Trinity Medical Center

Abstract Background: Latin American (LA) women are more likely to be diagnosed with aggressive early-stage breast cancer (EBC) compared to Non-Hispanic White (NHW) women, yet population-specific tumor biology remains underexplored. Previously, we reported elevated immune gene expression in BluePrint® (BP) Luminal B tumors in LA patients (pts) with EBC and obesity compared to Black and NHW cohorts. Here, we present updated clinical comparisons between LA, NHW and Black pts with EBC and whole transcriptome analysis (WTA) between BP Luminal B and Basal BC in pts with obesity. Methods: Clinical and WT data were analyzed from 15,577 EBC pts self-identified as LA, Black, or NHW enrolled in FLEX (NCT03053193), a prospective observational study with MammaPrint® risk of recurrence and BP molecular subtyping assays, and WT profiles. ImPrint, 53-gene immune signature, results (+/-) were generated for pts with hormone receptor positive (HR+) EBC. Chi-square and t-tests were conducted on clinical groups using arsenal R package. For WT comparisons, 215 obese LA pts with BP Luminal B and 77 with BP Basal EBC were matched to corresponding NHW and Black pts by age, T and N status. Differentially expressed genes (DEGs) were evaluated using limma, and pathway enrichment was performed using gene set enrichment analysis with Hallmark gene sets. Significant results were reported with adjusted p < 0.05. Results: Compared to Black and NHW pts, LA pts were younger and more often premenopausal (Table). Both LA and Black pts had statistically significantly higher rates of obesity compared to NHW pts. Significantly higher rates of MP High Risk 2, BP Basal and ImPrint+ tumors were observed in LA and Black pts vs NHW. WT comparisons among the obese subpopulations revealed that metabolic pathways, including adipogenesis, angiogenesis, epithelial-mesenchymal transition, and oxidative phosphorylation were significantly downregulated in EBC in LA pts vs NHW and Black cohorts. Conversely, immune-related pathways such as allograft rejection and interferon gamma response were enriched among LA pts with Basal cancers compared to NHW and Black groups. These coordinated pathway alterations suggest unique metabolic and immune profiles in LA EBC subtypes with a median absolute fold change of 1.3 among DEGs. Conclusion: The data suggest that signals from metabolic pathway alterations from modest immune-related gene upregulation may contribute to more aggressive tumor behavior in obese LA pts with EBC. Clinical and transcriptomic analyses demonstrated differences in Luminal B and Basal EBC biology among self-identified LA pts compared to NHW and Black cohorts, consistent with prior research. With further research, these findings may offer treatment targets which may enhance outcomes and reflect the importance of including racially and ethnically diverse pts in clinical trials to characterize population-specific differences in EBC outcomes. Citation Format: M. Mazo Canola, A. Santillan, J. Alberty-Oller, E. Dias, V. Kaklamani, A. Elkhanany, K. Hoskins, M. Habibi, R. Hampton, J. L. Barone, N. M. Johnson, N. Gordon, N. Sookhan, T. Bah, P. John, E. Aponte, S. Diab, V. Klimberg, N. Stivers, C. Page, S. Uygun, W. Audeh, J. O'Shaughnessy. Distinct Immune and Metabolic profiles in Latin American breast cancer patients with obesity enrolled in FLEX [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-09.

TPS279 Background: A total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone in those with locally advanced rectal cancer. Recent data indicate that optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to improve complete response rates. The use of FOLFIRINOX has shown to improve response and outcomes compared to CRT and surgery alone. Data have also shown that patients with clinical complete response (cCR) after TNT may be managed with a watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to improve cCR rates has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. We designed this NCI-sponsored study of chemotherapy intensification to address this and to increase cCR rates, provide opportunity for organ preservation, and survival outcomes. Methods: In this multigroup randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX (control arm)) or triplet chemotherapy (FOLFIRINOX (experimental arm)) for 3–4 months. LCRT in both arms involve 4500 cGy in 25 fractions over 5 weeks +900 cGy boost in 5 fractions with a fluoropyrimidine. Patients will undergo assessment 8–12 (±4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include overall survival, organ preservation time, time to distant metastasis, and adverse event rates. This study completed accrual as of July 2025 and is investigating exploratory correlatives (e.g., ctDNA). Support: U10CA180821, U10CA180882, U24 CA196171. https://acknowledgments.alliancefound.org. Clinicaltrials.gov ID: NCT05610163. Clinical trial information: NCT05610163 .

Epilepsy, and the treatments associated, involvebio-hormonal disruption, altered endocrine physiology, and maladaptive reproductive influence. All of which may impact seizure susceptibility. Gelastic seizures (GS), are often linked to hypothalamic hamartomas (HH), which are uncommon congenital abnormalities characterized by the often-pathognomonic triad of GS, early puberty, and developmental delay. This systematic review aims to revisit first-line therapeutics associated with GS, as well as the theoretical surgical and non-surgical approaches targeting management of this disease process. A comprehensive literature review was conducted using the databases PubMed, ProQuest, and Science Direct. A diverse range of studies were chosen. The search included the keywords "First-Line Therapeutics for Gelastic Epilepsy" and "Novel Management Strategy for Gelastic Epilepsy". Out of 31 screened papers, 16 articles in total met the criteria for inclusion. One article explored contained inaccessible full-text records; therefore 15 articles were systematically reviewed. Research suggests GS are typically the initial seizure manifestation of hypothalamic hamartomas. Current and emerging pharmaceutical therapeutic strategies are currently being investigated; however, research indicates the surgicalanterior transcallosal interforniceal approachextremely effectivelywith othertreatment methods utilizing endoscopic and radio surgical ablative techniques a promising alternative.

Atrial fibrillation (AF), a common cardiac arrhythmia, is often accompanied by aortic plaquesthat are associated with an increased risk of embolic events, including stroke. Evidence-based management in this population is lacking. We present a case of a 77-year-old female with new-onset AF who was found to have a high-risk aortic plaque at the level of the ascending aorta and ostium of the right coronary artery. Definitive treatment for AF, cardioversion, high-risk aortic plaque, and cardiothoracic surgery, could not be performed due to the elevated risk of ischemic stroke and embolic complications. Based on existing literature, the cardiologist and cardiothoracic surgeon collaboratively decided to treat both conditions with anticoagulation, statin, and periodic imaging surveillance of high-risk aortic plaque. The patient was successfully managed without any thromboembolic complications despite an elevated risk. This case report provides a comprehensive literature review of managing AF with high-risk aortic plaques. It delves into the integration of anticoagulation and antiplatelet agents in the dual challenge of stroke prevention in AF and mitigating embolic risks associated with aortic plaques. To date, there has been no consensus on managing AF and high-risk aortic plaques; thus, we aim to fill this gap.

Intussusception is highly uncommon in adults, with most cases caused by a pathological lead point that requires surgical resection. This case presentation highlights a rare example of idiopathic intussusception in a young male adult. Our patient is a 23-year-old African American male who presented at the Piedmont Macon Medical Center emergency department in February 2023 with acute-onset severe periumbilical pain, nausea, vomiting, and diarrhea. Computed tomography (CT) imaging was inconclusive, and his diagnosis of an ileo-ileal intussusception in the distal ileum was made during an exploratory (diagnostic) laparoscopy. Based on a visual inspection of the bowel demonstrating no evidence of inflammation, adhesions, lesions, ischemia, or a pathological lead point, manual reduction without resection was indicated. While intussusception is rare in adults, it is an important clinical prognosis that should be carefully considered in the differential diagnosis.

Hypoglycemia is a signicant constraint in the regulation of glycemic levels in individuals with diabetes. Type 1 diabetes (T1D) is classied as an autoimmune disorder wherein the immune system of the body initiates an assault on the pancreatic beta cells responsible for insulin production, leading to their subsequent destruction. Insulin is a hormone that facilitates the utilization of glucose as an energy source within the human body. In the absence of insulin, there is a build-up of glucose in the bloodstream, resulting in a range of health issues, such as hyperglycaemia. Occasional episodes of hypoglycemia can also occur in Type 1 diabetes due to multiple reasons such as increased physical activity, diet and Iatrogenic causes. Iatrogenic hypoglycemia commonly arises from the interaction between an excessive administration of insulin and impaired glucose counterregulation in individuals with Type I diabetes mellitus, which requires insulin for management. Iatrogenic hypoglycemia is a signicant obstacle in effectively managing glycemic levels in individuals with diabetes. The fall in glucose concentrations does not typically result in a decrease in insulin concentrations, nor does it lead to an increase in glucagon and epinephrine concentrations as would be expected under normal circumstances. The hypothesis of hypoglycemia-associated autonomic failure (HAAF) in Type I diabetes suggests that prior iatrogenic hypoglycaemia leads to impaired glucose counter-regulation characterised by a diminished epinephrine response in the absence of a glucagon response. Additionally, it is proposed that hypoglycemia unawareness occurs as a result of reduced autonomic function and subsequent attenuation of neurogenic symptom responses. The mediator and mechanism of HAAF remain unknown, although they are currently the subject of ongoing investigation. Hypoglycemia in individuals with insulin deciency, including those with Type 1 Diabetes Mellitus (T1DM) and advanced Type 2 Diabetes Mellitus (T2DM), occurs due to a combination of excessive therapeutic insulin administration and impaired physiological (such as improper glucose counter-regulation) and behavioural (such as hypoglycemia unawareness) mechanisms that normally protect against declining blood glucose levels. This study aims to review the physiological and psychological experiences of individuals living with Type 1 Diabetes and hypoglycemia, while also seeking to identify effective techniques to promote well-being and enhance adherence to treatment protocols.

Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines. An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians. A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India. There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted. Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM.