Digital Commons Network^™

Rethinking The Rise Of Early-Onset Gastrointestinal Cancers: A Call To Action, Jan K Blancato, Anne Blaes, John M Salsman, Y Nancy You, Hannah Arem, Reetu Mukherji, Priyanka Kanth, Xin Hu, Anne Fabrizio, Marion L Hartley, Marios Giannakis, John L Marshall

Faculty, Staff and Student Publications

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend. We formed a multidisciplinary Think Tank to develop a strategic, coordinated approach to studying early-onset gastrointestinal cancers. This area of research is challenging given multifactorial etiologies. We focused on epidemiology and the environment, the microbiome, and survivorship …

Utility Of Candidate Genes From An Algorithm Designed To Predict Genetic Risk For Opioid Use Disorder, Christal N Davis, Alexander S Hatoum, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

OBJECTIVE: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study examined the association of 15 candidate genetic variants with risk of OUD using electronic health record data from December 20, 1992, to September 30, 2022. Electronic health record …

Brain Age Modeling And Cognitive Outcomes In Young Adults With And Without Sickle Cell Anemia, Andria L Ford, Slim Fellah, Yan Wang, Kira Unger-Levinson, Maria Hagan, Martin N Reis, Amy Mirro, Josiah B Lewis, Chunwei Ying, Kristin P Guilliams, Melanie E Fields, Hongyu An, Allison A King, Yasheng Chen

2020-Current year OA Pubs

IMPORTANCE: Both sickle cell anemia (SCA) and socioeconomic status have been associated with altered brain structure and cognitive disability, yet precise mechanisms underlying these associations are unclear.

OBJECTIVE: To determine whether brains of individuals with and without SCA appear older than chronological age and if brain age modeling using brain age gap (BAG) can estimate cognitive outcomes and mediate the association of socioeconomic status and disease with these outcomes.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study of 230 adults with and without SCA, individuals underwent brain magnetic resonance imaging (MRI) and cognitive assessment. Brain age was estimated using DeepBrainNet, …

A Single-Cell Compendium Of Human Cerebrospinal Fluid Identifies Disease-Associated Immune Cell Populations, Claudia Cantoni, Roman A. Smirnov, Maria Firulyova, Prabhakar S. Andhey, Tara R. Bradstreet, Ekaterina Esaulova, Marina Terekhova, Elizabeth A. Schwarzkopf, Nada M. Abdalla, Maksim Kleverov, Anne H. Cross, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu, Et Al.

2020-Current year OA Pubs

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, …

Parent Ptsd, Social Support And Differential Associations With Facets Of Anxiety Sensitivity, Kristen Bermingham, Christopher Latourrette, Karen G. Chartier, Spit For Science Working Group, Ananda B. Amstadter, Kaitlin Bountress

Psychology Faculty Publications

Background: Anxiety Sensitivity (AS), the belief that anxiety experiences have negative implications, is a prospective predictor of posttraumatic stress disorder (PTSD) and has been linked to changes in PTSD in experimental studies. AS is comprised of three sub-components: cognitive, physical, and social concerns. PTSD is moderately heritable and parental PTSD may increase risk for these AS facets both directly and through environmental influences like reduced social support.

Objective: The present study will examine whether Parent PTSD is associated with reduced social support and in turn facets of AS.

Method: Participants were recruited from an ongoing longitudinal study of college student …

A Reflection-Spectroscopy Measured Skin Carotenoid Score Strongly Correlates With Plasma Concentrations Of All Major Dietary Carotenoid Species Except For Lycopene, Qiang Wu, Cheryl Webb Cherry, Stephanie Jilcott Pitts, Melissa N Laska, Neal Craft, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoids can be measured non-invasively using spectroscopy methods to provide a biomarker of total dietary carotenoid and carotenoid-rich fruit and vegetable intake. However, the degree to which skin carotenoid biomarkers reflect intakes of specific carotenoids must be determined for specific devices. Previously, findings were mixed regarding the correlation between reflection spectroscopy (RS)-assessed skin carotenoids and individual plasma carotenoid concentrations. The current study expands on prior analyses to examine the cross-sectional associations between adult RS-assessed skin carotenoids and individual carotenoid species intakes and plasma concentrations, controlling for potential covariates. We hypothesized that RS-assessed skin carotenoid scores would strongly correlate with …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

Efficacy And Safety Of 4-Month Rifapentine-Based Tuberculosis Treatments In Persons With Diabetes., Ekaterina V. Kurbatova, William C. Whitworth, Lakshmi Praveena Peddareddy, Patrick P. J. Phillips, Nigel A. Scott, Kia E. Bryant, Rodney Dawson, Sandra Wagner Cardoso, Wadzanai Samaneka, Melissa Engle, Ziyaad Waja, Erin Sizemore, Wendy Carr, Kelly E. Dooley, Radojka Savic, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Nhung V. Nguyen, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and …

Reliability Of Popliteal Artery Flow-Mediated Dilation In The Seated Position, Taskina Akhter, Patrick B. Wilson, J. David Branch, Leryn J. Reynolds

Exercise Science Faculty Publications

Flow-mediated dilation (FMD), a noninvasive measure of endothelial function, is commonly measured in the popliteal artery in the supine and upright body positions. However, reliability studies of the measurement in these positions are not well studied. This study aimed to examine the trial-retrial and visit-to-visit reliability of popliteal artery FMD in the seated position. Popliteal artery FMD was measured in 20 healthy adults across two visits in the seated and prone positions to assess visit-to-visit reliability. Two measurements were taken for each body position at each visit to assess trial-retrial reliability. %FMD was calculated as the percent change from baseline …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased …

Type 2 Diabetes Polygenic Risk Score Interactions With Lifestyle Risk Factors In Black Americans, Ashley W Scadden, Aastha Kakar, Elizabeth M Litkowski, Mariah C Meyer, Nicole D Armstrong, Steven Buyske, Yanwei Cai, Iona Cheng, Burcu F Darst, Myriam Fornage, Mariaelisa Graff, Boya Guo, Christopher A Haiman, Heather M Highland, Charles Kooperberg, Loïc Le Marchand, Kari North, Ulrike Peters, Stephen S Rich, Jerome I Rotter, Vinodh Srinivasasainagendra, Hemant K Tiwari, Stephanie Waldrop, Kristin Young, Sridharan Raghavan, Ethan M Lange, Leslie A Lange, Marguerite R Irvin, Maggie A Stanislawski

The Brown Foundation: Institute of Molecular Medicine

Introduction: Prior work in predominantly European ancestry populations has explained how the risk associated with demographic, lifestyle, and health factors differs with underlying genetic susceptibility to type 2 diabetes (T2D), but less is known about these relationships in Black Americans.

Methods: We used covariate-adjusted logistic regression models of T2D to examine interactions between a published trans-ancestry derived T2D polygenic risk score (PRS) and various demographic, lifestyle, and health-related factors among 28,251 self-identified Black Americans from six cohort studies.

Results: The results are generally consistent with prior work in White populations. The PRS showed a significant interaction with body mass index, …

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …

Association Of Insulin Resistance With Radiographic Lung Abnormalities And Incident Lung Disease: The Framingham Offspring Study, Kristen A Staggers, Meredith Mccormack, Dennis T Villareal, Ivan O Rosas, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Objective: Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study.

Research design and methods: Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Psychometric Evaluation Of A Novel Measure Of Trauma-Related Cannabis Use To Cope, Sage E. Hawn, Terrell A. Hicks, Christopher Latourrette, Anita Thomas, Daniela Chaname, Sarah Ehlke, Abigail Powers Lott

Psychology Faculty Publications

Background: Posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) are commonly comorbid and are associated with many negative public health outcomes. One plausible explanation for this comorbidity comes from a self-medication framework, which suggests people use cannabis to cope with PTSD symptoms. Despite theoretical and empirical evidence for PTSD-related cannabis use to cope, no measure of this construct exists.

Objective: We sought to address this gap by developing and validating a novel measure of PTSD-specific cannabis self-medication, which we have termed the Trauma-Related Cannabis Use to Cope (TRCU) questionnaire.

Method: The psychometric properties of the TRCU and how it …

A Directed Content Analysis For Greatest Problems Among People With And Without Traumatic Brain Injury, Brittany Wright, Alexa S Gonzalez, Luis Leon Novelo, Xiangyi Liu, Shannon B Juengst

Faculty, Staff and Student Publications

Objective: To characterize the greatest problem or need among individuals with a history of traumatic brain injury (TBI), as compared with individuals with a history of other neurologic conditions, mental health conditions, and no history of neurologic or mental health conditions.

Design: A directed content analysis of open-text responses to a single online survey question using a framework guided by the Mayo-Portland Adaptability Inventory-4.

Setting: Community.

Participants: A total of 2861 community-dwelling adults (n=274 with TBI; n=289 with other neurologic conditions besides TBI; n=454 with mental health conditions but no neurologic conditions; and n=1844 controls).

