2022
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Item 3D TUMOR MODELING TO IMPROVE BIOMARKER IDENTIFICATION AND CANCER OUTCOMES.(2022) Mylabathula, Preteesh Leo; Ranade, Payal; Trivedi, Rucha; Vishwanatha, JamboorPurpose: Cancer-associated proteins annexina2 (ANXA2) and MIEN1 are overexpressed in various cancers including triple negative breast cancer, prostate, and colorectal cancers. Therefore, these proteins are being investigated as potential biomarkers and therapeutic targets. We will use a 3D tumor model to mimic in vivo tumor growth and evaluate changes in tumor characteristics after silencing ANXA2 and MIEN1 to understand their correlative/causal relation to tumor behavior. Methods: Ultra-low attachment 3D culture plates were used to culture tumor spheroids in breast cancer cells(MDA-MD-231) with ANXA2 knock-down using sh-RNA and colorectal cancer cells(HT29) with MIEN1 knock-out (KO) using CRISPR-Cas9. Changes in spheroid growth, migration and invasion, drug sensitivity, and immune cell killing will be evaluated. Boyden chambers with Matrigel inserts were used to evaluate migration and invasion. Spheroids were imaged using confocal microscopy for size estimation. Results: Optimal initial seeding density was 5000 cells and spheroids were grown for 7-days. Average tumor spheroid size was 1360±420µm with no differences in spheroid size with MIEN1 KO. 50% reduction in migration and invasion potential were observed after MIEN1 KO in colorectal cancer cells in a 96-hour time-course experiment. Experiments with ANXA2 knock-down are ongoing with spheroid sizes averaging 1700±260µm. Future experiments include evaluating changes in protein expression, drug sensitivity, immune cell killing as a result of knockout of MIEN1. Conclusion: We expect the results to identify functional role of cancer-associated proteins ANXA2 and MIEN1 in tumor spheroid growth, metastasis, drug sensitivity, and susceptibility to immune cell killing. Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA220273 (JKV).Item A case presenting the obstacles to accurate diagnosis of pediatric mental health disorders(2022) Shahub, Nur-Alhuda; Fatima, Fariya; Hafeez, RaheelaBackground: The diagnosis of psychiatric disorders in children presents unique obstacles, including parental perceptions of mental health disorders, failure of providers to address behavioral concerns, and limited report of symptoms due to limited history from child and caregivers. The most common mental health disorder diagnosed in children in the United States is ADHD, with the CDC estimating the national prevalence is 6.1 million in those aged 2-17 years. The importance of accurately diagnosing a mental health disorder can greatly impact a child's outcomes, including access to resources. Case information: A 9-year old African-American male presented for a follow up visit for ADHD at an outpatient clinic. Past medical history included ADD/ADHD, intellectual disability, and asthma. The patient had been diagnosed with ADHD combined type, with initial testing being performed at the office of a primary care provider five years previously. ADHD medication had been trialed with no improvement of symptoms. In addition, patient's symptoms (including hyperactivity, excessive verbal repetition, and difficulty concentrating) had been prevalent at home, but had not been demonstrated at school. Family history included paternal intellectual disability. Physical examination, focused on neurological exam, revealed no abnormalities. Despite the previous diagnosis of ADD/ADHD, the case warranted further workup due to presence of symptoms in only one setting, and co-diagnosis of intellectual disability. The patient was referred for further psychological testing in order to ensure that the correct diagnosis is made, and was connected to community resources. Conclusion: This case illustrates the unique presentation of mental health disorders in children, and the obstacles to appropriate diagnosis and treatment. This case also illustrates the importance of appropriately diagnosing mental health disorders when there are multiple diagnoses; despite the diagnosis of ASD and intellectual disability, it is possible the patient may have an entirely different disorder, such as Autism Spectrum Disorder, and full psychological evaluation is warranted.Item A Case Report of Selective Skip Laminectomies and Subsequent Catheter Irrigation of a Holospinal Epidural Abscess(2022) Doederlein, Alexander R.; Beeton, George; Loeffelholz, Zachary; Sandu, CezarBackground: Holospinal epidural abscesses (HEAs) are exceedingly rare, with less than 25 case reports of the condition found in the literature. Broad-spectrum antibiotics are virtually always indicated in its treatment upon its diagnosis, which is typically made via magnetic resonance imaging (MRI). Furthermore, if fulminant neurological deterioration presents, surgical debridement of the infection can help reduce the infectious burden and improve long-term outcomes. Access to the epidural space is attained via laminectomies; however, extensive laminectomies can destabilize the spine. Various case reports noted that selective laminectomies at particular vertebrae can avoid this destabilization, while still allowing catheter access to the length of the spinal cord. Case Information: Our patient was a 60-year-old male who presented with altered mental status, neck pain, and fever. He was diagnosed with methicillin-resistant Staphylococcus aureus meningitis and bacteremia. An MRI revealed an epidural abscess running from the cervical spine through the lumbar spine with concomitant compression of the spinal cord, as well as numerous paraspinal musculature abscesses and a retropharyngeal/prevertebral abscess. The patient was started on broad-spectrum IV antibiotics; however, his condition continued to deteriorate. The decision was made to perform a surgical debridement. Laminectomies were performed at vertebrae T4 and T10, and catheters were then run cranially and caudally through these points to access the length of the spinal canal. The purulent material was aspirated, and an antibiotic solution was then used to irrigate the epidural space; meanwhile, the