Comparing barriers to early stage diagnosis of hepatocellular carcinoma between safety net hospitals and academic medical centers: An analysis from the United States Safety-Net Collaborative.

BACKGROUND AND OBJECTIVES: Early detection of hepatocellular carcinoma (HCC) is associated with improved survival. However, a greater proportion of patients treated at safety net hospitals (SNHs) present with late-stage disease compared to those at academic medical centers (AMCs). This study aims to identify barriers to diagnosis of HCC, highlighting differences between SNHs and AMCs. METHODS: The US Safety Net Collaborative-HCC database was queried. Patients were stratified by facility of diagnosis (SNH or AMC). Patient demographics and HCC screening rates were examined. The primary outcome was stage at diagnosis (AJCC I/II-"early"; AJCC III/IV-"late"). RESULTS: 1290 patients were included; 50.2% diagnosed at SNHs and 49.8% at AMCs. At SNHs, 44.4% of patients were diagnosed late, compared to 27.6% at AMCs. On multivariable regression, Black race was associated with late diagnosis in both facilities (SNH: odds ratio 1.96, p = 0.03; AMC: 2.27, <0.01). Screening was associated with decreased odds of late diagnosis (SNH: 0.46, p = 0.04; AMC: 0.37, p < 0.01). CONCLUSIONS: Black race was associated with late diagnosis of HCC, while screening was associated with early diagnosis across institutional types. These results suggest socially constructed racial bias in screening and diagnosis of HCC. Screening efforts targeting SNH patients and Black patients at all facilities are essential to reduce disparities.

A multi-organ chip with matured tissue niches linked by vascular flow.

Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions. Each tissue is cultured in its own optimized environment and is separated from the common vascular flow by a selectively permeable endothelial barrier. The interlinked tissues maintained their molecular, structural and functional phenotypes over 4 weeks of culture, recapitulated the pharmacokinetic and pharmacodynamic profiles of doxorubicin in humans, allowed for the identification of early miRNA biomarkers of cardiotoxicity, and increased the predictive values of clinically observed miRNA responses relative to tissues cultured in isolation and to fluidically interlinked tissues in the absence of endothelial barriers. Vascularly linked and phenotypically stable matured human tissues may facilitate the clinical applicability of tissue chips.