United States

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.


AMA Research Challenge 2025 

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

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Background: Pseudomonas aeruginosa continues to be a significant opportunistic pathogen, with growing antibiotic resistance and no available vaccine. Previous work showed that the P. aeruginosa type III secretion system (T3SS) protein, PopB, elicits a protective Th17 response after intranasal immunization using the Th17 adjuvant curdlan, but the protection is of low potency. In those studies, PopB was co-purified with its chaperone PcrH. In the current studies, we tested whether fusing or mixing PopB with PcrV, a T3SS protein known to elicit protective antibodies, would enhance protective efficacy. We also hypothesized that adding a Th17 antigen (PopB) to PcrV would improve mucosal IgA responses to PcrV.


Methods: Fusion proteins to the avidin homolog rhizavidin (Rhavi) were constructed to achieve multimeric antigen presentation as dimers and also for future coupling to biotinylated polysaccharides. A fusion protein of Rhavi to full-length PcrV and PopB (denoted RVB) was purified from E. coli using a pACYCDuet-1 vector co-expressing His-PcrH, where untagged RVB bound to His-PcrH was pulled down by nickel affinity resin, followed by ion exchange chromatography and then negative affinity chromatography with nickel resin using elution with 0.1% LDAO to dissociate RVB from His-PcrH. Recombinant His-tagged Rhavi-PcrV, PcrV, and PopB/PcrH were prepared by published methods. Mice were immunized intranasally using curdlan as adjuvant. IgA titers in bronchoalveolar lavage fluid (BALF) were assayed by ELISA, and Th17 responses were assessed by measuring IL-17 (ELISA) in supernatants of splenocytes stimulated with antigens in vitro. Protective efficacy was evaluated in a murine acute pneumonia model using P. aeruginosa strain N13.


Results: Our results show significantly higher IgA titers to PcrV in BALF of mice immunized with RVB when compared to mice immunized with either PcrV or Rhavi-PcrV, where IgA titers were undetectable. Th17 responses to PopB were significantly higher in RVB-immunized mice compared to mice immunized with PopB/PcrH. In the P. aeruginosa acute pneumonia model, RVB-immunized mice displayed 100% survival, whereas PcrV- and Rhavi-PcrV-immunized mice had approximately 60% survival (logrank P=0.06 compared to RVB), all significantly higher than curdlan-immunized mice (0% survival).


Conclusion: These results suggest that integrating PopB with PcrV into the same rhizavidin fusion protein elicits improved IgA titers to PcrV while maintaining a robust Th17 response to PopB, ultimately conferring broad and potent protection against P. aeruginosa lung infection.

Pseudomonas aeruginosa Fusion Protein Vaccines Containing the Th17-stimulating Antigen PopB Improve Mucosal IgA Responses and Protective Efficacy in Mice After Intranasal Immunization

Background: Crohn’s disease and ulcerative colitis are the two primary forms of inflammatory bowel disease (IBD) which are chronic autoimmune conditions that require timely diagnosis and appropriate lifelong management to prevent severe complications and preserve quality of life. Social Determinants of Health (SDOH), including economic stability, healthcare access, and social context, are known to impact chronic disease outcomes, yet their role in IBD remains underexplored. 

Methods: Existing studies on the relationship between SDOH and IBD often lack secondary layers of analysis, limiting deeper exploration of the structural or systemic drivers behind disparities in access. To build on this gap, we conducted a cross-sectional analysis using All-Payer Claims Databases (APCD) from the state of New York and the nationally representative Medical Expenditure Panel Survey (MEPS). APCD data was analyzed to assess associations between race, ethnicity, and hospital utilization metrics. MEPS analysis focused on SDOH impacting emergency room usage among IBD patients. We constructed a composite binary variable—“Underserved”—flagging individuals with one or more indicators of structural disadvantage.

Results: Analysis revealed that race had a modest but significant effect on length of stay (p = 0.044), with illness severity exerting a stronger influence (p < 0.001). Race and insurance type both significantly impacted total charges (p < 0.001), while ethnicity was associated with higher emergency and lower elective admissions (p < 0.001), though not with length of stay or cost. In the MEPS dataset, the composite Underserved variable was a statistically significant predictor of ER utilization among IBD patients. Individual components were not significant when entered together into multivariable models, likely due to multicollinearity. These findings suggest that cumulative social disadvantage is more predictive of healthcare access disparities than any single factor alone.

Conclusion: Economic stability and healthcare access emerged as the most influential and frequently co-occurring SDOH domains, particularly in relation to insurance and financial barriers. However, social and cultural drivers remain under examined in the current literature. Our results underscore the need for multidimensional analyses that reflect the compounding effects of disadvantage. Future directions include a geospatial analysis of IBD care access in marginalized populations and development of a public-facing, searchable disparities database to support patient and policymaker decision-making.


Social Determinants of Health and Adverse Outcomes in Inflammatory Bowel Disease

Background
Small vasculature, venous obstruction, or congenital anomalies can preclude transvenous access to the heart, often resulting in open chest surgery to implant cardiac therapy leads for pacing, defibrillation, or cardiac resynchronization. A minimally invasive approach under direct visualization to deliver pacing leads to the pericardium could reduce tissue damage, minimize pain, shorten recovery time, and obviate the need for fluoroscopy.

Methods
A single-use, low-cost pericardial access port was designed based on clinical requirements. The device includes collapsible flange for atraumatic insertion and crossed working channels to provide an optimal view of the surgical field under direct visualization.

Results
Finite element analysis and mechanical testing demonstrates that the tensile strength of its components is sufficient for use under clinical working conditions, with minimal risk of fracture. Prior animal work and a physician preliminary validation study suggest that PeriPath functions effectively for minimally invasive lead implantation procedures.

Conclusion
The mechanical design of the thoracic access port aids in safe placement of conductive leads to the pericardium. This device may obviate the need for open chest surgery, which may result in decreased incision length, associated pain, risk of infection, and length of hospital stay. The access port is also compatible with common lead implantation tools and may be readily adopted by interventional cardiologists and electrophysiologists, allowing for widespread implementation.

Design of a Thoracic Access Port for Pericardial Access and Pacemaker Implantation

Background
Feminine hygiene wipes are widely marketed for intimate care, yet few are evaluated for safety on vulvar skin. The American Academy of Dermatology (AAD) and the American College of Obstetricians and Gynecologists (ACOG) advise avoiding ingredients such as fragrance, parabens, phthalates, methylisothiazolinone (MI), botanical sensitizers, and certain surfactants, which are known to cause irritation, allergic contact dermatitis, or endocrine disruption. This study evaluates the dermatologic safety of commonly available feminine wipes in the U.S. using ingredient-level analysis based on AAD and ACOG guidance.

Methods
We identified 79 feminine wipes sold at major U.S. retailers. Product labels were reviewed for full ingredient transparency. Each product was assessed for presence of medically flagged ingredients based on AAD/ACOG recommendations. These included fragrance, MI/MCI, parabens, PEGs, propylene glycol, formaldehyde releasers, botanical allergens (e.g., lavender, menthol), dyes, and surfactants like sodium laureth sulfate. Each flagged ingredient contributed one point to a cumulative violation score. Products were stratified by safety tier: Excellent (0), Acceptable (1-2), Questionable (3-4), or Poor (≥5).

Results
Only 11 of 79 products (14%) received an “Excellent” safety score. Fragrance was present in 76% of products, despite being a leading cause of vulvar allergic reactions. Other frequently flagged ingredients included propylene glycol (39%), PEG compounds (33%), and botanical sensitizers such as linalool and eugenol. Notably, many products labeled as “sensitive,” “natural,” or “pH-balanced” still contained multiple allergens or irritants. Nearly half (48%) of all wipes fell into the “Questionable” or “Poor” categories.

Conclusion
Most feminine wipes on the U.S. market contain ingredients that AAD and ACOG recommend avoiding on vulvar skin. Fragrance, preservatives, and plant-derived allergens remain common, even in wipes marketed for sensitive use. These findings highlight a disconnect between marketing claims and medical safety guidelines. Dermatologists and gynecologists should counsel patients accordingly and advocate for safer formulations and clearer labeling standards.

Dermatologic Safety of Feminine Wipes for Vulvar Use: An Ingredient-Based Review of U.S. Products

Background
Urinary and sexual dysfunction are underrepresented complications in spine surgery literature, despite their significant impact on postoperative quality of life among male patients. These outcomes are particularly relevant in lumbar procedures, where autonomic and somatic structures critical to erectile, ejaculatory, and excretory functions are at risk. Anterior instrumentation may disrupt the hypogastric plexus and sympathetic chains, while posterior operations pose injury to nerve roots. However, comparative data on genitourinary complications by surgical approach in men remains limited.

Methods
The TriNetX Research Network was queried to identify adult males who underwent two- to seven-level vertebral instrumentation between 2010 and 2023 for lumbar, lumbosacral, or thoracolumbar stenosis, spondylolisthesis, scoliosis, or radiculopathy. Patients were categorized by anterior or posterior surgical approach. Those with complex spinal pathology, preexisting urogenital disorders, or a history of the opposite approach were excluded. Propensity score matching adjusted for age, ethnicity, and relevant comorbidities. Postoperative outcomes were identified using diagnostic and procedural codes.

The primary outcome was a composite measure of urinary complications (pain, incontinence, retention, extravasation, anuria, oliguria, polyuria, urethral discharge, and other specified and unspecified urinary dysfunction). The secondary outcome was a composite measure of sexual complications (pain, erectile/ejaculatory dysfunction, decreased libido, and other specified and unspecified sexual dysfunction). All outcomes were assessed at one, three, six, nine, and twelve months postoperatively.

Results
A total of 11,164 patients met all initial inclusion criteria (7,763 posterior, 3,401 anterior); following 1:1 propensity score matching, each cohort included 3,397 patients with comparable baseline characteristics. Post-matching analysis revealed that posterior instrumentation was associated with significantly higher odds of urinary complications at one month (OR=2.259), three months (OR=1.727), six months (OR=1.374), nine months (OR=1.339), and twelve months (OR=1.333). No significant difference in sexual complications was observed at earlier intervals, however, anterior instrumentation patients exhibited higher odds at twelve months (OR=0.630) postoperatively.

Conclusion
In this large, multicenter retrospective analysis of adult males undergoing multilevel spinal instrumentation, surgical approach was associated with distinct patterns of genitourinary complications. Posterior instrumentation carried consistently higher odds of urinary dysfunction, suggesting increased vulnerability of nerve roots involved in micturition. Sexual outcomes were comparable between groups until twelve months, when anterior instrumentation was linked to increased complications, potentially reflecting delayed effects on regional autonomic pathways. These findings underscore the importance of surgical approach in influencing long-term functional outcomes and may inform preoperative counseling and risk stratification in male spine surgery patients.

Comparative Analysis of Urinary and Sexual Dysfunction in Men Following Anterior versus Posterior Lumbar Instrumentation

Background
Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is widely used to treat diabetic eye disease (DED), yet systemic VEGF suppression may impair peripheral wound healing. The association between anti-VEGF treatment and risk of diabetic foot ulcers (DFUs) and lower extremity amputations (LEAs) remains unclear. We seeked to evaluate the risk of DFUs and LEAs associated with intravitreal anti-VEGF injections (IVI) in patients with DED and to compare risks among ranibizumab, aflibercept, and bevacizumab.
Methods
We conducted a retrospective cohort study (April 2005 - April 2025) using a multicenter, population-based electronic health records network encompassing over 120 million individuals from 71 United States healthcare organizations. Adults (≥18 years) diagnosed with DED (diabetic retinopathy or diabetic macular edema) who received ≥3 IVI were compared to those who received ≤2 injections (control group) during the study period, since prior evidence demonstrated systemic suppression of plasma VEGF levels following three monthly intravitreal injections. The exposure was IVI (ranibizumab, aflibercept, or bevacizumab). Main outcome measures included incidence of any LEAs, above-ankle LEAs, and DFUs following incident DED diagnosis. Propensity score matching (1:1) was applied to balance baseline characteristics between groups. Cox proportional hazards analyses were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) in the full cohort and among high-risk subgroups with proliferative diabetic retinopathy (PDR), peripheral artery disease (PAD), end-stage renal disease (ESRD), or DFUs.
Results
Of 448,100 patients with DED, 35,269 received ≥3 injections and 412,831 received ≤2 injections. After matching, 34,070 patients remained in each group. IVI cohort was associated with increased risk of LEA (HR 1.54, 95% CI 1.38–1.72), above-ankle LEA (HR 1.31, 95% CI 1.08–1.59), and DFU (HR 1.36, 95% CI 1.30–1.42) compared with the control group. In high-risk subgroups, IVI was associated with increased risk of LEA in patients with PDR (HR 1.44, 95% CI 1.27-1.62), PAD (HR 1.35, 95% CI 1.12–1.56), ESRD (HR 2.06, 95% CI 1.28–3.31), and DFU (HR 1.46, 95% CI 1.22–1.75). Risks were similar across anti-VEGF agents.
Conclusion
IVI therapy for DED was associated with increased risk of LEA, particularly with comorbid PDR, PAD, ESRD, or DFUs. These findings highlight the importance of monitoring for limb complications in patients undergoing intravitreal anti-VEGF treatment.

Intravitreal Anti-VEGF Therapy and Risk of Limb Complications in Patients with
Diabetic Eye 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

Vitamin B6 has been linked to neuropathy in patients who over-supplement. Current understanding suggests that high-dose vitamin B6 saturates the liver function in hepatic conversion, leading to accumulation in peripheral neurons, particularly in the dorsal root ganglia. This may lead to neuropathy seen in patients presenting as axonopathy or degeneration of neurons altogether. Unfortunately, vitamin B6 toxicity is frequently overlooked in general clinical practice, and especially in patients who have other comorbidities, such as diabetes mellitus, hypertension, and cardiovascular diseases. Going unnoticed, vitamin B6 toxicity may progress to a worsened neuropathy for the patient, such as irreversible nerve damage; it can also lead to unnecessary diagnostic testing and medical interventions. Here, we present a case of bilateral peripheral neuropathy in a patient with a past medical history of type II diabetes mellitus whose baseline plasma vitamin B6 level was twice the upper limit of the normal range. We provide justification for providers to obtain patients’ supplementation history and the importance of considering vitamin B6 toxicity when evaluating patients with sensory neuropathy.

Vitamin B6 Related Peripheral Neuropathy in a Diabetic Patient: A Case Study


Background
Osteoarthritis (OA) of the hip and knee are very common pathologies that affect thousands of people worldwide. Large database retrospective studies suggest that Hispanics and Blacks significantly underutilize joint replacement procedures compared to non-Hispanic Whites (NHW), even when health insurance access is controlled. Improvements in utilization require an understanding of the barriers to and attitudes of these minority populations. We assessed attitudes towards medical care and lower extremity joint replacement procedures in a predominantly Hispanic community in San Antonio, Texas.

Methods
Subjects had to be 50-89 years of age and residents of Bexar County, TX. The assessment included three answer blocks about demographics, financial and insurance status, education, attitudes towards seeking healthcare, faith, and opinions about total hip and knee replacement procedures. Respondents who self-identified as Hispanic or NHW were included in the primary
analysis (n = 315). 157 subjects who reported daily knee or hip pain completed the joint replacement attitudes section. Group differences were assessed using Wilcoxon rank-sum tests. Correlations with fear of surgery were analyzed using Spearman’s rho. An ordinal logistic regression model was used to assess multivariate predictors of surgical fear.

Results
Approximately 61% Hispanic and 35% NHW subjects were included. 61% of the subjects were male. Compared to NHW subjects, Hispanic subjects reported significantly greater fear of surgery (p = 0.0001) and indicated that the surgical experiences of others influenced their decision to seek treatment for OA (p = 0.02). Moreover, Hispanic subjects more strongly disagreed that total joint replacement was a successful treatments for OA (p = 0.03) compared to
NHW subjects. Fear of surgery negatively correlated with income (ρ = −0.199) and the regularity of primary care visits (ρ = −0.168). It also positively correlated with the belief that a doctor’s cultural background matters (ρ = 0.168).

Conclusion
Evidence consistently suggests that Hispanic individuals have worse post-operative outcomes after hip and knee joint replacement procedures, and they underutilize these procedures as a treatment for OA. Ameliorating underutilization will be difficult because Hispanic individuals are more greatly affected by the poor surgical outcomes experienced by acquaintances than NHW individuals. Unlike previously published reports, no ethnic differences were found in the
relationship between education level, insurance coverage, coping strategies, and fear of joint replacement surgery. Efforts to address orthopedic surgery utilization disparities must be tailored towards local attitudes that are shaped by ethnic and regional customs as well as personal experiences.

Community Attitudes Towards Lower Extremity Joint Replacement – Insights from South Texas

Background
Following the COVID-19 pandemic, public health dashboards have become an increasingly popular visualization tool. Public health dashboards display information in an understandable manner, allowing stakeholders from medicine and government to quickly identify pertinent information. This ease of access and translation is particularly useful for evolving public health issues such as the opioid epidemic. Many dashboards pertaining to opioid use and opioid-related harm have been developed by national and local organizations, but limited research exists examining their utility. The purpose of this narrative review is to describe how existing public health dashboards are being used to mitigate opioid-related harm.

Methods
We performed a narrative review of peer reviewed articles describing public health dashboards in the context of opioid use and opioid related harm using the PubMed, Cochrane Library, and Embase databases. Articles were identified using a search string with various combinations of “dashboard,” “public health,” “opioid,” and “opioid overdose,” as well as MeSH terms such as “public health surveillance,” “public health,” and “opioid epidemic.” 

Results
Nine studies met the inclusion criteria and were reviewed for common themes. Principal findings include that opioid dashboards are used to address opioid-related harm at both the state and community level, and to visualize changes in opioid trends following policy changes. However, there is limited evidence demonstrating how opioid specific dashboards influence public health policy. Dashboards utilize different local and national data sources, and have different target audiences including clinicians, public health professionals, policy makers and more. In addition, dashboards may be used in conjunction with other informatic tools to improve efficacy and delivery of opioid trends and information. No standard metric for dashboard development was identified. 

Conclusion
In conclusion, public health dashboards are currently being used in a variety of different contexts to reduce opioid overdose and abuse. Although dashboards help examine the impact of policy changes, their effectiveness in directly shaping public health policy remains unclear. The lack of consistency between public health dashboards makes evaluation difficult but also hinders user interpretation. Standardization of public health dashboards could greatly improve user experience and lead to more targeted evaluation of existing dashboards. Future studies evaluating the efficacy of public health dashboards in the context of the opioid epidemic may provide strong insights as to how informatics may improve public health outcomes.

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Pseudomonas aeruginosa Fusion Protein Vaccines Containing the Th17-stimulating Antigen PopB Improve Mucosal IgA Responses and Protective Efficacy in Mice After Intranasal Immunization

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