Medical Specialties Commons^™

The Mechanism And Therapy Of Aortic Aneurysms, Jianing Gao, Huanhuan Cao, Gaofei Hu, Yufei Wu, Yangkai Xu, Hongtu Cui, Hong S. Lu, Lemin Zheng

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis …

Acoustic Cry Characteristics In Preterm Infants And Developmental And Behavioral Outcomes At 2 Years Of Age., Andrew W. Manigault, Stephen J. Sheinkopf, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Michael O'Shea, Steven Pastyrnak, Lynne M. Smith, Todd M. Everson, Carmen J. Marsit, Lynne M. Dansereau, Sheri A. Dellagrotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Acoustic cry characteristics have been associated with severe medical problems in newborns. However, little is known about the utility of neonatal acoustic cry characteristics in the prediction of long-term outcomes of very preterm infants.

OBJECTIVES: To evaluate whether acoustic characteristics of infant cry at neonatal intensive care unit (NICU) discharge are associated with behavioral and developmental outcomes at age 2 years in infants born very preterm.

DESIGN, SETTING, AND PARTICIPANTS: Infants born less than 30 weeks postmenstrual age (PMA) were enrolled from April 2014 through June 2016 as part of a multicenter (9 US university affiliated NICUs) cohort study …

Circulation Of Rhinoviruses And/Or Enteroviruses In Pediatric Patients With Acute Respiratory Illness Before And During The Covid-19 Pandemic In The Us., Danielle A. Rankin, Andrew J. Spieker, Ariana Perez, Anna L. Stahl, Herdi K. Rahman, Laura S. Stewart, Jennifer E. Schuster, Joana Y. Lively, Zaid Haddadin, Varvara Probst, Marian G. Michaels, John V. Williams, Julie A. Boom, Leila C. Sahni, Mary A. Staat, Elizabeth P. Schlaudecker, Monica M. Mcneal, Christopher J. Harrison, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Susan I. Gerber, Meredith Mcmorrow, Brian Rha, James D. Chappell, Rangaraj Selvarangan, Claire M. Midgley, Natasha B. Halasa, Nvsn Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting.

OBJECTIVE: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought …

Design And Characterization Of An Aerosol Test Chamber For Emergency Response Patient Contamination Control Simulation And Research, Megan L. Steele, Emily M. Spatz, George P. Lemmer, Jacob M. Denney, Casey Cooper, Jeremy M. Slagley, Robert M. Eninger

Faculty Publications

Contaminated or infected patients present a risk of cross-contamination for emergency responders, attending medical personnel and medical facilities as they enter a treatment facility. The controlled conditions of an aerosol test chamber are required to examine factors of contamination, decontamination, and cross-contamination. This study presents the design, construction, and a method for characterizing an aerosol test chamber for a full-sized manikin on a standard North Atlantic Treaty Organization litter. The methodology combined air velocity measurements, aerosol particle counts and size distributions, and computational fluid dynamics modeling to describe the chamber’s performance in three dimensions. This detailed characterization facilitates future experimental …

Immunotherapeutic Targets In Non-Small Cell Lung Cancer, Habib Sadeghirad, Tayyeb Bahrami, Sepideh M. Layeghi, Hassan Yousefi, Meysam Rezaei, Seyed R. Hosseini-Fard, Payar Radfar, Majid E. Warkiani, Ken O'Byrne, Arutha Kulasinghe

School of Medicine Faculty Publications

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or …

Experiences Of Racism Among Black And African Children With Asthma, Esosa Adah, Rayanna Tucker, Bridgette Jones

Posters

Rationale: The relationship between adverse childhood experiences, toxic stress and asthma risk has been previously described in the literature among adult and pediatric populations. Studies have identified experiences of racism as a chronic stressor associated with asthma morbidity however, most studies have focused primarily on adults or parental perspectives. We initiated a pilot study to characterize described experiences of racism among Black/African American children with persistent asthma and describe some of our initial results. Methods: Children were asked to complete the “Perceptions of Racism in Children and Youth,” a validated questionnaire, measuring perceptions of racism and discrimination. Responses were analyzed …

Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage

Dissertations, Theses, and Capstone Projects

Nano-scale materials have gained much attention during the past few decades due to the stark differences in their properties compared to bulk material. Thus, they are being studied for a myriad of applications ranging from harnessing solar energy to diagnostics. This thesis focuses on the synthesis of hollow iron oxide nanoparticles using Galvanic replacement reactions and their application in drug delivery. Moreover, the use of a peptide precursor for the enhancement of exosomes is also discussed.

Chapter 1 discusses a simple and economical Galvanic approach used for the synthesis of hollow one-dimensional iron oxide nanotubes. In the initial reaction, the …

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays In Icu Admitted Patients, David J Roh, Tiffany R Chang, Aditya Kumar, Devin Burke, Glenda Torres, Katherine Xu, Winni Yang, Azzurra Cottarelli, Ernest Moore, Angela Sauaia, Kirk Hansen, Angela Velazquez, Amelia Boehme, Athina Vrosgou, Shivani Ghoshal, Soojin Park, Sachin Agarwal, Jan Claassen, E Sander Connolly, Gebhard Wagener, Richard O Francis, Eldad Hod

Faculty, Staff and Student Publications

Objectives: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU.

Design: Observational cohort study and separate in vitro laboratory study.

Setting: Multicenter tertiary referral ICUs.

Patients: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory …

Automated Field-In-Field Whole Brain Radiotherapy Planning, Kai Huang, Soleil Hernandez, Chenyang Wang, Callistus Nguyen, Tina Marie Briere, Carlos Cardenas, Laurence Court, Yao Xiao

Faculty, Staff and Student Publications

PURPOSE: We developed and tested an automatic field-in-field (FIF) solution for whole-brain radiotherapy (WBRT) planning that creates a homogeneous dose distribution by minimizing hotspots, resulting in clinically acceptable plans.

METHODS: A configurable auto-planning algorithm was developed to automatically generate FIF WBRT plans independent of the treatment planning system. Configurable parameters include the definition of hotspots, target volume, maximum number of subfields, and minimum number of monitor units per field. This algorithm iteratively identifies a hotspot, creates two opposing subfields, calculates the dose, and optimizes the beam weight based on user-configured constraints of dose-volume histogram coverage and least-squared cost functions. The …

Spatial Molecular And Cellular Determinants Of Stat3 Activation In Liver Fibrosis Progression In Non-Alcoholic Fatty Liver Disease, Jingjing Jiao, Jessica I Sanchez, Omar A Saldarriaga, Luisa M Solis, David J Tweardy, Dipen M Maru, Heather L Stevenson, Laura Beretta

Faculty, Staff and Student Publications

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice.

METHODS: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and …

Machine Learning And Acute Stroke Imaging, Sunil A Sheth, Luca Giancardo, Marco Colasurdo, Visish M Srinivasan, Arash Niktabe, Peter Kan

Faculty, Staff and Student Publications

BACKGROUND: In recent years, machine learning (ML) has had notable success in providing automated analyses of neuroimaging studies, and its role is likely to increase in the future. Thus, it is paramount for clinicians to understand these approaches, gain facility with interpreting ML results, and learn how to assess algorithm performance.

OBJECTIVE: To provide an overview of ML, present its role in acute stroke imaging, discuss methods to evaluate algorithms, and then provide an assessment of existing approaches.

METHODS: In this review, we give an overview of ML techniques commonly used in medical imaging analysis and methods to evaluate performance. …

A Multicenter Study Of Clinical Impact Of Variant Of Uncertain Significance Reclassification In Breast, Ovarian And Colorectal Cancer Susceptibility Genes, Sukh Makhnoon, Brooke Levin, Megan Ensinger, Kristin Mattie, Robert J Volk, Zhongming Zhao, Tito Mendoza, Sanjay Shete, Laila Samiian, Generosa Grana, Andrew Grainger, Banu Arun, Brian H Shirts, Susan K Peterson

Faculty, Staff and Student Publications

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences.

METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) …

Impact Of Us Preventive Services Task Force Lung Cancer Screening Update On Drivers Of Disparities In Screening Eligibility, Kristin G Maki, Rajesh Talluri, Iakovos Toumazis, Sanjay Shete, Robert J Volk

Faculty, Staff and Student Publications

BACKGROUND: In 2021, the U.S. Preventive Services Task Force (USPSTF) updated its recommendation to expand lung cancer screening (LCS) eligibility and mitigate disparities. Although this increased the number of non-White individuals who are eligible for LCS, the update's impact on drivers of disparities is less clear. This analysis focuses on racial disparities among Black individuals because members of this group disproportionately share late-stage lung cancer diagnoses, despite typically having a lower intensity smoking history compared to non-Hispanic White individuals.

METHODS: We used data from the National Health Interview Survey to examine the impact of the 2021 eligibility criteria on racial …

Aapm Btsc Report 377: Physicist Brachytherapy Training In 2021-A Survey Of Therapeutic Medical Physics Residency Program Directors, Manik Aima, Samantha J Simiele, Susan L Richardson, Christopher S Melhus

Faculty, Staff and Student Publications

BACKGROUND: Brachytherapy (BT) was the first radiotherapeutic technique used to treat human disease and remains an essential modality in radiation oncology. A decline in the utilization of BT as a treatment modality has been observed and reported, which may impact training opportunities for medical physics residents. A survey of therapeutic medical physics residency program directors was performed as part of an assessment of the current state of BT training during residency.

METHODS: In March 2021, a survey consisting of 23 questions was designed by a working unit of the Brachytherapy Subcommittee of the American Association of Physicists in Medicine (AAPM) …

Panoptosis Is A Prominent Feature Of Desmoplakin Cardiomyopathy, Melis Olcum, Leila Rouhi, Siyang Fan, Maya M Gonzales, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: Arrhythmogenic cardiomyopathy (ACM) is hereditary cardiomyopathy caused by pathogenic variants (mutations) in genes encoding the intercalated disc (ID), particularly desmosome proteins. ACM caused by mutations in the

AIM: The aim of this article was to gain insight into the pathogenesis of DSP cardiomyopathy.

METHODS AND RESULTS: The

CONCLUSION: The findings identify PANoptosis as a prominent phenotypic feature of DSP cardiomyopathy and set the stage for delineating the specific molecular mechanisms involved in its pathogenesis. The model also provides the opportunity to test the effects of pharmacological and genetic interventions on myocardial fibrosis and cell death.

Acoustic Voice And Speech Biomarkers Of Treatment Status During Hospitalization For Acute Decompensated Heart Failure, Olivia M Murton, G William Dec, Robert E Hillman, Maulik D Majmudar, Johannes Steiner, John V Guttag, Daryush D Mehta

Faculty, Staff and Student Publications

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared …

Structural Basis For Transcription Factor Zbtb7a Recognition Of Dna And Effects Of Zbtb7a Somatic Mutations That Occur In Human Acute Myeloid Leukemia, Ren Ren, John R Horton, Qin Chen, Jie Yang, Bin Liu, Yun Huang, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

ZBTB7A belongs to a small family of transcription factors having three members in humans (7A, 7B, and 7C). They share a BTB/POZ protein interaction domain at the amino end and a zinc-finger DNA-binding domain at the carboxyl end. They control the transcription of a wide range of genes, having varied functions in hematopoiesis, oncogenesis, and metabolism (in particular glycolysis). ZBTB7A-binding profiles at gene promoters contain a consensus G(a/c)CCC motif, followed by a CCCC sequence in some instances. Structural and mutational investigations suggest that DNA-specific contacts with the four-finger tandem array of ZBTB7A are formed sequentially, initiated from ZF1-ZF2 binding to …

The Orf7a Protein Of Sars-Cov-2 Initiates Autophagy And Limits Autophagosome-Lysosome Fusion Via Degradation Of Snap29 To Promote Virus Replication, Peili Hou, Xuefeng Wang, Hongmei Wang, Tiecheng Wang, Zhangping Yu, Chunqing Xu, Yudong Zhao, Wenqi Wang, Yong Zhao, Fengyun Chu, Huasong Chang, Hongchao Zhu, Jiahui Lu, Fuzhen Zhang, Xue Liang, Xingyu Li, Song Wang, Yuwei Gao, Hongbin He

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the …

Biosynthesis Of Chlorophyll And Other Isoprenoids In The Plastid Of Red Grape Berry Skins, António Teixeira, Henrique Noronha, Sarah Frusciante, Gianfranco Diretto, Hernâni Gerós

Faculty, Staff and Student Publications

Despite current knowledge showing that fruits like tomato and grape berries accumulate different components of the light reactions and Calvin cycle, the role of green tissues in fruits is not yet fully understood. In mature tomato fruits, chlorophylls are degraded and replaced by carotenoids through the conversion of chloroplasts in chromoplasts, while in red grape berries, chloroplasts persist at maturity and chlorophylls are masked by anthocyanins. To study isoprenoid and lipid metabolism in grape skin chloroplasts, metabolites of enriched organelle fractions were analyzed by high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and the expression of key genes was evaluated by real-time …

Biomarkers For Dementia In Latin American Countries: Gaps And Opportunities, Mario A Parra, Paulina Orellana, Tomas Leon, Cabello G Victoria, Fernando Henriquez, Rodrigo Gomez, Constanza Avalos, Andres Damian, Andrea Slachevsky, Agustin Ibañez, Henrik Zetterberg, Betty M Tijms, Jennifer S Yokoyama, Stefanie D Piña-Escudero, J Nicholas Cochran, Diana L Matallana, Daisy Acosta, Ricardo Allegri, Bianca P Arias-Suárez, Bernardo Barra, Maria Isabel Behrens, Sonia M D Brucki, Geraldo Busatto, Paulo Caramelli, Sheila Castro-Suarez, Valeria Contreras, Nilton Custodio, Sergio Dansilio, Myriam De La Cruz-Puebla, Leonardo Cruz De Souza, Monica M Diaz, Lissette Duque, Gonzalo A Farías, Sergio T Ferreira, Nahuel Magrath Guimet, Ana Kmaid, David Lira, Francisco Lopera, Beatriz Mar Meza, Eliane C Miotto, Ricardo Nitrini, Alberto Nuñez, Santiago O'Neill, John Ochoa, Maritza Pintado-Caipa, Elisa De Paula França Resende, Shannon Risacher, Luz Angela Rojas, Valentina Sabaj, Lucas Schilling, Allis F Sellek, Ana Sosa, Leonel T Takada, Antonio L Teixeira, Martha Unaucho-Pilalumbo, Claudia Duran-Aniotz

Faculty, Staff and Student Publications

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a …

Inhibition Of Myeloperoxidase Enhances Immune Checkpoint Therapy For Melanoma, Tracy W Liu, Seth T Gammon, Ping Yang, Wencai Ma, Jing Wang, David Piwnica-Worms

Faculty, Staff and Student Publications

BACKGROUND: The presence of a highly immunosuppressive tumor microenvironment has limited the success of immune checkpoint therapy (ICT). Immune suppressing myeloid cells with increased production of reactive oxygen species are critical drivers of this immunosuppressive tumor microenvironment. Strategies to limit these immune suppressing myeloid cells are needed to enhance response to ICT.

METHODS: To evaluate the contribution of myeloperoxidase (MPO), a myeloid lineage-restricted enzyme and a major source of reactive oxygen species, to mediating ICT response, we compared treatment outcome and immune composition in wild-type, MPO-deficient (

RESULTS: Tumor growth and survival studies demonstrated that either host deficiency (

CONCLUSION: …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Danesh H Sopariwala, Andrea S Rios, Guangsheng Pei, Anirban Roy, Meiricris Tomaz Da Silva, Hao Thi Thu Nguyen, Addison Saley, Rachel Van Drunen, Anastasia Kralli, Kristin Mahan, Zhongming Zhao, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how exercise improves fitness. Here, we have elucidated the role of nuclear receptors, estrogen-related receptor alpha and gamma (ERRα/γ) in regulating myofibrillar composition, contractility, and exercise capacity in skeletal muscle. We used muscle-specific single or double (DKO) ERRα/γ knockout mice to investigate the effect of ERRα/γ deletion on muscle and exercise parameters. Individual knockout of ERRα/γ did not have a significant impact on the skeletal muscle. On the other hand, DKO mice exhibit pale muscles compared to wild-type (WT) littermates. RNA-seq analysis …

Remote Care Adoption In Underserved Congenital Heart Disease Patients During The Covid-19 Era, Ruth M Vaughan, Judson A Moore, Jasmine S Moreno, Karla J Dyer, Abiodun O Oluyomi, Keila N Lopez

Faculty, Staff and Students Publications

The COVID-19 pandemic restricted in-person appointments and prompted an increase in remote healthcare delivery. Our goal was to assess access to remote care for complex pediatric cardiology patients. We performed a retrospective chart review of Texas Children's Hospital (TCH) pediatric cardiology outpatient appointments from March 2020 to December 2020 for established congenital heart disease (CHD) patients 1 to 17 yo. Primary outcome variables were remote care use of telemedicine and patient portal activation. Primary predictor variables were age, sex, insurance, race/ethnicity, language, and location. Descriptive statistics were used to analyze patient demographics. Multivariate logistic regression determined associations with remote care …

Psychosocial, Medical, And Demographic Variables Associated With Parent Mealtime Behavior In Young Children Recently Diagnosed With Type 1 Diabetes, Caroline Gonynor, Christine Wang, Carrie Tully, Maureen Monaghan, Randi Streisand, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: Managing young children's mealtime concerns can be challenging after type 1 diabetes (T1D) diagnosis because of developmental factors and diabetes management demands. To identify potential intervention targets, we evaluated medical, psychosocial, and demographic factors in relation to parents' engagement in problem mealtime behaviors (e.g., pressure to eat, restriction).

METHOD: Parents (N = 157) of young children (age 1-6 years) reported on psychosocial variables (parent fear of hypoglycemia, family functioning, parent problem solving, and parents' problem mealtime behavior frequency and perceptions of being problematic) within 2 months after T1D diagnosis. Hierarchical regression analyses examined associations among psychosocial variables, demographics (child …

Oral Ibrexafungerp For Vulvovaginal Candidiasis Treatment: An Analysis Of Vanish 303 And Vanish 306, Oluwatosin Goje, Ryan Sobel, Paul Nyirjesy, Steven R Goldstein, Mark Spitzer, Brooke Faught, Shelagh Larson, Thomas King, Nkechi E Azie, David Angulo, Jack D Sobel

Department of Obstetrics and Gynecology Faculty Papers

Background: Ibrexafungerp is a novel antifungal treatment for acute vulvovaginal candidiasis (VVC). Using pooled data from two phase three studies (VANISH 303 and 306) in the treatment of acute VVC, this analysis sought to determine the effectiveness of ibrexafungerp in various patient subgroups that may impact outcomes. Materials and Methods: Data from VANISH 303 (NCT03734991) and VANISH 306 (NCT03987620) evaluating ibrexafungerp 300 mg twice daily (BID) for 1 day versus placebo, were pooled and analyzed to determine clinical cure rate, clinical improvement, and mycological cure at the test-of-cure visit (day 11 ± 3) and symptom resolution …

Hypertrophic Pyloric Stenosis Protocol: A Single Center Study, Nelimar Cruz-Centeno, James A. Fraser Md, Shai Stewart Md, Derek Marlor, Rebecca M. Rentea, Pablo Aguayo, David Juang, Richard J. Hendrickson, Charles L. Snyder, Shawn D. St.Peter, Jason D. Fraser, Tolulope A. Oyetunji

Presentations

Introduction: Initial management of hypertrophic pyloric stenosis (HPS) is correction of electrolyte disturbances with fluid resuscitation. In 2015, our institution implemented a fluid resuscitation protocol based on previous data that focused on minimizing blood draws and allowing immediate ad libitum feeds postoperatively. Here we describe the protocol and subsequent outcomes. Methods: We conducted a single-center retrospective review of patients diagnosed with HPS from 2016-2020. All patients were managed per the protocol outlined in Figure 1. All were given formula or breast milk after the post-anesthesia care unit and discharged home after tolerating three consecutive feeds. Feedings were given every 2-3 …

Persistent Pediatric Breast Abscesses Following Initial Treatment At Tertiary And Community Centers, Derek Marlor, Kayla B. Briggs, Shai Stewart Md, Nelimar Cruz-Centeno, Charlene Dekonenko, Tolulope A. Oyetunji, Jason D. Fraser

Presentations

Introduction: Our institution previously reported on outcomes of children with untreated and not spontaneously draining breast abscesses. This study aimed to evaluate the outcomes of all patients with breast abscesses who were evaluated at our institution. Methods: Following IRB approval, all patients < 18-years-old with breast abscesses were included. A total of 145 patients treated from January 2008-December 2018 were identified. Patients were divided into 2 groups; Group 1 included patients initially evaluated at our institution and Group 2 included patients who were initially evaluated at referring centers. The primary outcome was disease persistence. Secondary outcomes were antibiotic utilization, number and type of procedures performed, and risk factors for recurrence. Statistical analysis was performed using STATA® 17 with a p-value of <0.05 indicating significance. Results: A total of 145 patients were identified: 111 (76.6%) in Group 1 and 34 (23.4%) in Group 2. Demographics were similar between groups. Of the 111 patients in Group 1, 2 (1.8%)) were treated with observation alone, 58 (52.3%) were treated with antibiotics alone, 26 (23.4%) were treated with aspiration, and 25 (22.5%) were treated with incision and drainage. Of the 34 patients in Group 2, 4 (11.8%) were treated initially with observation, 22 (64.7%) with antibiotics alone, 5 (14.7%) with manual expression, 2 (5.9%) with incision and drainage, and 1 (2.9%) with warm compresses. Patients in Group 1 were more likely to receive needle aspiration (23.4% vs. 0%; p<0.001) or incision and drainage (22.5.% vs. 5.9%; p<0.001) as initial treatment. Compared to Group 2, patients in Group 1 were more likely to be prescribed clindamycin when treated with antibiotics alone (69.9% vs 18.2%; p<0.001). They also had a 12.6% persistent disease rate (n=14). Second treatment in those with persistent disease included aspiration in 50% (n=7), incision and drainage 45.5% (n=5), antibiotics 7.1% (n=1), and manual expression 7.1% (n=1). No patients had persistent disease following second treatment. Patients in Group 2 were more likely to be treated with antibiotics alone (64.7% vs. 52.3%; p<0.001), with trimethoprim/sulfamethoxazole being the most commonly prescribed antibiotic (54.6%). In patients with persistent disease treated at our institution following initial evaluation at a referring center, 50.0% were treated with antibiotics alone, 26.5% with aspiration, 17.7% with incision and drainage, and 5.9% with manual expression. Following treatment at our institution, the rate of persistent disease was similar between groups (12.6% vs 11.8%;). Conclusions: Persistent breast abscesses may be treated with antibiotics alone in community and tertiary care centers. Disease persistence is similar regardless of the initial treatment setting.

Abl1/2 And Ddr1 Drive Meki Resistance In Nras-Mutant Melanomas By Stabilizing Raf/Myc/Ets1 And Promoting Raf Homodimerization, Anastasia Lyon, Rakshamani Tripathi, Christina Meeks, Daheng He, Yuanyuan Wu, Jinpeng Liu, Chi Wang, Jing Chen, Haining Zhu, Sujata Mukherjee, Saptadwipa Ganguly, Rina Plattner

Markey Cancer Center Faculty Publications

Melanomas harboring NRAS mutations are a particularly aggressive and deadly subtype. If patients cannot tolerate or the melanomas are insensitive to immune checkpoint blockade, there are no effective 2nd-line treatment options. Drugs targeting the RAF/MEK/ERK pathway, which are used for BRAF-mutant melanomas, do little to increase progression-free survival (PFS). Here, using both loss-of-function and gain-of-function approaches, we show that ABL1/2 and DDR1 are critical nodes during NRAS-mutant melanoma intrinsic and acquired MEK inhibitor (MEKi) resistance. In some acquired resistance cells, ABL1/2 and DDR1 cooperate to stabilize RAF proteins, activate ERK cytoplasmic and nuclear signaling, repress p27/KIP1 expression, and drive RAF …

Adolescent- And Adult-Initiated Alcohol Exposure In Mice Differentially Promotes Tumorigenesis And Metastasis Of Breast Cancer, Mei Xu, Hui Li, Danlei Chen, Huaxun Wu, Wen Wen, Hong Xu, Jacqueline Frank, Gang Chen, Jia Luo

Markey Cancer Center Faculty Publications

Background: Alcohol exposure increases the risk of breast cancer. Alcohol consumption by adolescents is a serious social and public health issue. This study investigated the impact of adolescent alcohol consumption on mammary tumorigenesis and progression and compared it to that of adult alcohol exposure in animal models. Methods: Female adolescent (5 weeks) and adult (8 weeks) MMTV-Wnt1 mice were exposed to alcohol either chronically or acutely. For chronic alcohol exposure, animals were fed a liquid diet containing 6.7% ethanol for 23 weeks. For acute exposure, animals were treated with ethanol (2.5 g/kg, 25% w/v) via intraperitoneal (IP) injection for 15 …

Bilirubin Nanoparticle Treatment In Obese Mice Inhibits Hepatic Ceramide Production And Remodels Liver Fat Content, Zachary A. Kipp, Genesee J. Martinez, Evelyn A. Bates, Agil B. Maharramov, Robert M. Flight, Hunter N. B. Moseley, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin’s effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated …