Medicine and Health Sciences Commons^™

Micbg406a Polymorphism Reduces Risk Of Mechanical Ventilation And Death During Viral Acute Lung Injury, Harry Pickering, Narges Alipanah-Lechner, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman, Steve Bosinger, Walter Eckalbar, Carolyn S Calfee, Oscar A Aguilar, Elaine F Reed, John R Greenland, Daniel R Calabrese

Faculty, Staff and Students Publications

MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower …

Subsets Of Follicular Lymphoma 3b Have Divergent Outcomes: Results From The Prospective Multicenter Mer And Leo Cohorts, Patrizia Mondello, David Russler-Germain, Brad Kahl, Et Al.

2020-Current year OA Pubs

Follicular lymphoma (FL) 3B is considered an aggressive lymphoma, however recent studies have challenged this paradigm. Additional controversy involves the clinical implication of pure FL3B (FL3Bp) vs FL3B with concurrent diffuse large B cell lymphoma (DLBCL) (FL3Bc). To address these questions, we performed a pooled study of the MER and LEO cohorts comparing 464 newly diagnosed, R-CHOP-treated patients with FL1-2 (n = 216), FL3A (n = 170), FL3B (n = 78) and 739 DLBCL. Among FL3B patients, 19 (24%) had FL3Bc and 59 (76%) FL3Bp. Baseline characteristics and outcomes were similar between the two FL3B subtypes. Compared to FL1-3A, FL3B …

Frontline Acalabrutinib, Lenalidomide And Rituximab For Advanced Stage Follicular Lymphoma With High Tumor Burden: Phase Ii Trial, Paolo Strati, Lei Feng, Jason R Westin, Ranjit Nair, Luis E Fayad, Maria A Rodriguez, Dai Chihara, Luis Malpica, Jared Henderson, Mariana Gallardo, Marissa Rivera, Iris Wang, Anastasiia Bolshakova, Anastasia Radko, David Kurtz, Stefan K Alig, Christopher R Flowers, Ash A Alizadeh, Sattva S Neelapu

Faculty, Staff and Student Publications

This phase II trial aims to determine the efficacy and safety of frontline acalabrutinib, lenalidomide and rituximab for patients with advanced stage follicular lymphoma (FL) and high tumor burden. The primary endpoint was best complete response (CR) rate; the secondary endpoints were overall response rate (ORR), duration of response measured as CR at 30 months (CR30), progression of disease at 24 months (POD24) rate, progression-free survival (PFS), overall survival and safety. Twenty-four patients with previously untreated FL were included in this phase 2 single arm study (NCT04404088). The most common grade 3-4 adverse events were neutropenia (58%) and …

Histologic And Immune Characterization Of Cutaneous Immune-Related Adverse Events Induced By Immune Checkpoint Inhibitors, Omar Pacha, Anisha B Patel, Jonathan L Curry, Cara L Haymaker, Nejla Ozirmak Lermi, Dzifa Yawa Duose, Ken Chen, Joud Hajjar, Aung Naing

Faculty, Staff and Student Publications

Background: Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods: Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE …

Adipokines And Transitions In Metabolic Health Over Time: The Atherosclerosis Risk In Communities (Aric) Study, Bige Ozkan, Sui Zhang, Justin B Echouffo-Tcheugui, Roberta Florido, Vijay Nambi, Erin D Michos, Layla A Abushamat, Kunihiro Matsushita, Gary Gerstenblith, Roger S Blumenthal, Ron Hoogeveen, Christie M Ballantyne, Josef Coresh, Elizabeth Selvin, Chiadi E Ndumele

Faculty, Staff and Students Publications

Context: Transitions in metabolic health status over time are strongly linked to risk for cardiovascular events, particularly among individuals with obesity. Adipokines are proteins with metabolic effects, but their role in transitions in metabolic health status over time is unknown.

Objective: To evaluate the associations of adiponectin and leptin with metabolic risk transitions over time.

