Comparison of Mirabegron plus Tamsulosin and Tamsulosin Monotherapy for the Treatment of Ureteral Stent-Related Symptoms: A Prospective Randomized Study.

INTRODUCTION: The aim of this study was to compare the efficacy of mirabegron plus tamsulosin to tamsulosin monotherapy in terms of ureteral stent-related discomfort after ureteroscopic lithotripsy. METHODS: A total of 102 patients undergoing ureteroscopic lithotripsy and silicone ureteral stent placement were enrolled in this study. Patients were randomized 1:1 to receive either tamsulosin 0.4 mg once daily or mirabegron 50 mg + tamsulosin 0.4 mg once daily during the stenting period. Before the operation, the IPSS, QOL, and pain score were collected. On the day of ureteral stent removal, the USSQ, analgesic usage amount was collected and recorded. RESULTS: The median USSQ-body pain score in the tamsulosin group and tamsulosin + mirabegron group was 15 and 16, respectively (p = 0.530). The median analgesic usage in the two groups was 3 and 2, respectively (p = 0.170). The median USSQ-urinary symptoms, USSQ-general health, USSQ-work performance, USSQ-sexual matters, and USSQ-additional problems in the two groups were 26 and 26 (p = 0.194), 11 and 12 (p = 0.068), 12 and 13 (p = 0.105), 2 and 2 (p = 0.437), 9 and 9 (p = 0.533), respectively. The international patients used more analgesics than Chinese patients (6 vs. 1, p = 0.015). CONCLUSION: Compared to tamsulosin alone, tamsulosin + mirabegron showed no additional benefit on the ureteral stent-related pain control after ureteroscopic lithotripsy and silicone stent placement. There was no significant difference on the analgesic usage and USSQ scores between the two groups. Chinese patients request fewer analgesics than international patients.

Anti-BCMA-engineered exosomes for bortezomib-targeted delivery in multiple myeloma.

ABSTRACT: Exosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared with conventional drug delivery systems. In this study, we developed a delivery platform using exosomes derived from monocytes, specifically designed for targeted delivery of bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B-cell maturation antigen (anti-BCMA), because BCMA selectively expresses on myeloma cells. This modified anti-BCMA was then efficiently incorporated into the monocyte-derived exosomes. These adapted exosomes effectively encapsulated Btz, leading to enhanced drug accessibility within MM cells and sustained intracellular accumulation over an extended period. Remarkably, our results demonstrated that anti-BCMA-modified exosome-loaded Btz (anti-BCMA-Exo-Btz) outperformed free Btz in vitro, exhibiting a more potent myeloma-suppressive effect. In orthotopic MM xenograft models, anti-BCMA-Exo-Btz exhibited a significant antitumor effect compared with free Btz. Furthermore, it demonstrated remarkable specificity in targeting Btz to myeloma cells in vivo. Importantly, we observed no significant histological damage in mice treated with anti-BCMA-Exo-Btz and a slight effect on peripheral blood mononuclear cells. In addition, our study highlighted the multifunctional potential of monocyte exosomes, which induced cell apoptosis, mediated immune responses, and enhanced the osteogenic potential of mesenchymal stromal cells. In conclusion, our study suggests that exosomes modified with targeting ligands hold therapeutic promise for delivering Btz to myelomas, offering substantial potential for clinical applications.