: Common pediatric musculoskeletal infections (MSKIs) require prompt recognition & treatment to prevent significant morbidity and mortality. Variation in initial workup of these infections & associations with clinical outcomes is not well studied and could aid development of evidence-based guidelines to provide high-value care for all MSKIs.

Objectives/Goal: Examine variation in initial lab testing & imaging obtained in patients hospitalized for common MSKIs and explore association with clinical outcomes (length of stay (LOS), cost, 30-day readmission).

Methods/Design: We performed a retrospective, multicenter cohort study of hospitalized children aged 6 months to 18 years with a …

A Novel Approach To Triosephosphate Isomerase Deficiency, Kyra Mccarty

Research Days

Background: Triosephosphate isomerase deficiency (TPID) is a glycolytic pathway enzymopathy causing hemolytic anemia and neurologic dysfunction. TPID is caused by mutations in the TPI1 gene. These patients experience severe hemolytic anemia in infancy followed by progressive neurodegeneration. Diagnosis of TPID is made by measuring decreased TPI enzyme activity elevated dihydroxyacetone phosphate (DHAP) levels in the blood. The diagnosis is confirmed by molecular genetic testing. Neurological involvement typically manifests between 6 and 24 months of age, causing progressive motor dysfunction. Chronic axonal neuropathy is often present on nerve biopsy, and peripheral neuropathy is evident on electrophysiologic studies. Splenectomy and blood transfusions …

Diagnosis, Management, And Treatment Of Lymphadenitis And Deep Neck Space Infections At A Children’S Hospital, Aaron Shaw

Research Days

Background: Although cervical lymphadenitis and deep neck space abscesses (DNSA) are relatively common pediatric diagnoses, no standardized approach exists for management of these infections.

Objectives/Goal: To assess variability in diagnosis and treatment of cervical lymphadenitis and DNSA in a children’s hospital.

Methods/Design: Charts were obtained using ICD9/10 codes for diagnoses of retropharyngeal and parapharyngeal abscess, and lymphadenitis between 1/1/10-12/31/20. 1,237 charts were identified. Patients with a retropharyngeal and/or parapharyngeal abscess were defined as DNSA. Charts were excluded if the diagnosis was not a bacterial infection (e.g. Kawasaki disease), if the lymphadenitis was not in the neck, or if caused by …

Sigirr Variants Identified In Nec Infants Exaggerate Toll-Like Receptor Mediated Inflammation, Jennie Godwin

Research Days

Background: A key event underlying uncontrolled inflammation in necrotizing enterocolitis (NEC) is pathologic activation of Toll-like receptors (TLR). TLR4 recognizes lipopolysaccharide (LPS), from Gramnegative bacteria, and TLR2 peptidoglycans (PAM3Csyk4, PAM), from Gram-positive bacteria. TLR4 and TLR2 signaling events induce an inflammatory cascade through NF-kB, a cytokine inducing transcription factor. Single-immunoglobulin interleukin-1-related receptor (SIGIRR) is a major negative regulator of TLR-mediated NF-kB activation. Previous work from our lab suggests that loss of function in SIGIRR may predispose to NEC. Our lab has identified four variants in NEC patients predicted to alter function of SIGIRR. We hypothesized that identified SIGIRR variants will …

Assessment Of Dental Care In Children With Congenital Heart Disease, Mollie Walton

Research Days

Background: The incidence of infective endocarditis (IE) is significantly higher in patients with congenital heart disease (CHD) compared to the general population. Studies have investigated the incidence of IE in adults with CHD to identify the factors that contribute to the development of IE. One such factor is suboptimal oral health. Several studies have shown that children with CHD have higher levels of untreated oral disease as compared to children without CHD.

Objectives/Goal: Identify factors that may affect compliance with routine dental care, including: age, sex, severity of CHD, repair/palliation, and qualification for prophylactic antibiotics.

Methods/Design: A retrospective chart review …

Use Of Artificial Intelligence To Identify Predictors Of Functional Outcomes In Patients With Facioscapulohumeral Muscular Dystrophy, Natalie K. Katz

Research Days

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy characterized by slowly progressive muscle weakness. Symptoms initially involve the facial and shoulder girdle muscles, with later involvement of the distal lower extremities, pelvic girdle and proximal lower extremities. FSHD type 1 (FHSD1) is the most common form (~95% of individuals) and is caused by deletion of microsatellite repeats in the D4Z4 region on chromosome 4 (4q35). Normal individuals have >10 repeats whereas individuals with FSHD1 have 1-10 repeats. There is significant variability in regards to disease severity, rates of progression and functional outcomes, but …

Financial Outcomes Of High Flow Nasal Cannula Use For Bronchiolitis On The General Pediatric Floor Across Children's Hospitals, Jonathan Hartley

Research Days

Background: Bronchiolitis is a leading cause of hospitalization for infants and results in over 1.7 billion dollars in yearly hospital charges (Hasegawa). The use of high flow nasal cannula (HFNC) on a general pediatrics floor may reduce hospital costs and length of stay (LOS, Kalburgi). However, the financial impact of HFNC use is not welldescribed.

Objective: The primary objective are the financial outcomes of HFNC utilization on the general pediatric floor. The secondary objective included financial outcomes stratified by All Patients Refined Diagnosis Related Groups (APRDRG) severity of illness (SOI) and payor type. We hypothesize that costs outweigh reimbursement for …

Impact Of High Flow Nasal Cannula On Resource Utilization In Bronchiolitis, Scott Biggerstaff

Research Days

Background: Bronchiolitis is one of the most common diseases requiring hospitalization in children 1-24 months of age, but presently treatment is primarily supportive. High flow nasal cannula is a newer method of oxygen delivery pediatric hospitals have been rapidly adopting to treat respiratory insufficiency caused by viral bronchiolitis.

Objectives/Goal: We sought to compare resource utilization, including cost, length of stay (LOS), and readmission among children who were treated with HFNC versus those who were not.

Methods/Design: In this cross-sectional, multicenter study, we obtained clinical and resource utilization data from the Pediatric Health Information System (PHIS) database for otherwise healthy children …

A Case Series Of Hyperglycemic Hyperosmolar State During The Global Covid-19 Pandemic, Benjamin Hoag

Research Days

Background: Hyperglycemic hyperosmolar state (HHS) is rare in pediatrics, particularly in patients with antibody positive diabetes mellitus (DM). Recent literature has implicated COVID-19 in the reported increase in new onset DM cases, as well as mixed diabetic ketoacidosis (DKA) and HHS cases; however, a rise in HHS cases alone has not been well reported [1,2]. We noted an anecdotal increase in the frequency of HHS cases in our pediatric tertiary care center following the onset of the global COVID-19 pandemic.

Objectives/Goal: To investigate further, a retrospective chart review evaluating all patients with DM admitted in the first 6 months of …

Antibiotic Durations For Skin And Soft Tissue Infections In Pediatric Urgent Care Clinics, Megan Hamner

Research Days

Background: Skin and soft tissue infections (SSTIs) are the second most common diagnosis leading to pediatric antibiotic prescriptions in the outpatient setting after respiratory diagnoses. However, most antibiotic stewardship programs have mainly focused on the latter. Children seen in the ambulatory setting for SSTIs often receive >7 days of antibiotics, although current society guidelines recommend 5-7 days for most diagnoses.

Objectives/Goal: To determine the baseline percentage of patients receiving antibiotic prescriptions for >7 days for SSTIs in Children’s Mercy urgent care clinics (UCC)s and to evaluate factors that influence providers towards longer durations.

Methods/Design: We built a report that extracted …

A Study Examining The Safety And Efficacy Of Ferric Carboxymaltose In A Large Pediatric Cohort, Chandni Dargan Md, David Simon Do

Research Days

Background: Iron deficiency anemia (IDA) is common in the pediatric population with varying high-risk factors. Intravenous (IV) iron supplementation has become more desirable in patients with moderate to severe anemia and in patients who are either unresponsive to or have adverse side-effects secondary to oral iron. Iron sucrose and Iron dextran have been traditionally used in pediatrics while ferric carboxymaltose (FCM) has only been FDA approved in adults. One of the major advantages of FCM is the ease of dosing and efficacy. Though FCM was approved for adults in 2013 and there have been no safety concerns, it is not …

Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson

Research Days

Background: Our center receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurately interpreting lab results. Bhasin et al showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little published about the referral patterns to pediatric hematology and the outcomes of these referrals.

Objectives/Goal: To characterize our hematology referrals for bleeding disorder …

Outcomes Of Infants With Severe Rop At Risk Of Treatment With Avastin Compared To Laser Surgery, Stephen Doxey

Research Days

Background: Retinopathy of prematurity (ROP) is a well-known complication occurring in the most premature infants leading to visual impairment and in the most severe cases associated with retinal detachment and childhood blindness. Factors contributing the development of ROP include chronic hypoxia and disordered vascular genesis primarily through the vascular endothelial growth factor (VEGF) signaling pathway. Infants at risk of developing ROP are screened with serial eye exam and treated with either laser surgery or intraocular injects of bevacizumab (Avastin) to prevent progression of ROP and preserve vision. Bevacizumab, an inhibitor of VEGF signaling, may have positive effects on preventing ROP …

Low Dose Doxorubicin Inhibits Immune Checkpoint Upregulation In Acute Leukemias, Bradley C. Stockard

Research Days

Background: Evasion of drug and immune response in therapy-resistant leukemic stem cells (LSCs) is a major cause of relapse. A previous study has identified an alternative mechanism of action for low-dose doxorubicin (DXR) that inhibits upregulation of immune checkpoints (IC) in LSCs.

Objectives/Goal: The objective of this study is to establish the DXR dose range that will achieve the inhibition of immune checkpoint expression in leukemic cell lines.

Methods/Design: Cells were analyzed for expression of CTLA-4, LAG-3, PD-1, TIGIT, and TIM-3 via flow cytometry. Analysis was performed on days 3, 5, and 8 of treatment at concentrations identified as low, …

Atrial Standstill In A Pediatric Patient With Scn5a Mutation Following Procainamide Challenge, Anmol Goyal

Research Days

Background: Atrial standstill (AS) is a rare arrhythmia characterized by absence of electrical and mechanical atrial activity associated with SCN5A channelopathy.

Case: An 18 year old male with structurally normal heart, frequent sinus pauses, nonsustained atrial tachycardia and high-grade block was found to have SCN5A mutation c.3823G>A (p.Asp1275Asn). An electrophysiology study (EPS) with high density voltage mapping of the right atrium was done (Fig 1a). Nonsustained multifocal atrial tachycardia was induced without ablative targets (Fib 1b). Procainamide challenge was negative for Brugada, however induced AS (Fig 1c-d). No atrial capture could be achieved at maximal output. Empiric atrial lead …

A Pediatric Case Of Treatment-Related Myelodysplastic Syndrome While On Therapy For Pre-B All, Sara Mcelroy

Research Days

Background: Treatment-related myelodysplastic syndrome (t-MDS) is a known, but rare, late effect of cancer therapy, specifically radiation, alkylating agents or topoisomerase II inhibitors. When secondary to treatment with alkylating agents, t-MDS typically occurs 4 to 7 years after therapy, and common cytogenetics include chromosomes 5 and 7 abnormalities. Treatment in children with t-MDS is typically allogeneic stem cell transplant, but the prognosis remains poor.

Objectives/Goal: To describe a rare case of a pediatric patient who developed t-MDS while receiving treatment for Pre-B Cell Acute Lymphoblastic Leukemia (pre-B ALL) and to outline the treatment regimen that he received.

Methods/Design: Case Report …

Reconsidering Perioperative Antibiotic Use In Elective Laparoscopic Cholecystectomy, Kayla B. Briggs

Research Days

Background: As rates of antimicrobial resistance increase, the use of prophylactic perioperative antibiotics (PPA) has been questioned in cases with a low risk of surgical site infection (SSI). In laparoscopic cholecystectomy performed for biliary dyskinesia, hyperkinetic gallbladder, and gallbladder polyps, the use of PPA varies with no widely accepted practice pattern.

Objectives/Goal: We examined institutional PPA usage and SSI rates for elective laparoscopic cholecystectomy to determine if PPAs are indicated.

Methods/Design: Following IRB approval, children/2010 and 8/2020 for symptomatic cholelithiasis, biliary dyskinesia, hyperkinetic gallbladder, and/or gallbladder polyps were included. Several surgeons changed practice to selective PPA use in 2016, decreasing …

The Role Of Fractionated Exhaled Nitric Oxide (Feno) In Eosinophilic Esophagitis And The Relationship With Downstream Eosinophils, Panamdeep Kaur

Research Days

Background: Eosinophilic Esophagitis (EoE) is a chronic immune mediated disease of the esophagus characterized by symptoms of esophageal dysfunction and eosinophilic-predominant inflammation of the esophagus. It can lead to feeding difficulties, failure to thrive, and esophageal stricturing. Currently, the gold standard for diagnosis and assessing response to therapy is upper endoscopy and histopathological analysis of biopsies. A noninvasive, cost-effective, and low risk alternative that can aid in the management of EoE is not currently available. Previous studies assessing correlation of fractionated exhaled nitric oxide (FeNO) with degree of esophageal eosinophilic inflammation were low powered but noted a trend for association. …

Pediatric Pulmonary Artery Aneurysms Causing Pulmonary Hemorrhage: A Case Of Transcatheter Intervention While On Va Ecmo Support, Igor Areinamo

Research Days

Background: The incidence of pulmonary artery aneurysm (PAA) in children remains unknown. There are few reports of a transcutaneous interventional approach to address this type of pathology. Management of PAAs while on VA ECMO has not been described in pediatrics.

Objectives/Goal:

Methods/Design:

Case: 9-year-old previously healthy male presented with MRSA associated ARDS and sepsis requiring urgent VA ECMO cannulation. Chest CT done on ECMO day 22 showed development of right sided PAAs. Patient had an episode of significant pulmonary hemorrhage. Angiogram demonstrated two fusiform right PAAs, one of which had ruptured and was bleeding into the lung parenchyma. Patient had …

Prenatal Diagnosis Of An Uncommon Form Of A Hypoplastic Left Heart Syndrome Variant., Anmol Goyal

Research Days

Background: Mitral valve dysplasia syndrome (MVDS) is a rare form of congenital heart disease, similar to hypoplastic left heart syndrome (HLHS). Prenatal identification is important for counseling, delivery planning and postnatal management.

Case: A 39 year-old woman underwent fetal echocardiography at ~34 weeks gestation for evaluation of fetal cardiomegaly and hydrops revealing: biatrial enlargement, mild-to-moderate mitral and tricuspid valve insufficiency, echobright mitral valve apparatus, biventricular dilation, severe LV fibroelastosis (EFE) and systolic dysfunction, mild hypoplasia of aortic valve annulus and aortic arch, and a thick restrictive atrial septum (RAS) with left to right flow (Fig 1a-c).

Decision‐making: Although critical aortic …

Diagnosis And Management Of Otitis Media With Effusion In Pediatric Urgent Care Clinics, Ashley Deschepper

Research Days

Background: Otitis media with effusion (OME)’s clinical presentation is often confused with acute otitis media (AOM) by providers. Despite OME guidelines recommending watchful waiting with no antibiotics, rates of antibiotic use remain elevated. In our pediatric urgent care clinics (UCCs), an estimated 50% of patients diagnosed with OME receive antibiotic prescriptions.

Objectives/Goal: To determine the provider diagnosis validity and the rates of antibiotics prescribed among pediatric OME patients evaluated in 3 UCCs within a pediatric healthcare system.

Methods/Design: We randomly selected 75% of encounters for children age 0-18 years who had a billing diagnosis of OME in 2019. Charts were …

Phenotypic Characterization Of Jarid2-Related Intellectual Disability: A Case Series, Maxime Cadieux-Dion

Research Days

Background: In recent years, wide implementation of research and clinical next generation sequencing has led to an astonishing number of novel disease-gene assertions. Recently, loss of function variants in JARID2 were reported in 16 patients with a clinically distinct neurodevelopmental phenotype that consisted of neurodevelopmental delay, intellectual disability (ID), learning disability, autism and behavioral abnormalities. Dysmorphic features were seen in most patients and included high anterior hairline, deep-set eyes, full lips, broad forehead, bulbous nasal tip, or depressed nasal bridge. Cleft lip/palate was observed in only 1/16 patients. Most cases were de novo, with only one inherited case from an …

Activation Of Aryl Hydrocarbon Receptor Signaling In Human Trophoblasts Alters Markers Of Growth And Differentiation, Asmaa Alsousi

Research Days

Background: It is estimated that 1.7% of pregnant women smoke during their pregnancy globally, with the highest levels observed in Europe at 8.1%, and lowest in Africa at 0.8. The association of maternal cigarette smoking with increased risk of poor birth outcomes such as preterm birth, congenital anomalies, and neonatal mortality is well-established. In addition, evidence suggests that intrauterine exposure to maternal smoking impacts the risk of developing diseases later in life; however, we still do not understand the exact mechanism(s) leading to these outcomes. Once components of cigarette smoke (CS) cross the placenta and enter the fetal compartment, several …

Setting A Threshold For Discharge Antibiotics In Children With Perforated Appendicitis: A Study Update, Kayla B. Briggs

Research Days

Background: To address concerns of antibiotic overutilization, normal white blood cell count (WBC) for age was previous l criteria for discontinuing antibiotics at discharge in perforated appendicitis. Retrospective review suggested a decrease in threshold for additional antibiotic administration to a discharge WBC(IAA).

Objectives/Goal: The purpose of our study is to determine if lowering the threshold for additional antibiotic administration decreased the rate of IAA after laparoscopic appendectomy for perforated appendicitis in children who were not discharged with additional antibiotics.

Methods/Design: Following IRB approval, prospective data was retrospectively reviewed. Children with perforated appendicitis identified during laparoscopic appendectomy at our institution between …