Medical Specialties Commons^™

Long-Term Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Children: An Open-Label Active Treatment (Realise Study), Jacqueline A Pongracic, Rémi Gagnon, Gordon Sussman, Dareen Siri, Roxanne C Oriel, Terri F Brown-Whitehorn, Sara Anvari, William E Berger, J Andrew Bird, Edmond S Chan, R Sharon Chinthrajah, Hey J Chong, Stanley M Fineman, David M Fleischer, Erika Gonzalez-Reyes, Edwin H Kim, Bruce J Lanser, Andrew Macginnitie, Hemalini Mehta, Daniel Petroni, Ned Rupp, Lynda C Schneider, Amy M Scurlock, Lawrence D Sher, Wayne G Shreffler, Sayantani B Sindher, Robert Wood, William H Yang, Hugh A Sampson, Timothée Bois, Todd D Green, Dianne E Campbell, Katharine J Bee, Philippe Bégin

Faculty, Staff and Students Publications

Background: Owing to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy.

Objective: This study assessed long-term safety of EPIT with VIASKIN peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial.

Methods: REALISE was a phase 3 trial in peanut-allergic children aged 4 through 11 years that included a 6-month, randomized, double-blind, placebo-controlled treatment phase, followed by an open-label, single-arm, active treatment period for up to 36 months.

Results: …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

The Central Role Of Cytochrome P450 Reductase (Cpr) In Hyperoxic Lung Injury, Deven Narke, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Introduction: Hyperoxic lung injury results from excessive supplemental oxygen therapy in conditions such as bronchopulmonary dysplasia (BPD) in preterm infants and acute respiratory distress syndrome (ARDS) in adults. This review explores the role of cytochrome P450 reductase (CPR) in hyperoxic lung injury.

Areas covered: Hyperoxia induces the production of reactive oxygen species in excessive amounts, overwhelming the body's antioxidant defenses and exacerbating lung injury in ARDS/BPD. This review examines the differential roles of CPR-dependent enzymes in the context of hyperoxic lung injury. Additionally, we highlight the potential of targeting CPR to study mechanisms of lung injury and leverage gene-editing technologies …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

The Influence Of The American Association For Thoracic Surgery On Clinical Trial Development By Cardiothoracic Surgeons, Adishesh K Narahari, Taylor M Horgan, Anirudha S Chandrabhatla, Abhinav Kareddy, Ajami Gikandi, Marco A Zenati, David Harpole, David Jones, Leora T Yarboro, Bryan Burt, A Sasha Krupnick, J Hunter Mehaffey

Faculty, Staff and Students Publications

Objective: Clinical trials play a critical role in the rapidly evolving field of cardiothoracic surgery and the American Association for Thoracic Surgery Clinical Trials Methods Course has provided a biannual symposium led by preeminent surgeons with vast experience in planning, conducting, and analyzing surgical clinical trials. This study hypothesizes that participation in the course is associated with future success in clinical trial leadership.

Methods: A list of course attendees (2014-2022) was queried in ClinicalTrials.gov, a database of clinical trials funded by the US Department of Health and Human Services and the National Institutes of Health. The type of clinical trial …

Treatment Of Rapid Recurrence Of Severe Steatosis With Combined Glucagon-Like Peptide-1 Agonist And Growth Hormone Therapy In A Pediatric Patient Transplanted For Metabolic Dysfunction-Associated Steatohepatitis Cirrhosis In The Setting Of Hypopituitarism, Stephanie R Saaybi, Henry Shiau, Goo Lee, Babak John Orandi, Luz Helena Gutierrez Sanchez

Faculty, Staff and Students Publications

The association between hypopituitarism and metabolic dysfunction-associated steatotic liver disease is increasingly recognized, although data about therapies targeting recurrence posttransplant is limited. An 8-year-old with hypopituitarism-associated metabolic dysfunction-associated steatotic liver disease underwent a liver transplant due to rapid progression of metabolic dysfunction-associated steatohepatitis. Hepatosteatosis recurred within weeks. Her therapeutic plan included a glucagon-like peptide-1 agonist and growth hormone replacement. Her transaminases normalized in 2.5 months, and her macrosteatosis significantly improved on the 1-year surveillance biopsy. This case highlights one of the youngest reported children with hypopituitarism to have undergone transplantation for rapidly progressing metabolic dysfunction-associated steatohepatitis and its recurrence post-operatively. …

Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges …

Digital Interventions For Suicide Prevention, Sean K Burr, Miao Yu, Danny Clark, Dana Alonzo, Robin E Gearing

Faculty, Staff and Students Publications

Background: Digital-based mobile interventions hold significant promise in preventing suicide. Although mixed, some evidence suggests these interventions are effective and capable of overcoming barriers such as cost and stigma. Aim(s): This review aimed to determine the effectiveness of digital interventions designed to address suicidal ideation and behaviors and the impacts of age, gender, and control group type on these outcomes.

Methods: Databases were searched for randomized controlled trials (RCTs) on digital suicide interventions (apps/online programs) published before January 1, 2022. Data were analyzed using a random-effects model in Stata 17.

Results: The search identified 4,317 articles, and 16 were included. …

Feasibility And Acceptability Of The Team Pilot Trial With African American And Latino Families, Ashley M Butler, Marisa E Hilliard, Krystal Christopher, Marissa Baudino, Charles Minard, Lefkothea Karaviti

Faculty, Staff and Students Publications

Objective: We adapted the empirically supported Family Teamwork intervention protocol to support collaborative parent involvement in type 1 diabetes (T1D) management among African American and Latino parents of children with T1D. This randomized pilot study aimed to evaluate feasibility and acceptability of the Type 1 Diabetes Empowerment and Management (TEAM) intervention.

Methods: African American and Latino parents (n = 59; 65% recruitment rate) of youth (ages 5-10 years, M = 8.9 ± 1.6 years; 59% female, M hemoglobin A1c 9.0% ± 1.9%) with diabetes duration of ≥1 year and who were fluent in English and not planning to leave the …

Safety, Efficacy, And Pharmacokinetics Of Oral Testosterone Undecanoate In Males With Hypogonadism, Martin Miner, Christina Wang, Jed Kaminetsky, Mohit Khera, Irwin Goldstein, Culley Carson, Nachiappan Chidambaram, Shelby King, Adrian Dobs

Faculty, Staff and Students Publications

Background: Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations.

Objective: The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie).

Materials and methods: In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted …

Uncovering Shared Genetic Features Between Inflammatory Bowel Disease And Systemic Lupus Erythematosus, Vikram R Shaw, Jinyoung Byun, Catherine Zhu, Rowland W Pettit, Jeffrey M Cohen, Younghun Han, Christopher I Amos

Faculty, Staff and Students Publications

Inflammatory bowel disease (IBD) is an autoimmune disease (AD) characterized by chronic, relapsing intestinal inflammation. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement and overactivation of both innate and adaptive immunity. The extra intestinal manifestations (EIMs) that commonly occur in IBD include many of the organ sites that are affected by SLE. ADs are often comorbid with one another and may have shared underlying genetic features and architectures contributing to their pathogenesis and disease course. We performed both epidemiological and post-genome wide association study (GWAS) analyses to investigate the shared genetic features between IBD and systemic …

Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease, Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

Over the last 20 years, research into the Meibomian glands of the eyelids has increased exponentially and is now widely recognized as a field of research. It is all the more astonishing that knowledge about another type of gland in the eyelids, the Moll glands or ciliary glands, has almost stagnated and there has been little to almost no progress, even though this type of gland as a whole takes up a relatively large volume in the upper and lower eyelids. There is not much information about the namesake Moll or the function of the glands although these are listed …

Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham

Faculty, Staff and Students Publications

Introduction: A growing number of studies implicate functional brain networks in intelligence, but it is unclear if network nodal structure relates to intelligence.

Methods: Using MRI, we studied the relationship of the general intelligence factor (g) with cortical thickness (CT), local gyrification index (LGI), and voxel-based morphometry in the nodes of the default mode network (DMN) and task-positive network (TPN) in a cohort of 44 young, healthy adults. Employing a novel strategy, we performed repeated analyses with multiple sets of g estimates to remove false positives.

Results: CT and LGI in medial and temporal nodes of the DMN were reliably …

Testing For Bleeding Disorders In Child Abuse: Aap Recommendation Adherence And Testing Results, Lyndsey Hultman, Angela Doswell, Henry T Puls, Shannon L Carpenter, Angela Bachim, Caitlin R Mcnamara, Farah W Brink, Lori D Frasier, Nancy S Harper, Natalie Laub, Kristine A Campbell, Daniel M Lindberg, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Objectives: Using a multicenter child abuse pediatrics research network (CAPNET), the study objectives were to characterize the adherence to American Academy of Pediatrics (AAP) recommendations for bleeding disorder testing and the frequency of bleeding disorder identification.

Methods: We performed a descriptive study of bleeding disorder evaluations among children younger than 10 years of age who presented with bruising and/or intracranial hemorrhage (ICH) concerning for abuse from February 2021-May 2022 utilizing CAPNET. Cases were classified as bruising without ICH or ICH with or without bruising. Based on AAP guidance, testing was not recommended in cases with concomitant suspicious injuries, inflicted injury …

Cdc’S Core Elements To Promote Diagnostic Excellence, Daniel J Morgan, Hardeep Singh, Arjun Srinivasan, Andrea Bradford, L Clifford Mcdonald, Preeta K Kutty

Faculty, Staff and Students Publications

Nearly a decade after the National Academy of Medicine released the "Improving Diagnosis in Health Care" report, diagnostic errors remain common, often leading to physical, psychological, emotional, and financial harm. Despite a robust body of research on potential solutions and next steps, the translation of these efforts to patient care has been limited. Improvement initiatives are still narrowly focused on selective themes such as diagnostic stewardship, preventing overdiagnosis, and enhancing clinical reasoning without comprehensively addressing vulnerable systems and processes surrounding diagnosis. To close this implementation gap, the US Centers for Disease Control and Prevention (CDC) released the Core Elements of …

The Contribution Of De Novo Coding Mutations To Meningomyelocele, Yoo-Jin Jiny Ha, Ashna Nisal, Isaac Tang, Chanjae Lee, Ishani Jhamb, Cassidy Wallace, Robyn Howarth, Sarah Schroeder, Keng Ioi Vong, Naomi Meave, Fiza Jiwani, Chelsea Barrows, Sangmoon Lee, Nan Jiang, Arzoo Patel, Krisha Bagga, Niyati Banka, Liana Friedman, Francisco A Blanco, Seyoung Yu, Soeun Rhee, Hui Su Jeong, Isaac Plutzer, Michael B Major, Béatrice Benoit, Christian Poüs, Caleb Heffner, Zoha Kibar, Gyang Markus Bot, Hope Northrup, Kit Sing Au, Madison Strain, Allison E Ashley-Koch, Richard H Finnell, Joan T Le, Hal S Meltzer, Camila Araujo, Helio R Machado, Roger E Stevenson, Anna Yurrita, Sara Mumtaz, Awais Ahmed, Mulazim Hussain Khara, Osvaldo M Mutchinick, José Ramón Medina-Bereciartu, Friedhelm Hildebrandt, Gia Melikishvili, Ahmed I Marwan, Valeria Capra, Mahmoud M Noureldeen, Aida M S Salem, Mahmoud Y Issa, Maha S Zaki, Libin Xu, Ji Eun Lee, Donghyuk Shin, Anna Alkelai, Alan R Shuldiner, Stephen F Kingsmore, Stephen A Murray, Heon Yung Gee, W Todd Miller, Kimberley F Tolias, John B Wallingford, Spina Bifida Sequencing Consortium, Sangwoo Kim, Joseph G Gleeson

Faculty, Staff and Students Publications

Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting. A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained1. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele2. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or …

Psychiatric Genetics In The Diverse Landscape Of Latin American Populations, Estela M Bruxel, Diego L Rovaris, Sintia I Belangero, Gabriela Chavarría-Soley, Alfredo B Cuellar-Barboza, José J Martínez-Magaña, Sheila T Nagamatsu, Caroline M Nievergelt, Diana L Núñez-Ríos, Vanessa K Ota, Roseann E Peterson, Laura G Sloofman, Amy M Adams, Elinette Albino, Angel T Alvarado, Diego Andrade-Brito, Paola Y Arguello-Pascualli, Cibele E Bandeira, Claiton H D Bau, Cynthia M Bulik, Joseph D Buxbaum, Carolina Cappi, Nadia S Corral-Frias, Alejo Corrales, Fabiana Corsi-Zuelli, James J Crowley, Renata B Cupertino, Bruna S Da Silva, Suzannah S De Almeida, Juan F De La Hoz, Diego A Forero, Gabriel R Fries, Joel Gelernter, Yeimy González-Giraldo, Eugenio H Grevet, Dorothy E Grice, Adriana Hernández-Garayua, John M Hettema, Agustín Ibáñez, Iuliana Ionita-Laza, Maria Claudia Lattig, Yago C Lima, Yi-Sian Lin, Sandra López-León, Camila M Loureiro, Verónica Martínez-Cerdeño, Gabriela A Martínez-Levy, Kyle Melin, Daniel Moreno-De-Luca, Carolina Muniz Carvalho, Ana Maria Olivares, Victor F Oliveira, Rafaella Ormond, Abraham A Palmer, Alana C Panzenhagen, Maria Rita Passos-Bueno, Qian Peng, Eduardo Pérez-Palma, Miguel L Prieto, Panos Roussos, Sandra Sanchez-Roige, Hernando Santamaría-García, Flávio M Shansis, Rachel R Sharp, Eric A Storch, Maria Eduarda A Tavares, Grace E Tietz, Bianca A Torres-Hernández, Luciana Tovo-Rodrigues, Pilar Trelles, Eva M Trujillo-Chivacuan, Maria M Velásquez, Fernando Vera-Urbina, Georgios Voloudakis, Talia Wegman-Ostrosky, Jenny Zhen-Duan, Hang Zhou, Latin American Genomics Consortium, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Paola Giusti-Rodríguez, Janitza L Montalvo-Ortiz

Faculty, Staff and Students Publications

Psychiatric disorders are highly heritable and polygenic, influenced by environmental factors and often comorbid. Large-scale genome-wide association studies (GWASs) through consortium efforts have identified genetic risk loci and revealed the underlying biology of psychiatric disorders and traits. However, over 85% of psychiatric GWAS participants are of European ancestry, limiting the applicability of these findings to non-European populations. Latin America and the Caribbean, regions marked by diverse genetic admixture, distinct environments and healthcare disparities, remain critically understudied in psychiatric genomics. This threatens access to precision psychiatry, where diversity is crucial for innovation and equity. This Review evaluates the current state and …

Computational And Functional Prioritization Identifies Genes That Rescue Behavior And Reduce Tau Protein In Fly And Human Cell Models Of Alzheimer Disease, Morgan C Stephens, Jiayang Li, Megan Mair, Justin Moore, Katy Zhu, Akash Tarkunde, Bismark Amoh, Alma M Perez, Arya Bhakare, Fangfei Guo, Joshua M Shulman, Ismael Al-Ramahi, Juan Botas

Faculty, Staff and Students Publications

Genome-wide association studies (GWASs) in Alzheimer disease (AD) have uncovered over 70 loci significantly associated with AD risk, but identifying the true causal gene(s) at these loci requires systematic functional validation that is rarely performed due to limitations of time and cost. Here, we integrate transcriptome-wide association study (TWAS) with colocalization analysis, fine-mapping, and additional annotation of AD GWAS variants to identify 123 genes at known and suggestive AD risk loci. A comparison with human AD brain transcriptome data confirmed that many of these candidate genes are dysregulated in human AD and correlate with neuropathology. We then tested all available …

Bi-Allelic Uggt1 Variants Cause A Congenital Disorder Of Glycosylation, Zain Dardas, Laura Harrold, Daniel G Calame, Claire G Salter, Takashi Kikuma, Kevin P Guay, Bobby G Ng, Kanae Sano, Ahmad K Saad, Haowei Du, Riccardo Sangermano, Sohil G Patankar, Shalini N Jhangiani, Semra Gürsoy, Mohamed S Abdel-Hamid, Mahmoud K H Ahmed, Reza Maroofian, Rauan Kaiyrzhanov, Kamran Salayev, Wendy D Jones, Ana Pérez Caballero, Lucy Mcgavin, Michael Spiller, Miranda Durkie, Nick Wood, Lauren O'Grady, Paula Goldenberg, Ann M Neumeyer, Amber Begtrup, Sherif F Abdel-Ghafar, Maha S Zaki, Hilde Van Esch, Jennifer E Posey, Olivia K Wenger, Ethan M Scott, Kinga M Bujakowska, Richard A Gibbs, Davut Pehlivan, Dana Marafi, Joseph S Leslie, Nishanka Ubeyratna, Jacob Day, Martina Owens, Jessica Settle, Soher Balkhy, Abdullah Tamim, Lama Alabdi, Fowzan S Alkuraya, Yoichi Takeda, Hudson H Freeze, Daniel N Hebert, James R Lupski, Andrew H Crosby, Emma L Baple

Faculty, Staff and Students Publications

Congenital disorders of glycosylation (CDGs) comprise a large heterogeneous group of metabolic conditions caused by defects in glycoprotein and glycolipid glycan assembly and remodeling, a fundamental molecular process with wide-ranging biological roles. Herein, we describe bi-allelic UGGT1 variants in fifteen individuals from ten unrelated families of various ethnic backgrounds as a cause of a distinctive CDG of variable severity. The cardinal clinical features of UGGT1-CDG involve developmental delay, intellectual disability, seizures, characteristic facial features, and microcephaly in the majority (9/11 affected individuals for whom measurements were available). The more severely affected individuals display congenital heart malformations, variable skeletal abnormalities including …

Interventions To Improve Timely Cancer Diagnosis: An Integrative Review, Mark L Graber, Bradford D Winters, Roni Matin, Rosann T Cholankeril, Daniel R Murphy, Hardeep Singh, Andrea Bradford

Faculty, Staff and Students Publications

Cancer will affect more than one in three U.S. residents in their lifetime, and although the diagnosis will be made efficiently in most of these cases, roughly one in five patients will experience a delayed or missed diagnosis. In this integrative review, we focus on missed opportunities in the diagnosis of breast, lung, and colorectal cancer in the ambulatory care environment. From a review of 493 publications, we summarize the current evidence regarding the contributing factors to missed or delayed cancer diagnosis in ambulatory care, as well as evidence to support possible strategies for intervention. Cancer diagnoses are made after …

Clerkship Students' Use Of Clinical Reasoning Concepts After A Pre-Clinical Reasoning Course, Shradha A Kulkarni, Gurpreet Dhaliwal, Arianne Teherani, Denise M Connor

Faculty, Staff and Students Publications

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Design: We used structured interviews to gain insight into medical students' experiences with CR concepts in clerkships.

Participants: We interviewed 16 students who had completed a pre-clinical CR course and subsequently completed …

Repeat Ascaris Challenge Reduces Worm Intensity Through Gastric Cellular Reprograming, Yifan Wu, Charlie Suarez-Reyes, Nina L Tang, Alexander R Kneubehl, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most prevalent parasitic nematode infection worldwide, impacting approximately 500 million people predominantly in low- and middle-income countries (LMICs). While people of all ages are infected with Ascaris, infection intensity (defined by worm burden) paradoxically peaks in pre-school and school-aged children but then declines with age. The cause of age-dependent Ascaris worm intensity is not well understood but may be dependent on cellular changes in mucosal barrier sites. We have previously found that the gastric mucosa is a critical barrier site for Ascaris infection as ingested Ascaris larvae use acidic mammalian chitinase (AMCase) secreted by gastric chief …

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …

Prevalence And Patterns Of Opioid Use In Chronic Pancreatitis, Anna Evans Phillips, Darwin L Conwell, Shuang Li, Jami L Saloman, Phil A Hart, Evan L Fogel, Santhi Swaroop Vege, Dana K Andersen, William E Fisher, Christopher E Forsmark, Stephen Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Liang Li, Dhiraj Yadav

Faculty, Staff and Student Publications

Introduction: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. …

Development Of A Reference Standard To Assign Bacterial Versus Viral Infection Etiology Using An All-Inclusive Methodology For Comparison Of Novel Diagnostic Tool Performance, Coburn Allen, J Kate Deanehan, Yaniv Dotan, Matthew A Eisenberg, Andrew M Fine, Jonathan Isenberg, Ann Kane, Dani Kirshner, Todd W Lyons, Yasmin Maor, Ami Neuberger, Daniel G Ostermayer, Sharona Paz, Oded Scheuerman, Shachaf Shiber, Victoria A Statler, Michal Stein, Renata Yakubov, Shirly Yanai, Roy Navon, Lior Kellerman, Tanya M Gottlieb, Eran Eden

Faculty, Staff and Student Publications

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with …

Neurotransmitter Power Plays: The Synaptic Communication Nexus Shaping Brain Cancer, Jayanta Mondal, Jason T Huse

Faculty, Staff and Student Publications

Gliomas and brain metastases are notorious for their dismal prognosis and low survival rates, a challenge exacerbated by our incomplete grasp of the complex dynamics that govern brain cancers. Recently, a groundbreaking paradigm shift has emerged, highlighting the crucial role of synaptic communication between neurons and brain tumor cells in reshaping neuronal signaling to favor tumor growth. This review delves into the pivotal interplay of synaptic mechanisms, focusing on excitatory glutamatergic and inhibitory GABAergic pathways. Glutamatergic synapses utilize glutamate to propagate excitatory signals, while GABAergic synapses employ gamma-aminobutyric acid (GABA) to inhibit neuronal firing. Glutamatergic signaling can be broadly classified …

Use Of Natural Language Processing To Identify Patients With Inflammatory Breast Cancer Across A Health-Care System, Ramez Kouzy, Megumi Kai, Huong T Le-Petross, Sadia Saleem, Wendy A Woodward

Faculty, Staff and Student Publications

Early identification and referral of inflammatory breast cancer remains challenging within large health-care systems, limiting access to specialized care. We developed and evaluated an artificial intelligence-driven platform integrating natural language processing (NLP) with electronic health records to systematically identify potential inflammatory breast cancer patients across 5 campuses. Our platform analyzed 8 623 494 clinical notes, implementing a sequential review process: NLP screening followed by human validation and multidisciplinary confirmation. Initial NLP screening achieved 55.4% positive predictive value, improving to 78.4% with human-in-the-loop review. Notably, among 255 confirmed patients with inflammatory breast cancer, our system demonstrated 92.2% sensitivity, identifying 57 patients …

Bilateral Germ Cell Tumor Of The Testis: Biological And Clinical Implications For A Stem Versus Genetic Origin Of Cancers, Jamaal C Jackson, Darren Sanchez, Aron Y Joon, Marcos R Estecio, Andrew C Johns, Amishi Y Shah, Matthew Campbell, John F Ward, Louis L Pisters, Charles C Guo, Miao Zhang, Niki M Zacharias, Shi-Ming Tu

Faculty, Staff and Student Publications

Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. …

Trends In Medicare Payments Within The First Year Of Cervical Cancer Diagnosis, 2010–2019, Mohammad A Karim, Ning Zhang, Hui Zhao, Ya-Chen Tina Shih, Lakshmi S M Kodali, Sharon H Giordano, Sanjay Shete

Faculty, Staff and Student Publications

Assessing Medicare payment trends for cervical cancer care is important to mitigate the financial impact on Medicare. This multiyear cross-sectional study included 65 years and older cervical cancer patients in SEER registries diagnosed between 2010 and 2019 who had continuous Part A and B Medicare coverage at least 6 months before diagnosis and at least within the first year of diagnosis and were not enrolled in any Health Maintenance Organization (HMO) in this duration. The main outcomes were trends in total and service-specific mean monthly Medicare payments within the first year of a cervical cancer diagnosis. This study included 2147 …