Digital Commons Network^™

Development Of An Outpatient Palliative Care Protocol To Monitor Fidelity In The Emergency Medicine Palliative Care Access Trial., Corita R. Grudzen, Abigail M. Schmucker, Deborah J. Shim, Aminat Ibikunle, Jeanne Cho, Frank R. Chung, Susan E. Cohen

Student Papers, Posters & Projects

Introduction: Palliative care is recommended for patients with life-limiting illnesses; however, there are few standardized protocols for outpatient palliative care visits. To address the paucity of data, this article aims to: (1) describe the elements of outpatient palliative care that are generalizable across clinical sites; (2) achieve consensus about standardized instruments used to assess domains within outpatient palliative care; and (3) develop a protocol and intervention checklist for palliative care clinicians to document outpatient visit elements that might not normally be recorded in the electronic heath record.

Methods: As part of a randomized control trial of nurse-led telephonic case management …

No Meaningful Drug Interactions With Doravirine, Lamivudine And Tenofovir Disoproxil Fumarate Co-Administration., Matt S. Anderson, Jocelyn Gilmartin, Li Fan, Ka Lai Yee, Walter K. Kraft, Ilias Triantafyllou, Christina Reitmann, Ying Guo, Rachael Liu, Marian Iwamoto

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration.

METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment …

Cytoplasmic Daxx Drives Sqstm1/P62 Phase Condensation To Activate Nrf2-Mediated Stress Response., Yi Yang, Thea L. Willis, Robert W. Button, Conor J. Strang, Yuhua Fu, Xue Wen, Portia R.C. Grayson, Tracey Evans, Rebecca J. Sipthorpe, Sheridan L. Roberts, Bing Hu, Jianke Zhang, Boxun Lu, Shouqing Luo

Department of Microbiology and Immunology Faculty Papers

Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters intracellular aberrant proteins and mediates cargo delivery for their selective autophagic degradation. The formation of p62 non-membrane-bound liquid compartments is critical for its function as a cargo receptor. The regulation of p62 phase separation/condensation has yet been poorly characterised. Using an unbiased yeast two-hybrid screening and complementary approaches, we found that DAXX physically interacts with p62. Cytoplasmic DAXX promotes p62 puncta formation. We further elucidate that DAXX drives p62 liquid phase condensation by inducing p62 oligomerisation. This effect promotes p62 recruitment of Keap1 and subsequent Nrf2-mediated …

Optimal Timing And Route Of Nutritional Support After Esophagectomy: A Review Of The Literature., Richard Zheng, Courtney L. Devin, Michael J. Pucci, Adam C. Berger, Ernest L. Rosato, Francesco Palazzo

Department of Surgery Faculty Papers

Some controversy surrounds the postoperative feeding regimen utilized in patients who undergo esophagectomy. Variation in practices during the perioperative period exists including the type of nutrition started, the delivery route, and its timing. Adequate nutrition is essential for this patient population as these patients often present with weight loss and have altered eating patterns after surgery, which can affect their ability to regain or maintain weight. Methods of feeding after an esophagectomy include total parenteral nutrition, nasoduodenal/nasojejunal tube feeding, jejunostomy tube feeding, and oral feeding. Recent evidence suggests that early oral feeding is associated with shorter LOS, faster return of …

Efficacy And Safety Of Intravenous Golimumab Plus Methotrexate In Patients With Rheumatoid Arthritis Aged < 65 Years And Those ≥ 65 Years Of Age., John Tesser, Shelly Kafka, Raphael J. Dehoratius, Stephen Xu, Elizabeth C Hsia, Anthony Turkiewicz

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: To evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged < 65 years and those ≥ 65 years who were enrolled in the GO-FURTHER study.

METHODS: In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, patients with active RA were randomized to intravenous (IV) golimumab 2 mg/kg + MTX or placebo + MTX at weeks 0 and 4, then every 8 weeks thereafter (with crossover to golimumab at week 16 [early escape] or week 24 [per-protocol]). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology (ACR) 20/50/70 response criteria. Efficacy and adverse events (AEs) were monitored through 2 years. …

Editorial: Cancer Ecosystems., Ubaldo E. Martinez-Outshoorn, Mireia Bartrons, Ramon Bartrons

Department of Medical Oncology Faculty Papers

No abstract provided.

Non-Parametric Combination Analysis Of Multiple Data Types Enables Detection Of Novel Regulatory Mechanisms In T Cells Of Multiple Sclerosis Patients., Sunjay Jude Fernandes, Hiromasa Morikawa, Ewoud Ewing, Sabrina Ruhrmann, Rubin Narayan Joshi, Vincenzo Lagani, Nestoras Karathanasis, Mohsen Khademi, Nuria Planell, Angelika Schmidt, Ioannis Tsamardinos, Tomas Olsson, Fredrik Piehl, Ingrid Kockum, Maja Jagodic, Jesper Tegnér, David Gomez-Cabrero

Computational Medicine Center Faculty Papers

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system with prominent neurodegenerative components. The triggering and progression of MS is associated with transcriptional and epigenetic alterations in several tissues, including peripheral blood. The combined influence of transcriptional and epigenetic changes associated with MS has not been assessed in the same individuals. Here we generated paired transcriptomic (RNA-seq) and DNA methylation (Illumina 450 K array) profiles of CD4+ and CD8+ T cells (CD4, CD8), using clinically accessible blood from healthy donors and MS patients in the initial relapsing-remitting and subsequent secondary-progressive stage. By integrating the output of a …

Ip3 Receptor Isoforms Differently Regulate Er-Mitochondrial Contacts And Local Calcium Transfer, Adam Bartok, David Weaver, Tünde Golenár, Zuzana Nichtova, Máté Katona, Száva Bánsághi, Kamil J. Alzayady, V. Kaye Thomas, Hideaki Ando, Katsuhiko Mikoshiba, Suresh K. Joseph, David I. Yule, György Csordás, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP₃ receptors (IP3R) and the mitochondrial calcium uniporter, and are central to cell survival. It remains unclear whether IP3Rs also have a structural role in contact formation and whether the different IP3R isoforms have redundant functions. Using an IP3R-deficient cell model rescued with each of the three IP3R isoforms and an array of super-resolution and ultrastructural approaches we demonstrate that IP3Rs are required for maintaining ER-mitochondrial contacts. This role is independent of calcium fluxes. We also show that, while each isoform can support contacts, type …

Feasibility Pilot Outcomes Of A Mammography Decision Support And Navigation Intervention For Women With Serious Mental Illness Living In Supportive Housing Settings., Lara Weinstein, Marianna Lanoue, Katelyn Hurley, Colleen Payton, Randa Sifri, Ronald Myers

Department of Family & Community Medicine Faculty Papers

Objective: People with serious mental illness (SMI) experience significant disparities in morbidity and mortality from preventable and treatable medical conditions. Women with SMI have low mammography screening rates. SMI, poverty, and poor access to care can have a significant effect on a woman’s opportunity to learn about and discuss breast cancer screening with health care providers. This study examines the feasibility pilot outcomes of mammography decision support and patient navigation intervention (DSNI) for women with SMI living in supportive housing settings. The primary research question was: Does the DSNI increase knowledge, promote favorable attitudes, and decrease decisional conflict relating to …

Equine Or Porcine Synovial Fluid As A Novel Ex Vivo Model For The Study Of Bacterial Free-Floating Biofilms That Form In Human Joint Infections, Jessica M. Gilbertie, Lauren V. Schnabel, Noreen J. Hickok, Megan E. Jacob, Brian P. Conlon, Irving Shapiro, Javad Parvizi, Thomas P. Schaer

Department of Orthopaedic Surgery Faculty Papers

Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such …

Patient Experience And Challenges In Group Concept Mapping For Clinical Research., Geoffrey D. Mills, Marianna Lanoue, Alexzandra T. Gentsch, Amanda M.B. Doty, Amy Cunningham, Garrison Nord, Kristin L. Rising

Department of Emergency Medicine Faculty Papers

BACKGROUND AND OBJECTIVE: Group concept mapping (GCM) is a research method that engages stakeholders in generating, structuring and representing ideas around a specific topic or question. GCM has been used with patients to answer questions related to health and disease but little is known about the patient experience as a participant in the process. This paper explores the patient experience participating in GCM as assessed with direct observation and surveys of participants.

METHODS: This is a secondary analysis performed within a larger study in which 3 GCM iterations were performed to engage patients in identifying patient-important outcomes for diabetes care. …

Inspiration For The Future: The Role Of Inspiratory Muscle Training In Cystic Fibrosis., Ren-Jay Shei, Robert L Dekerlegand, Kelly A Mackintosh, John D Lowman, Melitta A Mcnarry

Department of Physical Therapy Faculty Papers

Cystic fibrosis (CF) is an inherited, multi-system, life-limiting disease characterized by a progressive decline in lung function, which accounts for the majority of CF-related morbidity and mortality. Inspiratory muscle training (IMT) has been proposed as a rehabilitative strategy to treat respiratory impairments associated with CF. However, despite evidence of therapeutic benefits in healthy and other clinical populations, the routine application of IMT in CF can neither be supported nor refuted due to the paucity of methodologically rigorous research. Specifically, the interpretation of available studies regarding the efficacy of IMT in CF is hampered by methodological threats to internal and external …

Identification Of Emergency Care-Sensitive Conditions And Characteristics Of Emergency Department Utilization., Anita A. Vashi, Tracy Urech, Brendan Carr, Liberty Greene, Theodore Warsavage, Renee Hsia, Steven M. Asch

Department of Emergency Medicine Faculty Papers

Importance: Monitoring emergency care quality requires understanding which conditions benefit most from timely, quality emergency care.

Objectives: To identify a set of emergency care-sensitive conditions (ECSCs) that are treated in most emergency departments (EDs), are associated with a spectrum of adult age groups, and represent common reasons for seeking emergency care and to provide benchmark national estimates of ECSC acute care utilization.

Design, Setting, and Participants: A modified Delphi method was used to identify ECSCs. In a cross-sectional analysis, ECSC-associated visits by adults (aged ≥18 years) were identified based on International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis …

How To Untie A Protein Knot., Sitao Yin, Brittiny Dhital, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

The origin of protein backbone threading through a topological knot remains elusive. To understand the evolutionary origin of protein knots, in this issue of StructureKo et al. (2019) used circular permutation to untie a knotted protein. They showed that a domain-swapped dimer releases the knot and the associated high-energy state for substrate binding.

Non-Thermal Plasma-Induced Immunogenic Cell Death In Cancer: A Topical Review., Marian Khalili, Lynsey Daniels, Abraham Lin, Fred C. Krebs, Adam E. Snook, Sander Bekeschus, Wilbur B. Bowne, Vandana Miller

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational …

The Debate Over The Efficacy Of Federal Hate Crime Legislation: A Look At Arlen Specter’S Senatorial Efforts And Its Legacy, Sierra Reddi

Arlen Specter Center Research Fellowship

Bias-motivated violence is considered especially heinous in the United States of America. This research examines the Federal legislation that cements that value into law. Hate crimes are criminal acts where the target was specifically chosen because of their race, sexual orientation, gender expression, ethnicity, or religion. These crimes, whether intentionally or not, have a ripple effect on societal values, and especially spread fear within oppressed minority groups. This research begins by examining the context that precipitated a need for hate crime laws to begin with and then looks at federal developments as a reaction to landmark hate crime cases. One …

Appropriate Therapeutic Drug Monitoring Of Biologic Agents For Patients With Inflammatory Bowel Diseases., Konstantinos Papamichael, Adam S. Cheifetz, Gil Y. Melmed, Peter M. Irving, Niels Vande Casteele, Patricia L. Kozuch, Laura E. Raffals, Leonard Baidoo, Brian Bressler, Shane M. Devlin, Jennifer Jones, Gilaad G. Kaplan, Miles P. Sparrow, Fernando S Velayos, Thomas Ullman, Corey A. Siegel

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD.

METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) …

Understanding The Axonal Response To Injury By In Vivo Imaging In The Mouse Spinal Cord: A Tale Of Two Branches., Binhai Zheng, Ariana O Lorenzana, Le Ma

Department of Neuroscience Faculty Papers

Understanding the basic properties of how axons respond to injury in the mammalian central nervous system (CNS) is of fundamental value for developing strategies to promote neural repair. Axons possess complex morphologies with stereotypical branching patterns. However, current knowledge of the axonal response to injury gives little consideration to axonal branches, nor do strategies to promote axon regeneration. This article reviews evidence from in vivo spinal cord imaging that axonal branches markedly impact the degenerative and regenerative responses to injury. At a major bifurcation point, depending on whether one or both axonal branches are injured, neurons may choose either a …

The Case For Patient Navigation In Lung Cancer Screening In Vulnerable Populations: A Systematic Review., Christine S Shusted, Julie A Barta, Michael Lake, Rickie Brawer, Brooke Ruane, Teresa E Giamboy, Baskaran Sundaram, Nathaniel R Evans, Ronald E Myers, Gregory C Kane

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Patient navigation has been proposed to combat cancer disparities in vulnerable populations. Vulnerable populations often have poorer cancer outcomes and lower levels of screening, adherence, and treatment. Navigation has been studied in various cancers, but few studies have assessed navigation in lung cancer. Additionally, there is a lack of consistency in metrics to assess the quality of navigation programs. The authors conducted a systematic review of published cancer screening studies to identify quality metrics used in navigation programs, as well as to recommend standardized metrics to define excellence in lung cancer navigation. The authors included 26 studies evaluating navigation metrics …

Primary Care Providers' Attitudes And Practices Regarding Cancer Screening In Older Adults., Randa Sifri, Brooke Salzman, Amy Cunningham, Alexis Silverio, Madalene Zale, Christine Talerico

Department of Family & Community Medicine Faculty Papers

Introduction: Cancer-screening decisions for older adults should be individualized. However, conducting such complex shared decisions may be challenging for primary care providers (PCPs). Additionally, there is little information on how PCPs make these decisions. This study consisted of a provider survey and chart review to assess current PCP approaches to breast and colorectal cancer (CRC) screening with patients age ≥75.

Methods: PCP survey questions: panel age, comfort with discussion of screening harms and benefits, screening decision-making process, and discussion style. One Hundred charts were chosen from a random sample of male and female patients ≥75 with a recent office …

Unilateral Enophthalmos., Grace L. Su, Sara E. Lally, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Effects Of The 2017 Clinical Practice Guidelines On Hypertension In Children And Adolescents: A Commentary, Bonita Falkner

Department of Medicine Faculty Papers

No abstract provided.

Prevalence Of Dyskinesia And Off By 30-Minute Intervals Through The Day And Assessment Of Daily Episodes Of Dyskinesia And Off: Novel Analyses Of Diary Data From Gocovri Pivotal Trials., Robert A. Hauser, Daniel Kremens, Lawrence W. Elmer, David L. Kreitzman, Ryan R. Walsh, Reed Johnson, Robert Howard, Jack T. Nguyen, Rajiv Patni

Department of Neurology Faculty Papers

BACKGROUND: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing …

Fetal Fibronectin Testing For Reducing The Risk Of Preterm Birth., Vincenzo Berghella, Gabriele Saccone

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for …

What Can Ai Do For You?, Andrew Braverman, Jarrod Combs-Harris

School of Continuing and Professional Studies Student Papers

Simply put, most organizations do not know how to approach the incorporation of AI into their businesses, and few are knowledgeable enough to understand which concepts are applicable to their business models. Doing nothing and waiting is not an option: Mahidar and Davenport (2018) argue that companies that try to play catch-up will ultimately lose to those who invested and began learning early. But how do we bridge the gap between skepticism and adoption? We propose a toolkit, inclusive of people, processes, and technologies, to help companies with discovery and readiness to start their AI journey. Our toolkit will deliver …

Report Of The First Patient Treated For Pelvic Sarcoma With A Directional 103pd Brachytherapy Device., Serguei A. Castaneda, Marian Khalili, Jacqueline Emrich, Veronica M Zoghbi, Michael S Weingarten, Mark J Rivard, Wilbur B Bowne, Jaganmohan Poli

Department of Radiation Oncology Faculty Papers

No abstract provided.

Functionalization Of Cd36 Cardiovascular Disease And Expression Associated Variants By Interdisciplinary High Throughput Analysis., Namrata Madan, Andrew R. Ghazi, Xianguo Kong, Edward S. Chen, Chad A. Shaw, Leonard C. Edelstein

Department of Medicine Faculty Papers

CD36 is a platelet membrane glycoprotein whose engagement with oxidized low-density lipoprotein (oxLDL) results in platelet activation. The CD36 gene has been associated with platelet count, platelet volume, as well as lipid levels and CVD risk by genome-wide association studies. Platelet CD36 expression levels have been shown to be associated with both the platelet oxLDL response and an elevated risk of thrombo-embolism. Several genomic variants have been identified as associated with platelet CD36 levels, however none have been conclusively demonstrated to be causative. We screened 81 expression quantitative trait loci (eQTL) single nucleotide polymorphisms (SNPs) associated with platelet CD36 expression …

Do Employees From Less-Healthy Communities Use More Care And Cost More? Seeking To Establish A Business Case For Investment In Community Health., Russell K. Mcintire, Martha C. Romney, Greg Alonzo, Jill Hutt, Lauren Bartolome, Greg Wood, Gary Klein, Neil I. Goldfarb

College of Population Health Faculty Papers

INTRODUCTION: Few studies have examined the impact of community health on employers. We explored whether employed adults and their adult dependents living in less-healthy communities in the greater Philadelphia region used more care and incurred higher costs to employers than employees from healthier communities.

METHODS: We used a multi-employer database to identify adult employees and dependents with continuous employment and mapped them to 31 zip code regions. We calculated community health scores at the regional level, by using metrics similar to the Robert Wood Johnson Foundation (RWJF) County Health Rankings but with local data. We used descriptive analyses and multilevel …

Assessment Of The Risk And Characterization Of Non-Melanoma Skin Cancer In Kindler Syndrome: Study Of A Series Of 91 Patients., Sara Guerrero-Aspizua, Claudio J. Conti, Maria Jose Escamez, Daniele Castiglia, Giovanna Zambruno, Leila Youssefian, Hassan Vahidnezhad, Luis Requena, Peter Itin, Gianluca Tadini, Ivelina Yordanova, Ludovic Martin, Jouni Uitto, Cristina Has, Marcela Del Rio

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of …

Cleavage And Sub-Cellular Redistribution Of Nuclear Pore Protein 98 By Coxsackievirus B3 Protease 2a Impairs Cardioprotection., Paul J. Hanson, Al Rohet Hossain, Ye Qiu, Huifang M. Zhang, Guangze Zhao, Cheng Li, Veena Lin, Saheedat Sulaimon, Marli Vlok, Gabriel Fung, Victoria H. Chen, Eric Jan, Bruce M. Mcmanus, David J. Granville, Decheng Yang

College of Population Health Faculty Papers

Myocarditis, inflammation of the heart muscle, affects all demographics and is a major cause of sudden and unexpected death in young people. It is most commonly caused by viral infections of the heart, with coxsackievirus B3 (CVB3) being among the most prevalent pathogens. To understand the molecular pathogenesis of CVB3 infection and provide strategies for developing treatments, we examined the role of a key nuclear pore protein 98 (NUP98) in the setting of viral myocarditis. NUP98 was cleaved as early as 2 h post-CVB3 infection. This cleavage was further verified through both the ectopic expression of viral proteases and in …