Anatomy Commons^™

Chronobiology Of Meal Timing In Early-Stage Hypertension: A Controlled Feeding Pilot Study Investigating The Effects On Renal And Vascular Function, Natalie J. Bohmke, Brittany Barton, Patrice Wiecek, Paula Rodriguez-Miguelez, Dave L. Dixon, Youngdeok Kim, Salvatore Carbone, Danielle L. Kirkman

EVMS School of Health Professions Faculty Publications

Lifestyle intervention is critical for young adults with early-stage hypertension. A Western diet has negative effects on kidney function and blood pressure; however, time-of-day effects are understudied. We hypothesized that consumption of a Western-style meal that is misaligned with the endogenous circadian rhythm would have adverse effects on blood pressure, kidney function, and vascular function. Ten young adults with elevated blood pressure or stage 1 hypertension (means ± SD: 26 ± 8 yr, 50% female) underwent a randomized crossover, isocaloric controlled feeding intervention. Participants were allocated to receive a Western-style meal high in sodium, sugar, and saturated fat in the …

The Treatment Of Obesity In The Context Of The Obesity Paradox In Patients With Heart Failure: A Narrative Review, Pamela L. Alebna, Sarah Martey, Anurag Mehta, Carl J. Lavie, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Purpose of review

While excess adiposity is a known risk factor for incident heart failure ( HF), once the condition is established, observational data suggest that increased body mass index (BMI) may confer a survival advantage. This paradox has emphasized the underlying roles of cardiorespiratory fitness (CRF), and body composition, particularly lean mass (LM), in influencing clinical outcomes.

Recent findings

In this review, we explore the multifaceted nature of the obesity paradox in HF, with a focus on emerging anti-obesity incretin-mimetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. These agents …

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 …

Deletion Of Stim1 In Treg Cells Protects Against Lung Fibrosis And Associated Cardiovascular Complications In A Pre-Clinical Mouse Model, Nagaraja Nagre, Balaji Srinivas, Nicholas Richards, Ryan Washington, Gregory Nicholson, Yan Sanders, Beata Kosmider, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable lung disease characterized by excessive tissue remodeling and impaired gas exchange. Evidence highlights the critical interplay between immune regulation, calcium signaling, and redox biology implications in the pathogenesis of fibrotic lung disease. Regulatory T-cells (Tregs), known to modulate cardiovascular and immune function, are diminished in IPF, contributing to inflammation and tissue damage. Here, we demonstrate that the stromal interaction molecule 1 (STIM1), a key regulator of intracellular calcium homeostasis, is significantly upregulated in Treg cells isolated from IPF patients and mice subjected to bleomycin-induced lung injury. This upregulation is associated with …

Senescent Fibroblasts In Aging And Pulmonary Fibrosis, Sara B. Palega, Aiwei Y. Borengasser, Yan Y. Sanders

Department of Biomedical and Translational Sciences Faculty Publications

Aging is a major risk factor for many chronic lung diseases, including Idiopathic Pulmonary Fibrosis (IPF), a fatal and incurable disease characterized by progressive fibrotic remodeling. Age-associated structural alterations, impaired regenerative capacity, and dysregulated cellular signaling collectively create a pro-fibrotic microenvironment. A central driver of this pathological shift is the accumulation of senescent cells, which undergo irreversible growth arrest and develop a robust pro-inflammatory senescence-associated secretory phenotype (SASP). Emerging evidence identifies senescent lung fibroblasts as critical mediators of IPF pathogenesis. These cells promote excessive extracellular matrix deposition, myofibroblast differentiation, and tissue stiffening, while simultaneously impairing epithelial regeneration. Together, these effects …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Biomechanical Integrity Of The Female Pelvic Floor: A Comparison Of Military And Civilian Women, Vladimir Egorov, Peter Takacs, Vincent Lucente, Heather Van Raalte, Joy A. Greer, Noune Sarvazyan

Department of Obstetrics & Gynecology Faculty Publications

Introduction

The health of the pelvic floor depends on the integrity of its muscles, connective tissue, ligaments, and their innervation. The female pelvic floor may be more vulnerable to repetitive heavy loads in a military environment than the male pelvic floor because of anatomical and physiological differences. The study aim was to identify and explore possible differences in the female pelvic floor conditions between active military and civilian women with similar demographics.To identify and explore possible differences in the conditions of the female pelvic floor between active military women and civilian women with similar demographics.

Materials and Methods

Military active …

Cervicovaginal Lavage Fluid Iron And Manganese Levels In Women With And Without Vaginitis, Barbara Kozma, David Ratonyi, Bence Kozma, Peter Takacs, Attila G. Sipos

Department of Obstetrics & Gynecology Faculty Publications

Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host–pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women ≥ 18 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) …

Severe Maternal Morbidity According To Sickle Cell Disease Genotype, Tetsuya Kawakita, Natsume Furukawa, Sora A. Jones, Salimah Navaz Gangji

Department of Obstetrics & Gynecology Faculty Publications

Background

Sickle cell disease (SCD) is a genetic hemoglobinopathy that disproportionately affects individuals of African descent and is associated with elevated risks of maternal complications. However, the contribution of specific SCD genotypes to severe maternal morbidity (SMM) and postpartum readmission remains poorly characterized at the population level.

Objective

We sought to examine the association between SCD genotypes-hemoglobin SS (HbSS) disease, hemoglobin SC (HbSC) disease, sickle thalassemia, and sickle cell trait-and SMM, hospital readmission, and related adverse maternal outcomes.

Study design

This was a retrospective cohort study using the Nationwide Readmissions Database from 2016 through 2022, representing over 20 million weighted …

Intraoperative Positioning System-Guided Antegrade In Situ Laser Fenestration In An Aortic Model, Emily Burnett, Emidio Germano, Allie Olmstead, Benjamin Samberg, Robert Meisner, Hannah Hofacker, Michael Bronez, Vikash Goel, Animesh Rathore

Department of Medicine Faculty Publications

Objective

Fenestrated endovascular aneurysm repair (fEVAR) is routinely being used for visceral vessel incorporation in complex aneurysmal pathology; however, it is associated with prolonged procedure times, high radiation exposure, high contrast use, and multiple staged procedures. To combat these limitations, Centerline Biomedical developed the three-dimensional surgical navigation and visualization technology: intraoperative positioning system (IOPS). We previously presented our IOPS-guided antegrade in situ laser fenestration in a standard aortic model. This case report details our experience using IOPS guidance during a fEVAR procedure in a representative thoracoabdominal aortic aneurysm phantom model.

Methods

A silicone thoracoabdominal aortic segment was three-dimensional printed based …

Upadacitinib For Recalcitrant Extraintestinal Crohn Disease, Avery H. Seward, Jeffrey P. Callen

Department of Medicine Faculty Publications

[Introduction] Crohn disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract from the mouth to the anus. Extra-intestinal manifestations of Crohn disease are common, with the skin being the most commonly involved site.¹ Cutaneous manifestations of Crohn include lesions that directly extend from the bowel to the skin, whereas extraintestinal Crohn disease involves sites that do not directly extend from the bowel.¹ Extraintestinal Crohn disease is often resistant to treatments and often does not parallel the activity of the bowel disease.¹ There have only been 3 documented cases of extraintestinal Crohn disease responding to upadacitinib.²,³ We describe …

Educational Case: Meningioma, Ashley M. Carter, Harrison Dai, Harrison Klause, Alberto Musto, Richard M. Conran

Department of Medicine Faculty Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Replacement: Incidence, Predictors, And Association With Reduced Ischemic Stroke Risk, Omar Saleh, Nicholas J. Valle, Shinjer Li, Saleh Mostafa, Israa Saleh, Raymond Benza, Deepak R. Talreja, Matthew R. Summers

Department of Medicine Faculty Publications

Background

Development of conduction abnormalities requiring pacing after transcatheter aortic valve replacement (TAVR) is relatively common. The effects of post-TAVR permanent pacemaker (PPM) implantation on mortality, ischemic stroke, and cardiovascular outcomes remain incompletely characterized. AIMS: To evaluate the incidence, predictors, and cardiovascular outcomes of post-TAVR permanent pacemaker implantation, including its association with 1-year ischemic stroke risk.

Methods

Adults undergoing TAVR (2008-2019; n = 1101) were evaluated. Patients with prior PPM (n = 104) and/or valve-in-valve or redo TAVR (n = 11) were excluded. PPM placement was identified post-indexed TAVR admission based on procedure codes, including both in-hospital and post-discharge implantations. …

Successful Use Of Chimeric Antigen Receptor T-Cell (Car-T) Therapy With Lisocabtagene Maraleucel In A Renal Transplant Recipient With Refractory/Relapsed Diffuse Large B-Cell Lymphoma (Dlbcl), Waqqas Tai, Fatima Chaudhry, Nesreen Shahrour, Jessica Thomas, Afoma Anyadibe, Anuoluwa Oyetoran, Swathi Gopishetty, Precious Idogun, Dilip Samarapungavan, Jassim H. Sarmad, Ishmael Jaiyesimi

Department of Medicine Faculty Publications

This case describes a 53-year-old male with end-stage renal disease who developed monomorphic post-transplant lymphoproliferative disorder (PTLD) in the form of diffuse large B-cell lymphoma (DLBCL) after kidney transplantation. Despite initial treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), the patient's disease progressed, and he was referred for chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel (liso-cel). Given his post-transplant status, his immunosuppressive agents (tacrolimus and mycophenolate) were held, and prednisone was tapered to 5 mg daily to maintain minimal baseline immunosuppression. After lymphodepleting chemotherapy and liso-cel infusion, the patient experienced no significant toxicities, including cytokine release syndrome (CRS) …

Combined Snare And Buddy-Balloon Strategy For Failed Valve Crossing In Valve-In-Valve Transcatheter Aortic Valve Replacement, Hira Sarfraz, Muhammad U. Javed, Parth K. Parikh, Joshua A. Cohen, Raymond L. Benza, Matthew R. Summers, Deepak R. Talreja

Department of Medicine Faculty Publications

Background Retrograde valve crossing during valve-in-valve transcatheter aortic valve replacement (ViV TAVR) may fail despite modern delivery systems. Case Summary A 67-year-old man with a degenerated 27-mm Magna Ease bioprosthesis and unfavorable aortic geometry (kinked ascending aorta at a prior surgical graft site) underwent ViV TAVR, where retrograde valve crossing failed despite multiple stiff guidewires and snare traction alone. Successful delivery of a 29-mm Evolut FX+ was ultimately achieved by combining gooseneck-snare traction for coaxial realignment with a partially inflated Tyshak buddy balloon acting as a mechanical ramp across the surgical valve frame. Discussion This case demonstrates a structured, stepwise …

Percutaneous Closure Of Ventricular Septal Rupture After Myocardial Infarction:, Thomas A. Cook, Simone K. Schumaecker, Anjani Patibandla, Nicholas J. Valle, Matthew R. Summers

Department of Medicine Faculty Publications

BACKGROUND: Ventricular septal rupture (VSR) following acute myocardial infarction is a rare but deadly complication with mortality rates exceeding 90% when left untreated. Coronary ischaemia leads to myocardial necrosis and friability resulting in septal rupture, most commonly 3-5 days post-infarction. The sudden development of a left-to-right shunt causes volume overload in the right ventricle, pulmonary vasculature, and left atrium, precipitating biventricular failure, and cardiogenic shock. Management requires careful consideration of timing and modality of closure along with stabilization with mechanical circulatory support in severe cases.

CASE SUMMARY: A 65-year-old female presented with anterior ST-segment elevation myocardial infarction complicated by VSR …

Dietary Intake Of Micro- And Nanoplastics: Potential Adverse Gi Effects On Microbiome, Inflammation, And Neoplasia, Michael Saadeh, Gordon Hong, Sana Rabeeah, Priyata Dutta, Edward C. Oldfield, Iv, David A. Johnson

Department of Medicine Faculty Publications

Micro- and nanoplastics (MNPs) are pervasive in food-contact environments and the human diet, positioning the gastrointestinal (GI) tract as the primary portal of entry and a plausible site of early biological effects. Human exposure is supported by detection of microplastics in stool and colon tissue, and emerging clinical studies report associations between fecal microplastic burden and GI disease states, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Preclinical studies provide mechanistic plausibility, reporting that ingested MNPs can modulate microbial ecology, alter mucus membrane integrity, increase intestinal permeability through changes in cellular tight junction biology, and induce inflammatory gene expression. …

Open Transatrial Valve-In-Mitral Annular Calcification Mitral Valve Replacement With An Autologous Anterior Leaflet Sealing Skirt, Omar Saleh, Nicholas Valle, Rishab Agarwal, Israa Saleh, Joshua Dolsen, Connor Mckechnie, Dhruvi Patel, Deepak R. Talreja, Matthew R. Summers, Christopher M. Sciortino

Department of Medicine Faculty Publications

[Central Message] In patients undergoing ViMAC, surgical fixation of the native anterior mitral leaflet to a BEV cuff creates an autologous seal, reducing risk of paravalvular leak and neo-LVOT obstruction.

Glucagon-Like Peptide Receptor Agonists (Glp-1ras) As Cardiovascular Risk Modifiers In Obstructive Sleep Apnea And Obesity: A Real-World Study, Jaeun Ahn, Junmin Song, Kyle Admire, Yu Chang, Kuan-Yu Chi, Nathaniel T. Gordon, Joshua M. Sill

Department of Medicine Faculty Publications

Introduction

Obstructive sleep apnea (OSA) is a well-established risk factor for cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated potential in reducing cardiovascular risk and improving OSA severity. However, a significant knowledge gap remains regarding the impact of GLP-1RAs on cardiovascular events in OSA patients.

Methods

We examined patients with a BMI over 30 diagnosed with OSA between January 2010 and November 2021 without a previous diagnosis of heart failure, pulmonary hypertension, or myocardial infarction. Two cohorts were created: those prescribed GLP-1RAs within 1 year of their OSA diagnosis and patients who were never prescribed GLP-1RAs. Propensity score matching …

Baseline Lymphopenia Predicts Survival In Ici-Naïve Solid Tumor Patients Receiving Immune Checkpoint Inhibitors: A Propensity-Matched Real-World Pan-Cancer Analysis, Ahmed Ismail, Nina Balanchivadze, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia …