Digital Commons Network^™

Quality Of Life In Young Adults With Type 1 Diabetes, Marissa N Baudino, Samantha A Carreon, Randi Streisand, Tricia Tang, Sarah Lyons, Siripoom Mckay, Barbara J Anderson, Charles G Minard, Sridevi Devaraj, Ashley M Butler, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Challenges of young adulthood with type 1 diabetes (T1D) include transitioning to adult care, increased T1D self-management responsibilities, and normal developmental transitions. Recognizing patterns of health-related quality of life (HRQOL) across a demographically and clinically broad range of young adults with T1D may help identify who needs additional support as they transfer to adult healthcare. We hypothesized that young adults from specific demographic and clinical groups would report lower HRQOL.

Methods: At baseline of a behavioral RCT (≤2 months after last pediatric T1D clinic visit), 100 young adults (Mage=19.9 ± 1.3, MA1c=8.8 ± 2.0 %) self-reported demographics and HRQOL; …

Open Repair Of Isolated Internal Iliac Artery Aneurysm In A Young Patient With Loeys-Dietz Syndrome, Ezra Y Koh, Dianna M Milewicz, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Students Publications

Introduction: Isolated internal iliac artery aneurysms in the absence of aorto-iliac disease are exceedingly rare. The case of a 41 year old woman who presented after experiencing several weeks of lower abdominal pain is reported. She was diagnosed with a large, isolated right internal iliac artery aneurysm.

Report: Patient medical records were reviewed retrospectively. The patient underwent genetic evaluation, after which she was diagnosed with Loeys-Dietz syndrome type I. Given her age and heritable aortic disease, her aneurysm was treated by open surgical repair via a right retroperitoneal approach with an interposition bypass graft. The patient's hospital course was uneventful, …

Targeted Analysis Of Dyslexia-Associated Regions On Chromosomes 6, 12 And 15 In Large Multigenerational Cohorts, Nicola H Chapman, Patrick A Navas, Michael O Dorschner, Michele Mehaffey, Karen G Wigg, Kaitlyn M Price, Oxana Y Naumova, Elizabeth N Kerr, Sharon L Guger, Maureen W Lovett, Elena L Grigorenko, Virginia Berninger, Cathy L Barr, Ellen M Wijsman, Wendy H Raskind

Faculty, Staff and Students Publications

Dyslexia is a common learning impairment with a genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date have investigated only limited genomic variation within each locus with no confirmed pathogenic variants identified. Our study is the first to comprehensively sequence both coding and cis-acting regulatory regions of such genes in a large study sample. In a collection of >2000 participants in families from three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate risk genes (DNAAF4, CYP19A1, DCDC2, …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

Efficacy Of Nampt Inhibition In T-Cell Acute Lymphoblastic Leukemia, Chelsea Vrana, Matthew Zhang, Max Rochette, Michelle Alozie, Hailey Oviedo, Alan Gonzalez, Jaden Sherman, Barry Zorman, Pavel Sumazin, Karen R Rabin, Jacob J Junco

Faculty, Staff and Students Publications

Novel agents targeting upregulated signaling pathways are needed to improve outcomes in T-cell acute lymphoblastic leukemia (T-ALL), since conventional cytotoxic chemotherapy regimens have reached the limits of tolerability. We identified upregulated, targetable signaling pathways common to both human T-ALL samples and a KrasLSL-G12D/+.Mb1Cre/+ murine model of T-ALL. We found the NAMPT inhibitor FK866 had the greatest cytotoxicity of a panel of small molecule inhibitors tested in human and mouse T-ALL cell lines, and in patient derived xenograft (PDX)-expanded T-ALL patient samples. We subsequently tested FK866 in vivo in PDX mouse models of T-ALL, and found that it significantly reduced the …

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …

Averting Collapse: Reimagining The Ntds Ecosystem Through G20 Health Diplomacy And Science Innovation, Maple Goh, Peter J Hotez

Faculty, Staff and Students Publications

The recent termination of the U.S. Government's neglected topical diseases (NTD) mass treatment program, following similar cuts by the UK, threatens decades of progress. Without a strategic reset, NTDs may re-emerge, exacerbating poverty across Africa and beyond. We call for a broadened donor base and reframing NTD control as a shared global interest, especially as NTDs rise in G20 nations due to climate change and urbanization. This moment demands investment in sustainable tools, like NextGen vaccines and biologics, and greater leadership from G20 countries. While USAID's exit is a setback, opportunities arise for decolonizing global health and fostering new partnerships.

Microbiota Dynamics During Ascaris Suum Larval Migration: Implications For Host Microbial Communities In A Murine Model, Sergio Castañeda, Cristina Poveda, Charlie Suarez-Reyes, Yifan Wu, Noah Haugen, Luz H Patiño, Jill E Weatherhead, Juan David Ramírez

Faculty, Staff and Students Publications

The complex interactions between parasites, their hosts, and associated microbiota hold significant implications for host health and disease outcomes. Helminths like Ascaris lumbricoides and Ascaris suum can significantly alter the host's intestinal microbiota, affecting both parasite biology and host pathology. Despite extensive research on host-microbiota changes due to helminth infections, the study of helminth-associated microbiota remains limited. This study aims to characterize the microbiota associated with Ascaris larvae and surrounding host tissues at distinct developmental stages (day 4, day 8, day 14), during larval migration through the liver, lungs, and intestine, and its impact on the host's microbiota in a …

The Association Of Human Milk Intake And Outcomes In Biliary Atresia, Mary Elizabeth M Tessier, Jeremy M Schraw, Stacey Beer, Sanjiv Harpavat, M Kyle Jensen, John C Magee, Vicky Ng, Michael E Scheurer, Sarah A Taylor, Benjamin L Shneider

Faculty, Staff and Students Publications

Objectives: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

Methods: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

Results: At baseline, 211 infants received AHM and 215 received …

An Evaluation Of Genetic Predisposition To Congenital Anomalies And Pediatric Cancer Supports, Hyunjung Gu, Yao Yu, Saumya Dushyant Sisoudiya, Pamela Mishra, He Li, Jeremy M Schraw, Michael E Scheurer, Donna M Muzny, Danielle Mitchell, Olga Taylor, Shalini N Jhangiani, Shannon Dugan-Perez, Yifan Wu, Harsha Doddapaneni, Sravya Venkata Bhamidipati, Marie-Claude Gingras, Jennifer E Posey, Richard A Gibbs, Chad D Huff, Sharon E Plon, Philip J Lupo, Aniko Sabo

Faculty, Staff and Students Publications

Purpose: Although congenital anomalies are among the strongest risk factors for developing pediatric cancer, the genetic underpinnings remain unclear. Therefore, we evaluated germline susceptibility in children with congenital anomalies and cancer.

Methods: Through the Genetic Overlap Between Anomalies and Cancer in Kids Study, we recruited 47 participants with anomalies and cancer, along with their biological families. Genome sequencing was performed, focusing on single-nucleotide variants, indels, and structural variants. Pathogenic or likely pathogenic variants were identified by the American College of Medical Genetics and Genomics classification.

Results: We identified pathogenic or likely pathogenic variants in 23.4% (11 of 47) of participants. …

Designing And Implementing Solution-Oriented Team Science Initiatives-A Chronic Pain Example, Nele A Haelterman, Armen N Akopian, Kyle D Allen, Yenisel Cruz-Almeida, Christopher R Donnelly, Brendan Lee, Rebecca Lenzi, Anne-Marie Malfait, Marie Mancini, Maryann E Martone, Joost B Wagenaar, Kim C Worley

Faculty, Staff and Students Publications

Large, collaborative projects that combine researchers from multiple scientific disciplines have become an integral part of the scientific endeavor. While transdisciplinary team science projects hold great potential, they also come with a unique set of challenges compared to monodisciplinary projects. The Science of Team Science (SciTS) field has developed multiple conceptual models and frameworks that guide the design, implementation, and evaluation of team science initiatives to maximize their potential for making breakthrough discoveries and creating solutions for complex problems. While these conceptual models contain a trove of valuable information for successful team science, guidance on how to effectively implement them …

"How Can I Get Out Of This?": A Qualitative Study Of The Phenomenology And Functional Impact Of Misophonia In Youth And Families, Andrew Giles Guzick, Catherine Elizabeth Rast, Brenna Burns Maddox, Servando Rodriguez Barajas, Jane Clinger, Joseph Mcguire, Eric A Storch

Faculty, Staff and Students Publications

Introduction: Misophonia is an increasingly recognized disorder characterized by negative emotional and sensory reactions to specific noises. Although misophonia most often begins in childhood, there has been minimal research on its clinical presentation in youth. This qualitative study explored cognitive behavioral processes that are involved in misophonia and its associated functional impairment in young people and their families.

Methods: Focused interviews were conducted with 20 youth with misophonia (ages 10-17) and their parents. Thematic analyses of these interviews using a cognitive behavioral theoretical framework were conducted.

Results: A number of themes were identified, which included internalizing and externalizing cognitive behavioral …

Prevalence Of Abuse-Specific Injuries In Infants With Prior Injury Evaluated For Abuse, Nara Cho, Kristin G Crichton, Sara Helwig, Krista K Wheeler, Rachel M Stanley, Megan M Letson, Kristine A Campbell, Angela N Bachim, Colleen J Bressler, Carmen M Coombs, Lori Frasier, Nicole Johnson, Sara Kilbride, Jan Leonard, Daniel M Lindberg, Noelle T Tran, Joanne N Wood, Farah W Brink

Faculty, Staff and Students Publications

Background and objectives: Physical abuse is a common cause of morbidity in infants but is often missed in those with medically minor injuries, increasing the risk for escalating violence. Our objective was to compare the prevalence of abuse-specific injuries among infants with and without prior injuries.

Methods: This is a retrospective, multicenter study of infants (aged < 12 months) undergoing child abuse pediatrics provider (CAP) consultation for suspected physical abuse between 2/2021 and 12/2022 at 10 participating US centers. Encounters were dichotomized into those with and without history of prior injury. The groups were compared for rates of diagnostic screening and prevalence of abuse-specific injuries. The association of prior injuries with identification of abuse-specific injury was assessed using logistic regression controlling for demographics and presence of prior injury.

Results: We identified 2352 eligible encounters (median age: 4.2 months), of which 13% had a history of prior injury. In infants who underwent diagnostic testing, injury identification was significantly higher in those with prior injury (45% vs 22%, P < .05). Adjusting for patient characteristics, the presence of prior injury in infants was associated with higher odds of at least 1 type of abuse-specific injury being identified, compared with those without prior injury (adjusted odds ratio = 2.81, 95% CI = 2.10-3.76).

Conclusion: Infants with prior injury …

Gout Flare Burden In The United States: A Multiyear Cross-Sectional Survey Study, Jasvinder A Singh, Amy Morlock, Robert Morlock

Faculty, Staff and Students Publications

OBJECTIVE: The objective of this study was to assess the burden of gout flares and examine associated patient characteristics and outcomes in a sample of US adults.

METHODS: Data were collected via an online survey of US adults ≥18 years using a random stratified sampling framework. Participants with gout completed questions about treatments, serum urate (SU) levels, severity, satisfaction with control, and gout flares. All participants completed the Veterans RAND 12-Item Health Survey, the Generalized Anxiety Disorder 7-Item Scale, and the Patient Health Questionnaire 9-Item Scale. Data were summarized using descriptive statistics. Multivariable-adjusted logistic regression analyses examined factors predictive of …

Modeling Functional Connectivity With Learning And Memory In A Mouse Model Of Alzheimer’S Disease, Lindsay Fadel, Elizabeth Hipskind, Steen E Pedersen, Jonathan Romero, Caitlyn Ortiz, Eric Shin, Md Abul Hassan Samee, Robia G Pautler

Faculty, Staff and Students Publications

Introduction: Functional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used to explain behavior not only in healthy mice, but also in mouse models of Alzheimer's Disease (AD). Here, we investigated changes in FC and their relationship to learning and memory in a mouse model of AD across disease progression.

Methods: We assessed the APP/PS1 mouse model of AD and wild-type controls …

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: Jacc: Cardiovascular Imaging Position Statement, Gilbert H L Tang, Syed Zaid, Rebecca T Hahn, Vratika Aggarwal, Mohamad Alkhouli, Edris Aman, Sergio Berti, Y S Chandrashekhar, Scott M Chadderdon, Andreina D'Agostino, Neil P Fam, Edwin C Ho, Chad Kliger, Susheel K Kodali, Parasuram Krishnamoorthy, Azeem Latib, Stamatios Lerakis, D Scott Lim, Vaikom S Mahadevan, Devi G Nair, Jagat Narula, Patrick T O'Gara, Douglas L Packer, Fabien Praz, Jason H Rogers, Tobias F Ruf, Carlos E Sanchez, Alok Sharma, Gagan D Singh, Nicolas M Van Mieghem, Mani A Vannan, Pradeep K Yadav, Lina Ya'qoub, Firas E Zahr, Ralph Stephan Von Bardeleben

Faculty, Staff and Students Publications

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure …

Vascularized Iliac Crest Bone Graft For The Reconstruction Of Anterior Vertebral Corpus Defects: A Literature Review And Cadaveric Feasibility Study, Jonathan L Jeger, Casey J Martinez, Maria Shvedova, Alec Simoni, Alanna Rebecca, Sebastian Winocour, Alexander E Ropper, Michael Bohl, William J Casey, Maziyar Kalani, Edward M Reece

Faculty, Staff and Students Publications

BACKGROUND: Vertebral body defects pose a significant challenge in spinal reconstructive surgery. Compression fractures of the vertebral corpus are typically treated with vertebral augmentation procedures. There are significant risks associated with the introduction of foreign material in the spine, including infection and pseudarthrosis. Vascularized bone grafts (VBGs) have become a popular alternative for spinal reconstruction in the last decade thanks to their robust blood supply and autologous nature. VBGs have been described predominantly for the reconstruction of posterior vertebral defects. The objective of this study is to describe a novel procedure for the reconstruction of vertebral corpus defects in the …

Maintenance Therapy With A P2y12 Receptor Inhibitor After Cangrelor In Patients With Acute Coronary Syndrome The Electra-Sirio 2 Investigators’ Viewpoint, Jacek Kubica, Piotr Adamski, Robert Gajda, Aldona Kubica, Małgorzata Ostrowska, Gavino Casu, Diana A Gorog, Paul A Gurbel, Tomasz Hajdukiewicz, Miłosz Jaguszewski, Young-Hoon Jeong, Agata Kosobucka-Ozdoba, Zuzana Motovska, Piotr Niezgoda, Maciej Piasecki, Przemysław Podhajski, Paolo Raggi, Uzeyir Rahimov, Jolanta M Siller-Matula, Grzegorz Skonieczny, Łukasz Szarpak, Paweł Szymański, Udaya Tantry, Eliano P Navarese

Faculty, Staff and Students Publications

According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within …

Research For All: Building A Diverse Researcher Community For The All Of Us Research Program, Rubin Baskir, Minnkyong Lee, Sydney J Mcmaster, Jessica Lee, Faith Blackburne-Proctor, Romuladus Azuine, Nakia Mack, Sheri D Schully, Martin Mendoza, Janeth Sanchez, Yong Crosby, Erica Zumba, Michael Hahn, Naomi Aspaas, Ahmed Elmi, Shanté Alerté, Elizabeth Stewart, Danielle Wilfong, Meag Doherty, Margaret M Farrell, Grace B Hébert, Sula Hood, Cheryl M Thomas, Debra D Murray, Brendan Lee, Louisa A Stark, Megan A Lewis, Jen D Uhrig, Laura R Bartlett, Edgar Gil Rico, Adolph Falcón, Elizabeth Cohn, Mitchell R Lunn, Juno Obedin-Maliver, Linda Cottler, Milton Eder, Fornessa T Randal, Jason Karnes, Kitani Lemieux, Nelson Lemieux, Nelson Lemieux, Lilanta Bradley, Ronnie Tepp, Meredith Wilson, Monica Rodriguez, Chris Lunt, Karriem Watson

Faculty, Staff and Students Publications

OBJECTIVES: The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth.

MATERIALS AND METHODS: Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem …

Refinement Of A Published Gene-Physical Activity Interaction Impacting Hdl-Cholesterol: Role Of Sex And Lipoprotein Subfractions, Kenneth E Westerman, Tuomas O Kilpeläinen, Magdalena Sevilla-Gonzalez, Margery A Connelly, Alexis C Wood, Michael Y Tsai, Kent D Taylor, Stephen S Rich, Jerome I Rotter, James D Otvos, Amy R Bentley, Samia Mora, Hugues Aschard, D C Rao, Charles Gu, Daniel I Chasman, Alisa K Manning

Faculty, Staff and Students Publications

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). We explored this GxE in the Women’s Genome Health Study (WGHS; N=23,294; the strongest cohort-specific signal in the original meta-analysis), the UK …

The Influence Of Ultra-Widefield Fluorescein Angiography On The Diagnosis And Management Of Diabetic Retinopathy, Nicole K Scripsema, Tala Al-Khaled, Amy Song, Joelle A Hallak, Rawan Allozi, Aziz A Khanifar, Thanos D Papakostas, Christina Y Weng, Ronald C Gentile, J Peter Campbell, Jessica G Lee, Gennady Landa, Felix Y Chau, William F Mieler, Meenakashi Gupta, Amani A Fawzi, Judy E Kim, Jennifer I Lim, Robison Vernon Paul Chan

Faculty, Staff and Students Publications

Purpose: To study the influence of ultra-widefield fluorescein angiography (FA) on the diagnosis and management of diabetic retinopathy (DR).

Methods: Ten experts in DR completed an online survey in which they were asked to diagnose and manage DR cases using different imaging modalities. Experts independently reviewed 20 cases of DR and provided a diagnosis and management plan for each case, first based on ultra-widefield color-free and red-free images alone and again with the corresponding ultra-widefield FA images. Experts were polled on their diagnostic confidence, use of FA in clinical practice, and opinions on the value of ultra-widefield FA. Based on …

In Response To Comment On "Older And Better: A Narrative Review Of Successful Aging And Adaptation To Pain In Late Life", Emanuel Narcis Husu

Faculty, Staff and Students Publications

No abstract provided.

Cognitive Predictors Of Internalizing Symptoms In Clinically Anxious Youth, Dania Y Amarneh, Michael J Zvolensky, Eric A Storch, Andres G Viana

Faculty, Staff and Students Publications

Background: Internalizing disorders are the most common psychiatric disorders in youth and are associated with a host of deleterious outcomes (e.g., self-harm, substance use, interpersonal difficulties), highlighting the critical need for identifying risk factors that confer risk for these disorders. The present study investigated the unique and shared roles of two prominent cognitive biases-anxiety sensitivity and interpretation biases-as predictors of internalizing symptom severity in clinically anxious youth, above and beyond the effects of negative emotionality and after accounting for sociodemographic covariates.

Method: A diverse sample of clinically anxious youth (N = 105; Mage = 10.09 years, SD = 1.22; …

Genetic Newborn Screening For Retinoblastoma: A Belgian Initiative Baby Detect, Daniel A Rodriguez, Alex Song, Anshul Bhatnagar, Christina Y Weng

Faculty, Staff and Students Publications

Baby Detect Project, started in September 2022, aimed to create a newborn screening test using targeted next-generation sequencing for all early-onset, treatable, and serious conditions. The elaborated gene panel covers 405 genes, associated with 165 genetic conditions, and includes RB1, linked to retinoblastoma, the only oncological disease tested for. Germline RB1 mutations concern around 50% of all retinoblastoma cases and 100% of the most severe, bilateral cases. Ninety percent of them occur de novo, which delays the diagnosis by about a year with subsequent loss of vision and sometimes the eye itself. Detecting children with germline RB1 mutation at …

Diagnostic Delay In Type I Autoimmune Pancreatitis: Clinical, Imaging, Endoscopic And Histologic Predictors Of Timely Diagnosis, Andres Urias Rivera, Travis Josephs, Shilpa Jain, Wasseem Skef, Tara Keihanian, Salmaan Jawaid, Wasif Abidi, Kalpesh Patel, Mohamed O Othman, Fares Ayoub

Faculty, Staff and Students Publications

Background: The diagnosis of autoimmune pancreatitis (AIP) can be challenging due to nonspecific symptoms, low sensitivity of serologic markers, and some overlap in presentation with pancreatic ductal adenocarcinoma (PDAC). We aimed to quantify delays in the diagnosis of AIP and identify factors associated with diagnostic delay.

Methods: This was a single-center retrospective study between 2013 and 2023 of adult patients diagnosed with type 1 AIP based on HISORt criteria. Patients were compared to a randomly selected group of controls with PDAC. Data on clinical presentation, lab results, imaging, procedures, and initial treatment regimen were collected. Timing to diagnosis and predictive …

High Tumor Cd161 Expression Predicts A Survival Advantage And Marks A Th1-Skewed Microenvironment, Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

CD8+CD161+ T-cells exhibit augmented memory and cytolytic properties, mediating enhanced immunity in murine tumor models and improved survival in human non-small cell lung cancer. This T-cell subset might serve as a biomarker of positive response to therapy or even be isolated to augment current immunotherapeutic approaches yet limited knowledge of CD161 expression in human cancers restricts practical application. Here we bioinformatically tested the hypothesis that CD161 expression may be associated with positive outcomes in human cancers and investigated mechanisms underlying any observed advantages. Using TCGA-PANCAN dataset, we analyzed expression of CD161 in over 10,000 human tumors, correlating expression levels with …

Two-Dimensional Speckle Tracking Of The Ascending Aorta: A Novel Approach To Evaluate Arterial Stiffness In Pediatric Patients With Repaired Conotruncal Anomalies Using Echocardiography, Anmol Goyal, Anitha Parthiban, David A White, Daniel Forsha, Doaa Aly

Faculty, Staff and Students Publications

Background: Children with repaired conotruncal abnormalities (CTA) are at risk of progressive aortic dilation and deteriorating aortic elasticity even after surgical correction. Strain imaging, using a 2-dimensional speckle tracking echocardiography (2D-STE), has been used for arterial stiffness assessment, but pediatric data are still lacking. We investigated the feasibility, reproducibility, and clinical value of 2D-STE derived ascending aorta (AAo) stiffness in children with repaired CTA.

Methods: 22 pediatric patients with repaired CTA were included along with 25 age- and sex- matched healthy controls (mean age 10.2 ± 4.5 years). Conventional 2D echocardiographic and 2D-STE assessment of AAo mechanics was performed. M-mode …

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …

Risk Scores For Choledocholithiasis Perform Poorly In Patients With Hemolytic Diseases: A Pedi Database Report, Jennifer Thompson, Wenly Ruan, Douglas S Fishman, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Valerio Balassone, Filippo Torroni, Paola De Angelis, Simona Faraci, Cynthia Tsai, Michael Wilsey, Racha Khalaf, Petar Mamula, Quin Liu, Yuhua Zheng, Bradley A Barth, David Michael Troendle

Faculty, Staff and Students Publications

Patients with hemolytic diseases are at increased risk for gallstone-related complications. Modified scoring systems have been developed to assess which pediatric patients would benefit from endoscopic retrograde cholangiopancreatography (ERCP) to treat choledocholithiasis. This study aimed to evaluate the ability of the available criteria to determine which pediatric patients with hemolytic diseases are likely to benefit from ERCP. A secondary analysis was performed using the Pediatric ERCP Database Initiative database, which contains prospectively collected data from 1,124 ERCPs at tertiary-care institutions. We compared patients with a hemolytic disease to those without. Data was analyzed by two-tailed Fisher’s exact test and paired …

The Treatment Naïve Microbiome Of Pediatric Ulcerative Colitis And Microbial Therapeutics: A Humbling Challenge, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.