United States

Background: Patients with bone metastases bear poor prognosis. For surgically indicated patients, orthopedic interventions range from long-term reconstruction to short-term palliative stabilization. For both the patient and the orthopedic oncologist, survival estimates are crucial to guide decision making into which surgical intervention is best. To improve existing survival models, new methods of differentiating survival are needed. Despite the known contribution of cytokines and chemokines in the development and progression of bone metastases, few studies have examined the relationship between the concentrations of these immune signatures and survival in this population. The objective of this study was to examine the prognostic value of immune signatures in patients treated surgically for bone metastases.

Methods: A 35-plex cytokine panel was performed on serum from 173 patients prior to surgical intervention for bone metastases. Univariable analyses were performed between overall survival (OS) from time of surgery with lymph node and visceral metastases, solitary versus multiple bone metastases, and each serum marker using Cox proportional hazards models. Logistic regression models for three-month survival were used to assess the short-term prognostic capabilities of circulating cytokines and chemokines.

Results: The median age at surgery was 63 years (IQR 54 – 69). 58% of patients were female. The most common primary malignancies were lung (23.7%), breast (18.5%), and renal (17.9%). Concentrations of circulating cytokines and chemokines were not significantly associated with 3-month survival or OS. Median survival was 1.1 years (IQR 0.70, 1.4). Patients with lymph node (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.45, 2.88; p &lt; 0.001) or visceral metastases (HR 2.04, 95% CI 1.41, 2.95; p &lt;0.001) had significantly shorter OS. Having multiple bone metastases was not associated with worse OS (HR 1.40, 95% CI 0.96, 2.03; p = 0.08).

Conclusion: Patients with bone metastases have poor prognosis overall, with lymph node and visceral metastases associating with shorter survival. Our analyses did not reveal associations between concentrations of circulating cytokines and chemokines with survival. We hypothesize this is due to the redundant function of our immune system’s cytokines and chemokines, rendering individual markers non-prognostic. Future work is needed elucidate the clinical impact these immune markers hold in the setting of bone metastases.

2025 AMA Research Challenge – Member Premier Access

Can Circulating Immune Signatures Predict Post-Op Survival in Patients with Bone Metastases?

Background: Patients with bone metastases bear poor prognosis. For surgically indicated patients, orthopedic interventions range from long-term reconstruction to short-term palliative stabilization. For both the patient and the orthopedic oncologist, survival estimates are crucial to guide decision making into which surgical intervention is best. To improve existing survival models, new methods of differentiating survival are needed. Despite the known contribution of cytokines and chemokines in the development and progression of bone metastases, few studies have examined the relationship between the concentrations of these immune signatures and survival in this population. The objective of this study was to examine the prognostic value of immune signatures in patients treated surgically for bone metastases.

Methods: A 35-plex cytokine panel was performed on serum from 173 patients prior to surgical intervention for bone metastases. Univariable analyses were performed between overall survival (OS) from time of surgery with lymph node and visceral metastases, solitary versus multiple bone metastases, and each serum marker using Cox proportional hazards models. Logistic regression models for three-month survival were used to assess the short-term prognostic capabilities of circulating cytokines and chemokines.

Results: The median age at surgery was 63 years (IQR 54 – 69). 58% of patients were female. The most common primary malignancies were lung (23.7%), breast (18.5%), and renal (17.9%). Concentrations of circulating cytokines and chemokines were not significantly associated with 3-month survival or OS. Median survival was 1.1 years (IQR 0.70, 1.4). Patients with lymph node (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.45, 2.88; p < 0.001) or visceral metastases (HR 2.04, 95% CI 1.41, 2.95; p <0.001) had significantly shorter OS. Having multiple bone metastases was not associated with worse OS (HR 1.40, 95% CI 0.96, 2.03; p = 0.08).

Conclusion: Patients with bone metastases have poor prognosis overall, with lymph node and visceral metastases associating with shorter survival. Our analyses did not reveal associations between concentrations of circulating cytokines and chemokines with survival. We hypothesize this is due to the redundant function of our immune system’s cytokines and chemokines, rendering individual markers non-prognostic. Future work is needed elucidate the clinical impact these immune markers hold in the setting of bone metastases.

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Background
Perinatal hypoxic brain injury, commonly referred to as hypoxic-ischemic encephalopathy (HIE), is a birth complication with high rates of morbidity and mortality. Despite ongoing research, there is still significant variation in methods of describing and diagnosing affected infants, which has also contributed to variation in treatment. In this systematic review, we aimed to describe the variability in terminology and subsequent impact on diagnosis, description, and treatment of perinatal hypoxic brain injury as demonstrated by relevant studies published between 2000 and 2024.

Methods
Initial searches of EMBASE and MEDLINE databases returned 1073 results. Studies were excluded if they were not in English, were secondary analyses, included data from an already-included research collaboration, used animal models, focused on non-infant populations, or lacked clearly defined inclusion/exclusion criteria. Ultimately, 245 studies published between 2000 and 2024 were reviewed for study design, country of origin, terminology used, and inclusion/exclusion criteria.

Results
This systematic review included 245 studies from 6 continents and 49 countries. Of these, 138 (56.3%) studies were single center prospective, and 89 (36.3%) studies were multi-center prospective with the remaining 11 (6.5%) studies being retrospective. The total number of injured infants included per study ranged from 4 to 3095 (mean 105). There was considerable variation in the primary term used to describe the hypoxic injury (59.2% HIE, 30.6% asphyxia, 8.6% neonatal encephalopathy, 0.8% asphyxia encephalopathy) with 66.5% of studies including a secondary term. Inclusion criteria varied notably. Though the actual values used for cutoffs varied, commonly used criteria were minimum gestational age (89.4% of studies), need for resuscitation (57.6%), cord pH (56.3%), and modified Sarnat scoring (55.9%). There were varying categories of exclusion criteria including congenital anomalies (73.5%), postnatal age >6 hours at enrollment (26.5%), chromosomal abnormalities (25.7%), metabolic abnormalities (17.1%), congenital infection (16.3%), and imminent death (12.7%).

Conclusion
The goal of this systematic review was to demonstrate the significant variation in description, definition, and management of perinatal hypoxic brain injury. Primary terminology and inclusion criteria notably varied across studies. Our findings highlight a critical gap in consensus as far as primary terminology and inclusion criteria, leading to confusion and ambiguity in both clinical and research settings. Future efforts should focus on standardizing definitions along with inclusion and exclusion criteria in order to allow for greater generalizability, targeted research, and enhanced clinical care of patients with this diagnosis.

Defining Perinatal Hypoxic Brain Injury: A Systematic Review of Variability in Diagnosis and Terminology

Background
Infective endocarditis (IE) stems from bacterial adhesions to vascular endothelium or valve leaflets, and if untreated can result in pseudoaneurysm (PSA) or abscess formation in the aortic root. Risk factors for IE include congenital heart defect, injection drug use, and prosthetic valves. PSA/abscess can increase the risk for conduction abnormalities and systemic embolization, along with additional procedural challenges. This study aims to evaluate the differences in procedural choice and surgical outcomes of patients with aortic valve endocarditis with and without PSA or abscess. 

Methods
From 2019-2025, 110 patients at a single institution underwent surgical management of aortic valve IE. Patients were grouped based on the presence or absence of aortic root PSA/abscess intraoperatively, (PSA/abscess group n=57, No PSA/abscess group n=53). Data were analyzed using R statistical analysis software: continuous variables were compared using the Wilcoxon-Mann-Whitney test, categorical variables were compared using the Chi-squared test or Fisher’s exact test and Kaplan-Meier survival analysis was performed using the survival package. A p-value of less than 0.05 was considered statistically significant. 

Results
The PSA/abscess group had a significantly higher rate of prior myocardial infarction compared to the no PSA/abscess group (35.1% vs. 17.0% respectively, p=0.031). The PSA/abscess group had a higher rate of positive cultures for coagulase negative staph (17.9%) than the no PSA/abscess group (1.9%, p=0.003). The groups had no other significant differences in pre-operative characteristics. Operative results showed the PSA/abscess group more frequently underwent Bentall (43.9%) and commando (17.5%) procedures compared to the no PSA/abscess group (13.2%, 1.9%, p=<0.001). Peri-operative outcomes of median cardiopulmonary and cross clamp times, new hemodialysis requirement, post-operative pacemaker placement, prolonged inotrope need, and ICU length of stay were all significantly higher in the PSA/abscess group. There was no difference in in-hospital mortality between groups (p=0.061). Median follow-up of the cohort was 311 days (66, 890). There were no significant differences between the groups in valve-related reinterventions, ventricular function, recurrent IE or all-cause mortality. 

Conclusion
Management of IE with aortic root PSA/abscess remains a common challenge compared to IE without PSA/abscess. Patients with PSA/abscess more commonly experienced peri-operative hemodialysis requirement, permanent pacemaker placement, prolonged inotrope need, and longer ICU length of stay. There were no significant differences between groups in survival or repeat endocarditis during follow-up, although there was a trend towards increased risk of in-hospital mortality in the PSA/abscess group. Larger studies are needed to better elucidate perioperative risk associated with both complicated and uncomplicated aortic valve endocarditis.

Outcomes of Surgical Management of Aortic Valve Endocarditis With and Without
Pseudoaneurysm

Title:
Double Trouble, One Solution: Valve-in-Valve TAVR Corrects Both Aortic and Mitral Valve in a Complex Dual-Valve Pathology

Background:
Bioprosthetic valve degeneration, particularly involving the Trifecta surgical aortic valve, has become an increasingly recognized clinical challenge due to its propensity for early structural valve deterioration and failure. Severe aortic regurgitation (AR) resulting from immobile or flail valve leaflets often presents with complex hemodynamic consequences, including functional mitral stenosis—a condition also known as pseudo-mitral stenosis. This phenomenon occurs when the regurgitant aortic jet impinges upon the anterior mitral leaflet, restricting its motion and creating an obstruction to diastolic mitral inflow. Clinically, this manifests as an Austin Flint murmur and may mimic organic mitral valve disease, complicating diagnosis. Distinguishing functional mitral stenosis from intrinsic mitral pathology is critical because the treatment focus should be on correcting the primary aortic valve lesion. Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a less invasive, effective alternative to redo surgical valve replacement in patients with degenerated bioprosthetic valves who are at elevated surgical risk.
Case Presentation:
We report the case of an 84-year-old male with a history of a Trifecta bioprosthetic aortic valve replacement who presented with progressive exertional dyspnea, orthopnea, and acute hypoxic respiratory failure. Initial transthoracic and transesophageal echocardiography revealed severe eccentric AR due to an immobile bioprosthetic leaflet, accompanied by severe functional mitral stenosis characterized by a markedly elevated mean mitral valve gradient of 17 mmHg and reduced mitral valve area, despite structurally normal mitral leaflets. Right and left heart catheterization demonstrated elevated left atrial and pulmonary pressures, consistent with the dual-valve pathology. The patient’s comorbidities—including chronic kidney disease, severe obstructive sleep apnea, prior cerebrovascular accident with residual deficits, and frailty—rendered him high-risk for conventional redo surgery. After multidisciplinary evaluation, the patient underwent a transfemoral ViV-TAVR using a 23 mm Edwards SAPIEN Ultra valve with prophylactic coronary protection. Post-procedure imaging confirmed successful valve deployment with complete resolution of aortic regurgitation and significant reduction in mitral valve gradient to 6 mmHg. Mitral valve mobility and effective valve area improved, demonstrating reversal of functional mitral stenosis.
Discussion:
This case highlights the intricate pathophysiology of functional mitral stenosis secondary to severe AR caused by bioprosthetic valve degeneration. The findings underscore the importance of thorough echocardiographic and hemodynamic evaluation to differentiate pseudo-mitral stenosis from primary mitral valve disease. Correction of the aortic valve pathology alone can restore mitral valve function, obviating the need for direct mitral intervention. ViV-TAVR offers a safe and effective minimally invasive treatment option for high-risk patients with complex dual-valve dysfunction. Comprehensive pre-procedural imaging, including transthoracic and transesophageal echocardiography and computed tomography, is essential for accurate diagnosis and procedural planning, especially to mitigate risks such as coronary obstruction. This case adds to the growing evidence supporting ViV-TAVR in managing complex valvular heart disease and emphasizes the clinical relevance of recognizing the Austin Flint phenomenon in patients with severe aortic insufficiency.



Double Trouble, One Solution: Valve-in-Valve TAVR Corrects Both Aortic and Mitral Valve in a Complex Dual-Valve Pathology



Abstract Title 

Hepatosplenomegaly in Syphilis: An Unusual Association in Adults 

Background 

Hepatosplenomegaly is an uncommon manifestation of syphilis in adults; although, it is well recognized in pediatric population. Syphilitic hepatitis commonly presents with rash, abdominal pain, hepatomegaly, fatigue, and jaundice. It is less commonly associated with splenomegaly. We describe a case of a young female who was found to have hepatosplenomegaly and was diagnosed with syphilis of unclear duration on further evaluation. She was noted to have complete resolution of hepatosplenomegaly after completing the treatment for syphilis with no major adverse outcomes. 

Case Presentation 

A 28-year-old female with medical history significant for orolabial and genital Herpes simplex virus presents with 1-week history of macular palmar lesions of the right hand and a pruritic rash to bilateral upper extremities and abdomen. She also has associated sore throat, fever, nasal congestion, right upper quadrant abdominal pain and malaise ongoing for the same duration. Vitals were stable except mild tachycardia. Physical exam revealed posterior oropharyngeal erythema and a rash involving abdomen, bilateral palms, and upper extremities. Lab work revealed leukopenia with white cell count of 3.6 K/uL, hemoglobin 11.2 g/dL, and platelet count 189 K/uL. Liver enzymes were elevated with alkaline phosphatase 409 U/L, aspartate transaminase 162 U/L, and alanine transaminase 279 U/L. Ultrasound (US) abdomen was significant for hepatosplenomegaly. Evaluation for chlamydia, gonorrhea, group A streptococcus, COVID-19, influenza, respiratory syncytial virus, human immunodeficiency virus, hepatitis A, hepatitis B, hepatitis C, infectious mononucleosis, tuberculosis, toxoplasma, bartonella, and histoplasma were negative. The Treponema pallidum agglutination assay resulted reactive with rapid plasma reagin titer of 1:64. She was treated for early syphilis and prescribed doxycycline for 14 days. She was also referred to infectious diseases and hematology/oncology. An ultrasound guided liver biopsy revealed mild portal and lobular inflammation. After the course of doxycycline, liver enzymes trended down along with resolution of the right upper quadrant pain. Three months later, repeat rapid plasma reagin titer improved to 1:2, liver enzymes normalized, and computed tomography of the abdomen and pelvis revealed complete resolution of hepatosplenomegaly. 



Discussion 

Antibiotics are effective in most cases of syphilitic hepatitis; however, some cases that do not respond to antibiotics can lead to liver failure. Spontaneous resolution of hepatomegaly has also been described. This case demonstrates a rare association of hepatosplenomegaly with syphilis in adults and the importance of considering syphilis in the differential diagnoses of hepatomegaly/hepatitis. It also highlights the value of timely diagnosis resulting in successful treatment with good outcomes.

Hepatosplenomegaly in Syphilis: An Unusual Association in Adults

Abstract Title: Cracking the Code Early: Type I PPB as the First Sign of DICER1 Syndrome in Infancy

Background
The DICER1 gene encodes an endoribonuclease essential for microRNA (miRNA) processing, a key element of post-transcriptional gene regulation. Germline mutations in DICER1 cause a rare autosomal dominant tumor predisposition syndrome, predisposing individuals—primarily children and young adults—to a spectrum of neoplasms. Tumorigenesis typically involves a germline loss-of-function mutation followed by a somatic “hotspot” mutation in the RNase IIIb domain, impairing miRNA maturation and dysregulating gene expression.

Pleuropulmonary blastoma (PPB) is a hallmark tumor of this syndrome and often represents the initial clinical manifestation. PPB progresses histologically from cystic (Type I) to solid (Type III) forms, with earlier stages associated with better outcomes. DICER1-associated tumors may show primitive mesenchymal features and various differentiations, including rhabdomyoblastic or cartilaginous elements. Due to the syndrome’s multi-organ involvement—including the lungs, kidneys, thyroid, ovaries, and brain—early detection and genetic testing are vital in initiating timely treatment and identifying at-risk family members, including asymptomatic carriers.

Case Presentation
A 1-month-old male presented to his primary care physician with respiratory distress. Chest X-ray identified a left lower lung mass, prompting PICU admission and subsequent lobectomy. Postoperative recovery was smooth. Pathologic review raised suspicion for Type I PPB, with some inconclusive areas suggesting early Type II. Referral to the International PPB/DICER1 Registry confirmed Type I PPB. Genetic testing via next-generation sequencing revealed pathogenic DICER1 variants: c.3630del in exon 21 and c.5438A>G in exon 25, confirming a diagnosis of DICER1 tumor predisposition syndrome. The patient continues to be followed by pediatric oncology and genetics. Plans are underway for long-term surveillance and genetic counseling for first-degree relatives.

Discussion
This case highlights the importance of recognizing hereditary cancer syndromes like DICER1. This patient was diagnosed unusually early at 1 month—well before the typical 2–3 years for Type I PPB—it underscores the need for timely imaging in infants with unexplained respiratory symptoms. Early detection is key, as lower-grade lesions may be cured with surgery before progressing to more aggressive types.

The discovery of pathogenic DICER1 mutations transformed the clinical focus to lifelong surveillance for associated tumors and risk assessment for relatives. Although targeted therapies are lacking, identifying DICER1 syndrome early allows for multidisciplinary care that can improve outcomes and reduce morbidity. For clinicians, maintaining a high index of suspicion for DICER1 syndrome in the presence of early-onset, cystic, or rare tumors is key to improving outcomes and reducing the burden of undiagnosed familial cancer syndromes.

Cracking the Code Early: Type I PPB as the First Sign of DICER1 Syndrome in Infancy

Background: Each year, ~50,000 applicants register for the National Resident Matching Program, ~9% of whom are lesbian, gay, bisexual, or queer (LGBQ). These students face high rates of mistreatment and discrimination within and beyond medical school, as anti-LGBTQ+ legislation has been increasingly introduced across the country. 
Methods: Data from the Electronic Residency Application Service and Graduation Questionnaire included 151,772 applicants from 2017-2024. Each U.S. state was categorized using the Human Rights Campaign’s State Equality Index (SEI), an annual assessment of law and policy impacting LGBTQ+ equality, from states with strong, broad legal protections (SEI 1) to those without fundamental protections (SEI 4). To assess applicant behavior in relation to state policy environments, the proportion of applications submitted by each applicant to states in each SEI Tier were calculated. For example, if a student applied to 5 programs, 2 of which were in SEI 1, the proportion of SEI 1 applications would be 0.4. 
Results: LGBQ residency applicants submitted more of their applications to programs in states with strong legal protections for their community (SEI 1 and 2) than their non-LGBQ peers and submitted fewer of their applications to states without fundamental protections or with active bans (SEI 3 and 4). 
LGBQ applicants submitted a higher proportion of applications (Mean: 0.46, SD: 0.23) to states in SEI Tier 1 than non-LGBQ applicants (Mean: 0.40, SD: 0.24), t(144897) = -27.15, p = 0.0000, and a higher proportion of applications (Mean: 0.22, SD: 0.19) to states in SEI Tier 2 than non-LGBQ applicants (Mean: 0.20, SD: 0.19), t(144897) = -14.46, p = 0.0000.
LGBQ applicants submitted a lower proportion of applications (Mean: 0.12, SD: 0.16) to states in SEI Tier 3 than non-LGBQ applicants (Mean: 0.14, SD: 0.17), t(144897) = 12.24, p = 0.0000, and a lower proportion of their applications (Mean: 0.20, SD: 0.18) to states in SEI Tier 4 than non-LGBQ applicants (Mean: 0.26, SD: 0.22), t(144897) = 32.4209, p = 0.0000.
Summary: 
Our findings indicate that, from 2017-2024, LGBQ residency applicants submitted higher proportions of their applications to programs in states with strong legislative protections for their community when compared to their non-LGBQ peers. If anti-LGBTQ+ legislation continues to escalate, residency programs in states with weaker protections may see a decline in applications from this community, possibly creating less diverse residency programs and limiting chances for LGBTQ+ patients in these states to receive care from a physician who shares their identity.

Pride & Prejudice: Assessing the Impact of Anti-LGBTQ Legislation on Residency Application Trends

Background
Dating applications such as Tinder and Hinge provide convenient and accessible platforms for meeting potential partners, especially for busy medical students. However, prior research has associated social media and dating app usage with lower self-esteem and increased levels of depression, anxiety and stress. Due to the rigorous demands of medical school, medical students are especially vulnerable to developing mental health conditions that may lower their self-esteem, which can negatively impact academic performance and interpersonal relationships. Thus, this study investigated the effect of dating application usage on the self-esteem of medical students. 

Methods
An anonymous survey including demographic questions and the Rosenberg Self-Esteem Scale (RSES) was sent to MD and DO students across medical schools in the United States. Participants were categorized into 2 groups: (1) never users—single students who have never used a dating app and (2) active users—single students who reported using Tinder and/or Hinge within the past week. The RSES self-esteem score for each participant was calculated. Then, the mean score for each group was compared using a two-tailed Mann-Whitney test.

Results
We received a total of 208 responses. After excluding those not meeting inclusion criteria (e.g., not single, inactive users, not users of specifically Hinge/Tinder), the final sample included 45 never users and 58 active users (total n = 103). The average self-esteem score of the never user group was 21.00/30 and 21.50/30 for the active user group. A two-tailed Mann-Whitney test revealed that there was no significant difference between the two scores (p = 0.79). Subgroup analyses stratified by biological sex and year in medical school also showed no significant differences. Additionally, among the active users, the most reported motivation for dating application usage was to find a long-term partner. 

Conclusion
This study found that medical students who actively use Tinder and/or Hinge do not have a significant difference in self-esteem compared to those who have never used dating applications. As medical students navigate their high-stress training, these findings suggest that dating applications can offer a practical means for social connection and pursuit of a life partner without compromising psychological well-being. Given the heightened vulnerability of this population to mental health challenges and burnout, future research should further investigate the impact and underlying mechanisms of dating application usage on mental well-being, continuing the conversation to help support the personal fulfillment and emotional resilience of current and future healthcare professionals.

Swipe and Self-Worth: Analyzing the Impact of Dating Application Usage on the Self-Esteem of Medical Students

Background
Physician advocacy is widely recognized as a professional responsibility. Despite this, medical students often receive limited formal training in advocacy. Little is known about student perceptions of physician advocacy. Understanding these perspectives is essential to developing meaningful advocacy curricula. This study combined a scoping review of existing literature with institutional survey data to explore how U.S. medical students perceive advocacy and their interest in advocacy curricula.
Methods
A scoping review was conducted following PRISMA guidelines. Studies were included if they examined U.S. medical students’ perspectives on physician advocacy, including definitions, perceived relevance, or curricular needs. Eleven articles were analyzed, and common themes were identified. To complement these findings, we conducted a survey of medical students at the University of Illinois College of Medicine. The survey included three 5-point Likert-scale items assessing interest in physician advocacy, relevance to future careers, and enthusiasm for a proposed advocacy curriculum. Strong interest or relevance was defined as a rating of ≥4. 
Results
The scoping review identified four major themes: (1) definitions of advocacy, (2) engagement and identity, (3) perceived importance and professional responsibility, and (4) desire for education and perceived barriers. Students defined advocacy along a spectrum from individual patient-level actions to broader system-level reform. Many self-identified as advocates and expressed a desire to remain engaged throughout their careers. Advocacy was widely seen as a core professional responsibility, though the expected level of engagement varied. A strong desire for formal training emerged, alongside barriers to engagement such as restricted time, lack of mentorship, and limited opportunities to build relevant skills. Survey results mirrored these findings. 234 students were invited to complete the survey and 100 responded (43% response rate). Among respondents, 89% expressed strong interest in advocacy, 91% perceived advocacy as career-relevant, and 66% were interested in pursuing a structured advocacy program.
Conclusion
Findings from this study underscore medical students’ strong interest in advocacy and a clear desire for formalized, skills-based training. As physicians continue to play an essential role in addressing social determinants of health and influencing policy, integrating advocacy education into undergraduate medical training is critical. We must ensure that future doctors can navigate these responsibilities effectively and meet both societal needs and student expectations.

Medical Student Perspectives on Advocacy: A Mixed-Methods Exploration of Interest, Relevance, and Curricular Needs

Association between Shingles Vaccination and Skin Cancer among Older Adults in the United States: A Population-Based Cross-Sectional Study

Nicholas Hess1, Leigh Stavar2, Zelalem T. Haile3

1,2 Ohio University Heritage College of Osteopathic Medicine, Dublin, OH
3 Ohio University Heritage College of Osteopathic Medicine, Department of Social Medicine, Dublin, OH


Background: The herpes zoster (shingles) vaccine is widely recommended for adults aged 50 and older to prevent reactivation of the varicella-zoster virus. While its safety and efficacy in preventing shingles are well documented, limited research has examined potential links between shingles vaccination and other long-term health outcomes, including cancer risk. Skin cancer remains one of the most common malignancies among older adults in the United States. This study aimed to investigate the association between receiving the shingles vaccine and self-reported prevalence of skin cancer using nationally representative data.

Methods: We conducted a cross-sectional analysis of the 2023 Behavioral Risk Factor Surveillance System, focusing on adults aged 50 years and older (N = 219,545). The primary exposure was whether participants received the shingles vaccine (yes/no), and the outcome was self-reported history of skin cancer diagnosis. We used multivariable logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI), controlling for potential confounders such as age, sex, race/ethnicity, marital status, education, employment, income, insurance coverage, overall health, veteran status, rural/urban residence, smoking, alcohol consumption, physical activity, healthcare access and utilization, diabetes, chronic obstructive pulmonary disease, depression, and other cancers.

Results: The overall prevalence of skin cancer in the sample was 10.7%, and 45.4% of participants reported receiving the shingles vaccine. Skin cancer prevalence varied significantly by vaccination status: 14.2% among those vaccinated compared to 7.8% among those unvaccinated (p < 0.001). In unadjusted analyses, shingles vaccination was associated with increased odds of reporting skin cancer (OR 1.92; 95% CI 1.83–2.04; p < 0.001). After adjusting for sociodemographic, behavioral, and health-related factors, the association remained significant (aOR 1.33; 95% CI 1.25–1.41; p < 0.001). Sensitivity analyses that considered healthcare access and history of other cancers showed similar results (aOR 1.25; 95% CI 1.18–1.33; p < 0.001).

Conclusion: In this large, population-based study, receiving the shingles vaccine was positively linked to self-reported skin cancer prevalence among older adults. Although this association does not imply causality, it raises important questions and emphasizes the need for further longitudinal research to explore potential biological or behavioral mechanisms. These findings may guide clinical and public health discussions on post-vaccination monitoring and should be considered in future vaccine safety studies.

Association Between Herpes Zoster Vaccination and Skin Cancer among Older Adults in the US

Background: Muscle wasting syndromes—including cancer cachexia, chronic obstructive pulmonary disease (COPD), cirrhosis, and aging-related sarcopenia—contribute significantly to functional decline, hospital readmissions, and mortality. β-Hydroxy β-methylbutyrate (HMB), a leucine-derived metabolite, has demonstrated anti-catabolic effects by inhibiting protein degradation and stimulating protein synthesis, yet its clinical integration remains limited despite promising evidence. This review aims to evaluate clinical evidence on HMB supplementation for muscle preservation in patients with cachexia and chronic illness and identify opportunities for integration into recovery and palliative care models.
Methods: A structured narrative review was conducted using existing medical literature databases like PubMed (2005–2025). Search terms included "HMB," "β-hydroxy β-methylbutyrate," "cachexia," "sarcopenia," "muscle wasting," and specific disease states (cancer, COPD, cirrhosis). Inclusion criteria comprised randomized controlled trials, meta-analyses, and systematic reviews assessing HMB supplementation (alone or in combination with other nutrients) in adults with or at risk for muscle wasting. Primary outcomes evaluated included changes in lean body mass, muscle strength, physical function, and quality of life. Secondary outcomes included inflammatory markers, nutritional status, and hospitalization rates.
Results: HMB supplementation (typically 1.5–3g/day) has demonstrated benefits across multiple conditions. In studies of older adults with sarcopenia, HMB combined with other nutrients has been associated with preservation or modest increases in lean body mass. Research on bed rest in older adults has shown that HMB supplementation may attenuate muscle loss compared to placebo. In cancer and other catabolic conditions, evidence suggests HMB helps preserve muscle mass through reduced proteolysis and enhanced protein synthesis. For patients with liver disease, combining nutritional supplementation with exercise training has shown promising results for muscle function. Meta-analyses indicate improvements in muscle strength across randomized trials in elderly populations. Across studies, HMB has been well-tolerated with minimal adverse effects reported.
Conclusion: HMB represents a promising, evidence-based adjunct to nutritional therapy in cachexia and chronic illness. Current evidence supports the potential role of HMB in clinical nutrition protocols for patients at risk of muscle wasting, particularly during periods of increased catabolism. Implementation barriers include limited provider awareness and inconsistent insurance coverage. Future research should prioritize disease-specific dosing protocols and integration with exercise interventions to optimize functional outcomes and quality of life.


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