Interventions: Not applicable.

Main outcome …

Talking About Suffering In The Intensive Care Unit, Brent M Kious, Judith B Vick, Peter A Ubel, Olivia Sutton, Jennifer Blumenthal-Barby, Christopher E Cox, Deepshikha Ashana

Center for Medical Ethics and Health Policy Staff Publications

Background: Some have hypothesized that talk about suffering can be used by clinicians to motivate difficult decisions, especially to argue for reducing treatment at the end of life. We examined how talk about suffering is related to decision-making for critically ill patients, by evaluating transcripts of conversations between clinicians and patients' families.

Methods: We conducted a secondary qualitative content analysis of audio-recorded family meetings from a multicenter trial conducted in the adult intensive care units of five hospitals from 2012-2017 to look at how the term "suffering" and its variants were used. A coding guide was developed by consensus-oriented discussion …

Use Of Machine Learning Models To Predict Microaspiration Measured By Tracheal Pepsin A., Annette Bourgault, Ilana Logvinov, Chang Liu, Rui Xie, Jan Powers Phd, Rn, Ccrn, Mary Lou Sole

Nursing Publications, Posters, & Presentations

BACKGROUND: Enteral feeding intolerance, a common type of gastrointestinal dysfunction leading to underfeeding, is associated with increased mortality. Tracheal pepsin A, an indicator of microaspiration, was found in 39% of patients within 24 hours of enteral feeding. Tracheal pepsin A is a potential biomarker of enteral feeding intolerance.

OBJECTIVE: To identify predictors of microaspiration (tracheal or oral pepsin A). It was hypothesized that variables predicting the presence of tracheal pepsin A might be similar to predictors of enteral feeding intolerance.

METHODS: In this secondary analysis, machine learning models were fit for 283 adults receiving mechanical ventilation who had tracheal and …

Abdominal Versus Femoral Subcutaneous Fat Gene Expression In Non-Obese Insulin Resistant Individuals, Saif Badran, Shamma Almuraikhy, Maha Alser, Khaled Naja, Najeha Anwardeen, Hanan H Abunada, Mohamed Badie Ahmed, Salma Jarrar, Ghanem Aljassem, Sara Iskeirjeh, Atalla Hammouda, Suhail A Doi, Layla Al-Mansoori, Mohamed A Elrayess

2020-Current year OA Pubs

INTRODUCTION: Adipose tissue, once viewed primarily as an energy reservoir, is now recognized as an endocrine organ involved in various physiological functions, including energy balance and immune responses. Interestingly, recent insights suggest that not all overweight or obese individuals exhibit insulin resistance, guiding the focus towards depot-specific adipose gene expression and its metabolic implications. This pilot study investigates adipose depot-specific differences in gene expression in abdominal versus femoral subcutaneous adipose tissue (SAT) among non-obese, insulin-sensitive (IS) and insulin-resistant (IR) individuals, aiming to elucidate underlying mechanisms of metabolic dysfunction.

METHODS: Seventeen non-obese participants scheduled for body contouring surgery provided paired SAT …

Novel Loci For Triglyceride/Hdl-C Ratio Longitudinal Change Among Subjects Without T2d, Lihua Wang, Siyu Wang, Jason A Anema, Vaha A Moghaddam, Yanli Lu, Shiow Lin, E Warwick Daw, Allison L Kuipers, Iva Miljkovic, Michael Brent, Gary J Patti, Bharat Thygarajan, Joseph M Zmuda, Michael A Province, Ping An

2020-Current year OA Pubs

Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a …

Mapping Epidermal And Dermal Cellular Senescence In Human Skin Aging, Grace T Yu, Clarisse Ganier, David B Allison, Tamara Tchkonia, Sundeep Khosla, James L Kirkland, Magnus D Lynch, Saranya P Wyles

Children’s Nutrition Research Center Staff Publications

Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts. Photoaging due to ultraviolet light exposure was associated with higher burdens of senescent cells, a sign of biological aging, compared to chronological aging. A skin-specific cellular senescence gene set, termed …

Cardiac Timing Effects On Response Speed Are Modulated By Blood Pressure But Not Heart Rate Variability In Healthy Young Adults, Xiao Yang, Catalina Roldan, Michael Gazzanigo, Yasmine Nabulsi, Fang Fang

Research and Infrastructure Service Enterprise (RISE) Faculty Publications

Cardiac timing effects reflect the dynamic interplay between interoceptive and exteroceptive processes. Human information processing tends to be facilitated during cardiac diastole and inhibited during systole, reflecting autonomic regulation and the neuromodulation by baroreceptor afferents. Thus, blood pressure (BP) and vagally-mediated heart rate variability (vmHRV) are potential modulators of those effects. Additionally, cognitive control appears to play a critical role in the processes. However, whether cardiac timing effects are influenced by those factors remains unclear. The present study aimed to clarify these relationships. Fifty-one healthy young adults completed three experimental sessions to assess BP, short-term HRV, and cardiac timing effects. …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Dylan Jochum, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

International Multicenter Retrospective Study From The Ultra-Rare Sarcoma Working Group On Low-Grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, And Hybrid Forms: Outcome Of Primary Localized Disease, Claudia Giani, Abdulazeez Salawu, Silva Ljevar, Ryan A Denu, Andrea Napolitano, Elizabeth A Connolly, Daniel D Wong, Roberto Scanferla, Evan Rosenbaum, Jyoti Bajpai, Zola Chia-Chen Li, Susie Bae, Lorenzo D'Ambrosio, Steve Bialick, Andrew J Wagner, Alexander T J Lee, Hanna Koseła-Paterczyk, Giacomo G Baldi, Antonella Brunello, Yeh Chen Lee, Herbert H Loong, Sosipatros Boikos, Fernando Campos, Carlo M Cicala, Robert G Maki, Nadia Hindi, Costanza Figura, Shahd S Almohsen, Sheyaskumar Patel, Robin L Jones, Toni Ibrahim, Rooshdiya Karim, Akira Kawai, Richard Carey-Smith, Richard Boyle, Silvia M Taverna, Alexander J Lazar, Elizabeth G Demicco, Judith V M G Bovee, Angelo P Dei Tos, Christopher Fletcher, Daniel Baumhoer, Marta Sbaraglia, Inga-Marie Schaefer, Rosalba Miceli, Alessandro Gronchi, Silvia Stacchiotti

Faculty, Staff and Student Publications

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists. The primary endpoint was overall survival (OS). Secondary endpoints were crude cumulative incidence (CCI) of local recurrence (LR), CCI of distant metastases (DM), and post-metastases OS (p-OS). Two hundred ninety-four patients (239 LGFMS, 32 SEF, and 23 H-LGFMS/SEF) were identified. …

Burden Of Seasonal Human Coronavirus Infections In Hematopoietic Cell Transplant Recipients, Fareed Khawaja, Terri Lynn Shigle, Layale Yaghi, May Daher, Jeremy L Ramdial, Ying Jiang

Faculty, Staff and Student Publications

Background: Community respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.

Methods: We performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respiratory viral infections in HCT recipients. Patient data were collected to identify risk factors for HCoV LRI, and to calculate …

Histopathologic Progression And Metastatic Relapse Outcomes In Small Cell Neuroendocrine Carcinomas Of The Urinary Tract, Mohammad Jad Moussa, Georges C Tabet, Arlene O Siefker-Radtke, Lianchun Xiao, Nathaniel R Wilson, Christopher J Logothetis, Byron Lee, Amishi Y Shah, Pavlos Msaouel, Roger Li, Leticia Campos Clemente, Jianping Zhao, Nizar M Tannir, Ashish M Kamat, Donna E Hansel, Charles C Guo, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Student Publications

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials and methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

Results: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) …

A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Richard Williams, Ramesh Saxena, Tianfu Wu

Faculty, Staff and Student Publications

Introduction: Lupus nephritis (LN) leads to end stage renal disease (ESRD), and early diagnosis and disease monitoring of LN could significantly reduce the risk. however, there is not such a system clinically. In this study we aim to develop a biomarker-panel based point-of-care system for LN.

Methods: Immunoassay screening combined with genomic expression databases and machine learning techniques was used to identify a biomarker panel of LN. A quantitative biomarker-panel mini-array (BPMA) system was developed and the sensitivity, specificity, reproducibility, and stability of the were examined. The performance of BPMA in disease monitoring was validated with machine models using a …

Dedifferentiated Liposarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Experience, Madeline B Torres, Cheuk Hong Leung, Marianne Zoghbi, Rossana Lazcano, Davis Ingram, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Anthony Conley, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan Farooqi, Devarati Mitra, Alison K Yoder, Michael S Nakazawa, Dejka Araujo, Andrew Livingston, Ravin Ratan, Shreyaskumar Patel, Vinod Ravi, Alexander J Lazar, Christina L Roland, Neeta Somaiah, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center.

Methods: We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between …