Medical Specialties Commons^™

Changes In Cancer Diagnosis And Survival In The United States During The Covid-19 Pandemic, Justin T. Burus

Theses and Dissertations--Epidemiology and Biostatistics

The COVID-19 Pandemic led to global societal disruptions as political leaders and public health authorities attempted to control the spread of the newly discovered SARS- CoV-2 virus. While these measures were designed to lessen morbidity and mortality from a novel pathogen, their impact was also felt in many other, often unintended ways. The purpose of this dissertation is to use cancer surveillance research methods to examine the association between COVID-19 Pandemic-related disruptions and changes in the normal diagnosis and care of cancer in the United States.

The first two studies of this dissertation analyzed reductions in cancer diagnoses in the …

Using Hyperactive Shp-2 Mutants, A Phosphatase, To Identify Interactions With The Rna Helicase Ddx3, Devin Montgomery

Theses and Dissertations--Pharmacy

Protein-protein interactions are critical in cellular signaling pathways. This project investigates binding interactions between SHP-2, a tyrosine phosphatase, and DDX3, an RNA helicase. There is a specific focus on the impact that gain-of-function SHP-2 mutations may impact binding to DDX3 via conformational change. Using immunoprecipitation protocols as well as western blotting we were able to provide insights into SHP-2 molecular mechanisms and subsequent binding to DDX3.

M1 Macrophage-Engineered Vesicles Have Anti-Cancer Activity In Ovarian Cancer, Connie Du Cao

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles that function in specific cell-to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) derived from M1 macrophages are able to repolarize M2 macrophages to the M1 phenotype and target tumor cells in in vitro studies.

In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) in the presence and absence of cisplatin to generate …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Development And Clinical Validation Of Automated Same-Day Stereotactic Treatment Procedures For Multiple Brain Metastases And Recurrent Head And Neck Cancers, Shane Mccarthy

Theses and Dissertations--Radiation Medicine

As technology advances, more and more cancer patients are benefiting from the use of stereotactic radiosurgery and radiotherapy (SRS/SRT) to treat their disease. One such technology, Varian’s HyperArc high-definition radiosurgery module, a tool to help facilitate the treatment of brain metastases on a medical linear accelerator (LINAC), has been demonstrated to achieve comparable low dose spillage and target conformity compared to the current gold standard for intracranial malignancies, the Elekta Gamma Knife. Furthermore, due to HyperArc’s single-isocenter multiple lesion approach, the treatment can be delivered in a significantly shorter amount of time. Unfortunately, the manual process of creating these stereotactic …

Influence Of Perceived Health Provider Communication, Diabetes Duration And Age At Diagnosis With Confidence In Diabetes Self-Care, Courtney L. Ortz, Meredith S. Duncan, Oluwatosin Leshi, William B. Burrows, Brittany L. Smalls

Family and Community Medicine Faculty Publications

Introduction: Several factors influence individuals’ confidence to perform diabetes-related self-care activities, including perceived patient-provider communication, diabetes duration and age at diagnosis. It has been well-documented that patient-provider communication is essential when managing chronic diseases such as diabetes; however, the impact of this communication with diabetes duration and age at diabetes diagnosis on confidence in performing self-care behaviors is obscure.

Research design and methods: We utilized data from the 2021 Household Component of the Medical Expenditure Survey among participants 18 years or older who had completed the Diabetes Care Survey. Ordinal logistic regression models were utilized to assess the association between …

All-Cause And Exacerbation-Related Readmissions In Thrombotic Microangiopathy Requiring Plasmapheresis: A Population-Based Cohort Study, Alexander R. Thebert, Toru Yoshino, Sae X. Morita, Misa Ito, Ayman Qasrawi, Hirotaka Kato

Internal Medicine Faculty Publications

Objective: Thrombotic microangiopathy (TMA) is a serious condition characterized by microangiopathic hemolytic anemia and thrombocytopenia, with high exacerbation rates. This study examined all-cause and exacerbation-related readmission risks among patients hospitalized with TMA requiring plasmapheresis.

Materials and Methods: Secondary analysis of the 2020 Nationwide Readmission Database was conducted, including discharge data from non-federal hospitals in 31 U.S. states. Patients aged 18 years or older admitted non-electively with a primary or secondary diagnosis of TMA requiring plasmapheresis were included. Exacerbation-related readmission was defined as subsequent admission requiring plasmapheresis within 7 or 30 days after the original discharge. Multivariable logistic regression and Cox …

Clonal Hematopoiesis Of Indeterminate Potential And The Risk Of Cognitive Impairment In The Women’S Health Initiative Memory Study, Yasminka A. Jakubek, Aaron P. Smith, Xiaoyan I. Leng, Megan E. Hall, Daniel Ezzat, Yash Pershad, Jason M. Collins, Md Mesbah Uddin, David W. Fardo, Pradeep Natarajan, Alexander G. Bick, Jacob O. Kitzman, Michael C. Honigberg, Kathleen M. Hayden, Joann E. Manson, Siddhartha Jaiswal, Eric A. Whitsel, Alexander P. Reiner

Internal Medicine Faculty Publications

INTRODUCTION

Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.

METHODS

We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.

RESULTS

Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF …

Dual Biologic Therapy Induces Remission In Refractory Crohn’S Disease With Vedolizumab And Ustekinumab, Syed Adeel Hassan, Courtney Perry, Patrick Carey, Durham Colohan, Mohamed Gebril Eltaher, Nabila Dawoud, Mahmoud Elkammar, Waqas Rasheed, Casie Mayne, Amy Stuffelbeam, Deborah R. Auer Flomenhoft, Terrence A. Barrett

Internal Medicine Faculty Publications

Background

Despite advancements in the therapeutic armamentarium for Crohn’s disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential to increase efficacy in the treatment of refractory or partially responsive CD. Evidence pertaining to this strategy remains limited. Methods

We retrospectively examined refractory CD patients treated with a combination of ustekinumab and vedolizumab. Outcomes to DBT at week (wk) 52 were compared to monotherapy. The primary outcome constituted corticosteroid-free remission. Secondary outcomes included adverse events, infections, hospitalizations, surgeries, treatment persistence, and disease clearance. Results

Sixteen of 21 …

Serglycin Controls Megakaryocyte Retention Of Platelet Factor 4 And Influences Megakaryocyte Fate In Bone Marrow, Joshua Lykins, Isabelle C. Becker, Virginia Camacho, Hammodah Rawhi Hammodah Alfar, Joonwoo Park, Joseph Italiano, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Megakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)/CXCL4. Here, we show that the intra-α-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN–/– MKs released ~80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)/protein interactions. In …

Abcg5/Abcg8-Independent Mechanisms Fail To Maintain Sterol Balance In Mice Fed A High-Cholesterol Diet, Garrett B. Anspach, Rupinder Kaur, Isha Chauhan, Erika L. Savage, Brittney Poole, Victoria P. Noffsinger, Xiaoming Fu, Zeneng Wang, Clairity Voy, Ryan E. Temel, Scott M. Gordon, Robert N. Helsley, Gregory A. Graf

Saha Cardiovascular Research Center Faculty Publications

The ABCG5/ABCG8 (G5G8) sterol transporter opposes the accumulation of dietary xenosterols but is also the primary mediator of biliary cholesterol secretion. In humans and in mouse models of disrupted biliary cholesterol secretion, fecal neutral sterols (FNSs) remain constant, indicating the presence of an alternate pathway for cholesterol excretion. Transintestinal cholesterol elimination or excretion (TICE) is thought to compensate for biliary disruptions and G5G8 insufficiency. We sought to measure the compensatory increase in intestinal cholesterol secretion and provide mechanistic insight for how TICE maintains sterol balance in the absence of hepatic G5G8. Differences were not observed in FNSs between control, acute, …

Assessment Of Cerebrospinal Fluid And Blood-Based Biomarkers In Degenerative Cervical Myelopathy: Systematic Review And Meta-Analysis, Harshit Arora, Hassan Darabi, Cassandra C. Wolsh, Kelsey N. Karnik, John C. Gensel, Francis Farhadi

Neurosurgery Faculty Publications

Study Design: Systematic Review and Meta-Analysis.

Objectives: Degenerative cervical myelopathy (DCM), the leading cause of spinal cord injury globally, may clinically manifest with hand numbness and tingling, loss of hand dexterity and impaired balance and gait. Biomarkers have been identified as disease indicators with recent studies exploring the role of structural and inflammatory biomarkers in diagnostic and treatment outcome prediction. The review aims to identify relevant cerebrospinal fluid (CSF) and blood-based biomarkers associated with DCM diagnosis and prognostication.

Methods: The systematic review was conducted as per PRISMA guidelines. A comprehensive search strategy was devised to identify articles evaluating biomarkers in …

Frailty Indices In Patients Undergoing Functional Neurosurgical Procedures: A Systematic Review, Carmelo Venero Jr., Joanna M. Roy, Nirbha Ghurye, Akshay Warrier, Muhammad Usman Khalid, Niels Pacheco-Barrios, Farhan A. Mirza, Christian A. Bowers

Neurosurgery Faculty Publications

Introduction: Functional neurosurgery covers a wide array of neurological disorders with an equally vast array of treatment modalities, including neuromodulation, decompressive, and ablative therapies for disparate pathologies such as pain, neuromodulation, disconnection, and refractory epilepsy. One of the most common functional treatments is deep brain stimulation for movement disorders and select psychiatric diseases. Functional neurosurgery treats patients with reduced quality of life from pathological neuronal pathways. Optimal patient selection by preoperatively identifying high-risk patients is critical for avoiding as many operative complications as possible, in addition to managing complications better once they occur. Frailty indices have demonstrated superior discrimination in …

Comparison Of Machine Learning Models For Colon Cancer Survival: Predictive Modeling Approach, Reuben Adatorwovor, Motolani E. Ogunsanya, Bin Huang, Richard Charnigo, Olufunmilola Abraham

Biostatistics Faculty Publications

Background: Colon cancer is a leading cause of cancer-related deaths worldwide, with survival influenced by risk factors, treatment type, and patient characteristics. Traditional statistical models, such as Kaplan-Meier curves, have been widely used to estimate survival probabilities. However, these models often have difficulty handling complex interactions, covariates, and nonlinear relationships between risk factors. Recently, machine learning (ML) techniques have emerged as promising tools for improving survival prediction by handling large covariates and capturing complex patterns.

Objective: This study compares several ML models to accurately estimate colon cancer survival by leveraging data from the Kentucky Cancer Registry. By identifying key risk …

A Qualitative Study Of End-Stage Liver Disease And Liver Transplant Referral Practices Among Primary Care Providers In Nonurban America, Vashisht Madabhushi, Matthew Wright, Gabriel Orozco, Allison Murphy, Antonio R. Garcia, Natalie D. Pope, Xiaonan Mei, Alexandra Cocca, Roberto Gedaly, Meera Gupta

Surgery Faculty Publications

Purpose: In rural America, the road to obtaining a liver transplant (LTX) often starts at the primary care provider’s (PCP’s) office. Patients with end-stage liver disease (ESLD) in rural communities experience lower rates of wait-listing and higher mortality. This study identifies issues related to the knowledge and perceptions of ESLD and LTX referral among PCPs in rural Kentucky (KY).

Methods: The study protocol involved relying upon a semistructured outline to explore the knowledge, attitude, and perceptions of PCPs toward ESLD and LTX referral among PCPs in rural KY. Inductive thematic analysis was utilized to identify, analyze, and report themes.

Findings: …

A Community Effort To Develop Common Data Elements For Pre-Clinical Spinal Cord Injury Research., Britt A. Fedor, Abel Torres-Espin, Romana Vavrek, Maryann E. Martone, John L. Bixby, John C. Gensel, Vance Lemmon, Jeffrey S. Grethe, J. Russel Huie, Adam R. Ferguson, Karim Fouad, The Preclinical Sci Common Data Elements (Cde) Workshop Participants

Spinal Cord and Brain Injury Research Center Faculty Publications

For nearly 350 years, the process of disseminating scientific knowledge has remained largely unchanged. Scientists conduct experiments, analyze the data, and publish their findings in the form of scientific articles. Since the turn of the century, this process has been challenged by numerous open science and data sharing efforts to enhance transparency, reproducibility, and replicability of scientific research. Big data approaches, together with machine learning and artificial intelligence, are frequently used to gain insight into the ever-growing complexity of biological systems and biomedical research. To utilize these approaches and harness the continuously increasing computational power requires data to be both …

Cross-Species Comparisons Between Pigs And Mice Reveal Conserved Sex-Specific Intraspinal Inflammatory Responses After Spinal Cord Injury, Reena Kumari, Gabrielle V. Hammers, Robert H. Hammons, Andrew N. Stewart, Steven M. Maclean, Tracy Niedzielko, Lonnie E. Schneider, Candace L. Floyd, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Objective Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model.

Methods Adult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury.

Results SCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing …

Cytosolic Phospholipase A2 In Infiltrating Monocyte Derived Macrophages Does Not Impair Recovery After Spinal Cord Injury In Female Mice, Ethan Glaser, Timothy J. Kopper, William M. Bailey, Hassan K. Kashif, Reena Kumari, Andrew N. Stewart, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) leads to permanent motor and sensory loss that is exacerbated by intraspinal inflammation and persists months to years after injury. After SCI, monocyte-derived macrophages (MDMs) infiltrate the lesion to aid in myelin-rich debris clearance. During debris clearance, MDMs adopt a proinflammatory phenotype that exacerbates neurodegeneration and hinders recovery. The underlying cause of the lipid-mediated MDM phenotype shift is unclear. Our previous work suggests that cytosolic phospholipase A2 (cPLA2) plays a role in the proinflammatory potentiating effect of myelin on macrophages in vitro. Cytosolic phospholipase A2 (cPLA2) frees arachidonic acid from phospholipids, generating eicosanoids that play an …

Exploring The Links Among Brain Iron Accumulation, Cognitive Performance, And Dietary Intake In Older Adults: A Longitudinal Mri Study, Valentinos Zachariou, Colleen A. Pappas, Christopher E. Bauer, Elayna R. Seago, Brian T. Gold

Neurology Faculty Publications

This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60–86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5–3.0 years later. Dietary intake was evaluated at baseline using a validated questionnaire. Cognitive performance was assessed at TP2 using the uniform data set (Version 3) neuropsychological tests of episodic memory (MEM) and executive function (EF). Voxel-wise, linear mixed-effects models, adjusted for longitudinal gray matter volume …

Barriers To Adherence To Standard Of Care In Appalachia: A Qualitative Assessment In Gastrointestinal Cancers, Brittany Levy, Jennifer T. Castle, Roshmita Bardhan, Mark Dignan, Avinash S. Bhakta

Internal Medicine Faculty Publications

Purpose: Appalachian Kentucky, a 32-county region in the eastern part of the state, has elevated colon cancer mortality rates. While recommended as the standard of care, access to adjuvant chemotherapy treatment is limited in this region due to scarce health services and significant social and geographical barriers. The purpose of this investigation was to improve understanding of barriers that cancer patients residing in rural areas not served directly by tertiary medical systems must overcome in completing adjuvant therapy.

Methods: Participants were recruited from two medical centers: A tertiary care NCI designated Cancer Center and a regional hospital. Participants underwent a …

Circulating Molecular Drivers Of Bone Remodeling In Pancreatitis, Rachel L. Hill, Dhiraj Yadav, Phil A. Hart, David C. Whitcomb, Kristen J. Mcquerry, Kelsey N. Karnik, Kimberly M. Stello, Darwin L. Conwell, Madhumathi Rao

Internal Medicine Faculty Publications

INTRODUCTION: 

Pancreatitis-associated osteopathy is a clinically significant but mechanistically underexplored complication of pancreatic disease. We aimed to characterize stage-specific alterations in bone remodeling biomarkers across the spectrum of disease: recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP).

METHODS: 

In a cross-sectional analysis of North American Pancreatitis Study 2 participants, we measured serum mechanistic (sclerostin, dickkopf-1, receptor activator of nuclear factor κβ ligand, and osteoprotegerin), hormonal (fibroblast growth factor 23, insulin, and leptin), and modulatory (osteopontin, oncostatin, and osteoactivin) markers in controls (n = 30), RAP (n = 40), and CP (n = 40) using a multiplex assay. Group differences were …

Digital Health Interventions For Colorectal Cancer Screening Uptake: A Scoping Review, Sujin Kim, Andrew J. Whipkey, Jihye Bae, Avinash S. Bhakta

Internal Medicine Faculty Publications

Digital health interventions (DHIs) are increasingly employed to improve colorectal cancer (CRC) screening uptake, yet comprehensive syntheses of their effectiveness across diverse contexts remain scarce. This scoping review examines how individual, contextual, technological, and timing-related factors shape CRC screening outcomes in DHI-based trials. Following PRISMA-ScR guidelines, we conducted a systematic search of PubMed, Google Scholar, and ClinicalTrials.gov from March 1 to April 20, 2024, identifying 4,523 records through databases and an additional 2,039 through backward citation tracking. After deduplication and screening, 51 studies were included and charted using the PICOT (Population, Intervention, Comparison, Outcome, and Timing) framework. Included studies spanned …

Early-Onset Bevacizumab-Associated Knee Osteonecrosis In A Young Adult With Astrocytoma, Chandra L. Kakarala, Nicole A. Lisek, Clyde Coleman, John L. Villano, Katherine L. Copely, Patricia A. Santos

Internal Medicine Faculty Publications

We describe a rare case of knee osteonecrosis in a 22-year-old man with astrocytoma and neurofibromatosis type 1 after short-term treatment with bevacizumab and corticosteroids. Magnetic resonance imaging (MRI) identified infarctions and osteonecrosis of the distal femur and proximal tibia. Osteonecrosis associated with bevacizumab is typically limited to the jaw; this case highlights the potential for earlier, extra-jaw involvement. Clinicians should maintain a high index of suspicion for osteonecrosis in patients on vascular endothelial growth factor inhibitors, especially with concurrent steroid use, and consider prompt MRI in the evaluation of unexplained joint pain.

Impact Of Fast Advancement And Early Fortification Of Enteral Feedings In Preterm Infants, A Retrospective, Observational Study., Enrique Gomez-Pomar, Holly Clarke, Jamie Adams

Pediatrics Faculty Publications

UNLABELLED: We aimed to evaluate the outcomes and growth of preterm infants at a Neonatal Intensive Care Unit that focuses on early initiation, fast advancement, and early fortification of enteral feeds.

METHODS: Retrospective study conducted at a community hospital level III NICU. Extensive feeding data and outcomes were collected by utilizing a NutritionIQ software application, NICUtrition®. Infants born between 26- and 34-weeks gestational age were included, whereas infants with congenital defects, deceased or with incomplete data were excluded. Frequency and descriptive statistical analysis were conducted using chi-square and Fisher's exact test. Unadjusted odds ratios were computed for categorical variables and …

Rcpneoperu Trial: A Cluster Randomized Pilot Trial To Assess Traditional Neonatal Resuscitation Compared To Partially Virtual Training In Remote Areas., Carlos A Delgado, Enrique Gómez Pomar, Pablo Velásquez, Víctor Sánchez, Roberto Shimabuku, Luis Huicho

Pediatrics Faculty Publications

OBJECTIVE: To assess the effects of a neonatal resuscitation training program using traditional training and partial distance learning.

METHOD: Through an open cluster-randomized trial, the authors compared a traditional approach involving face-to-face theory and practice sessions using information and communication technology to offer theory and distance examination, followed by face-to-face practice. Twelve health facilities were allocated by blocked randomization. Comparisons were made adjusting for clustering in qualitative and quantitative data. The primary outcome was the percentage of infants with heart rates ≥100 per minute at the second minute after birth. The authors performed a cluster-level analysis for cluster randomized trials, …

Congenital Malignant Ectomesenchymoma Presenting As A Neck Mass In A Newborn, Ianna S. C. Blanchard, Ravi C. Bhavsar, Ashley M. Olszewski, Nathan R. Shelman, John A. D'Orazio, Prasad Bhandary, Thitinart Sithisarn

Pediatrics Faculty Publications

Background: Malignant Ectomesenchymoma (MEM) is a rare, aggressive soft tissue neoplasm with both neuroectodermal and mesenchymal differentiation. Congenital cases are extremely uncommon, posing significant diagnostic and therapeutic challenges.

Case Presentation: We report a case of a full-term male neonate presenting with a large congenital neck mass and respiratory distress at birth. Imaging revealed a lobulated, heterogeneously enhancing mass in the left submandibular region with a mass effect on the airway. Open biopsy and gross resection on day six of life confirmed MEM with rhabdomyoblastic and neuroectodermal differentiation. Post-surgical staging classified the tumor as Stage I, Clinical Group II. Despite initial …

A 40-Week Phase 2b Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating The Safety And Efficacy Of Memantine In Amyotrophic Lateral Sclerosis, Salman Bhai, Todd Levine, Dan Moore, Robert Bowser, Andrew J. Heim, Maureen Walsh, Aziz Shibani, Zachary Simmons, James Grogan, Namita A. Goyal, Raghav Govindarajan, Yessar Hussain, Tania Papsdorf, Tiffany Schwasinger-Schmidt, Nick Olney, Kim Goslin, Michael Pulley, Edward J. Kasarskis, Michael Weiss, Susan W. Katz, Suzan Moser, Duaa Jabari, Omar Jawdat, Jeffrey Statland, Mazen M. Dimachkie, Richard Barohn, Neuromuscular Study Group And Western Als Consortium Memantine Als Study Group

Neurology Faculty Publications

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

Aims: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio …

Interaction Between Riluzole Treatment And Dietary Glycemic Index In The Disease Progression Of Amyotrophic Lateral Sclerosis, Ikjae Lee, Hiroshi Mitsumoto, Seonjoo Lee, Edward J. Kasarskis, Michael Rosenbaum, Pam Factor-Litvak, Jeri W. Nieves

Neurology Faculty Publications

Objective: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

Methods: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from …

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer’S Disease Detection And Monitoring, Melissa E. Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah E. Pape, Juan Fortea, Nicholas J. Ashton, Chinedu Udeh-Momoh, Sid E. O’Bryant, Dwight German, Florin Despa, Mark Mapstone, Henrik Zetterberg

Neurology Faculty Publications

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer’s Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …