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Developing Humanized PNPLA3 Mice
(2023-08-08) Dempsey, Katherine; Wang, Yang; Liang, Guosheng; Cohen, Jonathan C.; Hobbs, Helen H.
Fatty liver disease (FLD) is the leading cause of liver disease in the world. The disorder begins with an accumulation of triglycerides (TG) in cytoplasmic lipid droplets (LDs). The strongest genetic risk factor for FLD is a missense variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3). PNPLA3 is an insulin-regulated gene that is expressed at high levels in liver and adipose tissues. In fasted mice, levels of PNPLA3 mRNA are low and increase after feeding. It has been previously shown that PNPLA3 is a direct target gene of sterol regulatory element (SRE) binding protein 1c (SREBP-1c), and the binding site of the transcription factor was mapped to intron 1. The I148M substitution is located in a region that is well-conserved between mice and humans, so knock-in mice with this variant also develop FLD. Another variant (S453I) in PNPLA3 is associated with reduced hepatic TG levels in humans, but this variant resides in a non-conserved region of the protein. To determine how the S453I variant reduces hepatic TG levels, CRISPR-Cas9 was used to generate mice expressing human PNPLA3. Genotyping indicated that the insertion was successful, and human PNPLA3 protein expression was verified by immunoblotting analysis. Comparing relative mRNA expression levels in fasted versus refed mice demonstrated that human PNPLA3 retained its responsivity to insulin. Future studies can now be conducted using humanized PNPLA3 mice with the S453I variant to identify potential therapeutic targets.
Quantitative Analysis of Barriers and Facilitators to Adopting Tenecteplase
(2023-05-12) Prasad, Sidarrth; Olson, Daiwai M.; Gebreyohanns, Mehari; Jones, Erica; Kwon, Yoonjee; Ifejika, Nneka L.; The Lone Star Stroke Research Consortium
INTRODUCTION: Tenecteplase (TNK) is an emerging treatment for acute ischemic stroke (AIS) being adopted in place of alteplase (ALT). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to TNK adoption as a treatment for AIS. OBJECTIVES: The objective of this study is to identify barriers and facilitators to TNK implementation at hospitals within the state of Texas and present them in a quantifiable presentation. MATERIALS & METHODS: This study examines questionnaire responses from 40 hospitals to examine barriers and facilitators to transition from ALT to TNK. Surveys were done via teleconference with stroke coordinators and physicians associated with the Lone Star Stroke Research Consortium and other regional Texas hospitals. The consortium comprises participants from 6 hub hospitals and 28 spoke hospitals including community-based facilities to Comprehensive Stroke Centers (CSC). Interviews lasting 10-20 minutes were conducted where nominal variables like hospital bed information, stroke information, thrombolytic use, and ordinal variables were recorded utilizing a Likert questionnaire. The participants were blinded to the survey questions to reduce bias. DISCUSSION/RESULTS: The 40 Texas hospitals had a mean of 40 ED beds, 49 stroke beds, 685 annual stroke admissions out of which 14.5%, were hemorrhagic, 18% Transient Ischemic Attack (TIA) and 66.5% AIS respectively. There were 20 (50%) CSC hospitals, 2 (5%) thrombectomy capable, 16 (40%) primary stroke centers, and 2 (5%) were acute stroke ready hospitals. Compared to hospitals that successfully adopted TNK, non-adopters had significantly different views on the barrier of adequate evidence (P <.05), TNK delivery times (P<.05), and legal issues regarding giving TNK (P<.05). However, hospitals were similar in respect to the barriers of having a TNK policy (P=.094), buy-in from administration (P=.276), the cost of TNK (P=.089), and the willingness of pharmacy to adopt TNK (P=.242). SUMMARY/CONCLUSION: There is a generalizable pattern of barriers and facilitators from the perspective of stroke coordinators and physicians. The results will be used to develop a TNK adoption Toolkit.
Definition of Anisocoria in Neurocritical Patients
(2023-05-12) Saju, Ciji; Barnes, Arianna; Kuramatsu, Joji B.; Marshall, Jade L.; Obinata, Hirofumi; Puccio, Ava M.; Yokobori, Shoji; Prasad, Sidarrth; Olson, Daiwai M.
INTRODUCTION: Anisocoria, defined as the absolute difference in left and right pupil diameter, is an important clinical finding. However, the definition of anisocoria varies and clinicians have limited reliability in estimating pupil size through subjective measurements. Using a quantitative pupillometer (QP) increases the accuracy and consistency in pupil measurement. OBJECTIVES: The primary objective of this study is to examine the presence of anisocoria at rest, and anisocoria after exposure to light, using QP in a cohort of Neuroscience intensive care unit (NSICU) patients. The secondary objective is to explore anisocoria using different cutpoints for differences in size. MATERIALS & METHODS: Retrospective analysis from an international registry was queried to obtain the first paired QP measurement from patients admitted to one of 4 US and 2 international NSICUs. DISCUSSION/RESULTS: Sample size includes 5769 patients with a mean age of 57.5 (17.6%) years. Of these, 2,558 (51.5%) were female, 3,669 (75.5%) were White, and 4,369 (89.2%) were non-Hispanic. Hospital length of stay was a median of 6 (3 to 14) days, and the median ICU length of stay was (1 to 8) days. Using the smallest cutpoint of > 0.5 mm, anisocoria was present at rest in 1,642 (28.2%) and after light stimulus in 885 (15.3%) observations (P<.0001). Using the largest cut-point of > 2.0 mm anisocoria was present at rest in 79 (1.4%) of our sample and after light stimulus in 74 (1.3%) observations (P<.0001). SUMMARY/CONCLUSION: There is a statistically significant difference in anisocoria before and after exposing the pupil to light. This difference persists across anisocoria cutpoints ranging from 0.5 to 2.0mm. Future study should examine anisocoria before and after light exposure for association with radiological or clinical findings.
A Multisite Qualitative Analysis of Barriers and Facilitators to Adopting Tenecteplase
(2023-05-11) Prasad, Sidarrth; Olson, Daiwai M.; Gebreyohanns, Mehari; Jones, Erica; Aguilera, Veronica; Ifejika, Nneka L.; The Lone Star Stroke Research Consortium
INTRODUCTION: Tenecteplase (TNK) is an emerging treatment for acute ischemic stroke (AIS) being adopted in place of alteplase (ALT). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to TNK adoption as a treatment for AIS. OBJECTIVES: The objective of this study is to identify thematic barriers and facilitators to TNK implementation at hospitals within the state of Texas. MATERIALS & METHODS: This qualitative research study uses a phenomenological approach with hermeneutic cycling. After initial question development, subsequent questions were identified during each hermeneutic cycle in preparation for the next interview. Using purposive sampling, we interviewed stroke coordinators and physicians associated with the Lone Star Stroke Research Consortium, a statewide research network in Texas. The consortium is comprised of participants from 6 hub hospitals and 28 spoke hospitals including both community-based facilities to Comprehensive Stroke Centers. Interviews lasting 20-40 minutes were recorded and transcribed verbatim. Transcribed material was dissected and grouped into cohesive themes. Each stage of thematic analysis required consensus from the research team to proceed to the next interview. Sampling ended when saturation was reached. RESULTS: Saturation was reached after four interviews. Three themes and eight sub-themes were identified. The theme Evidence had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme Process flow had four sub-themes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme Consensus had one sub-theme: Getting Buy-In. CONCLUSION: Through qualitative interviewing, we identified themes and sub-themes in an effort to understand barriers and facilitators faced by hospitals when transitioning from ALT to TNK. The next study will use implementation science techniques and will involve designing an implementation toolkit informed by the data from this study. It is anticipated that this toolkit will be used in a prospective interventional block randomized study.
Biomechanical Validation of Additively Manufactured Polymeric Femora
(2023-05-31) Oldham, Blaine; Nagaraja, Kishore Mysore; Weinschenk, Robert; Samade, Richard; Li, Wei
INTRODUCTION: Fourth generation composite bone models (Sawbones®) are biomechanically validated for testing loading conditions on normal human bone. However, for patients with altered anatomy, such as primary or metastatic bone neoplasms, accurate biomechanical models are unavailable. Rapid prototyping technologies, including additive manufacturing, can offer a solution if properly harnessed. The aim of this study was to develop and validate a 3-dimensional (3D) printed model of a normal human femur using polylactic acid (PLA) that can be adapted to variant anatomy. METHODS: A literature review was conducted to identify the material properties of human femur bone. Standard dog-bone shaped tensile and compressive testing specimens were created with consistent printing parameters to evaluate the anisotropic mechanical properties of 3D printed PLA. After reviewing the differences in material properties, it was determined that incorporating geometric variation in the models was necessary to accurately replicate the biomechanical behavior of bone. A digital model of a normal human femur was obtained from Sawbones and prepared for 3D printing with wall thicknesses ranging from 0.4mm to 2.4mm and an infill density of 20%. A total of 12 models were printed, and standard three-point bending tests were performed, with measurements recorded to evaluate the mechanical response. The data obtained from the mechanical testing was analyzed to determine the starting point for future print parameter modification. RESULTS: According to the literature review, values for material properties of the anatomic human femur are commonly reported as: flexural modulus of 11-20 gigapascals (GPa), flexural strength of 140-220 megapascals (MPa), ultimate tensile strength of 130 MPa, and ultimate compressive strength of 205 MPa. Testing of the dog-bone specimens yielded the following material properties: elastic modulus of 2.10 ± 0.03 GPa, ultimate tensile strength of 52.65 ± 1.90 MPa, and ultimate compressive strength of 57.70 ± 3.23 MPa. Testing of the 12 printed models produced a flexural modulus ranging from 7.46 to 18.35 GPa and a flexural strength of 342.4 to 832.7 MPa. CONCLUSIONS: Our working hypothesis was that an optimized PLA-printed femoral diaphysis could model the biomechanical properties seen in actual human bone. The flexural modulus of the printed models replicated values reported in the literature for anatomic human femora, and the flexural strength above that seen in bone can be modulated down with geometric adjustments. These results serve as proof of principle that a 3D printed femur is a viable option for biomechanical studies. However, given the difference in material properties between human bone and PLA, geometric modifications such as changes to simulated cortical thickness and infill density are necessary to achieve model validity. Moving forward, further fine-tuning of the print parameters will lead to an optimized biomechanical response. The models will then be validated against Sawbones models. The full scope of this project includes adapting the geometry to patients with altered anatomy. Additional research will further expose the potential of 3D printing technology in both clinical and educational settings, such as preoperative planning, intraoperative reference, and the facilitation of resident and student education in orthopedics.
Evaluation of a Student-Run Smoking Cessation Program in a Dallas Homeless Population
(2020-11-06) Sotelo, Jesus; Lue, Brian; Garigipati, Priya; Rossopoulos, Thanos; Min, Jennifer; Pagels, Patti; Day, Philip; Gimpel, Nora
BACKGROUND: Tobacco use has been shown to be modifiable risk factor for myriad chronic conditions and diseases. Amongst all smokers, homeless men continue to have high relative rates of smoking; it is estimated that 75% of homeless men use tobacco, compared to the general population. Given such high rates, targeted interventions for helping homeless men cease tobacco usage need to be developed. While most adult smokers will try to quit at least once, homeless individuals face very specific barriers to quitting. UT Southwestern medical students are addressing the disparity of tobacco use among the homeless men through a smoking cessation program in Dallas, Texas. Medical student volunteers, under the supervision of faculty, provide coaching and education for homeless men concerning smoking cessation and their general health. This study aims to demonstrate that this program improves tobacco cessation outcomes for homeless men in Dallas. A secondary objective of this project is to evaluate the efficacy of the smoking cessation efforts over time. METHODS: The smoking cessation program is conducted at a men’s homeless shelter in Dallas, Texas. The structure of the program involves weekly smoking-related health topic discussions led by a medical student. In addition, medical student volunteers lead individual and group coaching session via motivational interviewing. Data collected include addiction levels, willingness to quit, and CO levels, measured weekly. Paired t-tests in these categories, along with class attendance, retention, and use of nicotine replacement therapy are measured. RESULTS: Retention rates among participants improved from 11% in 2017 to 28% in 2018. 2019 saw a slight decrease in total number of visits; however, the difference in the average number of participants between 2018 and 2019 was not statistically significant. Returning clients reported higher willingness to quit scores and quit rates, verified by average CO values. CONCLUSIONS: The results of this study demonstrate that under the supervision of faculty, medical students are able to create a sustainable and effective smoking cessation program among underserved populations. Future directions include improved data collection to address longitudinal quality improvement.
Lean On Me: Proactive Multi-Disciplinary Support Services Introduction for New Patient/Family Education
(2018-05-30) Credeur, Catherine; Adams, Olivia; Vu, Lan; Hardi, Shelli; Stock, Christina; Bishop, Christofer
This poster describes an interdisciplinary education process utilizing staff social worker, dietitian, and music therapist and our students along with peer survivor volunteers from a national patient organization education. This weekly program is designed to give new pancreatic patients of the Simmons Cancer Center a proactive introduction to the Supportive Services staff and the resources of the Pancreatic Cancer Action Network.
Metastatic Penile Melanoma
(2018-04-08) Maredia, Navin; Goenka, Anamika
Melanoma, the most serious skin cancer and the sixth most common cancer in North America, is associated with UV light radiation from sun exposure. The majority of melanomas develop on sun-exposed areas, but melanoma can also occur on non-sun exposed areas. This case Illustrates the importance of doing a thorough physical exam, formulating an extensive differential diagnosis, and identifying possible cognitive biases that may lead to misdiagnosis.
High Midline Levator Myorrhaphy for Vaginal Vault Prolapse: Long-Term Results
(2016-01-19) Wu, Yuefeng (Rose); Christie, Alana; Alhalabi, Feras; Zimmern, Philippe E.
INTRODUCTION AND OBJECTIVE: To review long-term outcomes following a vaginal native tissue repair (High Midline Levator Myorrhaphy, HMLM) in women with symptomatic vault prolapse.1, 2 METHODS: Following IRB-approval, a prospectively maintained database of women who underwent HMLM for symptomatic vault prolapse (VP) alone or associated with other POP was reviewed for demographic data, history of prior POP, physical examination, hospital stay length, and long-term outcomes. Patients with <6 months follow up and no retrievable operative notes were excluded. Data was reviewed by a third party investigator not involved in patient care. Failure was defined as same compartment POP ≥ stage 2 or POP reoperation. Descriptive statistics and Kaplan-Meier curves were obtained. RESULTS: Between 1996 and 2014, 94 women who underwent HMLM were studied. Mean follow-up time was 7.7 (0.6-18.4) years, mean age was 69.6 (36-91), and 89% were Caucasian. Patients were grouped by POP indications: VP (6), vault and anterior (26), vault and posterior (35), and all 3 compartments (27) (Table 1). No intra-operative complications were reported. Ten (11%) early complications (<30 days) were noted (Clavien I/II). Sixty-seven (71%) women were cured of VP. Ten women (11%) had failure in a non-apical compartment and 17 (18%) had apical failure. Reoperation rate was 14% (13/94) and 5% (5/94) for vault and non-vault recurrences, respectively. VP recurrence-free probability between women with ≤ 2 versus 3 POP compartments was statistically significant (p = 0.0128). CONCLUSIONS: At a mean follow-up of 7-8 years, HMLM was successful in two thirds of women. Best outcome was noted in women with VP and one associated compartment prolapse. REFERENCES: 1. Lemack, G. E., et al. Urology, 56: 50, 2000. 2. Natale, F. et al. J Urol, 180: 2047, 2008
Improvement of Knowledge and Attitudes in Aging and Healthcare: Efficacy of an Integrative Undergraduate Geriatrics Educational Program
(2013-05-04) Longo, Palma M.; Kirk, Lynne M.; Rubin, Craig D.; Shah, Amit
What Color Is Your Library? How Color Impacts Library Promotion in a Hospital Setting
(2010-10) Patridge, Emily; Schack, Catherine; Scott, Jane; 0000-0003-2890-1030
Networking in North Texas: Connected by Assessment
(2010) Chapa, Kay; Wahl, Diane
Critical Sources Identified: Gathering, Organizing, and Analyzing Evidence -- Just like a CSI Unit!
(2010) Chapa, Kay; Scott, Jane; Carpenter, Scott

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