Medical Specialties Commons^™

Mutational Characteristics And Clinical Outcomes For Lung Adenocarcinoma With Egfr Germline Mutations, Kelsey Pan, Jennifer Owens, Yasir Elamin, Charles Lu, Mark Routbort, Jianjun Zhang, Frank Fossella, Marcelo V Negrao, Mehmet Altan, Jenny Pozadzides, Ferdinandos Skoulidis, Anne Tsao, Tina Cascone, John V Heymach, Edwin Ostrin, Xiuning Le

Faculty, Staff and Student Publications

Introduction: Germline mutations driving lung cancer have been infrequently reported in the literature, with EGFR T790M being a known germline mutation identified in 1% of NSCLCs. Typically, a somatic EGFR mutation is acquired to develop lung adenocarcinoma. Osimertinib has become a standard-of-care treatment for EGFR T790M-positive lung cancer.

Methods: We perform a retrospective analysis through the Lung Cancer Moon Shot GEMINI database at the University of Texas MD Anderson Cancer Center. Of the patients that underwent cell-free DNA analysis, germline mutations were identified by those with high variant allelic fraction approximating 50%, followed by further confirmation on genetic testing.

Results: …

Lower Intensity Therapy With Cladribine/Low Dose Cytarabine/Venetoclax In Older Patients With Acute Myeloid Leukemia Compares Favorably With Intensive Chemotherapy Among Patients Undergoing Allogeneic Stem Cell Transplantation, Jayastu Senapati, Hagop M Kantarjian, Alexandre Bazinet, Patrick Reville, Nicholas J Short, Naval Daver, Gautam Borthakur, Alex Bataller, Elias Jabbour, Courtney Dinardo, Fadi Haddad, Koji Sasaki, Uday Popat, Betul Oran, Amin M Alousi, Sanam Loghavi, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age …

Downregulation Of Uba1 Expression In Myelodysplastic Neoplasm, Yue Wei, Hong Zheng, Ziyi Li, Pamela Pennington Lockyer, Faezeh Darbaniyan, Rashmi Kanagal-Shamanna, Hui Yang, Danielle Hammond, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

Subsyndromes And Symptom Clusters: Multilevel Factor Analysis Of Behavioral And Psychological Symptoms Of Dementia With Intensive Longitudinal Data, Carolyn E Z Pickering, Vicki Winstead, Mustafa Yildiz, Danny Wang, Maria Yefimova, Andrew M Pickering

Faculty, Staff and Student Publications

Introduction: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between-person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within-person factors) that represent contextually driven daily symptom experiences.

Methods: This study used an intensive longitudinal design in which 68 co-residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient's daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries). A multilevel exploratory/confirmatory factor analysis was used to account …

Burden Of Mortality From Hepatocellular Carcinoma And Biliary Tract Cancers By Race And Ethnicity And Sex In Us, 2018–2023, Donghee Kim, Richie Manikat, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed

Faculty, Staff and Students Publications

BACKGROUNDS/AIMS: The trends in mortality of hepatocellular carcinoma (HCC) and biliary tract cancers stratified by sex and race/ethnicity in the US continue to evolve. We estimated the sex- and race/ethnicity-based trends in HCC and biliary tract cancers-related mortality in US adults with a focus on disease burden.

METHODS: We performed a population-based analysis using the US national mortality records from 2018 to 2023. We identified HCC and biliary tract cancer using appropriate ICD-10 codes. Temporal trends in mortality were calculated by joinpoint analysis with annual percentage change (APC).

RESULTS: Annual age-standardized mortality from HCC decreased steadily with an APC of …

Impact Of Race And Ethnicity On Outcomes After Umbilical Cord Blood Transplantation, Karen Ballen, Tao Wang, Naya He, Jennifer M Knight, Sanghee Hong, Haydar Frangoul, Leo F Verdonck, Amir Steinberg, Miguel A Diaz, C Fred Lemaistre, Sherif M Badawy, Jeffrey J Pu, Hasan Hashem, Bipin Savani, Akshay Sharma, Hillard M Lazarus, Muhammad Bilal Abid, Jason Tay, Hemalatha G Rangarajan, Tamila Kindwall-Keller, Cesar O Freytes, Amer Beitinjaneh, Lena E Winestone, Usama Gergis, Nosha Farhadfar, Neel S Bhatt, Raquel M Schears, David Gómez-Almaguer, Mahmoud Aljurf, Vaibhav Agrawal, Yachiyo Kuwatsuka, Sachiko Seo, David I Marks, Leslie Lehmann, William A Wood, Shahrukh Hashmi, Wael Saber

Faculty, Staff and Student Publications

Background: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients.

Objective: To compare outcomes by social determinants of health.

Study design: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, …

Diffusion Tensor Imaging For Characterizing Changes In Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy, Benjamin C Musall, David E Rauch, Rania M M Mohamed, Bikash Panthi, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Mary S Guirguis, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Jennifer K Litton, Tanya W Moseley, Sanaz Pashapoor, Miral M Patel, Brandy J Reed, Marion E Scoggins, Jong Bum Son, Debu Tripathy, Vicente Valero, Peng Wei, Jason B White, Gary J Whitman, Zhan Xu, Wei T Yang, Clinton Yam, Beatriz E Adrada, Jingfei Ma

Faculty, Staff and Student Publications

Background: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST).

Purpose: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST.

Study type: Prospective.

Population: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Targeting Multiple Receptor Tyrosine Kinases With Sitravatinib: A Phase 1b Study In Advanced Renal Cell Carcinoma And Castrate-Resistant Prostate Cancer, Shubham Pant, Byoung Chul Cho, Christos E Kyriakopoulos, Alexander Spira, Nizar Tannir, Theresa L Werner, Xiaohong Yan, Saskia Neuteboom, Richard Chao, Sanjay Goel

Faculty, Staff and Student Publications

Sitravatinib (MGCD516) is an oral inhibitor of several closely related oncogenic tyrosine kinase receptors that include VEGFR-2 (vascular endothelial growth factor receptor-2), AXL, and MET (mesenchymal-epithelial transition). The safety and antitumor activity of sitravatinib are reported in patients from two histologic cohorts (anti-angiogenesis-refractory clear cell renal cell carcinoma [RCC] and castrate-resistant prostate cancer [CRPC] with bone metastases) who participated in a Phase 1/1b study. The patients were enrolled using a 3-stage design that was based on observed objective responses. Objective response rate (ORR) was the primary endpoint. Duration of response, progression-free survival (PFS), overall survival (OS), and safety were also …

Extent Of Resection Thresholds In Molecular Subgroups Of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma, Antonio Dono, Ping Zhu, Takeshi Takayasu, Octavio Arevalo, Roy Riascos, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Background and objectives: Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, previous GBM studies have not addressed the EOR impact in molecular subgroups beyond IDH1/IDH2 status. In the current article, we evaluate whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups.

Methods: A retrospective cohort of newly diagnosed GBM isocitrate dehydrogenase (IDH)-wildtype undergoing resection were prospectively included in a database (n = 138). EOR and residual tumor volume (RTV) were quantified with semiautomated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations …

Imageable Radioembolization Microspheres For Treatment Of Unresectable Hepatocellular Carcinoma: Interim Results From A First-In-Human Trial, Robert J Abraham, Aravind Arepally, David Liu, Robert Lewandowski, S Cheenu Kappadath, Amit Verma, David Dobrowski, Andrew Holden

Faculty, Staff and Student Publications

Purpose: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial.

Materials and methods: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, …

Columbia-1: A Randomised Study Of Durvalumab Plus Oleclumab In Combination With Chemotherapy And Bevacizumab In Metastatic Microsatellite-Stable Colorectal Cancer, Neil H Segal, Jeanne Tie, Scott Kopetz, Michel Ducreux, Eric Chen, Rodrigo Dienstmann, Antoine Hollebecque, Matthew J Reilley, Elena Elez, Jan Cosaert, Jason Cain, Yee Soo-Hoo, Nicola Hewson, Zachary A Cooper, Rakesh Kumar, Josep Tabernero

Faculty, Staff and Student Publications

Background: To determine whether the addition of durvalumab (anti-PD-L1) and oleclumab (anti-CD73) to standard-of-care treatment (FOLFOX and bevacizumab) enhances the anti-tumour effect in patients with metastatic colorectal cancer (mCRC).

Methods: COLUMBIA-1 (NCT04068610) was a Phase Ib (feasibility; Part 1)/Phase II (randomised; Part 2) trial in patients with treatment-naïve microsatellite stable mCRC. Patients in Part 2 were randomised to receive standard-of-care (control arm) or standard-of-care plus durvalumab and oleclumab (experimental arm). Primary objectives included safety and efficacy.

Results: Seven patients were enrolled in Part 1 and 52 in Part 2 (n = 26 in each arm). Grade ≥3 treatment-emergent …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Identification Of Molecular Signatures In Epicardial Adipose Tissue In Heart Failure With Preserved Ejection Fraction, Shan He, Lei Zhao, Jianjun Zhang, Xinchun Yang, Huagang Zhu

Faculty, Staff and Student Publications

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.

METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Response To Letter To The Editor Concerning The Article "The Clinical And Economic Impact Of Extended Battery Longevity Of A Substernal Extravascular Implantable Cardioverter Defibrillator"., Bradley P Knight, Nicolas Clémenty, Anish Amin, Ulrika Maria Birgersdotter-Green, Henri Roukoz, Reece Holbrook, Jaimie Manlucu

Heart and Vascular Articles

No abstract provided.

Impact Of Functional Recovery On Patients Having Heart Surgery., Richard J Snow, Lauren Mckown, Geoffrey Blossom, Karen Vogel, Amy Creighton, Jason Shriver, Linda Will, Katie Lentz, Elizabeth Snow, Teresa Caulin-Glaser

Heart and Vascular Articles

OBJECTIVE: To describe the results of a program developed to manage institutional postacute care (IPAC) (postacute skilled nursing, inpatient rehabilitation facility, and long-term acute care) in a CMS Bundled Payments for Care Improvement (BPCI) project for coronary artery bypass graft (CABG) surgery.

STUDY DESIGN: We compared pre- and postutilization patterns during a 3-year period by evaluating risk-adjusted national, state, and other BPCI participant comparisons using a difference-in-differences (DID) analysis in a large urban community tertiary center with a CABG surgery program. Included in the analysis were all Medicare patients receiving CABG surgery at the institution (n = 504), across the …

Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial, Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S Lee, Ahmed O Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A Curran, Ji Hoon Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full …

Biomarker Trajectory For Earlier Detection Of Lung Cancer, Ehsan Irajizad, Johannes F Fahrmann, Iakovos Toumazis, Jody Vykoukal, Jennifer B Dennison, Yu Shen, Kim-Anh Do, Edwin J Ostrin, Ziding Feng, Samir Hanash

Faculty, Staff and Student Publications

Background: To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4 MP) for lung cancer risk assessment results in improved performance over a single time measurement.

Methods: We conducted data analysis of the 4 MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which …

Metagenomic Study Of The Mesa: Detection Of Gemella Morbillorum And Association With Coronary Heart Disease, Kent D Taylor, Alexis C Wood, Jerome I Rotter, Xiuqing Guo, David M Herrington, W Craig Johnson, Wendy S Post, Russell P Tracy, Stephen S Rich, Shaista Malik

Faculty, Staff and Students Publications

BACKGROUND: Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied.

METHODS AND RESULTS: CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the …

A Virtual Breakthrough Series Collaborative For Missed Test Results: A Stepped-Wedge Cluster-Randomized Clinical Trial, Lisa Zubkoff, Andrew J Zimolzak, Ashley N D Meyer, Jennifer Sloane, Umber Shahid, Traber Giardina, Sahar A Memon, Taylor M Scott, Daniel R Murphy, Hardeep Singh

Faculty, Staff and Students Publications

IMPORTANCE: Missed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment.

OBJECTIVE: To evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each …

Circulating Tumor Cell Count And Overall Survival In Patients With Metastatic Hormone-Sensitive Prostate Cancer, Amir Goldkorn, Catherine Tangen, Melissa Plets, Daniel Bsteh, Tong Xu, Jacek K Pinski, Sue Ingles, Timothy Junius Triche, Gary R Macvicar, Daniel A Vaena, Anthony W Crispino, David James Mcconkey, Primo N Lara, Maha H A Hussain, David I Quinn, Tanya B Dorff, Seth Paul Lerner, Ian Thompson, Neeraj Agarwal

Faculty, Staff and Students Publications

IMPORTANCE: In metastatic hormone-sensitive prostate cancer (mHSPC), new first-line combination therapies have enhanced overall survival (OS), but clinical outcomes for individual patients vary greatly and are difficult to predict. Peripheral blood circulating tumor cell (CTC) count is the most extensively validated prognostic liquid biomarker in metastatic castration-resistant prostate cancer (mCRPC), and recent studies have suggested that it may also be informative in mHSPC.

OBJECTIVE: To examine the prognostic value of CTC count in men with mHSPC.

DESIGN, SETTING, AND PARTICIPANTS: In this prognostic study, peripheral blood was drawn at registration (baseline) and at progression to mCRPC in the S1216 study …

Association Of Aortic Valve Calcium With Dementia And Stroke: The Multi-Ethnic Study Of Atherosclerosis, Natalie Marrero, Kunal Jha, Timothy M Hughes, Alexander C Razavi, Jelani K Grant, Ellen Boakye, Khalil Anchouche, Omar Dzaye, Matthew J Budoff, Jerome I Rotter, Xiuqing Guo, Jie Yao, Alexis C Wood, Roger S Blumenthal, Erin D Michos, George Thanassoulis, Wendy S Post, Michael J Blaha, Chinwe Ibeh, Seamus P Whelton

Faculty, Staff and Students Publications

Background and aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional …

Nongenetic And Genetic Factors Associated With White Matter Brain Aging: Exposome-Wide And Genome-Wide Association Study, Li Feng, Halley S Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L Elliot Hong, Peter Kochunov, David K Y Lei, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals.

METHODS: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor …

Exploring Racial Disparities In Awareness And Perceptions Of Oncology Clinical Trials: Cross-Sectional Analysis Of Baseline Data From The Mychoice Study, Ariel Hoadley, Linda Fleisher, Cassidy Kenny, Patrick Ja Kelly, Xinrui Ma, Jingwei Wu, Carmen Guerra, Amy E. Leader, Mohammed Alhajji, Paul D'Avanzo, Zoe Landau, Sarah Bauerle Bass

Kimmel Cancer Center Faculty Papers

BACKGROUND: Black/African American adults are underrepresented in oncology clinical trials in the United States, despite efforts at narrowing this disparity.

OBJECTIVE: This study aims to explore differences in how Black/African American oncology patients perceive clinical trials to improve support for the clinical trial participation decision-making process.

METHODS: As part of a larger randomized controlled trial, a total of 244 adult oncology patients receiving active treatment or follow-up care completed a cross-sectional baseline survey on sociodemographic characteristics, clinical trial knowledge, health literacy, perceptions of cancer clinical trials, patient activation, patient advocacy, health care self-efficacy, decisional conflict, and clinical trial intentions. Self-reported …

Effects Of White Matter Hyperintensity Burden On Functional Outcome After Mild Versus Moderate-To-Severe Ischemic Stroke, Dong-Seok Gwak, Wi-Sun Ryu, Dawid Schellingerhout, Jinyong Chung, Hang-Rai Kim, Sang-Wuk Jeong, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Jong-Moo Park, Man-Seok Park, Kang-Ho Choi, Tai Hwan Park, Kyungbok Lee, Sang-Soon Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi-Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Ji Sung Lee, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1-4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH …

Efficacy And Safety Of Glp-1 Analog Ecnoglutide In Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Dalong Zhu, Weimin Wang, Guoyu Tong, Guoqing Ma, Jianhua Ma, Jie Han, Xin Zhang, Yang Liu, Shenglian Gan, Hong Qin, Qing Zheng, Jing Ning, Zhiyi Zhu, Mengying Guo, Yue Bu, Yao Li, Catherine L Jones, Martijn Fenaux, Mohammed K Junaidi, Susan Xu, Hai Pan

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups …

Prevalence Of Cardiometabolic Risk Factors In Women: Insights From The Houston Heartreach Study, Arjun R Raghuram, Matthew W Segar, Stephanie Coulter, Joseph G Rogers

The Texas Heart Institute Journal

BACKGROUND: Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening.

METHODS: Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 …

Effects Of Sotagliflozin On Health Status In Patients With Worsening Heart Failure: Results From Soloist-Whf, Ankeet S Bhatt, Deepak L Bhatt, Ph Gabriel Steg, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Matthew C Riddle, Adriaan A Voors, Marco Metra, Lars H Lund, Jeffrey M Testani, Christopher S Wilcox, Michael Davies, Bertram Pitt, Mikhail N Kosiborod

Faculty, Staff and Student Publications

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown.

Objectives: These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status.

Methods: SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular …