Pharmacological Management of Ureteral Stent-related Symptoms: A Systematic Review, Bayesian Network Meta-analysis, and Meta-regression.

PURPOSE: Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms and discomfort. Prior studies have examined the effects of various medication regimens on ureteral stent symptoms. This study utilized Bayesian network meta-analysis to analyze all available evidence on the pharmacological management of ureteral stent-related symptoms. MATERIALS AND METHODS: In December 2022 a systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines on randomized prospective studies on pharmacological management of ureteral stent-related symptoms reporting outcomes using the Ureteral Stent Symptom Questionnaire score on urinary symptoms and pain. The data were analyzed in Review Manager 5.3 and R Studio where a Bayesian network meta-analysis was performed. Treatments were ranked using surface under the cumulative ranking curve and mean difference vs placebo with 95% credible intervals. RESULTS: A total of 26 studies were analyzed. These were used to build networks which were modeled to run 100,000 Markov Chain Montecarlo simulations each. Drug-class analysis revealed the most effective class for each domain: for urinary symptoms, sexual performance, general health, and work performance-combined α-blocker and anticholinergic and phosphodiesterase 5 inhibitors; for pain-combined anticholinergic and pregabalin. The following were the most effective drugs and dosages for specific symptoms: for urinary symptoms-combined silodosin 8 mg+solifenacin 10 mg; for pain-combined silodosin 8 mg+solifenacin 10 mg; for sexual performance-tadalafil 5 mg. Combined silodosin 8 mg+solifenacin 10 mg+tadalafil 5 mg has the best general health scores while solifenacin 10 mg had the best work experience scores. CONCLUSIONS: This network meta-analysis demonstrated that the most effective drug therapy is different for each symptom domain. It is important to consider a patient's chief complaint and domains in order to ascertain the optimal medication regimen for each patient. Further iterations of this analysis can be strengthened by trials that directly compare more of these drugs instead of relying on indirect evidence.

Optimizing pain management following kidney stone surgery: can we avoid narcotics?

INTRODUCTION: Opioids are often used to manage postoperative pain. Non-narcotic alternatives have increasingly been used to reduce opioid usage. We conducted an open-label randomized non-inferiority clinical trial to compare non-opioid to opioid therapy for pain management after nephrolithiasis surgery. METHODS: Patients undergoing elective ureteroscopy or percutaneous nephrolithotomy between July 2018 and May 2021 were randomized to receive ketorolac (non-opioid) or oxycodone-acetaminophen (opioid). Each patient was surveyed one week postoperatively to assess pain outcomes. Patient demographics, surgical variables, number of pills used, constipation, and adverse events were also assessed. We evaluated whether non-opioid analgesia was non-inferior to opioid analgesia for postoperative pain, assuming a non-inferiority margin of 1.3 in pain score between groups. RESULTS: Analyses were based on 90 patients with postoperative pain data: 44 in the ketorolac group and 46 in the oxycodone-acetaminophen group. The groups were similar regarding demographics, type of surgery, ureteral stent placement, and stone burden. Non-inferiority of non-opioids compared to opioids was demonstrated for all outcomes. At follow-up, the average pain scores were 3.20 ± 1.94 (SD) in the non-opioid group and 4.17 ± 1.84 in the opioid group (difference = - 0.96; 95% CI: - 1.76, - 0.17, p = 0.018). The mean proportions of unused pills were similar between groups (p = 0.47) as were rates of constipation (p = 0.32). CONCLUSIONS: Non-opioid analgesia was non-inferior to opioid analgesia in pain management after kidney stone surgery. This trial contributes to the evidence that non-opioid analgesics should be considered an effective option for pain management following non-invasive urologic procedures.

Systemic vs. in-irrigation tranexamic acid in percutaneous nephrolithotomy A systematic review, Bayesian network meta-analysis, and meta-regression.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the gold-standard treatment for large renal stones. One potentially significant complication of PCNL is blood loss, which can result in transfusion requirement and poorer stone-free outcomes. Tranexamic acid (TXA) has emerged as a promising intervention, administered systemically (TXA-S) or as part of irrigation fluid (TXA-I) in endourology. This study aimed to comprehensively analyze existing evidence regarding the applications of TXA in PCNL through a Bayesian network meta-analysis, offering insights into its efficacy and comparative effectiveness. METHODS: In February 2022, a PRISMA-compliant systematic review (PROSPERO registration number CRD 42021270593) was performed to identify randomized controlled clinical trials (RCT) on TXA as either systemic therapy or in irrigation fluid. Studies in languages other than English and Spanish were not considered. A Bayesian network was built using results from identified studies to create models that were later run through Markov Chain Monte Carlo sampling through 200 000 iterations. RESULTS: Eight RCTs compared TXA-S vs. placebo, one TXA-I vs. placebo, and one TXA-I vs. TXA-S. TXA-I had lower risk of transfusion (relative risk [RR] 0.63 [0.47,0.84], SUCRA 0.950) than TXA-S (RR 0.79 [0.65,0.95], SUCRA 0.545). TXA-I had a lower risk of complications (RR 0.38 [0.21,0.67], SUCRA=0.957) compared to TXA-S (RR 0.55 [0.39, 0.78], SUCRA 0.539). TXA-I had a lower postoperative decrease in hemoglobin (mean difference [MD] -1.2 [1.3, 1.0], SUCRA 0.849) compared to TXA-S (MD -0.97 [-1.0, -0.93], SUCRA 0.646]). CONCLUSIONS: TXA, regardless of the route of administration, is an effective intervention in decreasing bleeding, postoperative complications, and risk of transfusion when compared with placebo. Further studies directly comparing TXA-S to TXA-I would be useful to determine the optimal route of delivery.

SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.

Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 h post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral.

Efficacy of Primary Surgical Versus Medical Intervention for Treatment of Left-Sided Infective Endocarditis.

BACKGROUND: Left-sided staphylococcal, streptococcal, and enterococcal infective endocarditis (IE) is associated with poor clinical outcomes. Our primary aim is to compare clinical outcomes of staphylococcal, streptococcal, and enterococcal IE patients who undergo valve replacement surgery and outcomes of patients who are treated solely with antibiotics. METHODS: All patients were treated medically or surgically for left-sided staphylococcal, streptococcal, or enterococcal IE at our institution from 1998 to 2014 and were retrospectively studied. The primary outcome of interest was 30-day and 1-year mortality, and secondary outcomes included posttreatment septic shock, embolic events, stroke, and end-stage renal disease at 30 days. Inverse probability treatment weights, derived from propensity scores, were used to balance the medical and surgical cohorts across clinical risk factors, The Society of Thoracic Surgeon scores, and pathogens. Outcomes were compared comprehensively and in a staphylococcal-only subanalysis. RESULTS: Study population consisted of 245 surgical patients and 164 medical patients. Mortality at 30 days was higher in the medical cohort, both in aggregate and for staphylococcal only (all, 7% vs 16%, P < .001; staphylococcal only, 7% vs 22%, P < .001). Surgical patients had a higher incidence of septic shock and renal dysfunction; however, stroke and embolic events at 30 days were not different between cohorts. Cox survival analysis demonstrated that surgical treatment provided a 1-year survival benefit, with a hazard ratio of 0.48 (95% confidence interval, 0.36 to 0.64) that was robust regardless of pathogen. CONCLUSIONS: Compared with medical management, valve replacement surgery in patients with left-sided staphylococcal, streptococcal, or enterococcal IE appears to confer a survival advantage at 30 days and 1 year.