IMPRS 2022 works

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https://hdl.handle.net/1805/29657

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Analysis of Factors Contributing to Antenatal Corticosteroid Administration in Threatened Preterm Labor
(2022-07) Bode, Leah; McKinzie, Alexandra; Gidia, Nadia; Ibrahim, Sherrine; Haas, David
Introduction: Antenatal corticosteroids (ACS) are recommended for pregnant persons who are between 24 and 36+6/7 weeks’ gestational age (GA) and at risk for imminent delivery within 7 days. Many individuals diagnosed as having threatened preterm labor (tPTL) are given ACS but do not deliver until they reach term. This study aimed to describe characteristics of those seen for tPTL who receive ACS to better understand clinical decision-making. Methods: This retrospective cohort study consisted of mothers seen in triage at Eskenazi Hospital in 2021 for tPTL during pregnancy. Multiple demographic variables were evaluated against the primary outcome of ACS administration including maternal age, race/ethnicity, and prior preterm delivery, as well as obstetrical variables such as cervical dilation, effacement, membrane rupture, and tocolytic administration. Results: After exclusions, a cohort of 290 pregnant people with 372 unique encounters remained. The average maternal age was 26.7, and 15.6% of patients had a history of prior preterm birth. 107 patients in 111 encounters received ACS, which were associated with lower BMI, greater cervical dilation, greater effacement, membrane rupture, and more frequent contractions (all p<0.01). The mean GA at triage was 33.5 weeks. Logistic regression, adjusting for significant factors in the univariable analysis, found that BMI (OR 0.93, 0.89-0.97), cervical dilation (OR 1.34, 1.07-1.71), and cervical effacement (OR 1.02, 1.01-1.03) were significantly associated with giving ACS. 44% of those receiving ACS delivered within 7 days, compared to 11% of those who did not receive ACS (p<0.001). Conclusion: Greater cervical dilation and effacement and a lower BMI were associated with ACS administration, though most patients receiving ACS still did not deliver within 7 days. These findings will be further categorized and used to develop a clinical decisional model for administering ACS in those likely to imminently deliver preterm. Presentation recording available online: https://media.dlib.indiana.edu/media_objects/3b5922009
Brain folding increases in sharpness and complexity over third trimester-equivalent development
(2022-07-28) Basinski, Christopher; Garcia, Kara
Brain folding increases in sharpness and complexity over third trimester-equivalent development Christopher Basinski [1], Kara Garcia [2] [1] Indiana University School of Medicine; [2] Indiana University School of Medicine, Department of Radiology and Imaging Sciences >> Background and Hypothesis: Gyrification, or convolution, of the cerebral cortex is a promising transdiagnostic marker for early neurodevelopment. Previous studies have related differences in sulcogyral shape to schizophrenia, bipolar disorder, and autism spectrum disorder, but the physical mechanisms underlying these differences remain poorly understood. The focus of this study was to explore decomposed curvature metrics, the principal curvatures, as physically meaningful quantitative biomarkers to track brain development. We hypothesize that the average sharpness and complexity of sulci and gyri, reflected by principal curvatures, increase throughout third trimester-equivalent development. Methods: Cortical surfaces generated from magnetic resonance imaging (MRI) were obtained from the developing Human Connectome Project. Global sharpness was calculated from the principal curvature of maximum magnitude, with average sharpness defined separately for gyral (positive) and sulcal (negative) curvatures. Global complexity of folds (eg., curviness along the length of a fold) was calculated from variance in the principal curvature with minimum magnitude. Trajectory of each summary metric was fit over time using polynomial regression. Results: Forty-three subjects were removed due to incomplete curvature analysis or missing subject information, such that 541 preterm and term-born infants were evaluated with scan age ranging from 27 to 45 weeks postmenstrual age (PMA). Across this developmental range, sharpness and complexity increased until a plateau around term-equivalent. Average sharpness of gyri was best correlated with age of scan (R2 = 0.877). Conclusion and Potential Impact: During the pre- and postnatal development period, total cortical surface area continues to increase after birth, but the overall sharpness and complexity of folding plateaus at ~37 weeks post-menstrual age. Exploring these physically meaningful curvature metrics can provide improved parameters for comparison to mechanistic models of brain folding.
Targeted Inhibition of the HGF/c-Met Pathway by Merestinib Augments the Effects of Albumin-Bound Paclitaxel in Gastric Cancer
(2022-07-28) Kaurich, Quinn; Huang, Jennifer; Awasthi, Niranjan
BACKGROUND AND HYPOTHESIS: Combination chemotherapy regimens are commonly used to treat gastric adenocarcinoma (GAC), but the median survival time remains less than one year. Nab-paclitaxel has demonstrated high antitumor activity in previous GAC studies. Many growth factors and their receptors are overexpressed in GAC and have been implicated in its pathophysiology. We hypothesize that merestinib, a small-molecule inhibitor targeting c-Met, Axl, and DDR1/2 pathways, will have significant antitumor effects and will enhance the response to nab-paclitaxel in GAC preclinical models. PROJECT METHODS: In vitro proliferation and protein expression were assessed using WST-1 and immunoblot assays. Subcutaneous xenografts of MKN-45 and SNU-1 cell lines were implanted in mice to study tumor growth inhibition. Immunohistochemistry was performed to examine intratumor proliferation and microvessel density. RESULTS: In vitro assays showed that nab-paclitaxel and merestinib decreased cell proliferation in all three cell lines, with an additive effect in combination. Reduction in cell proliferation at low doses of nab-paclitaxel (10 nM), merestinib (100 nM), and their combination was 87%, 82%, and 94% (MKN-45 cell line, high phospho-c-Met expression), 59%, 50%, and 82% (SNU-1 cell line, low phospho-c-Met expression), and 53%, 19%, and 66% in gastric fibroblasts. Immunoblot analysis of merestinib treated MKN-45 cells revealed increased expression of apoptotic proteins and decreased expression of phospho-c-Met, phospho-EGFR, phospho-IGF-1R, phospho-ERK, and phospho-AKT. In gastric fibroblasts, merestinib decreased phospho-ERK and increased apoptotic protein expression. Phospho-c-Met and phospho-EGFR were not detected in SNU-1 immunoblots; however, phospho-ERK, phospho-VEGFR, and apoptotic protein expression increased after treatment. In MKN-45 xenografts, net tumor growth in control, nab¬-paclitaxel, merestinib, and combination groups was 503 mm3, 115 mm3, 91 mm3, and -9.7 mm3. Immunohistochemistry analysis of tumor cell proliferation and microvessel density corroborated tumor growth study results. CONCLUSION: The data suggest that merestinib in combination with nab-paclitaxel carry a promising potential for improving clinical GAC therapy.
Retraumatization in Undergraduate Medical Education: Evaluating the Prevalence and Support Resources Available to Students
(2022-07-29) Makhecha, Keith; Standfest, Makayla; Ritter, E. Matthew; Doster, Dominique L.; Stefanidis, Dimitrios
BACKGROUND: Retraumatization is the conscious or unconscious reminder of past trauma that results in a re-experiencing of the initial traumatic event. This phenomenon has been well-studied in primary and secondary education and has been shown to negatively impact the learning environment. Retraumatization in the context of undergraduate medical education has yet to be evaluated. Therefore, we sought to explore the prevalence of retraumatization in medical students, identify specific areas of UME that are retraumatizing, and evaluate effectiveness of psychological support available to students. METHODS: A survey was created by a multidisciplinary team of health professions educators, revised through an iterative process, and distributed to all medical students at a single, large, academic institution. Respondents who endorsed prior trauma exposure met inclusion criteria for completing the survey. Data was analyzed using Microsoft Excel. RESULTS: Of the school’s 1400 students, 85 responses were recorded for a response rate of 6.07%; this consisted of 20 males (23.5%), 46 females (54.1%), and 19 nonbinary (22.4%) students. 32 (37.6%) students reported no prior trauma and were excluded from survey completion. Of the 53 (62.4%) students completing the survey, retraumatization was experienced by 32 students (60.4%), which represents a prevalence of 37.6% among all medical students surveyed. 50% of females (n=23), 10% of males (n=2), and 36.8% of nonbinary (n=7) students reported retraumatization. Clinical rotations were identified as a retraumatizing setting by 59.3% (n=19) of students. Despite the availability of support services, 11 students (20.8%) reported being unaware of them when experiencing retraumatization. When asked about utilization of services, the majority of those who had experienced retraumatization did not utilize them (65.6%, n=21). CONCLUSION: Retraumatization is occurring in undergraduate medical education, particularly in the clinical years. Medical schools should attempt to enhance the ease of utilization of support resources to improve the learning environment for students.
The Impact of a Lack of Diversity in Leadership Positions on Self-Perceptions and Views of Success in Latino/a/x Youth
(2022-07-29) Thomas, Jordan; Zeh, Janie; Messmore, Niki
BACKGROUND: The Boys and Girls Club (BGC) is a national organization that cares for diverse youths ages 6-18. At a national level, BGC states that a commitment to inclusion is a core value. This research explores the demographic makeup of BGC of Tippecanoe County’s staff/volunteer members and analyzes its impact on the Latino/a/x youth that attend the club. METHODS: A 2-part anonymous survey was developed and distributed to all active staff/volunteers that work at BGC of Tippecanoe County. Part 1 consisted of basic demographic questions. Part 2 of the survey had participants answer questions about their Adverse Childhood Experiences (ACEs) and an ACEs score was calculated from their responses. RESULTS: Data analysis found that 89% of employees identified as “White/European”. In addition, 100% of responses labeled “English” as their primary language. Data revealed that 94% of respondents listed their sexual orientation as “heterosexual”. 100% of the participants selected either “male” or “female” as their gender identity, showing no divergence from the “male/female” binary at the club. In the final two demographics questions from the survey, 56% of the respondents indicated that their childhood household had an income greater than $50,000 and another 56% stated that they had an education level at or below a high school diploma. POTENTIAL IMPACT/CONCLUSIONS: The demographic makeup of BGC of Tippecanoe County puts Latino/a/x youth at risk of struggling when developing their social-emotional and ethnic identities. The current staff/volunteer list does not put Latino/a/x youth in the best possible developmental environment for cultural appreciation and self-confidence. Several strategic diversity recommendations have been created and passed on to the organization. These aim to increase the engagement level and cultural appreciation of Latino/a/x culture to empower youth that identify with this group.
Combinatorial Inhibition of Epigenetic Regulators to Treat Glioblastoma
(2022-07-29) Burket, Noah; Koenig, Jenna; Saratsis, Amanda
Glioblastoma (GBM) is a deadly primary brain cancer that affects 12,000 patients in the US annually with a median survival time of 15 months. Temozolomide is the standard-of-care chemotherapy for GBM; however, many tumors are resistant, necessitating the expansion of therapeutic options. EZH2 and JMJD3 are two proteins responsible for epigenetic regulation of the genome via histone methylation, with EZH2 also affecting non-histone targets. Prior studies showed that inhibition of these proteins decreased cell counts and induced radiosensitivity in GBM cells. Thus, we investigated combined use of EZH2 inhibitor, EPZ6438, and JMJD3 inhibitor, GSK-J4, in the treatment of temozolomide-resistant GBM10 cells. Non-irradiated cells were treated with both drugs singly and combined, and counted at 24-, 48-, and 72-hour intervals. Irradiated cells were pre-treated with each drug and combination therapy for three days, irradiated, and then counted at 24-, 48-, and 72-hour intervals. Western blot was used to investigate dsDNA damage biomarker y-H2AX, gene-silencing modification H3K27me3, tumor suppressor p53, EZH2, and JMJD3 expression in non-irradiated and irradiated cells following drug treatment. Single EPZ-6438 and GSK-J4 treatments reduced cell counts with increasing concentration and time. GSK-J4 appears to reduce cell counts more than EPZ-6438 alone, and combinatorial use reduces this further. Western blot reveals increased H3K27me3 expression with GSK-J4 treatment following radiation, but not with EPZ-6438. y-H2AX expression is increased after EPZ-6438 treatment but is not further increased with radiation. Meanwhile, GSK-J4 increased y-H2AX, but only after irradiation. Reduced cell counts following treatment with GSK-J4 may be due to its effects on gene silencing from inhibition of H3K27 demethylation. Additionally, increased dsDNA breaks seen in EPZ-6438 and GSK-J4 supports their roles in radiosensitizing GBM cells. This study highlights the importance of further investigation into GSK-J4 and EPZ-6438 combination therapy in temozolomide-resistant GBM tumors.
Clinical Characteristics and Complications in Patients with Complex Vascular Anomalies
(2022-07-29) Johnson, Megan; Haggstrom, Anita
BACKGROUND/OBJECTIVE: Vascular anomalies are rare complications of development, with some forms affecting less than 1% of the population. In addition to visible manifestations, they may cause pain, swelling, bleeding, thrombosis, and infection. These conditions often require more than one field of medical expertise, so incorporating multidisciplinary care is essential for optimizing management strategies. In an effort to better describe a cohort of these patients requiring complex interventions and understand the spectrum of care they need, we captured demographic, clinical, and quality-of-life data to serve as a launching point for future studies. METHODS: We designed a RedCap database and conducted a retrospective chart review of 100 patients who presented at the Vascular Lesions Clinic (VLC) at Riley Children’s Hospital from May 2020 to May 2022. Demographic, clinical, and quality-of-life data using the OVAMA scale was obtained from Cerner and captured on RedCap. Excel and RedCap software were used to characterize this patient population. RESULTS: The majority of patients had diagnoses of venous malformations and lymphatic malformations. These anomalies showed no male or female predominance and most lesions were segmental. Sclerotherapy was the most common intervention, with venous malformations receiving a higher median number of treatments than lymphatic malformations. Lymphatic malformations were associated with lower appearance satisfaction and a younger median age at the time of the VLC visit than venous malformations. Older age, larger lesion size, female sex, and lesion location on the lower extremities also correlated with worse quality-of-life outcomes. CONCLUSION AND POTENTIAL IMPACT: The characterization of this cohort will guide broader studies of treatments and quality-of-life trends among patients with complex vascular anomalies. Future directions could explore patient outcomes, complication rates, and influences on quality-of-life in a prospective study design.
Understanding the Impact of Adverse Childhood Experiences (ACEs) on Children at the Boys and Girls Club of Tippecanoe County, Indiana
(2022-07-29) Zeh, Janie; Thomas, Jordan; Messmore, Niki
BACKGROUND/OBJECTIVE: Children with multiple Adverse Childhood Experiences (ACEs) have been shown to be at greater risk for chronic health conditions. Providing Trauma-Informed Care (TIC) to children with ACEs has been linked to better downstream health outcomes. Out-of-school time (OST) programs, such as Boys and Girls Clubs (BGC), can play an important role in supporting children with ACEs. Currently, BGC of Tippecanoe County does not require staff or volunteers to participate in training on ACEs or TIC. This study aims to determine the number of ACEs that children at BGC experience, and subsequently if training for staff and volunteers should be required. METHODS: An anonymous survey was developed using a template from ACEs Aware. The survey included ten ACEs questions and nine Related Life Events questions (considered additional ACEs in this study). An optional demographics section was also included. Caregivers of children at BGC were asked to participate. Staff and volunteers were also surveyed regarding their history of training in TIC. RESULTS: A total of 64 surveys were distributed to parents and 52 were completed (81.3% response rate). Of the completed surveys, the mean number of ACEs experienced per child was 4.6, the median was 3, and the mode was 2. The maximum number of ACEs experienced by a child was 14. Fifty percent of the staff and volunteers surveyed (n = 18) had no formal TIC training. Further data analysis is still in progress. CONCLUSION AND POTENTIAL IMPACT: Children who attend BGC may experience on average a higher number of ACEs than the general population. Requiring training on ACEs and TIC for staff and volunteers may help better identify and respond to child behaviors linked to ACEs. Helping children feel safe and empowered through TIC provided at OST programs may have a positive impact on their physical and social health.
Clinical Features Distinguishing Diabetic Retinopathy Severity Using Artificial Intelligence
(2022-07-29) Happe, Michael; Gill, Hunter; Salem, Doaa Hassan; Janga, Sarath Chandra; Hajrasouliha, Amir
BACKGROUND AND HYPOTHESIS: 1 in 29 American diabetics suffer from diabetic retinopathy (DR), the weakening of blood vessels in the retina. DR goes undetected in nearly 50% of diabetics, allowing DR to steal the vision of many Americans. We hypothesize that increasing the rate and ease of diagnosing DR by introducing artificial intelligence-based methods in primary medical clinics will increase the long-term preservation of ocular health in diabetic patients. PROJECT METHODS: This retrospective cohort study was conducted under approval from the Institutional Review Board of Indiana University School of Medicine. Images were deidentified and no consent was taken due to the nature of this retrospective study. We categorized 676 patient files based upon HbA1c, severity of non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Retinal images were annotated to identify common features of DR: microaneurysms, hemorrhages, cotton wool spots, exudates, and neovascularization. The VGG Image Annotator application used for annotations allowed us to save structure coordinates into a separate database for future training of the artificial intelligence system. RESULTS: 228 (33.7%) of patients were diagnosed with diabetes, and 143 (62.7%) of those were diagnosed with DR. Two-sample t tests found significant differences between the HbA1c values of all diabetics compared to diabetics without retinopathy (p<0.007) and between all severities of DR versus diabetics without retinopathy (p<0.002). 283 eyes were diagnosed with a form of DR in this study: 37 mild NPDR, 42 moderate NPDR, 56 severe NPDR, and 148 PDR eyes. POTENTIAL IMPACT: With the dataset of coordinates and HbA1c values from this experiment, we aim to train an artificial intelligence system to diagnose DR through retinal imaging. The goal of this system is to be conveniently used in primary medical clinics to increase the detection rate of DR to preserve the ocular health of millions of future Americans.
Investigating the Role of Meal Quality and Food Look, Smell, and Taste on Perceived Health Improvement for Clients of Meals on Wheels of Central Indiana
(2022-07-29) Boyer, Jacob; Messmore, Niki
Meals on Wheels organizations across the country have the common goal of ending hunger among the elderly, malnourished, and disabled population. Meals on Wheels of Central Indiana (MOWCI) primarily serves Marion County and the rest of the state through one of its programs. The organization offers daily hot and cold meals Monday through Friday, frozen meal deliveries, and pantry boxes. Minus the pantry boxes, meals are assembled at one of nine participating health corporations: Community Health Network, Eskenazi Health, IU Health- Methodist, Marquette, Franciscan Health, Ascension St. Vincent, and Westminster Village. MOWCI offers traditional or Medicaid subsidized hot and cold meals (for Marion County clients), Ryan’s Meals for Life (HIV/AIDS clients), and Embrace Cancer programs (low-income cancer treatment clients from Eskenazi). In this study, phone surveys were conducted investigating food quality and delivery satisfaction for daily hot and cold clients (n=149). Results were analyzed in Excel using a Chi-Square analysis of independence (alpha 0.05, 3 degrees of freedom). It was found that overall food quality and food smell, taste, and appearance were associated with perceived health improvements in a significantly significant manner with a p-value of 0.0000113 and 0.0198 respectively. There are 248 clients who as of July 7th have not been evaluated and thus, is still an active area of focus for MOWCI. A model has been created and shared with the organization that continues to allow them to collect data on future clients and input the data in order to determine what effect meals have on all of their client population as opposed to the 37.5% of clients that have been evaluated in this project. These efforts will be used in the future to aid in writing grants to allow for the expansion of current and future programs.

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