Digital Commons Network^™

Building A Better Clinical Competency Committee: A Multi-Institutional Approach To Improving The Quality Of Resident Feedback Through Appreciative Inquiry, Nikita Khetan, Emma Omoruyi, Elizabeth Hanson

Faculty, Staff and Student Publications

Background: The Accreditation Council for Graduate Medical Education (ACGME) requires pediatric faculty to convene twice yearly as a Clinical Competency Committee (CCC) to review resident performance and provide feedback. Variability in review processes and limited feedback quality remain common challenges. Incorporating Appreciative Inquiry within a Deliberate Practice framework may enhance the quality of summative feedback provided to residents.

Methods: This project was conducted with pediatric residents and faculty during the 2019-20 academic year at The University of Texas Health Science Center at Health San Antonio (UTHSA) and during the 2021-22 academic year at The University of Texas Health Science Center …

Circulating Biomarkers In Subjects With Progressive Pulmonary Fibrosis: Data From The Inbuild Trial, Toby M Maher, R Gisli Jenkins, Francesco Bonella, Shervin Assassi, Claudia Diefenbach, Carina Ittrich, Klaus B Rohr, Martin Kolb

Faculty, Staff and Student Publications

Background: We investigated the prognostic potential of circulating biomarkers at baseline and the effects of nintedanib on changes in these biomarkers in subjects with progressive pulmonary fibrosis (PPF).

Methods: In the INBUILD trial, subjects with PPF received nintedanib (n=332) or placebo (n=331). Associations between biomarker levels at baseline and the rate of forced vital capacity (FVC) decline (mL·year-1) over 52 weeks, time to interstitial lung disease (ILD) progression (absolute decline in FVC % predicted ≥10%) or death over 52 weeks, time to first acute exacerbation or death over the whole trial, and time to death over the whole trial were …

Isolated Immune-Mediated Enteritis In Patients Treated With Immune Checkpoint Inhibitor Therapy, Sharada Wali, Rohan Srinivas Patel, Maria Julia Moura Nascimento Santos, Anirudha Chatterjee, Sophia Chenyu Fan, Sean Ngo, Tanvi Gupta, Kian Abdul Baki, Lucie Heinzerling, Bryan J Schneider, Kathryn Bollin, Jessica Philpott, Anusha Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) commonly cause colitis, but isolated immune-mediated enteritis (IMEN) is poorly characterized. This study describes the clinical features, diagnostic findings, and outcomes of IMEN.

Method: We retrospectively identified adults with cancer who developed IMEN within one year of ICI initiation, confirmed as duodenitis, ileitis, or both.

Results: Among 20,991 ICI-treated patients, 30 (0.143%) developed isolated IMEN. Median age was 69.5 years; 73.3% were male, and 80% white. The most common malignancies were gastrointestinal/hepatobiliary (26.7%) and melanoma (23.3%). Presenting symptoms included nausea (66.7%), diarrhea (53.3%), and vomiting (46.7%); 62.5% of patients with diarrhea had grade ≥2 severity. …

Conduction Abnormalities After Tavi And Their Role In Patient Management: A Systematic Review, Ionuț Tudorancea, Irene Paula Popa, Mihai Ștefan Cristian Haba, Ștefan Popa, Viviana Onofrei, Dragomir Nicolae Șerban, Ionela Lăcrămioara Șerban, Irina Iuliana Costache-Enache, Radu Iliescu, Cătălin Loghin

Faculty, Staff and Student Publications

Objective: Transcatheter aortic valve implantation (TAVI) is associated with a relatively high incidence of permanent pacemaker implantation (PPM-I). We aimed to evaluate the existing literature on electrocardiographic (ECG) changes before and after TAVI, identify predictors for PPM-I, and suggest a standardized post-TAVI ECG monitoring protocol.

Methods: A systematic literature review was conducted across multiple databases, including PubMed, Web of Science, and JSTOR, to identify studies published between 2001 and 2024.

Results: From an initial pool of 24,170 records, 17 studies met the inclusion criteria. Pre-existing right bundle branch block and significant prolongation of ECG intervals were identified as strong predictors …

Erratum: Assessment Of Skin Fibrosis In A Murine Model Of Systemic Sclerosis With Multifunctional Optical Coherence Tomography (Erratum), Harshdeep Singh Chawla, Yanping Chen, Minghua Wu, Pavel Nikitin, Jessica Gutierrez, Chandra Mohan, Manmohan Singh, Salavat R Aglyamov, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

This corrects the article "Assessment of skin fibrosis in a murine model of systemic sclerosis with multifunctional optical coherence tomography" in volume 30(3), 036007.

Overcoming Stigma In Women's Hiv And Syphilis Care: The Role Of Faith In Healing, Irene A Stafford, Phillip C Johnson, Robin L Beach

Faculty, Staff and Student Publications

Point-of-care (POC) testing for syphilis and HIV is an effective way to provide same-day testing, results management, counseling, and treatment. Although commonly used in antenatal or sexual health clinics, our field study aimed to offer POC testing to women attending a standard care clinic in Guatemala. Nearly all women accepted testing, highlighting the patient-centered benefits and acceptability of screening in non-stigmatizing settings. Upon disclosure of results, especially positive diagnoses, patients drew comfort and resilience from their faith, an often-underprioritized resource not typically considered when addressing sexual health. These results underscore the value of integrating POC testing into routine care and …

Risk Factors And Outcomes Of Reintubation Following Combined Heart-Lung Transplantation, Ye In Christopher Kwon, Michael Keller, Alan Lai, Brian Bao, Joshua Pei, Matthew Ambrosio, Jay Patel, Motaz Al-Yafi, Zachary Fitch, Josue Chery, Patricia Nicolato, Vigneshwar Kasirajan, Zubair A Hashmi

Faculty, Staff and Student Publications

Background: Unplanned reintubation after combined heart-lung transplantation (HLT) significantly affects morbidity and mortality, yet national data are limited. We evaluated the incidence, predictors, timing, and outcomes associated with reintubation after HLT.

Methods: We retrospectively reviewed adults undergoing primary HLT in the UNOS registry from January 2004 to September 2024. Patients were stratified by reintubation status (defined as re-established mechanical ventilation (MV) after initial extubation). Propensity matching (1:1) balanced recipient and donor characteristics. Multivariable logistic regression models identified independent risk factors.

Results: Among 609 adult HLT recipients, 165 (27.1%) required postoperative reintubation. After 1:1 propensity score matching, 146 patients who were …

Rituximab For The Treatment Of Immune Checkpoint Inhibitor-Induced Glomerulonephritis, Yazen Alasadi, Juan Cintron Garcia, Naszrin Arani, Valda Page, Yimin Geng, Clark R Andersen, Amanda Tchakarov, Abhijat Kitchlu, Omar Mamlouk, Ala Abudayyeh

Faculty, Staff and Student Publications

Background: Among patients receiving immune checkpoint inhibitor (ICI) therapy, the most common renal immune-related adverse event is interstitial nephritis, which is caused by severe T-cell infiltration and is typically responsive to steroids; although rarer, autoimmune induction in the kidney has also been reported. There is a paucity of data regarding ICI-induced autoimmune disease in the kidney and the challenges associated with continuing ICI therapy. Here, we present a single center case series of ICI-induced glomerulonephritis with data on treatment rechallenge.

Methods: We retrospectively reviewed 241 patients who underwent kidney biopsies at our institution between 2015 and 2024 and identified those …

Collision Tumors Involving Metastatic Carcinoma And Plasma Cell Myeloma: Report Of Two Cases, Ahmed A Ahmed, Muhammad Hassaan Khalid, Asad Ur Rehman, Nghia D Nguyen, Xinhai Robert Zhang

Faculty, Staff and Student Publications

Synchronous coexistence of plasma cell neoplasms (PCNs) and metastatic carcinoma is not a common phenomenon and poses a significant diagnostic challenge requiring meticulous histopathological and immunophenotypic analysis for accurate lineage assignment. We report two cases of collision tumors comprising PCN and metastatic lung carcinoma. Case 1 involved a 68-year-old male with metastatic non-small cell lung adenocarcinoma who developed intracranial lesions; resection revealed metastatic adenocarcinoma intermingled with clonal plasma cells. Case 2 was a 73-year-old woman with a lytic iliac crest lesion whose bone marrow and lesion biopsies showed diffuse infiltration by both carcinoma and atypical plasma cells. Comprehensive immunohistochemical profiling, …

“Do Everything” Versus Realistic Surgical Interventions: Navigating The Road To Shared Decision-Making In Trauma Surgery, Victoria E Wagner, Ashna S Karpe, Martin L Blakely, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

"DO EVERYTHING!!" How many times have you heard that phrase from a distressed family member? We routinely receive this desperate plea, and our knee-jerk reaction is to press on, push harder, be more aggressive. We, as acute care surgeons, have spent our lives learning a craft geared towards "doing everything" to heal patients so this response comes naturally. However, how do we respond to "do everything" when the probability of a meaningful recovery is extremely low or non-existent? These situations create moral tension for surgeons who must reconcile the desire to preserve life with the obligation to avoid harm, respect …

Neural Correlates Of Cognitive Fatigue In Regular Cannabis Users And Non-Users: A Pilot Fnirs Study, Mariia Vistyzenko

Theses and Dissertations (Comprehensive)

Background: Cognitive fatigue impairs performance across multiple domains, yet how regular cannabis use affects fatigue responses remains unclear. This pilot study investigated neural and behavioural correlates of cognitive fatigue in abstinent cannabis users versus non-users.

Methods: Twenty-six participants (18 non-users, 8 regular cannabis users after 24-hour abstinence) completed cognitive tasks before and after a 60-minute Sustained Attention to Response Task (SART) designed to induce fatigue. Tasks assessed working memory (N-Back), cognitive flexibility (Wisconsin Card Sorting), psychomotor speed (Digit Symbol Substitution), sustained attention (Continuous Performance Task), inhibition (Stroop, Stop Signal), and motion perception. Functional near-infrared spectroscopy (fNIRS) continuously monitored prefrontal cortex …

Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani

Faculty, Staff and Student Publications

This is a comprehensive review on current utilization and challenges of digital pathology adoption in clinical trials and aims to provide a broad view on its impact on pathology review processes in clinical trials. It provides an overview of current pathology review practices in clinical trials and unique advantages digital pathology adoption can offer. The key areas including existing workflows, use case scenarios in different disease areas in clinical trials, including but not limited to patient identification and pre-screening, and regulatory aspects have been described with relevance. In addition, the review delves into the integration of genomics, AI, image analysis, …

Ultra-Processed Foods And The Cardiovascular-Kidney-Metabolic Continuum: Integrating Epidemiological, Multi-Omics, And Translational Evidence, Saiful Singar, Amirhossein Ataei Kachouei, Leandro Lantigua-Somoano, David Manley, Anthony Cardinale, Muhammad Zulfiqah Sadikan, Saurabh Kadyan, Donya Shahamati, Lorena Dias, Amber Wood, Cinthia Chavarria, Sara K. Rosenkranz, Neda S. Akhavan

Department of Medicine Faculty Publications

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently …

Application Of The Lancet Commission Criteria For The Diagnosis Of Obesity To A Clinical Trials Population: The Leap Trial, Faith Anne N Heeren, Kathleen R Ruddiman, Courtney Simmons, Brian N White, Byron C Jaeger, Nicholas M Pajewski, Stephanie A Hooker, Deborah B Horn, Katy Martin-Fernandez, Kimberly A Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis

Faculty, Staff and Student Publications

Objective: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.

Methods: The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with "no obesity," "pre-clinical obesity," and "clinical obesity."

Results: Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m2 [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m2 [SD …

Physical Activity, Telomere Length, And Cardiometabolic Syndrome In Older Women: The Cardiovascular Health Study, Jeni Page, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Michelle C Odden, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background: Cardiometabolic syndrome (CMS) affects approximately 39% of US women and increases risk for cardiovascular disease, diabetes, and stroke. Telomere length, a biomarker of cellular aging, is associated with CMS and may be influenced by physical activity (PA), potentially mitigating telomere shortening. Black women have higher CMS prevalence compared to white women and may exhibit distinct telomere length dynamics influenced by interactions between CMS and PA.