patient was cycled between Trendelenburg and Reverse Trendelenburg positions to facilitate drainage of the purulent material. Following the procedure, the patient's neurological status started to improve. He was kept on vancomycin postoperatively until his elevated inflammatory markers resolved. The patient recovered fully, and at three months follow-up had no neurological deficits. Conclusions: This surgical technique is an effective way to identify the inciting organism in a HEA, reduce the infectious burden, decompress the spinal cord, minimize surgical time and blood loss, and maintain stability of the spine without the use of instrumentation.Item A Case Report of Situs Invertus Totalis and Polycystic Kidney Disease in a Newborn(2022) McCullough, JasonBackground: Situs Inversus Totalis is a rare disorder in which the internal organs are reflected laterally. The prevalence of Situs Inversus Totalis is 1 in 10,000 live births. Children born with Situs Inversus Totalis can go on to live normal lives if no other conditions are present. Polycystic Kidney Disease (PKD) has multiple patterns of inheritance. PKD has been reported to follow autosomal dominant, autosomal recessive, and X-linked patterns of inheritance. Autosomal Recessive Polycystic Kidney Disease (ARPKD), which used to be called infantile PKD, has a prevalence of 1 in 20,000 individuals. ARPKD has a low life expectancy with 1 in 3 infants dying within the first month of life due to breathing problems, and 9 out of 10 infants who make it past the first month will die before the age of five. Situs Inversus Totalis and ARPKD are not directly linked, but both been associated to primary ciliary dyskinesia which could lead to both disorders occurring in the same infant. Case Information: A newborn child was diagnosed with Situs Inversus Totalis and ARPKD soon after being delivered. The mother was informed during the pregnancy that there was a risk of some abnormalities during prenatal screenings. Family history was not fully obtained due to the father of the child being a sperm donor. The newborn did not experience any symptoms from the Situs Inversus Totalis, but experienced problems associated with ARPKD, such as underdeveloped lungs. The newborn was monitored in the NICU to ensure symptoms could be treated appropriately. After symptoms had resolved, the mother and child were both discharged and returned home and told to follow routine newborn visits. There are currently no cures for ARKPD, but if the child becomes eligible, a kidney transplant could provide an improvement to the child's condition. Conclusion: Situs Inversus Totalis and ARPKD have been associated with primary ciliary dyskinesia but have not been shown to be directly linked together, but this association could provide insight into the condition of this patient. ARPKD is also linked to mutations in the PHKD1 gene but requires inheritance from both parents to be present. Since ARPKD is found in the infant, it can be inferred that both parents would be carriers if this was the cause, instead of the primary ciliary dyskinesia. As previously mentioned, the father's medical history was not obtained. However, in other families, genetic testing can be conducted to determine risk of certain hereditary diseases such as ARPKD. In cases where genetic testing was not conducted, prenatal screenings can be used to determine if any abnormalities are present. Parents should be aware if certain disorders run in their family and should talk to their physician to see if genetic testing or prenatal screenings are necessary. Treatment options for ARPKD are still being explored but further research can develop solutions to increase life expectancy of newborns diagnosed with ARPKD. Cases like this are rare but could provide more information on causes of ARPKD and Situs Inversus Totalis leading to these new solutions.Item A Case Series of Atypical Back Pain in Pediatric Athletes(2022) Ali, Arsalan; Jacobs, Benjamin; Gandhi, Artee; Brooks, MeredithBackground: Baastrup's disease is a rare, often misdiagnosed, cause of back pain in children. It is characterized by degenerative changes of both spinous processes and interspinous soft tissues between two adjacent vertebrae. Repetitive spinal movements in the sagittal plane predispose to injury of the posterior elements of the spine. Chronic flexion and extension strain the interspinous ligament causing the neighboring spinous processes to adjoin. Pain is aggravated by extension and palpation and is alleviated with flexion. Some children with Baastrup's do not experience pain but present with swelling along the spinous processes. Moreover, increased interspinous spaces and bone remodeling may also be seen. Diagnosis is dependent on distinctive radiologic findings and characteristic exam features. This is the first report of children undergoing interventional modalities for the treatment of Baastrup's disease. Case Information: The first case study is a 16-year-old active gymnast who initially presented to the clinic in 2014 with complaints of a sore back that worsened with extension and arching. On physical exam, there were trigger points along her thoracic spinous processes. Diagnostic imaging revealed early suspicion for spinous process abnormality at the thoracolumbar junction region vertebra, particularly T12. A conservative treatment approach was initially taken however her symptoms did not resolve. The patient ultimately underwent bilateral T11, T12, L1 medial branch blocks. The second case is an 18-year-old female cheerleader and gymnast who initially presented to the clinic in 2016 complaining of one year duration of back pain that started after doing tumbling exercises in gymnastics. After multiple visits and imaging modalities, a working diagnosis of Baastrup's disease was suspected. The patient was treated with four trigger point injections in her interspinous ligament that were done at different times. Conclusion: While the current treatment for pain associated with Baastrup's is directed towards physical therapy, massage therapy, nonsteroidal anti-inflammatory medications, muscle relaxants and rest from activity, this is the first report of children undergoing interventional modalities for the treatment of back pain associated with Baastrup's disease. The epidemiology of the disease is very rare in the pediatric population, however, certain active groups such as gymnasts can be at an increased risk due to repeated spinal extension and flexion movements.Item A Comparison of Certain Pediatric Vaccination Rates in Fort Worth, TX Due to the COVID-19 Pandemic(2022) Asfoor, Naser; Fernando, Shane; Fairchild, AshlynPurpose: The COVID-19 pandemic is a prime example of how a disease can fundamentally affect daily living on a global scale. Vaccines are one of the most important preventive methods healthcare providers use to combat disease. This study compares certain pediatric vaccination rates from before and after the COVID-19 pandemic in an outpatient clinic. Methods: Data was obtained from the Electronic Health Record of patients at the University of North Texas Health Science Center (UNTHSC) Pediatrics and Women's Health Clinic in Fort Worth for a three-year period from 2019-2021. ICD-10 codes for immunization were used for analysis of data. Frequencies of vaccination were assessed in patients seen on or after March 18, 2020 and patients seen on or before March 17, 2020 as these dates correspond with the transition of patient interaction from in-person to virtual clinic visits. Bivariate analysis using t-test was used to assess for change in immunization rates for Hepatitis A, Diphtheria, and Influenza vaccines. Results: Among 9520 patients, 51.3% were White, 22.2% were Black or African American. 35.7% were Hispanic or Latino. Mean age was 8.03±5.75, while 49% of subjects were female. The vaccine counts Pre-Pandemic (March 2019 to October 2019) and Post-Pandemic (March 2020 to October 2020) were compared. Results were statistically non-significant in Hepatitis A, t = -0.71, p = 0.504; Diphtheria, t = 2.3, p = 0.054; and Influenza, t = 0.87, p = 0.413. Conclusion: Results from this study suggest that vaccinations for Hepatitis A, Diphtheria, and Influenza were not statistically significant when comparing pre-pandemic versus post-pandemic vaccination counts. This could also be due to a quick re-opening after initial lockdown measures and increased administration of vaccines to compensate for delayed immunizations from clinic closures. By increasing use and training of telehealth, clinics can adjust to future pandemic measures more efficiently and prevent a lull in pediatric immunizations.Item A Country-level Comparative Study on Knowledge, Perception and Readiness towards Drone-based Dengue Surveillance System(2022) Annan, Esther; Guo, Jinghui; Haque, UbydulDrone use in the health sector may serve the purpose of surveillance and monitoring of Aedes mosquitoes. However community concerns about drone use around homes may potentially affect the effectiveness of a drone surveillance program. This study aimed to address the gap in knowledge, readiness and perception about how individuals may respond to drone use for rapid alert systems. A cross-sectional study was conducted in three countries; Mexico, Turkey, and Malaysia and data were analyzed using SAS, Python, and R. Comparisons were made within and across countries and tested for statistical significance.The survey comprised of 1,826 participants, in Malaysia (619), Mexico (605), and Turkey (602). Of the three countries, Turkey had the lowest knowledge scores about mosquito-borne diseases. Compared to individuals living in Turkey, people living in Mexico had 14.3 (p< 0.0001) times higher odds and Malaysians had 4.0 (p = 0.7030) times the odds of being willing to download a mosquito surveillance app. About 75%, 78% and 32% of residents in rural Mexico, Turkey and Malaysia respectively, expressed no concern for the use of drones around homes for surveillance purposes. An individual's willingness to be trained and acceptance of drone use in mosquito-endemic countries may help to further discussions and application of mosquito surveillance using drones. Privacy concerns may be addressed through the enforcement of drone regulatory standards.Item A Drug-Loaded Nanoparticle to Target Bone-Metastatic Prostate Cancer(2022) Lampe, Jana B.; Desai, Priyanka; Tripathi, Amit K.; Ranjan, Amalendu; Vishwanatha, JamboorTreatment for localized prostate cancer (PCa) has a tremendous success rate. However, the fact that the five-year overall survival rate drops from 100% to 30.2% when tumor cells metastasize to distant sites, represents an unmet medical need. In 90% of metastatic cases, bone is the primary metastatic site. Our objective is to co-load a poly(lactic-co-glycolic) (PLGA) nanoparticle (NP) with Cabazitaxel (CBZ) and Bortezomib (BTZ) and to conjugate a bone-targeting moiety, Alendronate (ALN), to the outside of the nanoparticle to facilitate targeting to bone tumors and to ameliorate the resulting bone damage. We hypothesize that this targeted nanomedicine will affect genes and proteins that contribute to invasion and migration, anti-apoptotic signaling, and ultimately lead to tumor-cell apoptosis. Furthermore, we predict that the nano-delivery system will help ameliorate bone lesions inflicted by the tumors. Methods: Nanoparticles were engineered using an Emulsion-Diffusion-Evaporation Technique in which PLGA is dissolved in dichloromethane, 5% polyvinyl alcohol, and Bis(sulfosuccinimydyl)suberate (BS3) crosslinker. For targeting, Alendronate (ALN) is later conjugated to the outside of the nanoparticle via this crosslinker. Results: Our average NP size was around 240 nm in diameter, a PDI of < 0.2, with a Zeta Potential (ZP) of -28 mV. Our drug loading capacity (DL) for CBZ was 11.97% and for BTZ 0.9%. Encapsulation efficiency (EE) for CBZ was 25.26% and 8.9% for BTZ. The IC50 for the CBZ NPs is 5.6 nM and BTZ NPs is 15.6 nM. We have successfully shown that the gene expression for various migration and invasion markers as well as cell signaling proteins have been affected by the nanoparticles. Conclusions: Our nanoparticles have a desirable size, PDI, ZP, DL, and EE for our intended therapeutic purpose. Furthermore, we have shown alterations in the cell signaling and gene expression responsible for Epithelial-to-Mesenchymal Transition-Transcription Factors (EMT-TFs), indicating that our nanotherapeutic has significant potential to treat metastatic PCa and to mitigate the damage done by metastatic tumors.Item A Giant Ovarian Mucinous Cystadenoma and Low-Grade Appendiceal Mucinous Neoplasm in a Post-Menopausal Woman(2022) Aguirre, Brian; Bartels, HollisBackground: Ovarian mucinous cystadenomas are benign cystic tumors which originate from the surface epithelium of the ovary and rarely present during late age. Low grade appendiceal neoplasms (LAMN) are some of the rarest appendiceal tumors and only make up 0.7-1.7% of appendiceal tumor cases. Case Presentation: A 61-year-old woman was referred to the clinic due to a large abdominopelvic mass and complaints of abdominal pain, shortness of breath, and post-menopausal bleeding. She was a multiparous woman (G4P5), 160.02 cm, 121.109 kg and has a BMI of 47.4 kg/m2. She had a history of hypertension, and a previous history of spinal tumor surgery. Imaging studies were significant for a 37 x 27 x 28 cm cystic mass originating from the left adnexa and smaller cysts originating from the right adnexa. Pap smear and endometrial biopsy were negative. Laboratory studies included CA125, CA19-9, and CEA. Those were found to be 11 U/mL (normal < 35 U/mL), 174 U/mL (normal < 34 U/mL), and 0.6 ng/mL (normal < 2.5 ng/mL in an adult nonsmoker) respectively. Given the large size of the masses and elevated CA 19-9, the patient was referred to gynecological oncology for further assessment. After consideration of the imaging, labs, and patient's symptoms, the treatment plan suggested was a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) to remove the masses. During the TAHBSO, an incidental appendiceal mass was noted and an appendectomy was performed. The gross pathology report revealed that the adnexal masses were bilateral mucinous cystadenomas, and the appendiceal mass was a LAMN. The uterus with the cystic ovaries were found to weigh 11.3 kg and measure 45 x 40 x 30 cm. The large cyst measured 42 cm and the smaller cyst measured 7 cm. The appendix measured 4.5 x 0.7 x 0.7 cm with the LAMN measuring 1.5 cm. The LAMN involved the muscular wall, and the margins were negative. Accordingly, no further treatment was necessary. Conclusion: This case report brings forth a unique case of 61-year-old patient who presented with bilateral mucinous cystadenomas and a LAMN. Mucinous cystadenomas themselves comprise about 15% of ovarian tumors and LAMN make up less than 2% of appendiceal cancers.Item A Leak From Within: A Case Report on Flood Syndrome(2022) Srivastava, KumaramanFlood syndrome is a very rare complication that can be found in patients with end-stage liver cirrhosis with concurrent ventral hernias. If the hernia ruptures, ascites can begin to leak uncontrollably from the opening which can become a nidus for infection if left untreated. This scenario is known as Flood syndrome, which was first described by Frank Flood in 1961. Flood syndrome is very difficult to manage for physicians as these patients are poor candidates for surgery but the ascitic leak will continue without surgical intervention. Currently, there is no standard of care for Flood syndrome. A 66-year-old Caucasian male with a past medical history of NASH cirrhosis, type 2 diabetes, COPD, umbilical hernia, and CAD presented with a sudden burst of ascitic fluid after his umbilical hernia spontaneously ruptured with no inciting event or trauma. The ascites had been progressively getting worse since the patient underwent his last therapeutic paracentesis (two weeks prior to admission) which drained 12.5 liters. Empiric antibiotics were started due to increased risk of bacterial peritonitis. IV albumin was also given to maintain oncotic pressure and prevent "third-spacing". Of note, patient was not given any additional fluids due to his hyponatremic state. General surgery and hepatology was consulted and recommended a binder with gauze changes as necessary since patient was a very poor candidate for surgery with a MELD score of 26. MELD scores are an excellent predictor of morbidity and mortality for patients with end-stage liver disease. After the patient was admitted, an attempt was made to control the ascitic leak via a pursestring suture. The patient's abdomen was prepped and draped in the standard sterile fashion. Lidocaine was used to anesthetize the skin of his umbilicus. There was about 2 cm diameter of gangrenous area with a hole leaking ascites in the middle. A pursestring suture of 3-0 chromic gut absorbable suture was placed around the defect to tightly close the wound. The patient tolerated the procedure well. There was no leak detected with the Valsalva maneuver after the placement of the pursestring. Two days later, however, the pursestring failed and the ascites began to leak again around the pursestring through the previously existing defect. Six days later, the patient was transferred to palliative care and later discharged despite the continued ascitic leak since he was not a transplant candidate or a candidate for surgery per surgery and hepatology. Patient was advised to continue weekly therapeutic paracenteses to manage the ascitic leak. The patient presented again twelve days later due to abdominal pain from a loop of small bowel being incarcerated and strangulated at the umbilical hernia. Despite being a poor surgical candidate, the patient and his wife agreed to undergo an umbilical hernia repair with mesh and small bowel resection due to the emergent nature of his case. The surgery was performed successfully and the patient was discharged from the hospital eleven days later in stable condition.Item A Monoallelic DNM1L Mutation presenting with Epilepsia Partialis Continua: A Case Report(2022) Park, ChanhyunBackground: Variants in DNM1L are reported as a rare cause of refractory epilepsy and status epilepticus. We report a patient with epilepsia partialis continua (EPC) secondary to a monoallelic DNM1L mutation. Case Information: An 11-year-old boy with prior history of speech delay and well-controlled absence epilepsy on valproate presented in clinic with status epilepticus and posterior frontal diffusion restriction on MRI. Seizures were characterized by hemifacial clonus consistent with EPC. Extensive workup including EEG, MRI, cytokine, and encephalitis panels were unrevealing for etiology. Genetic peroxisomal panel revealed a monoallelic missense mutation (R403C) in the DNM1L locus as cause for his EPC. GDF15 was also elevated, reaffirming the presence of mitochondrial disease. This DNM1L mutation was determined to be the underlying etiology for his presentation. Lacosamide, clobazam and phenobarbital, among other interventions, were ultimately used to control the patient's epilepsy; he was sent home after extensive stays in the PICU and inpatient rehabilitation unit. Conclusions: DNM1L mutations can cause cerebral dysmyelinations, abnormal gyral patterns, microcephaly, and death within the first year of life. Yet several recent cases, including ours, have linked DNM1L variants with other neurological phenotypes, including a late onset of symptoms such as intractable epilepsy, myoclonus, and developmental delay. This case is strikingly like that of a previous report but with additional clinical features such as aphasia and EPC. The presentation of EPC in our patient, as well as the difficulty finding its etiology, exemplifies the unclear clinical pattern that remains with DNM1L mutations. The clinical ambiguity of this mutation complicates diagnosis and demonstrates the importance of prompt genetic testing.Item A NEW ERA: TARGETED THERAPY FOR RECURRENT GLOMUS TUMOR(2022) Faisal, Annum; Ray, AnishBackground: Glomus tumors (GT) are rare, vascular, benign soft tissue neoplasms that are composed of cells resembling modified smooth muscle originating from glomus bodies. Glomus bodies are specialized forms of arteriovenous anastomosis found in the reticular dermis that serve as thermoregulators. These glomus bodies are highly concentrated in the hands and feet, and thus, GT typically present as solitary lesions in the subungual region but may also occur elsewhere in the skin and soft tissues. Classically, GT are diagnosed with the following triad of symptoms: focal tenderness, spontaneous pain, and temperature sensitivity. Total surgical excision remains the mainstay of treatment. Here, we describe an atypical case of multifocal GT resistant to surgical excision and discuss alternative treatment modalities for recurrent cases in a pediatric patient. The treatment of recurrent GT remains a challenge due to lack of literature supporting alternative options. Management is especially difficult following a series of failed surgical excisions. Our objective is to explore the efficacy of non-surgical targeted-therapy treatment for recurrent GT based upon molecular genetic findings. Case Information: A 16-year-old female with a history of multifocal GT status post prior extensive removal through medial and lateral incisions in 2012, 2013, and 2015 presented back in 2021 with significant pain and swelling of the right lower extremity. History and PET Scan imaging confirmed extensive recurrence where the prior neoplasms had been present. Specifically, PET Scan demonstrated multifocal uptake within numerous masses in the right calf and ankle. Molecular genetic testing of GT in this patient revealed genomic changes in the platelet-derived growth factor receptor gene (PDGFRβ- R561_E563>Q). This gene transcribes platelet-derived growth factor receptor beta (PDGFRβ), which is part of a family of proteins called receptor tyrosine kinases. Accordingly, the patient started Sunitinib, a multi-receptor tyrosine kinase inhibitor which decreases phosphorylation of PDGFRβ and subsequently inhibits proliferation and survivability. Initially, treatment was intermittently held due to side effects of syncope, rash and plantar erythrodysesthesia. Nevertheless, as a result of improvements in pain and size of the tumors, she resumed treatment at a lower dose. Following trials of two dose reductions, she tolerated the medication well with resolution of side effects. The patient continued to note a decrease in the size of her GT, confirmed by imaging and her ability to return to work successfully. Conclusions: This case highlights the insufficiency in current mainstay treatment options of GT with surgical excision. Our findings emphasize the significance of incorporating molecular genetic testing into the treatment and management of recurrent GT to prevent disease relapse. Further research into alternative gene therapies is warranted.Item A Novel Approach for Stent Removal After Migration(2022) Sahu, Shweta; Roberts, JayBackground: Bariatric surgeries, including Roux-en-Y gastric bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch, are becoming increasingly prevalent in not only the US, but in the world as a whole. Though rare, complications after bariatric surgery can occur, with the most feared complication being gastric/ anastamotic leaks. One well known, safe and efficacious treatment of these leaks includes the placement of self-expandable metal stents (SEMS). Unfortunately, these SEMS have been known to move to a location other than where they were originally placed, a phenomenon known as "stent migration." Case Presentation: A 33-year-old Caucasian female with morbid obesity presented to clinic to pursue Roux-en-Y gastric bypass surgery after numerous failed attempts to lose weight. Though she was asymptomatic at the time, the patient elected to pursue the surgical weight loss management option after a trial of medical treatment for obesity, in which she was unable to maintain the weight loss for an extended period of time. This, in conjunction with her growing risk of medical comorbidities associated with her pre-existing morbid obesity, determined the management with laparoscopic Roux-en-Y gastric bypass, which proceeded with no complications during the time of surgery. Nine months later, the patient presented with dysphagia and epigastric pain, which prompted the need for esophagogastroduodenoscopy (EGD) which revealed erosive gastritis and a large marginal ulcer traversing the anastomosis. Though the patient tolerated robotic revision of the gastrojejunostomy (GJ) well, she developed another gastric perforation that required placement of a 12mm x 24 mm SEMS in order to close the leak at the GJ anastomosis. The patient presented to clinic with discomfort yet again, and this time, imaging revealed the stent had migrated distally, and was located just proximal to the jejunostomy. A typical endoscope (approximately 2.5 feet in length) is not sufficiently long enough to reach this area, and thus a unique 2 surgeon approach was taken to retrieve the migrated stent using a colonoscope, typically 5 feet in length. Conclusion: This case illustrates an innovative approach to removing a distally migrated stent, a known complication of endoscopic stent placement in the management of gastric/ anastamotic leaks after bariatric surgery.Item A Novel Method to Characterize Invasive Ductal Carcinoma Tumor Biopsies Using Contact Angle Measurements(2022) Rincon, Julio; Mishra, Ina; Kastellorizios, MichailPurpose: The goal of this work is to develop a preclinical method to characterize human breast cancer biopsies of different racial origin. Contact angle measurements are used to assess the biopsies' surface properties and examine possible correlation with race/ethnicity, tumor type, and cancer grade. This method enables us to study differences in interaction of drugs directly in tumor tissues based on available covariate data of the obtained samples. Here, we present a study of 80 invasive ductal carcinoma tumor samples compared against their matching normal and/or cancer adjacent tissues. Methods: To obtain contact angles of tumor tissues, we developed a contact angle instrument capable of delivering a ~45 nL drop on top of a 1.5 mm biopsy using a modified goniometer with added custom components (DataPhysics Instruments USA Corp.). The system allows us to measure contact angles from 3 different positions (0°, -45°, 90°), and viewing the tumor tissue through an inverted microscope to determine drop position and quality. For this study, breast cancer tissues were obtained as tumor micro arrays (TMA) and as FFPE tissues with matching normal adjacent tissue. For TMA slides, two drops per tissue were delivered and the test was repeated with a subsequent section of the same TMA, unless the TMA included duplicate cores. For FFPE samples, tissues were processed with a microtome at a thickness of 15 µm, a minimum of 6 drops were delivered per tissue. Results: Aggregated data showed normal adjacent tissue (NAT) had an average contact angle (CA) of 51.4° ± 6.5° n=19, cancer adjacent tissue (CAT) had an average CA of 62.8° ± 8° n=59, grade 1 tumors had an average CA of 71.1° ± 7° n=13, grade 2 tumors had an average CA of 67.4 ± 9.1° n=49, and grade 3 tumors had an average CA of 64.6° ± 10.3° n=11. When comparing normal adjacent tissue against any other tissue, p-values ≤ 0.05 and power ≥ 0.80 were observed. When comparing cancer adjacent tissue, only CAT vs NAT and CAT vs grade 2 tumors had p-values ≤ 0.05 and power ≥ 0.80. Individually, 37 cases reached p-values ≤ 0.05 and power ≥ 0.80, were tumor tissue showed contact angles greater than their NAT or CAT. An additional 7 cases met p-values ≤ 0.05 and power ≥ 0.80, however, tumor contact angles were lower than their NAT or CAT. Finally, ignoring type 2 errors, then an additional 11 cases reached p-values ≤ 0.05. Conclusions: Higher contact angles of deionized water were observed in tumor tissues when compared to matching normal or cancer adjacent tissue. It is clear that breast cancer tumors exhibit surface energy differences from normal adjacent tissues, with cancer tissue being more hydrophobic compared to normal tissue. Future work includes the determination of contact angles of Doxil-like liposomes in these tumors and the determination of surface energy of the tissues.Item A Rare Case of Multiple Sclerosis in a Pediatric Patient(2022) Akhtar, Rukaiya; Bui, Priya; Garcia, JoannaBackground: Multiple sclerosis (MS) is an immune-mediated, inflammatory disease primarily affecting the central nervous system (CNS). It is characterized by demyelination and axonal loss, and results from a combination of environmental and genetic factors. While rare, MS can develop in pediatric patients. Diagnosis of MS in pediatric patients can be very difficult as signs and symptoms appear differently in individuals and because it can mimic other diseases, such as acute disseminated encephalomyelitis (ADEM). Case Presentation: The patient is a 5-year-old female who began experiencing symptoms around 3 years old. In March 2020, she presented to the ER with unsteady gait, abnormal behavior, and decreased appetite. Upon completing a lumbar puncture and getting a brain MRI, she was initially diagnosed with ADEM. In the coming months, she was admitted to the ER two more times - once in May and again in June 2020. Each time she presented with different neurological symptoms. During her admission in June, brain imaging taken confirmed lesions consistent with MS and she was diagnosed with MS. Conclusion: Both ADEM and MS are inflammatory disorders of CNS characterized by demyelination. Distinguishing between the two diseases can be challenging as initial signs and symptoms, as well as imaging can look very similar. However, knowing key differences can help in establishing a proper diagnosis. Current treatment strategies include high dose corticosteroids for acute attacks, and disease modifying therapies for long-term treatment. Understanding how MS differs from similar diseases and how pediatric MS varies from adult MS is critical for proper diagnosis and treatment. Furthermore, while there is increasing recognition of pediatric MS, there is a need for more research and literature in this field to raise awareness and better diagnose, treat, and manage this disease.Item A Retrospective Chart Review of COVID-19 Infection and Pregnancy Outcomes(2022) Seale, Aimee; O'Neal, Morgan; Winn, AndiPurpose: Investigating possible effects, outcomes, and complications of the novel COVID-19 virus and related treatments during pregnancy is imperative to maintain proper care for women throughout pregnancy and postpartum. The COVID-19 pandemic has posed new challenges for physicians caring for patients during and after pregnancy. The aim of this study performed at UNTHSC Obstetrics and Gynecology clinic was to evaluate the effects of COVID-19 disease on pregnancy outcomes. Methods: This retrospective chart review included 43 patients who tested positive for COVID-19 during pregnancy. All patients delivered between November 2020 to August 2021. Patient demographics and delivery outcomes were collected from the electronic medical record. Demographic data included gestational age at diagnosis, severity of disease, incidence of outcomes such as preterm birth (PTB), preeclampsia (PEC), birth weight, method of delivery, and gestational diabetes (GDM). Following data collection, Texas statistics were gathered to compare incidence of these outcomes following COVID-19 diagnosis to the incidence in the general Texas population. Results: Data analysis found incidence of the most significant outcomes following data collection. Notably all patients presented with mild disease. When compared to Texas statistics, the incidence of low-risk cesarean section (28.40% Texas, 37.21% UNTHSC), gestational hypertension (8.90% Texas, 13.95% UNTHSC), and GDM (6.40% Texas, 6.98% UNTHSC) were comparable. Results for PEC (5% US, 4.65% UNTHSC) were compared to United States average rather to Texas average due to inconsistency in state specific data, and the outcomes remained comparable. Outcome for low birth weight (8.40% Texas, 2.33% UNTHSC) and PTB (10.80% Texas, 4.89% UNTHSC) were the outlier data points as these did not match closely with Texas statistics. Conclusion: This study was limited by small sample size. Further research is still warranted to evaluate the spectrum of effects of COVID-19 infection on pregnancy outcomes. Results from this study revealed incidence of the most common and severe complications associated with COVID-19 infection in pregnancy were not significantly increased from the general population when compared to published state data.Item A sensitive LC-MS/MS method to quantitate nitrite in human plasma(2022) Wang, Jianmei; Hemingway, Holden; Coyle, Donna; Romero, StevenPurpose: Numerous methods are available to quantitate nitrite in biological samples, including fluorescence, chemi-luminescence, capillary electrophoresis, colorimetric and ultraviolet (UV) spectrophotometry and gas chromatography-mass spectrometry (GC-MS). However, limitations associated with these techniques (e.g., lack of specificity, low sensitivity, etc.) prompted us to develop a LC-MS/MS method to quantitate nitrite in biological samples. Methods: We compared two derivatization methods which are used to convert the endogenous nitrite to a more stable organic compound that is able to be analyzed by LC-MS/MS. The first S-nitrosoglutathione (GSNO)-based method was performed by selected-reaction monitoring specific mass transition m/z 337 ([M+H]+)→m/z 307 ([M+H-14NO]+•) for GS14NO and GS15NO as internal standard (IS) by reaction of nitrite and glutathione (GSH). The second 2,3-naphthotriazole (NAT)-based method was performed by measuring NAT m/z 170 ([M+H]+)→m/z 115 ([C9H7+] and NAT-N15 as IS following the reaction of 2,3-diaminonaphthalene (DAN) with nitrite to produce NAT. We found that the latter NAT-based derivatization method is reproducible, stable, and 100 times more sensitive than the GSNO method. In addition, we validated the NAT-based method for precision and accuracy, recovery, stability and derivatization time and temperature. We then utilized the optimized method to quantitate nitrite in human plasma. Results: We found that nitrite stability in human plasma filtrate can be affected by freeze-thaw cycles and storage temperature which were evidenced by a decrease in nitrite levels over 50% after 24 hours at -20°C. However, the derivatized and extracted samples were stable for 24 hours at room temperature. When derivatization is fully complete and performed at 370C and 45 minute incubation, the recovery is 108%. The precision and accuracy are 15%, and 106%, respectively. The linearity range is 0.13-16 µM with linear regression, 1/x weighing correlation coefficients = (r), R2>0.9990. The same amount of labeled isotope as IS was added to each sample to keep track of signal fluctuation between study samples, In doing so, it was confirmed that the quantitation of endogenous nitrite was indeed affected by individual complex sample content. And the use of isotope-labeled nitrite reduced the impact of high background levels of nitrite in biological matrices, which other methods cannot achieve. Conclusion: We have developed and validated a reproducible and highly sensitive LC-MS/MS method for quantitation of nitrite in biological samples. In addition, we anticipate that our method can be utilized in other fluidic human biological samples.Item Acute Heat Exposure Improves Microvascular Function in Skeletal Muscle of Aged Humans(2022) Richey, Rauchelle; Hemingway, Holden; Moore, Amy; Yurvati, Albert; Romero, StevenAcute heat exposure improves microvascular function in the leg of aged adults as assessed using post-occlusive reactive hyperemia. However, reactive hyperemia measures whole-limb blood flow and cannot isolate perfusion among various tissues. Thus, it is unclear if the skeletal muscle circulation contributes to the improvement in microvascular function observed following acute heat exposure. We tested the hypothesis that acute hot water immersion would improve microvascular function in the vastus lateralis of aged adults. Seven aged adults (1 man, 71 ± 4 yrs) were immersed to the umbilicus for 60 min in thermoneutral (36 °C) or hot (40 °C) water. Body core temperature was measured via a telemetric pill. Two microdialysis probes were placed in the vastus lateralis ~30 min after immersion. Microdialysis was utilized to bypass the cutaneous circulation and directly assess endothelial-dependent and endothelial-independent microvascular function in skeletal muscle by measuring the local blood flow response to a graded infusion of acetylcholine (ACh, 27.5 and 55.0 mM) and sodium nitroprusside (SNP, 21 and 42 mM), respectively. Local blood flow was measured using the ethanol washout technique. Body core temperature increased by Δ1.1 ± 0.3 °C during hot water immersion but was relatively unchanged during thermoneutral immersion (Δ0.1 ± 0.3 °C). Baseline skeletal muscle blood flow did not differ between thermal conditions for the ACh probe (P = 0.9), nor the SNP probe (P = 0.7). The hyperemic response to 27.5 mM ACh did not differ between thermal conditions (thermoneutral immersion, Δ11.3 ± 11.5 ml/min/100g vs. hot water immersion, Δ18.6 ± 16.8 ml/min/100g; P = 0.7). However, the hyperemic response to 55.0 mM ACh was increased with prior hot water immersion (thermoneutral immersion, Δ30.7 ± 16.9 ml/min/100g vs. hot water immersion, Δ56.2 ± 19.7 ml/min/100g; P < 0.01). Similarly, the hyperemic response to 21 mM SNP did not differ between thermal conditions (thermoneutral immersion, Δ16.9 ± 16.8 ml/min/100g vs. hot water immersion, Δ18.2 ± 18.8 ml/min/100g; P = 0.9), but was increased with prior hot water immersion during the infusion of 42 mM SNP (thermoneutral immersion, Δ29.3 ± 14.4 ml/min/100g vs. hot water immersion, Δ58.5 ± 31.2 ml/min/100g; P = 0.02). These data suggest that acute heat exposure improves endothelial-dependent and endothelial-independent microvasculature function in skeletal muscle of aged humans. Furthermore, these data highlight the therapeutic potential of heat therapy to attenuate the hypoperfusion of skeletal muscle that occurs in aged adults during conditions that require an elevated blood supply such as exercise.Item Acute Heat Exposure Protects Against Endothelial Ischemia-reperfusion Injury in Aged Humans(2022) Hemingway, Holden W.; Richey, Rauchelle; Moore, Amy; Yurvati, Albert; Romero, StevenNon-pharmacological therapies that protect against endothelial ischemia-reperfusion injury (I/R) remain limited in aged adults. Acute heat exposure protects against endothelial I/R injury in young adults, but its efficacy has never been explored in aged adults. Therefore, we tested the hypothesis that acute heat exposure would protect endothelial-dependent vasodilation following I/R injury in aged adults. Nine (2 men, 69 ± 8 yrs) aged adults were exposed to a thermoneutral control condition or whole-body passive heating (water-perfused suit) sufficient to increase body core temperature by 1.2 °C. Experiments were separated by at least 7 days. Heat exposure was always performed first in order to time-match the thermoneutral control condition. Endothelium-dependent vasodilation was assessed via flow-mediated dilation of the brachial artery before (pre-I/R) and after I/R injury (post-I/R), which was induced by 20 min of arm ischemia followed by 20 min of reperfusion. Ischemia-reperfusion injury reduced flow-mediated dilation following the thermoneutral control condition (pre-I/R, 4.5 ± 2.9 % vs. post-I/R, 0.9 ± 2.8 %, P < 0.01), but was well maintained with prior heat exposure (pre-I/R, 4.4 ± 2.8 % vs. post-I/R, 3.5 ± 2.8 %, P = 0.5). Taken together, acute heat exposure protects against endothelial I/R injury in aged adults. These results highlight the therapeutic potential of heat therapy to prevent endothelial dysfunction associated with I/R injury in aged adults who are most at risk for an ischemic event.Item Additive Effects of Diabetes and Lower-Limb Amputation on Osteoarthritis with Comparison to Diabetic and Healthy Controls(2022) Ngo, Wayne; Finnerty, Cait; Finco, MG; Holley, Bethany; Menegaz, Rachel A.Purpose: Individuals with type II diabetes and individuals with lower-limb amputation each have increased risks of developing osteoarthritis compared to the general population. Despite the high co-occurrence of type II diabetes with lower-limb amputations, the additive effects of these conditions are unclear. In order to better manage the risk of developing osteoarthritis in these populations, a better understanding of how diabetes and amputation might compound osteoarthritis risk is needed. Methods: We measured hip and knee joint space, as indicators of osteoarthritis, in four groups of individuals: 1) lower-limb amputees with diabetes, 2) lower-limb amputees without diabetes 3) diabetic controls, and 4) healthy controls. We hypothesized lower-limb amputees with diabetes would have the most impaired musculoskeletal health, followed by amputees without diabetes, diabetic controls, then healthy controls. 30 total CT scans of males (42-79 years; BMI 19.7 - 48.9 kg/m2) were obtained from the New Mexico Decedent Image Database. 10 scans were identified for amputees, diabetic controls, and healthy controls. Half of the lower-limb amputees had diabetes while half did not, to differentiate effects of diabetes and amputation on musculoskeletal health. 3D Slicer software was used to measure hip and knee joint spaces as indicators of osteoarthritis. Comparisons between groups were assessed using Kruskal-Wallis with Dunn's post hoc tests. Results: Amputees with and without diabetes showed significantly narrower hip (p=0.01) and knee (p=0.08) joint space bilaterally compared to diabetic and healthy controls. This result suggests amputees could be at a higher risk of developing lower-limb osteoarthritis compared to diabetic and healthy individuals, which is in line with prior work demonstrating the prevalence of osteoarthritis in the amputee population. Conclusions: In agreement with our hypothesis, box plots showed trends of amputees with diabetes having the most narrowed joint space, followed by amputees without diabetes, then diabetic controls, and healthy controls. While not statistically significant, these trends suggest amputees with diabetes are at increased risk of developing osteoarthritis compared to amputees without diabetes. Perhaps the aggressive management of blood glucose and post-amputation physiotherapy treatments could help reduce joint deterioration in these patients. Future work will focus on increasing sample size to assess if these findings are generalizable to a larger population. Increased risks of osteoarthritis can lead to pain, limited mobility, and decreased quality of life. This study can potentially inform clinical standards of care for patients with amputations. Earlier interventions such as proactive musculoskeletal screenings and targeted exercises may reduce risks of developing osteoarthritis, leading to improved clinical outcomes.