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... Prevalence and Management of Constipation in Pediatric Patients Undergoing Chemotherapy: A Retrospective Review *Megan Parod, OMSIII1,*Trisha Reddy, MD2, Jennifer A. Belsky DO, MS1,2,3 1Marian University College of Osteopathic Medicine 2Department of Pediatrics, Indiana University School of Medicine 3Division of Oncology, Riley Hospital for Children Background Children with acute lymphoblastic leukemia (ALL) suffer a litany of therapy induced side effects Methotrexate is a common chemotherapy agent administered for the treatment of ALL Failure to clear methotrexate from the body can result in toxicities including mouth sores, mucositis, and organ dysfunction, which have been well documented in the literature To date, no studies have examined the correlative relationship between delayed methotrexate clearance and constipation This study aims to examine chemotherapy induced constipation, current management practices, and the relationship between delayed clearance of methotrexate and constipation Methods Single institution, retrospective cohort study, analyzed data from Riley Hospital for Children Patients birth to 21 years of age with ALL, hospitalized for high dose intravenous methotrexate therapy from January 2010 to September 2021 Constipation definition: no stool for greater than 48 hours documented in the inpatient EMR Cerner system Demographics and Clinical Characteristics Entire Cohort N (%) 23 6.7 (0 - 26) Characteristic Unique Patients Median age (years) at Induction (range) Sex Female Male Race White Black Asian American Indian Pacific Islander Other/Unknown Ethnicity Hispanic or Latino Non-Hispanic or Latino Management of Constipation 5 (26) 17 (74) 20 (87) 1 (4.3) 2 (8.6) 0 (0) 0 (0) 0 (0) 2 (8.7) 21 (91.3) Table 1: Demographics and clinical characteristics of pediatric patients with ALL (Pediatric Hospital Information System, 2010-2021) Admission Information Characteristic Unique Admissions Average Length of Stay Range of Length of Stay Historical Constipation During Previous Admissions N (%) 61 5 days 3-29 days 31 (50.8) Did Not Have Last Stool Documented Prior to Admission 53 (91.4) Concomitant Chemotherapy Medications Given 57 (96.6) Vincristine Given with High Dose Methotrexate 56 (91.8) Mercaptopurine Given with High Dose Methotrexate 57 (93.4) Concomitant Opioids Prescribed During Admission 13 (22.7) Constipation During Admission 17 (27.9) Table 3: Evaluating methotrexate clearance and management of constipation in patients during admission Discussion and Next Steps We identified that 27.9% of patients with ALL who received methotrexate therapy during hospitalization suffered from constipation, with 88.2% of these patients experiencing delayed methotrexate clearance Half of admitted, constipated patients were prescribed constipation medications PRN that were then given 5.9% of the time In addition to their prolonged hospitalizations, majority of patients received vincristine, contributing to constipation Future prospective studies should focus on standardizing bowel regimens and increased attention must be paid to patients receiving constipating chemotherapy agents References and Complete Poster Available Table 2: Exploring admission data of patients receiving high dose methotrexate INDIANA UNIVERSITY SCHOOL OF MEDICINE Marian University College of Osteopathic Medicine References 1. Surveillance, Epidemiology, and End Results (SEER) Program. National Cancer Institute, 2019. (Accessed October 25, 2019) 2. Collins JJ, Devine TD, Dick GS, et al. The Measurement of Symptoms in Young Children With Cancer: The Validation of the Memorial Symptom Assessment Scale in Children Aged 712. J Pain Symptom Manag 2002;23:10-6. 3. Hedstrm M, Ljungman G, Von Essen L. Perceptions of distress among adolescents recently diagnosed with cancer. Journal of Pediatric Hematology/Oncology 2005;27:15-22. 4. McQuade RM, Stojanovska V, Abalo R, Bornstein JC, Nurgali K. Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments. Front Pharmacol 2016;7:414. 5. Pashankar FD, Season JH, McNamara J, Pashankar DS. Acute Constipation in Children Receiving Chemotherapy for Cancer. Journal of Pediatric Hematology/Oncology 2011;33:e300-e3. 6. Wickham RJ. Managing Constipation in Adults With Cancer. J Adv Pract Oncol 2017;8:149-61. 7. Sood M, Lichtlen P, Perez MC. Unmet Needs in Pediatric Functional Constipation. Clinical pediatrics 2018;57:1489-95. 8. Rajindrajith S, Devanarayana NM, Crispus Perera BJ, Benninga MA. Childhood constipation as an emerging public health problem. World journal of gastroenterology 2016;22:6864-75. 9. Hoekman DR, Benninga MA. Functional constipation in childhood: current pharmacotherapy and future perspectives. Expert Opin Pharmacother 2013;14:41-51. 10. Mujagic Z, Tigchelaar EF, Zhernakova A, et al. A novel biomarker panel for irritable bowel syndrome and the application in the general population. Sci Rep 2016;6:26420. INDIANA UNIVERSITY SCHOOL OF MEDICINE Marian University College of Osteopathic Medicine  ...

... 3D Visualization of Multiple Sclerosis Matthew Lashmet, MS, OMS II MU-COM and David Dufeau, PhD MU-COM mlashmet480@marian.edu; ddufeau@marian.edu Introduction Multiple sclerosis (MS), one of the most prevalent immune-mediated neurological disorders, is a chronic demyelinating disease of the central nervous system that affects both white and grey matter (Avasarala et. al.). According to the National Multiple Sclerosis Society, more than two million individuals are affected worldwide, with current estimates suggesting more than 400,000 affected patients in the United States (Reynolds et. al.). Primary demyelinating diseases, i.e., those with an idiopathic etiology, affect not only the myelin sheath, but also have the tendency to affect axons and neuronal cell bodies as well (Smith et. al.). Data Acquisition Patient is a 60-year-old Caucasian male who presented to his neurologist with complaints of peripheral neuropathy in his lower extremities in 2007. An MRI was completed at the Cleveland Clinic that showed multiple lesions in both the brain and thoracic spinal column. A diagnosis of Primary Progressive Multiple Sclerosis (PPMS) was made in 2015 and patient has been on disease modifying therapies with no significant improvement since. Disease modifying therapies have included: 2 infusions of Ocrevus (ocrelizumab), oral Mayzent, and multiple courses of solumedrol. Patient has been adhering to strict dietary restrictions, focusing on a version of the Paleolithic diet, the Wahls Protocol. Patient admits to continued gait instability that has become progressively worse sense diagnosis in 2015. Results Figure 1. Reconstructed 3D brain images from 9/7/2011 shown in axial, sagittal and coronal views. Lesions depicted in green, yellow, red, and blue. Figure 2. Reconstructed 3D brain images from 12/5/2019 shown in axial, sagittal and coronal views. Lesions depicted in green, yellow, red, and blue. Over an 8-year period, all lesions in this patient increased in size. Of particular interest, the green and yellow lesions surrounding the ventricles had more than quadrupled and sextupled in size, respectively. Due to their proximity to the internal capsule and the surrounding white matter motor tracks, it is likely that the lesions depicted in green and yellow are contributing to the worsening gait instability seen since onset of diagnosis. Total lesion load in this patient was calculated to be 958.391 mm3 in 2011 and 3144.670 mm3 in 2019. The total lesion load was significantly reduced when compared to the total lesion load (95,774 mm3) reported by Avasarala et. al. Conclusion Conventional methods of viewing MS lesions have been accomplished primarily using 2D MRI imaging. Using the 3D analytical software Amira, we have created two separate 3D brain renderings that depict the transient nature of MS from 2011 to 2019. Monitoring the progression and regression of MS lesions not only improves patient education, but aids clinicians in the monitoring of this disease, which has no surgical remedies. Research into the efficacy of MS disease modifying drugs makes clinical implementation of 3D constructs applicable and necessary. We hope this study will provide a platform to which demyelinating diseases can be tracked longitudinally in 3D, thereby improving patient care. Consent Verbal consent was obtained from the patient prior to the publication of this study and the included images. Methods The study was performed in the Marian University College of Osteopathic Medicine 3D Visualization Laboratory. MRI data sets were obtained from the Cleveland Clinic and Northwest Radiology in Carmel, Indiana. MRI data sets were originally analyzed using the Digital Imaging and Communications in Medicine (DICOM) viewer HOROS and 3D renderings were constructed using the analytical software, Amira. 3D constructs were overlayed onto the cross-sectional images of the MRI slices to verify the accuracy of the construct prior to final renderings. Lesions were differentiated visually, and mathematical algorithms were implemented that allowed us to quantify the lesion load between 2011 and 2019. Discussion Works Cited Jagannadha Avasarala, Todd Pietila.: The first 3D printed multiple sclerosis brain: Towards a 3D era in medicine. F1000 Research. 2018, 6; 1603. Table 1. Lesion load volume from 2011 and 2019. Volume recorded in millimeters cubed (mm3). Eric Reynolds et. al.: Multiple Sclerosis and Exercise: A Literature Review. Current Sports Medicine Rep. 2018, 17; 31-35. Alice Smith, James Smirniotopoulos. Imaging evaluation of demyelinating process of the central nervous system. Postgraduate Medical Journal. 2010, 86; 218-229.  ...

... 3D Visualization for Young Athlete Education on Potential Risk of Injury Alec Rhodes, OMS-II; Marque Kriebel, OMS-II; Daniel Wright, OMS-II; and David Dufeau, PhD MU-COM arhodes860@marian.edu mkriebel452@marian.edu dwright482@marian.edu ddufeau@marian.edu Introduction Results 3D visualization software is a useful tool in patient education because it allows patients to put an image to what a physician is describing to them. With an emphasis on education of young athletes on the potential injuries, 3D images can create a more complete understanding of their risks. The software used in this study provides young athletes with insight on joint structure, joint movement, mechanism of injury, inherent risks of sport, and tips to help prevent injury in a way that is easier to visualize. This gives these patients the ability to make an informed decision on their participation in sports. Methods Results Figure 3: Anterior view of the knee joint created with 3D visualization software Figure 4: Posterior view of knee joint with femur and tibia theoretically pulled apart using 3D visualization software The study was performed in the Marian University College of Osteopathic Medicine 3D Visualization Laboratory. It used MRI data from Indiana Orthopedic Hospital and other various sources to reconstruct the knee, hip and shoulder joint. The anatomical structures were discerned and extracted through various slices of images using FEI Amira software. SLAP tears occur when the humerus is abducted and externally rotated. This usually occurs during sports involving overhead throwing or swinging motions. Figure 7: 3D model of SLAP tear A Sad Triad is a tear to the ACL, MCL and the medial meniscus. This occurs when a large lateral contact force applied to the outside of the knee with a planted leg. Figure 8: 3D model of terrible triad Conclusion The intention of this study was to demonstrate the usefulness of 3D visualization and how it can be used in patient education. Specifically, the final video products use this technology to help educate young athletes on the risks of sports, anatomy, and prevention of injury. Future Direction Figure 1: MRI of Knee Figure 2: MRI of shoulder The resulting extracted structures were manipulated in Amira and MeshMixer to assemble a 3D image or movie that can easily convey the intended educational message. The images and movies were compiled and edited in Camtasia to create a visual presentation to be viewed by juvenile athletes. Figure 5: Anterior view of right glenohumeral joint created with 3D visualiztion software Figure 6: Anterior view of right hip joint created with 3D visualization software Ultimately, the team would like every juvenile athlete to watch an educational video, similar to that of the final product made in this study, that outlines their risks before making an informed decision on whether to participate in their sport. 3D printing these models could allow patients to get their hands on these structures to better conceptualize their functions.  ...

... Klotho in Aging and Disease David Choe*, Elizabeth Delery*, Andrew MacLean Marian University College of Osteopathic Medicine*, Tulane University INTRODUCTION Klotho is a regulatory anti-aging protein that is significantly expressed in the choroid plexus, plays an important role in regulating the immune response in the CNS, and diminishes with age Klotho deficiency is characterized by significant neuroinflammation, oxidative damage in the neural parenchyma, and decline in neurocognitive functions The choroid plexus is a reservoir for HIV, and as HIV infection can cause HIV-associated neurocognitive disorders (HAND)an inflammaging phenotype, we hypothesized that klotho may play a role in the development of this neurocognitive deficit Approximately 30-60% of adults with HIV develop HAND (Rosca 2021) RESULTS D G Although klotho expression was varied in the uninfected Rhesus macaques, there was an overall decreasing trend with the advancement of age past adulthood In SIV-infected Rhesus macaques, the choroid plexus had significantly less klotho expression than the uninfected control group regardless of age (p=0.01) A OBJECTIVES In this project, we sought to characterize patterns of age-related klotho decline in primates as well as to determine if there was a correlation between klotho expression in the choroid plexus and HIV infection. Figure D shows klotho expression in the uninfected based on age. There seems to be a general decrease in klotho expression past adulthood. However, the neonatal data is unclear as there is significant difference between the two neonates. METHODS Immunofluorescence: Choroid plexus samples of Rhesus macaques of various ages and SIV infection status were studied The tissues were stained using immunohistochemistry for polyclonal klotho and ZO-1 Tissues were first blocked with 5% normal goat serum 200uL of primary antibody solution were applied to each slide for 1 hour in a dark setting The previous step was then repeated with the respective secondary antibody solution Polyclonal Klotho primary antibody (Invitrogen), 1:50 dilution of 1mg/mL stock Klotho secondary goat ant rabbit 488 (Invitrogen), 1:1000 dilution of 2 mg/mL stock ZO-1 primary antibody (Invitrogen), 1:100 dilution of .5 mg/mL stock ZO-1 secondary goat anti- mouse 568 (Invitrogen), 1:1000 dilution of 2mg/mL stock Quantification of Mean Fluorescence Intensity: To measure MFI, 10 images were taken of the choroid plexus at 40x on each slide SIV analysis images were captured on a Nikon Ti2 microscope, while the aging analysis images were obtained using a Keyence BZ-X810 For each image, 10 choroid plexus epithelial cells were selected and analyzed in Fiji The background fluorescence was also measured and subtracted from the epithelial fluorescence All 10 calculations of corrected total cell fluorescence (CTCF) were then averaged for the final MFI value E Figure A shows the dramatic decrease in klotho expression in SIV infected individuals compared to the uninfected control group. The SIV infected group had much more narrow range of klotho expression compared to the uninfected. This could be due to natural genetic variance in the uninfected. B Figure E shows klotho expression in the uninfected based on different age groups. There was an increase in klotho expression from neonates to adults and a subsequent decrease between adults and aging groups. Figure B compares klotho expression groups separated by both SIV status and age. Both uninfected neonates and uninfected adults had significantly higher klotho expression compared to their infected counterparts. C Figure C is a comparison of klotho expression between SIV positive (left) and negative (middle) subjects. The SIV positive image has significantly diminished fluorescence compared to the SIV negative. www.PosterPresentations.com Status Unin. Neonate Unin. Neonate Unin. Neonate Sex M M M SIV Strain Uninfected Uninfected Uninfected SIV (Age at Infection) N/A N/A N/A Length of Infection (Days) 15A233 15A302 11A489 11A490 Unin. Neonate Infected Neonate Infected Neonate Infected Neonate M M F M Uninfected SIVmac251 SIVmac251 SIVmac251 N/A 0 0 0 N/A 12A611 10A718 11A067 11A204 14A100 14A318 14A319 14A644 Infected Neonate SIV Juveniles SIV Juveniles SIV Juveniles Unin. Adults Unin. Adults Unin. Adults Unin. Adults F F F F M M M M SIVmac251 SIVmac251 SIVmac252 SIVmac251 Uninfected Uninfected Uninfected Uninfected 0.01 0.36 0.21 0.34 N/A N/A N/A N/A 62 14A745 11A439 11A837 Unin. Adults SIVnoE Adults SIVnoE Adults M M M Uninfected SIVmac251 SIVmac251 N/A 9.03 7.68 N/A 13A307 39413 37747 32752 28282 26813 19845 19691 SIVnoE Adults Unin. Neonate Unin. Neonate Unin. Adults Unin. Adults Unin. Adults Unin. Adults Unin. Adults F F F M F F F F SIVmac239 Uninfected Uninfected Uninfected Uninfected Uninfected Uninfected Uninfected 21.47 N/A N/A N/A N/A N/A N/A N/A 146 N/A N/A N/A 380 76 37 79 154 209 N/A N/A N/A N/A 49 223 N/A N/A N/A N/A N/A N/A N/A Figure G presents additional information on the animals used in this study such as their age, gender, and SIV status. CONCLUSIONS This significant decrease of klotho in SIV infected individuals show that SIV has a significant affect on klotho expression Compared to the uninfected, which had natural variances of klotho levels, the SIV infected all had similar levels of klotho despite being diverse in age The lower klotho level in uninfected neonates can be due to klotho expression not reaching its peak until adulthood. A study in mice found klotho levels increased after birth and into adulthood and decreased with aging (Vo 2018) One limitation to the study was that most of slides analyzed were that of female macaques. As macaques are considered an acutely scarce resource, we could not have a balance between male and female subjects Relationship between klotho and HIV could help to explain the development of HIV-associated neurocognitive disorders (HAND) However, the exact mechanism in which SIV diminishes klotho expression is unknown and additional studies are warranted to examine this phenomenon REFERENCES Rosca, E.C.; Tadger, P.; Cornea, A.; Tudor, R.; Oancea, C.; Simu, M. International HIV Dementia Scale for HIV-Associated Neurocognitive Disorders: A Systematic Review and Meta-Analysis. Diagnostics 2021, 11, 1124. https://doi.org/10.3390/ diagnostics11061124 Vo, H. T., Laszczyk, A. M., & King, G. D. (2018). Klotho, the Key to Healthy Brain Aging? Brain Plasticity (Amsterdam, Netherlands), 3(2), 183194. https://doi.org/10.3233/BPL-170057 Acknowledgements Statistics: All statistical analyses of counts were performed with GraphPad Prism 7. -klotho mean fluorescence intensity was analyzed using a MannWhitney one- and two-tailed t-test. Significance was defined a p<0.05 RESEARCH POSTER PRESENTATION DESIGN 2019 F Animal ID 16A076 15A164 15A202 Figure F compares images of klotho staining between an uninfected adult (left) and aging (right) subject. The intensity of fluorescence is greater in the adult subject. Funding: This research was supported by grants: Tulane National Primate Research Center: P51OD011104 (formerly RR00164) from the National Institutes of Health Andrew MacLean: NS104016, MH113517 This investigation used resources that were supported by the Southwest National Primate Research Center grant P51 OD011133 from the Office of Research Infrastructure Programs and the U42OD010442 grant from the National Institutes of Health We would like to thank Dr. Chris Chen and Dr. Marie-Claire Gauduin for the use of their samples, and Debbie Christian for the procurement of the samples.  ...

... Kisspeptin together with its receptor, GPR54 (Kiss1R), are known for their function as the principal regulators of the onset of mammalian puberty. Given the characteristic growth spurt and bone development that occurs during puberty, recent studies have provided insights into the role kisspeptin has in the control of skeletal homeostasis as well as bone cell differentiation. Both kisspeptin and Kiss1R knockout mice display decreased trabecular bone mass. The present study hypothesizes kisspeptin communicates with bone cells which may aid to regulate growth and differentiation. The objective of this work was to establish the expression patterns of kisspeptin and Kiss1R in bone and uncover for the cell signaling networks it can affect. Mesenchymal bone cells, W-20-17 (W20), were analyzed via western blot analysis and found to express Kiss1R. W20s were then treated with the kisspeptin peptide (50M) for approximately 18 hours in starving media. Signal transduction antibody microarrays were run to compare changes in the intracellular signaling networks affected by kisspeptin treatment (n=3). Of the 165 specific antibodies targets related to signaling cascades, 23 targets were significantly increased or decreased (p<0.05). Interleukin-5 (IL-5) and Tumor necrosis factor- (TNF-) expression was significantly increased by kisspeptin treatment (1.86 and 1.24 respective fold; p<0.05). Work is ongoing to identify if this response is Kiss1Rdependent. These data suggest kisspeptin treatment can induce an inflammatory response in bone. MATERIALS & METHODS W-20-17 (W20), analyzed via western blot analysis for GPR54 A mesenchymal bone cell line expresses kisspeptin receptor protein GPR54 Protein expression in W20 cells 20 SDS-PAGE: Standard PageRuler Plus Prestained Protein Ladder and W20 samples were loaded on polyacrylamide 12% Mini-PROTEAN gel at 30 ug, protein concentrations determined by BCA assay. W-20-17 (W20) cells were treated with kisspeptin and analyzed by signal transduction array W20 cells were treated with either 50 M kisspeptin in starving media and incubated for approximately 18 hours or PBS control. Cells were then harvested, pelleted, and then lysed for protein isolation. BCA assay was used to determine total protein concentration. Samples from both the treatment and control group (50 g) were run on the Full Moon BioSystems Signal Transduction Antibody Array. Results were normalized to bactin. Data are presented as mean fold change +/- standard error of the mean (SEM) of each signal transduction protein target relative to b-actin from n=3 sample replicates. RESULTS The mesenchymal bone cell line (W20) expresses kisspeptin receptor protein Antibody arrays were run on protein samples collected from both kisspeptin-treated and control mesenchymal bone cells (W20) in three separate runs (n=3). Samples were normalized to beta-actin. Of the 165 specific antibody targets related to signal transduction, 6 targets had a statistically significant change in protein expression (p<0.01). To determine if protein expression results were statistically significant, average fold change was normalized via T-test to beta-actin, p-value was set to <0.01, and protein expression was said to be increased if average fold change was >1.50 or decreased if average fold change was <0.50. Of the 165 proteins tested, 6 pertinent proteins were selected to be highlighted. Of interest, interleukin-5 (IL-5), interleukin-6 (IL-6), and granzyme B expression were significantly increased by kisspeptin treatment (2.38, 1.82, and 1.81 respective fold change; p<0.01). Also of interest, Hypoxia-inducible factor 1-alpha (HIF-1a, HIF-1a), amylin peptide, and nitric oxide synthase type 1 (NOS-i) were significantly increased with kisspeptin treatment (2.22, 1.73, and 1.63 respective fold change; p<0.01). 10 5 0 Control Amylin Peptide Granzyme B HIF-1a IL-5 IL-6 NOS-i W20 Average Standard Error Fold Change of the Mean 1.73 0.13 P-value 0.01 1.81 0.02 0.000001 2.22 0.16 0.002 2.38 0.21 0.003 1.82 0.12 0.002 1.63 0.05 0.0002 Jordan Matz, Mariah Castanon, Chynna Fahrholz, Kasey Kruse, Shelby Lemmon, Joe Vroegop, Jonathan Lowery, Julia Hum College of Osteopathic Medicine, Marian University Kiss1R (GPR54) protein expression was detected in W20-17 (W20). Densitometry results from western blots were generated from ImageJ. Kisspeptin-treated mesenchymal bone cells increase the expression of markers of inflammation 15 Cell Culture - W20 cells were cultured for normal maintenance in DMEM, combined with 10% (v/v) FBS, 1% (v/v) AntibioticAntimyotic Solution (100x), and 1:5000 (v/v) puromycin. Rabbit Polyclonal Anti-Kisspeptins Receptor antibody (OriGene) were used to probe membranes at a dilution factor of 1:1000. Mouse polyclonal anti-b-actin 1% antibodies were then used to probe as a loading control at a dilution factor of 1:2000. Chemiluminescent Detection Reagent from the Advansta Western was used for blotting detection. Blot image density was analyzed using ImageJ via NIH. Kisspeptin treatment in mesenchymal bone cells induces markers of inflammation Densitometry Units ABSTRACT FUTURE DIRECTIONS Future work will quantify expression of Kiss1R by qPCR in W20 cells and other bone cell lines. Work to identify if the findings of the signaling array are Kiss1R-dependent are underway and the elucidation of the mechanism(s) by which these findings occurred. This work is cause for speculation that kisspeptin may play a role in the inflammatory response of bone.  ...

... Outcomes Using the Reinforced Biologic Augmented Repair (ReBAR) Technique in Robotic Transabdominal Preperitoneal Ventral Hernia Repair Briana 1 Sowers , 1Marian 2Ascension Cory Banaschak, 2 DO , Paul Szotek, 3 MD University College of Osteopathic Medicine, St. Vincent Hospital Indianapolis, 3Indiana Hernia Center Introduction Conclusion Due to the availability of information on the internet, patients are well informed of the several types of hernia repair available to them. They are also increasingly made aware of the litigious environment surrounding synthetic mesh use through advertising [1]. With increasing concern for complications, patients are seeking methods of hernia repair that reduce foreign material while providing lasting results. Patients are encouraged to pursue the choice of hernia repair with which they are most comfortable while receiving maximum medical benefit. The ReBAR technique combines data driven principles while addressing patient concerns. The recurrence rate in this population of 58 patients undergoing vental hernia repair was 1.7% and no other postoperative complications were identified. The recurrence was identified 6 months postoperatively in a smoker who had a witnessed coughing event during extubation. In response to patients concerns, we developed a novel technique known as the reinforced biologic augmented repair (ReBAR), which incorporates data proven principles of hernia repair. This includes (1) primary closure of hernia defects and (2) reinforcement of the primary repair using mesh (figure 1). These principles have been proven to decrease ventral hernia recurrence rates [2,3]. Limitations of this study include the small number of patients and the average duration of follow up. Additionally, each patient was not evaluated in office as patient communication was primarily completed through a smartphone application. The purpose of this study is to analyze the postoperative outcomes in robotic assisted reinforced biologic augmented repair of ventral hernias. The primary outcome is ventral hernia recurrence. Secondary outcome was incidence of surgical site occurrence. In conclusion, rTAPP ReBAR technique is a safe and durable option for VHR in the short term. Continued follow-up of this cohort is warranted. Methods This study is a retrospective review of data from a single surgeon performing elective ventral hernia repairs (VHR) from 8/9/19 to 4/29/21. Repairs utilizing the robotic transabdominal preperitoneal (rTAPP) approach with the ReBAR technique were included. After gaining access to the abdominal cavity, docking the robot and performing a standard rTAPP ventral hernia dissection, the ReBAR technique was then utilized (figure 2). This consists of: 1. Suture closure of the ventral defect(s) and plication of any significant diastasis recti greater than 2 cm. 2. Augmenting the repair with a reinforced biologic mesh. Primary outcome was ventral hernia recurrence. The secondary outcome was incidence of surgical site occurrence (SSO), defined as surgical site infection, wound dehiscence, seroma, or enterocutaneous fistula. Patients were followed using a HIPAA compliant texting application which allowed for surgeon to patient communication regarding any post-operative concerns. References Results 58 patients underwent rTAPP VHR using the ReBAR technique. Follow up ranged 192 days to 821 days, with an average follow up period of 373 days. Patients were contacted through a HIPAA compliant smartphone application at routine intervals to inquire about new concerns or complications. Outcomes: 1 recurrence (1.7%) 0 SSO (1) Miller MP, Blatnik JA. Evaluation of information on the Internet regarding surgical mesh for hernia repair: analysis of websites found through three popular search engines. Hernia. 2021. (2) Martin-Del-Campo LA, Miller HJ, Elliott HL, Novitsky YW. Laparoscopic ventral hernia repair with and without defect closure: comparative analysis of a single-institution experience with 783 patients. Hernia. 2018;22(6):1061-1065. (3) Luijendijk RW, Hop WC, van den Tol MP, de Lange DC, Braaksma MM, IJzermans JN, Boelhouwer RU, de Vries BC, Salu MK, Wereldsma JC, Bruijninckx CM, Jeekel J. A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med. 2000;343(6):392-8.  ...

... The synthesis of IFN- during genital tract Chlamydia muridarum infection is important in minimizing the genital tract pathology caused by the immune responses to chlamydial infection Benjamin C. Nick1, Faith Donner1, Ramesh Kumar2, and Wilbert A. Derbigny1* 1Department of Microbiology and Immunology; Marian University College of Osteopathic Medicine, Indianapolis, Indiana, United States of America 2Herman B Wells Center for Pediatric Research; Indiana University School of Medicine, Indianapolis, Indiana, United States of America BCN and FD are currently OMSII students and are equal contributors to this project INTRODUCTION Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted pathogen and is a significant threat to the reproductive health of women. With an estimated 2.8 million new infections domestically and 131 million new Ct infections acquired annually globally, chlamydia is costing health care systems billions of dollars to treat not only the acute infections but also the complications they cause. Ct genital tract infections are associated with cervicitis, urethritis, and endometritis; complications from chronic infections include pelvic inflammatory disease (PID) and its sequelae of chronic pelvic pain, ectopic pregnancy, and tubal infertility. Although treatable with antibiotics, individuals infected with Ct are often unaware of the infection, and the asymptomatic nature of the disease facilitates the spread of the bacterium through further sexual contact with uninfected individuals. As a result, Ct infections have continued to increase over the past two decades, despite the implementation of screening and early intervention strategies. OBJECTIVES Our long-term goal is to understand the pathophysiologic processes that contribute to Chlamydia-induced reproductive tract pathology. We are focused on identifying the inflammatory mediators that induce scarring of the oviduct epithelium and identifying therapeutic counter-measures that can prevent this. We were the first to demonstrate, and others have now confirmed, that TLR3 is a key pattern recognition receptor (PRR) in the immune response to Chlamydia muridarum (Cm) in mice. Controversy regarding the role of IFN- in Chlamydia pathogenesis: The exact role of IFN- and its contribution to the overall immune response to Chlamydia infection is unclear. Experiments conducted in mice defective in the interferon alpha-beta receptor (IFNAR) suggest that Type-1 IFNs are detrimental to the host in both the genital tract and lung infection models. In contrast, our data suggest a different role for IFN- in the context of TLR3-deficiency: Our preliminary data show that TLR3-deficiency results in defective IFN- synthesis, increased Chlamydia replication, and that oviduct epithelial (OE) cells derived from TLR3-/- mice exhibit significant reductions in the expression of several inflammatory cytokines and chemokines. Because the diminished C. muridarum-induced IFN- synthesis is one of the possible contributors that will make TLR3-/- mice more susceptible to Chlamydia-induced pathology, our contrasting findings suggest that IFN- is important for an effective immune response to Chlamydia infections and is thus beneficial to the host. METHODS To conclusively determine whether IFN- is either beneficial or detrimental to the host during genital tract Chlamydia infection, we examined the course of C. muridarum (Cm) infection in wild-type versus mice deficient in IFN- synthesis via the following methodology: 1.Vaginal sponges to determine the effect of IFN-s absence on cytokine secretion into the genital tracts of C. muridarum infected mice 2.Flow cytometry for analyzing the impact of IFN- on total T-cell populations in the genital tract of C. muridarum infected mice 3.Vaginal swabs to determine the effect of IFN-s absence on Chlamydia clearance 4.Gross and microscopic examination of genital tract tissue to determine oviduct pathology (with emphasis on hydrosalpinx, inflammatory induced damages, and oviduct dilatation). RESULTS IFN- deficiency dysregulates the Chlamydia-induced syntheses of multiple inflammatory mediators: We infected groups of 10 wild-type (C57BL/6NJ mice) and 10 IFN- KO mice intra-vaginally with 105 IFU Cm 7 days after treatment with Depo Provera, and we measured the syntheses of several cytokines in the first 20 days post-infection by multiplex ELISA (Fig 1). To confirm the multiplex data and to ascertain if the epithelial cells lining the lumen of the oviduct responded to in vitro Cm infection in a manner reflective of the in vivo findings, we isolated OE cells from WT and IFN- KO mice and infected the cells with 5 IFU/ cell Cm. As shown in Fig 2, the Cm-induced syntheses of IL-6 and CCL5 were both significantly lower in the supernatants of the IFN-(-) OE cells at 24hrs post-infection in our standard ELISA assays. Cm-induced IFN- synthesis has an impact on genital-tract T-cell populations: To examine the impact of IFN- on T-cell recruitment into the genital tract during Cm infection, five WT and five IFN- KO mice were infected intravaginally with 105 IFU Cm before being sacrificed at either day 7 or day 21 of infection and their lower genital tracts processed for flow cytometry. As shown in Fig 3, the percentage of CD4+ T-cells were lower in the genital tracts of Cm-infected IFN- KO mice at both day 7 and day 21; however, it was only statistically significant at day 7. The CD8+ T-cell percentages trended lower at both day 7 and day 21 in the IFN- KO mice as well; however, the amount lower at day 21 only was statistically significant. IFN- is required for more efficient clearance of Cm from the genital tracts of infected mice: We infected groups of 10 WT and 10 IFN- KO mice intra-vaginally infected with 105 IFU Cm 7 days after treatment with Depo Provera, and we examined the impact of IFN- deficiency signaling on chlamydial shedding. As shown in Fig 4, Cm was virtually eliminated by day 42 in the WT mice but was still detectable in the genital tracts of IFN- KO mice. Additionally, the IFN- KO mice shed significantly more Cm throughout infection than the wild-type mice. IFN- deficiency leads to more severe late-stage genital tract pathology: Groups of 10 WT and IFN- KO mice were intravaginally inoculated with 105 IFU Cm for qualitative histological evaluation of lesions in the lower and upper genital tract at day 56 of infection by microscopy and quantitatively scored by a pathologist on a 0-4 scale. Fig 5 shows a chart summarizing the histological changes that are related to IFN- deficiency. Collectively, these findings showed that IFN- deficiency can lead to more pronounced chronic sequelae, such as uterine horn dilatation and oviduct hydrosalpinx, during late stages of Cm genital tract infections in mice. Summary and Ongoing Studies: Our data show that IFN- has a host beneficial role in the immune response to genital tract Chlamydia infections, challenging the paradigm that type-1 IFN is detrimental established by other investigators. We are currently repeating in vitro experiments in OE cells to complete manuscripts and grant submissions. We are awaiting completion of a novel CRISPR KO mouse line that is defective in IFN expression to assess its role in genital tract Chlamydia infections ACKNOWLEDGEMENTS: NIH 1R01AI104944-01, IUSM CTSI Pilot grant; MUCOM FRD Grant #2102  ...

... Racial and Accessibility Disparities with Mechanical Thrombectomy Usage for Acute Ischemic Stroke Benjamin Abraham (M2-3)*1,2,3, Weston Troja (M4) 2,3, Jai Horsey (M1) 2, Johnathan Weyhenmeyer MD 2,3, Guang Xu PhD MPH 1, Bradley N. Bohnstedt MD 2,3 author 1Marian University College of Osteopathic Medicine 2Indiana University, School of Medicine 3Indiana University, Department of Neurological Surgery *presenting Background Transportation methods Counties transferred from Recent studies describe racial and socioeconomic (SES) disparities with mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Our study investigated whether such disparities are present at our institution and surrounding region. MT is the gold standard treatment for AIS. AIS comprises more than 80% of cases of stroke (another major category of stroke includes hemorrhagic). IUH Methodist sees patients transferred over from a variety of counties within the entire state of Indiana. Results From a total of 456 patients, the racial status of 394 patients was reported as White and 62 patients as nonWhite. All patients were diagnosed with AIS and underwent MT. Key findings are summarized below: - The racial disparity in stroke-onset-to-arrival time (p = 0.03) and arrival-to-puncture time (p < 0.0001) was resolved after adjusting for transfer status. - In multivariate analysis, shorter times for stroke-onset-to-arrival (p < 0.001), arrival-to-puncture (p = 0.03), and puncture-to-recanalization (p = 0.004) along with Thrombolysis in Cerebral Infarction scores 2b-3 (p = 0.03), younger age (0.009), and female sex (0.002) increased the likelihood of good neurological outcomes. - Diabetes mellitus (OR 0.45 CI 0.25-0.79, p= 0.006) and higher NIHSS admission scores (p = 0.02) decreased this likelihood. Stroke-onset-to-arrival time was an effect modifier of transfer status. Table 1. Hierarchical binomial logistic regression model for a good neurological outcome (mRS of 0-2) Before Addition of Effect Modifier OR (95% CI) p Value Figure 1. A detailed representation of which counties with 20+ patients Methods A retrospective cohort study of 456 patients was conducted at a single institution between January 1, 2017 to August 29, 2019. Patients were grouped based based on racial status. We compared demographics, clinical presentation, treatment characteristics, and outcomes. We utilized univariate analysis and multivariate logistical regression to adjust for confounders and effect modifiers, repspectively. were transferred from to IUH Methodist, located in Marion County. From the total 62 non-White patients, 21 were transferred from an outside hospital (OSH), indicating that most non-White patients were from Marion county. Contrastingly, 318 of the 394 White patients were transferred from an outside hospital, indicating that most of the White treated patients came from elsewhere. Interestingly, there were only three non-White patients that were transported by helicopter compared to 170 White patients. While racial status was not implicated in the difference between outcomes, transfer status was, and this may be an area of future research. Variable Age, per yr Race, non-White as reference Female sex HTN DM AFib Distance, mi Transferred from OSH Admission NIHSS score, per unit After Addition of Effect Modifier OR (95% CI) p Value 0.97 (0.95-0.99) 1.97 (0.88-4.45) 2.03 (1.23-3.33) 0.89 (0.48-1.64) 0.45 (0.26-0.80) 0.88 (0.51-1.52) 1.00 (0.99-1.01) 0.46 (0.21-1.00) 0.007 0.10 0.005 0.702 0.006 0.65 0.89 0.051 0.04 0.97 (0.95-0.99) 1.78 (0.77-4.11) 2.24 (1.33-3.75) 0.87 (0.467-1.64) 0.45 (0.25-0.79) 0.86 (0.50-1.50) 1.00 (0.99-1.01) 0.68 (0.30-1.55) 0.009 0.18 0.002 0.674 0.006 0.60 0.92 0.357 0.02 Arrival-to-puncture, mins 0.992 (0.986-0.998) 0.01 0.993 (0.987-0.999) 0.03 Puncture-to-recanalization, mins 0.988 (0.979-0.996) 0.006 0.987 (0.978-0.996) 0.004 3.17 (1.28-7.81) 0.01 2.80 (1.109-7.08) 0.03 TICI score 2b-3 Effect modifier was the stroke-onset-to-arrival time; p values are calculated with respect to mRS score of 0-2 as the outcome of interest. Conclusion Racial status was not associated with a difference in clinical presentation, treatment characteristics, nor outcomes. However, nuances in interhospital transportation seem to play a significant role and future studies should be aimed at those disparities in stroke accessibility.  ...

... Using Palliative Leaders In Facilities to Transform care for Alzheimers Disease (UPLIFT-AD) palliative care clinical trial in nursing homes 1,2Kathleen Unroe, MD, MHA, 3Arthur Equihua 1Regenstrief Institute - Indiana University, 2IU-Center for Aging Research, 3Marian University-COM ABSTRACT Nursing Homes (NH) often struggle to provide Palliative Care (PC) to their residents with Alzheimers and other Related Dementias (ADRDs). As a result, many NHs are searching for external PC consultants to help facilitate care within their facilities. Unfortunately, there are no clinical trials that provide examples of sustainable models of PC or their effectiveness in this population. Although, there is evidence that knowledge of or training in PC by NH staff can have benefits in patient care. The purpose of this study is to assess the effectiveness of the UPLIFT- PC implementation model in enhancing capacity of nursing homes to train in primary PC and improving the quality of life and quality of care for ADRD nursing home patients. TIMELINE The trial is currently on-going and will be implemented over a total of 36 months and include 740 residents in 16 diverse NHs in IN and MD. Palliative Care vs Hospice Palliative Care REPRODUCIBLE PALLIATIVE CARE IMPLEMENTATION STRATEGY FOR NURSING HOMES MANAGING DEMENTIA PATIENTS TRAINING IMPLEMENTATION ~8hrs PC Leads in-house Symptom management Disease management Managing scenarios involving patients with ADRD Hospice Eligibility Advanced care planning conversations with family Pre-implementation meetings with research team (tailored process) Establish relationship with external PC leads Meetings with families ASSESSMENT/REPORTING Regular reviews of PC staff Identification and tracking of patients within EHR Assessing progress of patient symptoms Meeting with families gauging efficacy Timing of Care any stage of illness Treatment approach Comfort and Disease treatment Hospice Timing of Care last 6 months of life Treatment approach Comfort care only Focus of Care = symptom management, quality of Life and honoring resident and family wishes Location = Any CONCLUSION The UPLIFT-AD intervention is a model of care for increasing access to palliative care services for nursing home residents, relying on a combination of internal capacity building and external specialty consultant support ACKOWLEDGEMENTS I thank Dr. Kathleen Unroe, Regenstrief Institute Indiana University, Maryland University and the UPLIFT Research team for providing me this great summer experience. This research is funded by National Institute of Health (NIH).  ...

... MUCOM Research Day Contact: Amanda Arand, MS Marian University COM 3200 Cold Spring Rd, Indianapolis, IN 46222 aarand145@marian.edu Osteopathic Medicine Supportive Care in Pediatric Oncology - A Pilot Study The authors have no conflict of interest. Authors: Amanda Arand, MS Joseph Stanek, MS Jennifer Belsky, DO, MS Affiliations: Marian University College of Osteopathic Medicine Division of Pediatrics, Indiana University College of Medicine Division of Pediatric Hematology Oncology, Riley Hospital for Children Nationwide Childrens Hospital Background: Research Design: Chemotherapeutic agents, such as vincristine, are well known antineoplastic and cytotoxic drugs, affecting patients broadly during treatment of cancer. Well known side effects, such as constipation and neuropathic pain, affect the quality of life of these patients recovering from cancer as well as its treatment. An option that alleviates troublesome side effects while still allowing the treatment to work would assist patients with wellbeing and comfort. This is a single institutional, randomized control trial, investigating patients aged 2 -21 years receiving chemotherapy for leukemia at Riley Childrens Hospital. Patients will be enrolled and sign informed consent after an explanation of OMT with a previously published script and education video. Subjects will then complete 4 weeks of consolidation during which all participants will utilize the standard of care (SOC) chemotherapy treatment. Osteopathic manipulative treatments (OMT) are often utilized for various ailments in both pediatric and adult populations. A previous pilot study investigated the safety and feasibility of OMT in pediatric oncology patients and reported no serious adverse events attributed to OMT intervention. We hypothesized that OMT intervention during cancer therapy will improve constipation and neuropathic pain for children with leukemia undergoing chemotherapy. During consolidation, no OMT treatments will be used, only home calendars and validated clinical reporting tools. Afterwards they will be randomized to either OMT plus standard of care, or standard of care alone, for a total of 4 OMT treatments during interim maintenance if on the former arm. Osteopathic treatments will include muscle energy, myofascial release, balanced ligamentous tension, visceral inhibition, and counterstain in a specific order, and last no longer than 20 minutes each at the Riley Outpatient Center. Feedback will be elicited with use of the FACES pain scale before and after each OMT treatment and the PedsQL3.0 measuring quality of life before OMT treatments. Objectives: The main objective of this study is to investigate the efficacy of osteopathic medicine on constipation and neuropathic pain as side effects of chemotherapy in pediatric oncology outpatient clinics. Throughout the entirety of the study, patients and caregivers will be given a calendar to record home as needed medication administration and a Bristol stool chart with which to track bowel movements in order to reduce recall bias. A qualitative interview for patients and caregivers will follow the final OMT treatment for patients randomized to the OMT arm. The interviews will be conducted independently. Conclusion/ Future Directions: The aim of the present study is to examine the direct association between OMT treatment and chemotherapy side effects of constipation and neuropathic pain in pediatric oncology patients through the Bristol stool chart and FACES scale. Results of this study will begin to answer the questions of which OMT work for specific chemotherapy induced side effects in children. Multicenter randomized trials of adequate sample size are needed to evaluate the efficacy of OMT in the treatment of chemotherapy induced side effects. Future studies should focus on utilizing OMT as an adjunctive supportive care option of pediatric patients.  ...