United States

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.

AMA Research Challenge 2025 

Forodesine has anticancer immunomodulatory properties through the adenosine pathway

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Background
Platelet-activating factor (PAF) is a potent signaling phospholipid produced by embryos to facilitate standard embryonic development and subsequent implantation. Along with PAF, intracellular calcium is required for the initiation and facilitation of developmental transitions in embryos. Previous literature has revealed that PAF and intracellular calcium are interconnected during early embryo development; however, the signaling mechanism is unknown. This study reports enhanced induction of intracellular calcium release in response to exogenous PAF administration in sea urchin embryos at the two-cell stage.
Methods
Gravid Lytechinus variegatus sea urchins were injected with 0.5M KCl to induce release of gametes. In a 100 µL drop of seawater, 20 µL of eggs and 2 µL of sperm were combined. Once the inseminated eggs developed a fertilization membrane, a 5 µM concentration of a fluorescent calcium indicator (Fluo-4) was added and maintained in culture. Embryos were subsequently cultured to the two-cell stage over the next 90 minutes. Following incubation, 45 µL of two cell embryos were transferred to a poly-L-lysine-coated microscope slide, after which PAF (10-7M) was added. This addition of PAF was performed while the slide was imaged under a fluorescent microscope (Echo Revolve) to observe the fluorescence of calcium release, which was recorded as relative fluorescence units (RFU). The procedure was repeated using the biologically inactive form of PAF (Lyso-PAF) as a negative control. Data was analyzed via paired t test (Sigma Plot). 
Results
A total of 16 two-cell stage embryos were utilized as described. PAF (mean= 70.9 RFU) induced a significant (P< 0.01) rise in intracellular calcium levels over background (controls; mean= 44.5 RFU). Lyso-PAF was not observed to induce any rise in intracellular calcium levels over background levels.
Conclusion
These results indicate that there is increased intracellular calcium release in embryos that have been exposed to exogenous PAF in comparison to control embryos and embryos that have received Lyso-PAF. Due to the known separate actions of PAF and intracellular calcium during development combined with our findings, this demonstrates that PAF likely induces the release of intracellular calcium, facilitating the development of sea urchin embryos. 



Platelet-Activating Factor Enhances Intracellular Calcium Release in Sea Urchin Embryos

Introduction:

The application of therapeutic hypothermia (TH) following acute myocardial infarction (AMI) remains underexplored in the United States. This study aims to assess the national prevalence and predictors of TH use in post-AMI patients.
Methods:

A retrospective cross-sectional analysis was conducted using the Nationwide Inpatient Sample (NIS) from 2016 to 2018. Adult AMI hospitalizations were identified using ICD-10-CM code I21, and TH utilization was determined using procedure codes 6A4Z1ZZ and 6A4Z0ZZ. Statistical analyses included univariate chi-square tests and multivariable logistic regression to identify factors independently associated with TH use. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported, with a significance threshold of p < 0.05.
Results:

Of 41,180 adult patients hospitalized with AMI, only 1,805 (4.38%) received TH. Patients more likely to receive TH were Hispanic, had higher household incomes, and exhibited comorbidities such as obesity, renal failure, and metabolic syndrome. In multivariable analysis, independent predictors of TH use included older age (OR 1.32; 95% CI: 0.94–1.86; p < 0.001), higher income

(OR 1.32; 95% CI: 1.0–1.7), obesity (OR 1.42; 95% CI: 1.06–1.89), renal failure (OR 1.69; 95%

CI: 1.31–2.17), and metabolic syndrome (OR 2.97; 95% CI: 0.5–20.14). (p< 0.001)

Conclusion:

Therapeutic hypothermia was utilized in approximately 4% of AMI hospitalizations, particularly among patients with obesity and renal failure. Further research is warranted to better define the patient populations most likely to benefit from this intervention.





Nationwide Trends in the Utilization of Therapeutic Hypothermia After Acute Myocardial Infarction in the United States

Background
In obesity, excess adipose tissue drives systemic low-grade inflammation and insulin resistance through the secretion of pro-inflammatory cytokines such as TNF-α and IL-6. While current treatments mitigate obesity via weight loss or glycemic control, they often fail to address the underlying inflammatory source. Liposuction, by surgically removing adipose tissue, may offer benefits beyond aesthetics by potentially altering inflammatory and endocrine profiles. This review evaluates existing data examining this hypothesis on the metabolic benefits of liposuction in the context of insulin resistance and inflammation.
Methods
A scoping review following PRISMA guidelines was conducted using PubMed to identify clinical studies examining the effects of liposuction on metabolic and inflammatory markers in obese individuals. 122 articles were initially identified, with 9 meeting the inclusion criteria: human studies reporting pre- and post-liposuction levels of IL-6, TNF-α, HOMA or adiponectin. Case studies, animal-based studies, and review articles were excluded. Results from the 9 studies were analyzed for the variables: volume of aspiration, HOMA, TNF-α, IL-6 and adiponectin.
Results
Volume of fat aspirated negatively correlated acute (1-3 months) changes in HOMA (R2=0.991) and chronic (6-12 months) changes in HOMA (R2=0.52). Furthermore, we observed a moderate negative correlation between volume of fat aspirated and chronic changes in TNF-α levels (R2=0.567). However, chronic IL-6 levels had a weak negative correlation with fat aspirated (R2=0.396). Adiponectin appeared to be negatively correlated with volume of fat aspirated in the short-term (R2=-0.2509) but was observed to have a moderate increase in the long-term (R2=0.5485). Interestingly, adiponectin increases in the long-term were strongly correlated with reduction of IL-6 levels (R2=-0.9963). Adiponectin had a weak acute correlation (R2=0.1065) with TNF-α and was not studied in the chronic phase.
Discussion
Liposuction appears to attenuate obesity-associated inflammation and insulin resistance, as evidenced by sustained reductions in HOMA, TNF-α, and IL-6 levels six months postoperatively. Interestingly, adiponectin levels increased during this period, suggesting an overall improvement in the inflammatory profile. Acute inflammatory markers showed weak correlations, likely reflecting transient surgical trauma. These findings highlight adiponectin as a promising long-term biomarker for studying metabolic improvement post-liposuction, warranting continued monitoring beyond 6 months to further elucidate its relationship with TNF-α. 
Conclusion
This study offers early clinical evidence that liposuction shows potential as an adjunctive therapy for metabolic dysfunction in obese individuals alongside lifestyle modifications and pharmacological therapy. However, its therapeutic role requires further validation through rigorous, sex-stratified trials with extended follow-up.

The Impact of Liposuction on Metabolic Health in Obese Women with Insulin Resistance: A Clinical Perspective

Background
Hepatocellular carcinoma (HCC) has a high mortality rate and is often diagnosed late, limiting treatment options. ​​Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are common interventional treatments for HCC, particularly for patients ineligible for curative options. While randomized controlled trials (RCTs) have validated these therapies, their real-world applicability and clinical utility remain uncertain. Other fields have critically evaluated RCT limitations, but interventional radiology has yet to do so systematically. Using the van ’t Hooft et al. framework, we assessed RCTs on TACE/TARE in HCC and liver metastases to identify limitations in generalizability and reporting and offer suggestions to improve future trials in interventional radiology.

Methods
A systematic review of RCTs published from 2004 to 2024 was conducted via MEDLINE and Embase. Screening and assessment was conducted by two reviewers based on the van ’t Hooft et al. criteria, which scores 13 clinical utility and transparency items on a 0-2 scale; including context placement, information gain, feasibility, patient-centeredness, pragmatism, value for money, and transparency. Descriptive statistics and regression analyses explored trends over time. 

Results
Among 135 included RCTs out of the 912 records, most performed well in areas like context placement and conflict-of-interest disclosure. However, major gaps were found in raw data availability (9.6%), self-evaluated cost-value analysis (0%), and self-evaluation for pragmatism (0.7%). Total usefulness improved over time, with transparency rising more than clinical utility between 2004 and 2024. A significant positive correlation was found between transparency and clinical utility (r = 0.50, p < .001), highlighting the need for more pragmatic and transparent trials to guide interventional radiology practice.

Conclusion
This study aimed to identify and quantify the usefulness and clinical applicability of RCTs evaluating TACE/TARE in hepatic malignancies by addressing study design limitations, using the van ‘t Hooft et al. usefulness framework, and determining areas for improvement in transparency and applicability. Despite improvements, critical elements such as budget impact calculation, pragmatism, and data sharing remain underreported. Given the multiple factors that influence treatment choice for HCC, future clinical trials should aim to increase real-world applicability in their design through multi-site collaborations that reflect the range of treatment resources across different communities. Closing these gaps in transparency and pragmatism will make research outcomes in TACE/TARE for HCC more trustworthy, clinically relevant and beneficial to patients.

Assessing the Clinical Usefulness of Randomized Trials for Transarterial Chemoembolization and Transarterial Radioembolization: A Systematic Review

Background:
Stenotrophomonas maltophilia is an uncommon but increasingly recognized cause of healthcare-associated infections, known for its intrinsic resistance to many broad-spectrum antibiotics. While it primarily affects immunocompromised individuals, its role in chronic wound infections such as diabetic foot ulcers remain underreported. This case underscores the clinical significance of S. maltophilia in diabetic foot osteomyelitis, especially in the context of polymicrobial infection with drug-resistant Gram-negative organisms.

Case Presentation:
A 64-year-old woman with longstanding type 2 diabetes and peripheral neuropathy presented with a draining ulcer over her left lateral ankle, months after an inadequately treated ankle injury. Initial evaluation revealed a necrotic ulcer with underlying bone exposure. Imaging demonstrated advanced osseous destruction involving the distal tibia and tarsal bones, consistent with osteomyelitis. Deep tissue cultures identified S. maltophilia resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and intermediately susceptible to fluoroquinolones, as well as an extended-spectrum beta-lactamase (ESBL) producing Escherichia coli strain. Initial antibiotic therapy was adjusted multiple times due to resistance patterns and hepatotoxicity. Despite appropriate antimicrobial management with cefiderocol, subsequent imaging revealed a progressing infection with abscess formation and talar necrosis. Surgical consultation resulted in a below-the-knee amputation to manage infection and preserve functional mobility.

Discussion: 
Although rare in diabetic foot osteomyelitis, S. maltophilia may contribute to more severe disease and poorer outcomes, particularly when co-infecting with resistant organisms such as ESBL-producing E. coli. The pathogen’s resistance to most β-lactams and increasing non-susceptibility to standard agents like TMP-SMX limit therapeutic options. Evidence suggests that S. maltophilia may be independently associated with a greater likelihood of major amputation in limb-threatening diabetic foot infections. This case highlights the importance of early pathogen identification, consideration of atypical organisms in non-healing ulcers, and the need for timely, individualized treatment approaches when managing complex diabetic foot infections.

When the Usual Suspects Aren’t to Blame: A Case of Stenotrophomonas Osteomyelitis in a Diabetic Foot

Abstract Title
KRAS Q61L Mutation in an African American Male with Stage IV Colorectal Cancer

Background
KRAS mutations occur in 35–45% of colorectal cancer cases, mainly at codons 12 and 13. Codon 61 mutations, including Q61L, are rare and appear in 2-5% of cases. It involves substitution of glutamine with leucine. This leads to constitutive KRAS activation and downstream signaling, resulting in resistance to anti-EGFR therapies and poor prognosis. This mutation is underrepresented in both research and clinical trials, particularly in African American populations.

Case Presentation
A 73-year-old African American male with stage 3a chronic kidney disease, hypertension, and asthma presented in September 2022 with hematemesis, melena, and altered sensorium. Workup revealed liver cirrhosis with upper gastrointestinal bleeding and iron-deficiency anemia. Colonoscopy identified an 18 mm pedunculated sigmoid polyp and a rectosigmoid mass. Biopsy confirmed moderately differentiated intramucosal adenocarcinoma arising from a high-grade tubular adenoma. CT scan at that time showed no metastases, indicating stage II colorectal carcinoma. Molecular testing identified a KRAS Q61L mutation, along with APC and TP53 mutations, intact mismatch repair gene expression, and high tumor mutational burden (TMB:10 mut/Mb). The patient was initiated on FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) treatment, completing 12 cycles by June 2023. Intravenous iron and epoetin-alfa were used to treat anemia. However, subsequent CT scan in May 2023 revealed progression to stage IV colorectal carcinoma, with metastases to the L3 vertebra, left kidney, right lung apex, and subcarinal lymph nodes. The patient transitioned to palliative care and died in 2024.

Discussion
The KRAS Q61L mutation is a poorly characterized variant that activates mitogen-activated protein kinase (MAPK) signaling and confers resistance to anti-EGFR therapy. Loree et al. found that non-G12/13 KRAS mutations are associated with worse outcomes, though specific data on Q61L are limited. Our case highlights this rare mutation in an African American patient who progressed from stage II to stage IV cancer while on chemotherapy. Standard chemotherapy remains the cornerstone of treatment since no approved targeted therapy is available for Q61L. Clinical trials are investigating MEK inhibitors, SHP2 inhibitors, and combination therapies for Q61 mutations. This case underscores the urgent need for inclusive research and mutation-specific therapies in colorectal carcinoma, as KRAS mutations, including Q61L, are associated with poor prognosis.

KRAS Q61L Mutation in an African American Male with Stage IV Colorectal Cancer

Background: Swallow syncope (also known as deglutition syncope), is an uncommon form of situational reflex syncope that is triggered by swallowing. It is associated with esophageal or cardiac reflex pathways, with the vagus nerve being central to its pathogenesis. The rare and vague presentation of swallow syncope lends itself to difficulties in timely diagnosis.
Case Presentation: An 89-year-old wheelchair-bound male with a complex medical history including hypertension, iatrogenic adrenal insufficiency, chronic kidney disease, bilateral frontoparietal chronic subdural hematomas (status post middle meningeal artery embolization), benign prostatic hyperplasia, and recurrent syncopal episodes of unknown etiology, was brought in by EMS after being found unresponsive by his wife.
Comprehensive workup (labs, vital signs, echocardiogram, CT head (non-contrast), brain MRI, long-term video EEG, CT angiogram of the neck, EKG, and telemetry) were unremarkable aside from orthostatic hypotension. Cardiology, endocrinology, and neurology were consulted for evaluation.
Then, the patient experienced a syncopal episode following breakfast, prompting a speech-language pathology (SLP) evaluation due to concerns of aspiration. During this assessment, the possibility of swallow syncope was raised. When questioned, the patient reported a potential temporal association between food intake and previous syncopal events.
Diagnosis of swallow syncope requires an established temporal relationship between swallowing and the syncopal event, necessitating further testing. However, the patient and his wife declined further invasive diagnostics.
The patient was discharged with a 30-day event monitor for outpatient cardiology follow-up. Conservative measures (adjusting the timing of antihypertensive medications, compression stockings, avoiding potential food triggers such as cold or carbonated beverages) were recommended.
Discussion: Swallow syncope is a rare subtype of situational reflex syncope. It is thought to result from an abnormal vagal reflex triggered by deglutition, leading to bradycardia, atrioventricular block, or vasodilation. It has commonly been reported in patients with esophageal disorders, but can also occur in individuals without structural abnormalities. Swallow syncope requires temporal correlation of syncopal episodes with esophageal provocation, evidenced through continuous ECG monitoring. The diagnosis can be delayed due to having to perform extensive diagnostics to exclude other pathologies, and further delayed in elderly patients with communication barriers or multiple comorbidities. 
This case highlights the importance of a multidisciplinary approach in diagnosing complex presentations of syncope. The involvement of the Speech-Language Pathologist (SLP), typically consulted for aspiration risk, led to the possible diagnosis of swallow syncope. Non-traditional contributors, such as SLPs, can provide crucial and timely perspectives in complex cases such as geriatric or cognitively impaired patients.

An Unusual Case of Swallow Syncope in an Elderly Male: The Value of
Multidisciplinary Collaboration

Introduction:
Huntington's disease (HD) is the most common monogenic neurodegenerative disorder in the Western world, first described by George Huntington in 18721. 
It is a hereditary choreiform disorder with behavioral and neuropsychiatric manifestations. 
Unlike many similar diseases, HD typically presents in adulthood. While rare in Asia, its devastating progression makes it an important clinical consideration globally.

Case-presentation:
40-year-old female presented with a two-year history of progressive, involuntary, non-rhythmic movements involving the upper limbs, tongue, and lips. 
She was alert and oriented (GCS 15/15). Examination showed a wide-based gait, reduced power (4/5) in the left limbs, and weakness of intrinsic hand muscles. MMSE was 14/30.
Routine lab work, including CBC, TSH, LFTs, and RFTs, was unremarkable. A workup to rule out other causes of chorea was negative, with normal serum ceruloplasmin and ASO titers.
A brain MRI showed no significant intracranial abnormality2,3. 
Given the clinical picture, genetic testing was performed. It confirmed the diagnosis of Huntington's disease, revealing a pathogenic expansion in the HTT gene (18/39 CAG repeats)4.5.
Symptomatic treatment was initiated with Deutetrabenazine (25 mg twice daily) to manage chorea and Alprazolam for anxiety, with the goal of improving quality of life.

Discussion:
This case highlights the importance of maintaining clinical suspicion for HD in patients with progressive chorea and cognitive decline, even with normal imaging. While no curative treatment exists, symptomatic management with agents like Deutetrabenazine can control chorea and improve quality of life6. Timely genetic confirmation is essential for providing multidisciplinary care and patient-centered management.

Conclusion:
A normal brain MRI does not exclude a diagnosis of Huntington's disease. Clinical presentation, coupled with genetic testing for CAG repeats, remains the gold standard for diagnosis.




Huntington’s Disease in a 40-Year-Old Female with Normal Brain MRI: Case Report

Abstract Title
Neurotrophic Keratopathy in an Infant with Moebius Syndrome
Background

Moebius Syndrome is a rare congenital condition characterized by dysfunction of the sixth and seventh cranial nerves, leading to facial weakness and impaired abduction of the eyes. While facial nerve palsy is the hallmark, other cranial nerves, particularly the trigeminal nerve, may be involved. Neurotrophic keratopathy, a rare but serious complication, results from impaired corneal innervation, leading to epithelial breakdown, impaired healing, and risk of vision loss. We report a rare case of neurotrophic keratopathy in an infant with Moebius Syndrome, highlighting the importance of early recognition of trigeminal involvement to prevent permanent damage.

Case Presentation

A 10-month-old male with unilateral cerebellar hypoplasia and spastic hemiplegia presented with one week of irritability and two days of left eye redness. Examination revealed conjunctival erythema with crusty yellow discharge. He was prescribed moxifloxacin drops and gentamicin ointment. Due to lack of improvement, he was evaluated two days later in the ophthalmology clinic.
On examination, the patient demonstrated intermittent fixation, alternating esotropia, and bilateral abduction deficits. A corneal ulcer was noted in the left eye; the remainder of the exam was normal. Despite continued antibiotic therapy, the left eye worsened over the next week, with corneal clouding. He was referred to a corneal specialist. Maxitrol was discontinued, cultures were obtained, and erythromycin 0.5% ointment was initiated. The guardian was instructed on frequent lubrication, and 24-hour patching was recommended.
Based on unilateral facial nerve palsy, alternating esotropia, bilateral lateral gaze palsy, absent corneal reflex, and imaging showing unilateral cerebellar hypoplasia, Moebius Syndrome was diagnosed. The corneal ulcer was attributed to neurotrophic keratopathy. Despite aggressive lubrication and patching, the ulcer did not improve, and cultures remained negative. The patient underwent corneal epithelial debridement, amniotic membrane transplantation using the sandwich technique, and temporary tarsorrhaphy. Ten days later, tarsorrhaphy reversal revealed complete corneal healing.

Discussion

This case highlights a rare presentation of Grade 2 neurotrophic keratopathy secondary to corneal anesthesia in an infant with Moebius Syndrome. Diagnosis was supported by literature. While neurotrophic keratopathy is well-documented in older patients, it may be overlooked in infants. Early recognition is critical, as delayed diagnosis increases the risk of permanent corneal damage. In this case, treatment with amniotic membrane transplantation promoted epithelial healing and prevented further scarring. Long-term management may require corneal neurotization to restore sensation and protect vision. This case underscores the importance of early diagnosis and intervention in pediatric neurotrophic keratopathy to prevent irreversible vision loss.



Neurotrophic Keratopathy in an Infant with Moebius Syndrome

Background: Trust in health insurance plays a crucial role in shaping individuals’ engagement with healthcare services, particularly as insurers assume more proactive roles in care delivery. However, limited research has examined which factors influence trust in health insurance plans and companies at the national level.

Methods: We used data from 7,702 adults in the 2021 Health Reform Monitoring Survey (HRMS) to assess factors associated with trust in health insurance. The primary outcome was a binary indicator of trust, derived from agreement with the statement: “I trust my health insurance plan and company.” Weighted bivariate analyses were employed to assess the relationships between trust and sociodemographic, health-related, and insurance-related characteristics. Variables significantly associated with trust in bivariate analyses were included in a multivariate logistic regression model to assess their independent effects. All analyses accounted for the survey’s probability weights.

Results: Among the 7,702 respondents, 69.1% reported trusting their health insurance provider. In bivariate analyses, trust varied significantly by age, race, education, income, self-rated health, usual source of care, type of insurance, perceived respect from the insurer, and perceived affordability of care (all p < 0.01). In the multivariate logistic regression model, individuals with better health status, lower income, lower education, a usual source of care, or non-private insurance had higher odds of trusting their insurance. Notably, respondents who felt respected by their insurer had substantially higher odds of reporting trust (adjusted odds ratio (OR) = 67.41; 95% confidence interval (CI): 52.25–86.97). Perceived affordability of care was also positively associated with trust (adjusted OR = 1.21 per unit increase in score; 95% CI: 1.11–1.31). After adjustment, Hispanic respondents were 65% more likely to report trust (95% CI: 1.29–2.11) than White individuals.

Conclusion: Both access-related experiences and perceived interpersonal respect from insurers shape conclusions about trust in health insurance. These findings underscore the importance of fostering dignity and responsiveness in insurance interactions, as well as addressing affordability barriers to strengthen beneficiaries’ trust, particularly as insurers assume a greater role in population health and care coordination.

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