Medicine and Health Sciences Commons^™

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Dysregulated Mitochondrial Energy Metabolism Drives The Progression Of Mucosal Field Effects To Invasive Bladder Cancer, Sangkyou Lee, Sung Yun Jung, Pawel Kuś, Jolanta Bondaruk, June Goo Lee, Roman Jaksik, Nagireddy Putluri, Khanh N Dinh, David Cogdell, Huiqin Chen, Yishan Wang, Jiansong Chen, Neema Navai, Colin Dinney, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Charles C Guo, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Students Publications

Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. …

Molecular Mechanisms In Masld/Mash-Related Hcc, Xiaobo Wang, Liang Zhang, Bingning Dong

Faculty, Staff and Students Publications

Liver cancer is the third leading cause of cancer-related deaths and ranks as the sixth most prevalent cancer type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, and its more severe manifestation, NASH or metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% of the population. The increased prevalence of metabolic dysfunction-associated steatotic liver disease and MASH is parallel to the increasing rates of obesity-associated metabolic diseases, including type 2 diabetes, insulin resistance, and fatty liver diseases. MASH can progress to MASH-related HCC (MASH-HCC) in about 2% of cases each year, influenced by various factors such …

Chemical Modulation Of Gut Bacterial Metabolism Induces Colanic Acid And Extends The Lifespan Of Nematode And Mammalian Hosts, Guo Hu, Marzia Savini, Matthew Brandon Cooke, Xin Wei, Dinghuan Deng, Shihong M Gao, Ruyue Alps Xia, Youchen Guan, Alice X Wen, Xin Yu, Jin Wang, Chao Jiang, Christophe Herman, Jiefu Li, Meng C Wang

Faculty, Staff and Students Publications

Microbiota-derived metabolites have emerged as key regulators of longevity. The metabolic activity of the gut microbiota, influenced by dietary components and ingested chemical compounds, profoundly impacts host fitness. While the benefits of dietary prebiotics are well-known, chemically targeting the gut microbiota to enhance host fitness remains largely unexplored. Here, we report a novel chemical approach to induce a pro-longevity bacterial metabolite in the host gut. We discovered that wild-type Escherichia coli strains overproduce colanic acids (CAs) when exposed to a low dose of cephaloridine, leading to an increased life span in the host organism Caenorhabditis elegans. In the mouse gut, …

Pleiotropy And The Increasing Complexity Of Parkinson's Disease Genetics, Jonggeol Kim, Joshua M Shulman

Faculty, Staff and Students Publications

No abstract provided.

Cognitive Reserve Predicts Baseline Tau Burden In The Us Pointer Trial Imaging Cohort, Valory N Pavlik, Chris J Weber, Joseph C Masdeu, Laura D Baker, Melissa M Yu, Michele York, Rachel A Whitmer, Susan M Landau, Theresa M Harrison, Tomas M Holland, Laura Lovato

Faculty, Staff and Students Publications

Introduction: Higher cognitive reserve (CR) is associated with reduced dementia risk. We hypothesized that higher CR is associated with less baseline Alzheimer's disease (AD) pathology in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort.

Methods: A subsample of participants underwent amyloid beta and tau positron emission tomography imaging. Regression analysis was used to model the association between educational attainment (EA) as a CR proxy measure, amyloid positivity, and entorhinal cortex (ERC) and meta-temporal region of interest (meta-ROI) tau standardized uptake value ratio (SUVR).

