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HIV associated lymphoma – a single center experience
No full textPresenter: Allison Solby Authors: Allison Solby, Elif Yilmaz, Kalyani Narra Title: HIV associated lymphoma – a single center experience Background: Among people living with HIV, different types of lymphoma are seen in about 10% of patients and are generally aggressive. Safety net hospitals like John Peter Smith hospital (JPS) treat disproportionately more HIV patients than other hospitals. Compliance with anti-retroviral therapy (ART) and chemotherapy is essential for overall treatment outcomes. Here, we describe the outcomes of patients with HIV lymphoma at JPS to obtain resources necessary to improve outcomes. Methods: We identified patients diagnosed with lymphoma and HIV from February 9, 2018 to November 10, 2022 from John Peter Smith hospital to determine the impact of demographics, HIV status, histologic type, stage and status of lymphoma, and compliance and outcomes of treatment on 1 year survival rates. National Comprehensive Cancer Network (NCCN) guidelines were used to calculate the IPI for diffuse large B-cell lymphoma. Results: A total of 38 patients were included, 4 were excluded due to lymphoma diagnosis not being a HIV associated lymphoma. The mean age was 47 years, 26 (76.5%) were male, 20 (58.8%) were Black/African American, 6 (17.6%) were non-Hispanic white, 11 (32.4%) were diagnosed with lymphoma under 40 years of age, 12 (35.3%) were self-pay at diagnosis, 34 (100%) lived in Fort Worth, 21 (61.8%) had presence of a psychiatric comorbidity, 26 (76.5%) had history of an opportunistic infection, 20 (58.8%) had hospital admissions preceding the lymphoma diagnosis, 22 (64.7%) had diffuse large B-cell lymphoma, 4 (11.8%) had plasmablastic lymphoma, 3 (8.8%) had classical Hodgkin lymphoma, 2 (5.9%) had nodular sclerosis classical Hodgkin lymphoma, 1 (2.9%) had Burkitt lymphoma, and 2 (5.9%) had malignant lymphoma. 27 (79.4%) patients underwent chemotherapy, 22 (81.5%) completed treatment, 3 (11.1%) of treatments resulted in progressions, 15 (55.6%) resulted in complete remission, 6 (22.2%) response was partial, 3 (11.1%) response is unknown. 12 (35.3%) of patients are dead, and 24 (70.6%) had 1 year survival rates. 33 (97.1%) patients were diagnosed with HIV prior to their lymphoma diagnosis, 9 (27.3%) were compliant with ART before lymphoma diagnosis, and 18 (69.2%) were compliant with ART during chemotherapy. Conclusion: At safety-net hospitals such as JPS, minority patients were the predominate population affected by HIV associated lymphomas. The average survival rate of these patients, 64.7%, is lower than the national average of 81-85% (Rubinstein PG, AIDS, 2014). The aggressive nature of the lymphomas implies the need for improved access to specialists in HIV lymphoma at tertiary care centers such as UT Southwestern to increase patients chance of survival
Postoperative Risks Associated with Non-Tobacco Nicotine Dependence in Radical Prostatectomy Patients
No full textIntroduction: Non-tobacco nicotine dependence (NTND), including the use of e-cigarettes and smokeless tobacco, has become increasingly prevalent, with many users perceiving these products as safer alternatives to traditional tobacco. However, the potential impact of NTND after radical prostatectomy (RP), is not well understood. The objective of this study is to evaluate if patients with NTND have a higher incidence of complications compared to non-nicotine users. Methods: A retrospective cohort analysis was conducted using the TriNetX global health research network, which aggregates deidentified medical records from 97 healthcare organizations. Patients who underwent radical prostatectomy (CPT Code 55866) between January 2000 and October 2022 were identified. Two cohorts were analyzed. Cohort A comprised nicotine-dependent patients without tobacco product usage (e.g cigarettes or chewing tobacco). Cohort B consisted of patients without any nicotine dependence. Propensity score matching was performed. Postoperative complications within 90 days, as well as outcomes at 1 and 2 years were assessed. Risk ratios for each complication were calculated. Results: A total of 47,099 non-nicotine dependent patients and 9,560 non-tobacco nicotine-dependent patients were included in this study. After 1:1 propensity matching, 9,471 patients were analyzed in each cohort. During the 90-day postoperative period, NTND cohort experienced significantly higher rates of urinary tract infection (RR 1.294, P<0.001), sepsis (RR 1.373, P<0.005), readmission (RR 1.684, P<0.001), and blood transfusion (RR 2.801, P<0.001). No significant difference was observed for urinary retention (RR 1.052, P=0.549). At 1 year follow-up, the NTND cohort had significantly higher rates of erectile dysfunction (RR 1.051, P<0.022) and stress incontinence (RR 1.144, P<0.001). At 2 year follow-up, NTND groups continued to demonstrate an increased incidence of erectile dysfunction (RR 1.052, P<0.009) and stress incontinence (RR 1.116, P <0.001). Conclusion: Non-tobacco nicotine dependence is associated with an increased risk of urinary tract infections, sepsis, readmission, blood transfusions at 90 days, as well as increased rates of stress incontinence and erectile dysfunction at 1 and 2 years postoperatively RP. These findings highlight the need for NTND screening, patient counseling, and the development of evidence-based guidelines to mitigate these risks
Optimizing Lipid Nanoparticle Formulations for Pancreatic Targeting: Advancing RNA Delivery for PDAC Therapy
No full textPurpose: Lipid nanoparticles (LNPs) have emerged as a promising non-viral delivery system for nucleic acid-based therapies. In the context of pancreatic cancer and other malignancies, small interfering RNA (siRNA) holds significant potential for oncogene silencing; however, efficient and targeted delivery remains a challenge. This study aims to optimize LNP formulations to enhance RNA delivery efficiency, with the goal of advancing siRNA-based oncogene silencing strategies. Initial work focuses on formulation characterization, and in vitro studies assessing transfection efficiency over time are being explored. Methods: Two experimental objectives are designed to optimize LNP formulations. Aim 1 involves the synthesis and characterization of LNPs using different lipid compositions (MC3, ALC-0315, and SM-102) and the evaluation of their stability over seven days. LNP size distribution, polydispersity index (PDI), and zeta potential are analyzed using dynamic light scattering and nanoparticle tracking analysis. Encapsulation efficiency is quantified via fluorescence assays. Aim 2 will encompass in vitro transfection studies using MC3-based LNPs encapsulating enhanced green fluorescent protein (eGFP) mRNA, with cellular uptake and intracellular release being assessed at 24 and 48 hours post-transfection. Results: MC3-based LNPs demonstrate an optimal size range (~85–95 nm) and a stable zeta potential (-10 to +30 mV), ensuring colloidal stability and efficient cellular uptake. Fluorescence-based assays expect to confirm high mRNA encapsulation efficiency. Transfection outcomes at 24 and 48 hours provide insights into mRNA delivery effectiveness in order to support further validation of LNP-mediated RNA delivery and its potential for gene silencing applications. Conclusions: The optimized MC3-LNP formulation demonstrates favorable physicochemical properties, including an optimal size range (~85–95 nm), a stable zeta potential (-10 to +30 mV), and high colloidal stability. It is expected to exhibit high mRNA encapsulation efficiency, supporting the feasibility of LNP-based RNA therapies. Future studies will evaluate in vitro transfection efficiency and gene silencing applications using siRNA. Long-term objectives include in vivo biodistribution studies and therapeutic oncogene knockdown, advancing RNA-based precision medicine strategies for cancer therapy
Fabrication of a 3D Corneal Model Using Collagen Bioink and Human Corneal Stromal Cells
Full text linkCorneal transplantation remains a critical treatment option for individuals with corneal disorders, but it faces challenges such as rejection, high associated medical costs, and donor scarcity. A promising alternative for corneal replacement involves fabricating artificial cornea from a patient's own cells. Our study aimed to leverage bioprinting to develop a corneal model using human corneal stromal cells embedded in a collagen-based bioink. We generated both cellular and acellular collagen I (COL I) constructs. Cellular constructs were cultured for up to 4 weeks, and gene expression analysis was performed to assess extracellular matrix (ECM) remodeling and fibrotic markers. Our results demonstrated a significant decrease in the expression of COL I, collagen III (COL III), vimentin (VIM), and vinculin (VCL), indicating a dynamic remodeling process towards a more physiologically relevant corneal ECM. Overall, our study provides a foundational framework for developing customizable, corneal replacements using bioprinting technology. Further research is necessary to optimize the bioink composition and evaluate the functional and biomechanical properties of these bioengineered corneas.This research was funded by an intramural "UNTHSC Team Science Grant"
Design and Synthesis of Novel Flavonoid Derivatives as Antifibrotic Agents
No full textPurpose: Corneal wound healing following trauma is essential to restoring corneal clarity and maintaining vision. The process involves a complex sequence of events leading to restoration of the corneal epithelium, stroma, and endothelium. Improper healing often results in fibrosis or scarring which can impair vision. Flavonoids are an important class of phytochemicals with potential wound healing properties. By minimizing excessive collagen deposition, flavonoids help maintain a balance between tissue regeneration and fibrosis, which can result in reduced scar formation. As proof of concept, certain flavonoids, like quercetin, luteolin, fisetin and galangin showed promising effects in our preliminary studies by significantly downregulating the expression of fibrotic markers such as alpha-smooth muscle actin (α-SMA) and collagen type III. Flavonoid scaffolds are generally considered safe, as they are naturally occurring chemical structures found in fruits, beverages, and supplements, making them suitable agents for managing corneal fibrosis. Despite their remarkable pharmacological properties, low aqueous solubility and poor permeability limit their therapeutic effectiveness. We therefore hypothesize that medicinal chemistry approaches can be used to functionalize flavonoids to improve their antifibrotic effects by optimizing their physicochemical and pharmacological properties. Our aim is to develop structure-activity relationships (SAR) for novel synthetic flavonoids (sFNs) using an iterative, systematic optimization plan and evaluate their potential as antifibrotics. We seek to generate quercetin, luteolin, fisetin and 3,3',4'-trihydroxyflavone based synthetic analogs bearing flexible functional groups such as basic amines which offer the possibility to create salts, helping with formulation and solubility in aqueous systems. Additionally, the hydroxyl groups can be functionalized to tune lipophilicity and membrane permeability. Chemical modification of flavonoids may increase affinity for targets (e.g., TGF-β receptors) able to suppress fibroblast activation, reducing fibrosis and improving target specificity. Method: Our synthetic approach involved using Claisen-Schmidt condensation and cyclization reactions to synthesize the flavonoid scaffold. The hydroxyl groups were then functionalized to obtain a late-stage versatile intermediate which can be diversified to produce a small library of sFNs. Analogs will be evaluated in 2D and 3D assays using human corneal stromal and epithelial cells from healthy donors. Results: Synthesized compounds were obtained in appreciable yields with purities ≥ 95% as determined by Agilent 6230 time-of-flight LC/MS and ¹H NMR. To date, regions of the synthetic analogs have been identified that are tolerant of modification and sFN analog generation continues. Conclusion: The vast structural diversity and flexible synthesis of flavonoid derivatives make them attractive candidates for various pharmacological applications. The potential for these compounds to be further explored and optimized will offer the opportunity to generate SAR to enhance properties suitable for the treatment of corneal fibrosis
Using AT(N) Plasma Biomarkers to Predict Tau Pathology in Diverse Communities
No full textPurpose: Investigation of whether plasma biomarkers within the AT(N) framework (i.e., Amyloid Beta 40, 42, Aβ42/40, Total Tau, Ptau-181, and Neurofilament Light Chain) can predict Tau PET positivity in a diverse cohort. Methods: Data were examined among n = 794 participants (n= 422 non-Hispanic black [NHB], n= 148 Hispanic, and n= 224 non-Hispanic white [NHW]) from the Health and Aging Brain Study - Health Disparity (HABS-HD) study. Plasma biomarkers were derived using the SIMOA platform. Participants underwent Tau Positron Emission Tomography (PET) scans. AT(N) plasma biomarkers were examined for predicting Tau PET positivity using support vector machine models. Results: Adding the amyloid biomarkers to T-Tau, Ptau-181, and NfL decreased detection accuracy (i.e., area under the curve [AUC]) among Hispanics and non-Hispanic Blacks; however, the AUC among non-Hispanic Whites increased from 0.85 to 0.90. Adding NfL to the T-Tau, Ptau-181 model improved the AUC significantly among Hispanics and non-Hispanic Blacks and decreased it among non-Hispanic Whites from 0.89 to 0.85. The T-Tau, Ptau-181, and NfL model performed exceptionally well among non-Hispanic Blacks and outperformed all the other models, yielding an AUC of 0.91, sensitivity (SN) of 0.91, specificity (SP) of 0.73, and an NPV of 99% in this group. The SVM algorithm assigned the highest importance score to T-Tau in this model. The total combined model outperformed the single Ptau-181 model within each ethnic group while the Ptau-181 model (AUC = 0.78) slightly exceeded the total combined model (AUC = 0.76) across the entire cohort. All the models, apart from the T-Tau, Ptau-181, and NfL model, performed the best among non-Hispanic Whites compared to the other ethnic groups. Removing T-Tau and NfL decreased the AUCs in both non-Hispanic Blacks and Hispanics. All the models relying only on T-Tau performed poorly with AUCs of 0.66 or lower. Conclusions: The outstanding performance of the T-Tau, Ptau-181, and NfL models among non-Hispanic Blacks compared to other biomarker combinations underscores the importance of investigating how these biomarkers perform in diverse ethnic groups when developing screening tests. Additionally, the superior performance of the combined model over the single model strongly supports the greater utility of a multiplex panel of biomarkers as the basis for such tests
Deep brain stimulation to treat dystonia secondary to NMDA receptor encephalitis: A case study
No full textBackground: N-methyl-D-aspartate receptor encephalitis (NMDARE) is caused by the production of antibodies reactive to portions of the NMDA receptor that normally bind glutamate, the body’s excitatory neurotransmitter. This autoimmune condition clinically presents with fever, focal neurological signs, such as seizures and language impairment, altered mental status, and the development of movement disorders. Status dystonicus is an emergent condition that can develop secondary to NMDA receptor encephalitis. Status dystonicus presents with frequent and worsening episodes of dystonia (involuntary muscle contractions causing repetitive movements and abnormal posturing), which poses risk of skeletal muscle damage and respiratory failure if involving muscles of respiration. Case information: A 3-year-old boy presents to the emergency department with symptoms of fever, congestion, agitation, and an episode of seizure-like activity lasting 30-35 minutes. He was diagnosed with acute febrile illness at the time. Patient returned to ED 4 days later with symptoms of left sided weakness, difficulty speaking, and loss of appetite. He was admitted to the hospital, and continued to show symptoms of agitation, abnormal posturing, and spontaneous movements. He was treated immunologically with intravenous immunoglobulin and methylprednisone, and pharmologically with anticonvulsants, sedatives, and anti-psychotic medications. Upon positive antibody titer, the diagnosis of NMDARE was confirmed. Despite further immunological treatment, additional anti-epileptic medications, and a neuromuscular blockade, his abnormal movements and seizure-like activity continued to worsen. At 4 weeks in the hospital, he was diagnosed with status dystonicus and was transferred to the ICU in a state of worsening mental status and respiratory failure. Because of his worsening movement disorder and extensive medication regimen, the patient underwent emergency Deep Brain Stimulation (DBS) placement to target the globus pallidus internus (GPi) of the basal ganglia. In the two post-operative weeks, physicians programmed the electrodes, monitoring his dyskinesias, PRN sedative count, and tolerance of the settings to establish baseline programs. In the 15 weeks between the surgery and discharge, he had improvements in symptoms and weaned off many medications, including the neuromuscular blockade and various anticonvulsants. Although still presenting with dyskinesias and seizure-like activity, the patient was decannulated, taking supported steps, and progressing well without concerning movements. Conclusions: Because NMDA receptor encephalitis presents with ambiguous, varying symptoms that can develop into secondary conditions, it is difficult to diagnose and treat pharmacologically. With possible development of movement disorders, seizures, and cognitive and psychiatric changes, the number of medications used to treat symptoms can increase rapidly and lead to polypharmacy. In the case of status dystonicus secondary to NMDARE, deep brain stimulation can be an effective treatment when first-line therapies are not improving symptoms, and can be considered when trying to treat movement disorders while avoiding polypharmacy. Physicians recognizing and diagnosing NMDA encephalitis quickly, and watching carefully for development of associated conditions can greatly improve outcomes in disease management
Molluscum Dermatitis in a Pediatric Patient
No full textBackground: Atopic dermatitis (AD) is a chronic relapsing condition characterized by irritation, redness, inflammation, and itching of the skin. The cause of AD is theorized to be multifactorial, including genetic components, such as mutations in filaggrin, environmental exposures, and immune predisposition. AD often presents in childhood and adolescence, but can appear at any age. AD eruptions can arise through various triggers, which commonly include soaps, detergents, fabrics, and cold or hot weather. Importantly, viral infections can also serve as a trigger, causing systemic inflammation via host defense mechanisms, resulting in eruptions of AD. Molluscum contagiosum (MC) is a double-stranded DNA virus that classically manifests as small, dome-shaped, skin-colored to pink, umbilicated papules. MC is very common, highly contagious, and often spreads via direct person to person contact. It can also spread from an affected to unaffected area of the body through autoinoculation. Molluscum dermatitis is the manifestation of an AD episode, triggered by MC. Patients with a history of atopic dermatitis are more likely to have eruptions associated with MC lesions. Interestingly, molluscum dermatitis is deemed the “beginning of the end” (BOTE), a positive finding indicative of host mechanisms working to resolve MC infection. We share this case as a presentation of an AD flare secondary to molluscum contagiosum infection in a pediatric patient. Case Presentation: An 8 year-old boy with a family history of asthma and atopic dermatitis presented with his parents for a red itchy rash and bumps. The patient’s mother reported that the patient’s symptoms initially began with a rash on the back of the patient's neck, following a haircut in May 2024. Shortly afterwards, this rash began to spread across his body, with bumps becoming more numerous. They had been occasionally applying hydrocortisone 2.5% ointment (his brother’s prescription) with mild symptomatic relief of pruritus, but without improvement in the rash. On examination there were eczematous plaques on the anterior neck, supraclavicular region, upper chest, right arm, and axilla. Within these plaques there were numerous small skin-colored umbilicated papules. There were also umbilicated papules in a linear arrangement. Conclusion: We share this case demonstrating a case of molluscum dermatitis in a pediatric patient. The manifestation of AD in this patient was likely directly linked to recent infection with MC, due to systemic inflammation caused by viral load, thus subsequently causing the eruption. Physical exam findings including multiple umbilicated papules superimposed on erythematous plaques around the anterior neck, supraclavicular region, upper chest, right arm, and axilla emphasizes the likely cause and effect of AD eruptions secondary to local inflammation from MC. Molluscum dermatitis is often referred to as the “beginning of the end” (BOTE) sign and represents host responses preceding the resolution of MC infection. Molluscum dermatitis is commonly mistaken for a complication of MC, and all physicians should take this point into great consideration when diagnosing patients
Can’t Scope or Swallow a Clogged Pipe with No End in Sight: Complete Esophageal Occlusion
No full textBackground: Complete esophageal occlusion (CEO) occurs when the esophageal lumen is obliterated leading to retainment of fluid, food, and salivary secretions in the proximal portion of the esophagus. Due to limitations in oral intake, this can increase the risk of malnutrition, esophagitis, and aspirational events. Incidence of CEO is estimated to affect 3-4 per 100,000 individuals annually in the United States. Potential causes of CEO include intraluminal tumors, strictures from uncontrolled severe gastroesophageal reflux disease (GERD), and even inflammatory conditions like eosinophilic esophagitis. Notably, radiation therapy for supradiaphragmatic malignancies, especially those in the chest or neck, can lead to radiation-induced esophageal narrowing with eventual luminal obliteration due to fibrosis. Symptoms included progressive dysphagia, atypical chest pain, regurgitation of food, and unintentional weight loss. Diagnostic work up may include different imaging modalities; however, esophagogastroduodenoscopy (EGD) should be considered in those individuals with alarm symptoms. Case Information: A 72-year-old male with a notable history of chronic debility and altered mental status secondary to a brain tumor presented with dislodgement of a gastric feeding tube. Notably, our patient had an extensive history of previously diagnosed Los Angeles Grade D esophagitis, esophageal ulceration(s), and progressive distal esophageal stenosis at the distal third. These findings were noted over time on repeat EGD, which were performed due to intolerance of food and dysphagia eventually requiring gastrostomy tube placement. Due to gastrostomy tube dislodgment, the patient was taken for repeat EGD, which demonstrated complete obliteration of the distal esophageal lumen. The blind pouch was unable to be traversed safely due to increased resistance and no obvious tract. Due to concerns for perforation, EGD was aborted, and further imaging was ordered. Computed tomography of the abdomen demonstrated proximal esophageal dilation and significant esophagogastric junction narrowing (EGJ). Conclusion: In conclusion, this case illustrates the severe progression of esophageal stenosis and luminal obliteration in a patient with a history of esophagitis and gastrostomy tube dependence. Prompt diagnostic imaging revealed significant narrowing at the esophagogastric junction, emphasizing the need for careful monitoring and intervention to prevent further complications
Retail Availability and Price of Ready-to-Drink Alcohol Products, Fort Worth, Texas, 2024
No full textBackground: Policies increasing taxes and reducing availability of high alcohol-by-volume (abv) products are evidence-based measures to reduce alcohol consumption. Despite their ability to identify the need for these policies, alcohol retail surveillance studies are rarely conducted. We developed and used a surveillance tool in Fort Worth, TX to examine the retail availability and price of high abv ready-to-drink (RTD) products, which have become increasingly available throughout the United States. Methods: We collected data on the retail availability and price of 17 RTD alcohol products (13 with ≥8% abv) and two non-alcoholic products for reference (Coca-Cola and Simply Orange Juice) in Fort Worth, Texas (n=393 retail locations). The study utilized both random (n=300) and convenience (n=93) sampling. Results: The least expensive alcohol was single-serve containers of Steel Reserve and Four Loko. Steel Reserve 211 (8.1% abv) cost 0.83 for 24oz containers of 211, and 0.67 per standard drink (14% abv, 23.5oz) or $0.76 for the 12% abv version. The products sold at most locations were non-alcoholic Coca-Cola (20oz, 74.0%), Bud Light (4.2% abv, 25oz, 70.2%), and Steel Reserve Seltzer (8% abv, 24oz, 58.6%). Sensitivity analyses indicated no statistically significant differences in product availability or prices by sampling method. Discussion: Findings demonstrate the widespread availability of low price, high-abv RTD products, underscoring the need for policies including minimum unit pricing, tax increases, and limits on total alcohol content to reduce hazardous consumption