United States

Introduction: Mutations in the ABCG8 gene are classically associated with sitosterolemia, a rare autosomal recessive disorder characterized by excessive intestinal absorption and decreased biliary excretion of plant sterols. With only 100 cases of sitosterolemia worldwide, hemolytic anemia has an estimated occurrence of 6.8%. Stomatocytosis, macrothrombocytopenia, and increased osmotic fragility of RBC were described, hypothetically caused by the abnormal incorporation of plant sterols into RBC and platelet membranes due to elevated plasma levels, altering membrane composition
Case Presentation: A 32-year-old Yemeni woman with IBS in remission, presented with worsening fatigue, dizziness, headaches, and regular menstrual cycles with moderate flow. On initial evaluation:
Microcytic anemia with beta-thalassemia trait. Iron deficiency was excluded.
Peripheral blood smear showed teardrop cells, schistocytes, elliptocytes, basophilic stippling and giant platelets with high mean platelet volume. 
Undetectable haptoglobin, high LDH and reticulocyte count, but negative Direct Coombs and moderately increased osmotic fragility.
Abdominal ultrasonography showed moderate splenomegaly. 
Anemia persisted despite folic acid, iron and corticosteroids oral treatment. A comprehensive hereditary HA panel identified a heterozygous mutation in the ABCG8 gene. Transient improvement was achieved with intravenous iron infusions and 2 cycles of intravenous immunoglobulin. Her hemoglobin declined accompanied by worsening exertional dyspnea and palpitations when she was pregnant. Following uneventful delivery, the patient&#39;s hemoglobin stabilized at 9 g/dL. Postpartum PBS showed a few tear drops and schistocytes, hypo and polychromasia, micro and anisocytosis. She remains on oral folate and iron and is monitored outpatient.
Discussion: To our knowledge, this is the first documented case of a heterozygous ABCG8 mutation presenting without any of the characteristic clinical features of sitosterolemia. The presence of a heterozygous ABCG8 mutation raises suspicion for a genetic contribution to this patient’s hemolytic anemia, especially in the absence of other identifiable causes. A definitive link cannot be established without further studies, but this mutation remains the most likely contributor.
Conclusion: This case highlights the need to consider rare genetic mutations in unexplained anemia and the importance of ongoing research in such presentations, particularly in treatment-resistant cases where anemia does not respond to ongoing steroid therapy.


AMA Research Challenge 2025 

Cracking the ABCG8 Code: The Mystery of Hemolytic Anemia

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Introduction: Mutations in the ABCG8 gene are classically associated with sitosterolemia, a rare autosomal recessive disorder characterized by excessive intestinal absorption and decreased biliary excretion of plant sterols. With only 100 cases of sitosterolemia worldwide, hemolytic anemia has an estimated occurrence of 6.8%. Stomatocytosis, macrothrombocytopenia, and increased osmotic fragility of RBC were described, hypothetically caused by the abnormal incorporation of plant sterols into RBC and platelet membranes due to elevated plasma levels, altering membrane composition
Case Presentation: A 32-year-old Yemeni woman with IBS in remission, presented with worsening fatigue, dizziness, headaches, and regular menstrual cycles with moderate flow. On initial evaluation:
Microcytic anemia with beta-thalassemia trait. Iron deficiency was excluded.
Peripheral blood smear showed teardrop cells, schistocytes, elliptocytes, basophilic stippling and giant platelets with high mean platelet volume. 
Undetectable haptoglobin, high LDH and reticulocyte count, but negative Direct Coombs and moderately increased osmotic fragility.
Abdominal ultrasonography showed moderate splenomegaly. 
Anemia persisted despite folic acid, iron and corticosteroids oral treatment. A comprehensive hereditary HA panel identified a heterozygous mutation in the ABCG8 gene. Transient improvement was achieved with intravenous iron infusions and 2 cycles of intravenous immunoglobulin. Her hemoglobin declined accompanied by worsening exertional dyspnea and palpitations when she was pregnant. Following uneventful delivery, the patient's hemoglobin stabilized at 9 g/dL. Postpartum PBS showed a few tear drops and schistocytes, hypo and polychromasia, micro and anisocytosis. She remains on oral folate and iron and is monitored outpatient.
Discussion: To our knowledge, this is the first documented case of a heterozygous ABCG8 mutation presenting without any of the characteristic clinical features of sitosterolemia. The presence of a heterozygous ABCG8 mutation raises suspicion for a genetic contribution to this patient’s hemolytic anemia, especially in the absence of other identifiable causes. A definitive link cannot be established without further studies, but this mutation remains the most likely contributor.
Conclusion: This case highlights the need to consider rare genetic mutations in unexplained anemia and the importance of ongoing research in such presentations, particularly in treatment-resistant cases where anemia does not respond to ongoing steroid therapy.


poster

Background: Spanish-speaking patients face persistent barriers to health information due to limited availability and poor readability of online Spanish-language educational resources. Generative artificial intelligence (AI) presents a promising solution to address this gap. This study modeled a practical, scalable AI intervention to generate accessible Spanish-language orthopedic educational materials that institutions can readily adopt to address language disparities.

Methods: We conducted a cross-sectional analysis of the 203 U.S. academic orthopedic institutions listed on the 2024 ERAS directory to assess the availability of Spanish-language patient resources on each institution’s website. We then modeled an AI intervention using 30 articles from [Institution]’s orthopedic patient library using ChatGPT-4o, as currently no Spanish resources are available, with the goal of improving readability and translation quality. Prompt development was performed using proven prompt engineering strategies including context/persona building, few-shot prompting, structured chain prompting, and iterative testing until satisfactory outputs were achieved. Readability was assessed using validated readability tests in both languages. A modified DISCERN tool scored by two Spanish-speaking orthopedic surgeons assessed content and translation quality. Scores before and after ChatGPT intervention were compared with paired t-tests while correlation between changes in reading grade level and quality was assessed with Pearson’s correlation (p<0.05).

Results: Of the 203 institutions included in our search, 142 (70%) provided patient educational resources in English on their websites. Of these 142 institutions, only 17 (12%) provided Spanish-language resources. The cumulative average reading grade level of our model’s original articles was 10.7±2.3 in English and 10.1±1.7 in Spanish (“original” Spanish articles were approximated with Google Translate). ChatGPT significantly reduced the reading level in both languages, achieving an average of 6.9±1.5 in English (p<0.01) and 6.8±1.2 in Spanish (p<0.01). ChatGPT-generated Spanish articles demonstrated improvement in DISCERN content quality scores according to Grader 1 (p<0.05), and noninferiority according to Grader 2 (p=0.37). The quality of translation was scored significantly higher by both graders for ChatGPT content (p<0.05). No significant negative correlation was observed between improvements in readability and content quality scores for either grader (Grader 1: r=0.34, p=0.23; Grader 2: r=0.12, p=0.67).

Conclusion: Our model demonstrates the effectiveness of AI for enhancing the accessibility, readability, and quality of online Spanish-language education materials, representing a cost-effective and practical approach institutions may implement in real-time to address language barriers and promote equity in patient education. 


Prompt engineering for health equity: A modeled AI intervention to improve online Spanish-language orthopedic patient resources

Background
Statins are important for cardiovascular disease prevention, yet muscle toxicity leading to myopathy is a common adverse effect.¹ Statin-induced myopathy presents as muscle pain or weakness with elevated creatine kinase in the context of statin therapy. Our objectives were to: 1) Recognize the typical incidence and duration of statin myopathy. 2) Describe the utility of SLCO1B1 genetic testing as a personalized medicine tool to predict statin myopathy.

Case Presentation
A 73-year-old female was initiated on statin therapy in 2012. She developed leg pain and weakness after starting pravastatin, which persisted despite trials of atorvastatin and an unknown third statin, prompting discontinuation. Despite statin cessation, her lower extremity weakness progressed to involve her shoulders, upper arms, and core. Physical therapy provided mild strength improvement. Trials of methylprednisolone, hydroxychloroquine, and prednisone were discontinued due to side effects. Examination in January 2025 revealed weakness in the left proximal upper limb and bilateral hip flexors, with intact distal and proximal strength elsewhere. MRI of the thighs demonstrated diffuse fatty infiltration and asymmetric muscle edema. Serologic testing revealed an ANA titer of 1:1280 (cytoplasmic pattern), elevated Anti-SSA antibodies (107.68 units/mL), and myositis-specific antibodies were negative. Quadriceps biopsy demonstrated frequent atrophic fibers with mixed myopathic and neurogenic changes, along with scattered T lymphocyte infiltration. 

Discussion
Statin myopathy affects ~27.8% of users and commonly leads to medication intolerance.2 Simvastatin 40 mg has the highest incidence (50%), while fluvastatin XL 80 mg and rosuvastatin 10 mg are lowest (8% and 10.8% respectively). Symptoms typically resolve within 2.3 months of cessation, unlike this patient’s prolonged course.3 Statins regulate cholesterol metabolism by inhibiting HMG-CoA reductase after entering hepatocytes through OATP1B1 transporters encoded by the SLCO1B1 gene.1 The study SLCO1B1 Genotype Informed Statin Therapy found that ~15% of patients have the variant SCLO1B1, which results in increased systemic statin concentration and myopathy risk.4 Individuals could use an over-the-counter test called Statin Smart to determine if they had a genetic predisposition to myopathy; though data reporting has been criticized as inaccurately high.5 Providers may order SLCO1B1 testing, though insurance coverage is inconsistent. While this patient’s inflammatory myopathy was likely statin-induced and potentially preventable with genetic screening, she might also possess an inherent predisposition to myopathy. Perhaps in the future, personalized medicine will be more accessible, helping patients better understand their risk of medication side effects like statin myopathy.

Statin Myopathy: Understanding Its Incidence and the Utility of Personalized Medicine to Predict It

Background:
Acute ischemic stroke is a time-sensitive emergency, with thrombolysis guided by strict American Heart Association/American Stroke Association (AHA/ASA) protocols emphasizing door-to-needle metrics. Tenecteplase (TNK) is widely accepted as an alternative to alteplase in eligible patients. However, Type A aortic dissection remains an absolute contraindication to thrombolytics due to risk of hemorrhage or hemodynamic collapse. This report describes a rare case of silent aortic dissection in a young woman treated with TNK for presumed MCA syndrome, highlighting the challenges of protocol adherence, diagnostic uncertainty, and the need to reevaluate stroke pathways for atypical presentations.

Case Presentation:
A 45-year-old woman with hypertension was found unresponsive after a witnessed seizure. EMS administered midazolam, and upon arrival she was somnolent with a GCS 6, leftward gaze deviation, right hemiplegia, and global aphasia (NIHSS 19). Non-contrast head CT was negative, and with a last known well time under 4.5 hours, she met criteria for TNK, which was administered.

Within 30 minutes, she became hypotensive and unresponsive. Bedside ultrasound confirmed tamponade physiology; emergent pericardiocentesis and 1 g tranexamic acid (TXA) were administered to reverse TNK. CTA revealed extensive Stanford Type A aortic dissection involving arch vessels. She underwent ascending aortic grafting.

Postoperative MRI revealed multifocal infarcts in bilateral cerebral and cerebellar hemispheres, basal ganglia, thalami, and watershed zones, consistent with embolic and hypoperfusion etiologies. Despite aggressive care, she was transitioned to hospice.

Discussion:
This case underscores the difficulty of diagnosing painless aortic dissection presenting as isolated stroke without typical features such as chest pain or pulse deficits. This is particularly rare in younger patients, as aortic dissections commonly affect men over 50. Subtle or silent dissections account for approximately 6.4% of cases and carry increased mortality.

AHA/ASA guidelines contraindicate thrombolysis in dissection, but without suspicion, screening via CTA is not routine and would delay reperfusion therapy. While alteplase use in dissection-related strokes is reported, literature on TNK with successful TXA reversal is extremely limited. MRI confirmed true infarction, supporting the decision to thrombolyse. In hindsight, dissection-related hypoperfusion likely outweighed any benefit of thrombolysis.

Future stroke pathways may consider optional chest imaging in atypical presentations. However, indiscriminate imaging risks compromising treatment times. The balance between speed and diagnostic breadth remains delicate. This case illustrates the tension between guideline adherence and diagnostic uncertainty. Despite catastrophic outcome, thrombolysis was appropriate. It highlights the limitations of current protocols in detecting rare but fatal mimics and underscores the need for flexible, real-time clinical judgment.

Stroke by the Book, Dissection in the Shadows: A Case of TNK in a Silent Type A Aortic Catastrophe

Background
Neuropsychiatric systemic lupus erythematosus (NPSLE)—also known as lupus cerebritis—is a severe manifestation of systemic lupus erythematosus (SLE) that affects the central nervous system. Its clinical spectrum ranges from mild symptoms, such as headache and cognitive dysfunction, to severe complications like seizures, psychosis, and stroke. Reported prevalence varies widely (37%–95%) depending on diagnostic criteria. This case report describes a rare instance of NPSLE complicated by supra-refractory status epilepticus (SRSE), successfully treated with complete remission—an outcome rarely reported.
Major central nervous system involvement in SLE is associated with significantly higher mortality, particularly in cases of treatment-resistant seizures such as SRSE. SRSE carries a mortality rate approximately four times that of standard status epilepticus, and when compounded by NPSLE, overall mortality may exceed 50%.¹ ² Given these risks, maintaining a high index of clinical suspicion and initiating early, targeted therapy—after excluding non-SLE causes—is critical.

Case Presentation
A 23-year-old woman with SLE complicated by class V lupus nephritis on dialysis and an unclear treatment history presented with status epilepticus and hypertensive emergency. Infectious and other non-SLE causes were swiftly ruled out. Prompt brain MRI revealed high signal intensity in the parietal and frontal lobe gyri and subcortical white matter of the bilateral cerebellum, consistent with NPSLE. Her clinical course was further complicated by SRSE, significantly increasing the risk of mortality.
Aggressive disease-specific treatment was initiated given the high associated mortality. This included high-dose corticosteroids, mycophenolate mofetil, plasma exchange, and multiple antiepileptic drugs. The patient gradually improved and ultimately achieved complete remission. She was discharged seizure-free and without neurological deficits.

Discussion
This case illustrates a rare but treatable presentation of NPSLE-induced SRSE. Early recognition and prompt multimodal intervention were key to the favorable outcome. Burst suppression with antiepileptic therapy controlled SRSE, while prompt immunosuppression and plasma exchange dampened B-cell activation and inflammatory cytokines such as interleukin-6. This case underscores the importance of early diagnosis due to a high index of suspicion, exclusion of alternative causes, and immediate initiation of immunosuppressive therapy to improve survival and outcomes in life-threatening NPSLE.

Neuroimmunologic Thunderstorm: Super-Refractory Status Epilepticus in Neuropsychiatric Systemic Lupus Erythematosus

Abstract Title: 
Why aren’t Women Choosing Orthopaedic Surgery? Barriers to Gender Diversity in Orthopaedics as Perceived by Current U.S Medical Students

Background:
Orthopaedic surgical residencies are among the least gender diverse, trailing behind other surgical specialties with only 15% of trainees identifying as female, compared to urology (25%), neurosurgery (18%), and otolaryngology (36%). While research detailing the extent of the gender gap in orthopaedic surgery exists, there is a lack of diversity in representation from allopathic, osteopathic, and LGBTQ+ students regarding barriers experienced during specialty consideration. Our goal was to investigate their perceived barriers. 

Methods:
An anonymous 27-question RedCap survey was distributed by 81 U.S. medical schools (20 osteopathic, 61 allopathic). This assessed students’ perceptions of factors like patient care, practice duties, training, and life outside of medicine. Anecdotal experiences were welcomed with open text boxes. 

Results:
245 total responses were collected. 177 (69%) self-identified as female, 69 (27%) as male, 5 (2%) as non-binary, and 2 (<1%) chose not to disclose. Orthopaedics was the top choice for 24% (60/254) of students, 26% (65/254) were previously interested, and 37% (95/254) were never interested. More females considered ‘physical strength required’ and ‘culture of specialty’ as negative aspects of orthopaedic surgery, while more males identified both as positive. Open responses cited access to research and mentorship as a barrier for 18% (23/130) of which 69% (16/23) were female. 

Conclusion:
Our results highlight the persistent diversity gap within orthopaedics, despite evidence that students identifying as male and female are both equally concerned about the toll a career in orthopaedics could have on their future family planning. This study additionally revealed specific barriers that diverse medical students face influencing their career plans – most notably access to research and mentorship. Furthermore, these data suggest that orthopaedics as a field is no longer the limiting factor, and instead diverse medical students are self-selecting away from the field based on their perceived barriers elucidated above. We recommend more expansive and inclusive efforts to further narrow the gender and diversity gap within the field – specifically by improving access to shadowing and mentorship for students in their preclinical training. 


Why Aren’t Women Choosing Orthopaedic Surgery? Barriers to Gender Diversity in Orthopaedics as Perceived by Current US Medical Students

Objectives: The rise in popularity of electronic cigarettes (e-cigarettes) among U.S. adolescents in the past decade is cause for concern due to the device’s novelty and potential long-term health effects. In response to the concerns, a federal Tobacco 21 law (T21) was passed to raise the minimum age for purchasing tobacco products and e-cigarettes from 18 to 21. This study aims to determine the effectiveness of this federal legislation in reducing e-cigarette usage rates among middle and high school students.

Methods: This study utilized data from both the 2019 and 2020 National Youth Tobacco Survey (NYTS) to examine changes in vaping among 54,575,023 middle and high school students after passage of the federal T21. Odds ratios and logistic regression models were used to assess the association between vaping prevalence rates and the policy change while controlling for perceived harm and addictiveness of e-cigarettes. 

Results: Following the implementation of the federal T21 in December 2019, adolescents were significantly less likely to use e-cigarettes, with the odds of current use reduced by 29% (OR=0.71, with CI [0.58-0.86] and p-value=.001). During the same period, there was an increase in both perceived harm and addictiveness from 71% to 79% and 61% to 66%, respectively. Perceived harm was associated with lower e-cigarette use (OR=0.27 with CI [.25 to .30] and p-value <.0001) whereas perceived addictiveness had a positive association with use (OR=1.12 with CI [1.01 to 1.24] and p-value= .033). 

Conclusions: Federal legislation such as increasing the minimum age of sale of tobacco and nicotine products is an effective strategy in reducing and preventing tobacco and e-cigarette use among adolescents. 


Evaluating the Impact of the Federal Tobacco 21 Legislation on Adolescent E-Cigarette Use and Risk Perceptions 

The global rise in obesity has led to a parallel increase in type 2 diabetes mellitus (T2DM), a chronic disease with significant morbidity and economic burden. While bariatric surgery is widely accepted as an effective treatment for obesity and established T2DM, its potential role as a preventive intervention in high-risk obese individuals remains underexplored. Emerging evidence suggests that early metabolic surgery, particularly in prediabetic patients, may significantly reduce the progression to T2DM by improving insulin sensitivity, enhancing beta-cell function, and promoting long-term glycemic stability. This project aims to explore the preventative benefits of early bariatric surgery through a comprehensive review of current literature. Articles from Embase and Pubmed spanning from early 2015 to the most recent clinical trials were collected following a systematic approach using the Prisma Protocol guidelines. Different modalities of bariatric surgery and how the procedure affected patients’ metabolic comorbidities were reviewed. By compiling and analyzing available data, this project seeks to determine whether earlier surgical intervention offers meaningful benefits in reducing T2DM risk. Bariatric surgery can be effective in managing and even reversing T2DM; however, the optimal timing of surgery for maximum preventive benefit is still under investigation. It was concluded that bariatric surgery significantly increased life expectancy in patients with T2DM compared with patients who managed their T2DM with pharmacologic agents alone. There is strong evidence of its benefits even when T2DM is already well established. By shifting the focus from treatment to prevention, this research highlights the clinical and public health value of earlier surgical referral for obese patients at high risk for T2DM.

Early Bariatric Surgery in the Prevention of Type 2 Diabetes Mellitus in Obese Individuals

Background
The increasing convenience of access to online information may lead to patient consumption of incomplete or misleading information about ocular problems. The purpose of this study is to evaluate the quality and accuracy of videos on glaucoma treatment options.
Methods
A search of “glaucoma” and “eye pressure” combined with “treatment” or “cure” was performed for Facebook (FB) and YouTube (YT) videos. YT videos with at least 25,000 views and 25 views per day and top FB videos with at least 1,000 views were included. Videos were evaluated using a modified Currency, Relevance, Authority, Accuracy, and Criteria (CRAAP) metric.
Results
74 YT and 19 FB videos were included. Of the YT videos, 74% defined glaucoma, 65% discussed untreated disease course, 64% stated treatment goals, 84% described treatment options, 17% discussed treatment risks, and 15% contained misinformation. Of the FB videos, 66% defined glaucoma, 47% discussed untreated disease course, 34% stated treatment goals, 68% described treatment options, 0% discussed treatment risks, and 18% contained misinformation. Higher accuracy and increased quantity was seen for educational videos containing “glaucoma treatment” on both platforms.
Conclusion
Commonly utilized YT and FB videos may lack important information and/or promote misinformation.


Quality Analysis of YouTube and Facebook Videos for Glaucoma Treatment Options

Background: Complementary health approaches (CHAs) are increasingly integrated into whole-person care strategies aimed at enhancing well-being across a range of clinical settings. While patient engagement with CHAs is shaped by multiple cognitive and behavioral factors, emerging research suggests that subconscious processes may play a critical role. Subconscious connectedness—defined as the extent to which an individual’s conscious mind interacts with non-conscious mental processes in daily life—offers a novel cognitive dimension relevant to health behavior. Despite its theoretical relevance, little is known about how
subconscious connectedness influences CHA use, satisfaction, and expectations. This study examined whether levels of subconscious connectedness, as measured by the Thought Impact Scale (TIS), are associated with CHA engagement and beliefs in a nationally representative sample of U.S. adults.

Methods: We conducted a cross-sectional online survey of 3,022 U.S. adults in 2024 using quota sampling aligned with U.S. Census benchmarks to ensure demographic
representativeness. Subconscious connectedness (SC) was measured via the 17-item Thought Impact Scale (TIS) and categorized into quartiles. Outcomes included past-year use of complementary health approaches (CHAs), self-reported favorability of prior CHA experiences, and expected benefit from CHA modalities not previously used. CHA engagement was assessed both overall and by category (nutritional, physical, psychological, system based, and combined psychological/physical) as well as by individual modality. Multivariate logistic
regression models estimated adjusted odds ratios (AORs) for each outcome, controlling for demographic, socioeconomic, and health-related variables.

Results: Higher levels of subconscious connectedness were significantly associated with greater engagement in complementary health approaches. Compared to the lowest TIS quartile, participants in the highest quartile had increased odds of past-year CHA use (AOR = 3.62, 95% CI: 2.14-6.14), favorable CHA experiences (AOR = 2.20, 95% CI: 1.32-3.68), and high expectations of benefit from modalities not yet tried (AOR = 2.54, 95% CI: 2.00-3.21). A clear dose-response pattern was observed, with odds of CHA engagement increasing progressively across TIS quartiles. These associations held across CHA categories—nutritional, physical, psychological, system based, and combined psychological/physical—with the strongest effects
seen for psychologically oriented modalities.

Conclusion: Subconscious connectedness is positively associated with CHA utilization, satisfaction, and expectations among U.S. adults. These findings support the inclusion of subconscious cognitive traits in behavioral health models and suggest opportunities for improving patient-centered care strategies through cognitive profiling.

High Subconscious Connectedness is Associated with Greater Use, More Favorable Experience, and Higher Expectations of Complementary Health Approaches in the U.S. Adult Population

Intro: Our study examines the rate of Emergency Department (ED) visits for asthma in Mariposa County and its relationship to days unhealthy to sensitive groups, median air quality index (AQI), and Ozone (O3) days.

Methods: Annual AQI reports for each county from 2015 to 2022 were obtained from the United States Environmental Protection Agency website. The yearly age-adjusted asthma ED visit rate from the California Health and Human Services Open Data Portal website. California’s entirely rural counties were
determined by the Public Policy Institute of California’s Rural California Fact Sheet. Counties with incomplete data sets were excluded. Variables were plotted on Microsoft Excel, and linear regression was calculated with an R2 of 0.15 used to define significance.

Results: The yearly age-adjusted asthma ED visit rate was trended from 2015 to 2022, showing a decrease in visits from 2019 to 2021 with a subsequent increase from 2021 to 2022. There is no meaningful correlation between annual age adjusted ED visit rate and days unhealthy for sensitive groups, R2=0.05.

Conclusion: Further studies are required to examine the numerous socioeconomic and environmental factors related to rural asthma ED visits in California.

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