Pediatrics Commons^™

Atomic Structure Of The Predominant Gii4 Human Norovirus Capsid Reveals Novel Stability And Plasticity, Liya Hu, Wilhelm Salmen, Rong Chen, Yi Zhou, Frederick Neill, James E Crowe, Robert L Atmar, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being used in vaccine development. The atomic structure of the GII.4 capsid in the native T = 3 state has not been determined. Here we present the GII.4 VLP structure with T = 3 symmetry determined using X-ray crystallography and cryo-EM at 3.0 Å and 3.8 Å resolution, respectively, which reveals unanticipated novel features. A novel aspect in the crystal structure determined without imposing icosahedral symmetry is the remarkable adaptability of the capsid protein VP1 …

Identification Of A Novel Microdeletion Causative Of Nance-Horan Syndrome, Mariana Lopez Martinolich, Hope Northrup, Pedro Mancias, Paul Hillman, Kavya Rao, Kate Mowrey

Faculty, Staff and Student Publications

BACKGROUND: Nance-Horan syndrome (NHS) is a rare X-linked genetic disorder characterized by ophthalmologic and dental anomalies as well as dysmorphic facies. The clinical phenotype in males includes congenital cataracts, vision loss, microcornea, nystagmus, microphthalmia, glaucoma, screwdriver blade-shaped incisors, supernumerary maxillary incisors, diastema, delays, intellectual disability, and dysmorphic facies. With the evolution of array-CGH technology, a total of five kindreds with NHS have been reported in the medical literature with microdeletions encompassing the NHS gene rather than sequencing variants.

METHODS: The patient is a 19-year-old male born to non-consanguineous parents with a past medical history of bilateral congenital cataracts, nystagmus, poor …

Symptom Clusters, Physical Activity, And Quality Of Life: A Latent Class Analysis Of Children During Maintenance Therapy For Leukemia, Mary C Hooke, Michelle A Mathiason, Audrey Blommer, Jessica Hutter, Pauline Mitby, Olga Taylor, Michael E Scheurer, Alicia S Kunin-Batson, Wei Pan, Marilyn J Hockenberry

Faculty, Staff and Students Publications

BACKGROUND: Children undergoing treatment for acute lymphocytic leukemia (ALL) report co-occurring symptoms of fatigue, sleep disturbances, and depression as a symptom cluster. Physical activity (PA) may influence symptom severity and quality of life (QOL).

OBJECTIVES: This study examined changes in symptoms and QOL during ALL maintenance in children categorized by symptom cluster and explored the influence of PA and symptoms on QOL.

METHODS: Self-report of fatigue, sleep disturbance, and depression; QOL; and PA were measured at the beginning and end of maintenance in 42 children aged 3 to 18 years with ALL. Children were categorized into symptom cluster groups based …

Constipation In Patients With Symptoms Of Gastroparesis: Analysis Of Symptoms And Gastrointestinal Transit, Henry P Parkman, Emily Sharkey, Richard W Mccallum, William L Hasler, Kenneth L Koch, Irene Sarosiek, Thomas L Abell, Braden Kuo, Robert J Shulman, Madhusudan Grover, Gianrico Farrugia, Ron Schey, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Nih/Niddk Gastroparesis Consortium

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC).

METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD+GI), 10 children with ASD but no GI symptoms (ASD−GI), and 20 from typically developing (TD) children (TD) in this pilot study. Fecal mycobiome taxa were analyzed by ITS sequencing. GI symptoms (GI Severity Index (GSI)), behavioral symptoms (Social Responsiveness Scale −2 (SRS-2)), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 (ELISA)) were evaluated. …

Tissue-Targeted Crispr-Cas9-Mediated Genome Editing Of Multiple Homeologs In F0 Generation Xenopus Laevis Embryos, Mark E Corkins, Bridget D Delay, Rachel K Miller

Faculty, Staff and Student Publications

Xenopus laevis frogs are a powerful developmental model that enables studies combining classical embryology and molecular manipulation. Because of the large embryo size, ease of microinjection, and ability to target tissues through established fate maps, X. laevis have become the predominant amphibian research model. Given that their allotetraploid genome has complicated the generation of gene knockouts, strategies need to be established for efficient mutagenesis of multiple homeologs to evaluate gene function. Here we describe a protocol to utilize CRISPR-Cas9-mediated genome editing to target either single alleles or multiple alloalleles in F0 X. laevis embryos. A single guide (sg) RNA is …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Kaposiform Lymphangiomatosis Presenting With A Group A Streptococcus Pericardial Effusion, Taylor Koerner, Mehul D Patel, Vinay Pai, Gitanjali Indramohan

Faculty, Staff and Student Publications

A 4-year-old child was transferred to the paediatric intensive care unit with acute respiratory failure following 4 days of fever, nausea and vomiting. Chest X-ray on admission had an enlarged cardiac silhouette and transthoracic echo confirmed a large pericardial effusion. An emergent pericardiocentesis was performed at bedside which drained nearly 1000 mL of purulent fluid. Postdrainage course was complicated by acute systolic and diastolic heart failure, thrombocytopenia and acute renal failure. A chest CT and MRI were concerning for a diffuse mediastinal soft-tissue density, so the patient underwent interventional radiology-guided biopsy complicated by haemorrhage requiring mediastinal exploration and subtotal thymectomy. …

Otosyphilis: A Rare Cause Of Reversible Hearing Loss In A Teenage Male, Shan He, Anna H Messner, Gayatri Mirani

Faculty, Staff and Students Publications

A high index of suspicion and a thorough neurotologic examination at the onset of presentation are imperative to generate the diagnosis of otosyphilis. Complete audiologic recovery is rare but possible in approximately 20%-25% of patients after appropriate treatment. We present a case of reversible hearing loss secondary to otosyphilis in a teenage male patient with a new diagnosis of human immunodeficiency virus (HIV). Audiology findings were consistent with mixed hearing loss. Lumbar puncture results were consistent with neurosyphilis. Prompt treatment with a 14-day course of intravenous penicillin led to the complete recovery of hearing. In this case report, the pathophysiology, …

The Acute Influence Of Vasopressin On Hemodynamic Status And Tissue Oxygenation Following The Norwood Procedure, Ronald A Bronicki, Sebastian Acosta, Fabio Savorgnan, Saul Flores, Barbara-Jo Achuff, Rohit Loomba, Mubbasheer Ahmed, Nancy Ghanayem, Jeffrey S Heinle, Vicken Asadourian, Javier J Lasa

Faculty, Staff and Students Publications

OBJECTIVES: Arginine vasopressin (AVP) is used to treat hypotension. Because AVP increases blood pressure by increasing systemic vascular resistance, it may have an adverse effect on tissue oxygenation following the Norwood procedure.

METHODS: Retrospective analysis of continuously captured hemodynamic data of neonates receiving AVP following the Norwood procedure.

RESULTS: We studied 64 neonates exposed to AVP within 7 days after the Norwood procedure. For the entire group, AVP significantly increased mean blood pressure (2.5 ± 6.3) and cerebral and renal oxygen extraction ratios (4.1% ± 9.6% and 2.0% ± 4.7%, respectively;

CONCLUSIONS: The right ventricle to pulmonary artery shunt cohort …

Design, Usability, And Acceptability Of A Needs-Based, Automated Dashboard To Provide Individualized Patient-Care Data To Pediatric Residents, Julia K W Yarahuan, Huay-Ying Lo, Lanessa Bass, Jeff Wright, Lauren M Hess

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Pediatric residency programs are required by the Accreditation Council for Graduate Medical Education to provide residents with patient-care and quality metrics to facilitate self-identification of knowledge gaps to prioritize improvement efforts. Trainees are interested in receiving this data, but this is a largely unmet need. Our objectives were to (1) design and implement an automated dashboard providing individualized data to residents, and (2) examine the usability and acceptability of the dashboard among pediatric residents.

METHODS: We developed a dashboard containing individualized patient-care data for pediatric residents with emphasis on needs identified by residents and residency leadership. To …

Randomised Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain, Robert J Shulman, Bruno P Chumpitazi, Susan M Abdel-Rahman, Uttam Garg, Salma Musaad, Gregory L Kearns

Faculty, Staff and Students Publications

AIMS: Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.

METHODS: Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, …

Factors Associated With Penicillin Allergy Labels In Electronic Health Records Of Children In 2 Large Us Pediatric Primary Care Networks, Margaret G Taylor, Torsten Joerger, Yun Li, Michael E Scheurer, Michael E Russo, Jeffrey S Gerber, Debra L Palazzi

Faculty, Staff and Students Publications

IMPORTANCE: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.

OBJECTIVE: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, …

Effect Of Domperidone Therapy On Gastroparesis Symptoms: Results Of A Dynamic Cohort Study By Niddk Gastroparesis Consortium, Irene Sarosiek, Mark Van Natta, Henry P Parkman, Thomas Abell, Kenneth L Koch, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Madhusudan Grover, Frank A Hamilton, Pankaj J Pasricha, Katherine P Yates, Laura Miriel, Laura Wilson, Goro Yamada, James Tonascia, Richard W Mccallum

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR).

METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. …

Mild Encephalitis/Encephalopathy With A Reversible Splenial Lesion Associated With Systemic Mycoplasma Pneumoniae Infection In North America: A Case Report, Nafee T Talukder, Ashlea Feezel, Jeremy E Lankford

Faculty, Staff and Student Publications

BACKGROUND: Mild encephalitis/encephalopathy with reversible splenial lesion is a clinical-radiological entity found to occur in the setting of an acute systemic inflammatory state with isolated lesions of the splenium of the corpus callosum and mild encephalopathy. Mild encephalitis/encephalopathy with reversible splenial lesion is commonly found to occur in children in the setting of viral infections. It has rarely been associated with Mycoplasma pneumoniae in the United States, unlike in Eastern and Southern Asia where this is much more prominent.

CASE PRESENTATIONS: A 5-year-old African-American boy with autism spectrum disorder presented to our emergency department with acute onset intractable vomiting, diarrhea, …

Virtual Simulated Implantation Of An Adult-Sized Left Ventricular Assist Device In A Pediatric Patient, Dilachew A Adebo, Santosh C Uppu, Avichal Aggarwal, Jorge D Salazar, Damien J Lapar

Faculty, Staff and Student Publications

There is very limited experience with simulated virtual implantation of left ventricular assist devices (LVADs) to assess device fitness in pediatric patients. In this clinical vignette, we report the case of a 9-year-old male patient with dilated cardiomyopathy who underwent successful placement of an LVAD after virtual simulated implantation was performed. (Level of Difficulty: Advanced.)

Developing Microbial Co-Culture System For Enhanced Polyhydroxyalkanoates (Pha) Production Using Acid Pretreated Lignocellulosic Biomass, Rijuta Ganesh Saratale, Si-Kyung Cho, Avinash Ashok Kadam, Gajanan Sampatrao Ghodake, Manu Kumar, Ram Naresh Bharagava, Sunita Varjani, Supriya Nair, Dong-Su Kim, Han-Seung Shin, Ganesh Dattatraya Saratale

Faculty, Staff and Student Publications

In the growing polymer industry, the interest of researchers is captivated by bioplastics production with biodegradable and biocompatible properties. This study examines the polyhydroxyalkanoates (PHA) production performance of individual Lysinibacillus sp. RGS and Ralstonia eutropha ATCC 17699 and their co-culture by utilizing sugarcane bagasse (SCB) hydrolysates. Initially, acidic (H2SO4) and acidified sodium chlorite pretreatment was employed for the hydrolysis of SCB. The effects of chemical pretreatment on the SCB biomass assembly and its chemical constituents were studied by employing numerous analytical methods. Acidic pretreatment under optimal conditions showed effective delignification (60%) of the SCB biomass, leading to a maximum hydrolysis …

The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Oi-Wa Chan, Wan-Hsuan Chen, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, Icns Group

Faculty, Staff and Student Publications

BACKGROUND: In general clinical practice, neonatal seizures are identified visually by direct clinical observation. The study aimed to examine the frequency of clinical seizures in paroxysmal events in a neonatal intensive care unit.

METHODS: We conducted a prospective study of continuous video-EEG monitoring in a neonatal intensive care unit between January 2017 and December 2020. The demographic data were also reviewed.

RESULTS: Sixty-four neonates were enrolled. The median total video-EEG monitoring duration was 24.1 h (IQR 17.5-44.8 h). There were 309 clinically suspected seizure episodes, of which 181 (58.6%) were the motor type and 128 (41.4%) were the non-motor type. …

Translating Research Into Practice-Implementation Recommendations For Pediatric Rheumatology; Proceedings Of The Childhood Arthritis And Rheumatology Research Alliance 2020 Implementation Science Retreat, Cagri Yildirim-Toruner, Rajdeep Pooni, Y Ingrid Goh, Emily Becker-Haimes, James W Dearing, Maria E Fernandez, Esi M Morgan, Gareth Parry, Jon M Burnham, Stacy P Ardoin, Fatima Barbar-Smiley, Joyce C Chang, Peter Chiraseveenuprapund, Vincent Del Gaizo, Guy Eakin, Lisa C Johnson, Yukiko Kimura, Andrea M Knight, Melanie Kohlheim, Erica F Lawson, Mindy S Lo, Nancy Pan, Andrea Ring, Tova Ronis, Rebecca E Sadun, Emily A Smitherman, Alysha J Taxter, Janalee Taylor, Richard K Vehe, Sheetal S Vora, Jennifer E Weiss, Emily Von Scheven, Mas For The Carra Implementation Science Workgroup

Faculty, Staff and Student Publications

The translation of research findings into clinical practice is challenging, especially fields like in pediatric rheumatology, where the evidence base is limited, there are few clinical trials, and the conditions are rare and heterogeneous. Implementation science methodologies have been shown to reduce the research- to- practice gap in other clinical settings may have similar utility in pediatric rheumatology. This paper describes the key discussion points from the inaugural Childhood Arthritis and Rheumatology Research Alliance Implementation Science retreat held in February 2020. The aim of this report is to synthesize those findings into an Implementation Science Roadmap for pediatric rheumatology research. …

Maximum Dose Food Challenges Reveal Transient Sustained Unresponsiveness In Peanut Oral Immunotherapy (Poimd Study), Carla M Davis, Aikaterini Anagnostou, Sridevi Devaraj, Daisy T Vita, Fabian Rivera, Kathleen Pitts, Melissa Hearrell, Charles Minard, Danielle Guffey, Meera Gupta, Levi Watkin, Jordan S Orange, Sara Anvari

Faculty, Staff and Students Publications

BACKGROUND: The maximum tolerated dose of peanut protein following peanut oral immunotherapy (POIT) is unknown because most research studies have not examined very high thresholds.

OBJECTIVE: To define the maximum dose tolerated by patients on POIT and severity of allergic reactions after a 1-month period of treatment discontinuation.

METHODS: In a phase 2 3-year POIT open-label study, we enrolled participants age 5 to 13 years with a 1-year build-up period followed by a 2-year daily maintenance dose of 3900 mg with assessment of the maximum tolerated dose using double-blind placebo-controlled food challenges (DBPCFCs) of 26,225 mg cumulative dose of peanut …

Body Region-Specific 3d Age-Scaling Functions For Scaling Whole-Body Computed Tomography Anatomy For Pediatric Late Effects Studies, Aashish C Gupta, Constance A Owens, Suman Shrestha, Choonsik Lee, Susan A Smith, Rita E Weathers, Tucker Netherton, Peter A Balter, Stephen F Kry, David S Followill, Keith T Griffin, James P Long, Gregory T Armstrong, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose:

Radiation epidemiology studies of childhood cancer survivors treated in the pre-computed tomography (CT) era reconstruct the patients’ treatment fields on computational phantoms. For such studies, the phantoms are commonly scaled to age at the time of radiotherapy treatment because age is the generally available anthropometric parameter. Several reference size phantoms are used in such studies, but reference size phantoms are only available at discrete ages (e.g.: newborn, 1, 5, 10, 15, and Adult). When such phantoms are used for RT dose reconstructions, the nearest discrete-aged phantom is selected to represent a survivor of a specific age. In this work, …

Rapunzel Syndrome Complicated By Escherichia Coli Sepsis, Bowel Perforation, And Pancreatitis In An 11-Year-Old Malnourished Female, Rhea Daniel, Mary Arbuthnot, Srinivas Ramireddy, Supriya Nair

Faculty, Staff and Student Publications

The most common presenting symptoms of Rapunzel syndrome include abdominal pain (37%), nausea and vomiting (33.3%), obstruction (25.9%), and peritonitis (18.3%). Less commonly, patients may present with weight loss (7.4%) or intussusception (7.4%). Exceedingly rare complications of Rapunzel syndrome include gastric ulceration, obstructive jaundice, and acute pancreatitis as well as other malabsorptive-related complications including protein-losing enteropathy, iron deficiency, and megaloblastic anemia. This report details the case of an 11-year-old female with Rapunzel syndrome complicated by sepsis, a rare complication reported in only 2% of patients.

Medical Management Of Infants With Supraventricular Tachycardia: Results From A Registry And Review Of The Literature, Nathan Wei, Avani Lamba, Sonia Franciosi, Ian H Law, Luis A Ochoa, Christopher L Johnsrude, Sit Yee Kwok, Teng Hong Tan, Santokh S Dhillon, Anne Fournier, Stephen P Seslar, Elizabeth A Stephenson, Andrew D Blaufox, Michel Cabrera Ortega, Jeffrey N Bone, Ash Sandhu, Carolina A Escudero, Shubhayan Sanatani

Faculty, Staff and Student Publications

BACKGROUND: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT.

METHODS: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. …

Fecal Microbiota Transplantation Commonly Failed In Children With Co-Morbidities, Richard Kellermayer, Qinglong Wu, Dorottya Nagy-Szakal, Karen Queliza, Faith D Ihekweazu, Claire E Bocchini, Abria R Magee, Numan Oezguen, Jennifer K Spinler, Emily B Hollister, Robert J Shulman, James Versalovic, Ruth Ann Luna, Tor C Savidge

Faculty, Staff and Students Publications

OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.

METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared …

Multidisciplinary Care For Refractory Pediatric Functional Abdominal Pain Decreases Emergency And Inpatient Utilization, Andrew S Chu, Laura Torres, Grace Kao, Caroyl Gilbert, Evelyn Caro Monico, Bruno P Chumpitazi

Faculty, Staff and Students Publications

Children with refractory functional abdominal pain (FAP) experience functional disability and may utilize emergency department (ED) and/or inpatient services. Whether multidisciplinary programs which help care for children with refractory FAP affect acute healthcare utilization is unknown. A retrospective chart review of children initially evaluated by the outpatient Multidisciplinary Abdominal Pain Program (MAPP) from October 2016 to May 2019 was completed. Patient characteristics and number of ED visits and hospitalizations for abdominal pain in the year prior to versus year after MAPP evaluation were captured. Thirty-eight children (ages 9-17 years [median 13 years]) were included. The median number of ED visits/patient/year …

Sars-Cov-2 Anti-Spike Antibodies After Vaccination In Pediatric Heart Transplantation: A First Report, Joseph A Spinner, Christopher L Julien, Lily Olayinka, William J Dreyer, Claire E Bocchini, Flor M Munoz, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.

METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.

RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a …

Comprehensive Evaluation Of Left Ventricular Deformation Using Speckle Tracking Echocardiography In Normal Children: Comparison Of Three-Dimensional And Two-Dimensional Approaches, Doaa Aly, Nitin Madan, Laura Kuzava, Alison Samrany, Anitha Parthiban

Faculty, Staff and Students Publications

BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) can overcome some of the inherent limitations of two-dimensional (2D) STE; however, clinical experience is lacking. We aimed to assess and compare the feasibility, agreement, and reproducibility of left ventricular (LV) global longitudinal (GLS), and regional strain by 3D vs 2D STE in normal children.

METHODS: Healthy pediatric subjects (n = 105, age mean = 11.2 ± 5.5 years) were prospectively enrolled. Three-dimensional and 2D LV GLS, as well as regional strain in 16 myocardial segments were quantified. Bland Altman analysis, intra- class correlation coefficients (ICC), percent error and linear regression were used …

Disruption Of Mecp2-Tcf20 Complex Underlies Distinct Neurodevelopmental Disorders, Jian Zhou, Hamdan Hamdan, Hari Krishna Yalamanchili, Kaifang Pang, Amy E Pohodich, Joanna Lopez, Yingyao Shao, Juan A Oses-Prieto, Lifang Li, Wonho Kim, Mark A Durham, Sameer S Bajikar, Donna J Palmer, Philip Ng, Michelle L Thompson, E Martina Bebin, Amelie J Müller, Alma Kuechler, Antje Kampmeier, Tobias B Haack, Alma L Burlingame, Zhandong Liu, Matthew N Rasband, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

MeCP2 is associated with Rett syndrome (RTT), MECP2 duplication syndrome, and a number of conditions with isolated features of these diseases, including autism, intellectual disability, and motor dysfunction. MeCP2 is known to broadly bind methylated DNA, but the precise molecular mechanism driving disease pathogenesis remains to be determined. Using proximity-dependent biotinylation (BioID), we identified a transcription factor 20 (TCF20) complex that interacts with MeCP2 at the chromatin interface. Importantly, RTT-causing mutations in MECP2 disrupt this interaction. TCF20 and MeCP2 are highly coexpressed in neurons and coregulate the expression of key neuronal genes. Reducing Tcf20 partially rescued the behavioral deficits caused …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Duncan NRI Faculty and Staff Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …