Medical Specialties Commons^™

Bi-Allelic Variants In Ogdhl Cause A Neurodevelopmental Spectrum Disease Featuring Epilepsy, Hearing Loss, Visual Impairment, And Ataxia, Zheng Yie Yap, Stephanie Efthymiou, Simone Seiffert, Karen Vargas Parra, Sukyeong Lee, Alessia Nasca, Reza Maroofian, Isabelle Schrauwen, Manuela Pendziwiat, Sunhee Jung, Elizabeth Bhoj, Pasquale Striano, Kshitij Mankad, Barbara Vona, Sanmati Cuddapah, Anja Wagner, Javeria Raza Alvi, Elham Davoudi-Dehaghani, Mohammad-Sadegh Fallah, Srinitya Gannavarapu, Costanza Lamperti, Andrea Legati, Bibi Nazia Murtaza, Muhammad Shahid Nadeem, Mujaddad Ur Rehman, Kolsoum Saeidi, Vincenzo Salpietro, Sarah Von Spiczak, Abigail Sandoval, Sirous Zeinali, Massimo Zeviani, Adi Reich, Synaps Study Group, University Of Washington Center For Mendelian Genomics, Cholsoon Jang, Ingo Helbig, Tahsin Stefan Barakat, Daniele Ghezzi, Suzanne M Leal, Yvonne Weber, Henry Houlden, Wan Hee Yoon

Faculty, Staff and Students Publications

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the …

Imaging And Treatment Of Posttraumatic Ankle And Hindfoot Osteoarthritis, Tetyana Gorbachova, Yulia V. Melenevsky, L. Daniel Latt, Jennifer S. Weaver, Mihra S. Taljanovic

Department of Radiology Faculty Papers

Posttraumatic osteoarthritis of the ankle and hindfoot is a common and frequently debil-itating disorder. 70% to 90% of ankle osteoarthritis is related to prior trauma that encompasses a spectrum of disorders including fractures and ligamentous injuries that either disrupt the articular surface or result in instability of the joint. In addition to clinical evaluation, imaging plays a sub-stantial role in the treatment planning of posttraumatic ankle and hindfoot osteoarthritis. Imaging evaluation must be tailored to specific clinical scenarios and includes weight bearing radiography that utilizes standard and specialty views, computed tomography which can be performed with a standard or a …

Durable Response To Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, And Prednisone (Bv-Chp) In A Patient With Cd30-Positive Ptcl Arising As A Post-Transplant Lymphoproliferative Disorder (Ptld), Jennifer Hong, William T Johnson, Saritha Kartan, Anitha S Gonsalves, Jonathan M. Fenkel, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. …

Reduced Risk Of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From A United States Claims Database, Chengyuan Wu, Sean J Nagel, Rahul Agarwal, Monika Pötter-Nerger, Wolfgang Hamel, Ashwini Sharan, Allison T Connolly, Binith Cheeran, Paul S Larson

Department of Neurosurgery Faculty Papers

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson's disease (PD) or essential tremor (ET) in the United States.

Design: Retrospective, contemporaneous cohort study.

Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018.

Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, …

Genetic Susceptibility To Hepatocellular Carcinoma In Chromosome 22q13.31, Findings Of A Genome-Wide Association Study., Zhanwei Wang, Anuradha S Budhu, Yi Shen, Linda Lou Wong, Brenda Y Hernandez, Maarit Tiirikainen, Xiaomei Ma, Melinda L Irwin, Lingeng Lu, Hongyu Zhao, Joseph K Lim, Tamar Taddei, Lopa Mishra, Karen Pawlish, Antoinette Stroup, Robert Brown, Mindie H Nguyen, Jill Koshiol, Maria O Hernandez, Marshonna Forgues, Hwai-I Yang, Mei-Hsuan Lee, Yu-Han Huang, Motoki Iwasaki, Atsushi Goto, Shiori Suzuki, Koichi Matsuda, Chizu Tanikawa, Yoichiro Kamatani, Dean Mann, Maria Guarnera, Kirti Shetty, Claire E Thomas, Jian-Min Yuan, Chiea Chuen Khor, Woon-Puay Koh, Harvey Risch, Xin Wei Wang, Herbert Yu

Surgery Faculty Publications

Background and Aim: Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS).

Methods: Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and …

Accidental Ocular Rocuronium Exposure., Ayal Z Pierce, Sonal Batra, Bailey Norberg

Emergency Medicine Faculty Publications

No abstract provided.

Gender Analysis Of Publishing Among Medical Students In Dermatology, Michelle Militello, Mindy D. Szeto, Kayd J. Pulsipher, Abigail L. Meckley, Kristen H. Ward, Taylor Harp, Colby L. Presley, Cara Barber, Hope R. Rietcheck, Taylor M. Runion, Chandler W. Rundle, Robert P. Dellavalle

Research and Historical Works - 2021

No abstract provided.

Ambulatory Patients With A Central Line Presenting With A Fever, Children's Mercy Kansas City

Clinical Pathways (Formally Known As Care Process Models)

No abstract provided.

Pulmonary Embolism, Suspected, Children's Mercy Kansas City

Clinical Pathways (Formally Known As Care Process Models)

No abstract provided.

Placental Infarction And Intrauterine Growth Restriction Following Sars-Cov-2 Infection, Stephanie Moltner, Barbra De Vrijer, Harrison Banner

Paediatrics Publications

No abstract provided.

The Fatigue Paradox: Team Perceptions Of Physician Fatigue, Emily Field, Lorelei Lingard, Richard Cherry, Julie Ann Van Koughnett, Sandra Deluca, Taryn Taylor

Obstetrics & Gynaecology Publications

OBJECTIVES: Ongoing calls to implement fatigue risk management in residency education assume a shared understanding of physician fatigue as a workplace hazard, yet we lack empirical evidence that all health care team members maintain this assumption. Thus, this study seeks to explore how health care team members understand the role of physician fatigue in an effort to inform the implementation of fatigue risk management in residency training and medical practice.

METHODS: This study uses constructivist grounded theory to explore perceptions of workplace fatigue and its impact on clinical practice. We conducted individual semi-structured interviews with physicians, nurses and senior residents …

The Intranasal Dexmedetomidine Plus Ketamine For Procedural Sedation In Children, Adaptive Randomized Controlled Non-Inferiority Multicenter Trial (Ketodex): A Statistical Analysis Plan, Anna Heath, Juan David Rios, Eleanor Pullenayegum, Petros Pechlivanoglou, Martin Offringa, Maryna Yaskina, Rick Watts, Shana Rimmer, Terry P. Klassen, Kamary Coriolano, Naveen Poonai, Darcy Beer, Scott Sawyer, Maala Bhatt, April Kam, Quynh Doan, Vikram Sabhaney, Serena Hickes, Samina Ali, Karly Stillwell, Tannis Erickson, Chelsea Bowkett, Chelsea Bowkett, Carolyn Shimmin, Brendon Foot, Candace Mcgahern, Redjana Carciurmaruj, Jeannine Schellenberg

Paediatrics Publications

Background: Procedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide …

Choosing Wisely Canada – Pediatric Otolaryngology Recommendations, Mitchell Mcdonough, Kalpesh Hathi, Gerard Corsten, Christopher J. Chin, Paolo Campisi, Jonathan Cavanagh, Neil Chadha, M. Elise Graham, Murad Husein, Liane B. Johnson, Jodi Jones, Bruce Korman, John Manoukian, Lily H.P. Nguyen, Doron D. Sommer, Julie Strychowsky, Trina Uwiera, Warren Yunker, Paul Hong

Paediatrics Publications

The Choosing Wisely Canada campaign raises awareness amongst physicians and patients regarding unnecessary or inappropriate tests and treatments. Using an online survey, members of the Pediatric Otolaryngology Subspecialty Group within the Canadian Society of Otolaryngology – Head & Neck Surgery developed a list of nine evidence based recommendations to help physicians and patients make treatment decisions regarding common pediatric otolaryngology presentations: (1) Don’t routinely order a plain film x-ray in the evaluation of nasal fractures; (2) Don’t order imaging to distinguish acute bacterial sinusitis from an upper respiratory infection; (3) Don’t place tympanostomy tubes in most children for a single …

Parents’ Report Of Canadian Elementary School Children’S Physical Activity And Screen Time During The Covid-19 Pandemic: A Longitudinal Study, Emma Ostermeier, Patricia Tucker, Andrew Clark, Jamie A. Seabrook, Jason Gilliland

Paediatrics Publications

COVID-19 public health protocols have altered children’s daily routines, limiting their physical activity opportunities. The purpose of this study was to examine how the COVID-19 pandemic affected children’s (ages 10–12 years) physical activity and screen time, and to explore the impact of gender, socioeconomic status (SES), and public health constraints (i.e., facility use and social interaction) on the changes in children’s health behaviors. Online surveys were disseminated to parents at two time points: before COVID-19 (May 2019 to February 2020) and during COVID-19 (November to December 2020). Wilcoxon signed-rank tests were used to assess changes in physical activity and screen …

Objective Structured Clinical Evaluation For Supraclavicular And Femoral Nerve Blocks Utilizing Ultrasound Guidance For Student Nurse Anesthetists, Mitchell Fowler, Christopher Bond

Doctoral Projects

The purpose of this DNP project was to create a tool to teach and evaluate student registered nurse anesthetists (SRNAs) at TheUniversity of Southern Mississippi (USM) on supraclavicular and femoral nerve blocks to promote safety in the clinical setting. An objective structured clinical evaluation (OSCE) for ultrasound-guided supraclavicular and femoral nerve blocks was created as the basis for this project. Best-practice techniques as identified by the AANA’s 14^thstandard of nurse anesthesia practice were researched and used in the development of the OSCE to promote a culture of safety for SRNAs and patients (AANA, 2019).

A culture of safety …

Epidural Blood Patch For Pediatric Patients Only, Children's Mercy Kansas City

Clinical Pathways (Formally Known As Care Process Models)

No abstract provided.

Effects Of Il-10 On Local Cell Populations And Functional Recovery Following Vml Injury, Zain Blackwell

Biomedical Engineering Undergraduate Honors Theses

Volumetric muscle loss (VML) injuries are prevalent in both military personnel suffering from battlefield related incidents, and civilians following severe motor accidents. Despite its prevalence, VML has no pro-regenerative clinical treatments in place to recover some of the functional capabilities of the damaged muscle. Free flap grafting, debridement of damaged tissue, and physical therapy are the only clinical standards available that offer little functional recovery benefits, even after years of consistent treatment. In this study, anti-inflammatory cytokine interleukin-10 in conjunction with autologous minced muscle was assessed as a possible treatment for VML injuries and its influences on cellular behavior within …

Neonatal Outcomes And Congenital Anomalies In Pregnancies Affected By Hypothyroidism, Zareen Kiran,, Aisha Sheikh, Khadija N Humayun, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Background: Maternal hypothyroidism has been reported to have concerns over neonatal outcomes, not only in the context of neurocognitive development but also in the short term as birth weight and neonatal jaundice.
Patients and methods: We conducted a cross-sectional retrospective study on 638 cases who delivered live births in the Aga Khan University Hospital after ethical approval. Data were collected on hypothyroid pregnant females who were diagnosed before conception or during their antenatal visits during the year 2008-2016. Neonatal outcomes were noted for birth weight, maturity, and neonatal jaundice, neonatal hypothyroidism, neonatal respiratory distress syndrome, sepsis, hypocalcaemia, congenital anomalies, need …

The Truth About Brain Cells: Is Adult Neurogenesis Possible?, Ekene Nnagha, Queen-Helen Egbai, Ahtesham Khizar

Pakistan Journal of Neurological Sciences (PJNS)

Brain cells regeneration involves renewal and repair of neurons and other cells in the brain, with restoration of their functions. Although this phenomenon was thought to end in early childhood, research has proven that adult neurogenesis is highly possible with some limitations. Regeneration of axons in the central nervous system is very slow and more complicated than neuronal regeneration, especially regeneration of peripheral nerves. Brain cell regeneration in the adult brain can help in recovery of damaged brain cells and correct cellular and brain tissue dysfunction that are commonly seen in some neurological disorders such as Stroke, Traumatic Brain Injury …

Clinical Spectrum And Eeg Findings Of Non-Convulsive Status Epilepticus In Children, Shaila Ali, Natasha Ghani, Ather Khalily, Zia-Ur- Rehman, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT

OBJECTIVE:

To determine the clinical spectrum and EEG findings ofnon-convulsive status epilepticus in children. METHODS: A total of 38 children were included in this prospective cross sectional study, having EEG suggestive of NCSE after taking informed consent from guardians, keeping EEG as gold standard tracings were reviewed according to criteria of non-convulsive status epilepticus. Their clinical features were also noted leading to non- convulsive status epilepticus. Diagnostic workup will be done to find out the underlying cause, according to the suspected etiology of non-convulsive status epilepticus.

RESULTS: There were 26 male and 12 female patients, with ratio of 2:1. …

Frequency And Types Of Cerebral Infarctions On Brain Imaging In 2257 Hospitalized Patients With Covid-19, Raima Kaleemi, Zainab Rauf, Muhammad Azeemuddin, Muhammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT BACKGROUND AND OBJECTIVE:

SARS-COV (COVID-19) virus is not solely a pulmonary disease but affect multiorgan system including the brain. The objective of this study was to see the frequency of neuroimaging findings especially cerebral infarcts in our covid population. METHODS: This study is a retrospective observational study conducted in a large tertiary care hospital which was also a Covid center from March 1, 2020 to December 30, 2020.The frequency of neurological manifestations in COVID19 positive patients admitting in the hospital was observed through charts review. All scans were reviewed by two trained neuroradiologists. RESULTS: Total of 2257 patients enrolled …

Qualitative Exploration Of Feasibility And Acceptability Of The Modified Atkins Diet Therapy For Children With Drug Resistant Epilepsy In Kenya, Pauline Samia, Violet Naanyu, J. Helen Cross, Richard Idro, Paul Boon, Jo Wilmshurst, Stanley Luchters

Paediatrics and Child Health, East Africa

Purpose: Approximately one-third of children with epilepsy have clinical syndromes characterized by drug resistance. Modified Atkins dietary therapy (MADT) can reduce seizures and improve health out- comes for these children. This intervention is yet to be consistently offered as standard of care in sub- Saharan Africa.

Objectives: This study aimed to assess feasibility and acceptability of MADT for children with drug- resistant epilepsy and identify enabling strategies for implementation and adherence to the MADT. Methods: This qualitative inquiry utilized in-depth interviews with purposively selected caregivers and adolescent patients having used MADT for drug-resistant epilepsy. A qualified team consisting …

Metabolic Syndrome And Acute Respiratory Distress Syndrome In Hospitalized Patients With Covid-19, Joshua L Denson, Aaron S Gillet, Yuanhao Zu, Margo Brown, Thaidan Pham, Yilin Yoshida, Franck Mauvais-Jarvis, Ivor S Douglas, Mathew Moore, Kevin Tea, Andrew Wetherbie, Rachael Stevens, John Lefante, Jeffrey G Shaffer, Donna Lee Armaignac, Katherine Belden, Margit Kaufman, Smith F Heavner, Valerie C Danesh, Sreekanth R Cheruku, Catherine A St Hill, Karen Boman, Neha Deo, Vikas Bansal, Vishakha K Kumar, Allan J Walkey, Rahul Kashyap, Society Of Critical Care Medicine Discovery Viral Infection And Respiratory Illness Universal Study (Virus): Covid-19 Registry Investigator Group

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome.

Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19.

Design, setting, and participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined …

Development And Testing Of The Stakeholder Quality Improvement Perspectives Survey (Squips), Eric Fris, Emily Sedlock, Jason Etchegaray, Madelene J Ottosen, Ronald Pucio, Tejal Mistry, Tamara Saunders, Andrada Tomoaia-Cotisel, Eric J Thomas

Faculty, Staff and Student Publications

BACKGROUND: To create a theory-informed survey that quality improvement (QI) teams can use to understand stakeholder perceptions of an intervention.

METHOD: We created the survey then performed a cross-sectional survey of QI stakeholders of three QI projects. The projects sought to: (1) reduce unplanned extubations in a neonatal intensive care unit; (2) maintain normothermia during colorectal surgery and (3) reduce specimen processing errors for ambulatory gastroenterology procedures. We report frequencies of responses to survey items, results of exploratory factor analysis, and how QI team leaders used the results.

RESULTS: Overall we received surveys from 319 out of 386 eligible stakeholders …

Increasing Exercise Adherence Among Elderly Patients With Chronic Disease In Primary Care: A Prospective Cohort Study, Seth Vanderveer, Ronald J. Markert, Brant Bickford, Joseph Yuhas, Paul Pikman, Tim Wall, Kathryn Burtson

Internal Medicine Faculty Publications

Background: Currently, the evidence for exercise in maintaining health, well-being, and physical functioning is overwhelming. Despite these benefits, more than 50% of the population fails to meet the recommended exercise requirements for age and health status. In our study, we sought to provide a method to increase exercise adherence that was both effective and time-efficient for physicians and their patients. Methods: The primary objective of this research study was to evaluate the effectiveness of a graded exercise protocol and biweekly monitoring on increasing the duration of aerobic exercise to 150 min per week in a population of elderly individuals with …

Elevated Stool Inflammatory Markers In Early Onset Polymorphic Post-Transplant Lymphoproliferative Disease Following Orthotopic Heart Transplant, Jeremy Stewart, Keith August, Thomas M. Attard

Posters

Acute gastrointestinal hemorrhage in the context of a recent organ transplant with immunosuppression, antibiotic exposure, drug exposures and other comorbidities is a challenging clinical scenario with coordinated multidisciplinary effort needed to optimize management and outcomes. We present a patient with recent solid organ transplant with severe acute gastrointestinal bleeding attributable to EBV associated post-transplant lymphoproliferative disease. The patient is a 13-year-old Female with Williams syndrome who is EBV negative and CMV positive who received an EBV/CMV positive orthotopic heart transplant 5.5 months prior to presentation. She presented with bloody diarrhea, anemia (7.8 gm/dL), hypovolemia, and acute kidney injury (BUN 25 …

Grading Of Improvement In Hypsarrhythmia With Standard Epileptic Spasms Treatment At A Large Pediatric Tertiary Care Center, Julie Grace Gianakon, Roha Khalid, Mohammed Ilyas

Posters

Background Epileptic spasm is a peculiar type of epileptic seizure, entailing the clinical spasms and a characteristic electroencephalogram (EEG) abnormality often called hypsarrhythmia or its variants. The main goal of epileptic spasm treatment with standard therapy is to suppress clinical spasms and abolish the hypsarrhythmia and its variant EEG pattern. This interictal EEG pattern frequently heralds developmental regression. The elimination of hypsarrhythmia is a principal goal of therapy and a key outcome measure in clinical trials. There have been several studies in the interpretation or grading of hypsarrhythmia (Watanabe et al.1993 & Jeavons & Bower et al.1961). Still, there have …

Standardizing Resident Education On Gi Service, Jennifer Halma, Kenneth Schmidt

Posters

Introduction: The pediatric residency curriculum at Children’s Mercy Hospital is standardized to offer each trainee the same rotational experience. As a result, each resident spends one month on the inpatient gastroenterology (GI) service during training. This invites variability in the quantity and quality of GI education that residents receive. Therefore, there is a need to design a standard curriculum to provide comprehensive GI education. The aim of this project is to standardize resident education by identifying most requested topics and providing didactic education to increase resident general GI knowledge. Methods: Each month, residents were provided with a survey to assess …

Temperature Changes During Implant Osteotomy Preparations In Human Cadaver Tibiae Comparing Mis® Straight Drills With Densah® Burs, Andrew C Griggs, Crystal M Fausett, Richard J Simonson, Kimberly N Williams, Tiffany M Bisbey, Elizabeth H Lazzara, Joseph R Keebler, Deborah Diazgranados, Vimal K Mishra, Eric J Thomas, Eduardo Salas

Faculty, Staff and Student Publications

INTRODUCTION: Telerounding is slated to become an important avenue for future healthcare practice. As utilization of telerounding is increasing, a review of the literature is necessary to distill themes and identify critical considerations for the implementation of telerounding. We provide evidence of the utility of telerounding and considerations to support its implementation in future healthcare practice based on a scoping review.

METHOD: We collected articles from nine scientific databases from the earliest dated available articles to August 2020. We identified whether each article centered on telerounding policies, regulations, or practice. We also organized information from each article and sorted themes …

Novel Peptide Biomaterials For Enhanced Delivery Of Sirna Cargo For Treatment Of Ovarian Cancer, Timothy Samec

All Dissertations

Ovarian cancer is the 7^th leading cause of cancer related death and the 5^th most commonly diagnosed cancer among women. Primarily diagnosed in stage III or stage IV, aggressive treatment is necessary and involves surgical debulking and administration of systemic chemotherapeutics. Unfortunately, these strategies fall short in effectively treating ovarian cancer and many patients experience local disease recurrence, development of multidrug resistant tumors, regional or distant metastatic events, or a combination of the three. As such, there is a significant need for additional treatment options and methods of delivery to improve therapeutic efficacy and disease survivability.

RNA interference …