Medical Sciences Commons^™

Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu

School of Medicine Faculty Publications

Basal-like breast cancer (BLBC) is a major subtype of triple-negative breast cancer (TNBC), characterized by aggressive behavior, limited treatment options, and poor prognosis. While HER3 overexpression is frequently observed in TNBC and associated with poor outcomes, its subtype-specific expression and therapeutic potential remain unclear. Here, we demonstrated that HER3 signaling is selectively hyperactivated in BLBC compared to claudin-low breast cancer (CLBC) using transcriptomic profiling. Histone deacetylase inhibitors (HDACi), Romidepsin and Panobinostat, exerted potent antitumor effects on BLBC by selectively downregulating HER3 expression. HER3 levels were positively correlated with FOXA1, a key transcriptional activator. Mechanistically, we identified GATA2 and GATA3 as …

A Hard Problem: Managing Constipation In The Geriatric Population, William G. Jones, Veeraen Jonnalagadda, Alexandra E. Thomson, Victoria Grumbles, Chase Cottle, Christian Robertson, Maulikkumar Patel

HCA Healthcare Journal of Medicine

Constipation is a common condition among geriatric patients with different presenting symptoms and potential serious complications. Additionally, the condition causes a significant burden on our healthcare system. Here, we summarized recommendations from several societies, including the American College of Gastroenterology, American Geriatrics Society, and American Academy of Family Physicians to provide guidance on managing constipation with geriatric patients. Our aim was to emphasize the importance of prevention of constipation in this population and methods to do so. We also give recommendations on how to manage constipation when it does develop and how to manage it across different healthcare settings. These …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Hydrogen Sulfide Deficiency And Therapeutic Targeting In Cardiometabolic Hfpef: Evidence For Synergistic Benefit With Glp-1/Glucagon Agonism, Jake E. Doiron, Mahmoud H. Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D. Gehred, Tatiana Gromova, Jingshu Chen, Ian H. Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W. H.Wilson Tang, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D. Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J. Shah, Josef Pfeilschifter, Karl Friedrich Beck, Thomas M. Vondriska, Zhen Li, David J. Lefer

School of Graduate Studies Faculty Publications

Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H2S) bioavailability in HFpEF patients and 2 animal models: the "2-hit" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H2S levels were significantly reduced in patients and both models, linked to decreased cystathionine-γ-lyase expression and increased sulfide quinone oxidoreductase. Cystathionine-γ-lyase knockout worsened HFpEF, whereas pharmacological supplementation with an H2S donor improved diastolic function and reduced cardiac fibrosis. H2S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H2S bioavailability may provide a novel therapeutic strategy for HFpEF.

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Immunopathogenic Crosstalk Between Cancer And The Kidney: A Central Role For Macrophages As Potential Mediators., Dana Hammouri

Electronic Theses and Dissertations

Cisplatin remains a mainstay in the treatment of solid tumors, yet its therapeutic efficacy is frequently compromised by dose-limiting nephrotoxicity. Approximately 30% of patients receiving cisplatin develop acute kidney injury (AKI), which increases the risk of chronic kidney disease (CKD), a leading cause of morbidity and mortality. Despite extensive preclinical efforts, no FDA-approved therapy currently exists to prevent or treat cisplatin-induced nephrotoxicity (CIN). This in part is due to the reliance of preclinical studies on non-cancer animal models that fail to capture the complex physiological alterations associated with malignancy. To address this limitation, we developed a clinically relevant model in …

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. …

Targeting Obesity: The Role Of Glp-1 Receptor Agonists In Achieving Sustainable Weight Loss, Brad Vamplew

Lynchburg Journal of Medical Science

This review critically evaluates the effectiveness of glucagon-like peptide-1 receptor agonist pharmacotherapy in managing obesity. Obesity is a health epidemic that affects 100 million Americans, and it puts individuals at higher risk for numerous health comorbidities over a lifetime. A comprehensive literature review was completed by utilizing PubMed and its clinical queries function to locate relevant research. The research information was narrowed down with a focus on obesity management and glucagon-like peptide-1 receptor agonists for therapy. Numerous current clinical studies and trials were incorporated into this review. Many clinical trials substantiated the benefits of this pharmacotherapy for the management of …

Concurrent Use Of Skeletal Muscle Relaxants And Nsaids In Low Back Pain Management: A Critical Review Of Current Evidence And Future Directions, Rupesh A. Saindane, Nilima A. Thombre

The Thai Journal of Pharmaceutical Sciences

Low back pain (LBP) represents a leading cause of non-fatal disability globally. Its high prevalence and disabling nature highlight the urgent need for effective management strategies. The exact cause of LBP still remains unclear, and thus, its treatment remains symptomatic. LBP is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs) and skeletal muscle relaxants (SMRs). These agents are frequently used in combination to target both inflammation and muscle spasms. However, the clinical guidelines vary widely on the recommendation for the use of such combination therapy. The present review evaluates evidence from randomized clinical trials and systematic reviews on the concurrent use …

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.

Comparative Impact Of Thiazides Vs. Dihydropyridines On Heart Failure Risk In Hypertensive Patients: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Safaa M. Alsanosi, Yosra Z. Alhindi

Saudi Toxicology Journal

Background: Uncontrolled hypertension (HTN) is a progressive condition that significantly elevates the risk of heart failure (HF). The selection of antihypertensive agents plays a critical role in modulating HF risk. Thiazide diuretics and dihydropyridine calcium channel blockers (DHPs) are frequently utilized in clinical practice, yet their comparative long-term cardiovascular outcomes, particularly regarding HF incidence, remain underexplored. Methods: A systematic literature review was undertaken, drawing four key databases—MEDLINE, EMBASE, Web of Science, and Cochrane—covering the period from 1994 to October 2024. The scope was limited to randomized controlled trials (RCTs) evaluating thiazides or DHPs, with a minimum of 100 participants diagnosed …

Renal Denervation Improves Cardiac Function And Exercise Duration In A Miniswine Model Of Heart Failure With Preserved Ejection Fraction, David J. Lefer, Thomas E. Sharp, Amy L. Scarborough, Amelia G. Haydel, Sanjiv J. Shah, Zhen Li, Traci T. Goodchild

School of Medicine Faculty Publications

Aims: Overactivity of the sympathetic nervous system is a common underlying mechanism in development and progression of several heart failure with preserved ejection fraction (HFpEF) comorbidities. Decreasing renal sympathetic nerve activity using catheter-based renal denervation (RDN) systems have shown efficacy in treating resistant hypertension and cardiac dysfunction in heart failure with reduced ejection fraction. The purpose of this study was to determine if modulation of renal sympathetic nerve activity by RDN improves cardiac function and exercise tolerance in a clinically-relevant minipig model of cardiometabolic HFpEF. Methods and results: Multiple HFpEF comorbidities were induced in adult female Göttingen minipigs by mineralocorticoid …

Current Paradigm And Futuristic Vision On New-Onset Diabetes And Pancreatic Cancer Research, Russell Moreland Iii, Abigail Arredondo, Anupam Dhasmana, Swati Dhasmana, Shabia Shabir, Asfia Siddiqua, Bonny Bannerjee, Murali Yallapu, Stephen Behrman, Subhash Chauhan, Sheema Khan

School of Medicine Publications

New-onset diabetes (NOD) has emerged as a potential early indicator of pancreatic cancer (PC), necessitating a refined clinical approach for risk assessment and early detection. This study discusses critical gaps in understanding the NOD-PC relationship and proposes a multifaceted approach to enhance early detection and risk assessment. We present a comprehensive clinical workflow for evaluating NOD patients, incorporating biomarker discovery, genetic screening, and AI-driven imaging to improve PC risk stratification. While existing models consider metabolic factors, they often overlook germline genetic predispositions that may influence disease development. We propose integrating germline genetic testing to identify individuals carrying pathogenic variants in …

Reducing Surgery For Pediatric Posttonsillectomy Hemorrhage Using Tranexamic Acid: A Quality Improvement Initiative, Laura A. Petrauskas, Janavi Sethurathnam, Ansley J. Kunnath, Rahul K. Sharma, John Ceremsak, Ryan H. Belcher, James D. Phillips, Jay A. Werkhaven, Amy S. Whigham, Lyndy J. Wilcox, Christopher T. Wootten, Frank W. Virgin, Jason S. Park

School of Medicine Faculty Publications

Objective: Evaluate the use of tranexamic acid (TXA) and observation as a management option for pediatric patients presenting with posttonsillectomy hemorrhage (PTH). Study Design: Retrospective analysis of a prospectively implemented quality improvement initiative with a historical control comparison group. Setting: Tertiary children's hospital. Methods: Patients < 18 years of age who underwent adenotonsillectomy (AT) and returned to the Emergency Department for PTH were included. Patients who were stable without large volume or active bleeding were given intravenous TXA and admitted for overnight observation. Data were compared in a before-and-after analysis: preprotocol (April 2022 to March 2023) versus postprotocol (April 2023 to March 2024). For cost-effectiveness analysis, we analyzed aggregated claims data from a commercial claims database. Results: Preprotocol 1800 adenotonsillectomies were performed, and 40 procedures were performed for control of hemorrhage (2.2 per 100 AT). Postprotocol 2356 adenotonsillectomies were performed, and 30 procedures were performed to control hemorrhage (1.3 per 100 AT) showing a significant reduction in return to the operating room (relative risk [RR] = 0.59, 95% confidence interval [CI] [0.358, 0.916], P-value.020). There were no reported adverse events attributable to TXA. An estimated 21 surgeries were avoided, and 26 additional patients were observed in the hospital during the postprotocol period, for an estimated net cost savings of $174,970. Conclusion: The implementation of a standardized TXA protocol significantly reduced the need for return to the operating room for PTH in pediatric patients, without complications and with net cost savings to the health care system.

Fda Approval Of Cobenfy: A New Therapeutic Option For Schizophrenia, Brenna Hissong, Penlope Mazivanhanga, Alexander Defranco, Linda Azap, Haley Brown, Megan Rizo, Joshua Honaker, Samantha Mccord, Lindsey Ferraro

Pharmacy and Wellness Review

Schizophrenia is a complex illness characterized by behavioral, emotional, and cognitive dysfunctions. Common symptoms include hallucinations, delusions, cognitive decline, and social withdrawal. The disorder is related to structural brain abnormalities, neurotransmitter imbalances, and a combination of genetic and environmental elements, and affects about 24 million individuals globally. Currently, two medication classes are most commonly used to treat schizophrenia. These medications are first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). Due to the side effect profiles that both medication classes carry, research is being conducted for new drug classes.

Cobenfy (xanomeline/trospium chloride), also known investigationally as KarXT, is a new class of …

Effects Of Genetic Polymorphisms On The Oct1 And Oct2-Mediated Uptake Of Atenolol, Mollie Margaret Walton Md, Jonathan Wagner Do, Ceclia E. Villanueva Phd, Bruno Hagenbuch Phd

Research Days

This project characterizes the role of OCT1 and OCT2 on cellular uptake of atenolol and tests the hypothesis that OCT1 and OCT2 proteins with genetic polymorphisms, when expressed in vitro, will result in altered cellular uptake of atenolol relative to the reference genotype. This approach utilizes transiently transfected OCT1 and OCT2 cell assays to perform time-dependent atenolol uptake experiments to generate kinetics information. The goal is to provide a better understanding of polymorphisms associated with OCT1 and OCT2 expression and function as a means to individualize pharmacologic therapy for atenolol.

Pcsk-9 Inhibitors Treatment: The Cardiovascular Disparity, Julia Lees, Seana-Pierre Williams, Tahir Razzaq, Michael B. Roberts

The Journal of Integrated Primary Care

Introduction: According to the Center for Disease Control and Prevention (CDC) and American Heart Association (AHA), cardiovascular disease is the leading cause of death in the United States. This phenomenon disproportionally affects the African American population, who have a 31% higher mortality rate than non-Hispanic Caucasian individuals. A retrospective review of PCSK-9 medication use, specifically in a patient population that had minimal representation in the large, landmark clinical trials, can lead to better understanding about the therapeutic potential in cardiovascular disease reduction and patient outcomes attributed to medication use. Education regarding this novel drug class, medication access and patient support, …

Low-Dose Bevacizumab Treatment For Retinopathy Of Prematurity, Makayla Ayres, Katherine Brown Md

Research Days

Background: Retinopathy of prematurity (ROP) is an eye disease that affects very premature infants and causes blindness. Treatment for ROP consists of anti-VEGF intravitreal injections (e.g., bevacizumab), laser therapy, and cryotherapy. The concern of anti-VEGF intravitreal injections is systemic toxicity and potential detrimental effects on these developing infants. In research trials, doses as low as 0.031 mg of bevacizumab have been shown to be effective in treating ROP. However, in clinical practice, the most common doses used are 0.125-0.25 mg.

Objectives/Goal: At CMKC, 0.075 mg doses of bevacizumab have been used to treat Type 1 ROP since 2022. We aim …

Sugammadex For Reversal Of Neuromuscular Blocking Agents Versus Neostigmine - Safety Comparison, Amanda K. Butler, Daniel Belu, Bailey Accardo, Courtney Ayana Bullard, Tracy Mcclinton Dnp, Aprn, Agacnp-Bc, Hget-C, Ebp-C, Dwayne Accardo Dnp, Crna, Faana

Doctor of Nursing Practice Projects

Purpose/Background

Sugammadex and neostigmine are two common drugs used to reverse neuromuscular blockade in anesthesia, but they differ in mechanism of action, side effects, and cost.

Sugammadex provides rapid reversal, has fewer side effects, and has a lower risk of bradycardia than neostigmine. This scoping review examines the frequency of bradycardia in adult surgical patients receiving sugammadex versus neostigmine.

Methods

A scoping review was completed of peer-reviewed articles comparing the incidence of bradycardia in adult surgical patients after the administration of sugammadex and neostigmine for neuromuscular blockade reversal. Findings indicate that sugammadex resulted in fewer adverse events, including bradycardia, than …

Circrna-Based Antimir Therapy: A Novel Approach To Hypertension Treatment, Vahideh Tarhriz, Kamran Hosseini, Leila Abkhooie, Eric Lazartigues

School of Medicine Faculty Publications

The increasing recognition of the types and functions of non-coding RNAs has opened new avenues for their use as novel therapeutic strategies in the treatment of chronic diseases such as hypertension. While most preclinical and clinical studies on hypertension focus on prognosis and treatment, there are still no specific therapeutic approaches for primary and essential hypertension. Modest efficacy and reduced long-term adherence to treatment underscore the need for novel, mechanism-based strategies to address the underlying molecular mechanisms. AntimiRs, as synthetic RNA molecules, and circular RNAs (circRNAs), as naturally occurring RNA species that function as microRNA sponges, could play a crucial …

Low Dose Aspirin Is Associated With Improved 30-And 92-Day Outcomes In Patients With Acute Pancreatitis: A Multinational Multicenter Analysis, Do Han Kim Md, Donghyun Ko Md, Pedro Palacios Argueta Md, Wilhelm S. Basegoda Md, Jose A. Porres, Frank J. Lukens Md, Paul T. Kroner Md

Posters

Currently, no medications are known to formally treat or prevent acute pancreatitis (AP). Significant attention has been devoted to aspirin (ASA), with rodent models showing that it is associated with decreased inflammatory cytokine levels and protects against acinar cell necrosis. Current human studies, which are limited to retrospective inpatient outcomes only on the index hospitalization for AP, do suggest that patients on ASA have improved outcomes. The aim of our study was to explore de 30- and 90- day outcomes of patients with AP on long-term ASA use.

Valproate Use Is Associated With Higher Mortality And Hepatic Decompensationin Patients With Masld/ Mash: A Multinational Analysis, Donghyun Ko, Do Han Kim Md, Wilhelm S. Basegoda Md, Jose A. Porres, Luis M. Nieto Md, Pedro Palacios Argueta Md, Paul T. Kroner Md, Frank J. Lukens Md

Posters

Valproate is a widely used anti-seizure medication for treating epilepsy. However, it significantly impacts lipid metabolism by interfering with the beta-oxidation pathway of fatty acids in mitochondria. This disruption is expected to accelerate the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) in patients on chronic valproate therapy. The aim of this study is to determine whether the chronic use of valproate increases the risk of liver-related and cardiovascular events

Sglt-2 Inhibitor Use Is Associated With Lower Mortality In Patients With Alcoholic Cirrhosis And Type 2 Diabetes Mellitus: A Multinational Analysis, Do Han Kim Md, Donghyun Ko, Jose A. Porres, Wilhelm S. Basegoda Md, Cristina H. Makarian, Luis M. Nieto Md, Pedro Palacios Argueta Md, Paul T. Kroner Md, Frank J. Lukens Md

Posters

In our study, we aimed to investigate whether SGLT2 inhibitors are associated with a reduced risk of all-cause mortality, liver-related events, and cardiovascular outcomes in patients with alcoholic cirrhosis and T2DM.

Valproate Use Is Associated With Lower Hepatic And Cardiovascular Outcomes When Compared To Levetiracetam In Patients With Masld/Mash: A Multinationalanalysis, Donghyun Ko, Do Han Kim Md, Wilhelm S. Basegoda Md, Jose A. Porres, Luis M. Nieto Md, Pedro Palacios Argueta Md, Paul T. Kroner Md, Frank J. Lukens Md

Posters

Valproate and levetiracetam are commonly used to manage epilepsy. While valproate is well-documented to significantly affect lipid metabolism, less is known about the effects of levetiracetam. Given this, worse outcomes in MASLD/MASH are anticipated in patients treated with valproate.

The aim of our study is to compare hepatic and cardiovascular outcomes in MASLD/MASH patients treated with valproate versus levetiracetam.

Immune-Related Adverse Events Associated With Pembrolizumab In Dmmr/Msi-H Colorectal Cancer: A Single Arm Safety Meta-Analysis, Joshi Simran, Saman Javid, Gaurav Sharma, Corinne Caissie, Armando Dominguez-Diaz

Posters

Pembrolizumab, a PD-1 checkpoint inhibitor, enhances immune response and has proven effective against various cancers, including melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma.

Clinical trials have also shown its efficacy in treating various types of cancers with different mismatch-repair statuses. However, the spectrum and frequency of immune-related adverse events (irAEs) in the dMMR (deficient mismatch repair) / MSI-H (microsatellite instability-high) colorectal cancer remain underexplored.

Therefore, this meta-analysis aims to evaluate pembrolizumab's safety profile in this colorectal cancer subset.

A Curious Case Of Heart Failure With Reduced Ejection Fraction In A Lupus Patient, Farah Khan Md

Posters

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with cardiovascular risks, including coronary artery disease (CAD) and typically heart failure (HF) with preserved ejection (HFpEF). We report an SLE patient with ventricular arrhythmias and HF with reduced ejection fraction (HFrEF) due to myocarditis, responding positively to Guideline-Directed Medical Therapy (GDMT) for both conditions

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 …

Combined Inhibition Of Lysine-Specific Demethylase 1 And Kinase Signaling As A Preclinical Treatment Strategy In Glioblastoma, Lea Stitzlein

Dissertations and Theses (Open Access)

Glioblastoma is the most common primary malignant brain tumor in adults, with limited treatment options resulting in a poor prognosis. Lysine-specific demethylase 1 (LSD1) is overexpressed in glioblastoma and contributes to tumor growth and treatment resistance. Inhibitors of LSD1 have shown preclinical promise but have had limited clinical development for glioblastoma. Given the frequent kinase pathway alterations in glioblastoma, the interplay between LSD1 inhibition and kinase signaling pathways was investigated to identify vulnerabilities that could be exploited through rationally designed combination therapies. We hypothesized that LSD1 inhibitors would activate kinase signaling pathways, such as MAPK, and the addition of kinase …

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, …

Diabetes Mellitus And Associated Vascular Disease: Pathogenesis, Complications, And Evolving Treatments, Kazi Islam, Rahib Islam, Ivan Nguyen, Hassan Malik, Humza Pirzadah, Barsha Shrestha, Isabella B. Lentz, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Diabetes mellitus is a metabolic disorder, characterized by elevated blood sugar levels (hyperglycemia) and insulin dysregulation. This disease is associated with morbidity and mortality, including significant potential vascular complications. High levels of hyperglycemia lead to not only elevated levels of reactive oxygen species but also advanced glycation end products, which are detrimental to the vascular endothelium and reduce protective compounds such as nitric oxide and prostacyclin. This damage contributes to the development of both macrovascular and microvascular complications. The present investigation explores the pathophysiological mechanisms of diabetic vascular complications and evaluates current management strategies, including lifestyle modifications, pharmacological treatments, and …