Open Access Journals at IU Indianapolis
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Long-Term Outcomes in Stage II/III Thymic Epithelial Tumor Patients Treated with Post- Operative Radiotherapy
Get PDFThymic epithelial tumors (TETs) are rare malignancies that originate in the anterior mediastinum. Unlike other tumors of the chest, TETs recur most often in the pleura. The primary treatment of early stage TETs is surgical resection, with the role of adjuvant chemotherapy/radiotherapy controversial. Mixed results have been reported as to whether postoperative radiotherapy (PORT) decreases tumor recurrence or time to recurrence, but PORT can cause short-term and long-term toxicity. Therefore, assessing the benefit of PORT is important. For the present retrospective study, we created a database of stage II/III TET patients seen at Simon Cancer Center from 2000-2023 to examine long-term outcomes. Of the 214 stage II/III TET patients that underwent surgery in the database, 67 patients treated with PORT were isolated. Subsequently, 67 patients who did not receive PORT were matched to the PORT population based on similarities in histology, surgical margins, and chemotherapy received. Local vs. distant tumor recurrence, long-term complications, and overall survival were then compared. The PORT population had the following histologic distribution: 3 Type A, 3 Type AB, 47 Type B1/B2/B3, and 14 carcinoma; for the non-PORT population: 8 Type A, 13 Type AB, 36 Type B1/B2/B3, and 10 carcinoma. There were 16 stage IIA, 6 stage IIB, and 45 stage III patients in the PORT population, and 17 stage IIA, 9 stage IIB, and 41 stage III patients in the non-PORT population. The PORT population had 57 recurrences, whereas the non-PORT population had 20 recurrences (p=1.02 x 10-9). The PORT population had 5 deaths and 50 instances of long-term complications, while the non-PORT population had 3 deaths and 25 instances of long-term complications. Overall, these data do not support the routine usage of PORT in resected Stage II/III TET. Further analysis in larger data sets are warranted
Blood Culture Contaminations: Interventions and Culture Characteristics
Get PDFBackground/Objective:Blood cultures are collected in patients with serious illnesses who are at risk of bacteremia. However, some blood cultures are contaminated which may lead to adverse health outcomes for patients such as an increased length of stay and the unnecessary utilization of antibiotics. The emergency department (ED) has been found to be a frequent source of blood culture contamination. We aimed to identify characteristics and consequences of blood culture contamination at IUH Bloomington.
Methods:Chart review of blood cultures collected at IUH Bloomington in January 2023 was utilized to extract variables including intravenous location and hospital location of blood draw, number and identification of antibiotics given, length of stay, and organisms identified in the blood cultures. Data were securely maintained in REDCap.
Results:The median length of stay for individuals with contaminated cultures in January was found to be 4 days which was comparable to individuals with negative cultures. Most commonly, contamination occurred from the ED with it being responsible for 33/34 contaminated cultures. The most frequently utilized antibiotic across all groups was vancomycin – with both the positive and contaminated groups having a greater percentage of individuals receiving a course of the antibiotic with a mean course of 3.43 days. The most common contaminant was found to be coagulase negative Staphylococcus.
Conclusion and Implications:Lower rates of blood culture contamination may contribute to lower length of stay and improved antibiotic de-escalation strategy. Identification of culture characteristics may guide future endeavors in infection control policies
Fracture-Induced Effects on the Onset & Progression of Alzheimer’s Disease
Get PDFAlzheimer’s disease and related dementias (AD/ADRD) are multifactorial, highly heterogeneous, and complex age-dependent disorders that severely affect memory and cognitive function, impacting nearly 35.6 million people worldwide. In the elderly, dementia increases the risk of falls and fractures by 2-3 times, due in part to neurovascular instability, low bone mineral density due to pre-existing osteoporosis, and poor musculature supporting joints due to cachexia and/or sarcopenia.
While the occurrence of fractures due to AD/ADRD is well documented, an association between fractures and AD/ADRD onset or progression is underappreciated and warrants additional investigation. We aim to investigate the mechanistic actions underlying fracture healing as a precipitating event for AD/ADRD pathogenesis.
Four-month-old, male, 5xFAD (AD model) and wild-type control (C57BL/6) mice were divided into 2 groups: surgically induced femoral fractures and uninjured mice. Prior to surgery mice underwent baseline AD behavior testing including: spontaneous alternation in the y-maze, light-dark exploration in the open field, and active place avoidance assays. Mice are undergoing weekly x-ray imaging to monitor fracture healing progression and longitudinal AD behavior testing. 22 weeks post-surgery mice will be euthanized, and femurs and brains collected. Femurs will undergo uCT imaging and histological assessment of bone healing and immunohistochemical assessment of inflammatory markers. Brains will be processed for histology and neuroinflammatory marker analysis, including Aβ plaque deposition, tau tangles, neuronal survival, neurogenesis, and activation/proliferation of microglia and astrocytes.
At the conclusion of the study, we expect to see an increase in neuroinflammatory markers and delayed fracture healing in the experimental 5xFAD group. We anticipate that compared to uninjured controls, femoral fracture results in cognitive decline, Aβaccumulation/neurodegeneration, increases in neuroinflammation, and vascular impairment. We anticipate finding a correlation between fracture and worsened AD outcomes. By uncovering the mechanisms underlying this relationship, we hope to guide future studies to develop more robust therapeutics
Exploring Community-Based Strategies to Overcome Barriers to Hypertension Education and Management in Underserved Areas
Get PDFObjective:In the United States, there are over 119.9 million adults who have been diagnosed with hypertension, representing nearly half of the adult population. Of this population with high blood pressure, 75% of Americans’ hypertension remains uncontrolled. Such control rates are significantly lower among individuals of racial and ethnic minorities as compared to their white counterparts, especially those in underserved areas. We hypothesize that the identification of community-based interventions and strategies to combat barriers to hypertension treatment and education could improve management in these populations.
Project Methods:In this study, we looked through various peer reviewed articles on community-based care and hypertension rates among minorities, exploring study design and limitations to develop a questionnaire focused on access to hypertension education. This survey was distributed randomly during outreach events around Muncie, Indiana to anyone who wished to participate, non-minority groups included. The questionnaire asked about various hypertension and healthcare barrier identification factors with a final question of whether said participant would benefit from a hypertension education course.
Results:The participants’ responses were across the board. Regarding hypertension knowledge, participants were asked about their diagnosis, as well as their level of knowledge of hypertension and its management; participants exhibited varying levels of knowledge. Understanding key aspects of management, including medication adherence, diet, physical activity, and potential complications and warning signs, also varied among participants. Overall, these preliminary survey results highlight the diverse characteristics and experiences of participants related to hypertension, access to healthcare, and hypertension knowledge.
Potential Impact:This study could provide information for those looking to establish community-based organizations in underserved areas. Increasing the magnitude of such teams and advocating for more interventions against barriers to hypertension education could increase not only the health of those in such communities, but also the overall wellbeing of all people in the United States
The Role of SHROOM3 in Congenital Heart Disease
Get PDFBackground and Hypothesis: Congenital heart defects (CHD) are the most common, and most frequently fatal birth defects, but most etiology remains unknown. We identified a patient with CHD and implicated a gene called SHROOM3. SHROOM3 binds Dishevelled2 which is the central cytoplasmic component of both canonical and noncanonical Wnt/planar cell polarity (PCP) signaling pathways. PCP drives cell movement and is important to embryogenesis and disruption causes CHD. We hypothesize CHD can result from SHROOM3-loss-of-function due to PCP disruption.
Project Methods: To interrogate SHROOM3’s role in CHD and PCP we utilized an established in vivo SHROOM3-loss-of-function model, Shroom3 gene trap mice (Shroom3gt). We also utilized a loss-of-function model for PCP membrane component VANGL2, (Vangl2+/-). We assayed genetic interaction between Shroom3 and Vangl2 during cardiac development by crossing singly heterozygous null mice to produce compound heterozygous embryos, harvested embryos, and performed histologic analysis for cardiac defects. We also utilized a human in vitro SHROOM3-loss-of-function model, a CRISPR-Cas9 edited SHROOM3 knockout HELA cell line. We assayed cell movement using a scratch assay.
Results: Compound heterozygous Shroom3+/gt;Vangl2+/- embryos had a three fold increase in heart defects compared to singly heterozygous Shroom3+/gt;Vangl2+/+ or Shroom3+/+;Vangl2+/- embryos (3 of 19 or 15.7%, versus 1 of 17 or 5.2%, and 1 of 19 or 4.8%, respectively), demonstrating a trend towards genetic interaction between SHROOM3 and VANGL2/PCP during cardiac development. The scratch assays demonstrated cell movement defects due to SHROOM3-loss-of-function consistent with increased cell movement.
Conclusion and Potential Impact: We demonstrate SHROOM3 interacts with Wnt/PCP during cardiac development. Further interrogation of SHROOM3’s role in Wnt signaling will provide insight into the mechanisms by which a novel CHD candidate participates in cardiogenesis and will improve CHD diagnosis, management, and therapeutic development
Assessing Skin Sympathetic Nerve Activity and Cardiac Effects in Patients with Gastric Electrical Stimulation
Get PDFBackground:Gastric Electrical Stimulation (GES) is a therapy for gastroparesis patients, alleviating symptoms like nausea, vomiting, and poor gastric emptying. The therapeutic impact of GES is believed to stem from changes in autonomic nerve activity, particularly parasympathetic activity via the vagal nerves. This study examines skin sympathetic nerve activity (SKNA) to assess autonomic nerve bursts, investigating the effects of GES on nerve activity and cardiac function.
Methods:SKNA signals were recorded from 48 patients at three locations: left side of the neck (SKNA1), right side of the neck (SKNA2), and via ECG Lead 1 across the chest (SKNA3). Signals were band pass filtered (500 Hz to 1000 Hz) to eliminate ECG and muscle artifacts and highlight nerve activity. Using Labchart software, the absolute value integral (iSKNA) was calculated for each 100-millisecond sample, with resulting values exported to Excel. Data was collected during different GES conditions: GES On, GES at ½ voltage, GES Off, and GES back on. The threshold for nerve activity bursts was determined as the mean of iSKNA values + two times the standard deviation in each section.
Results:Histograms of average aSKNA values showed reduced nerve activity with GES off. Left and vagal nerve activity on SKNA1 was significantly lower with GES fully on or off compared to GES at ½ voltage. No other significant differences were observed in variabilities or average aSKNAs in SKNA1 or SKNA2.
Future Directions & Potential Impact:Burst analysis of iSKNA data will address key questions. Variations in burst activity with different GES conditions may elucidate GES\u27s therapeutic effects on gastroparesis. Subsequent segmentation of data into patients with resolved and unresolved symptoms could reveal the relationship between burst activity and therapeutic efficacy. Additionally, correlation of burst data with heart rate variability analysis will provide insights into the impact of GES on cardiac function. This study will advance our understanding of GES effects and safety, potentially improving patient outcomes
Prophylactic Posterior Targeted Muscle Reinnervation (TMR) Approach in Below Knee (BKA) Amputation Settings
Get PDFBackground/Objective: Targeted muscle reinnervation (TMR) is a nerve reconstruction technique focused on improving phantom limb pain (PLP), residual limb pain (RLP), prosthesis function, and limiting neuroma formation. In below-knee-amputations (BKA), TMR performed "through-the-wound" is heavily documented. Alternatively, the "posterior approach" was developed to help increase visibility of peripheral nerves from the posterior fossa. This study focuses on the surgical efficiency and patient outcomes of the posterior approach compared to the through-the-wound approach. We hypothesize the posterior approach will be comparable toor improve time-to-prosthesis fitting, OR time, and pain scores.
Methods: 157 patients underwent TMR at two hospitals in Indianapolis, IN, and were identified using CPT 64890. 39 patients underwent posterior approach TMR post-BKA. Data on demographics, follow-up/rehabilitation visits, post-operative complications, prosthesis fitting, and total OR time were collected. Additionally, 32 patients received TMR "through-the-wound", and total OR time, post-operative complications, and time-to-prosthesis fitting were tracked. Patient-reported outcome (PRO) surveys are being sent to patients pending IRB approval.
Results: Of the 39 who received the posterior approach between 1/10/2020 and 4/6/2023, 25 received TMR in the right leg and 14 in the left. Following BKA, average time to TMR was 144 days. However, 18 patients received TMR directly after undergoing BKA (46.2%). Average OR time for acute and delayed posterior TMR patients was 208.06 minutes and 199.47 minutes, respectively. 10 patients reported post-operative complications (25.6%): dehiscence (12.8%) or infection (7.7%). 23 patients received prosthesis fitting on average 3 months post-op. Average OR time and time-to-prosthesis fitting for "through-the-wound" TMR surgeries were 192.84minutes and 5.81 months, respectively.
Potential Impact: Posterior approach TMR had no significant impact on OR time, but time-to-prosthesis fitting significantly decreased. Once PRO surveys return, average long-term PLP and RLP can be determined. Preliminarily, posterior approach TMR improves aspects of patient outcomes while not compromising surgical efficiency
A Predictive Model for Cardiomyopathy Progression in a Longitudinal Cohort of DMD Patients
Get PDFBackground: Cardiomyopathy (CM) is currently the leading cause of mortality in patients with Duchenne muscular dystrophy (DMD). DMD CM is asymptomatic during the early stages of disease and age of onset and clinical progression vary. We previously showed that 4D kinematic analysis of cardiovascular magnetic resonance (CMR) imaging is a robust method to visualize strain and function changes in DMD patients. Our objective, using 4D CMR image analysis, is to build a predictive model to quantify disease progression, and predict functional decline as measured by left ventricular ejection fraction (LVEF) in a longitudinal cohort of DMD patients.
Methods: We obtained 4D CMR images from 40 DMD patients imaged every 12 months for three years. Localized surface area strain (Ea) values were derived from compiled 4D CMR images. Patient demographics, presence or absence (+/-) of late gadolinium enhancement (LGE) and LVEF were obtained by a trained cardiologist. Principal component analysis was used to identify prominent variables contributing most to variability. These variables, along with clinically relevant variables, were selected to build the predictive model. We built a linear mixed effects model using visit, age, basal Ea, and LGE presence. Each patient was considered a random effect to account for variability in initial CM severity.
Results: Study patients were grouped into stages of heart failure according to the American Heart Association: Stage A, LVEF>55%, LGE(-); Stage B, LVEF>55%, LGE(+); Stage C, 40%<LVEF<55%, LGE(+); Stage D, LVEF<40%, LGE(+). Linear mixed effects model showed a good prediction of LVEF on year 3 with a root mean squared error of 3.6% and an R2 value of 0.75 (p<0.0001.).
Conclusion: Early detection is crucial for appropriate clinical intervention. This novel predictive model was developed to determine if Ea derived from 4D imaging, LVEF, and (+/-) LGE can be used to predict functional outcomes in DMD CM. 
Changes in Transport Mode for Pediatric Trauma Patients Before and After the COVID-19 Pandemic
Get PDFBackground: The Emergency Medical Services (EMS) system has faced significant stress due to the COVID-19 pandemic and now workforce issues. This study was performed to evaluate potential changes in pediatric trauma patient transport over that time period. We hypothesized that more trauma patients would use private transportation/personal vehicles to arrive at the ED in the post-pandemic time frame when compared pre-pandemic.
Methods: This was a retrospective cohort study of patients that were admitted to the Emergency Department of Riley Hospital for Children between 01/01/2017 to 12/31/2022. Patients were excluded if they were transferred from another hospital or had mechanisms of injury including burns, suffocations, drownings, hangings, medical, and ingestions. Pre- and post-COVID patients were defined as admission to the ED before or after March 25, 2020, the day after a stay at home orders were implemented in Indiana. Univariate and multivariate analyses were performed.
Results: A total of 4,116 patients matching the criteria were identified with 52% arriving after the start of the COVID-19 shut down orders. 30.6% of patients arrived by private operated vehicles (POV) during pre-covid times and 30.3% in the post-covid years (p=0;39). A logistic regression analysis was performed for mortality which demonstrated that transport mode (ground ambulance vs helicopter vs POV) was not statistically associated with mortality rate (OR 0.36, 95% CI 0.12 – 1.10, p=0.07), when controlling for important clinical variables associated with injury severity.
Conclusion: There was no statistical difference in arrival by POV before and after the COVID-19 pandemic in our cohort. Additionally, there was no significant data to suggest that transport mode was associated with mortality. Further research should be done to assess potential barriers to transport to pediatric trauma centers, particularly considering ongoing EMS workforce strains. 
