Digital Commons Network^™

Estimating The Number Of Polygenic Diseases Among Six Mutually Exclusive Entities Of Non-Tumors And Cancer, C I Edvard Smith, Jan A Burger, Rula Zain

Faculty, Staff and Student Publications

In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of …

Probabilistic Presurgical Language Fmri Atlas Of Patients With Brain Tumors, Jian Ming Teo, Vinodh A Kumar, Jina Lee, Rami W Eldaya, Ping Hou, Mu-Lan Jen, Kyle R Noll, Peng Wei, Sherise D Ferguson, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background and purpose: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

Materials and methods: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, …

High Incidence And Geographic Distribution Of Cleft Palate In Finland Are Associated With The Irf6 Gene, Fedik Rahimov, Pekka Nieminen, Priyanka Kumari, Emma Juuri, Tiit Nikopensius, Kitt Paraiso, Jakob German, Antti Karvanen, Mart Kals, Abdelrahman G Elnahas, Juha Karjalainen, Mitja Kurki, Aarno Palotie, Estonian Biobank Research Team, Finngen, Arja Heliövaara, Tõnu Esko, Sakari Jukarainen, Priit Palta, Andrea Ganna, Anjali P Patni, Daniel Mar, Karol Bomsztyk, Julie Mathieu, Hannele Ruohola-Baker, Axel Visel, Walid D Fakhouri, Brian C Schutte, Robert A Cornell, David P Rice

Faculty, Staff and Student Publications

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence …

Skn-1 Activation During Infection Of Caenorhabditis Elegans Requires Cdc-48 And Endoplasmic Reticulum Proteostasis, Carolaing Gabaldón, Ozgur Karakuzu, Danielle A Garsin

Faculty, Staff and Student Publications

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 …

Gpr56: Gpcr As A Guardian Against Ferroptosis, Yuelong Yan, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Transmembrane receptor proteins are proficient in sensing external signals and initiating downstream pathways to control cell survival. Lin et al. demonstrated that GPR56, a G-protein-coupled receptor, can be activated by its agonist to suppress ferroptosis-a form of cell death-and effectively mitigate ferroptosis-associated liver damage.

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Jennifer R Landes, Wannes Renders, Laura Muiño Mosquera, Julie De Backer, David W Jantzen, Anji T Yetman, Gisela Teixido-Tura, Arturo Evangelista, Richmond Jeremy, Edward G Jones, Shaine Morris, Tam Doan, Maral Ouzonian, Alan Braverman, Guillaume Jondeau, Olivier Milleron, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods and results: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) …

White Matter Hyperintensities And Mild Tbi In Post-9/11 Veterans And Service Members, David F Tate, Erin D Bigler, Gerald E York, Mary R Newsome, Brian A Taylor, Andrew R Mayer, Mary Jo Pugh, Angela P Presson, Zhining Ou, Elizabeth S Hovenden, Josephine Dimanche, Tracy J Abildskov, Rajan Agarwal, Heather G Belanger, Aaron M Betts, Timothy Duncan, Blessen C Eapen, Carlos A Jaramillo, Michael Lennon, Jennifer E Nathan, Randall S Scheibel, Matthew B Spruiell, William C Walker, Elisabeth A Wilde

Faculty, Staff and Student Publications

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium.

Materials and methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica P Ryu, Yoshina Gautam, Diana M Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David A Relman, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Federally Qualified Health Centers And Performance Of Medicare Accountable Care Organizations, Kun Li, Yucheng Hou, Frank Mcstay, Jonathan Gonzalez-Smith, Robert S Saunders

Faculty, Staff and Student Publications

IMPORTANCE: Federally qualified health centers (FQHCs) have increasingly participated in the Medicare Shared Savings Program (MSSP) accountable care organizations (ACOs), one of the most widespread value-based programs. Although FQHCs may strengthen ACOs' ability to provide affordable care to diverse Medicare beneficiaries, evidence on ACOs' performance by FQHC participation is limited.

OBJECTIVES: To compare beneficiary characteristics, utilization, expenditure, and quality between ACOs with and without FQHC participation and assess changes in ACO performance after including first FQHCs.

DESIGN, SETTING, AND PARTICIPANTS: Using MSSP public use files, this cross-sectional study compared performance of ACOs that always had FQHC participation with ACOs that …

Expansion And Evaluation Of Level Ii And Iii Recovery Residences For People Taking Medications For An Opioid Use Disorder: Project Homes (Housing For Mar Expanded Services) Study Protocol, J M Wilkerson, Kathryn R Gallardo, Serena Rodriguez, Henry Shelton Brown, Cecilia M Ganduglia Cazaban, James J Yang, Estevan R Herrera, Isaiah Niles Zoschke, Hannah L N Stewart, Sheryl A Mccurdy

Faculty, Staff and Student Publications

Introduction: As the US continues to battle the opioid epidemic, recovery residences remain valuable services for people in recovery. While there is a growing body of literature describing positive outcomes experienced by people who live in recovery residences, little is known about the experience of people who live in these residences while taking medications for an opioid use disorder (MOUD) as part of their recovery. Thus, this study has three aims: (1) expand the availability of recovery residences that meet the National Alliance for Recovery Residences standards in Texas and serve individuals taking medications for an opioid use disorder as …

Genetic Risk Factors Underlying White Matter Hyperintensities And Cortical Atrophy, Yash Patel, Jean Shin, Eeva Sliz, Ariana Tang, Aniket Mishra, Rui Xia, Edith Hofer, Hema Sekhar Reddy Rajula, Ruiqi Wang, Frauke Beyer, Katrin Horn, Max Riedl, Jing Yu, Henry Völzke, Robin Bülow, Uwe Völker, Stefan Frenzel, Katharina Wittfeld, Sandra Van Der Auwera, Thomas H Mosley, Vincent Bouteloup, Jean-Charles Lambert, Geneviève Chêne, Carole Dufouil, Christophe Tzourio, Jean-François Mangin, Rebecca F Gottesman, Myriam Fornage, Reinhold Schmidt, Qiong Yang, Veronica Witte, Markus Scholz, Markus Loeffler, Gennady V Roshchupkin, M Arfan Ikram, Hans J Grabe, Sudha Seshadri, Stephanie Debette, Tomas Paus, Zdenka Pausova

Faculty, Staff and Student Publications

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical 'atrophy' identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical 'atrophy' showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. …

Racial And Sociodemographic Disparities In The Use Of Targeted Therapies In Advanced Ovarian Cancer Patients With Medicare, Anne Knisely, Chi-Fang Wu, Alexa Kanbergs, Nuria Agusti, Kirsten A Jorgensen, Alexander Melamed, Sharon H Giordano, Jose Alejandro Rauh-Hain, Roni Nitecki Wilke

Faculty, Staff and Student Publications

Objective: To describe sociodemographic and racial disparities in receipt of poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab among insured patients with ovarian cancer.

Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients with advanced stage, high grade serous ovarian cancer diagnosed between 2010 and 2019. The primary outcome of interest was receipt of PARPi or bevacizumab at any time after diagnosis. χ2 tests were used to compare categorical variables. Factors independently associated with the receipt of PARPi and/or bevacizumab were identified using a multivariable logistic regression.

Results: The cohort included 6242 patients; 276 …

Age-Related Decline In Blood-Brain Barrier Function Is More Pronounced In Males Than Females In Parietal And Temporal Regions, Xingfeng Shao, Qinyang Shou, Kimberly Felix, Brandon Ojogho, Xuejuan Jiang, Brian T Gold, Megan M Herting, Eric L Goldwaser, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial …

Obesity And Outcomes In Adoptive Cellular Therapy In Solid Tumors, Derrick L Tao, Mirella Nardo, Cheuk Hong Leung, Heather Y Lin, Lei Kang, Hung Le, Ecaterina E Dumbrava, David S Hong

Faculty, Staff and Student Publications

This cohort study investigates the association of obesity with adoptive cell therapy outcomes in patients with solid tumors.

