United States

Posterior circulation strokes can present with a range of subtle or fluctuating symptoms, often delaying diagnosis and complicating treatment decisions. We present the case of a 59-year-old woman with a prior history of transient ischemic attack (TIA), ischemic stroke, and antiphospholipid syndrome who was brought to the emergency department with acute dysarthria, vertigo, tinnitus, and vomiting. Imaging was initially unrevealing, but brain MRI confirmed acute infarcts in the superior vermis and right cerebellar hemisphere. Further workup revealed a patent foramen ovale (PFO) and May-Thurner syndrome (MTS), which were suspected contributors to a paradoxical embolic stroke. She underwent successful PFO closure and stent placement for left iliac vein compression. This case highlights the diagnostic challenge of posterior strokes and underscores the importance of considering underlying embolic and structural contributors in cryptogenic stroke presentations.



AMA Research Challenge 2025 

Posterior Circulation Stroke in a Patient with May-Thurner Syndrome and Patent Foramen Ovale

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poster

Background
Delivery of messenger RNA (mRNA) offers potential to ameliorate numerous pathologies by translation of therapeutic proteins. Nevertheless, clinical translation of mRNA technologies has been limited due to a lack of delivery efficiency. Here we describe the development of a novel mRNA delivery system that overcomes barriers faced by existing systems.

Methods
We demonstrate that co-encapsulating gold nanoparticles (AuNPs) and mRNA within non-ionic surfactant vehicles (AuNSVs, termed “Aurniosoves”) improves tumor accumulation and vector uptake into cancer cells. This delivery system was validated through in vitro and in vivo studies with ovarian and hepatocellular carcinoma models utilizing reporter GFP-coding mRNA and therapeutic p53-coding mRNA. The mechanism of action was elucidated through fluorescence-based cellular uptake assays with relevant protein-AuNP interactions identified via pulldown assays.

Results
AuNSVs show improved tumor accumulation, protein expression, and therapeutic efficacy in delivery of p53 mRNA to p53-null cancer cells in comparison to NSV analogs (without AuNPs). Mechanistically, these effects are the result of a nanoengineered “iterative delivery” process in which AuNSVs enter the cell initially through clathrin-mediated endocytosis (CME) and release AuNPs into the cytoplasm. AuNPs subsequently adsorb and inactivate cellular trafficking regulators PP2A and Rab7, producing two primary effects: 1) rapid entry of additional AuNSVs through preferential activation of caveolin-mediated endocytosis (CvME), and 2) endosomal escape through inhibited endo-lysosomal fusion. These two mechanisms combine to drastically increase the delivery efficacy of therapeutic mRNA.

Conclusion
We have made two major advances: 1) nanoengineer a gold nanoparticle (AuNP)-mRNA hybrid therapeutic with translatable characteristics, and 2) improve the therapeutic efficacy of exogenous mRNA in cancer cells using an iterative delivery mechanism. We propose that this class of Aurniosoves and its associated mechanism of action may be exploited as next generation mRNA delivery systems for basic and translational biomedical applications.


Enhancing mRNA Therapy Through Iterative Delivery

Background:
Primary and metastatic brain tumors are clinically refractory to immunotherapies that demonstrate efficacy in peripheral cancer settings. While many immunotherapies aim to enhance effector CD8+ T cell action in established brain tumors, immunopreventative techniques leveraging memory CD8+ T cells remain understudied. Numerically enriched and functionally potent tissue-resident memory (TRM) CD8+ T cells can be generated in the brain following peripheral infection and vaccination. Unlike circulating memory T cells (TCIRCM) that continuously recirculate, TRM embed within the brain, providing local and immediate surveillance against antigenic threats. Our lab has previously shown that the generation of brain TRM can potently protect mice against otherwise lethal intracranial infections. However, the ability of tumor-specific brain TRM to protect against intracranial malignancy remains unknown. 

Methods:
Here, we first developed models where tumor-specific or bystander memory CD8+ T cells were generated in mice via attenuated peripheral infection. We were then able to deplete all tumor-specific TCIRCM using an antibody depletion strategy to isolate the protective action of brain TRM alone. Mice were then challenged with model melanoma or glioblastoma cell lines via orthotopic intracranial injections. To increase the translational value of this work, we later designed and synthesized an mRNA-lipid nanoparticle (LNP) vaccine encoding tumor epitopes or control viral epitopes to determine the immunogenicity and protective action of this emerging immunization strategy. Cellular outcomes were assessed by flow cytometry, tumor burden was surveyed via bioluminescent imaging, and survival outcomes were monitored across time. 

Results:
Here, we demonstrate that tumor-specific, but not bystander, brain TRM durably protected mice against intracranial malignancy even in the absence of TCIRCM. These brain TRM persisted in tumor surviving mice long-term and offered protection against a secondary challenge. Mechanistically, we show that TRM activation reduces brain tumor-associated neuroinflammation and peripheral immunosuppression to enhance survival outcomes. We also demonstrate that mRNA-LNP vaccines generate protective brain TRM upon intramuscular immunization. These vaccine-induced brain TRM abrogated adverse outcomes associated with brain malignancy and neurovirulent disease in an antigen-defined manner. 


Conclusion:
Altogether, this work points to the utility of brain TRM in tumor immunoprevention and supports the development of anti-cancer mRNA vaccines as a non-invasive approach to bolster brain immunity. Ongoing work will determine the therapeutic utility of mRNA vaccine technology against established tumors and will investigate whether protective anti-tumor TRM can be generated at distant organ sites (i.e. brain) after administration. 


Brain-resident memory CD8+ T cells provide durable protection against intracranial malignancy

Background
Decreased levels of gangliosides have been observed in the brain tissue of patients with Parkinson’s (PD) and Huntington’s disease (HD), complex neurodegenerative disorders which currently have no established treatment. Further understanding of the neuroprotective and neurotrophic effects of gangliosides have driven investigation into their pathogenic and clinical role in PD, HD, and other neurodegenerative disorders. Several studies reported the reversal of neurochemical, neurohistological, and clinical signs of PD and HD in animal models after receiving GM1 injections. Additionally, motor symptom improvement was documented in clinical studies of PD patients who received a series of GM1 injections. Although GM1 has shown early clinical promise in PD/HD animal models and PD patients, a comprehensive mechanism for its role in the pathogenesis of these disorders has not yet been elucidated. C. Elegans, a hermaphrodite nematode with easily manipulated genetics, can prove to be a time saving and cost-effective animal model to explore further research on gangliosides and neurodegenerative disorders. 

Methods
C. Elegans N2 Bristol wild-type strain (control), WLZ3 strain transgenic for LRRK2:G2019S mutation (Parkinson’s disease model), and AM101 strain with 40 CAG repeats (Huntington’s disease model) from the Caenorhabditis Genetics Center in Minneapolis, MN. Worms were maintained on NGM plates seeded with E. coli OP50 at 20 °C. Age-synchronized L4 larvae were plated across three replicate plates per condition. GM1 or GM3 was applied to the bacterial lawn at 50uM or 100uM. Control plates received no gangliosides. On day 1 of adulthood, worms underwent 3 hours of heat stress at 35°C. After, worms were documented as alive or dead. This heat stress protocol was repeated until all worms were dead. The survival data was then analyzed using the OASIS 2 Kaplan-Meier log-rank test. 

Results
GM1 altered heat-stress survival in a strain- and dose-dependent manner. GM1 significantly enhanced survival under heat stress in the PD model (WLZ3) at both 50 µM and 100 µM, whereas effects in the HD model (AM101) were modest and limited to 50 µM. In WT worms (N2), GM1 at 50 µM unexpectedly decreased survival. GM3 (50 & 100 µM) showed no significant changes in survival in any strain.

Conclusion
GM1 enhances survival under heat stress in the PD model, with strain- and dose-dependent effects also observed in HD and WT. GM3 shows no survival benefit under these conditions. Results are consistent with prior GM1 neuroprotective literature, particularly in PD, and point to non-linear dose–response and context dependence. Future work in C. elegans should leverage genetic tools, dose mapping, and timing studies to define when and why GM1 is protective. These results support the use of C. elegans as a rapid platform to dissect ganglioside biology in neurodegeneration


Effects of Gangliosides on Heat Stress Survival in Caenorhabditis Elegans Models of Huntington’s and Parkinson’s Diseases


Background: The rising prevalence of metabolic syndrome (MetS) is linked to modern lifestyle factors, including disruptions to circadian rhythms. These endogenous 24-hour cycles regulate key physiological processes, and their disruption through factors like irregular sleep patterns or late meal timing is increasingly common. MetS is characterized by chronic inflammation, often exacerbated by gut-derived inflammation from a compromised intestinal barrier. We hypothesized that the link between circadian disruption and MetS is mediated by alterations in the gut microbiome and subsequent gut barrier dysfunction. This study investigates this proposed mechanistic pathway in an at-risk obese population.

Methods: This secondary analysis used data from a trial of 87 obese adults. MetS was scored using NCEP-ATP III criteria. Circadian phenotypes were assessed using the Munich Chronotype Questionnaire (central) and a Food Timing Screener (peripheral). Intestinal permeability was measured via urinary excretion of sugar probes. Using a multi-omics approach, we developed a continuous Metabolic-Inflammatory (MI) score to capture underlying dysregulation. A moderated sequential mediation analysis tested the hypothesis that the gut microbiome and barrier function mediate the relationship between circadian disruption and the MI score.

Results: After adjustments, a late chronotype was associated with a 4.20-fold increased odds of having MetS (95% CI: 1.33–13.27, p=0.014). A graded association was observed where a greater degree of combined circadian disruption (late chronotype and late eating) was associated with a progressively higher prevalence of MetS. Late eating (after 8 PM) was linked to significantly increased small bowel and colonic permeability, evidenced by higher urinary mannitol (p=0.037) and sucralose (p=0.013). A 19-feature multi-omic signature strongly predicted MetS status (R²=0.71), forming a continuous MI score. This MI score increased with greater circadian disruption and was strongly correlated with markers of gut permeability (24h mannitol, R²=0.65). Crucially, mediation analysis demonstrated that the effect of circadian disruption on the MI score was significantly mediated by gut barrier dysfunction. A final sequential model confirmed this mechanism, identifying a pathway where circadian disruption alters specific gut microbes, which in turn impacts gut permeability, ultimately driving metabolic and inflammatory dysregulation.

Conclusion: Circadian disruption is strongly associated with metabolic dysregulation in obese individuals. Our findings provide evidence for a novel mechanistic pathway where misaligned circadian behaviors influence the gut microbiome, leading to increased intestinal permeability and subsequent systemic inflammation. This highlights the circadian-microbiome-gut axis as a key mediator and a potential therapeutic target for mitigating the adverse metabolic consequences of circadian disruption.



Assessing the Contribution of Circadian Misalignment and Gut Dysfunction to Metabolic Syndrome

Background 

The modified frailty index (mFI-5) is a National Surgical Quality Improvement Program (NSQIP)-derived 5-factor index that has been validated as a reliable measure of frailty. mFI-5 has demonstrated utility in predicting postoperative complications and mortality following various otolaryngologic procedures, including skull base surgery, laryngectomies, composite resections, and transoral robotic surgery. Cochlear implantation (CI) has become an increasingly common intervention for restoring auditory function, particularly as the aging population grows and the prevalence of hearing loss rises significantly with age. However, the predictive role of frailty in postoperative complications of CI remain unclear. Thus, we evaluated whether the mFI-5 is predictive of complications following CI surgery. 

Methods 

We used a multicenter national database within the TriNetX US Collaborative Network. Patients aged 18 or older who underwent CI between June 2005 and June 2025 were included (N=33,556). Patients were categorized based on their mFI-5 scores (0 to 5, with higher scores indicating increased frailty). mFI-5 criteria included: heart failure, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, and non-independent functional status. Comparative analyses were conducted between patients with mFI-5 scores >0 vs. those with mFI-5 = 0. Cohorts were propensity score-matched by age, gender, race, and ethnicity. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated 6 months post-CI for mortality, major complications (prolonged intubation, sepsis, thrombophlebitis, pulmonary embolism, cerebrovascular accident, surgical site infection, acute kidney injury, pneumonia), minor complications (blood transfusion, urinary tract infection), and otologic complications (facial nerve injury, vertigo, fall, labyrinthitis, tympanic membrane perforation, otitis, device displacement/revision/removal). 

Results 

Among 33,556 patients who underwent CI, 11,585 were identified as non-frail (mFI-5 = 0, 34.5%), 4,666 were identified as pre-frail (mFI-5 = 1, 13.9%), 2,445 were identified as frail (mFI-5 =2, 7.3%), and 1,116 were identified as severely frail (mFI-5 ≥ 3, 3.3%)after matching. Compared to non-frail, pre-frail patients had significantly increased risk of mortality (OR = 2.00, 95% CI: 1.08-3.70), major complications (OR 2.27, 95% CI: 1.64-3.23), minor complications (OR 2.38, 95% CI: 1.39-4.17). Similarly, frail patients had increased risk of mortality and major and minor complications compared to non-frail patients. There were no significant differences in otologic complications among non-frail, pre-frail, and frail patients. When comparing non-frail patients and severely-frail patients, severely-frail patients had significantly increased risk of mortality and major, minor, and otologic complications (OR 2.86, 95% CI: 1.67-5.00). 

Conclusion 

The mFI-5 may serve as a useful tool in preoperative counseling to help inform patients about potential outcomes following CI.

The Modified Frailty Index-5 Predicts Postoperative Complications Following Cochlear Implantation: A Propensity Score-Matched Cohort Study

Background:
Musculoskeletal infections are challenging to diagnose and treat in the elderly. Comorbidities make older patients more susceptible to infection with atypical pathogens. Here, we report a rare case of necrotizing fasciitis, septic bursitis, and osteomyelitis due to co-infection with Mycobacterium avium-intracellulare (MAI) and coagulase-negative Staphylococcus (CoNS). A broader diagnostic approach is warranted in patients with specific characteristics or risk factors for atypical infection or lack of response to standard treatment. 

Case Presentation:
We describe a 90-year-old male who presented to the emergency department with a threeday history of progressive swelling, erythema, and pain localized to the left elbow, associated with restricted joint movement. His medical history was significant for diabetes mellitus, hypertension, interstitial lung disease, heart failure, and chronic kidney disease. Clinical examination, laboratory and imaging findings revealed the presence of osteomyelitis, olecranon bursitis, and forearm fasciitis. Following surgical debridement of necrotic tissue, cultures revealed growth of CoNS after 48 hours. Postoperatively, the patient was treated with intravenous antibiotics. However, after brief improvement, the patient developed fever and altered mentation necessitating transfer to the ICU. No clear cause for the clinical deterioration was found until postoperative day # 10 when tissue cultures from the debridement yielded the growth of MAI. No evidence of disseminated MAI was found. After the antibiotic regimen was modified to include azithromycin and ethambutol, the patient showed significant clinical improvement and was discharged. 

Discussion:
This case highlights the diagnostic challenges associated with atypical infections in elderly patients. Early diagnosis and treatment are imperative but the slow growth of atypical pathogens like MAI can lead to delayed diagnoses. In our case, although a timely diagnosis of necrotizing fasciitis led to debridement of necrotic tissue, antibiotic therapy was initially directed towards typical bacterial pathogens. However, the cultured pathogens – CoNS and MAI – were unusual. CoNS is a known, albeit uncommon, cause of necrotizing fasciitis, but MAI has never been reported as a causative agent. MAI typically affects the lungs or lymphatic system, making its presence in skin and soft tissue infections an unusual and important finding, especially in the absence of disseminated disease. Delayed diagnosis underscores the need for early use of AFB staining and broader microbiological workups when treating persistent or atypical infections. Timely surgical intervention combined with tailored antimicrobial therapy resulted in clinical improvement in this patient thereby reinforcing the significance of maintaining a high index of suspicion for atypical organisms in elderly patients.

Unlikely Culprits: Necrotizing Fasciitis Caused By Mycobacterium-Avium Intracellulare and Coagulase-Negative Staphylococci in a Geriatric Patient


From Benign to Critical: Acute Idiopathic Pericarditis Complicated by Delayed Cardiac Tamponade 

Background 

Pericarditis is a common diagnosis comprising around five percent of patients presenting with non-ischemic chest pain and 0.1-0.2 % of hospitalizations. It is usually idiopathic and often presents as a mild disease resolving on its own or with 
minimum treatment. 

Pericarditis is frequently accompanied by small pericardial effusions. A less common life-threatening event that can be associated with it is cardiac tamponade (CT). In the case of acute idiopathic pericarditis, CT is only seen in around 1.2 % of 
cases. 

CT is a medical emergency and its prompt diagnosis and treatment is crucial to avoid fatal complications including death. In this report we present a case of acute idiopathic pericarditis with associated CT. 

Case Presentation 

A 43 year-old male was evaluated in the emergency department for chest pain. On admission, a normal chest x-ray, EKG reflecting acute pericarditis, elevated D-dimer and CRP, normal troponin, normal ESR, and echocardiogram showing a small pericardial effusion were noted. He was started on Colchicine and Ibuprofen, monitored overnight, then discharged the following day on Colchicine for three months. 

Six days later, he presented with worsening chest pain, shortness of breath, hypotension, and heart palpitations. Echocardiogram showed diastolic compression of the right ventricle with a circumferential pericardial effusion confirming the 
diagnosis of CT. He underwent an emergent pericardial window and left thoracotomy. Fluid analysis confirmed exudative effusion. Cultures did not grow any organisms. 

After recovering, he was discharged with a one month supply of Prednisone and Colchicine. 

Discussion 

Patients with acute pericarditis present with a myriad of symptoms that distinguish it from other cardiovascular diseases. The most common abnormality reported on echocardiograms are small pericardial effusions. Hemodynamically significant 
pericardial effusions, especially those causing tamponade are rare. 

Other findings include leukocytosis, elevated ESR and C-reactive proteins. The combined presence of effusion and elevated C-reactive protein has been associated with an increased risk of recurrence and complications. 

Our patient initially presented with both of these signs; however, he was discharged without further workup. 

Patients with evidence of large and symptomatic effusions and those causing tamponade should undergo pericardiocentesis, pericardial window or placement of chest tube to avoid cardiovascular collapse. High risk features including fever, evidence of cardiac tamponade, failure to clinically improve after receiving at least 7 days of therapy with colchicine and NSAID, trauma, among others should prompt a hospital admission and possible emergent intervention. On the second admission, these features were recognized and treated. 



From Benign to Critical: Acute Idiopathic Pericarditis Complicated by Delayed Cardiac Tamponade

Background

According to the AMA, the new Pass/Fail STEP 1 “reduc[es] the burden of exam preparation for medical students and creat[es] a more holistic residency-application selection process.” However, following the USMLE Step 1 transition to pass/fail in 2022, students began reporting pressure to accumulate research experience as a way of standing out among other applicants. This project seeks to evaluate the impact of research participation on medical student well-being
as well as student perceptions of the value and utility of their research.

Methods
Our team distributed a survey to medical students that included Likert-Scale questions on research participation, student well-being, perceived value of research, and if they feel pressure to participate in research. Response options included: Strongly Disagree, Disagree, Neither Agree nor Disagree, Agree, Strongly Agree, Not Applicable (do not plan to do research). Inclusion criteria included currently enrolled medical students. We received 122 responses to our survey. Of these respondents, 26 were M-1 year, 63 were M-2 year, 14 were M-3 year, and 22
were M-4 year. The remaining 8 students marked “other” or left that choice blank. Although not every student answered every question, we included all data that we received.


Results
Our data showed that 60% (strongly agree or agree) of students say that research participation has a negative impact on their well-being, with 87% stating that the main reason they are doing research is to help their residency application. With regard to the potential of their research to decrease healthcare costs, 27% answered affirmatively (strongly agree or agree). However, 51% of students believe (strongly agree or agree) that their research can help improve outcomes. In
addition, 38% believe (strongly agree or agree) that it can change treatment guidelines. When asked if students would still participate in research if it had no impact on their ERAS application, 32% said that they would still do research, while 56% answered they would not participate in research, 11% students were unsure if they would still participate.


Conclusion
Results showed that students feel pressure to participate in research, which is adversely affecting the majority of students’ well-being. Further many students are not finding value or utility in the research they do. Our data shows that students are mainly driven to participate in research to strengthen their ERAS application and improve their chance of a successful residency match.

Evaluating the Value and Purpose of Medical Student Research

An Assessment of Service Awareness for the Unhoused Population in San Diego County

Mapping Support: An Assessment of Service Awareness for the Unhoused Population in San Diego County

Background: Eyeglasses may influence children’s self-image and social perceptions, and as animated films are widely consumed by children and caregivers, the way spectacle-wearing characters are portrayed may shape attitudes toward spectacle use. This study aimed to determine common character traits associated with spectacle-wearing characters in animated films across major studios. 

Methods: A comprehensive review of 167 animated films from seven major studios was conducted. Characters who wore corrective eyewear and had at least one line of dialogue were included. Traits were evaluated by five independent reviewers, and statistical comparisons were performed using Fisher’s exact and two-sample proportion tests. 

Results: Among the 167 films, only 39% featured at least one character wearing glasses, totaling 121 characters from 66 films. Glasses-wearing characters were significantly more likely to be supporting (91%) than main characters (9%). Among children with glasses, the most frequent traits were socially awkward (52%) and weak (36%), both significantly more common than in Ó 2025 American Medical Association. All rights reserved. other age groups (p = 0.001 and p = 0.006). In contrast, children with glasses were least likely to be portrayed as mature (8%) or authoritative (8%; p < 0.001 and p = 0.002). Elderly spectacle-wearing characters were significantly more likely to be portrayed as mature (59% vs. 31%; p = 0.026), with a trend toward authority (50% vs. 30%; p = 0.087). Intelligence was a common trait across all age groups (~41%) but did not differ significantly by age (p > 0.8). 

Conclusion: Younger characters with glasses are commonly portrayed as socially awkward and weak, while older spectacle wearers are depicted as mature and authoritative. The relative scarcity and marginalization of glasses-wearing characters in animated films may limit positive identification for children who wear glasses. These age-dependent portrayals may reinforce stereotypes about spectacle wearers and influence how children perceive themselves and others who wear glasses.

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