United States

Background
Sickle cell disease (SCD) is a hereditary hemoglobinopathy affecting ~100,000 individuals in the United States. While SCD increases the risk of hematologic malignancies, large cohort studies report the incidence of solid tumors—including breast cancer—remains below 2%, lower than in age-matched controls. This rarity likely reflects the chronic hypoxic, antiangiogenic, and inflammatory environment in SCD, which may suppress tumor angiogenesis and growth. As management improves and survival increases, age-related cancers are rising. This vignette illustrates diagnostic and management challenges of breast cancer in SCD and highlights emerging evidence on this rare co-occurrence.

Case Presentation
A 58-year-old African American woman with homozygous SCD, hypertension, and
proteinuria, compliant with routine screenings, underwent annual mammography. In 2022, grouped microcalcifications were detected in the left breast, but an initial biopsy was inconclusive. Repeat imaging and biopsy in 2024 revealed a 0.5 cm, moderately to poorly differentiated invasive ductal carcinoma (IDC) with high-grade ductal carcinoma in situ (DCIS) and microcalcifications. The tumor was hormone receptor-positive and HER2- negative. She underwent lumpectomy and re-excision; sentinel lymph nodes were negative. Oncotype DX testing showed a Recurrence Score of 38(0-100), calculated from RT-PCR analysis of 21 genes, corresponding to a 9-year distant recurrence risk of 26% (95% CI: 20%–34%) and chemotherapy benefit exceeding 15% (95% CI: 9%–37%). Due to concern about complications, she declined chemotherapy and received radiotherapy and anastrozole. She is eligible for Ribociclib plus endocrine therapy under NATALEE trial criteria, supporting its use as a new adjuvant option.

Discussion
Recent population-based studies provide insights into cancer risk in SCD. A 23-year
California registry analysis found SCD patients had a 38% lower risk of solid tumors,
including breast cancer, despite a 72% higher risk of hematologic malignancies. Similar findings emerged from North Carolina, where only 1.9% of SCD patients developed solid tumors, with breast cancer a small minority. Mechanistic studies suggest chronic hypoxia in SCD upregulates hypoxia-inducible factors
and alters immune function, potentially suppressing angiogenesis and modulating immune surveillance. Experimental data indicate the SCD microenvironment impairs
neovascularization and may limit solid tumor growth and spread. However, as management advances and lifespan increases, cumulative risk of age-related malignancies, including breast cancer, is expected to rise.
This case highlights individualized screening and treatment in SCD, balancing benefit with the risk of complications. It emphasizes the need for continued epidemiological surveillance and mechanistic research to clarify risk and guide treatment in this population.

AMA Research Challenge 2025 

Invasive Breast Carcinoma in a Patient with Sickle Cell Anemia: A
Rare Clinical Intersection

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Adenosine is an immunosuppressive metabolite that is overproduced in the tumor microenvironment and a major player in tumor-induced immunosuppression. Work from our group has contributed to show that adenosine binding to the Adenosine A2A Receptor (A2AR) suppresses CD8 T cell function and activation in the tumor microenvironment, whereas blocking A2AR restimulates anticancer CD8 T cell responses. In this study, I aimed to identify novel therapeutics that can block A2AR signaling, thus restoring CD8 T cell anticancer function. Using molecular docking modeling, I have found that the nucleoside analog forodesine binds to A2AR with a similar ∆G and similar binding residues as adenosine. I tested forodesine in primary CD8 T-cells against an adenosine agonist and measured functional markers associated with T-cell activation and A2AR signaling. I found that forodesine rescues CD8 T-cell activation by binding to A2AR and counteracting adenosine-mediated immunosuppression. I also tested forodesine in highly immunosuppressive Triple-Negative Breast Cancer (TNBC) mouse models and found that forodesine reduces tumor growth via stimulation of CD8 T-cell responses. Based on our findings, nucleoside analogs, like forodesine, could be investigated as novel Immunotherapeutics to successfully stimulate T-cell responses against cancer.

Forodesine has anticancer immunomodulatory properties through the adenosine pathway

Mirchandani S¹, Paryani R¹, Bhawnani N², Ray I³, Kantheti H⁴
¹ UConn Health, ² Bharati Vidyapeeth Medical College, Pune, India, ³ MGM Medical College, Indore, India, ⁴ Baylor Scott & White Saints Medical Center
Background
Dizziness has a broad differential diagnosis. The coexistence of Mobitz atrioventricular (AV)
block, postural orthostatic tachycardia syndrome (POTS), and superior canal dehiscence
syndrome (SCDS) creates a significant diagnostic challenge, especially with symptom overlap
from endocrine conditions like adrenal insufficiency. A systematic evaluation is crucial, as SCDS
remains an underrecognized diagnosis.

Case Presentation
We present the case of a 23-year-old woman (G2P1) whose complex postpartum course was
marked by overlapping cardiovascular, vestibular, and autoimmune features. Initially admitted at
31 weeks gestation in June 2024 with headache and right upper quadrant pain, she developed
preeclampsia with severe features and HELLP syndrome, requiring an emergent Cesarean
section. Postpartum, she had severe hypertension requiring multi-agent therapy and persistent
leukocytosis and tachycardia consistent with SIRS of unclear etiology.
Six weeks later, she was readmitted with new-onset right upper extremity weakness, chest pain,
and cognitive symptoms along with lower extremity swelling. Workup revealed proteinuria,
elevated ESR, and high C3 complement, with negative ANA and unremarkable ECHO and MRI
aside from a small thoracic syrinx. Given her family history of lupus and stroke, she was referred
to Rheumatology and Psychology.
Outpatient Holter monitoring showed frequent supraventricular tachycardia and asymptomatic
second-degree Mobitz Type I AV block. Her antihypertensive regimen was switched from
labetalol to losartan. In September 2024, she was rehospitalized with exertional tachycardia up
to 170 bpm and orthostatic symptoms. Formal vitals showed a >30 bpm rise on standing without
hypotension, consistent with POTS. Ivabradine was initiated with favorable effect.
Despite treatment, she continued to experience debilitating dizziness, tinnitus, and imbalance
and complained of autophony. In March 2025, high-resolution temporal bone CT and MRI
identified bilateral superior semicircular canal dehiscence (SCDS), explaining her vestibular
symptoms. She was referred to ENT for possible surgical repair. Given persistent fatigue and
hypotension, endocrine workup revealed low-normal ACTH and indeterminate morning cortisol,
prompting referral for dynamic adrenal testing.This case highlights the diagnostic challenge of postpartum multisystem disorders and the
importance of a multidisciplinary approach when cardiovascular, vestibular, endocrine, and
autoimmune features coexist.

Discussion
In patients presenting with multifaceted dizziness, particularly with a complex medical history, it
is crucial to consider concurrent cardiac, autonomic, and vestibular disorders. This case
underscores the importance of thorough investigation, including Holter monitoring and
orthostatic testing, to identify distinct but coexisting conditions like AV block and POTS. Heart
Rhythm Society's 2015 Expert Consensus Statement also mentions ivabradine as a promising
treatment for POTS, noting that approximately 60% of patients experienced symptom
improvement in an open-label study.



Vertigo, Vital Signs, and Hormones: A Triple Threat of SCDS, POTS with Heart block and Addison's

Ependymomas are rare tumors that arise from ependymal cells lining the brain and spinal cord, accounting for 1.2% to 7.8% of intracranial tumors and 2% to 6% of gliomas. In children, they are the most common primary brain tumors after pilocytic astrocytomas and medulloblastomas. Elevated intracranial pressure (ICP) is common in children with CNS tumors and can result from the tumor's mass effect or obstructive hydrocephalus.
Current Paradigm: Managing acute hydrocephalus typically involves cerebrospinal fluid (CSF) diversion methods such as endoscopic third ventriculostomy (ETV), external ventricular drainage (EVD), or ventriculoperitoneal (VP) shunt.
Challenges: EVDs carry risks like infection and dysfunction. VP shunts can lead to mechanical failures and infections, often requiring further surgery. ETV, while generally safe, can have complications like hemorrhage, damage to brain structures, CSF leaks, and rare instances of sudden death. 
Novelty of Case: This case demonstrates a successful alternative: immediate tumor resection in a critically ill toddler without prior CSF diversion, challenging the conventional approach.

Resection First: Avoiding Preoperative Shunting in a Critically Ill Toddler with Posterior Fossa Ependymoma and Acute Hydrocephalus

Migraine is a prevalent neurological disorder characterized by unilateral, pulsating headaches that may be accompanied by photophobia, phonophobia, and nausea. It is broadly categorized into migraine with aura and without aura, with the former presenting transient neurological disturbances, most notably visual phenomena that can mimic stroke. This diagnosticoverlap is compounded by limitations in conventional stroke assessment tools, which often underrepresent visual field deficits. Emerging evidence suggests that migraine, particularly with frequent auras, is associated with an elevated risk of stroke. Though there is good evidence to support the association of migraine with aura and ischemic stroke, there is limited understanding of the pathophysiology and underlying causation. 
A case study of a 68-year-old male with a history of acephalgic ocular migraines exemplifies these challenges. This patient presented to the emergency department (ED) with a chief complaint of headache and visual changes, specifically right-sided scintillating scotoma, for a period of 9 hours. Notably, the patient did not have a history of headache with his migraines, and the visual phenomenon would terminate approximately 6–8 hours on its own, without any residual deficit. Non-contrast CT of the head showed no abnormality. Joint decision-making by the patient and provider concluded that these symptoms were highly suggestive of migraine, and no further workup was done, even with SNOOP criteria being met. Two days later, the patient presented to the ED again with a chief complaint of the right-sided scintillating scotoma transforming into right-sided inferior quadrantanopia. MRI revealed acute infarction of the left occipital lobe. The remaining laboratory studies, CT angiogram of the head and neck, echocardiogram, and telemetry were unremarkable. Upon neurology outpatient follow-up, with a history of acephalgic migraines in the same cerebral territory, with no evidence of thrombotic or embolic activity, migrainous stroke was diagnosed. 
There is a well-established association between migraine with aura and increased risk of stroke. However, migrainous stroke remains a diagnosis of exclusion due to lack of definitive causation. This synthesis highlights the association between the two disease processes and suggests probable pathophysiology regarding neurogenic inflammation, vascular risk factors, and hypercoagulable states (e.g., endothelin-1 and von Willebrand factor). Furthermore, it emphasizes the significance of a thorough workup including non-contrast CT, MRI, and laboratory testing to differentiate migrainous events from strokes, particularly important when SNOOP criteria are met. Further research is needed to continue to assess the pathophysiology of stroke in patients with migraine with aura.

Case of Migrainous Stroke: Visual Aura to Visual Deficit

Background
Climate change increasingly disrupts healthcare systems through more frequent and severe extreme weather events. In order to build climate-resilient health systems, it is essential to understand how climate-responsive hazards, such as extreme heat, affect healthcare operations at the facility level.

Methods
We analyzed 484,282 ED visits at an urban teaching hospital in the Northeast US during the warm season months (May–September) from 2002 to 2023. Health record data was merged with daily weather data from the National Oceanic and Atmospheric Administration Climate Data Online Database, and each ED visit was assigned the corresponding maximum daily temperature (Tmax). We examined four operational metrics derived from ED database timestamps: total length of stay (LOS), door-to-doc time, doc-to-decision time, and boarding time (time from determining a patient’s disposition to the time they leave the ED, e.g. if waiting for inpatient admission). Using generalized additive models (GAMs) with Gamma distributions and log links, we assessed the nonlinear relationship between Tmax and each operational outcome, adjusting for patient demographics, clinical acuity (using the Emergency Severity Index), imaging and consult use, and temporal variables (day of week, month, and year).

Results
We observed a statistically significant nonlinear relationship between Tmax and both total ED LOS (EDF = 3.002, p = 0.033) and door-to-doc time (EDF = 3.856, p < 0.001). On both metrics, delayed throughput was observed between 80 ̊F and 95 ̊F; throughput appears to be more rapid below 70 ̊F. No significant associations were observed between Tmax and doc-to-decision time or boarding time (p > 0.5).

