Medical Specialties Commons^™

Nitric Oxide Generating/Releasing Materials, Honying Liang, Parimala Nacharaju, Adam J. Friedman, Joel Friedman

Dermatology Faculty Publications

Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to …

Complications And Predictors Of Need For Return To The Operating Room In The Treatment Of Supracondylar Humerus Fractures In Children, Matthew E. Oetgen, Gudrun E. Mirick, Lara Atwater, John F. Lovejoy

Orthopaedic Surgery Faculty Publications

Supracondylar humerus fractures are common pediatric injuries. Little is known about the risk factors for repeat operative procedures. A retrospective chart review of 709 patients treated for a displaced supracondylar humerus fracture was performed to identify risk factors for return to the operating room during the initial post-operative period. Deviations of routine fracture care were recorded and complication rates were compared between Gartland type 2 and 3 fractures using logistic regression. Type 3 fractures were found to have a higher complication rate, and, specifically, more peri-operative nerve palsies, more likely to need to return to the operating room for hardware …

Initial Report Of The Osteogenesis Imperfecta Adult Natural History Initiative., Laura L. Tosi, Matthew E. Oetgen, Marianne K Floor, Mary Beth Huber, Ann M Kennelly, Robert J. Mccarter, +5 Additional Authors

Orthopaedic Surgery Faculty Publications

BACKGROUND: A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition.

METHODS: The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed …

Optical Measurement Of Skin Temperature In Mr-Hifu, Daniel Yang, Haydar Celik, Doug Wackerle, David Kinnaird, Avinash Eranki, Matthew E. Oetgen, Aerang Kim, Karun Sharma, Harry Kim, Peter Kim, Pavel Yarmolenko

Pediatrics Posters and Presentations

No abstract provided.

An Innovative Interactive Modeling Tool To Analyze Scenario-Based Physician Workforce Supply And Demand, Saurabh Gupta, W. Stephen Black-Schaffer, James M. Crawford, David Gross, Donald S. Karcher, Jill Kaufman, +13 Additional Authors

Pathology Faculty Publications

Effective physician workforce management requires that the various organizations comprising the House of Medicine be able to assess their current and future workforce supply. This information has direct relevance to funding of graduate medical education. We describe a dynamic modeling tool that examines how individual factors and practice variables can be used to measure and forecast the supply and demand for existing and new physician services. The system we describe, while built to analyze the pathologist workforce, is sufficiently broad and robust for use in any medical specialty. Our design provides a computer-based software model populated with data from surveys …

The Transcriptional Profile Of Coronary Arteritis In Kawasaki Disease., Anne H Rowley, Kristine M Wylie, Kwang-Youn A Kim, Adam J Pink, Amy Yang, Jan M. Orenstein, +6 Additional Authors

Pathology Faculty Publications

BACKGROUND: Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.

METHODS: Deep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association …

Cervical Instability In Klippel-Feil Syndrome: Case Report And Review Of The Literature, Aaron Wessell, Peter Derosa, Abraham Cherrick, Jonathan H. Sherman

Neurological Surgery Faculty Publications

Background

The authors present a case of cervical myelopathy and radiculopathy in the setting of multiple Klippel-Feil syndrome abnormalities treated surgically with a single-level C3–C4 anterior cervical discectomy and fusion. We discuss the clinical presentation, radiographic findings, and various treatment options for cervical spine abnormalities in Klippel-Feil syndrome.

Case Presentation

This 22-year-old female with Klippel-Feil syndrome presented with intermittent neck pain, left upper extremity weakness, and paresthesias. Preoperative MRI, CT, and X-rays of the cervical spine revealed anterolisthesis at C3/4 with unstable movement on flexion and extension imaging. In addition, there were multiple segmental fusion abnormalities including hemivertebrae and other …

Impact Of Prenatal Environmental Stress On Cortical Development, Seiji Ishii, Kazue Hashimoto-Torii

Pediatrics Faculty Publications

Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development …

Dual Transcriptomic Profiling Of Host And Microbiota During Health And Disease In Pediatric Asthma., Marcos Pérez-Losada, Eduardo Castro-Nallar, Matthew L. Bendall, Robert J. Freishtat, Keith A. Crandall

Pediatrics Faculty Publications

BACKGROUND: High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for …

Levetiracetam-Induced Pancytopenia., Talal Alzahrani, Dana Kay, Saeed A. Alqahtani, Yamane Makke, Linda Lesky, Mohamad Z. Koubeissi

Neurology Faculty Publications

Pancytopenia is a rare side effect of levetiracetam (LEV) that is associated with severe morbidity that requires hospitalization. Here, we report a patient with a right temporoparietal tumor who underwent a temporal craniotomy with resection of the mass and was started on LEV for seizure prophylaxis per the neurosurgery local protocol. The patient developed LEV-induced pancytopenia, which was successfully managed by discontinuation of this medication. Our report aims to increase awareness of this rare cause of pancytopenia among clinicians.

Adar1 Facilitates Hiv-1 Replication In Primary Cd4+ T Cells., Eloy Cuadrado, Thijs Booiman, John L Van Hamme, Machiel H Jansen, Karel A Van Dort, Adeline Vanderver, Gillian I Rice, Yanick J Crow, Neeltje A Kootstra, Taco W Kuijpers

Neurology Faculty Publications

Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of …

Mitral Subvalvular Aneurysm In A Patient With Chagas Disease And Recurrent Episodes Of Ventricular Tachycardia., Tereza Augusta Grillo, Guilherme Rafael S Athayde, Ana Flávia L Belfort, Reynaldo C Miranda, Andrea Z. Beaton, Bruno R Nascimento

Neurology Faculty Publications

Subvalvular left ventricular aneurysm is a rare disease of obscure origin suggesting unique causes such as congenital, traumatic, and inflammatory or infectious diseases. Its mortality is closely related to heart failure, mitral insufficiency, thromboembolic phenomena, and cardiac arrhythmias. Although association with coronary artery disease is not described, the compression of epicardial vessels by the aneurysm may lead to ischemic manifestations. We report here a case of mitral subvalvular left ventricular aneurysm of probable chagasic origin, in a patient with normal left ventricular function evolving with repeated episodes of monomorphic ventricular tachycardia, despite noninducible electrophysiological testing and the use of optimal …

Dyspnea Associated With Silicone Breast Implant Rupture, Katherine Rider, Hatice Kaya, Guillermo Gutierrez

Medicine Faculty Publications

We present a case of a 48-year-old woman with a significant history of atopy. She presented with a 1-month history of dyspnea on exertion. Pulmonary function testing was normal, with no obstruction or reversibility post-bronchodilation. Bilateral breast implant rupture was detected on further investigation for a left upper lobe nodule, and the patient underwent bilateral implant removal. There was an improvement in her respiratory symptoms. Systemic symptoms, labeled as “Autoimmune/Inflammatory Syndrome Induced by Adjuvants,” are known to be associated with breast implants, with 14% of women in a cohort developing autoimmune disease secondary to their implants. An improvement in symptoms …

May Circulating Micrornas Be Gastric Cancer Diagnostic Biomarkers?, Xiaoling Wu, Xiaohui (Jane) Tan, Sidney W. Fu

Medicine Faculty Publications

Gastric cancer (GC) is the third leading cause of cancer-related deaths. More than 80% of the diagnosis was made at the advanced stages of the disease, highlighting the urgent demand for novel biomarkers that can be used for early detection. Recently, a number of studies suggest that circulating microRNAs (miRNAs) could be potential biomarkers for GC diagnosis. Cancer-related circulating miRNAs, as well as tissue miRNAs, provide a hopeful prospect of detecting GC at early stages, and the prospective participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic tests for GC. As miRNAs in blood are …

Quality Control Measures Over 30 Years In A Multicenter Clinical Study: Results From The Diabetes Control And Complications Trial / Epidemiology Of Diabetes Interventions And Complications (Dcct/Edic) Study., Gayle M Lorenzi, Barbara H Braffett, Valerie L Arends, Ronald P Danis, Lisa Diminick, Kandace A Klumpp, Anthony D Morrison, Elsayed Z Soliman, Michael W Steffes, Patricia A Cleary

GW Biostatistics Center

No abstract provided.

The Cost-Effectiveness Of Diabetes Prevention: Results From The Diabetes Prevention Program And The Diabetes Prevention Program Outcomes Study, William Herman

GW Biostatistics Center

Background

The Diabetes Prevention Program (DPP) was a randomized, controlled clinical trial. It demonstrated that among high-risk individuals with impaired glucose tolerance, diabetes incidence was reduced by 58 % with lifestyle intervention and 31 % with metformin compared to placebo. During the Diabetes Prevention Program Outcomes Study (DPPOS), all DPP participants were unmasked to their treatment assignments, the original lifestyle intervention group was offered additional lifestyle support, the metformin group continued metformin, and all three groups were offered a group-implemented lifestyle intervention. Over the 10 years of combined DPP/DPPOS follow-up, diabetes incidence was reduced by 34 % in the lifestyle …

Integrating Microbial And Host Transcriptomics To Characterize Asthma-Associated Microbial Communities., Eduardo Castro-Nallar, Ying Shen, Robert J. Freishtat, Marcos Pérez-Losada, Solaiappan Manimaran, Et Al.

