Digital Commons Network^™

Prioritizing Specialized Children's Surgery In Canada During The Covid-19 Pandemic, Erik D. Skarsgard, Juan Bass, Paul Beaudry, Gerard Corsten, James Drake, Mark Evans, Jean Pierre Farmer, Helene Flageole, Richard Keijzer, Elke Mau, Sandeep Mayer, Pascale Prasil, David Price, Leslie Scott, Dominic Venne

Paediatrics Publications

No abstract provided.

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 …

Adaptive Randomised Controlled Non-Inferiority Multicentre Trial (The Ketodex Trial) On Intranasal Dexmedetomidine Plus Ketamine For Procedural Sedation In Children: Study Protocol, Naveen Poonai, Kamary Coriolano, Terry Klassen, Anna Heath, Maryna Yaskina, Darcy Beer, Scott Sawyer, Maala Bhatt, April Kam, Quynh Doan, Vikram Sabhaney, Martin Offringa, Petros Pechlivanoglou, Serena Hickes, Samina Ali

Paediatrics Publications

Introduction Up to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduction. Methods and analysis This is a six-centre, four-arm, adaptive, randomised, blinded, controlled, non-inferiority trial. We will include children 4-17 years with a simple upper limb fracture or dislocation that requires sedation for a closed …

Adaptive Randomised Controlled Non-Inferiority Multicentre Trial (The Ketodex Trial) On Intranasal Dexmedetomidine Plus Ketamine For Procedural Sedation In Children: Study Protocol, Naveen Poonai, Kamary Coriolano, Terry Klassen, Anna Heath, Maryna Yaskina, Darcy Beer, Scott Sawyer, Maala Bhatt, April Kam, Quynh Doan, Vikram Sabhaney, Martin Offringa, Petros Pechlivanoglou, Serena Hickes, Samina Ali

Paediatrics Publications

Introduction Up to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduction. Methods and analysis This is a six-centre, four-arm, adaptive, randomised, blinded, controlled, non-inferiority trial. We will include children 4-17 years with a simple upper limb fracture or dislocation that requires sedation for a closed …

Higher-Dose Sitagliptin And The Risk Of Congestive Heart Failure In Older Adults With Ckd, Flory T. Muanda, Matthew A. Weir, Lavanya Bathini, Kristin K. Clemens, Vlado Perkovic, Manish M. Sood, Eric Mcarthur, Jessica M. Sontrop, Richard B. Borobia, Hoi Y. Tong, Cristina Dávila-Fajardo, Mariana Rodrigues Botton, Stephane Bourgeois, Panos Deloukas, Michael D. Caldwell, Jim K. Burmester, Richard L. Berg, Larisa H. Cavallari, Katarzyna Drozda, Min Huang, Li Zi Zhao, Han Jing Cen, Rocio Gonzalez-Conejero, Vanessa Roldan, Yusuke Nakamura, Taisei Mushiroda

Paediatrics Publications

Background and objectives Sitagliptin, a dipeptidylpeptidase-4 inhibitor, is commonlyprescribed to patientswith type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses.Wecompare the 1-year risk of death or hospitalizationwith congestive heart failure in patients with CKD newly prescribed sitagliptin at <50 versus ≤50 mg/d. Design, setting, participants, & measurements This population-based cohort study included older adults (>66 years) with type 2 diabetes and an eGFR<45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95%confidence intervalswere obtained using bootstrap variance estimators. Results Of 9215 patients, 6518 started sitagliptin at >50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not …

Blast In Context: The Neuropsychological And Neurocognitive Effects Of Long-Term Occupational Exposure To Repeated Low-Level Explosives On Canadian Armed Forces' Breaching Instructors And Range Staff, Oshin Vartanian, Catherine Tenn, Shawn G. Rhind, Ann Nakashima, Alex P. Di Battista, Lauren E. Sergio, Diana J. Gorbet, Douglas D. Fraser, Angela Colantonio, Kristen King, Quan Lam, Doug Saunders, Rakesh Jetly

Paediatrics Publications

Currently, there is strong interest within the military to better understand the effects of long-term occupational exposure to repeated low-level blast on health and performance. To gain traction on the chronic sequelae of blast, we focused on breaching—a tactical technique for gaining entry into closed/blocked spaces by placing explosives and maintaining a calculated safe distance from the detonation. Using a cross-sectional design, we compared the neuropsychological and neurocognitive profiles of breaching instructors and range staff to sex- and age-matched Canadian Armed Forces (CAF) controls. Univariate tests demonstrated that breaching was associated with greater post-concussive symptoms (Rivermead Post Concussion Symptoms Questionnaire) …

Md2 Activation By Direct Age Interaction Drives Inflammatory Diabetic Cardiomyopathy, Yi Wang, Wu Luo, Jibo Han, Zia A. Khan, Qilu Fang, Yiyi Jin, Xuemei Chen, Yali Zhang

Paediatrics Publications

Hyperglycemia activates toll-like receptor 4 (TLR4) to induce inflammation in diabetic cardiomyopathy (DCM). However, the mechanisms of TLR4 activation remain unclear. Here we examine the role of myeloid differentiation 2 (MD2), a co-receptor of TLR4, in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. We show increased MD2 in heart tissues of diabetic mice and serum of human diabetic subjects. MD2 deficiency in mice inhibits TLR4 pathway activation, which correlates with reduced myocardial remodeling and improved cardiac function. Mechanistically, we show that HG induces extracellular advanced glycation end products (AGEs), which bind directly to MD2, leading to formation of AGEs-MD2-TLR4 complex …

Risk Of Suicide And Self-Harm In Kids: The Development Of An Algorithm To Identify High-Risk Individuals Within The Children’S Mental Health System, Shannon L. Stewart, Angela Celebre, John P. Hirdes, Jeffrey W. Poss

Paediatrics Publications

Suicide is the second leading cause of death in adolescents within Canada. While several risk factors have been found to be associated with increased risk, appropriate decision-support tools are needed to identify children who are at highest risk for suicide and self-harm. The aim of the present study was to develop and validate a methodology for identifying children at heightened risk for self-harm and suicide. Ontario data based on the interRAI Child and Youth Mental Health Screener (ChYMH-S) were analyzed to develop a decision-support algorithm to identify young persons at risk for suicide or self-harm. The algorithm was validated with …

The Mechano-Response Of Murine Annulus Fibrosus Cells To Cyclic Tensile Strain Is Frequency Dependent, Min Kyu M. Kim, Marissa J. Burns, Meaghan E. Serjeant, Cheryle A. Séguin

Paediatrics Publications

The intervertebral disk (IVD) is a composite structure essential for spine stabilization, load bearing, and movement. Biomechanical factors are important contributors to the IVD microenvironment regulating joint homeostasis; however, the cell type-specific effectors of mechanotransduction in the IVD are not fully understood. The current study aimed to determine the effects of cyclic tensile strain (CTS) on annulus fibrosus (AF) cells and identify mechano-sensitive pathways. Using a cell-type specific reporter mouse to differentiation NP and AF cells from the murine IVD, we characterized AF cells in dynamic culture exposed to CTS (6% strain) at specific frequencies (0.1 Hz, 1.0 Hz, or …

Vascularization Of The Human Intervertebral Disc: A Scoping Review, Dale E. Fournier, Patti K. Kiser, J. Kevin Shoemaker, Michele C. Battié, Cheryle A. Séguin

Paediatrics Publications

Intervertebral discs (IVDs) are often referred to as the largest avascular structures of the human body, yet a collective resource characterizing the vascularization of the IVD does not exist. To address this gap, the objective of this study was to conduct a comprehensive search of the literature to review and summarize current knowledge of the prevalence and localization of blood supply in human IVDs, with a scoping review. A comprehensive search of peer-reviewed publications on the topic of IVD vascularization in humans was conducted across six electronic databases: PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and BIOSIS Previews. Studies of …

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 …

A Randomized Trial Evaluating Virus-Specific Effects Of A Combination Probiotic In Children With Acute Gastroenteritis, Stephen B. Freedman, Jianling Xie, Jianling Xie, Alberto Nettel-Aguirre, Xiao Li Pang, Linda Chui, Linda Chui, Sarah Williamson-Urquhart, Sarah Williamson-Urquhart, David Schnadower, David Schnadower, Suzanne Schuh, Suzanne Schuh, Philip M. Sherman, Bonita Lee, Serge Gouin, Serge Gouin, Ken J. Farion, Ken J. Farion, Naveen Poonai, Naveen Poonai, Katrina F. Hurley, Katrina F. Hurley, Yuanyuan Qiu, Yuanyuan Qiu, Binal Ghandi

Paediatrics Publications

Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillushelveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms …

Adding Team-Based Financial Incentives To The Carrot Rewards Physical Activity App Increases Daily Step Count On A Population Scale: A 24-Week Matched Case Control Study, Emma Pearson, Harry Prapavessis, Christopher Higgins, Robert Petrella, Lauren White, Marc Mitchell

Paediatrics Publications

Background: Mobile health applications (mHealth apps) targeting physical inactivity have increased in popularity yet are usually limited by low engagement. This study examined the impact of adding team-based incentives (Step Together Challenges, STCs) to an existing mHealth app (Carrot Rewards) that rewarded individual physical activity achievements. Methods: A 24-week quasi-experimental study (retrospective matched pairs design) was conducted in three Canadian provinces (pre-intervention: weeks 1–12; intervention: weeks 13–24). Participants who used Carrot Rewards and STCs (experimental group) were matched with those who used Carrot Rewards only (controls) on age, gender, province and baseline mean daily step count (±500 steps/d). Carrot Rewards …

Attenuation Of Bile Acid-Mediated Fxr And Pxr Activation In Patients With Crohn’S Disease, Aze Wilson, Ahmed Almousa, Wendy A. Teft, Richard B. Kim

Paediatrics Publications

Bile acids are endogenous ligands of nuclear receptors pregnane X (PXR) and farnesoid X (FXR). PXR and FXR regulate pathways that are impaired in inflammatory bowel disease (IBD). Decreases in PXR and FXR activity are documented in IBD; however reasons for this are unknown. We aimed to assess the effect of Crohn’s disease (CD) on the plasma bile acid composition in vivo and the resultant impact on PXR and FXR activation. A cross-sectional study evaluated the plasma concentrations of 12 bile acids in addition to 4β-hydroxycholesterol (4βOHC), an in vivo probe of the PXR target-gene cytochrome 3A4 (CYP3A4) and the …

Content Development For A Physical Activity And Sedentary Behaviour E-Learning Module For Early Childhood Education Students: A Delphi Study, Brianne A. Bruijns, Andrew M. Johnson, Patricia Tucker

Paediatrics Publications

Background: Early childhood educators play a prominent role in promoting healthy activity behaviours in childcare. However, they have expressed that they lack the appropriate pre-service training to confidently lead physical activity (PA), and minimize sedentary behaviour (SB), in childcare. As such, the purpose of this Delphi study was to generate and reach agreement on content areas for inclusion in a PA and SB e-Learning module for Early Childhood Education (ECE) students. Methods: Purposeful sampling of Canadian/international researchers was used to form two expert panels: a PA/SB expert panel (n = 26), and a Canadian ECE panel (n = 35). The …

Diagnostic Utility Of Genome-Wide Dna Methylation Analysis In Mendelian Neurodevelopmental Disorders, Sadegheh Haghshenas, Pratibha Bhai, Erfan Aref-Eshghi, Bekim Sadikovic

Paediatrics Publications

Mendelian neurodevelopmental disorders customarily present with complex and overlapping symptoms, complicating the clinical diagnosis. Individuals with a growing number of the so-called rare disorders exhibit unique, disorder-specific DNA methylation patterns, consequent to the underlying gene defects. Besides providing insights to the pathophysiology and molecular biology of these disorders, we can use these epigenetic patterns as functional biomarkers for the screening and diagnosis of these conditions. This review summarizes our current understanding of DNA methylation episignatures in rare disorders and describes the underlying technology and analytical approaches. We discuss the computational parameters, including statistical and machine learning methods, used for the …

Dynamic Response Of Cerebral Blood Flow To Insulin-Induced Hypoglycemia, Ruth Mcmanus, Seva Ioussoufovitch, Elizabeth Froats, Keith St Lawrence, Stan Van Uum, Mamadou Diop

Paediatrics Publications

The dynamics of cerebral blood flow (CBF) at the onset of hypoglycemia may play a key role in hypoglycemia unawareness; however, there is currently a paucity of techniques that can monitor adult CBF with high temporal resolution. Herein, we investigated the use of diffuse correlation spectroscopy (DCS) to monitor the dynamics of CBF during insulin-induced hypoglycemia in adults. Plasma glucose concentrations, cortisol levels, and changes in CBF were measured before and during hypoglycemia in 8 healthy subjects. Cerebral blood flow increased by 42% following insulin injection with a delay of 17 ± 10 min, while the onset of hypoglycemia symptoms …

Erratum: Correction To: Predicting Dropout From Children's Mental Health Services: Using A Need-Based Defnition Of Dropout (Child Psychiatry And Human Development (2020) 51 1 (13-26)), Kimberly W. Dossett, Graham J. Reid

Paediatrics Publications

The original version of this article was unfortunately published with an error in Table 2. The confidence intervals listed in Table 2 were published incorrectly. The correct version of confidence intervals in Table 2 should read as below.

Genetic Variation In The Farnesoid X-Receptor Predicts Crohn’S Disease Severity In Female Patients, Aze Wilson, Qian Wang, Ahmed A. Almousa, Laura E. Jansen, Yun Hee Choi, Ute I. Schwarz, Richard B. Kim

Paediatrics Publications

The farnesoid X receptor (FXR) is implicated in Crohn's disease (CD) pathogenesis. It is unclear how genetic variation in FXR impacts CD severity versus genetic variation in nuclear receptors such as pregnane X receptor (PXR) and the multi-drug resistance protein 1 (MDR1, ABCB1). To evaluate FXR-1G > T as a genomic biomarker of severity in CD and propose a plausible molecular mechanism. A retrospective study (n = 542) was conducted in a Canadian cohort of CD patients. Genotypic analysis (FXR-1G > T, MDR1 3435C > T and PXR -25385C > T) as well as determination of the FXR downstream product, fibroblast growth factor (FGF) …

Hysteroscopy In The Management Of Endometrial Hyperplasia And Cancer In Reproductive Aged Women: New Developments And Current Perspectives, Salvatore Giovanni Vitale, Gaetano Riemma, Jose Carugno, Benito Chiofalo, George Angelos Vilos, Stefano Cianci, Mehmet Sukru Budak, Bernardo Portugal Lasmar, Antonio Raffone, Ilker Kahramanoglu

Paediatrics Publications

Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the …

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.

Evaluation Of Dna Methylation Episignatures For Diagnosis And Phenotype Correlations In 42 Mendelian Neurodevelopmental Disorders, E. Aref-Eshghi, J. Kerkhof, V. Pedro, Groupe Di France, M. Barat-Houari, N. Ruiz-Pallares, M. Alders, M. Mannens, P. Henneman, R.C. Hennekam, A. Ciolf, S. Pizzi, M. Tartaglia, P.M. Campeau, J. Rousseau, M.A. Levy, L. Brick, M. Kozenko, T.B. Balci, V.M. Siu, A. Stuart, M. Kadour, J. Masters, K. Takano, T. Kleefstra, N. De Leeuw, M. Field, M. Shaw, J. Gecz, G. Merla, P.J. Ainsworth, H. Lin, D.I. Rodenhiser, M.J. Friez, M. Tedder, J.A. Dupont, R.E. Stevenson, S.A. Skinner, C.E. Schwartz, D. Genevieve, B. Sadikovic

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.

Impact Of Class Iii Obesity On Outcomes And Complications Of Transvaginal Ultrasound-Guided Oocyte Pickup, Tina Liang, Kelsey Ruetz, Olga Haakman, Angelos Vilos, George Vilos, Basim Abu-Rafea

Paediatrics Publications

Objective: To assess the impact of class III obesity on outcomes and complications of transvaginal ultrasound-guided oocyte pickup (OPU). Design: Retrospective cohort study. Setting: Hospital-based fertility clinic. Patient(s): All women undergoing OPU procedures during autologous in vitro fertilization (IVF) and oocyte banking cycles, grouped by patient body mass index (BMI: <25, 25–29.9, 30–34.9, 35–39.9, ≥40 kg/m2). Intervention(s): Transvaginal OPU under conscious sedation. Main Outcome Measure(s): Sedation and procedure-related parameters and complications. Result(s): A total of 2,141 OPU procedures in 1,579 patients were analyzed, including 121 OPU procedures in 94 patients with BMI ≥40 kg/m2. There was a statistically significant increase in total fentanyl and midazolam doses and procedure duration as BMI increased. Compared with patients with BMI <25 kg/m2, those with BMI ≥40 kg/m2 were more likely to require additional sedation during the procedure (adjusted odds ratio [aOR] 1.99; 95% confidence interval [CI], 1.14–3.49). The rate of difficult access was 28.9% for procedures with BMI ≥40 kg/m2 compared with 5.2% with BMI <25 kg/m2 (aOR 7.57; 95% CI, 4.66–12.29). The OPU was incomplete due to inaccessible follicles through a transvaginal approach in 18.2% of procedures with BMI ≥40 kg/m2 compared with 1.3% with BMI <25 kg/m2 (aOR 16.94; 95% CI, 8.24–34.84). The rates of sedation and procedure-related complications were low, and none occurred in patients with BMI ≥40 kg/m2. Conclusion(s): There was no increased risk of complications for women with class III obesity undergoing OPU with conscious sedation. However, the operator was more likely to encounter difficult access and to incompletely aspirate follicles through a transvaginal approach.