Digital Commons Network^™

Transcriptional Profiling Of Leukocytes In Critically Ill Covid19 Patients: Implications For Interferon Response And Coagulation, Sean E Gill, Claudia C Dos Santos, David B O'Gorman, David E Carter, Eric K Patterson, Marat Slessarev, Claudio Martin, Mark Daley, Michael R. Miller, Gediminas Cepinskas, Douglas Fraser

Paediatrics Publications

BACKGROUND: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and …

Transcriptional Profiling Of Leukocytes In Critically Ill Covid19 Patients: Implications For Interferon Response And Coagulation, Sean E Gill, Claudia C Dos Santos, David B O'Gorman, David E Carter, Eric K Patterson, Marat Slessarev, Claudio Martin, Mark Daley, Michael R. Miller, Gediminas Cepinskas, Douglas Fraser

Paediatrics Publications

BACKGROUND: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and …

Lactate Preconditioning Promotes A Hif-1Α-Mediated Metabolic Shift From Oxphos To Glycolysis In Normal Human Diploid Fibroblasts, Alexandra M. Kozlov, Asad Lone, Dean H. Betts, Robert C. Cumming

Paediatrics Publications

Recent evidence has emerged that cancer cells can use various metabolites as fuel sources. Restricting cultured cancer cells to sole metabolite fuel sources can promote metabolic changes leading to enhanced glycolysis or mitochondrial OXPHOS. However, the efect of metabolite-restriction on non-transformed cells remains largely unexplored. Here we examined the efect of restricting media fuel sources, including glucose, pyruvate or lactate, on the metabolic state of cultured human dermal fbroblasts. Fibroblasts cultured in lactate-only medium exhibited reduced PDH phosphorylation, indicative of OXPHOS, and a concurrent elevation of ROS. Lactate exposure primed fbroblasts to switch to glycolysis by increasing transcript abundance of …

Automated Office Blood Pressure Measurement For The Diagnosis Of Hypertension, Guido Filler, Maria E Díaz-González De Ferris

Paediatrics Publications

Editorial

Parental Psychosocial Aspects And Stressors Involved In The Management Of Inborn Errors Of Metabolism., Prashanth Rajasekar, Srinitya Gannavarapu, Melanie Napier, Asuri N Prasad, Akshya Vasudev, Andrew Mantulak, Beth K Potter, Chitra Prasad

Paediatrics Publications

Parents of children with inborn errors of metabolism (IEM) face numerous psychosocial challenges. An increased understanding and awareness of these stressors can ensure better overall outcomes for the entire family. We conducted semi-structured, in-person interviews with ten parents to identify psychosocial stressors, strategies, and supports they utilized to overcome their challenges. Our interview guide was designed to elicit familial experiences during the pre- and post-diagnosis periods. The themes and sub-themes were identified through qualitative descriptive textual analysis of audio-recorded transcripts. Major themes identified include ambiguity of illness, changing family and spousal dynamics, and navigating the healthcare system. Sub-themes revolved around …

Survival Benefit For Individuals With Constitutional Mismatch Repair Deficiency Syndrome And Brain Tumors Who Undergo Surveillance Protocol. A Report From The International Replication Repair Consortium, Ayse Bahar Ercan, Carol Durno, Vanessa J. Bianchi, Melissa Edwards, Melyssa Aronson, Eric Bouffet, Abeer Al-Battashi, Musa Alharbi, Donald Basel, Elizabeth Cairney

Paediatrics Publications

BACKGROUND

Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome resulting in early onset central nervous system (CNS) and other cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. METHODS

We surveyed all confirmed CMMRD patients in the International Replication Repair Deficiency Consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging (CNS and total body MRI) studies were employed. Survival analyses and efficacy of each method were assessed. RESULTS

Surveillance data were collected from 105 CMMRD individuals from 41 countries. Of the 193 malignant tumors, CNS malignancies …

Isolated Sulfite Oxidase Deficiency: A Founder Mutation., Aizeddin A Mhanni, Cheryl R Greenberg, Elizabeth L Spriggs, Ronald Agatep, Reena Ray Sisk, Chitra Prasad

Paediatrics Publications

Isolated sulfite oxidase deficiency is a rare autosomal recessive inborn error of sulfur metabolism. Clinical features generally include devastating neurologic dysfunction, ectopia lentis, and increased urinary excretion of sulfite, thiosulfate, and

Five-Month-Old Male With Chronic Diarrhea., Hailey C Barootes, Erin R Peebles, Dhandapani Ashok, Suzanne Ratko, Andrea C Yu

Paediatrics Publications

No abstract provided.

Machine Learning Identifies Clinical And Genetic Factors Associated With Anthracycline Cardiotoxicity In Pediatric Cancer Survivors, Marie-A Chaix, Neha Parmar, Caroline Kinnear, Myriam Lafreniere-Roula,, Oyediran Akinrinade, Roderick Yao, Anastasia Miron, Emily Lam, Guoliang Meng, Anne Christie, Ashok Kumar Manickaraj, Stacey Marjerrison, Rejane Dillenburg, Mylène Bassal, Jane Lougheed, Shayna Zelcer, Herschel Rosenberg, David Hodgson, Leonard Sender, Paul Kantor, Cedric Manlhiot, James Ellis, Luc Mertens, Paul C. Nathan, Seema Mital

Paediatrics Publications

BACKGROUND Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. OBJECTIVES This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. METHODS We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (<= 250 mg/m(2)), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m(2) were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in …

Frameshift Mutations At The C-Terminus Of Hist1h1e Result In A Specific Dna Hypomethylation Signature, A. Ciolfi, E. Aref-Eshghi, S. Pizzi, L. Pedace, E. Miele, J. Kerkhof, E. Flex, S. Martinelli, F.C. Radio, C.A.L Ruivenkamp, G.W.E. Santen, E.K. Bijlsma, D.Q.C.M. Barge-Schaapveld, K. Ounap, V. Mok Siu, F. F. Kooy, B. Dallapiccola, B. Sadikovic, M. Tartaglia

Paediatrics Publications

No abstract provided.

Hyoscine Butylbromide Versus Acetaminophen For Nonspecific Colicky Abdominal Pain In Children: A Randomized Controlled Trial., Naveen Poonai, Kriti Kumar, Kamary Coriolano, Graham Thompson, Shaily Brahmbhatt, Emily Dzongowski, Holly Stevens, Priti Gupta, Michael Miller, Sharlene Elsie, Dhandapani Ashok, Gary Joubert, Rod Lim, Andreana Bütter, Samina Ali

Paediatrics Publications

BACKGROUND: Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain.

METHODS: We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 …

Drug Therapy During Pregnancy., Dongmei Sun, Janine R. Hutson, Facundo Garcia-Bournissen Md Phd

Paediatrics Publications

No abstract provided.

A Live-Online Mindfulness-Based Intervention For Children Living With Epilepsy And Their Families: Protocol For A Randomized Controlled Trial Of Making Mindfulness Matter©., Klajdi Puka, Karen Bax, Andrea Andrade, Margo Devries-Rizzo, Hema Gangam, Simon Levin, Maryam N Nouri, Asuri N Prasad, Mary Secco, Guangyong Zou, Kathy N Speechley

Paediatrics Publications

BACKGROUND: Epilepsy extends far beyond seizures; up to 80% of children with epilepsy (CWE) may have comorbid cognitive or mental health problems, and up to 50% of parents of CWE are at risk for major depression. Past research has also shown that family environment has a greater influence on children's and parents' health-related quality of life (HRQOL) and mental health than epilepsy-related factors. There is a pressing need for low-cost, innovative interventions to improve HRQOL and mental health for CWE and their parents. The aim of this randomized controlled trial (RCT) is to evaluate whether an interactive online mindfulness-based intervention …

Tp63-Mutation As A Cause Of Prenatal Lethal Multicystic Dysplastic Kidneys, Isabel Friedmann, Carla Campagnolo, Nancy Chan, Ghislain Hardy, Maha Saleh

Paediatrics Publications

BACKGROUND: Ectrodactyly-ectodermal dysplasia-clefting syndrome 3 (EEC) is one of the six overlapping syndromes caused by mutations in the tumor protein p63 gene (TP63). EEC is suspected when patients have cleft hands or feet, polydactyly, and syndactyly, abnormal development of the ectodermally derived structures, and orofacial clefting. Genitourinary (GU) anomalies have been identified in patients with EEC, yet these are often under-recognized and under-reported. The available literature on sonographic prenatal findings is sparse, especially when considering GU anomalies.

METHODS: We present the case of a male stillborn fetus, who was found antenatally to have multicystic dysplastic kidneys and anhydramnios. Following the …

A National Spinal Muscular Atrophy Registry For Real-World Evidence., Victoria L Hodgkinson, Maryam Oskoui, Joshua Lounsberry, Saïd M'Dahoma, Emily Butler, Craig Campbell, Alex Mackenzie, Hugh J Mcmillan, Louise Simard, Jiri Vajsar, Bernard Brais, Kristine M Chapman, Nicolas Chrestian, Meghan Crone, Peter Dobrowolski, Susan Dojeiji, James J Dowling, Nicolas Dupré, Angela Genge, Hernan Gonorazky, Simona Hasal, Aaron Izenberg, Wendy Johnston, Edward Leung, Hanns Lochmüller, Jean K Mah, Alier Marerro, Rami Massie, Laura Mcadam, Anna Mccormick, Michel Melanson, Michelle M Mezei, Cam-Tu E Nguyen, Colleen O'Connell, Erin K O'Ferrall, Gerald Pfeffer, Cecile Phan, Stephanie Plamondon, Chantal Poulin, Xavier Rodrigue, Kerri L Schellenberg, Kathy Selby, Jordan Sheriko, Christen Shoesmith, Garth Smith, Monique Taillon, Sean Taylor, Jodi Warman Chardon, Scott Worley, Lawrence Korngut

Paediatrics Publications

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items …

A Novel Sting1 Variant Causes A Recessive Form Of Sting-Associated Vasculopathy With Onset In Infancy (Savi)., Bin Lin, Roberta Berard, Abdulrahman Al Rasheed, Buthaina Aladba, Philip J Kranzusch, Maggie Henderlight, Alexi Grom, Dana Kahle, Sofia Torreggiani, Alexander G Aue, Jacob Mitchell, Adriana A De Jesus, Grant S Schulert, Raphaela Goldbach-Mansky

Paediatrics Publications

No abstract provided.

High Molecular Weight Adiponectin Levels Are Inversely Associated With Adiposity In Pediatric Brain Tumor Survivors., Rebecca Ronsley, Shahrad Rod Rassekh, Adam Fleming, Brianna Empringham, William Jennings, Carol Portwine, Sarah Burrow, Shayna Zelcer, Donna L Johnston, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin's profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) …

Cardiovascular Disease Risk Assessment In Patients With Familial Mediterranean Fever Related Renal Amyloidosis., Micol Romano, David Piskin, Roberta A Berard, Bradley C Jackson, Cengizhan Acikel, Juan J Carrero, Helen J Lachmann, Mahmut I Yilmaz, Erkan Demirkaya

Paediatrics Publications

Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and …

Tam Family Receptors In Conjunction With Mapk Signalling Are Involved In Acquired Resistance To Pi3kα Inhibition In Head And Neck Squamous Cell Carcinoma., Kara M Ruicci, Jalna Meens, Paul Plantinga, William Stecho, Nicole Pinto, John Yoo, Kevin Fung, Danielle Macneil, Joe S Mymryk, John W Barrett, Christopher J Howlett, Paul C Boutros, Laurie Ailles, Anthony C Nichols

Paediatrics Publications

BACKGROUND: Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Despite pre-clinical and clinical studies, outcomes from targeting the PI3K pathway have been underwhelming and the development of drug resistance poses a significant barrier to patient treatment. In the present study, we examined mechanisms of acquired resistance to the PI3Kα inhibitor alpelisib (formerly BYL719) in HNSCC cell lines and patient-derived xenografts (PDXs).

METHODS: Five unique PDX mouse models and three HNSCC cell lines were used. All cell lines and xenografts underwent genomic characterization prior to study. Serial drug …

Developing And Implementing A Novel Mentorship Model (4+ 1) For Maternal, Newborn And Child Health In Rwanda, Anaclet Ngabonzima, Cynthia Kenyon, Celestin Hategeka, Aimee Josephine Utuza, Paulin Ruhato Banguti, Isaac Luginaah, David F Cechetto

Paediatrics Publications

BACKGROUND: There are a number of factors that may contribute to high mortality and morbidity of women and newborns in low-income countries. These include a shortage of competent health care providers (HCP) and a lack of sufficient continuous professional development (CPD) opportunities. Strengthening the skills and building the capacity of HCP involved in the provision of maternal, newborn and child health (MNCH) is essential to ensure quality care for mothers, newborns and children. To address this challenge in Rwanda, mentorship of HCPs was identified as an approach that could help build capacity, improve the provision of care and accelerate the …

Genetic And Epigenetic Profiling Of Brca1/2 In Ovarian Tumors Reveals Additive Diagnostic Yield And Evidence Of A Genomic Brca1/2 Dna Methylation Signature, Erfan Aref-Eshghi, Jacob D. Mcgee, Victor P. Pedro, Jennifer Kerkhof, Alan Stuart, Peter J. Ainsworth, Hanxin Lin, Michael Volodarsky, Catherine Meg Mclachlin, Bekim Sadikovic

Paediatrics Publications

Poly-ADP-ribose-polymerase inhibitor (PARPi) treatment is indicated for advanced-stage ovarian tumors with BRCA1/2 deficiency. The “BRCAness” status is thought to be attributed to a tumor phenotype associated with a specific epigenomic DNA methylation profile. Here, we examined the diagnostic impact of combined BRCA1/2 sequence, copy number, and promoter DNA methylation analysis, and evaluated whether genomic DNA methylation patterns can predict the BRCAness in ovarian tumors. DNA sequencing of 172 human tissue samples of advanced-stage ovarian adenocarcinoma identified 36 samples with a clinically significant tier 1/2 sequence variants (point mutations and in/dels) and 9 samples with a CNV causing a loss of …

A Second Cohort Of Chd3 Patients Expands The Molecular Mechanisms Known To Cause Snijders Blok-Campeau Syndrome, Theodore G Drivas, Dong Li, Divya Nair, Joseph T Alaimo, Mariëlle Alders, Janine Altmüller, Tahsin Stefan Barakat, E Martina Bebin, Nicole L Bertsch, Patrick R Blackburn, Alyssa Blesson, Arjan M Bouman, Knut Brockmann, Perrine Brunelle, Margit Burmeister, Gregory M Cooper, Jonas Denecke, Anne Dieux-Coëslier, Holly Dubbs, Alejandro Ferrer, Danna Gal, Lauren E Bartik, Lauren B Gunderson, Linda Hasadsri, Mahim Jain, Catherine Karimov, Beth Keena, Eric W Klee, Katja Kloth, Baiba Lace, Marina Macchiaiolo, Julien L Marcadier, Jeff M Milunsky, Melanie P Napier, Xilma R Ortiz-Gonzalez, Pavel N Pichurin, Jason Pinner, Zoe Powis, Chitra Prasad, Francesca Clementina Radio, Kristen J Rasmussen, Deborah L Renaud, Eric T Rush, Carol Saunders, Duygu Selcen, Ann R Seman, Deepali N Shinde, Erica D Smith, Thomas Smol, Lot Snijders Blok, Joan M Stoler, Sha Tang, Marco Tartaglia, Michelle L Thompson, Jiddeke M Van De Kamp, Jingmin Wang, Dagmar Weise, Karin Weiss, Rixa Woitschach, Bernd Wollnik, Huifang Yan, Elaine H Zackai, Giuseppe Zampino, Philippe Campeau, Elizabeth Bhoj

Paediatrics Publications

There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further …

Delay In Diagnosis Of Patients With Head-And-Neck Cancer In Canada: Impact Of Patient And Provider Delay., S Kassirian, A Dzioba, S Hamel, K Patel, A Sahovaler, D A Palma, N Read, V Venkatesan, A C Nichols, J Yoo, K Fung, A Mendez, S D Macneil

Paediatrics Publications

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting.

Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time …

Proceedings Of The 2019 Canadian Inflammatory Myopathy Study Symposium: Clinical Trial Readiness In Myositis., Valérie Leclair, Océane Landon-Cardinal, Rohit Aggarwal, Nick Bansback, Craig Campbell, Brian M Feldman, Martin Jarry, Suzan Mcnamara, Barbara White, Marie Hudson

Paediatrics Publications

The Canadian Inflammatory Myopathy Study (CIMS) is a multicenter prospective cohort recruiting in 8 centers across Canada. One of the aims of CIMS is to conduct and participate in clinical trials in autoimmune inflammatory myopathies (AIM). Conducting clinical trials in rare diseases such as AIM presents challenges. During this symposium, experts in the field presented different solutions to successfully conduct clinical trials in AIM, including the importance of collaboration and careful trial design, as well as training and mentoring of young investigators.

Instituting Robotic Pediatric Urologic Surgery In The Canadian Healthcare System: Evaluating The Feasibility And Outcomes Of Robot-Assisted Pyeloplasty And Ureteric Reimplantation, Noah Stern, Peter Wang, Sumit Dave

Paediatrics Publications

Introduction: Robotic pediatric urologic surgery has gained widespread adoption over the last decade. This article describes our experience in instituting the first pediatric urologic robotic surgery program in Canada. We evaluated the feasibility and safety of instituting pediatric robot-assisted urologic surgery and report our early outcomes for robot-assisted pyeloplasty (RAP) and ureteric reimplantation (RUR). Methods: We prospectively evaluated all patients undergoing RAP and RUR by a single surgeon from June 2013 to March 2019. Demographic and clinical data were prospectively collected and included sex, age, and preoperative grade of hydronephrosis or reflux. Descriptive statistics were performed, and comparisons were made …

Non-Steroidal Or Opioid Analgesia Use For Children With Musculoskeletal Injuries (The No Ouch Study): Statistical Analysis Plan., Anna Heath, Maryna Yaskina, Gareth Hopkin, Terry P Klassen, Christopher Mccabe, Martin Offringa, Petros Pechlivanoglou, Juan David Rios, Naveen Poonai, Samina Ali

Paediatrics Publications

BACKGROUND: Pediatric musculoskeletal injuries cause moderate to severe pain, which should ideally be addressed upon arrival to the emergency department (ED). Despite extensive research in ED-based pediatric pain treatment, recent studies confirm that pain management in this setting remains suboptimal. The No OUCH study consist of two complementary, randomized, placebo-controlled trials that will run simultaneously for patients presenting to the ED with an acute limb injury and a self-reported pain score of at least 5/10, measured via a verbal numerical rating scale (vNRS). Caregiver/parent choice will determine whether patients are randomized to the two-arm or three-arm trial. In the two-arm …

Priority Outcomes In Critically Ill Children: A Patient And Parent Perspective, Nora Fayed, Saoirse Cameron, Douglas Fraser Md, Phd, Frcpc, Jill I Cameron, Samah Al-Harbi, Racquel Simpson, Maha Wakim, Lily Chiu, Karen Choong

Paediatrics Publications

BACKGROUND: Outcomes in pediatric critical care research are typically selected by the researcher.

OBJECTIVES: (1) To identify outcomes prioritized by patients and their families following a critical illness and (2) to determine the overlap between patient-centered and researcher-selected study outcomes.

METHODS: An exploratory descriptive qualitative study nested within a longitudinal cohort study conducted in 2 pediatric intensive care units (PICUs). Participants were purposively sampled from the primary cohort to ensure adequate demographic representation. Qualitative descriptive approaches based on naturalistic observation were used to collect data and analyze results. Data were coded by using the International Classification of Functioning, Disability, and …

Quantification And Characterization Of Granulocyte Macrophage Colony-Stimulating Factor Activated Human Peripheral Blood Mononuclear Cells By Fluorine-19 Cellular Mri In An Immunocompromised Mouse Model, C Fink, M Smith, O C Sehl, J M Gaudet, T C Meagher, N A Sheikh, Jimmy Dikeakos, Michael Rieder, P J Foster, G A Dekaban

Paediatrics Publications

PURPOSE: The purpose of this study was to test fluorine-19 (19F) cellular magnetic resonance (MRI) as a non-invasive imaging modality to track therapeutic cell migration as a surrogate marker of immunotherapeutic effectiveness.

MATERIALS AND METHODS: Human peripheral blood mononuclear cell- (PBMC)-derived antigen presenting cell (APC) were labeled with a 19F-perfluorocarbon (PFC) and/or activated with granulocyte macrophage colony-stimulating factor (GM-CSF). Viability, phenotype and cell lineage characterization preceded 19F cellular MRI of PFC

RESULTS: A high proportion of PBMC incorporated PFC without affecting viability, phenotype or cell lineage composition. PFC

CONCLUSION: 19F cellular MRI is a non-invasive imaging technique capable of detecting …

New Aspects Of The Epigenetics Of Pancreatic Carcinogenesis., Murat Toruner, Martin E. Fernandez-Zapico, Christopher Pin

Paediatrics Publications

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA …

A Pragmatic Randomized Controlled Trial Of Multi-Dose Oral Ondansetron For Pediatric Gastroenteritis (The Dose-Age Study): Statistical Analysis Plan., Anna Heath, Juan David Rios, Sarah Williamson-Urquhart, Petros Pechlivanoglou, Martin Offringa, Christopher Mccabe, Gareth Hopkin, Amy C Plint, Andrew Dixon, Darcy Beer, Serge Gouin, Gary Joubert, Terry P Klassen, Stephen B Freedman

Paediatrics Publications

BACKGROUND: Acute gastroenteritis is a leading cause of emergency department visits and hospitalizations among children in North America. Oral-rehydration therapy is recommended for children with mild-to-moderate dehydration, but children who present with vomiting are frequently offered intravenous rehydration in the emergency department (ED). Recent studies have demonstrated that the anti-emetic ondansetron can reduce vomiting, intravenous rehydration, and hospitalization when administered in the ED to children with dehydration. However, there is little evidence of additional benefit from prescribing ondansetron beyond the initial ED dose. Moreover, repeat dosing may increase the frequency of diarrhea. Despite the lack of evidence and potential adverse …