Medicine and Health Sciences Commons^™

A Screening Question To Assess Risk Of Using Antibiotics Without A Prescription: A Diagnostic Study, Ashley Collazo, Eva Amenta, Kiara Olmeda, Marissa Valentine-King, Lindsey Laytner, Azalia Mancera, Roger Zoorob, Michael K Paasche-Orlow, Richard L Street, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Objectives: Non-prescription antibiotic use (using antibiotics without medical advice) is potentially unsafe and promotes antimicrobial resistance. We studied predictors of prior non-prescription use and whether screening for prior non-prescription antibiotic use predicted intention of future non-prescription antibiotic use.

Methods: The survey was performed from January 2020 - June 2021 in six public primary care clinics and two private emergency departments. Prior non-prescription users were respondents who reported taking oral antibiotics for symptoms without contacting a clinician. Intended use was defined by answering yes to the question, "would you use antibiotics without contacting a doctor/nurse/dentist/clinic." We examined predictors for prior non-prescription …

Mri Distance Measures As A Predictor Of Subsequent Clinical Status During The Preclinical Phase Of Alzheimer's Disease And Related Disorders, Xinyi Zhang, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Brain atrophy over time, as measured by magnetic resonance imaging (MRI), has been shown to predict subsequent cognitive impairment among individuals who were cognitively normal when first evaluated, indicating that subtle brain atrophy associated with Alzheimer's disease (AD) may begin years before clinical symptoms appear. Traditionally, atrophy has been quantified by differences in brain volume or thickness over a specified timeframe. Research indicates that the rate of atrophy varies across different brain regions, which themselves exhibit complex spatial and hierarchical organizations. These characteristics collectively emphasize the need for diverse summary measures that can effectively capture the multidimensional nature of degeneration. …

Left Ventricular Entry To Reduce Brain Lesions During Catheter Ablation: A Randomized Trial, Gregory M Marcus, Roderick Tung, Edward P Gerstenfeld, Trisha F Hue, Feng Lin, Jing Cheng, J Peter Weiss, Wendy S Tzou, Henry Hsia, Ashkan Ehdaie, Daniel H Cooper, T Jared Bunch, Jeffrey Arkles, Babak Nazer, Adam Lee, Alexios Hadjis, Duy T Nguyen, Mihail G Chelu, Joshua Moss, Jonathan C Hsu, Miguel Valderrábano, Prashant D Bhave, Andrew D Beaser, Arvindh Kanagasundram, Oussama Wazni, Jason Bradfield, Grace Wall, Kathleen Chang, Michelle Yang, Gabrielle Montenegro, Sabrina Jarrott, Joel H Kramer, Anthony S Kim, Yvonne M Morris, William P Dillon

Faculty, Staff and Students Publications

Background: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging-detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach.

Methods: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left …

Cerebrospinal Fluid Proteomics Identification Of Biomarkers For Amyloid And Tau Pet Stages, Zhibo Wang, Yuhan Chen, Katherine Gong, Bote Zhao, Yuye Ning, Meilin Chen, Yan Li, Muhammad Ali, Jigyasha Timsina, Menghan Liu, Carlos Cruchaga, Jianping Jia

2020-Current year OA Pubs

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as …

Outcomes Evidence Must Keep Up With The Implementation Of The 4ms Framework To Ensure Age-Friendly Health System Transformation, James D Harrison, Stephanie E Rogers, Benjamin Rosner, Estelle Martin, Sunny C Lin, Jarmin Yeh, Julia Adler-Milstein

2020-Current year OA Pubs

The Age-Friendly Health System (AFHS) movement was conceptualized as a transformative solution to reliably deliver evidence-based care to older adults. Guided by the 4Ms framework: What Matters, Mobility, Mentation, and Medication, AFHS healthcare systems have been given the flexibility to tailor 4Ms interventions and care processes to their context, preferences and populations. This flexibility has facilitated the widespread adoption of 4Ms care. However, as our understanding of 4Ms implementation grows, evidence of the impact of 4Ms care on outcomes must keep up with implementation to ensure AFHS transformation. It is only through assessing the 4Ms as a whole and understanding …

Association Between High Triglyceride-Glucose Index And Macce In Hypertriglyceridemia Patients Undergoing Percutaneous Coronary Intervention, Yichuan Wang, Yanfeng Lu, Shanshan Gao, Zhong Zhong, Jasmine Bao, Bo Liu, Ruihan Fan, Ning Guo

SKMC Student Presentations and Publications

BACKGROUND: With a focus on metabolism-related cardiovascular diseases, the triglyceride-glucose (TyG) index has been used as a surrogate marker of insulin resistance in the prognosis of coronary heart disease. However, the prognostic role of the TyG index in patients with elevated triglycerides, still requires further research. This study aimed to investigate the association between the TyG index and Major Adverse Cardiac and Cerebrovascular Events (MACCE) in patients with hypertriglyceridemia undergoing drug-eluting stent percutaneous coronary intervention (DES-PCI).

METHODS: Out of 2250 patients, 813 with hypertriglyceridemia who underwent DES-PCI were retrospectively analyzed. MACCE was regarded as the primary endpoint. Kaplan-Meier (KM) curves …

Results Of The Phase I/Ii Study And Preliminary B-Cell Gene Signature Of Combined Inhibition Of Glutamine Metabolism And Egfr In Colorectal Cancer, Kristen K Ciombor, Seong-Woo Bae, Jennifer G Whisenant, Gregory D Ayers, Quanhu Sheng, Todd E Peterson, Gary T Smith, Kangyu Lin, Saikat Chowdhury, Preeti Kanikarla Marie, Alexey Sorokin, Allison S Cohen, Laura W Goff, Dana B Cardin, John Paul Shen, Scott Kopetz, Cathy Eng, Yu Shyr, Jordan Berlin, H Charles Manning

Faculty, Staff and Student Publications

Purpose: EGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression.

Patients and methods: We conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET …

Surgical Mitral Valve Repair Vs Replacement After Failed Mitral Transcatheter Edge-To-Edge Repair: The Cutting-Edge Registry., Mateo Marin-Cuartas, Jagdip Kang, Thilo Noack, Manuela De La Cuesta, Markus Krane, Volkmar Falk, Lenard Conradi, Christian Hagl, Maurizio Taramasso, Tom C Nguyen, D Scott Lim, Gorav Ailawadi, Michael J Mack, Robert L Smith, Anita W Asgar, Kendra J Grubb, Luigi Pirelli, Paolo Denti, Thomas Modine, Michael J Reardon, Tamim M Nazif, Vinayak N Bapat, Tsuyoshi Kaneko, Philipp Kiefer, Michael A Borger, Gilbert H L Tang, Syed Zaid

Faculty, Staff and Students Publications

Background: The impact of mitral valve (MV) surgery type after failed mitral transcatheter edge-to-edge repair (M-TEER) has not been well studied.

Objectives: The aim of this study was to compare the outcomes of MV repair vs replacement after failed M-TEER.

Methods: From 2009 to 2020, a total of 332 patients across 34 centers from the CUTTING-EDGE registry underwent MV surgery after M-TEER. Outcomes were compared between MV repair and replacement. Primary outcomes included 30-day mortality and 1-year survival after MV surgery.

Results: Among enrolled patients (mean age 73.8 ± 10.1 years, median Society of Thoracic Surgeons Predicted Risk of Mortality …

Left Ventricular Hypertrophy Among Adults In A Population-Based Cohort In Haiti, Anju Ogyu, Lisa De Las Fuentes, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

Left ventricular hypertrophy (LVH) is one of the strongest predictors of cardiovascular disease (CVD) and mortality; yet the means to diagnose LVH in resource-constrained settings remain limited. The objectives of this study were to determine LVH prevalence by transthoracic echocardiography (TTE) in a high-risk group, and compare TTE vs. electrocardiography (ECG-LVH) for LVH detection. We analyzed enrollment data from the Haiti cardiovascular disease cohort study on adults (≥ 18 years, n = 3,005) in Port-au-Prince between 2019 and 2021. All participants underwent questionnaires, vital signs, physical exams, and 12-lead ECGs. TTEs were acquired on those with hypertension or exhibiting CVD …

Pilot First-In-Human Ccr2 Pet/Ct To Detect Abdominal Aortic Aneurysm Wall Instability, Santiago Elizondo-Benedetto, Deborah Sultan, Ryan Wahidi, Mahdjoub Hamdi, Mohamed S Zaghloul, Shahab Hafezi, Batool Arif, Laura K Mcdonald, Kitty Harrison, Dakkota Thies, Gyu Seong Heo, Hannah Luehmann, Lisa Detering, J Westley Ohman, Zachary J Wanken, Luis A Sanchez, Joseph E Ippolito, Jie Zheng, Robert J Gropler, Richard Laforest, Yongjian Liu, Mohamed A Zayed

2020-Current year OA Pubs

No abstract provided.

Where Have All The Doctors Gone?, Paul B. Freeman Od

Optometric Clinical Practice

Editorial

Do Patients Want Their Spirituality Addressed During Their Hospital Journey; A Cross-Sectional Study At A Tertiary Care Center In Lebanon, Mohammad Assaf, Ali Ahmad, Hanine Atwi, Joseph Habib, Magda Haj, Reham Yehia, Amal C Rahi, Marianne Majdalani

Faculty, Staff and Student Publications

Background: Spirituality (including religiosity) is a powerful concept in Middle Eastern populations for members of all religious affiliations. This study aims to assess the desire of cancer and critically ill adult inpatients to be asked about their spiritual history, the impact their religious and spiritual beliefs have on their medical decisions, and if such beliefs help them cope with their illnesses.

Methods: A questionnaire consisting of demographics and spirituality questions was developed and administered to 100 patients in a cross-sectional study. We performed psychometric analysis of the questionnaire through reliability and validity testing including construct validity using PCA with a …

Lipoprotein(A) And Risk Of Incident Atherosclerotic Cardiovascular Disease: Impact Of High-Sensitivity C-Reactive Protein And Risk Variability Among Human Clinical Subgroups, Ron C Hoogeveen, Margaret R Diffenderfer, Elise Lim, Ching-Ti Liu, Hiroaki Ikezaki, Weihua Guan, Michael Y Tsai, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Behavioral And Psychological Symptoms Of Dementia And Alzheimer's Disease Progression In Down Syndrome, Melissa R Jenkins, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults with Down syndrome (DS) have a 90% lifetime risk for Alzheimer's disease (AD), with neurobiological pathology present decades prior to dementia onset. The profile and timing of cognitive decline in DS is well-documented. However, there is a small body of research on whether Behavioral and Psychological Symptoms of Dementia (BPSD) occur early on in the progression of AD in DS and are associated with early AD pathology (i.e., amyloid-beta [Aβ] and neurofibrillary tau tangles [NFT]).

METHODS: Data were analyzed from 337 adults with DS (M = 45.13 years, SD = 9.53 years) enrolled in a large cohort study. …

Effects Of Metformin Use On Aneurysmal Subarachnoid Hemorrhage Outcomes, Angel Bueno, Andrea Becerril-Gaitan, Collins Mokua, Kristina Ramirez-Garcia, Justin Nguyen, Faris Shaker, Tien Nguyen, Antonio Dono, Spiros Blackburn, Peng Roc Chen, Mark Dannenbaum, H Alex Choi, Arthur L Day, Jacques J Morcos, Ching-Jen Chen

Faculty, Staff and Student Publications

Background: Metformin is widely prescribed and has neuroprotective effects in animals, but its impact on brain injury after aneurysmal subarachnoid hemorrhage (aSAH) in humans is unclear.

Methods: This single-center retrospective review assessed patients with aSAH from 2009 to 2023, categorizing them based on pre-admission metformin use. The primary outcome was delayed cerebral ischemia (DCI), while secondary outcomes included in-hospital mortality, rebleeding, angiographic cerebral vasospasm (CVS), and favorable modified Rankin Scale (mRS) scores at discharge and the 3-month follow-up. Outcomes were analyzed using logistic regression. Sensitivity analysis was performed after excluding patients receiving comfort care.

Results: A total of 900 patients …

Her2-Selective Tyrosine Kinase Inhibitor, Zongertinib (Bi 1810631), In Patients With Advanced/Metastatic Solid Tumors With Her2 Alterations: A Phase Ia Dose-Escalation Study, John V Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto

Faculty, Staff and Student Publications

Purpose: Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors.

Materials and methods: Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); …

Impact Of Perioperative Organ Injury On Morbidity And Mortality In 28 Million Surgical Patients, Felix Kork, Yafen Liang, Adit A Ginde, Xiaoyi Yuan, Rolf Rossaint, Hongfang Liu, Alex S Evers, Holger K Eltzschig

Faculty, Staff and Student Publications

Perioperative organ injury contributes to morbidity and mortality of surgical patients. This cohort study included all elective and emergent surgeries in Germany over 4 years to address the impact of perioperative organ injuries on outcomes. We analyzed 28,350,953 cases. In-hospital mortality was 1.4% (n = 393,157), and 4.4% of cases (n = 1,245,898) experienced perioperative organ injury. Perioperative organ injury was associated with 9-fold higher odds of death and prolonged hospital stay by 11.2 days. Acute kidney injury had the highest incidence (2.0%) and was associated with 25.0% mortality. While delirium had the second highest incidence (1.5%), it was associated …

Impact Of Perioperative Organ Injury On Morbidity And Mortality In 28 Million Surgical Patients, Felix Kork, Yafen Liang, Adit A Ginde, Xiaoyi Yuan, Rolf Rossaint, Hongfang Liu, Alex S Evers, Holger K Eltzschig

2020-Current year OA Pubs

Perioperative organ injury contributes to morbidity and mortality of surgical patients. This cohort study included all elective and emergent surgeries in Germany over 4 years to address the impact of perioperative organ injuries on outcomes. We analyzed 28,350,953 cases. In-hospital mortality was 1.4% (n = 393,157), and 4.4% of cases (n = 1,245,898) experienced perioperative organ injury. Perioperative organ injury was associated with 9-fold higher odds of death and prolonged hospital stay by 11.2 days. Acute kidney injury had the highest incidence (2.0%) and was associated with 25.0% mortality. While delirium had the second highest incidence (1.5%), it was associated …

Phase 2 Trial Of Ibrutinib And Nivolumab In Patients With Relapsed Cns Lymphomas, Dai Chihara, Raphael E Steiner, Ranjit Nair, Lei Feng, Sairah Ahmed, Paolo Strati, Luis Malpica, Donna P Griffith, Shivon A Mathew, Wirt Montinez, Gita Masand, Felipe Samaniego, Maria A Rodriguez, Fredrick B Hagemeister, Luis E Fayad, Swaminathan P Iyer, Loretta J Nastoupil, Sattva S Neelapu, Christopher R Flowers, Jason R Westin

Faculty, Staff and Student Publications

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years …

Differential Antibody Response To Ebv Proteome Following Ebvst Immunotherapy In Ebv-Associated Lymphomas, Yomani D Sarathkumara, Nathan W Van Bibber, Zhiwei Liu, Helen E Heslop, Rayne H Rouce, Anna E Coghill, Cliona M Rooney, Carla Proietti, Denise L Doolan

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is associated with a diverse range of lymphomas. EBV-specific T-cell (EBVST) infusions have shown promise in safety and clinical effectiveness in treating EBV-associated lymphomas; however, not all patients respond to T-cell immunotherapies. To identify EBV antigen–specific antibody responses associated with clinical outcomes, we comprehensively characterized antibody responses to the complete EBV proteome using a custom protein microarray in 56 patients with EBV-associated lymphoma who received EBVST infusions in phase 1 clinical trials. Responders (nonprogressors) and nonresponders (progressors) had distinct antibody profiles against EBV. Twenty-five immunoglobulin G (IgG) antibodies were significantly elevated in higher levels in nonresponders than …

Association Of Age, Sex And Education With Access To The Intravenous Thrombolysis For Acute Ischemic Stroke, Yoona Ko, Beom Joon Kim, Youngran Kim, Jong-Moo Park, Kyusik Kang, Jae Guk Kim, Jae-Kwan Cha, Tai Hwan Park, Kyungbok Lee, Jun Lee, Keun-Sik Hong, Byung-Chul Lee, Kyung-Ho Yu, Dong-Eog Kim, Joon-Tae Kim, Jay Chol Choi, Jee Hyun Kwon, Wook-Joo Kim, Kyu Sun Yum, Sung-Il Sohn, Hyungjong Park, Sang-Hwa Lee, Kwang-Yeol Park, Chi Kyung Kim, Sung Hyuk Heo, Moon-Ku Han, Anjail Z Sharrief, Sunil A Sheth, Hee-Joon Bae

Faculty, Staff and Student Publications

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients.

Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed …

A Phase Ii Trial Of Sitravatinib + Nivolumab After Progression On Immune Checkpoint Inhibitor In Patients With Metastatic Clear Cell Rcc, Andrew W Hahn, Nabil Adra, Ulka Vaishampayan, Lianchun Xiao, Nazli Dizman, Ying Yuan, Sagar S Mukhida, Matthew T Campbell, Jianjun Gao, Amado J Zurita, Eric Jonasch, Nizar M Tannir, Amishi Y Shah, Pavlos Msaouel

Faculty, Staff and Student Publications

Background: Sitravatinib, an oral multi-kinase inhibitor targeting VEGFR, TAM, and MET, has been shown to resensitize the tumor microenvironment to immune checkpoint inhibitors (ICI) by reducing immune-suppressive myeloid cells in metastatic clear cell RCC (ccRCC). ICI is the standard first-line (1L) treatment of metastatic ccRCC, and there is unmet need for improved treatment outcomes after progression on ICI. We hypothesized that sitravatinib plus nivolumab would revert an immunosuppressive tumor microenvironment (TME) to improve clinical outcomes.

Methods: In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into 3 …

Year 1 Of Medicare's Accountable Care Organization Realizing Equity, Access, And Community Health Model, Gmerice Hammond, Sunny Lin, Sukruth A Shashikumar, R J Waken, Fengxian Wang, Khavya Avula, Vi-Anh Hoang, Kenton J Johnston, Karen Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: The US Centers for Medicare & Medicaid Services launched the Accountable Care Organization (ACO) Realizing Equity, Access, and Community Health (REACH) payment model in January 2023. In contrast to prior ACO initiatives, such as the Medicare Shared Savings Program (MSSP), ACO REACH includes equity-focused measures and payment adjustments, including an equity plan and financial risk adjustment for ACOs with higher proportions of underserved beneficiaries. However, it is unknown whether these changes have incented participation from organizations that serve beneficiaries from marginalized communities.

OBJECTIVE: To compare characteristics between participants in ACO REACH with those in MSSP and the broader pool …

Polygenic Score Analysis Identifies Distinct Genetic Risk Profiles In Alzheimer’S Disease Comorbidities, Carlos F Hernández, Camilo Villaman, Costin Leu, Dennis Lal, Ignacio Mata, Andrés D Klein, Eduardo Pérez-Palma

Faculty, Staff and Student Publications

Alzheimer’s disease (AD) is usually accompanied by comorbidities such as type 2 diabetes (T2D), epilepsy, major depressive disorder (MDD), and migraine headaches (MH) that can significantly affect patient management and progression. As AD, these comorbidities have their own cumulative common genetic risk component that can be explored in a single individual through polygenic scores. Utilizing data from the UK Biobank, we investigated the correlation between polygenic scores (PGS) for these comorbidities and their actual presentation in AD patients. We show that individuals with higher PGS values showed an elevated risk of developing T2D (OR 2.1, p = 1.07 × 10−11) …

Methylome-Wide Association Analyses Of Lipids And Modifying Effects Of Behavioral Factors In Diverse Race And Ethnicity Participants, Yao Hu, Jeff Haessler, Jessica I Lundin, Burcu F Darst, Eric A Whitsel, Megan Grove, Weihua Guan, Rui Xia, Mindy Szeto, Laura M Raffield, Scott Ratliff, Yuxuan Wang, Xuzhi Wang, Alison E Fohner, Megan T Lynch, Yesha M Patel, S Lani Park, Huichun Xu, Braxton D Mitchell, Joshua C Bis, Nona Sotoodehnia, Jennifer A Brody, Bruce M Psaty, Gina M Peloso, Michael Y Tsai, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Sharon L R Kardia, Alex P Reiner, Leslie Lange, Myriam Fornage, James S Pankow, Mariaelisa Graff, Kari E North, Charles Kooperberg, Ulrike Peters

Faculty, Staff and Student Publications

Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG …

Long-Term Patient-Reported Bowel And Urinary Quality Of Life In Patients Treated With Intensity-Modulated Radiotherapy Versus Intensity-Modulated Proton Therapy For Localized Prostate Cancer, Kimberly R Gergelis, Miao Bai, Jiasen Ma, David M Routman, Bradley J Stish, Brian J Davis, Thomas M Pisansky, Thomas J Whitaker, Richard Choo

Faculty, Staff and Student Publications

Purpose: This study aimed to compare long-term patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) for localized prostate cancer.

Methods and materials: Patients with clinical T1-T2 prostate cancer receiving IMRT or IMPT at a tertiary cancer center from 2015-2018 were analyzed to determine the changes in the prospectively collected bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26. The mean changes in EPIC-26 scores were evaluated from pretreatment to 24 months post-radiotherapy for each modality. A score change >50% of the baseline standard deviation was considered a …

Cross-Ancestry Genome-Wide Association Study Identifies Implications Of Sorl1 In Cerebral Beta-Amyloid Deposition, Jun Pyo Kim, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

GWAS of Alzheimer's disease have been predominantly based on European ancestry cohorts with clinically diagnosed patients. Increasing the ancestral diversity of GWAS and focusing on imaging brain biomarkers for Alzheimer's disease may lead to the identification of new genetic loci. Here, we perform a GWAS on cerebral β-amyloid deposition measured by PET imaging in 3,885 East Asians and a cross-ancestry GWAS meta-analysis with data from 11,816 European participants. Our GWAS analysis replicates known loci (APOE4, CR1, and FERMT2) and identifies a novel locus near SORL1 that is significantly associated with β-amyloid deposition. Single-nucleus expression analysis shows that SORL1 is differentially …

A Prospective, Multicenter Analysis Of Recurrence-Free Survival After Sentinel Lymph Node Biopsy Decisions Influenced By The 31-Gep., J Michael Guenther, Andrew Ward, Brian J Martin, Mark Cripe, Timothy Beard, Oliver Wisco, Rohit Sharma, Stanley P Leong, Richard Essner, Joseph I Clark, John Hamner, Brenda Sickle-Santanello, Maki Yamamoto

Oncology Articles

BACKGROUND: Although most patients with cutaneous melanoma (CM) will have a negative sentinel lymph node biopsy (SLNB), up to 20%-30% of these patients will recur. The 31-gene expression profile (31-GEP) test has been prospectively validated to identify patients at low (Class 1A), intermediate (Class 1B/2A), and high (Class 2B) risk of SLN positivity and recurrence.

METHODS: DECIDE is a prospective, multicenter study to assess the effect of 31-GEP testing on SLNB performance rates in patients with T1-T2 tumors considering SLNB and to study long-term outcomes. Here, we assessed outcomes in patients with a Class 1A 31-GEP result (n = 130). …

Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon

Kimmel Cancer Center Faculty Papers

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib …

Hbv Transmission Knowledge Among Korean-American Chronic Hepatitis B Patients In The United States, Giyoung Lee, Hee-Soon Juon, Eunji Kim, Katherine C Smith, Hie-Won Hann, Mimi Chang, Ann C. Klassen

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B (CHB) is a condition that disproportionately affects Asian Americans in the United States. Knowledge of transmission is crucial for CHB patients to practice prevention methods to limit the spread of the hepatitis B virus (HBV), but also live their lives free from unwarranted fears or restrictions. Among Asian CHB patients, several misperceptions about HBV transmission have been identified. This analysis aims to assess the current state of HBV knowledge among a cohort of Korean-American CHB patients. This mixed-methods study includes 363 respondents who completed a survey in either Korean (N = 298) or English (N = 65) …