The relationship between neutrophil/lymphocyte ratio, platelet/neutrophil ratio, and risk of urosepsis in patients who present with ureteral stones and suspected urinary tract infection.

PURPOSE: Patients presenting with ureteral stones and concurrent urinary tract infections require prompt kidney drainage as per standard care guidelines. However, even in patients who are promptly drained and treated with appropriate antibiotics, the mortality rate due to urosepsis has been reported to be nearly 9%. Therefore, Predictive tools for early sepsis detection have become essential. The Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) are potential biomarkers for predicting infection risk in these patients. METHODS: A retrospective cohort analysis involving patients diagnosed with obstructing ureteral stones who underwent urgent stent placement due to suspected urinary tract infection (UTI) in the emergency room (ER) was conducted. The baseline characteristics of patients were age, sex, comorbidities, and urological history. Laboratory data collected during hospitalization included total leukocyte and platelet counts and blood cultures. Ratios were calculated from the serum studies obtained upon admission to the ER. A logistic regression model was utilized to predict the incidence of positive qSOFA score (sepsis prediction score), the need for vasopressors, intensive care unit (ICU) admission, and sepsis, using NLR and PLR as independent variables. RESULTS: Between January 2016 and December 2020, 143 patients with a diagnosis of obstructing ureteral stone were admitted to the ER with a suspected UTI. 11.9% showed a positive qSOFA score, 20.3% required vasopressor support for > 1 h after ureteral stent placement, 28.7% required ICU admission, and 16.8% met sepsis criteria. Sepsis was defined as patients who were qSOFA positive and vasopressors needed for more than 1 h following stent placement. Logistic regression analysis revealed that PLR and positive blood cultures correlated significantly with positive qSOFA scores. Using logistic regression analysis, PLR, NLR, and positive blood culture were each independent predictors of vasopressor requirements, ICU admission, and urosepsis. CONCLUSIONS: NLR and PLR may be valuable prognostic markers for predicting urosepsis risk in urolithiasis patients who present with obstructing stones and concern for systemic infection. Their utility may be in helping clinicians in early risk stratification, prompt intervention, and resource allocation.

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.

Oncologic outcomes of pelvic organ-preserving radical cystectomy vs. Standard radical cystectomy: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Radical Cystectomy is indicated in muscle-invasive bladder cancer and select cases of nonmuscle invasive bladder cancer. Women often undergo additional reproductive organ removal, greatly impacting sexual function and quality of life. Pelvic organ-preserving radical cystectomy aims to mitigate these effects, but its oncologic outcomes are not well-defined. This presents a meta-analysis of available literature on oncological outcomes of pelvic organ-preserving radical cystectomy in women with muscle invasive disease. METHODS: A systematic search across PubMed, Web of Science, Scopus, and Google Scholar was performed to identify studies comparing oncological outcomes between pelvic organ-preserving radical cystectomy and standard radical cystectomy in women with muscle-invasive bladder cancer or high-risk or recurrent nonmuscle invasive cancer. The search included English or Spanish studies, statistically comparing overall survival, cancer-specific survival, and recurrence-free survival. Statistical analysis used Review Manager, employing fixed or random-effects models based on heterogeneity. KEY FINDINGS AND LIMITATIONS: Six retrospective studies met inclusion criteria, totaling 597 patients of which 303 received pelvic organ-preserving radical cystectomy and 294 received standard radical cystectomy. Overall Survival was not different between the 2 groups (HR 1.05 [0.77, 1.43]; P = 0.77). Cancer-Specific Survival also was found to be not different between the 2 groups (HR 1.27 [0.86, 1.87]; P = 0.22). Additionally, recurrence-free survival was not different between the 2 groups (HR 0.85 [0.41, 1.75]; P = 0.65. Four of the included studies exhibited a moderate risk of bias, with 1 study demonstrating low risk and the remaining study manifesting a serious risk of bias. CONCLUSION: The comparison showed no significant differences in overall survival, cancer-specific survival, or recurrence-free survival rates.

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.