Pediatrics Commons^™

Impact Of Antiparasitic Therapy On Cardiovascular Outcomes In Chronic Chagas Disease A Systematic Review And Meta-Analysis, Anis Rassi, Alyssa Grimshaw, Ashwin Sarwal, Ranjit Sah, Sangam Shah, Nelson I Agudelo Higuita, Fabio Mahamed Rassi, Michaele Francesco Corbisiero, Hannah M Kyllo, Jordan Stellern, Samantha Kaplan, Luis A Marcos, Edgar A Ramírez-García, Martin Casapia, Peter Hotez, Maria Elena Bottazzi, Shital Patel, Carlos Franco-Paredes, José Antonio Marin-Neto, Andrés F Henao-Martínez

Faculty, Staff and Students Publications

BACKGROUND: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints. This study aims to evaluate the impact of antitrypanosomal therapy in preventing or reducing disease progression and mortality in chronic Chagas disease.

METHODS: We performed a systematic review and meta-analysis of studies reporting the cardiovascular outcomes of antitrypanosomal therapy in patients with chronic Chagas disease. We searched Ovid Embase, Ovid MEDLINE, Ovid Global Health, Scopus, Web of Science …

Diagnosis And Management Of Cardiometabolic Disease After Spinal Cord Injury: Identifying Gaps In Physician Training And Practices, Chinenye Christa Nnoromele, Du Pham, Felicia Skelton, Ryan Solinsky

Faculty, Staff and Students Publications

CONTEXT: Cardiometabolic disease (CMD) frequently occurs in individuals with spinal cord injury (SCI), with growing awareness surrounding the expansive scope of this problem. As CMD has significant morbidity and mortality, early guidelines-based screening and management have been established. However, the extent to which these guidelines have been adopted are unclear.

OBJECTIVE: Describe physicians' screening and management pattern for CMD in patients with SCI, as compared to SCI-specific CMD screening guidelines, and elucidate variables linked to screening and management patterns.

METHODS: SCI medicine-boarded physicians were surveyed on screening timing for CMD following acute SCI, along with their practice pattern and comfort …

Prospective Multicenter Longitudinal Measurement Of Liver Stiffness In School-Age Children With Cholestatic Liver Disease, Benjamin L Shneider, Nathan P Goodrich, Wen Ye, Jean P Molleston, Daniel H Leung, Ronald J Sokol, Laurel Cavallo, Kasper Wang, Pamela L Valentino, Jeffery H Teckman, James E Squires, Shikha S Sundaram, Philip Rosenthal, Rene Romero, Alexander G Miethke, Kathleen M Loomes, Rohit Kohli, Saul J Karpen, Binita M Kamath, M Kyle Jensen, Jorge A Bezerra, Lee M Bass, John C Magee, Children

Faculty, Staff and Students Publications

Background and aims: A multicenter prospective longitudinal study of vibration-controlled transient elastography (VCTE) in school-age children with biliary atresia (BA), alpha-1 antitrypsin deficiency (a1-AT) and Alagille syndrome (ALGS) was undertaken to test the hypothesis that there would be measurable disease progression over 2 years.

Methods: Vibration-controlled transient elastography was performed annually for 2 years in children with BA, a1-AT and ALGS.

Results: Valid liver stiffness measurement (LSM) was determined at baseline/second follow-up in 254/180 (71%), 104/58 (56%) and 100/61 (61%) participants (mean elapsed time 2.27 years) with BA, a1-AT and ALGS, respectively. Modeling did not reveal a relationship between LSM …

Risk Scores For Choledocholithiasis Perform Poorly In Patients With Hemolytic Diseases: A Pedi Database Report, Jennifer Thompson, Wenly Ruan, Douglas S Fishman, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Valerio Balassone, Filippo Torroni, Paola De Angelis, Simona Faraci, Cynthia Tsai, Michael Wilsey, Racha Khalaf, Petar Mamula, Quin Liu, Yuhua Zheng, Bradley A Barth, David Michael Troendle

Faculty, Staff and Students Publications

Patients with hemolytic diseases are at increased risk for gallstone-related complications. Modified scoring systems have been developed to assess which pediatric patients would benefit from endoscopic retrograde cholangiopancreatography (ERCP) to treat choledocholithiasis. This study aimed to evaluate the ability of the available criteria to determine which pediatric patients with hemolytic diseases are likely to benefit from ERCP. A secondary analysis was performed using the Pediatric ERCP Database Initiative database, which contains prospectively collected data from 1,124 ERCPs at tertiary-care institutions. We compared patients with a hemolytic disease to those without. Data was analyzed by two-tailed Fisher’s exact test and paired …

Comment On “Effectiveness And Safety Of Oral Vancomycin For The Treatment Of Inflammatory Bowel Disease Associated With Primary Sclerosing Cholangitis: A Systematic Review And Pooled Analysis”, Richard Kellermayer, Peter Lewindon, Cynthia Buness, James Tabibian, Kevin Johnson, Shamita Shah, Parambir Dulai, Ahmad H Ali, Ayesha Shah, Gerald Holtmann, Harland S Winter

Faculty, Staff and Students Publications

No abstract provided.

Detection Of Viral Rna And Dna And Immune Response Following Administration Of Live Attenuated Measles And Varicella Vaccines In Children With Chronic Liver Disease, Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman

Faculty, Staff and Students Publications

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all …

Interval Advanced Adenomas And Neoplasia In Patients With Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test, Kyle S Liu, Rollin George, Caleb Shin, Jia Q Xiong, Taher Jamali, Yan Liu, Priya Roy, Sonia Singh, Samuel Ma, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

METHODS: We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or …

Tb And Diabetes In Eswatini: Addressing Suboptimal Treatment Outcomes Through Integrated Services, Yael Hirsch-Moverman, Dana Bezuidenhout, Sakthi Senthilvelan, Lobsang Palmo, Debrah Vambe, Ntombifuthi Ginindza, Nonhlanhla Dlamini, Andrea A Howard, Joanne E Mantell

Faculty, Staff and Students Publications

Tuberculosis (TB) remains a significant public health challenge in Eswatini, a country with the highest global HIV prevalence. Diabetes mellitus (DM) is increasingly common among people newly diagnosed with TB, contributing to suboptimal TB treatment outcomes, including relapse and death. The DETECT study employed a multi-method approach to assess the prevalence and DM impact on TB treatment outcomes among adults with TB in 10 Ministry of Health facilities in Eswatini, and explore barriers and facilitators to integrating TB/DM services. DM screening was conducted using laboratory-based glycated hemoglobin (A1c) testing, with DM defined as A1c ≥ 6.5% and preDM as A1c …

Screening And Targeted Sequencing Of Stool For Microbiologic Confirmation And Drug Resistance Determination In Paucibacillary Tuberculosis, Tara E Ness, Mangaliso Ziyane, Nontobeko Maphalala, Abigail Seeger, Anca Vasiliu, Wethusonke Khumalo, Mdigo Thunzini, Sindisiwe Dlamini, Gugu Maphalala, Clement Gascua, Christoph Lange, Samantha Meyer, Bryce Inman, Viola Dreyer, Christian Utpatel, Tanja Niemann, Andrew Dinardo, Alexander Kay, Stefan Niemann, Anna Mandalakas

Faculty, Staff and Students Publications

In 2023, an estimated 10.8 million people developed tuberculosis, and 1.25 million people died from this disease, including 161,000 deaths in people with HIV (PWH) in whom tuberculosis remains the leading cause of death. Detecting Mycobacterium tuberculosis drug resistance remains a challenge among patients with paucibacillary tuberculosis; since there is such low bacterial load in their sputum it's unable to be detected via microscopy, there is also not enough bacteria for other sputum-based tests which could provide resistance testing. At an outpatient clinic in Eswatini from 2020-2023, stool and sputum samples were provided by a subset of children, adolescents, and …

The Catastrophic Cost Of Tb Care: Understanding Costs Incurred By Individuals Undergoing Tb Care In Low-, Middle-, And High-Income Settings – A Systematic Review, Olivia Alise D'Silva, Samantha Lancione, Oviya Ananthakrishnan, Angelina Addae, Suvesh Shrestha, Hannah Alsdurf, Kednapa Thavorn, Nompumelelo Mzizi, Anca Vasilu, Alexander Kay, Anna Maria Mandalakas, Alice Anne Zwerling

Faculty, Staff and Students Publications

Eliminating the burden of catastrophic costs experienced by individuals undergoing tuberculosis (TB) treatment is one of the World Health Organization (WHO) End TB Strategy targets. To help inform decisions on TB patient burden and cost-effective TB care, we conducted a systematic review to summarize current evidence around the burden of catastrophic costs incurred by individuals undergoing TB treatment and identified the main drivers of costs to aid in developing mitigation strategies. A literature search was performed in August 2024 using Embase, Web of Science, Scopus and Medline targeting studies using WHO, or WHO adapted patient costing questionnaires to measure direct …

Hidden Markov Model For Acoustic Pesticide Exposure Detection And Hive Identification In Stingless Bees, Alex Otesbelgue, Amara Jean Orth, Chandler David Fong, Carol Anne Fassbinder-Orth, Betina Blochtein, Maria João Ramos Pereira

Faculty, Staff and Students Publications

Pollinator populations are declining globally at an unprecedented rate, driven by factors such as pathogens, habitat loss, climate change, and the widespread application of pesticides. Although colony losses remain difficult to prevent, precision beekeeping has introduced non-invasive strategies for monitoring hive conditions. Acoustic data, combined with machine learning techniques, has proven effective in detecting stressors and specific events in honeybee colonies; however, such methodologies remain underexplored for stingless bees, a group of native pantropical pollinators. Meliponiculture, the practice of keeping stingless bees, is an expanding field that offers significant economic and conservation benefits. Stingless bees are particularly susceptible to pesticide …

An Innovative Approach To Assessing The Psychosocial Impacts On Liver Transplant Recipients: The Prediction-By-Correspondence Analysis, Se-Kang Kim, Rachel A Annunziato

Faculty, Staff and Students Publications

Background: Innovative analytic techniques are applied to the psychological functioning of liver transplant (LT) recipients to comprehend its effect on post-transplant survival, hypothesizing that adherence will be predicted by psychosocial functioning.

Methods: The psychosocial functioning of 248 LT recipients (88 females) aged 19 to 74 is assessed using the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT). In addition, the Medication Level Variability Index (MLVI) and biopsy-proven rejection are utilized to evaluate successful adherence. The Z-scores of the SIPAT scores are used to transform them into an ordinal variable with excellent, good, minimally acceptable, and poor categories. We employ a modified …

Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, Emily R Waskow, Lisa T Emrick, Jill A Rosenfeld, Shamika Ketkar, Lindsay C Burrage, Daryl A Scott

Faculty, Staff and Students Publications

Fine-Lubinsky syndrome is a rare clinically defined syndrome sometimes referred to as brachycephaly, deafness, cataract, microstomia, and impaired intellectual development syndrome. Here we provide a clinical and molecular update for a sibling pair diagnosed with Fine-Lubinsky syndrome. An extensive genetic work-up, including chromosomal microarray analysis and quad exome sequencing, was nondiagnostic. However, a research reanalysis of their exome sequencing data revealed that both were homozygous for an intronic c.749+39G>A [NM_001383.6] variant in DPH1. RNAseq analysis performed on RNA from fibroblasts revealed significantly reduced expression of DPH1 transcripts suggestive of abnormal splicing followed by nonsense mediated mRNA decay. Since the …

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, Isabel Haviland, Ralph D Hector, Lindsay C Swanson, Aubrie Soucy Verran, Emma Sherrill, Zoë Frazier, Annemarie M Denny, Jenna Lucash, Bo Zhang, Holly A Dubbs, Eric D Marsh, Judith L Weisenberg, Helen Leonard, Milena Crippa, Francesca Cogliati, Silvia Russo, Bernhard Suter, Rajsekar Rajaraman, Alan K Percy, John M Schreiber, Scott Demarest, Timothy A Benke, Maya Chopra, Timothy W Yu, Heather E Olson

Faculty, Staff and Students Publications

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 …

Clinical Variation In Lowe Syndrome: What And How?, Eileen D Brewer

Faculty, Staff and Students Publications

Lowe syndrome is an X-linked disorder caused by mutations of the OCRL gene which encodes the enzyme inositol polyphosphate-5-phosphatase OCRL (Ocrl1) and is expressed in almost all body cells. Clinical characteristics involve kidney, brain, eye, muscle, bone, teeth, testes, skin and thrombocytes. Clinical phenotypes are heterogenous among families and even among affected boys in the same family. All have kidney disease varying from severe manifestations of Fanconi syndrome to only low molecular weight proteinuria, hypercalciuria and little kidney disease in the first decade of life. All develop chronic kidney disease (CKD) that typically progresses slowly and reaches stages 4–5 after …

Increasing Premedication For Neonatal Intubation: A Quality Improvement Initiative, Michelle H Lucena, Toshiba Morgan-Joseph, Alecia Thompson-Branch

Faculty, Staff and Students Publications

INTRODUCTION: Endotracheal intubation is frequent in the neonatal intensive care unit (NICU) but may result in neonatal distress and instability. Premedication reduces adverse effects, such as hypoxia, bradycardia, and pain. The Specific, Measurable, Achievable, Relevant and Time-Bound aim for this project was to increase premedication use for nonemergent neonatal intubation in a specific NICU from 22% to 80% from March 2021 to May 2023.

METHODS: We use quality improvement methodology to explain our theory for improvement. Our key driver diagram depicts this initiative's aims, key drivers, and interventions to increase premedication use for neonatal intubation. We defined exclusion criteria and …

Atherogenic Lipoproteins Associate With Loss Of Glycemic Control In Youth-Onset Type 2 Diabetes: Results From The Today Study, Lorraine E Levitt Katz, Samuel S Gidding, James D Otvos, Kimberly L Drews, Fida Bacha, Steven Willi, Santica Marcovina, Siripoom Mckay, Ruth S Weinstock, Today Study Group

Faculty, Staff and Students Publications

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Results: At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic …

Towards A Common Approach For Managing Food Allergy And Serious Allergic Reactions (Anaphylaxis) At School. Ga2len And Efa Consensus Statement, Antoine Deschildre, Montserrat Alvaro-Lozano, Antonella Muraro, Marcia Podesta, Debra De Silva, Mattia Giovannini, Simona Barni, Timothy E Dribin, Mónica Sandoval-Ruballos, Aikaterini Anagnostou, Alessandro Fiocchi, Alice Toniolo, Andrew Bird, Angel Sánchez Sanz, Anna Asarnoj, Anna Nowak-Wegrzyn, Berber Vlieg-Boerstra, Brian P Vickery, Carina Venter, Caroline Nilsson, Cecilia Parente, Céline Demoulin, David M Fleischer, Diola Bijlhout, Edward F Knol, Eleanor Garrow, Emma E Cook, Fallon Schultz, Francesca Lazzarotto, Francesca Mori, Gary Wong, Gideon Lack, Graham Roberts, Gustavo Andres Marino, H N G Oude Elberink, Helen A Brough, Hugh A Sampson, Jay Lieberman, Jennifer Gerdts, Jing Zhao, Josefine Gradman, Julia E M Upton, Julie Wang, Kati Palosuo, Kirsi M Järvinen, Kirsten Beyer, Kunling Shen, Laura Polloni, Lianne Mandelbaum, Luciana Kase Tanno, Lucy A Bilaver, Marcus S Shaker, Margitta Worm, Maria Said, Mary Kelly, Mary Jane Marchisotto, Michael Makris, Mikaela Odemyr, Montserrat Fernandez-Rivas, Motohiro Ebisawa, Nandinee Patel, Pablo Rodríguez Del Río, Pakit Vichyanond, Paul Turner, Pete Smith, Pilar Morón Gaspar, R Sharon Chinthrajah, Rima Rachid, Roberta Bonaguro, Ruchi Gupta, Sabine Schnadt, Sakura Sato, Stefania Arasi, Stephanie Leonard, Sung Poblete, Susanne Halken, Thuy-My Le, Guillaume Pouessel, Tracey Dunn, Victoria Cardona, Torsten Zuberbier

Faculty, Staff and Students Publications

GA2LEN and EFA propose minimum specifications for all industrialised countries/regions to work towards to support students with food allergies in educational settings. We reviewed research and legislation and gained feedback from over 100 patient and professional groups. We built shared expectations around: 1. training all school staff about what food allergy is, the symptoms of allergic reactions, what to do in an emergency, and when and how to use and store devices that laypeople can use to administer adrenaline (epinephrine). 2. preventing allergic reactions by using clear labelling on school menus and prepacked and non‐prepacked foods and regular cleaning where …

Refinement Of A Published Gene-Physical Activity Interaction Impacting Hdl-Cholesterol: Role Of Sex And Lipoprotein Subfractions, Kenneth E Westerman, Tuomas O Kilpeläinen, Magdalena Sevilla-Gonzalez, Margery A Connelly, Alexis C Wood, Michael Y Tsai, Kent D Taylor, Stephen S Rich, Jerome I Rotter, James D Otvos, Amy R Bentley, Samia Mora, Hugues Aschard, D C Rao, Charles Gu, Daniel I Chasman, Alisa K Manning

Faculty, Staff and Students Publications

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). We explored this GxE in the Women’s Genome Health Study (WGHS; N=23,294; the strongest cohort-specific signal in the original meta-analysis), the UK …

Prevalence Of Abuse-Specific Injuries In Infants With Prior Injury Evaluated For Abuse, Nara Cho, Kristin G Crichton, Sara Helwig, Krista K Wheeler, Rachel M Stanley, Megan M Letson, Kristine A Campbell, Angela N Bachim, Colleen J Bressler, Carmen M Coombs, Lori Frasier, Nicole Johnson, Sara Kilbride, Jan Leonard, Daniel M Lindberg, Noelle T Tran, Joanne N Wood, Farah W Brink

Faculty, Staff and Students Publications

Background and objectives: Physical abuse is a common cause of morbidity in infants but is often missed in those with medically minor injuries, increasing the risk for escalating violence. Our objective was to compare the prevalence of abuse-specific injuries among infants with and without prior injuries.

Methods: This is a retrospective, multicenter study of infants (aged < 12 months) undergoing child abuse pediatrics provider (CAP) consultation for suspected physical abuse between 2/2021 and 12/2022 at 10 participating US centers. Encounters were dichotomized into those with and without history of prior injury. The groups were compared for rates of diagnostic screening and prevalence of abuse-specific injuries. The association of prior injuries with identification of abuse-specific injury was assessed using logistic regression controlling for demographics and presence of prior injury.

Results: We identified 2352 eligible encounters (median age: 4.2 months), of which 13% had a history of prior injury. In infants who underwent diagnostic testing, injury identification was significantly higher in those with prior injury (45% vs 22%, P < .05). Adjusting for patient characteristics, the presence of prior injury in infants was associated with higher odds of at least 1 type of abuse-specific injury being identified, compared with those without prior injury (adjusted odds ratio = 2.81, 95% CI = 2.10-3.76).

Conclusion: Infants with prior injury …

The Treatment Naïve Microbiome Of Pediatric Ulcerative Colitis And Microbial Therapeutics: A Humbling Challenge, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Occult Abdominal Trauma Screening In The Evaluation Of Suspected Child Physical Abuse, Tagrid M Ruiz-Maldonado, Joanne N Wood, Antoinette L Laskey, Christopher S Greeley, Angela Bachim, Daniel M Lindberg, James Anderst, John Melville, Carmen Coombs, Nancy S Harper, Lori Frasier, Farah W Brink, Caitlin E Crumm, Kristine A Campbell

Faculty, Staff and Students Publications

Background and objectives: Occult abdominal trauma (OAT) screening with transaminases, followed by abdominal computed tomography (CT) for transaminase values greater than 80 IU/L, has been recommended in cases of suspected physical abuse. This study aimed to evaluate case characteristics associated with OAT evaluation and determine OAT prevalence in these children.

Methods: Injured children aged younger than 60 months undergoing Child Abuse Pediatrics (CAP) consultation for suspected physical abuse from February 2021 to May 2023 were identified in CAPNET, a multicenter research network. Children with symptoms or signs of intra-abdominal injury were excluded. We identified case characteristics associated with transaminase screening …

A New Interpolated Pseudodifferential Preconditioner For The Helmholtz Equation In Heterogeneous Media, Sebastian Acosta, Tahsin Khajah, Benjamin Palacios

Faculty, Staff and Students Publications

This paper introduces a new pseudodifferential preconditioner for the Helmholtz equation in variable media with absorption. The pseudodifferential operator is associated with the multiplicative inverse to the symbol of the Helmholtz operator. This approach is well suited for the intermediate and high-frequency regimes. The main novel idea for the fast evaluation of the preconditioner is to interpolate its symbol, not as a function of the (high-dimensional) phase-space variables, but as a function of the wave speed itself. Since the wave speed is a real-valued function, this approach allows us to interpolate in a univariate setting even when the original problem …

Two-Dimensional Speckle Tracking Of The Ascending Aorta: A Novel Approach To Evaluate Arterial Stiffness In Pediatric Patients With Repaired Conotruncal Anomalies Using Echocardiography, Anmol Goyal, Anitha Parthiban, David A White, Daniel Forsha, Doaa Aly

Faculty, Staff and Students Publications

Background: Children with repaired conotruncal abnormalities (CTA) are at risk of progressive aortic dilation and deteriorating aortic elasticity even after surgical correction. Strain imaging, using a 2-dimensional speckle tracking echocardiography (2D-STE), has been used for arterial stiffness assessment, but pediatric data are still lacking. We investigated the feasibility, reproducibility, and clinical value of 2D-STE derived ascending aorta (AAo) stiffness in children with repaired CTA.

Methods: 22 pediatric patients with repaired CTA were included along with 25 age- and sex- matched healthy controls (mean age 10.2 ± 4.5 years). Conventional 2D echocardiographic and 2D-STE assessment of AAo mechanics was performed. M-mode …

Healthcare Providers’ Knowledge, Attitudes, And Perceptions From Using Targeted Sequencing To Diagnose And Manage Drug-Resistant Tuberculosis (Dr-Tb) In Eswatini, Maia Madison, Debrah Vambe, Sein Sein Thi, Mangaliso Ziyane, Nosisa Shiba, Babongile Blisset Nkala, Tara Ness, Agostinho Viana Lima, Sindisiwe Dlamini, Siphiwe Ngwenya, Anna Mandalakas, Alexander Kay

Faculty, Staff and Students Publications

Challenges in diagnosing drug-resistant tuberculosis (DR-TB) contribute to a diagnostic gap. Design-locked Targeted Sequencing (TS) assays have the potential to improve DR-TB diagnosis and management. TS assays are now being introduced into low-income, high TB burden settings. Eswatini is among the first high burden countries to have implemented TS for patient care. To evaluate the impact of the current program and optimize future implementation, we evaluated healthcare provider knowledge, attitudes, and perceptions (KAP) of TS and its implementation. We conducted semi-structured interviews with healthcare providers. Interviews were continued until data saturation was reached and analyzed by directed thematic analysis. The …

Altering The Intracellular Trafficking Of Necator Americanus Gst-1 Antigen Yields Novel Hookworm Mrna Vaccine Candidates, Athos Silva De Oliveira, Leroy Versteeg, Neima Briggs, Rakesh Adhikari, Maria Jose Villar, Jeanna R Redd, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

BACKGROUND: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

METHODOLOGY/FINDINGS: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to …

Bcg-Induced Dna Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing The Risk For Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Santiago Carrero Longlax, Kent J Koster, Ashish M Kamat, Marisa Lozano, Seth P Lerner, Rebecca Hannigan, Tomoki Nishiguchi, Abhimanyu, Daanish Sheikh, Malik Ladki, Alexandra Portillo, Amrit Koirala, Tajhal D Patel, Zoe Spieler, Aaron B Benjamin, Maxim Lebedev, Theresa U Ofili, Robert W Hutchison, George Udeani, Lynne A Opperman, Gabriel Neal, Anna M Mandalakas, Mihai G Netea, Moshe Arditi, Pablo Avalos, Sandra L Grimm, Cristian Coarfa, Jeffrey D Cirillo, Andrew R Dinardo

Faculty, Staff and Students Publications

BACKGROUND: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

METHODS: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19-specific vaccines.

RESULTS: Study enrollment was halted early, prior to reaching …

Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier

Faculty, Staff and Students Publications

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

Artificial Intelligence In Fetal And Pediatric Echocardiography, Alan Wang, Tam T Doan, Charitha Reddy, Pei-Ni Jone

Faculty, Staff and Students Publications

Echocardiography is the main modality in diagnosing acquired and congenital heart disease (CHD) in fetal and pediatric patients. However, operator variability, complex image interpretation, and lack of experienced sonographers and cardiologists in certain regions are the main limitations existing in fetal and pediatric echocardiography. Advances in artificial intelligence (AI), including machine learning (ML) and deep learning (DL), offer significant potential to overcome these challenges by automating image acquisition, image segmentation, CHD detection, and measurements. Despite these promising advancements, challenges such as small number of datasets, algorithm transparency, physician comfort with AI, and accessibility must be addressed to fully integrate AI …

Multiparametric Cardiovascular Magnetic Resonance Is Associated With Outcomes In Pediatric Heart Transplant Recipients, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Joshua D Robinson, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Multiparametric cardiovascular magnetic resonance (CMR) has an emerging role in non-invasive surveillance of pediatric heart transplant recipients (PHTR). Higher myocardial T2, higher extracellular volume fraction (ECV), and late gadolinium enhancement (LGE) have been associated with adverse clinical outcomes in adult heart transplant recipients. The purpose of this study was to investigate the prognostic value of CMR-derived T1 and T2 mapping, ECV, and LGE for clinical outcomes in PHTR.

METHODS: We performed a single-center, retrospective chart review of consecutive, gadolinium-enhanced CMR studies in PHTR over a 7.5-year period, excluding follow-up studies. Standard CMR ventricular volume and function analysis, T1 mapping …