Detrusor relaxing agents for neurogenic detrusor overactivity: a systematic review, meta-analysis and network meta-analysis.

OBJECTIVE: To evaluate the evidence regarding the therapeutic benefits and safety of oral detrusor relaxing agents (DRAs) in treating neurogenic detrusor overactivity (NDO). METHODS: A comprehensive search was performed on 1 September 2022. Two authors independently reviewed the articles to extract data using a pre-designed form. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A common-effect or random-effects model was used based on the heterogeneity among studies. Bayesian network meta-analysis (NMA) was further performed to make indirect comparisons of antimuscarinics and mirabegron. RESULTS: A total of 23 randomised controlled trials (RCTs) comprising 1697 patients were included in our analysis. Compared to placebo, the clinical benefits of oral DRAs, along with more adverse events (AEs), were demonstrated in the treatment of NDO. In the subgroup analysis, antimuscarinics significantly improved both urodynamic and bladder diary outcomes (including urinary incontinence episodes, urinary frequency, and residual volume), with a higher rate of AEs, such as xerostomia. Mirabegron improved some of the parameters and had fewer bothersome side-effects in patients with NDO. The NMA showed that none of the antimuscarinics or mirabegron was superior or inferior to the other. CONCLUSIONS: Detrusor relaxing agents are associated with improved outcomes in patients with NDO and our analysis has added new evidence regarding antimuscarinics. Evidence concerning mirabegron as first-line therapy for NDO is still limited. Well-designed RCTs are still required in this specific population.

Systemic therapies for high-volume metastatic hormone-sensitive prostate cancer: a network meta-analysis.

BACKGROUND: We compared the effectiveness of currently available systemic therapies for high-volume metastatic hormone-sensitive prostate cancer (mHSPC) and aimed to establish the optimal treatment regimen. MATERIAL AND METHODS: We searched multiple databases for randomized controlled trials (RCTs) that evaluated the efficacy of systemic therapy in patients with high-volume mHSPC. Bayesian network meta-analysis was used to indirectly compare overall survival (OS) and progression-free survival (PFS) of various systemic therapies. RESULTS: Eleven RCTs (6708 participants) finally met the eligibility criteria. Compared with androgen deprivation therapy (ADT) alone, rezvilutamide (REZ) [hazard ratio (HR) = 0.58, 95% confidence interval (CI): 0.44-0.77], abiraterone (ABI) (HR = 0.61, 95% CI: 0.53-0.71), apalutamide (APA) (HR = 0.70, 95% CI: 0.56-0.88), enzalutamide (ENZ) (HR = 0.65, 95% CI: 0.53-0.80), docetaxel (DOC) (HR = 0.72, 95% CI: 0.63-0.84), darolutamide (DAR) + DOC (HR = 0.49, 95% CI: 0.39-0.62), and ABI + DOC (HR = 0.52, 95% CI: 0.38-0.71) significantly improved OS in patients with high-volume mHSPC. Compared with DOC, no advantages were observed for doublet therapies, including REZ, ABI, APA, and ENZ on the basis of ADT, whereas DAR + DOC (HR = 0.68, 95% CI: 0.57-0.82) and ABI + DOC (HR = 0.72, 95% CI: 0.55-0.95) was associated with better OS. The ranking analysis showed that triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT) had the greatest improvement in OS, followed by REZ + ADT. All the regimens showed improved PFS in patients with high-volume mHSPC. Compared with DOC, significant differences were detected for DAR + DOC, ABI + DOC, ENZ + DOC, REZ, and ENZ. According to the ranking analysis, triplet therapy ranked first, followed by ENZ and REZ. CONCLUSIONS: REZ + ADT were the highest ranked doublet therapy for improvement in OS of patients with high-volume mHSPC, second only to triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT).

Typical value ranges and signal patterns in patients with neurogenic bladder: Quality control in urodynamics using an air-charged catheter system.

PURPOSE: To establish typical value ranges (TVRs) of the air-charged catheter (ACC) system, and analyze the typical signal patterns (TSPs) of cough under different bladder volumes for quality control of a urodynamic study using the ACC system. MATERIALS AND METHODS: The urodynamic traces of 1977 patients with neurogenic bladder (NB) were analyzed for intravesical pressure (pves ), abdominal pressure (pabd ), and detrusor pressure (pdet ) in the cough test at our center from July 2017 to December 2021. The pdet cough signals were described and classified. The pdet cough signal patterns in different bladder volumes and postures were analyzed. RESULTS: The 50% range of the initial resting pves , pabd , and pdet in the supine and sitting positions were 7-15, 7-14, and 0-0 cmH2 O, and 24-33, 24-33, and 0-0 cmH2 O, respectively. The cough amplitudes for pves and pabd were similar in the 50% range, as follows: 10-27 and 8-25 cmH2 O in the supine position, respectively; and 18-43 and 17-40 cmH2 O in the sitting position, respectively. The cough amplitude of pves and pabd was not related to bladder volume (p > 0.05). The cough spikes of pdet were divided into three types: type I, in which pdet has a minimal change (<5 cmH2 O); type II, a monophasic cough spike, in which could be a positive (IIa, ≥5 cmH2 O) or negative spike (IIb, ≥5 cmH2 O); and type III, a biphasic spike, in which could be a positive-to-negative biphasic (IIIa) or negative-to-positive spike (IIIb). Under different bladder volumes, the cough signals of pdet were all expressed as type I, II, or III, and the cough signals were unrelated to bladder volume (p > 0.05). CONCLUSIONS: TVRs of the initial resting state in patients with NB were established to provide guidance for quantitative quality control of the ACC system. The TSPs of the pdet cough signal under different bladder volume and posture were described, which could be used for qualitative quality control of the ACC system.

Diagnosis and treatment of neurogenic bladder secondary to aortic dissection: A 8-year retrospective study at a single center.

PURPOSE: To review the characteristics of the neurogenic lower urinary tract dysfunction (NLUTD) secondary to aortic dissection (AD), analyze the clinical features, and discuss the treatment options. METHODS: Ten individuals complaining of lower urinary tract syndrome following AD were enrolled in this study. Clinical characteristics, urological and neurological symptoms/signs, imaging examination, and intervention were reviewed. Liao's comprehensive classification system was used to precisely assess the lower and upper urinary dysfunction. RESULTS: The urinary symptoms can be varied, including dysuria, incontinence, and frequency. Individuals were divided into the detrusor overactivity (DO) and detrusor underactivity (DU) subgroups. Continence, impaired upper urinary tract functions (renal insufficiency, vesicoureteral reflux, upper urinary tract dilatation, and lower urinary tract functions (DO and/or detrusor external sphincter dyssynergia/detrusor bladder neck dyssynergia, DU, low bladder capacity, and compliance) were examined using video-urodynamics. The principle of treatment is "low-pressure bladder storage with complete bladder emptying," and close follow-up was recommended due to the volatile course of NLUTD. CONCLUSIONS: Both cardiovascular surgeons and urologists should pay attention to the occurrence of NLUTD following AD, and determine the most appropriate therapeutic option.

Reliability assessment of the upper urinary tract dilation grading system based on magnetic resonance urography in patients with neurogenic bladder.

BACKGROUND: To assess the inter-observer and intra-observer reliability of the magnetic resonance urography (MRU)-upper urinary tract dilation (UUTD) grading system. METHODS: A total of 40 patients with a diagnosis of NB were enrolled in this study. The images were assembled in an electronic presentation randomly. The presentations were reviewed and graded by 4 junior and 4 senior urologists. One week later, the images were randomized again and reassessed. The inter-observer reliability was estimated by Kendall's coefficient of concordance and intra-class correlation coefficient (ICC), and the intra-observer reliability was estimated by weighted Cohen's kappa. RESULTS: The inter-observer reliability strength was excellent for all urologists, with the ICC value of 0.939 (0.908-0.963) and Kendall's W value of 0.967. The highest agreement was shown in Grade 4 at 92.50%, and the lowest in Grade 2 at 82.14%. All disagreements were within one grade of difference. Moreover, the Intra-observer reliability was excellent, with the weighted kappa value ranging from 0.904 to 0.954. CONCLUSIONS: The inter-observer and intra-observer reliability of this novel MRU-UUTD grading system is confirmed, providing adequate evidence for broader clinical application.

Optogenetic Neuromodulation of the Urinary Bladder.

OBJECTIVES: Nerve stimulation and neuromodulation have become acceptable interventions for bladder dysfunction. However, electrical stimulation indiscriminately affects all types of cells and can lead to treatment failure and off-target effects. In recent years, advancement of knowledge of optogenetics provides a powerful tool to enable precise, minimally invasive neuromodulation. MATERIALS AND METHODS: In this review, we introduce basic knowledge about optogenetics; discuss the progression of engineered opsins, gene-targeting methods, and light-delivery approaches; we also summarize the application of optogenetics in neuromodulation of the bladder and discuss the possible clinical translation in the future. RESULTS AND CONCLUSION: Optogenetics offers a powerful tool to investigate the neural circuit of bladder storage and voiding and provides a promising approach for manipulating neurons and muscles. It is possible to achieve coordinated modulation of the bladder and its sphincter through a "closed-loop" system. Optogenetics neuromodulation could also be applied in urinary bladder control in the clinic in the future.

The concerns of mechanical upper urinary tract obstruction in neurogenic lower urinary tract dysfunction: Beyond augmentation cystoplasty.

Purpose: To evaluate the efficacy of augmentation uretero-enterocystoplasty (AUEC), a modified surgical procedure that focuses the mobilization of the ureter and the necessity of ureteroplasty in a series of neurogenic lower urinary tract dysfunction (NLUTD) patients with mechanical upper urinary tract obstruction (mUUTO). Methods: We retrospectively reviewed the medical records of NLUTD patients who underwent an AUEC from 2005 to 2022. mUUTO was diagnosed by preoperative bladder drainage, magnetic resonance urography (MRU), and isotope renography. Upper urinary tract dilatation (UUTD) was evaluated using MRU with the Liao MRU-UUTD system. Results: A total of 58 patients and 103 ureters were analyzed. Improvement in maximum bladder capacity (from 79.0 [41.3-163.8] to 500.0 [450.0-597.5] ml, P < 0.001), maximum detrusor pressure (from 32.0 [13.0-50.8] to 5.5 [4.0-10.0] cmH2O, P < 0.001) and bladder compliance (from 6.5 [3.0-11.9] to 50.1 [37.5-65.0] ml/cmH2O, P < 0.001), and stabilization of serum creatine (93.4 [73.0-142.7] to 94.9 [72.2-148.7] µmol/L, P = 0.886) were observed. The proportion of high-grade UUTD was significantly reduced after the surgery (92.3% vs. 13.5%, 92.1% to 9.8%, P < 0.001), and the typical imaging signs of preoperative obstruction disappeared. Conclusion: Beyond traditional augmentation cystoplasty, more attention should be paid to the relief of mUUTO and mobilization of the ureter in NLUTD patients.

The Comparative Effectiveness of Botulinum Toxin-A Injection Therapy Versus Augmentation Uretero-Enterocystoplasty for the Treatment of Lower Urinary Tract Dysfunction.

PURPOSE: We investigated the effectiveness of intravesical botulinum toxin-A (BTX-A) injection therapy in patients with lower urinary tract dysfunction (LUTD) and upper urinary tract (UUT) deterioration and evaluated whether BTX-A injection therapy could substitute for augmentation uretero-enterocystoplasty (AUEC). METHODS: Data from a prospective, single-center cohort from 2017-2021 were analyzed. Patients were divided into 2 treatment groups: AUEC and BTX-A (i.e., patients who declined AUEC). Bladder and UUT functions were assessed by comparing clinical information, urodynamic data, laboratory results, and imaging records. RESULTS: In total, 121 patients were enrolled (BTX-A group: 41 patients; AUEC group: 80 patients). The BTX-A group showed a reduced maximum detrusor pressure and increases in the maximum bladder volume and bladder compliance (P<0.05). However, in follow-up evaluations, significantly smaller improvements (all P<0.05) in urodynamic parameters were found in the BTX-A group than in the AUEC group. Notably, there was no significant improvement in vesicoureteral reflux (VUR; P=0.66) or upper urinary tract dilatation (UUTD; P=0.75) in the BTX-A group, and no statistically significant difference in serum creatinine (Scr) levels or the estimated glomerular filtration rate (eGFR) was observed in the follow-up evaluations (all P>0.05). Both VUR and UUTD improved significantly in the AUEC group, and the Scr and eGFR levels significantly improved after AUEC relative to baseline levels (P<0.05). The reduction in the Scr level was significantly lower in the BTX-A group than in the AUEC group during 0-15 months of follow-up (Scr reduction differences, -1.36; P<0.01). CONCLUSION: Although BTX-A injection therapy was effective for improving bladder function, BTX-A injections did not alleviate UUT deterioration in this study, particularly in patients with advanced-stage LUTD. Conversely, AUEC for LUTD has a well-established role in improving UUT function. Hence, BTX-A injection therapy should not replace AUEC to ameliorate UUT impairment and protect UUT function.

A bibliometric profile of optogenetics: quantitative and qualitative analyses.

Introduction: Optogenetics is a rapidly developing field combining optics and genetics, with promising applications in neuroscience and beyond. However, there is currently a lack of bibliometric analyses examining publications in this area. Method: Publications on optogenetics were gathered from the Web of Science Core Collection Database. A quantitative analysis was conducted to gain insights into the annual scientific output, and distribution of authors, journals, subject categories, countries, and institutions. Additionally, qualitative analysis, such as co-occurrence network analysis, thematic analysis, and theme evolution, were performed to identify the main areas and trends of optogenetics articles. Results: A total of 6,824 publications were included for analysis. The number of articles has rapidly grown since 2010, with an annual growth rate of 52.82%. Deisseroth K, Boyden ES, and Hegemann P were the most prolific contributors to the field. The United States contributed the most articles (3,051 articles), followed by China (623 articles). A majority of optogenetics-related articles are published in high-quality journals, including NATURE, SCIENCE, and CELL. These articles mainly belong to four subjects: neurosciences, biochemistry and molecular biology, neuroimaging, and materials science. Co-occurrence keyword network analysis identified three clusters: optogenetic components and techniques, optogenetics and neural circuitry, optogenetics and disease. Conclusion: The results suggest that optogenetics research is flourishing, focusing on optogenetic techniques and their applications in neural circuitry exploration and disease intervention. Optogenetics is expected to remain a hot topic in various fields in the future.

Transdermal tibial nerve optogenetic stimulation targeting C-fibers.

Purpose: To explore whether stimulation of C-fibers in tibial nerves can induce bladder inhibition by optogenetic transdermal illumination. Methods: Ten rats were injected with AAV2/6-hSyn-ChR2(H134R)-EYFP into the tibial nerves. Transurethral cystometry was performed 4 weeks after the virus injection. Illumination (473-nm blue light at 100 mW) was performed with the fiber positioned above the right hind paw near the ankle. The light transmission efficiency was examined with a laser power meter. The effects on cystometry were compared before and after illumination with the bladder infused with normal saline and acetic acid, respectively. Result: Upon transdermal delivery of 473-nm light at a peak power of 100 mW, the irradiance value of 0.653 mW/mm2 at the target region was detected, which is sufficient to activate opsins. The photothermal effect of 473-nm light is unremarkable. Acute inhibitory responses were not observed during stimulation regarding any of the bladder parameters; whereas, after laser illumination for 30 min, a statistically significant increase in bladder capacity with the bladder infused with normal saline (from 0.53 ± 0.04 mL to 0.72 ± 0.05 mL, p < 0.001) and acetic acid (from 0.25 ± 0.02 mL to 0.37 ± 0.04 mL, p < 0.001) was detected. A similar inhibitory response was observed with pulsed illumination at both 10Hz and 50Hz. However, illumination did not significantly influence base pressure, threshold pressure, or peak pressure. Conclusion: In this preliminary study, it can be inferred that the prolonged bladder inhibition is mediated by the stimulation of C-fibers in the tibial nerves, with no frequency-dependent characteristics. Although the 473-nm blue light has limited penetration efficacy, it is sufficient to modulate bladder functions through transdermal illumination on the superficial peripheral nervous system.

Corrigendum: A bibliometric profile of optogenetics: quantitative and qualitative analyses.

[This corrects the article DOI: 10.3389/fnins.2023.1221316.].

Efficacy of a novel wearable transcutaneous tibial nerve stimulation device on bladder reflex compared to implantable tibial nerve stimulation in cats.

OBJECTIVE: To determine the efficacy of novel wearable transcutaneous tibial nerve stimulation (TTNS) device on bladder reflex in cats compared to implantable tibial nerve stimulation (ITNS). MATERIALS AND METHODS: Two self-adhesive electrodes of the TTNS device were placed at the left leg, and ITNS was applied to stimulate the tibial nerve of the right leg, respectively. The intensity threshold (T) was defined as inducing observable toe movement. Multiple cystometrograms (CMGs) with normal saline (NS) infusion were performed to determine the inhibitory effects of TTNS and ITNS on the micturition reflex. RESULTS: TTNS at 4 times T (4 T), 6 times T (6 T), and the maximum output current intensity 24 mA significantly increased the bladder capacity (BC) compared to the control level (8.70 ± 2.46 ml) (all p < 0.05); however, there was no statistical significance among the three intensities. At the same time, ITNS at 2 times T (2 T), 4 T, 6 T, and the current intension 24 mA could significantly increase the BC compared to the control level (all p < 0.05). Likewise, no significant difference was observed among the four intensities (p > 0.05). The T values of TTNS were higher than those of ITNS (p = 0.02). The inhibitory effects of TTNS and ITNS revealed no significant difference at their respective 2 T, 4 T, 6 T, and 24 mA. Neither TTNS nor ITNS changed the contraction duration and amplitude (all p > 0.05). CONCLUSIONS: TTNS was effective in increasing BC. The non-invasive neuromodulation technique could achieve a similar effect as ITNS.

Augmentation Uretero-enterocystoplasty Is an Effective Procedure in Protecting the Upper Urinary Tract Without Accelerating Deterioration of Renal Function.

Background: Augmentation uretero-enterocystoplasty (AUEC) provides a low-pressure urinary storage capsule that can preserve renal function in patients with lower urinary tract dysfunction for whom conservative treatments have failed. Objective: To summarize the effectiveness and safety of augmentation uretero-enterocystoplasty (AUEC) and evaluate whether it aggravates renal function deterioration in patients with renal insufficiency. Design setting and participants: This was a retrospective cohort study of patients who underwent AUEC from 2006 to 2021. Patients were grouped according to whether they had normal renal function (NRF) or renal dysfunction (serum creatinine >1.5 mg/dl). Outcome measurements and statistical analysis: Follow-up of upper and lower urinary tract function was assessed via review of clinical records, urodynamic data, and laboratory results. Results and limitations: We included 156 patients in the NRF group and 68 in the renal dysfunction group. We confirmed that urodynamic parameters and upper urinary tract dilation were significantly improved for patients after AUEC. Serum creatinine declined during the first 10 mo in both groups and remained stable thereafter. The reduction in serum creatine was significantly greater in the renal dysfunction group than in the NRF group in the first 10 mo (difference in reduction 4.19 units; p < 0.05). A multivariable regression model showed that baseline renal dysfunction was not a significant risk factor for deterioration of renal function in patients who had undergone AUEC (odds ratio 2.15; p = 0.11). The main limitations are selection bias because of the retrospective design, loss to follow-up, and missing data. Conclusions: AUEC is a safe and effective procedure to protect the upper urinary tract and will not hasten deterioration of renal function in patients with lower urinary tract dysfunction. In addition, AUEC improved and stabilized residual renal function in patients with renal insufficiency, which is important in preparation for renal transplantation. Patient summary: Bladder dysfunction is usually treated with medication or Botox injections. If these treatments fail, surgery to increase the bladder size using a portion of the patient's intestine is a possible option. Our study shows that this procedure was safe and feasible and improved bladder function. It did not lead to a further decrease in function in patients who already had impaired kidney function.

Feasibility of a Transcutaneous Tibial Nerve Stimulation Device Use in Overactive Bladder Patients: A Pilot Study From a Single Tertiary Care Center.

Purpose: To evaluate the preliminary efficacy, safety, and acceptability of a transcutaneous tibial nerve stimulation (TTNS) device in overactive bladder (OAB) patients. Methods: Twenty OAB patients who failed with conservative treatments were recruited consecutively. All patients received 60 min of daily unilateral stimulation for 4 weeks using a smart wearable transcutaneous tibial nerve stimulation device and the stimulations were at 20 Hz frequency, 200 µs pulse width. OAB symptoms were observed at baseline and week 4, using a 3-days voiding diary, the overactive bladder symptom score (OABSS), the perception of bladder condition (PPBC), and the American Urological Association Symptom Index Quality of Life Score (AUA-SI-QoL). Urodynamic characteristics were measured to determine the pilot efficacy of the device during the treatment comparing the baseline parameters to the post-treatment parameters. Results: Among the patients, 15 cases were OAB-dry and five cases were OAB-wet. All patients were evaluated at the end of the study and no significant side effects were found during the treatment. The daily micturition frequency and the number of incontinence episodes per day were reduced from 15.10 ± 1.61 to 12.00 ± 4.56, and 3.20 ± 0.80 to 0.47 ± 0.38, respectively. The mean voiding volume was increased from 130.10 ± 53.07 to 157.30 ± 66.95 mL. The OABSS, AUA-SI-QoL, and PPBC were reduced from 9.35 ± 1.39 to 5.9 ± 2.36, 5.70 ± 0.47 to 3.85 ± 1.04, and 5.70 ± 0.47 to 4.35 ± 0.86, respectively. The first sensation of bladder filling (1st SBF), maximal bladder capacity (MBC), and mean compliance were increased from 87.50 (60.00-167.50) to 150.00 (104.00-211.30) mL, 175.00 (120.30-354.00) to 255.00 (151.50-491.50) mL, and 36.67 (12.44-39.69) to 40.00 (20.00-52.50) mL/cmH2O, respectively. The maximum detrusor pressure (Pdet. max) was reduced from 14.50 (5.00-35.25) to 11.00 (6.00-20.00) cmH2O. Conclusion: The preliminary results demonstrated that the TTNS device was safe, effective, and acceptable to use in OAB patients, but the results need to be substantiated by conducting more randomized controlled studies further.

Upper urinary dilatation and treatment of 26 patients with diabetes insipidus: A single-center retrospective study.

Objective: To describe the urinary tract characteristics of diabetes insipidus (DI) patients with upper urinary tract dilatation (UUTD) using the video-urodynamic recordings (VUDS), UUTD and all urinary tract dysfunction (AUTD) systems, and to summarize the experience in the treatment of DI with UUTD. Methods: This retrospective study analyzed clinical data from 26 patients with DI, including micturition diary, water deprivation tests, imaging data and management. The UUTD and AUTD systems were used to evaluate the urinary tract characteristics. All patients were required to undergo VUDS, neurophysiologic tests to confirm the presence of neurogenic bladder (NB). Results: VUDS showed that the mean values for bladder capacity and bladder compliance were 575.0 ± 135.1 ml and 51.5 ± 33.6 cmH2O in DI patients, and 42.3% (11/26) had a post-void residual >100 ml. NB was present in 6 (23.1%) of 26 DI patients with UUTD, and enterocystoplasty was recommended for two patients with poor bladder capacity, compliance and renal impairment. For the 24 remaining patients, medication combined with individualized and appropriate bladder management, including intermittent catheterization, indwelling catheter and regular voiding, achieved satisfactory results. High serum creatinine decreased from 248.0 ± 115.8 µmoI/L to 177.4 ± 92.8 µmoI/L in 12 patients from a population with a median of 108.1 µmoI/L (IQR: 79.9-206.5 µmoI/L). Forty-four dilated ureters showed significant improvement in the UUTD grade, and the median grade of 52 UUTD ureters decreased from 3 to 2. Conclusion: Bladder distension, trabeculation and decreased or absent sensations were common features for DI patients with UUTD. Individualized therapy by medication combined with appropriate bladder management can improve UUTD and renal function in DI patients.

Effects of Intravesical Electrical Stimulation on Urinary Adenosine Triphosphate and Nitric Oxide in Rats With Detrusor Underactivity Induced By Bilateral Pelvic Nerve Crush Injury: The Possible Underlying Mechanism.

PURPOSE: To explore the effect of intravesical electrical stimulation (IVES) on urinary adenosine triphosphate (ATP) and nitric oxide (NO) in rats with detrusor underactivity (DU) induced by bilateral pelvic nerve crush (bPNC), and to determine the underlying peripheral mechanism. METHODS: Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: sham; bPNC; and IVES. Rats in the IVES group began to receive IVES treatment 10 days after bPNC (20 minutes per day for 14 consecutive days). After the 14th IVES, rat urine was collected and cystometry was performed. The serum creatinine, blood urea nitrogen, and urinary ATP and NO levels were measured, and a routine urinalysis was performed. RESULTS: The maximum cystometric capacity (MCC), maximum changes in bladder pressure during filling (∆FP), and postvoid residual urine (PVR) in the IVES group were significantly lower than the bPNC group, and the maximum changes in bladder pressure during voiding (∆VP) was significantly higher than the bPNC group. Compared with the sham group, the MCC, ∆FP and PVR were significantly increased, and the maximum voiding pressure (MVP) and ∆VP were significantly decreased in the bPNC group. After bPNC, urinary ATP was significantly decreased, and urinary NO was significantly increased. In IVES-treated rats, urinary ATP was significantly higher than the bPNC group, and NO was significantly lower than the bPNC group. In addition, the ATP-to-NO ratio of the rats in the bPNC group was significantly lower than the sham and IVES groups. Correlation analysis showed that the ATP and NO were not correlated with the MCC, ∆FP, MVP, ∆VP, and PVR. CONCLUSION: Promoting the release of urothelial ATP and inhibiting the release of urothelial NO may be one of the peripheral mechanisms underlying IVES in the treatment of DU. Specifically, IVES may shift the balance between excitation and inhibition toward excitation.

Sacral Neuromodulation Using a Novel Device with a Six-contact-point Electrode for the Treatment of Patients with Refractory Overactive Bladder: A Multicenter, Randomized, Single-blind, Parallel-control Clinical Trial.

BACKGROUND: A novel sacral neuromodulation system (SacralStim) which has an electrode with six contact points was recently designed. OBJECTIVE: To evaluate the effectiveness and safety of the SacralStim system for treating patients with refractory overactive bladder (OAB). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, randomized, single-blind clinical trial. Patients with refractory OAB were enrolled from January 2018 to May 2020. INTERVENTION: Participants were randomly allocated to the treatment group (SNM on) or the control group (SNM off) for a single-blind period of 12 ± 2 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the percentage of patients with a reduction in the average number of voids/24 h of at least 50% at the 12-wk follow-up visit. Other follow-up evaluations, including voiding diary outcomes, questionnaires on Overactive Bladder Symptom Score (OABSS), quality of life (QoL), device satisfaction, and causes of adverse events (AEs), were performed over the first 48 wk after implantation. RESULTS AND LIMITATIONS: The therapeutic success rate at 12 wk was 56.76% in the treatment group and 11.11% in the control group (p < 0.001). There were significant differences in voiding diary variables between the two groups, including changes in the average number of voids/24 h, micturition volume/void, and improvement in the urge incontinence ratio. No severe AEs occurred. A limitation is the sham stimulation used as a control in the study. A head-to-head study is required to make a direct comparison of devices with six and four contact points. CONCLUSIONS: This clinical trial provides strong evidence that patients with refractory OAB benefit from the novel SacralStim system. More research is required for direct comparison of the SacralStim system with traditional four-contact-point devices. PATIENT SUMMARY: This study confirms the effectiveness and safety of a novel SacralStim system that stimulates the sacral nerve for treatment of overactive bladder. The system has an electrode with six contact points and can provide more programming options after implantation.

Development and validation of a nomogram including lymphocyte-to-monocyte ratio for initial prostate biopsy: a double-center retrospective study.

Here, we developed a prostate cancer (PCa) risk nomogram including lymphocyte-to-monocyte ratio (LMR) for initial prostate biopsy, and internal and external validation were further conducted. A prediction model was developed on a training set. Significant risk factors with P < 0.10 in multivariate logistic regression models were used to generate a nomogram. Discrimination, calibration, and clinical usefulness of the model were assessed using C-index, calibration plot, and decision curve analysis (DCA). The nomogram was re-examined with the internal and external validation set. A nomogram predicting PCa risk in patients with prostate-specific antigen (PSA) 4-10 ng ml-1 was also developed. The model displayed good discrimination with C-index of 0.830 (95% confidence interval [CI]: 0.812-0.852). High C-index of 0.864 (95% CI: 0.840-0.888) and 0.871 (95% CI: 0.861-0.881) was still reached in the internal and external validation sets, respectively. The nomogram exhibited better performance compared to the nomogram with PSA only (C-index: 0.763, 95% CI: 0.746-0.780, P < 0.001) and the nomogram with LMR excluded (C-index: 0.824, 95% CI: 0.804-0.844, P < 0.010). The calibration curve demonstrated good agreement in the internal and external validation sets. DCA showed that the nomogram was useful at the threshold probability of >4% and <99%. The nomogram predicting PCa risk in patients with PSA 4-10 ng ml-1 also displayed good calibration and discrimination performance (C-index: 0.734, 95% CI: 0.708-0.760). This nomogram incorporating age, PSA, digital rectal examination, abnormal imaging signals, PSA density, and LMR could be used to facilitate individual PCa risk prediction in initial prostate biopsy.

Identification of Long Noncoding RNA APOC1P1 as an Oncogene in Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is one of the most common genitourinary cancers worldwide. Previous evidence shows that long noncoding RNA (LncRNA) APOC1P1 plays an important role in cancer development. However, the role of LncRNA APOC1P1 in ccRCC remains to be explored. LncRNA APOC1P1 expression in 283 ccRCC tissues and 30 normal kidney tissues was detected by quantitative real-time PCR, and its prognostic association with ccRCC was assessed by the Kaplan-Meier method and Cox proportional hazard model. Cell proliferation, apoptosis, migration, and invasion were determined in RCC cells with downregulation of LncRNA APOC1P1 expression. LncRNA APOC1P1 expression was increased in ccRCC tissues compared with normal kidney tissues (P < 0.001). Its expression was higher in the Fuhrman grade III and IV group than in the Fuhrman grade I and II group (P < 0.05) and significantly upregulated in the advanced stage group (P < 0.05). Kaplan-Meier analyses revealed that elevated LncRNA APOC1P1 expression was significantly associated with poor overall survival (P < 0.05) but may not be an independent prognostic factor. Knockdown of LncRNA APOC1P1 inhibited cell proliferation, induced apoptosis, and arrested cells at the G1/S phase (P < 0.05). Silencing of LncRNA APOC1P1 also led to decreased cell migration and invasion (P < 0.05). LncRNA APOC1P1 acts as an oncogene, plays an important role in ccRCC development, and can be considered a prognostic biomarker and therapeutic target in ccRCC patients.

Ureter - an unusual site of breast cancer metastasis: A case report.

BACKGROUND: Breast cancer (BCa) is one of the most common malignancies in women; however, ureteral metastasis of BCa has rarely been reported in the literature. CASE SUMMARY: A 55-year-old Chinese woman with an 8-year history of BCa presented with lower back pain that had persisted for 3 mo. The patient underwent bilateral modified radical mastectomy and subclavian and submandibular clearance, and received systemic treatment, including chemotherapy, radiotherapy, and targeted therapy during treatment. Ureteroscopy did not acquire a satisfactory biopsy. Thus, laparoscopic nephroureterectomy was performed, and ureteral metastases of BCa were pathologically confirmed. As suggested by her oncologist, she continued to receive apatinib. Postoperative 3-mo follow-up indicated further progression of axillary lymph node metastases. CONCLUSION: Ureteral metastasis of BCa shows nonspecific symptoms. Diagnosing ureter metastasis from BCa can be established by histopathology and immunohistochemistry.