Diseases Commons^™

Ultrasound-Derived Liver Composition And Metabolic Flexibility Under Exercise Stress, Rhodes Van Houten

All Master's Theses

Metabolic Associated Fatty Liver Disease (MAFLD) is characterized by abnormal liver fat accumulation in conjunction with metabolic syndromes. MAFLD affects 33% of individuals worldwide, though little is known about how increased liver fat impacts physiological responses to exercise. This study aimed to analyze the relationship between liver composition and metabolic flexibility during a graded exercise test.  Body composition was analyzed via dual-energy X-ray absorptiometry. Liver ultrasound was evaluated for echogenicity, where elevated mean gray volume (MGV) indicates abnormal liver tissue. Rates of fat (FATox) and carbohydrate (CHOox) oxidation (g/min), respiratory exchange ratio (RER), and blood lactate concentrations ([LA^-], …

Microgravity-Induced Alterations In Left Atrial Hemodynamics And Thrombogenic Risk: Insights From Healthy And Atrial Fibrillation Models, Grace M. Hoeppner

Dissertations, Master's Theses and Master's Reports

Background: Microgravity exposure alters cardiovascular loading, yet its impact on left atrial flow dynamics and thrombotic risk remains poorly understood. This study investigates how spaceflight-relevant microgravity-induced changes in cardiac outflow affect left atrial hemodynamics in healthy individuals and patients with atrial fibrillation.

Methods: Patient-specific left atrial models were generated for three healthy individuals and three AF patients. Computational fluid dynamics (CFD) simulations were performed using each patient’s baseline mitral outflow waveform and two modified waveforms representing short- and long-duration post-flight cardiac loading changes derived from echocardiographic observations. Hemodynamic metrics included left atrial velocity, time averaged wall shear stress, oscillatory shear …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek

University of Kentucky Doctoral Dissertations

Spinal cord injury is a severe and debilitating condition that often results in lifelong complications, including paralysis. Many of these chronic outcomes are driven by a sustained inflammatory response at the injury site, which limits tissue regeneration and functional recovery. As a result, therapeutic strategies that modulate this immune response have gained significant interest. Polymer based nanoparticle therapies have emerged as a promising approach due to their ability to interact with and influence immune cell behavior. Importantly, the physicochemical properties of nanoparticles can be precisely tuned to optimize these effects. Among these properties, size has been shown to influence key …

Successful Anesthetic Management Of Patient With Marfan Syndrome: Optimizing Cardiovascular Stability And Maternal Outcomes, M Roberts, C Cox, K Leavitt

South Atlantic Division GME Research Days 2026

No abstract provided.

A Painful Diffuse Rash, Bruce M. Lo, Melanie Shoemaker, Kiersten Potter, Katherine Schaffer

Department of Emergency Medicine Faculty Publications

[Patient presentation]

A 41-year-old male with no past medical history presented with 1 week of ulcers to the left side of his face, followed by several days of a painful rash to the trunk and back after a sexual encounter. The patient denies any fever or previous rash and any illicit drug use. Initial vital signs included a temperature of 97 °F, a heart rate of 89 beats per minute, and blood pressure of 135/79 mm Hg. Physical examination revealed a macular papular rash across his trunk and back (Fig 1) and facial ulcerations with eschar (Fig 2) at the …

Comparative Mass Spectrometry Analysis Of High And Low Centrifugation Extracellular Vesicle (Ev) Pellets From Healthy Urine Following Tamm-Horsfall Protein Removal, Dana Bielopolski, Luca Musante, Henrik Molina, Douglas Barrows, Samantha Upson, Lifang Yang, Thomas Carrol, Jonathan N. Tobin, Rhonda G. Kost, U. Erdbrügger

Department of Biomedical and Translational Sciences Faculty Publications

Objectives

Urinary extracellular vesicles (uEVs) are potential biomarkers for renal physiology and disease. Their isolation is challenged by Tamm-Horsfall protein (THP) contamination, particularly in high-speed ultracentrifugation (P100) fractions. Low-speed (P20) fractions contain biologically relevant uEVs, yet their proteomic composition is underexplored. This study evaluates strategies for THP removal to optimize mass spectrometry analysis and characterizes P20 and P100 uEV proteomes and its combination in healthy urine.

Methods

Urine from a healthy volunteer was processed via sequential centrifugation at 21,200 g (P20) and 164,244 g (P100). THP removal was performed using low ionic strength buffer (P20) and size-exclusion chromatography (P100). Western …

Partial Post-Exposure Protection By Topical Inserts Containing Tenofovir Alafenamide Fumarate/Elvitegravir In A Macaque Model Of Rectal Simian Hiv (Shiv) Infection, Natalia Makarova, Tyana Singletary, M. Melissa Peet, Kristen Kelley, Ryan Johnson, Vivek Agrahari, Maria Mendoza, Yi Pan, Walid Heneine, Meredith R. Clark, J. Gerardo García Lerma, Gustavo F. Doncel, James W. Smith

CONRAD Publications

On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis 4 hours before SHIV exposure. Here, we show that the same inserts provide significant postexposure protection (82.9% efficacy) when applied 4 hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.

Shaping The Future Of Respiratory Care: A Look Into The Next Decade And Strategic Recommendations By The European Forum For Research And Education In Allergy And Airways Diseases, Xander Bertels, Glenis K. Scadding, Vibeke Backer, Susanne Lou, Wytske J. Fokkens, Peter J. Barnes, Manuel Bernal Sprekelsen, Leif Bjermer, Michael Blaiss, Elena Borzova, Marie-Charlotte Brüggen, Guy G. Brusselle, Lars Olaf Cardell, Diego M. Conti, Marjolein Cornet, Eugenio De Corso, Bernard De Groeve, Ratko Djukanovic, Adam T. Fox, Mina Gaga, Philippe Gevaert, Peter Gibson, Claudia L. Gray, Joseph Han, Liam Heaney, Enrico Heffler, Hans Jürgen Hoffmann, Claire Hopkins, Daniel Jackson, Outi Jauhola, Milos Jesenak, Pål Johansen, Ekaterina Khaleva, Basile Landis, Stella Lee, Valerie Lund, Mika Mäkelä, Marinda Mcdonald, Erik Melén, Joaquim Mullol, Antonio Nieto-García, Ian Pavord, Anju Peters, David Price, Santiago Quirce, Dermot Ryan, Pernilla Sahlstrand-Johnson, Sophie Scheire, Peter Schmid-Grendelmeier, Sven Schneider, Brent A. Senior, Catherine M.E. Shire, Peter K. Smith, Zsolt Szépfalusi, M. Thijs A. Teeling, Michael E. Wechsler, Philippe Houssiau, Klaus F. Rabe, Peter W. Hellings, José Luis Castro

Department of Otolaryngology (ENT) Faculty Publications

Chronic respiratory diseases (CRDs) remain 1 of the leading causes of preventable morbidity and disability worldwide, affecting up to one-third of the total Western population in 2025. Recognizing the substantial burden of inflammatory airway diseases such as asthma, COPD, chronic rhinosinusitis, and respiratory allergy, the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized the symposium “Shaping the Future of Respiratory Care” in April 2025 in Brussels, Belgium, at the occasion of the 10-year jubilee. Featuring keynote speakers from the World Health Organization and EUFOREA, this initiative had the following aims: (1) promoting dialogue on translating …

A Comparison Of F/Taf And F/Tdf As Hiv Pre-Exposure Prophylaxis In A Predominantly Cisgender Women Population In East And South Africa: A Randomised, Factorial, Non-Inferiority Trial, Sheena Mccormack, David Dunn, Sylvia Kusemererwa, Patricia Munseri, Nishanta Singh, Wiston William, Gertrude Mutonyi, Henry Bern, Lauriane Goldwirt, Cherry Kingsley, Arne Kkroidl, Christian Holm Hansen, Song Ding, Rachel Kawuma, Mary Amondi, Ubaldo Bahemuka, Deus Buma, Daniel Clutterbuck, Zakir Gaffoor, Angus Jennings, Agricola Joachim, Ayoub Kakande, Berna Kalanzi, Abisai Kisinda, Mabela Matsoso, Thomas Miller, Neetha Mmedsci Morar, Jacqueline Musau, Jane Nabbuto, Ayanda Nzuza, Doreen Pamba, Simona Salomone, Thandiwe Sithole, Edith Tarimo, Kubashni Woeber, Kundai Chinyenze, Glenda Gray, Eligius Lyamuya, Muhammad Bakari, Said Aboud, Lucas Maganga, Gustavo Doncel, Janet Seeley, Jonathan Weber, Pontiano Kaleebu, Julie Fox, Eugene Ruzagira, On Behalf Of The Prepvacc Study Group

CONRAD Publications

Background:

F/TAF was shown to be non-inferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial.

Setting:

Five study sites in three African countries (Uganda, Tanzania, South Africa).

Methods:

The two regimens were compared by the averted infections ratio (AIR) - the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was …

Proof-Of-Concept Development And Preclinical Evaluation Of A Microarray Patch Platform For Codelivery Of Multiple Broadly Neutralizing Antibodies For Hiv Prevention, M. Melissa Peet, Vivek Agrahari, Parbeen Singh, Lam Luong Hoai Nguyen, Louise A. Ouattara, Eun Sung Yang, Carolina Herrera, Amarendra Pegu, Theodore C. Pierson, Thanh D. Nguyen, Gustavo F. Doncel

CONRAD Publications

Broadly neutralizing antibodies (bnAbs) are advancing as a preventative or treatment option for HIV infection, but currently must be administered parenterally, typically as a large injection or infusion, an invasive method of delivery, especially for the pediatric population. Here, we present proof-of-concept data on a minimally invasive microneedle (MN) patch platform codelivering three bnAbs, PGT121, VRC07-523LS, and PGDM1400LS, from separate MN patch units or pixels. Each 1 cm² patch pixel, fabricated via solvent casting, contained ∼2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS buffer, MNs …

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

Self-Assembly Of Anti-Inflammatory Peptide Amphiphiles For Mucosal Health, Maria José Gómara, Ignacio Pérez-Pomeda, Ramon Pons, Paul Ziprin, Carolina Herrera, Isabel Haro

CONRAD Publications

Broad spectrum anti-inflammatory peptide amphiphiles (AIF-PAs) have been developed as an innovative strategy for the treatment of chronic mucosal inflammation and the prevention of HIV transmission. Novel lipopeptides based on two linear sequences of anti-inflammatory peptides were obtained by solid-phase peptide chemistry. In a pilot study, ex vivo exposure of colorectal tissue explants from Crohn's disease patients to AIF-PAs induced a downregulation of the proinflammatory profile. Furthermore, the HIV inhibitory potency of AIF-PAs was evaluated ex vivo in colorectal tissue explants, obtaining sub-micromolar IC₅₀ values. Characterization of AIF-PAs self-aggregation in aqueous solution revealed that the net charge distribution within the …

The Effect Of The Affordable Care Act Medicaid Expansion On The Risk Of Hospital Closure And Adolescent Hpv Immunization In Rural Counties, Juliette Des Rosiers

Scripps Senior Theses

From 2005 to 2025, over 200 rural hospitals shut their doors, often citing increased operational costs, staffing shortages, low patient volume, regulatory barriers, financial challenges exacerbated by the COVID-19 pandemic, and uncompensated care as common contributors to the closures. Rural patients are often referred by their primary care physician to a hospital for regular immunizations, since smaller clinics have less capacity to provide immunizations due to a shortage of pediatricians and limited vaccine stock. A crucial vaccine that is not required by schools and underutilized in rural areas is that against human papillomavirus (HPV), a virus that infects cutaneous and …

Ethanol And Iron Absorption Interactions Within Crayfish Invertebrate Models, James Rollman, Andrew Wissmar

Williams Honors College, Honors Research Projects

Analysis of the effects of alcohol consumption (ethyl-alcohol) on iron absorption within crayfish model. The use of tube-feeding provides a novel, more precise output, and less invasive procedure compared to the traditional approach of dissolving the target substance in tank water and measuring hemolymph changes. The project aims to determine the extent to which alcohol influences iron absorption. Ultimately, the choice of iron reflect the future potential to aid in research with genetic hemochromatosis and or Iron overload.

The Connection Between Medicaid And Obesity In Northeast Ohio, Emmie Kelley, Sophie Kheder

Williams Honors College, Honors Research Projects

Obesity is a major public health concern in the United States that is projected to increase exponentially over the next few years. Obesity is commonly associated with a lower socioeconomic status. Lower-income individuals tend to be supported by Medicaid, a federal insurance program for low-income Americans. Prior studies have shown a positive correlation between income status and obesity prevalence. Our goal was to find if there was a correlation between Medicaid patients and obesity in Northeast Ohio, to provide physicians with a set of characteristics to better combat obesity, since preventative and treatment guidelines are tailored to national trends. We …

Neighborhood Socioeconomic Deprivation And Physical Activity Associate With Extracellular Vesicle Size And Cargo In A Community-Based Cohort Of Women, Yvonne Baumer, Elizabeth M. Aquino Peterson, Matthew R. Bavuso, Noel Miller, Cristhian A. Gutierrez-Huerta, Nithya P. Vijayakumar, Sam J. Neally, Kaveri Curlin, Valerie M. Mitchell, Billy S. Collins, Neelam R. Redekar, Subrata Paul, Anca D. Dobrian, Tiffany M. Powell-Wiley

Department of Biomedical and Translational Sciences Faculty Publications

African American (AA) women face disproportionate cardiovascular disease (CVD) risk due to adverse social determinants of health (SDoH), including lower socioeconomic status (SES). Physical activity (PA) and plasma extracellular vesicles (EVs) modulate CVD risk, but their relationships with SDoH remain unclear. This study examines associations between SDoH, PA, and plasma EVs in a Washington, DC-based cohort of at-risk AA women. Participants (N = 24, Age: 57 ± 12, BMI: 35 ± 6, ASCVD: 9 ± 5) joined the Step It Up Community-Engaged, Digital Health Physical Activity Intervention pilot study. EVs were isolated from fasting plasma samples. Multivariable regression, adjusted for …

The Connection Between Medicaid And Obesity In Northeast Ohio, Sophie Kheder, Emmie Kelley

Williams Honors College, Honors Research Projects

Obesity is a major public health concern in the United States that is projected to increase exponentially over the next few years. Obesity is commonly associated with a lower socioeconomic status. Lower-income individuals tend to be supported by Medicaid, a federal insurance program for low-income Americans. Prior studies have shown a positive correlation between income status and obesity prevalence. Our goal was to find if there was a correlation between Medicaid patients and obesity in Northeast Ohio, to provide physicians with a set of characteristics to better combat obesity, since preventative and treatment guidelines are tailored to national trends. We …

Repurposing Cyclin-Dependent Kinase Inhibitors For The Discovery Of Novel Antiplasmodial Compounds, Ritam Bhowmik

Honors Undergraduate Theses

Malaria remains a major global health burden with over 282 million cases annually and rising resistance to artemisinin-based combination therapies. Plasmodium falciparum, the most lethal malaria parasite species in humans, relies on tightly regulated cell cycle progression during replication within red blood cells. Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell division and transcription, and several CDK-like enzymes in P. falciparum, including Pfmrk and PfPK6, are essential for parasite growth and structurally distinct from human kinases. This study evaluated whether commercially available human CDK inhibitors (CDKIs) targeting cancer pathways could be repurposed as novel antimalarial compounds. A library of …

Investigating Racial And Ethnic Disparities In Cardiometabolic Outcomes Among Women With Polycystic Ovarian Syndrome: An Umbrella Review, Gianna C. Santoni

Honors Undergraduate Theses

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological disorders affecting women of reproductive age. Due to the possibility of a genetic component affecting women with PCOS, evidence supports varying health outcomes among racial and ethnic groups. This literature aims to answer the question: Does the prevalence of cardiometabolic outcomes differ among women with polycystic ovarian syndrome across racial/ethnic groups? This umbrella review was conducted in accordance with JBI Manual for Evidence Synthesis and PRIOR reporting guidelines and was registered on PROSPERO (CRD420261303872) before completion. PubMed, MEDLINE via EBSCOhost, and Web of Science via EBSCOhost were searched from …

Transition To Home Guideline For Patients With Diabetes, Kathleen R. Burgner

Doctor of Nursing Practice (DNP) Scholarly Projects

Background: Diabetes is a leading contributor to preventable hospital readmissions. These hospital readmissions often result from fragmented discharge planning, poor care coordination, and limited post-discharge support. At a 915-bed academic medical center in Southern California, the diabetes-related readmission rate was 13.3%, compared with 11.4% among patients without diabetes. This project aimed to develop an evidence-based Transition-to-Home (TTH) guideline for hospitalized patients with diabetes and evaluate the strength of its recommendations through multidisciplinary stakeholder review.

Methods: An evidence-based guideline development project was conducted over 8 weeks. A comprehensive literature search in CINAHL, MEDLINE, PubMed, and ScienceDirect identified current evidence on transitional …

Does Guideline-Directed Breast Mri Improve Early Identification In The High-Risk Breast Cancer Population, Cemile Littlepage

Doctor of Nursing Practice (DNP) Scholarly Projects

Introduction: In the United States, one in eight women will be diagnosed with breast cancer. The American Cancer Society's 2007 guidelines (Onishi & Kataoka, 2020) and the American College of Radiology recommend that MRI screening, alongside annual mammography, be used for women at high risk for breast cancer (Lamb et al., 2023; Sardanelli et al., 2024). Currently, there are various screening models, and no standardized tool or national guideline exists for MRI screening in high-risk patients. This guideline project aims to establish a screening model and recommendations for MRI screening in high-risk women for use in primary care.

Methods: A …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Mortality From Or With Covid-19 Infection, Dagan Coppock, Joseph Glowacki, Constantine Daskalakis, John Zurlo, Nikita Jaggernauth, Daniel Taupin

Division of Infectious Diseases and Environmental Medicine Faculty Papers

In this retrospective study, we compared the cause of death among hospitalized patients who died with a diagnosis of COVID-19 across two periods of the pandemic two years apart: an early period (admissions June to October 2020), when the population was immunologically naïve, and a later period (admissions April to October 2022), when an estimated 96% of the population had immunity from prior infection, vaccination, or both. Two investigators independently reviewed the medical records of 100 in-hospital deaths (50 per period) and classified each death as COVID-19 related, uncertain, or not COVID-19 related, using logistic regression to compare the two …

Microsolvation Effects Of 1,1-Dimethyl-Biguanide (Metformin), Jasmine L. Sanders

Honors Theses

The microsolvation of a 1,1-dimethyl-biguanide hydrochloride molecule in the presence of water molecules illustrates the initial interactions between the common drug metformin and water. This explicit water-solvation approach employs coupled-cluster theory with an explicit-correlation F12 correction and the cc-pVTZ-F12 basis set to determine the optimalgeometry of the molecule and to observe intermolecular interaction energies. 1,1-dimethyl-biguanide hydrochloride (an antidiabetic agent, metformin) is constantly in contact with water molecules in the human body, where it reduces intestinal glucose absorption, lowers hepatic glucose sensitivity, and improves overall insulin sensitivity to lower blood-glucose concentration. The B3LYP method with an aug-cc-pVTZ basis set is used …

Comparative Analysis Of M1 And M2 Macrophage Distribution And Localization In Chronic Wounds Of Metabolically Healthy And Diabetic Hosts Using A C57bl/6 Mouse Model, Bryan Liu, Ramiro Cisneros, Nathaniel Primous, Estephania Garcia, Bhuvana Lakkasetter Chandrashekar, Claudia Biguetti

School of Podiatric Medicine - Student Research

Introduction/Purpose: Type 2 diabetes and obesity are major risk factors for delayed wound healing in chronic foot ulcers. This study investigated whether a high-fat diet induces diabetes-like metabolic dysfunction in mice and characterized associated morphological changes and macrophage polarization during wound healing. Macrophages exist as pro-inflammatory M1 and anti-inflammatory M2 phenotypes that regulate tissue repair.

Methods: Ten male C57BL/6J mice (8 weeks old) were divided into high-fat diet (HFD) and regular diet (RD) (IACUC Protocol 22-33) groups.  After 12 weeks, body weight and intraperitoneal glucose tolerance test were measured to confirm metabolic phenotypes, after which a 6mm dorsal excision wound …

Oropharyngeal Syphilis Presenting As Tongue Based Ulcer With Lymphadenopathy, Serena F. Pu, Kevin J. Carlson, Jonathan R. Mark, Benjamin J. Rubinstein

Department of Otolaryngology (ENT) Faculty Publications

Within the aerodigestive tract, syphilis presents with varied signs and symptoms, some of which may mimic malignancy or other disease processes. We present the case of a 29-year-old man with otalgia and odynophagia who was found on physical examination and office laryngoscopy to have a 4-cm ulcerative mass of the tongue base and cervical lymphadenopathy. While planning for tissue diagnosis, the patient’s serologies revealed positive treponemal antibody testing and elevated rapid plasma reagin (RPR) titers, confirming syphilitic infection, likely representing secondary syphilis. While awaiting operative biopsy, the patient received intramuscular penicillin with complete resolution of the mass and symptoms, and …

Depemokimab: A Twice Yearly Anti-Il 5 Biologic For Chronic Rhinosinusitis With Nasal Polyps (Crswnp) - A Narrative Review, Marn Joon Park, Joseph K. Han, Kent K. Lam

Department of Otolaryngology (ENT) Faculty Publications

Depemokimab is a monoclonal antibody that targets interleukin-5 with enhanced binding affinity and an extended terminal elimination half‑life of 6-8 weeks. The unique pharmacodynamic features of depemokimab enable sustained suppression of type 2 inflammation with twice‑yearly subcutaneous dosing. This narrative review provides details of depemokimab's molecular profile, pharmacokinetics, and pharmacodynamics and results regarding the clinical efficacy and safety of depemokimab from recently published Phase 3 clinical trials for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). In 528 severe adult CRSwNP patients (ANCHOR‑1/‑2 trials), depemokimab achieved Δ total endoscopic nasal polyp score by -0.70 (p <  .001) and Δ nasal obstruction verbal response scale by -0.24 (p = .003) at week 52, compared to placebo. Twice‑yearly 100 mg depemokimab provides durable eosinophil suppression and with a safety profile comparable to placebo in Phase 3 trials for CRSwNP. Future work should refine biomarkers and assess comparative cost‑effectiveness and long‑term adherence, safety, and effectiveness.

Dupilumab In Chronic Rhinosinusitis Without Nasal Polyps: Randomized Phase 2 Trial (Orion), Stella E. Lee, Anju T. Peters, Philippe Gevaert, Joseph K. Han, Claus Bachert, Francisco Moreira Da Silva, Andrés Rosenblüt, Chih-Chi Hu, Jennifer Maloney, Paolo Caferra, Adrianna Michalak, Andrew P. Fontenot, Lacey B. Robinson, Neelam A. Phadke

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Chronic rhinosinusitis (CRS) is often driven by type 2 inflammation and is characterized by nasal obstruction/ discharge, facial pain/pressure, and/or reduced smell, either with or without nasal polyps (CRSwNP or CRSsNP).

OBJECTIVE: To test whether dupilumab improves radiographic features in CRSsNP. Methods: ORION (NCT04678856), a phase 2, randomized, multicenter, double blind, placebo-controlled study, assessed dupilumab efficacy and safety in adults with uncontrolled CRSsNP. Patients were randomized 1:1 to dupilumab or placebo for 24 to 52 weeks. Endpoints included changes from baseline at week 24 in Lund–Mackay computed tomography (LMK-CT) score (dupilumab only [primary] and vs placebo [secondary]), sinus Total …

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …