United States

Background
The obesity paradox refers to the unexpected observation that individuals with obesity (BMI ≥ 30) sometimes experience better clinical outcomes than those with lower BMI, despite obesity being associated with worse prognoses in breast cancer. Some subgroups, such as premenopausal women and patients with advanced HER2+ disease, have shown improved survival with higher BMI. Factors like methodological bias, reverse causation, high BMI’s association with high muscle mass, or BMI’s limitations as a measure of adiposity have been suggested as possible explanations for this paradox. Given adipose tissue’s varying metabolic effects across races, we aimed to further characterize this paradox and assess its impact on racial differences in survival outcomes.

Methods
Using anonymized electronic health records from the TriNetX network, we conducted a retrospective cohort study of metastatic (Stage IV) breast cancer patients with BMI data within one month of their diagnosis. Patients with other primary cancers were excluded. Four cohorts were created based on race and BMI: obese and non-obese African-American and Caucasian patients. Propensity score matching (1:1) controlled for age, sex, comorbidities, tumor characteristics, treatment modalities, and receptor status. The primary outcome was 10-year overall survival.

Results
After matching, each African-American subgroup included 1,219 patients; each Caucasian subgroup included 5,448 patients. Obese African-American patients had significantly longer median survival than non-obese counterparts (2,074 vs. 1,236 days; p &lt; 0.0001). Among Caucasian patients, no significant survival difference was observed (1,908 vs. 2,067 days; p = 0.70).

Conclusion
The obesity paradox has a notable impact on survival among African-American patients with metastatic breast cancer but not among Caucasian patients. These findings suggest a need for race-specific prognostic assessments and further investigation into underlying biological mechanisms.


AMA Research Challenge 2025 

The Weight of Race: Understanding the Obesity Paradox in Metastatic Breast Cancer

Background
The obesity paradox refers to the unexpected observation that individuals with obesity (BMI ≥ 30) sometimes experience better clinical outcomes than those with lower BMI, despite obesity being associated with worse prognoses in breast cancer. Some subgroups, such as premenopausal women and patients with advanced HER2+ disease, have shown improved survival with higher BMI. Factors like methodological bias, reverse causation, high BMI’s association with high muscle mass, or BMI’s limitations as a measure of adiposity have been suggested as possible explanations for this paradox. Given adipose tissue’s varying metabolic effects across races, we aimed to further characterize this paradox and assess its impact on racial differences in survival outcomes.

Methods
Using anonymized electronic health records from the TriNetX network, we conducted a retrospective cohort study of metastatic (Stage IV) breast cancer patients with BMI data within one month of their diagnosis. Patients with other primary cancers were excluded. Four cohorts were created based on race and BMI: obese and non-obese African-American and Caucasian patients. Propensity score matching (1:1) controlled for age, sex, comorbidities, tumor characteristics, treatment modalities, and receptor status. The primary outcome was 10-year overall survival.

Results
After matching, each African-American subgroup included 1,219 patients; each Caucasian subgroup included 5,448 patients. Obese African-American patients had significantly longer median survival than non-obese counterparts (2,074 vs. 1,236 days; p < 0.0001). Among Caucasian patients, no significant survival difference was observed (1,908 vs. 2,067 days; p = 0.70).

Conclusion
The obesity paradox has a notable impact on survival among African-American patients with metastatic breast cancer but not among Caucasian patients. These findings suggest a need for race-specific prognostic assessments and further investigation into underlying biological mechanisms.


poster

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Background: Microglial metabolic dysfunction is a key contributor to the progression of Parkinson’s Disease (PD), a neurodegenerative disorder marked by dopaminergic neuronal loss in the substantia nigra and pathological α-synuclein accumulation. As the primary immunoregulatory cells of the central nervous system (CNS), microglia play a critical role in maintaining neuronal health. In PD, they help phagocytose α-synuclein to clear misfolded protein aggregates, release neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and IGF-1 to support neuronal survival, conduct immune surveillance for injury or infection, and regulate synaptic pruning, ion balance, and clearance of apoptotic cells. Microglia can adopt pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotypes; the latter secretes cytokines such as IL-10 and TGF-β to limit inflammation and promote neuroprotection.
However, in PD, chronic microglial activation impairs their ability to clear α-synuclein and maintain their immunoregulatory functions. This dysfunctional state is associated with elevated oxidative stress and sustained neuroinflammation. Metabolically, these chronically activated microglia shift from oxidative phosphorylation (OXPHOS) to glycolysis, favoring rapid but less efficient ATP production to sustain their inflammatory activity. Interestingly, this glycolytic reprogramming mirrors the Warburg effect observed in cancer cells, in which cells preferentially undergo aerobic glycolysis despite sufficient oxygen availability, supporting increased functional output at the expense of metabolic efficiency.
Therapeutic strategies that restore mitochondrial respiration and reestablish metabolic balance may reverse this pro-inflammatory phenotype and promote neuroprotection. To address this, we screened a library of approximately 400 mitochondria-targeted small molecules for their ability to enhance OXPHOS and suppress glycolysis in α-synuclein–exposed microglia under PD-like inflammatory conditions. Overall, this study aims to identify promising therapeutic candidates that restore homeostatic microglial function, reduce neuroinflammation, and support the development of targeted treatments for PD.
Methods: A three-phase in vitro study was designed using mouse microglial cells (MV2). In Phase I, we optimized cell density and α-synuclein fibril (PFF) dose to model PD-relevant inflammation and metabolic disruption. The optimal seeding density (~20,000 cells/well) and PFF concentration (10 μM) were selected based on morphology and cytokine output. In Phase II, approximately 400 mitochondria-targeted small molecules from the TargetMol library were screened. PFF-treated cells were exposed to compounds and analyzed via Seahorse XF technology for Oxygen Consumption Rate (OCR), Extracellular Acidification Rate (ECAR), and ATP production. Phase III will validate lead compounds mechanistically, assessing cytokine suppression and mitochondrial effect in microglial cells (MV2).
Results Preliminary Phase I data confirmed that 10 μM PFF induces robust microglial activation with elevated TNF-α, IL-6, and nitric oxide. Seahorse assay setup confirmed consistent OCR and ECAR measurements. Compound screening is ongoing; several candidates show potential to enhance mitochondrial oxidative respiration and suppress glycolytic flux in α-synuclein–treated microglia.
Conclusion: This ongoing study outlines a novel screening approach to identify therapeutics that restore microglial homeostasis in PD. By combining disease modeling with real-time metabolic analysis, we aim to discover compounds that reverse glycolytic bias and mitigate neuroinflammation. These findings may inform the development of microglia-targeted therapies to protect against neurodegeneration in PD and related disorders.

Targeted Screening to Restore Microglial Bioenergetics in Parkinson’s Disease Using Seahorse XF Technology

Abstract
Hip osteoarthritis (OA) is a chronic, progressive degenerative joint disorder associated with significant morbidity and limited non-surgical treatment options. Over the past 20 years, Platelet-rich plasma (PRP) has garnered increasing interest as a conservative intervention in the setting of OA; however, its clinical efficacy in hip OA remains inconclusive due to substantial heterogeneity in preparation protocols and administration methods. This systematic review aims to examine randomized controlled trials (RCTs) published between 2019 and 2024 that evaluated the efficacy of PRP in the management of hip osteoarthritis, with specific criteria including the use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and/or the Visual Analog Scale (VAS) for outcome measurement. Three RCTs met the eligibility criteria. While short-term improvements in pain and function were observed in patients with mild to moderate OA, long-term benefits were inconsistent. Considerable variability in PRP composition (leukocyte-rich versus leukocyte-poor), activation techniques, injection schedules, and follow-up durations was evident across studies. Particularly, one trial demonstrated no significant advantage of PRP over placebo. Methodological limitations, including lack of blinding, underreporting of PRP characteristics, and protocol heterogeneity, impeded the ability to draw definitive conclusions. Although PRP may provide short-term symptomatic relief in early-stage hip osteoarthritis, the absence of standardized protocols highlights the need for rigorous, long-term randomized controlled trials that employ consistent classification systems (e.g., PAW or MARSPILL) and stratified patient populations to inform evidence-based clinical guidelines.


A Systematic Review of Recent Developments in Platelet-Rich Plasma Therapy in Hip Osteoarthritis: Variability in Protocols and Clinical Outcomes (2019–2024)

Background:
Deep brain stimulation (DBS) has emerged as a transformative intervention for motor symptom control in patients with Parkinson’s disease (PD). While its benefits are well-established, concerns persist regarding the potential exacerbation or emergence of psychiatric conditions—particularly depression, psychosis, and disinhibition—following DBS. Clarifying these risks is essential for comprehensive patient counseling and long-term management planning.
Methods:
Using the TriNetX Global Collaborative Network, we conducted a retrospective cohort study comparing psychiatric outcomes in PD patients with and without dystonia or tremor who underwent DBS. After 1:1 propensity score matching on demographics and baseline characteristics, each group included 10,200 patients. Psychiatric outcomes were assessed using risk ratios, Kaplan-Meier survival analysis, and Cox proportional hazards models.
Results:
Depression was the most prevalent psychiatric outcome, affecting approximately 24% of both groups. While risk ratios and survival curves showed no significant differences (RR: 0.98; HR: 1.08; p > 0.7), the dystonia/tremor (D/T) group exhibited a trend toward a higher frequency of recurrent depressive episodes (mean: 2.2 vs. 1.1; p = 0.09), although this difference was not statistically significant. Other outcomes—including disinhibition (2.3% vs. 2.1%), delirium (6.5% vs. 5.4%), euphoria (1.3% both), and psychosis (2.3% vs. 2.7%)—were rare and showed no meaningful differences in risk, frequency, or time to onset (all p > 0.3). Overall, Kaplan-Meier curves demonstrated no accelerated onset of psychiatric symptoms in the D/T group.
Conclusion:
In the setting of DBS in PD, these findings indicate that dystonia or tremor does not significantly alter psychiatric risk following DBS in PD. However, ongoing surveillance for depression is warranted as part of post-operative care.


Psychiatric outcomes in Parkinson’s Disease treated with Deep Brain Stimulation as compared with Dystonia and Tremor

Background
Aggression—defined as the intentional behavior of causing harm to oneself or others—is a symptom of various psychiatric and neurological disorders. It significantly reduces quality of life and is often resistant to standard therapies, sometimes requiring ethically complex interventions. Neuroimaging has linked regions such as the prefrontal cortex, amygdala, and hypothalamus to aggression regulation.
Deep brain stimulation (DBS), a neurosurgical technique using implanted electrodes to modulate neural activity, has shown potential for treating refractory aggression. While established for conditions like Parkinson’s and OCD, its role in managing aggression remains under-explored. This review evaluates the feasibility and outcomes of DBS for aggression.

Methods
This systematic review followed PRISMA-ScR guidelines. We searched Embase, MEDLINE, and Web of Science from inception to June 4, 2023, using terms related to “aggression” and “DBS.” After duplicate removal, six reviewers screened titles and abstracts in Covidence; full-text review and conflict resolution involved additional reviewers. Inclusion criteria were English-language original studies or case reports using DBS to treat aggression with reported outcomes. Non-human studies, reviews, and non-DBS interventions were excluded. Extracted data included demographics, DBS parameters, outcomes, and study characteristics. Risk of bias was assessed using QUIPS for original studies and the JBI checklist for case reports. The primary outcome measured changes in aggressive behavior following DBS.

Results
After screening 1905 papers, 37 studies, from December 1970 to May 2023, consisting of 976 patients (586 males, 319 females, and 71 unspecified), across 12 countries, were included in the final analysis, of which 882 were adults. The mean age of all participants was 55.3 years. The mean follow-up length was 32.26 months (SD 36.29, range 3-144). At least 799 patients (81.66%) were receiving medication prior to surgery. The most common indication for DBS was movement disorders in 232 patients (23.77%), followed by aggression for 200 individuals (20.49%). The subthalamic nucleus was the most common neuroanatomical target site for 744 patients (76.2%), followed by the hypothalamus in 162 patients (16.6%). The Overt Aggression Scale (AOS) was the most frequently used tool for obtaining aggression scores across 9 studies. Improvements in aggression were observed in 144 patients.

Conclusion
Deep brain stimulation shows promise as a safe and viable surgical treatment in reducing aggression across a range of populations, particularly when targeting regions like the hypothalamus and nucleus accumbens. However, future large-scale studies, ideally with long-term follow-ups and unified aggression scale measurements from diverse patient demographics, are required to validate and extend these findings. 


Deep Brain Stimulation in Aggression: A Systematic Review

Background:
Major aortopulmonary collateral arteries (MAPCA) are rare congenital vessels arising from the aorta that supply pulmonary circulation, typically as a response to reduced native pulmonary blood flow. These vessels often present in association with complex congenital heart disease (CHD), prematurity, low birth weight, or chronic lung disease. They commonly provide redundant perfusion to lung lobes, supplementing the pulmonary circulation. This case, however, demonstrates a MAPCA presentation without these common associations nor additional pulmonary circulation.

Case Presentation:
Our patient was born at term with benign prenatal history and delivery. The maternal history was also unremarkable. In the following months, the patient experienced multiple non-specific dermatologic issues and viral-related upper respiratory infections (URI). A heart murmur was first heard at 6 months. In response to the murmur, in conjunction with a history of poor growth, a pediatric cardiology referral was made. Initial evaluation with electrocardiogram and transthoracic echocardiography showed secondary left-sided chamber dilation and pulmonary venous flow turbulence, which raised concern for a possible collateral vessel. Additional cardiac computed tomography angiography (CTA) imaging was obtained, revealing a solitary MAPCA supplying the entire left lower lobe. Despite normal bronchial anatomy identified by CTA, the lobe received only systemic blood flow, effectively functioning as a physiologic pulmonary sequestration. After thorough conference discussion, the patient was scheduled for a cardiac catheterization and bronchogram to assess hemodynamics and bronchial anatomy. These results will inform future management. At his recent follow-up visits, weight gain continues to be an issue along with an ongoing respiratory illness.

Discussion:
This infant’s clinical course—limited to recurrent URIs and slow weight gain—contrasts with typical MAPCA presentation, associated with more severe risk factors, and is more so related to large shunt physiology. The MAPCAs role as the sole blood supply to the left lower lobe further amplifies the uniqueness of this presentation. The absence of CHD or pulmonary pathology makes the etiology of this MAPCA unclear. This report expands the clinical spectrum of MAPCA presentations and emphasizes the importance of early cardiac evaluation, even in low-risk infants with subtle symptoms.

Isolated Major Aortopulmonary Collateral Physiologically Mimicking Pulmonary Sequestration

Chylothorax, a rare complication of hepatic cirrhosis, is often under-recognized in the absence of ascites or other classical signs of portal hypertension. The diagnosis can be challenging due to its infrequent presentation, which highlights the clinical significance of this case. A 57-year-old male with a history of decompensated liver cirrhosis presented with progressive dyspnea. Imaging showed a right-sided pleural effusion. Pleural fluid analysis confirmed chylothorax, with elevated triglycerides and normal cholesterol levels. The patient underwent chest tube placement, which resulted in drainage of 2L of chylous fluid and marked symptomatic improvement. Further management included admission to the intensive care unit, initiation of total parenteral nutrition, and transition to a low-fat diet. The patient was transferred to an academic center as his clinical status failed to improve. This case portrays the diagnostic challenges of the etiology of chylothorax in patients with hepatic cirrhosis and emphasizes the role of portal hypertension in disrupting lymphatic drainage. Increased awareness of this rare complication is essential for timely recognition and appropriate management.

Leaky Lymphatics: Uncovering an Uncommon Complication of Hepatic Cirrhosis

Background
Behçet’s Disease (BD) is a multisystem vasculitis with variable manifestations, including gastrointestinal involvement in 10–15% of cases. Intestinal BD often mimics Crohn’s disease or ulcerative colitis, making diagnosis challenging due to overlapping endoscopic and histologic features. While ileocecal involvement is typical, atypical patterns can obscure recognition. This case highlights an unusual presentation of intestinal BD without ileocecal predominance, underscoring the need for clinical vigilance and systemic evaluation to differentiate it from primary IBD.
Case Presentation
We present a 40-year-old woman with a known 10-year history of BD, on colchicine and hydroxychloroquine, was admitted with hematochezia, recurrent vomiting, and severe anemia (Hb 5.1 g/dL). Clinical examination revealed oral aphthous ulcers, genital ulcers, and erythema nodosum. Colonoscopy showed skip lesions, mucosal erythema, and superficial ulcers throughout the colon, terminal ileum, and ileocecal valve. Biopsy revealed edematous lamina propria infiltrated by lymphocytes, neutrophils, and eosinophils without granulomas, transmural lymphoid aggregates and granulomatous lymphangitis consistent with intestinal BD. The diagnosis was confirmed using the International Criteria for Behçet’s Disease (ICBD score = 6). The patient responded well to colchicine, with resolution of GI symptoms within four weeks.
Discussion
This case illustrates an uncommon presentation of intestinal Behçet’s Disease with diffuse gastrointestinal involvement without the typical ileocecal predilection. The similarity in clinical presentation and colonoscopy findings to inflammatory bowel disease highlights the diagnostic challenge. In such circumstances, histopathological evaluation becomes crucial. In our patient, the diagnosis was guided by systemic features and confirmed with ICBD criteria and biopsy study. The novelty lies in the atypical distribution of lesions, reinforcing the need to consider intestinal BD in patients with unexplained GI bleeding and mucocutaneous symptoms. Early recognition and appropriate immunomodulatory therapy can prevent misdiagnosis, reduce morbidity, and avoid unnecessary surgical interventions.

Gastrointestinal Bleeding in Behçet’s Disease: A Dual Pathology or Mere IBD Mimicry?

Like the governmental control that led to the involuntary sterilization of Civil Rights Activist Fannie Lou Hamer and thousands of others, Project 2025, a political proposal written by the Heritage Foundation, plans to restrict the reproductive rights and bodily autonomy of women by eliminating abortion access. Individuals should have the right to choose how and when to reproduce without risking their health or feeling unprepared. 
As defined by Critical Race Theory, using colorblind perspectives when creating policies does not change the implicit biases of people or how social structures are maintained throughout history, and policies should be evaluated based on how they impact the most disadvantaged groups. Project 2025 aims to fully ban abortion to “heal the family crisis”, the idea that the lack of fathers and healthy families are what cause poverty, crime, etc. However, a complete abortion ban only furthers systemic racism and increases barriers to care for marginalized groups, a practice that has historically discriminated against women of color. In addition to harming citizens, the proposal for a nationwide abortion ban is in violation of international standards that the US has agreed to as a member of the United Nations.

Restriction of Reproductive Autonomy: From Eugenics to Abortion

Background 
Eating disorders (EDs) are complex psychiatric conditions with systemic implications, including a range of dermatologic manifestations. Cutaneous findings related to nutritional deficiencies and disordered behaviors may appear early in the disease course, sometimes preceding a formal diagnosis. Despite their diagnostic relevance, these manifestations are frequently overlooked in clinical practice. This review highlights the critical role of recognizing dermatologic signs in EDs to enable earlier detection, support comprehensive evaluation, and promote interdisciplinary management.

Methods
A systematic literature review and meta-analysis were conducted using PubMed and Google Scholar, encompassing studies published between 2020 and 2025. Nine peer-reviewed studies were selected based on their relevance and inclusion of data on the dermatologic manifestations of eating disorders, focusing on nutritional deficiencies, clinical presentation, and diagnostic value.

Results 
Xerosis was the most frequently reported cutaneous finding in both anorexia nervosa and bulimia nervosa, often accompanied by cheilitis, hypertrichosis, alopecia, acrocyanosis, periungual erythema, nail changes, and oral manifestations related to nutritional deficiencies and purging behaviors. Similar dermatologic patterns were noted in pediatric populations, with additional features such as lanugo and signs of self-injury. Several studies also reported a significant association between atopic dermatitis and eating disorders, potentially linked to negative body image and immune dysregulation.

Conclusion
Dermatologic manifestations of eating disorders are often overlooked, despite their potential to support earlier diagnosis and intervention. Greater clinical recognition of these signs can promote timely, multidisciplinary care and improve patient outcomes. Continued research is needed to clarify the underlying mechanisms and define the role of dermatologic findings in comprehensive eating disorder management.

Dermatologic Manifestations of Eating Disorders: An Underrecognized Diagnostic Intersection

Background

Ensuring alignment between lecture content and defined learning objectives is critical for LCME accreditation (Standards 6, 7, and 8) and improving student outcomes. Traditional curriculum mapping is time-intensive, manual, and variable. This project introduces a web-based tool that automates the analysis of medical lecture transcripts against defined course objectives. The tool enables medical school deans to rapidly perform gap analyses, provide faculty feedback, and improve outcomes. It integrates with Learning Management System (LMS) platforms to quantify objective alignment.

Methods

We developed a process using a Large Language Model (LLM) to parse pre-clinical lecture transcripts and compare them against predefined learning objectives. The project consists of three phases. In Phase 1, we developed a 100-point scoring system to quantify alignment. As a preliminary experiment, we analyzed eight publicly available medical school lectures and their corresponding objectives using ChatGPT’s o3 LLM model. We tested three unique prompt engineering workflows with objectives and transcripts as input. The outputs included alignment scores and narrative reports based on the Bloom Rating System for each objective then identifying opportunities for improvement. In Phase 2, we will refine the scoring system in collaboration with deans and faculty to ensure feedback is actionable. Phase 3 will incorporate this feedback and finalize the scoring process, along with building a simple web interface for non-technical users.

Results

After calculating alignment scores for each objective across all eight lectures, the scores were averaged to determine the overall alignment for each of the three distinct LLM workflows. The workflows produced average scores of 88.65, 84.6, and 65.89 across the lectures. Reports included specific feedback and timestamps highlighting improvement areas (e.g., topic depth, anecdotal stories, unaddressed objectives). Anticipated findings include average objective coverage per lecture, frequency of missed objectives, and early feedback on the tool’s utility.

Conclusion

This project offers a reproducible, scalable method to evaluate alignment between lecture content and curricular objectives in undergraduate medical education. By automating the review process, it supports data-driven faculty development and curriculum improvement while reducing administrative burden. Preliminary findings demonstrate that LLMs can quantify alignment using lecture transcripts. The project builds on institutional experience with AI-assisted curriculum mapping and targets broad use, especially in programs lacking curriculum analytics infrastructure. Next steps include integrating user feedback and piloting the tool with institutional content.

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