Impact of Metabolic Syndrome on Post-Operative Infection in Patients Undergoing Flexible Ureteroscopy Lithotripsy.

Background: To investigate retrospectively whether metabolic syndrome (MetS) of flexible ureteroscopy (fURS) lithotripsy can be used to predict post-operative infection. Patients and Methods: After screening, 1,110 patients who received fURS lithotripsy for upper urinary tract stones in our center between January 2015 and December 2022 were analyzed retrospectively. Patients were divided into MetS-positive group and MetS-negative group. Post-operative infection was divided into fever, urosepsis, and septic shock. Relevant data during the peri-operative period were collected. Univariable and multivariable logistic regression analyses were adopted to estimate the impact of metabolic syndrome on post-operative infection in patients undergoing fURS lithotripsy. Results: Among the 1,110 patients, 427 tested positive for MetS, whereas 683 tested negative. Eighty-eight patients suffered from fever (67 patients in the MetS-positive group and 21 in the MetS-negative group). Forty-nine patients had urosepsis (29 patients in the MetS-positive group and 20 in the MetS-negative group), of whom seven patients developed septic shock. No patient developed multiple organ failure or died because of infection. The prevalence of post-operative infections in the MetS-positive group was higher than that in the MetS-negative group (p < 0.001). Multivariable logistic regression analyses showed that diabetes mellitus, MetS-positive, positive urine culture, and longer operation time were positively correlated with post-operative fever. Positive MetS, positive urine culture, and longer operation time were strongly correlated with post-operative urosepsis. Conclusions: Metabolic syndrome was found to be associated with post-operative infection in patients undergoing fURS lithotripsy, suggesting it can serve as a predictive factor.

Hypoxia-inducible factor-1α inhibition augments efficacy of programmed cell death 1 antibody in murine prostatic cancer models.

This study was designed to explore whether hypoxia-inducible factor-1α (HIF-1α) inhibitor could enhance immunotherapy efficacy in prostate cancer. Western blot was used to detect the expression of HIF-1α in the tumor and peritumor tissues from prostate cancer patients. The analysis from Cancer Genome Atlas database was used to show an association between HIF-1α expression and survival rate in prostate cancer patients. Murine prostate cell-derived xenograft (CDX) model was set up in both nude mice and BALB/c mice to observe the therapeutic effect of HIF-1α inhibitor IDF-11774. Protein expression of HIF-1α, as well as changes in the immune microenvironment, was detected. Moreover, the synergistic antitumor effect of IDF-11774 and PD-1 antibody was detected in another murine prostate cancer model. HIF-1α was found to have higher expression in prostate cancer tumor tissue than in peritumor tissue, and the expression level was negatively correlated with survival rate (P = 0.0157). HIF-1α inhibitor IDF-11774 reduced tumor volume and exhibited better efficacy in BALB/c mouse model (P < 0.0001) with normal immune system, with the same suppression level against HIF-1α. HIF-1α inhibitor reduced CD45+CD11b+Gr-1+ myeloid-derived suppressor cells (P = 0.0027) and CD45+ CD11b+F4/80+CD206hi M2 macrophages (P = 0.0059) but increased the abundance of CD45+CD3+CD8+ T cells (P = 0.0002) and CD45+CD3+CD4+ T cells (P = 0.0001) in tumor-infiltrating immune cells. The same synergistic effect was observed in RM-1 murine prostate CDX tumor model. HIF-1α inhibition augmented the antitumor efficacy of immune checkpoint inhibitor PD-1 antibody in murine prostate cancer models, probably through modulating the immunosuppressive microenvironment.