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A Reduction in Mitophagy Is Associated with Glaucomatous Neurodegeneration in Rodent Models of Glaucoma
No full textGlaucoma is a heterogenous group of optic neuropathies characterized by the degeneration of optic nerve axons and the progressive loss of retinal ganglion cells (RGCs), which could ultimately lead to vision loss. Elevated intraocular pressure (IOP) is a major risk factor in the development of glaucoma, and reducing IOP remains the main therapeutic strategy. Endothelin-1 (ET-1), a potent vasoactive peptide, has been shown to produce neurodegenerative effects in animal models of glaucoma. However, the detailed mechanisms underlying ET-1-mediated neurodegeneration in glaucoma are not completely understood. In the current study, using a Seahorse Mitostress assay, we report that ET-1 treatment for 4 h and 24 h time points causes a significant decline in various parameters of mitochondrial function, including ATP production, maximal respiration, and spare respiratory capacity in cultured RGCs. This compromise in mitochondrial function could trigger activation of mitophagy as a quality control mechanism to restore RGC health. Contrary to our expectation, we observed a decrease in mitophagy following ET-1 treatment for 24 h in cultured RGCs. Using Morrison's model of ocular hypertension in rats, we investigated here, for the first time, changes in mitophagosome formation by analyzing the co-localization of LC-3B and TOM20 in RGCs. We also injected ET-1 (24 h) into transgenic GFP-LC3 mice to analyze the formation of mitophagosomes in vivo. In Morrison's model of ocular hypertension, as well as in ET-1 injected GFP-LC3 mice, we found a decrease in co-localization of LC3 and TOM20, indicating reduced mitophagy. Taken together, these results demonstrate that both ocular hypertension and ET-1 administration in rats and mice lead to reduced mitophagy, thus predisposing RGCs to neurodegeneration.The work was supported by National Eye Institute [R01EY028179] to RRK and in part by funding from a National Institutes of Health training grant [T32AG020494] to CDB
Synchronous bilateral lipoma arborescens of the bicipitoradial bursa
No full textBackground: Lipoma arborescens (LA) is a rare intra-articular lesion formed by subsynovial villous proliferation in which subsynovial tissue is replaced by mature adipose cells. It is most commonly reported to appear in the knee joint but has also been seen to involve the shoulder, elbow, hip, ankle, and wrist joints. This report adds to the current understanding of lipoma arborescens by providing a rare presentation, and, to our knowledge, the second case reported in literature of bilateral synchronous lipoma arborescens of the elbow joints.
Case report: We present a case of bilateral lipoma arborescens in a 36-year-old male with a history of untreated psoriatic arthritis who presented to an outpatient musculoskeletal clinic with a 6-month history of bilateral elbow pain and mass with the left being worse than the right and no history of trauma or injury. He reported morning exacerbation and accompanying stiffness, locking, and noticeable grinding and clicking in the left elbow. Physical examination revealed limited range of motion in flexion in the left elbow, a palpable mobile mass over the area of the distal biceps tendon bilaterally, and tenderness with resisted pronation and elbow flexion in the left elbow. Radiographs of both elbows showed no structural abnormalities, while a diagnostic ultrasound of the elbows revealed cystic anechoic structures adjacent to the biceps tendon with increased vascularity seen on color doppler and several frond-like appendages that entered into the cystic structure. MRI was obtained which showed severe bicipitoradial bursitis with synovitis, frondlike fat projection suggestive of lipoma arborescens within the bursa, mild insertional biceps tendinopathy, and reactive edema in the proximal radius centered at the radial tuberosity. Surgical intervention was recommended. The patient had the left-sided mass resected by a hand orthopedic surgeon. The patient was doing well at his 4-week follow-up and had no pain with range of motion. The pathology report showed a 4.2x1.8x1.8 cm pink-white pigmented soft tissue fragment with mature adipose tissue with marked chronic inflammation and fibrinous exudate which further confirmed the diagnosis of lipoma arborescens. His contralateral mass will be resected if it becomes symptomatic.
Conclusion: Lipoma arborescens is a rare, slowly progressive benign lesion that should be on the differential diagnosis of those with a periarticular mass and a chronic inflammatory condition. In this patient, given his untreated psoriatic arthritis, chronic inflammation is likely responsible for its development. Though harmless, it may be resected if it becomes symptomatic due to the mass effect on surrounding tissues
Tapinarof-Induced Folliculitis Outside of Treated Psoriasis Plaques: A Case Report
No full textBackground:
Tapinarof 1% cream is a novel non-steroidal topical medication recently FDA-approved for plaque psoriasis. Plaque psoriasis is a chronic inflammatory skin disorder that manifests as erythematous plaques with micaceous scale on the body, often associated with pruritus. Appearance and symptoms of the plaques can greatly impact patients’ quality of life. Tapinarof’s non-steroidal mechanism allow for longer treatment periods without topical corticosteroid side effects e.g. skin atrophy, hypopigmentation, telangiectasia, and striae. Adverse events identified during pivotal trials may not be completely defined before widespread clinical use. This case reports a new presentation of folliculitis with tapinarof use.
Case Presentation:
A 25-year-old female with trisomy-21 presented for a rash on her left lower leg. The eruption began one year earlier. The eruption was not associated with pruritus, joint pain or nail changes. A clinical diagnosis of plaque psoriasis was made. Due to unsuccessful response with topical steroids and topical vitamin D analogues, alternative treatment was started with topical tapinarof. After approximately two months of treatment, the patient presented with a new concern of an itchy rash. On exam she had follicular papules around the original plaque. In addition, she had follicular papules and pustules following a linear distribution ascending the affected leg. These papules were distant from the original eruption. There were similar scattered papules on the unaffected leg. A clinical diagnosis of folliculitis was made. Bacterial and fungal cultures were negative. A biopsy demonstrated folliculitis and special stains did not show organisms.
Conclusion:
Tapinarof cream is a novel non-steroidal treatment option for plaque psoriasis. Tapinarof is considered by many to have a better safety profile when compared to topical steroids. Adverse events reported in tapinarof clinical trials included folliculitis at or near the site of psoriatic /plaque. This case is unique as the folliculitis occurred not just at the site of application, but also occurred distant to the site. The distribution has not been previously reported. Our case provides histological confirmation of folliculitis as a side effect. This unusual distribution of folliculitis may be due to external factors such as transfer of the medication by bed sheets or clothing. An alternative theory may be scratching of the plaque then subsequent spread to the areas where folliculitis is now evident. Further experience with tapinarof will more completely define tapinarof associated folliculitis. In the meantime, clinicians treating patients with tapinarof who develop folliculitis need to consider this possibility in their differential diagnosis
Two Presentations of Neuroglial Heterotopias with Cleft Palate
No full textIntroduction: Neuroglial heterotopias, commonly known as nasal gliomas, are rare masses composed of brain tissue located outside of the cranial vault. These masses are composed of dysplastic glial cells which have lost their intracranial connections and can present as extranasal, intranasal, or mixed masses. They are thought to result from the incomplete closure of the anterior fontanelle between the nasal and frontal bones; this can result in an irregular connection between embryonic ectoderm and neuroectodermal tissue. Although the presentation of a neuroglial heterotopia in a child is uncommon, even more notable is the finding of neuroglial heterotopias visible from a concurrent cleft palate, as this can present additional difficulties in future cleft palate repair and mass excision.
Case Presentation: Presented in this report are two cases of a neuroglial heterotopia found simultaneously with cleft palate. Although these lesions are typically considered benign growths, unmanaged neuroglial heterotopias can result in improper craniofacial development resulting in cosmetic complications and airway obstructions. For accurate diagnosis, thorough histological identification of the embryological tissue origins after surgical biopsy should be performed. Although neuroglial heterotopias and other masses of the nasopharynx such as teratomas have similar treatment methods (namely surgical resection), detailed histological evaluation of tissue biopsies allows physicians to properly manage cases such as these post-treatment. Early surgical removal of neuroglial heterotopias are encouraged in order to minimize nasal and craniofacial distortion early in development as well as to slow or prevent further growth of the lesion.
Conclusions: Imaging diagnostics, histological evaluation, surgical procedures, and patient management of the two cases are highlighted in the report in an effort to provide more insight into possible differential diagnoses and treatment options to physicians with similar case presentations
Oral Health Educational Needs Among HIV Health Care Providers in North Texas
No full textPurpose:
Understanding connections between HIV and oral health is vital for providing comprehensive care to people with HIV (PWH). Due to compromised immune function associated with HIV, PWH are more susceptible to oral health disease and infections. In Texas, there is a need for improved access and provision of oral healthcare services for PWH, particularly amongst marginalized populations. The purpose of this study is to identify HIV/AIDS healthcare providers’ (HCPs) and non-clinical providers’ gaps in oral health knowledge and preferred educational strategies and models. Results can inform educational programming for providers, ultimately improving the quality of oral healthcare to PWH in North Texas.
Methods:
A targeted needs assessment (Qualtrics survey) was conducted among a sample of major HIV organizations in North Texas to assess the educational and training needs of their HCPs. The survey, administered in January 2024, featured multiple-choice and open-ended questions. Participants were presented with lists of topics based on existing programming and literature: (i) topics on oral health and HIV, such as oral microbiome and antiretroviral therapy; (ii) key populations, such as pregnant persons; and (iii) preferred learning models, such as workshops, webinars, and case studies. They were asked to select all topics of interest.
Results:
Of the 33 total responses, 8 were excluded due to incomplete surveys. The respondent’s credentials included DMD/DDS (n=4), MD/DO (n=1), PharmD (n=1), RN/NP (n=2), RDH (n=2), LSW/LPC (n=2).
When prompted about general areas of interest within the HIV/AIDS care continuum, there was interest in learning about approaches to reduce patients lost to care, reduce HIV stigma in healthcare settings, and expand pre-exposure prophylaxis in routine oral care. Substance use disorder as it relates to HIV and oral healthcare was reiterated as an educational need.
Specific educational gaps included oral manifestations of HIV (60%), HIV-related oral cancers (56%), and therapeutics such as antiretroviral therapy (48%) and other emerging treatments (48%). Clinical management of oral health conditions and HIV, dental implants and prosthetics, and innovations in diagnostics in the dental setting were other educational needs selected.
Additionally, respondents indicated a need to learn more about specific key populations such as people living with substance use disorders (80%), people living without housing (76%), and transgender and gender diverse communities (64%). Pregnant persons, incarcerated persons, and aging populations were other groups of interest.
Results indicate a significant preference for webinar (68%), seminar (52%), and workshop (44%) learning models. Podcasts (24%) and case studies (20%) were also selected often, but other major telementoring models (ECHO, self-paced learning and adapted community health clubs) did not receive the same preference.
Conclusion:
The results of this survey reveal knowledge gaps and oral healthcare needs among HCPs that should be addressed in order to enhance oral healthcare for PWH in North Texas. While synchronous educational methods like webinars and workshops were favored, HCPs may benefit from additional active learning models (e.g., ECHO) into their continuing education. By developing and implementing education on the identified topics, HCPs can advance efforts to end the HIV epidemic and ensure PWH receive comprehensive care, including addressing their oral health needs.This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS). Under grant number U1OHA33225 (South Central AIDS Education and Training Center). It was awarded to the University of New Mexico. No percentage of this project was financed with non-governmental sources. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government
Bilateral Accessory Piriformis Variant and its Implications – A Case Report
No full textThe piriformis muscle is a major muscle of the gluteal region and can be a cause of sciatic pain known as piriformis syndrome. Routine dissection of a cadaver of unknown age presented with bilateral accessory piriformis muscles. The main piriformis muscle was noted bilaterally with a smaller, accessory muscle separate and distinct from the main piriformis muscles. These accessory muscles originated and attached at the same anatomical landmarks as the main piriformis. The tibial nerve exited from below both piriformis muscles and the common fibular nerve exited between the two muscle bellies. This presentation of accessory piriformis is unique and has seldom been presented in the literature. Anatomical accessory muscles such as this one has important clinical considerations including in surgery, radiology, and the diagnosis of sciatic pain caused by piriformis syndrome
Unilateral to Bilateral Progressive Sciatic Neuropathy After Radiotherapy: A Case Report
No full textBackground:
Radiation therapy is often an adjunct treatment for prostate cancer. However, this procedure is not without risks; as the lumbosacral plexus is not routinely contoured during radiotherapy treatment plans, this raises potential for unintended consequences. As this case, especially this particular presentation, is an extremely rare occurrence, we will examine relevant literature and discuss the challenging diagnosis.
Case Presentation:
In this report, we detail the case of a 66-year-old male patient who suffered from unilateral sciatic neuropathy. Unfortunately, this unilateral neuropathy became bilateral, and was deemed idiopathic at the time, causing the patient severe distress. However, further workup which consisted of examination of patient history, scrutinizing imaging, and electromyography (EMG), painted a different picture. The onset of the patient’s complaints appeared to be initiated by adaptive radiotherapy, which the patient underwent during his treatment regimen for prostate cancer.
Conclusions:
As radiation-induced lumbosacral plexopathy (RILSP) may present in a delayed fashion after treatment, diagnosis could become difficult. While radiculopathy was the differential diagnosis which initially led to neurosurgical consultation, the patient’s presentation did not align with this diagnosis. Further workup, especially strategic usage of EMG, allowed for discernment of a neuropathic condition, versus a mechanically induced radiculopathy. While RILSP appears to be an underreported phenomenon subsequent to pelvic radiation, there exists only one other case of such neuropathy after prostate radiotherapy. Knowledge of this case will enable clinicians to modify their workup and avoid spine surgery in cases where it may cause harm
Evaluating Equity in XGBoost Predictions of High Healthcare Expenditures for Older Women with Osteoarthritis in the United States
No full textResearch Appreciation Day Award Winner - Texas College of Osteopathic Medicine, 2024 Women's Health Research AwardPurpose:
Osteoarthritis (OA) is a highly prevalent and debilitating condition among older adults. Studies suggest that women are more prone to develop symptomatic disease than men. OA is associated with high direct healthcare costs, attributable to its complex disease management. Furthermore, a small segment of this population may incur very high costs. Identifying these high-cost users is important for allocation of resources, cost containment, quality improvement, and population health management.
However, current research in the prediction of high-cost users in OA using machine learning (ML) models is limited. Furthermore, ML model predictions of high-cost users must be equitable across sensitive attributes such as race and ethnicity and socio-economic status.
This study investigated the leading predictors of high-cost users among older women with OA utilizing ML methods and the fairness of the ML algorithm in its predictions across subgroups of race and ethnicity, poverty, and education.
Methods:
A cross-sectional study was conducted using data from older women (age>65 years) with OA from the 2021 Medical Expenditure Panel Survey, a nationally representative survey of the non-institutionalized civilian households in the US. High-cost users were identified as having higher than the 90th percentile (>$39,388) in total healthcare expenditures. Key predictors were identified using interpretable ML model eXtreme Gradient Boosting (XGBoost) Classification and SHapley Additive exPlanations (SHAP). Overall model fit was evaluated with AUC, recall, and precision. Fairness was measured with demographic parity (equalization of odds, disparate impact, and equal opportunity) across racial and ethnic groups (Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic ethnicity), education (no college and college) and poverty status (low income and high income). Counterfactual fairness was evaluated to ensure consistency in high-cost predictions between actual scenarios and counterfactual situations where individuals belong to different groups.
Results:
A higher percentage of Hispanic (12.2%) and NHB (14.4%) were high-cost users compared to NHW (9.0%). A higher percentage of older women without college education (10.7%) and with low income (11.2%) compared to those with college education (2.5%) and high income (5.2%) were high-cost users. The overall model fit was acceptable with AUC 0.81, recall 0.62, and precision 0.91. Multimorbidity, high school education level, and anxiety were the top 3 predictors of high-cost users. Prediction was lower among older women without college education (AUC = 0.80) and low income compared (AUC = 0.77) compared to overall prediction (AUC = 0.81). Demographic parity revealed little to no differences across racial and ethnic, education, and income groups.
Conclusion:
The fairness metrics indicated no bias in the predictions, likely attributable to the nationally representative nature of the survey sample and its large size. These findings need to be confirmed with other data that contain diverse populations. Leading predictors indicated that effective management of multimorbidity may reduce the risk of high-cost use in older women with OA
Weighing Inequities: The Role of Obesity, Social Determinants of Health, with Glucagon-like Peptide-1 Receptor Agonist Use in Adults with Type 2 Diabetes in the United States
No full textResearch Appreciation Day Award Winner - HSC College of Pharmacy, 2024 Clinical/Outcomes/Education Research Award - 2nd PlaceTitle
Weighing Inequities: The Role of Obesity, Social Determinants of Health, with Glucagon-like Peptide-1 Receptor Agonist Use in Adults with Type 2 Diabetes in the United States
Authors
Dallas Collins, Brittany Kelly, Ashlyn Aguiniga, Jahnavi Pinnamraju, Usha Sambamoorthi
Abstract
Background
Glucagon-like peptide-1 receptor agonists (GLP-1) contribute to glycemic control and weight loss in patients with type 2 diabetes mellitus (T2DM). Although obesity is an important determinant of GLP-1 use, research studies have suggested racial, ethnic, and socioeconomic inequities in GLP-1 use may also exist. The purpose of this study is to determine associations of obesity and social determinants of health (SDOH) with GLP-1 use in a large, nationally representative sample of US households.
Methods
This is a cross-sectional analysis of adults (age > 18 years) with T2DM using pooled data from multiple years of the Medical Expenditure Panel Survey (2016, 2018, and 2020). The MEPS is a nationally representative survey of civilian non-institutionalized households in the US. Diabetes was identified from both medical conditions and household files. GLP-1 use was extracted from prescription drug event files using the multum classification therapeutic sub-sub class codes. Obesity was measured using body mass index categories using the CDC standards. We restricted our analysis to adults without missing data on body mass index. Rao-Scott chi-square tests were used to assess the unadjusted associations of categorical variables with GLP-1 use. Multivariable logistic regression with survey weights was conducted to analyze the association of obesity and SDOH variables (education, poverty, health insurance, metro area, and marital status) after controlling for gender, age, and health conditions. All analyses were conducted with SAS 9.4 survey procedures.
Results
There were 7,298 participants representing ~27.3 million US adults with T2DM. Overall, 7.7% of adults reported using GLP-1 and 55.2% had obesity. A higher percentage of obese adults reported GLP-1 use compared to normal and underweight adults (10.2% vs. 4.2%). Those with college education had higher rates of GLP-1 use compared to those with less than high school education (10.2 vs. 4.0%). Multivariable fully adjusted logistic regression confirmed that obesity was associated with higher odds of GLP-1 use (AOR=2.44, 95% CI= 1.58-3.76 p < 0.001) and lower less than high school (AOR=0.40, 95% CI=0.25-0.62 p <0.001) and high school education (AOR=0.72, 95% CI= 0.52-0.99, p=0.0434) were associated with lower odds of GLP-1 use.
Conclusion
Approximately one in 14 adults used GLP-1, with obesity being an important correlate. Our study findings suggest that socioeconomic status may act as a barrier to a medication with established benefits and may contribute to exasperating inequalities in diabetes care leading to disparities in health outcomes of adults with diabetes. Cohort studies may be needed to better understand the association of SDOH with GLP-1 use
Osteoblastoma: A Case Series
No full textBackground: Osteoblastoma (OB) is a rare tumor constituting only 1% of all primary bone tumors. It typically occurs in males, in the second decade of life, and primarily affects the vertebral column and long bones. While it is generally considered benign due to its slow-growing nature and inability to metastasize, OB can occasionally exhibit aggressive features of growth, causing significant bone destruction, infiltration of the soft tissues, and epidural extension. The current treatment of choice is complete surgical resection, reserving radiotherapy, and chemotherapy for aggressive or surgically unresectable tumors. Next-generation sequencing (NGS) is not included in the typical evaluation and may offer novel insight into genetic alterations associated with OB. Case Information: With the description of these three cases, we aim to highlight the extraordinarily diverse ways that OB can present and behave, from a highly aggressive course in the cervical spine that progressed even after 4 surgeries to a dormant disease affecting the clavicle, requiring only local curettage for diagnosis and no further treatment. Additionally, we present genetic information acquired by NGS testing, not conventionally part of the work-up for OB. This case series examined NGS results, surgical margin outcomes, treatment modalities, imaging, and relevant scientific literature for each case, as well as pertinent information from each patient’s medical history. Of the three cases we reviewed, all were female, ages 8, 9 and 11. Tumor locations varied, affecting the thoracic vertebrae T8-9, cervical vertebra C7, and clavicle. The disease courses of these patients ranged from inoperable spinal tumor necessitating radiotherapy to residual disease after 4 vertebrectomy surgeries to dormant disease of the clavicle with resolution after curettage. Furthermore, the differential diagnoses considered among these cases consisted of primary aneurysmal bone cyst, chondroblastoma, osteosarcoma, Ewing sarcoma, lymphoma, rhabdomyosarcoma, giant cell tumor, and chronic recurrent multifocal osteomyelitis, demonstrating the potential difficulty in diagnosing OB. NGS testing was performed on tumor samples of 2 out of 3 of the patients and revealed a WWTR1-FOSB translocation and a germline ATM mutation. The two patients with vertebral involvement experienced progressive disease within 7 months postoperatively and the remaining patient presented with normally maturing bone 3 months postoperatively. Conclusions: This case series emphasizes the capability of OB to present and progress in incredibly diverse ways. Moreover, there is currently a lack of knowledge regarding the genetic drivers of this disease process and we believe that NGS testing may assist in furthering the genetic characterization of this tumor