United States

Background: Dysregulation of mRNA localization to neuronal dendrites and loss of neuronal activity-induced localized mRNA translation at synapses is a common cause of neurodevelopmental disorders such as Fragile X syndrome (FXS). FXS is the most prevalent cause of inherited autism and learning disability, caused by the mutation of an RNA-binding protein, Fragile X messenger ribonucleoprotein (FMRP). FXS is characterized by widespread disruptions in hippocampal memory circuitry as well as abnormalities in dendritic spine (where synapses are formed) density and morphology. FMRP binds to and regulates ~15-20% of mRNAs crucial for synaptic remodeling and neurodevelopment. It is not clearly understood how FMRP target synaptic mRNAs are regulated across different cell types in the brain that might explain the wide range of neuro-cognitive deficits in FXS. We hypothesize that, in the absence of FMRP, cell-specific dysregulation of FMRP target mRNAs underlie the wide range of functional implications in FXS pathophysiology in FMRP-null mice (Fmr1-/Y). 

Methods: We have shortlisted 12 high-confidence putative FMRP-target mRNAs identified previously by high-throughput sequencing. These 12 mRNAs are localized to the dendrite-enriched hippocampal neuropil layer, are differentially expressed in hippocampal cell types and encode proteins critical for synaptic function. To examine the spatial organization of these FMRP mRNA targets in vivo, we have used highly multiplexed single molecule in situ hybridization (HiPlex smFISH) and high-resolution microscopy in juvenile WT and Fmr1-/Y mouse hippocampus. We have quantified mRNA abundance, fluorescent puncta area distribution (proxy measure of copy number state) and their co-distribution (proxy of RNA-RNA coassembly) in CA1 and CA2 neuronal dendrites, two anatomically &amp; functionally distinct cell types relevant to FXS phenotypes. To investigate the dendritic spine abnormality in CA1 and CA2 dendrites, we used golgi-cox impregnation. 

Results: Our preliminary data analyzing a subset of three FMRP-target mRNAs (Adcy1, Psd and Dlg4) in CA1 and CA2 dendrites show a trending decrease in mRNA abundance in CA1 but not in CA2 dendrites of Fmr1-/Y compared to WT. Further analysis is ongoing for the rest of the dataset. Interestingly, these findings also correlate with our ongoing analysis of spine density that shows no significant difference in CA2 dendrites (WT vs FMRP KO) and an observed increased spine density phenotype in FMRP KO CA1 dendrites compared to WT mice.

Conclusion: Integrated with the recent evidence, these data suggest that FMRP deficiency has cell-specific cellular and molecular alterations that would possibly correlate with the functional implications associated with these circuits in FXS pathology.

AMA Research Challenge 2025 

Multiplex smFISH to study cell-specific RNA dysregulation in a mouse model of 
Fragile X Syndrome

This annual scholarly program is designed to provide undergraduate students with a structured introduction to laboratory research within their home institution. Participants are matched with principal investigators and mentored by graduate students, enabling them to engage directly in ongoing research projects and develop foundational skills in scientific inquiry.

Indicium 2025

This annual scholarly program is designed to provide undergraduate students with a structured introduction to laboratory research within their home institution.
This year’s cohort focused on projects in the field of longevity science, exploring diverse topics such as bioinformatics, molecular biology, and cognitive science.

Background: Dysregulation of mRNA localization to neuronal dendrites and loss of neuronal activity-induced localized mRNA translation at synapses is a common cause of neurodevelopmental disorders such as Fragile X syndrome (FXS). FXS is the most prevalent cause of inherited autism and learning disability, caused by the mutation of an RNA-binding protein, Fragile X messenger ribonucleoprotein (FMRP). FXS is characterized by widespread disruptions in hippocampal memory circuitry as well as abnormalities in dendritic spine (where synapses are formed) density and morphology. FMRP binds to and regulates ~15-20% of mRNAs crucial for synaptic remodeling and neurodevelopment. It is not clearly understood how FMRP target synaptic mRNAs are regulated across different cell types in the brain that might explain the wide range of neuro-cognitive deficits in FXS. We hypothesize that, in the absence of FMRP, cell-specific dysregulation of FMRP target mRNAs underlie the wide range of functional implications in FXS pathophysiology in FMRP-null mice (Fmr1-/Y). 

Methods: We have shortlisted 12 high-confidence putative FMRP-target mRNAs identified previously by high-throughput sequencing. These 12 mRNAs are localized to the dendrite-enriched hippocampal neuropil layer, are differentially expressed in hippocampal cell types and encode proteins critical for synaptic function. To examine the spatial organization of these FMRP mRNA targets in vivo, we have used highly multiplexed single molecule in situ hybridization (HiPlex smFISH) and high-resolution microscopy in juvenile WT and Fmr1-/Y mouse hippocampus. We have quantified mRNA abundance, fluorescent puncta area distribution (proxy measure of copy number state) and their co-distribution (proxy of RNA-RNA coassembly) in CA1 and CA2 neuronal dendrites, two anatomically & functionally distinct cell types relevant to FXS phenotypes. To investigate the dendritic spine abnormality in CA1 and CA2 dendrites, we used golgi-cox impregnation. 

Results: Our preliminary data analyzing a subset of three FMRP-target mRNAs (Adcy1, Psd and Dlg4) in CA1 and CA2 dendrites show a trending decrease in mRNA abundance in CA1 but not in CA2 dendrites of Fmr1-/Y compared to WT. Further analysis is ongoing for the rest of the dataset. Interestingly, these findings also correlate with our ongoing analysis of spine density that shows no significant difference in CA2 dendrites (WT vs FMRP KO) and an observed increased spine density phenotype in FMRP KO CA1 dendrites compared to WT mice.

Conclusion: Integrated with the recent evidence, these data suggest that FMRP deficiency has cell-specific cellular and molecular alterations that would possibly correlate with the functional implications associated with these circuits in FXS pathology.

poster

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Background
Hantaviruses are fatal human pathogens that cause hemorrhagic fevers and are classified into either Old World or New World groups. They are primarily transmitted zoonotically from rodents to humans through the respiratory route, with no currently approved antivirals or widely available vaccines. The Old World Hantaan virus (HTNV), one of the first known hantaviruses, caused cases of hemorrhagic fever and severe pulmonary illness in over 3000 deployed United Nations troops during the Korean War. New World Sin Nombre virus (SNV) is endemic primarily to the United States. The mass spread of these two pathogens was initially prevented by the inability of the virus to spread directly between humans; instead, it spread only from rodent hosts to humans. The recent discovery of the New World Andes virus (ANDV), the first identified hantavirus to spread between humans, necessitates the systematic elucidation of cell tropism, infective potential, and the development of potent therapeutic agents.

Methods
In this study, we utilized human primary lung endothelial cells, various pluripotent stem cell-derived heart and brain cell types, and established human lung organoid models to evaluate the tropisms of Old World Hantaan (HTNV) and New World ANDV and Sin Nombre (SNV) viruses.

Results
ANDV exhibited broad tropism for all cell types assessed, suggesting that lung and heart comorbidities would increase mortality risk in the event of ANDV outbreaks. SNV readily infected pulmonary endothelial cells, while HTNV robustly amplified in endothelial cells, cardiomyocytes, and astrocytes. Human 3D distal lung organoids effectively modeled these differential tropisms. ANDV infection transcriptionally promoted cell injury and inflammatory responses, and downregulated lipid metabolic pathways in lung epithelial cells. Drug screening and pharmacotranscriptomics revealed that the host-directed small molecule compound urolithin B inhibited ANDV infection and restored cellular metabolism with minimal changes in host transcription.

Conclusion
Given the scarcity of academic BSL-4 facilities that enable in vivo hantaviral studies, this investigation presents advanced human cell-based model systems that closely recapitulate host cell tropism and responses to infection, thereby providing critical platforms to evaluate potential antiviral drug candidates.

Differential Tropisms of Old and New World Hantaviruses Influence Virulence and Developing Host-Directed Antiviral Candidates

Background
A machine learning model (MLM)-generated surgical risk score (SRS) was integrated into the electronic health record to automate real-time predictions of inpatient postoperative complications (POC). We hypothesized that with the integration of the SRS, complication rates would decrease.

Methods
Between 2018 and 2024, inpatients undergoing surgery during index hospitalizations were captured. Patients were dichotomized to “SRS-exposed” and “SRS-Non-exposed” based on whether the surgeon had access to the SRS. SRS-exposed patients were dichotomized to “high” or “low” risk SRS. The patient’s SRS was presented to the primary surgeon as a “Best Practice Advisory (BPA)” and InBasket message requiring acknowledgment. Patients were further split into pre- and post-implementation groups and analyzed based on type of surgery (open, laparoscopic, or robotic). Rates of severe POC (Clavien-Dindo Grade ≥3), return to the operating room, and mortality were recorded and compared using proportion tests.

Results
483 inpatients were deemed SRS-exposed. 260 were in the pre-implementation cohort and 223 in the post. Severe complication rates significantly decreased from 58.8% in the pre-implementation cohort to 46% for high-risk patients (p=0.029). In the high-risk open surgery group, complications significantly decreased from 61.5% to 46.6% (p=0.028). These trends were not observed in the SRS-Non-exposed cohort severe complication rates (37.2% to 39.4%, p=0.81). The rate of return to the operating room significantly decreased after implementation in the open high-risk group (17.6% v 5.5%, p=0.009). No significant differences were observed in minimally invasive surgery patients or mortality. 

Conclusion
Integration of a real-time, automated SRS resulted in a significant decrease in severe post-operative complications, especially in the high-risk group undergoing open operations. Utilization of the MLM SRS may improve clinical outcomes, optimization of medical care, and shared decision-making.

Implementation of A Real-Time, Automated, Artificial Intelligence Preoperative Risk Score Decreases Rate of Serious Postoperative Complications

Background
Left atrial enlargement (LAE) is a common feature in patients with aortic stenosis (AS) and may reflect chronic pressure overload and diastolic dysfunction. Left ventricular (LV) systolic dysfunction is a late and adverse development in AS. While LAE is associated with adverse cardiovascular outcomes, its relationship with LV systolic dysfunction in severe AS remains unclear. This study investigates whether LAE predicts impaired LV systolic function in patients with severe AS.

Methods
We retrospectively analyzed transthoracic echocardiograms (TTEs) performed from 1984 to 1998 at the University of California, Irvine. Severe AS was defined as an aortic valve peak flow velocity (AoPFV) ≥ 400 cm/s. LV systolic dysfunction was defined as fractional shortening (FS) < 25%. LAE was defined by American Society of Echocardiography guidelines as ≥ 40 mm in men or ≥ 38 mm in women (non-indexed), or ≥ 23 mm/m² when indexed to body surface area (BSA). Diagnostic performance of LAE for identifying systolic dysfunction was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results
Among 222 patients with severe AS, 31 had concurrent LV systolic dysfunction. LAE was significantly associated with systolic dysfunction. Systolic impairment occurred in 16.8% of patients with LAE versus 2.3% without (p = 0.013). Mean FS was lower in patients with LAE (36.2 ± 10.9%) compared to those with normal LA size (40.1 ± 9.3%, p = 0.047). In the BSA-indexed cohort, systolic dysfunction was observed in 18.7% with LAE vs. 2.0% with normal LA size (p = 0.003). LAE demonstrated high sensitivity (non-indexed: 96.8%, indexed: 95.8%) and NPV (non-indexed: 97.7%, indexed: 98.0%), but low specificity and PPV for detecting systolic dysfunction.

Conclusion
In patients with severe aortic stenosis, the absence of LAE is a strong predictor of preserved LV systolic function. LAE demonstrated high sensitivity and NPV for detecting systolic impairment, regardless of indexing. Given its ease of measurement, LA size may serve as a simple, non-invasive screening tool to preliminarily assess systolic function when advanced imaging is unavailable. These findings highlight a novel application of LA size as a potential indicator of preserved contractile performance in severe AS.

In Patients with Severe Aortic Stenosis, Normal Left Atrial Size Suggests Preserved Left Ventricular Systolic Function

Background: Surgical resection of thalamic lesions poses significant challenges due to the deep location of the thalamus, complex architecture, and proximity to critical white matter tracts and vascular structures. Over the past several decades, multiple surgical and anatomical taxonomies of the thalamus have been proposed to improve operative orientation, ranging from four- to eight-region classifications based on sulcal, ventricular, or vascular relationships. These evolving schemes underscore ongoing efforts to standardize thalamic subdivision for both anatomical study and surgical planning. Despite extensive knowledge of thalamic neurophysiology, a unified surface-based framework linking these subregions to specific surgical access routes is lacking. While the concept of safe entry zones (SEZs) revolutionized brainstem surgery, its application to thalamic lesions remains limited and inconsistently defined. This study synthesizes cadaveric and clinical evidence to delineate the anatomical organization of thalamic subregions and their corresponding surgical approaches, aiming to clarify potential region-specific SEZs.
Methods: A systematic review of PubMed, Scopus, Embase, and the Cochrane Library was conducted to identify original articles that proposed or modified thalamic regional subdivisions, emphasizing studies that detailed the anatomical organization, white matter relationships, and operative accessibility of each region.
Results: Eight studies met inclusion criteria, comprising anatomical dissections and retrospective case series. The included studies organized the thalamus into subregions (anterior, medial, lateral, geniculate/thalamopeduncular junction, pulvinar/posterior, and choroidal) with distinct approach patterns and tract associations across subregions. Pulvinar and posterior lesions demonstrated the greatest approach diversity, while anterior and medial regions were constrained by proximity to critical tracts such as the mammillothalamic, fornical, and internal capsule fibers. Lateral and thalamopeduncular junction lesions were reported as more amenable to resection through transparietal or subtemporal routes with preservation of neurological function in selected cases. Only a limited subset of studies explicitly proposed relatively safe surgical corridors or preferential approach trajectories, and these were largely restricted to posterior lesions.
Conclusion: Comprehensive and standardized assessment of thalamic surgery remains exceptionally challenging due to anatomical complexity. While certain thalamic areas may be more surgically accessible and permit reproducible approaches, overall strategies remain heterogeneous, and region-specific SEZs are inconsistently characterized. Future efforts should focus on developing standardized anatomical-surgical maps, integrating advanced imaging modalities, and conducting prospective studies to validate the existence and utility of region-specific SEZs to improve surgical planning and patient outcomes.

Exploring Region-Specific Surgical Approaches to the Thalamus: Defining Safe Entry Zones

Purpose: To demonstrate an open-source global nomogram platform for SMILE surgery that combines individual surgeon nomograms with collective data, utilizing deep learning to predict optimal laser correction values.

Methods: A proof-of-concept web platform was developed with a neural network trained on 136 eyes requiring post-operative care. The platform generates personalized and global nomograms for outcome benchmarking and predicts VisuMax laser parameters from preoperative measurements.

Results: The platform successfully generated dual-view nomograms and demonstrated promising prediction accuracy (R-squared=0.956 sphere, 0.952 cylinder, 0.999 axis, 0.966 spherical equivalent, RMSE = 0.274D sphere, 0.084D cylinder, 0.258D spherical equivalent, MAE = 1.2 degrees axis) despite using a limited dataset of primarily follow-up cases.

Conclusion: This study demonstrates the feasibility of combining personalized and global SMILE nomograms with deep learning prediction, though current accuracy is limited by dataset size and selection bias.

Shallow Neural Network for Multi-Parameter Prediction and Nomogram Optimization for SMILE Surgery

Background: Chronic pain, particularly fibromyalgia, has a sizable prevalence of 0.2 to 5% in the adult population. Previous research indicates fibromyalgia is more common in patients with comorbidities like diabetes mellitus (DM). However, fewer studies discuss the impact of DM on fibromyalgia symptomology. Our study hypothesized that adult fibromyalgia patients with DM will have increased fibromyalgia symptom severity.
Methods: This retrospective TriNetX study included queries from adults (>18 years old) with a fibromyalgia diagnosis (ICD-10: M79.7). Patients were divided into cohorts with DM (ICD-10: E10-E11) and without DM. We then examined the presence of symptoms relevant to the severity of fibromyalgia with record of relevant ICD-10 codes after the index date. Measures of association, including odds ratios (OR) and 95% confidence intervals (CI), were calculated to evaluate the strength of relationships. The study was IRB exempt.
Results: A total of 1,450,715 patients were diagnosed with fibromyalgia in the TriNetX database, and 24% (350,883 patients) were also diagnosed with DM. Fibromyalgia occurred in a population that was 75% female, 67.6% white, and 13.1% Black/AA. After matching to minimize any confounding variables (both cohort N=293,490), across all six analyzed outcomes, fibromyalgia patients with DM are significantly more likely to report the presence of fibromyalgia symptoms (p<0.001). The highest difference was in sleep disturbances and mood disorders, with 46.9% of patients with DM reporting sleep disturbances and 60.9% reporting mood disorders, compared to 36.9% and 55.6% respectively without DM. Patients with DM were 51% more likely to have sleep disturbances (OR: 1.51, 95% CI: 1.50-1.53) and 24% more likely to have mood disorders (OR: 1.24, 95% CI: 1.23-1.26). These associations were statistically significant.
Conclusion: Fibromyalgia patients with DM have a significantly higher association of severe fibromyalgia symptoms, specifically sleep disorders and mood disorders. This demonstrates an importance for clinicians to consider comorbidities such as DM, when evaluating fibromyalgia patients, as they are at greater risk for developing severe symptoms, impacting their treatment needs and quality of life.


Exploring the Impact of Diabetes Mellitus on Severity of Symptoms Among Patients with Fibromyalgia

Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors affecting the gastrointestinal tract, most often localized to the stomach (50-60%), small intestine (30-35%), and colon or rectum (5%). GISTs typically present with vague symptoms, contributing to diagnostic delays1. Global incidence of GIST is 10-22 per million persons, with prevalence of 135-155 cases per million people2 and median age of presentation between 60-65 years. 
Early detection is crucial, as approximately 40% of localized GISTs metastasize, and 10%-20% patients have overt metastases at presentation. Nine-year survival rate is 35% in patients with advanced GIST receiving chemotherapy. Larger tumors (>5cm) are more likely to metastasize so detection is crucial.
We present a case of a high-grade GIST presenting with syncope and anemia.

Case Presentation
A 58-year-old male with past medical history of hypertension, hyperlipidemia, and type II diabetes mellitus presented to emergency department with dizziness and a syncopal episode. He reported melena over few days following travel. Examination revealed pallor and non-tender palpable lump in left lumbar region but otherwise unremarkable. Laboratory investigations revealed severe anemia with hemoglobin of 6.9 g/dL. Further investigation of the suspicious mass with an upper endoscopy revealed a 3 mm non-bleeding gastric ulcer and chronic active gastritis with biopsies positive for Helicobacter pylori. CT of abdomen and pelvis identified a colossal mass, 13×12×14cm, in left mid-abdomen specifically in proximal duodenum near lower border of pancreas. Percutaneous biopsy and histopathological evaluation confirmed a high-grade GIST with immunohistochemistry positive for CD117, DOG-1, CD34, caldesmon, SMA and negative for S100 and SOX-10.
Patient underwent an open exploratory laparotomy with partial small bowel resection, partial omentectomy, and excision of GIST, followed by small bowel anastomosis and drainage of peritoneal cavity. Postoperatively, he developed intra-abdominal bleeding requiring transfusions. Mesenteric angiography revealed no contrast extravasation, so no embolization was performed. Patient was discharged in stable condition with plans to follow up with oncology. 

Discussion
This case highlights importance of considering GIST in patients with unexplained anemia and gastrointestinal bleeding. 
High-grade GISTs are aggressive, often presenting with complications such as bleeding and rapid growth. Early surgical resection remains the cornerstone of treatment, offering a favorable prognosis, particularly when combined with adjuvant therapy. GISTs vary in size and location and are often incidental findings on imaging, as demonstrated in our patient. 
Timely diagnosis, surgical resection, and multidisciplinary coordination are essential to optimize outcomes. Clinicians should maintain a high index of suspicion for GIST with similar clinical presentations.


A Colossal Surprise: The Case of a Massive 19-cm High-Grade Gastrointestinal Stromal Tumor (GIST)

Background
Secondary iron overload is a common complication in patients with chronically transfused sickle cell disease (SCD) and can lead to multi-organ dysfunction and increased mortality. Extrahepatic iron deposition is rare in SCD, and pancreatic involvement has not been well described. Here, we present a unique case of a patient with SCD who developed pancreatitis in the setting of severe iron overload, with further workup also revealing multiple endocrinopathies also related to iron overload. 

Case Presentation
A 56-year-old woman with SCD requiring chronic blood transfusions was admitted to the hospital with worsening weakness, fatigue, and poor oral intake for three months. Her labs demonstrated a hemoglobin of 6.2, white blood cell count of 21, total bilirubin of 3.3 (direct 2.1, indirect 1.3), AST 91, ALT 70, alkaline phosphatase 119, lipase 71, and a ferritin of 9,395. An MRCP revealed pancreatitis with acute to subacute peripancreatic fluid collections, an auto-infarcted spleen, and iron deposition in the liver, kidneys, bone marrow, and pancreas. Multiple etiologies of pancreatitis in a patient with SCD were ruled out, including microvascular ischemia, infection, gallstones, drug-related causes, autoimmune disease, alcohol use, and hypertriglyceridemia. Her pancreatitis was therefore suspected to be secondary to direct pancreatic inflammation and injury from excessive iron accumulation. A follow up MRI using T2 weighted images specific for liver iron quantification demonstrated 460 micromoles/g of liver iron, consistent with severe iron overload. She also underwent a workup for endocrine dysfunction due to ongoing hypotension and fatigue, which revealed hypothyroidism, hyperparathyroidism, hypogonadism, and central adrenal insufficiency suspected to be a result of iron deposition in multiple endocrine organs. She was started on chelation therapy, levothyroxine, and hydrocortisone, and was discharged in stable condition. 

Discussion
Secondary iron overload can involve multiple organ systems and may lead to life-threatening consequences. There are a few reported cases of pancreatitis in the setting of severe iron overload due to hereditary hemochromatosis, as well as animal models showing that chronic transfusion-related iron overload can lead to pancreatitis. However, to our knowledge, this is the first reported case of pancreatitis due to iron overload in a chronically transfused patient with SCD. Diagnosis includes serum ferritin levels and MRI, particularly using noninvasive techniques to quantify iron overload. This case underscores the need for greater clinical awareness of this rare pancreatitis etiology to enable timely recognition of iron overload, evaluation of associated complications such as endocrinopathies, and prompt initiation of chelation therapy.


Severe Iron Overload Presenting as Pancreatitis in a Patient with Chronically Transfused Sickle Cell Disease

Background
Giant cell tumors of bone (GCTB) are generally benign but locally aggressive neoplasms composed of multinucleated osteoclastic giant cells within a fibrous stromal background. Malignant transformation is rare, reported in approximately 4 - 5% of cases. Even less frequently described are cases of GCTB with soft tissue recurrence or distant metastases. We present a case of a proximal femoral neck giant cell tumor (GCT) with secondary aneurysmal bone cyst features that underwent rapid progression and widespread metastasis following initial resection.

Methods
Our patient is now deceased. We received IRB exemption (HSC-MS-24-0387) to obtain patient consent for this case report.

Case Report
A 46-year-old woman presented with a 5 cm cystic lesion of the right femoral neck, diagnosed as a benign giant cell tumor of bone. Surgical biopsy was complicated by a pathologic fracture, necessitating proximal femoral resection and total hip arthroplasty, followed by adjuvant Denosumab therapy. Three months postoperatively, a local recurrence was identified. She underwent repeat resection, including partial excision of adjacent gluteal and quadriceps musculature. Histopathology revealed GCT with extensive aneurysmal bone cyst changes, focal necrosis, osteoid formation, and cytologic atypia. Immunohistochemistry was negative for S100, p53, and CD99, and MDM2 amplification was not detected. Diagnosis of atypical GCT was confirmed on extramural review.

Eighteen months later, the patient developed a 30 cm soft tissue recurrence involving the ipsilateral thigh and pelvis. She declined further systemic therapy and underwent pelvic resection with positive margins. Postoperatively, she developed persistent leukocytosis and anemia. Within three months, she developed pulmonary and spinal metastases. Despite undergoing a palliative hemipelvectomy, her disease progressed rapidly. She died six weeks postoperatively, approximately three years after the initial diagnosis.

Conclusion 
Giant cell tumor of bone (GCTB) can rarely undergo malignant transformation, resulting in pulmonary, skeletal, or soft tissue metastases despite an initially benign histologic appearance. 

This case illustrates the potential for aggressive clinical behavior in GCTB with atypical histological features. Although the initial diagnosis was benign, the tumor rapidly progressed following surgery, culminating in massive soft tissue recurrence and systemic metastases. Histologic findings of necrosis, osteoid formation, cytologic atypia, and aneurysmal changes raised concern for malignant transformation. Clinicians should maintain vigilance for malignant progression in GCTB, especially in cases with atypical pathology or rapid local recurrence.


Beware of “Atypical” or “Aneurysmal” Giant Cell Tumors of Bone: A Case Report

Background
Pediatric otolaryngologic conditions, such as chronic otitis media, hearing loss, and obstructive sleep apnea, can significantly affect language development, academic performance, and long-term health. These conditions require timely diagnosis and specialized care, yet not all children have equitable access to such services. Racial/ethnic and socioeconomic disparities in pediatric healthcare are well-documented, but their specific impact on otolaryngologic care has received less focused attention. Understanding how structural and systemic barriers influence access, treatment, and outcomes is essential for developing targeted, equity-driven solutions in this specialty.

Methods
This review presents a structured literature review of 45 peer-reviewed sources published between 2004 and 2024. Guided by the social-ecological model, the analysis examines pediatric otolaryngology disparities across five levels: structural, organizational, community, interpersonal, and individual. Sources include national datasets, health policy reports, qualitative studies, and clinical outcome evaluations related to pediatric otolaryngology access and equity.

Results
Evidence from the literature demonstrates that children from historically marginalized backgrounds, particularly those who are publicly insured, low-income, or from racial/ethnic minority groups, experience disproportionately long wait times, lower referral completion rates, and delayed surgical care. Medicaid patients often face administrative burdens and live in regions with no pediatric otolaryngology providers. Barriers such as language discordance, transportation limitations, and low caregiver health literacy further compound disparities. Promising interventions include care coordination hubs, Medicaid fee parity, video interpreter services, mobile diagnostic vans, and one-stop weekend clinics. However, many studies are small, single-site, and lack long-term outcome tracking or demographic stratification.

Conclusion
Disparities in pediatric otolaryngology are pervasive yet modifiable. While innovative interventions have demonstrated success in improving access and timeliness of care, broader implementation and rigorous, equity-focused evaluation are needed. Future research should prioritize multi-site trials, community-informed program design, and metrics that measure not just improvement, but gap closure.

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Differential Tropisms of Old and New World Hantaviruses Influence Virulence and Developing Host-Directed Antiviral Candidates

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