Digital Commons Network^™

A Novel Approach To The Removal Of A Silastic Band Via The Peroral Endoscopic Tunneling-Silastic Bandectomy Technique

Faculty, Staff and Students Publications

The peroral endoscopic tunneling-silastic bandectomy technique to remove a silastic band causing a vertical banded gastroplasty stenosis. This method is a viable alternative to surgical removal of foreign bodies outside the gastrointestinal lumen.

Proteomes Of Extracellular Vesicles From Pancreatic Cancer Cells And Cancer-Associated Fibroblasts, David W Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A Brentnall

Faculty, Staff and Students Publications

OBJECTIVES: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis.

METHODS: Proteomic and functional analyses were applied to characterize the proteomes of EVs released from 5 pancreatic cancer lines, 2 CAF cell lines, and a normal pancreatic epithelial cell line (HPDE).

RESULTS: More than 1400 nonredundant proteins were identified …

A Telemedicine Alternative To The 6-Minute Walk Test Using Personal Activity Trackers In Liver Transplant Candidates, Marie Nunez Duarte, Rachel K Grubbs, Ruben Hernaez

Faculty, Staff and Students Publications

The COVID-19 pandemic has limited liver transplant (LT) candidates access to clinics. Telehealth methods to assess frailty are needed. We developed a method to estimate the step length of LT candidates, which would permit remotely obtaining the 6-min walk test (6MWT) distance with a personal activity tracker (PAT).

METHODS: 6MWT was performed while candidates wore a PAT. On first 21 subjects (stride cohort), the step length was measured and compared with calculated one (6MWT-distance/6MWT steps). On a second cohort (PAT-6MWT; n = 116), we collected the 6MWT step count and used multivariable models to generate formulas estimating step length. We …

Cell Plasticity In Regeneration In The Stomach And Beyond

Faculty, Staff and Students Publications

Recent studies using cell lineage-tracing techniques, organoids, and single-cell RNA sequencing analyses have revealed: 1) adult organs use cell plasticity programs to recruit progenitor cells to regenerate tissues after injury, and 2) plasticity is far more common than previously thought, even in homeostasis. Here, we focus on the complex interplay of normal stem cell differentiation and plasticity in homeostasis and after injury, using the gastric epithelium as a touchstone. We also examine common features of regenerative programs and discuss the evolutionarily conserved, stepwise process of paligenosis which reprograms mature cells into progenitors that can repair damaged tissue. Finally, we discuss …

Salivary Biomarker Evaluation Of Chronic Pancreatitis Patients Reveals Alterations In Human Proteins, Cytokines, Prostaglandin E2 Levels, And Bacterial Diversity, Jolaine M Hines, Jing Zhao, Aurelia Lugea, Marcio A Diniz, Sungjin Kim, Aida Habtezion, Kristi L Hoffman, Joseph F Petrosino, William E Fisher, Liang Li, Ryan J Lennon, Ravinder Jit Singh, Santhi Swaroop Vege, Stephen J Pandol, Mark D Topazian

Faculty, Staff and Students Publications

OBJECTIVES: Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified.

METHODS: Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls.

RESULTS: Our results …

Patients With Lung Cancer Of Different Racial Backgrounds Harbor Distinct Immune Cell Profiles, Sunny Mai, Dimuthu Nuwan Perera, Jilu Zhang, Ping-Ying Pan, Cristian Coarfa, Kenneth Ramos, Shu-Hsia Chen, Randa El-Zein

Faculty, Staff and Students Publications

UNLABELLED: Tumors accumulated with infiltrated immune cells (hot tumors) have a higher response rate to immune checkpoint blockade, when compared with those with minimal T-cell infiltration (cold tumors). We report here that patients with lung cancer with different racial backgrounds harbored distinct immune cell profiles in the tumor microenvironment. Compared with African Americans (AA), Caucasian Americans (CA) exhibited increased immune cell infiltration and vasculature, and increased survival. Changes of survival and immune profile were most pronounced among active smokers and nonsmokers, compared with former smokers and total patients. Neighborhood analysis showed that immune cells accumulated around cancer cells in CAs …

Exome Sequencing Identifies Genetic Variants In Anophthalmia And Microphthalmia, Chen Ma, Cynthia J Curry, Daniel Mcgoldrick, Deborah A Nickerson, Jessica X Chong, Elizabeth E Blue, James C Mullikin, Jennita Reefhuis, Wendy N Nembhard, Paul A Romitti, Martha M Werler, Marilyn L Browne, Andrew F Olshan, Richard H Finnell, Marcia L Feldkamp, Faith Pangilinan, Lynn M Almli, Mike J Bamshad, Lawrence C Brody, Mary M Jenkins, Gary M Shaw, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 …

Gestational Age And Quintero Staging As Predictors Of Single Fetal Demise In Twin-Twin Transfusion Syndrome After Fetoscopic Laser Photocoagulation: A Systematic Review And Meta-Analysis, Roopali Donepudi, Magdalena Sanz Cortes, Michael A Belfort, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

BACKGROUND: Single fetal demise after intervention for twin-twin transfusion syndrome is a relatively common complication and is often devastating for the patients.

OBJECTIVE: This meta-analysis aimed to evaluate the risk of single fetal demise based on gestational age and Quintero staging at the time of interventions in twin-to-twin transfusion syndrome after fetoscopic laser photocoagulation.

STUDY DESIGN: Systematic search was performed in PubMed, Web of Science, and Scopus from inception to August 2021. The primary outcome was to compare the incidence of fetal demise between low (I and II) and high (III and IV) twin-to-twin transfusion syndrome Quintero stages. The rate …

Identifying Factors Associated With Detection Of Sessile Gastric Polyps In Patients With Familial Adenomatous Polyposis, Amit Bhatt, David Liska, Carol A Burke

Faculty, Staff and Students Publications

Background and study aims  Gastric cancer (GC) is increasingly reported and a leading cause of death in patients with familial adenomatous polyposis (FAP). Identifying features in patients with FAP who harbor sessile gastric polyps, likely precursors to GC, may lead to alterations in endoscopic surveillance in those patients and allow endoscopic intervention to decrease the risk of GC. The aim of this study was to identify demographic and clinical factors in patients with FAP who harbor sessile gastric polyps.

Patients and methods  We retrospectively compared demographic, clinical, and endoscopic features in consecutive adult patients with FAP who presented for a …

Identifying Bone Matrix Impairments In A Mouse Model Of Neurofibromatosis Type 1 (Nf1) By Clinically Translatable Techniques, Joshua Meyer, Jacquelyn S Pennings, Florent Elefteriou, Jeffry S Nyman

Faculty, Staff and Students Publications

Three-to-four percent of children with neurofibromatosis type 1 (NF1) present with unilateral tibia bowing, fracture, and recalcitrant healing. Alkaline phosphatase enzyme therapy prevented poor bone mineralization and poor mechanical properties in mouse models of NF1 skeletal dysplasia; but transition to clinical trials is hampered by the lack of a technique that i) identifies NF1 patients at risk of tibia bowing and fracture making them eligible for trial enrollment and ii) monitors treatment effects on matrix characteristics related to bone strength. Therefore, we assessed the ability of matrix-sensitive techniques to provide characteristics that differentiate between cortical bone from mice characterized by …

Combined Laryngeal Cleft Injection Laryngoplasty And Salivary Botulinum Toxin For Saliva Aspiration, Elton M Lambert

Faculty, Staff and Students Publications

OBJECTIVES: Children with type I laryngeal clefts and sialorrhea can have posterior drooling, aspiration of oral secretions, and respiratory complications. Laryngeal cleft injection laryngoplasty (LCIL) and salivary botulinum injections (Sal-Bot) have been used separately for short-term treatment of type I laryngeal clefts and sialorrhea. Our goal was to evaluate combined LCIL and Sal-Bot and create recommendations for further treatment based on response to initial treatment.

METHODS: Retrospective chart review of nine patients who underwent direct laryngoscopy and bronchoscopy with combined LCIL and Sal-Bot from 2012 to 2019. Charts were reviewed for patient characteristics, response to treatment, and pre and post-op …

Reconstructive Outcomes Of Multilayered Closure Of Large Skull Base Dural Defects Following Open Anterior Craniofacial Resection, Akash J Patel, Ali Jalali, David J Hernandez, Angela D Haskins, Vlad C Sandulache, Erich M Sturgis, Andrew T Huang

Faculty, Staff and Students Publications

Introduction  Standardized reconstruction protocols for large open anterior skull base defects with dural resection are not well described. Here we report the outcomes and technique of a multilayered reconstructive algorithm utilizing local tissue, dural graft matrix, and microvascular free tissue transfer (MVFTT) for reconstruction of these deformities.

Design  This study is a retrospective review.

Results  Eleven patients (82% males) met inclusion criteria, with five (45%) having concurrent orbital exenteration and eight (73%) requiring maxillectomy. All patients required dural resection with or without intracranial tumor resection, with the average dural defect being 36.0 ± 25.9 cm ² . Dural graft matrices …

Oropharyngeal Cancer Outcomes Correlate With P16 Status, Multinucleation And Immune Infiltration, Syeling Lai, Anant Madabhushi, German Corredor, Can Koyuncu, James S Lewis, Cheng Lu, Mitchell J Frederick, Allan M Frederick, Avery E Haugen, Jose P Zevallos, Erich M Sturgis, Justin Shi, Andrew T Huang, David J Hernandez, Heath D Skinner, Jan O Kemnade, Wendong Yu, Andrew G Sikora, Vlad C Sandulache

Faculty, Staff and Students Publications

Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells …

Performance Evaluation Of The Xt Microslide Assay Pairs On The Vitros Xt 7600 Compared To Vitros Single Microslide Assays On Vitros 5600

Faculty, Staff and Students Publications

OBJECTIVES: Pediatric hospitals are always challenged by specimen volumes and thus any innovation in this realm is very welcome. With the introduction of Microslide assay pairs, we aimed to evaluate the analytical performance of the Vitros XT MicroSlide assay pairs on the Vitros XT 7600 compared to single MicroSlides.

DESIGN: Performance characteristics included within-run precision, analytical measurable range, method comparison, and interference verification. We compared six XT MicroSlide pairs on the Vitros XT 7600 with twelve corresponding single slide assays on the Vitros 5600 system.

RESULTS: The XT MicroSlides on Vitros XT 7600 demonstrated excellent precision, equivalent analytical measurable range, …

Conventional And Advanced Mr Imaging Findings In A Cohort Of Pathology-Proven Dermoid Cysts Of The Pediatric Scalp And Skull, Nilesh Desai, Stephen Kralik, Thierry Agm Huisman

Faculty, Staff and Students Publications

BACKGROUND: In the pediatric population, dermoid cysts are among the most frequent lesions of the scalp and skull. Imaging plays a key role in characterizing scalp and skull lesions in order to narrow the differential diagnoses. In general, dermoids are described as heterogeneous T1-/T2-hypo- to hyperintense lesions on magnetic resonance imaging.

METHODS: The goal of this retrospective study is to evaluate the diffusion weighted imaging findings while reviewing the conventional T1-/T2-/T1+C-weighted MR characteristics in a pathology-proven series of 14 dermoids of the pediatric scalp and skull.

RESULTS: In our pediatric cohort (eight boys, six girls, age range 3-95 months), half …

Aspirin Use Is Associated With Decreased Inpatient Mortality In Patients With Covid-19: A Meta-Analysis, Brendon Cornett, Ramesh Babu Kesavan, Siva T Sarva, Syed Arman Raza, Waleed Tallat Kayani

Faculty, Staff and Students Publications

Thromboembolism is a major cause of death in patients who suffer from COVID-19. Studies examining the effects of aspirin (ASA) on mortality relating to this phenomenon have showed conflicting results with varying degrees and certainties of evidence. We performed an aggregate data meta-analysis of fourteen studies encompassing 164,539 COVID-19 patients, which showed a reduced risk of in-hospital mortality associated with ASA use in eight studies that reported risk ratios (RR 0.90; 95 % CI 0.82–0.98; I2 = 27.33 %, P = 0.01), six studies that reported hazard ratios (HR 0.56; 95 % CI 0.41–0.76, P ≤ 0.01; I2 = 85.92 …

Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 Regulates Hepatic Fuel Metabolism, Pradip Saha, Nagireddy Putluri, Maricarmen D Planas-Silva, Iqbal Mahmud, Kimal Rajapakshe, Cristian Coarfa, Stefan Knapp, Philip L Lorenzi, Bruce E Kemp, Benjamin E Turk, John W Scott, Anthony R Means, Brian York

Faculty, Staff and Students Publications

OBJECTIVE: The liver is the primary internal metabolic organ that coordinates whole body energy homeostasis in response to feeding and fasting. Genetic ablation or pharmacological inhibition of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) has been shown to significantly improve hepatic health and peripheral insulin sensitivity upon overnutrition with high fat diet. However, the precise molecular underpinnings that explain this metabolic protection have remained largely undefined.

METHODS: To characterize the role of CaMKK2 in hepatic metabolism, we developed and challenged liver-specific CaMKK2 knockout (CaMKK2

RESULTS: Consistent with previous findings, we show that hepatic CaMKK2 ablation significantly improves indices of peripheral insulin …

Cross-Ancestry Genome-Wide Meta-Analysis Of 61,047 Cases And 947,237 Controls Identifies New Susceptibility Loci Contributing To Lung Cancer, Jun Xia, Erping Long, Jiyeon Choi, Xiangjun Xiao, Meng Zhu, Wen Zhou, Ryan Sun, Yohan Bossé, Zhuoyi Song, Ann Schwartz, Christine Lusk, Thorunn Rafnar, Kari Stefansson, Tongwu Zhang, Wei Zhao, Rowland W Pettit, Yanhong Liu, Xihao Li, Hufeng Zhou, Kyle M Walsh, Ivan Gorlov, Olga Gorlova, Dakai Zhu, Susan M Rosenberg, Susan Pinney, Joan E Bailey-Wilson, Diptasri Mandal, Mariza De Andrade, Colette Gaba, James C Willey, Ming You, Marshall Anderson, John K Wiencke, Demetrius Albanes, Stephan Lam, Adonina Tardon, Chu Chen, Gary Goodman, Stig Bojeson, Hermann Brenner, Maria Teresa Landi, Stephen J Chanock, Mattias Johansson, Thomas Muley, Angela Risch, H-Erich Wichmann, Heike Bickeböller, David C Christiani, Gad Rennert, Susanne Arnold, John K Field, Sanjay Shete, Loic Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Hongbing Shen, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Alpa Patel, Qing Lan, Nathaniel Rothman, Fiona Taylor, Linda Kachuri, John S Witte, Lori C Sakoda, Margaret Spitz, Paul Brennan, Xihong Lin, James Mckay, Rayjean J Hung, Christopher I Amos

Faculty, Staff and Students Publications

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung …

A Large-Scale Genome-Wide Gene-Gene Interaction Study Of Lung Cancer Susceptibility In Europeans With A Trans-Ethnic Validation In Asians, Ying Zhu, Yi Li, Jiajin Chen, Jinxing Guan, Zoucheng Pan, Yuzhuo Wang, Meng Zhu, Junxing Xie, Xiangjun Xiao, Dakai Zhu, Yafang Li, Demetrios Albanes, Maria Teresa Landi, Neil E Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angela Cox, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Juncheng Dai, Hongxia Ma, Yang Zhao, Zhibin Hu, Rayjean J Hung, Christopher I Amos, Hongbing Shen, Feng Chen, David C Christiani

Faculty, Staff and Students Publications

INTRODUCTION: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).

METHODS: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms …

Use Of Point-Of-Care Ultrasound And Focus-Assessed Transthoracic Echocardiography To Diagnose Acute Right Heart Failure Due To Fat Emboli In A Parturient, Gavin T Best

Faculty, Staff and Students Publications

Fat embolism syndrome (FES), causing right heart dysfunction, is a rare disease that is often difficult to diagnose with imaging modalities such as computed tomography (CT). FES is the clinical presentation that follows the entry of fat globules into the systemic circulation, which typically results in respiratory failure, scattered petechiae, cardiovascular collapse, and neurological sequelae. It is mostly observed in the cases of orthopedic trauma but may occur in any circumstance where fat can enter the circulatory system. In this case report, the authors describe an atypical presentation of FES in a 24-week parturient. The use of bedside point-of-care ultrasonography …

Effect Of The Covid-19 Pandemic Lockdown On The Management Of Diabetic Retinopathy: A Cross-Sectional Study, Mayur B Wanjari, Deepika Singhal

Faculty, Staff and Students Publications

Introduction Worldwide, diabetic retinopathy (DR) is one of the leading causes of vision loss. Early treatment and screening for DR have a major role in reducing the rate of the disease and the coronavirus disease 2019 (COVID-19) pandemic-related restrictions have altered real-world practice patterns in managing DR. Aims and objectives To evaluate the impact of the COVID-19 pandemic on the management of DR amongst patients presenting to a tertiary eye care center in Gujarat, India. Methods This is a cross-sectional study comparison of ophthalmic findings of 72 patients who presented to a tertiary care hospital with the manifestation of DR …

Surgical Extraction Of Traumatic Lodgment Of A Pen Nib Between The Eye And Nasal Bridge Of An Infant: A Case Report, Karishma Dhaval Desai, Mayur B Wanjari, Deepika Singhal

Faculty, Staff and Students Publications

Unintentional eye injuries are common in small children. If left unobserved by parents or caretakers, it is challenging to assess as the kids are in distress and pain. Penetrating trauma in or near the eye requires urgent treatment as it can lead to infection and other complications. Early diagnosis and management help avoid further complications. An 11-month-old female was presented by her parents at a tertiary care clinic with inconsolable crying and swelling over the right eye's upper lid for one day. There was a history of possible trauma with a pen while the child was playing. During the examination, …

Sex-Specific Phenotypes In The Aging Mouse Heart And Consequences For Chronic Fibrosis, Anilkumar K Reddy, Anna Malovannaya, Antrix Jain, Mark L Entman, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional …

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Genome Sequencing In The Parkinson Disease Clinic, Emily J Hill, Laurie A Robak, Rami Al-Ouran, Jennifer Deger, Jamie C Fong, Paul Jerrod Vandeventer, Emily Schulman, Sindhu Rao, Hiba Saade, Joseph M Savitt, Rainer Von Coelln, Neeja Desai, Harshavardhan Doddapaneni, Sejal Salvi, Shannon Dugan-Perez, Donna M Muzny, Amy L Mcguire, Zhandong Liu, Richard A Gibbs, Chad Shaw, Joseph Jankovic, Lisa M Shulman, Joshua M Shulman

Duncan NRI Faculty and Staff Publications

Background and objectives: Genetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics.

Methods: In 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well …

Outcomes Associated With Timing Of Neurologic Dysfunction Onset Relative To Pediatric Sepsis Recognition, Alicia M Alcamo, Scott L Weiss, Julie C Fitzgerald, Matthew P Kirschen, Laura L Loftis, Swee Fong Tang, Neal J Thomas, Vinay M Nadkarni, Sholeen T Nett

Center for Medical Ethics and Health Policy Staff Publications

Objectives: To compare outcomes associated with timing-early versus late-of any neurologic dysfunction during pediatric sepsis.

Design: Secondary analysis of a cross-sectional point prevalence study.

Setting: A total of 128 PICUs in 26 countries.

Patients: Less than 18 years with severe sepsis on 5 separate days (2013-2014).

Interventions: None.

Measurements and main results: Patients were categorized as having either no neurologic dysfunction or neurologic dysfunction (i.e., present at or after sepsis recognition), which was defined as Glasgow Coma Scale score less than 5 and/or fixed dilated pupils. Our primary outcome was death or new moderate disability (i.e., Pediatric Overall [or Cerebral] …

Is Detection Of Relapse By Surveillance Imaging Associated With Longer Survival In Patients With Rhabdomyosarcoma?, Stephanie Fetzko, Adriana Fonseca, Mary Frances Wedekind, Abha A Gupta, Bhuvana A Setty, Jeremy Schraw, Philip J Lupo, Robert P Guillerman, Anish A Butala, Heidi Russell, Lauren Nicholls, David Walterhouse, Douglas S Hawkins, Mehmet F Okcu

Center for Medical Ethics and Health Policy Staff Publications

Background: We investigated whether surveillance imaging had an impact on post-relapse survival in patients with rhabdomyosarcoma (RMS). We hypothesized that relapse detected by imaging (group IM) would be associated with longer survival compared with relapse detected with a clinical sign or symptom (group SS).

Materials and methods: We performed an observational multi-institutional study in 127 patients with relapsed RMS comparing overall survival (OS) after relapse using Kaplan-Meier and Cox proportional hazards analyses.

Results: Relapse was detected in 60 (47%) group IM and 67 (53%) SS patients. Median follow-up in survivors was 4 years (range 1.0 to 16.7 y). Four-year OS …

De Novo Heterozygous Variants In Slc30a7 Are A Candidate Cause For Joubert Syndrome, Monica Penon-Portmann, Mohammad K Eldomery, Lorraine Potocki, Dana Marafi, Jennifer E Posey, Zeynep Coban-Akdemir, Tamar Harel, Christopher M Grochowski, Hailey Loucks, Walter Patrick Devine, Jessica Van Ziffle, Dan Doherty, James R Lupski, Joseph T Shieh

Center for Medical Ethics and Health Policy Staff Publications

Joubert syndrome (JS), a well-established ciliopathy, is characterized by the distinctive molar tooth sign on brain MRI, ataxia, and neurodevelopmental features. Other manifestations can include polydactyly, accessory frenula, renal, or liver disease. Here, we report individuals meeting criteria for JS with de novo heterozygous variants in SLC30A7 (Chr1p21.2). The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. Exome sequencing detected a de novo heterozygous missense variant in SLC30A7: NM_133496.5: c.407 T > C, (p.Val136Ala). The second individual had bilateral postaxial polydactyly, molar …

Addressing Human Trafficking As A Public Health Issue, Frances Recknor, Erica Di Ruggiero, Elsabeth Jensen

Center for Medical Ethics and Health Policy Staff Publications

Human trafficking is increasingly recognized as a significant global public health issue. Human trafficking (HT) exists in all nations, including Canada, and is estimated to impact 25 million people globally. HT is a crime that is not always visible. It is associated with a myriad of deleterious health outcomes arising from adverse living and working conditions, and the physical, sexual, and/or psychological violence often accompanying it. Human trafficking also disproportionately affects people living under vulnerable circumstances, particularly those with intersecting vulnerabilities. Public health can advance health equity for trafficked persons and add value to existing anti-trafficking (AT) efforts. Among its …