Exocrine pancreatic cancer and living near to waste sites containing hazardous organic chemicals, New York State, USA - an 18-year population-based study.

OBJECTIVES: The etiology of exocrine pancreatic cancer (EPC) remains unknown except for family history and smoking. Despite recent medical advances, rates of pancreatic cancer incidence and mortality are increasing. Although existing evidence suggests a potentially causal relationship between environmental chemical exposures and pancreatic cancer, whether residential exposure impacts pancreatic cancer rates remains unknown. MATERIAL AND METHODS: The authors identified 28 941 patients diagnosed with exocrine pancreatic cancer in New York State exclusive of New York City for the years 1996-2013. Descriptive statistics and negative binomial regression were used in this ecological study to compare pancreatic cancer hospitalization rates among patients who lived in zip codes with hazardous waste sites (HWSs) containing persistent organic pollutants (POPs) and volatile organic pollutants (VOCs) compared with clean zip codes with no identified hazardous waste sites. The authors assessed the effect of selected known and suspected human carcinogens on the EPC hospitalization rates by subgroup analyses. RESULTS: Compared with the clean sites, the pancreatic cancer hospital discharge rate in the "VOCs without POPs" and "VOCs and POPs" sites, after adjustment for potential confounders were 1.06 (95% CI: 1.03-1.09) and 1.05 (95% CI: 1.01-1.08), respectively. In the analysis by specific chemicals, rate ratios (RR) for the benzene (RR = 1.12) and ethylbenzene (RR = 1.34) in the non-chlorinated VOCs group, trichloroethylene (RR = 1.07) and tetrachloroethylene (RR = 1.11) in the chlorinated VOCs group, chlorinated pesticides (RR = 1.11) and PCBs (RR = 1.05) in the POPs groups were statistically significant (p-values <0.05) compared with clean sites. CONCLUSIONS: Compared with the clean sites, the pancreatic cancer hospital discharge rate in the "VOCs without POPs" and "VOCs and POPs" sites, after adjustment for potential confounders were 1.06 (95% CI: 1.03-1.09) and 1.05 (95% CI: 1.01-1.08), respectively. In the analysis by specific chemicals, rate ratios (RR) for the benzene (RR = 1.12) and ethylbenzene (RR = 1.34) in the non-chlorinated VOCs group, trichloroethylene (RR = 1.07) and tetrachloroethylene (RR = 1.11) in the chlorinated VOCs group, chlorinated pesticides (RR = 1.11) and PCBs (RR = 1.05) in the POPs groups were statistically significant (p-values <0.05) compared with clean sites. Int J Occup Med Environ Health. 2022;35(4):459-71.

Precision Mapping of COVID-19 Vulnerable Locales by Epidemiological and Socioeconomic Risk Factors, Developed Using South Korean Data.

COVID-19 has severely impacted socioeconomically disadvantaged populations. To support pandemic control strategies, geographically weighted negative binomial regression (GWNBR) mapped COVID-19 risk related to epidemiological and socioeconomic risk factors using South Korean incidence data (January 20, 2020 to July 1, 2020). We constructed COVID-19-specific socioeconomic and epidemiological themes using established social theoretical frameworks and created composite indexes through principal component analysis. The risk of COVID-19 increased with higher area morbidity, risky health behaviours, crowding, and population mobility, and with lower social distancing, healthcare access, and education. Falling COVID-19 risks and spatial shifts over three consecutive time periods reflected effective public health interventions. This study provides a globally replicable methodological framework and precision mapping for COVID-19 and future pandemics.

Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review.

Despite favorable results of CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete response, immune-mediated toxicity, and antigen-loss relapse. We delineated the relative clinical benefit of the novel approaches compared to the currently approved CAR T-cell therapies. In the absence of head-to-head comparisons and randomized controlled trials, we performed Matching Adjusted Indirect Comparisons to quantify the relative efficacy and safety of experimental CARs against Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) were pooled into eight populations by their CAR T-cell constructs and +/- ASCT status. The study endpoints were Progression-Free Survival (PFS), grade ≥ 3 cytokine release syndrome (CRS), and grade ≥ 3 neurotoxicity (NT). Tandem CD19.CD20.4-1BBζ CARs indicated favorable efficacy and safety, whereas the co-infusion of CD19 & CD20 with 4-1BBζ showed no clinical benefit compared to Yescarta. Third generation CD19. CD28. 4-1BBζ, and sequential administration of autologous stem cell transplantation (ASCT) and CD19. CARs presented statistically insignificant yet improved PFS and safety except for ASCT combined intervention which had suggestively higher NT risk than Yescarta. CARs with modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zζ and CD19. BBz.86ζ) presented remarkable safety with no severe adverse events; however, both presented worse PFS than Yescarta. Third-generation CARs demonstrated statistically significantly lower NT than Yescarta. CD20. 4-1BBζ data suggested targeting CD20 antigen alone lacks clinical or safety benefit compared to Yescarta. Further comparisons with other FDA-approved CARs are needed.