Medical Pathology Commons^™

Complications And Management Of Idiopathic Multicentric Castleman Disease, Kavanya Feustel, Jacob W. Keeling, Olivia Makos, Dmitriy Scherbak

HCA Healthcare Journal of Medicine

Background

The pathophysiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood compared to the other subtypes of MCD, which has contributed to limited treatment options and poor prognosis for iMCD patients. The pathogenesis of iMCD is thought to be mediated in part by dysregulation of interleukin (IL)-6.

Case Presentation

We present a case report of a 39-year-old Caucasian man with siltuximab-refractory iMCD. He presented with severe lower extremity lymphedema and wounds. His disease progressed through standard-of-care siltuximab. Due to his severe disease-related morbidity, he contracted recurrent infections, often complicated by sepsis. Ultimately, he required a left lower extremity amputation. …

Topical Lifitegrast Therapy For Dry Eye Disease, Lama Assi, Salim C. Lutfallah, Tsz Wing Yim, Su Hsun Liu, Sharon J. Duffy, Jayne Weiss

School of Medicine Faculty Publications

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effectiveness and safety of topical lifitegrast therapy alone or in combination with artificial tears, compared with a placebo, artificial tears alone, or no treatment for dry eye disease.

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

Human Endogenous Retroviruses (Hervs) Associated With Glioblastoma Risk And Prognosis, Harun Mazumder, Hui Yi Lin, Melody Baddoo, Wojciech Gałan, Diana Polania-Villanueva, Chindo Hicks, David Otohinoyi, Francesca Peruzzi, Zbigniew Madeja, Victoria P. Belancio, Erik K. Flemington, Krzysztof Reiss, Monika Rak

School of Medicine Faculty Publications

Emerging evidence suggests expression from human endogenous retrovirus (HERV) loci likely contributes to, or is a biomarker of, glioblastoma multiforme (GBM) disease progression. However, the relationship between HERV expression and GBM malignant phenotype is unclear. Applying several in silico analyses based on data from The Cancer Genome Atlas (TCGA), we derived a locus-specific HERV transcriptome for glioma that revealed 211 HERVs significantly dysregulated in the comparisons of GBM vs. normal brain (NB), GBM vs. low-grade glioma (LGG), and LGG vs. NB. Our analysis supported development of a unique HERV scoring algorithm that segregated GBM, LGG, and NB. Interestingly, lower HERV …

Diagnostic Considerations For Gastrointestinal Stromal Tumors With Altered Immunophenotype Following Imatinib Treatment: A Case Report And Literature Review, Jihuan Chen, Liz M. Yang, Jonathan Somma, Yujun Gan, Zengying Wu, Zhiyan Fu

School of Medicine Faculty Publications

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract and have a high rate of recurrence and metastasis. Using an immunohistochemical (IHC) panel including KIT/CD117 and DOG1 allows for accurate diagnosis in more than 98% of cases. However, after tyrosine kinase inhibitor treatment, some cases can exhibit histologic dedifferentiation and loss of KIT/CD117 and DOG1 expression that may cause difficulty in confirming recurrent or persistent disease. We present such a case of an Imatinib treated, CD117 and DOG1 dual negative, metastatic GIST to the liver in a 55-year-old female which required molecular analysis to confirm …

Discrepancy Between Hyaluronic Acid Levels And Mri-Based Measurements Of Hepatic Fat And Fibrosis, Daniel Aaron Borman, Rachel L. Chevalier, Jonathan Body Ingestion Clinical Wagner, Michele T. Pritchard, Sherwin S. Chan, Nathan S. Artz, Johnston K. Fite, Yoon Y. Cho, Valentina Shakhnovich, Veronica Williams, Voytek Slowik

Research Days

Introduction

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the United States and, when left untreated, can progress to liver fibrosis. Clinicians currently utilize imaging and biopsy to assess fibrosis in this patient population as there is no validated serum biomarker available for detecting fibrosis. Previous research suggests that serum hyaluronic acid levels are predictive of hepatic fibrosis in children with MASLD.

Methods

Retrospective data were obtained from the Children’s Mercy Hospital Liver Lab study. Pediatric subjects with both hyaluronic acid (HA) samples and MRI evaluation within a month were identified and included for …

A Fatal Triad: Concurrent Pulmonary Infections With Candida, Mucorales, And Aspergillus In An Immunocompromised Patient With Underlying Vasculitis And Diabetes, Paridhi Ghai, Kavitha Gopalratnam

Posters

We present a case of disseminated fungal disease involving simultaneous infections with Candida, Mucorales, and Aspergillus.

Pseudomonas Aeruginosa Exoenzyme Y Enzymatic Activity Inhibits Exoenzyme S-Induced Caspase Activation But Not Cytotoxicity In Pulmonary Microvascular Endothelial Cells, Connor Holm

Honors Theses

Pseudomonas aeruginosa (P. aeruginosa) is the most common cause of ventilator-associated pneumonia in intensive care unit patients. P. aeruginosa utilizes a type III secretion system that injects exoenzymes U, S, T, and/or Y into the host cell cytosol. A majority of clinically isolated P. aeruginosa strains express ExoY often in combination with ExoU and ExoT, or ExoS and ExoT. Host signaling mechanisms in response to intoxication with individual exoenzymes have been extensively studied, yet little is known about host cell response to co-intoxication. In this study, pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains expressing different combinations …

A Review Of Praziquantel Resistance In Schistosomes And The Future Of Schistosomiasis Control, Gabriela G. Eastham

Senior Honors Theses

Schistosomiasis is a group of both acute and chronic parasitic trematode infections of the genus Schistosoma. Praziquantel (PZQ) has been the drug of choice to treat schistosomiasis for decades. Though it is effective against all three clinically relevant species, heavy reliance on PZQ has led to concerns of schistosome resistance, especially in areas that have implemented this drug in mass drug administration (MDA) programs. Although there is currently insufficient evidence to conclude that schistosomes are becoming resistant to PZQ on a large scale, other control methods are a necessity to best treat and eliminate schistosomiasis. This article summarizes the …

Age-Dependent Mineralization And Osteogenesis In Intact & Injured Murine Bones: A Histological And Immunochemical Study, Amogh Chittajallu

Honors Scholar Theses

Bones function as living organs through their mineralized matrix and specialized cell populations, which provide structural support and enable movement, while storing minerals and creating a space for blood cell production in the marrow¹. As individuals age, hormonal changes reduce osteoblast activity while osteoclast-mediated bone resorption persists, resulting in lower mineral density and heightened fracture risk². We examined how aging impacts young and old murine femurs because these models display bone structure and cellular organization that closely resemble human long bones. This research study used six distinct histological stains to observe essential features of bone tissue …

Histomorphology Of Sharp-Force Trauma On Partially Cremated Remains, Horaceena Findley

Student Theses

Identifying sharp-force trauma in thermally altered human remains presents a significant challenge in forensic investigations, particularly in arson-related deaths where traditional autopsy techniques may be limited. This study explores the efficacy of histological methods in detecting sharp-force trauma on partially cremated remains using pig ribs (Sus scrofa) as a human analog. Simulated tool marks from a knife, screwdriver, and flathead screwdriver were inflicted at varying angles (60° and 90°) and subsequently exposed to high temperatures in an open fire setting. Histological analyses, including Hematoxylin and Eosin Y (H&E) and Gomori’s Prussian Blue staining, were employed to assess tissue structure and …

Pembrolizumab-Associated Acute Esophageal Necrosis: A Case Report And Literature Review, Mark Tawfik, Elie Bou Sanayeh, Stephanie Chain, Ahmed Elfiky, Stephen Mulrooney

HCA Healthcare Journal of Medicine

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. They pose challenges, particularly in the form of immune-related adverse events (irAEs). Although cases of gastrointestinal irAEs have been well-documented, acute esophageal necrosis (AEN) characterized by a circumferential blackening and fragility of the esophagus, weeks after immunotherapy discontinuation, has not been reported.

Case Presentation

A 75-year-old diabetic male who was recently diagnosed with high-grade papillary urothelial cancer with liver and retroperitoneal metastases and had undergone radical cystectomy with ileal conduit urinary diversion, presented to the hospital for sepsis secondary to a urinary tract infection. While in the hospital, he experienced hematemesis, …

Intracolonic Migration Of A Dislocated Acetabular Cup Prosthesis, Jack R. Lubka, Cyrus Tamboli, Philip Brunetti, Sarosh Tamboli, Alex Davis, Hamish Patel, Olugbenga Oyesanmi, Michael Strobbe, Shaival Thakore, Subhasis Misra, Jeffrey Mino

HCA Healthcare Journal of Medicine

Background

Acetabular cup migration is a rare complication of hip replacement surgery. If the acetabular socket of the ilium is weak, the prosthesis can erode or pass through it. There have been multiple reports of acetabular cup prosthesis migration to the colon, creating a coloarticular fistula between the hip joint and the cecum, sigmoid colon, or rectum. We report a rare presentation of a complete intracolonic migration of a prosthetic acetabular cup without creating a fistula.

Case Presentation

A 53-year-old female patient with a remote history of a total right hip replacement presented with abdominal pain and rectal bleeding. Computed …

Surgical Specimen Management Protocols In The Pre-Analytical Phase, Jordan L. Hall

Doctor of Nursing Practice Final Project Abstract

Purpose

This quality improvement (QI) project aimed to decrease surgical specimen errors during the pre-analytical phase at the target institution by 50% by January 2025 by developing best practices for specimen labeling and documentation.

Background

The QI project was implemented within a level two trauma center with a 24-suite operating room (OR) in The Woodlands, Texas, which provides care across all surgical specialties except ophthalmology.

Methodology

The target institution changed from nurse-hand-written specimen labels and requisition sheets to electronic medical record (EMR) generated specimen labels and requisition sheets. The change was congruent with the target institution’s shift to a new …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Study Of Proportion Of Cardiac Involvement Secondary To Dengue Infection In Pediatric Population Admitted In A Tertiary Hospital- A Prospective Cross-Sectional Study, Neha Bhongale, Qudsiya Ansari, Ravindra Chittal

Digital Journal of Clinical Medicine

Background- Dengue is one of the most important mosquito-borne illnesses worldwide. Cardiac manifestations of dengue illness can range from asymptomatic bradycardia to life-threatening myocarditis. There is an overall paucity of published Indian studies of clear demonstration of cardiac manifestations secondary to dengue in the pediatric population. Aim- To study the proportion of patients with cardiac involvement secondary to dengue viral infection in the pediatric age group based on clinical manifestations of cardiac enzymes (CKMB, Troponin I) and ECG (electrocardiography), in a tertiary center. Methodology- This study is undertaken to find out the proportion of patients with cardiac manifestations secondary to …

Deep Learning For Fine-Grained Digital Histopathology Image Analysis, Joseph Dipalma

Computer Science Technical Reports

As digital pathology becomes increasingly popular, it is critical to develop machine learning solutions to utilize this data. While other image modalities have seen exponential increases in methodology availability, the same has not been true for histopathology images. This is likely in part because histopathology whole slide images possess unique characteristics that prevent simply applying existing methods as-is.

In this thesis, we identify and propose solutions to 3 open problems with histopathology images: 1. large raw image size (up to 150,000×150,000 pixels in size), 2. low class-positivity (low ratio of positive to negative patches), and 3. limited image availability with …

Emergence Of Transferable Daptomycin Resistance In Gram-Positive Bacteria, Tessa Marciniak, Lukas Kirchner, Silver A. Wolf, Birgit Walther, Thorsten Bischler, Justin Nyasinga, R Gunturu, Torsten Semmler, Tom Gräfenhan, Andrew Whitelaw

Pathology, East Africa

Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from …

Liver Tet1 Promotes Metabolic Dysfunction-Associated Steatotic Liver Disease, Hongze Chen, Muhammad Azhar Nisar, Joud Mulla, Xinjian Li, Kevin Cao, Shaolei Lu, Katsuya Nagaoka, Shang Wu, Peng Sheng Ting, Tung Sung Tseng, Hui Yi Lin, Xiao Ming Yin, Wenke Feng, Zhijin Wu, Zhixiang Cheng, William Mueller, Amalia Bay, Layla Schechner, Xuewei Bai, Chiung Kuei Huang

School of Public Health Faculty Publications

Global hepatic DNA methylation change has been linked to human patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DNA demethylation is regulated by the TET family proteins, whose enzymatic activities require 2-oxoglutarate (2-OG) and iron that both are elevated in human MASLD patients. We aimed to investigate liver TET1 in MASLD progression. Depleting TET1 using two different strategies substantially alleviated MASLD progression. Knockout (KO) of TET1 slightly improved diet induced obesity and glucose homeostasis. Intriguingly, hepatic cholesterols, triglycerides, and CD36 were significantly decreased upon TET1 depletion. Consistently, liver specific TET1 KO led to improvement of MASLD progression. Mechanistically, TET1 promoted …

Periclavicular Multifocal, Infiltrative Extraneural Soft Tissue Perineuriomas: Illustrative Case, Ankur Khanna, Matthew Darlow, Rachna Jetly Shridhar, Matthew G. Cable

School of Medicine Faculty Publications

BACKGROUND Perineuriomas are benign, typically solitary tumors with intraneural and extraneural subtypes presenting distinct clinical manifestations and symptomatology. Here, the authors report a unique case of multifocal, infiltrative extraneural soft tissue perineuriomas localized to the shoulder. OBSERVATIONS A 33-year-old female presented with 1 year of right neck and shoulder pain accompanied by a new onset of numbness and tingling down her right arm. MRI of a mass apparent over her right trapezius and scapula revealed several mixed cystic and solid neoplasms encroaching on the C5–6 nerve roots and brachial plexus. The tumors were biopsied and confirmed by immunohistochemical staining to …