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Bone Erosion in Allergic Fungal Rhinosinusitis Exposes Epidural Surface
No full textBackground: Allergic Fungal Rhinosinusitis is a chronic allergic reaction to a noninvasive fungal species in the sinuses. The chronic inflammation produces allergic mucin, nasal polyps, and mucosal edema that block normal sinus drainage patterns, trapping the fungus to further proliferate. Because AFRS presents similarly to allergic rhinitis, sinusitis, or simply nasal congestion, patients often overlook symptoms and thus cases are underdiagnosed. Allowing fungal proliferation can lead to multiple complications such as airway obstruction, cranial bone erosion, or nerve compression. Case Information: A 15 year old girl presented with worsening nasal congestion and difficulty breathing. Nasal endoscopy showed unilateral nasal polyps, mucosal hypertrophy, and 75% nasal obstruction. The patient failed to comply with the recommended course of treatment, including obtaining a CT of the sinuses and follow up for surgery. Two years later, she returned with nasal drainage, facial pain, and headaches. CT showed heterogenous opacification throughout all sinuses, bony thinning, and erosion of the skull base exposing the epidural surface by the brain stem. She underwent functional endoscopic sinus surgery (FESS) and post operative medical therapy. Failure to adhere to the recommended postoperative medical therapy resulted in a recurrence of polyps and symptoms. Conclusion: AFRS usually follows a slow, indolent course. However, if allowed to progress, massive bone destruction can occur with extension of the disease process outside of the confines of the sinuses. This can include erosion of the skull base and lamina papyracea, which in turn can lead to serious complications such as meningitis or loss of vision. Even with surgical resection, the high rate of recurrence continue to pose significant challenges. Current treatment strategies range from oral corticosteroids, to surgery, to targeted immunotherapy. Research on systemic and topical antifungal therapy is limited and requires much more investigation. It is important for patients to recognize the importance of their diagnosis and for physicians to take advantage of the range of therapies to combat this highly recurrent condition. Collaboration between ENT, allergy/immunology, and other related specialties, such as neurosurgery in this case, is critical for complete eradication
Evaluating the Therapeutic Potential of Cannabidiol in Traumatic Brain Injury
No full textPurpose: Traumatic brain injury (TBI) is brain damage following an impact to the head, affecting tens of millions of individuals globally, potentially leading to the development of long-term neurological deficits. These deficits can be brought about by a complex neuropathological immune response to the injury, with CD8 T-cells being specifically implicated in increased central nervous system (CNS) cell death and contribution to secondary injury. This emphasizes a need for a pharmacological approach to attenuate for the CD8 T-cell response. Cannabidiol (CBD), a non-psychoactive component of cannabis has gained attention for its potential neuroprotective properties in TBI, as it has been shown to suppress activated T-cell activity in a murine model of multiple sclerosis. The goal of this project is to elucidate the role of CD8 T-cells in TBI neuropathology while evaluating the therapeutic potential of CBD in TBI, hypothesizing that CBD will suppress CD8 T-cell effector activity, decreasing CNS cell death and improving motor and cognitive outcomes. Methods: To test this, we induced a mild TBI in male 8-week-old C57BL/6 mice using the closed head impact model of engineered rotational acceleration (CHIMERA), a TBI model that recapitulates brain damage typically sustained in car crashes, falls, and sports-related injuries. Flow cytometry was then used to characterize the CD8 T-cell response to injury over an eight-week period, analyzing the phenotype and function of the cells. In conjunction with the immune response, motor, cognitive, and sensory deficits were evaluated over eight weeks using rotarod, Barnes maze, and the Von Frey test, respectively. Results: Three days after injury, we saw no differences in CD8 T-cells within the brain or cervical lymph nodes. By day seven, there was an increase in both CD25+CD8+ T-cells and CD69+CD8+ T-cells within the brain, indicating an increased population of activated CD8 T-cells infiltrating the brain within the acute phase of TBI. When analyzing behavior over eight weeks, we have not found significant differences in performances in the Barnes maze or rotarod between sham and TBI groups. Slight differences were seen in the Von Frey test with mice showing increased tactile sensitivity following TBI, although additional experiments will be required to ensure a statistically powered analysis. Conclusions: These findings confirm the involvement of CD8 T-cells in TBI neuroinflammation. Future experiments will continue to investigate the CD8 T-cell response, with the expectation of increased effector memory CD8 T-cell populations in the chronic phase of TBI. We will then incorporate CBD-treated conditions, allowing for the investigation of CBD-mediated modulation of TBI neuroinflammation. We will also employ alternative assays and imaging techniques to uncover more subtle deficits in behavior and neuropathology
Transmural adaptations of coronary circulation in the setting of heart failure with preserved ejection fraction
No full textOral Presentations: College of Biomedical and Translational Science, RAD 2025 Award Winning Posters & Oral PresentationsHeart failure with preserved ejection fraction (HFpEF) is a multi-organ syndrome with poor prognosis and limited therapeutic options. This study tested the hypothesis that the passive and active properties of the coronary circulation vary transmurally the setting of HFpEF and are associated with impaired myocardial blood flow and ventricular performance. Epicardial and endocardial arteries of similar size from swine without and with pacing-induced HFpEF were isolated and isometric studies performed via wire myography. No differences in optimal length (Lo) for epicardial or endocardial arteries were observed between groups (L₀ = 427 ± 42 µm; P = 0.56). Repetitive artery contractions at increasing lengths were achieved by the addition of high extracellular K+ (60 mM). Arteries from HFpEF swine exhibited greater active tension development at L₀ relative to arteries from control swine independent of their transmural origin (endocardial HFpEF: 11.6 ± 2.2 mN/mm vs. endocardial control: 9.9 ± 1.9 mN/mm and epicardial HFpEF: 14.0 ± 3.2 vs. epicardial control: 9.8 ± 2.4 mN/mm (P < 0.05)). Passive length-tension relationship indicates diminished compliance of endocardial arteries from HFpEF swine. No difference in passive length-tension relationship of epicardial arteries was noted in between groups. Transmural adaptations in HFpEF were associated with a 50% reduction in baseline coronary blood flow (P < 0.05) and 35% decrease in coronary vasodilation to Regadenoson (P < 0.05). Left ventricular end-diastolic pressure was increased from 5 ± 2 mmHg in control swine to 27 ± 4 mmHg following chronic high-rate pacing. Echocardiographic analyses revealed a 40% decrease in regional systolic wall thickening (P < 0.05) but no differences in ejection fraction (50 vs 53 % (P >0.05)). Our findings support the hypothesis that HFpEF is associated with transmural adaptations of the coronary circulation that are associated with reductions in myocardial perfusion and ventricular performance. Determination of whether such coronary adaptations represent as causal mechanism as opposed to a consequence of the underlying HFpEF phenotype merits further investigation
Application of Surgical Adhesive Reduces Ureteroureterostomy Leakage
Full text linkTheir close proximity to abdominal structures and organs places the ureters at risk of iatrogenic injury during abdominal and pelvic surgical procedures. Ureteroureterostomy is the mainstay intervention for the repair of the proximal and middle ureter. However, the anastomosis may be subject to leakage, leading to potentially serious complications, including urinary tract infection, peritonitis, sepsis, and kidney damage. This study addressed the hypothesis that topical application of surgical adhesive reduces acute anastomotic leakage without increasing ureteric resistance. Nine ureters from domestic swine were pump-perfused with 0.9% sodium chloride (NaCl) at approximately 5, 10, 12, 15, and 20 mmHg (2 min/step), while flow and ureteral resistance were monitored, under three conditions: pre-transection, following ureteroureteral anastomosis with suture, and after topical application of Dermabond(R) surgical adhesive around the anastomosis circumference. Leakage was taken as the loss of fluid volume between the perfusate reservoir and the post-ureter receptacle. Values were compared by two-factor repeated measures ANOVA combined with the post hoc Tukey test. Leakage from the perfused ureter increased severalfold following transection and surgical anastomosis vs. pre-transection at all five perfusion pressures. Application of surgical adhesive to the anastomosis returned leakage to the pre-transection rate across the entire perfusion pressure range. There were no significant differences in ureteral flows and resistances among the three conditions. Thus, the application of surgical adhesive to the ureteroureteral anastomosis effectively prevented ureteric leakage at physiologic luminal pressures without increasing ureteral flow resistance.This research was supported by grant #RP00027 to Dr. Albert O. Yurvati from the Dallas Southwest Osteopathic Physicians Foundation
Post-Reperfusion Syndrome in Kidney Transplant Case Study
No full textBackground: Kidney transplants happen everyday, one of the most serious risks associated with this procedure is Post-Reperfusion Syndrome (PRS). PRS is a phenomenon of a more than 15% drop in mean arterial pressure (MAP) in the first 5 minutes post reperfusion. This hemodynamic instability usually lasts for at least 1 minute. The exact cause of PRS is unknown, but there may be ways to pretreat a patient, which would limit the effects experienced long term. Case Information: This case review investigates the procedures performed by the anesthesiologist on a 45-year-old female to manage severe hypotension that occurred during a kidney transplant. It also looks to educate others on the steps necessary to take when caring for a kidney transplant patient and how to lower the risk of severe hypotension. Our patient was intubated with an endotracheal tube at time 1007. Normotensive pressures for the patient, with a MAP around 100 mmHg, were initially achieved through the use of a dual anesthesia method using both a propofol drip and inhaled sevoflurane along with multimodal pain control. The sevoflurane inhalation was constant while the propofol drip was adjusted to control blood pressure. Vasopressors were avoided in the management of hypotension, thus limiting the vasoconstrictive effects on the new kidney to allow max reperfusion. The new kidney was placed in the right lower abdomen, and the renal artery was attached to the external iliac artery, and the renal vein was attached to the external iliac vein with the ureter being connected to the bladder. Reperfusion occurred at approximately 1300 after which at 1304 the patient went severely hypotensive with a MAP of nearly 40 mmHg. A dopamine infusion was initiated at this time at a rate of 5 mcg/kg/min. 1 gram of calcium carbonate was then given. The patient began to recover to a MAP of 80 over the course of 15 minutes. Another 1 gram of calcium carbonate was given and the dopamine infusion was adjusted to 7.5 mcg/kg/min when the MAP began to drop again. After which the patient’s pressures remained relatively normotensive until extubation and transfer to recovery. Discussion: PRS has been shown to increase transplant failure within 6 months and increased hospital stays. The exact cause of PRS is unknown, but resources suggest that it may be produced by hypothermia plus the sudden increase in cardiac preload, hyperkalemia, and possibly other vasoactive substances present. These factors may trigger a reflex response by the vagus nerve. Some suggest preemptively addressing PRS by treating with atropine to increase HR and thus hope to minimize the decreased MAP. As anesthesia providers, we need to be aware of this potential complication of kidney reperfusion. Pretreatment and anticipatory medicine will facilitate better outcomes for patients and a better overall surgical experience
AI Large Language Model shows Greater Efficacy with Novel Medical Triage Method over Conventional Triage
No full textPoster Highlight: Texas College of Osteopathic Medicine - Research, RAD 2025 Award Winning Posters & Oral PresentationsPurpose: This study explored a novel application of Large Language Models (LLM) beyond conventional categorical triage. We compared the reliability of conventional triage methods with an ordinal prioritization approach for patients with Diabetic Macular Edema (DME) using the ChatGPT Plus model (GPT-4) in comparison with two board-certified retina specialists (RS; also denoted individually as RS1 or RS2). We also assessed GPT-4’s prioritization of clinically atypical profiles, simulating scenarios where clinicians must evaluate medical record patient data inputted erroneously as could occur with human error. Ultimately, this was a comparison study between two triage methods — conventional categorical triage and a novel ordinal prioritization method — using a LLM and two retina specialists. Methods: Anonymized data of 28 patients with Diabetic Macular Edema (DME) from a tertiary retina-focused practice was divided evenly across four sets (Set 1-4). The evaluators (denoting GPT-4 and the two RS) then prioritized patients in both categorical (Triage Rating; TR) and ordinal manners (Priority Rating; PR). GPT-4’s reliability was measured by its agreement with the two RS using the mean Cohen’s Kappa (k) across all four sets: k = .40–.59 (weak), .60–.79 (moderate), .80–.90 (strong), >.90 (almost-perfect)). k < .60 indicates inadequate agreement. ‘Median RS’ indicates the consensus evaluation between the two RS calculated using the median of the RS’s evaluations. In Set 4, BCVAs were intentionally modified to assess the evaluator’s response to clinically atypical patient profiles. The main outcome measures included the agreement between GPT-4 and RS in categorical triage and ordinal prioritization, as measured by mean Cohen’s Kappa (k). Results: Results revealed inadequate GPT-4-RS agreement through conventional categorical triage (Set 4 excluded: RS1-GPT-4 mean set k (TR) = 0.593; RS2-GPT-4 mean set k (TR) = 0.521). However, results showed moderate GPT-4-RS agreement through ordinal prioritization (Set 4 excluded: RS1-GPT-4 mean set k (PR) = 0.631; RS2-GPT-4 mean set k (PR) = 0.679). Results also showed moderate GPT-4-Median RS agreement after inclusion of Set 4 in mean set k calculations. Conclusions: Results revealed that GPT-4 was consistently more reliable with ordinal patient prioritization over conventional categorical triage. GPT-4 also consistently agreed most with the consensus RS evaluation, even when evaluating clinically atypical profiles
Successful Utilization of Aquapheresis in a Neonate with Congenital Hepatoblastoma – Case Study
No full textBackground: Hepatoblastoma, though rare among all pediatric cancers, is the most common liver malignancy in young children. Congenital hepatoblastomas represent 10% of all cases and can present as a large abdominal mass that may be symptomatic at birth. Treatment involves the use of cisplatin, an aggressive chemotherapy agent that carries a risk of significant renal toxicity. Renal dysfunction and hypervolemia may also develop secondary to abdominal compartment syndrome and cisplatin therapy. Aquapheresis using Aquadex has been proven to be an effective treatment for hypervolemic conditions, making it particularly ideal for pediatric patients. Case information: A 39-week gestation neonate was born with significant abdominal distension and acute respiratory failure secondary to a right sided abdominal mass. Imaging revealed a large liver mass, and upon biopsy, the diagnosis of congenital hepatoblastoma was made. The patient was treated with single-agent Cisplatin chemotherapy. Over the following days renal failure manifested with progressive worsening edema and oliguria. The decline in renal function was attributed to cisplatin nephrotoxicity and abdominal compartment syndrome. Aquadex therapy was initiated leading to steady improvement in fluid removal and renal function, facilitating the continuation of full dose aggressive chemotherapy. Conclusion: This case highlights the challenges of providing aggressive anti-neoplastic therapy in a neonate with congenital hepatoblastoma complicated by renal failure. The integration of Aquadex therapy in managing congenital hepatoblastoma represents a promising adjunctive approach that effectively addresses fluid imbalance and helps mitigate complications associated with chemotherapy-induced and mass compression-induced nephrotoxicity. This case draws attention to the importance of individualized treatment strategies and aggressive supportive measures to deliver the necessary intensive treatment and optimize outcomes for pediatric patients facing complex oncological conditions
Retrospective Review of time to Antiepileptic drugs (AEDs) in a Pediatric Emergency Department
No full textPurpose: Status epilepticus (SE) is a potentially life-threatening emergency that necessitates immediate intervention. Management often extends beyond the use of benzodiazepines, requiring the administration of additional anti-epileptic drugs (AEDs) such as levetiracetam (LEV) to achieve seizure control. Timely infusion of AEDs is crucial to mitigate the harmful effects of prolonged seizure activity. This study aimed to evaluate the time to AED infusion in the emergency department (ED) at Cook Children’s Hospital in Fort Worth, Texas. Design/Methods: We conducted a retrospective chart review of pediatric patients presenting to the ED with seizures. Patients with pseudo-seizure-like activity or seizures secondary to trauma and asphyxia were excluded. A total of 60 patient charts were reviewed, documenting the time of AED order placement, infusion start, and completion. LEV was the most administered AED, used in 55% of cases. Results: Our findings revealed a statistically significant increase in the time from order placement to infusion completion for LEV (average 38.5 minutes) compared to all other AEDs in patients with SE (z=3.90, p< 0.001). Additionally, there was a significant delay from infusion start to completion for LEV (z=3.63, p< 0.001). Conclusion(s): These results underscore the need to further investigate AED delivery times to enhance the management of SE in the ED. LEV, the most frequently used AED, demonstrated a longer time to infusion completion compared to other AEDs. Our future objectives include strategies to reduce the time to AED infusion in this patient population to improve treatment outcomes
Investigation of hydrolysis of olmesartan medoxomil in different pH buffers by simultaneously measuring olmesartan medoxomil and olmesartan
Full text linkOlmesartan medoxomil (OLM) is an ester prodrug of olmesartan (OL) developed to overcome the poor permeability of OL. OLM is an angiotensin receptor blocker and is commonly used to treat hypertension. However, OLM has low water solubility and low bioavailability of 26%. It is understood that OLM is unstable in aqueous media; however, this hydrolysis has not been specifically studied in a way that has produced reliable, publishable data. Previously published analytical methods tend to focus mainly on quantitative measurement of OLM, but not quantitative measurement of OL. The objective of this study was to investigate the solubility and aqueous hydrolysis of OLM in different pH buffers by developing an analytical method for the simultaneous measurement of OLM and OL. A novel HPLC method was developed and validated to simultaneously quantify OLM and OL. The solubility of OLM was pH-dependent 37 degrees C, which could lead to food effects and precipitation of OLM in the small intestine. The aqueous hydrolysis of OLM was rapid and significant and followed the zero-order kinetic model with different hydrolysis rates varying across different pH levels in the order: pH 1.2 < pH 3.5 < pH 4.6 approximately pH 6. These findings indicate that, in addition to low water solubility, aqueous hydrolysis in the gastrointestinal tract contributes to OLM's low bioavailability. The study emphasizes the importance of fully understanding the solubility and hydrolysis of ester-based prodrugs. Strategies that protect OLM from hydrolysis could have the potential to enhance its bioavailability. Considering ester prodrugs are a key strategy to improve bioavailability, our study in this manuscript is significant for drug formulation development.This work was supported by the National Institute of General Medical Sciences [1R35GM138225-01, Dong, X.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Oncogenic effects of ECM remodeling in obesity and breast cancer
Full text linkExtracellular matrix (ECM) components are key regulators in breast cancer progression, as ECM remodeling is essential for breast cancer cells to invade into surrounding tissue. This process is characterized by the alignment of fibrillar collagens, breakdown of basement membrane components, and increased interstitial collagen stiffness. In patients with obesity, pre-existing ECM changes, including excessive collagen deposition and heightened matrix stiffness, mimic alterations detected in breast cancer. Given that obesity is a predictor of poor prognosis and resistance to treatment in breast cancer, it is crucial to understand how ECM conditioned by obesity affects disease outcomes. In this review, we highlight known ECM changes that occur with breast cancer and obesity and describe how these changes impact cancer cell metastasis, disease progression, and the breast cancer tumor microenvironment. We examine how obesity driven ECM remodeling affects treatment response and resistance. Further, we discuss how the compounding factor of age contributes to remodeling and current preclinical models of ECM in breast cancer.This work is partially funded through a NACA agreement with the USDA Project #6054-41000-112-000D and La-CATs U54 GM104940. This work is additionally funded through the Interdisciplinary Predoctoral Training in Bioinnovation program - 5T32EB027632-05. We would like to thank the National Cancer Institute of the National Institutes of Health (3R01CA273095-01S1), the Tulane Cancer Center, part of Tulane Medical School, and a consortium partner of the Louisiana Cancer Research Center. We appreciate Mark Heiman for reviewing and providing valuable feedback. All figures were created with BioRender.com. We are grateful to Krewe de Pink, an organization of breast cancer survivors, their families, and community members based in New Orleans, devoted to supporting local breast cancer research