Therapeutics Commons^™

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Comprehensive Review And Update Of Burning Eye Syndrome, Stephen Giacomazzi, Ivan Urits, Briggs Hoyt, Ashley Hubble, Elyse M. Cornett, Kyle Gress, Karina Charipova, Amnon A. Berger, Hisham Kassem, Alan D. Kaye, Omar Viswanath

Journal of Patient-Centered Research and Reviews

Keratoconjunctivitis sicca (“dry eye”) is a common (14%–30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as “burning eye syndrome.” This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome.

Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment …

Intraoperative Administration Of An Nsaid And An Opioid Vs. An Opioid Alone Effect On Postoperative Ileus Development, Brooke H. Ulsh, Delaney N. Vedros, Rebekah G. Whaley, Sharon Little Dnp, Aprn, Fnp-Bc

Doctor of Nursing Practice Projects

The purpose of this DNP project is to examine what is known from existing literature about postoperative ileus development in the adult surgical patient population after receiving intraoperative opioids versus a combination of intraoperative opioids and NSAIDs.

Intraoperative Dexmedetomidine For Reduction Of Postoperative Delirium In The Elderly: A Scoping Review, Gregory B. Harris Bsn, Rn, Srna, Brooke N. Hatchell Bsn, Rn, Srna, Davelin D. Woodard Bsn, Rn, Srna, Dwayne Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background/Purpose: Post-operative delirium leads to significant morbidity in elderly patients, yet there is no regimen to prevent POD. Opioid use in the elderly surgical population is of the most significant risk factors for developing POD. The purpose of this scoping review is to recognize that Dexmedetomidine mitigates cognitive dysfunction secondary to acute pain and the use of narcotic analgesia by decreasing the amount of norepinephrine (an excitatory neurotransmitter) released during times of stress. This mechanism of action also provides analgesia through decreased perception and modulation of pain.

Methods: The authors developed eligibility criteria for inclusion of articles and performed a …

Pain Control: Opioid Vs. Nonopioid Analgesia During The Immediate Postoperative Period, Shamsie M. Lumpkin Bsn, Srna, Isaac W. Parrish Bsn, Srna, Austin S. Terrell Bsn, Srna, Dwayne S. Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background Opioid analgesia has become the mainstay for acute pain management in the postoperative setting. However, the use of opioid medications comes with significant risks and side effects. Due to increasing numbers of prescriptions to those with chronic pain, opioid medications have become more expensive while becoming less effective due to the buildup of patient tolerance. The idea of opioid-free analgesic techniques has rarely been breached in many hospitals. Emerging research has shown that opioid-sparing approaches have resulted in lower reported pain scores across the board, as well as significant cost reductions to hospitals and insurance agencies. In addition to …

Why We Can’T Wait, Mary I. Fisher

Physical Therapy Faculty Publications

No abstract provided.

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Seeking Similarities Rather Than Differences With Adults To Aid In Therapeutic Advancement For Children., Mara L. Becker, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

No abstract provided.

Evaluation Of Somatic Mutations In Solid Metastatic Pan-Cancer Patients, Moom Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Joseph Chao, Chen Chen, Mohd W. Nasser, Ramakanth Chirravuri-Venkata, Maneesh Jain, Lynette Smith, Susan E. Yost, Karen L. Reckamp, Raju Pillai, Leonidas Arvanitis, Michelle Afkhami, Edward W. Wang, Vincent Chung, Mihaela Cristea, Marwan Fakih, Marianna Koczywas, Erminia Massarelli, Joanne Mortimer, Yuan Yuan, Surinder K. Batra, Sumanta Pal, Ravi Salgia

Pharmacy Faculty Articles and Research

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations …

Iatrogenic Electrocautery Damage And Cellular-Based Corrosion Of Total Joint Arthroplasty Biomaterials, Kirsten Carol Miller

Theses and Dissertations (ETD)

Introduction. The number of patients undergoing a Primary Total Knee Arthroplasty (PTKA) has been increasing steadily each year. Of those PTKA patients, 20% report long-term pain and/or some functional deficit. Cobalt-Chromium-Molybdenum (CoCrMo) alloy is one of the most used materials in Total Joint Arthroplasty (TJA) implants due the material’s high strength, high corrosion resistance, and biocompatibility. The release of metal ions and potential occurrence of metallosis in TJA has been shown to be detrimental to the longevity of the implant. The mechanisms leading to this increase in metal ion concentrations have been up for debate, with some believing it is …

Financial Outcomes Of High Flow Nasal Cannula Use For Bronchiolitis On The General Pediatric Floor Across Children's Hospitals, Jonathan Hartley

Research Days

Background: Bronchiolitis is a leading cause of hospitalization for infants and results in over 1.7 billion dollars in yearly hospital charges (Hasegawa). The use of high flow nasal cannula (HFNC) on a general pediatrics floor may reduce hospital costs and length of stay (LOS, Kalburgi). However, the financial impact of HFNC use is not welldescribed.

Objective: The primary objective are the financial outcomes of HFNC utilization on the general pediatric floor. The secondary objective included financial outcomes stratified by All Patients Refined Diagnosis Related Groups (APRDRG) severity of illness (SOI) and payor type. We hypothesize that costs outweigh reimbursement for …

Infliximab As Rescue Therapy In Pediatric Severe Colitis, Kayla B. Briggs

Research Days

Background: Infliximab has been shown to be effective in achieving clinical remission in patients with ulcerative colitis (UC) refractory to conventional therapy. However, there is conflicting data in the literature regarding its effectiveness as rescue therapy in acute severe colitis. Furthermore, most studies were conducted in adults, and pediatric onset of inflammatory bowel disease (IBD) is associated with more severe disease that may be less amenable to rescue therapy.

Objectives/Goal: We reviewed our experience with pediatric severe colitis and report outcomes following attempted rescue therapy with infliximab.

Methods/Design: A retrospective review was conducted of patients with UC or indeterminate colitis …

Impact Of High Flow Nasal Cannula On Resource Utilization In Bronchiolitis, Scott Biggerstaff

Research Days

Background: Bronchiolitis is one of the most common diseases requiring hospitalization in children 1-24 months of age, but presently treatment is primarily supportive. High flow nasal cannula is a newer method of oxygen delivery pediatric hospitals have been rapidly adopting to treat respiratory insufficiency caused by viral bronchiolitis.

Objectives/Goal: We sought to compare resource utilization, including cost, length of stay (LOS), and readmission among children who were treated with HFNC versus those who were not.

Methods/Design: In this cross-sectional, multicenter study, we obtained clinical and resource utilization data from the Pediatric Health Information System (PHIS) database for otherwise healthy children …

Outcomes Of Infants With Severe Rop At Risk Of Treatment With Avastin Compared To Laser Surgery, Stephen Doxey

Research Days

Background: Retinopathy of prematurity (ROP) is a well-known complication occurring in the most premature infants leading to visual impairment and in the most severe cases associated with retinal detachment and childhood blindness. Factors contributing the development of ROP include chronic hypoxia and disordered vascular genesis primarily through the vascular endothelial growth factor (VEGF) signaling pathway. Infants at risk of developing ROP are screened with serial eye exam and treated with either laser surgery or intraocular injects of bevacizumab (Avastin) to prevent progression of ROP and preserve vision. Bevacizumab, an inhibitor of VEGF signaling, may have positive effects on preventing ROP …

Triad Of Acute Pancreatitis Coexisting With Diabetic Ketoacidosis And Very Severe Hypertriglyceridemia Successfully Resolved With Insulin Therapy Alone, Akash Patel, Monica Patel, Yvette Wang

Rowan-Virtua Research Day

Diabetic ketoacidosis (DKA) is known to cause mild elevations in triglyceride levels.

Severe hypertriglyceridemia (HTG) is a well-known cause of acute pancreatitis; however, in unique cases, DKA has been shown to cause severe HTG leading to the development of acute pancreatitis (AP).

HTG causing AP only accounts for 1-4% of cases of AP

From the few cases in literature that have reported this triad of DKA, HTG, and AP, even fewer have shown to be successfully treated with insulin therapy alone with the severe degree of HTG that we discuss.

In our case, we have treated a triad of DKA, …

430— Ifnγ And 5-Aza Drug Effects On Hla Expression In Human Leukemia And Epidermoid Carcinoma, Nick Turnquist

GREAT Day Posters

Human Leukocyte Antigen (HLA) is a gene that codes for cell-surface proteins that are the basis of our bodies’ immune response, and are crucial for the combatting of pathogens or infections. For our experiment we observed two cell lines, a human Leukemia cell line (HL-60), and an epidermoid carcinoma cell line A-431. Our purpose for this experiment was to observe the effects of two drugs as well as the combination of them on the expression of HLA antigens in these cancerous cell lines. The drugs being used in this experiment are Gamma interferon, which is known to increase antigen presentation …

C25: The “Spot Sign”: A Predictor Of Hematoma Expansion, Mckenzie Merritt

Annual Research Symposium

No abstract provided.

We Are People First, Mary I. Fisher

Physical Therapy Faculty Publications

No abstract provided.

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

The Utility Of Hyperbaric Oxygen Therapy In Post-Transplant Cyclophosphamide-Induced Hemorrhagic Cystitis: A Case Report And Review Of The Literature., Moayed Ibrahim, Kshama Bhyravabhotla, Basil Khalaf, Keith Van Meter, Nakhle S Saba, Hana Safah, Francisco Socola

School of Medicine Faculty Publications

Background: To date, there are only a few case reports of cyclophosphamide (Cy)-induced hemorrhagic cystitis (HC) in adult or pediatric allogeneic stem cell transplant (SCT) patients treated successfully with hyperbaric oxygen (HBO). In all the reported cases, Cy was used as a part of the conditioning regimen, rather than post-transplant for graft-versus-host-disease (GVHD) prophylaxis. More recently, the risk of HC in allogeneic SCT is further increased by the widespread use of post-transplantation cyclophosphamide (PTCy) as a highly effective strategy for GVHD prophylaxis. This is the first case reported of PTCy-induced HC successfully treated with HBO to the best of our …

Management Of Refractory Ventricular Fibrillation With Double Sequential Defibrillation, Kaitlyn A. Brown

Capstone Showcase

Patients experiencing cardiac arrest are treated according to ACLS protocols, however current protocols lack recommendations for the treatment of refractory Ventricular Fibrillation which persists after more than 3 cycles of CPR and defibrillation. One potential intervention for these cases that is being researched is the use of simultaneous or sequential activation of two defibrillators. This literature review analyzed the results of several studies to determine if double sequential defibrillation (DSD) is a viable treatment to achieve return of spontaneous circulation (ROSC) and improved patient survival. The results of the studies were mixed with some showing positive outcomes, and others showing …

Efficacy Of Platelet-Rich Plasma (Prp) Injections Vs Topical Minoxidil In Adults With Androgenetic Alopecia, Yuan-Jane Qiu

Capstone Showcase

Androgenetic alopecia is a condition mediated by androgen (specifically DHT) and genetic factors that causes hair loss and thinning of the scalp in men and women. The hairs’ anagen phase is shortened and terminal hairs transition into vellus hairs. Although this condition is considered cosmetic in nature, it has psychologically detrimental effects. There are medical treatments available to prevent further hair loss but there is currently no cure. Topical minoxidil (Rogaine) is the most commonly used medication for androgenetic alopecia that stops hair loss and, in some cases, helps hair regrowth. However, it can cause an allergic contact dermatitis, local …

A Multivariable Model Of Parent Satisfaction, Pain, And Opioid Administration In A Pediatric Emergency Department, Candice D. Donaldson, Thomas W. Heyming, Louis Ehwerhemuepha, Brooke N. Jenkins, Michelle A. Fortier, William Feaster, Zeev N. Kain

Psychology Faculty Articles and Research

Introduction: Children and adolescents are not impervious to the unprecedented epidemic of opioid misuse in the United States. In 2016 more than 88,000 adolescents between the ages of 12–17 reported misusing opioid medication, and evidence suggests that there has been a rise in opioid-related mortality for pediatric patients. A major source of prescribed opioids for the treatment of pain is the emergency department (ED). The current study sought to assess the complex relationship between opioid administration, pain severity, and parent satisfaction with children’s care in a pediatric ED.

Methods: We examined data from a tertiary pediatric care facility. A health …

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

The Use Of Life-Like Robotic Animals In The Acute Care Setting To Assist In The Care Of Patients With Dementia, Abby Denby

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

The purpose of this pilot project was to describe the effect of life-like robotic animals on the nurses’ ability to provide care, patients’ level of agitation, use of antipsychotic medications, restraint and sitter use for patients with dementia in an acute care setting. Nurses report challenges and feelings of helplessness while caring for patients with dementia. Dementia may cause depression, agitation, aggression (physical or verbal) and a decrease quality of life. Animal Assisted Therapy (ATT) is a growing therapy in many healthcare settings but there is a lack of literature specifically related to the use of AAT in the acute …

Anesthetic Use In Status Epilepticus: A Concise Review, Furkan M. Yilmaz, Lauren A. Igneri, Yasir A. Yilmaz, Evren Burakgazi-Dalkilic

Cooper Rowan Medical Journal

The purpose of this review is to summarize the recent literature focusing on intravenous (IV) administration of commonly used anesthetics, including midazolam, pentobarbital/ thiopental, propofol, and ketamine in the treatment of status epilepticus (SE). Anesthetics should be reserved as third-line therapy for the treatment of SE when benzodiazepines and other second-line agents fail to terminate the seizure. We have reviewed the literature related to the treatment of status epilepticus, refractory status epilepticus, super-refractory status epilepticus, anesthetics, midazolam, pentobarbital/thiopental, propofol, and ketamine. This paper focuses on the pharmacology, dosages, major side effects, and clinical use of IV anesthetics in the treatment …

Cyclosporine Shows Benefit As Compared To Methotrexate For Treatment Of Pediatric Atopic Dermatitis Refractory To Topical Medications When Rapidity Of Clinical Response Is Of Key Importance To The Patient, Connor R. Buechler, Steven Daveluy Md

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Training For A Marathon – Responding To A Pandemic, Mary I. Fisher

Physical Therapy Faculty Publications

No abstract provided.

The Clinical Relevance Of Cement Volume In Percutaneous Vertebral Augmentation, Ravi G. Mirpuri, Madhuri Are, Virginia Hardie, Michael J. Warden, Robin High

Graduate Medical Education Research Journal

Introduction: Vertebroplasty and Kyphoplasty are two forms of percutaneous vertebral augmentation (PVA), in which polymethylmethacrylate cement is used to stabilize vertebral compression fractures (VCF). This study sought to evaluate the relationship between cement volume and clinical outcomes, including pain reduction, opioid use, and complication rate.

Methods: Retrospective chart review produced 88 patients who received PVA at a tertiary care outpatient pain clinic. Cement volume, type of PVA, gender, level (thoracic vs lumbar) were collected, as well as clinical outcomes of numeric pain score (NPS) reduction, opioid percent change (OPC), and complications. Both pre-procedure and post-procedure (between 2-4 weeks) data were …