Diseases Commons^™

Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla

Faculty, Staff and Students Publications

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up …

Platelet Function In Trauma: Is Current Technology In Function Testing Missing The Mark In Injured Patients?, Jacob B Schriner, Mitchell J George, Jessica C Cardenas, Scott D Olson, Kimberly A Mankiewicz, Charles S Cox, Brijesh S Gill, Charles E Wade

Faculty, Staff and Student Publications

Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. Following injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure 1 or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays …

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …

Association Of Rare Apoe Missense Variants V236e And R251g With Risk Of Alzheimer Disease, Yann Le Guen, Michael E Belloy, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo-Morales, Iris Jansen, Aude Nicolas, Céline Bellenguez, Carolina Dalmasso, Fahri Küçükali, Sarah J Eger, Katrine Laura Rasmussen, Jesper Qvist Thomassen, Jean-François Deleuze, Zihuai He, Valerio Napolioni, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Cornelia Van Duijn, Magda Tsolaki, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Wiesje M Van Der Flier, Alfredo Ramirez, Ole A Andreassen, Ruth Frikke-Schmidt, Julie Williams, Agustín Ruiz, Jean-Charles Lambert, Michael D Greicius, Members Of The Eadb, Gr@Ace, Degesco, Demgene, Gerad, And Eadi Groups, Beatrice Arosio, Luisa Benussi, Anne Boland, Barbara Borroni, Paolo Caffarra, Delphine Daian, Antonio Daniele, Stéphanie Debette, Carole Dufouil, Emrah Düzel, Daniela Galimberti, Vilmantas Giedraitis, Timo Grimmer, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Deckert Jürgen, Teemu Kuulasmaa, Aad Van Der Lugt, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Susanne Moebus, Benedetta Nacmias, Gael Nicolas, Robert Olaso, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Oliver Peters, Yolande A L Pijnenburg, Julius Popp, Innocenzo Rainero, Inez Ramakers, Steffi Riedel-Heller, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Hilkka Soininen, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Thomas J Tegos, Lucio Tremolizzo, Frans Verhey, Martin Vyhnalek, Jens Wiltfang, Mercè Boada, Pablo García-González, Raquel Puerta, Luis M Real, Victoria Álvarez, María J Bullido, Jordi Clarimon, José María García-Alberca, Pablo Mir, Fermin Moreno, Pau Pastor, Gerard Piñol-Ripoll, Laura Molina-Porcel, Jordi Pérez-Tur, Eloy Rodríguez-Rodríguez, Jose Luís Royo, Raquel Sánchez-Valle, Martin Dichgans, Dan Rujescu

Faculty, Staff and Students Publications

IMPORTANCE: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly.

OBJECTIVE: To determine whether rare missense variants on APOE are associated with AD risk.

DESIGN, SETTING, …

Postprandial Symptoms In Patients With Symptoms Of Gastroparesis: Roles Of Gastric Emptying And Accommodation, Henry P Parkman, Mark L Van Natta, Alan H Maurer, Kenneth L Koch, Madhusudan Grover, Zubair Malik, Irene Sarosiek, Thomas L Abell, Robert Bulat, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Richard W Mccallum

Faculty, Staff and Students Publications

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, …

Regulation Of Pgc1Α Downstream Of The Insulin Signaling Pathway Plays A Role In The Hepatic Proteotoxicity Of Mutant Α1-Antitrypsin Deficiency Variant Z, David A Rudnick, Jiansheng Huang, Tunda Hidvegi, Andrew S Chu, Pamela Hale, Admire Munanairi, Dennis J Dietzen, Paul F Cliften, Eric Tycksen, Andrew J Lutkewitte, Brian N Finck, Stephen C Pak, Gary A Silverman, David H Perlmutter

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Insulin signaling is known to regulate essential proteostasis mechanisms.

METHODS: The analyses here examined effects of insulin signaling in the PiZ mouse model of α1-antitrypsin deficiency in which hepatocellular accumulation and proteotoxicity of the misfolded α1-antitrypsin Z variant (ATZ) causes liver fibrosis and cancer.

RESULTS: We first studied the effects of breeding PiZ mice to liver-insulin-receptor knockout (LIRKO) mice (with hepatocyte-specific insulin-receptor gene disruption). The results showed decreased hepatic ATZ accumulation and liver fibrosis in PiZ x LIRKO vs PiZ mice, with reversal of those effects when we bred PiZ x LIRKO mice onto a FOXO1-deficient background. …

United States Healthcare Burden Of Pediatric Functional Gastrointestinal Pain Disorder Hospitalizations From 2002 To 2018, John M Hollier, Jason L Salemi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: The healthcare burden of pediatric functional gastrointestinal pain disorders (FGIDs) is unclear. Our study aimed to characterize the burden of these hospitalizations in the United States (US).

METHODS: We utilized the US National Inpatient Sample from 2002 to 2018 to capture pediatric hospitalizations (ages 4 to 18 years old) with a primary discharge diagnosis of abdominal pain, constipation, irritable bowel syndrome, dyspepsia, abdominal migraine, cyclic vomiting syndrome, or fecal incontinence. We calculated the FGID hospitalization prevalence rate, length of stay (LOS), and inflation-adjusted costs annually and assessed for statistically significant trend changes using joinpoint analyses.

KEY RESULTS: 22.3 million …

Cholestasis Alters Brain Lipid And Bile Acid Composition And Compromises Motor Function In Neonatal Piglets, Nicole Lind Henriksen, Svend Høime Hansen, Matthew Domenic Lycas, Xiaoyu Pan, Thomas Eriksen, Lars Søndergaard Johansen, Richard R Sprenger, Christer Stenby Ejsing, Douglas G Burrin, Kerstin Skovgaard, Vibeke Brix Christensen, Thomas Thymann, Stanislava Pankratova

Faculty, Staff and Students Publications

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more …

Mediating Effects Of Neighborhood-Level Socioeconomic Deprivation On The Association Between Race/Ethnicity And Advanced Hepatocellular Carcinoma, Abiodun O Oluyomi, Kusha A Mohammadi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Racial/ethnic minorities are more likely than non-Hispanic whites (NHW) to be diagnosed with advanced stage hepatocellular carcinoma (HCC). We examined the role of neighborhood disadvantage as a mediator of the association between race/ethnicity and HCC stage at diagnosis.

METHODS: We used data from HCC cases diagnosed in Texas from 2007 to 2015. HCC cases were classified as local versus regional/advanced stage. A mediation model approach was used to estimate the average direct effect, average mediated (indirect) effect, total effect, and proportion mediated by the Area Deprivation Index (ADI), a composite measure of disadvantage.

RESULTS: 7,622 had local while 6303 …

Pathogenesis Of Tuberculosis: The 1930 Lübeck Disaster Revisited, Peter Donald, Stefan Kaufmann, Stephanie Thee, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

During the 1930 Lübeck Mycobacterium bovis bacille Calmette–Guérin (BCG) disaster, 251 neonates received three oral BCG doses accidentally contaminated by virulent Mycobacterium tuberculosis; 67 (26.7%) infants died of tuberculosis. BCG reversion to pathogenicity did not occur. Detailed post mortem examinations clarified contested aspects of tuberculosis pathogenesis. Gastrointestinal infection was seldom “silent” and did not cause typical primary pulmonary lesions. In 15 infants, primary pulmonary foci were found but these resulted from vaccine ingestion and aspiration and were not caused by gastrointestinal infection spreading to the lungs without trace of its journey, as claimed by prominent researchers such as Calmette …

Viral Infections In Pakistan: Prevalence, Factors Affecting Spread, And Recommendations For Control, Zehra Naseem, Maaha Ayub, Sharaf Ali Shah, Syed Asad Ali, Syed Hani Abidi

Medical College Documents

Pakistan is endemic to a number of viral infections, owing to its humid climate, topographical variation, soaring population, and lack of education and awareness. These viruses may have several different modes of transmission, including respiratory or airborne transmission, sexual transmission, blood-borne, fecal-oral transmission, vector-borne transmission, and transmission following an organ transplant. Although several different microorganisms are responsible for causing these infections, a few viruses are found more commonly in Pakistan and are primarily responsible for causing infections. In this study, we present a review of the most recent studies on different viruses, transmitted through various transmission routes, found commonly in …

Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group

Faculty, Staff and Students Publications

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data …

Pneumococcal Carriage In Infants Post-Pcv10 Introduction In Pakistan: Results From Serial Cross-Sectional Surveys, Shahira Shahid, Amala Khan, Muhammad Imran Nisar, Farah Khalid, Muhammad Farrukh Qazi, Sheraz Ahmed, Furqan Kabir, Aneeta Hotwani, Sahrish Muneer, Syed Asad Ali, Anita K. M. Zaidi, Fyezah Jehan

Department of Paediatrics and Child Health

The 10-valent pneumococcal vaccine was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2013 as a 3 + 0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014-2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from two union councils of Matiari. Samples were then transported to the Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6-8 h of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture-positive for pneumococcus. …

Complications Of Pediatric Cochlear Implant Surgery, Andrew Stefan, Sabrina Bernardo, William Azkoul Ii, Bianca Siegel

Medical Student Research Symposium

Background:

Cochlear implantation (CI) surgery is the standard of care treatment for pediatric patients diagnosed with severe to profound sensorineural hearing loss. While considered a relatively safe operation, any invasive procedure involving the cranium has risks. However, there are few recent studies in the United States that have analyzed complication rates among children who have received CI. Furthermore, existing studies fail to discuss specific risk factors that led to post-operative complications, nor offer solutions to reduce their incidence. This study aims to 1) determine the incidence of specific complications in pediatric CI patients and 2) identify evidence-based risk factors for …

Estimating Circadian Phase In Elementary School Children: Leveraging Advances In Physiologically Informed Models Of Circadian Entrainment And Wearable Devices, Jennette P Moreno, Kevin M Hannay, Olivia Walch, Hafza Dadabhoy, Jessica Christian, Maurice Puyau, Abeer El-Mubasher, Fida Bacha, Sarah R Grant, Rebekah Julie Park, Philip Cheng

Faculty, Staff and Students Publications

STUDY OBJECTIVES: Examine the ability of a physiologically based mathematical model of human circadian rhythms to predict circadian phase, as measured by salivary dim light melatonin onset (DLMO), in children compared to other proxy measurements of circadian phase (bedtime, sleep midpoint, and wake time).

METHODS: As part of an ongoing clinical trial, a sample of 29 elementary school children (mean age: 7.4 ± .97 years) completed 7 days of wrist actigraphy before a lab visit to assess DLMO. Hourly salivary melatonin samples were collected under dim light conditions (<5 >lx). Data from actigraphy were used to generate predictions of circadian …

Maternal And Fetal Bile Acid Homeostasis Regulated By Sulfated Progesterone Metabolites Through Fxr Signaling Pathway In A Pregnant Sow Model, Peng Wang, Peiqiang Yuan, Sen Lin, Heju Zhong, Xiaoling Zhang, Yong Zhuo, Jian Li, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, De Wu, Douglas G Burrin, Zhengfeng Fang

Faculty, Staff and Students Publications

Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s t-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was …

Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data, Briana Christophers, Michael A Lopez, Vandana A Gupta, Hannes Vogel, Mary Baylies

Faculty, Staff and Student Publications

Nemaline myopathy is a skeletal muscle disease that affects 1 in 50 000 live births. The objective of this study was to develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with NM. A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, NM, nemaline rod, and rod myopathy. Case studies focused on pediatric NM and published in English between January 1, 2010, and December 31, …

Lmod2-Related Dilated Cardiomyopathy Presenting In Late Infancy, Erica Lay, Mahshid S Azamian, Susan W Denfield, William Dreyer, Joseph A Spinner, Debra Kearney, Lilei Zhang, Kim C Worley, Weimin Bi, Seema R Lalani

Faculty, Staff and Students Publications

Leiomodin-2 (LMOD2) is an important regulator of the thin filament length, known to promote elongation of actin through polymerization at pointed ends. Mice with Lmod2 deficiency die around 3 weeks of age due to severe dilated cardiomyopathy (DCM), resulting from decreased heart contractility due to shorter thin filaments. To date, there have been three infants from two families reported with biallelic variants in LMOD2, presenting with perinatal onset DCM. Here, we describe a third family with a child harboring a previously described homozygous frameshift variant, c.1243_1244delCT (p.L415Vfs*108) with DCM, presenting later in infancy at 9 months of age. Family history …

A Novel Automated Junctional Ectopic Tachycardia Detection Tool For Children With Congenital Heart Disease, Jamie L S Waugh, Raajen Patel, Yilong Ju, Ankit B Patel, Craig G Rusin, Parag N Jain

Faculty, Staff and Students Publications

BACKGROUND: Junctional ectopic tachycardia (JET) is a prevalent life-threatening arrhythmia in children with congenital heart disease (CHD), with marked resemblance to normal sinus rhythm (NSR) often leading to delay in diagnosis.

OBJECTIVE: To develop a novel automated arrhythmia detection tool to identify JET.

METHODS: A single-center retrospective cohort study of children with CHD was performed. Electrocardiographic (ECG) data produced by bedside monitors is captured automatically by the Sickbay platform. Based on the detection of R and P wave peaks, 2 interpretable ECG features are calculated: P prominence median and PR interval interquartile range (IQR). These features are used as input …

Risk For Post-Colonoscopy Irritable Bowel Syndrome In Patients With And Without Antibiotic Exposure: A Retrospective Cohort Study, Ravy K Vajravelu, Jordan M Shapiro, Josephine Ni, Shivani U Thanawala, James D Lewis, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure.

METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 …

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …

Relationship Between Arterial Stiffness And Subsequent Cardiac Structure And Function In Young Adults With Youth-Onset Type 2 Diabetes: Results From The Today Study, Amy S Shah, Samuel S Gidding, Laure El Ghormli, Jeanie B Tryggestad, Kristen J Nadeau, Fida Bacha, Lorraine E Levitt Katz, Steven M Willi, Joao Lima, Elaine M Urbina

Faculty, Staff and Students Publications

BACKGROUND: Higher arterial stiffness may contribute to future alterations in left ventricular systolic and diastolic function. We tested this hypothesis in individuals with youth-onset type 2 diabetes from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Arterial stiffness (pulse wave velocity [carotid-femoral, femoral-foot, and carotid-radial], augmentation index, brachial distensibility) was measured in 388 participants with type 2 diabetes (mean age, 21 years; diabetes duration, 7.7 ± 1.5 years). To reflect overall (composite) vascular stiffness, the five arterial stiffness measures were aggregated. An echocardiogram was performed in the same cohort 2 years later. Linear regression …

Prune1 C933g>A Synonymous Variant Induces Exon 7 Skipping, Disrupts The Dhha2 Domain, And Leads To An Atypical Nmihba Syndrome Presentation: Case Report And Review Of The Literature, Christina L Magyar, David R Murdock, Lindsay C Burrage, Hongzheng Dai, Seema R Lalani, Richard A Lewis, Yuezhen Lin, Marcela F Astudillo, Jill A Rosenfeld, Alyssa A Tran, James B Gibson, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous …

Evolution Of International Pediatric Endoscopic Practice Changes During The Coronavirus Disease 2019 Pandemic, Wenly Ruan, Douglas S Fishman, Diana G Lerner, Raoul I Furlano, Mike Thomson, Catharine M Walsh

Faculty, Staff and Students Publications

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered endoscopic practices. We initially reported the international impact of COVID-19 on pediatric endoscopic practice. This follow-up study aimed to assess changes 7 months following the initial survey to delineate practice change patterns as the pandemic evolved.

METHODS: Pediatric gastroenterologists who responded to the initial survey were re-surveyed seven months later using Research Electronic Data Capture (REDCap). The survey recorded information on changes in pediatric endoscopic practice patterns, including COVID-19 screening and testing processes and personal protective equipment (PPE) utilization. Additionally, endoscopists' risk tolerance of COVID-19 transmission was evaluated.

RESULTS: Seventy-five …

Rapid Molecular Diagnostics Of Tuberculosis Resistance By Targeted Stool Sequencing, Doctor B Sibandze, Alexander Kay, Viola Dreyer, Welile Sikhondze, Qiniso Dlamini, Andrew Dinardo, Godwin Mtetwa, Bhekumusa Lukhele, Debrah Vambe, Christoph Lange, Muyalo Glenn Dlamini, Tara Ness, Rojelio Mejia, Barbara Kalsdorf, Jan Heyckendorf, Martin Kuhns, Florian P Maurer, Sindisiwe Dlamini, Gugu Maphalala, Stefan Niemann, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Stool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

METHODS: We evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a …

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

Watch recording of live presentation.

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 …

Paradoxical Dat In A Term Newborn With Physiological Jaundice, Abiram Sivanandam, Tomas Rotschild

Rowan-Virtua Research Day

The Direct Antigen Test (DAT) is used to find out if a newborn has maternally-produced antibodies against the newborn’s red blood cells. We discuss the case of a term newborn male with an O+ blood type born to a mother whose blood type is A+. As a part of routine screening, DAT of umbilical cord blood was obtained, which resulted positive. While the neonate had jaundice, the overall clinical picture pointed more toward neonatal physiological jaundice rather than a potential hemolytic anemia expected with a positive DAT. This discrepancy prompted us to review literature to explain our findings.

A Case Of Intracranial Empyema After Bacterial Sinusitis, Eric Doane, Bhumi Shah, Robert Belfer

Rowan-Virtua Research Day

Acute sinusitis in the pediatric population is a common presentation in the emergency department. Most cases are viral and can be managed conservatively and will resolve spontaneously in 7-10 days. Even in cases of bacterial sinusitis, patients can typically be discharged with oral antibiotics and close follow up with the pediatrician.

There is however a small subset of patients who will develop a rare lethal complication, an intracranial empyema. While the incidence in the developed world has decreased as antibiotics become more available, it is still estimated to occur in up to 5% of severe cases requiring hospitalization (1) . …

Bilateral Teratomas In Pediatric Patient With Unilateral Ovarian Torsion, David Ho, Maya Borowczak, Archana Verma

Rowan-Virtua Research Day

Ovarian torsion is a surgical emergency found in both pediatric and adult populations. It involves the full or partial rotation of the vessels that supply the ovary, resulting in ischemia. In this report, we present the case of a pediatric patient arriving to the Pediatric Emergency Department (PED) for evaluation of right lower quadrant (RLQ) abdominal pain, who was found to have an ovarian torsion. In this particular case, the patient’s ovarian torsion was due to a teratoma, and imaging would later identify an additional smaller teratoma on the contralateral side. This case shows the importance of considering ovarian pathologies …