Patient-Reported Convenience And Effectiveness Of Telehealth For Breast Cancer Management, Akshara Singareeka Raghavendra, Kristofer Jennings, Gil Guerra, Debu Tripathy, Meghan S Karuturi

Faculty, Staff and Student Publications

Background: Before the coronavirus disease 2019 (COVID-19) pandemic, telehealth was rarely used for breast cancer management at tertiary care centers. We sought to examine patient satisfaction, experiences, preferences, and perceived effectiveness and technical quality of telehealth visits in follow-up patients receiving routine outpatient care in the breast medical oncology practice at The University of Texas MD Anderson Cancer Center.

Methods: We administered a survey to 60 follow-up patients for a duration of 9 months (January 5, 2021 to October 27, 2021) who had at least one telehealth consultation during the COVID-19 pandemic, from April 10, 2020 to October 21, 2021. …

Fc-Enhanced Anti-Ctla-4, Anti-Pd-1, Doxorubicin, And Ultrasound-Mediated Blood-Brain Barrier Opening: A Novel Combinatorial Immunotherapy Regimen For Gliomas, Kwang-Soo Kim, Karl Habashy, Andrew Gould, Junfei Zhao, Hinda Najem, Christina Amidei, Ruth Saganty, Víctor A Arrieta, Crismita Dmello, Li Chen, Daniel Y Zhang, Brandyn Castro, Leah Billingham, Daniel Levey, Olivia Huber, Marilyn Marques, David A Savitsky, Benjamin M Morin, Miguel Muzzio, Michael Canney, Craig Horbinski, Peng Zhang, Jason Miska, Surya Padney, Bin Zhang, Raul Rabadan, Joanna J Phillips, Nicholas Butowski, Amy B Heimberger, Jian Hu, Roger Stupp, Dhan Chand, Catalina Lee-Chang, Adam M Sonabend

Faculty, Staff and Student Publications

Background: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers.

Methods: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs).

Results: FcE-aCTLA-4 demonstrated high-affinity binding …

Thrombosis, Brain Metastasis Formation, And The Perivascular Metastatic Niche-Novel Insights From The Tumor Microvascular Circulation, Christopher Alvarez-Breckenridge, Priscilla K Brastianos, Daniel P Cahill

Faculty, Staff and Student Publications

No abstract provided.

The Emerging Field Of Viroimmunotherapy For Pediatric Brain Tumors, Marc Garcia-Moure, Virginia Laspidea, Sumit Gupta, Andrew G Gillard, Soumen Khatua, Akhila Parthasarathy, Jiasen He, Frederick F Lang, Juan Fueyo, Marta M Alonso, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the …

Impa1-Derived Inositol Maintains Stemness In Castration-Resistant Prostate Cancer Via Impdh2 Activation, Che-Chia Hsu, Guihua Wang, Chien-Feng Li, Xian Zhang, Zhen Cai, Tingjin Chen, Bo-Syong Pan, Rajesh Kumar Manne, Gagan Deep, Haiwei Gu, Yuzhuo Wang, Danni Peng, Vasudevarao Penugurti, Xiaobo Zhou, Zhigang Xu, Zhongzhu Chen, Ming Chen, Andrew J Armstrong, Jiaoti Huang, Hong-Yu Li, Hui-Kuan Lin

Faculty, Staff and Student Publications

Acquisition of prostate cancer stem cells (PCSCs) manifested during androgen ablation therapy (ABT) contributes to castration-resistant prostate cancer (CRPC). However, little is known about the specific metabolites critically orchestrating this process. Here, we show that IMPA1-derived inositol enriched in PCSCs is a key metabolite crucially maintaining PCSCs for CRPC progression and ABT resistance. Notably, conditional Impa1 knockout in the prostate abrogates the pool and properties of PCSCs to orchestrate CRPC progression and prolong the survival of TRAMP mice. IMPA1-derived inositol serves as a cofactor that directly binds to and activates IMPDH2, which synthesizes guanylate nucleotides for maintaining PCSCs with ARlow/- …

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy In High-Grade Epithelial Ovarian Cancer: A Lance Randomized Clinical Trial, J Alejandro Rauh-Hain, Alexander Melamed, René Pareja, Taymaa May, Abdulrahman Sinno, Leah Mcnally, Neil S Horowitz, Pierandrea De Iaco, Chad M Michener, Luc Van Lonkhuijzen, Maria D Iniesta, Ying Yuan, Pedro T Ramirez, Anna Fagotti

Faculty, Staff and Student Publications

Importance: Despite the absence of high-quality evidence of its safety and effectiveness, minimally invasive surgery (MIS) is increasingly used to treat advanced epithelial ovarian cancer (EOC).

Objective: To assess the feasibility of conducting a full-scale randomized clinical trial (RCT) designed to compare the efficacy of MIS vs laparotomy in patients with advanced-stage EOC and a complete or partial response to neoadjuvant chemotherapy (NACT).

Design, setting, and participants: This lead-in pilot phase of LANCE (Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy), an international, open-label, noninferiority RCT, opened to enrollment in September 2020 and enrolled the 100th eligible patient in February 2023. It was …

Acute Kidney Injury Associated With Anticancer Therapies: Small Molecules And Targeted Therapies, Jaya Kala, Teresa Joseph, Marta Pirovano, Roberta Fenoglio, Laura Cosmai

Faculty, Staff and Student Publications

Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as "targeted," many of these agents lack specificity and selectivity, and they tend to inhibit multiple targets, including those in the kidneys. The side …

Association Between E-Scooter Temporal Usage Patterns With Injuries Resulting In Admission To A Level One Trauma Center, Kevin C Rix, Andrew E Springer, Katelyn Jetelina, Nalini Ranjit, Catherine C Mcdonald, Douglas J Wiebe, Thomas B Coopwood

Faculty, Staff and Student Publications

Background: As e-scooters have become common modes of transportations in urban environments, riding e-scooters has become a common mechanism of injury. This study examines the relationship between when riders are using these devices (i.e. day of week, and time of the day) and injury incidence based on data from a large U.S. city.

Methods: This study is a retrospective cohort study of patients in the trauma registry at a level one trauma center. Registry data were combined with a publicly available dataset of all e-scooter trips that occurred during the study period. Frequency of injuries and trips were analyzed using …

Roflumilast Cream, 015%, For Atopic Dermatitis In Adults And Children: Integument-1 And Integument-2 Randomized Clinical Trials, Eric L Simpson, Lawrence F Eichenfield, Javier Alonso-Llamazares, Zoe D Draelos, Laura K Ferris, Seth B Forman, Melinda Gooderham, Mercedes E Gonzalez, Adelaide A Hebert, Leon H Kircik, Mark Lomaga, Angela Moore, Kim A Papp, Vimal H Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C Higham, David H Chu, David R Berk

Faculty, Staff and Student Publications

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.

Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.

Design, setting, and participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic …

Toward A Responsible Future: Recommendations For Ai-Enabled Clinical Decision Support, Steven Labkoff, Bilikis Oladimeji, Joseph Kannry, Anthony Solomonides, Russell Leftwich, Eileen Koski, Amanda L Joseph, Monica Lopez-Gonzalez, Lee A Fleisher, Kimberly Nolen, Sayon Dutta, Deborah R Levy, Amy Price, Paul J Barr, Jonathan D Hron, Baihan Lin, Gyana Srivastava, Nuria Pastor, Unai Sanchez Luque, Tien Thi Thuy Bui, Reva Singh, Tayler Williams, Mark G Weiner, Tristan Naumann, Dean F Sittig, Gretchen Purcell Jackson, Yuri Quintana

Faculty, Staff and Student Publications

BACKGROUND: Integrating artificial intelligence (AI) in healthcare settings has the potential to benefit clinical decision-making. Addressing challenges such as ensuring trustworthiness, mitigating bias, and maintaining safety is paramount. The lack of established methodologies for pre- and post-deployment evaluation of AI tools regarding crucial attributes such as transparency, performance monitoring, and adverse event reporting makes this situation challenging.

OBJECTIVES: This paper aims to make practical suggestions for creating methods, rules, and guidelines to ensure that the development, testing, supervision, and use of AI in clinical decision support (CDS) systems are done well and safely for patients.

MATERIALS AND METHODS: In May …

Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …

Temporal Trends In The Management Practices Of Clinically Important Perioperative Atrial Fibrillation After Noncardiac Surgery, Michael Ke Wang, P J Devereaux, Maura Marcucci, Vladimir Lomivorotov, Daniel I Sessler, Matthew T V Chan, Flavia K Borges, Sandra N Ofori, Pilar Paniagua, James D Douketis, Alben Sigamani, Joel L Parlow, Chew Y Wang, Juan Carlos Villar, Sadeesh K Srinathan, Wojciech Szczeklik, María José Martínez-Zapata, German Malaga, Soori Sivakumaran, William F Mcintyre, María-Virginia Rodríguez Funes, Patricia Cruz, Jesús Alvarez-Garcia, Isabelle Greiss, Ekaterine Popova, Martin E Hemels, Axel Brandes, Clara K Chow, Satish Prasad Barnawal, Jeff S Healey, David Conen

Faculty, Staff and Student Publications

Background: Clinically important perioperative atrial fibrillation (POAF) is a common cardiac complication after noncardiac surgery. Little is known about how patients with POAF are managed acutely and whether practices have changed over time.

Methods: We conducted an observational substudy of patients who had POAF, were at elevated cardiovascular risk, and were enrolled in the PeriOperative Ischemic Evaluation (POISE)-1, 2 and 3 trials between 2002 and 2021. POAF was defined as new, clinically important atrial fibrillation occurring within 30 days after surgery. We assessed the use of rhythm-control and anticoagulation treatment in response to POAF, at hospital discharge and at 30 …

Protein Biomarkers Of Ultra-Processed Food Consumption And Risk Of Coronary Heart Disease, Chronic Kidney Disease, And All-Cause Mortality, Shutong Du, Jingsha Chen, Hyunju Kim, Alice H Lichtenstein, Bing Yu, Lawrence J Appel, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health.

Objectives: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk.

Methods: A total of 9361 participants from the Atherosclerosis Risk in Communities visit 3 (1993-1995) were included. Dietary intake was assessed using a 66-item food-frequency questionnaire and …

Trends In The Use Of Biologic Disease-Modifying Antirheumatic Drugs In Patients With Rheumatoid Arthritis And Recently Diagnosed Colorectal, Lung, Or Prostate Cancer, Maria E Suarez-Almazor, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Suja S Rajan, Sharon H Giordano

Faculty, Staff and Student Publications

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer.

METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic …

Association Between Risk Of Alzheimer’S Disease And Related Dementias And Angiotensin Receptor Ⅱ Blockers Treatment For Individuals With Hypertension In High-Volume Claims Data, Sori Kim Lundin, Xinyue Hu, Jingna Feng, Karl Kristian Lundin, Lu Li, Yong Chen, Paul Ernest Schulz, Cui Tao

Faculty, Staff and Student Publications

Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive.

Methods: Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses.

Findings: From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM …

History Of Incarceration And Dental Care Use Among Older Adults In The United States, Alexander Testa, Dylan B Jackson, Carmen Gutierrez, Chantal Fahmy, Vahed Maroufy, Rafael Samper-Ternent, Ana C Neumann

Faculty, Staff and Student Publications

INTRODUCTION: Dental care is a critical component of healthy aging; however, emerging evidence suggests that having been previously incarcerated is a risk factor for not using dental care services. This study investigates the relationship between prior incarceration and dental care among older adults and assesses whether wealth and dental insurance explain this relationship.

METHODS: Data are from the Health and Retirement Study, a nationally representative sample of community-dwelling older adults in the United States, collected in 2012 and 2014. Multivariable logistic regression is used to assess the relationship between a history of incarceration and dental care. Mediation analyses were conducted …