Pediatrics Faculty Publications

BACKGROUND: The relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma.

METHODS: Using whole metagenomic shotgun RNA sequencing, we characterized and compared the microbial …

Pharmacologically-Induced Mitotic Synchrony In Airway Epithelial Cells As A Mechanism Of Action Of Anti-Inflammatory Drugs, Robert J. Freishtat, Gustavo Nino, Y. Tsegaye, Sarah E. Alcala, Angela S. Benton, Alan M. Watson, E.K.M. Reeves, S. K. Haider, Jesse M. Damsker

Pediatrics Faculty Publications

Background

Mitotic synchrony is the synchronous progression of a population of cells through the cell cycle and is characteristic of non-diseased airway epithelial cells. However, we previously showed that asthmatic airway epithelial cells are characterized by mitotic asynchrony and are pro-inflammatory as a result. Glucocorticoids can induce mitotic synchrony that in turn suppresses the pro-inflammatory state of diseased cells, suggesting a novel anti-inflammatory mechanism of action. Herein, we benchmarked traditional glucocorticoids against the ability of a new clinical-stage dissociative steroidal drug, VBP15, for mitotic resynchronization and associated anti-inflammatory activity in asthmatic airway epithelial cells.

Methods

Primary airway epithelial cells differentiated …

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L.C. Luban, Joseph M. Devaney, Anthony D. Sandler

Pediatrics Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

Functional Properties Of Resting State Networks In Healthy Full-Term Newborns., Josepheen De Asis-Cruz, Marine Bouyssi-Kobar, Iordanis Evangelou, Gilbert Vezina, Catherine Limperopoulos

Radiology Faculty Publications

Objective, early, and non-invasive assessment of brain function in high-risk newborns is critical to initiate timely interventions and to minimize long-term neurodevelopmental disabilities. A prerequisite to identifying deviations from normal, however, is the availability of baseline measures of brain function derived from healthy, full-term newborns. Recent advances in functional MRI combined with graph theoretic techniques may provide important, currently unavailable, quantitative markers of normal neurodevelopment. In the current study, we describe important properties of resting state networks in 60 healthy, full-term, unsedated newborns. The neonate brain exhibited an efficient and economical small world topology: densely connected nearby regions, sparse, but …

St Segment Depression After Norwood/Systemic-Pulmonary Artery Shunt, Ashraf Harahsheh, Craig A. Sable, Pranava Sinha, Richard A. Jonas

Pediatrics Faculty Publications

A three-month-old girl with double inlet left ventricle (S;D;D), hypoplastic outlet ventricle, restrictive bulboventricular foramen, d-transposition of great arteries and interrupted aortic arch underwent Norwood stage 1 operation, systemic to pulmonary artery (PA) shunt and atrial septectomy, and developed ectopic atrial tachycardia that responded to digoxin therapy. She developed fussiness lasting two hours, not associated with cyanosis, and not relieved by feeding. Her pulse oximetry was 88% while breathing room air, and she had no differential blood pressure gradient.

Expert Consensus Document: Mind The Gaps—Advancing Research Into Short-Term And Long-Term Neuropsychological Outcomes Of Youth Sports-Related Concussions, Aaron J. Carman, Rennie Ferguson, Robert Cantu, R. Dawn Comstock, Penny A. Dacks, Gerard A. Gioia, +20 Additional Authors

Psychiatry and Behavioral Sciences Faculty Publications

Sports-related concussions and repetitive subconcussive exposure are increasingly recognized as potential dangers to paediatric populations, but much remains unknown about the short-term and long-term consequences of these events, including potential cognitive impairment and risk of later-life dementia. This Expert Consensus Document is the result of a 1-day meeting convened by Safe Kids Worldwide, the Alzheimer's Drug Discovery Foundation, and the Andrews Institute for Orthopaedics and Sports Medicine. The goal is to highlight knowledge gaps and areas of critically needed research in the areas of concussion science, dementia, genetics, diagnostic and prognostic biomarkers, neuroimaging, sports injury surveillance, and information sharing. For …

Directional Secretory Response Of Double Stranded Rna-Induced Thymic Stromal Lymphopoetin (Tslp) And Ccl11/Eotaxin-1 In Human Asthmatic Airways, Gustavo Nino, Shehlanoor Huseni, Geovanny F. Perez, Krishna Pancham, Humaira Mubeen, Aleeza Abeesi, Justin Wang, Stephen Eng, Anamaris M. Colberg-Poley, Mary C. Rose

Pediatrics Faculty Publications

Background

Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.

Methods

Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) …

Integrative Therapy Use For Management Of Side Effects And Toxicities Experienced By Pediatric Oncology Patients, Shana Jacobs

Pediatrics Faculty Publications

Integrative Therapies (IT), otherwise known as Complementary and Alternative Medicine, are widely used among pediatric oncology patients, despite a paucity of available evidence. This review summarizes surveys that describe the prevalence of IT use by pediatric oncology patients, both during therapy and in survivorship, as well as the modalities being used. Additionally, the evidence that exists for specific treatments that appear to be efficacious in controlling specific symptoms is described. Finally, there are recommendations for practitioners on how to best counsel patients about IT use.

Utility Of Heidelberg Retinal Tomography As A Screening Tool For Analyzing Retinal Nerve Fiber Layer Defects, David A. Belyea, Rashed Alhabshan, Sankaranarayana P. Mahesh, Gregory S. Gertner, Mirsad M. Ibisevic, Abdullah S. Habib, Jacob A. Dan

Ophthalmology Faculty Publications

Context

Although Heidelberg retinal tomography (HRT)-generated topographic images have been studied extensively for the detection of retinal nerve fiber layer (RNFL) defects, little is known about the role of HRT-generated surface reflectivity images in the detection of RNFL defects in either patients with glaucoma or glaucoma suspects.

Aims

To evaluate the effectiveness of HRT version II (HRT II) optic nerve reflectivity images in uncovering RNFL defects in an outpatient population evaluated for glaucoma.

Study design/materials and methods

In 102 consecutive eyes from 60 patients evaluated for glaucoma in an academic-based practice, HRT II optic nerve images were prospectively imaged and …

Current Perspectives On Primary Care Workforce, Kathleen Klink

Health Workforce Speaker Series

No abstract provided.

Corticosteroids And Pediatric Septic Shock Outcomes: A Risk Stratified Analysis, Sarah J. Atkinson, Natalie Z. Cvijanovich, Neal J. Thomas, Geoffrey L. Allen, Nick Anas, Robert J. Freishtat, +17 Additional Authors

Pediatrics Faculty Publications

Background

The potential benefits of corticosteroids for septic shock may depend on initial mortality risk.

Objective

We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk.

Methods

We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression …

The Translational Biology Of Remyelination: Past, Present, And Future, Robin J.M. Franklin, Vittorio Gallo

Pediatrics Faculty Publications

Amongst neurological diseases, multiple sclerosis (MS) presents an attractive target for regenerative medicine. This is because the primary pathology, the loss of myelin-forming oligodendrocytes, can be followed by a spontaneous and efficient regenerative process called remyelination. While cell transplantation approaches have been explored as a means of replacing lost oligodendrocytes, more recently therapeutic approaches that target the endogenous regenerative process have been favored. This is in large part due to our increasing understanding of (1) the cell types within the adult brain that are able to generate new oligodendrocytes, (2) the mechanisms and pathways by which this achieved, and (3) …

Vitamin A, Vitamin E, Iron And Zinc Status In A Cohort Of Hiv-Infected Mothers And Their Uninfected Infants, Jacqueline Pontes Monteiro, Maria Leticia Santos Cruz, Marisa Marcia Mussi-Pinhata, Roberta Garcia Salomao, Alceu Jordao Junior, Jennifer S. Read, Jose Henrique Da Silva Pilotto, Rachel Ann Cohen, Sonia Karolina Stoszek, George Kelly Siberry

Pediatrics Faculty Publications

Introduction

We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants.

Methods

Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI).

Results

Among the 97 women 19.6% were underweight. …

Antibiotic Prophylaxis And Reflux: Critical Review And Assessment, Bernarda Viteri Baquerizo, Craig A. Peters

Urology Faculty Publications

The use of continuous antibiotic prophylaxis (CAP) was critical in the evolution of vesicoureteral reflux (VUR) from a condition in which surgery was the standard of treatment to its becoming a medically managed condition. The efficacy of antibiotic prophylaxis in the management of VUR has been challenged in recent years, and significant confusion exists as to its clinical value. This review summarizes the critical factors in the history, use, and investigation of antibiotic prophylaxis in VUR. This review provides suggestions for assessing the potential clinical utility of prophylaxis.