Pediatrics Commons^™

Should Targeted Temperature Management Be Used In Cardiogenic Shock Patients? Systematic Review And Meta-Analysis, Adam Nieborek, Jerzy R Ladny, Milosz J Jaguszewski, Andrea Denegri, Aleksandra Sikora, Szymon Pucylo, Aleksandra Gasecka, Michal Pruc, Ivan Savytsky, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: Therapeutic hypothermia, or targeted temperature management (TTM), is a strategy of reducing the core body temperature of survivors of sudden cardiac arrest, cardiogenic shock (CS) or stroke. Therefore, a systematic literature review and meta-analysis were performed to tackle the question about whether the implementation of TTM is actually beneficial for patients with CS.

METHODS: Study was designed as a systematic review and meta-analysis. PubMed, Cochrane Library, Web of Science and Scopus were searched from these databases inception to July 17, 2022. Eligible studies were those comparing TTM and non-TTM treatment in CS patients. Data were pooled with the Mantel-Haenszel …

Association Between Remote Monitoring And Interstage Morbidity And Death In Patients With Single-Ventricle Heart Disease Across Socioeconomic Groups., Bianca Cherestal, Lori A. Erickson, Janelle R. Noel-Macdonnell Phd, Girish S. Shirali, Hayley S. Hancock, Doaa Aly, Matthew Files, Sarah Clauss, Natalie Jayaram

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in survival over time, the mortality rate for infants with single-ventricle heart disease remains high. Infants of low socioeconomic status (SES) are particularly vulnerable. We sought to determine whether use of a novel remote monitoring program, the Cardiac High Acuity Monitoring Program, mitigates differences in outcomes by SES.

METHODS AND RESULTS: Within the Cardiac High Acuity Monitoring Program, we identified 610 infants across 11 centers from 2014 to 2021. All enrolled families had access to a mobile application allowing for near-instantaneous transfer of patient information to the care team. Patients were divided into SES tertiles on the …

Acute And Chronic Kidney Injury During Therapy For Pediatric Acute Leukemia: A Report From The Leukemia Electronic Abstraction Of Records Network (Learn), Wendy Hsiao, Yimei Li, Kelly Getz, Lusha Cao, Edward Krause, Mark Ramos, Judy Lee, Maria Monica Gramatges, Karen R Rabin, Michael E Scheurer, Richard Aplenc, Michelle Denburg, Tamara P Miller

Center for Medical Ethics and Health Policy Staff Publications

Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in …

Trajectories Of Egfr And Risk Of Albuminuria In Youth With Type 2 Diabetes: Results From The Today Cohort Study, Laure El Ghormli, Hui Wen, Diane Uschner, Morey W Haymond, Kara S Hughan, Katherine Kutney, Lori Laffel, Sherida E Tollefsen, Elia N Escaname, Jane Lynch, Petter Bjornstad, Today Study Group

Faculty, Staff and Students Publications

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

RESULTS: At baseline, participants' mean age …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Clinical Factors Associated With Need For Neurosurgical Care In Young Children With Imaging For Macrocephaly: A Case Control Study, Jessica F. Rohde, Jeffrey Campbell, Julie Barbera, Elena Taylor, Ashok Ramachandra, Christopher Gegg, Andrea Scherer, Joseph Piatt

Department of Pediatrics Faculty Papers

BACKGROUND: Macrocephaly is present in 2.3% of children with important neurosurgical conditions in the differential diagnosis. The objective of this study was to identify clinical associations with actionable imaging findings among children with head imaging for macrocephaly.

METHODS: We conducted a case-control study of head imaging studies ordered for macrocephaly among children 24 months and younger in a multistate children's health system. Four neurosurgeons reviewed the images, determining cases to be a 'concern' if neurosurgical follow-up or intervention was indicated. Electronic health records were reviewed to collect patient-level data and to determine if surgery was performed. Controls were matched 3:1 …

The Androgen Receptor Does Not Directly Regulate The Transcription Of Dna Damage Response Genes, Joshua D Samuels, Katelyn A Moore, Hannah E Ennerfelt, Alexis M Johnson, Adeline E Walsh, Richard J Price, John R Lukens

Faculty, Staff and Student Publications

INTRODUCTION: Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.

