Digital Commons Network^™

Mental Health Stigma In Latin American Youth With Obsessive-Compulsive Disorder, Ryan J Mccarty, Matias Jensen, Elissa Paz Jensen Santa Cruz, Melisa N Sagarnaga, Pamela Claisse Quiroz, Tomás Miño, Paola Giusti-Rodriguez, Mayra C Martinez Mallen, Maria B Moyano, Dayan Berrones, Jacey L Anderberg, Renee M Frederick, Hannah C Moore, Josselyn S Muñoz, Vanessa Zavala Cruz, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Working Group (Gttoc), Ogechi C Onyeka, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is an impairing mental health condition that affects individuals across the lifespan. Some literature has evaluated mental health stigma in adults with OCD but limited attention has been given to youth, as well as those of Latino ancestry. The present study reported the extent of stigma experiences among Latin American youth with OCD, as well as examined sociodemographic, clinical and psychological correlates. 235 youth with clinician confirmed diagnoses of OCD from 10 North and South American countries completed questionnaires assessing stigma experiences, symptomatology, and functioning. Sociodemographic and clinical variables were also collected. The average OCD stigma response …

Caregiver Satisfaction With Anxiety Treatment For Autistic Youth: A Mixed Methods Examination, Lesley A Norris, Jonathan C Rabner, Marika Marklin, Margaret E Crane, Kathrin Renschler, Emma Jenkins, Joshua Kemp, Eric A Storch, Jeffrey J Wood, Connor M Kerns, Adam B Lewin, Brent J Small, Philip C Kendall

Faculty, Staff and Students Publications

For Cognitive Behavioral Therapy to best meet the specific needs of autistic youth with co-occurring anxiety and to continue to grow as a sustainable treatment option, it is important to incorporate caregiver perspectives and feedback. Data were drawn from a randomized controlled trial and included 148 caregivers of autistic youth (ages 7-13 years, M = 9.89, SD = 1.79; 23% female; 77.7% White) with co-occurring anxiety disorders randomized to one of two active treatment conditions (Coping Cat, n = 72, or Behavioral Interventions for Anxiety in Children with Autism [BIACA], n = 76). A systematic inductive thematic analysis was used …

Mapping Dna Methylation Signatures To Identify Epigenetic Variation Across Subcortical Regions Of The Human Posttraumatic Stress Disorder Brain, Hongyu Li, Yujing Liu, Yiming Shi, Jiawei Wang, Tuan P Nguyen, Yuhan Xie, Wangjie Zheng, Youshu Cheng, Dianne A Cruz, Jennifer L Modliszewski, Rosemarie Terwilliger, Alexa-Nicole Sliby, José Jaime Martínez-Magaña, Janitza L Montalvo-Ortiz, John D Roache, Lynnette A Averill, Stacey Young-Mccaughan, Paulo R Shiroma, Bertrand R Huber, David A Lewis, Jill Glausier, Paul Holtzheimer, Matthew J Friedman, Jing Zhang, Alan L Peterson, Chadi G Abdallah, Amir Valizadeh, Xinyu Zhang, Ke Xu, John H Krystal, Ronald S Duman, Hongyu Zhao, David L Corcoran, Douglas E Williamson, Matthew J Girgenti

Staff and Researcher Publications

Background: Posttraumatic stress disorder (PTSD) is a mental disorder that may occur in the aftermath of severe psychological trauma. Epigenetic changes in the brain may play a critical role in understanding the neurobiology of PTSD by linking environmental traumatic stress exposure to lasting alterations in gene expression that shape neuronal function.

Methods: We examined 1,065,750 DNA methylation (DNAm) sites from 171 donors including neurotypical controls and PTSD and major depressive disorder (MDD) cases across 6 regions implicated in the fear circuitry of the brain. We performed RNA sequencing (RNA-seq) to examine changes in gene expression and linked these changes to …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Patient Perspectives On Psychiatric Polygenic Risk Scores In Reproductive Decision-Making And Polygenic Embryo Screening., Lauren A Ginn, Amanda R Merner, Page M Trotter, Kaitlynn P Craig, Abigail C Martinez, Ana Lucía Battaglino, Dorit Barlevy, Daphne M Ayton, Takahiro Soda, Eric A Storch, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Polygenic risk scores (PRS) estimate individuals' genetic risk for developing multifactorial conditions. Recent genome-wide association studies have enabled development of psychiatric PRS, which hold potential to streamline diagnosis and treatment of psychiatric conditions. As individuals with mental illness often identify concern about passing on psychiatric conditions as a key factor in family planning, some may also seek to use psychiatric PRS in reproductive decisions like childbearing or embryo selection for in vitro fertilization. Despite calls for increased regulation, there remains no clinical consensus on the utility of psychiatric PRS in reproductive contexts. Therefore, we conducted semi-structured interviews of adults with …

An Integrated Cardiometabolic Genetic Testing Program In A Predominantly Hispanic Population Within A Community Setting, Bo Yuan, Layla A Abushamat, Stacey Pereira, Surya Narayan Mulukutla, Grace E Tietz, Eric Venner, Sara E Kalla, Breanna Lee, Donna Muzny, Ginger Metcalf, Mullai Murugan, Sarah H Elsea, Senkottuvelan Kadirvel, Lele Li, Joshi Stephen, Shengfeng Xu, Victoria Yi, Monica Sulit, Christie L Kovar, Kimberly Walker, Marie-Claude Gingras, Jianhong Hu, Fei Yan, Taeko Gerber, Viktoriya Korchina, C Michael Fordis, Ruchi Gaba, Mahesh Changlani, Herschl Silberman, Hadley Stevens Smith, Christine M Eng, Jennifer E Posey, Clarisa Medina, Lisa R Treviño, Christie M Ballantyne, Richard A Gibbs, Ashok Balasubramanyam

Center for Medical Ethics and Health Policy Staff Publications

Purpose: This study aimed to apply cardiometabolic genetic testing in a community setting with a predominantly Hispanic population and assess feasibility and perspectives toward genetic testing.

Methods: A genome-sequencing-based genetic panel for cardiometabolic disorders (177 genes related to monogenic conditions, 2 LPA risk alleles, 2 pharmacogenomic loci, and ancestry-adjusted polygenic risk scores for type 2 diabetes and coronary artery disease) was deployed in community cardiology and endocrinology clinics in South Texas. A survey on perceptions toward genetic testing was administered after return of results.

Results: Testing was completed for 776 patients (18-92 years old, 92% Hispanic). 26 patients (3.4%) were …

Fluocinolone Acetonide Implant As A Baseline Therapy For Diabetic Macular Edema: Results From The Randomized Phase 4 New Day Study, Michael A Singer, Charles C Wykoff, Christopher D Riemann, Victor H Gonzalez, Christina Y Weng, Kamel Alkhatib, Rohit A Amarshi, Scott Moody, Mary Pao

Faculty, Staff and Students Publications

Purpose: The NEW DAY (ClinicalTrials.gov identifier, NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME).

Design: Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study.

Participants: Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST).

Methods: Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 17 months versus aflibercept loading dose (2 mg every 4 weeks for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if …

Social Determinants As Pathways In Disparities In Oral Cavity Cancer Stage At Diagnosis: A Registry-Based Analysis From 2010–2020, Guillermo A Tortolero, Erich M Sturgis, Itunu O Sokale, Abiodun Oluyomi, Kristina R Dahlstrom, Aaron P Thrift

Faculty, Staff and Students Publications

Purpose: Racial and ethnic differences in oral cavity cancer (OCC) stage at diagnosis are substantial, but the reasons remain unclear. We assessed insurance status and social neighborhood factors as potential pathways.

Methods: Using the Texas Cancer Registry, we identified adults diagnosed with OCC between 2010 and 2020. We examined the crude and multivariable associations of race and ethnicity, insurance status, and social neighborhood factors with stage at diagnosis. We investigated the mediating effects of insurance status and neighborhood-level social factors on racial and ethnic differences in stage at diagnosis using four-way decomposition with modified Poisson regression and robust standard errors. …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

Maternal Health And Sociodemographic Characteristics Influence Infant Growth To 24 Months In The Tunza Mwana Cohort: A Prospective Cohort Study, David Taylor Hendrixson, Mark J Manary, Et Al.

2020-Current year OA Pubs

Upstream pathways influencing child growth are complex. Weight-for-age z-score (WAZ) reflects both ponderal and linear growth and can identify children at high mortality risk. Using data from a prospective cohort of 326 mother-child pairs in Kenya, we evaluated whether associations between maternal exposures and child growth outcomes in early and later childhood. Growth trajectories were examined using locally weighted scatterplot smoothing and piecewise linear mixed-effect models with a knot at age 3 months. Poisson regression models examined associations between maternal characteristics and child underweight (WAZ <  -2) and stunting (LAZ <  -2) before and after 3 months. Mean WAZ increased to a peak at 3 months before declining steadily through 24 months. Lower maternal education (adjusted β [aβ] -0.18; 95% CI: -0.24, -0.13), household crowding (aβ -0.2; 95% CI: -0.28, -0.11), lower wealth quintile (aβ -0.04; 95% CI: -0.06, -0.02) and multiparity (aβ -0.16; 95% CI: -0.23, -0.1) were associated with lower monthly rate of change in WAZ prior to age 3 months. Younger maternal age was associated with an increased monthly rate of change in WAZ (aβ = 0.13; 95% CI: 0.08, 0.18) before 3 months and decreased monthly WAZ (aβ -0.02; 95% CI: -0.03, -0.01) after 3 months. Preterm birth was associated with increased risk of underweight in both periods (aRR 2.77; 95% CI: 1.39-5.50). Maternal mental health, intimate partner violence and adverse childhood experiences were not significantly associated with child growth. Maternal nutritional, socio-economic and household-level factors shape early growth, emphasising the need for cross-sectoral programs to support growth.

Patient-Centered Approach To Surgical Prevention Of Ovarian Cancer: A Nonrandomized Clinical Trial, Karen H Lu, Andrea R Hagemann, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative.

OBJECTIVE: To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October …

Factors Associated With Pre-Donation Health-Related Quality-Of-Life Among Pediatric Sibling Hematopoietic Cell Donors: A Donorkids Ql Study., Galen E. Switzer, Jessica G. Bruce, Bronwen E. Shaw, Vidya Kuniyil, James W. Varni, Brandan J. Butler, Connor Erickson, Alisha Mussetter, Allison Neutzling, Hisham Abdel-Azim, Paibel Aguayo-Hiraldo, Eric J. Anderson, Victor M. Aquino, Karlie Boone, Farid Boulad, Joseph H. Chewning, Jessica Cooper, Ann Dahlberg, Christopher C. Dvorak, Jorge Galvez-Silva, Ann E. Haight, Jennifer A. Hoag, Michelle Hudspeth, David Jacobsohn, Kimberly A. Kasow, Carrie L. Kitko, Lakshmanan Krishnamurti, Lisa Madden, Holly K. Miller, Erin Morales, Timothy S. Olson, Anna B. Pawlowska, Vinod K. Prasad, Troy C. Quigg, Andromachi Scaradavou, Niketa C. Shah, Shalini Shenoy, Nancy Terwilliger, Lori Wiener, Gregory A. Yanik, Lolie C. Yu, Michael A. Pulsipher

Manuscripts, Articles, Book Chapters and Other Papers

Due to limited published data assessing pediatric hematopoietic cell donor experiences, we previously conducted one of the largest quantitative investigations of pediatric donor experiences and health-related quality-of-life (HRQoL) at the time (RDSafe). Findings from RDSafe demonstrated that a subset of pediatric HC donors experienced very poor HRQoL; unfortunately, that dataset addressed only a limited number of factors, and key associations explaining this poor HRQoL were not found. In this study, our goal was to address that deficit by describing pre-donation donor HRQoL in detail and identifying factors across five key domains that were associated with donor HRQoL. We conducted a …

Current Practices And Variations Among Pediatric Severe Asthma Programs In The United States-The North American Severe Pediatric Asthma Consortium., Kristina Gaietto, Nadia Krupp, Avani V. Shah, Erhan Ararat, Samantha H. Averill, Sachin Baxi, Matejka Cernelc-Kohan, Jeffrey M. Chambliss, Heather De Keyser, Monica Federico, Bob Geng, Akilah A. Jefferson, Parisa Kaviany, Lila C. Kertz, Kirsten Kloepfer, Allyson Larkin, Sydney Leibel, Tanya Martinez-Fernandez, Samira Naime, Robert D. Pesek, Dinesh K. Pillai, Deepa Rastogi, Katherine Rivera-Spoljaric, Kristie R. Ross, Franziska J. Rosser, Tregony C. Simoneau, Jade Tam-Williams, Kelan G. Tantisira, William Anderson, Jonathan M. Gaffin, Theresa W. Guilbert, Erick Forno

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Severe and difficult to treat asthma in children is a complex condition causing significant morbidity and associated healthcare costs. While treatment guidelines exist for severe asthma, optimal treatment approaches for the pediatric population are less well established. Furthermore, best practices regarding real world management and implementation of guidelines for the severe pediatric asthma population are lacking. In order to provide care for this population, institutions around the United States have developed multidisciplinary severe pediatric asthma programs (SPAPs). In recent years, the North American Severe Pediatric Asthma Consortium (NASPAC) was established as a mechanism for SPAPs to collaborate and share …

Relationship Between Sociodemographic Characteristics At Presentation And Outcomes Of Provoked Venous Thromboembolism In United States Children: A Secondary Analysis Of The Multinational Kids-Duration Of Therapy For Thrombosis Trial., Hope P. Wilson, Maua M. Alleyne, Sanjay Ahuja, Ernest Amankwah, Aisha Bruce, Shannon L. Carpenter, Fernando F. Corrales-Medina, Craig A. Mullen, Arun Panigrahi, Lakshmi Srivaths, Courtney D. Thornburg, Anupam Verma, Gary Woods, Neil A. Goldenberg, Madhvi Rajpurkar

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Venous thromboembolism (VTE) is associated with adverse long-term sequelae, including recurrence and development of chronic venous insufficiency following limb deep vein thrombosis (postthrombotic syndrome [PTS]). Adult VTE studies have demonstrated that lower socioeconomic status, Black race, and Latinx ethnicity are associated with an increased risk of recurrence. Clinical trial-derived pediatric VTE data are limited.

OBJECTIVES: The objective of this study was to assess whether clinical features of provoked VTE and outcomes vary across sociodemographic characteristics and proxies for social determinants of health among children enrolled in the Kids-duration of therapy for thrombosis trial.

METHODS: We conducted a secondary analysis …

Clinical Ethics Training Needs Among Pediatricians And Pediatric Residents In Ethiopia: Conference-Based Cross-Sectional Survey., Betelehem Kassa, Addishiwot Melesse, Eyob Kebede Etissa, Bitseat W. Haile, Atnafu Mekonnen Tekleab, Stephanie Kukora

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatricians encounter ethically challenging cases in clinical practice throughout the world. In Ethiopia, ethically distressing pediatric cases are heightened by limited resources, lack of ethical frameworks to guide clinical care and withdrawal of supportive therapies, absence of child protection laws, and dearth of trained ethics consultants or institutional ethics committees providing clinical ethics consultation. Ethics training remains limited in undergraduate medical programs and absent in the resident curriculum at most institutions.

METHODS: A survey of Pediatric Residents and Pediatricians attending the Ethiopian Pediatric Society's 24th Annual Conference on March 2023 was conducted using a self-administered, clinical ethics needs assessment. …

Cytokine-Based Strategies To Improve Prognostic Enrichment Of Pediatric Ards., E Scott Halstead, Todd M. Umstead, Zissis C. Chroneos, Cainan Riccio-Baum, S Rameeza Allie, Daniel J. Mckeone, Debbie Spear, Ryan A. Nofziger, Ronald C. Sanders, Danielle Ahn, Jasmine C. Dowell, Asdis Finnsdottir Wagner, Neal J. Thomas, Prithvi Sendi, W Joshua Frazier, Courtney M. Rowan, Parag N. Jain, Dalia A. Bashir, Stuart H. Friess, Brian M. Varisco, Jocelyn Grunwell, Aline B. Maddux, Stephen T. Famularo, Nadir Yehya

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines.

METHODS: We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome [LEOPARDS]; NCT04113434) study. Plasma samples were obtained within 24 h of …

Insurance Type And Menopausal Hormone Therapy Use Among Us Women, Arina Chesnokova, Sunni Mumford, Allison Schachter, Rebecca Hamm, Scott Lorch, Matthew Klebanoff, Sarah Lindley, Erika Harness, Makeba Williams, Marilyn Schapira

Student Papers, Posters & Projects

IMPORTANCE: Access to menopausal hormone therapy (MHT) in the US remains low. Understanding whether insurance type is associated with MHT underuse and racial disparities in menopausal care is critical for designing interventions that increase evidence-based and equitable menopause care.

OBJECTIVE: To examine whether Medicaid compared with private insurance is associated with lower MHT use among US women. A secondary objective explored the degree that payer type is associated with observed racial differences in MHT use.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the 2013-2014, 2015-2016, and 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES) to identify …

Donor-Derived Cell-Free Dna As A Prognostic Biomarker After Heart Transplantation: The Define-Ht Study, Palak Shah, Paul J. Kim, Kelly H. Schlendorf, David A. Baran, Monica M. Colvin, Adam D. Devore, Howard Eisen, Kambiz Ghafourian, Michael M. Givertz, Eileen Hsich, Jaime L. W. Kennedy, Evan P. Kransdorf, Jose N. Nativi-Nicolau, Jignesh Patel, Eleni Tseliou, Omar Wever-Pinzon, Andrew Doud, Michelle S. Bloom, Sandra A. Carey, Navchetan Kaur, D Giovanni Biagini, Kyle E. Marshall, Michael Olympios, Mandeep R. Mehra, Josef Stehlik

Department of Medicine Faculty Papers

BACKGROUND: Measurement of donor-derived cell-free DNA fraction (dd-cfDNA%) and donor quantity score (DQS) is a noninvasive biomarker of acute rejection in heart transplantation (HT). Its prognostic value beyond histopathology remains uncertain.

OBJECTIVES: This study sought to evaluate associations between donor-derived cell-free DNA (dd-cfDNA) and clinically meaningful outcomes using a composite endpoint of treated rejection, graft dysfunction, retransplantation, or death within 1 year post-HT.

METHODS: The DEFINE-HT (Development of Noninvasive Cell-free DNA to Supplant Invasive Biopsy in Heart Transplantation) was a prospective, observational study following adult HT recipients at 10 U.S. centers for 1-year post-HT; blood was collected for dd-cfDNA testing …

Fluoroquinolone Use And Risk Of Pneumothorax In Adults Hospitalized With Community Acquired Pneumonia: A Retrospective Cohort Study, Steven Yi B. S., Saurav Sumughan B.S., Jessica Cobb M. D., Erika J. Yoo

Department of Medicine Faculty Papers

Objectives: The objective of this study is to examine the relationship between fluoroquinolone exposure and pneumothorax risk in patients hospitalized with pneumonia.

Methods: This retrospective cohort study used the TriNetX US Collaborative Network. We defined two mutually exclusive cohorts of hospitalized adults based on exposure to antibiotic classes commonly used to treat community acquired pneumonia: fluoroquinolone (ciprofloxacin, moxifloxacin, levofloxacin, and ofloxacin) versus nonfluoroquinolone (amoxicillin, azithromycin, ceftriaxone, and doxycycline). Patients with connective tissue disorders were excluded. The primary outcome was the occurrence of pneumothorax within 60 days. We used Cox proportional hazards regression to estimate hazard ratios (HRs) adjusted for demographics, …

Arrhythmia Burden And Clinical Responses Under Continuous Monitoring In Heart Failure: Observations From The Alleviate-Hf Trial., Rami Kahwash, Javed Butler, Muhammad Shahzeb Khan, David Zhang, Jonathan Dukes, Madhu Reddy, Rachel M Kaplan, Anish Amin, Rahul Kanwar, Shantanu Sarkar, Verla Laager, Jennifer Wehking, Brian Van Dorn, Bart Gerritse, Nirav Patel, Aimee Laechelt, Michael R Zile, Alleviate-Hf Investigators

OhioHealth Research Institute Articles

BACKGROUND: Arrhythmia burden in ambulatory patients with symptomatic heart failure (HF) without cardiac implantable electronic devices (CIEDs) is not well defined, and it remains uncertain whether device-guided remote congestion management modifies arrhythmia occurrence.

OBJECTIVES: The goal was to assess whether arrhythmia burden differed between randomized congestion-management strategies and characterize the occurrences and associations of insertable cardiac monitor (ICM)-detected arrhythmias with therapeutic actions and clinical events.

METHODS: In ALLEVIATE-HF, patients with NYHA functional class II-III HF with any ejection fraction (EF) and a recent HF event, without prior CIEDs, underwent ICM implantation and were randomized to ICM-guided, physician-directed, nurse-facilitated congestion management …

Risk-Based Nurse-Managed Personalized Heart Failure Interventions: The Alleviate-Hf Trial., Javed Butler, Rami Kahwash, Muhammad Shahzeb Khan, David Zhang, Jonathan W Dukes, Madhu Reddy, Anupam Basuray, Elie Gharib, Bart Gerritse, Aimee Laechelt, Jennifer Wehking, Shantanu Sarkar, Brian Van Dorn, Nirav Patel, Verla Laager, Michael R Zile, Alleviate-Hf Investigators

Heart and Vascular Articles

BACKGROUND: Early identification of worsening heart failure (HF) may improve outcomes.

OBJECTIVES: This study aims to assess if insertable cardiac monitor (ICM)-based high-risk detection combined with centrally managed, nurse-facilitated, individually protocolized diuretic interventions is safe and improves HF outcomes.

METHODS: A Reveal LINQ (Medtronic) ICM with an investigational HF risk-status software was implanted in participants with HF who were randomized 1:1 to an intervention arm (high-risk HF alert triggering protocolized diuretic regimen) or an observation arm (standard care). The primary safety endpoint was intervention-related serious adverse events and the primary efficacy endpoint was a 5-component hierarchical composite including cardiovascular death …

Fractionated Stereotactic Radiotherapy (Fsrt) For Symptomatic Who Grade 1 Cavernous Sinus Meningiomas: Long-Term Local Control, Clinical Response, And Toxicity Outcomes, Ryan Shah, Shray Jain, Nilanjan Haldar, Lauren A. Holt, Robert Walker, Christopher J Farrell, Md, Debanjan Haldar, James J. Evans, Gregory S. Alexander, Wenyin Shi

Department of Radiation Oncology Faculty Papers

PURPOSE: Cavernous sinus meningiomas represent a significant clinical challenge, given the high prevalence of neurological deficits and limited surgical options. Radiation therapy is often the preferred treatment. This study evaluates the effectiveness of fractionated stereotactic radiation therapy (fSRT) in achieving local control and symptomatic relief in patients with cavernous sinus meningiomas.

METHODS: This is a single-institution retrospective analysis of patients with symptomatic presumed WHO grade 1 cavernous sinus meningiomas treated with fSRT (1.8-2 Gy per fraction). Clinical data were collected by chart review. Kaplan-Meier curves were generated to assess local control. Clinical responses were evaluated for symptom improvement, stability, or …

Oncocytic Intraductal Carcinoma Of The Parotid Gland With Strn::Alk Fusion, Reham H Soliman, Chris Shi, Kevin E Fisher, Hong Yu, Fouad El-Dana, Xu Cao, Li Liang, Pei Ying, Songlin Zhang

Faculty, Staff and Students Publications

Intraductal carcinoma (IDC) of the salivary gland is an uncommon epithelial neoplasm characterized by a predominantly intraductal or intracystic proliferation rimmed by a myoepithelial cell layer. Advances in molecular profiling have revealed recurrent gene fusions in IDC, most frequently involving RET, although fusions implicating other kinase genes have also been described. Among these, ALK rearrangements are rare and remain poorly characterized. Herein, we report a case of oncocytic IDC of the parotid gland harboring a STRN::ALK fusion, further expanding the molecular landscape of this tumor. Although this fusion has been previously reported in intercalated duct IDC, to our knowledge, this …

Obesity And Keratoconus: A Mediation Study Based On The Chinese Keratoconus Cohort, Kaili Yang, Anqi Chang, Runqi Tu, Liyan Xu, Yuwei Gu, Qi Fan, Shanshan Yin, Yi Yuan, Yifan Wang, Chenchen Yin, Yonghao Zang, Changxiu Li, Chenjiu Pang, Daniela Oehring, Yibin Hao, Shengwei Ren

School of Health Professions

Purpose: Growing evidence indicates a strong association between obesity and keratoconus (KC), although the potential mediating factors remain largely unknown. This study aimed to explore the potential pathways through which corneal biomechanical and topographic parameters might link obesity and KC using structural equation modeling (SEM). Methods: This case-control study included 759 participants (363 patients with KC and 396 controls) from the Chinese Keratoconus (CKC) Cohort Study. Associations among body mass index (BMI), corneal biomechanical parameters, topographic parameters, and KC were analyzed using generalized linear regression models. SEM was used to construct latent variables for corneal biomechanical and topographic parameters. Three …

Chemotherapeutic Induction Of Cytosolic Single-Stranded Dna Accumulation Sensitizes Triple-Negative Breast Cancer To Immunotherapy, Yong Du, Li Yang, Hui Dai, Jianli Zhou, Zhicheng Zhou, Ruoxi Yuan, Rui Ye, Anh Thai Quynh Nguyen, Kishor Bhatia, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Background: Despite the widespread adoption of chemoimmunotherapy in triple-negative breast cancer (TNBC), the mechanisms by which cytotoxic chemotherapy engages antitumor immunity remain poorly defined. Identifying tumor-intrinsic immunogenic programs that predict and enhance responsiveness to immune checkpoint blockade (ICB) is therefore of critical clinical importance.

Methods: Transcriptomic signatures of TREX1 deficiency were generated from CRISPR-engineered TNBC models and applied to multiple independent TNBC cohorts treated with chemoimmunotherapy. Cytosolic single-stranded DNA (ssDNA) accumulation was quantified using a flow cytometry-based assay to functionally screen chemotherapeutic agents. Immune activation and therapeutic efficacy were evaluated using in vitro assays, syngeneic mouse tumor models, flow cytometry, …

Folr1-Targeted Actinium-225-Based Alpha-Particle Therapy Eliminates Ovarian Cancer, Neetu Singh, Esther Need, Ayden Berndt, Matthew Goff, Lydia J. Wilson, Firas Mourtada, Feng Guo, Tara Mastren, Taslim Al-Hilal, Anil K. Sood, Amit Maity, Scott C. Miller, Satoshi Minoshima, Shreya Goel, Sixiang Shi

Department of Radiation Oncology Faculty Papers

Despite the advancement in therapies, ovarian cancer treatment is challenging because of poor prognosis and high relapse associated with acquired resistance. Emerging targeted alpha particles, particularly actinium-225 (225Ac), for treating refractory cancers have opened avenues for improved therapeutic options. Here, we describe a successful example of folate receptor 1 (FOLR1)–targeted 225Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal positron emission tomography imaging demonstrated high tumor-specific uptake of αFOLR1 (anti-FOLR1 antibody) in SKOV3 xenografts. FOLR1-targeted 225Ac demonstrated high therapeutic efficacy, achieving marked tumor regression, 80% survival, and 40% complete tumor elimination. The therapy resulted in tumor-specific double-stranded DNA damage, and …

Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker

Faculty, Staff and Students Publications

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. …

Intersection Of Pediatric Hypertension And Cardiovascular-Kidney-Metabolic Disease, Jessica O'Keeffe, Christina Kingshill, Jack Tompson, Andrew M. South, Carissa M. Baker-Smith

Department of Medicine Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to describe the intersection between pediatric hypertension and advancing stages of cardiovascular, kidney metabolic syndrome in children and adolescents.

RECENT FINDINGS: Cardiovascular-kidney-metabolic syndrome is highly prevalent in the pediatric population. The onset of CKM in childhood is influenced by the presence of antenatal risk factors such as maternal hypertensive disorders of pregnancy. Advancing stages of CKM in children and adolescents are strongly influenced by food insecurity and social determinants of health that impact the risk for childhood obesity. Activation of the renin-angiotensin-aldosterone system is a key mediator in the relationship between …

Chiari Malformation Type 1 Is Associated With A Smaller Fourth Ventricle Volume - A Multi-Cohort Replication Study, Jarod L Roland, Thanda Meehan, Alexandra Gabliani, Scott Marek, Nico Dosenbach, Joshua S Shimony, Nilay Jakati, Yi Li, Leo Sugrue, Jennifer M Strahle, Chenyang Lu, David D Limbrick, Gabe Haller

2020-Current year OA Pubs

Chiari Malformation Type 1 (CM1) is canonically defined by ectopic position of the cerebellar tonsils with additional anatomic variations described inconsistently. Effect on fourth ventricle volume is controversial with prior studies reporting disparate results and methodologically limited to single institution series that hinder generalizability. This limitation was addressed utilizing multiple data sources, longitudinal replication, and reproducible methods using both FreeSurfer and the deep learning-based DL+DiReCT tools for automated volumetrics. First, we analyzed a local retrospective clinical cohort of individuals with CM1 and controls. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we analyzed volumes at baseline then replicated …

Prmt5 As A Key Driver Of Stemness And Metastatic Potential In Triple-Negative Breast Cancer, Jae Jin Jeong, Mauli Maniar, Shahrzad Ghane, Sakshi Deshpande, Claire Ellis, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) mediates arginine methylation of a wide range of proteins and plays context-dependent oncogenic or tumor-suppressive roles. In cancer, PRMT5 represses several tumor suppressor genes, including E-cadherin, TP53BP1, ST7, PTEN, and RB (retinoblastoma). Elevated PRMT5 expression has been reported across multiple cancer types, notably triple-negative breast cancer (TNBC). In TNBC, high PRMT5 levels are associated with enhanced cancer stem cell self-renewal, increased tumor growth and metastasis, and reduced patient survival. Mechanistically, PRMT5 promotes breast cancer stem cell maintenance and proliferation through stabilization of the transcription factors KLF4 and KLF5. Disruption of the PRMT5-KLF4 axis results in …