Conclusion
Warmer temperatures in the summer months are associated with delays in ED throughput, with strain intensifying beyond certain temperature thresholds. While the operational impacts observed were modest, their cumulative effect across large volumes of patients and repeated hot days may be substantial, particularly in less-resourced settings. These findings support targeted adaptation strategies such as preemptive staffing and triage optimization, even on days not officially classified as extreme heat days. While these results are institution-specific, the modeling approach offers a scalable method to assess climate vulnerability in other health systems.

The Effects of Temperature on Emergency Department Throughput

Background 
Hospitalized older adults frequently experience age-associated conditions, such as delirium, adverse drug events, or functional decline, that require specialized attention. The Institute for Healthcare Improvement uses the 4Ms framework (What Matters Most, Medications, Mentation, and Mobility) to describe the key components of age-friendly healthcare. The evidence base for 4Ms has not kept up with its implementation; few studies examine the impact of the 4Ms package on patient outcomes. The purpose of this study is to investigate the impact of all 4Ms on length of stay, changes in functional capacity, 30-day post-discharge inpatient readmissions and returns to the ED, and in-hospital mortality of older adults in a large healthcare setting. 

Methods 
This study was a prospective cohort study of 3,045 patients ≥65 y/o admitted to eight hospitals (5 community, 2 tertiary, 1 quaternary) between July and September 2024. Data abstracted by manual EMR review and using Age-Friendly Health System (AFHS) dashboards that extracted patient-level demographics, M assessments, and clinical data. Patients were grouped by whether they screened for all 4Ms (n=296) or 0-3Ms. Manual review of the 4Ms group determined if identified 4Ms issues led to clinical interventions (“act-ons”). 

Results 
The patients with all 4Ms were older (84 vs 77, p<0.001), had a higher clinical acuity, as seen with the Lace score (14 vs 13, p<0.001), and higher burden of illness, as indicated by Charleson comorbidity index (9.0 vs 4.0, p<0.001). No significant differences were found between the 4Ms and 0-3Ms groups in length of stay, change in mobility/ADL, or 30-day inpatient readmission. However, the 4Ms group was associated with 43% lower odds of being returned to the ED (p=0.002). While the 4Ms group showed higher odds of mortality in the unmatched sample, this association was not statistically significant after propensity score matching (OR: 1.71, 95% CI: 0.94, 3.10, p = 0.08). Manual review revealed that delirium (Mentation) was the least commonly identified (4.4% of 296) and acted on (15.4% of 13) domain among the 4Ms. 

Conclusion 
Comprehensive 4Ms assessment was associated with lower post-discharge 30-day ED returns, suggesting potential benefits for patient-centered care in older adults. Mortality rate was similar for 4Ms vs. 0-3Ms, controlling age, illness burden and acuity with propensity matching. Enhancing integration of 4Ms, especially delirium screening, into routine workflows may improve implementation and reveal additional benefits in outcomes.

Emergency Department Recidivism and Mortality in an Age-Friendly Health System

Background: Burn injuries are a significant public health concern, causing considerable morbidity, long hospital stays, and economic costs. The severity of burns ranges from minor injuries to life-threatening conditions that require specialized long-term care. Factors such as age, comorbidities, socioeconomic status, and access to burn centers significantly influence patient outcomes. By utilizing national datasets, this study will examine patterns in third-degree burn incidence, hospitalizations, and mortality to inform future prevention efforts and treatment strategies. 
Methods: We conducted a retrospective cohort study using data from the Nationwide Readmissions Database (NRD) from 2016 to 2021. Adults aged 18 or older with ICD-10 codes indicating third-degree burns were included. Primary outcomes were 30-day readmission and in-hospital mortality. Secondary outcomes included length of stay (LOS), hospital charges, and complications. Multivariable logistic and linear regression models adjusted for demographics, insurance, comorbidities, and hospital characteristics.
Results: Of 38,706 weighted hospitalizations, 76.9% were urban and 23.1% rural. Rural patients were older (50.4 vs. 48.6 years, p < 0.001), more often from the lowest income quartile (59.5% vs. 31.6%, p < 0.001), and more commonly insured by Medicare. Rurality was not independently linked to 30-day mortality (OR 1.59, p = 0.23) or readmission. Medicaid patients had higher costs (β = $29,487; p < 0.001) and longer LOS (β = 4.42 days; p < 0.001) but showed reduced 30-day readmission risk (OR = 0.69, p = 0.004). Urban patients were more likely to sustain vehicle-related burns and be treated at teaching hospitals (92.8%). Rural female patients with burns to the genitals or buttocks had significantly higher odds of psychological trauma diagnoses (OR = 2.15, p < 0.001).
Conclusion: This nationally weighted analysis shows that, despite rural patients being older, more socioeconomically disadvantaged, and less likely to receive care at teaching hospitals, they had similar outcomes to urban patients. While 30-day mortality and readmission rates did not vary significantly by location, notable differences in burn size, injury mechanism, and payer distribution were observed. Medicaid coverage was linked to longer hospital stays and higher costs, but lower odds of readmission. Additionally, female patients from rural areas with burns to the genital or buttocks faced significantly higher odds of psychological trauma, highlighting the need for targeted mental health support. These findings emphasize the importance of improving access to specialized burn care, strengthening discharge planning, and overcoming the barriers rural areas impose on burn outcomes. 


Geographic Disparities in Outcomes of Third-Degree Burn Injuries:
A Nationwide Analysis of Urban vs. Rural Patients 

ABSTRACT

TITLE
Screening Colonoscopy/Cologuard Reinforced by Effective Education and Nurture (SCREEN)
AUTHOR
Chelsea Boykov, DO
AFFILIATIONS
Choctaw Nation Health Services Authority Family Medicine Residency
PURPOSE
Native American populations experience disproportionately low colorectal cancer (CRC) screening rates, contributing to higher morbidity and mortality. This quality improvement project aimed to increase CRC screening rates from a baseline of 56.8% to a target of 75% or more by applying Behavioral Economics Interventions (BEIs) during clinic visits, aligning with osteopathic principles of preventive and holistic care.
DESIGN METHODS
Starting January 2025, BEIs—including reminders, default options, framing effects, salience, reciprocity, personalization, and simplification—were consistently integrated into routine primary care visits. ACG trifold brochures were distributed to increase patient engagement. A chart review was conducted pre- and post-intervention to measure changes in patient willingness to undergo CRC screening.
RESULTS/EXPECTED RESULTS
Post-intervention analysis revealed an increase in CRC screening rates from 56.8% to 88.09%, surpassing both the project’s goal and national average. These results demonstrate the impact of low-cost, scalable behavioral strategies in improving adherence to preventive health services in a high-risk, underserved population.
DISCUSSION / CONCLUSION
This study supports the use of BEIs to improve CRC screening in Native American communities, emphasizing the importance of personalized communication and patient physician connection. The findings contribute to growing evidence on behavioral strategies in preventive care and highlight the synergy between osteopathic philosophy, preventative medicine, and modern behavioral science. Behavioral Economics Interventions are low-cost, effective ways of promoting preventative medicine and could prove innovative in increasing screening rates and decreasing preventable death. The results from this particular study are extremely successful, and more research is indicated with the goal of reshaping effective primary care outpatient visits.


Screening Colonoscopy/Cologuard Reinforced by Effective Education and Nurture (SCREEN)

Background
Prostate cancer is the most diagnosed non-cutaneous cancer in men, with 1 in 8 men in the US will be diagnosed during their lifetime. But most men diagnosed with prostate cancer do not die from it, especially for low-risk prostate cancer (LRPC). Men newly diagnosed with low-risk prostate cancer (LRPC) face a very difficult decision as they have multiple treatment options and often consult multiple specialists during their decision-making process. Besides curative treatment (surgery or radiation), Active Surveillance (AS) is the newer, guideline-preferred initial option to minimize overtreatment of LRPC. While curative treatment can treat the cancer, they may be unnecessary but often lead to long-term side effects (urinary incontinence and sexual dysfunction). AS is to carefully monitor the cancer (via periodic testing and imaging) while holding off on surgery or radiation until there are signs of cancer progression. This study investigates whether treatment recommendations for LRPC vary by physician specialty.

Methods
A population-based sample of Black and White men ≤75 years with newly diagnosed with LRPC from 2014 to 2017 were recruited from two cancer registries. Participants self-reported demographic variables, prostate cancer knowledge, type of specialist seen and their respective treatment recommendations and their final treatment choice.

Results
Of the 1688 patients, 1490 (88.3%) consulted a urologist, 653 (38.7%) a primary care physician (PCP), and 524 (31.0%) a radiation oncologist (RO). Patients reported different rates of AS recommendation by specialists, with urologists most frequently recommending AS (52.6%), followed by PCPs (42.6%), and then ROs (30.3%). Patients reported that ROs most frequently recommended curative treatment (49.2%). Logistic regression GEE with specialist’s recommendation as outcome (AS vs curative treatment) confirmed that compared to urologists, ROs were two times more likely to recommend curative treatment (OR=2.1, p<0.001) while PCPs curative treatment recommendations didn’t differ significantly from urologists (OR=1.2, p=0.17) after adjusting for covariates. Age and prostate cancer knowledge were positively associated with AS recommendation, while reported cancer seriousness and desire for cure were positively associated with curative treatment recommendation. Race, education, and current health status were not significantly associated with type of treatment recommendation.

Conclusion
PCPs were equally likely to recommend AS compared to urologists while ROs more likely to recommend curative treatment even after adjusting for other covariates in men with LRPC. Varying treatment recommendations by different specialists to the same patient could lead to patient confusion or frustration and complicate the already difficult treatment decision-making process.


Variation in Treatment Recommendations for Low-Risk Prostate Cancer: A Focus on Active Surveillance Across Physician Specialties

Abstract Title
Cancer Associated Retinopathy Presenting with Paraneoplastic Cerebellar Ataxia in Tonsillar Squamous Cell Carcinoma

Background
Cancer associated retinopathy (CAR) is a rare paraneoplastic autoimmune retinopathy caused by antibodies against tumor antigens that cross-react with retinal proteins. Patients experience sudden or subacute painless vision loss, often associated with photopsias, nyctolopia, scotomas, or constriction of the visual field. Similarly, paraneoplastic cerebellar degeneration (PCD) is a rare paraneoplastic autoimmune condition driven by antibodies directed against cerebellar antigens initiated by onconeural proteins, causing a progressive truncal cerebellar syndrome. Here, we present a patient with a poorly differentiated squamous cell carcinoma of tonsil who manifested simultaneously features of PCD and CAR, two conditions that have previously not been reported to occur together. 

Case Presentation
A 66-years old man presented with progressive, painless bilateral peripheral and night vision loss, alongside truncal ataxia, dysmetria in the extremities, and dysarthria over several months. Optical coherence tomography showed diffuse outer retinal loss and depressed multifocal electroretinogram (mfERG) in both eyes. Visual acuity further declined over the next two months. Concomitantly, a poorly differentiated squamous cell carcinoma was identified in the right tonsil. CAR panel showed strong diffuse staining on immunohistochemistry with elevated titers for recoverin, enolase and carbonic anhydrase II antibodies. Magnetic resonance imaging showed cerebellar atrophy consistent with PCD, but screening paraneoplastic antibodies linked to cerebellar ataxia were negative. Robotic right tonsillectomy with neck dissection was performed and the patient underwent immunotherapy with intravenous immunoglobulin (IVIG) and high dose corticosteroids. Six months later, the patient demonstrated no recurrence of his cancer with improvements in his visual acuity, retinal structure, and mfERG. His ataxia also improved. One year later, rituximab therapy was initiated. Now five years later, there are sustained improvements in vision and gait.

Discussion
We highlight a case of CAR that coincided with cerebellar ataxia caused by seronegative PCD that responded well to treatment of the underlying squamous cell carcinoma of the tonsil, followed by corticosteroid therapy, IVIG, and rituximab therapy. In this case, several autoantibodies known to cause CAR were identified while no autoantibodies linked to PCD were detected. Up to a third of patients with PCD (and CAR) are seronegative for known antibodies. Given the wide range of aberrant proteins expressed by poorly differentiated malignant cells, patients often develop circulating autoantibodies to more than one target. Although no autoantibodies are known to link PCD to CAR, a yet unidentified cross-reactive antibody may explain the overlapping syndrome seen in our case.

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Forodesine has anticancer immunomodulatory properties through the adenosine pathway

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