METHODS: We generated and investigated 5xFAD Inpp5d

RESULTS: SHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health. Further, SHIP-1 loss enhanced microglial plaque containment and Aβ engulfment when compared to microglia from Cre-negative 5xFAD Inpp5d

DISCUSSION: …

Associations Between Metabolomic Biomarkers Of Avocado Intake And Glycemia In The Multi-Ethnic Study Of Atherosclerosis, Alexis C Wood, Mark O Goodarzi, Mackenzie K Senn, Meghana D Gadgil, Goncalo Graca, Matthew A Allison, Ioanna Tzoulaki, Michael Y Mi, Philip Greenland, Timothy Ebbels, Paul Elliott, Russell P Tracy, David M Herrington, Jerome I Rotter

Faculty, Staff and Students Publications

BACKGROUND: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.

OBJECTIVES: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.

METHODS: Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an …

Guidelines On Cholangioscopy For Indeterminate Biliary Strictures: One Step Closer To Consensus, Fares Ayoub, Mohamed O Othman

Faculty, Staff and Students Publications

No abstract provided.

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors And Poor Reliability Of Causality Scoring: Report From Insppire, Veronique D Morinville, Sohail Z Husain, Fuchenchu Wang, Gretchen A Cress, Maisam Abu-El-Haija, Ankur Chugh, Elissa Downs, Kate Ellery, Douglas S Fishman, Alvin Jay Freeman, Cheryl E Gariepy, Matthew Giefer, Tanja Gonska, Quin Liu, Asim Maqbool, Jacob Mark, Brian Arthur Mcferron, Megha Mehta, Jaimie D Nathan, Ken Ng, Chee Y Ooi, Emily Perito, Wenly Ruan, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children.

METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med …

Adjunctive Diagnostic Studies Completed Following Detection Of Candidemia In Children: Secondary Analysis Of Observed Practice From A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Rachel L Wattier, Robert F T Bucayu, Craig L K Boge, Rachael K Ross, Inci Yildirim, Theoklis E Zaoutis, Debra L Palazzi, Surabhi B Vora, Elio Castagnola, Martha Avilés-Robles, Lara Danziger-Isakov, Alison C Tribble, Tanvi S Sharma, Antonio C Arrieta, Gabriela Maron, David M Berman, Dwight E Yin, Lillian Sung, Michael Green, Emmanuel Roilides, Kiran Belani, José Romero, Pere Soler-Palacin, Eduardo López-Medina, Dawn Nolt, Ibrahim Zaid Bin Hussain, William J Muller, Sarmistha B Hauger, Natasha Halasa, Daniel Dulek, Alice Pong, Blanca E Gonzalez, Mark J Abzug, Fabianne Carlesse, Anna R Huppler, Sujatha Rajan, Catherine Aftandilian, Monica I Ardura, Arunaloke Chakrabarti, Benjamin Hanisch, Christine M Salvatore, Lena Klingspor, Elizabeth D Knackstedt, Irja Lutsar, Maria E Santolaya, Sydney Shuster, Sarah K Johnson, William J Steinbach, Brian T Fisher

Faculty, Staff and Students Publications

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown.

METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics …

Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma: Pathogenesis And Treatment, Josep M Llovet, Catherine E Willoughby, Amit G Singal, Tim F Greten, Mathias Heikenwälder, Hashem B El-Serag, Richard S Finn, Scott L Friedman

Faculty, Staff and Students Publications

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity …

Genomic Landscape Of Down Syndrome-Associated Acute Lymphoblastic Leukemia, Zhenhua Li, Ti-Cheng Chang, Jacob J Junco, Meenakshi Devidas, Yizhen Li, Wenjian Yang, Xin Huang, Dale J Hedges, Zhongshan Cheng, Mary Shago, Andrew J Carroll, Nyla A Heerema, Julie Gastier-Foster, Brent L Wood, Michael J Borowitz, Lauren Sanclemente, Elizabeth A Raetz, Stephen P Hunger, Eleanor Feingold, Tracie C Rosser, Stephanie L Sherman, Mignon L Loh, Charles G Mullighan, Jiyang Yu, Gang Wu, Philip J Lupo, Karen R Rabin, Jun J Yang

Faculty, Staff and Students Publications

Trisomy 21, the genetic cause of Down syndrome (DS), is the most common congenital chromosomal anomaly. It is associated with a 20-fold increased risk of acute lymphoblastic leukemia (ALL) during childhood and results in distinctive leukemia biology. To comprehensively define the genomic landscape of DS-ALL, we performed whole-genome sequencing and whole-transcriptome sequencing (RNA-Seq) on 295 cases. Our integrated genomic analyses identified 15 molecular subtypes of DS-ALL, with marked enrichment of CRLF2-r, IGH::IGF2BP1, and C/EBP altered (C/EBPalt) subtypes compared with 2257 non-DS-ALL cases. We observed abnormal activation of the CEBPD, CEBPA, and CEBPE genes in 10.5% of DS-ALL cases via a …

Candidate Biomarkers As Predictors Of Future Kidney Disease And Cardiovascular Dysfunction In Adolescents With Type 2 Diabetes, Fida Bacha, Laure El Ghormli, Barbara H Braffett, Amy S Shah, Santica M Marcovina, Lorraine E Levitt Katz, Steven M Willi, Sonia Caprio, Ruban Dhaliwal, Samuel S Gidding

Faculty, Staff and Students Publications

AIMS: Evaluate changes in circulating biomarkers as predictors of kidney disease, and cardiac/vascular dysfunction in participants from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Candidate biomarkers were assessed annually in 507 participants over a mean follow-up of 6.9 ± 2.4 years. Moderate albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g and hyperfiltration as eGFR ≥ 135 mL/min/1.73 m

RESULTS: At baseline, 35.7% were male, with a mean age 13.9 years, diabetes duration 7.8 months, and HbA1c 6.0%. Higher concentrations of E-selectin and proinsulin were associated with incident moderate albuminuria and hyperfiltration. …

Genetic Associations Between Modifiable Risk Factors And Alzheimer Disease, Jiao Luo, Jesper Qvist Thomassen, Céline Bellenguez, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Küçükali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Jürgen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre De Mendonça, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven Van Der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Magda Tsolaki, Giacomina Rossi, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt

Faculty, Staff and Students Publications

IMPORTANCE: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.

OBJECTIVE: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for …

Distribution Of Serum Uric Acid Concentration And Its Association With Lipid Profiles: A Single-Center Retrospective Study In Children Aged 3 To 12 Years With Adenoid And Tonsillar Hypertrophy, Jiating Yu, Xin Liu, Honglei Ji, Yawei Zhang, Hanqiang Zhan, Ziyin Zhang, Jianguo Wen, Zhimin Wang

Faculty, Staff and Student Publications

BACKGROUND: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy.

METHODS: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were …

Assessment Of Psychosocial And Neonatal Risk Factors For Trajectories Of Behavioral Dysregulation Among Young Children From 18 To 72 Months Of Age., Julie A. Hofheimer, Monica Mcgrath, Rashelle Musci, Guojing Wu, Sarah Polk, Courtney K. Blackwell, Annemarie Stroustrup, Robert D. Annett, Judy Aschner, Brian S. Carter, Jennifer Check, Elisabeth Conradt, Lisa A. Croen, Anne L. Dunlop, Amy J. Elliott, Andrew Law, Leslie D. Leve, Jenae M. Neiderhiser, T Michael O'Shea, Amy L. Salisbury, Sheela Sathyanarayana, Rachana Singh, Lynne M. Smith, Andréa Aguiar, Jyoti Angal, Hannah Carliner, Cindy Mcevoy, Steven J. Ondersma, Barry Lester, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children.

OBJECTIVE: To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Risk Factors For Hcc In Contemporary Cohorts Of Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Xiangjun Gu, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk.

APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on …

Risk Factors And Prognostic Significance Of Platelet Count Abnormalities In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Taylor O Kim, Gladstone Airewele, Amanda Grimes, Shaun Bulsara, Erin Peckham, Sebastian R Wanless, Heather Haq, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Michael Scheurer, Jenny Despotovic

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH).

DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014.

METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with …

Novel And Replicated Clinical And Genetic Risk Factors For Toxicity From High-Dose Methotrexate In Pediatric Acute Lymphoblastic Leukemia, Mark Zobeck, M Brooke Bernhardt, Kala Y Kamdar, Karen R Rabin, Philip J Lupo, Michael E Scheurer

Faculty, Staff and Students Publications

STUDY OBJECTIVE: Methotrexate (MTX) is a key component of treatment for high-risk pediatric acute lymphoblastic leukemia (ALL) but may cause acute kidney injury and prolonged hospitalization due to delayed clearance. The purpose of this study is to identify clinical and genetic factors that may predict which children are at risk for creatinine increase and prolonged MTX clearance.

DESIGN: We conducted a single-center, retrospective cohort study of pediatric patients with ALL who received 4000-5000 mg/m

MAIN RESULTS: Hispanic ethnicity, body mass index (BMI) < 3%, BMI between 85%-95%, and Native American genetic ancestry were found to be associated with an increased risk for creatinine elevation. Older age, Black race, and use of the intensive monitoring protocol were associated with a decreased risk for creatinine elevation. Older age, B- compared to T-ALL, and the minor alleles of rs2838958/SLC19A1 and rs7317112/ABCC4 were associated with an increased risk for delayed clearance. Black race, MTX dose reduction, and the minor allele of rs2306283/SLCO1B1 were found to be associated with a decreased risk for delayed clearance.

CONCLUSIONS: These predictors of MTX toxicities may allow for more precise individualized toxicity risk prediction.

Prevalence Of Abnormal Spirometry In Individuals With A Smoking History And No Known Obstructive Lung Disease, Thuonghien V Tran, Gregory L Kinney, Alejandro Comellas, Karin F Hoth, Arianne K Baldomero, A James Mamary, Jeffrey L Curtis, Nicola Hanania, Richard Casaburi, Kendra A Young, Victor Kim, Barry Make, Emily S Wan, Alejandro A Diaz, John Hokanson, James D Crapo, Edwin K Silverman, Surya P Bhatt, Elizabeth Regan, Spyridon Fortis, Copdgene® Investigators – Core Units, Copdgene® Investigators – Clinical Centers

Faculty, Staff and Students Publications

INTRODUCTION: Recent evidence suggests a high prevalence of undiagnosed chronic obstructive pulmonary disease (COPD). These individuals are at risk of exacerbations and delayed treatment. We analyzed an at-risk population for the prevalence of abnormal spirometry to provide clarity into who should undergo early spirometry.

METHODS: We analyzed data from the COPDGene study. Participants with ≥10 pack-years of smoking were included. Individuals with self-reported or physician-diagnosed COPD, asthma, chronic bronchitis, emphysema and/or were on inhalers were excluded. Parsimonious multivariable logistic regression models identified factors associated with abnormal spirometry, defined as either airflow obstruction (AFO) or preserved ratio impaired spirometry. Variables were …

Sex-Related Differences In Acuity And Postoperative Complications, Mortality And Failure To Rescue, Qi Yan, Jeongsoo Kim, Daniel E Hall, Myrick C Shinall, Katherine Moll Reitz, Karyn B Stitzenberg, Lillian S Kao, Chen-Pin Wang, Zhu Wang, Susanne Schmidt, Bradley B Brimhall, Laura S Manuel, Michael A Jacobs, Paula K Shireman

Faculty, Staff and Student Publications

INTRODUCTION: Yentl syndrome describing sex-related disparities has been extensively studied in medical conditions but not after surgery. This retrospective cohort study assessed the association of sex, frailty, presenting with preoperative acute serious conditions (PASC), and the expanded Operative Stress Score (OSS) with postoperative complications, mortality, and failure-to-rescue.

METHODS: The National Surgical Quality Improvement Program from 2015 to 2019 evaluating 30-d complications, mortality, and failure-to-rescue.

RESULTS: Of 4,860,308 cases (43% were male; mean [standard deviation] age of 56 [17] y), 6.0 and 0.8% were frail and very frail, respectively. Frailty score distribution was higher in men versus women (P < 0.001). Most cases were low-stress OSS2 (44.9%) or moderate-stress OSS3 (44.5%) surgeries. While unadjusted 30-d mortality rates were higher (P < 0.001) in males (1.1%) versus females (0.8%), males had lower odds of mortality (adjusted odds ratio (aOR) = 0.92, 95% confidence interval [CI] = 0.90-0.94, P < 0.001) after adjusting for frailty, OSS, case status, PASC, and Clavien-Dindo IV (CDIV) complications. Males have higher odds of PASC (aOR = 1.33, CI = 1.31-1.35, P < 0.001) and CDIV complications (aOR = 1.13, CI = 1.12-1.15, P < 0.001). Male-PASC (aOR = 0.76, CI = 0.72-0.80, P < 0.001) and male-CDIV (aOR = 0.87, CI = 0.83-0.91, P < 0.001) interaction terms demonstrated that the increased odds of mortality associated with PASC or CDIV complications/failure-to-rescue were lower in males versus females.

CONCLUSIONS: Our …

Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson

Faculty, Staff and Students Publications

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.

METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification …

Current Challenges And Future Direction In Surveillance For Hepatocellular Carcinoma In Patients With Nonalcoholic Fatty Liver Disease, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related …

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …

Cumulative Comorbid Conditions Influence Mortality Risk After Staged Palliation For Hypoplastic Left Heart Syndrome And Variants, Emily R Backes, Natasha S Afonso, Danielle Guffey, James S Tweddell, Sarah Tabbutt, Nancy A Rudd, Ginny O'Harrow, Silvana Molossi, George M Hoffman, Garick Hill, Jeffrey S Heinle, Priya Bhat, Jeffrey B Anderson, Nancy S Ghanayem

Faculty, Staff and Students Publications

Objective: Prematurity, low birth weight, genetic syndromes, extracardiac conditions, and secondary cardiac lesions are considered high-risk conditions associated with mortality after stage 1 palliation. We report the impact of these conditions on outcomes from a prospective multicenter improvement collaborative.

Methods: The National Pediatric Cardiology Quality Improvement Collaborative Phase II registry was queried. Comorbid conditions were categorized and quantified to determine the cumulative burden of high-risk diagnoses on survival to the first birthday. Logistic regression was applied to evaluate factors associated with mortality.

Results: Of the 1421 participants, 40% (575) had at least 1 high-risk condition. The aggregate high-risk group had …

Risk Factors And Prognostic Significance Of Anemia In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Amanda Grimes, Gladstone Airewele, Shaun Bulsara, Taylor Olmsted Kim, Heather Haq, Erin Peckham-Gregory, Sebastian R Wanless, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Jenny Despotovic, Michael Scheurer

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival.

RESULTS: Two thousand, one hundred and thirty-seven children were …

Analysis Of Insppire-2 Cohort: Risk Factors And Disease Burden In Children With Acute Recurrent Or Chronic Pancreatitis, Aliye Uc, Gretchen A Cress, Fuchenchu Wang, Maisam Abu-El-Haija, Kate M Ellery, Douglas S Fishman, Cheryl E Gariepy, Tanja Gonska, Tom K Lin, Quin Y Liu, Megha Mehta, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).

METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP.

RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR …

Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba

Faculty, Staff and Students Publications

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in …