PITPNC1 Suppress CD8+ T cell immune function and promote radioresistance in rectal cancer by modulating FASN/CD155.

BACKGROUND: Radioresistance is a primary factor contributing to the failure of rectal cancer treatment. Immune suppression plays a significant role in the development of radioresistance. We have investigated the potential role of phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1) in regulating immune suppression associated with radioresistance. METHODS: To elucidate the mechanisms by which PITPNC1 influences radioresistance, we established HT29, SW480, and MC38 radioresistant cell lines. The relationship between radioresistance and changes in the proportion of immune cells was verified through subcutaneous tumor models and flow cytometry. Changes in the expression levels of PITPNC1, FASN, and CD155 were determined using immunohistochemistry and western blotting techniques. The interplay between these proteins was investigated using immunofluorescence co-localization and immunoprecipitation assays. Additionally, siRNA and lentivirus-mediated gene knockdown or overexpression, as well as co-culture of tumor cells with PBMCs or CD8+ T cells and establishment of stable transgenic cell lines in vivo, were employed to validate the impact of the PITPNC1/FASN/CD155 pathway on CD8+ T cell immune function. RESULTS: Under irradiation, the apoptosis rate and expression of apoptosis-related proteins in radioresistant colorectal cancer cell lines were significantly decreased, while the cell proliferation rate increased. In radioresistant tumor-bearing mice, the proportion of CD8+ T cells and IFN-γ production within immune cells decreased. Immunohistochemical analysis of human and animal tissue specimens resistant to radiotherapy showed a significant increase in the expression levels of PITPNC1, FASN, and CD155. Gene knockdown and rescue experiments demonstrated that PITPNC1 can regulate the expression of CD155 on the surface of tumor cells through FASN. In addition, co-culture experiments and in vivo tumor-bearing experiments have shown that silencing PITPNC1 can inhibit FASN/CD155, enhance CD8+ T cell immune function, promote colorectal cancer cell death, and ultimately reduce radioresistance in tumor-bearing models. CONCLUSIONS: PITPNC1 regulates the expression of CD155 through FASN, inhibits CD8+ T cell immune function, and promotes radioresistance in rectal cancer.

Clinical activity and safety of sintilimab, bevacizumab, and TMZ in patients with recurrent glioblastoma.

PURPOSE: There are limited and no standard therapies for recurrent glioblastoma. We herein report the antitumour activity and safety of sintilimab, bevacizumab and temozolomide (TMZ) in recurrent glioblastoma. METHODS: We retrospectively analysed eight patients with recurrent glioblastoma treated with sintilimab (200 mg) every three weeks + bevacizumab (10 mg/kg) every three weeks + TMZ (200 mg/m²orally) (5 days orally every 28 days for a total of four weeks). The primary objective was investigator-assessed median progression-free survival(mPFS). Secondary objectives were to assess the 6-month PFS, objective response rate (ORR) and duration of response (DOR) accroding to RANO criteria. RESULTS: The mPFS time for 8 patients was 3.340 months (95% CI: 2.217-4.463), The longest PFS was close to 9 months. Five patients were assessed to have achieved partial response (PR), with an overall remission rate of 62.5%, Four patients experienced a change in tumour volume at the best response time of greater than 60% shrinkage from baseline, and one patient remained progression free upon review, with a DOR of more than 6.57 months. The 6-month PFS was 25% (95% CI: 5.0-55.0%). Three patients had a treatment-related adverse events, though no grade 4 or 5 adverse events occurred. CONCLUSION: In this small retrospective study, the combination regimen of sintilimab, bevacizumab and TMZ showed promising antitumour activity in treatment of recurrent glioblastoma, with a good objective remission rate.

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.

Efficacy and safety of tibial nerve stimulation using a wearable device for overactive bladder.

OBJECTIVE: To evaluate the efficacy and safety of a wearable, smartphone-controlled, rechargeable transcutaneous tibial nerve stimulation (TTNS) device in patients with overactive bladder (OAB). PATIENTS AND METHODS: This multicentre, prospective, single-blind, randomised clinical trial included eligible patients with OAB symptoms who were randomly assigned to the stimulation group or sham group. The primary efficacy outcome was change from baseline in voiding frequency/24 h after 4 weeks of treatment. The secondary efficacy outcomes included changes in bladder diary outcomes (urgency score/void, nocturia episodes/day, micturition volume/void, and incontinence episodes/day), questionnaires on Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and American Urological Association Symptom Index Quality of Life Score (AUA-SI-QoL) at baseline and after 4 weeks of treatment. Device-related adverse events (AEs) were also evaluated. RESULTS: In the full analysis set (FAS), the mean (sd) change of voiding frequency/24 h in the stimulation group and sham group at 4 weeks were -3.5 (2.9) and -0.6 (2.4), respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -3.5 (2.9) vs -0.4 (2.3) (P < 0.01). In the FAS and PPS, micturition volume/void significantly improved at 4 weeks (P = 0.01 and P = 0.02). PPBC improvement almost reached significance in the FAS (P = 0.05), while it was significant in the PPS (P = 0.02). In the FAS and PPS, AUA-SI-QoL significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas there were no significant differences in urgency score/void, nocturia episodes/day or OABSS between the groups. Also, no device-related serious AEs were reported. CONCLUSIONS: The non-invasive neuromodulation technique using the novel ambulatory TTNS device is effective and safe for treating OAB. Its convenience and easy maintenance make it a new potential home-based treatment modality. Future studies are warranted to confirm its longer-term efficacy.

Applications of machine learning in urodynamics: A narrative review.

BACKGROUND: Machine learning algorithms as a research tool, including traditional machine learning and deep learning, are increasingly applied to the field of urodynamics. However, no studies have evaluated how to select appropriate algorithm models for different urodynamic research tasks. METHODS: We undertook a narrative review evaluating how the published literature reports the applications of machine learning in urodynamics. We searched PubMed up to December 2023, limited to the English language. We selected the following search terms: artificial intelligence, machine learning, deep learning, urodynamics, and lower urinary tract symptoms. We identified three domains for assessment in advance of commencing the review. These were the applications of urodynamic studies examination, applications of diagnoses of dysfunction related to urodynamics, and applications of prognosis prediction. RESULTS: The machine learning algorithm applied in the field of urodynamics can be mainly divided into three aspects, which are urodynamic examination, diagnosis of urinary tract dysfunction and prediction of the efficacy of various treatment methods. Most of these studies were single-center retrospective studies, lacking external validation, requiring further validation of model generalization ability, and insufficient sample size. The relevant research in this field is still in the preliminary exploration stage; there are few high-quality multi-center clinical studies, and the performance of various models still needs to be further optimized, and there is still a distance from clinical application. CONCLUSIONS: At present, there is no research to summarize and analyze the machine learning algorithms applied in the field of urodynamics. The purpose of this review is to summarize and classify the machine learning algorithms applied in this field and to guide researchers to select the appropriate algorithm model for different task requirements to achieve the best results.

Elucidating the causal landscape: Mendelian randomization analysis of lifestyle and physiological factors in stress urinary incontinence.

PURPOSE: To explore the potential causal links between obesity, type 2 diabetes (T2D), and lifestyle choices (such as smoking, alcohol and coffee consumption, and vigorous physical activity) on stress urinary incontinence (SUI), this study employs a Mendelian Randomization approach. This research aims to clarify these associations, which have been suggested but not conclusively established in prior observational studies. METHODS: Genetic instruments associated with the exposures at the genome-wide significance (p < 5 × 10-8) were selected from corresponding genome-wide association studies. Summary-level data for SUI, was obtained from the UK Biobank. A two-sample MR analysis was employed to estimate causal effects, utilizing the inverse-variance weighted (IVW) method as the primary analytical approach. Complementary sensitivity analyses including MR-PRESSO, MR-Egger, and weighted median methods were performed. The horizontal pleiotropy was detected by using MR-Egger intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran's Q statistics. RESULTS: Our findings demonstrate a significant causal relationship between higher body mass index (BMI) and the risk of SUI, with increased abdominal adiposity (WHRadjBMI) similarly linked to SUI. Smoking initiation is also causally associated with an elevated risk. However, our analysis did not find definitive causal connections for other factors, including T2D, alcohol consumption, coffee intake, and vigorous physical activity. CONCLUSIONS: These findings provide valuable insights for clinical strategies targeting SUI, suggesting a need for heightened awareness and potential intervention in individuals with higher BMI, WHR, and smoking habits. Further research is warranted to explore the complex interplay between genetic predisposition and lifestyle choices in the pathogenesis of SUI.

Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

BACKGROUND: Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. OBJECTIVE: To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. DESIGN: Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. PATIENTS: A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. METHODS: The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. RESULTS: The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). CONCLUSION: The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Effect of Pilates combined with pelvic floor muscle training on continence of post-prostatectomy incontinence in patients with different body mass index.

BACKGROUND: Urinary incontinence symptoms severely affect older people with different body mass index (BMI).To compare the efficacy of the pelvic floor muscle training (PFMT) in patients with post-prostatectomy incontinence with different BMI. METHODS: Thirty-seven patients with post-prostatectomy incontinence were included. They were divided into group A (BMI ≤ 25,12), group B (26 ≤ BMI ≤ 30,14), and group C (BMI ≥ 31,11) based on difference BMI. Three groups of patients underwent the same Pilates combined with kegel training. Participants were assessed with 1-hour pad test, the number of incontinence episodes, International Consultation on Incontinence Questionnaire and Oxford Grading Scale. RESULTS: In the 1-hour pad test, the differences before and after training were statistically significant in all three groups of participants. Group A decreased from 81.83 ± 8.79 to 31.08 ± 5.64 g (P < 0.01). Group B decreased from 80.57 ± 8.87 to 35.85 ± 5.66 g (P < 0.01). Group C decreased from 83.55 ± 10.24 to 40.18 ± 7.01 g (P < 0.01). The number of incontinent episodes in group A decreased from 9.33 ± 1.07 to 3.25 ± 0.62 (P < 0.01). Group B decreased from 8.86 ± 1.09 to 3.79 ± 0.80 (P < 0.01). Group C decreased from 9.27 ± 1.10 to 4.09 ± 0.70 (P < 0.01). The correlation between the three groups of participants and the 1-hour pad test, with an R2 of 0.51. The correlation between the three groups of participants and the number of urinary incontinence episodes with a R2 of 0.43. CONCLUSIONS: Pelvic floor muscle training can affect the recovery of urinary continence in patients with different BMI. Maintaining a lower BMI can be beneficial for improving urinary control. TRIAL REGISTRATION: Date of trial registration: November 27, 2023.

Mechanism of Action of Tibial Nerve Stimulation in the Treatment of Lower Urinary Tract Dysfunction.

BACKGROUND AND OBJECTIVE: Tibial nerve stimulation (TNS) has long been used to effectively treat lower urinary tract dysfunction (LUTD). Although numerous studies have concentrated on TNS, its mechanism of action remains elusive. This review aimed to concentrate on the mechanism of action of TNS against LUTD. MATERIALS AND METHODS: A literature search was performed in PubMed on October 31, 2022. In this study, we introduced the application of TNS for LUTD, summarized different methods used in exploring the mechanism of TNS, and discussed the next direction to investigate the mechanism of TNS. RESULTS AND CONCLUSIONS: In this review, 97 studies, including clinical studies, animal experiments, and reviews, were used. TNS is an effective treatment for LUTD. The study of its mechanisms primarily concentrated on the central nervous system, tibial nerve pathway, receptors, and TNS frequency. More advanced equipment will be used in human experiments to investigate the central mechanism, and diverse animal experiments will be performed to explore the peripheral mechanism and parameters of TNS in the future.

Randomized controlled trial of intravesical electrical stimulation for underactive bladder.

AIM: To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB). PATIENTS AND METHODS: This was a multicentre, prospective, single-blind, randomized controlled clinical trial of patients with UAB in China. Eligible patients were randomly assigned in a 1:1 ratio to receive conventional IVES (n = 38) or IVES with an open circuit (n = 38). The primary efficacy measure was change from baseline in post-void residual urine volume (PVR) after 4 weeks of treatment. Secondary efficacy measures included changes in maximum urinary flow rate (Qmax ), bladder voiding efficiency (BVE), number of 24-h clean intermittent catheterization (CIC) procedures, and Patient Perception of Bladder Condition-Scale (PPBC-S) and American Urological Association Symptom Index Quality of Life (AUA-SI-QoL) scores from baseline after 4 weeks of treatment. Adverse events (AEs) were monitored throughout the trial. RESULTS: In the full analysis set (FAS), the mean (sd) PVR changes in the trial and control groups at 4 weeks were -97.1 (107.5) mL and -10.5 (86.7) mL, respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -102.9 (100.0) mL vs 0.7 (82.5) mL (P < 0.01). In the FAS and PPS, Qmax improved significantly at 4 weeks (P = 0.04 and P = 0.03). In the FAS and PPS, BVE was significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas no significant differences in the number of 24-h CIC procedures, PPBC-S score or AUA-SI-QoL score were observed between the groups. Six possible therapy-related AEs occurred in six patients (four in the trial group and two in the control group; P = 0.67), all of which were urinary tract infections. No severe AEs were reported. CONCLUSIONS: The results of this clinical study strongly demonstrate that UAB patients benefit from this novel IVES device. More research is needed to validate the clinical utility of this device.

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.

Creatinine-based equations to estimate glomerular filtration rate should be used with caution in patients with neurogenic bladder.

BACKGROUND: Patients with neurogenic bladder (NGB) are at an increased risk of developing chronic kidney disease (CKD). However, data related to the real performance of the serum creatinine (Cr)-based estimated glomerular filtration rate (eGFR) equation in patients with NGB are limited. This study is to evaluate the performance of new Cr-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without race and the GFR estimation equation for Chinese CKD patients for the estimation of GFR in Chinese patients with NGB. MATERIALS AND METHODS: GFR was determined simultaneously by three methods: a) GFR measured by renal dynamic imaging with 99mTc-DTPA (G-GFR), which was used as the reference GFR; b) GFR estimated by the new Cr-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without race (EPI-GFR); and c) GFR estimated by the equation for Chinese CKD patients (C-GFR). Pearson correlation and linear regression were used to compare eGFR and G-GFR. Differences, absolute differences, precision, and accuracy were compared to identify which equation showed better performance in evaluating GFR in patients with NGB. RESULTS: A total of 171 patients with NGB, including 121 men and 50 women from 20 provinces, 4 autonomous regions, and 3 municipalities in China, were enrolled in the final analysis, and the average age was 31.3 ± 11.9 years. Both C-GFR and EPI-GFR were moderately correlated with G-GFR and overestimated G-GFR. The difference between EPI-GFR and G-GFR was similar to that between C-GFR and G-GFR (median of 9.97 vs. 9.95 mL/min/1.73m2 for difference, Wilcoxon signed ranks test, Z = -1.704, p = 0.088), but the absolute difference between EPI-GFR and G-GFR was significantly lower than that between C-GFR and G-GFR (median of 22.3 vs. 25.1 mL/min/1.73m2 for absolute difference, Wilcoxon signed ranks test, Z = -4.806, p < 0.001). Both EPI-GFR and C-GFR displayed similar results of 15, 30, and 50% accuracies (χ2-test, p > 0.05), and there were no significant differences between EPI-GFR and C-GFR in misclassification percentages at different G-GFR levels (χ2-test, p > 0.05). CONCLUSION: Our study indicated that for patients with NGB in China, Cr-based eGFR equations, which include the new CKD-EPI equation without race and the Chinese GFR estimation equation, showed suboptimal performance, and limited their application in GFR estimation. Further studies are needed to investigate whether incorporating additional biomarkers, such as cystatin C, could improve their performance of GFR estimating equations in patients with NGB.

The Asia-Pacific AMS800 artificial urinary sphincter consensus statement.

This Asia-Pacific (AP) AMS 800™ artificial urinary sphincter (AUS) consensus statement aims to provide a set of practical recommendations to assist surgeons with the AMS 800 device surgery. The AP consensus committee consisted of key opinion leaders with extensive experience with AMS 800 surgery across several AP countries. The panel reviewed and discussed relevant findings with emphasis on locoregional and specific clinical challenges relevant to the AP region. Recommendations were made in key areas namely (1) patient selection and informed consent process; (2) preoperative assessment; (3) dealing with co-existing urological disorders; (4) surgical principles and intraoperative troubleshooting; (5) postoperative care; (6) special populations; and (7) cost analysis and comparative review. The AMS 800 device should be offered to males with moderate to severe stress urinary incontinence (SUI). Full informed consent should be undertaken, and emphasis is placed on surgical contraindications and high-risk candidates. The presence of a surgical mentor or referral to experts is recommended in complex AUS candidates. Preoperative cystoscopy with or without multichannel urodynamic study is necessary and patients with pre-existing urological disorders should be treated adequately and clinically stable before surgery. Adherence to strict patient selection and safe surgical principles are critical to ensure excellent clinical outcomes and minimize complications. Given that InhibiZone-coated device is not available in many AP countries, the use of prophylactic antibiotics pre-and post-operatively are recommended. The AMS 800 device should be prepared according to the manufacturer's guidelines and remains a cost-effective treatment for male SUI. The AMS 800 device remains the surgical benchmark for male SUI but is associated with certain mechanical limitations and a unique set of complications.

Sacral Neuromodulation Improves Abnormal Prefrontal Brain Activity in Patients with Overactive Bladder: A Possible Central Mechanism.

PURPOSE: We explored the central pathogenesis of overactive bladder (OAB) and the central mechanism of action of sacral neuromodulation (SNM). MATERIALS AND METHODS: We prospectively enrolled patients with OAB who chose SNM and healthy controls (HCs). At baseline, all subjects completed a 72-hour voiding diary, OAB symptom score and prefrontal cortex functional near-infrared spectroscopy scan synchronous urodynamic monitoring. All OAB patients were tested after implantation of the SNM electrode, and both success and failure groups were reevaluated. NIRS_KIT software was used to analyze prefrontal activity (p <0.05 and corrected by false discovery rate). SPSS® 22.0 was used to analyze clinical parameters, and p <0.05 was considered statistically significant. RESULTS: A total of 16 HC and 20 OAB patients were enrolled. SNM treatment was successful in 18 OAB patients and failed in 2. The parameters of the voiding diary, OAB symptom score and urodynamic monitoring of OAB group were significantly improved after SNM treatment in success group, not in the failure group. Compared with HCs, Brodmann's area 9 (left dorsolateral prefrontal cortex [DLPFC]) was significantly deactivated in the preoperative OAB success group and significantly activated after SNM treatment. Before surgery, compared with the success group, the failure group showed significantly deactivated Brodmann's area 9 (left DLPFC). CONCLUSIONS: Our study provides novel neuroimaging evidence for the possible central pathogenesis of OAB (ie abnormal deactivation of the left DLPFC) and the possible central mechanism of action of SNM (ie restore activation of the left DLPFC).

Inhibitory effects of a smartphone-controlled wearable transcutaneous tibial nerve stimulation device on bladder reflexes in anesthetized cats.

OBJECTIVES: To explore the inhibitory effects of a novel, smartphone-controlled, and wearable tibial nerve stimulation device on nonnociceptive and nociceptive bladder reflexes in anesthetized cats and to compare the stimulus results of two current waveforms outputted by this new stimulator. MATERIALS AND METHODS: A novel, intelligent tibial nerve stimulator was put on the ankles of 14 cats and controlled by a mobile application. Cystometrograms (CMGs) were performed repeatedly by infusing 0.9% normal saline (NS) and 0.5% acetic acid (AA) through a urethral catheter. Inhibitory effects were explored by measuring the bladder capacity (BC) in two areas: (1) on nonnociceptive bladder reflex (infused with NS) and on nociceptive bladder reflex (filled with AA to induce overactive bladder [OAB] model); and (2) under the stimulation of two different current waveforms (waveforms A and B). RESULTS: In Group 1, the BC of AA-induced OAB (41.48 ± 8.40%) was significantly different compared with the capacity of a NS-infused bladder (104.89 ± 1.32%, p < 0.05). Both NS-filled (151.35 ± 5.71%, p < 0.05) and AA-instilled (71.41 ± 9.34%, p < 0.05) bladder volumes significantly increased after tibial nerve stimulation (TNS). In Group 2, the BC increased to 166.18 ± 15.17% (p = 0.026) and 127.64 ± 13.00% (p = 0.239), respectively, after TNS with waveforms A and B current. CONCLUSIONS: Results revealed that this novel, smartphone-based, wearable, and wireless tibial nerve stimulation system could inhibit the micturition reflex on physiological condition, serving as a potential option for OAB treatment. In addition, the waveforms of stimulation current had an important influence on the effects of TNS.

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.

Abnormal functional connectivity within the prefrontal cortex in interstitial cystitis/bladder pain syndrome (IC/BPS): A pilot study using resting state functional near-infrared spectroscopy (rs-fNIRS).

PURPOSE: To investigate the abnormalities of functional connectivity (FC) within the prefrontal cortex (PFC) of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) based on resting state functional near-infrared spectroscopy (rs-fNIRS) data using FC matrix analysis. MATERIALS AND METHODS: Ten patients with IC/BPS (females, 9; mean age, 56.9 ± 12.432 years) and 15 age- and gender-matched healthy controls (HC) (females, 12; mean age, 55.067 ± 7.46 years) participated in this rs-fNIRS study. Two rs-fNIRS scans were performed (when the bladder was empty and when the desire to void was strong). The Pearson's correlation coefficient between the time series of the 22 channels was calculated to obtain a 22 × 22 FC matrix for each subject. A two-sample t-test (p < .05) was performed to compare group differences in the FC matrix between patients with IC/BPS and HC. RESULTS: FC was significantly decreased within the PFC in the IC/BPS group based on a two-sample t-test (p < .05) compared with HC. FC decreased in a wider range of brain regions during the strong desire to void state (4 brain regions and 28 edges) when compared with the empty bladder state (3 brain regions and 18 edges). CONCLUSION: FC abnormalities in IC/BPS patients may lead to frontal lobe disorders involved in processing sensory integration, motivation drive, emotional control, and decision-making whether to urinate, leading to urinary control dysfunction manifested as typical clinical IC/BPS symptoms. Our results may provide new insight into the pathogenesis of IC/BPS and new brain biomarkers for diagnosis.

Augmentation uretero-enterocystoplasty for refractory urinary tract dysfunction: a long-term retrospective study.

OBJECTIVES: To report the long-term efficacy and complications of the augmentation uretero-enterocystoplasty (AUEC), including augmentation cystoplasty with simultaneous ureteroplasty and ureteral anti-reflux implantation in a single center. METHODS: We retrospectively reviewed clinical records, video-urodynamic data, and magnetic resonance urography of 210 patients who underwent the procedure for refractory lower urinary tract dysfunction (LUTD) from 2003 to 2019. International vesicoureteral reflux (VUR) and upper urinary tract dilatation (UUTD) grading systems were applied to assess upper urinary tract function, and post-operative complications were assessed. RESULTS: Mean age was 28.1 years, with a mean follow-up time of 57.4 months. A total of 338 ureters were simultaneously re-implanted, and ureteroplasty was performed on all ureters. There was a significant postoperative improvement in the bladder capacity, intravesical pressure, and compliance (P < 0.05). VUR improvement rate was 97.7% and postoperative improvement of UUTD presented in 72.5% ureters. Mean serum creatinine (Scr) level was significantly improved compared to preoperative Scr values (226.0 ± 89.4 µmol/L vs. 217.5 ± 133.9 umol/L, P < 0.05). The 1.0% patients had unacceptably postoperative urinary incontinence and 85.4% preoperative megaureters were improved. Primary complications included metabolic acidosis (9.5%), vesicoureteral anastomosis stenosis (6.2%), persistent VUR (2.7%), urinary calculi (6.6%), and intestinal dysfunction requiring laparotomy (3.3%). CONCLUSION: In the study, a large series of patients treated with a complex surgical procedure was reported. It is novel, as this case series represents patients with aggressive surgical correction of VUR, ureteral tortuosity and upper tract dilation at the time of AC. AUEC was shown to have a positive role in treating patients with refractory LUTD associated with hydronephrosis and ureteral dilatation, stenosis or obstruction, with or without high- or low-pressure VUR. It was effective in improving renal function and protecting the UUT function from further deterioration in most patients with renal insufficiency.

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.