Medical Specialties Commons^™

Next-Generation Sequencing In The Diagnosis Of Rare Pediatric Sinonasal Tumors., Atif A. Ahmed, Divya Vundamati, Midhat Farooqi, Elena Repnikova, Timothy Zinkus, Maxine Hetherington, Lorien Paulson

Manuscripts, Articles, Book Chapters and Other Papers

The diagnosis of desmoid fibromatosis or other spindle cell tumors in the sinonasal region is very rare in children and needs to be thoroughly confirmed with immunohistochemical and/or molecular tests. We report 2 patients with such rare tumors and describe the use of next-generation sequencing in their evaluation. A 3-year-old female had a 4.4-cm midline nasal cavity mass involving the bony septum and extending into the base of the skull bilaterally. The moderate cellular fibroblastic proliferation revealed areas of thick keloid-like collagen bands and other areas with myxoid edematous stroma. Deep targeted sequencing identified a novel G34V mutation in the

Extracellular Superoxide Dismutase (Ec-Sod) Regulates Gene Methylation And Cardiac Fibrosis During Chronic Hypoxic Stress., Ayan Rajgarhia, Kameshwar R. Ayasolla, Nahla Zaghloul, Jorge M. Lopez Da Re, Edmund J. Miller, Mohamed Ahmed

Manuscripts, Articles, Book Chapters and Other Papers

Chronic hypoxic stress induces epigenetic modifications mainly DNA methylation in cardiac fibroblasts, inactivating tumor suppressor genes (RASSF1A) and activating kinases (ERK1/2) leading to fibroblast proliferation and cardiac fibrosis. The Ras/ERK signaling pathway is an intracellular signal transduction critically involved in fibroblast proliferation. RASSF1A functions through its effect on downstream ERK1/2. The antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), decreases oxidative stress from chronic hypoxia, but its effects on these epigenetic changes have not been fully explored. To test our hypothesis, we used an in-vitro model: wild-type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG). …

Transcription Factor Β-Catenin Plays A Key Role In Fluid Flow Shear Stress-Mediated Glomerular Injury In Solitary Kidney., Tarak Srivastava, Daniel P. Heruth, R Scott Duncan, Mohammad H. Rezaiekhaligh, Robert E. Garola, Lakshmi Priya, Jianping Zhou, Varun C. Boinpelly, Jan Novak, Mohammed Farhan Ali, Trupti Joshi, Uri S. Alon, Yuexu Jiang, Ellen T. Mccarthy, Virginia J. Savin, Ram Sharma, Mark L. Johnson, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3β-β-catenin signaling. The present study was undertaken to confirm (i) the activation of β-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL mice with the β-galactosidase reporter gene for β-catenin activation, (ii) β-catenin translocation in FFSS-treated mouse podocytes, and (iii) β-catenin signaling using publicly available data from UNX mice. The UNX of TOPGAL mice resulted in glomerular hypertrophy and increased the mesangial matrix consistent with hemodynamic adaptation. Uninephrectomized TOPGAL mice showed an increased β-galactosidase expression at 4 weeks …

A Multicenter Evaluation Of Viral Bloodstream Detections In Children Presenting To The Emergency Department With Suspected Systemic Infection., Christina A. Rostad, Neena Kanwar, Jumi Yi, Claudia R. Morris, Jennifer Dien Bard, Amy Leber, James Dunn, Kimberle C. Chapin, Anne J. Blaschke, Judy A. Daly, Leslie Hueschen, Matthew Jones, Elizabeth Ott, Jeffrey Bastar, Kevin M. Bourzac, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections.

METHODS: We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted.

RESULTS: Of the 1114 subjects enrolled, …

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 …

Prevalence Of Adolescent Sexual Health Outcomes At Children’S Hospitals During Covid-19, Margarita Abella

Research Days

Background: The Coronavirus Disease 2019 (COVID-19) pandemic mitigation strategies, including social distancing, decreased structured environments, and decreased sexual and reproductive health (SRH) care access, could negatively impact adolescent SRH behaviors and related outcomes. To date, little is known regarding changes in adolescent SRH outcomes during COVID-19.

Objectives/Goal: Our goals were to assess changes in adolescent SRH outcomes, including sexually transmitted infections (STIs), pregnancy, and sexual assault in the hospital (emergency department [ED] and inpatient [IP]) during COVID-19 compared to pre-COVID-19.

Methods/Design: We conducted a retrospective cohort study of adolescent (11-18 years old) IP or ED hospital visits using the Pediatric …

Factors Associated With Suicide Screenings For An Autism Spectrum Disorder Population In A Pediatric Medical Setting, Cheng Qian, Dawn Greathouse

Research Days

Background: Individuals with autism spectrum disorder (ASD) are at least 3 times more likely to attempt suicide than those without ASD (Kolves et al., 2021; Richa et al., 2014). Core features of ASD (e.g., deficits in communicating emotions, difficulty with change) are associated with known suicide attempt antecedent events, and rates of co-occurring mental health concerns (e.g., depression) that increase suicide risk are higher than in the general population (Richa et al., 2014). However, mental health clinicians perceive patients with ASD to be at lower risk for suicide, and report lower self-efficacy in screening in this population (Jager-Hyman et al., …

Bmi And Associated Variables In A Pediatric Gender Clinic Sample, Mirae J. Fornander

Research Days

Background: Studies of transgender/gender diverse (TGD) youth indicate a high prevalence of overweight/obesity and concern for unhealthy weight control behavior.

Objectives/Goal: Describe BMI and the association of medication use, well-being, and recreational activities in treatmentnaïve pediatric TGD patients.

Methods/Design: Chart review of 302 patients (age 3-19, 73.5% sex assigned at birth (SAB) female; 85.8% white) from 2017-20. BMI was calculated by age and SAB using CDC growth charts. Parents reported medication use. Parent and self-reported Pediatric Quality of Life (PEDS-QL) Well-Being and activities were surveyed electronically.

Results: By BMI category, 3.3% were underweight (BMI85% and 29.5% fell >95%. Overweight and …

Transgender Identity Among Adolescents With Pcos, Cintya Schweisberger

Research Days

Background: The estimated prevalence of transgender identity among US adolescents is 0.5% to 1.3%. Some studies have suggested an increased prevalence of PCOS in transmasculine adults before testosterone therapy. There is a paucity of data describing the relationship between gender dysphoria and PCOS in adolescents.

Objectives/Goal: The objective of our study was to describe the prevalence of transgender identity among adolescents with PCOS.

Methods/Design: A secondary data analysis was conducted in 169 adolescents (16.1 ±1.64 yrs) from our Multidisciplinary Adolescent medicine and Pediatric endocrine PCOS (MAPP) clinic who met NIH criteria for PCOS and had gender identity recorded. Variables analyzed …

Characterization Of Comorbidities In Patients With A Dual Diagnosis Of Down Syndrome And Autism Spectrum Disorder Using Cerner Health Facts, Michael Slogic

Research Days

Background: Up to 19% of patients with Down syndrome (DS) meet diagnostic criteria for autism spectrum disorder (ASD) (Channell, et al, 2019). While the medical and psychological comorbidities for patients with DS or ASD are well characterized, comorbidities and outcomes for patients with a dual diagnosis (DS-ASD) are poorly understood. A large cohort of patients with DS-ASD, as well as those with ASD and DS alone, are needed to better understand this. Methods for grouping and analyzing complex diagnostic phenotypes are also needed.

Objectives/Goal: Our objective is to utilize Cerner Health Facts, a multi-institutional healthcare database, to identify large populations …

Effectiveness And Safety Of Repeat Dexamethasone For Bronchopulmonary Dysplasia, Christian Oliveros

Research Days

Background: Although a short course of steroids maybe beneficial in infants at high risk for bronchopulmonary dysplasia, response to treatment is variable. In infants with persistent lung disease despite initial treatment, repeat courses of steroids have been described but not well-studied. This 10-year observational study from a single tertiary referral center evaluates the effectiveness and safety of repeat steroid treatment for bronchopulmonary dysplasia.

Objectives/Goal: To describe effectiveness of repeat dexamethasone treatment for bronchopulmonary dysplasia (BPD) and to evaluate potential detrimental effects on growth and neurodevelopment.

Methods/Design: This was a 10-year single-center observational study of infants <30 >weeks’ gestational age at birth …

Prevalence Of Mycoplasma Genitalium And Macrolide Resistance In Adolescent Females Receiving Care At A Pediatric Hospital, Kayla Barnes

Research Days

Background: Mycoplasma genitalium is an established sexually transmitted cause of nongonococcal urethritis in males and macrolide resistance is increasing. The pathogenic role is less well-defined in adolescent females and guidelines recommend M. genitalium testing only be considered in cases of persistent or recurrent cervicitis and pelvic inflammatory disease (PID). We lack understanding of the prevalence and macrolide resistance of M. genitalium among adolescent females.

Objectives/Goal: To determine the prevalence of M. genitalium and rate of detected macrolide resistance among adolescent females seeking care at a pediatric children’s hospital.

Methods/Design: We collected 200 salvaged urogenital samples (56 urine and 144 vaginal) …

Infliximab As Rescue Therapy In Pediatric Severe Colitis, Kayla B. Briggs

Research Days

Background: Infliximab has been shown to be effective in achieving clinical remission in patients with ulcerative colitis (UC) refractory to conventional therapy. However, there is conflicting data in the literature regarding its effectiveness as rescue therapy in acute severe colitis. Furthermore, most studies were conducted in adults, and pediatric onset of inflammatory bowel disease (IBD) is associated with more severe disease that may be less amenable to rescue therapy.

Objectives/Goal: We reviewed our experience with pediatric severe colitis and report outcomes following attempted rescue therapy with infliximab.

Methods/Design: A retrospective review was conducted of patients with UC or indeterminate colitis …

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 …

Neonatal Arch Obstruction: Not Always A Coarctation, Karoline Krzywda

Research Days

Background: Spontaneous neonatal arch thrombosis is a rare, highly lethal cause of aortic arch obstruction.

Case: A 1-day-old male infant presented failing CCHD screen, on prostaglandin infusion for echocardiographic concerns of aortic coarctation. Repeat echocardiogram revealed severe arch obstruction due to a large, 7.5x5mm echogenic mass, at the aortic isthmus (Fig1A) with right to left systolic PDA flow. CT angiography confirmed presence of a large aortic arch thrombus (Fig1B). Bivalirudin infusion was initiated without change in thrombus size after 2 days. Tissue plasminogen activator (tPA) was subsequently administered with significant reduction in thrombus size to 3x4mm (Fig1C) on day 1 …

Unique Evaluation And Management Considerations For Adolescents With Late Gynecologic And Colorectal Issues In The Setting Of Anorectal Malformations, Wendy Jo Svetanoff

Research Days

Background: Females born with anorectal malformations (ARMs) and bladder exstrophy have a greater incidence of Mullerian and genital anomalies requiring early gynecologic assessment and frequent surgical intervention. However, there is little guidance for management considerations of pubertally identified Mullerian anomalies in these patients

Objectives/Goal: We sought to assess the unique colorectal, gynecologic, and psychological issues present during the adolescent years.

Methods/Design: A retrospective review was performed of 10-25 year old female patients born with an ARM, cloaca, or exstrophy that presented to our multidisciplinary clinic between 2009 and 2019. Data abstracted included the presenting problem, history, imaging studies, psychological evaluation, …

Attitudes Of Pediatric Residents In The Care Of Transgender Youth, Michelle Knoll

Research Days

Background: Transgender individuals have health disparities compared to the general population and face several barriers to medical care. Prior studies indicate physician knowledge on transgender topics is poor and that transphobia is associated with poor knowledge even after educational interventions. Objectives/Goal: We sought to examine pediatric residents’ attitudes about transgender individuals and assess concerns related to the treatment of transgender youth. Methods: A survey was sent to 89 US Pediatric and combined (e.g. Med-Peds) residency programs and advertised on social media. Approximately 32 programs forwarded the survey to an estimated 1325 residents; 138 residents completed it. The survey consisted of …

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 …

Portable Low Field Strength Mri: Preliminary Experience In Neonates And Children, Johnston Fite

Research Days

Background: High field strength MRI (HF-MRI) is a pediatric imaging staple. However, HF-MRI access is limited by strong (1.5 – 3.0 T) magnetic fields with associated safety concerns, space requirements, and cost. To address these limitations, Hyperfine (Guilford, CT) developed a low magnetic field (0.064 T) portable MRI device, named Swoop. Preliminary data in adults shows benefits despite decreased image quality. In this study, initial evaluation of Swoop’s image quality in pediatric patients was assessed.

Objectives/Goal: The objective in this study was the initial evaluation of Swoop’s image quality in pediatric patients to serve as a baseline.

Methods/Design: The study …

Variability In Blood Gas Levels During Non-Invasive Ventilatory Support Following Planned Extubation And Association To 36-Week Bronchopulmonary Dysplasia In Preterm Neonates, Michelle Klueppelberg

Research Days

Background: Despite shifts to non-invasive support, as of 2012, 87% of preterm infants admitted to the neonatal intensive care unit (NICU) continued to receive some form of invasive mechanical ventilation1 . As a result, research around how prolonged respiratory support may impact the development of chronic lung disease, specifically bronchopulmonary dysplasia (BPD) has flourished. To date, literature has established associations between the time on invasive mechanical ventilation and incidence BPD2,3. Resulting in the development of standardized extubation strategies and bringing with them objective measures of extubation readiness4,5. Yet, due to their volatile conditions, some neonates will inevitably need to be …

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 …

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 …

Potential Role Of Methotrexate Polyglutamates In Therapeutic Drug Monitoring For Pediatric Inflammatory Bowel Disease., Ryan Morrow, Ryan Funk, Mara Becker, Ashley K. Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)-promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional secondary analysis, we assessed the relationships between MTX-Glu and MTX dose and treatment response in pediatric IBD. Twenty-one children with IBD, receiving maintenance therapy with infliximab (IFX) and MTX, had MTX-Glu1-6 concentrations and IFX troughs/antibodies measured and disease activity assessed for comparison in remission vs. active IBD using non-parametric tests, with associations explored using Spearman's correlation (ρ) …

Germline Variants Associated With Cancer Predisposition And Bone Marrow Failure Are Common In Kmt2a-R Infant Acute Lymphoblastic Leukemia Patients, Sarah E. Mc Dermott

Research Days

Background: Infant acute lymphoblastic leukemia (ALL), is a particularly aggressive subtype of leukemia with an early onset and unfavorable clinical outcome. Most (~70%) cases of infant ALL involve chromosomal rearrangement of KMT2A (KMT2A- r) on chromosome 11q23, the strongest independent predictor of a poor prognosis. To date, genomics studies have consistently demonstrated KMT2A-r infant ALL to have a strikingly silent landscape of DNA mutations. Germline mutations in cancer predisposition genes are found in 8.6% of pediatric malignancies and 4.4% of pediatric leukemias, compared to 1.1% in persons in the 1000 Genomes Project.

Objectives/Goal: We hypothesized that germline variants may contribute …

A New Paradigm: Ecmo Therapy In Pediatric Hematology/Oncology Patients, Igor Areinamo

Research Days

Background: The use of extracorporeal membrane oxygenation (ECMO) for support of pediatric patients has significantly increased in the past years. Patients with known oncologic diseases, immunodeficiencies, or bone marrow transplants (BMT) have traditionally not been considered candidates for Extracorporeal membrane oxygenation (ECMO) due to perceived high risk for mortality. Ongoing advances have continued to push the boundaries of ECMO use and we report our recent experience with this patient population

Objectives/Goal: To evaluate survival to discharge of pediatric patients who require ECMO support and who also have an underlying hematologic or oncologic disease process. To determine specific patient characteristics that …

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 …

Understanding Illness Encouragement And Pain Acceptance In Pediatric Patients With Abdominal Pain, Scott Wagoner

Research Days

Background: Parents can respond to their child’s abdominal pain in a variety of ways, and parental illness encouragement (e.g., spoiling, letting child stay home from school) is known to relate to longer periods of illness. Modeling and reinforcement of the “sick role” has been used to explain these processes. Many pediatric patients with abdominal pain will continue to experience symptoms in adulthood, so having a full understanding of what pain management techniques patients adopt is crucial. This study explored the impact of parental illness encouragement on how patients engage in valued activities (i.e., activity engagement) and prioritize controlling their pain …

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, …

Psychosocial Factors Affecting Quality Of Life In Patients With Anorectal Malformations And Hirschsprung’S Disease – A Qualitative Systematic Review, Wendy Jo Svetanoff

Research Days

Background: While great strides have been made in surgical techniques and bowel management therapies for patients with anorectal malformations (ARM) and Hirschsprung’s disease (HSCR), little is known about psychosocial and behavioral factors that impact the quality of life at each stage of development.

Objectives/Goal: We aimed to perform a qualitative literature review to highlight the psychosocial, emotional, and behavioral themes that affect the quality of life as patients born with congenital colorectal disease.

Methods/Design: A systematic literature review of all articles published between 1980-2019 was performed in the PubMed and CINAHL databases. Inclusion criteria included articles that reported on the …