Methods: Among 8423 individuals who attended ARIC Visits 2 (1990-1992) and 4 (1996-1998), we evaluated prospective associations of Visit 2 levels of the adipokines adiponectin and leptin (per 1-SD higher) with 6-year transitions in metabolic health. Metabolic health was categorized as metabolically "healthy" [no metabolic …

Discontinuation Rates And Predictors Of Medical Cannabis Cessation For Chronic Musculoskeletal Pain, Mohammad Khak, Sina Ramtin, Juliet Chung, Asif M. Ilyas, Ari Greis

Rothman Institute Papers

Medical cannabis (MC) is increasingly used as a treatment for chronic musculoskeletal pain, but there is limited data on factors influencing its discontinuation. This study aims to investigate the rates of MC discontinuation and explore factors influencing it in patients with chronic musculoskeletal pain. A retrospective analysis was conducted on 78 patients certified for medical cannabis over a 2 year period. Patient demographics, pain origin, and Global Physical Health (GPH) and Global Mental Health (GMH) scores were collected before intervention. Discontinuation rates were measured at three-month and one-year follow-up. Statistical analyses, including Fisher's Exact Test and two-sample t-tests, were performed …

Feasibility And Preliminary Efficacy Of A Lymphedema And Fibrosis Self-Management Program For Head And Neck Cancer Survivors: A Pilot Randomized Controlled Trial, Jie Deng, Barbara Murphy, Lucy Andersen, Erin Mcmenamin, John Lukens, Joy Cohn, Karthik Rajasekaran, Ryan Quinn, Bryan Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

OBJECTIVES: Survivors of head and neck cancer (HNC) are at high risk for developing lymphedema and fibrosis (LEF). Once diagnosed with LEF, survivors must engage in a lifelong program of self-care to minimize long-term adverse effects. However, evidence-based LEF self-management (SM) programs are lacking. To fill this void, we developed and pilot-tested a LEF-SM program for HNC survivors.

MATERIALS AND METHODS: The LEF-SM Program was developed using the Information-Motivation-Behavioral Skills model of health behavior change as a framework. The program was pilot tested in a three-group randomized controlled trial evaluating feasibility and preliminary efficacy. Fifty-nine participants were randomized to: Usual …

Development Of A Customizable Web-Based Dashboard For Remote Blood Pressure Monitoring: Feasibility And Usability Implementation Study, Joshua Wollen, Thuy Nguyen, Charles Coton, Gina Dewildt, Gabretta Cooksey, Audrey Cohen, Nicholas Hoang, Munachi Okpala, Michael Gonzalez, Mengxi Wang, Chigozirim Izeogu, Elmer Bernstam, Charles Green, Sean Savitz, Jose-Miguel Yamal, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Effective blood pressure (BP) management is essential for several disease states, including secondary stroke prevention. Remote BP monitoring used in combination with an electronic data capture (EDC) system offers potential for improved BP control for patients. While such systems currently exist, there are many patient-, provider-, and system-specific challenges these systems currently do not address. In addition, such systems are rarely described transparently and comprehensively in the literature with enough detail to be reproduced by other clinicians.

Objective: This study aims to describe the development and design of a web-based EDC system tailored for remote BP monitoring and management …

Exploring Factors Affecting The Adoption And Use Of Digital Health Technologies Among Older Adults With Cancer: A Qualitative Study, Misun Hwang, Youmin Cho, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Although digital health technologies (DHTs) are promising to improve health outcomes in older adults with cancer, the low adoption and limited use remain significant gaps in their effective digital health care. Little is known about their concerns about adopting and using DHTs in routine life, particularly in the continued use phase. This study aims to explore factors affecting the initial adoption and continued use of DHTs among older adults with cancer.

Methods: A secondary analysis of qualitative data was conducted based on interviews with 21 older adults (≥ 65 years) with breast, prostate, lung, or colorectal cancer. The transcripts …

Rapid And Sustainable Deep Testosterone Reduction Predicts Effective Androgen Deprivation Therapy For Metastatic Hormone-Sensitive Prostate Cancer., Ze Wang, Haiyang Xiao, Chongliang Zheng, Jian Chen, Qiming Chen, Zhenzhen Chen, Dianzheng Zhang, Luofu Wang, Weihua Lan, Qiuli Liu, Jun Jiang

PCOM Scholarly Works

The testosterone (TT)/androgen receptor axis plays a crucial role in the initiation and progression of prostate cancer (PCa). We aimed to investigate the predictive value of serum TT levels on metastatic PCa progression. A total of 219 patients with metastatic PCa were included in this study. Analyses performed included Pearson's correlation test, Wilcoxon rank test, Chi-square test, Cox regression, and Kaplan-Meier analysis. High serum TT levels (> 405 ng/dL) before ADT treatment, deep testosterone reduction (DTR) within the first year of ADT, rapid DTR within 3 months of ADT, and sustained DTR in the first year of ADT are associated …

Association Between Allostatic Load And Accelerated White Matter Brain Aging: Findings From The Uk Biobank, Li Feng, Zhenyao Ye, Zewen Du, Yezhi Pan, Travis Canida, Hongjie Ke, Song Liu, Shuo Chen, L Elliot Hong, Peter Kochunov, Jie Chen, David K Y Lei, Edmond Shenassa, Tianzhou Ma

Faculty, Staff and Student Publications

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting, …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Integrating Ctdna Analysis And Radiomics For Dynamic Risk Assessment In Localized Lung Cancer, Everett J Moding, Mohammad Shahrokh Esfahani, Cheng Jin, Angela B Hui, Barzin Y Nabet, Yufei Liu, Jacob J Chabon, Michael S Binkley, David M Kurtz, Emily G Hamilton, Aadel A Chaudhuri, Chih Long Liu, Zhe Li, Rene F Bonilla, Alice L Jiang, Brianna C Lau, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing Liao, Millie Das, Kavitha J Ramchandran, Sukhmani K Padda, Joel W Neal, Heather A Wakelee, Michael F Gensheimer, Billy W Loo, Ruijiang Li, Steven H Lin, Ash A Alizadeh, Maximilian Diehn

Faculty, Staff and Student Publications

The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. Circulating tumor DNA (ctDNA) minimal residual disease after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. Here, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration …

Depletion Of Effector Regulatory T Cells Associates With Major Response To Induction Dual Immune Checkpoint Blockade, Xianli Jiang, Nils-Petter Rudqvist, Bo Jiang, Shengbin Ye, Shan He, Qingnan Liang, Jinzhuang Dou, Michelle D Williams, Joe Dan Dunn, Jason M Johnson, Keiko Akagi, Weihong Xiao, Shaoheng Liang, Satvik Elayavalli, Baohua Sun, Edwin R Parra, Renata Ferrarotto, Adam S Garden, Clifton David Fuller, Jay Reddy, Neil D Gross, Miriam N Lango, Cheuk Hong Leung, Suyu Liu, Diane D Liu, Meng Li, J Jack Lee, Michael A Curran, Jack Phan, Ken Chen, Maura L Gillison

Faculty, Staff and Student Publications

In a phase II trial, patients with local-regionally advanced human papillomavirus-positive oropharyngeal carcinoma (n = 35) received ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1) as induction immunotherapy and concurrently with radiotherapy (NCT03799445). Coprimary endpoints included 6-month complete metabolic response rate (94%) and 2-year progression-free survival (84%). Induction yielded a 46% major histopathologic response rate. Single-cell profiling revealed responders had higher baseline intratumoral CD8+ T cells with a tumor-reactive, tissue-resident memory (TRM) phenotype and a treatment-related decrease in effector regulatory T (eTreg) cells. The eTreg decrease correlated with CD8+ T-cell clonotype transitioning from TRM to effector memory and IFNG+ effector cells. …

Detection Of Brain Cancer Using Genome-Wide Cell-Free Dna Fragmentomes, Dimitrios Mathios, Et Al.

2020-Current year OA Pubs

UNLABELLED: Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection of brain cancers could accelerate brain cancer diagnosis. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles and repeat landscapes, from the plasma of individuals with (n = 148) or without (n = 357) brain cancer. Machine learning analyses of cfDNA fragmentome features detected brain cancer across all-grade gliomas (AUC = 0.90; 95% confidence interval, 0.87-0.93), and these results were validated in an independent prospectively collected cohort. cfDNA fragmentome changes in patients with gliomas represented …

Comparative Outcomes Of Coil Embolization And Surgical Clipping In Elderly Patients With Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis, Yohanna Idsabella Rossi, Gabriel Bolner, Jonathan Costa Dall'acqua, Fabiana Dolovitsch De Oliveira, Lucas V. Zacaria, Taís L. Denicol, Michel Frudit, Natália Vasconcellos De Oliveira Souza

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Elderly patients with subarachnoid hemorrhage (SAH) face a disproportionately high burden of morbidity and mortality. While endovascular coiling is often favored in this population, direct comparisons with surgical clipping are limited. We conducted a meta-analysis to compare outcomes of clipping versus coiling in SAH patients aged ≥ 60 years.

METHODS: A systematic search of PubMed, Embase, and Cochrane databases identified studies comparing the two treatments in this age group. The primary outcome was a composite of unfavorable outcomes (modified Rankin Scale [mRS] > 2 and mortality). Secondary outcomes included mortality, favorable outcome (mRS 0-2), rebleeding, and hospital length …

A Phase 2 Trial Of Niraparib Plus Bevacizumab Maintenance Therapy Following First-Line Platinum-Based Chemotherapy With Bevacizumab In Advanced Ovarian Cancer: Final Analysis And Overall Survival Results From Ovario., Melissa M Hardesty, Thomas C Krivak, Gail S Wright, Erika Hamilton, Evelyn L Fleming, Jimmy Belotte, Shelby Gorman, Natalie Compton, Aine Clements, Heidi J Gray, Gottfried E Konecny, Richard G Moore, Debra L Richardson

Oncology Articles

OBJECTIVE: To report long-term outcomes from the OVARIO trial of niraparib plus bevacizumab maintenance following first-line platinum-based chemotherapy with bevacizumab in advanced ovarian cancer.

METHODS: The phase 2, single-arm, open-label trial enrolled adult patients with stage IIIB-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have attempted debulking surgery and have a complete or partial response or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was 18-month progression-free survival (PFS) rate, per RECIST. Secondary endpoints included PFS, overall survival (OS), safety, and health-related quality of life (HRQOL) …

Use Of Cognitive-Behavioral Therapy In A Nation-Wide Veterans Health Administration Sample: The Role Of Clinic, Therapist, And Patient Factors., Alan Mcguire, Mindy Flanagan, Madison E Stout, Jessica Coffing, Marina Kukla, Morgan Traylor, Laura Myers, Nancy Henry, Jessica Carter, Marianne Matthias

Health Services and Informatics Research

OBJECTIVE: To examine the use of CBT-CP (Cognitive-behavioral therapy for chronic pain) by CBT-CP-trained therapists to treat patients with pain over a five-year period (October 2015-February 2020).

DATA SOURCES AND STUDY SETTING: CBT-CP is a core evidence-based practice that is central to multidisciplinary chronic pain care. However, research suggests that CBT-CP is underused. The current study used national Veterans Health Administration data to examine the use of CBT-CP by CBT-CP-trained therapists to treat patients with pain over a five-year period.

STUDY DESIGN: Multilevel modeling was used to evaluate clinic, therapist, and patient-level factors as predictors of CBT-CP receipt.

DATA COLLECTION: …

Association Of Epigenetic Aging With Plasma Cbiomarkers Of Amyloid, Tau, Neurodegeneration, And Neuroinflammation In Hispanic/Latino Adults, Myriam Fornage, Wassim Tarraf, Martha L Daviglus, Charles Decarli, Kevin A Gonzalez, Carmen R Isasi, Sayaka Kuwayama, Melissa Lamar, Bonnie E Levin, Humberto Parada, Alberto R Ramos, Tatjana Rundek, Bharat Thyagarajan, Hector M González

The Brown Foundation: Institute of Molecular Medicine

Background: Blood-based biomarkers hold significant promise for the early detection and diagnosis of Alzheimer's disease (AD) and other dementias. Age-related changes in blood levels of AD biomarkers are well-documented but poorly understood. Epigenetic clocks are mathematical models based on DNA methylation patterns that reflect various aspects of the multidimensional aging process. We investigated the associations of epigenetic aging with five blood-based AD biomarkers in 2656 Hispanic/Latino adults (mean age 62.5 years; 65% females) from the Hispanic Community Health Study/Study of Latinos. We used multivariable linear regression models to estimate the associations of acceleration in each of five epigenetic clocks with …