Results: In 911 participants with complete imaging data, higher …

Neural Signatures And Personalized Neuromodulation In A Subject Experiencing Context-Dependent Inhibitory Control Deficits, Layth S Mattar, Shraddha Shah, Lily S Chamakura, Denise Oswalt, Yue Zhang, Davin Devara, Jung Uk Kang, Zahra Jourahmad, Ryan Jafri, Geoffrey Liu, Joshua Adkinson, Isabel A Danstrom, Xiaoxu Fan, Yvonne Y Reed, Kelly R Bijanki, Alica Goldman, Lu Lin, Vaishnav Krishnan, Nicole R Provenza, Andrew J Watrous, Sameer A Sheth, Sarah R Heilbronner, Garrett P Banks, Eleonora Bartoli

Faculty, Staff and Students Publications

The ability to override prepotent actions is critical to control impulses and adjust behavior depending on goals and contextual needs. In this study, we investigate the inhibitory control abilities of a patient diagnosed with Klüver-Bucy Syndrome following a left temporal resection. The patient presented with disruptive hypersexuality symptoms akin to compulsions, leading to the inability to control and suppress inappropriate actions. The patient was recruited for the current research study while undergoing intracranial monitoring for epilepsy, to investigate the cognitive and neural processes underlying the patient's inhibitory control symptoms. We formulated the hypothesis that a reactive inhibitory control deficit emerges …

Coco-St Detects Global And Local Biological Structures In Spatial Transcriptomics Datasets, Muhammad Aminu, Bo Zhu, Natalie Vokes, Hong Chen, Lingzhi Hong, Jianrong Li, Junya Fujimoto, Mehdi Chaib, Yuqiu Yang, Bo Wang, Alissa Poteete, Monique B Nilsson, Xiuning Le, Tina Cascone, David Jaffray, Nicholas Navin, Tao Wang, Lauren A Byers, Don L Gibbons, John Heymach, Ken Chen, Chao Cheng, Jianjun Zhang, Jia Wu

Faculty, Staff and Students Publications

Spatial domain detection methods often focus on high-variance structures, such as tumour-adjacent regions with sharp gene expression changes, while missing low-variance structures with subtle gene expression shifts, like those between adjacent normal and early adenoma regions. Here, to address this, we introduce ‘compare and contrast spatial transcriptomics’ (CoCo-ST), a graph contrastive feature representation framework. By comparing a target sample with a background sample, CoCo-ST detects both high-variance, broadly shared structures and low-variance, tissue-specific features. It offers technical advantages, including multisample integration, batch-effect correction and scalability across technologies from spot-level Visium data to single-cell Xenium Prime 5K and subcellular Visium HD …

Ubiquitous Dysregulation Of The Wnt Pathway In Immune Thrombocytopenia Genetic Susceptibility, Estelle Lecluze, Stennio Da Silva Faria, Manon Saby, Jason Yu, Véronique Lisi, Vincent-Philippe Lavallée, Taylor Olmsted Kim, Michael E Scheurer, Amanda B Grimes, Thomas Pincez

Faculty, Staff and Students Publications

The pathogenesis of immune thrombocytopenia (ITP) is complex and incompletely understood. Multiple cell types have been implicated, and their respective contribution is unclear. A recent genome-wide association study identified single-nucleotide polymorphisms (SNPs) associated with pediatric ITP within or near 5 genes in the canonical Wnt signaling pathway. To investigate whether this pathway was dysregulated in ITP and identify which cell types were involved, we leveraged extensive functional genomics and single-cell RNA sequencing (scRNA-seq) data. By linking the identified SNPs to likely regulated genes, we showed an enrichment in the Wnt pathway and identified 2 additional genes in this pathway involved …

The Ifit2-Ifit3 Antiviral Complex Targets Short 5′ Untranslated Regions On Viral Mrnas For Translation Inhibition, Dustin R Glasner, Candace Todd, Brian Cook, Agustina D'Urso, Shivani Khosla, Elena Estrada, Jaxon D Wagner, Mason D Bartels, Chuan-Tien Hung, Pierce Ford, Jordan Prych, Kathryn S Hatch, Brian A Yee, Kaori M Ego, Qishan Liang, Sarah R Holland, James Brett Case, Kevin D Corbett, Michael S Diamond, Benhur Lee, Gene W Yeo, Mark A Herzik, Eric L Van Nostrand, Matthew D Daugherty

Faculty, Staff and Students Publications

Recognition of foreign RNA is critical for the innate immune response to viruses. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFIT) 2 and 3 are highly upregulated following viral infection, but mechanistic insight into their antiviral role is lacking. Here we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can serve as a molecular pattern for innate immune recognition via IFIT2 and IFIT3. Structure determination of the IFIT2-IFIT3 complex at 3.2 Å using cryo-EM reveals a domain-swapped heterodimer that is required for recognition of the viral mRNA 5' end, translation inhibition and antiviral activity. Critically, viral …

The Efficacy Of Longevity Interventions In Caenorhabditis Elegans Is Determined By The Early Life Activity Of Rna Splicing Factors, Sneha Dutta, Maria Camila Perez Matos, Caroline Heintz, Ayse Sena Mutlu, Mary Piper, Meeta Mistry, Arpit Sharma, Christopher S Morrow, Hannah Smith, Porsha Howell, Rohan Sehgal, Anne Lanjuin, Meng C Wang, William B Mair

Faculty, Staff and Students Publications

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between predicted life span and alternative splicing of mRNAs related to lipid metabolism. The activity of two RNA splicing factors, Reversed Polarity-1 (REPO-1) and Splicing Factor 1 (SFA-1), early in life is …

Paediatric Difficult Intubations And The Impact Of Timing Of Weekend Versus Weekday Cases: An Analysis Of The Pediatric Difficult Intubation Registry, Christy J Crockett, Judit Szolnoki, Sabina Khan, Angela C Lee, Alexander Kaizer, Patrick Olomu, Melissa Brooks Peterson

Faculty, Staff and Students Publications

Background: Off-hours presentation has been shown to be independently associated with tracheal intubation-related adverse events in patients with predicted difficult airway. The comparison of the complication rates of paediatric difficult intubations on weekends vs weekdays is unknown. The primary objective of this retrospective review is to determine the complication rates for paediatric difficult intubation cases that occur on a weekend vs a weekday.

Methods: We performed a retrospective review of data from the Pediatric Difficult Intubation registry, with service dates June 8, 2012 to May 9, 2023, to compare complication rates (total complications, hypoxaemia, non-hypoxaemia complications, and first-attempt success rate) …

Bicontinuous Interconnected Porous Biomaterials For Tissue Engineering And Regeneration, Aihik Banerjee, Anjana Khanal, Prince D Okoro, Shankar P Kharal, Kevin Dalsania, Baishali Kanjilal, Shiril B Iragavarapu, Yiqing Chen, Janitha M Unagolla, Huinan H Liu, Joshua T Morgan, Robert P Hesketh, Arash Pezhouman, Reza Ardehali, Bahman Anvari, Martin F Haase, Iman Noshadi

Faculty, Staff and Students Publications

Biomaterials mimicking natural extracellular matrix are necessary to create an optimal microenvironment for cell adhesion, migration, proliferation, and differentiation. These scaffolds must possess bicontinuous interconnected porosity to ensure the effective exchange of oxygen, nutrients, and metabolic waste, which are crucial for developing functional tissues. Here, a novel bicontinuous interfacially jammed emulsion (BIJEL)-Integrated PORous Engineered System (BIPORES) is developed to confer bioinert synthetic polyethylene glycol diacrylate (PEGDA) with unique bicontinuous interconnected porosity and surface topography. This platform is fabricated through controlled phase separation and interfacial stabilization of two continuous phases by nanoparticles. Functional validation using human mesenchymal stem cells, and human …

High Risk Of Persistence And Risk Of Dysplasia After Diagnosis Of Ultrashort Barrett's Esophagus, Wasseem Skef, Jasmine Haydel, Ashwin Rao, Ronan Allencherril, Rollin George, Gyanprakash A Ketwaroo, Aaron P Thrift, Hashem B El-Serag, Theresa Nguyen Wenker

Faculty, Staff and Students Publications

Introduction: The management of ultrashort (< 1 cm) Barrett's esophagus (BE) remains unclear. We aimed to determine the prevalence of ultrashort BE (USBE) at index diagnosis, identify factors associated with persistent BE after USBE diagnosis, and identify risk of dysplasia after initial USBE in a population of US veterans.

Methods: This was a retrospective cohort study at the Veterans Affairs hospital in Houston, TX, of consecutive patients with new BE diagnosis from November 1990 to June 2022 with follow-up through April 2023. Using a pathology database, we identified patients with a new USBE diagnosis and any subsequent follow-up esophagogastroduodenoscopy (EGD). We examined the association of sociodemographic and clinical risk factors of persistent USBE cohort compared with longer-length segment BE and those with a negative follow-up EGD after index USBE with χ 2 tests and logistic regression models. Last, we calculated the prevalence and …

Ambulatory Acute Kidney Injury In Patients With Cirrhosis Is Common And Burdensome, Kavish R Patidar, Ruben Hernaez, Yan Liu, George Cholankeril, Jennifer R Kramer, Thom Taylor, Prasun Jalal, Tzu-Hao Lee, Avegail G Flores, Giuseppe Cullaro, Andrew S Allegretti, Pere Gines, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: Little is known about ambulatory acute kidney injury (A-AKI), which develops in an outpatient setting.

Methods: We conducted a retrospective cohort study of patients diagnosed with cirrhosis between January 1, 2018, and December 31, 2019 from 130 hospitals in the Veterans Affairs healthcare system. Patients were classified as having incident A-AKI if they met the International Club of Ascites AKI criteria in an outpatient setting. We used multivariable regression models to identify factors associated with A-AKI development within 1 year of cirrhosis diagnosis. We also conducted a structured implicit review of patients' medical charts to determine the …

Targeting Steroid Receptor Coactivators For The Treatment Of Benign Female Reproductive Disorders, Yuri Park, Jaeyeong Jeong, Eunsu Kim, Nuri Sung, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of nuclear receptor signaling and play essential roles in female reproductive physiology. By integrating steroid hormone signaling with growth factors and metabolic pathways, SRC-1, SRC-2, and SRC-3 coordinate key processes such as decidualization, placental development, and ovarian function. Dysregulation of SRCs is strongly linked to the progression of benign gynecologic disorders, including polycystic ovary syndrome (PCOS), endometriosis, and uterine fibroids, largely through enhancing hormonal hypersensitivity and disrupting nuclear receptor-mediated cellular pathways. Emerging evidence further implicates specific SRC isoforms in disease pathogenesis, underscoring their potential as biomarkers and therapeutic targets. To inhibit SRC activity, …

Gregor: Accelerating Genomics For Rare Diseases, Moez Dawood, Ben Heavner, Marsha M Wheeler, Rachel A Ungar, Jonathan Lotempio, Laurens Wiel, Seth Berger, Jonathan A Bernstein, Jessica X Chong, Emmanuèle C Délot, Evan E Eichler, James R Lupski, Ali Shojaie, Michael E Talkowski, Alex H Wagner, Chia-Lin Wei, Christopher Wellington, Matthew T Wheeler, Gregor Partner Members, Claudia M B Carvalho, Richard A Gibbs, Casey A Gifford, Susanne May, Danny E Miller, Heidi L Rehm, Kaitlin E Samocha, Fritz J Sedlazeck, Eric Vilain, Anne O'Donnell-Luria, Jennifer E Posey, Lisa H Chadwick, Michael J Bamshad, Stephen B Montgomery, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium

Faculty, Staff and Students Publications

Rare diseases are collectively common, affecting approximately 1 in 20 individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in next-generation sequencing, development of new computational and functional genomics approaches to prioritize genes and variants and increased global sharing of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize and evaluate emerging genomics technologies …

Optic Nerve Injury Impairs Intrinsic Mechanisms Underlying Electrical Activity In A Resilient Retinal Ganglion Cell, Thomas E Zapadka, Nicholas M Tran, Jonathan B Demb

Faculty, Staff and Students Publications

Retinal ganglion cells (RGCs) are the sole output neurons of the retina and convey visual information to the brain via their axons in the optic nerve. Following injury to the optic nerve, RGCs axons degenerate and many cells die. For example, a model of axon injury, the optic nerve crush (ONC), kills ~80% of RGCs after two weeks. Surviving cells are biased towards ‘resilient’ types, including several with sustained firing to light stimulation. RGC survival may depend on activity, and there is limited understanding of how or why activity changes following optic nerve injury. Here we quantified the electrophysiological properties …

Neurodevelopmental Abnormalities Underlying Behavioral Deficits In A Model Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Michael R Williamson, Vaishnav Krishnan, Mahyar J Hedayatpour, Adam C Adler, Nandani Adyapak, Chris S Ward, Russell Ray, David Durgan, Farrah Kheradmand, Benjamin Deneen

Faculty, Staff and Students Publications

Rationale: Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.

Objectives: To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.

Methods: We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in the …

Genome Sequencing Reveals The Impact Of Pseudoexons In Rare Genetic Disease, Georgia Pitsava, Megan Hawley, Light Auriga, Ivan De Dios, Arthur Ko, Sofia Marmolejos, Miguel Almalvez, Ingrid Chen, Kaylee Scozzaro, Jianhua Zhao, Rebekah Barrick, Nicholas Ah Mew, Vincent A Fusaro, Jonathan Lotempio, Matthew Taylor, Luisa Mestroni, Sharon Graw, Dianna Milewicz, Dongchuan Guo, David R Murdock, Kinga M Bujakowska, Changrui Xiao, Emmanuèle C Délot, Seth I Berger, Eric Vilain

Faculty, Staff and Student Publications

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.

Results: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) …

Restricting Metabolic Plasticity Enhances Stress Adaptation Through The Modulation Of Pdh And Hif1a In Trap1-Depleted Colon Cancer, Hong-Yuan Tsai, Miao-Hsueh Chen, Jihye Yun, Lisa A Lai, John F Valentine, Mary P Bronner, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. …

Risk Score Roulette: A Cautionary Tale Of Polygenic Risk Score Reliability, Diane Xue, Elizabeth E Blue, Alexis C Wood, Jerome I Rotter, Alison E Fohner

Children’s Nutrition Research Center Staff Publications

Genetic risk prediction for Alzheimer's disease (AD) has high potential impact, yet few studies have assessed the reliability of various polygenic risk score (PRS) methods at the individual level. Here, we evaluated the reliability of AD PRS estimates among 6338 participants from the Multi-Ethnic Study of Atherosclerosis. We compared four PRS models that have been previously associated with dementia risk. Despite similar population-level performance metrics, inter-model reliability of individual-level risk assessment was low, even among individuals classified in the top and bottom deciles. These findings raise serious concerns about the downstream application of PRS for guiding interventions for AD.

Safety And Efficacy Of Liver-Directed Radiotherapy After Chemoimmunotherapy For Advanced Cholangiocarcinoma: An Early Report From A Large Tertiary Cancer Center, Abdulmoiz Asif, Abdulmoid Asif, Michael K Rooney, Enoch Chang, Felicity Namayanja, Kimana Quentin, Sunyoung Lee, Ian Hu, Vincent Bernard, Prajnan Das, Emma B Holiday, Sonal Noticewala, Grace L Smith, Albert C Koong, Ethan B Ludmir, Milind Javle, Lianchun Xiao, Eugene J Koay

Faculty, Staff and Student Publications

BACKGROUND: Recent randomized controlled trials have established chemoimmunotherapy as the standard of care for patients with advanced biliary cancers with a median overall survival (OS) of about thirteen months. No data exist to demonstrate the safety and efficacy of liver-directed radiotherapy (RT) for extrahepatic and intrahepatic cholangiocarcinoma (CCA) in the era of chemoimmunotherapy. The purpose of this study is to report our early experience treating patients with CCA using RT and chemoimmunotherapy.

METHODS: Twenty-eight patients with CCA who received chemoimmunotherapy sequentially and/or concurrently with RT were retrospectively analyzed. The median biologic equivalent dose (BED) of RT was 84.0 [interquartile range …

Urinary Vitamin D Binding Protein And Kidney Injury Molecule-1 Are Potent Predictors Of Acute Kidney Injury After Left Ventricular Assist Device Implantation, Shiyi Li, Iván Murrieta-Álvarez, Katherine V Nordick, Zachary Gray, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Carl P Walther, Nandan K Mondal

Faculty, Staff and Students Publications

Background/Objectives: Acute kidney injury (AKI) is a frequent and serious complication following left ventricular assist device (LVAD) implantation. This study aimed to predict AKI within 90 days post-LVAD by evaluating urinary levels of vitamin D binding protein (VDBP) and kidney injury molecule-1 (KIM-1).

Methods: We prospectively enrolled 29 advanced heart failure patients undergoing LVAD implantation and categorized them into four groups based on pre-LVAD kidney function and hemodynamic stability. Early-morning urine samples were collected 24 h before and 1 week after surgery. Urinary VDBP and KIM-1 levels, normalized to creatinine, were measured.

Results: Thirteen patients developed AKI …

Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia Patients Have Dismal Outcomes Irrespective Of Allogeneic Hematopoietic Stem Cell Transplant: A Single-Center Experience, Gabriela Llaurador, Matthew Willis, Michele S Redell, M Monica Gramatges, Andrea N Marcogliese, Swati Naik, Robert Krance, Erin Doherty, Alexandra M Stevens

Faculty, Staff and Students Publications

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1).

Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort.

Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children's Hospital from 2000 to 2022 was conducted.

Results: Twenty-nine …

Resolving Slc6a1 Variable Expressivity With Deep Clinical Phenotyping And Drosophila Models, Kristy L Jay, Nikhita Gogate, Paige I Hall, Kimberly M Ezell, Jonathan C Andrews, Sharayu V Jangam, Hongling Pan, Kelvin Pham, Ryan German, Vanessa Gomez, Emily Jellinek-Russo, Eric A Storch, Brain Gene Registry Consortium, Undiagnosed Diseases Network, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Herman A Dierick, Joy D Cogan, John A Phillips, Rizwan Hamid, Thomas Cassini, Lynette Rives, Sumit Pruthi, Hua-Chang Chen, Jennifer E Posey, Michael F Wangler

Faculty, Staff and Students Publications

Variants in SLC6A1 result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. SLC6A1 haploinsufficiency has been confirmed as the predominant pathway of SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD); however, the molecular mechanism underlying the variable clinical presentation remains unclear. Here, through work of the Undiagnosed Diseases Network, we identify an individual with an inherited p.A334S variant of uncertain significance. To resolve this variant and better understand the variable expressivity associated with SLC6A1, we assess the phenotypes of the proband in comparison with a cohort of 13 individuals …

Erratum To <[Transplant Cell Ther 2023 Jul;29(7):438e1-438e16 Epub 2023 Mar 9]>, Melissa R Hines, Tristan E Knight, Kevin O Mcnerney, Mark B Leick, Tania Jain, Sairah Ahmed, Matthew J Frigault, Joshua A Hill, Michael D Jain, William T Johnson, Yi Lin, Kris M Mahadeo, Gabriela M Maron, Rebecca A Marsh, Sattva S Neelapu, Sarah Nikiforow, Amanda K Ombrello, Nirav N Shah, Aimee C Talleur, David Turicek, Anant Vatsayan, Sandy W Wong, Marcela V Maus, Krishna V Komanduri, Nancy Berliner, Jan-Inge Henter, Miguel-Angel Perales, Noelle V Frey, David T Teachey, Matthew J Frank, Nirali N Shah

Faculty, Staff and Student Publications

No abstract provided.

