United States

Abstract Title: Impact of the Renin-Angiotensin System on Left Ventricular Hypertrophy in Polycystic Ovary Syndrome

Background: Polycystic Ovary Syndrome (PCOS) is characterized by androgen excess and ovulatory dysfunction, affecting 5 to 26% of reproductive-aged women. Recent studies suggest that women with PCOS may be at an increased risk for diastolic dysfunction. However, it remains unclear whether the activation of the renin-angiotensin system (RAS) contributes to left ventricle (LV) hypertrophy in PCOS. Using a well-characterized hyperandrogenemic female (HAF) rat model, we aim to test the hypothesis that RAS activation plays a role in the development of left ventricular hypertrophy in HAF rats.

Methods: Twenty Sprague Dawley female rats were randomly assigned to receive either silastic tubes containing dihydrotestosterone (DHT; 8 mg/90 days) or empty silastic tubes (control) via subcutaneous implantation. The LV was weighed and corrected by tibia length (TL). For histopathological examination, Masson Trichome staining was used to assess the myocardial fibrosis. Digital polymerase chain reaction (dPCR) was performed to measure mRNA expression of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin type-1 receptor (AT1R) and androgen receptor (AR). Protein expression of AGT, ACE, and AR was analyzed by Western blotting. Data were analyzed using Student’s t-test. A p-value of &lt;0.05 was considered statistically significant. GraphPad Prism was used for analyses.

Results: The HAF rat model exhibited an increase in LV/TL weight compared to controls (19.5 vs. 15.5 mg/mm). Quantification of fibrosis in the LV revealed significantly higher levels in DHT rats than in controls (34.2 vs. 16.2 μm³). dPCR analysis showed upregulation of AGT, ACE, and AT1R mRNA expression in DHT rats, whereas ACE2 and AR mRNA expression was reduced. Consistently, Western blotting demonstrated increased AGT and ACE protein levels and decreased AR protein levels in DHT rats compared to controls.

Conclusion: Despite downregulation of androgen receptor expression, chronic hyperandrogenemia in the HAF rat model led to LV hypertrophy and increased myocardial fibrosis. These changes were associated with upregulation of key RAS components, including AGT, ACE, and AT1R. This suggests that hyperandrogenemia may indirectly activate the RAS, contributing to cardiac remodeling independently of direct AR signaling.

2025 AMA Research Challenge – Member Premier Access

Impact of the Renin-Angiotensin System on Left Ventricular Hypertrophy in Polycystic Ovary Syndrome

Abstract Title: Impact of the Renin-Angiotensin System on Left Ventricular Hypertrophy in Polycystic Ovary Syndrome

Background: Polycystic Ovary Syndrome (PCOS) is characterized by androgen excess and ovulatory dysfunction, affecting 5 to 26% of reproductive-aged women. Recent studies suggest that women with PCOS may be at an increased risk for diastolic dysfunction. However, it remains unclear whether the activation of the renin-angiotensin system (RAS) contributes to left ventricle (LV) hypertrophy in PCOS. Using a well-characterized hyperandrogenemic female (HAF) rat model, we aim to test the hypothesis that RAS activation plays a role in the development of left ventricular hypertrophy in HAF rats.

Methods: Twenty Sprague Dawley female rats were randomly assigned to receive either silastic tubes containing dihydrotestosterone (DHT; 8 mg/90 days) or empty silastic tubes (control) via subcutaneous implantation. The LV was weighed and corrected by tibia length (TL). For histopathological examination, Masson Trichome staining was used to assess the myocardial fibrosis. Digital polymerase chain reaction (dPCR) was performed to measure mRNA expression of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin type-1 receptor (AT1R) and androgen receptor (AR). Protein expression of AGT, ACE, and AR was analyzed by Western blotting. Data were analyzed using Student’s t-test. A p-value of <0.05 was considered statistically significant. GraphPad Prism was used for analyses.

Results: The HAF rat model exhibited an increase in LV/TL weight compared to controls (19.5 vs. 15.5 mg/mm). Quantification of fibrosis in the LV revealed significantly higher levels in DHT rats than in controls (34.2 vs. 16.2 μm³). dPCR analysis showed upregulation of AGT, ACE, and AT1R mRNA expression in DHT rats, whereas ACE2 and AR mRNA expression was reduced. Consistently, Western blotting demonstrated increased AGT and ACE protein levels and decreased AR protein levels in DHT rats compared to controls.

Conclusion: Despite downregulation of androgen receptor expression, chronic hyperandrogenemia in the HAF rat model led to LV hypertrophy and increased myocardial fibrosis. These changes were associated with upregulation of key RAS components, including AGT, ACE, and AT1R. This suggests that hyperandrogenemia may indirectly activate the RAS, contributing to cardiac remodeling independently of direct AR signaling.

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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.

Extracellular-cAMP Suppresses Pulmonary Hypertension-induced Ventricular Arrhythmias

Traumatic injuries are the leading cause of death for individuals under the age of 46, with 30% to 40% of these deaths resulting from blood loss. In order to minimize the delay between presentation to the hospital and administration of blood products, Artificial Intelligence (AI) techniques were used to predict the need of transfusions in trauma patients. The Trauma Quality Improvement Program (TQIP) was used in an 80-20 train-test split for several different Machine Learning (ML) models. XGBoost was the best performing model with an AUROC of 0.845. Shapley values were then calculated, showing the 5 most important features for the model were ISS, SBP, Highest Activation, and Pulse Rate. This work showed that XGBoost was able to effectively predict transfusion requirements while Shapley values provided interpretability and trustworthiness. Future work includes comparing with additional AI models such as neural networks, as well as deploying the model for use in a clinical environment.

Prediction of Transfusions Using Machine Learning

Background
Quantitative analysis of nerve histomorphology is essential for nerve regeneration research. Manual quantification of axon numbers, diameters, and myelin thickness is time-consuming and labor-intensive. . Semi-automated processes have improved this process, but newer computational technologies may offer further opportunities for enhanced efficiency. Recently developed open access deep learning software, AxonDeepSeg, does offer many advantages for certain imaging analysis but is less proficient at analyzing brightfield microscopy images. We believed that this software could be further optimized for this application.

Methods
A modified UNet++ architecture was used to develop “DeepAxon”, an fully automated segmentation tool for nerve toluidine blue image analysis. Images were pre-processed into patches, segmented using the UNet++ model, and restitched using a Hann window algorithm. Morphometric analysis was automatically performed on segmented images to extract key parameters. Improved “DeepAxon” efficiency and proficiency was validated in comparison to alternative analysis techniques

Results
DeepAxon demonstrated comparable accuracy to manual segmentation in measuring g-ratio and axon diameter but reduced analysis time by 99.9% compared to manual segmentation and 96.2% compared to AxonDeepSeg.

Conclusions
DeepAxon is a novel automated segmentation tool for nerve immunohistochemistry images. It significantly reduces analysis time and provides accurate morphometric measurements. By addressing limitations of existing methods, DeepAxon offers a valuable tool for researchers in the field of nerve regeneration. Future improvements, such as a user-friendly interface and enhanced model training, will further expand its utility

DeepAxon: Automatic Morphometric Analysis of Axon Brightfield Microscopy

Abstract Title: Lung Lesion CT Imaging Features Associated with Sufficient Tissue Sampling by Monarch Platform Bronchoscopy 

Background 

Monarch Platform is a robot-assisted bronchoscopy (RAB) used to biopsy pulmonary lesions suspicious of lung cancer. Multiple studies have evaluated the safety and diagnostic yield of RAB, but the criteria used to calculate the diagnostic yield have varied leading to inconsistent results. This study aims to assist by identifying CT imaging features of lung lesions, such as diameter, associated with sufficient tissue sampling to calculate diagnostic yield. 

Methods 

Data was retrospectively collected of patients who underwent a Monarch Platform bronchoscopy at Penn State Hershey Medical Center for the past two years. Patients with a previous chest CT scan in which a diameter of the lesion was reported by a radiologist were included as well as the Monarch planning CT examination. Pathology results of the biopsy collected via RAB were determined. Biopsies relying on analysis of lymph node biopsy or cytology brushing were excluded. Diagnostic yield was calculated as the proportion of biopsies with a diagnostic result using the Conservative Criteria introduced by Vachani et al. Malignant and specific-benign diagnoses were diagnostic while all other results were non-diagnostic. 

Results 

The total number of patients analyzed in this retrospective study was 142. The average age was 69 with 56% being female (n=80). The median diameter of all lesions biopsied was 22 mm. The calculated diagnostic yield was 57%, with 81 patients having a diagnostic biopsy and 61 patients having a non-diagnostic biopsy. 

The median size of diagnostic lesions was 29 mm while the median size of non-diagnostic lesions was 17 mm (p=0.001). The total number of lesions with a diameter ≥15 mm was 114, and the total number of lesions with a diameter ≥30 was 50. The diagnostic yield of lesions ≥15 mm was 61%, while the diagnostic yield of lesions ≥30 mm was 80% (p=0.02). 

Conclusion 

Monarch Platform RAB is a valuable tool in diagnosing lung lesions. This study found that as the diameter of the lung nodule increased, the diagnostic yield also significantly improved, with an increased diagnostic yield from 61% to 80% between 15 mm and 30 mm. The size of the lesion identified on CT scan and its associated likely diagnostic yield could prove helpful to radiologists in determining if RAB is recommended.

Lung Lesion CT Imaging Features Associated with Sufficient Tissue Sampling by Monarch Platform Bronchoscopy


Background
Frequent monitoring of lung function with spirometry in chronic pulmonary disease can help detect early disease progression. The CMI Health SpiroLink device ($79.99) and the Sonmol Digital Spirometer ($29.99) are home spirometers that are commercially available and may help patient monitor their pulmonary status between formal testing. These two devices, however, are not FDA-approved, and pulmonologists may be reluctant to place credence in their measurements. This study aims to assess whether these non-FDA-approved devices provide similar trends to the FDA-approved Jaeger/Vyaire Vyntus Spiro (>$5,000).

Methods
A retrospective review was conducted utilizing spirometric forced expiratory volume in one second (FEV1) data collected by a physician-patient with chronic hypersensitivity pneumonitis. FEV1 values were tracked in parallel on three different spirometers (Sonomol, SpiroLink, and Vyntus) for a year, and a comparative analysis, using Vyntus as a reference standard, was done to assess the variability in measurements. FEV1 trends were visualized using logically estimated scatterplot smoothing (LOESS) across the study time, and data were modeled using nonlinear sinusoidal regression for each device. Regression models were used to obtain 95% confidence intervals of model estimates to compare trend capture across each device.

Results
Despite differences in absolute numerical values, all three devices, upon visual assessment, exhibited consistent trends for FEV1 that reflected the patient’s lung function. LOESS smooth curving of FEV1 data showed a sinusoidal, or wave-like pattern, throughout the year. 95% confidence intervals of these models’ estimates (Amplitude and Frequency) show a high amount of overlap, indicating that each of the three devices captured similar trends of FEV1 over time. However, the confidence interval for displacement (Vertical Shift) didn’t overlap, indicating that the FEV1 measurements of each device were different on average.

Conclusion
The non-FDA-approved Spirolink and Sonmol devices could be used by patients to provide accurate tracking of lung function trends over time, based on the similar variation in FEV1 values over the study period. This can potentially inform pulmonary care by allowing patients to identify changes in their function trends at home earlier than periodically scheduled measurements in a clinic. Future directions include analysis of other spirometry measures, increasing sample size, and increasing study timeframe.

Home-Based Spirometry for Chronic Hypersensitivity Pneumonitis: A Year-Long Comparative Study of Consumer and Medical-Grade Devices

Background:
Undescended testis (UDT), or cryptorchidism, is a common congenital anomaly in male infants, affecting
approximately 3% of full-term and up to 30% of preterm males. Untreated UDT increases the risk of infertility
and malignancy. Orchidopexy is recommended between 6 and 18 months of age, but delays in diagnosis and
treatment remain common in low-resource settings. This study evaluates the clinical presentation and
surgical outcomes of UDT in children at a tertiary care center in Mizoram, India.
Case Presentation:
This cross-sectional observational study was conducted from November 2020 to April 2022 at Civil Hospital,
Aizawl. Twenty male patients under 15 years with unilateral or bilateral UDT were included, excluding
retractile testes and patients above 15 years. Clinical examination and ultrasonography were used to assess
preoperative testicular position, volume, and viability. All patients underwent open inguinal orchidopexy under
general anesthesia. Postoperative follow-ups were done at 2 weeks, 3 weeks, and 6 months, with
ultrasonographic evaluation of testicular volume and viability. Statistical analysis used paired t-tests to
compare pre- and postoperative volumes, with significance set at p<0.05.
Discussion:
The mean age at presentation was 1.93 ± 0.23 years, with 90% presenting before 2.5 years. Low birth weight
was noted in 80% of cases. Most testes (95%) were palpable and 75% were right-sided. The most common
testicular locations were the right superficial inguinal pouch (30%), deep inguinal ring (25%), and inguinal
canal (20%). A significant increase in mean testicular volume was observed postoperatively (from 0.62 ± 0.15
mL to 0.76 ± 0.12 mL; p<0.01). At 6 months, 95% of testes remained viable and properly positioned. One
patient developed testicular atrophy and one had a surgical site infection.
Timely diagnosis and surgical intervention lead to favorable outcomes in children with UDT. This study
demonstrated significant postoperative improvement in testicular volume and high viability rates, supporting
the benefits of early orchidopexy. The minimal complication rate further emphasizes the safety of this
approach. However, delays in presentation highlight the need for increased awareness among caregivers
and primary care providers. Larger-scale studies with extended follow-up are necessary to assess long-term
fertility outcomes and refine care strategies for better population-level impact.

Clinical and Surgical Outcomes in Pediatric Undescended Testis: Experience 
from Mizoram, India

Background
Rapid recognition and standardized management of genitourinary (GU) emergencies can significantly impact clinical outcomes, morbidity, and mortality. Variability in imaging practices and intervention protocols across health systems contributes to treatment delays and suboptimal outcomes. This review synthesizes current evidence to establish standardized approaches to imaging selection and interventional radiology (IR) strategies for hospitalized patients experiencing GU emergencies.
Methods
An extensive literature review was conducted, focusing on radiologic imaging (ultrasound, CT, MRI) and IR techniques (e.g., percutaneous nephrostomy, selective arterial embolization) relevant to GU emergencies encountered in inpatient and intensive care settings. Clinical scenarios such as urinary obstruction, infections, vascular emergencies, trauma, and iatrogenic injuries were comprehensively assessed. Literature was selected based on clinical relevance, timeliness, and applicability to acute management settings.
Results
This review summarizes evidence-based imaging and IR approaches for critical GU conditions. For obstructive uropathy complicated by sepsis, rapid imaging via non-contrast CT is recommended; ultrasound-guided percutaneous nephrostomy provides immediate stabilization, particularly in unstable or pregnant patients. For vascular emergencies (renal infarction, aneurysm rupture), contrast-enhanced CT and IR embolization techniques demonstrate optimal patient stabilization. Clear differentiation of imaging indications based on clinical presentation enhances timely decision-making. Evidence supports multidisciplinary coordination among hospitalists, radiologists, urologists, and interventional radiologists to streamline management pathways.
Conclusion
Standardizing radiologic imaging strategies and IR interventions for common GU emergencies can improve patient outcomes, reduce variability in clinical practice, and optimize resource utilization. Health systems should implement structured interdisciplinary protocols informed by current evidence, emphasizing timely recognition and definitive intervention.

Imaging and Interventional Strategies in Genitourinary Emergencies: 
A Practical Guide for Acute Care

Background
Based on the current guidelines from The Endocrine Society and The World Professional Association for Transgender Health, transgender and gender diverse (TGD) adolescents diagnosed with gender dysphoria, in certain circumstances, may be candidates for gender-affirming mastectomy (GAM). Roughly half of U.S. states have outlawed this procedure. However, similar surgeries for cisgender adolescents (e.g., breast reduction, gynecomastia correction, and breast augmentation) have not been similarly regulated. In this presentation, we discuss whether there is valid justification in treating chest surgeries for these two populations differently from a public policy lens. While the United States Supreme Court (US vs Skrmetti) decision shuts down litigation from federal court, litigation may still move forward in state courts.

Methods
We conducted a systematic search using the PubMed database in January 2025. The search was guided by the health sciences librarian to develop the search strategy. The searches were divided into three main concepts (1) type of chest surgery, (2) outcome measure, and (3) age group of interest. A total of 20 articles were included for analysis.

Results
Breast Reduction
A matched comparison study evaluated the health outcomes of 78 patients who underwent breast reduction and 22 who expressed interest but did not receive surgery. Adolescents were included but were not analyzed separately. The postoperative group reported statistically significant improvement across all four domains. In contrast, the matched nonoperative group experienced no improvement in quality of life (QoL) and a decline in psychosocial and sexual well-being.

Gynecomastia Correction
One study used three validated scales to assess QoL after gynecomastia correction in adolescents aged between 12-21 years, including 76 minors. Adolescents and young adults (AYA) reported statistically significant postoperative improvements in health-related QoL and self-esteem on two of the three scales.

Gender-Affirming Mastectomy
A qualitative study of 30 AYA who had undergone GAM found that participants reported resolution of chest dysphoria, improved QoL and functioning, and lack of surgical regret. A study of 209 TGD adolescents who underwent GAM found a regret rate of 0.95% within a two-year follow-up period.

Conclusion
TGD and cisgender adolescents undergo similar chest surgeries with similar outcomes and data gaps, yet state public policies have banned only gender-affirming mastectomies for TGD adolescents. The risks associated with these surgeries appear comparable in TGD and cisgender youth. With similar risks and data, there does not appear to be a clear rationale for differential public policy treatment of these chest surgeries.

Access to Trans Adolescent in a Shifting Sociopolitical Landscape

Introduction
The Taliban’s takeover in 2021 warrants attention to Afghanistan’s compromised economy and healthcare system from prolonged states of conflict since Russia’s invasion in 1978. Maternal mortality (MM), as defined by the World Health Organization, is “the death of a woman while pregnant or within 42 days of termination of pregnancy” from non-accidental causes. This paper presents a literature review of maternal mortality in Afghanistan, along with recent solutions and prospects for the future. 

Methods
A comprehensive literature search was conducted across PubMed, Google Scholar, UNICEF, and WHO to identify relevant studies and data using keywords and Boolean operators such as "maternal mortality," "Afghanistan," "healthcare," "women’s health," and "education". Studies were excluded if not available in full text, not written in English, or irrelevant to the topic of focus. Nineteen sources were eligible and underwent a full-text review.

Results
Despite reaching a record low MM in 2023, and demonstrating a downward MMR trend since 2000, Afghanistan’s MM still far exceeds that of neighboring countries such as Pakistan and Iran at a staggering 521 compared to 155 and 16 deaths per 100,000 births, respectively. This is explained by a unique combination of the destruction of economy and infrastructure from war, women’s education barriers imposed by the Taliban, a lack of skilled birth attendants present, and a deficit of transportation in rural areas. As of 2023, 73.3% of female healthcare workers in a survey reported not feeling safe when commuting to work due to harassment from the Taliban, and 43% of women reported an overall decrease in the availability of maternal care.

Conclusions
Introduced in 2003, the Basic Package of Health Services (BPHS) increased health facilities across Afghanistan in 2011 and resulted in an overall increase in health facility utilization. Maternal mortality ratios decreased significantly from 2002 to 2010, however, women in rural areas remain especially vulnerable. To combat maternal mortality, it is critical to place international pressure on the Taliban to allow women’s autonomy and to adopt programs akin to “Ride-on Transportation” in rural areas to improve the quality of life for countless Afghan women and their families.

Maternal Mortality in Afghanistan: A Systematic Review

Title:
Hand-Sewn vs. Stapled Colorectal Anastomosis: A Meta-Analysis of Postoperative Outcomes and Anastomotic Integrity
Edwin Medina MS2, Ian Olmeda MS3
University of Puerto Rico School of Medicine, Universidad Central del Caribe School of Medicine
Introduction
The integrity of colorectal anastomosis is critical in minimizing postoperative morbidity, particularly anastomotic leak a leading cause of mortality in colorectal surgery. While both hand-sewn and stapled techniques are widely practiced, evidence remains inconclusive regarding superiority in clinical outcomes. This systematic review and meta-analysis aimed to compare both techniques with respect to leak rate, stricture formation, operative time, and overall postoperative complications.
Methods
Following PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library for studies published up to April 2025. Eligible studies compared hand-sewn and stapled anastomoses in adult colorectal resections. Primary outcome was anastomotic leak rate; secondary outcomes included stricture formation, reoperation, operative duration, and length of hospital stay. Pooled odds ratios (OR) and weighted mean differences (WMD) were calculated using a random-effects model.
Results
A total of 42 studies (9 RCTs, 33 cohort studies) were included. Stapled anastomoses demonstrated a modestly lower leak rate (OR 0.82; 95% CI 0.71–0.94; p = 0.004), particularly in low anterior resections. Stricture rates were slightly higher in stapled groups, although not statistically significant (OR 1.14; p = 0.08). Operative time was shorter by an average of 22 minutes with stapling (WMD -21.6 min; p < 0.001). No significant difference was found in overall morbidity or reoperation rates. Subgroup analysis showed no clear advantage for either method in right-sided resections.
Conclusion
Stapled anastomosis is associated with lower anastomotic leak rates and shorter operative times, particularly in low pelvic procedures. However, the increased stricture tendency warrants caution in specific anatomic settings. These findings may guide surgical decision-making based on location, patient comorbidities, and institutional expertise. Further large-scale randomized trials are needed to establish evidence-based guidelines for technique selection in colorectal surgery.


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Extracellular-cAMP Suppresses Pulmonary Hypertension-induced Ventricular Arrhythmias