Medical Specialties Commons^™

Ventricular Fibrillation Due To A Likely Pathogenic Sos1 Variant: An Unrecognized Etiology Of Infantile Sudden Death?, Christopher Follansbee, Lindsey Malloy-Walton

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We present the case of a female infant presenting after a ventricular fibrillation arrest found to have ectopic atrial tachycardia (EAT). Evaluation revealed a likely pathogenic variant in SOS1 not previously reported in affected individuals. SOS1 variants are associated with Noonan syndrome, which belongs to a family of related genetic syndromes affecting the RAS/MAPK signaling pathway. To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy.

Atypical Presentation Of Systemic Arthritis In A Toddler With Down Syndrome., Emily Worley, Weijie Li, Jordan T. Jones

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Systemic juvenile idiopathic arthritis (sJIA) is a chronic, inflammatory disease of childhood, which is characterized by the combination of arthritis, serositis, daily, high-spiking fevers, and evanescent macular rash and can present with the life-threatening complication of macrophage activation syndrome (MAS). Children with Down syndrome (DS) have complex medical challenges related to abnormalities in their immune system, which can cause a broad spectrum of disease manifestations, which can occur atypically. Children with DS are at increased risk for arthritis and interstitial lung disease (ILD) associated with sJIA that has high mortality. This case report outlines an atypical presentation of sJIA in …

An Update On The Assessment And Management Of Pediatric Abdominal Pain., Craig A. Friesen, Jennifer Colombo, Amanda D. Deacy, Jennifer Verrill Schurman

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Chronic abdominal pain is very common in children and adolescent and results in high personal and social costs. Most youth with chronic abdominal pain fulfill criteria for a functional abdominal pain disorder (FAPD) as defined by Rome criteria. These are complex conditions with a wide array of biological, psychological, and social factors contributing to the experience of pain. The purpose of the current review is to provide an overview of the pathophysiology of FAPDs and an up-to-date summary of the literature related to FAPDs in children and adolescents, with additional focus on several areas (eg, diet and probiotics) where patients …

Pooled Safety Analysis Of Tisagenlecleucel In Children And Young Adults With B Cell Acute Lymphoblastic Leukemia., John E. Levine, Stephan A. Grupp, Michael A. Pulsipher, Andrew C. Dietz, Susana Rives, Douglas Myers, Keith August, Michael R. Verneris, Jochen Buechner, Theodore W. Laetsch, Henrique Bittencourt, Andre Baruchel, Michael W. Boyer, Barbara De Moerloose, Muna Qayed, Stella M. Davies, Christine L. Phillips, Timothy A. Driscoll, Peter Bader, Krysta Schlis, Patricia A. Wood, Rajen Mody, Lan Yi, Mimi Leung, Lamis K. Eldjerou, Carl H. June, Shannon L. Maude

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Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.

Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.

Results: Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of …

Impact Of Genotype, Serum Bile Acids, And Surgical Biliary Diversion On Native Liver Survival In Fic1 Deficiency., Daan B E Van Wessel, Richard J. Thompson, Emmanuel Gonzales, Irena Jankowska, Benjamin L. Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipiński, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Talal Algoufi, Nejat Mazhar, Emanuele Nicastro, Deirdre Kelly, Gabriella Nebbia, Henrik Arnell, Björn Fischler, Jan B F Hulscher, Daniele Serranti, Cigdem Arikan, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Muñoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsőfi, Pier Luigi Calvo, Dorothee Krebs-Schmitt, Steffen Hartleif, Wendy L. Van Der Woerd, Jian-She Wang, Li-Ting Li, Özlem Durmaz, Nanda Kerkar, Marianne Hørby Jørgensen, Ryan T. Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noémie Laverdure, Cristina Targa Ferreira, Felipe Ordonez, Heng Wang, Valerie Sency, Kyung Mo Kim, Huey-Ling Chen, Elisa Carvalho, Alexandre Fabre, Jesus Quintero Bernabeu, Estella M. Alonso, Ronald J. Sokol, Frederick J. Suchy, Kathleen M. Loomes, Patrick J. Mckiernan, Philip Rosenthal, Yumirle Turmelle, Girish S. Rao, Simon Horslen, Binita M. Kamath, Maria Rogalidou, Wikrom W. Karnsakul, Bettina Hansen, Henkjan J. Verkade, Natural Course And Prognosis Of Pfic And Effect Of Biliary Diversion Consortium

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BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date.

APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound …

Effect Of Low Lactose Formula On The Short-Term Outcomes Of Neonatal Abstinence Syndrome: A Systematic Review., Mahdi Alsaleem, Jarrod Dusin, Gangaram Akangire

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The use of low lactose formula (LLF) in term and near-term infants in infants with neonatal abstinence syndrome (NAS) has been increasing recently. However, the clinical evidence of such use is limited. Our aim in this paper was to systematically review the current literature about the use of LLF in infants with NAS. We searched PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Database of Systematic Reviews for articles published between 2015 and 2020. Only randomized controlled trials, prospective, and retrospective studies. The risk of bias was assessed by using published tools appropriate for the study …

Pharmacoepidemiology Of Drug Exposure In Intubated And Non-Intubated Preterm Infants With Severe Bronchopulmonary Dysplasia., Tamorah R. Lewis, William E Truog, L Nelin, N Napolitano, R L Mckinney

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Background: Infants with severe bronchopulmonary dysplasia (BPD) are commonly treated with off-label drugs due to lack of approved therapies. To prioritize drugs for rigorous efficacy and safety testing, it is important to describe exposure patterns in this population.

Objective: Our objective was to compare rates of drug exposure between preterm infants with severe bronchopulmonary dysplasia based on respiratory support status at or beyond 36 weeks post-menstrual age.

Methods: A cross-sectional cohort study was performed on October 29, 2019. Preterm infants with severe BPD were eligible and details of respiratory support and drug therapy were recorded. Wilcoxon paired signed rank test …

Momhealth: A Feasibility Study Of A Multibehavioral Health Intervention For Pregnant And Parenting Adolescent Mothers., Karen A. Wambach, Ann M. Davis, Eve Lynn Nelson, Kelli Snow, Annie Yungmeyer, Rachel Muzzy, Karman Romero, Megan Murray

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Introduction: In 2016, 209,809 babies were born to mothers 15 - 19 years of age, for a live birth rate of 20.3 per 1,000 in this age group. Many health issues surround adolescent mothers and their infants, many of which can be addressed through behavioral change. The main purpose of this study was to examine the feasibility, acceptability, usability, and relevance of momHealth, an innovative multiple health behavior change (MHBC) education and support mHealth intervention, focused on breastfeeding, healthy eating and active living, and depression prevention among pregnant and parenting adolescents. We also evaluated the proposed online surveys and physical …

Survey Of Telemedicine By Pediatric Nephrologists During The Covid-19 Pandemic., Rupesh Raina, Nikhil Nair, Hui Kim Yap, Guido Filler, Sidharth K. Sethi, Arvind Bagga, Pankaj Hari, Timothy Bunchman, Sharon Bartosh, Katherine Twombley, Gaurav Kapur, Mignon Mcculloch, Bradley A. Warady, Maria Díaz-González De Ferris, Sarah Rush

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Introduction: The slow increase in use of telemedicine began to expand rapidly, along with reimbursement changes, during the coronavirus disease-2019 (COVID-19) pandemic. Standardized protocols for these services are lacking but are needed for effective and equitable health care. In this study, we queried pediatric nephrologists and their patients about their telemedicine experiences during the pandemic.

Methods: Surveys that were in compliance with the Health Insurance Portability and Accountability Act were deployed online to patients and physicians.

Results: We collected survey responses from 400 patients and 197 pediatric nephrologists. Patients reported positive experiences with telemedicine visits as it was logistically easier …

Pharmacologic Management Of Post-Tonsillectomy Pain In Children., Daniel R. Jensen

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Tonsillectomy is a very common procedure in children, often performed on an outpatient basis. Severe postoperative pain is common, and can be prolonged. Despite a large number of available analgesic medications, often employed in combination, achieving adequate pain control remains a persistent challenge. Research suggests a tendency among caregivers to undertreat pain, and a need for detailed care instructions and education to ensure adequate pain management. Furthermore, ongoing questions regarding the safety and efficacy of the most commonly used medications have led to wide variance in practice patterns and continuous reassessment through research that yields sometimes conflicting results. This review …

Update On The Safety Of Anesthesia In Young Children Presenting For Adenotonsillectomy., Stephanie R. Mcguire, Nichole M. Doyle

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Tonsillectomy with and without adenoidectomy is a frequently performed surgical procedure in children. Although a common procedure, it is not without significant risk. It is critical for anesthesiologists to consider preoperative, intraoperative, and postoperative patient factors and events to optimize safety, especially in young children. In the majority of cases, the indication for adenotonsillectomy in young children is obstructive breathing. Preoperative evaluation for patient comorbidities, especially obstructive sleep apnea, risk factors for a difficult airway, and history of recent illness are crucial to prepare the patient for surgery and develop an anesthetic plan. Communication and collaboration with the otolaryngologist is …

Anatomy And Physiology Of The Palatine Tonsils, Adenoids, And Lingual Tonsils., Alexandra Arambula, Jason R. Brown, Laura Neff

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Objective: This review aims to discuss the basic anatomy and physiology of the palatine and pharyngeal tonsils, with reference to how this foundational understanding may affect patient management and surgical procedures in these regions of the upper airway.

Methods: A literature search was performed using PubMed and Google Scholar using the MeSH terms tonsils, adenoids, anatomy, physiology, and adenotonsillectomy. Primary sources were excluded if they were abstracts only, non-English language, or non-human studies. Thirty-five sources were included in this review.

Results and conclusions: The pharyngeal and palatine tonsils are compact yet physiologically complex mucosa-associated lymphoid tissues that make up a …

Pediatric Drug-Induced Sleep Endoscopy: An Updated Review Of The Literature., Jill M. Arganbright, Jason C. Lee, Robert A. Weatherly

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The field of drug-induced sleep endoscopy (DISE) has grown considerably over the last 10∼15 years, to now include its use in pediatric patients. In this review article, we outline our approach to the use of this technology in Children with Airway Obstruction, most specifically in the management of children with airway obstruction and known or suspected adenotonsillar enlargement.

Profiling Pretomanid As A Therapeutic Option For Tb Infection: Evidence To Date., Stephani L. Stancil, Fuad Mirzayev, Susan M. Abdel-Rahman

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Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and …

Comparing Plastic Surgery And Otolaryngology Surgical Outcomes And Cartilage Graft Preferences In Pediatric Rhinoplasty: A Retrospective Cohort Study Analyzing 1839 Patients., Andres F. Doval, Ariel Ourian, Kieran S. Boochoon, Vishwanath Chegireddy, Michael Lypka, Anthony Echo

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Rhinoplasty in children has raised concerns about its safety in the pediatric population. There is scarcity of evidence describing outcomes and surgical techniques performed in pediatric rhinoplasty. We analyzed post-operative complications and cartilage preferences between plastic surgeons and otolaryngologists.Data was collected through the Pediatric National Surgical Improvement Program from 2012 to 2017. Current Procedure Terminology codes were used for data extraction. Patients were grouped according to type of rhinoplasty procedures (primary, secondary, and cleft rhinoplasty). A comparison between plastic surgeons and otolaryngologists was made in each group in terms of postoperative complications. Additionally, a sub-group analysis based on cartilage graft …

A Mouse Model Of Prenatal Exposure To Interleukin-6 To Study The Developmental Origin Of Health And Disease., Tarak Srivastava, Trupti Joshi, Daniel P. Heruth, Mohammad Rezaiekhaligh, Robert E. Garola, Jianping Zhou, Varun C. Boinpelly, M. Farhan Ali, Uri S. Alon, Madhulika Sharma, Gregory B. Vanden Heuvel, Pramod Mahajan, Lakshmi Priya, Yuexu Jiang, Ellen T. Mccarthy, Virginia J. Savin, Ram Sharma, Mukut Sharma

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Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC-MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.

