Medical Specialties Commons^™

Primary Care Patient Interest In Multi-Cancer Early Detection For Cancer Screening, Ronald Myers, Mie Hallman, Ayako Shimada, Melissa Dicarlo, Kaitlyn Davis, William Leach, Hattie Jackson, Amanda Indictor, Christopher Chambers

Department of Medical Oncology Faculty Papers

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. …

Cytomulate: Accurate And Efficient Simulation Of Cytof Data, Yuqiu Yang, Kaiwen Wang, Zeyu Lu, Tao Wang, Xinlei Wang

Faculty, Staff and Student Publications

Recently, many analysis tools have been devised to offer insights into data generated via cytometry by time-of-flight (CyTOF). However, objective evaluations of these methods remain absent as most evaluations are conducted against real data where the ground truth is generally unknown. In this paper, we develop Cytomulate, a reproducible and accurate simulation algorithm of CyTOF data, which could serve as a foundation for future method development and evaluation. We demonstrate that Cytomulate can capture various characteristics of CyTOF data and is superior in learning overall data distributions than single-cell RNA-seq-oriented methods such as scDesign2, Splatter, and generative models like LAMBDA.

Endoscopic Retrograde Cholangiopancreatography-Related Early Perforations: A Study Of Effects Of Procedure Duration, Complexity, And Endoscopist Experience, Mark Aloysius, Hemant Goyal, Tejas Nikumbh, Niraj James Shah, Ghassan M Hammoud, Pritesh Mutha, Mairin Joseph-Talreja, Savio John, Ganesh Aswath, Vaibhav Wadhwa, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: Perforations (Perf) during endoscopic retrograde cholangiopancreatography (ERCP) are rare (< 1%) but potentially fatal events (up to 20% mortality). Given its rarity, most data is through case series studies from centers or analysis of large databases. Although a meta-analysis has shown fewer adverse events as a composite (bleeding, pancreatitis, Perf) during ERCP performed at high-volume centers, there is very little real-world data on endoscopist and center procedural volumes, ERCP duration and complexity on the occurrence of Perf.

AIM: To study the profile of Perf related to ERCP by center and endoscopist procedure volume, ERCP time, and complexity from a national endoscopic repository.

METHODS: Patients from clinical outcomes research initiative-national endoscopic database (2000-2012) who underwent ERCP were stratified based on the endoscopist and center volume (quartiles), and total procedure duration and complexity grade of the ERCP based on procedure details. The effects of these variables on the Perf that occurred were studied. Continuous variables were compared between Perf and no perforations (NoPerf) using the Mann-Whitney U test …

Internet Analytics Of An Innovative Digital Educational Resource Of Type 1 Diabetes Hellotype1 In Local Languages For People Living With Diabetes Families And Healthcare Professionals In Southeast Asia, Sze May Ng, I V Malene, Thy Khue Nguyen, Khuong Le, Yang Xian Lucas Lim, Ngee Lek, Samantha Seal, Steffen Yun Tange, Azriyanti Anuar Zaini, Taninee Sahakitrungruang, Anne Charlotte Ficheroulle

Faculty, Staff and Student Publications

BACKGROUND: There is minimal data of health outcomes for Type 1 Diabetes (T1D) in Southeast Asia (SEA) where government funding of insulin and blood glucose monitoring either do not exist or is limited. The full impact of Covid-19 pandemic on the national economies of SEA remain unknown. In the midst of the pandemic, in 2021, HelloType1 was developed by Action4Diabetes (A4D), a non-government organisation charity in collaboration with Southeast Asia local healthcare professionals as an innovative digital educational resource platform of T1D in local languages. HelloType1 was launched in Cambodia, Vietnam, Thailand and Malaysia in 2021 to 2022 with Memorandums …

Utilizing Stakeholder Input Within The Tennessee Heart Health Network To Improve Cardiovascular Health Outcomes In Tennessee, Abigail C. Bennett

Longitudinal Scholar's Project

Background: Tennessee ranks sixth nationwide for most deaths related to heart disease. The Tennessee Heart Health Network (TN-HHN), an initiative coordinated by the Tennessee Population Health Consortium (TN-PHC), was created to combat this issue. The TN-HHN is a statewide network of primary care practices, health systems, and academic centers committed to implementing patient-centered outcomes research (PCOR) approaches to demonstrably improve cardiovascular disease (CVD) health outcomes and health equity across Tennessee.

Objective: Evaluate stakeholder experiences in participating in the Network in an effort to assess partner satisfaction and improve the TN-HHN as a whole.

Methods: Eligible stakeholders were invited via …

Weight Loss In Obese Adults On The Ketogenic Diet, Abigail Velasquez

Master of Science in Nursing Family Nurse Practitioner

The ketogenic diet is a successful and sustainable diet for obese adults to lose weight. One aim of this project is to provide evidentiary support for the ketogenic diet. An additional aim is to disseminate up to date literature to primary care providers in order to offer the ketogenic diet as a sustainable option for weight loss, to reverse disease risk, and, essentially, regain optimal health.

Risk Factors For Cmv And Bk Infections In An Elderly Veteran Population Following Kidney Transplantation: Implications For Immunosuppression Induction And Management, Anne Thorndyke, Cara Joyce, Manpreet Samra, Laura Cotiguala, Christine Trotter, Oswaldo Aguirre, W. James Chon, Rupinder Sodhi, Reynold I. Lopez-Soler

Biostatistics Collaborative Core: Faculty Publications and Other Works

Cytomegalovirus (CMV) and BK Polyomavirus (BKPyV) are the most common opportunistic pathogens following kidney transplantation. We evaluated 102 patients with a median age of 63 at Edward Hines VA Hospital from November 2020 to December 2022. Our primary interest was the incidence of CMV and BKPyV infections, as well as CMV and BKPyV coinfection. Secondary interests included time to infection, rejection, and graft and patient survival. There were no statistically significant differences in patient age, donor age, race, transplant type, incidence of delayed graft function, or induction in both cohorts (any infection (N = 46) vs. those without (N = …

Depression And Anxiety Of Care Partners During The Emergency Department Visit Of Older Adults With Cognitive Impairment, Nancy Glober, Anthony Perkins, Joshua Chodosh, Karen Connor, Sujuan Gao, Frank Messina, Malaz Boustani, Soo Borson, Nicole R. Fowler

Journal of Geriatric Emergency Medicine

Background: Older adults with cognitive impairment (CI) are more likely to visit the emergency department (ED) than those without CI. They are also more likely to suffer poor outcomes after an ED visit. Family and friends who serve as care partners contribute significant time and resources to the care of these patients and may need particular attention to their emotional needs during and after the ED encounter. In this study, we examined the association between patient and care partner characteristics on care partner depression and anxiety at the time of the ED visit.

Methods: Baseline data from 640 patient-care partner …

Acute Myocardial Infarction From A Lower-Middle Income Country-A Comprehensive Report On Performance Measures And Quality Metrics Using National Cardiovascular Data Registry, Farhala Mari Baloch, Ainan Arshad, Sher Sethi, Javed Tai

Section of Cardiology

Introduction: Epidemic of cardiovascular disease (CVD) is widely projected in South Asian population and estimated to get double in two decades. Ischemic heart disease (IHD) is one of the spectrums of CVD and acute myocardial infarction (AMI) being the common manifestations of IHD. National Cardiovascular Data Registry (NCDR) is a registry data that measure their practices and improve quality of care. In this project we aim to see our performance trends in the care of IHD including AMI patients over two year's period.
Material & methods: A cross sectional study conducted at the Aga Khan University Hospital, Karachi, Pakistan. All …

Galectin-3 Cooperates With Cd47 To Suppress Phagocytosis And T-Cell Immunity In Gastric Cancer Peritoneal Metastases, Yibo Fan, Shumei Song, Yuan Li, Shilpa S Dhar, Jiankang Jin, Katsuhiro Yoshimura, Xiaodan Yao, Ruiping Wang, Ailing W Scott, Melissa Pool Pizzi, Jingjing Wu, Lang Ma, George A Calin, Samir Hanash, Linghua Wang, Michael Curran, Jaffer A Ajani

Faculty, Staff and Student Publications

UNLABELLED: The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a "don't eat me" signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that …

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …

Association Of Cardiovascular Disease And Pancreatitis: What Came First, The Chicken Or The Egg?, Bing Chen, Aleena Moin, Hafeez Ul Hassan Virk, Hani Jneid, Salim S Virani, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Background: Recent studies suggest an association between pancreatitis and cardiovascular disease. This article aims to review the available evidence linking cardiovascular disease with acute and chronic pancreatitis.

Methods: A comprehensive search was conducted on the PubMed/MEDLINE database from inception to April 2022 using Medical Subject Heading and keywords related to pancreatitis and cardiovascular disease. The search was limited to English-language literature involving human subjects, and various study types, including observational studies, case-control studies, cohort studies, and clinical trials, were screened for eligibility. Following data extraction, the authors conducted a narrative synthesis of the studies.

Results: Longitudinal studies indicate that a …

Pharmacokinetics And Safety Of A Single Dose Of Telavancin In Pediatric Subjects 2-17 Years Of Age., John S. Bradley, Jennifer Goldman, Laura P. James, Byron Kaelin, Breanne H Y Gibson, Antonio Arrieta

Manuscripts, Articles, Book Chapters and Other Papers

Antimicrobial resistance increases infection morbidity in both adults and children, necessitating the development of new therapeutic options. Telavancin, an antibiotic approved in the United States for certain bacterial infections in adults, has not been examined in pediatric patients. The objectives of this study were to evaluate the short-term safety and pharmacokinetics (PK) of a single intravenous infusion of telavancin in pediatric patients. Single-dose safety and PK of 10 mg/kg telavancin was investigated in pediatric subjects >12 months to ≤17 years of age with known or suspected bacterial infection. Plasma was collected up to 24-h post-infusion and analyzed for concentrations of …

Nad+ Rescues Aging-Induced Blood-Brain Barrier Damage Via The Cx43-Parp1 Axis, Rui Zhan, Xia Meng, Dongping Tian, Jie Xu, Hongtu Cui, Jialei Yang, Yangkai Xu, Mingming Shi, Jing Xue, Weiwei Yu, Gaofei Hu, Ke Li, Xiaoxiao Ge, Qi Zhang, Mingming Zhao, Jianyong Du, Xin Guo, Wenli Xu, Yang Gao, Changyu Yao, Fan Chen, Yue Chen, Wenxin Shan, Yujie Zhu, Liang Ji, Bing Pan, Yan Yu, Wenguang Li, Xuyang Zhao, Qihua He, Xiaohui Liu, Yue Huang, Shengyou Liao, Bin Zhou, Dehua Chui, Y Eugene Chen, Zheng Sun, Erdan Dong, Yongjun Wang, Lemin Zheng

Faculty, Staff and Students Publications

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Indices Of Narrative Language Associated With Disability, Norah M Almubark, Gabriela Silva-Maceda, Matthew E Foster, Trina D Spencer

Faculty, Staff and Student Publications

Narratives skills are associated with long-term academic and social benefits. While students with disabilities often struggle to produce complete and complex narratives, it remains unclear which aspects of narrative language are most indicative of disability. In this study, we examined the association between a variety of narrative contents and form indices and disability. Methodology involved drawing 50 K-3 students with Individual Education Programs (IEP) and reported language concerns from a large diverse sample (n = 1074). Fifty typically developing (TD) students were matched to the former group using propensity score matching based on their age, gender, grade, mother’s education, …

Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano

Faculty, Staff and Student Publications

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 …

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

Importance Of Geriatrics In Psychiatric Postgraduate Education, Dr Anand R, Dr Kishor M, Dr Murali M R

Digital Journal of Clinical Medicine

Introduction

To assess the importance of Geriatrics in Psychiatric postgraduate education

Methodology

Marks allotted in question papers from Geriatrics in Psychiatry postgraduate examination from a university for a 5-year period was evaluated.

Discussion

1-6% of entire theory evaluation was related to Geriatric mental health topics predominantly on dementia and related disorders.

Retrieval Of Large Balloon Fragments During Transcatheter Pulmonary Valve Implantation Using A Novel Retrieval System, Anne C Taylor, Mohamed Ali H Ghandour, Asra Khan, Srinath T Gowda, Flora Nunez-Gallegos, Lynn F Peng, Jamil A Aboulhosn, Daniel S Levi, Doff B Mcelhinney, Athar M Qureshi

Faculty, Staff and Students Publications

The removal of balloon fragments from the pulmonary artery without damaging the pulmonary and tricuspid valves can be difficult. Four cases during transcatheter pulmonary valve replacement are described in which a novel retrieval system was used to facilitate safe removal. (Level of Difficulty: Advanced.)

Knowledge, Attitude, And Perception Of The General Public Towards The Impact Of Hemoglobinopathies On Pregnancy Outcomes: A Questionnaire-Based Study, Kumud Dhankhar, Kiran Dahiya, Shobha Chikkavaddaragudi Ramachandra, Akila Prashant

International Journal of Health and Allied Sciences

Background: Knowledge about hemoglobinopathies in the general public is unsatisfactory. Many couples are unaware of their carrier status and a child can be born with unexpected, serious hemoglobinopathies. Willingness to participate in screening programs can substantially help in bringing down the birth of children affected with hemoglobinopathies. To understand the knowledge, attitude, and perception of the general public on various hemoglobinopathies and their pregnancy outcomes we performed a questionnaire-based descriptive survey. Methods: After obtaining approval from the institutional ethics committee and validation by an expert panel we circulated a Google form consisting of 21 questions via WhatsApp which was made …

Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

EXPERIMENTAL DESIGN: This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor …

Impact Of Climate Change On Surgery: A Scoping Review To Define Existing Knowledge And Identify Gaps, Tina Bharani, Rebecca Achey, Harris Jamal, Alexis Cherry, Malcolm K. Robinson, Guy J. Maddern, Deirdre K. Tobias, Divyansh Agarwal

Department of Surgery Faculty Papers

With climate change accelerated at a worrisome rate, global warming also will have implications for surgery and surgical practice. The goal of this current study was to systematically survey the literature and better understand how climate change has affected surgical disease burden, surgical care delivery, and surgical outcomes. We performed a comprehensive scoping review, screening 3334 unique citations from three databases – 1766 from Embase, 1329 from Pubmed and 239 from Scopus – to identify studies that had associated climate change with surgery. After systematic searching, quality appraisal, and data extraction, we synthesized findings from qualitative and quantitative studies. Twenty-six …

Novel Clinical Trial Designs With Dose Optimization To Improve Long-Term Outcomes, Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel

Faculty, Staff and Student Publications

Conventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective and fail to optimize progression-free survival time, overall survival time, or response/remission duration. We explain and illustrate limitations of conventional dose-finding designs and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses. As illustrations, we review three designs that include one or more of these features. The first illustration is a trial that randomized patients …

Post-Acute Sequelae Of Covid-19 (Pasc) In Pediatrics: Factors That Impact Symptom Severity And Referral To Treatment., Catherine Soprano, Ryan Ngo, Casey A Konys, Ashley Bazier, Katherine Salamon

Department of Medicine Faculty Papers

The post-acute sequelae of COVID-19 (PASC) is a complex condition. While there are emerging studies on its effects in adults, there is scarce research regarding the long-term effects of COVID-19 infection among youth. Several researchers have likened long-haul COVID-19 to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and postural orthostatic tachycardia syndrome (POTS). In adults, the prognosis for these diagnoses is less promising than that in youth; however, there is currently very little information available on the presentation of youth with PASC. A better understanding of the specific symptom presentation for youth diagnosed with PASC is necessary. Retrospective chart reviews were conducted …

Reducing Prescribing Of Antibiotics For Acute Respiratory Infections Using A Frontline Nurse-Led Ehr-Integrated Clinical Decision Support Tool: Protocol For A Stepped Wedge Randomized Control Trial, Elizabeth R Stevens, Ruth Agbakoba, Devin M Mann, Rachel Hess, Safiya I Richardson, Thomas Mcginn, Paul D Smith, Wendy Halm, Marlon P Mundt, Katherine L Dauber-Decker, Simon A Jones, Dawn M Feldthouse, Eun Ji Kim, David A Feldstein

Faculty, Staff and Students Publications

Background: Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model.

Methods: Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested …

Tlr7 Promotes Smoke-Induced Experimental Lung Damage Through The Activity Of Mast Cell Tryptase, Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro

Faculty, Staff and Students Publications

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. …

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …

Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula, Jeramie B Hanson, John R Williams, Emily H Garmon, Phillip M Morris, Russell K Mcallister, Courtney N Shaver, William C Culp

Faculty, Staff and Student Publications

PURPOSE: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates.

METHODS: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, …

The Landscape Of Alterations From 1407 Ultra-Rare Sarcomas From The Aacr Genie Database: Clinical Implications, Ryan A Denu, Justin T Moyers, Mohamed A Gouda, Anthony P Conley, Alexander J Lazar, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental design: Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data.

Results: Soft tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most …