United States

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&gt;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.

2025 AMA Research Challenge – Member Premier Access

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

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.

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BACKGROUND:
Increased inflammatory cytokines and biomarkers have been related to the degradation of the blood brain barrier. The fragility of this barrier can increase the number of proteins that can enter the central nervous system circulation, which has been postulated to cause brain dysfunction like delirium. GM-CSF, granulocyte-macrophage colony stimulating factor, and MCP-1, monocyte chemoattractant protein 1, both stimulate pro-inflammatory macrophages. Medications like propofol and dexmedetomidine have been shown to mitigate inflammation by downregulating pro-inflammatory macrophages. Anti-inflammatory macrophages produce cytokines like IL-13 which attenuate inflammation and thus have a protective effect on the brain. Dexmedetomidine has been shown to cause greater attenuation of inflammation than propofol in mouse models.

METHODS:
Samples that were analyzed were from a double-blind, randomized, controlled trial conducted at 13 different medical centers. The population of this trial includes 422 adults who were sequentially admitted to a medical or surgical ICU, with suspected or known infection, and were treated with continuous sedation for invasive mechanical ventilation. The medication used for sedation was either dexmedetomidine (5 μg per milliliter) or propofol (10 mg per milliliter). The samples from this trial were collected on enrollment days 1, 3, 5, and 7 then sent for analysis to calculate the biomarker levels per sample.

RESULTS:
The results indicate the approximate baseline physiologic rate for MCP-1, GM-CSF, and IL-13 are significantly less than biomarkers of critically ill adults with sepsis. This highlights that an inflammatory state results in a subsequent increase in the biomarkers studied. The sample population is randomized to propofol or dexmedetomidine for continuous sedation, we did not identify a significant difference between biomarker and inflammatory cytokine levels. These results agree with primary study findings that demonstrated no difference in delirium outcomes between propofol and dexmedetomidine recipients. 

CONCLUSION:
Analyzing the inflammation pathway can help determine how acute brain dysfunction and delirium develops. The confirmation of this correlation can provide mechanistic pathways to attenuate the inflammatory response to help reduce the risk for brain disease. Should one medication prove to be more efficient in attenuating the inflammatory response, further prospective work on implications among high-risk participants can be formulated to study. This can encourage further research into regulating the inflammatory response to protect the brain from developing acute dysfunction, including delirium. Results should be interpreted with limitations including 48 hours administration limitations, relatively low medication doses to achieve light sedation, and potential significance of alternative biomarker or cytokines not investigated.

Biomarker Analysis of Mechanically Ventilated Adults using Propofol or Dexmedetomidine

Background
Gastrointestinal (GI) complaints are the most common categorical presentations in emergency departments (EDs), accounting for approximately 11% of all ED visits in the United States. Many of these GI emergencies do not involve a structural cause and are presumed to be disorders of the gut-brain interaction (DGBIs). DGBIs such as irritable bowel syndrome, functional constipation, and functional dyspepsia affect approximately 40% of the world’s population and pose a major public health concern. Despite this, little is known about patient characteristics, comorbidities, and outcomes of DGBIs in the ED setting. Consequently, many patients with DGBIs undergo repeat ED visits, testing, and opioid exposure, posing a strain on both the patient and the broader healthcare system. 

Methods
We conducted a prospective, multi-center observational cohort study at four U.S. hospitals, enrolling adults presenting to the ED who were determined by three independent physicians to have recurrent abdominal pain without clear structural etiology. Participants completed standardized surveys assessing pain severity, psychiatric symptoms, substance use, and social determinants of health. Chart review captured clinical management, diagnostic testing, and health care utilization at the index visit, and at 30 days and 12 months post-visit. 

Results
Analysis is ongoing, and preliminary results from George Washington University Hospital (GWUH) are provided. A total of 95 participants at GWUH were enrolled. The mean age was 36.29 years, 65.3% were female, and 69.5% identified as Black. Unmet social needs were frequently identified in finances (43.2%), food insecurity (37.9%), and housing (29.5%). Past medical history of anxiety and depression were found in 46.3% and 41.1% of study participants, respectively. Moderate- to high-risk cannabis use was present in 40.0% of the participants. Opioids were administered to 20.0% of eligible patients during their ED visit, and 3.2% were discharged with an opiate prescription. Thirty days following the index visit, 12.6% returned to the ED. At 12 months, 25.3% have had at least one additional ED visit.

Conclusions
Adults presenting to the ED with recurrent abdominal pain and no structural cause are predominantly young, female, and from minoritized populations. Comorbidities, including anxiety and depression, are common among eligible patients, as well as food insecurity and financial distress. Repeat ED visits, CT scans, and opioid prescriptions are frequent, yet structural causes are rarely identified. Many eligible patients additionally engage in moderate- to high-risk substance use, particularly with cannabis. Identification of key risk factors may inform targeted interventions to improve outcomes in patients experiencing DGBIs.

Unmasking the Mystery: Outcomes of Recurrent Abdominal Pain Without Structural Cause in U.S. Emergency Departments

Background

Angiotensin-converting enzyme inhibitors (ACEI) are among the most prescribed class of antihypertensives worldwide. ACEIs influence carcinogenesis through suppression of vascular endothelial growth factor (VEGF), a key mediator of tumor angiogenesis. Animal models and in vitro studies show ACEIs inhibit tumor growth and angiogenesis independent of angiogenesis II type 1 receptor blockade, and reduced VEGF levels in tumor tissue. However, large-scale real-world evidence on site-specific cancer risks associated with ACEI use is limited. This study evaluated the association between ACEI use and incident solid tumors, including breast, colorectal, and lung cancers, in a large hypertensive population. 

Methods

This retrospective cohort study used the TriNetX Research Network, a global federated network of de-identified electronic health records from over 92 healthcare organizations, encompassing > 100 million patient charts (2003-2024). Adults aged ≥ 40 years with a history of hypertension and ≥ 2 prescriptions for an ACEI (exposure group) or a non-ACEI antihypertensive (control group) were included. The index event was the second prescription. Patients with prior cancer diagnoses were excluded. Outcomes were new diagnoses of solid tumors (ICD-10 C00-C80), breast cancer (C50), colorectal cancer (C18-C20), and lung cancer (C34) occurring ≥ 90 days post-index to reduce confounding. Propensity score matching (1:1) used 11 covariates, including age, sex, race/ethnicity, BMI, smoking, type 2 diabetes, and chronic kidney disease. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). 

Results

A total of 4,715,467 ACEI users and 6,363,948 non-ACEI users met inclusion criteria; after matching, 4,455,986 patients remained in each cohort. Breast cancer occurred in 51,069 ACEI users vs 43,255 non-ACEI users, colorectal cancer in 34,104 vs 26,037, and lung cancer in 56,484 vs 42,775. ACEI use was not associated with overall solid tumor risk (HR 1.005, 95% CI: 1-1.009), but breast cancer risk was reduced (HR 0.934, 95% CI: 0.922-0.946; p<0.0001), whereas colorectal cancer (HR 1.04, 95% CI: 1.024-1.057; p<0.0001), and lung cancer (HR 1.034, 95% CI: 1.021-1.047; p<0.0001) risks were significantly higher.

Conclusion

ACEI use was associated with site-specific cancer risks, suggesting tissue-dependent effects of renin-angiotensin system modulation. The protective breast cancer effect may reflect anti-angiogenic or estrogen-mediated mechanisms, whereas the increased colorectal and lung cancer risks may involve inflammatory or bradykinin-related pathways. These findings warrant mechanistic studies and may inform cancer surveillance strategies and antihypertensive prescribing decisions. Evaluating whether these associations differ by sex or race will be crucial for equitable screening recommendations.



ACE Inhibitors Show Site-Specific Cancer Risks: A Multi-Center Retrospective Study

Abstract Title 
Neurological Symptom Mapping for Acute Ischemic Stroke - A Novel Tool for Predicting Occlusion Location
Jean Bernard Salloum, Tarek Belhadad, Matthew Dinh, Rocky Rafi, Arshan Halkor, Ahmed Pasha, Dr. John Ashurst 

Background 
Timely stroke localization is critical for effective treatment; however, CTA—the current standard for identifying vessel occlusions—has accessibility and diagnostic limitations. Only 39% of frontier hospitals have 24-hour CT access, and over 20% of the population lives more than an hour from advanced stroke centers. Rural patients are half as likely to receive thrombolytics and one-third less likely to undergo thrombectomy than urban patients. Even with CTA available, renal impairment, patient stability, and motion artifacts limit efficacy. To address this, we developed a questionnaire with an embedded algorithm that translates overlooked 
clinical signs into stroke localization. As a non-imaging tool, our tool may support rapid diagnostic and treatment decisions when CTA is delayed or inconclusive. 

Methods 
To construct a clinically grounded model for ischemic stroke localization, we integrated major neurovascular territories, clinical syndromes, and symptoms into a stroke database. Validation was performed using reputable medical textbooks corroborated with data from peer-reviewed literature. This provided a framework to program our software - encoded with a structured clinical questionnaire and algorithm that predicts ischemic stroke locations. 

To evaluate accuracy of the algorithm, we curated a validation dataset from published peer reviewed case reports (2000–present). Inclusion criteria for cases required documentation of at least two focal neurological signs and confirmatory imaging findings (CT or MRI). 

We implemented a triple-blind protocol for testing to minimize bias: 
• Researcher A extracted clinical data and imaging results from reports. 
• Researcher B entered anonymized clinical data into the algorithm. 
• Researcher C analyzed algorithm predicted stroke locations as compared to imaging confirmed locations.

Results 
The stroke database included 21 ischemic strokes with characteristic symptomology. We identified 103 potential case reports for algorithm testing, of which 77 met inclusion criteria. 
Regarding major vessel territories, such as the MCA, ACA, PCA, ICA and Basilar Artery, the model demonstrated an average sensitivity of 97.0% and specificity of 78.6%. For each of their respective sub-branches, an average sensitivity of 87.0% and specificity of 90.3% was achieved. Of note, lacunar infarcts showed a sensitivity of 100% and specificity of 90.9%.

Conclusion 
Our model demonstrated high sensitivity for major vessel strokes and strong specificity for sub-branch level infarcts. Notably, it accurately detected deep, diagnostically challenging infarcts such as brainstem or lacunar strokes with consistent reliability. These findings support the model's potential to enable early and accurate stroke localization using physical exam findings, which may assist in triage and initiating treatment in settings with limited imaging access or ambiguous 
findings.

Neurological Symptom Mapping for Acute Ischemic Stroke - A Novel Tool for Predicting Occlusion Location

Background
Preterm labor is the leading cause of infant mortality and morbidity worldwide, yet no pharmacological treatments currently exist to combat it. Although potentially effective therapies exist to suppress undesirable uterine contractions, these drugs often transport across the placental barrier, leading to adverse consequences on the developing fetus. Formulation strategies to limit fetal exposure may enable the safe and effective use of currently approved drugs for the prevention of preterm birth. Poly(lactic-co-glycolic) acid (PLGA) is a biocompatible copolymer that is used in a variety of drug formulations and in ‘dissolvable’ sutures. We hypothesize that optimally sized PLGA particles formulated with an anti-tocolytic will limit placental transport and suppress uterine contractions.
Methods
Therefore, we synthesized PLGA particles loaded with cargo and tested two formulations via an oil-in-water emulsion fabrication technique. One formulation used dichloromethane (DCM) with polyvinyl alcohol (PVA), and the other used ethyl acetate (EtAc) with D-α-tocopheryl polyethylene glycol succinate (Vitamin E-TPGS); both have been reported to successfully prepare PLGA particles in the target diameter range. Further studies to prove model translatability were performed, including kinetic release using two common tocolytics (indomethacin and nifedipine), in-vivo biodistribution, and ex-vivo experiments using murine uterine strips.
Results
The resulting EtAc/Vit E-TPGS emulsion produced average particle diameters of 1350 (± 64.5) nm (PDI: 0.3037). However, this formulation was more polydisperse compared to the DCM/PVA emulsion with average particle diameters of 1251 (±300.4) nm (PDI: 0.2020) that also exhibited acceptable day-to-day variability, ranging from 1137 to 1734 nm. We showed successful drug encapsulation in the absence of variation in particle size for indomethacin 1267 (± 82.72) nm and nifedipine 1142 (± 1.155) nm. Both tocolytics show the capacity for sustained release with total cumulative release of indomethacin (30 days) and nifedipine (24 days). In-vivo biodistribution studies demonstrate localization of the targeted PLGA particles to the uterus, and ex-vivo studies present a clear effect of the tocolytic drug after loading. 
Conclusion
Through optimized physiochemical characteristics and clinical translation, this formulation has the potential to effectively inhibit preterm labor contractions in a novel delivery system. Next steps include decoration of particles with a uterine-selective antibody corona. The function of drug-loaded PLGA particles to inhibit uterine contractions will be tested in a model system with human tissue in organ baths. Results of these studies will be used to refine the drug to PLGA ratio and the PLGA characteristics to optimize efficacy and toxicity.

Developing a Nanoparticle Drug Delivery System to Treat Preterm Labor

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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Biomarker Analysis of Mechanically Ventilated Adults using Propofol or Dexmedetomidine