The Yin And The Yang Of Transformative Research During The Covid-19 Pandemic-A Perspective., Venkatesh Sampath, Ramani Ramchandran

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The COVID-19 pandemic has highlighted the necessity for scientists from diverse disciplines to collaboratively mitigate the singular calamity facing humanity this century. The ability of researchers to combine exponential advances in technology and scientific acumen has resulted in landmark discoveries in pediatric research and is surmounting the COVID-19 challenge. Several of these discoveries exist in a realm of research that is not classically "basic" or "clinical." Translational research characterizes this domain partially, but does not fully capture the integrated research approaches that have spurred these discoveries. Herein, we share our perspective on the common themes underpinning the basic and clinical …

Dclk1 Isoforms And Aberrant Notch Signaling In The Regulation Of Human And Murine Colitis., Badal C. Roy, Ishfaq Ahmed, Jason Stubbs, Jun Zhang, Thomas M. Attard, Seth Septer, Danny Welch, Shrikant Anant, Venkatesh Sampath, Shahid Umar

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Alternative promoter usage generates long and short isoforms (DCLK1-L and DCLK1-S) of doublecortin-like kinase-1 (DCLK1). Tight control of Notch signaling is important to prevent and restitute inflammation in the intestine. Our aim was to investigate whether Notch1-DCLK1 axis regulates the mucosal immune responses to infection and whether this is phenocopied in human models of colitis. In the FFPE (formalin-fixed paraffin-embedded) sections prepared from the colons of ulcerative colitis (UC) and immune-mediated colitis (IRAEC) patients, expression of DCLK1 isoforms correlated positively with Notch1 and negatively with a transcriptional repressor, FoxD3 (Forkhead Box D3). DCLK1 protein staining in these sections was predominantly …

Variability In Ckd Biomarker Studies: Soluble Urokinase Plasminogen Activator Receptor (Supar) And Kidney Disease Progression In The Chronic Kidney Disease In Children (Ckid) Study., Alison G. Abraham, Yunwen Xu, Jennifer L. Roem, Jason H. Greenberg, Darcy K. Weidemann, Venkata S. Sabbisetti, Joseph V. Bonventre, Michelle Denburg, Bradley A. Warady, Susan L. Furth

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Rationale & Objective: Biomarker studies are important for generating mechanistic insight and providing clinically useful predictors of chronic kidney disease (CKD) progression. However, variability across studies can often muddy the evidence waters. Here we evaluated real-world variability in biomarker studies using two published studies, independently conducted, of the novel plasma marker soluble urokinase-type plasminogen activator receptor (suPAR) for predicting CKD progression in children with CKD.

Study Design: A comparison of 2 prospective cohort studies.

Setting & Participants: 541 children from the Chronic Kidney Disease in Children (CKiD) study, median age 12 years, median glomerular filtration rate (GFR) of 54 mL/min/1.73m …

Update On The Role Of Allergy In Pediatric Functional Abdominal Pain Disorders: A Clinical Perspective., Craig A. Friesen, Jennifer Colombo, Jennifer Verrill Schurman

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Both functional abdominal pain disorders (FAPDs) and food allergies are relatively common in children and adolescents, and most studies report an association between FAPDs and allergic conditions. FAPDs share pathophysiologic processes with allergies, including both immune and psychological processes interacting with the microbiome. No conclusive data are implicating IgE-mediated reactions to foods in FAPDs; however, there may be patients who have IgE reactions localized to the gastrointestinal mucosa without systemic symptoms that are not identified by common tests. In FAPDs, the data appears stronger for aeroallergens than for foods. It also remains possible that food antigens initiate an IgG reaction …

A Novel Approach To Explore Safety-I And Safety-Ii Perspectives In In Situ Simulations-The Structured What If Functional Resonance Analysis Methodology., Ralph James Mackinnon, Karin Pukk-Härenstam, Christopher S. Kennedy, Erik Hollnagel, David Slater

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OBJECTIVES: With ever increasingly complex healthcare settings, technology enhanced simulation (TES) is well positioned to explore all perspectives to enhance patient safety and patient outcomes. Analysis from a Safety-II stance requires identification of human adjustments in daily work that are key to maintaining safety. The aim of this paper is to describe an approach to explore the consequences of human variability from a Safety-II perspective and describe the added value of this to TES.

METHODS: The reader is guided through a novel application of functional resonance analysis methodology (FRAM), a method to analyse how a system or activity is affected …

Digital Health Technology In Asthma: A Comprehensive Scoping Review., Giselle Mosnaim, Guilherme Safioti, Randall Brown, Michael Depietro, Stanley J. Szefler, David M. Lang, Jay M. Portnoy, Don A. Bukstein, Leonard B. Bacharier, Rajan K. Merchant

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BACKGROUND: A variety of digital intervention approaches have been investigated for asthma therapy during the past decade, with different levels of interactivity and personalization and a range of impacts on different outcome measurements.

OBJECTIVE: To assess the effectiveness of digital interventions in asthma with regard to acceptability and outcomes and evaluate the potential of digital initiatives for monitoring or treating patients with asthma.

METHODS: We evaluated digital interventions using a scoping review methodology through a literature search and review. Of 871 articles identified, 121 were evaluated to explore intervention characteristics, the perception and acceptability of digital interventions to patients and …

The Dietary Management Of Potassium In Children With Ckd Stages 2-5 And On Dialysis-Clinical Practice Recommendations From The Pediatric Renal Nutrition Taskforce., An Desloovere, José Renken-Terhaerdt, Jetta Tuokkola, Vanessa Shaw, Larry A. Greenbaum, Dieter Haffner, Caroline Anderson, Christina L. Nelms, Michiel J S Oosterveld, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, Bradley A. Warady, Rukshana Shroff, Johan Vande Walle

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Dyskalemias are often seen in children with chronic kidney disease (CKD). While hyperkalemia is common, with an increasing prevalence as glomerular filtration rate declines, hypokalemia may also occur, particularly in children with renal tubular disorders and those on intensive dialysis regimens. Dietary assessment and adjustment of potassium intake is critically important in children with CKD as hyperkalemia can be life-threatening. Manipulation of dietary potassium can be challenging as it may affect the intake of other nutrients and reduce palatability. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations …

Covid-19 In Children-Not Just Little Adults., Jennifer E. Schuster, Annabelle De St Maurice

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Comment on

• Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children. Kompaniyets L, Agathis NT, Nelson JM, Preston LE, Ko JY, Belay B, Pennington AF, Danielson ML, DeSisto CL, Chevinsky JR, Schieber LZ, Yusuf H, Baggs J, Mac Kenzie WR, Wong KK, Boehmer TK, Gundlapalli AV, Goodman AB.JAMA Netw Open. 2021 Jun 1;4(6):e2111182. doi: 10.1001/jamanetworkopen.2021.11182.PMID: 34097050 Free PMC article.

Next-Generation Sequencing In The Diagnosis Of Rare Pediatric Sinonasal Tumors., Atif A. Ahmed, Divya Vundamati, Midhat Farooqi, Elena Repnikova, Timothy Zinkus, Maxine Hetherington, Lorien Paulson

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The diagnosis of desmoid fibromatosis or other spindle cell tumors in the sinonasal region is very rare in children and needs to be thoroughly confirmed with immunohistochemical and/or molecular tests. We report 2 patients with such rare tumors and describe the use of next-generation sequencing in their evaluation. A 3-year-old female had a 4.4-cm midline nasal cavity mass involving the bony septum and extending into the base of the skull bilaterally. The moderate cellular fibroblastic proliferation revealed areas of thick keloid-like collagen bands and other areas with myxoid edematous stroma. Deep targeted sequencing identified a novel G34V mutation in the

Extracellular Superoxide Dismutase (Ec-Sod) Regulates Gene Methylation And Cardiac Fibrosis During Chronic Hypoxic Stress., Ayan Rajgarhia, Kameshwar R. Ayasolla, Nahla Zaghloul, Jorge M. Lopez Da Re, Edmund J. Miller, Mohamed Ahmed

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Chronic hypoxic stress induces epigenetic modifications mainly DNA methylation in cardiac fibroblasts, inactivating tumor suppressor genes (RASSF1A) and activating kinases (ERK1/2) leading to fibroblast proliferation and cardiac fibrosis. The Ras/ERK signaling pathway is an intracellular signal transduction critically involved in fibroblast proliferation. RASSF1A functions through its effect on downstream ERK1/2. The antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), decreases oxidative stress from chronic hypoxia, but its effects on these epigenetic changes have not been fully explored. To test our hypothesis, we used an in-vitro model: wild-type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG). …

Transcription Factor Β-Catenin Plays A Key Role In Fluid Flow Shear Stress-Mediated Glomerular Injury In Solitary Kidney., Tarak Srivastava, Daniel P. Heruth, R Scott Duncan, Mohammad H. Rezaiekhaligh, Robert E. Garola, Lakshmi Priya, Jianping Zhou, Varun C. Boinpelly, Jan Novak, Mohammed Farhan Ali, Trupti Joshi, Uri S. Alon, Yuexu Jiang, Ellen T. Mccarthy, Virginia J. Savin, Ram Sharma, Mark L. Johnson, Mukut Sharma

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Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3β-β-catenin signaling. The present study was undertaken to confirm (i) the activation of β-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL mice with the β-galactosidase reporter gene for β-catenin activation, (ii) β-catenin translocation in FFSS-treated mouse podocytes, and (iii) β-catenin signaling using publicly available data from UNX mice. The UNX of TOPGAL mice resulted in glomerular hypertrophy and increased the mesangial matrix consistent with hemodynamic adaptation. Uninephrectomized TOPGAL mice showed an increased β-galactosidase expression at 4 weeks …

A Multicenter Evaluation Of Viral Bloodstream Detections In Children Presenting To The Emergency Department With Suspected Systemic Infection., Christina A. Rostad, Neena Kanwar, Jumi Yi, Claudia R. Morris, Jennifer Dien Bard, Amy Leber, James Dunn, Kimberle C. Chapin, Anne J. Blaschke, Judy A. Daly, Leslie Hueschen, Matthew Jones, Elizabeth Ott, Jeffrey Bastar, Kevin M. Bourzac, Rangaraj Selvarangan

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BACKGROUND: Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections.

METHODS: We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted.

RESULTS: Of the 1114 subjects enrolled, …

Potential Role Of Methotrexate Polyglutamates In Therapeutic Drug Monitoring For Pediatric Inflammatory Bowel Disease., Ryan Morrow, Ryan Funk, Mara Becker, Ashley K. Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, Valentina Shakhnovich

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Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)-promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional secondary analysis, we assessed the relationships between MTX-Glu and MTX dose and treatment response in pediatric IBD. Twenty-one children with IBD, receiving maintenance therapy with infliximab (IFX) and MTX, had MTX-Glu1-6 concentrations and IFX troughs/antibodies measured and disease activity assessed for comparison in remission vs. active IBD using non-parametric tests, with associations explored using Spearman's correlation (ρ) …

Survival Following Relapse In Children With Acute Myeloid Leukemia: A Report From Aml-Bfm And Cog., Mareike Rasche, Martin Zimmermann, Emma Steidel, Todd Alonzo, Richard Aplenc, Jean-Pierre Bourquin, Heidrun Boztug, Todd Cooper, A S. Gamis, Robert B. Gerbing, Iveta Janotova, Jan-Henning Klusmann, Thomas Lehrnbecher, Nora Mühlegger, Nils V. Neuhoff, Naghmeh Niktoreh, Lucie Sramkova, Jan Stary, Katharina Waack, Christiane Walter, Ursula Creutzig, Michael Dworzak, Gertjan Kaspers, Edward Anders Kolb, Dirk Reinhardt

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Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM …