Medicine and Health Sciences Commons^™

Development And Standardization Of An Osteoradionecrosis Classification System In Head And Neck Cancer: Implementation Of A Risk-Based Model, Erin E Watson, Katrina Hueniken, Junhyung Lee, Shao Hui Huang, Amr El Maghrabi, Wei Xu, Amy C Moreno, C Jillian Tsai, Ezra Hahn, Andrew J Mcpartlin, Christopher M K L Yao, David P Goldstein, John R De Almeida, John N Waldon, Clifton D Fuller, Andrew J Hope, Salvatore L Ruggiero, Michael Glogauer, Ali A Hosni

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.

Methods: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity …

Dyadic Yoga For Head And Neck Cancer Patients Undergoing Chemoradiation And Their Family Caregivers, Kathrin Milbury, David I Rosenthal, Yisheng Li, An Thuy Ngo-Huang, Smitha Mallaiah, Sania Yousuf, Clifton D Fuller, Carol Lewis, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Objectives: Concurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants.

Methods: HNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. …

Prospective Performance Of The Iwg-2023 Criteria And Ipss-M In A Phase 2 Trial Of Guadecitabine For Higher-Risk Mds Or Cmml, Samuel Urrutia, Prithviraj Bose, Yesid Alvarado, Gautam Borthakur, Farhad Ravandi, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Koichi Takahashi, Tapan Kadia, Courtney Dinardo, Steven Kornblau, Rashmi Kanagal-Shamanna, Xuelin Huang, Kristy Bodden, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had TP53 mut . By the International Working Group …

Automated Spontaneous Echo Contrast Detection Using A Multisequence Attention Convolutional Neural Network, Ouwen Huang, Zewei Shi, Naveen Garg, Corey Jensen, Mark L Palmeri

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OBJECTIVE: Spontaneous echo contrast (SEC) is a vascular ultrasound finding associated with increased thromboembolism risk. However, identification requires expert determination and clinician time to report. We developed a deep learning model that can automatically identify SEC. Our model can be applied retrospectively without deviating from routine clinical practice. The retrospective nature of our model means future works could scan archival data to opportunistically correlate SEC findings with documented clinical outcomes.

METHODS: We curated a data set of 801 archival acquisitions along the femoral vein from 201 patients. We used a multisequence convolutional neural network (CNN) with ResNetv2 backbone and visualized …

Immune Checkpoint Blockade Resistance In Lung Cancer: Emerging Mechanisms And Therapeutic Opportunities, Jessica M Konen, Haoyi Wu, Don L Gibbons

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) therapy works by inhibiting suppressive checkpoints that become upregulated after T cell activation, like PD-1/PD-L1 and CTLA-4. While the initial FDA approvals of ICB have revolutionized cancer therapies and fueled a burgeoning immuno-oncology field, more recent clinical development of new agents has been slow. Here, focusing on lung cancer, we review the latest research uncovering tumor cell intrinsic and extrinsic ICB resistance mechanisms as major hurdles to treatment efficacy and clinical progress. These include genomic and non-genomic tumor cell alterations, along with host and microenvironmental factors like the microbiome, metabolite accumulation, and hypoxia. Together, these factors …

Utilization Of Biologic Disease-Modifying Antirheumatic Therapy In Patients With Rheumatoid Arthritis And Recently Diagnosed Breast Cancer, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Sharon H Giordano, Suja S Rajan, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Objective: Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis.

Methods: We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after …

Prostein Expression On Circulating Tumor Cells As A Prognostic Marker In Metastatic Castration-Resistant Prostate Cancer, Zhenchao Zhang, Rui Luo, William K Kelly, Joshua Chen, Shane Donahue, Kevan Ip, Nathan R Handley, William J Tester, Miranda L Tsang, Felix J Kim, Ronald Myers, Grace Lu-Yao, Jian Gu, Jianqing Lin, Bingshan Li, Chun Wang, Hushan Yang

Faculty, Staff and Student Publications

Background: Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC.

Methods: CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival …

Cardiovascular Disease In Childhood, Adolescent, And Young Adult Cancer Survivors: The Impact Of Family History Of Premature Heart Disease, Amy M Berkman, Clark R Andersen, Andrew P Landstrom, Michelle A T Hildebrandt, Susan C Gilchrist, Michael E Roth

Faculty, Staff and Student Publications

No abstract provided.

Deformable Motion Compensation In Interventional Cone-Beam Ct With A Context-Aware Learned Autofocus Metric, Heyuan Huang, Yixuan Liu, Jeffrey H Siewerdsen, Alexander Lu, Yicheng Hu, Wojciech Zbijewski, Mathias Unberath, Clifford R Weiss, Alejandro Sisniega

Faculty, Staff and Student Publications

Purpose: Interventional Cone-Beam CT (CBCT) offers 3D visualization of soft-tissue and vascular anatomy, enabling 3D guidance of abdominal interventions. However, its long acquisition time makes CBCT susceptible to patient motion. Image-based autofocus offers a suitable platform for compensation of deformable motion in CBCT, but it relies on handcrafted motion metrics based on first-order image properties and that lack awareness of the underlying anatomy. This work proposes a data-driven approach to motion quantification via a learned, context-aware, deformable metric, VIFDL , that quantifies the amount of motion degradation as well as the realism of the structural anatomical content in the image. …

Novel Cancer Prevention Strategies In Individuals With Hereditary Cancer Syndromes: Focus On Brca1, Brca2, And Lynch Syndrome, Charles M Bowen, Kaitlin Demarest, Eduardo Vilar, Payal D Shah

Faculty, Staff and Student Publications

Germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation strategies have focused on pharmacologic risk reduction, enhanced surveillance, and preventive surgeries. While these approaches can be effective, they stand to be improved on because of either limited efficacy or undesirable impact on quality of life. The current review summarizes ongoing investigational efforts in cancer risk prevention strategies for patients with germline PVs in BRCA1, BRCA2, or LS-associated …

Author Correction: Concurrent Intrathecal And Intravenous Nivolumab In Leptomeningeal Disease: Phase 1 Trial Interim Results, Isabella C Glitza Oliva, Sherise D Ferguson, Roland Bassett, Alexandra P Foster, Ida John, Tarin D Hennegan, Michelle Rohlfs, Jessie Richard, Masood Iqbal, Tina Dett, Carol Lacey, Natalie Jackson, Theresa Rodgers, Suzanne Phillips, Sheila Duncan, Lauren Haydu, Ruitao Lin, Rodabe N Amaria, Michael K Wong, Adi Diab, Cassian Yee, Sapna P Patel, Jennifer L Mcquade, Grant M Fischer, Ian E Mccutcheon, Barbara J O'Brien, Sudhakar Tummala, Matthew Debnam, Nandita Guha-Thakurta, Jennifer A Wargo, Fernando C L Carapeto, Courtney W Hudgens, Jason T Huse, Michael T Tetzlaff, Elizabeth M Burton, Hussein A Tawbi, Michael A Davies

Faculty, Staff and Student Publications

No abstract provided.

Endothelial Knockdown Of The Tumor Suppressor, Wwox, Increases Inflammation In Ventilator-Induced Lung Injury, Zhenguo Zeng, Eltyeb Abdelwahid, Weiguo Chen, Christian Ascoli, Trinh Pham, Jeffrey R Jacobson, Steven M Dudek, Viswanathan Natarajan, C Marcelo Aldaz, Roberto F Machado, Sunit Singla

Faculty, Staff and Student Publications

Chronic cigarette smoke exposure decreases lung expression of WWOX which is known to protect the endothelial barrier during infectious models of acute respiratory distress syndrome (ARDS). Proteomic analysis of WWOX-silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). WWOX-silenced ECs as well as those isolated from endothelial cell Wwox knockout (EC Wwox KO) mice were subjected to cyclic stretch (18% elongation, 0.5 Hz, 4 h). Cellular lysates and media supernatant were harvested for assays of cellular signaling, protein expression, and cytokine release. These were repeated with dual silencing of WWOX and zyxin. Control and …

Venetoclax And Cobimetinib In Relapsed/Refractory Aml: A Phase 1b Trial, Marina Y Konopleva, Monique Dail, Naval G Daver, Jacqueline S Garcia, Brian A Jonas, Karen W L Yee, Kevin R Kelly, Norbert Vey, Sarit Assouline, Gail J Roboz, Stefania Paolini, Daniel A Pollyea, Agostino Tafuri, Joseph M Brandwein, Arnaud Pigneux, Bayard L Powell, Pierre Fenaux, Rebecca L Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Diana R Dunshee, Habib Hamidi, Marion G Ott, Wan-Jen Hong, Michael Andreeff

Faculty, Staff and Student Publications

Background: Therapies for relapsed/refractory acute myeloid leukemia remain limited and outcomes poor, especially amongst patients who are ineligible for cytotoxic chemotherapy or targeted therapies.

Patients and methods: This phase 1b trial evaluated venetoclax, a B-cell lymphoma-2 (BCL-2) inhibitor, plus cobimetinib, a MEK1/2 inhibitor, in patients with relapsed/refractory acute myeloid leukemia, ineligible for cytotoxic chemotherapy. Two-dimensional dose-escalation was performed for venetoclax dosed daily, and for cobimetinib dosed on days 1-21 of each 28-day cycle.

Results: Thirty patients (median [range] age: 71.5 years [60-84]) received venetoclax-cobimetinib. The most common adverse events (AEs; in ≥40.0% of patients) were diarrhea (80.0%), nausea (60.0%), vomiting …

Barriers To The Assessment And Recommendation Of Hpv Vaccination Among Healthcare Providers In Texas, Onyema G Chido-Amajuoyi, Ikponmwosa Osaghae, Henry K Onyeaka, Sanjay Shete

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BACKGROUND: Healthcare providers (HCPs) recommendations for HPV vaccination plays a critical role in increasing vaccination uptake. This study assesses the prevalence of reported barriers to HPV vaccination assessment and recommendation among HCPs in Texas.

METHODS: Study data were obtained from a population-based survey of HCPs currently practicing in Texas. Participants were asked about their HPV vaccination assessment and recommendation practices and the reasons for not assessing or recommending the vaccine. Barriers were stratified by HCP characteristics including age, sex, race/ethnicity, location of practice, provider type, and type of facility.

RESULTS: Among the 826 HCPs included in this study, 47.3 % …

A Bayesian Quasi-Likelihood Design For Identifying The Minimum Effective Dose And Maximum Utility Dose In Dose-Ranging Studies, Feng Tian, Ruitao Lin, Li Wang, Ying Yuan

Faculty, Staff and Student Publications

Most existing dose-ranging study designs focus on assessing the dose-efficacy relationship and identifying the minimum effective dose. There is an increasing interest in optimizing the dose based on the benefit-risk tradeoff. We propose a Bayesian quasi-likelihood dose-ranging design that jointly considers safety and efficacy to simultaneously identify the minimum effective dose and the maximum utility dose to optimize the benefit-risk tradeoff. The binary toxicity endpoint is modeled using a beta-binomial model. The efficacy endpoint is modeled using the quasi-likelihood approach to accommodate various types of data (e.g. binary, ordinal or continuous) without imposing any parametric assumptions on the dose-response curve. …

Adaptive Bayesian Information Borrowing Methods For Finding And Optimizing Subgroup-Specific Doses, Jingyi Zhang, Ruitao Lin, Xin Chen, Fangrong Yan

Faculty, Staff and Student Publications

In precision oncology, integrating multiple cancer patient subgroups into a single master protocol allows for the simultaneous assessment of treatment effects in these subgroups and promotes the sharing of information between them, ultimately reducing sample sizes and costs and enhancing scientific validity. However, the safety and efficacy of these therapies may vary across different subgroups, resulting in heterogeneous outcomes. Therefore, identifying subgroup-specific optimal doses in early-phase clinical trials is crucial for the development of future trials. In this article, we review various innovative Bayesian information-borrowing strategies that aim to determine and optimize subgroup-specific doses. Specifically, we discuss Bayesian hierarchical modeling, …

Comparative Analysis Of Brain Language Templates With Primary Language Areas Detected From Presurgical Fmri Of Brain Tumor Patients, Jina Lee, Vinodh A Kumar, Jian Ming Teo, Rami W Eldaya, Ping Hou, Kyle R Noll, Sherise D Ferguson, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

INTRODUCTION: Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients.

METHODS: Four language templates (A-D) based on anatomy, task-based fMRI, resting-state fMRI, and meta-analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by …

Salpingectomy For Ovarian Cancer Prevention: Video Education For The Surgeon, Emily Macarthur, Kara Long Roche, Joseph Sakran, Sunil H Patel, Peter Najjar, Karen H Lu, Megan Gornet, Anja S Frost, Meghan Walrath, Tom Bauer, Gyyong Oh, Rebecca Stone

Faculty, Staff and Student Publications

Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on …

Longitudinal Changes In The Carotid Arteries Of Head And Neck Cancer Patients Following Radiation Therapy: Results From A Prospective Serial Imaging Biomarker Characterization Study, Efstratios Koutroumpakis, Abdallah Sherif Radwan Mohamed, Peter Chaftari, David I Rosenthal, Dorothy Gujral, Christopher Nutting, Serageldin Kamel, Mohamed A Naser, Peter Kim, Roland Bassett, Clifton D Fuller, Elie Mouhayar, Md Anderson Head Neck Radiation Oncology Cardiovascular Working Group

Faculty, Staff and Student Publications

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer.

METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated.

RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; …

Dietary Fiber And Gut Bacteria Shape Infection Susceptibility, Aqsa Mohammed, Robert R Jenq

Faculty, Staff and Student Publications

Gut microbiota composition has been reported to affect pathogen susceptibility but its specific effects, the underlying mechanisms and the potential influence of the diet remain unexplored. In their recent study, Desai and colleagues (Wolter et al, 2024), explore the complex interaction between diet, the gut microbiota and pathogen susceptibility, highlighting a diet-dependent role of the mucin-degrading microbe Akkermansia muciniphila.

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma\, Angela E Alnemri, Sruti Tekumalla, Annie E Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David M Cognetti, Joseph M Curry, Athanassios Argiris, Alban Linnenbach, Andrew P South, Larry A Harshyne, Jennifer M Johnson, Adam J Luginbuhl

Faculty, Staff and Student Publications

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

Stmnd1 Is A Phylogenetically Ancient Stathmin Which Localizes To Motile Cilia And Exhibits Nuclear Translocation That Is Inhibited When Soluble Tubulin Concentration Increases, Xiang Deng, Bryan O Seguinot, Gary Bradshaw, Jong Suk Lee, Shannon Coy, Marian Kalocsay, Sandro Santagata, Timothy Mitchison

Faculty, Staff and Student Publications

Stathmins are small, unstructured proteins that bind tubulin dimers and are implicated in several human diseases, but whose function remains unknown. We characterized a new stathmin, STMND1 (Stathmin Domain Containing 1) as the human representative of an ancient subfamily. STMND1 features a N-terminal myristoylated and palmitoylated motif which directs it to membranes and a tubulin-binding stathmin-like domain (SLD) that contains an internal nuclear localization signal. Biochemistry and proximity labeling showed that STMND1 binds tubulin, and live imaging showed that tubulin binding inhibits translocation from cellular membranes to the nucleus. STMND1 is highly expressed in multiciliated epithelial cells, where it localizes …

A Phase I Study Of Tak-659 And Paclitaxel In Patients With Taxane-Refractory Advanced Solid Tumors, M A Gouda, J Shunyakova, A Naing, E Dumbrava, D S Hong, Y Yuan, P Yang, A Myers, Y Liang, J Peng, D Karp, A M Tsimberidou, J Rodon, T A Yap, S A Piha-Paul, F Meric-Bernstam, S Fu

Faculty, Staff and Student Publications

BACKGROUND: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.

PATIENTS AND METHODS: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients …

Associations Between Radiation Oncologist Demographic Factors And Segmentation Similarity Benchmarks: Insights From A Crowd-Sourced Challenge Using Bayesian Estimation, Kareem A Wahid, Onur Sahin, Suprateek Kundu, Diana Lin, Anthony Alanis, Salik Tehami, Serageldin Kamel, Simon Duke, Michael V Sherer, Mathis Rasmussen, Stine Korreman, David Fuentes, Michael Cislo, Benjamin E Nelms, John P Christodouleas, James D Murphy, Abdallah S R Mohamed, Renjie He, Mohammed A Naser, Erin F Gillespie, Clifton D Fuller

Faculty, Staff and Student Publications

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors.

METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference …

Current Methods For Hyperpolarized [1-Current Methods For Hyperpolarized [1-13c]Pyruvate Mri Human Studies, Peder E Z Larson, Jenna M L Bernard, James A Bankson, Nikolaj Bøgh, Robert A Bok, Albert P Chen, Charles H Cunningham, Jeremy W Gordon, Jan-Bernd Hövener, Christoffer Laustsen, Dirk Mayer, Mary A Mclean, Franz Schilling, James B Slater, Jean-Luc Vanderheyden, Cornelius Von Morze, Daniel B Vigneron, Duan Xu

Faculty, Staff and Student Publications

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is …

Us Filipino Adults Have Elevated Prevalence Of Hypertension Across The Adult Lifespan: Findings From A Cross-Sectional Electronic Health Record Study, Nancy P Gordon, Irvin C Lien, Jamal S Rana, Joan C Lo

Faculty, Staff and Student Publications

INTRODUCTION: The prevalence of hypertension increases with age and differs by race and ethnicity. Among U.S. Asian adults, prevalence is higher for Filipino adults than for other major Asian subgroups, but whether this disparity exists across the adult lifespan is unknown. This study examined hypertension prevalence by age decade, comparing Filipino adults with South Asian, Chinese, Black, Hispanic, and White adults.

METHODS: This cross-sectional study used 2015-2016 electronic health record data from a Northern California integrated healthcare delivery system for 1,839,603 adults aged 30-79 years, including 128,124 Filipino adults. Hypertension was defined by diagnosis codes. Sex-specific prevalence was calculated by …

Understanding The Treatment Paradigm And The Sequencing Of Antiglaucoma Fixed-Dose Combinations In A Tertiary Center In South India, Ronnie George, Praggya Mishra, Balekudaru Shantha, Lingam Vijaya, Nitin Maksane, Neha Gurha

Faculty, Staff and Student Publications

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India.

METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications …

The Combination Of Tumor Mutational Burden And T-Cell Receptor Repertoire Predicts The Response To Immunotherapy In Patients With Advanced Non-Small Cell Lung Cancer, Yalun Li, Liyan Ji, Yingqian Zhang, Jiexin Zhang, Alexandre Reuben, Hao Zeng, Qin Huang, Qi Wei, Sihan Tan, Xuefeng Xia, Weimin Li, Jianjun Zhang, Panwen Tian

Faculty, Staff and Student Publications

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (

Escalated-Dose Radiotherapy For Unresected Locally Advanced Pancreatic Cancer: Patterns Of Care And Survival In The United States, Christopher Shi, Brian De, Hop S Tran Cao, Suyu Liu, Marcus A Florez, Ramez Kouzy, Adam J Grippin, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Michael P Kim, Sunyoung Lee, Jason Willis, Sonal S Noticewala, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes.

METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 …

Mesenchymal-Specific Alms1 Knockout In Mice Recapitulates Metabolic Features Of Alström Syndrome, Eleanor J Mckay, Ineke Luijten, Xiong Weng, Pablo B Martinez De Morentin, Elvira De Frutos González, Zhanguo Gao, Mikhail G Kolonin, Lora K Heisler, Robert K Semple

Faculty, Staff and Student Publications

OBJECTIVE: Alström Syndrome (AS), caused by biallelic ALMS1 mutations, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and fatty liver. Prior studies suggest that hyperphagia is accounted for by loss of ALMS1 function in hypothalamic neurones, whereas disproportionate metabolic complications may be due to impaired adipose tissue expandability. We tested this by comparing the metabolic effects of global and mesenchymal stem cell (MSC)-specific Alms1 knockout.

METHODS: Global Alms1 knockout (KO) mice were generated by crossing floxed Alms1 and CAG-Cre mice. A Pdgfrα-Cre driver was used to abrogate Alms1 function selectively in MSCs and their descendants, including preadipocytes. We combined …