dutasteride + tamsulosin (Jalyn / Combodart / Duodart)

Effect of Tamsulosin Combined With Flexible Ureteroscopic Holmium Laser Lithotripsy on Renal Function and Postoperative Inflammatory Response in Patients With Renal Calculi.

Jiang Xiaoxiang X, Ying Lihong L

To investigate the association between perioperative tamsulosin use and outcomes of flexible ureteroscopic holmium laser lithotripsy (FURL). This retrospective cohort study was performed on 122 patients who underwent FURL at Cixi People's Hospital, Wenzhou Medical University. Patients were divided into an observation group (perioperative tamsulosin + FURL, n = 62) and a control group (FURL alone, n = 60) according to routine clinical protocols and patient preference. Operation time, stone clearance rate at 4 weeks postoperatively, renal function indicators, inflammatory markers, and complication rates were compared between the two groups. Compared with the control group, the observation group had shorter operation time (51.34 ± 9.28 vs. 58.62 ± 10.35 min, p < 0.001), shorter postoperative hospital stay (3.62±1.05 vs. 4.85±1.23 days, p < 0.001), and a higher stone clearance rate (93.55% vs. 75.00%, p = 0.005). On postoperative day 1 and at week 1, renal function indicators were significantly lower in the observation group (all p < 0.05). Serum inflammatory marker levels on postoperative days 1 and 3 were also significantly lower in the observation group (all p < 0.001). The total complication rate was lower in the observation group (8.06% vs. 21.66%, p = 0.036). In this retrospective study, perioperative tamsulosin combined with FURL was associated with shorter operation times, higher stone clearance, and lower renal function, inflammatory, and complication markers. However, due to potential selection bias, these associations require confirmation via prospective randomized controlled trials.

ASIV Attenuates Cisplatin-Induced Proximal Tubular Injury by Enhancing Mitochondrial Biogenesis and Mitophagy Through the ADRA1A/AMPK/FOXO3A Pathway.

Wang Meng M, Peng Wang W, Wei Yani Y, Yu Hangxing H et al.

Cisplatin causes nephrotoxicity by accumulating in renal tubular epithelial cells (RTECs). Astragaloside IV (ASIV) shows renoprotective potential, but its mechanisms remain poorly understood. Cisplatin induced nephrotoxicity was established in 8-week-old male C57BL/6 mice via intraperitoneal administration of cisplatin at 20 mg/kg for 48 h. For in vitro studies, HK-2 human proximal tubular epithelial cells were exposed to 50 μM cisplatin for 24 h. Multi-omics approaches were employed to identify novel mechanisms by which ASIV ameliorates cisplatin-induced proximal tubular injury. ASIV markedly reduced serum creatinine and urea nitrogen levels in mice, and ameliorated cisplatin-induced proximal tubular injury both in vivo and in vitro. Moreover, ASIV restored mitochondrial damage, upregulated protein expression of PGC-1α, TOMM20, and PINK1 in RTECs. Mechanistically, RNA-seq and scRNA-seq revealed that cisplatin predominantly affected ADRA1A-mediated mitochondrial biogenesis and mitophagy in proximal tubular cells, accompanied by suppression of the AMPK/FOXO3A pathway. Notably, ASIV upregulated ADRA1A expression, thereby facilitating AMPK and FOXO3A phosphorylation and consequently enhancing mitochondrial biogenesis and mitophagy. Furthermore, dabuzalgron (a selective ADRA1A agonist) recapitulated the protective effects of ASIV. In contrast, the renoprotective action of ASIV against cisplatin-induced proximal tubular injury was largely abrogated by the ADRA1A antagonist tamsulosin in vivo and by ADRA1A-specific siRNA in vitro. These findings identify ASIV as a highly promising renoprotective agent that upregulates ADRA1A expression and activates the AMPK/FOXO3A axis to enhance mitochondrial biogenesis and mitophagy, thereby counteracting cisplatin-induced proximal tubular injury.

Black Race Predicts Poor Compliance and Higher Prostate Cancer Risk in a Multinational Repeat Biopsy Cohort: Secondary Analysis From the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Clinical Trial.

Freedland Alexis R AR, Moriera Daniel M DM, Gong Jun J, Freedland Stephen J SJ

On a population level, black patients have more prostate cancer (PC), particularly aggressive PC. Similarly, on initial biopsy, black race has been linked with higher PC and high-grade PC risk. Whether this extends to first repeat biopsy is unknown. We tested if black race predicts PC risk, grade, and biopsy compliance within a phase 3 PC prevention trial with study-mandated biopsies among patients with an initial negative prestudy biopsy. Analysis of 7445 patients (2.4% black, 97.6% white) from REDUCE, a 4-year, double-blind, placebo-controlled trial testing dutasteride versus placebo on PC risk. Patients had a single, negative, prestudy biopsy, PSA 2.5-10 ng/mL, and study-mandated biopsies at 2 and 4-years. Multivariable logistic and multinomial regressions were used to test if self-reported race predicted PC, grade (low, Grade-Group 1 [GG1] vs. high, Grade-Group > 2 [GG2+]), and biopsy compliance. Given concerns about noncompliance affecting analyses, primary analyses for PC examined 2-year biopsy outcomes among patients who underwent biopsy. On multivariable analysis, black patients were less likely to receive the 2-year biopsy (OR: 0.53, 95%CI: 0.39-0.74), but had higher PC risk, which approached, but did not reach significance (OR 1.56, 95%CI: 0.98-2.46). When stratified by grade, on multivariable analysis, black race was unrelated to GG1 (RRR: 1.17, 95%CI: 0.65-2.12) but associated with GG2 + PC (RRR: 2.44, 95%CI: 1.29-4.64) at the 2-year biopsy. Among patients with a negative prestudy biopsy on a phase 3 trial, black patients had lower compliance with study-mandated biopsy but were 2.44 times more likely to have GG2 + PC on the 2-year biopsy versus white patients. These data extend population and initial biopsy data to first repeat biopsy, strongly supporting that black race is linked with aggressive PC. Given differential biopsy compliance may be greater in the real-world, these data suggest population data may underestimate true racial disparities in PC risk and aggressiveness.

The silent signal is tadalafil counterbalancing tamsulosin induced ejaculatory dysfunction.

Zhang Tao T, Yu Maobin M