Winthrop Rockefeller Foundation

This study aimed to evaluate the associations of baseline income, cumulative income exposure, and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort. We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service (NHIS) health screening. Income level was derived from insurance premium data assessed over the five years preceding baseline (2008-2012) and categorized into baseline income quartiles, cumulative exposure to low or high income, and income volatility based on annual percentage changes. Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry. Associations were evaluated using Cox proportional hazards models with adjustment for demographic, lifestyle, and clinical covariates, and cumulative incidence was compared using Kaplan-Meier curves. During a median follow-up of 9.6 years, 14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed. Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers, whereas sustained high-income exposure was associated with reduced risk. Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence. Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model. These associations were generally consistent across subgroups, with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes. Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers. Lower baseline income was associated with higher risk, whereas sustained high-income exposure was protective. Income volatility was associated with increased cancer risk, particularly for biliary tract cancer. These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.

ObjectivesHead and neck cancer (HNC) has a high recurrence rate. Safety and effectiveness of PepCan in reducing recurrence for HNC patients were assessed.Methods and analysisPepCan consists of four human papillomavirus 16 (HPV 16) E6 peptides and a Candida skin testing reagent (Candin®, Nielsen Biosciences) as a vaccine adjuvant. Since Candida was known to have a general immune stimulating effects, patients were recruited regardless of their HPV status. Men and women with HNC who had no evidence of disease after standard surgery, chemotherapy, and/or radiation treatments were enrolled. They were randomized at 3:1 to PepCan versus placebo. Seven intradermal injections of PepCan or placebo (saline) were given every 3 weeks (first 4 injections) or 3 months (last 3 injections). They were followed with two visits 6 months apart. Safety was assessed using Common Terminology Criteria for Adverse Events version 5, and efficacy was assessed based on not having recurrence within 2 years. In addition, immune responses were examined using enzyme-linked immunospot assay for HPV 16 E6 response, fluorescent-activated cell sorter analysis for peripheral immune cells, and T cell repertoire analysis. Peripheral cytokines and gut and oral microbiome were also analyzed.ResultsSeventeen patients were enrolled. The most common adverse events were grades 1 and 2 injection site reactions, and they occurred more frequently in the PepCan group (p<0.0001). Two patients had allergic reactions (grade 2 and grade 3), at the 6th vaccination, which were considered to be a dose-limiting toxicity (DLT). No serious adverse events were reported. In the intention-to-treat analysis (ITT), 45% (5/11) had non-recurrence in the PepCan group while 80% (4/5) had non-recurrence in the placebo group. For the per-protocol (PP) analysis, non-recurrence was 56% (5/9) for PepCan and 80% (4/5) for placebo. These differences were not statistically significant. Those who received PepCan and experienced non-recurrence had higher new T cell immune responses to HPV 16 E6 (p=0.05 for ITT and p=0.02 for PP). Pre-vaccination T helper type 1 cells were higher in the PepCan non-recurrence group compared to the PepCan recurrence group (p=0.01 for ITT and PP).ConclusionsPepCan is safe although DLT can occur after multiple injections of PepCan. PepCan does not seem to be effective in reducing recurrence; however, the results are inconclusive given the small patient numbers.Trial registration numberNCT03821272

Breast cancer risk varies across metabolic obesity phenotypes, but its associations with premenopausal status and carcinoma in situ remain unclear. The objective of this study was to investigate breast cancer risk across metabolic obesity phenotypes before and after menopause. For this retrospective cohort study, the authors used data from the Korean National Health Insurance Service, including 2,156,798 women who underwent health screening in 2009 (883,250 premenopausal and 1,273,548 postmenopausal). Metabolic obesity phenotypes were classified by the presence or absence of obesity and metabolic syndrome: metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity, with metabolically healthy normal weight as the reference category. Breast cancer risk was estimated by using multivariable-adjusted Cox proportional hazards models. Over a mean follow-up period of 11.94 years, 17,052 premenopausal and 18,870 postmenopausal women developed breast cancer. Before menopause, no significant associations were identified except for a reduced risk of carcinoma in situ among women with metabolically healthy obesity (adjusted hazard ratio, 0.80; 95% confidence interval [CI], 0.74-0.87) and metabolically unhealthy obesity (adjusted hazard ratio, 0.84; 95% CI, 0.74-0.95). After menopause, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity were associated with increased breast cancer risk (adjusted hazard ratio: 1.20 [95% CI, 1.15-1.25], 1.11 [95% CI, 1.06-1.15], and 1.40 [95% CI, 1.35-1.45], respectively). After menopause, obesity was associated with elevated breast cancer risk, which was further increased by metabolic syndrome. In contrast, no elevated risk was observed before menopause. The current findings highlight differences in breast cancer risk by menopausal status across metabolic obesity phenotypes, emphasizing the need for targeted prevention strategies and further research into underlying mechanisms.

To evaluate the association between baseline glycemic status and mortality among patients with cancer and to examine whether these associations differ by stage and cancer type. We performed a nationwide cohort study using the Korean Cancer Public Library Database (K-CURE), which integrates national cancer registry, health screening, and cause-of-death records. A total of 671 366 adults newly diagnosed with one of 24 cancers between 2013 and 2019 were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), or diabetes mellitus (DM). Multivariable Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause, cancer-specific, cardiovascular, and respiratory mortality. Analyses were stratified by Surveillance, Epidemiology, and End Results stage and cancer type, with sensitivity analyses applying 1-, 3-, and 5-year lag periods. Over a mean follow-up of 3.5 years, 171 104 deaths occurred. Compared with NGT, DM was associated with higher risks of all-cause (HR 1.34, 95% CI 1.32-1.35), cancer-specific (HR 1.31, 95% CI 1.30-1.33), cardiovascular (HR 1.46, 95% CI 1.35-1.58), and respiratory mortality (HR 1.43, 95% CI 1.30-1.56). IFG was associated with modestly increased risks of all-cause (HR 1.06, 95% CI 1.05-1.08) and cancer-specific mortality (HR 1.07, 95% CI 1.05-1.08). Stage-stratified analyses demonstrated the strongest associations in localised cancers with attenuation in advanced stages. DM and IFG were linked to poorer survival after cancer diagnosis, with the greatest impact in early-stage disease. These findings support integrating metabolic risk assessment and management into survivorship care.

Calcific aortic valve disease (CAVD) arises from coupled interactions between blood flow, tissue mechanics, and cellular signaling. Hemodynamic forces influence endothelial and interstitial cell behavior, while the resulting tissue remodeling alters valve motion and flow patterns. Capturing this two-way feedback requires models that integrate fluid-structure mechanics with biochemical regulation, yet such multiscale coupling remains technically challenging. Previous computational models have focused on isolated aspects of the disease: fluid-structure interaction (FSI) simulations reproduce valve deformation and flow, and systems biology (SB) models describe molecular signaling that drives fibrosis and calcification. However, without coupling, these approaches cannot predict how mechanical dysfunction initiates biochemical remodeling or how biochemical changes feed back on mechanics. Here, we present a multi-physics computational framework that couples three-dimensional FSI simulations of aortic valve dynamics with a mechanistic SB model of calcification signaling. The FSI module resolves pulsatile blood flow and leaflet deformation, yielding local wall shear stresses and tissue strains throughout the cardiac cycle. These mechanical quantities are used as inputs to the SB module, which represents key biochemical pathways governing inflammation, TGF- β /SMAD signaling, and nitric-oxide (NO)-mediated inhibition within valvular cells. Simulations predict long-term calcification trajectories for valves of varying thickness, showing that fibrosis-induced stiffening lowers shear stress, reduces NO synthesis, and enhances TGF- β activation, thereby accelerating calcification. The framework is modular and extensible, allowing future incorporation of additional pathways, as well as implementation of full two-way coupling between the FSI and SB models. By integrating physics-based hemodynamics with systems-level biochemistry, this study provides a proof-of-principle demonstration of a next-generation, multi-scale modeling platform for studying cardiovascular disease that unites blood flow dynamics and biochemical signaling.