Final Analysis Of The Resonate-2 Study: Up To 10 Years Of Follow-Up Of First-Line Ibrutinib Treatment For Cll/Sll, Jan A Burger, Paul M Barr, Tadeusz Robak, Carolyn Owen, Alessandra Tedeschi, Anita Sarma, Piers E M Patten, Sebastian Grosicki, Helen Mccarthy, Fritz Offner, Edith Szafer-Glusman, Cathy Zhou, Anita Szoke, Lynne Neumayr, James P Dean, Paolo Ghia, Thomas J Kipps

Faculty, Staff and Student Publications

With up to 10 years of follow-up, we report results from the final analysis of RESONATE- 2, a phase 3 study of first-line ibrutinib vs chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients aged ≥65 years with previously untreated CLL/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg/d; n = 136) or chlorambucil (0.5-0.8 mg/kg; ≤12 cycles; n = 133). With a median follow-up of 9.6 years in the ibrutinib arm, the median progression-free survival (PFS) was 8.9 years (95% confidence interval [CI], 7.0 to not estimable [NE]) vs 1.3 years (95% …

Longitudinal Characterization Of Males With X-Linked Creatine Transporter Deficiency: Final Results Of A Multiyear Observational Study, Judith S Miller, Cristan Farmer, Susan Blair, Simona Bianconi, Natacha Akshoomoff, Irina Anselm, Bruce A Barshop, Lindsey Becker, Amanda E Bennett, Leandra N Berry, Elizabeth M Berry-Kravis, Aleksandra Bruchey, Anna W Byars, Tricia Cimms, Kim M Cecil, Maxine Covello, Laura S Cubit, Tanvi Das, Robert J Davis, Madison Drye, Can Ficicioglu, John B Fulton, Robin P Goin-Kochel, Whitney Guthrie, Barbara E Hallinan, Fady Hannah-Shmouni, Kathryn E Gustafson, Dwight D Koeberl, Nicola Longo, Eva Mamak, Saadet Mercimek-Andrews, Claire Michalak, Forbes D Porter, Samar Rahhal, Linda Rees, Gail A Spiridigliozzi, Caitlin Stone, Nancy R Sullivan, V Reid Sutton, Rebecca P Thomas, Manisha Udhnani, Susan Waisbren, Michelle Xu, Lin Zhang, Melanie Brandabur, Audrey Thurm

Faculty, Staff and Students Publications

Background: The purpose of the Vigilan observational study (ClinicalTrials.gov, NCT02931682) was to prospectively assess the natural history and developmental course of creatine transporter deficiency (CTD).

Methods: Males with CTD aged 6 months to 65 years were evaluated at 6-month intervals for up to 4 years. Evaluations included neurodevelopmental assessments of intellectual functioning, adaptive functioning, and challenging behaviors and the onset and progression of medical comorbidities.

Results: Fifty participants (median age, 7.6 years) were enrolled. The predominant CTD phenotype consisted of significant intellectual disabilities and limited skill development over time. Most participants had a history of febrile or nonfebrile seizures, …

Distinct Molecular Responses Of Human Intestinal Organoids To Proton And Photon Radiation, Victoria Poplaski, Tajhal D Patel, Hoa Nguyen-Phuc, Amal Kambal, Lawrence Bronk, Mary K Estes, Cristian Coarfa, Sarah E Blutt

Faculty, Staff and Students Publications

Radiation exposure impairs rapidly renewing tissues like the intestinal epithelium, yet translational insights from murine models have been limited by species-specific responses. Here, we use human intestinal organoids (HIOs) derived from jejunal epithelium to evaluate human epithelial responses to low dose proton and photon (gamma) radiation. Gamma irradiation induces a unique developmental and metabolic shift in crypt-like organoids, including enrichment of amino acid metabolism pathways and activation of fetal-associated transcription factors and morphology. Integrated multi-omic profiling reveals serotonin biosynthesis as a central regenerative node. Human intestinal organoids can complement animal models and are emerging as a powerful tool in modeling …