Digital Commons Network^™

Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy

Department of Emergency Medicine Faculty Papers

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as …

A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey

Department of Medicine Faculty Papers

PURPOSE: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease.

METHODS: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as …

Utstein Recommendation For Emergency Stroke Care, A. Rudd, P. Panagos, Et Al

2020-Current year OA Pubs

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient.

AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients.

METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain …

Mechanism Of Ligand Activation Of A Eukaryotic Cyclic Nucleotide-Gated Channel, Xiangdong Zheng, Ziao Fu, Deyuan Su, Yuebin Zhang, Minghui Li, Yaping Pan, Huan Li, Shufang Li, Robert A Grassucci, Zhenning Ren, Zhengshan Hu, Xueming Li, Ming Zhou, Guohui Li, Joachim Frank, Jian Yang

Faculty, Staff and Students Publications

Cyclic nucleotide-gated (CNG) channels convert cyclic nucleotide (CN) binding and unbinding into electrical signals in sensory receptors and neurons. The molecular conformational changes underpinning ligand activation are largely undefined. We report both closed- and open-state atomic cryo-EM structures of a full-length Caenorhabditis elegans cyclic GMP-activated channel TAX-4, reconstituted in lipid nanodiscs. These structures, together with computational and functional analyses and a mutant channel structure, reveal a double-barrier hydrophobic gate formed by two S6 amino acids in the central cavity. cGMP binding produces global conformational changes that open the cavity gate located ~52 Å away but do not alter the structure …

Renal Trajectory Patterns Are Associated With Postdischarge Mortality In Patients With Cirrhosis And Acute Kidney Injury, Ayse L Mindikoglu, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Thomas Taylor, Abbas Rana, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Little is known about long-term outcomes of acute kidney injury (AKI) in patients with cirrhosis. Outcomes can vary with stage of AKI, chronic kidney disease, and trajectory of renal function.

METHODS: We collected data from the Department of Veterans Affairs and identified 6917 patients with cirrhosis who developed AKI during hospitalization at any of its 127 hospitals, from 2004 through 2014. We used latent class analysis of serial creatinine measurements during the index hospitalization to determine trajectories of renal function.

RESULTS: Overall, 32% of patients died within 90 days of discharge from the hospital and 48% of …

Systematic Review With Meta-Analysis: Prevalence Of Prior And Concurrent Barrett’S Oesophagus In Oesophageal Adenocarcinoma Patients, Mimi C Tan, Nabil Mansour, Donna L White, Amy Sisson, Hashem B El-Serag, Aaron P Thrift

Library Staff Publications

BACKGROUND: The proportions of patients with oesophageal adenocarcinoma (OAC) diagnosed by Barrett's oesophagus surveillance or with pre-existing Barrett's oesophagus are unclear.

AIM: To estimate the prevalence of prior and concurrent Barrett's oesophagus diagnosis among patients with OAC or oesophagogastric junction adenocarcinomas (OGJAC).

METHODS: We searched PubMed and Embase to identify studies published 1966-1/8/2020 that examined the prevalence of prior (≥6 months) or concurrent Barrett's diagnosis (at cancer diagnosis) among OAC and OGJAC patients. Random effects models estimated overall and stratified pooled prevalence rates.

RESULTS: A total of 69 studies, including 33 002 OAC patients (53 studies) and 2712 patients with …

Nuclear Localization Of A Novel Calpain-2 Mediated Junctophilin-2 C-Terminal Cleavage Peptide Promotes Cardiomyocyte Remodeling, Satadru K Lahiri, Ann P Quick, Benoit Samson-Couterie, Mohit Hulsurkar, Ies Elzenaar, Ralph J Van Oort, Xander H T Wehrens

Faculty, Staff and Students Publications

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Patients with HF exhibit a loss of junctophilin-2 (JPH2), a structural protein critical in forming junctional membrane complexes in which excitation-contraction takes place. Several mechanisms have been proposed to mediate the loss of JPH2, one being cleavage by the calcium-dependent protease calpain. The downstream mechanisms underlying HF progression after JPH2 cleavage are presently poorly understood. In this study, we used Labcas to bioinformatically predict putative calpain cleavage sites on JPH2. We identified a cleavage site that produces a novel C-terminal JPH2 peptide (JPH2-CTP) using several domain-specific antibodies. Western …

Vitamin A And Fish Oils For Preventing The Progression Of Retinitis Pigmentosa., Stephen G. Schwartz, Xue Wang, Pamela Chavis, Ajay E. Kuriyan, Samuel A. Abariga

Wills Eye Hospital Papers

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.

OBJECTIVES: The objective of this review was to …

Veterinarians’ Attitudes And Practices Regarding Opioid-Related Vet Shopping Practices In Tri-State Appalachian Counties: An Exploratory Study, Falguni C Patel, Jeffrey A Raines, Richard W Kim, Karen Gruszynski, Robert E Davis, Manoj Sharma, Gilbert Patterson, Jason W Johnson, Vinayak K Nahar

Faculty, Staff and Students Publications

BACKGROUND: The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States.

RESULTS: …

Cost-Effectiveness And Diagnostic Accuracy Of Telemedicine In Macular Disease And Diabetic Retinopathy: A Systematic Review And Meta-Analysis., Waqas Ullah, Sana Khan Pathan, Ankur Panchal, Swapna Anandan, Kaiser Saleem, Yasar Sattar, Ejaz Ahmad, Maryam Mukhtar, Haq Nawaz

Abington Jefferson Health Papers

OBJECTIVE: To determine cost-effectiveness and the diagnostic accuracy of teleophthalmology (TO) in the detection of macular edema (ME) and various grades of diabetic retinopathy (DR).

METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for TO, ME, and DR on May 25, 2016. The search was updated on April 2, 2019. Pooled sensitivity and specificity for ME and various grades of DR were determined using Meta-Disc software. A systematic review of the articles discussing the cost-effectiveness of TO screening was also performed.

RESULTS: Thirty-three articles on the diagnostic accuracy and 28 articles on the cost-effectiveness were selected.

CONCLUSIONS: Telescreening is moderately …

Quantitative Measures Of Health Policy Implementation Determinants And Outcomes: A Systematic Review, Peg Allen, Meagan Pilar, Callie Walsh-Bailey, Cole Hooley, Stephanie Mazzucca, Cara C Lewis, Kayne D Mettert, Caitlin N Dorsey, Jonathan Purtle, Maura M Kepper, Ana A Baumann, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Public policy has tremendous impacts on population health. While policy development has been extensively studied, policy implementation research is newer and relies largely on qualitative methods. Quantitative measures are needed to disentangle differential impacts of policy implementation determinants (i.e., barriers and facilitators) and outcomes to ensure intended benefits are realized. Implementation outcomes include acceptability, adoption, appropriateness, compliance/fidelity, feasibility, penetration, sustainability, and costs. This systematic review identified quantitative measures that are used to assess health policy implementation determinants and outcomes and evaluated the quality of these measures.

METHODS: Three frameworks guided the review: Implementation Outcomes Framework (Proctor et al.), Consolidated …

Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A …

Linking Activity, Nutrition, And Child Health (Launch): Protocol For A Longitudinal Cohort Study Of Children As They Develop From Infancy To Preschool Age, Russell R. Pate, Edward A. Frongillo Jr., Kerry Cordan, Marsha Dowda, Alexander C. Mclain, Myriam E. Torres, William H. Brown, Agnes Bucko, Emily R. Shull

Faculty Publications

Background

Physical activity is known to provide important health benefits in children ages 3 years and above, but little is known about the effects of physical activity on health in very young children under age 3. LAUNCH (Linking Activity, Nutrition, and Child Health) is a study designed to expand the body of knowledge on development of physical activity behavior and associations between physical activity and other health characteristics as children transition from infancy to preschool age.

Methods

Physical activity and sedentary behavior will be measured objectively in young children over a period of 30 months. Each child will complete a …

Covid-19 Medical Papers Have Fewer Women First Authors Than Expected., Jens Peter Andersen, Mathias Wullum Nielsen, Nicole L Simone, Resa E Lewiss, Reshma Jagsi

Department of Radiation Oncology Faculty Papers

The COVID-19 pandemic has resulted in school closures and distancing requirements that have disrupted both work and family life for many. Concerns exist that these disruptions caused by the pandemic may not have influenced men and women researchers equally. Many medical journals have published papers on the pandemic, which were generated by researchers facing the challenges of these disruptions. Here we report the results of an analysis that compared the gender distribution of authors on 1893 medical papers related to the pandemic with that on papers published in the same journals in 2019, for papers with first authors and last …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Zooming-Out Covid-19: Virtual Clinical Experiences In An Emergency Medicine Clerkship., Shruti Chandra, Chaiya Laoteppitaks, Nina Mingioni, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

In the setting of the novel 2019 coronavirus (COVID‐19) pandemic, it has been challenging to provide medical students in the Emergency Medicine (EM) clerkship meaningful clinical experiences that would meet clinical course goals and objectives, as well as satisfy Liaison Committee for Medical Education (LCME) requirements. During the EM clerkship, students play an integral role in interviewing patients, formulating treatment plans, facilitating patient discharges, and counseling patients. Immediately available direct and indirect supervision are paramount to ensure student learning and safe patient care. The authors present a novel clinical educational experience for senior medical students in an EM clerkship that …

Aav-Crispr Gene Editing Is Negated By Pre-Existing Immunity To Cas9, Ang Li, Mark R Tanner, Ciaran M Lee, Ayrea E Hurley, Marco De Giorgi, Kelsey E Jarrett, Timothy H Davis, Alexandria M Doerfler, Gang Bao, Christine Beeton, William R Lagor

Faculty, Staff and Students Publications

Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by …

Randomized Controlled Trial Of A Multilevel Intervention To Address Social Determinants Of Refugee Mental Health, Jessica R. Goodkind, Deborah Bybee, Julia Meredith Hess, Suha Amer, Martin Ndayisenga, R Neil Greene, Ryeora Choe, Brian Isakson, Brandon Baca, Mahbooba Pannah

Pediatrics Research and Scholarship

Understanding processes that support the well-being of the unprecedented numbers of forcibly displaced people throughout the world is essential. Growing evidence documents post-migration stressors related to marginalization as key social determinants of refugee mental health. The goal of this RCT was to rigorously test a social justice approach to reducing high rates of distress among refugees in the United States. The 6-month multilevel, strengths-based Refugee Well-being Project (RWP) intervention brought together university students enrolled in a 2-semester course and recently resettled refugees to engage in mutual learning and collaborative efforts to mobilize community resources and improve community and systems responsiveness …

Does Empathy Decline In The Clinical Phase Of Medical Education? A Nationwide, Multi-Institutional, Cross-Sectional Study Of Students At Do-Granting Medical Schools, Mohammadreza Hojat, Stephen C. Shannon, Jennifer Desantis, Mark R. Speicher, Lynn Bragan, Leonard H. Calabrese

CRMEHC Faculty Papers

PURPOSE: To examine differences in students' empathy in different years of medical school in a nationwide study of students of U.S. DO-granting medical schools.

METHOD: Participants in this cross-sectional study included 10,751 students enrolled in 41 of 48 campuses of DO-granting medical schools in the United States (3,616 first-year, 2,764 second-year, 2,413 third-year, and 1,958 fourth-year students). They completed a web-based survey at the end of the 2017-2018 academic year that included the Jefferson Scale of Empathy and the Infrequency Scale of the Zuckerman-Kuhlman Personality Questionnaire for measuring "good impression" response bias. Comparisons were made on empathy scores among students …

Relationships Of P16 Immunohistochemistry And Other Biomarkers With Diagnoses Of Cervical Abnormalities: Implications For Last Terminology, Philip E. Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E. Torrez-Martinez, Salina M. Torres, Mark H. Stoler, Brigitte M. Ronnett, Nancy E. Joste, Teresa M. Darragh, Patti E. Gravitt, Mark Schiffman, William C. Hunt, Walter K. Kinney, Cosette M. Wheeler

Pathology Research and Scholarship

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16

OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Prediction Of Trimethoprim/Sulfamethoxazole Resistance In Community-Onset Urinary Tract Infections, Madeline Demarsh, P Brandon Bookstaver, Caroline Gordon, Juanne Lim, Nicole Griffith, Nicole K. Bookstaver, Julie Ann Justo, Joseph Kohn, Majdi N. Al-Hasan

Faculty Publications

OBJECTIVES: This study aimed to predict trimethoprim/sulfamethoxazole (SXT) resistance in patients with community-onset urinary tract infection (UTI) due to Enterobacteriaceae based on patient-specific risk factors. METHODS: This was a retrospective case-control study in Prisma Health facilities in central South Carolina, USA, including three community hospitals, affiliated emergency departments and ambulatory clinics, including adult patients with community-onset UTI due to Enterobacteriaceae (1 April 2015 to 29 February 2016). Multivariate logistic regression was used to examine risk factors for SXT resistance. RESULTS: Among 351 unique patients with community-onset UTI, 71 (20.2%) had SXT-resistant Enterobacteriaceae urinary isolates. Overall, median age was 64 years …

Elagolix Treatment For Up To 12 Months In Women With Heavy Menstrual Bleeding And Uterine Leiomyomas, James A Simon, Ayman Al-Hendy, David F Archer, Kurt T Barnhart, Linda D Bradley, Bruce R Carr, Thomas Dayspring, Eve C Feinberg, Veronica Gillispie, Sandra Hurtado, Jinhee Kim, Ran Liu, Charlotte D Owens, Ozgul Muneyyirci-Delale, Alice Wang, Nelson B Watts, William Schlaff

Department of Obstetrics and Gynecology Faculty Papers

Objective: To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas.

Methods: Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of …

Our Duty Of Care In Pandemic Times, Perryn Ng

The Texas Heart Institute Journal

No abstract provided.

Incidental Cannulation Of Left Ventricular Thebesian Vein, Kalyan Chakravarthy Potu, Jay N Patel, Majd Ibrahim, Sujitha Sree Ketineni, Sudhir Mungee

The Texas Heart Institute Journal

No abstract provided.

Beyond An Updated Graded Prognostic Assessment (Breast Gpa): A Prognostic Index And Trends In Treatment And Survival In Breast Cancer Brain Metastases From 1985 To Today, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Faculty, Staff and Student Publications

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 …

Role Of Micro-Rna For Pain After Surgery: Narrative Review Of Animal And Human Studies, Juan P Cata, Aysegul Gorur, Xiaoyi Yuan, Nathaniel K Berg, Anil K Sood, Holger K Eltzschig

Faculty, Staff and Student Publications

One of the most prevalent symptoms after major surgery is pain. When postoperative pain treatment is unsatisfactory, it can lead to poor surgical recovery, decreased quality of life, and increased health care costs. Current analgesics, single or in combination, have limited efficacy due to low potency, limited duration of action, toxicities, and risk of addiction. The lack of nonaddictive strong analgesics along with the over prescription of opioids has led to an opioid epidemic in the United States. Therefore, there is an urgent need for the development of newer analgesics. Microribonucleic acids (miRNAs) are small noncoding RNA molecules that modulate …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase Ii, Randomized, Double-Blind, Placebo-Controlled Study (Energize), W Frank Peacock, Zubaid Rafique, Konstantin Vishnevskiy, Edward Michelson, Elena Vishneva, Tatiana Zvereva, Rajaa Nahra, Dao Li, Joseph Miller

Faculty, Staff and Students Publications

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum …

Surgical Endoepicardial Linear Ablation For Ventricular Tachycardia With Postinfarction Left Ventricular Aneurysm, Changcheng Liu, Zhaoping Su, Liangshan Wang, Bo Li, Jin Wang, Yang Yu, Chengxiong Gu

The Texas Heart Institute Journal

This retrospective study evaluated the feasibility of surgical endoepicardial linear ablation for ventricular tachycardia in patients with postinfarction left ventricular aneurysm. Sixty-four patients with multivessel coronary artery disease and left ventricular aneurysm but no mural thrombosis of the aneurysm or valve disease were treated at our institution from March 2012 through July 2015. All underwent off-pump coronary artery bypass grafting and left ventricular aneurysm repair by linear plication. Twenty-three patients (35.9%) had ventricular tachycardia and underwent surgical endoepicardial linear ablation on the beating heart guided by epicardial substrate mapping with the Carto 3 system. The remaining 41 patients (64.1%) composed …