Medical Specialties Commons^™

Discovery Of Novel, Potent, And Orally Bioavailable Smarca2 Proteolysis-Targeting Chimeras With Synergistic Antitumor Activity In Combination With Kirsten Rat Sarcoma Viral Oncogene Homologue G12c Inhibitors, Sasikumar Kotagiri, Yawen Wang, Yanyan Han, Xiaobing Liang, Nicholas Blazanin, Hira Mazhar, Manu Sebastian, Phuong Kieu Nguyen, Yongying Jiang, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex, including SMARCA4 in nonsmall cell lung cancer with a frequency of up to 33% in advanced-stage disease, making it the most frequently mutated complex. We and others have identified SMARCA2 to be synthetic lethal to SMARCA4, indicating that SMARCA2 is a high-value therapeutic target. Here, we disclose the discovery and characterization of potent, selective, and orally bioavailable cereblon-based SMARCA2 PROTACs. Biochemically, we showed that YDR1 and YD54 are potent SMARCA2 degraders. Further, we showed the antitumor growth inhibitory activity of YDR1 and YD54 in SMARCA4 …

Zanidatamab Monotherapy Or Combined With Chemotherapy In Her2-Expressing Gastroesophageal Adenocarcinoma: A Phase 1 Trial, Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Syma Iqbal, Keun-Wook Lee, Jeeyun Lee, Muralidhar Beeram, Do-Youn Oh, Jorge Chaves, Rachel A Goodwin, Jaffer A Ajani, Lin Yang, Rajen Oza, Elena Elimova

Faculty, Staff and Student Publications

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, …

Improved Outcomes Of Acute Lymphoblastic Leukemia After Allogeneic Blood Or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide In The Era Of More Effective Pre-Transplant Therapy, Jonathan A Webster, Madison Reed, Hua-Ling Tsai, Philip H Imus, Douglas B Smith, Alexander J Ambinder, Mark J Levis, Amy E Dezern, Gabrielle T Prince, Tania Jain, Javier Bolaños-Meade, Lukasz P Gondek, Gabriel Ghiaur, William Brian Dalton, Theodoros Karantanos, Suman Paul, Ephraim J Fuchs, Cole Sterling, Lode J Swinnen, Nina Wagner-Johnston, Richard F Ambinder, Christian B Gocke, Syed Abbas Ali, Carol Ann Huff, Leo Luznik, Ravi Varadhan, Richard J Jones, Ivana Gojo

Faculty, Staff and Students Publications

The therapeutic landscape in ALL has changed dramatically over the last decade. Allogeneic blood or marrow transplantation (AlloBMT) has also evolved and remains an important option for consolidation. We assessed the interplay between these factors by analyzing the outcomes of 251 adult ALL (214 B and 37 T ALL) patients undergoing alloBMT with post-transplantation cyclophosphamide (PTCy) across two eras: 2008-2014 (ERA1) and 2015-2022 (ERA2). ERA1 patients were younger (median age 45.5 vs. 50, p=0.03), less likely to have an HCT-CI ≥4 (9% vs. 21%, p=0.01), more likely to have MRD by flow cytometry (20% vs. 9%, p=0.01) and receive myeloablative …

Human Genetic Variation Determines 24-Hour Rhythmic Gene Expression And Disease Risk, Ying Chen, Panpan Liu, Aniko Sabo, Dongyin Guan

Faculty, Staff and Students Publications

24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. Biological rhythms are known to have a genetic basis formed by core clock genes, but how individual genetic variation shapes the oscillating transcriptome and contributes to human chronophysiology and disease risk is largely unknown. Here, we mapped interactions between temporal gene expression and genotype to identify quantitative trait loci (QTLs) contributing to rhythmic gene expression. These newly identified QTLs were termed as rhythmic QTLs (rhyQTLs), which determine previously unappreciated rhythmic genes in human subpopulations with specific genotypes. Functionally, rhyQTLs and their …

Development Of A Risk Score To Aid With The Diagnosis Of Infections After Spinal Cord Injury: Protocol For A Retrospective Cohort Study, Felicia Skelton, Larissa Grigoryan, Joann Pan, Ashley Collazo, Barbara Trautner

Faculty, Staff and Students Publications

Background: Patients with spinal cord injury (SCI) who develop urinary tract infection (UTI) present differently than the non-SCI population. UTIs can cause loss of quality of life and even lead to life-threatening complications including urosepsis. Challenges in SCI management include distinguishing symptomatic UTI from asymptomatic bacteriuria (ASB), which occurs often in patients with SCI, and the lack of standardization in UTI diagnosis in SCI.

Objective: This study aims to set the foundation for the development of a risk score to improve diagnostic accuracy of UTI after SCI.

Methods: This study will use data from the Veterans Health Administration Corporate Data …

A Clinical Review Of Suicide Risks In Dermatology, Rahib K. Islam, Victoria T. Tong, Shari R. Lipner

School of Medicine Faculty Publications

Patients with visible skin diseases, including acne, psoriasis, and atopic dermatitis, face heightened risks of psychological distress, depression, and suicidal ideation, often exacerbated by social stigma and reduced quality of life. This review explores the intersection between dermatology and suicide, highlighting the psychosocial impact of visible skin conditions and the controversies surrounding treatment-related risks, including isotretinoin and biologic exposure. Current evidence suggests that while isotretinoin has been historically linked to mood changes, robust studies do not support a direct association with suicide. Incorporating mental health screenings into dermatological practice is essential for early identification and management of at-risk patients. By …

Making Training Stick: Transferring Learning Back To The Job, Amanda Woods Herron, Phoebe Hessen, Katelyn J. Cavanaugh, Wykesha C. Hayes, Victor Hassid, Courtney L. Holladay

Advances in Cancer Education and Quality Improvement

Communication remains a central priority in healthcare, making it a key component of many training efforts. The positive impacts of communication training in healthcare settings have been well-established; however, the linkage of communication training to key organizational outcomes (e.g., engagement, performance, retention) remains underexplored. The present study investigated a training program targeting interpersonal communication within a large academic oncology center. We drew from Cognitive Load Theory and Social Cognitive Theory to evaluate the impact of the training on participant learning (retention and utilization), transfer (communication, decision-making, performance), and results-level outcomes (engagement and turnover). The program centered around a personality framework …

A Multi-Modal Intervention To Improve Identification, Management, And Prevention Of Recurrent Urinary Tract Infections In The Urgent Care Clinic, Stephanie Krol

Evidence-Based Practice Project Reports

Nearly 60% of women will suffer from a urinary tract infection (UTI) in their lifetime, with 20- 40% of them suffering from multiple (Anger et al., 2022). The primary purpose of this evidence-based project was to implement a multi-modal intervention to improve identification of women who suffer from recurrent urinary tract infections (rUTIs) and to assist in the prevention and treatment of future UTIs. Additionally, the project aimed to increase the number of referrals to urology for better management of these patients. This project was implemented at an Urgent Care Clinic (UCC) in northwest Indiana. Eligible participants who presented with …

Comparing Treatment Effectiveness And Patient-Reported Outcome Measures Of Four Treatment Options For Obstructive Sleep Apnea, Robert Diecidue, Dmd, Md, Phd, Mba, Msph, Joseph Harrington, Bs, Erika L. Manning, Phd, Md, Mph, Colin T. Huntley, Md

Department of Otolaryngology - Head and Neck Surgery Posters

Abstract

- There are four common treatment modalities for obstructive sleep apnea (OSA)

• CPAP, MAD, UAS, MMA

- Retrospective data was examined to compare efficacies between these treatments for patients treated with one of these four OSA therapies.

• Primary outcome: Mean disease alleviation (MDA) - calculated value based on improvement of AHI adjusted by compliance.
• Secondary outcomes: Patient reported outcome measures (PROMs) - ESS, PRAQ, SAQLI

- It was found that the greatest mean disease alleviation was found in patients who underwent MMA. PROMs showed the most significant improvement in daytime sleepiness (ESS) for MMA.

Towards The Performance Characterization Of A Robotic Multimodal Diagnostic Imaging System, George Papaioannou, Christos Mitrogiannis, Mark Schweitzer, Nikolaos Michailidis, Maria Pappa, Pegah Khosravi, Apostolos Karantanas, Sean Starling, Christian Ruberg

Publications and Research

Characterizing imaging performance requires a multidisciplinary approach that evaluates various interconnected parameters, including dosage optimization and dynamic accuracy. Radiation dose and dynamic accuracy are challenged by patient motion that results in poor image quality. These challenges are more prevalent in the brain/cardiac pediatric patient imaging, as they relate to excess radiation dose that may be associated with various complications. Scanning vulnerable pediatric patients ought to eliminate anesthesia due to critical risks associated in some cases with intracranial hemorrhages, brain strokes, and congenital heart disease. Some pediatric imaging, however, requires prolonged scanning under anesthesia. It can often be a laborious, suboptimal …

Sugammadex For Reversal Of Neuromuscular Blocking Agents Versus Neostigmine - Safety Comparison, Amanda K. Butler, Daniel Belu, Bailey Accardo, Courtney Ayana Bullard, Tracy Mcclinton Dnp, Aprn, Agacnp-Bc, Hget-C, Ebp-C, Dwayne Accardo Dnp, Crna, Faana

Doctor of Nursing Practice Projects

Purpose/Background

Sugammadex and neostigmine are two common drugs used to reverse neuromuscular blockade in anesthesia, but they differ in mechanism of action, side effects, and cost.

Sugammadex provides rapid reversal, has fewer side effects, and has a lower risk of bradycardia than neostigmine. This scoping review examines the frequency of bradycardia in adult surgical patients receiving sugammadex versus neostigmine.

Methods

A scoping review was completed of peer-reviewed articles comparing the incidence of bradycardia in adult surgical patients after the administration of sugammadex and neostigmine for neuromuscular blockade reversal. Findings indicate that sugammadex resulted in fewer adverse events, including bradycardia, than …

Characterising Acute And Chronic Care Needs: Insights From The Global Burden Of Disease Study 2019, A. A. Asadi-Pooya

Department of Neurology Faculty Papers

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic …

Human Pain Neuroscience And The Next Generation Of Pain Therapeutics, Bryan A Copits, Michele Curatolo, Patrick M Dougherty, Robert W Gereau, Wenqin Luo, Maryann Martone, Hakan Olausson, Theodore J Price, William Renthal, Clifford J Woolf, Guoyan Zhao

Faculty, Staff and Student Publications

The recent approval of suzetrigine for acute pain treatment highlights both the success of targeting peripheral sensory neurons for pain management and the potential of developing new pain therapies primarily in human-based systems. To realize this transformative potential, further research into somatosensation and pain neuroimmunology in human systems is essential.

Variance In Heart Rate Variability Between Healthy And Concussed Individuals, Sebastian Herrera Vargas, Joonsuk Choi

Student Scholar Symposium Abstracts and Posters

Heart-Rate Variability (HRV) is the interval between each individual heartbeat, from p-wave to p-wave on an electrocardiogram (ECG). In general, a high HRV indicates that a person has a healthy heart with effective stress management skills. This value means that one branch of the nervous system is not overpowering the other, sympathetic vs parasympathetic–for example. Generally, HRV is related to vagal tone, the ability for your body to activate the parasympathetic system and relax when imminent danger is not present. However, when someone is concussed, the entirety of their autonomic regulation can be affected such that their HRV is altered. …

A Honduran Prevalence Study On Soil-Transmitted Helminths Highlights Serological Antibodies To Tm-Wap49 As A Diagnostic Marker For Exposure To Human Trichuriasis, Neima Briggs, Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Bin Zhan, Graeme Segal, Stephanie Novak, Patricia Lenihan, Paul Musgrave, Viviana Ellis, Carol Florencia Coello, K Jagannadha Sastry, Joe Craft, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Student Publications

Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic …

Stethoscope Hygiene And Its Relationship To Healthcare Acquired Infections: A Research Proposal, Thomas P. Baker

Aurora

Problem: Healthcare Acquired Infections (HAIs) are an increasingly prevalent issue in healthcare. While hand hygiene is the most effective method to prevent HAIs, stethoscope hygiene may be an underutilized practice that can further prevent HAIs.

Purpose: The purpose of the research proposal is to determine if patients are more at risk of acquiring a HAI from improperly sanitized stethoscopes in comparison to stethoscopes that are cleaned in accordance with best practice methods while being treated in a hospital.

Methods: This proposal is a mixed-methods study. A 30-minute educational seminar on the importance of stethoscope hygiene and evidence-based …

Using A Pharmacokinetic Model To Design And Evaluate An Early Ctdna Biomarker For Response To Targeted Therapy, Aaron Li

Spora: A Journal of Biomathematics

Early prediction of response to therapy or lack thereof can help physicians plan treatment more efficiently. Biomarkers based on circulating tumor DNA (ctDNA) are promising. However, biomarkers beyond direct comparison to baseline have not been thoroughly explored. We develop a model for ctDNA shedding under targeted therapy that incorporates pharmacokinetics. Using a simulated cohort of virtual patients with varied parameters, we define and analyze a biomarker based on ctDNA samples at baseline, 12 hours, and 24 hours after initiation of treatment. The biomarker identified patients who would achieve partial or complete response with high sensitivity and specificity and was able …

Long-Term Care Services And Support In The Mountain West, 2023, Taylor Volk, Ivan Sun, Miguel Soriano Ralston, Kristian Thymianos, Caitlin J. Saladino, William E. Brown Jr.

Health

This fact sheet presents data from the American Association of Retired Persons (AARP) report, “Long-Term Services and Supports 2023 State Scorecard Report,” comparing Long-Term Services and Supports (LTSS) systems across multiple dimensions of performance for older adults, people with physical disabilities, and family caregivers for all 50 states. This fact sheet focuses on state-level LTSS system data for the Mountain West states of Arizona, Colorado, Nevada, New Mexico, and Utah.

The Lasting Legacy Of Dr. Fritz Smith And Dr. Aminah Raheem: Founders Of Zero Balancing And Soul Lightening/Insight Acupressure, Deanna Waggy Otr

Journal of Transformative Touch

Dr. Fritz Smith and Dr. Aminah Raheem were pioneers in the field of holistic bodywork. Their innovative techniques, Zero Balancing (ZB) and Insight Acupressure (formerly Soul Lightening International), helped shape integrative medicine practitioners around the globe. Their marriage not only symbolized a personal union but also a professional synergy, with their complementary therapies offering a yin-yang approach to mind-body healing. Their legacy continues through the many practitioners trained in Zero Balancing and Soul Lightening/Insight Acupressure and the various organizations that uphold their commitment to research, education, and professional standards.

Decedent Management Station, Providence Special Pathogens Program

Conferences

No abstract provided.

Next Steps In Spreading Preparedness, Not Pathogens..., Christa Arguinchona

Conferences

No abstract provided.

Getting An “A” In Category A Waste, Christa Arguinchona

Conferences

No abstract provided.

Influenza Talk Proposed Titles, Henry Arguinchona

Conferences

No abstract provided.

An Overview Of The Lassa Fever Responce In Iowa, Michael Hartley

Conferences

No abstract provided.

Region 10 Special Pathogen Transport Preparedness, Providence - Special Pathogens Program

Conferences

No abstract provided.

When Zebras Attack: Special Pathogens Preparedness In An Ever-Changing World, Jonathan Grien

Conferences

No abstract provided.

Learning From Real Life: Alaska Edition, Christina Tuomi, Eugene Wiseman, Nathan Wormington, Travis Cruse, Lindsey Sprinkle

Conferences

No abstract provided.

Parvovirus B19 Infection In Kidney Transplant Recipients, Hatem Najar, Kiran Goli, Maria P. Martinez Cantarin

Division of Nephrology Faculty Papers

On August 14, 2024, the Centers for Disease Control issued a Health Alert Network (HAN) health advisory due to a surge in Parvovirus B19 (B19V) infections in the United States. Our report presents two cases of suspected donor-derived Parvovirus B19 infection in kidney transplant patients. Both cases had refractory anemia requiring treatment with intravenous immunoglobulin. These cases highlight the importance of awareness and monitoring of B19V infection in the context of recent epidemiologic trends to improve clinical outcomes in kidney transplant recipients.

Multilevel Factors Influencing Perceived Barriers To Adjuvant Endocrine Therapy Among Breast Cancer Patients At Medication Onset, Timothy Cocozza, Rita Smith, Ana Maria Lopez, Shari Rudoler, Rachel Slamon, Tingting Zhan, Jazmarie L. Vega, Minal Dhamankar, Aruna Padmanabhan, Suzanne M. Miller, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

Purpose: Adjuvant endocrine therapy (AET) significantly diminishes recurrence and mortality risks in hormone receptor-positive breast cancer (BCa) patients. Nonetheless, suboptimal adherence and premature discontinuation during the initial year of treatment undermine these positive outcomes. This study aims to understand the potential diverse factors associated with perceived barriers to AET compliance at the onset of medication. Methods: We assessed perceived barriers to AET using the ASK-20 instrument for BCa patients initiating AET within 3 months. Our survey also included demographic variables (e.g., musculoskeletal symptoms) and clinical traits (e.g., medication type). Stepwise regression analyses were employed to elucidate the links between multilevel …

Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang

Faculty, Staff and Student Publications

Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.

Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206+) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth …