Comparison of stent related symptoms in patients taking mirabegron, solifenacin, or tamsulosin: A double blinded randomized clinical trial.

BACKGROUND: The present study aims to assess the efficacy of mirabegron, a novel beta-3 agonist for ameliorating stent related symptoms (SRSs) as compared to tamsulosin and solifenacin. METHODS: Total of 150 patients undergoing ureteral stent placement following ureteroscopic lithotripsy, percutaneous nephrolithotomy, or laparoscopic/robotic pyeloplasty were randomized in 1:1:1 fashion to receive mirabegron 50 mg (group A), solifenacin 5 mg (group B), and tamsulosin 0.4 mg (group C) OD respectively. Patients were followed at POD10 (I visit), 4 weeks (II visit) after surgery, and 2 weeks post-stent removal. Validated vernacular version of ureteric stent symptoms questionnaire (USSQ) was administered to the patients at each visit. RESULTS: Out of 150 patients randomized, 123 patients (A; n = 41, B; n = 40, and C; n = 42) completed the study. The groups were comparable in terms of urinary index score of USSQ at I and II visits (p = 0.119 and 0.076, respectively). A lower proportion of patients in group B experiencing bodily pain at II visit (p = 0.039), however, pain scores were comparable. Significantly lower general health index scores were observed in group A at I visit and over 4 weeks (p = 0.007). No significant differences were observed in other domains of USSQ. Age, sex, and surgical procedure undertaken did not significantly impact the scores in various USSQ domains. CONCLUSION: Mirabegron demonstrates comparable benefit in alleviating SRSs with better general health indices and may be an effective alternative for SRSs, especially when tamsulosin or solifenacin are contra-indicated or poorly tolerated.

Systematic Review and Meta-analysis on Effect of Carnitine, Coenzyme Q10 and Selenium on Pregnancy and Semen Parameters in Couples With Idiopathic Male Infertility.

OBJECTIVE: To study the effect of 3 antioxidants viz. selenium, carnitine and coenzyme Q10, alone or in combination, on both semen parameters and pregnancy rates in couples with male factor infertility. METHODS: Using PRISMA guidelines, a systematic search was performed of the PubMed, Scopus, EMBASE, and Web of Science databases for randomized studies comparing selenium, carnitine or coenzyme Q10 with placebo in the treatment of male infertility and reporting semen and pregnancy outcomes. RESULTS: A total of 3304 studies were screened of which 20 were included. The study protocol was registered with PROSPERO (CRD42020210284). Pregnancy rate in the treatment group (69/426, 16.2%) was not different from the placebo (45/401, 11.2%) (P = .05). Treatment group showed higher motility [mean difference 5.05, 95% CI (2.77, 7.34), P =<.0001], progressive motility [mean difference 5.72, 95% CI (2.77, 8.66), P = .0001], sperm concentration [mean difference 6.58, 95% CI (3.22, 9.93), P = .0001] than placebo. CONCLUSION: Although antioxidants and their combinations are associated with improvement in sperm concentration, motility, and semen volume, the differences are small. There is no difference in pregnancy rates between patients receiving selenium, carnitine, and coenzyme Q10, or placebo. The quality of studies is poor, limiting the level of evidence.

Autophagy in cancer: Recent advances and future directions.

Autophagy is being explored as a potential therapeutic target for enhancing the cytotoxic effects of chemotherapeutic regimens in various malignancies. Autophagy plays a very important role in cancer pathogenesis. Here, we discuss the updates on the modulation of autophagy via dynamic interactions with different organelles and the exploitation of selective autophagy for exploring therapeutic strategies. We further discuss the role of autophagy inhibitors in cancer preclinical and clinical trials, novel autophagy inhibitors, and challenges likely to be faced by clinicians while inducting autophagy modulators in clinical practice.