Gut microbiota and metabolites associate with outcomes of immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are promising agents for unresectable hepatocellular carcinoma (uHCC), but lack effective biomarker to predict outcomes. The gut microbiome can modulate tumor response to immunotherapy, but its effect on HCC remains unclear. METHODS: From May 2018 to February 2020, patients receiving ICI treatment for uHCC were prospectively enrolled; their fecal samples were collected before treatment. The fecal microbiota and metabolites were analyzed from 20 patients with radiology-proven objective responses (OR) and 21 randomly selected patients with progressive disease (PD). After March 2020, 33 consecutive Child-Pugh-A patients were recruited as a validation cohort. Additionally, feces from 17 healthy volunteers were collected for comparison of background microbes. RESULTS: A significant dissimilarity was observed in fecal bacteria between patients with OR and patients with PD before immunotherapy. Prevotella 9 was enriched in patients with PD, whereas Lachnoclostridium, Lachnospiraceae, and Veillonella were predominant in patients with OR. Ursodeoxycholic acid and ursocholic acid were significantly enriched in the feces of patients with OR and strongly correlated with the abundance of Lachnoclostridium. The coexistence of Lachnoclostridium enrichment and Prevotella 9 depletion significantly predicted better overall survival (OS). In the validation cohort, better progression-free survival (PFS) and OS were noted in patients who had a preferable microbial signature in comparison with counter-group (PFS: 8.8 months vs 1.8 months; OS: not reached vs 6.5 months, both p<0.001). CONCLUSIONS: Fecal microbiota and bile acids were associated with outcomes of immunotherapy for uHCC. These findings highlight the potential role of gut microbiota and metabolites as biomarkers to predict outcomes of ICI-treated HCC.

Scale Development and Model Validation for the Process of Exercise Engagement for People with Prediabetes

Purpose@#This study had two objectives: 1) to develop a scale for the process of exercise engagement (SPEE) for prediabetic individuals (PDIs); 2) to validate a structural model for the process of exercise engagement for PDIs. @*Methods@#A cross-sectional survey with simple random sampling was conducted from September 2013 to December 2015 (in Taiwan). A total of 310 PDIs were enrolled for scale development and model validation via item analysis, factor analyses, and structural equation modeling. The Kuo model was used as the basis for developing the Chinese version of the SPEE for PDIs. @*Results@#The SPEE contains five subscales with a total of twenty-one items that account for 54.9% to 65.9% of the total variance explained for assessing participants’ process of engagement during exercise. For Kuo model validation, the model measures indicated goodness of fit between the Kuo model and sample data. Analysis further revealed a direct effect between the creating health blueprints (CHB) stage and the spontaneous regular exercise (SRE) stage (b=.60). @*Conclusion@#The SPEE includes five subscales for assessing the psychological transition and behavioral expression at each stage of the process of exercise engagement for PDIs. The SPEE for people with prediabetes provides deeper insights into the factors of behavioral change stages that are required to initiate long-term health care outcomes and avoid developing diabetes. These insights are significant as they allow for patient- specific mapping and behavior modification to effect exercise.