Methods: Data were drawn from the Cardiovascular Health Study and included black and white women who provided data on PA, CMS risk factors, and telomere length (N = 417). Linear regression models examined the …

Combating Antibiotic Resistance With Plasmid-Dependent Phages, Rhiannon T. Mariano

Electronic Theses & Dissertations (2024 - present)

The alarming rise of carbapenem-resistant bacteria poses an urgent global health threat, driven in large part by the horizontal spread of carbapenemase-encoding plasmids (Ma et al., 2023). These plasmids are often highly mobile and transmissible, enabling rapid dissemination of resistance genes across diverse bacterial populations. Their mobility is largely mediated by conjugation, a process dependent on the formation of pili, which serve as physical bridges for plasmid transfer between cells (Murray et al. 2022; San Millan and MacLean 2017; Virolle et al. 2020). Beyond their role in gene exchange, these pili also act as entry points for a unique class …

Evaluating The Impact Of Telemedicine-Based Medication Education On Glycemic Control In Adult Male Veterans With Type 2 Diabetes Mellitus, Megan N. Calter

West Chester University Graduate Theses, Dissertations, and Final Projects

Veterans experience disproportionately high rates of type 2 diabetes mellitus (20.5% vs 11.6% nationally), driven by military-related factors such as PTSD, deployment-related obesity, and service-connected disabilities. At a large urban primary care clinic, 28% (40/141) of veterans with type 2 diabetes mellitus had persistently elevated HbA1c levels of ≥8%, indicating a high risk for diabetes-related complications. This quality improvement project aimed to reduce the proportion of veterans with HbA1c of ≥8% by implementing tailored telemedicine-based medication education, leveraging underutilized virtual care infrastructure to address access barriers and improve diabetes self-management. Participants received two 30-minute telemedicine medication and disease management education …

Genome-Wide Association Study Identifies And Validates Genetic Variation In The Rig-I/Mavs Signaling Pathway Associated With Hiv-Related Kaposi Sarcoma In Children And Adults, Casey L Mcatee, Erin Peckham-Gregory, Pagna Sok, Melissa Richard, Luis Olivares, Deborah Marquez-Do, Grace Kisitu, Jeffrey Martin, Nader Kim El-Mallawany, Carl E Allen, Joseph Lubega, Michael E Scheurer

Faculty, Staff and Students Publications

Introduction: Immune deficiency and infection with human herpesvirus-8 (HHV-8) are established component causes of Kaposi sarcoma (KS), but they are insufficient to cause disease in most people at risk. Therefore, we hypothesized that genetic variation may contribute to KS risk in children and adults, as well as contribute to its unique epidemiology in sub-Saharan Africa.

Methods: To test this hypothesis, we conducted a two-phase genome-wide association study (GWAS): a discovery study in perinatally HIV-infected children (45 KS cases, 91 controls), followed by validation of significant results in a sample of adults living with HIV (215 cases, 262 controls). After standard …

A Comprehensive Overview Of Neurophysiological Correlates Of Cognitive Impairment In Amyotrophic Lateral Sclerosis, Seyyed Bahram Borgheai, Brie E. Achorn, Alyssa H. Zisk, Sarah M. Hosni, Karl E. G. Richter, Frank S. Menniti, Yalda Shahriari

Computer Science Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the gradual loss of motor control, typically resulting in paralysis and death within 3 to 5 years of diagnosis. ALS shares neuropathological and genetic associations with fronto-temporal dementia (FTD), a neurodegenerative condition primarily impacting cognitive functions. These two conditions are increasingly viewed as manifestations of a single molecular disease process that affects distinct brain systems, impacting motor neuronal pathways in ALS and fronto-cortical functions in FTD. However, this simple dichotomy belies the complexity of these conditions. In particular, patients with primary motor ALS can also experience significant cognitive …

Perspective: Radiotherapy And Body Composition: Unmet Needs In Low- And Middle-Income Countries, Alexia J Murphy-Alford, Aaron J Grossberg, Vickie E Baracos, Maha Barbar, Judy Bauer, Jonathan P Bennett, Elena Fidarova, Clifton D Fuller, Anastassia Löser, Amy C Moreno, Anurima Patra, Deepa Puttaswamy, David I Rosenthal, Judy Schoeman, Yavuz Anacak

Faculty, Staff and Student Publications

Radiotherapy plays a vital role in cancer treatment, yet its effects on patients' nutritional status can precipitate muscle loss, with significant implications for treatment tolerance and outcomes. Evidence from high-income countries increasingly links radiation-induced muscle loss to adverse clinical outcomes. In contrast, low- and middle-income countries face a stark evidence gap, despite the heightened vulnerability of cancer patients in these settings due to delayed diagnosis, limited access to care, and high rates of co-morbidities. This paper highlights the critical gaps in nutritional care for radiotherapy patients in low- and middle-income countries.

Genomic Determinants Of Response And Resistance To Pirtobrutinib In Relapsed/Refractory Chronic Lymphocytic Leukemia, Jennifer R Brown, Bastien Nguyen, Sai Prasad Desikan, Helen Won, Shady I Tantawy, Samuel C Mcneely, Narasimha Marella, Hetal S Randeria, Lauren M Hanson, Andrew Parker, Salomé Calado Botelho, Jennifer A Woyach, Krish Patel, Constantine S Tam, Toby A Eyre, Chan Y Cheah, Nirav N Shah, Paolo Ghia, Wojciech Jurczak, Minna Balbas, Binoj Nair, Paolo Abada, Chunxiao Wang, Denise Wang, Lindsey E Roeker, Varsha Gandhi, William G Wierda

Faculty, Staff and Student Publications

Pirtobrutinib, a noncovalent, reversible Bruton tyrosine kinase inhibitor (BTKi), demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), resistant to covalent BTKi (cBTKi). We analyzed genomic correlations with response and resistance to pirtobrutinib in relapsed/refractory (R/R) patients with CLL pretreated with cBTKi enrolled in the phase 1/2 BRUIN trial. DNA sequencing was performed on peripheral blood mononuclear cells at baseline, on treatment, and at progressive disease (PD). Common alterations at baseline included mutations in BTK (43%), TP53 (38%), SF3B1 (25%), NOTCH1 (23%), ATM (19%), XPO1 (11%), PLCG2 (9%), BCL2 (8%), and 17p deletion (28%). Common baseline BTK mutations included C481S …

Metastasis-Directed Radiotherapy For Oligometastatic Urothelial Carcinoma Of The Bladder And Upper Tract, Patrick Carriere, Omar Alhalabi, Jianjun Gao, Amishi Shah, Sangeeta Goswami, Matthew Campbell, Ruitao Lin, Lauren Mayo, Osama Mohamad, Karen Hoffman, Henry Mok, Charmaigne Lozano, Ashish Kamat, Neema Navai, Kelly Bree, Byron Lee, Charles Guo, Michael Rooney, Chad Tang, Seungtaek Choi, Comron Hassanzadeh

Faculty, Staff and Student Publications

Background: Metastasis-directed therapy (MDT) for oligometastatic cancer is utilized for genitourinary malignancies including prostate and kidney cancers. Clinical research on MDT for urothelial carcinoma (UC) remains sparse, especially as systemic therapy advances have improved outcomes.

Objective: We investigated the role of MDT, specifically radiotherapy, for patients with oligometastatic bladder or upper-tract UC.

Methods: Data were collated on patients with metastatic UC with 5 or fewer metastatic sites undergoing MDT with ablative radiotherapy with or without preceding systemic therapy during January 2016 to July 2024. Endpoints were progression-free survival (PFS), and overall survival (OS). Cox proportional hazards analysis was conducted to …

The Effects Of Fitness Self-Testing With Instant Feedback On Changes In Health-Related Fitness Among Chinese Male College Students, Yongshun Wang, Xiaofen D Hamilton, Rulan Shangguan, Anlu Yang, Na Xiao, Chenhao Wu, Sizhe Liu, Ren Yang, Jiren Zhang, Mark F Hamilton

Faculty, Staff and Student Publications

Background: The decline in health-related physical fitness resulting from physical inactivity remains a critical global public health concern. Technology-supported fitness self-testing has the potential not only to improve students' testing experiences but also to enhance their health-related fitness. However, the effectiveness of such approaches has not yet been systematically examined, and their validity within university populations remains largely unestablished.

Method: A quasi-experimental research design with a control group (n = 45) and an experimental group (n = 44), incorporating pre- and post-tests, was employed in this study. The experimental group completed monthly self-testing sessions accompanied by GAI-generated instant feedback over …

The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra

Faculty, Staff and Student Publications

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …

Contralateral Breast Cancer After Radiotherapy And Hormone Therapy In Two Cohorts Of Us Breast Cancer Survivors, Lene H S Veiga, Gretchen L Gierach, Susan A Smith, Rebecca M Howell, Matthew M Mille, Monjoy Saha, Rochelle E Curtis, Cody Ramin, Clara Bodelon, Heather Spencer Feigelson, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Jacqueline B Vo, Choonsik Lee, Amy Berrington De Gonzalez

Faculty, Staff and Student Publications

Background: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

Methods: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use.

Results: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); SEER cohort (n = 244,834) included 10,470 cases (72% ER+). Among women with ER+ …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

Trial Interviews To Explore Glycogen Storage Disease Type Ia Patient Experiences Following Gene Therapy, Diane M Turner-Bowker, Jessica Butler, Shayna Egan, David A Weinstein, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, Rebecca Riba-Wolman, John J Mitchell, Christina Theodore-Oklota

Faculty, Staff and Student Publications

Background: Glycogen storage disease type Ia (GSDIa) is a rare, inherited, autosomal recessive deficiency of glucose-6-phosphatase (G6Pase), an enzyme necessary in glycogenolysis and gluconeogenesis. To maintain normal blood glucose levels and ensure survival, individuals living with GSDIa must frequently consume complex carbohydrates (eg, uncooked cornstarch). Dietary management can result in chronic complications and significant patient burden. DTX401 (pariglasgene brecaparvovec) is an investigational adeno-associated virus serotype 8 vector (AAV8)-based gene therapy designed to restore endogenous glucose production.

Objectives: Patient experience interviews were conducted as part of an open-label, phase 1/2 dose-escalation trial (NCT03517085) evaluating the safety and efficacy of …

Evaluation Of Organ-Specific Relative Biological Effectiveness Of Proton Therapy Using Radiation-Induced Pneumonitis As An Endpoint, Li Liao, Ting Xu, Mei Chen, Tingshi Su, Narayan Sahoo, Xiaorong Zhu, Steven J Frank, Quynh-Nhu Nguyen, Zhongxing Liao, Xiaodong Zhang

Faculty, Staff and Student Publications

Background and purpose: Proton therapy has become widely used for non-small cell lung cancer (NSCLC) due to its ability to spare normal tissue. However, the commonly assumed relative biological effectiveness (RBE) of 1.1 may underestimate the therapy's true biological effects on lung, potentially leading to a higher than expected incidence of radiation-induced pneumonitis (RP). In this retrospective study, we evaluated the variability of organ-specific RBE of proton therapy using RP grade 2 or higher (RP2+) as an endpoint.

Materials and methods: Data from 270 NSCLC patients across two clinical trials were analyzed, with 134 given photon therapy and 136 given …

Dietetic Guidance For Nutritional Management Of People With Phenylketonuria Receiving Sepiapterin, Anita Macdonald, Kirsten Ahring, Alexa Bledsoe, Hiroki Fujimoto, Sara Giorda, Christian Kogelmann, Jessica Kopesky, Laura Nagy, Sara O'Neill, Alex Pinto, Soraia Poloni, Paige Roberts, Annemiek M J Van Wegberg, Suzanne Hollander

Faculty, Staff and Student Publications

Background/objectives: Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. If untreated, elevated blood phenylalanine (Phe) levels lead to neurological and behavioral impairments. Phe levels can be managed through a lifelong Phe-restricted diet; however, this can be challenging to maintain. Sepiapterin is an adjunct therapy for PKU that has shown efficacy in reducing blood Phe levels in both tetrahydrobiopterin (BH4)-responsive and BH4-non-responsive people with PKU in clinical trials. Practical guidance is needed for dietitians and other healthcare professionals supporting the dietary management of people with PKU who are initiating or receiving sepiapterin.

Methods: A group of international dietitians participated …

Infliximab For Grade Iii Or Iv Immune Checkpoint Inhibitor Nephritis Clinical And Translational Evidence, Nada Youssef, Masroor Habeeb, Hong Chen, Zainab Alhamal, Omar Mamlouk, Heather Lin, Valda Page, Amanda Tchakarov, Sreyashi Basu, Adi Diab, Padmanee Sharma, Ala Abudayyeh

Faculty, Staff and Student Publications

Introduction: Acute interstitial nephritis (AIN) is a common presentation of immune checkpoint inhibitor (ICI) toxicity. Increased tumor necrosis factor (TNF)-α expression has been observed in ICI-induced AIN (ICI-AIN). In this study, we compared treatment with glucocorticoids plus infliximab to glucocorticoids only in stage III or IV ICI-AIN. We conducted retrospective NanoString analysis of ICI-exposed kidney samples to identify associated gene signatures and possible association with TNF-α expression.

Methods: We reviewed the records of patients who received ICI, developed acute kidney injury (AKI), and underwent kidney biopsy at MD Anderson Cancer Center from January 2022 to October 2024. Fifty-five patients had …