Summit Max: A Randomized Trial Of The Super Large Bore Hipoint Reperfusion System Versus Vecta System For Aspiration Thrombectomy., Thanh N Nguyen, Guilherme Dabus, Ben Mcguinness, James Caldwell, Ryan Priest, Ansaar T Rai, Osama O Zaidat, Bradley A Gross, Ricardo Hanel, Shane Lee, Shazam Hussain, Hamza Shaikh, Mohamad Abdalkader, Ronald Budzik, Craig Kilburg, Keith Woodward, Marco Colasurdo, Jesse Liu, Albert J Yoo, Priyank Khandelwal, Sohyun Boo, Phong Vu, Eugene Lin, Mohammad Almajali, Jasmeet Singh, Alhamza Al-Bayati, Michael J Lang, Michael Abraham, Ameer E Hassan, Peter Pema, Coleman Martin, Ramesh Grandhi, Daniel A Tonetti, Harry R Hixson, Amin Aghaebrahim, Eric Sauvageau, Santiago Ortega-Gutierrez, Dileep R Yavagal, Esteban Cheng-Ching, Jane Khalife, Italo Linfante, Volodymyr Vulkanov, Jazba Soomro, Johanna T Fifi, Lucien Maidan, Alexander Copelan, Clemens M Schirmer, Mark Bain, Gabor Toth, Mahesh Jayaraman, Roberta Novakovic-White, Sudhakar Satti, Nicolas Villelli, Pascal Jabbour, Matthew Page, Davina J Mcallister, Robert Araujo Contreras, Edgar A Samaniego, David S Liebeskind, Steven W Hetts, Raul G Nogueira, Joey English, Ajit S Puri

Neuroscience Articles

BACKGROUND: Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (0.088″ inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial.

METHODS: SUMMIT MAX (A Prospective, Randomized, Controlled, Interventional Clinical Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical MonoPoint Reperfusion System for Aspiration Embolectomy in Acute Ischemic Stroke Patients) was a prospective, randomized, controlled, open-label clinical trial of patients with internal carotid artery and middle cerebral artery M1 occlusions, comparing …

Impaired Rest-Activity Rhythm Characteristics Predict Higher Risk Of Incident Type 2 Diabetes In Uk Biobank Participants, Chris Ho Ching Yeung, Alison K Wright, Daniel P Windred, Angus C Burns, Andrew J K Phillips, Sean W Cain, Martin K Rutter, Qian Xiao

Faculty, Staff and Student Publications

Objective: Circadian rhythms play a key role in metabolic health. Rest-activity rhythms, which are in part driven by circadian rhythms, may be associated with diabetes risk. There is a need for large prospective studies to comprehensively examine different rest-activity metrics to determine their relative strength in predicting risk of incident type 2 diabetes.

Research design and methods: In actigraphy data from 83,887 UK Biobank participants, we applied both parametric and nonparametric algorithms to derive 13 different metrics characterizing different aspects of rest-activity rhythm. Diabetes cases were identified using both self-reported data and health records. We used Cox proportional hazards models …

Trends In Glucagon-Like Peptide 1 Receptor Agonist Prescribing Patterns, Maria Ukhanova, Joseph S Wozny, Chau N Truong, Lopita Ghosh, Trudy M Krause

Faculty, Staff and Student Publications

Objective: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes.

Study design: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other …

Autoantibody Profiling To Predict Response To The Anti-Pd-1 Therapy, Pembrolizumab, In Rare Tumors, M H Derbala, J Hajjar, B Stephen, S A Gurses, E Kwiatkowski, P Budde, H-D Zucht, M Bräutigam, A-S Lindemann, B A Abhari, M A Gouda, L Castillo, A Zarifa, J A How, E Rodriguez, J T Moyers, D S Hong, S Fu, F Meric-Bernstam, A Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have limited response rates in selected patients and can cause potentially life-threatening immune-related adverse events (irAEs). This underscores the urgent need for the development of biomarkers predictive of ICI response. Pre-existing autoantibodies (AAbs) have been linked with responses to ICIs and the development of irAEs. We conducted AAb profiling to assess associations between baseline AAbs and clinical benefit (CB) in patients with rare tumors treated with anti-programmed cell death protein 1-based therapy.

Patients and methods: We conducted AAb profiling using Oncimmune's SeroTag multiplex antibody discovery technology and immune oncology array containing 1168 antigens. The study …

Racial Disparities In The Receipt Of Therapies For Cancer, Hypertension, And Diabetes, And In Mortality In A Large Population-Based Cohort Of Older Men With Prostate Cancer, Zhuoyun Li, Xianglin L Du

Faculty, Staff and Student Publications

Background: Racial disparities in treatment and mortality were widely studied among prostate cancer patients; however, few studies considered the prevalence of hypertension and diabetes and their treatment status.

Objectives: To determine whether there are racial discrepancies in the use of anti-cancer, antihypertensive, and antidiabetic drugs in a cohort of long-term survivors of prostate cancer diagnosed in 2007-2015; and to examine racial disparities in mortality after adjustments for their differences in those treatments.

Methods: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database and included records for patients with prostate cancer at age 65 years or older diagnosed from …

A Large-Scale Genome-Wide Study Of Gene-Sleep Duration Interactions For Blood Pressure In 811,405 Individuals From Diverse Populations, Pavithra Nagarajan, Thomas W Winkler, Amy R Bentley, Clint L Miller, Aldi T Kraja, Karen Schwander, Songmi Lee, Wenyi Wang, Michael R Brown, John L Morrison, Ayush Giri, Jeffrey R O'Connell, Traci M Bartz, Lisa De Las Fuentes, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Zhijie Huang, Mart Kals, Minjung Kho, Christophe Lefevre, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Yuri Milaneschi, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Botong Shen, Stefan Stadler, Quan Sun, Jingxian Tang, Sébastien Thériault, Adriaan Van Der Graaf, Peter J Van Der Most, Yujie Wang, Stefan Weiss, Kenneth E Westerman, Qian Yang, Tabara Yasuharu, Wei Zhao, Wanying Zhu, Drew Altschul, Md Abu Yusuf Ansari, Pramod Anugu, Anna D Argoty-Pantoja, Michael Arzt, Hugues Aschard, John R Attia, Lydia Bazzanno, Max A Breyer, Jennifer A Brody, Brian E Cade, Hung-Hsin Chen, Yii-Der Ida Chen, Zekai Chen, Paul S De Vries, Latchezar M Dimitrov, Anh Do, Jiawen Du, Charles T Dupont, Todd L Edwards, Michele K Evans, Tariq Faquih, Stephan B Felix, Susan P Fisher-Hoch, James S Floyd, Mariaelisa Graff, Charles Gu, Dongfeng Gu, Kristen G Hairston, Anthony J Hanley, Iris M Heid, Sami Heikkinen, Heather M Highland, Michelle M Hood, Mika Kähönen, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Setoh Kazuya, Tanika N Kelly, Pirjo Komulainen, Daniel Levy, Henry J Lin, Peter Y Liu, Pedro Marques-Vidal, Joseph B Mccormick, Hao Mei, James B Meigs, Cristina Menni, Kisung Nam, Ilja M Nolte, Natasha L Pacheco, Lauren E Petty, Hannah G Polikowsky, Michael A Province, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Stephen S Rich, Renata L Riha, Lorenz Risch, Martin Risch, Edward A Ruiz-Narvaez, Rodney J Scott, Colleen M Sitlani, Jennifer A Smith, Tamar Sofer, Maris Teder-Laving, Uwe Völker, Peter Vollenweider, Guanchao Wang, Ko Willems Van Dijk, Otis D Wilson, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Xiaofeng Zhu, Jennifer E Below, Carsten A Böger, David Conen, Simon R Cox, Marcus Dörr, Mary F Feitosa, Ervin R Fox, Nora Franceschini, Sina A Gharib, Vilmundur Gudnason, Sioban D Harlow, Jiang He, Elizabeth G Holliday, Zoltan Kutalik, Timo A Lakka, Deborah A Lawlor, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Reedik Mägi, Fumihiko Matsuda, Alanna C Morrison, Brenda Wjh Penninx, Patricia A Peyser, Jerome I Rotter, Harold Snieder, Tim D Spector, Lynne E Wagenknecht, Nicholas J Wareham, Alan B Zonderman, Kari E North, Myriam Fornage, Million Veteran Program, Adriana M Hung, Alisa K Manning, James Gauderman, Han Chen, Patricia B Munroe, Dabeeru C Rao, Diana Van Heemst, Susan Redline, Raymond Noordam, Heming Wang

Faculty, Staff and Student Publications

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health …

Accelerometer-Measured Chronoactivity And Type 2 Diabetes Risk: A Prospective Study In Uk Biobank Participants, Qiuyu Feng, Gali Albalak, Ko Willems Van Dijk, Jeroen H P M Van Der Velde, Qian Xiao, Raymond Noordam, Diana Van Heemst

Faculty, Staff and Student Publications

Objective: We assessed whether timing of physical activity, independent from the total activity amount, - which we refer to as chronoactivity - is associated with type 2 diabetes (T2D) risk.

Methods: We included UK Biobank participants with valid accelerometry data (UK, exposure measurement: 2013-2015, follow-up till November 2023) and without diabetes mellitus at baseline (N = 89,439; mean age: 61.7 [SD:7.9] years). Relative hourly physical activity was calculated by dividing the average hourly clock time physical activity by the average hourly physical activity in a week. Participants were categorized into different chronoactivity clusters using k-means cluster analysis on relative hourly …

Effectiveness And Safety Of Chronic Diuretic Use In Older Adults: An Umbrella Review Of Recently Published Systematic Reviews And Meta-Analyses Of Randomized-Controlled Trials, Eveline Van Poelgeest, Konstantinos Prokopidis, Tuğba Erdogan, Min Ji Kwak, Karolina Piotrowicz, Luca Paoletti, Annette Eidam, Fatma Özge Kayhan Koçak, Birkan Ilhan, Alessia Beccacece, George Soulis, Serdar Özkök, Gulistan Bahat, Eva Topinková, Joost Daams, M Louis Handoko, Parag Goyal, Jerzy Gąsowski, Antonio Cherubini, Nicola Veronese, Giuseppe Dario Testa, Wade Thompson, Nathalie Van Der Velde, European Geriatric Medicine Society Special Interest Groups Of I. Pharmacology; Ii. Cardiovascular Disease And Iii. Systematic Review And Meta-Analysis

Faculty, Staff and Student Publications

Background: Healthcare providers should balance the potential risks and benefits of chronic diuretic use, particularly in older adults, as with age, diuretic benefits may decline and risks increase. A comprehensive synthesis and critical evaluation of the available evidence on chronic diuretic treatment effects is currently lacking.

Methods: We conducted an umbrella review of systematic reviews and meta-analyses published since 2018 on health outcomes associated with diuretic use in randomized-controlled trials (RCTs). We conducted random-effects meta-analysis for pooled effect estimates and narratively summarized data that could not be pooled.

Results: We included 741 effect estimations from 117 systematic reviews (SRs) on …

Does Midbrain Atrophy Distinguish Progressive Supranuclear Palsy From Frontotemporal Dementia?, Mauro César Quintão E Silva Cunningham, Sarah Teixeira Camargos, Vinícius Ribeiro Jeunon, Natalia Pessoa Rocha, Antônio Lúcio Teixeira, Thiago De Oliveira Maciel, Elisa De Paula França Resende, Francisco Eduardo Costa Cardoso, Paulo Caramelli, Leonardo Cruz De Souza

Faculty, Staff and Student Publications

Background: The diagnostic value of midbrain atrophy for distinguishing behavioral variant frontotemporal dementia (bvFTD) from progressive supranuclear palsy (PSP) is unclear.

Objective: To investigate whether measures of midbrain atrophy differentiate PSP from bvFTD.

Methods: We included four groups: healthy controls (n = 19), PSP-Richardson syndrome (n = 20), bvFTD (n = 19) and Parkinson's disease (PD; n = 12). The following quantitative and qualitative measures were calculated: Hummingbird sign rating scale [HBS-RS], global midbrain atrophy [GMA], midbrain area, midbrain/pons ratio, the Magnetic Resonance Parkinsonism Index (MRPI), the MRPI 2.0 and brainstem volume.

Results: Compared to controls, PSP and bvFTD had …

Transcriptomic Analysis Of Localized High-Risk Prostate Cancer Improves Prognostication And Identifies Benefit From Adding Docetaxel To Definitive Radiotherapy With Androgen Suppression In The Nrg Oncology/Rtog 0521 Phase 3 Trial, Ryan M Phillips, James A Proudfoot, Elai Davicioni, Yang Liu, Daniel E Spratt, Jeff M Simko, Robert B Den, Alan Pollack, Seth A Rosenthal, A Oliver Sartor, Christopher J Sweeney, Gerhardt Attard, Leslie Longoria, Samir Patel, Michael W Straza, Jason A Efstathiou, Amit B Shah, Karen E Hoffman, Joseph P Rodgers, Howard M Sandler, Felix Y Feng, Phuoc T Tran

Faculty, Staff and Student Publications

Background and objective: NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response.

Methods: Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …