Allergy and Immunology Commons^™

Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Kdm4a Promotes Nepc Progression Through Regulation Of Myc Expression, Celia Sze Ling Mak, Ming Zhu, Jie Fu, Xin Liang, Xiaoxuan Wang, Fei Yuan, Feng Wang, Anh G Hoang, Xingzhi Song, Peter Shepherd, Derek Liang, Jessica Suh, Jordan Contreras, Thisawin Dang, Cindy Yan, Brandon Figueroa, Mathias Mazzocco, Athena Luo, Bijeta Pradhan, Jiwon Park, Mirrah Bashir, Miao Zhang, Eric Metzger, Roland Schüle, Abhinav K Jain, Ellen Karasik, Daniel Frigo, Barbara A Foster, Min Gyu Lee, Paul Corn, Christopher J Logothetis, Ana Aparicio, Nora Navone, Patricia Troncoso, Zhi Tan, Jianhua Zhang, Sue-Hwa Lin, Guocan Wang

Faculty, Staff and Students Publications

Neuroendocrine prostate cancer (NEPC) is a highly aggressive and lethal subtype of prostate cancer (PCa) that often emerges in response to androgen receptor pathway inhibitors (ARPIs), which are widely used in treating metastatic castration-resistant and hormone-sensitive prostate cancer. The incidence of NEPC is increasing, yet effective therapeutic strategies remain limited due to an incomplete understanding of its molecular drivers. Through transcriptomic analyses of human prostate tumor samples, we identified the histone lysine demethylase KDM4A as uniquely overexpressed in human and mouse NEPC compared to prostate adenocarcinoma. Functional validation demonstrated that KDM4A is a key regulator of NEPC progression and a …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

Tgfbr2 Coordinates The Endometrial Response To Estrogen, Regulating Endometrial Hyperplasia And Fertility, Sydney E Parks, Suni Tang, Anna Catherine Unser, Ananya L Bhonsley, Eunbi M Chung, Peixin Jiang, Audrey Savolainen, Vanessa J Joseph, Dominique I Cope, Ramya P Masand, Renata Prunskaite-Hyyryläinen, Diana Monsivais

Faculty, Staff and Students Publications

Proper endometrial function is critical for establishing and maintaining healthy pregnancies, as well as preventing the pathogenesis of conditions such as endometrial hyperplasia and endometrial cancer. The TGFβ signaling pathway regulates key aspects of endometrial biology, although the direct effects of many individual receptors remain unstudied. In this study, we characterize the role of TGFβR2 within the endometrium using a progesterone receptor-cre conditional knock-out mouse model (Tgfbr2flox/flox;Pgrcre/+; “Tgfbr2 cKO”). We found that conditional deletion of TGFβR2 resulted in female infertility, endometrial hyperplasia, altered estrogen and progesterone response, and, only in bred females, reproductive tract …

International Consensus Guidelines For The Conduct And Reporting Of Car T-Cell Clinical Trials In Aml, Swati Naik, Richard Aplenc, Susanne H C Baumeister, Marco Becilli, Anand S Bhagwat, Challice L Bonifant, Lihua E Budde, Christopher D Chien, Kevin J Curran, Anthony F Daniyan, Alexandra Dreyzin, Rebecca A Gardner, Sara Ghorashian, Stephen Gottschalk, Laquisa C Hill, M Eric Kohler, Adam Lamble, Franco Locatelli, Maksim Mamonkin, Bilal Omer, Jae H Park, Concetta Quintarelli, Benedetta Rambaldi, Rebecca M Richards, David A Sallman, Tim Sauer, Nirali N Shah, Marion Subklewe, Corinne Summers, Sarah K Tasian, Naomi Taylor, Sarah Tettamanti, Michael R Verneris, M Paulina Velasquez, Saar I Gill

Faculty, Staff and Students Publications

Early clinical experience with the use of chimeric antigen receptor (CAR) T-cell therapies for patients with acute myeloid leukemia (AML) has been beset by high rates of toxicities and low rates of response. We convened an international workshop with the goal of bringing investigators in the field of AML-directed CAR T-cell therapy together to facilitate discussion of challenges and to brainstorm potential solutions. Based on discussions at the workshop, it was evident that (1) treating and targeting AML with CAR T cells is associated with unique clinical challenges, and (2) variability in clinical trial design, definitions of toxicities, correlative data …

A Mouse Model Of Lipoatrophy Reveals Relationships Between Beige Fat Appearance And Female Fertility, Elizabeth S Anaya, William Dion, Pradip K Saha, Aaron R Cox, Evelyn De Groot, Avery A Ahmed, Jessica B Felix, Bokai Zhu, Stephanie A Pangas, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) performs vital metabolic and endocrine functions, but roles in female reproduction remain understudied and poorly understood. Here, we report that female mice experiencing progressive lipoatrophy after knockout of Ubc9 in adipocytes (Ubc9fKO) displayed disrupted estrous cycles, reduced ovarian reserve, and subfertility. During aging, female Ubc9fKO mice lose subcutaneous WAT more quickly than their male counterparts and weigh less than littermate controls. Subcutaneous WAT excised from female Ubc9fKO mice strongly enriched for thermogenesis genes generally associated with metabolic benefits. Female Ubc9fKO mice exhibited hypermetabolism and accumulated thermogenic, Uncoupling Protein 1-expressing beige fat cells in residual subcutaneous WAT …

Dinaciclib Improves Treatment Response In Chemoresistant Hepatoblastoma, Brian T Hickner, Andres F Espinoza, Rohit K Srivastava, Roma H Patel, Priyanka Rao, Nicholas A O'Brien, Kalyani R Patel, Andrew A Badachhape, Abhishek Kona, Dolores H López-Terrada, Sarah E Woodfield, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

Chemoresistant hepatoblastoma (HB) is associated with poor outcomes. Cyclin-dependent kinases (CDKs) are potential therapeutic targets because of their critical role in cell growth and chemoresistance. To evaluate the efficacy of CDK inhibition, HB cell lines were treated with dinaciclib and evaluated with cytotoxic, cell-death reversal, and immunoblotting assays. A HB patient-derived xenograft (PDX) model was treated with placebo, vincristine + irinotecan (VI), dinaciclib, or VI + dinaciclib to evaluate tumor growth and response to therapy. We found that dinaciclib had a marked effect on HB cell viability, induced PARP cleavage, and decreased CDK9 protein expression in vitro. Overexpression of CDK9 …

Soluble C5b-9 (Sc5b-9) In Pediatrics-A Clinical Assessment, Ridwan B Ibrahim, Radwa Almamoun, Sarah E Sartain, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The soluble C5b-9 (sC5b-9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement-mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted.

Methods: We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [n = 26; median age 18.5 years (range …

Hemophagocytic Lymphohistiocytosis In A Pediatric Lung Transplant Recipient, Sunil Chickmagalur, Anna Schrader, Dallas Parrish, David Moreno Mcneill, Maria C Gazzaneo, Ernestina Melicoff-Portillo, Nahir Cortes-Santiago

Faculty, Staff and Students Publications

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication of solid organ transplantation and is a syndrome of systemic hyperinflammation secondary to dysregulation of the inflammatory response, primarily involving lymphocytes and macrophages. It is often fatal and therefore early recognition and treatment are crucial. Among 11 adult cases of HLH in post-lung transplant cases found in the literature, only one patient survived.

Case: We report the first known pediatric case of HLH following lung transplantation. The patient, a previously healthy adolescent, developed end-stage bullous lung disease secondary to acute respiratory distress syndrome (ARDS) and underwent bilateral lung transplantation. Two months posttransplant, …

Cerebellar Purkinje Cell Stripe Patterns Reveal A Differential Vulnerability And Resistance To Cell Loss During Normal Aging In Mice, Sarah G Donofrio, Cheryl Brandenburg, Amanda M Brown, Tao Lin, Hsiang-Chih Lu, Roy V Sillitoe

Faculty, Staff and Students Publications

Age-related neurodegenerative diseases involve reduced cell numbers and impaired behavioral capacity. Neurodegeneration and behavioral deficits also occur during aging, and notably in the absence of disease. The cerebellum, which modulates movement and cognition, is susceptible to cell loss in both aging and disease. Here, we demonstrate that cerebellar Purkinje cell loss in aged mice is not spatially random but rather occurs in a pattern of parasagittal stripes. We also find that aged mice exhibit impaired motor coordination and more severe tremor compared to younger mice. However, the relationship between patterned Purkinje cell loss and motor dysfunction is not straightforward. Examination …

Transcriptional Coregulator Zmiz1 Modulates Estrogen Responses That Are Essential For Healthy Endometrial Function, Sylvia C Hewitt, Frank Orellana, Ryan M Marquardt, Myeongjin Yi, Cynthia J Willson, Mark Y Chiang, Yong Song, Goutham Venkata Naga Davuluri, Christopher Day, Ramakrishna Kommagani, Joseph Rodriguez, Asgerally T Fazleabas, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen is a critical regulator of endometrial health. Aberrant estrogen stimulation can result in infertility, endometrial cancer, and endometriosis. Here, we identified Zinc Finger MIZ-Type Containing 1 (Zmiz1) as a coregulator of uterine estrogen signaling. ZMIZ1 is colocalized with an estrogen receptor α–binding (ESR1-binding) super enhancer. ZMIZ1 mutations are found in endometrial cancer and its RNA levels trend toward reduction in endometrium of patients with endometriosis. ZMIZ1 is dynamically expressed in human endometrial tissues during the menstrual cycle. Disrupting ZMIZ1 in cultured human endometrial stromal cells resulted in impaired cell proliferation and decidual differentiation. Ablation of Zmiz1 using …

Hemolysis Detection Using The Gem 7000 At The Point Of Care In A Pediatric Hospital Setting: Does It Affect Outcomes?, Ridwan B Ibrahim, Nazmin Bithi, Charlene Hernandez, Hanna Uhrova, Brandy D Recio, Sridevi Devaraj

Faculty, Staff and Students Publications

No abstract provided.

Diras3-Derived Cyclic Peptides Disrupt Kras-Raf Interaction And Kras Nanoclustering, Suppressing Kras-Driven Pancreatic And Ovarian Tumors, Joshua P Gray, Gamze Bildik, Ha-Neul Kim, Margie N Sutton, Jing Wang, Amarachi O Osuji, Nefeli Batistatou, Hailing Yang, Weiqun Mao, Zhi Tan, Geneviève M C Gasmi-Seabrook, Junchen Liu, John F Hancock, Christopher B Marshall, Joshua A Kritzer, Mitsuhiko Ikura, Robert C Bast, Steven W Millward, Zhen Lu

Faculty, Staff and Students Publications

Mutations in KRAS drive 88% of pancreatic ductal adenocarcinomas (PDAC) and up to 40% of low-grade serous ovarian cancers (LGSOC), making KRAS a long-standing therapeutic target. We previously showed that DIRAS3 binds RAS, forming heterodimers that disrupt RAS clustering and downstream MAPK signaling. Building on this, we developed conformationally constrained DIRAS3-derived peptides using two cyclization strategies and characterized them by NMR and biolayer interferometry. These cyclic peptides attenuate the interaction between KRAS and the BRAF RAS-binding domain, penetrate cells efficiently, and inhibit KRAS nanoclustering on the inner leaflet of the plasma membrane. Functionally, they reduce cell viability and suppress PDAC …

Design, Optimization, And Development Of Ripk1 Degraders With Improved Pharmacokinetic And Pharmacodynamic Properties, Dong Lu, Xin Yu, Hanfeng Lin, Ran Cheng, Bin Yang, Min Zhang, Jingjing Chen, Feng Li, Xiaoli Qi, Jin Wang

Faculty, Staff and Students Publications

Pharmacological degradation of receptor-interacting protein kinase 1 (RIPK1) offers a compelling therapeutic strategy to overcome its scaffolding role in tumor resistance and to enhance the efficacy of immune checkpoint blockade (ICB) therapies. In this study, we report the discovery of a novel RIPK1 degrader, LD5097(24b), developed through systematic optimization of its precursor compound, LD4172—specifically refining the linker, RIPK1 warhead exit vector, and VHL ligand components. LD5097(24b) exhibits potent and selective RIPK1 degradation, triggering rapid and efficient downregulation of RIPK1 and significantly enhancing TNFα-mediated apoptosis in Jurkat cells. Compared to LD4172, LD5097(24b) demonstrates markedly improved metabolic stability and pharmacokinetic properties. In …

Real-World Outcomes Of Infections Following Tisagenlecleucel In Patients With B-Cell All: A Cibmtr Analysis, Hemalatha G Rangarajan, Prakash Satwani, Megan M Herr, Min Chen, Michael J Martens, Kitsada Wudhikarn, Samuel John, Vanessa A Fabrizio, Emily M Hsieh, Amar H Kelkar, Erin Doherty, David I Marks, Olle Ringden, Brian Friend, Matthew S Kelly, Nosha Farhadfar, Tim Prestidge, Nasheed M Hossain, Hongtao Liu, Shahrukh Hashmi, Dipenkumar Modi, Lena E Winestone, Zeinab El Boghdadly, Hemant S Murthy, Miguel-Angel Perales, Roy F Chemaly, Christopher E Dandoy, Joshua A Hill, Anna Huppler, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. …

Infection After Cd19 Chimeric Antigen Receptor T-Cell Therapy For Large B-Cell Lymphoma: Real-World Analysis From Cibmtr, Kitsada Wudhikarn, Megan M Herr, Min Chen, Michael J Martens, John H Baird, Lohith Gowda, Hemalatha G Rangarajan, Muhammad Bilal Abid, Mohamed A Kharfan-Dabaja, Kirsten M Williams, Siddhartha Ganguly, Jo-Anne H Young, Akshay Sharma, Giancarlo Fatobene, Tania Jain, Christopher G Kanakry, Dipenkumar Modi, Natalie S Grover, Baheyeldin Salem, Marjorie Vieira Batista, Paschalis Vergidis, Dwight E Yin, Amer M Beitinjaneh, Amar H Kelkar, Taiga Nishihori, Jennifer Holter Chakrabarty, Usama Gergis, Melody Smith, Zeinab El Boghdadly, Christopher E Dandoy, Hemant S Murthy, Anna R Huppler, Miguel-Angel Perales, Roy F Chemaly, Joshua A Hill, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, …

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 …

Prevalence And Clinical Impact Of Pseudohypercalcemia In Paraproteinemia: A Case And Cohort Study, Usman Sunusi, Li Chen, Nianyi Li, Jason K Y Lee, Irmeen Siddiqui, Erin Goodhue, Rongrong Huang, Jieli Li

Faculty, Staff and Students Publications

Background: Hypercalcemia is a common and serious complication of malignancy, often contributing to morbidity and mortality. In patients with paraproteinemia, elevated total calcium with normal ionized calcium, termed pseudohypercalcemia, can complicate diagnosis and lead to inappropriate treatment. While this phenomenon has been described in case reports, its prevalence and clinical impact in routine practice remain poorly defined.

Methods: We report a case of pseudohypercalcemia in a patient with IgG κ multiple myeloma and conducted a retrospective review of de-identified data to assess the prevalence and biochemical associations of pseudohypercalcemia in paraproteinemia. Available data included serum protein electrophoresis (SPEP), …

Mechanistic Study Of Pexidartinib-Induced Toxicity In Human Hepatic Cells, Si Chen, Yuxi Li, Xilin Li, Nan Mei, Xiaobo He, Matthew S Bryant, Xuan Qin, Feng Li, Lei Guo

Faculty, Staff and Students Publications

Pexidartinib, a tyrosine kinase inhibitor, was approved by the U.S. Food and Drug Administration in 2019 for treating adult patients with symptomatic tenosynovial giant cell tumors. Because of its hepatotoxicity risks, pexidartinib received a boxed warning; however, mechanistic studies on this hepatotoxicity remain limited. In this study, we demonstrate that pexidartinib decreases cell viability in primary human hepatocytes and hepatic HepG2 cells. A 24-h treatment with pexidartinib led to apoptosis in HepG2 cells, as evidenced by increased caspase 3/7 activity and the induction of cleaved PARP and γ-H2A.X. Pexidartinib-induced endoplasmic reticulum (ER) stress was observed at early time points of …

Nonexposed Endoscopic Full Thickness Resection Of Residual Disease After Definitive Chemoradiation For Locally Advanced Gastric Cancer, Brennan W Gioe, Bryan C Luu, Michael M Ittmann, George Chen, Yvonne H Sada, Wasseem Skef

Faculty, Staff and Students Publications

Salvage endoscopic resection of residual esophageal neoplasia for patients that prefer to avoid surgery or are poor surgical candidates has been reported. We report a case of gastric signet ring cell carcinoma with residual disease after definitive chemoradiotherapy, that was treated with nonexposed endoscopic full thickness resection. This endoscopic resection achieved negative margins, with postresection surveillance endoscopy and imaging showing no evidence of disease. This case highlights the potential use of salvage endoscopic resection as a therapy for residual gastric cancer after chemoradiation in patients where surgery is not an option.

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Fructose And Glucose From Sugary Drinks Enhance Colorectal Cancer Metastasis Via Sord, Tianshi Feng, Qin Luo, Yanlin Liu, Zeyu Jin, David Skwarchuk, Rumi Lee, Miso Nam, John M Asara, Daya R Adye, Philip L Lorenzi, Lin Tan, Guangsheng Pei, Zhongming Zhao, Neda Zarrin-Khameh, Adriana Paulucci-Holthauzen, Brian W Simons, Ju-Seog Lee, Scott Kopetz, Jihye Yun

Faculty, Staff and Students Publications

The consumption of sugar-sweetened beverages (SSBs), which contain high levels of fructose and glucose, has been causally and mechanistically linked to an increased risk of colorectal cancer (CRC). However, the effects of SSB consumption on advanced stages of disease progression, including metastasis, remain poorly understood. Here we show that exposure of CRC cells to a glucose and fructose formulation-reflecting the composition of both high-fructose corn syrup and sucrose found in SSBs-enhances cellular motility and metastatic potential compared to glucose alone. Given that CRC cells grow poorly in fructose alone, and cells in vivo are not physiologically exposed to fructose without …

Pediatric Heart Failure: A Practical Guide For Primary Care Providers Supporting Families Across The Care Continuum, Shahnawaz Amdani, Kriti Puri, Julie Glickstein, Joseph A Spinner, Jonathan N Johnson, Ashraf S Harahsheh, Majd Makhoul, Susan Denfield

Faculty, Staff and Students Publications

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF.

Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF.

Results: HF in children most commonly results from congenital heart disease and …

Disparities In Liver Transplantation For Metabolic Dysfunction-Associated Steatohepatitis-Associated Hepatocellular Carcinoma, David W Victor, Sudha Kodali, Mazen Noureddin, Elizabeth W Brombosz, Analisa Lopez, Tamneet Basra, Edward A Graviss, Duc T Nguyen, Ashish Saharia, Ashton A Connor, Maen Abdelrahim, Yee Lee Cheah, Caroline J Simon, Mark J Hobeika, Constance M Mobley, R Mark Ghobrial

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly common, as is hepatocellular carcinoma (HCC) in the background of MASH. Liver transplantation (LT) provides superior long-term survival for patients with unresectable MASH-HCC, but not all patients have equal access to transplant. MASH-HCC disproportionately affects Hispanic patients, but minorities are less likely to undergo LT for HCC. Additionally, females also undergo LT at lower rates than males.

Aim: To investigate whether race/ethnicity and sex affect LT waitlist outcomes.

Methods: Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed. …

Dissecting The Effect Of Mitochondrial Bcat Inhibition In Methylmalonic Acidemia, Madeline G Hemmingsen, Guo-Fang Zhang, Yunhan Ma, Hannah Marchuk, Kalyani R Patel, Tong Chen, Xinning Li, Mark Chapman, Sabrina Collias, Dolores H Lopez-Terrada, James Beasley, Ashlee R Stiles, Randy J Chandler, Charles P Venditti, Sarah P Young, Mercedes Barzi, Beatrice Bissig-Choisat, Doug Krafte, Christopher B Newgard, Karl-Dimiter Bissig

Faculty, Staff and Students Publications

Methylmalonic acidemia (MMA) is a severe metabolic disorder affecting multiple organs because of a distal block in branched-chain amino acid (BCAA) catabolism. Standard of care is limited to protein restriction and supportive care during metabolic decompensation. Severe cases require liver/kidney transplantation, and there is a clear need for better therapy. Here, we investigated the effects of a small molecule branched-chain amino acid transaminase (BCAT) inhibitor in human MMA hepatocytes and an MMA mouse model. Mitochondrial BCAT is the first step in BCAA catabolism, and reduction of flux through an early enzymatic step is successfully used in other amino acid metabolic …

Direct Oral Anticoagulant Transition Strategies Using Anti-Xa Concentrations Upon Intensive Care Unit Admission, Mariah I Sigala, Corey V Dinunno, Chelsea N Lopez, Luma Succar, Jenny H Petkova, Edward A Graviss, Duc T Nguyen, Kevin R Donahue

Faculty, Staff and Students Publications

Background: The increased utilization of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of FXaI-specific anti-Xa concentrations. Critically ill populations are at risk of bleeding secondary to FXaI accumulation in the setting of end-organ dysfunction. To mitigate this risk, an FXaI anti-Xa concentration-guided approach to transitioning between oral and parenteral anticoagulation has been explored.

Objective: To compare the incidence of bleeding upon intensive care unit (ICU) admission between 2 different FXaI transition strategies: concentration versus non-concentration-guided.

Methods: We performed a retrospective chart review of patients admitted between January 2019 and May 2022 with …

Validation Of An Assay For Ngal In A Pediatric Population, Nazmin Bithi, Ridwan B Ibrahim, Estella L Tam, Radwa Almamoun, Annette C Frenk Oquendo, Ayse Akcan-Arikan, Sridevi Devaraj

Faculty, Staff and Students Publications

Background and objectives: Acute kidney injury (AKI) poses a serious clinical challenge, particularly in high-risk environments, due to its association with increased morbidity and mortality. Traditional diagnostic markers, such as serum creatinine, often detect AKI only after significant kidney damage has occurred, limiting opportunities for early intervention. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising early biomarker due to its rapid upregulation following kidney ischemia. NGAL supports renal recovery by reducing toxicity and promoting tubular regeneration via heme oxygenase-1 activity. This study aimed to validate the BioPorto ProNephro AKI™ turbidimetric immunoassay for urinary NGAL on the Ortho Vitros XT7600 …

Corrigendum To "Validation Of An Assay For Ngal In A Pediatric Population" [Practical Laboratory Medicine, Plabm 486, E00486], Nazmin Bithi, Ridwan B Ibrahim, Estella Tam, Radwa Almamoun, Annett C Frenk Oquendo, Ayse Akcan-Arikan, Sridevi Devaraj

Faculty, Staff and Students Publications

This corrects the article "Validation of an assay for NGAL in a pediatric population", e00486.

Acute Loss Of Tactile Input Leads To General Compensatory Changes In Eye-Hand Coordination During Object Manipulation, Kevin Ung, John F Magnotti, Brandon Kim, Jeffrey M Yau, Per F Nordmark

Faculty, Staff and Students Publications

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants …

Excision And Regional Flap Reconstruction With Radiation Therapy Of Granuloma Annulare Of The Digit: A Case Report, Austin Y Jiang, Linda K Green, David Netscher

Faculty, Staff and Students Publications

Granuloma annulare (GA) is a benign, often self-limited granulomatous skin condition that typically resolves spontaneously. Treatment is often not required, but topical and injectional corticosteroids are the most common interventions. Excision is effective for diagnosis and temporary treatment, but usually not considered curative. This case report describes the unconventional treatment of a recurrent biopsy-proven GA of the index finger. Due to the combination of the recalcitrant nodules interfering with function and patient preference, the nodules were excised multiple times. Ultimately requiring reconstruction with a pedicled radial forearm flap, the patient thereafter received radiation therapy to prevent recurrence, the combination of …