KUMC Faculty Research Day 2021 - Virtual Poster Session - October 12, 2021

University of Kansas Medical Center

Faculty Research Day 2021 - View Posters and Join Links to Visit with Authors

Posters Available for Viewing starting on Monday, October 11.

Live poster sessions/visit with presenters from 10:00 AM to Noon on Tuesday, October 12

More info: https://www.kumc.edu/kumcri/sponsored-programs-administration/finding-funding/internal-funding-opportunities/faculty-research-day-and-posters-session.html

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Applicant Savings in the 2020-2021 Residency Recruitment Cycle: One Institution's Experience

Kari Nilsen PhD, Anne Walling MB ChB, Mark Meyer MD, Gretchen Irwin MD MBA, Gregory Unruh MD

Abstract: Purpose This study aimed to assess the impact of virtual interviewing on the National Residency Matching Program (NRMP©) residency application process. The study team has collected applicant NRMP© experiences for seven consecutive years, enabling comparisons from before and after the change to virtual interviewing. Participating in the NRMP© can be expensive and time-consuming for applicants, and it was anticipated that virtual interviewing would lead to reductions in expenses and time but increases in number of applications and ranked programs due to the removal of travel barriers. Method Fourth-year medical students applying for first year residency positions via the NRMP© completed an electronic 46-item questionnaire after submission of rank lists. Statistical analyses included descriptive statistics and t-tests for demographics and questions related to number of applications and interviews, as well as cost and time spent. We used thematic analysis to code narrative comments about the virtual interviewing experience. Results The institution has collected data from 1,040 (83.3%) applicants over seven years. For 2020/2021 the response rate was 68.1%. The largest number of applicants were to family medicine (21.7%) and internal medicine (13.3%). Average total costs dropped $3,566 and average estimated time dropped 13.3 days. The average number of applications dropped by 3.4, interviews completed was virtually unchanged, and applicants ranked an average 2.3 fewer programs. Open-ended comments from 113 (79%) applicants revealed four major themes related to the virtual interviewing format. Conclusion This study demonstrates an approximately 80% reduction in costs and an approximately 50% decrease in time interviewing for residency positions. Match outcomes were virtually unchanged from previous years. In our institution, remote interviewing due to the COVID-19 pandemic resulted in reductions in cost and time associated with the NRMP© without massive increases in number of applications, interviews, or ranked programs by applicants, and was generally perceived positively by applicants.
Presented by: Kari Nilsen
Institution: University of Kansas School of Medicine- Wichita KS; University of Kansas School of Medicine- Kansas City KS

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Qigong Exercise may modify stress coping strategies and improve distress in breast cancer survivors – a pilot study

Liu W, Handke D, Yeung A, Oh B, Boolittle CC.

Abstract: INTRODUCTION: Up to two-thirds of cancer patients experience distress during and after cancer treatment. Coping is an individual’s attempt to mitigate that stress. This pilot study explores effect of a Qigong exercise on depression, perceived stress, coping strategies, cognitive appraisal of health in breast cancer (BC) survivors. METHODS: Participants were recruited at the tertiary teaching hospital. Participants completed an 8-week intervention program including two training sessions within the first 2 weeks and followed by 6 weeks of two daily Qigong exercise sessions each about 20 minutes. Outcomes were assessed with the Center for Epidemiological Studies Depression Scale (CES-D), Perceived Stress Scale (PSS-10), Ways of Coping Questionnaire (WCQ), and Cognitive Appraisal of Health (CAH). RESULTS: Eight participants with a mean age of 55.4 (±9.4) years and a mean duration of 46.4 (±68.5) months post cancer treatments participated in the Qigong exercise program. Participants reported significant decrease in CES-D (p<0.001) and PSS-10 scores (p<0.001). The significant changes were also observed in the decreased scores of WCQ domains of escape avoidances (p<0.01) and accepting responsibility (p<0.05), and increased sub-score of CAH benign category (p<0.05). DISCUSSION: Results of this study suggested that Qigong may be a beneficial approach for reducing stress and depressive symptoms in breast cancer survivors. Decreases in two coping strategies of escape avoidance and accepting responsibility suggested that the Qigong exercise helped the participants better cope with their stressors with less passive emotional strategy and less self-blame. Finally, an increase in benign appraisal suggested that participants considered their stressors less threat to their well-being after the Qigong exercise. This pilot study is the first to report changes in coping strategies after a Qigong exercise in breast cancer survivors.
Presented by: Wen Liu
Institution: University of Kansas Medical Center, Massachusetts General Hospital, and Royal North Shore Hospital, Australia

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A structured brain-wide and genome-wide association study using ADNI PET images

Yanming Li

Abstract
Presented by: Yanming Li
Institution: KUMC Department of Biostatistics and Data Science

Diffuse Large B-Cell lymphoma with BCL6-MYC translocation due to a rare t(3;8)(q27;q24) - A Case Report

Angela France, DO, Da Zhang, MD, and Shivani Golem, PhD

Abstract: Diffuse large B cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma. It comprises a heterogenous group of diseases that vary in morphology, immunophenotype and molecular features. Evaluation of prognostic factors is important in determining the risk category of patients newly diagnosis with DLBCL. Analysis of a MYC, BCL2 and BCL6 is essential in identifying high-risk patients. Lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known as double-hit lymphoma (DHL) or Triple-Hit Lymphoma (THL) and are associated with a poor clinical outcome. We report a rare case of a patient with DLBCL with a unique t(3;8)(q27;q24) that involves the BCL6 and MYC genes.
Presented by: Angela France, DO
Institution: University of Kansas Medical Center - Department of Pathology

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Poster: Peptides Derived from the Stalk Region of the Polycystin-1 C-terminal Fragment (CTF) Function as Ligands to Regulate Signaling and to Ameliorate Cystogenesis

Peptides Derived from the Stalk Region of the Polycystin-1 C-terminal Fragment (CTF) Function as Ligands to Regulate Signaling and to Ameliorate Cystogenesis

Brenda S. Magenheimer and Robin L. Maser

Abstract: Background: Polycystin-1 (PC1) modulates G protein signaling by as yet unknown regulatory mechanisms. Like the Adhesion class of GPCRs, PC1 undergoes auto-catalyzed cleavage at a GPS motif, which generates a large extracellular, N-terminal fragment and a membrane-embedded, C-terminal fragment (CTF) composed of 11 transmembrane domains preceded by an N-terminal extracellular stalk of 25 residues. We previously reported that PC1 CTF-mediated signaling to an NFAT reporter is dependent on the presence of the stalk, and is reduced by specific amino acid substitutions within its sequence. To ascertain if this stalk-dependent mechanism contributes to the inhibition of cyst formation, the ability of stalk-derived peptides to rescue signaling by a ‘stalk-less’ CTF expression construct (ΔCTF) and to ameliorate cAMP-driven cystogenesis was determined. Methods: HEK293T cells transiently transfected with the ΔCTF construct lacking the first 21 residues of the stalk region were treated with soluble peptides (P) ranging from 7 to 21 residues in length whose sequences were derived from the stalk region. Activation of a co-transfected NFAT promoter-luciferase reporter was compared between ΔCTF- and empty expression vector control-transfected cells. Metanephric organ cultures derived from E15.5 Pkd1 fetal mice were stimulated with 8-Br-cAMP, and were treated with stalk peptides for up to 4 days in culture. The cystic area was compared between non-treated and peptide-treated kidneys. Results: All of the stalk peptides (P7-P21) enhanced signaling from ΔCTF to the NFAT reporter, albeit to varying degrees, possibly due to differences in peptide structure. Peptides P7, P9, P13, P15 and P17 significantly reduced the cystic index of treated embryonic kidneys to different extents (e.g., ~25% for P7 to ~90% for P17), while P11 had no ameliorating effect. Treatment with P19 or P21 prevented kidney growth and decreased kidney survival. A mutant peptide containing a human ADPKD-associated missense mutation was also detrimental in organ culture unlike its wild type parental peptide. Conclusions: These results support an Adhesion GPCR-like, stalk-dependent mechanism for regulation of signaling by PC1, implicate a physiological and disease-relevant role for this mechanism in renal tubulogenesis, and suggest a novel therapeutic avenue for ADPKD.
Presented by: Robin Maser
Institution: University of Kansas Medical Center

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ICH Outcomes and Reversal of Moderately Elevated INR 1.5 - 1.9

Aaron LacKamp MD, Jacob Reeder PharmD, Adrien Caye BS JD, Chaeli Stenuf RN, Justin Daniels MD, Kathrin Hussman MD, Kushal Shah MD

Abstract: Background: For ICH the Joint Commission CSTK-04 stroke measure encourages anticoagulant reversal when initial INR > 1.4. Other guidelines are less definitive: AHA guidelines suggest reversing INR elevated due to VKA antagonist, and NCS/SCCM guidelines allow discretion regarding reversal for INR <2, but strongly encourages reversal of VKA-associated INR >1.4.

While evidence supports reversal for INR≥2.0, little has been published on patients with INR 1.5-1.9. Given the lack of data, it is unclear whether this cohort of patients experiences benefit or harm from anticoagulant reversal.

Methods: We conducted a retrospective review of patients admitted to our institution from January 2015 through March 2021 to determine the rate of reversal and outcome for ICH with INR between 1.5-1.9. This date range was selected due to the completeness of the data.

Results: Thirty-nine patients presented with ICH and an INR of 1.5-1.9. These patients represented 5% of the 756 total ICH patients. Reversal was at the discretion of the physician team. 19 patients received reversal for mild elevation in INR, while twenty patients did not. • The patients who received reversal were older (70.1yrs vs 60.3yrs), had higher INR (1.7 vs 1.6), and had higher ICH score (1.83 vs 1.4). • Warfarin was a less common cause of moderately elevated INR than was either direct oral anticoagulant or liver dysfunction • Nonetheless reversal of elevated INR was successful in maintaining INR less than 1.5 at 24 to 48 hours. (p value 0.04) • Mortality was not statistically different between the treated and untreated groups. (p value 0.63) • For low ICH scores there was a trend toward improved discharge MRS.

Discussion: • INR was successfully reversed in 75% of patients who were given reversal whereas in patients without reversal, 42% had INR less than the INR 1.5 within 48hours. • There were no thrombotic complications in the 39 patients. This may be related to the small size of the sample, or it may be related to the short period of observation allowed in the sample, or it may be related to the way thrombotic complications were adjudicated. • Liver failure was present in 11 patients. Only 3 of whom received reversal. 8 did not receive reversal. • There were relatively few warfarin patients: Vitamin K antagonists:8 (20.5%), Direct oral anticoagulants: 13 (33.3%). • A disproportionate number of patients had ICH during lovenox bridge for warfarin—3 patients out of 39. (7.6%) • A disproportionate number of patients with moderately elevated INR had dural venous sinus thromboses— 3 patients out of 39. (7.6%)

Conclusion: The use of reversal successfully lowered INR in patients with elevations 1.5-1.9. This successful reversal was without thrombotic complications. The decision to reverse was likely influenced by patient characteristics such as ICH score. Receiving reversal lessened the correlation between ICH score and discharge mRS. Further studies are warranted to determine causality.
Presented by: Aaron LacKamp
Institution: KUMC

Investigation of high output heart failure among obese patients: Current state and implications

Qiuhua Shen, PhD, APRN, RN; John Hiebert, MD; Faith Rahman, BA; Kathryn Krueger, MPH, CPH; Bhanu Gupta, MD, Janet Pierce, PhD, APRN, CCRN, FAAN

Abstract
Presented by: Qiuhua Shen, PhD, APRN, RN
Institution: University of Kansas Medical Center, School of Nursing

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Targeted Intervention for At-Risk Patients with Diabetes to Reduce Readmissions

A. Harris, DO, H. Cheng, MS, J. He, PhD, and K. Grdinovac, MD

Abstract: Introduction: The goal of reducing hospital readmissions for patients with diabetes mellitus (DM) is multifaceted, with benefits to patient outcomes, provider burden, and health system costs. Current studies and data analysis have yet to elucidate a clear approach to accurately identify at-risk patients and implement effective interventions to reduce readmissions. We trialed a QI pilot program that utilized a NP/CDCES (Nurse Practitioner/Certified Diabetes Care and Education Specialist) to manage and educate at-risk patients during initial hospitalization as well as close follow-up post discharge with an end point of reduction in readmissions.

Methods: Over the course of 21 months, 79 hospitalized patients with diabetes were identified as high-risk for intervention based on: previous admission, diabetes ketoacidosis/ hyperosmolar hyperglycemic syndrome, new DM diagnosis, new to insulin, high-dose steroid use/tapers, or per provider discretion. The NP/CDCES provided DM management, education, and coordinated discharge plans during hospitalization. Patients were also called post-discharge for acute management/interventions and had a 2-4 week DM clinic follow-up visit with the same NP/CDCES. Results: The major endpoint was number of readmissions within 180 days of discharge after intervention compared to number of previous readmissions pre-intervention. Change in hemoglobin A1C, time to post-hospital phone call, and time to outpatient follow up were also evaluated. Pre- and post-intervention readmission rates remained unchanged; average pre-intervention readmissions per patient was 1.7 versus 1.88 post-intervention readmissions (p=0.74). However, a secondary endpoint of reduction in hemoglobin A1C was found to be statistically significant, with a mean decrease in A1C of 0.97% per patient (p=0.0025). Time to post-hospital phone call and early follow up did not affect readmission rates.

Conclusion: While targeted inpatient-to-outpatient intervention for high-risk patients with diabetes did not reduce future readmission rates, our data suggests that coordinated inpatient intervention with close hospital follow-up may improve A1c in high-risk patients with diabetes.
Presented by: Kristine Grdinovac
Institution: University of Kansas Medical Center

You Up? Creation of a "First-Call" Role for Voalte Communication

Michael Rouse, DO; Aroop Pal, MD; Mejalli Al-Kofahi, MD; John Fritzlen, MD

Abstract: Effective high-quality communication is essential for patient care. The transition from pagers to bidirectional texting platforms is associated with improved communication and user satisfaction. Despite TUKHS’s transition to Voalte, communication delays were reported due to incorrect or outdated physician assignments, multiple physicians listed, or unclear activity status. We hypothesized that creating an exclusive role on Voalte will improve communication.
Presented by: Mike Rouse
Institution: University of Kansas Health System

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Creation of IPASS Checklist for Handoff Training and Feedback

Michael Rouse, DO; Natalia Roldan, MD; Abebe Abebe, MD; David Naylor, MD

Abstract: Handoff training is required for residency and use of IPASS is associated with reduction in errors Internal Medicine resident orientation has traditionally included IPASS training. We hypothesized creation and use of a faculty checklist would improve objective completion of IPASS handoff training and improve faculty feedback to residents.
Presented by: Mike Rouse
Institution: University of Kansas Health System

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Can deviation from analytic intent affect the recommendations of a clinical practice guideline?

Badgett RG, Wissman K, Riaz IB

Abstract: Background

Deviations from analytic intent (DAIs) include 1) publication bias and 2) selective reporting bias. We previously identified an instance of selective reporting bias (PMID 28192789), that per the authors of a well-done clinical practice guideline (CPG), ‘probably’ affected their clinical recommendation. We now quantify the possibility that both DAIs affected another well-done CPG's recommendation.

Methods

We studied the clinical recommendation for topical non-steroidal anti-inflammatory drugs (NSAIDs) to reduce acute (PMIDs 32805126, 32805127), non-back pain for 1 to 7 days per a guideline by the American College of Physicians (ACP). For the clinical recommendation, we quantified the proportion of patients registered at one trial registry (ClinicalTrials.gov) that were later published at PubMed, and the proportion of patients published at PubMed that were previously registered. We extracted results from the published CPG, its evidence review, and information graciously provided by the review’s authors. In addition, we searched clinicaltrials.gov for relevant trials.

Results

The CPG reported finding 27 relevant trials with 4777 subjects at PubMed (ACP Supplement Table 6). Of the 27 trials, 2 were registered at ClinicalTrials.gov and 5 at other registries. This resulted in 1179 of 4777 (25%) of published subjects being registered.

The CPG found that 11 additional trials were registered at ClinicalTrials.gov but not published (ACP Appendix 2). We located one additional registration. The CPG found two additional trials were both registered and published yielding a total of 3787 subjects registered in 14 trials. Of these, 314 subjects were in 2 trials (8% of registered subjects) that were subsequently published. Two of the trials were registered but not published posted negative results at ClinicalTrials.gov. The ten registered trials without results were registered by industry between the years 2007 and 2019 (median year of registration 2009).

Discussion

In the current analysis, 75% of published subjects are susceptible to selective reporting bias due to not being registered while 92% of registered subjects are susceptible to publication bias due to not being published. Supporting this concern are the two trials that posted but did not publish results are negative.

Both guidelines comply with the Appraisal of Guidelines for Research and Evaluation II (AGREEII), comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and are considered Trustworthy. The current analysis, along with our previous analysis, support that CPGs, even when following best practice, are subject to DAIs.

We suggest that CPGs routinely report these two rates of possible biases to aid interpretation of recommendations. Further research is needed of signals that DAI rates may be affecting conclusions of CPGs.
Presented by: Robert Badgett
Institution: KUK School of Medicine Wichita, Internal Medicine. Mayo Clinic

Poster: Chronic house dust mite exposure shows time-of-day difference in immune-inflammatory response and circadian clock gene expression in the lung

Chronic house dust mite exposure shows time-of-day difference in immune-inflammatory response and circadian clock gene expression in the lung

Ashokkumar Srinivasan, Allan Giri, and Isaac Kirubakaran Sundar

Abstract: Rationale: Asthma is a chronic inflammatory lung disease that shows a time-of-day effect characterize by increased eosinophilic infiltration associated with Th2 cytokine release and mucus production. Recent studies support that altered rhythms of immune cells and inflammatory mediators (cytokines/chemokines) contribute to dysregulated innate/adaptive immune response during chronic lung diseases. However, whether a time-of-day response to allergen exposure leads to the difference in immune-inflammatory response and circadian clock function in the lung remains unclear. We hypothesize that chronic exposure to house dust mite (HDM) allergen shows time-of-day effects in innate and adaptive immune response and altered circadian clock function in the lungs. Methods: NCI C57BL/6NCr (Wild-type) mice were administered with PBS or HDM (30 μg) (intranasally; 5 days/week for 5 weeks, with 2 days interval) at specific time-of-day [Zeitgeber time ZT0 (6:00 am) or ZT12 (6:00 pm)]. Lung immunophenotyping of myeloid cells was performed using flow cytometry. Gene expression of Th2 cytokines and circadian genes were analyzed by qRT-PCR. Total and HDM-specific immunoglobulins (IgG and IgE) in serum were measured by ELISA. Results: Chronic HDM exposure at ZT12 caused a significant increase in resident eosinophils (EOS: Siglec F+, CCR3-), inflammatory EOS (Siglec F+, CCR3+), GR1+ EOS, neutrophils, and dendritic cells in the lung compared to ZT0. Alveolar macrophages (AV-MACs) were significantly reduced in airway lumen of the ZT12 HDM exposed group compared to ZT0, and interstitial MACs did not show any time-of-day difference but were increased in the HDM exposed group at ZT0 and ZT12. Gene expression analysis of Th2 cytokines (IL-4, IL-5, and IL-13) was augmented at ZT12 compared to ZT0 in the HDM exposed group. Except for total IgG, total IgE and HDM-specific IgE were higher in HDM exposed group at ZT12 compared to ZT0. However, HDM-specific IgG response was decreased in HDM exposed group at ZT12 compared to ZT0. HDM exposure showed altered expression of core clock genes Nr1d1, Nr1d2, Per1, Per2 and Dbp in the lungs at ZT12 compared to ZT0. Conclusion: HDM exposure at ZT12 showed strong time-of-day effects on the status of immune-inflammatory cellular influx, Th2 cytokine expression, and humoral response associated with circadian clock disruption in the lungs. This study demonstrates that time-of-day allergen exposure affects circadian gene expression leading to an exaggerated immune-inflammatory response in the lung. Our study demonstrates the link between the circadian clock and time-of-day variation in asthmatic lung phenotype.
Presented by: Isaac Sundar <isundar@kumc.edu>
Institution: University of Kansas Medical Center

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Concept Mapping as a participatory Research Methodology to Address Health Inequities

Natabhona Mabachi(1), Crystal Lumpkins(1), Hope Krebill(2), & Jill Peltzer(3)

Abstract: Aims: To describe concept mapping as a participatory research methodology to foster health equity among minoritized populations, using a breast cancer equity project as an exemplar. Methods: Concept mapping engages participants throughout the process using qualitative methods. The Equity, Empowerment and Social Accountability (EESA) framework, a contextual, trauma informed model, will guide the project to ensure shared language and collective inputs throughout the process. The six steps are 1) Prepare for concept mapping. Our research team of health equity researchers, oncology nurse researchers, community health educator, and breast cancer survivors, will develop recruitment and mapping sessions strategies. 2) Generate the ideas. We will recruit Black breast cancer survivors to gather in-depth data about their experiences across the breast cancer continuum. 3) Structure the statements. Our team will analyze the data using inductive qualitative analysis to develop and structure the statements. 4 & 5) Co-create, co-analyze, and co-interpret the concept maps. We will host focus groups with survivors and health care workers to map the concepts, co-analyze, and co-interpret the maps. 6) Utilize the maps to develop interventions. In the proposed study, we will complete steps 1-5 and prepare for step 6. Results: Concept mapping framed by the EESA framework ‘centers’ minoritized populations in research. This process can transform racial equity by recognizing that Black Americans continue to live with a legacy of exclusion, marginalization, oppression, and exploitation; and addressing social, historical, and spiritual suffering. Conclusions: Concept mapping is a structured research approach to engage participants in co-creating meaningful solutions to health inequities.
Presented by: Natabhona Mabachi, Crystal Lumpkins, Hope Krebill, and Jill Peltzer
Institution: University of Kansas School of Medicine Department of Family Medicine and Community Health(1), & Masonic Cancer Alliance(2), & University of Kansas School of Nursing(3)

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Exploring Caregiver Quizzing Behavior of People Living with Dementia during In-Home Care Situations using Sequential Analysis

Carissa K. Coleman, PhD, Kristine Williams RN, PhD, FGSA, FAAN, University of Kansas School of Nursing, & Amy Berkley, RN, PhD, Lawrence Memorial Hospital

Abstract
Presented by: Carissa Coleman
Institution: University of Kansas, School of Nursing

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Hyperexcitability in Preclinical Alzheimer's

Hannes Devos, Kathleen Gustafson, Ke Liao, Pedram Ahmadnezhad, Brad Estes, William Brooks, Laura Martin, Jonathan Mahnken, Jeffrey Burns

Abstract: Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential in cognitively normal (CN) older adults. The second aim was to compare event-related power between CNAβ+ and CNAβ. Methods: CNAβ+ participants (n = 17, age: 73 ± 5, 11 women, MOCA scores 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel EEG net. P3 peak amplitude and latency of the target, nontarget and task difference (nontarget – target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz were compared between groups using linear mixed models. P3 amplitude of the task effect at Fz, and event-related spectral power in the delta band were considered main outcomes. Mean Aβ standard uptake value ratios (SUVR) using positron emission tomography were correlated with P3 amplitude and latency of the task effect using Pearson r. Results: P3 peak amplitude of the task effect (p = 0.048) at Fz was lower in the CNAβ+ group. Similarly, power was lower in the delta band (p = 0.04) for nontargets at Fz in CNAβ+ participants. CNAβ+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between mean Aβ SUVR and latency of the 1-back (r = -0.69; p = 0.003) and 2-back (r = -0.69; p = 0.004) of the task effect at channel Fz in the CNAβ+ group. Conclusions: Our data suggests that elevated amyloid in cognitive normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.
Presented by: Hannes Devos
Institution: University of Kansas Medical Center

Bispecific Co-Targeting of EGFR and B7-H3 in Chimeric antigen receptor (CAR) T-cell Therapy for Treatment of Intracranial Meningiomas

Bryan Schatmeyer, MD, John Jeppson, MS, Siddharth Subham, Jie Zhao, MD, Nelli Lakis, MD, David Akhavan, MD, PhD

Abstract: Meningiomas are common primary tumors of the central nervous system. The majority of meningiomas are benign, low-grade tumors, however approximately 10-15% may demonstrate concerns for malignancy. Surgical resection is currently the first-line treatment, however occasionally the tumor may involve critical or eloquent structures that inhibit complete resection. A proposal for these patients is the use of an immune-effector cellular therapeutic agent known as a Chimeric Antigen Receptor (CAR) T cell. CAR T-cells are engineered immune T-cells with de novo anti-tumor activity via recognition of specific tumor associated antigens (TAAs). CAR T-cell therapies have demonstrated substantial results in leukemia and lymphoma research, however solid tumors have demonstrated many challenges, including tumor antigen heterogeneity. Currently, CAR-T cell therapy has utilized single tumor antigen targeting. However, studies have shown that with this CAR-T cell treatment, the tumor will lose that specific antigen expression. To overcome this barrier, the use of a dual antigen CAR has been suggested. Meningiomas express a variety of TAAs that are under clinical study in high grade brain tumors, including B7-H3, EGFR6, and IL13Ra2. We propose the use of a bispecific CAR against the tumor associated antigens of B7-H3 and EGFR-806 for the treatment of incompletely resected benign or malignant intracranial meningiomas.
Presented by: Bryan Schatmeyer, MD
Institution: The University of Kansas Health System

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Counteracting molecular mechanisms of pancreatic cancer progression

Austin Eades, Bailey Bye, McKinnon Walsh, Mariana Ruckert, Joe Ambrose, Jarrid Jack, Fanuel Messaggio, Sharon Manley, Appolinaire Olou, and Michael VanSaun

Abstract: Pancreatic cancer ranks as one of the top three deadliest cancers, due to late diagnosis and very few therapeutic options. Pancreatic cancer presents with multiple genetic mutations, of which KRAS mutations are found in over 90% of PDAC and is thought to be the drivers of disease. Unfortunately, therapeutic targeting of KRAS has not shown to be efficacious. Additionally, the acquisition of genetic mutations in PDAC remains unknown and implies an increased understanding of risk factors on its development is critical to understanding this disease. Obesity is one such modifiable risk factor that research has shown to positively correlate with disease progression. Our goal is to determine the molecular mechanism through which obesity potentiates the development and progression of cancer. More specifically, our studies are focused on determining how factors derived from adipose tissue, or adipokines, effect tumor behavior and function. To understand the mechanisms of adipose-tumor crosstalk, we have utilized novel co-cultures and media transfer experiments coupled with cytokine arrays and RNAseq analysis to determine how adipocytes influence pancreatic tumor cells. We have found that obesity associated adipocytes secrete factors that directly upregulate tumor growth, but they also induce tumor cells to alter immune recruitment and immune activation to facilitate disease progression. Additionally, we have found that phosphatases play a critical role in the molecular mechanisms of these tumor functions. In particular, we have shown that the protein tyrosine phosphatase, SHP2, is essential for pancreatic cancer development. SHP2 functions by regulating the activity of KRAS as well as regulating secretion of critical soluble factors. In conclusion, we have shown that adipocytes play an active role in pancreatic cancer progression and are actively developing a comprehensive understanding of the molecular mechanisms involved.
Presented by: Michael VanSaun
Institution: University of Kansas Medical Center

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Autonomic Nervous System Markers of Music-elicited Analgesia in People with Fibromyalgia: A Pilot Study

Rebecca J. Lepping, PhD 1, Miranda L. McMillan, MS, CRC 2, Kathleen M. Gustafson, PhD 1,3, Andrea L. Chadwick, MD, MSC, FASA 2, Laura E. Martin, PhD 1,4

Abstract: Patients with fibromyalgia (FM) have reduced self-reported pain, increased mobility, and brain activation after even a short, 5 to10-minute music listening intervention. Our pilot study is the first to investigate whether objectively measured pain sensitivity is reduced by music listening. We report results from a two-arm parallel randomized controlled pilot study in 9 participants with FM. Pain tolerance and threshold were measured using quantitative sensory tests; autonomic nervous system (ANS) reactivity was measured with electrocardiogram. Participants had two sessions: testing as usual with no-sound and testing while listening to instrumental Classical music or a nature sound placebo control to test whether music listening elicits greater analgesic effects over simple auditory distraction. Participants were randomized 1:1 to music or nature sounds (5 Music, 4 Nature). Although the groups were not different on FM score, the Music group had marginally worse pain tolerance (p=.09) and threshold (p=.13). The Nature group had higher Anxiety scores (p=.03). A significant Group by Session interaction for pain tolerance (p=.04) revealed the Nature group had greater pain reduction during audio compared to silence. No significant effects were observed for ANS testing. There was a pattern of vagal response that increased from baseline to music listening, and further increased during pain testing not observed in the Nature group. Heart rate was significantly related to anxiety (p=.02). Auditory listening significantly altered pain responses. Results could be due to group differences in pain and anxiety. There may be greater vagal response to music versus nature sounds, but the small sample is underpowered to detect effects. This line of study will help determine whether music could be prophylactic when acute pain is expected. Our next step will be a larger trial, correlating pain and ANS measures with subjective measures of anxiety, pain catastrophizing, resilience, and measures of music experience and enjoyment.
Presented by: Rebecca J. Lepping (she/her/hers)
Institution: 1 Hoglund Biomedical Imaging Center, 2 Dept. of Anesthesiology, 3 Dept. of Neurology, 4 Dept. of Population Health, University of Kansas Medical Center

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Androgen Deprivation Therapy for Prostate Cancer: An Exploratory Study of Cognitive Function & the Role of Central Adiposity

Jamie S. Myers, Alana Manson, Sandra A. Billinger, William Parker, Francisco J. Diaz, Sally Maliski

Abstract
Presented by: Jamie Myers
Institution: University of Kansas Medical Center, School of Nursing

Poster: Emerging from the Haze: Feasibility pilot of a virtual multi-dimensional psycho-educational cognitive rehabilitation intervention for cancer survivors with decreased perceived cognitive function after cancer therapy

Emerging from the Haze: Feasibility pilot of a virtual multi-dimensional psycho-educational cognitive rehabilitation intervention for cancer survivors with decreased perceived cognitive function after cancer therapy

Arash Asher, Celina Shirazipour, Jeffrey Wertheimer, Jamie Myers

Abstract: PRESENTER AVAILABLE VIA CHAT FROM 10:00 AM to 11:00 AM
Presented by: Jamie Myers
Institution: University of Kansas Medical Center, School of Nursing

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Androgen Deprivation Therapy & Sleep Disturbance: Remote Assessment and Intervention

Jamie S. Myers, Catherine Siengsukon, Xinglei Shen, Lauren Ptomey, William Parker, Sally Maliski

Abstract: PRESENTER AVAILABLE VIA CHAT FROM 11:00 AM to 12:00 AM
Presented by: Jamie Myers
Institution: University of Kansas Medical Center, School of Nursing

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Forming and Fostering a Professional Identity in Nursing

Nelda Godfrey and Anita Fitzgerald

Abstract: The International Society for Professional Identity in Nursing (ISPIN) convened in 2018 to call out and define professional identity in nursing, and to add language and new knowledge to the discipline on this topic. To date, two 50-person, international think tanks and one virtual forum have produced 46 publications, webinars and podcasts, 15 national and international presentations and a conceptual model that has been tested and validated with both US educated and foreign-educated nurses.

More than 250 nurse leaders have come forward to participate in various ISPIN work groups, including propelling the science, educational dissemination, and using science to define and claim the brand image of nursing. Five research studies are in progress, including one on instrument development. The international impact is noted in that 48 countries were represented on five Sigma webinars on Professional Identity in Nursing in the fall of 2020.

Through an intense, scientific process of gleaning subject matter expert knowledge, the ISPIN has defined Professional Identity in Nursing as " a sense of oneself, in relationship with others, that is influenced by the characteristics, norms and values of the nursing discipline, resulting in the individual thinking, acting and feeling like a nurse." Again, through a thoughtful iterative process the ISPIN has named the four domains of Professional Identity in Nursing: 1) Values and Ethics, 2) Knowledge, 3) Leadership, and 4) Professional Comportment. This work and the instrument development that is in process will make explicit what professional Identity in nursing means.

The hope is that every student nurse and every nurse in practice--worldwide--can gain a clearer understanding of professional identity of nursing using the ´signposts´ of values and ethics, knowledge, leadership and professional comportment.
Presented by: Nelda Godfrey
Institution: University of Kansas Medical Center (SSO) and California State University Long Beach

A Qualitative Evaluation of a Nurse-Led Pre-Operative Stoma Education Program for Bladder Cancer Patients

Elizabeth Wulff-Burchfield, Maryellen Potts, Katie Glavin, Moben Mirza

Abstract: Introduction: Radical cystectomy remains the standard of care for muscle-invasive bladder cancer and high-risk non-muscle invasive bladder cancer. Postoperative ostomy education is standard, but patients struggle to maintain self-management practices. A preoperative ostomy education program was developed to meet this need, and we conducted a qualitative study with participating patient-caregiver dyads to evaluate the educational and psychosocial impacts of the program and examine alignment with program objectives. Materials and Methods: A qualitative descriptive study was conducted utilizing a thematic analysis approach. Sixteen patients, eighteen caregivers, and three program educators completed semistructured interviews from 3 to 18 months post the program. Interviews were audio-recorded, and transcribed. Thirteen end-of-course surveys from the initial educational program cohort were transcribed, coded, analyzed; this data was triangulated with patient, caregiver, and educator interviews. Results: Analysis uncovered three themes: (1) Patient and caregiver motivation to attend the program, (2) attitudes toward this life changing event, and (3) education. For theme 1, patients and caregivers cited lack of knowledge, fear, and concern about ostomy surgery and care as motivation. For theme 2, there were a variety of attitudes toward the ostomy, ranging from avoidance to acceptance, and a similar breadth of attitudes toward caregiving, with some patients and caregivers describing ongoing dependence and other patients seeking complete independence. For theme 3, the interactive curriculum was determined to be effective, and the patient advocate was cited as the most memorable program component. Conclusions: A formal preoperative ostomy education program employing an interactive educational approach and featuring a patient advocate can prepare bladder cancer patients and caregivers for ostomy self-management and post-ostomy life.
Presented by: Maryellen Potts
Institution: University of Kansas Medical Center and School of Nursing

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Acute exercise rapidly activates hepatic mitophagic flux

Colin S. McCoin, Edziu Franczak, Fengyan Deng, Dong Pei, Wen-Xing Ding, John P. Thyfault

Abstract: Exercise is critical for improving metabolic health and putatively maintains or enhances mitochondrial quality control in metabolic tissues. While previous work has shown exercise elicits hepatic mitochondrial biogenesis, it is unknown if acute exercise activates hepatic mitophagy, the selective degradation of damaged or low-functioning mitochondria. We tested if an acute bout of treadmill running increased hepatic mitophagic flux both immediately after and 2 hours post-exercise in 15–24-week-old C57BL/6J female mice. Acute exercise did not significantly increase markers of autophagic flux, however, mitophagic flux was activated 2 hours post-treadmill running as measured by accumulation of both LC3-II and p62 in isolated mitochondria in the presence of leupeptin, an inhibitor of autophagosome degradation. Further, mitochondrial associated ubiquitin, which recruits the autophagy receptor protein p62, was also significantly increased at 2 hours. Further examination via western blot and proteomics analysis revealed acute exercise elicits a time-dependent, dynamic activation of mitophagy pathways. Moreover, the results suggest that exercise induced hepatic mitophagy is likely mediated by both poly-ubiquitination and receptor mediated signaling pathways. Overall, we provide evidence that acute exercise activates hepatic mitophagic flux while also revealing novel receptor-mediated pathways by which exercise maintains mitochondrial quality control in the liver. Overall, we provide evidence that acute exercise activates hepatic mitophagic flux while also revealing novel receptor-mediated pathways by which exercise maintains mitochondrial quality control in the liver.
Presented by: Colin McCoin
Institution: University of Kansas Medical Center

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Albumin Use and Associated Outcomes in Cardiac Surgical Patients

Sejla Turnadzic, Patrycja Wilczynska, Tiffany Mills, Elizabeth Cotter, MD, Katy Wirtz, RN, Brigid Flynn, MD

Abstract: Background: This was a retrospective database review analyzing the use of albumin in cardiac surgical patients. Albumin as a volume expander is much more costly than crystalloid therapy which some studies demonstrate as equivalent while other studies cite that albumin use is associated with kidney injury, sepsis, and bleeding in cardiac surgical patients. Due to high costs and controversial evidence for albumin administration, we sought to determine if adverse outcomes were associated with higher dose of albumin.

Methods: Following institutional review board approval, all data was collected from the electronic medical record. We developed a novel albumin:crystalloid (mg/mL) ratio (A:C) based on natural cut-offs for A:C dose as a continuous variable. High A:C was determined to be > 2.7. The primary outcome was acute kidney injury based on the Kidney Disease: Improving Global Outcomes (KDIGO) score. Secondary outcomes included sepsis, re-operation for bleeding and 30-day mortality. In order to avoid confounding by preexisting cardiac dysfunction, we stratified patients into three groups based on ejection fraction (EF) (<30%, 31-50% and >50%).

Results: Preoperative baseline characteristics were similar among the cohorts stratified by EF, except diabetes was more common in patients with EF < 30%. (Table 1) Patients who received higher doses of albumin based on A:C ratio > 2.7, had no difference in incidence of renal dysfunction (Table 2, Figure 1). There was also no difference in 30-day mortality or sepsis. Furthermore, higher albumin doses do not appear to increase risk of bleeding as there were no differences in blood product administration or need for re-operation for bleeding. These findings hold true despite patients in the low EF group possibly being more critically ill as demonstrated by increased length of stay, increased ventilation time and more diabetes.

Summary: Based on these results, albumin appears to be safe in cardiac surgical patients without risk of increased renal failure or other previously associated adverse outcomes such as bleeding and sepsis. Due to the retrospective nature of this study, these results are hypothesis generating for a future randomized controlled trial.
Presented by: Sejla Turnadzic
Institution: The University of Kansas Health System, Anesthesiology Critical Care

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Cyanokit for Vasoplegic Shock in Cardiac Surgical Patients

Joseph Jeffrey, BS; Patrycja Wilczynska; Tiffany Mills; Elizabeth Cotter, MD; Katy Wirtz, RN; Brigid Flynn, MD

Abstract: Background

Vasoplegic syndrome (VS) following cardiopulmonary bypass (CPB) may occur in up to 50% of patients undergoing cardiac surgery and is associated with increased incidence of morbidity, mortality and length of stay. Several mechanisms are involved in post-CPB VS, including: 1) an increase in proinflammatory regulators, 2) an increase in endogenous nitric oxide (NO), and 3) depletion of endogenous vasoconstrictors. [1,2] Patients have historically been treated with norepinephrine, epinephrine, dopamine, vasopressin, and methylene blue.[1-3] Hydroxocobalamin (Cyanokit) has historically been used as an antidote in cyanide poisoning,[1] but has recently been utilized for the treatment of post-CPB VS despite lack of FDA approval or evidence for this use.[1] We sought to analyze outcomes in patients who received Cyanokit for post-CPB VS.

Methods

We performed a retrospective review of patients who underwent cardiac surgery March 2019 - June 2021. Of the 1333 patients, 26 received Cyanokit for VS. Patients who did not receive Cyanokit during the same time period were analyzed for historical comparison of outcomes. Data obtained included the pre-operative usage of angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blocker (ARB) drugs, presence of diabetes, hypertension, liver disease, re-operation for bleeding, change in hemoglobin levels, change in glomerular filtration rate (GFR) and mortality.

Results

Of the 26 patients who received Cyanokit for post-CPB VS, 38.46% were taking an ACE-I or ARB compared with 37.87% of the comparison group. Table 1 displays characteristics of patients who received Cyanokit for VS and those who did not. Patients who received Cyanokit had an increased incidence of renal dysfunction, reoperation for bleeding (38.46% versus 3.14%), and 30 day mortality (42.3% versus 3.7%). (Table 2).

Discussion

Cyanokit increases blood pressure by inhibiting nitric oxide synthase, inhibiting production of hydrogen sulfide, and scavenging nitric oxide and hydrogen sulfide.[1,4] While VS may improve for a period of time, our data demonstrate that cardiac surgical patients who received Cyanokit had and 11-fold increase in mortality and a 3-fold worsening of renal function. It is unclear if Cyanokit is associated with mortality or renal failure versus patients who received Cyanokit were more critically ill, but this is a signal for hypothesis generation.

Importantly, patients who received Cyanokit required reoperation for bleeding 12-fold more often indicating that the cause of shock may have included hemorrhagic shock. In these cases it is unclear if Cyanokit, which treats only VS, was indicated. Following this signal, prospective studies are warranted to fully understand the indication, risks and benefits associated with Cyanokit use for post-CPB VS.
Presented by: Joseph Jeffrey
Institution: The University of Kansas School of Medicine

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Fathers' History of Alcoholism and the Drinking Outcomes of their Sons: A 50-year Prospective Study

Darren J. Garcia, PhD; EC Penick PhD; WA Hossain MD MPH; J Knop Dr Med Sci; AM Manzardo PhD; EL Mortensen Cand Psych; UMD Becker Dr Med Sci; HJ Sorensen MD PhD; E Just-Østergaard PhD; WF Gabrielli MD PhD

Abstract: Abstract Objective: This prospective longitudinal study was designed to identify premorbid factors that predict maladaptive drinking over a 50-year span in males at high-paternal risk (HR) versus low paternal risk (LR) for alcoholism. This poster compares the drinking outcomes of the high- and low-risk males using multiple methods of assessment over three decades. Method: Subjects were drawn from a Danish birth cohort of 9,182 babies born between 1959 and 1961, which included 223 sons of alcoholic fathers (high-risk) and 106 matched controls (low-risk). Using a variety of assessment methods, Subjects were evaluated in their teens (n = 238), at age 30 (n = 241), at age 40 (n = 202), and at age 50 (n=156). Assessments included diagnoses by an experienced psychiatrist who distinguished alcohol dependence from abuse according to the DSM-III-R, structured interviews (Psychiatric Diagnostic Interview), psychometric tests (Michigan Alcoholism Screen Test), and a DSM-5 approximation of Alcohol Use Disorder. Results: Over the 30-year period, problem drinking was found more prevalent among high-risk sons of alcoholic fathers with all four measures. Life-time alcohol dependence by a psychiatrist = 38% for HR and 22% for LR; Life-time alcoholism with structured interview = 41% for HR and 23% for LR; Life-time self-report measure = 44% for HR and 26% for LR; DSM-5 = 66% for HR and 52% for LR. This trend was found across all phases of the study. Dimensional measures of alcohol severity were significantly higher in the high-risk subjects at the 30, 40 and 50-year follow-ups. Conclusion: High-risk sons of alcoholic fathers more likely than low-risk males to develop alcohol problems according to all four measures. Risk was only related to alcohol dependence but not alcohol abuse. Alcoholism severity was greater for the high-risk subjects at each phase of the study. Lifetime prevalence for an alcohol problem was highly similar for three of the four measures across the three decade. The DSM-5 approximation for an alcohol use disorder (2/11 criteria) strongly differentiated high-risk and low-risk males but appears to overestimate alcohol problems.
Presented by: Darren Garcia, PhD
Institution: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center ▪ Department of Public Health, University of Copenhagen ▪ Center for Healthy Aging, University of Copenhagen ▪ National Institute of Public Health, University of Southern Denmark ▪ Gastrounit Medical Division, Copenhagen University Hospital Hvidovre, Denmark ▪ CORE Copenhagen Mental Health Research Centre, Copenhagen University Hospital Gentofte, Denmark.

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Cortical tracking of acoustic and linguistic features of continuous speech under focused and divided attention

Zilong Xie

Abstract
Presented by: Zilong Xie
Institution: University of Kansas Medical Center

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Poster: Intrinsic Anthropometric Factors are Associated with Bone Stress Injuries in Collegiate Distance Runners: New Risk Metrics & Screening Tools?

Intrinsic Anthropometric Factors are Associated with Bone Stress Injuries in Collegiate Distance Runners: New Risk Metrics & Screening Tools?

Aaron Carbuhn, Daniel Yu, Lawrence Magee, Patrick McCulloch, Bradley Lambert

Abstract
Presented by: Aaron Carbuhn
Institution: Department of Dietetics and Nutrition, University of Kansas Medical Center; Sports Medicine, Kansas Athletics, Inc.; Department of Orthopedics & Sports Medicine, Houston Methodist Hospital

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