Effects of Platelet-Activating Factor (PAF) on the Mechanical Activities of Lower Urinary Tract and Genital Smooth Muscles.

Since its first discovery as a bioactive phospholipid inducing potent platelet aggregation, platelet-activating factor (PAF) has been shown to be involved in a wide variety of inflammatory and allergic disease states. Many pharmacological studies in the 1980s and 1990s also showed that PAF induces endothelium-dependent vascular relaxation and contraction of various smooth muscles (SMs), including those in the airway, gastrointestinal organs, and uterus. However, since the late 1990s, there have been few reports on the SM contractions induced by PAF. The lower urinary tract (LUT), particularly the urinary bladder (UB) has attracted recent attention in SM pharmacology research because patients with LUT dysfunctions including overactive bladder are increasing as the population ages. In addition, recent clinical studies have implicated the substantial role of PAF in the inflammatory state in LUT because its production increases with smoking and with cancer. However, the effects of PAF on mechanical activities of LUT SMs including UBSM have not been investigated to date. Recently, we found that PAF very strongly increased mechanical activities of UBSM in guinea pigs and mice, and partly elucidated the possible mechanisms underlying these actions of PAF. In this review, we describe the effects of PAF on LUT SMs by introducing our recent findings obtained in isolated UBSMs and discuss the physiological and pathophysiological significance. We also introduce our data showing the effects of PAF on the SM mechanical activities of genital tissues (prostate and vas deferens).

PDE5 inhibitor potentially improves polyuria and bladder storage and voiding dysfunctions in type 2 diabetic rats.

PURPOSE: Bladder dysfunction associated with type 2 diabetes mellitus (T2DM) includes urine storage and voiding disorders. We examined pathological conditions of the bladder wall in a rat T2DM model and evaluated the effects of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil. MATERIALS AND METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats were used as the T2DM and control groups, respectively. Tadalafil was orally administered for 12 weeks. Micturition behavior was monitored using metabolic cages, and bladder function was evaluated by cystometry. Bladder blood flow was evaluated by laser speckle imaging, and an organ bath bladder distention test was used to measure adenosine triphosphate (ATP) release from the bladder urothelium. The expression levels of vesicular nucleotide transporter (VNUT), hypoxia markers, pro-inflammatory cytokines and growth factors in the bladder wall were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Bladder wall contractions in response to KCl and carbachol were monitored using bladder-strip tests. RESULTS: With aging, OLETF rats had higher micturition frequency and greater urine volume than LETO rats. Although bladder capacity was not significantly different, non-voiding bladder contraction occurred more frequently in OLETF rats than in LETO rats. Bladder blood flow was decreased and ATP release was increased with higher VNUT expression in OLETF rats than in LETO rats. These effects were suppressed by tadalafil administration, with accompanying decreased HIF-1α, 8-OHdG, IL-6, TNF-α, IGF-1, and bFGF expression. The impaired contractile responses of bladder strips to KCl and carbachol in OLETF rats with aging were restored by tadalafil administration. CONCLUSIONS: The T2DM rats had polyuria, increased ATP release induced by decreased bladder blood flow and impaired contractile function. PDE5 inhibition improved these changes and may prevent T2DM-associated urinary frequency and bladder storage and voiding dysfunctions.

Effects of Hibiscus sabdariffa supplementation on metabolism and bladder in obese rats.

PURPOSE: Hibiscus sabdariffa (HS) extract has several health benefits and anti-obesogenic effects. The aim of the present study was to assess whether the medicinal properties attributable to HS would prevent or mitigate bladder changes induced by obesity in an experimental model. METHODS: Forty-eight male Wistar rats were submitted to one of four different dietary interventions (12 animals each): G1, standard diet and water (controls); G2, standard diet and HS tea; G3, a palatable high-fat diet and water; and G4, high-fat diet diet and HS tea. The animals were monitored for body weight, feed, and water and tea intake, according to the allocated group. After 16 weeks, the animals were euthanized, and the levels of creatinine, inflammatory cytokines, testosterone, cholesterol, triglycerides, and electrolytes were evaluated. In addition, histopathological analysis of the animals' bladder was performed. RESULTS: Groups receiving HS (G2 and G4) showed decreased levels of the pro-inflammatory cytokine interleukin-1α. HS tea was able to reduce low-density lipoprotein and triglyceride levels in the G2 group compared to other groups. Only in the G3 there was a significant increase in the body weight when it was compared the 12th and 16th weeks. Leptin was shown to be elevated in the groups that received a high-fat diet. There was a significant decrease in the muscle fibers thickness and in the total collagen count in G4 bladder when compared with G1 and G3. CONCLUSIONS: HS has an anti-inflammatory role, can reverse hyperlipidemia in rats, and reduced deleterious effects of obesity on these animals' bladder.

Definition Change and Update of Clinical Guidelines for Interstitial Cystitis and Bladder Pain Syndrome.

The clinical guidelines for interstitial cystitis (IC) and bladder pain syndrome (BPS) have been revised by updating our previous guidelines. The symptoms of IC and BPS, collectively called as hypersensitive bladder (HSB) symptoms, are virtually indistinguishable between IC and BPS; however, IC and BPS should be considered as a separate entity of disorders. We define IC as a bladder disease with Hunner lesions, usually associated with HSB symptoms and bladder inflammation, and BPS as a condition with HSB symptoms in the absence of Hunner lesions and any confusable diseases. Pathophysiology totally differs between IC and BPS. IC involves immunological inflammation probably resulting from autoimmunity, while BPS is associated with the interaction of multiple factors such as neurogenic inflammation, exogenous substances, urothelial defects, psychological stress, and neural hyperactivity. Histopathology also differs between IC and BPS. IC is associated with severe inflammation of the whole bladder accompanied by plasma cell infiltration and urothelial denudation, while BPS shows little pathological changes. Management should begin with a differential diagnosis of IC or BPS, which would require cystoscopy to determine the presence or absence of Hunner lesions. The patients should be treated differently based on the diagnosis following the algorithm, although pain management would be common to IC and BPS. Clinical studies are also to be designed and analyzed separately for IC and BPS.

Bladder and Kidney Transplantation En Bloc: Review of Experience and Prospects for Development.

Although urine bladder transplantation is currently being conducted, the procedure is an incompletely resolved problem in clinical transplantology. A small number of en bloc bladder and kidney transplants from pediatric donors to adult recipients in humans have been reported. A small number of bladder transplants with and without combinations with kidneys have also been performed in experiments on different animal models. Here, we aimed to highlight the experiences of various scientists in bladder transplantation in humans and animals. We also presented our small experience in conducting transplant of 1 kidney, ureters, and a segment of the bladder in an experiment on pigs in 2023 (5 cases), which is a promising direction for further successful development of this technology in humans. In 2024, we plan to conduct another 10 transplants of a single block ofthe kidney and bladderin pigs, results of which will be published after the completion of the experimental work.

Development and Validation of a Contrast-Enhanced US VI-RADS for Evaluating Muscle Invasion in Bladder Cancer.

Background Contrast-enhanced US (CEUS) can be used preoperatively for evaluating muscle invasion in bladder cancer, which is important for determining appropriate treatment. However, diagnostic criteria for assessing this at CEUS have not been standardized. Purpose To develop and validate a CEUS Vesical Imaging Reporting and Data System (VI-RADS) for evaluating muscle invasion in bladder cancer. Materials and Methods This single-center prospective study consecutively enrolled patients with suspected bladder cancer. Participants underwent transabdominal or intracavity CEUS between July 2021 and May 2023. Participants were divided into a training set and a validation set at a 2:1 ratio based on the chronologic order of enrollment. The training set was used to identify major imaging features to include in CEUS VI-RADS, and the likelihood of muscle invasion per category was determined using a pathologic reference standard. The optimal VI-RADS category cutoff for muscle invasion was determined with use of the maximum Youden index. The validation set was assessed by novice and expert readers and used to validate the diagnostic performance and interreader agreement of the developed system. Results Overall, 126 participants (median age, 64 years [IQR, 57-71 years]; 107 male) and 67 participants (median age, 64 years [IQR, 56-69 years]; 49 male) were included in the training and validation set, respectively. In the training set, the optimal CEUS VI-RADS category cutoff for muscle invasion was VI-RADS 4 or higher (Youden index, 0.77). In the validation set, CEUS VI-RADS achieved good performance for both novice and expert readers (area under the receiver operating characteristic curve, 0.80 [95% CI: 0.70, 0.90] vs 0.88 [95% CI: 0.80, 0.97]; P = .09). The interreader agreement regarding the evaluation of CEUS VI-RADS category was 0.77 (95% CI: 0.65, 0.85) for novice readers, 0.87 (95% CI: 0.79, 0.92) for expert readers, and 0.78 (95% CI: 0.70, 0.84) for all readers. Conclusion The developed CEUS VI-RADS showed good performance and interreader agreement for the assessment of muscle invasion in bladder cancer. Chinese Clinical Trial Registry no. ChiCTR2100049435 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Morrell in this issue.

A Smart Water Bottle and Companion App (HidrateSpark 3) to Improve Bladder-Filling Compliance in Patients With Prostate Cancer Receiving Radiotherapy: Nonrandomized Trial of Feasibility and Acceptability.

BACKGROUND: Patients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE). OBJECTIVE: Herein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE. METHODS: In total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both pieces alert the patient to empty his bladder and drink a personalized volume goal, based on simulation bladder volume, 1.25 hours before his scheduled RT. Patients were trained to adjust their volume goal and notification times to achieve comfortably full bladders. The primary end point was met if qualitative (QLC) and quantitative compliance (QNC) were >80%. For QLC, patients were asked if they prepared their bladders before daily RT. QNC was met if bladder volumes on daily cone-beam tomography were >75% of the simulation's volume. The Service User Technology Acceptability Questionnaire (SUTAQ) was given in person pre- and post-SBI. Additional acceptability and engagement end points were met if >3 out of 5 across 4 domains on the SUTAQ and >80% (15/18) of patients used the device >50% of the time, respectively. Finally, the impact of SBI on PV and TE was measured by time spent in a clinic and on the linear accelerator (linac), respectively, and contrasted with matched controls. RESULTS: QLC was 100% in 375 out of 398 (94.2%) total treatments, while QNC was 88.9% in 341 out of 398 (85.7%) total treatments. Of a total score of 5, patients scored 4.33 on privacy concerns, 4 on belief in benefits, 4.56 on satisfaction, and 4.24 on usability via SUTAQ. Further, 83% (15/18) of patients used the SBI on >50% of treatments. Patients in the intervention arm spent less time in a clinic (53.24, SEM 1.71 minutes) compared to the control (75.01, SEM 2.26 minutes) group (P<.001). Similarly, the intervention arm spent less time on the linac (10.67, SEM 0.40 minutes) compared to the control (14.19, SEM 0.32 minutes) group (P<.001). CONCLUSIONS: This digital intervention trial showed high rates of bladder-filling compliance and engagement. High patient value and TE were feasibly quantified by shortened clinic times and linac usage, respectively. Future studies are needed to evaluate clinical outcomes, patient experience, and cost-benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT04946214; https://www.clinicaltrials.gov/study/NCT04946214.

Effectiveness of homogenized nursing care intervention in postoperative bladder irrigation of urological system in primary hospitals-Taking the incidence of postoperative complications as an example: A retrospective study.

To explore the effect of homogenized nursing interventions for bladder irrigation after urological surgery in primary hospitals, and to further analyze the incidence of postoperative complications according to the different nursing methods. The experiment selected 110 patients with urological disorders who underwent bladder irrigation, and the subjects were admitted to the hospital from January 2020 to October 2023. The subjects were chronologically divided into a control group and an experimental group, with the admission time of the control group being between between January 2020 and October 2022. The experimental group was admitted between October 2022 and October 2023. Conventional nursing care and homogenized nursing care were used respectively, and the intervention effect of homogenized nursing care was assessed by comparing the patients' psychological state indexes, vital characteristic indexes, and the incidence of various postoperative complications under the 2 interventions. None of the indicators were statistically significant before the nursing intervention. In the comparison of nursing satisfaction and clinical comfort, the experimental group's nursing satisfaction was 94.5% and clinical comfort was 90.9%, which was significantly higher than that of the control group. In the comparison of the incidence of postoperative complications, the incidence of urinary retention in the experimental group was 1.82%, which was significantly lower than that of the control group. In addition, the total incidence of complications in the experimental group was 1.82%, which proved that the homogenized nursing intervention was effective in reducing the complications after urinary bladder irrigation. In multifactorial logistic regression analysis, after homogenized nursing intervention. The relative risks of the 4 complications were 1.836, 1.445, 1.993, and 2.138, respectively, which were significantly lower than those of conventional nursing intervention. In the ROC analysis, the AUC values of the 4 complications were 0.832, 0.731, 0.746, and 0.723, respectively. proving the superiority of homogenized care in preventing postoperative complications. Homogenized nursing intervention can effectively reduce the incidence of postoperative complications in patients with urological postoperative bladder irrigation, improve patients' symptoms and prognosis, and improve the quality of care and patients' quality of life.

Reducing pain by improving brain and muscle activity with motor cortical neuromodulation in women with interstitial cystitis/bladder pain syndrome: a study protocol for a randomized controlled trial.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction. This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes. ETHICS AND DISSEMINATION: All aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20-01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT04734847. Registered on February 1, 2021.

Optical Surface Management System and BladderScan for Patient Setup During Radiotherapy of Postoperative Prostate Cancer.

Background: The precision of postoperative prostate cancer radiotherapy is significantly influenced by setup errors and alterations in bladder morphology. Utilizing daily cone beam computed tomography (CBCT) imaging allows for the correction of setup errors. However, this naturally leads to the question of the issue of peripheral dose and workload. Thus, a zero-dose, noninvasive technique to reproduce the bladder volume and improve patient setup accuracy was needed. Purpose: The aim of this study is to investigate if the setup method by combining Optical Surface Management System (OSMS) and BladderScan can improve the accuracy of setup and accurately reproduce the bladder volume during radiotherapy of postoperative prostate cancer and to guide CTV-PTV margins for clinic. Method: The experimental group consisted of 15 postoperative prostate cancer patients who utilized a setup method that combined OSMS and BladderScan. This group recorded 103 setup errors, verified by CBCT. The control group comprised 25 patients, among whom 114 setup errors were recorded using the conventional setup method involving skin markers; additionally, patients in this group also exhibited spontaneous urinary suppression. The errors including lateral (Lat), longitudinal (Lng), vertical directions (Vrt), Pitch, Yaw, and Roll were analyzed between the two methods. The Dice similarity coefficient (DSC) and volume differences of the bladder between CBCT and planning CT were compared as the bladder concordance indicators. Results: The errors in the experimental group at Vrt, Lat, and Lng were 0.17 ± 0.12, 0.22 ± 0.17, and 0.18 ± 0.12 cm, and the control group were 0.25 ± 0.15, 0.31 ± 0.21, 0.34 ± 0.22 cm. The rotation errors of Pitch, Roll, and Yaw in the experimental group were 0.18 ± 0.12°, 0.11 ± 0.1°, and 0.18 ± 0.13°, and in the control group, they were 0.96 ± 0.89°, 1.01 ± 0.86°, and 1.02 ± 0.84°. The DSC and volume differences were 92.52 ± 1.65% and 39.99 ± 28.75 cm3 in the patients with BladderScan, and in the control group, they were 62.98 ± 22.33%, 273.89 ± 190.62 cm3. The P < 0.01 of the above performance indicators indicates that the difference is statistically significant. Conclusion: The accuracy of the setup method by combining OSMS and BladderScan was validated by CBCT in our study. The method in our study can improve the setup accuracy during radiotherapy of postoperative prostate cancer compared to the conventional setup method.

Bladder duplication in the male cat: the first case report in China.

BACKGROUND: Bladder duplication is a rare congenital lower urinary tract anomaly disease characterized by the presence of two bladders, possibly with duplication of the urethra. This disease is rarely reported in cats. The clinical symptoms are commonly occult, with increased difficulty in making a definitive diagnosis, especially if there is no obvious urethral duplication. The diagnosis is typically based on radiographs and ultrasound, with computer tomography serving as a more advanced imaging diagnostic modality. Cases of duplicated bladders with accessory tubular tissues are even scarcer in both human and veterinary medicine. CASE PRESENTATION: A 6-year-old male neutered cat was brought to the hospital because of vomiting and constipation. Cystography revealed increased soft tissue density of a fusiform structure in the lower middle abdomen. The purulent-filled cavitary structure and the accessory tubular structure were removed via surgery, and histopathological examination confirmed a double bladder with attached accessory tubular tissue. After antibiotic treatment, the cat recovered uneventfully. CONCLUSION: This is the first case of bladder duplication in China and the first case of feline bladder duplication with tubular structure attachment in the world. This information will provide a reference for the diagnosis and treatment of similar cases in the future.

Rare vesicourethral foreign body caused by sexual eccentricity - case report.

BACKGROUND: There are many types of foreign bodies in the bladder and urethra. The most common way is to insert foreign bodies through the external urethra by oneself or by others. It is often seen in situations such as masturbation, mental disorder, curiosity, etc. This article discusses the clinical diagnosis and treatment methods and preventive measures for foreign bodies in the bladder and urethra caused by sexual fetishes. CASE PRESENTATION: This article introduces a rare case. The patient was a 54-year-old male who inserted a thermometer into his urethra during masturbation and could not remove it. During the operation, we tried various methods to remove the thermometer many times, but due to the angle of the thermometer embedded in the bladder and urethra and the smooth tip of the thermometer, it could not be removed with foreign body forceps. Finally, a homemade negative pressure aspirator (consisting of a section of infusion tube and a 50 ml syringe) was used to completely remove the thermometer from the bladder and urethra. The Written informed consent was obtained from patient did not experience complications such as mercury leakage and bladder and urethral perforation. A telephone follow-up 4 months later showed that the patient urinated smoothly without discomfort such as frequent urination and urgency. DISCUSSION: There are many types of vesicourethral foreign bodies. When treating vesicourethral foreign bodies clinically, these can be removed through endoscopy, laparoscopy or open surgery according to the size, type and nature of the foreign bodies. At the same time, in order to effectively prevent the occurrence of bladder and urethra foreign bodies, sex education should be vigorously promoted.

A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery.

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.

Using Urine Biomarkers to Differentiate Bladder Dysfunctions in Women with Sensory Bladder Disorders.

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner's interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management.

Effect of accumulating experience on diagnostic performance of VI-RADS in bladder cancer.

PURPOSE: MRI-based VI-RADS score aids in differentiating MIBC and NMIBC, but the experience's impact remains unexplored. We aimed to determine the effect of accumulating experience in the diagnostic performance of VI-RADS. METHODS: In our previously published series 71 primary bladder cancer patients who underwent multiparametric MRI before the transurethral resection were analyzed. The radiologist who assessed the VI-RADS scores at the time the study was performed, re-evaluated all cases after 3 years, in a blinded fashion. During these three years, more than 300 additional bladder MRIs were performed for VI-RADS assessment. The diagnostic performances of the initial and subsequent VI-RADS analyses were compared. Moreover, VIRADS results obtained by a newly trained abdominal radiologist was also compared with experienced radiologist's results. For this study, VI-RADS ≥3 was accepted for predicting MIBC. RESULTS: Overall 71 patients [62 (87.3 %) males, 67.4 ± 10.2 years] who underwent bladder MRI before TURBT were included. Histopathology revealed MIBC in 16 (26.2 %) cases. The initial MRI analysis revealed VI-RADS score ≥ 3 in 36 (50.7 %) cases. The sensitivity and specificity for depicting MIBC were 75 % and 56.4 % respectively. The subsequent MRI analysis revealed VI-RADS score ≥ 3 in 23 (32.4 %) cases. The sensitivity and specificity were 93.8 % and 85.5 % respectively. The MRI analysis performed by the recently trained abdominal radiologist revealed VI-RADS score ≥ 3 in 24 (33.8 %) cases. The sensitivity and specificity were 87.5 % and 56.4 % respectively. CONCLUSION: The diagnostic performance of VI-RADS for the interpretation of bladder MRI can improve over time by increasing the experience of the urogenital radiologist.

Impact of contrast agents on organ dosimetry in pediatric diagnostic fluoroscopy: the voiding cystourethrogram.

Objective.International Commission on Radiological Protection (ICRP) Task Group 113 is developing reference values of organ and effective dose coefficients (DCs) for radiography, fluoroscopy, and computed tomography imaging exams. In support of these efforts, our focus is on pediatric diagnostic fluoroscopy. Contrast agents used during clinical examinations are an important consideration of the work undertaken by the Task Group. This work demonstrates the importance of including organ contrast volume concentrations for the calculation of reference organ DCs in the voiding cystourethrogram (VCUG).Approach.The ICRP newborn and 15 year female reference phantoms were utilized within the Particle and Heavy Ion Transport code system for the calculation of organ DCs. A pediatric radiologist with over 30 years of clinical experience defined the imaging fields for a VCUG examination consistent with clinical practice. Of these, four imaging fields were selected for investigation. The transport simulations modeled an iodinated contrast solution similar to Bracco Group's 18% weight per volume, cystografin diatrizoate meglumine and typical bladder content was supplemented to make up the remainder volume. Iodinated contrast volumes of 0%, 25%, 50%, 75%, and 100% concentration by volume were modeled and associated DCs for in-field organs were computed.Main results.Organ DCs were calculated for the urinary bladder wall, colon wall, ovaries, and uterus for both female phantoms under irradiation geometries representative of a VCUG examination. Some organ DCs increased with iodine volume in the bladder and other organ DCs decreased as the iodine contrast volume completely filled the bladder (100%).Significance.The study results demonstrate for the newborn phantom percent differences in organ DCs varied between 0%-10% for the organs of interest, while they varied between 0%-22% in the 15 year phantom suggesting the importance of including contrast media in Monte Carlo radiation transport simulations of the VCUG examination.

The impact of bladder cuff excision on outcomes after nephroureterectomy for upper tract urothelial carcinoma: An analysis of the ROBUUST 2.0 registry.

OBJECTIVES: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups. RESULTS: Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision. CONCLUSIONS: Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear.

Mechanosensitive Piezo1 channels promote neurogenic bladder fibrosis via regulating TGF-ß1/smad and Hippo/YAP1 pathways.

Bladder fibrosis is the final common pathway of neurogenic bladder (NB), and its underlying mechanisms are not fully understood. The current study aims to evaluate the involvement of Piezo1, a mechanosensitive channel, in bladder fibrosis. A full-thickness bladder specimen was taken during ileocystoplasty or ureteral reimplantation from the surgical cut's edge. By chopping off the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves, NB rat models were produced. Utilizing both pharmacological inhibition and Piezo1 deletion, the function of Piezo1 in the TGF-ß1-induced fibrosis model of SV-HUC-1 cells was delineated. RNA-seq, immunofluorescence, immunohistochemistry (IHC), and Western blotting were used to evaluate the degrees of fibrosis and biochemical signaling pathways. Piezo1 protein expression was noticeably elevated in the human NB bladder. The abundance of Piezo1 protein in bladder of NB rats was significantly increased. RNA-seq analysis revealed that the ECM-receptor interaction signaling pathway and collagen-containing ECM were increased in spinal cord injury (SCI)-induced bladder fibrosis. Moreover, the bladder of the NB rat model showed activation of YAP1 and TGF-ß1/Smad. In SV-HUC-1 cells, siRNA suppression of Piezo1 led to profibrotic responses and activation of the TGF-ß1/Smad pathway. However, Yoda1, a Piezo1-specific agonist, significantly reduced these effects. TGF-ß1 increased Piezo1 activation and profibrotic responses in SV-HUC-1 cells. In the TGF-ß1-induced fibrosis model of SV-HUC-1 cells, the TGF-ß1/Smad pathway was activated, whereas the Hippo/YAP1 signal pathway was blocked. Inhibition of Piezo1 further prevented this process. Piezo1 is involved in the progression of NB bladder fibrosis and profibrotic alterations in SV-HUC-1 cells, likely through regulating the TGF-ß1/Smad and Hippo/YAP1 pathways.

Lactobacillus-Polydopamine System for Targeted Drug Delivery in Overactive Bladder: Evidence from Bladder Cell Spheroids, Rat Models, and Urinary Microbiome Profiling.

Introduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy. Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model. Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy. Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery.