Medicine and Health Sciences Commons^™

Approach To Pivie In Pediatrics: Standardization For Early Detection, Jamie Green, Jill Gregory, Elizabeth Murphy, Jessica Miller, Nicole Manchester, Frank Harris, Meaghan Wildes, Cecilia Inman, Jenn Paradis, Faye Weir

Operations Transformation

PIVIE (Peripheral Intravenous Infiltration & Extravasation) can have devastating effects, especially in the pediatric population. The condition may disrupt vasculature severe enough for permanent skin and tissue loss that can lead to impaired limb function due to severe scarring. Problem: No standardized process existed either to prevent or review these events at Barbara Bush Children’s Hospital at Maine Medical Center prior to the study. PIVIEs were measured through the event reporting platform and only severe PIVIEs were being documented in this report. All infiltrations (1-4 on the infiltration scale) should be measured for accurate benchmarking. Occurrences in the electronic medical …

Seasonality, Clinical Characteristics, And Outcomes Of Respiratory Syncytial Virus Disease By Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020., Ariana P. Toepfer, Justin Z. Amarin, Andrew J. Spieker, Laura S. Stewart, Mary Allen Staat, Elizabeth P. Schlaudecker, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Marian G. Michaels, John V. Williams, Rangaraj Selvarangan, Christopher J. Harrison, Joana Y. Lively, Pedro A. Piedra, Vasanthi Avadhanula, Brian Rha, James Chappell, Meredith Mcmorrow, Heidi Moline, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established.

METHODS: During 2016-2020, children aged/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction.

RESULTS: Among 6398 RSV-positive …

Prognostic Impact Of Cooccurring Mutations In Flt3-Itd Pediatric Acute Myeloid Leukemia., Katherine Tarlock, Robert B. Gerbing, Rhonda E. Ries, Jenny L. Smith, Amanda Leonti, Benjamin J. Huang, Danielle Kirkey, Leila Robinson, Jack H. Peplinksi, Beverly Lange, Todd M. Cooper, Alan S. Gamis, E Anders Kolb, Richard Aplenc, Jessica A. Pollard, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

We sought to define the cooccurring mutational profile of FLT3-ITD-positive (ITDpos) acute myeloid leukemia (AML) in pediatric and young adult patients and to define the prognostic impact of cooperating mutations. We identified 464 patients with FLT3-ITD mutations treated on Children's Oncology Group trials with available sequencing and outcome data. Overall survival, event-free survival (EFS), and relapse risk were determined according to the presence of cooccurring risk stratifying mutations. Among the cohort, 79% of patients had cooccurring alterations across 239 different genes that were altered through mutations or fusions. Evaluation of the prognostic impact of the cooccurring mutations demonstrated that patients …

Improving Pneumococcal Vaccination Rates In Immunosuppressed Pediatric Patients With Rheumatic Disease., Julia G. Harris, Jordan T. Jones, Leslie Favier, Emily Fox, Michael J. Holland, Amy Ivy, Cara M. Hoffart, Maria Ibarra, Ashley M. Cooper

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year.

METHODS: …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design., Rachel S. Gross, Tanayott Thaweethai, Erika B. Rosenzweig, James Chan, Lori B. Chibnik, Mine S. Cicek, Amy J. Elliott, Valerie J. Flaherman, Andrea S. Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L. Jernigan, Elizabeth W. Karlson, Stuart D. Katz, Patricia A. Kinser, Lawrence C. Kleinman, Michelle F. Lamendola-Essel, Joshua D. Milner, Sindhu Mohandas, Praveen C. Mudumbi, Jane W. Newburger, Kyung E. Rhee, Amy L. Salisbury, Jessica N. Snowden, Cheryl R. Stein, Melissa S. Stockwell, Kelan G. Tantisira, Moriah E. Thomason, Dongngan T. Truong, David Warburton, John C. Wood, Shifa Ahmed, Almary Akerlundh, Akram N. Alshawabkeh, Brett R. Anderson, Judy L. Aschner, Andrew M. Atz, Robin L. Aupperle, Fiona C. Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M. Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C. Bind, Amanda L. Bogie, Tamara Bradford, Natalie C. Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B. Clark, Rebecca G. Clifton, Katharine N. Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B. Dummer, Matthew D. Elias, Shari Esquenazi-Karonika, Danielle N. Evans, E Vincent S. Faustino, Alexander G. Fiks, Daniel Forsha, John J. Foxe, Naomi P. Friedman, Greta Fry, Sunanda Gaur, Dylan G. Gee, Kevin M. Gray, Stephanie Handler, Ashraf S. Harahsheh, Keren Hasbani, Andrew C. Heath, Camden Hebson, Mary M. Heitzeg, Christina M. Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R. Horowitz, Daniel S. Hsia, Matthew Huentelman, Kathy D. Hummel, Katherine Irby, Joanna Jacobus, Vanessa L. Jacoby, Pei-Ni Jone, David C. Kaelber, Tyler J. Kasmarcak, Matthew J. Kluko, Jessica S. Kosut, Angela R. Laird, Jeremy Landeo-Gutierrez, Sean M. Lang, Christine L. Larson, Peter Paul C. Lim, Krista M. Lisdahl, Brian W. Mccrindle, Russell J. Mcculloh, Kimberly Mchugh, Alan L. Mendelsohn, Torri D. Metz, Julie Miller, Elizabeth C. Mitchell, Lerraughn M. Morgan, Eva M. Müller-Oehring, Erica R. Nahin, Michael C. Neale, Manette Ness-Cochinwala, Sheila M. Nolan, Carlos R. Oliveira, Onyekachukwu Osakwe, Matthew E. Oster, R Mark Payne, Michael A. Portman, Hengameh Raissy, Isabelle G. Randall, Suchitra Rao, Harrison T. Reeder, Johana M. Rosas, Mark W. Russell, Arash A. Sabati, Yamuna Sanil, Alice I. Sato, Michael S. Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M. Squeglia, Shubika Srivastava, Michelle D. Stevenson, Jacqueline Szmuszkovicz, Maria M. Talavera-Barber, Ronald J. Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M. Udosen, Megan R. Warner, Sara E. Watson, Alan Werzberger, Jordan C. Weyer, Marion J. Wood, H Shonna Yin, William T. Zempsky, Emily Zimmerman, Benard P. Dreyer, Recover-Pediatric Consortium

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Availability And Utilization Of Endoscopic Retrograde Cholangiopancreatography At Children's Hospitals., Sagar J. Pathak, Thomas M. Attard, Matthew Hall, Mustafa Arain, Melvin B. Heyman, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors.

METHODS: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service.

RESULTS: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses …

Population Pharmacokinetic Analysis Of Atomoxetine And Its Metabolites In Children And Adolescents With Attention-Deficit/Hyperactivity Disorder., Shen Cheng, Mahmoud Al-Kofahi, J Steven Leeder, Jacob T. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Atomoxetine (ATX) is a non-stimulant used to treat attention-deficit/hyperactivity disorder (ADHD) and systemic exposure is highly variable due to polymorphic cytochrome P450 2D6 (CYP2D6) activity. The objective of this study was to characterize the time course of ATX and metabolites (4-hydroxyatomoxetine (4-OH); N-desmethylatomoxetine (NDA); and 2-carboxymethylatomoxetine (2-COOH)) exposure following oral ATX dosing in children with ADHD to support individualized dosing. A nonlinear mixed-effect modeling approach was used to analyze ATX, 4-OH, and NDA plasma and urine, and 2-COOH urine profiles obtained over 24-72 hours from children with ADHD (n = 23) following a single oral ATX dose. Demographics and CYP2D6 …

Approach For Defining Human Adenovirus Infection And Disease For Central Review Adjudication In Clinical Studies., Brian T. Fisher, Jesse Blumenstock, Craig L K Boge, Sydney Shuster, Alix E. Seif, Michael Green, Marian G. Michaels, Jessie L. Alexander, Monica I. Ardura, Tamara P. Miller, Diego R. Hijano, William J. Muller, Jennifer E. Schuster, Abby M. Green, Daniel E. Dulek, Adriana E. Kajon, Lara Danziger-Isakov

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials.

METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were …

Recurrent Diffuse Alveolar Hemorrhage And Extracorporeal Membrane Oxygenation Utilization In A Hematopoietic Stem Cell Transplant Patient With Hunter's Syndrome., Nasreen Noor, Gene Peir, Asdis Finnsdottir Wagner, Jay Rilinger, Jenna Miller

Manuscripts, Articles, Book Chapters and Other Papers

We describe the natural history of a three-month-old patient with Hunter Syndrome with hematopoietic stem cell transplant (HSCT) who developed recurrent diffuse alveolar hemorrhage (DAH) requiring extracorporeal membrane oxygenation (ECMO). The patient underwent HSCT with several complications, including veno-occlusive disease and DAH. He was managed with ECMO. Unfortunately, despite initial success he developed recurrent DAH and ultimately died. This is a novel report of this severe adverse event requiring ECMO following the use of HSCT in this rare patient population. We share the clinical strategies employed to address the complications associated with HSCT and the progression of his disease over …

Prognostic Values Of Serum Lactate-To-Bicarbonate Ratio And Lactate For Predicting 28-Day In-Hospital Mortality In Children With Dengue Shock Syndrome, Thanh Nguyen Tat, Nhu Vo Hoang-Thien, Dat Nguyen Tat, Phuc Hoang Nguyen, Lien Thi Ho, Duong Hung Doan, Dung Tuan Phan, Yen Nguyen-Hoang Duong, Truc Huynh Nguyen, Tuyet Kim Nguyen, Ha Thi-Thu Dinh, Thuy Thi-Diem Dinh, Anh Thi-Mai Pham, Viet Do Chau, Tung Huu Trinh, Luan Vo Thanh

Journal Articles

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of …

Structural Variants Involving Mllt10 Fusion Are Associated With Adverse Outcomes In Pediatric Acute Myeloid Leukemia., Oussama Abla, Rhonda E. Ries, Tim Triche, Robert B. Gerbing, Betsy Hirsch, Susana Raimondi, Todd Cooper, Jason E. Farrar, Nathaniel Buteyn, Lauren M. Harmon, Hong Wen, Aniruddha J. Deshpande, E Anders Kolb, Alan S. Gamis, Richard Aplenc, Todd Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

MLLT10 gene rearrangements with KMT2A occur in pediatric acute myeloid leukemia (AML) and confer poor prognosis, but the prognostic impact of MLLT10 in partnership with other genes is unknown. We conducted a retrospective study with 2080 children and young adults with AML registered on the Children's Oncology Group AAML0531 (NCT00372593) and AAML1031 trials (NCT01371981). Transcriptome profiling and/or karyotyping were performed to identify leukemia-associated fusions associated with prognosis. Collectively, 127 patients (6.1%) were identified with MLLT10 fusions: 104 (81.9%) with KMT2A::MLLT10, 13 (10.2%) with PICALM::MLLT10, and 10 (7.9%) X::MLLT10: (2 each of DDX3X and TEC), with 6 partners (DDX3Y, CEP164, SCN2B, …

Immunophenotypic Predictors Of Influenza Vaccine Immunogenicity In Pediatric Hematopoietic Cell Transplant Recipients., Justin Z. Amarin, Daniel E. Dulek, Joshua Simmons, Haya Hayek, James D. Chappell, Cindy Hager Nochowicz, Carrie L. Kitko, Jennifer E. Schuster, Flor M. Muñoz, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Jason L. Freedman, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Lara Danziger-Isakov, Paul A. Carpenter, Janet A. Englund, Natasha B. Halasa, Andrew J. Spieker, Spyros A. Kalams

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and …

Antiviral Cellular Therapy For Enhancing T-Cell Reconstitution Before Or After Hematopoietic Stem Cell Transplantation (Aces): A Two-Arm, Open Label Phase Ii Interventional Trial Of Pediatric Patients With Risk Factor Assessment., Michael D. Keller, Patrick J. Hanley, Yueh-Yun Chi, Paibel Aguayo-Hiraldo, Christopher C. Dvorak, Michael R. Verneris, Donald B. Kohn, Sung-Yun Pai, Blachy J. Dávila Saldaña, Benjamin Hanisch, Troy C. Quigg, Roberta H. Adams, Ann Dahlberg, Shanmuganathan Chandrakasan, Hasibul Hasan, Jemily Malvar, Mariah A. Jensen-Wachspress, Christopher A. Lazarski, Gelina Sani, John M. Idso, Haili Lang, Pamela Chansky, Chase D. Mccann, Jay Tanna, Allistair A. Abraham, Jennifer L. Webb, Abeer Shibli, Amy K. Keating, Prakash Satwani, Pawel Muranski, Erin Hall, Michael J. Eckrich, Evan Shereck, Holly Miller, Ewelina Mamcarz, Rajni Agarwal, Satiro N. De Oliveira, Mark T. Vander Lugt, Christen L. Ebens, Victor M. Aquino, Jeffrey J. Bednarski, Julia Chu, Suhag Parikh, Jennifer Whangbo, Michail Lionakis, Elias T. Zambidis, Elizabeth Gourdine, Catherine M. Bollard, Michael A. Pulsipher

Manuscripts, Articles, Book Chapters and Other Papers

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST …

Durability Of Original Monovalent Mrna Vaccine Effectiveness Against Covid-19 Omicron-Associated Hospitalization In Children And Adolescents - United States, 2021-2023., Laura D. Zambrano, Margaret M. Newhams, Regina M. Simeone, Amanda B. Payne, Michael Wu, Amber O. Orzel-Lockwood, Natasha B. Halasa, Jemima M. Calixte, Pia S. Pannaraj, Kanokporn Mongkolrattanothai, Julie A Boom, Leila C Sahni, Satoshi Kamidani, Kathleen Chiotos, Melissa A Cameron, Aline B Maddux, Katherine Irby, Jennifer E. Schuster, Elizabeth H. Mack, Austin Biggs, Bria M. Coates, Kelly N. Michelson, Katherine E. Bline, Ryan A. Nofziger, Hillary Crandall, Charlotte V. Hobbs, Shira J. Gertz, Sabrina M. Heidemann, Tamara T. Bradford, Tracie C. Walker, Stephanie P. Schwartz, Mary Allen Staat, Samina S. Bhumbra, Janet R. Hume, Michele Kong, Melissa S. Stockwell, Thomas J. Connors, Melissa L. Cullimore, Heidi R. Flori, Emily R. Levy, Natalie Z. Cvijanovich, Matt S. Zinter, Mia Maamari, Cindy Bowens, Danielle M. Zerr, Judith A. Guzman-Cottrill, Ivan Gonzalez, Angela P. Campbell, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite …

Coronary Microvascular Dysfunction In Childhood: An Emerging Pathological Entity And Its Clinical Implications, Takeshi Tsuda, Gina Patel

Department of Pediatrics Faculty Papers

Coronary microvascular dysfunction (CMD) encompasses a spectrum of structural and functional alterations in coronary microvasculature resulting in impaired coronary blood flow and consequent myocardial ischemia without obstruction in epicardial coronary artery. The pathogenesis of CMD is complex involving both functional and structural alteration in the coronary microcirculation. In adults, CMD is predominantly discussed in context with anginal chest pain or existing ischemic heart disease and its risk factors. The presence of CMD suggests increased risk of adverse cardiovascular events independent of coronary atherosclerosis. Coronary microvascular dysfunction is also known in children but is rarely recognized due to paucity of concommitent …

Chromatin Profiles Are Prognostic Of Clinical Response To Bortezomib-Containing Chemotherapy In Pediatric Acute Myeloid Leukemia: Results From The Cog Aaml1031 Trial., Anneke D. Van Dijk, Fieke W. Hoff, Yihua Qiu, Stefan E. Hubner, Robin L. Go, Vivian R. Ruvolo, Amanda R. Leonti, Robert B. Gerbing, Alan S. Gamis, Richard Aplenc, Edward A. Kolb, Todd A. Alonzo, Soheil Meshinchi, Eveline S J M De Bont, Terzah M. Horton, Steven M. Kornblau

Manuscripts, Articles, Book Chapters and Other Papers

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and higher 3-year …

Multicenter Study Of Long-Term Outcomes And Quality Of Life In Phace Syndrome After Age 10., Mitchell Braun, Ilona J. Frieden, Dawn H. Siegel, Elizabeth George, Christopher P. Hess, Christine K. Fox, Sarah L. Chamlin, Beth A. Drolet, Denise Metry, Elena Pope, Julie Powell, Kristen Holland, Caden Ulschmid, Marilyn G. Liang, Kelly K. Barry, Tina Ho, Chantal Cotter, Eulalia Baselga, David Bosquez, Surabhi Neerendranath Jain, Jordan K. Bui, Irene Lara-Corrales, Tracy Funk, Alison Small, Wenelia Baghoomian, Albert C. Yan, James R. Treat, Griffin Stockton Hogrogian, Charles Huang, Anita Haggstrom, Mary List, Catherine C. Mccuaig, Victoria Barrio, Anthony J. Mancini, Leslie P. Lawley, Kerrie Grunnet-Satcher, Kimberly A. Horii, Brandon D. Newell, Amy J. Nopper, Maria C. Garzon, Margaret E. Scollan, Erin F. Mathes

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome.

STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains.

RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma …

Influence Of Novel Cyp2c-Haplotype On Proton Pump Inhibitor Pharmacokinetics In Children., Kathyrn Kyler, Andrea Gaedigk, Susan Abdel-Rahman, Vincent S. Staggs, Robin E. Pearce, Paul C. Toren, J Steven Leeder, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

In this brief report, we provide an analysis of the influence of a novel CYP2C haplotype (CYP2C:TG) on proton pump inhibitor (PPI) pharmacokinetics (PK) in children. The CYP2C:TG haplotype has been proposed to be associated with increased CYP2C19 activity. We sought to determine if this CYP2C:TG haplotype resulted in similar alterations in metabolism for proton pump inhibitors, which are primarily metabolized by CYP2C19. In a cohort of 41 children aged 6-21 participating in a PPI pharmacokinetic study, effects of the CYP2C:TG allele were assessed by fitting two linear regression models for each of the six PK outcomes assessed, the second …

Accuracy Of Influenza Icd-10 Diagnosis Codes In Identifying Influenza Illness In Children., James W. Antoon, Tess Stopczynski, Justin Z. Amarin, Laura S. Stewart, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Janet A. Englund, Eileen J. Klein, Mary A. Staat, Elizabeth P. Schlaudecker, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Ariana Perez, Heidi L. Moline, Andrew J. Spieker, Carlos G. Grijalva, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown.

OBJECTIVE: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings.

DESIGN, SETTING, AND PARTICIPANTS: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 …

Kawasaki Disease In Kenya And Review Of The African Literature, Angela Migowa, Catherine Njeri, Edwin Were, Thomas Ngwiri, L Colmegna

Paediatrics and Child Health, East Africa

Background: Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report.

Methods: A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature.

Results: Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had …

Time To Full Enteral Feeds In Hospitalised Preterm And Very Low Birth Weight Infants In Nigeria And Kenya, Zainab Imam, Helen Nabwera, Olukemi Tongo, Pauline Andang’O, Isa Abdulkadir, Chinyere Ezeaka, Beatrice Ezenwa, Iretiola Fajolu, Martha Mwangome, Dominic Umoru

Paediatrics and Child Health, East Africa

Background: Preterm (born < 37 weeks’ gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnera- ble infants in sub-Saharan Africa.

Aim: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/ kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan Afri- can countries.

Methods: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds.

Results: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before …

Wcn24-931 Aki Phenotypes In Ugandan Children Hospitalized With Hypoxemia And Malaria, Andrea Conroy, Anthony Batte, Rodney Ogwang, Sophie Namasopo, Robert Opoka, Michael Hawkes

Paediatrics and Child Health, East Africa

Introduction: Acute kidney injury (AKI) is a frequent life-threatening complication in hospitalized children. Emerging data suggest AKI is a heterogeneous condition that varies based on the underlying cause and is composed of distinct phenotypes. The objective of this study was to define AKI phenotypes using proposed classification systems in Ugandan children hospitalized with hypoxemia and to evaluate differences in phenotypes by malaria infection.

Methods: Between 2019 and 2021, 2402 Ugandan children <5 years of age hospitalized with hypoxemia were enrolled in a cluster randomized trial of solar powered oxygen delivery across 20 districts in Uganda. At enrollment, urine NGAL was measured using a point-of-care lateral flow test with a positive test defined as a level ≥150ng/mL. Malaria was assessed using a threeband rapid diagnostic test. In an extended sub-study, 491 children had creatinine measured to define AKI. AKI was defined using a single creatinine measure at enrolment and phenotypically characterized using two acute dialysis quality initiative (ADQI) proposed AKI phenotypes. The AKI biomarker definition incorporated urine NGAL into the KDIGO definition[group 1, no AKI; group 2, subclinical AKI (biomarker positive); group 3, AKI; group 4, biomarker positive AKI]. The ADQI sepsis AKI phenotype groups stage 1 AKI as sepsis phenotype (SP)-1 irrespective of biomarker status and differentiates severe AKI (stage 2/3) based on biomarker positivity where severe AKI that is biomarker negative is (SP2) and severe biomarker positive AKI is SP3.

Results: Overall, 491 children were included in the extended study with AKI defined and uNGAL measured. The median age was 1.3 years (interquartile range, 0.7 to 2.3) and 53.8% …

Wcn24-2067 Regional Differences In Acute Kidney Injury In Ugandan Children Hospitalized For Hypoxemia, Anthony Batte, Rodney Ogwang, Robert Opoka, Sophie Namasopo, Michael Hawkes, Andrea Conroy

Paediatrics and Child Health, East Africa

Introduction: Acute kidney injury (AKI) is associated with increased mortality in hospitalized patients and incidence is highest in resource limited settings. The objective of this study was to assess sub-National regional differences in the incidence of AKI in children <5 years of age hospitalized with an acute febrile illness and hypoxemia.

Methods: This was a secondary analysis of a stepped wedge cluster randomized controlled trial, which enrolled children <5 years of age hospitalized with hypoxemia between 2019 and 2021. At least one measure of kidney function was available in 1452 children. A single creatinine was measured at enrolment in a sub-set of 495 children with serum stored and AKI defined using KDIGO criteria where baseline creatinine was estimated using the age-based Pottel equation assuming a normal glomerular filtration rate of 120mL/min per 1.73m2. Markers were divided into structural (uNGAL positive, proteinuria, hematuria) or functional (AKI, saliva urea nitrogen (SUN)) measures of kidney injury.

Results: 1452 children were included in this AKI sub-study (Figure 1). The mean age of participants was 1.49 years (standard deviation (SD), 1.21) and 55.7% were male (809/1452). Overall 2.6% of children died (38/1452). The majority of participants enrolled were from the West (31.3%) …

Learning Circles: Promoting Inclusive Care Starting In The Classroom, April Graham, Kindsey Gattman, Tobias Johnson

Articles, Abstracts, and Reports

No abstract provided.

Quality Of Life In A Cohort Of Kenyan Children With Cerebral Palsy, Pauline Samia, Melissa Tirkha, Amina Kassam, Richard Muindi, Wahu Gitakah, Susan Wamithi, James Orwa, Eugene Were, Michael Shevell

Paediatrics and Child Health, East Africa

Aim: The objective of the study was to evaluate the quality of life in Kenyan children (age 4–18 years) with cerebral palsy (CP).

Methods: A cross-sectional descriptive study was conducted. Children with CP were recruited from the pediatric clinics at the Aga Khan hospital Nairobi (AKUHN). Parent proxy-reports using CPQoL-child and CPQoL-adolescents were obtained. Clinical and demographic data were compiled from medical records and parent interviews. A Likert scale was utilized to determine QoL across several domains.

Results: One hundred and fourteen child–parent dyads with CP were recruited. The median age of study participants was 8 years (IQR 3–13 years), …

Delayed Onset Of Neonatal Compartment Syndrome Associated With Compound Fetal Presentation, Nicholas Manini, Hayato Unno

Department of Medicine Faculty Papers

Neonatal compartment syndrome, although rare, has a classic presentation with sentinel skin findings and development of swelling, erythema, and tenderness of the affected extremity. Neonatal compartment syndrome requires prompt surgical intervention to preserve the affected limb and ensure its normal growth and development. Our patient was born at term via vaginal delivery complicated by a compound presentation involving the left upper extremity. No physical exam abnormalities were noted at birth, but she developed signs of neonatal compartment syndrome by 15 h of life. She was surgically treated at 22 h of life and recovered well. At one year of age, …

Investigating The Use Of Finerenone In Children With Chronic Kidney Disease And Proteinuria: Design Of The Fiona And Open-Label Extension Studies., Franz Schaefer, Giovanni Montini, Hee Gyung Kang, Johan Vande Walle, Joshua Zaritsky, Michiel F. Schreuder, Mieczyslaw Litwin, Andrea Scalise, Helen Scott, James Potts, Pablo Iveli, Stefanie Breitenstein, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.

OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that …

Pediatric Beta Blocker Therapy: A Comprehensive Review Of Development And Genetic Variation To Guide Precision-Based Therapy In Children, Adolescents, And Young Adults., Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review …

Infant Appendicitis: A Case Presentation Of Appendicitis In A Nine-Month-Old Infant With Respiratory Syncytial Virus (Rsv) And Otitis Media And Review Of Literature., Leslie Hueschen, April Mcneill-Johnson

Manuscripts, Articles, Book Chapters and Other Papers

Appendicitis in children < 5 years old is uncommon and even less common in children < 1 year old. Symptoms of appendicitis can be non-specific and mimic other common pediatric diseases, causing delays in diagnosis. Without a timely diagnosis, young children with appendicitis are at risk of developing worsening disease, intra-abdominal abscess, perforation, and bacteremia. We submit a case of a nine-month-old male infant presenting with fever, vomiting, and irritability seen the day prior and treated for otitis media, who was ultimately diagnosed with appendicitis with concomitant viral infection (respiratory syncytial virus and human rhinovirus/enterovirus) and treated with intravenous antibiotics and laparoscopic appendectomy. This case illustrates how easy it is to misdiagnose infant appendicitis due to factors including normal developmental speech barriers, nonspecific presentations, and overlap of symptoms with many other common childhood illnesses, along with a challenging abdominal examination. Delay in diagnosis leads to increased rates of perforation and complications. Providers should trust abnormal physical examination findings, especially abdominal guarding against palpation, and keep a wide differential diagnosis in order to diagnose appendicitis in young children.

Nf-Κb As An Inducible Regulator Of Inflammation In The Central Nervous System, Sudha Anilkumar, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type-specific and, in the majority of cases, result in the activation of pro-inflammatory cascades. Acting as …