United States

Background: Renal cell carcinoma (RCC) presenting with extension of tumor thrombus into the inferior vena cava (IVC) and right atrium is a rare, life-threatening condition that requires surgical treatment with the simultaneous involvement of multiple surgical subspecialties.
Case Description: We present a case of a 65-year-old male who presented to the hospital with syncope, and was subsequently diagnosed with a level four cavoatrial sinus tumor thrombus extending from a primary renal mass. The patient had no concerning physical exam and electrocardiogram (EKG) findings, however, transthoracic and transesophageal echocardiography revealed severely reduced systolic function with a hyperechoic, vascular, and cystic mass extending from the IVC into the right atrial cavity that originated from a renal mass that involved the right renal vein and IVC.
Conclusions: The purpose of this case is to highlight the critical importance of early recognition and timely intervention in patients who present with nonspecific symptoms, such as syncope, which may signal underlying fatal conditions. This case illustrates RCC with tumor thrombus extending into the IVC and right atrium. This rare but serious manifestation highlights the need for a high index of suspicion and comprehensive evaluation when faced with vague clinical presentations. Early recognition not only facilitates appropriate management but can also alter the patient’s prognosis and survival outcomes.

AMA Research Challenge 2025 

The Atrial Mass without an Auscultatory “Plop”: Renal Cell Carcinoma
Presenting with Cardiac Syncope

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AMA Research Challenge 2022

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Background 
The placenta is a complex organ with multiple immune and non-immune cell types that promote fetal tolerance and facilitate the transfer of nutrients and oxygen. The nonhuman primate (NHP) is a key experimental model for studying human pregnancy complications, in part due to similarities in placental structure. However, the heterogenous cellular landscape of the NHP placenta, and how it compares to that of humans, remains poorly defined. Characterizing the NHP maternal-fetal interface and identifying similarities and differences to that of humans at the single-cell level is critical for refining the translational use of the NHP models. 
Methods 
We constructed a single-cell RNA-Seq (scRNA-Seq) atlas of the placenta from the pigtail macaque (Macaca nemestrina) in late gestation, comprising three different tissues at the maternal-fetal interface: the basal plate, chorioamniotic membranes, and the maternal decidua. Each tissue was separately dissociated into single cells and processed through the 10X Genomics and Seurat pipeline, followed by aggregation, unsupervised clustering, and cluster annotation. Next, we determined the maternal-fetal origins of cell populations and analyzed single-cell RNA trajectory, Gene Ontology enrichment, and cell-cell communication. 
Results 
Single-cell populations in the pigtail macaque were strikingly similar in their identity and frequency to those found in the human placenta, including cells from trophoblast, stromal cell, immune, and macrophage lineages. While canonical markers that characterize human cell populations were applicable in annotating the cells in the pigtail macaque placenta, some genes were not annotated in the macaque genome, complicating the identification of cell populations like extravillous trophoblasts (EVT). However, immunohistological stains of cytokeratin 7 
confirmed the absence of EVTs in the late pigtail macaque placenta. An advantage of our approach was the deep sequencing of three tissues at the maternal-fetal interface, which yielded a rich diversity of common and rare single-cell populations. We identified fetal-origin populations such as erythroblasts and Hofbauer cells, as well as a broad array of immune subsets, including three distinct natural killer (NK) cell populations, CD4⁺ regulatory T cells, tissue-resident memory (TRM) CD8⁺ T cells, neutrophils, two unique B cell populations, and a small subset of mast cells. 
Conclusion 
The third-trimester pigtail macaque single-cell atlas enables the identification of cellular subclusters analogous to those in humans and provides a powerful resource for understanding experimental perturbations on the NHP placenta.

Single-cell transcriptomic atlas of the late gestation pigtail macaque placenta

BACKGROUND/PURPOSE: Post-traumatic osteoarthritis is a degenerative joint disease that leads to the exposure of type II collagen (CII) fibers and increased matrix metalloproteinase (MMP) activity. Injection of adipose-derived stem cells (ADSCs) into the diseased joint has been explored as a promising treatment option due to its strong potential to repair damaged cartilage tissue through immunomodulation and chondrogenic differentiation. However, clinical translation of stem cell therapy has been limited by poor retention and targeting within the joint cavity. This study aims to evaluate the effectiveness of an injectable type I collagen (Col I) scaffold conjugated with a monoclonal antibody against CII (MabCII) for targeted delivery of ADSCs to damaged cartilage in a murine PTOA model.

GOALS: To determine whether MabCII-Col I scaffolds enhance the localization and therapeutic potential of ADSCs in reducing cartilage degradation and inflammatory markers in PTOA.

METHODS/DESIGNS: PTOA was induced in 10-week-old female CBA mice via non-invasive mechanical knee overloading. At 6 weeks post-loading, the subjects were divided into five groups of 6 mice: 1) normal mice (no mechanical loading), 2) PBS injection, 3) treatment with ADSCs only, 4) treatment with non-targeted CI scaffolds containing embedded ADSC or 5) treatment with Col I scaffolds linked to MabCII and containing embedded ADSC. ADSCs were integrated into scaffolds using EDC/NHS crosslinking. Functional assessment of pain-related behavior using dynamic weight bearing was done at 9 weeks post-treatment. IVIS imaging for free CII exposure and MMP activity was done at 12 weeks post-treatment.

RESULTS/FINDINGS: Mice treated with MabCII-targeted ADSC scaffolds showed significantly reduced IVIS fluorescence for MMP activity and exposed CII fibers compared to untreated PTOA controls, indicating decreased inflammation and cartilage degradation. Dynamic weight-bearing analysis revealed improved limb loading in the treated group. Non-targeted scaffold and ADSC-only groups showed intermediate results. Untreated PTOA controls had the poorest outcomes.

CONCLUSIONS/IMPLICATIONS: The results from this study demonstrate that targeted delivery of ADSCs using MabCII-linked Col I scaffolds in vivo improves localization to damaged cartilage tissue and reduces cartilage degradation, inflammation, and pain-related behavior. This strategy represents a promising platform for the development of targeted ADSC therapies for osteoarthritis.


In Vivo Analysis of Stem Cell Loaded Scaffolds Targeted with Antibodies to Type-II Collagen for Treatment of Post-Traumatic Osteoarthritis

Background
Cesarean section (C-section) is the most common surgical procedure performed in the United States and a known contributor to initial opioid exposure among women of reproductive age. While neuraxial (epidural) anesthesia is the preferred technique for cesarean delivery, general anesthesia is still used in select clinical scenarios. Given the ongoing opioid crisis, it is critical to understand how anesthesia modality influences postoperative opioid prescribing patterns.

Methods
We conducted a retrospective cohort study using the TriNetX Global Collaborative
Network, a federated health research platform of electronic medical records from 148 healthcare organizations. Women aged 18–50 who underwent cesarean delivery between 2005 and 2025 were identified. Patients were grouped based on anesthesia type using CPT codes: general anesthesia (01961 only) and epidural anesthesia (01967 or 01968). Propensity score matching was performed on demographics, comorbidities, and prior medication exposures, resulting in two balanced cohorts each containing 78,572 patients. The primary outcome was receipt of an opioid prescription (morphine, oxycodone, hydromorphone, codeine, or tramadol) from day 1 to day 90 after surgery. Risk and survival analyses were conducted using TriNetX tools.

Results
Opioid prescriptions were more common in the general anesthesia group (74.3%)
compared to the epidural group (64.2%), with a risk difference of 10.1% and an odds ratio of 1.616. Kaplan-Meier survival analysis showed a significantly lower probability of remaining opioid-free at 90 days in the general anesthesia group (25.4% vs. 35.5%, log-rank p < 0.001). The hazard ratio for opioid use was 1.264 (95% CI: 1.249–1.279).

Conclusion
Women receiving general anesthesia for cesarean section were more likely to receive postoperative opioids and had a higher overall risk of opioid use within 90 days compared to those receiving epidural anesthesia. These findings underscore the importance of anesthesia choice in minimizing opioid exposure and guiding perioperative pain management strategies.

Association of Anesthesia Modality with Opioid Prescriptions After Cesarean Delivery: A Comparative Study of General and Epidural Techniques

Background
Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations constitutes a significant subset of lung cancer cases, particularly among non-smoking women of Asian descent. Brain metastases (BM) and leptomeningeal disease (LMD) occur more frequently in this disease, highlighting the unique biology of EGFR-mut NSCLC. Osimertinib, a third-generation oral tyrosine kinase inhibitor (TKI), has excellent central nervous system (CNS) penetration. However, there is a notable lack of guidelines regarding its use in combination with or sequentially with radiation therapy. This gap is particularly significant given the elevated rates of both CNS disease and LMD, highlighting an important unmet need in this population.
Methods
We retrospectively evaluated patients diagnosed with EGFR-mutated NSCLC with CNS disease over a 19-year period (2004-2023).
Results
Demographics: Our study included 158 patients with a median diagnosis age of 66 years. 68% were
female and 48% self-identified as Asian. Most patients did not have a smoking history (63%). Disease Characteristics: 80% of patients were diagnosed at stage IV, with 69% having CNS involvement. 23% of patients had LMD throughout their disease course. 23% of patients had poorly differentiated disease, and 85% had an exon 19 deletion or an L858R mutation.
Ó 2025 American Medical Association. All rights reserved.
Response: Among the evaluated patients, 48% received first-line Osimertinib, achieving a response rate (RR) of 79%. In comparison, 35% of patients were treated with non-Osimertinib TKI, demonstrating a RR of 85%. Focusing on the 55 patients who presented with CNS disease and received first-line Osimertinib, the CNS response rate was 67%, with a median duration of response (mDoR) of 44 months. For patients requiring subsequent therapy due to CNS progression, 73% received high-dose Osimertinib (120mg or 160mg), resulting in CNS RR of 44% and mDoR of 15 months. Meanwhile, 6 patients received chemotherapy, achieving an RR of 33%.
Conclusion
EGFR-mutated NSCLC with CNS disease mainly affects Asian females and is often diagnosed at stage IV with BMs. Osimertinib demonstrates significant and durable efficacy, outperforming earlier generation TKIs in systemic and CNS disease control. At CNS progression, high-dose Osimertinib was the preferred treatment strategy and showed superior efficacy in controlling CNS disease compared to chemotherapy. These results underscore Osimertinib’s critical role in frontline treatment and highlight the need for continued research to optimize CNS progression strategies. Data from our institution regarding outcomes in LMD and combination strategies with cranial local therapy across different EGFR mutations are forthcoming.

Osimertinib in EGFR-Mutant NSCLC with CNS Metastases: A 19-Year Single-Institution Retrospective Study

Abstract Title: Unmasking Tuberculosis: A Case of Pericardial Effusion in a Young Adult with Recurrent Pneumonia
Background
Tuberculosis (TB) remains a major global health concern. While pulmonary TB is the most common manifestation, extrapulmonary tuberculosis (EPTB), particularly involving the pericardium, can lead to life-threatening complications such as cardiac tamponade. TB pericarditis accounts for 1–2% of TB cases and is a leading cause of large pericardial effusions and constrictive pericarditis in developing countries. Diagnosis can be challenging in immunocompetent patients without classic TB symptoms.
Case Presentation
A 25-year-old Indian male with no significant past medical history presented to the emergency department (ED) with a two-week history of productive cough and pleuritic chest pain. He had previously presented to the ED five days prior and was discharged against medical advice with azithromycin, which offered minimal relief. On readmission, he was diagnosed with multifocal pneumonia and started on intravenous antibiotics before being discharged on oral therapy. He returned one month later with worsening respiratory symptoms. Imaging revealed a left-sided pleural effusion and a large pericardial effusion. Echocardiogram confirmed tamponade physiology. A CT chest also demonstrated cavitary lesions in the left upper lobe. Pericardial window was performed, yielding 1 liter of clear pericardial fluid. Sputum acid-fast bacilli (AFB) smear was strongly positive, confirming Mycobacterium tuberculosis infection. The patient was started on RIPE therapy and TB control authorities were notified.
Discussion
This case illustrates a rare but critical presentation of extrapulmonary tuberculosis as pericardial effusion with tamponade physiology in a young, immunocompetent adult without classic constitutional symptoms. Initial misdiagnosis as community-acquired pneumonia delayed TB-specific testing and treatment. This highlights the need to maintain high clinical suspicion for TB in patients with recurrent pneumonia, pleural or pericardial effusions, especially those with epidemiologic risk factors such as prior travel to endemic areas. Early chest CT and echocardiography were key in identifying extrapulmonary involvement, prompting timely intervention. Pericardial TB, though rare, carries significant morbidity if undiagnosed and should be considered in patients with unexplained pericardial effusions. Comprehensive evaluation including imaging and microbiological studies is crucial for timely diagnosis and management to prevent complications and reduce disease transmission.

Unmasking Tuberculosis: A Case of Pericardial Effusion in a Young Adult With Recurrent Pneumonia

Background: Dieulafoy lesions are a relatively uncommon but important cause of gastrointestinal (GI) bleeding, accounting for around 5% of gastrointestinal bleeds. Characterized by a dilated, aberrant submucosal artery that erodes through overlying mucosa, these lesions can result in life-threatening hemorrhage. Small intestinal Dieulafoy lesions are exceedingly rare and often evade early detection due to location and their intermittent bleeding pattern. In this report, a rare case of massive and recurrent hematochezia caused by a Dieulafoy lesion in the terminal ileum is presented.
Case Presentation: A 68-year-old female with a complex medical history including chronic kidney disease stage V on intermittent hemodialysis, type 2 diabetes, severe aortic stenosis post aortic valve replacement, systolic heart failure, chronic hypoxic respiratory failure, and chronic anemia was transferred to a quaternary medical center for evaluation of severe, recurrent hematochezia. Hemoglobin on presentation was 5.2 g/dL (baseline 8.5–9.5). Prior to transfer, the patient underwent extensive diagnostic evaluation, including esophagogastroduodenoscopy (EGD), colonoscopy, tagged RBC scan, and CT angiography of the abdomen and pelvis, all of which failed to localize a source of bleeding.

Subsequent capsule endoscopy reported active small bowel bleeding from an undetermined source. Double balloon retrograde enteroscopy demonstrated blood throughout the colon and distal ileum, but without an obvious culprit lesion. Due to continued overt hematochezia requiring ongoing transfusions, repeat CT angiography was performed, which suggested possible arterial extravasation but subsequent angiography by interventional radiology team again failed to localize the source.

A final effort at identifying the lesion with repeat retrograde push enteroscopy successfully encountered a solitary Dieulafoy lesion in the terminal ileum with active pulsatile bleeding. Durable hemostasis was achieved with argon plasma coagulation, PuraStat application, and the placement of two hemostatic clips. In total, the patient received 33 units of packed red blood cells, in addition to five units of other blood products prior to achieving hemostasis. 

Discussion: This case highlights the diagnostic complexity and multidisciplinary approach required in managing life-threatening lower GI bleeding secondary to Dieulafoy lesions. A high index of suspicion is required for Dieulafoy lesions in patients with recurrent GI bleeding of unknown origin. It is crucial to consider deep enteroscopy and capsule endoscopy in cases of small intestine bleeding. Moreover, procedures may need to be repeated due to Dieulafoy lesions' sporadic, severe bleeding pattern. We emphasize the importance of further research on optimal timing and sequencing of diagnostic modalities regarding small intestinal Dieulafoy lesions.

Terminal Ileal Dieulafoy Lesion Resulting in Massive Hematochezia

Background 
Rhinoplasty is a surgical procedure that focuses on the nasal structure, enhancing both the appearance and function of the nose. Managing a cleft palate is incomplete without addressing secondary nasal deformities. An important aspect of correcting a cleft nose is addressing depressed and hypoplastic cartilage frameworks, which is key to the success of secondary rhinoplasty. 
Facial recognition is used to verify individuals based on their unique facial features, which is used for unlocking phones, conducting transactions, security purposes, and more. 
This case highlights emerging challenges at the intersection of modern technology and medicine. 
Case Presentation 
A 20-year-old Indian man with a previously operated right cleft lip & palate before 18 years, had a depressed right nostril, nasal tip, hypoplastic alar cartilage, and columella deviated to the left side. He underwent open rhinoplasty, right alar cartilage hitching to opposite upper lateral cartilage, and conchal cartilage graft to augment alar depression. This secondary rhinoplasty was performed for the aesthetic congenital deformity of the nose that is almost always associated with grade III cleft lip & palate deformity. After the operation, his face was unrecognizable to his latest smartphone, which made it difficult for him to get access to his phone as he did not know the backup password. This issue persisted for nearly 20 days, resolving once the swelling and inflammation subsided. 
Discussion 
This case highlights an unexpected challenge between modern technology and facial surgeries like rhinoplasty and smartphone facial recognition. With a lot of use of facial biometrics recently, in unlocking phones, accessing personal data, or authorizing payments, even a small problem like this can cause a lot of inconvenience. In this case, the patient was unable to access the mobile phone due 
to not remembering the backup password. 
This emphasizes the importance of patients’ preoperative counselling regarding possible problems with facial surgeries or rhinoplasty. Patients should be advised to disable facial recognition features or guarantee password access before surgery. These minor actions can make the patient stress-free from unnecessary issues. 
This case promotes a more comprehensive, technologically conscious method of surgery planning and patient education. 
As the world and technology emerge, interactions between cosmetic surgeries and digital systems are going to increase, further discussions and research would be needed for surgeries and their effects on new digital systems, and how to improve them.

Locked Out: A Case of Smartphone Facial Recognition Failure Following Cosmetic Rhinoplasty

Background
Physician remuneration plays a central role in shaping provider behavior and healthcare system resource allocation. In the U.S., Medicare reimbursement rates often serve as a benchmark for payment across both public and private payers, making them highly influential in determining pricing for health services. This study investigates the relationship between relative value unit (RVU)-based pricing and patient utility, as measured by quality-adjusted life years (QALYs), across commonly performed surgical procedures and preventive screenings in Medicare. While RVUs capture provider effort and resource inputs, and QALYs reflect patient-centered health gains, evaluating their alignment offers insight into whether Medicare’s pricing structure inherently supports value-based reimbursement strategies.

Methods
A comparative analysis of 19 common medical interventions based on Medicare utilization data and literature review was conducted. Procedure-specific RVUs were systematically retrieved from the Centers for Medicare & Medicaid Services Physician Fee Schedule Lookup Tool. Patient utilities were quantified as incremental QALY gains per year extracted from population- matched peer-reviewed cost-utility analyses. Correlations between RVU pricing and incremental QALYs/year were assessed through Spearman’s rank correlation. Further subgroup analyses included comparisons between fatal and nonfatal interventions, orthopedic versus non- orthopedic procedures, and preventive versus therapeutic interventions.

Results
A significant positive correlation (r=0.746, p<0.001) was observed between RVUs and incremental QALY gains among all 19 interventions. Fatal procedures, although priced higher, did not significantly differ in RVUs (p=0.788) or incremental QALYs (p=0.243) from nonfatal procedures. Orthopedic interventions demonstrated higher incremental QALY gains compared to non-orthopedic procedures, yet differences in RVUs were not statistically significant (p=0.157 for RVU; p=0.105 for QALYs). Preventive screenings displayed significantly lower RVUs (p=0.003) and lower incremental QALYs per year (p<0.001) compared to therapeutic interventions.

Conclusion
This study provides robust evidence highlighting the association between higher RVU-based procedure pricing and greater incremental patient utility as measured by QALYs per year within the Medicare population. However, notable discrepancies persist, particularly in preventive screenings, which are markedly undervalued relative to therapeutic procedures despite their established population health benefits. Orthopedic surgeries, despite not showing significant pricing differences, emerged as notably cost-effective in delivering patient utility. This study demonstrates that Medicare’s procedural pricing partially reflects patient-centered utility, suggesting that value-based principles are already present within a traditionally volume-driven reimbursement system. However, the undervaluation of preventive services highlights persistent misalignments. Incorporating explicit utility measures like QALYs into pricing frameworks could enhance Medicare’s ability to support high-value care and optimize resource allocation.

Measuring Value in Medicare: Do Revenue Value Unit-based Fees Reflect Quality-Adjusted Life Year Gains?

Background
Narrative evaluations are a key component of competency-based medical education, providing insights beyond numerical grades. However, their quality often varies due to lack of specificity and limited utility for learners (Kelly et al., 2020; Ginsburg et al., 2020). The Narrative Evaluation Quality Instrument (NEQI), a validated 12-point rubric, scores feedback across three domains: performance, specificity, and usefulness (Mooney et al., 2022). This study used NEQI to assess the quality of narrative evaluations and their associations with faculty and contextual factors.

Objective
To evaluate narrative feedback quality using NEQI and examine associations with evaluator demographics, course type, clinical service, academic title, and evaluation characteristics.

Methods
We retrospectively scored 281 internal medicine clerkship evaluations from the University of Toledo College of Medicine and Life Sciences as part of an ongoing multi-institutional study. All NEQI scores were assigned by a single trained reviewer using the published NEQI rubric to ensure consistency. Group comparisons (e.g., elective vs. core, gender, academic title, clinical service, age group) were analyzed using independent t-tests and one-way ANOVA. Pearson correlation was used to assess relationships between continuous variables (e.g., comment length, evaluator age, and time to evaluation completion).
This study was reviewed and deemed exempt by the University of Toledo Institutional Review Board.

Results
The mean NEQI score was 7.84 (SD 2.6), with 77.2% of evaluations meeting the quality threshold (≥7). Non-elective rotations had higher scores than elective ones (7.98 vs. 7.63, p = 0.30). The Academic Internal Medicine rotation had the highest average NEQI score (12.0), while Geriatric and Vascular Medicine scored the lowest (4.0 and 1.0, respectively).
Evaluator gender was reported in 77.6% of cases: 51.6% male, 26.0% female, and 22.4% unknown or unreported. Female evaluators scored slightly higher than males (7.74 vs. 7.65, p = 0.82). Comment length correlated strongly with NEQI score (r = 0.62, p < 0.001). NEQI scores varied by academic title: associate professors (8.15), residents (8.12), and assistant professors (7.44), though not statistically significant (p = 0.38). Evaluator age group was significantly associated with NEQI score (p = 0.017), with those under 30 scoring highest. Time to evaluation completion was not significant.

Conclusion
NEQI scores varied by evaluator age group, comment length, and service. These findings highlight the value of structured tools and faculty development to improve narrative feedback quality. Inter-institutional analyses are underway.


Assessing the Quality of Narrative Feedback in Internal Medicine Clerkships Using NEQI: A Multi-Institutional Study in Progress


Elevating Education: The Transformative Power of Student-Led Medical Journals 
Risha Mehta, OMS-III1, Alexa R. Neff, MS, OMS-III1, Jillian C. Niceley, OMS-IV1, Chelsea A. Moore, OMS-IV1, Robyn K. Fuchs, PhD1 
1Division of Biomedical Sciences, Marian University Wood College of Osteopathic Medicine, Indianapolis, IN 

Background 
Osteopathic medical students often encounter significant barriers to publishing, including the time and cost associated with reputable peer-reviewed journals. Despite the importance of developing skills in writing about complex scientific topics, medical students often lack opportunities to publish work that reflects their interests, such as art, community service, and global health. This student-led journal aims to bridge this gap by offering a platform for students to express their passions beyond traditional research, enhance their comprehension and writing skills, and achieve publication. 

Methods 
To capture the diverse experiences of medical students, the journal accepted a range of submissions beyond traditional scientific research, including clinical mini-reviews, testimonials, spotlights, and artwork. Submissions were collected through a Qualtrics survey and reviewed and critiqued by at least three members of the editorial board. The editorial board was comprised of eight students and one faculty mentor; all were required to complete training provided by the American Physiologic Society. Following the standardized review process, authors were provided with comprehensive feedback and offered the opportunity to revise their submissions based on the editorial board’s recommendations. Once revisions were made, the manuscripts underwent a final review prior to acceptance. 

The graphics team compiled and formatted these submissions into a cohesive and polished journal. Adobe Acrobat INDesign was used to format and style the journal into a finished anthology. To distinguish the journal from other publications, the team submitted an application on behalf of the journal to the Library of Congress for an International Standard Serial Number (ISSN). Once the final version was complete, it was submitted to PALNI Press, a free online publishing platform, and a URL was created: https://press.palni.org/ojs/beyondthewhitecoat. The editorial board collaborated with PALNI Press to assign DOI numbers to each piece, creating an identifiable digital footprint. 

Results 
The journal is scheduled for publication in July 2025 with both print and online copies available to ensure easy access for all students and faculty. Data was collected regarding the number of students from each class who submitted work, and the types of publications submitted. This inaugural issue engaged authors from all levels of training, including students from all classes, as well as faculty, with the largest number of submissions received from second- and third-years medical students. 

Conclusion 
It is anticipated that the journal will have a significant impact on trainees of all levels and enhance confidence in writing and publishing.

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