Chronic inflammation is a cancer hallmark and chronic exposure to interleukin-1 (IL-1) transforms castration-sensitive prostate cancer (PCa) cells into more fit castration-insensitive PCa cells. p62 is a scaffold protein that protects cells from nutrient deprivation via autophagy and from cytotoxic reactive oxygen via NFκB and NRF2 antioxidant signaling. Herein, we report that the LNCaP PCa cell line acquires high basal accumulation of the p62-KEAP1 complex when chronically exposed to IL-1. p62 promotes non-canonical NRF2 antioxidant signaling by binding and sequestering KEAP1 to the autophagosome for degradation. But despite high basal p62-KEAP1 accumulation, only two of several NRF2-induced genes analyzed, GCLC and HMOX1, showed high basal mRNA levels, suggesting that the high basal p62-KEAP1 accumulation does not result in overall high basal NRF2 activity. Nutrient starvation induces NRF2-dependent GCLC upregulation and HMOX1 repression, and we found that chronic IL-1-exposed LNCaP cells show hypersensitivity to serum starvation-induced GCLC and HMOX1 regulation. Thus, chronic IL-1 exposure affects cell response to nutrient stress. While HMOX1 expression remains NRF2/KEAP1-dependent in chronic IL-1-exposed LNCaP cells, GCLC expression is NRF2/KEAP1-independent. Furthermore, the high basal p62-KEAP1 complex accumulation is not required to regulate GCLC or HMOX1 expression, suggesting cells chronically exposed to IL-1 evolve a novel NRF2-independent role for the p62/KEAP1 axis.

Chronic inflammation is a hallmark of the breast cancer tumor microenvironment and is also known to be associated with disease progression and therapeutic response. Interleukin-1 (IL-1) signaling has been widely studied in breast cancer biology; however, the long-term effect of sustained IL-1 exposure on hormone receptor-positive breast cancer cells remain poorly understood. In this study, we investigated how chronic IL-1 exposure influences inflammatory response, hormone dependency, and therapeutic sensitivity in ERα+/PR+ breast cancer models, MCF7 and T47D. Chronic IL-1 exposure attenuated response to subsequent acute IL-1 treatment, but the chronically exposed cells remained sensitive to serum deprivation, retained dependence on estrogen or progesterone receptor signaling, and responded robustly to endocrine and chemotherapeutic treatments. Extensive changes in basal gene expression and histone modification revealed that chronic IL-1 exposure alters transcriptional reprogramming and chromatin remodeling. Together, these findings demonstrate that chronic IL-1 signaling drives selective inflammatory response in hormone receptor-positive MCF7 and T47D breast cancer cells. This work underscores the continued therapeutic relevance of hormone receptor-targeted strategies in chronically inflamed tumors and provides insight into how sustained inflammatory stress shapes tumor behavior and gene regulation predicted to promote tumor progression.

Objective: To evaluate the effect of multidisciplinary tracheostomy team (MDT) interventions on emergency department utilization in pediatric patients with tracheostomy. Methods: This retrospective cohort study analyzed a prospective registry of 364 children who underwent tracheostomy from 2015 to 2023 at a single tertiary pediatric center. The study period encompassed pre‐intervention, post‐intervention pre‐COVID, COVID‐19, and post‐COVID recovery phases. Primary outcomes were time to ED visits and ED visit frequency, analyzed using parametric survival analysis and mixed‐effects negative binomial regression. Results: Among 364 patients (mean age 3.5 ± 5.4 years; 53% male), MDT implementation was associated with a 50% reduction in ED visit rates (incidence rate ratio 0.50, 95% CI: 0.43–0.57, p < 0.001) during the post‐intervention, pre‐COVID period. Benefits sustained through COVID (65% reduction) and post‐COVID recovery (91% reduction). Time to first ED visit increased significantly across post‐intervention periods (post‐intervention, pre‐COVID: time ratio 1.22, 95% CI: 1.12–1.32, p < 0.001; post‐COVID recovery: time ratio 1.25, 95% CI: 1.11–1.40, p < 0.001). During median follow‐up of 2.8 years, 1056 of 1842 total encounters (57%) involved ED visits. Respiratory conditions accounted for 34% of ED visits. Hispanic ethnicity (time ratio 0.88, p = 0.003) and respiratory‐related visits (time ratio 0.78, p < 0.001) were associated with shorter return intervals but did not affect overall visit frequency. Conclusion: MDTs were associated with sustained 50% reductions in pediatric ED utilization, with reductions continuing through the COVID‐19 pandemic. Levels of Evidence: 3.

Objectives: To develop and validate a risk stratification model for postoperative dysphagia in pediatric cardiac surgery patients, focusing on factors relevant to otolaryngologic assessment and implications for Otolaryngology management. Methods: Analysis of 174 pediatric patients undergoing cardiac surgery at a tertiary care center between January 1, 2022 and December 31, 2023. Logistic regression was used to develop a risk score based on preoperative and intraoperative factors. Patients were categorized into low, moderate, and high‐risk groups for dysphagia requiring Otolaryngology consultation. Secondary outcomes included impaired vocal fold mobility. Results: Of 174 patients, postoperative dysphagia necessitating Otolaryngology evaluation was identified in 102 (58.6%) children. The final predictive model included age at surgery (OR, 0.80; 95% CI, 0.72–0.90; p < 0.001), cardiopulmonary bypass duration (OR, 1.73; 95% CI, 1.23–2.45; p = 0.002), and high‐risk complex procedures (e.g., Norwood) (OR, 6.49; 95% CI, 2.70–15.61; p < 0.001). Model discrimination was good (AUC 0.82). Predicted risk categories showed distinct dysphagia rates among the cohort: low‐risk (24.7% of the cohort, with 30.2% experiencing dysphagia), moderate‐risk (31.6%, with 38.2% experiencing dysphagia), and high‐risk (43.7%, with 89.5% experiencing dysphagia). Among high‐risk patients, 70.6% exhibited impaired vocal fold mobility at long‐term follow‐up. Conclusion: This Otolaryngology‐focused risk stratification model identifies pediatric cardiac surgery patients at high risk for postoperative dysphagia and associated impaired vocal fold mobility. Early identification of this population can aid consultation and therapeutic interventions like injection laryngoplasty. Level of Evidence: Level 3.

Purpose: To evaluate the risk of diabetic retinopathy (DR) progression and associated ophthalmic complications after YAG laser capsulotomy in patients with nonproliferative DR (NPDR) after cataract surgery. Setting: Multicenter study using deidentified electronic health records from 69 U.S. healthcare organizations across outpatient and academic ophthalmology settings. Design: Retrospective cohort study using propensity score matching to balance baseline characteristics. Methods: Patients aged 18 years or older with type 1 or 2 diabetes and NPDR who underwent cataract surgery with or without subsequent YAG laser capsulotomy were identified. Patients were followed for 1-year postcataract surgery. Exclusion criteria included less than 6 months of follow-up. Primary outcomes included development of proliferative DR (PDR), vitreous hemorrhage (VH), tractional retinal detachment (TRD), neovascular glaucoma, and need for panretinal photocoagulation (PRP) or pars plana vitrectomy. Results: 10 750 patients (10 750 eyes) were included after matching: 5375 YAG-treated and 5375 control eyes. At 1 year, YAG-treated patients had higher risk of PDR (hazard ratio [HR], 1.91; 95% CI, 1.67-2.18), VH (HR, 1.40; 95% CI, 1.15-1.72), TRD (HR, 2.04; 95% CI, 1.32-3.13), and PRP (HR, 1.48; 95% CI, 1.14-1.91). A secondary analysis of patients with ≥5 years of NPDR showed similar elevated risks. Conclusions: YAG laser capsulotomy in patients with NPDR is associated with increased risk of DR progression and vision-threatening complications. Ophthalmic screening and close follow-up are recommended in this population after YAG treatment.