Medicine and Health Sciences Commons^™

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

"C.H.A.M.P. Families": Description And Theoretical Foundations Of A Paediatric Overweight And Obesity Intervention Targeting Parents-A Single-Centre Non-Randomised Feasibility Study., Kristen Reilly, Trish Tucker, Jennifer D. Irwin Phd, Andrew Johnson, Erin S Pearson, Dirk E Bock, Shauna M. Burke

Paediatrics Publications

Childhood obesity represents a significant global health challenge, and treatment interventions are needed. The purpose of this paper is to describe the components and theoretical model that was used in the development and implementation of a unique parent-focussed paediatric overweight/obesity intervention. C.H.A.M.P. Families was a single-centre, prospective intervention offered to parents of children aged between 6⁻14 years with a body mass index (BMI) ≥85th percentile for age and sex. The intervention included: (1) eight group-based (parent-only) education sessions over 13-weeks; (2) eight home-based activities; and (3) two group-based (family) follow-up support sessions. The first section of the manuscript contains a …

Autoimmune Hyperphosphatemic Tumoral Calcinosis In A Patient With Fgf23 Autoantibodies., Mary Scott Roberts, Peter D. Burbelo, Daniela Egli-Spichtig, Farzana Perwad, Christopher J. Romero, Shoji Ichikawa, Emily G. Farrow, Michael J. Econs, Lori C. Guthrie, Michael T. Collins, Rachel I. Gafni

Manuscripts, Articles, Book Chapters and Other Papers

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 …

Phenytoin Activates Smad3 Phosphorylation And Periostin Expression In Drug-Induced Gingival Enlargement., Shawna S Kim, Georgia Nikoloudaki, Mark Darling, Michael J Rieder, Douglas W Hamilton

Paediatrics Publications

Drug-induced gingival enlargement (DIGE) is a fibrotic condition associated with systemic administration of the anti-epileptic drug, phenytoin. We have previously demonstrated that periostin, which is transforming growth factor-beta (TGF-β) inducible gene, is upregulated in various fibrotic conditions including gingival enlargement associated with nifedipine. The objective of this study was to assess periostin expression in phenytoin-induced gingival enlargement (PIGE) tissues and to investigate the mechanisms underlying periostin expression. Human PIGE tissues were assessed using Masson's trichrome, with cell infiltration and changes in extracellular matrix composition characterized through labeling with antibodies to periostin, phospho-SMAD 3, TGF-β, as well as the macrophage markers …

Risk Stratification Of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture., Paul L. Aronson, Marie E. Wang, Eugene D. Shapiro, Samir S. Shah, Adrienne G. Deporre, Russell J Mcculloh, Christopher M. Pruitt, Sanyukta Desai, Lise E. Nigrovic, Richard D. Marble, Rianna C. Leazer, Sahar N. Rooholamini, Laura F. Sartori, Fran Balamuth, Christopher Woll, Mark I. Neuman, Febrile Young Infant Research Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

Video Abstract: media-1vid110.1542/5840460609001PEDS-VA_2018-1879

OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing.

METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a …

Evaluation Of The Hiv Infant Tracking System (Hitsystem) To Optimise Quality And Efficiency Of Early Infant Diagnosis: A Cluster-Randomised Trial In Kenya., Sarah Finocchario-Kessler, Brad Gautney, Anlin Cheng, Catherine Wexler, May Maloba, Niaman Nazir, Samoel Khamadi, Raphael Lwembe, Melinda Brown, Thomas A. Odeny, Jacinda K. Dariotis, Matthew Sandbulte, Natabhona Mabachi, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The HIV Infant Tracking System (HITSystem) is a web-based intervention linking providers of early infant diagnosis, laboratory technicians, and mothers and infants to improve outcomes for HIV-exposed infants. We aimed to evaluate the efficacy of the HITSystem on key outcomes of early infant diagnosis.

METHODS: We did a cluster-randomised trial at six hospitals in Kenya, which were matched on geographic region, resource level, and volume of patients (high, medium, and low). We randomly allocated hospitals within a matched pair to either the HITSystem (intervention; n=3) or standard of care (control; n=3). A random number generator was used to assign …

The Impact Of Pulmonary Hypertension In Preterm Infants With Severe Bronchopulmonary Dysplasia Through 1 Year., Joanne M. Lagatta, Erik B. Hysinger, Isabella Zaniletti, Erica M. Wymore, Shilpa Vyas-Read, Sushmita Yallapragada, Leif D. Nelin, William E. Truog, Michael A. Padula, Nicolas F M Porta, Rashmin C. Savani, Karin P. Potoka, Steven M. Kawut, Robert Digeronimo, Girija Natarajan, Huayan Zhang, Theresa R. Grover, William A. Engle, Karna Murthy, Children's Hospital Neonatal Consortium Severe Bpd Focus Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe bronchopulmonary dysplasia.

STUDY DESIGN: This was a multicenter, retrospective cohort study of 1677 infants bornChildren's Hospital Neonatal Consortium with records linked to the Pediatric Health Information System.

RESULTS: Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P < .001), ventilator support at 36 weeks of postmenstrual age (60% vs 40%, P < .001), duration of ventilation (72 IQR 30-124 vs 41 IQR 17-74 days, P < .001), and higher respiratory severity score (3.6 IQR 0.4-7.0 vs 0.8 IQR 0.3-3.3, P < .001). At discharge, pulmonary hypertension was associated with tracheostomy (27% vs 9%, P < .001), supplemental oxygen use (84% vs 61%, P < .001), and tube feeds (80% vs 46%, P < .001). Through 1 year of corrected age, pulmonary hypertension was associated with increased frequency of readmission (incidence rate ratio [IRR] = 1.38, 95% CI 1.18-1.63, P < .001).

CONCLUSIONS: Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through …

A Multicenter Study To Evaluate Pulmonary Function In Osteogenesis Imperfecta., Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Members Of The Brittle Bone Disorders Consortium, Eric T. Rush, Sandesh C S Nagamani

Manuscripts, Articles, Book Chapters and Other Papers

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the …

When Parents Have Misunderstandings About The Risks And Benefits Of Palliative Surgery., Berklee Robins, Adam Booser, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

When a child needs surgery, both the surgeon and the anesthesiologist must obtain informed consent from the parents. In theory, each specialist obtains permission for their respective portion of the procedure, with the anesthesiologist only obtaining informed consent for the administration of anesthesia and management in the operating room and recovery room. However, he or she may occasionally realize that the parents have misunderstandings about what the surgery and perioperative course entail. In such cases, he or she must decide whether their role is only to discuss the issues related to anesthesia care or whether he or she should also …

Multicenter Trial Of A Combination Probiotic For Children With Gastroenteritis., Stephen B Freedman, Sarah Williamson-Urquhart, Ken J Farion, Serge Gouin, Andrew R Willan, Naveen Poonai, Katrina Hurley, Philip M Sherman, Yaron Finkelstein, Bonita E Lee, Xiao-Li Pang, Linda Chui, David Schnadower, Jianling Xie, Marc Gorelick, Suzanne Schuh

Paediatrics Publications

Background

Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves outcomes in these children are lacking.

Methods

We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×10

Results

Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) …

One-Day Oral Polyethylene Glycol Based Cleanout Is Effective For Pre-Colonoscopy Preparation In Children., Ashwath S. Kumar, Brooke L. Beutler, Thomas M. Attard

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The adequacy of pre-procedure preparation is the principal determinant of the quality of colonoscopy in pediatric as in adult patients. There is a lack of consensus, among providers on a standard pre-procedure regimen. Professional society guidelines include the use of Polyethylene glycol (PEG). Herein we report on the provider-assessed adequacy of a one day, age-categorized dosing, PEG based cleanout regimen in children undergoing colonoscopy in a tertiary institution.

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METHODS: The standard bowel preparation regime at our institution includes an age dependent minimum PEG dosing regimen in addition to clear liquids the day prior to the procedure. We retrospectively …

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO₂) …

Continuous Glucose Monitoring And Glycemic Control Among Youth With Type 1 Diabetes: International Comparison From The T1d Exchange And Dpv Initiative., Daniel Jj Desalvo, Kellee M. Miller, Julia M. Hermann, David M. Maahs, Sabine E. Hofer, Mark A. Clements, Eggert Lilienthal, Jennifer L. Sherr, Martin Tauschmann, Reinhard W. Holl, T1d Exchange And Dpv Registries

Manuscripts, Articles, Book Chapters and Other Papers

Background: To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry).

Methods: Registry participants aged≥1 year encompassed 29 007 individuals in 2011 and 29 150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records.

Results: CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic …

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Recurrence Of Nephrotic Syndrome Following Kidney Transplantation Is Associated With Initial Native Kidney Biopsy Findings., Jonathan H. Pelletier, Karan R. Kumar, Rachel Engen, Adam Bensimhon, Jennifer D. Varner, Michelle N. Rheault, Tarak Srivastava, Caroline Straatmann, Cynthia Silva, T Keefe Davis, Scott E. Wenderfer, Keisha Gibson, David Selewski, John Barcia, Patricia Weng, Christoph Licht, Natasha Jawa, Mahmoud Kallash, John W. Foreman, Delbert R. Wigfall, Annabelle N. Chua, Eileen Chambers, Christoph P. Hornik, Eileen D. Brewer, Shashi K. Nagaraj, Larry A. Greenbaum, Rasheed A. Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence.

METHODS: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were …

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …

Magnetic Resonance Imaging In The Diagnosis Of White Matter Signal Abnormalities., Ravi Datar, Asuri Narayan Prasad, Keng Yeow Tay, Charles Anthony Rupar, Pavlo Ohorodnyk, Michael Miller, Chitra Prasad

Paediatrics Publications

Background White matter abnormalities (WMAs) pose a diagnostic challenge when trying to establish etiologic diagnoses. During childhood and adult years, genetic disorders, metabolic disorders and acquired conditions are included in differential diagnoses. To assist clinicians and radiologists, a structured algorithm using cranial magnetic resonance imaging (MRI) has been recommended to aid in establishing working diagnoses that facilitate appropriate biochemical and genetic investigations. This retrospective pilot study investigated the validity and diagnostic utility of this algorithm when applied to white matter signal abnormalities (WMSAs) reported on imaging studies of patients seen in our clinics. Methods The MRI algorithm was applied to …

The Effect Of Lowering Public Insurance Income Limits On Hospitalizations For Low-Income Children., Jessica L. Bettenhausen, Matt Hall, Jeffrey D. Colvin, Henry T. Puls, Paul J. Chung

Manuscripts, Articles, Book Chapters and Other Papers

Background and objectives: Thirty million children are currently covered by public insurance; however, the future funding and structure of public insurance are uncertain. Our objective was to determine the number, estimated costs, and demographic characteristics of hospitalizations that would become ineligible for public insurance reimbursement under 3 federal poverty level (FPL) eligibility scenarios.

Methods: In this retrospective cohort study using the 2014 State Inpatient Databases, we included all pediatric (age

Results: In 775 460 publicly reimbursed hospitalizations in 14 states, reductions in eligibility limits to 300%, 200%, or 100% of the FPL would have resulted in large numbers of newly …

Ursodeoxycholic Acid Versus Phenobarbital For Cholestasis In The Neonatal Intensive Care Unit., Tamorah Lewis, Simisola Kuye, Ashley Sherman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Although neonates and young infants with cholestasis are commonly treated with either phenobarbital or ursodeoxycholic acid (ursodiol), there is no evidence that phenobarbital is effective for this indication. Our objective was to compare the effectiveness of ursodiol and phenobarbital for the treatment of cholestasis in a diverse NICU population.

METHODS: This is a retrospective cohort study including infants with cholestasis who were admitted to a Level IV NICU between January 2010 and December 2015. Drug courses of phenobarbital and ursodiol were identified within the medical record, and medical, demographic, and drug information were extracted. The primary outcome was reduction …

Phenotypical Characterization Of Human Rhinovirus Infections In Severely Premature Children, Geovanny F. Perez, Bassem Kurdi, Rosemary Megalaa, Krishna Pancham, Shehlanoor Huseni, Natalia Isaza, Carlos E. Rodriguez-Martinez, Dinesh Pillai, Gustavo Nino

Pediatrics Faculty Publications

Background: Human Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV.

Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤ 3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve …

Protocol For A Randomised Trial Of Higher Versus Lower Intensity Patient-Provider Communication Interventions To Reduce Antibiotic Misuse In Two Paediatric Ambulatory Clinics In The Usa., Kathy Goggin, Andrea Bradley-Ewing, Angela Myers, Brian R. Lee, Emily A. Hurley, Kirsten B. Delay, Sarah Schlachter, Areli Ramphal, Kimberly Pina, David Yu, Kirsten Weltmer, Sebastian Linnemayr, Christopher C. Butler, Jason G. Newland

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Children with acute respiratory tract infections (ARTIs) are prescribed up to 11.4 million unnecessary antibiotic prescriptions annually. Inadequate parent-provider communication is a chief contributor, yet efforts to reduce overprescribing have only indirectly targeted communication or been impractical. This paper describes our multisite, parallel group, cluster randomised trial comparing two feasible interventions for enhancing parent-provider communication on the rate of inappropriate antibiotic prescribing (primary outcome) and revisits, adverse drug reactions and parent-rated quality of shared decision-making, parent-provider communication and visit satisfaction (secondary outcomes).

METHODS/ANALYSIS: We will attempt to recruit all eligible paediatricians and nurse practitioners (currently 47) at an academic …

Longitudinal Measures Of Deformation Are Associated With A Composite Measure Of Contractility Derived From Pressure-Volume Loop Analysis In Children., Shahryar M. Chowdhury, Ryan J. Butts, Carolyn L. Taylor, Varsha M. Bandisode, Karen S. Chessa, Anthony M. Hlavacek, Arni Nutting, Girish S. Shirali, G Hamilton Baker

Manuscripts, Articles, Book Chapters and Other Papers

Aims: The relationship between echocardiographic measures of left ventricular (LV) systolic function and reference-standard measures have not been assessed in children. The objective of this study was to assess the validity of echocardiographic indices of LV systolic function via direct comparison to a novel composite measure of contractility derived from pressure-volume loop (PVL) analysis.

Methods and results: Children with normal loading conditions undergoing routine left heart catheterization were prospectively enrolled. PVLs were obtained via conductance catheters. A composite invasive composite contractility index (ICCI) was developed using data reduction strategies to combine four measures of contractility derived from PVL analysis. Echocardiograms …

Benchmarking Rectal Cancer Care: Institutional Compliance With A Longitudinal Checklist., William C. Chapman, Pamela Choi, Alexander T. Hawkins, Steven R. Hunt, Matthew L. Silviera, Paul E. Wise, Matthew G. Mutch, Sean C. Glasgow

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In 2012, the American Society of Colon and Rectal Surgeons published the Rectal Cancer Surgery Checklist, a consensus document listing 25 essential elements of care for all patients undergoing radical surgery for rectal cancer. The authors herein examine checklist adherence in a mature, multisurgeon specialty academic practice.

MATERIALS AND METHODS: A retrospective medical record review of patients undergoing elective radical resection for rectal adenocarcinoma over a 23-mo period was conducted. Checklists were completed post hoc for each patient, and these results were tabulated to determine levels of compliance. Subgroup analyses by compliance and experience levels of the treating surgeon …

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol

Articles, Abstracts, and Reports

In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …

Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes?, Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf

Paediatrics Publications

Background

Pediatrician and pediatric subspecialist density varies substantially among the various Canadian provinces, as well as among various states in the US. It is unknown whether this variability impacts health outcomes. To study this knowledge gap, we evaluated pediatric asthma admission rates within the 2 Canadian provinces of Manitoba and Saskatchewan, which have similarly sized pediatric populations and substantially different physician densities.

Methods

This was a retrospective cross-sectional cohort study. Health regions defined by the provincial governments, have, in turn, been classified into "peer groups" by Statistics Canada, on the basis of common socio-economic characteristics and socio-demographic determinants of health. …

Prenatal Exposure To Methadone Or Buprenorphine: Early Childhood Developmental Outcomes., Karol Kaltenbach, Kevin E O'Grady, Sarah H. Heil, Amy L. Salisbury, Mara G. Coyle, Gabriele Fischer, Peter R. Martin, Susan Stine, Hendrée E. Jones

Department of Pediatrics Faculty Papers

BACKGROUND: Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent.

METHODS: Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined.

RESULTS: Tests of mean differences between children …

Opioid-Related Critical Care Resource Use In Us Children's Hospitals., Jason M. Kane, Jeffrey D. Colvin, Allison H. Bartlett, Matt Hall

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: There has been a rapid increase in the rate of pediatric opioid-related hospitalizations. It is unknown how this increase has impacted the use of pediatric critical care. Our objective in this study was to assess the trends in pediatric hospitalization for opioid ingestions in a cohort of US children's hospitals and, specifically, to evaluate the impact on pediatric critical care resource use.

METHODS: A retrospective cohort study of the Pediatric Health Information System was performed to identify hospitalizations for opioid ingestions from 2004 to 2015. Admission to the PICU and the use of naloxone, vasopressors, and ventilation …

Hla-Dqa1 And Apol1 As Risk Loci For Childhood-Onset Steroid-Sensitive And Steroid-Resistant Nephrotic Syndrome., Adebowale Adeyemo, Christopher Esezobor, Adaobi Solarin, Asiri Abeyagunawardena, Jameela A. Kari, Sherif El Desoky, Larry A. Greenbaum, Margret Kamel, Mahmoud Kallash, Cynthia Silva, Alex Young, Tracey E. Hunley, Nilka De Jesus-Gonzalez, Tarak Srivastava, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association.

Study design: Case-control study.

Setting & participants: African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium.

Factor: Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles.

Outcomes: SSNS …

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy., Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …