United States

ABSTRACT

Extracellular-cAMP Suppresses Pulmonary Arterial Hypertension-induced Ventricular Arrhythmias


Background: Pulmonary Arterial Hypertension (PAH), a major cause of right ventricular failure, is associated with a high 5-year mortality rate. Arrhythmias account for a significant proportion of morbidity and mortality in PAH patients. Hence, there is a critical need for new therapies to effectively treat PAH-related cardiac arrhythmias.

Objective: The purpose of this study was to evaluate the efficacy of extracellular cyclic adenosine monophosphate (e-cAMP) treatment in reversing pathophysiological electrophysiological (EP) remodeling and arrhythmia propensity caused by PAH.

Methods: After three weeks of subcutaneous injection of Monocrotaline (MCT) or left pneumonectomy within VEGFR inhibition by Sugen-5416 (Su/Pn), rats were randomly assigned to receive miniosmotic pumps containing cAMP or a saline solution. At the 5-week terminal time-point, rats were sacrificed for ex-vivo optical action potential (AP) mapping, real-time reverse transcription–polymerase chain reaction, immunostaining, morphological and histologic analyses.

Results: As expected, PAH diseased rats from both models exhibited a high propensity of inducible ventricular tachycardia. Remarkably, e-cAMP treatment suppressed the incidence of ventricular tachycardia in both models. Examination of the EP substrate revealed action potential duration (APD) prolongation and marked conduction slowing in PAH-diseased animals. These features, however, were significantly reversed by e-cAMP treatment. Moreover, the analysis of alternans showed that e-cAMP treatment prevented the incidence of alternans behavior altogether (P = 0.0291 for e-cAMP-treated MCT vs. MCT group, P = 0.021 for e-cAMP-treated Su/Pn vs. Su/Pn group). PAH-diseased rats displayed right ventricular as well as cardiomyocyte hypertrophy, whereas e-cAMP-treated rats exhibited a significant decrease in hypertrophic remodeling both at the chamber and cellular levels. We also uncovered a marked decrease in myocardial fibrosis by e-cAMP treatment in PAH-diseased rats. Reversal of EP remodeling by e-cAMP was accompanied by decreased pulmonary vascular remodeling and by restored cardiac expression of key ion channel transcripts.

Conclusion: Extracellular cAMP treatment reduces the incidence of ventricular arrhythmias and suppresses pathological EP remodeling. This approach may represent a new therapeutic modality for arrhythmia suppression in PAH patients.

2025 AMA Research Challenge – Member Premier Access

Extracellular-cAMP Suppresses Pulmonary Hypertension-induced Ventricular Arrhythmias

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Background 

The right atrioventricular (tricuspid) valve (RAV) separates the right atrium and ventricle to inhibit retrograde blood flow during ventricular systole. Although traditionally described as having three leaflets — anterior, posterior, and septal — it is not uncommon for the RAV leaflet number to vary with previous studies finding three leaflets in 28% to 71.1%, four leaflets in 28.9% to 52%, and as few as 2 and as many as 6 have been documented. An understanding of RAV functional morphology is essential for successful transcatheter tricuspid valve repair (TTVR) procedures for the treatment of tricuspid regurgitation. Although less common than mitral valvular disorders, tricuspid regurgitation has been shown to correlate with poor cardiac sequela and increased cardiac mortality, leading to increasing incidence of TTVR procedures. This ongoing study explores the prevalence of variation in RAV leaflet numbers using cadaveric donors at Midwestern University to contribute to the understanding of its morphology and implications for TTVR. 

Methods 

Thirty-seven cadaveric donor hearts consisting of 19 males and 18 females were examined and classified according to the schema—Type 1 (three leaflets), Type 2 (two leaflets), and Type 3 (four leaflets). The presence of a fourth leaflet was further subdivided based on additional leaflet location—type 3A (anterior), 3B (posterior), and 3C (septal). Individual leaflets were defined during dissection as existing within a distinct gross margin of the valve and having unique papillary muscle attachments. This procedure allowed us to distinguish discrete additional leaflets from commissural leaflets that exist between two leaflet margins but function in tandem with a single leaflet. 

Results 

This study found that of the 37 hearts, 29 (78.4%) were Type 1, three (8.1%) were Type 2, and five (13.5%) were Type 3. Of the Type 3, one was Type 3A (2.7%), two were Type 3B (5.4%), and two were Type 3C (5.4%). 

Conclusion 

This study found lower frequencies of a fourth leaflet than previous studies. However, the findings of these studies vary widely, primarily due to procedural differences in defining and distinguishing leaflets from commissural leaflets arising from a lack of universal naming protocols. Regarding TTVR, the presence of a fourth RAV leaflet is clinically significant as it is associated with increased residual regurgitation following procedure in those treated for isolated tricuspid regurgitation. These preliminary data contribute to the growing understanding of RAV morphology, which has the potential to contribute to current and future advancements in the treatment of tricuspid regurgitation.

Anatomical Variation in Cadaveric Tricuspid Valves and Implications for Transcatheter Tricuspid Repair

Testosterone is the primary androgen upregulated during puberty that is known to promote tumor growth and metastasis in hormone-dependent cancers such as prostate cancer. However, its role in osteosarcoma is relatively unknown. Using a subcutaneous tumor growth model, we show that castrated mice do not form tumors whereas uncastrated mice form tumors in a striking 40% of cases. This suggests that testosterone may have a role in tumor growth and metastasis. In a further study, we observed that treatment with testosterone in vivo is able to increase tumor formation in both a heterotopic and orthotopic xenograft mouse model in a non-tumorigenic cell line (MG-63). However, it was unable to accelerate tumor growth in a tumorigenic cell line (143B). Utilizing a tail vein model, we demonstrate that treatment with testosterone was able to accelerate metastasis and decrease overall survival in a metastatic cell line but was unable to initiate metastasis in a non-metastatic cell line. Understanding the mechanism of testosterone in osteosarcoma could provide new insights into the biology of this devastating disease. These findings suggest that current anti-androgen therapies may provide novel therapeutic options for patients suffering from osteosarcoma.

Testosterone Increases Tumorigenesis and Metastasis of Human Osteosarcoma In Vivo

Abstract Title
Preclinical Alzheimer’s Disease: Trends in Amyloid β Oligomer Levels in TBI Patients and a Mouse Model of CTE

Background
In this study, we investigate the potential connection between Chronic Traumatic Encephalopathy (CTE) and Alzheimer's disease (AD), highlighting their shared pathologic and behavioral features. Utilizing transgenic AD mouse model, APPswe/PSen1ΔE9 (APP/PSEN), and employing the Morris Water Maze (MWM) to assess cognitive impairment, we examine the impact of repetitive head injuries. We hypothesize that diffuse axonal injury leads to the release of amyloid precursor protein (APP), triggering a subsequent pulse of soluble amyloid beta oligomers (AβO). This theoretical framework aims to deepen our understanding of the overlapping features between CTE and AD.

Methods
This investigation employed three-month-old mice to simulate a young adult, particularly selecting APP/PSEN mice in their pre-symptomatic phase. The study involved a 5-day series of acquisition trials using the MWM for both wild-type (WT) and APP/PSEN mice. Bilateral repetitive close head injuries were subsequently administered to each group over a 10-day period, followed by a 6-week recovery phase to avoid studying mice in a post-concussive state. After recovery, reverse trials were conducted over 5 days in the MWM. Probe trials were carried out on the 5th day after a 24-hour rest during acquisition and reversal swims. CSF was collected from the extra ventricular drain (EVD) of hospital trauma patients and analyzed with ELISA for the presence of AβO’s.

Results
In the acquisition trials preceding impactions, latency to platform were similar for WT and APP/PSEN mice. Following impactions, both groups demonstrated increased latency to platform. Impacted APP/PSEN mice exhibited significantly greater latency to platform when compared to impacted WT control. A subsequent 60-second probe trial, conducted 24 hours after the last acquisition trial, demonstrated decreased time in target quadrant of APP/PSEN compared to the other groups. Human CSF analysis of AβO levels were higher in the early post- trauma period and decreased over time. Three of five patients AβO levels were significantly higher than that of the pooled control group.

Conclusion
Three-month-old APP/PSEN mice perform similarly to three-month old WT mice during the acquisition trials. Possibly modeling a pre-symptomatic state. After repetitive close head impacts, APP/PSEN and WT mice experience behavioral and cognitive decline. APP/PSEN cognitive/behavioral deficits appear exacerbated when compared to injured WT mice.
This finding suggests that the AD background in APP/PSEN mice predisposes them to heightened cognitive behavioral decline. Possibly modeling the cognitive behavioral deficits seen in CTE. Additionally, trends in preliminary data on CSF collected from trauma EVD patients further supports our AβO theory of CTE.

Preclinical Alzheimer’s Disease: Trends in Amyloid β Levels in TBI Patients and a Mouse Model of Chronic Traumatic Encephalopathy


In the rapidly evolving landscape of surgical techniques, virtual reality (VR) and augmented reality (AR) have emerged as innovative tools to enhance surgical precision, training, and efficiency. VR creates a fully immersive, computer-generated environment for simulation-based learning, while AR overlays digital information onto the real-world surgical field to enhance visualization and precision. This study evaluates the impact of VR and AR on surgical accuracy, procedural efficiency, and skill acquisition through a comprehensive analysis of peer-reviewed literature from 2010 to 2024. A systematic review of seven databases identified studies comparing VR/AR-assisted surgical techniques to traditional methods, highlighting improvements in clinical outcomes.
Findings reveal that VR/AR-assisted surgeries consistently demonstrate higher accuracy rates and reduced operative times in several procedures. For example, glioma resections and pedicle screw placements showed significantly improved accuracy (p < 0.01), while breast biopsies and femur bone tumor resections also exhibited enhancements (p < 0.05). However, percutaneous coronary interventions (p = 0.583) did not show a statistically significant benefit, suggesting that the advantages of VR/AR may be procedure-specific.
Similarly, surgical procedure times were significantly reduced in reverse shoulder arthroplasty (p < 0.001) and tibial intramedullary nailing (p = 0.034) when VR/AR-assisted methods were used. The most pronounced improvement was observed in pedicle screw insertions, with a marked reduction in time (p < 0.001). These results suggest that VR/AR optimizes surgical workflows, enhances precision, and accelerates skill acquisition, particularly in complex procedures requiring high spatial accuracy.
While the findings highlight the transformative potential of VR/AR in modern surgery, limitations include high costs, extended learning curves, and patient skepticism. Future studies should explore cost-effectiveness, long-term outcomes, and broader applications in both urban and rural healthcare settings. These technologies represent a promising advancement in surgical training and patient outcomes, emphasizing their role in improving global surgical proficiency and reducing complications. With continued innovation and integration, VR and AR have the potential to revolutionize surgical education and practice, setting new standards for precision and efficiency in the operating room.

Enhancing Surgical Precision and Training: The Integration of Virtual Reality and Augmented Reality in Modern Surgical Practices

Introduction: Obesity is an increasingly prevalent comorbidity that confers greater risks of postoperative complications following total joint arthroplasty, underscoring the need for viable preoperative weight loss. The objective of this study was to compare the risk of 90-day adverse events in patients undergoing total knee arthroplasty (TKA) following bariatric surgery versus treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA).

Methods: A retrospective review of a national research network from May 1, 2005, to February 12, 2025, identified patients undergoing TKA with bariatric surgery or GLP-1 RA prescriptions in the 18 months preceding their joint arthroplasty. Following propensity score matching, 4,652 patients were selected for comparison in both the bariatric surgery and GLP-1 RA cohorts. For each cohort, patient demographics, 90-day orthopaedic and surgical complications, readmissions, and emergency department (ED) visits were collected. Statistical differences in relative risk (RR) between each complication were calculated with t-tests and Chi-square tests. 

Results: In the 90-day postoperative period, patients who underwent bariatric surgery before TKA experienced greater rates of periprosthetic fractures (RR: 2.4; P = 0.016), periprosthetic joint infections (RR: 1.7; P = 0.002), revision surgeries (RR: 1.926; P = 0.005), cardiac events (RR: 1.255; P < 0.001), readmissions (RR: 1.316; P = 0.015), and ED visits (RR: 1.2; P < 0.001). 

Conclusion: A significantly increased risk of postoperative events was identified in patients who underwent bariatric surgery. These findings, along with existing literature, suggest that GLP-1 RA use may be a preferred option for preoperative weight loss optimization in TKAs. Overall, greater clinical understanding is provided for this drug and may inform surgical decision-making regarding weight management strategies and their associated risks.

Short-Term Complications After TKA in Patients with Prior Bariatric Surgery or GLP-1 Agonist Use

Introduction: Inhaled triple therapy is a combination of an inhaled corticosteroid (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA), and is used to treat chronic obstructive pulmonary disease (COPD). This therapy is indicated in GOLD class E patients – those with ≥2 moderate COPD exacerbations or ≥1 leading to hospitalization. ICS in these groups reduces exacerbations and improves lung function and patient reported outcomes. ICS benefits decrease with serum eosinophil count <100 cells/uL and increase with counts ≥300 cells/uL. However, ICS therapy has been associated with a higher incidence of pneumonia, especially in those with frequent or severe COPD exacerbations and blood eosinophils <2%.

Methods: This retrospective cohort study evaluated inhaled triple therapy prescribing practices and subsequent pneumonia incidence in patients with COPD located in rural Indiana between January 1, 2020, and January 1, 2025. A query of the electronic medical record system Epic was done to assess if ICS addition met guideline-based indications (GOLD class E criteria, defined as ≥2 moderate exacerbations or ≥1 exacerbation requiring hospitalization in the prior year) and to record serum eosinophil count prior to initiation. To evaluate subsequent pneumonia incidence, participants were stratified according to eosinophil count – ≤100 cells/uL, 101-299 cells/uL, and ≥300 cells/uL. Chi-square tests were used to compare categorical variables. Logistic regression was used to determine odds ratios adjusted for GOLD indications for triple inhaler therapy. Statistical significance was defined as p ≤0.05.

Results: Among 227 patients prescribed triple inhaler therapy, 36.5% met GOLD class E criteria for initiation. Pneumonia incidence the following year was increased in those with serum eosinophil count ≤100 cells/µL, whereas higher eosinophil count ≥300 cells/uL was associated with a decreased incidence of pneumonia, though these trends were insignificant. Stratifying according to exacerbation severity & frequency and GOLD grade did not yield statistically significant associations. There was no confounding based on GOLD grade or exacerbations.

Conclusion: In this rural Indiana cohort, a substantial proportion of patients receiving triple inhaler therapy did not meet guideline-based indications for ICS initiation. Though lower eosinophil counts were associated with increased pneumonia incidence, these findings did not achieve statistical significance. Further investigation using a larger patient population is required to further delineate the relationship between eosinophil count and risk of pneumonia after initiating triple inhaler therapy.

Prescribing Practices of Inhaled Triple Therapy in Rural Indiana​

Background
The standard of care for localized renal carcinoma is nephrectomy, but this procedure carries a risk of complications like chronic kidney disease (CKD) and end-stage renal disease (ESRD). Current predictive models for these outcomes are limited by the underrepresentation of Black patients and do not investigate how racial differences are mediated. This project aims to identify which treatment decisions might be impacted by race and to use causal inference to investigate whether those treatment differences impact outcomes.

Methods
A cohort of 2,931 patients who underwent nephrectomy were identified from University of Florida medical records, including 489 (17%) Black patients. After filtering, the analysis cohort consisted of 2,571 patients (948 partial vs. 1,623 radical nephrectomy). A causal forest model was used to determine the average (ATE) and conditional (CATEs) treatment effects of partial versus radical nephrectomy on ESRD development. Logistic regression determined the association between race and both treatment type and ESRD outcomes after controlling for clinical variables. As race is not a manipulable variable, it was included as a covariate in the causal forest to explore heterogeneity in treatment effects across racial subgroups.

Results
Surprisingly, after adjusting for other factors, Black patients had 1.36 times the odds of receiving a partial nephrectomy compared to White patients (95% CI: 1.197, 1.554). However, Black patients still had 1.30 times the odds of developing post-nephrectomy ESRD (95% CI: 1.026, 1.646). While patients who received a radical nephrectomy developed ESRD at a higher raw rate than those who received a partial nephrectomy (4.5% vs 2.5%), the causal forest model found no statistical significance after accounting for patient characteristics (ATE: 0.011; 95% CI: -0.046 to 0.069; p=0.703). This indicates the difference may be explained by clinicians’ patient selection. The suitability of the data for this analysis was demonstrated by good overlap in propensity scores between treatment groups and balanced covariates.

Conclusion
These findings suggest that Black patients are more likely to receive a partial nephrectomy, yet still have a higher risk of developing ESRD post-operatively. This highlights a significant racial disparity in outcomes that is not explained by surgery type alone. Additionally, the lack of a clear causal link between nephrectomy type and ESRD calls into question whether the differences in post-nephrectomy ESRD are due to surgeons choosing healthier patients for partial instead of radical nephrectomy.


Addressing Racial Disparities with Causal Forests: Black Race is Associated with more Post-Nephrectomy End-Stage Renal Disease, but Nephrectomy Type is not a Causative Factor

Abstract Title
Adult Rectal Duplication Cyst Presenting as Chronic Back Pain
Background
Alimentary tract duplications are rare congenital anomalies with an incidence of approximately 1
in 4,500 live births. They are most commonly identified in infancy or childhood. Rectal
duplication cysts (RDCs), a particularly uncommon subtype, account for just 1%-6% of all
alimentary tract duplications. These lesions typically present as cystic structures containing
layers of gastrointestinal wall histology. While often asymptomatic, their presentation can vary
significantly depending on patient age. In children, RDCs may present as bowel obstruction,
recurrent perianal infections, or be discovered on physical examination. In contrast, adults may
present with vague or unrelated symptoms, found incidentally on imaging. In rare cases, RDCs
may become symptomatic due to compression of adjacent structures, infection, fistula
formation, or even malignant transformation. Given their deep pelvic location and nonspecific
symptomatology, they are often misdiagnosed or overlooked. Reports of RDCs in adults are
rare, and their varied presentation poses significant challenges in diagnosis and management.
We present the case of an adult woman who presented with chronic back pain and was found to
have an RDC, emphasizing the importance of considering congenital anomalies in the
differential diagnosis of pelvic masses in adults.
Case Presentation
A 41-year-old female presented with a five-year history of low back pain radiating to both legs,
initially attributed to lumbar radiculopathy. She denied gastrointestinal or urinary symptoms. On
physical examination, a firm mass was palpated posterior to the rectum. Pelvic MRI revealed a 7
cm heterogenous mass in the presacral space. CT showed the posterior pelvic mass abutting
the distal coccyx without involving the sacrum. Given the concern for malignancy, she
underwent robotic-assisted laparoscopic resection. Intraoperatively, a 5-6 cm well-encapsulated
presacral mass was identified and excised via a Pfannenstiel incision. She was discharged
home the same day without complications. Histopathologic analysis revealed squamous
epithelium overlying smooth muscle and connective tissue, consistent with a benign rectal
duplication cyst.
Discussion
Adult RDCs are rare and often present with nonspecific symptoms, making diagnosis difficult.
MRI is preferred for soft tissue evaluation, while CT can assess for bony involvement. Complete
surgical resection remains the definitive treatment and diagnostic modality. Robotic resection
offers superior visualization with improved post-operative pain. This case emphasizes the need
to include RDCs in the differential diagnosis of chronic pelvic or back pain in adults.

Adult Rectal Duplication Cyst Presenting as Chronic Back Pain

Background
TikTok, a popular social media platform for short-form mobile videos, provides a source for individuals to share and receive information regarding permanent sterilization methods. TikTok has become the primary source for young adults to receive a majority of their daily information, including contraceptive health information among young women. While TikTok has become beneficial in connecting individuals with shared concerns, users can also be exposed to significant misinformation.
Methods
101 TikTok videos under #tubal, #tuballigation, and #tubestied were collected using Apify web-scraping software for analysis. Each video was evaluated for creator demographics, tonality, and medical content by two separate reviewers, a third reviewer mediating discrepancies in assessment. DISCERN and PEMAT (Patient Education Materials Assessment Tool) criteria were used to evaluate the quality and accuracy of medical information presented through the TikTok videos regarding tubal ligation. DISCERN scores range from a low of 1 and a high of 5 regarding medical information quality. PEMAT scores range from 10%-100% and evaluate the understandability of patient education audiovisual materials.
Results
Results indicated that video tonality was split between positive (32.7%), negative (31.7%), and neutral (27.7%). While 25.7% of the videos explicitly referenced a negative experience with female permanent contraception a majority did not, with 5.9% mentioning both a positive and negative experience. 16 videos (15.8%) explicitly focused on failure of the tubal ligation procedure resulting in unexpected pregnancy. Of the 28.7% of videos showcasing a personal experience, changes in menstruation, hormones, and increased pain and cramping were highlighted as notable and debilitating side effects, with the colloquial term “post-tubal syndrome” emerging among women. Only a minority of videos were created by healthcare professions (24.8%), and among those, most (80%) were board certified Obstetric Gynecologists who often shared content regarding the logistics of procedures, risks, complications, and outcomes. Of the 15 videos containing medical content created by healthcare professionals the average DISCERN score was 3.8 compared to a score of 3 by laypeople (n=22). The average PEMAT score for videos with medical content was 84.2%, higher among healthcare professionals (93.3%) than lay people (81.8%). 
Conclusion
#tuballigation, #tubal, and #tubestied videos on TikTok commonly showcase negative experiences and failed procedures resulting in pregnancy through the sharing of individual’s personal experiences as well as content regarding procedural logistics and sterilization education from healthcare professionals. Qualified health professionals may consider utilizing TikTok as a platform to effectively share credible medical knowledge regarding female permanent contraception, as many individuals seek and obtain health information from the platform. Awareness of the content patients consume can help healthcare professionals address misinformation and guide informed medical decision-making. 



Use of TikTok as a Source of Medical Information Regarding Tubal Ligation

Intimate Partner Violence (IPV) is a significant public health concern that remains insufficiently addressed in medical education. A national survey indicates that nearly one in two women (47.3%) and more than 40% of men (44.2%) in the United States have experienced IPV in their lifetime. Despite the high prevalence and serious health implications of IPV, comprehensive training on this topic has not been widely incorporated into medical school curricula. Current research shows integrating interactive simulations into medical school curriculum is the best practice for providing lasting knowledge on the training topic at hand. This study aims to bridge the educational gap of IPV in medical students by implementing an interactive, simulation-based curriculum. This will not only enhance future physicians' competency in recognizing IPV but also equip them with the skills to provide appropriate resources to victims. Participants will engage in a structured training session, featuring a role-playing exercise and guided case discussions. A pre- and post-survey model will be used to assess changes in knowledge, confidence, and attitudes toward IPV management. Preliminary data has demonstrated statistically significant improvements in both preparedness and knowledge among participants following the intervention. These preliminary findings suggest the intervention was effective in enhancing medical students’ confidence and understanding related to identifying and managing intimate partner violence in clinical settings. Additionally, initial data suggests students feel more adequately equipped with practical tools for screening and intervention, alongside a heightened sense of empathy, compassion, and understanding of IPV victims - an essential step in providing trauma-informed, supportive care. Notable limitations of this study include the immediate timing of participant responses, which may have been influenced by the emotional impact of the intervention, as well as a small final sample size (n=20). Although 59 participants completed the pre-survey, only 24 completed the post-survey, and just 20 submitted fully completed responses. This low yield of responses raises concerns about feasibility and integration of such a curriculum within an already demanding medical school schedule. Alongside a larger sample size, longitudinal investigation of participants would be needed to assess efficacy of the curriculum in clinical practice. However, by implementing a curriculum that is interactive and attitudinally transformative, we aim to bridge the existing educational gap and, ultimately, provide more comprehensive patient care in clinical practice.

Next from 2025 AMA Research Challenge – Member Premier Access

Anatomical Variation in Cadaveric Tricuspid Valves and Implications for Transcatheter Tricuspid Repair