Intravesical Injection of OnabotulinumtoxinA (Botulinum Toxin Type A) in Japanese Patients With Refractory Overactive Bladder.

BACKGROUND/AIM: Botulinum toxin intravesical injection therapy (hereafter, botulinum therapy) is approved in Japan for treating urinary urgency, frequency, and urinary incontinence due to refractory overactive bladder or neurogenic bladder. Although botulinum therapy is classified as urinary incontinence surgery, it is minimally invasive, effective, and safe. However, there are few reports on the actual use of botulinum therapy and examination of its effects and side-effects. Herein, we report real-world data on botulinum therapy. PATIENTS AND METHODS: Patients who received botulinum therapy for refractory overactive bladder at the Nara Medical University and affiliated facilities from May 2020 to May 2022 were enrolled. The patient background, treatment efficacy, and safety were retrospectively reviewed. RESULTS: Twenty-three cases of refractory overactive bladder (age: 68.4±14.1 years; 7 males, 16 females; 17 outpatient, 6 hospitalized) were enrolled. Pretreatment, the overactive bladder symptom score (OABSS) was 10.1±2.7, and post-void residual urine volume was 27.1±31.6 ml. Botulinum was administered once, twice, thrice, and four times in 11, eight, three, and one cases, respectively. OABSS decreased to 6.1±3.2 2 weeks after botulinum therapy (p<0.0001), and the effect persisted at 6.6±3.2 after 12 weeks (p<0.0001). Post-void residual urine volume increased to 74.6±79.2 ml after 2 weeks (p=0.0010), but subsequently improved to 33.9±42.0 ml after 12 weeks (p=0.0002). Adverse events included post-void residual urine volume of 200 ml or more in three patients (7.5%) and urinary retention grade 2 in two (5.0%). CONCLUSION: Botulinum therapy is effective and relatively safe for refractory overactive bladders.

Dysgeusia in patients with advanced urothelial carcinoma receiving enfortumab vedotin, platinum-based chemotherapy, or immune check point inhibitors: time-course assessment using chemotherapy-induced taste alteration scale.

A time-course questionnaire survey using the chemotherapy-induced taste alteration scale (CiTAS) was conducted in patients with advanced urothelial carcinoma (UC) treated with systemic chemotherapy and/or immunotherapy. A total of 37 patients receiving systemic therapy with enfortumab vedotin (EV), platinum-based chemotherapy and immune checkpoint inhibitors were included in this study. No significant changes were observed in any of the CiTAS subscales during platinum-based chemotherapy and immune checkpoint inhibitor treatment, while EV therapy induced significant dysgeusia. Among 10 patients treated with EV, dysgeusia was associated with a substantial negative effect on the health-related quality-of-life domains, particularly global health status/QOL (mean ± standard deviation: 52 ± 19 in dysgeusia group vs 89 ± 13 in non-dysgeusia group) and mental component summary (47 ± 5.1 vs 53 ± 2.0). The fatigue symptom score was higher in the dysgeusia group at the post-third cycle of EV (47 ± 16 vs 15 ± 17). Severe dysgeusia can be induced by EV therapy, which is usually not observed in other systemic therapies for advanced UC.

Risks of infection and severity of coronavirus disease 2019 in kidney transplant recipients: A single-center cohort study.

BACKGROUND: The severity of coronavirus disease 2019 (COVID-19) is known to be high in kidney transplant recipients; however, the risk factors for COVID-19 infection in these patients has not been studied extensively. Therefore, we explored the predictors of COVID-19 infection and severity in kidney transplant recipients in Japan. METHODS: This study included kidney transplant recipients who were regularly followed-up at our hospital from February 2021 to March 2023. We retrospectively reviewed the patients' medical charts; obtained their clinical information, including comorbidities, immunosuppressant usage, and presence of COVID-19 infection; and assessed the risk of COVID-19 infection and severity. Severe illness was defined as a decrease in oxygen saturation. RESULTS: Among the 155 patients, 50 (32.3%) were infected with COVID-19. Multivariate analysis revealed that recipients taking >5 mg of prednisolone or taking tacrolimus instead of cyclosporine were at higher risk of infection (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.01-5.40; OR 2.29, 95% CI 1.03-5.07, respectively). Furthermore, of the 50 infected recipients, 42 had minor illness and eight had severe illness. Multivariate analysis revealed that recipients taking >5 mg of prednisolone were at a higher risk of severity (OR, 11.60, 95% CI 1.19-113.00). CONCLUSION: In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking >5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection.

Pseudoaneurysm after arterial reconstruction in kidney transplant nephrectomy: A case report and literature review.

Background: Pseudoaneurysm formation sometimes complicates transplant nephrectomy. We report a case of bleeding from a pseudoaneurysm after transplantation nephrectomy that resulted in shock and emergency endovascular treatment. Case presentation: A 56-year-old man underwent transplant nephrectomy 3 years and 9 months following transplantation for pyelonephritis-related infection control. On postoperative day 7, he developed sudden pain in the lower abdomen and subsequently went into shock. A pseudoaneurysm at the anastomosis was detected, and urgent endovascular treatment was performed to stem the bleeding. Conclusion: Vascular complications, including pseudoaneurysms, following transplant nephrectomy can be life-threatening, and comprehensive awareness is needed in careful postoperative management.

Trisomy 13 with retroiliac ureter diagnosed by assessment for recurrent febrile urinary tract infections.

Introduction: Patients with trisomy 13 have multiple malformations, including urological anomalies, and severe cognitive and psychomotor disabilities. We conducted a ureteroureterostomy for a mid-ureteral stricture due to a retroiliac ureter in a patient with trisomy 13. Case presentation: A 6-month-old girl with trisomy 13 developed a urinary tract infection. Computed tomography for assessing recurrent urinary tract infection revealed a left mid-ureteral stricture due to the retroiliac ureter. At the age of 2, a ureteroureterostomy was performed. Two years after surgery, the urinary tract infection did not recur. Conclusion: Ureteroureterostomy is a safe procedure for children with trisomy 13 and multiple comorbidities. Surgical treatment should be considered for patients with trisomy 13 when agreed upon by the family and comorbidities are well-controlled.

Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

Long-term follow-up of congenital hydronephrosis in a single-center study.

OBJECTIVES: Many congenital hydronephroses spontaneously resolve. This study evaluated a long-term follow-up of more than 4 years of patients with congenital hydronephrosis at a single center. METHODS: In total, 215 patients (286 kidneys) with congenital hydronephrosis were included. Hydronephrosis outcomes (resolution, improvement, and persistence) and time-to-outcome were evaluated. RESULTS: Fourteen patients underwent early surgical intervention until the age of 2 years. A total of 189 congenital hydronephrosis cases (66%) showed resolution at a median of 16 months (interquartile range: 7-21 months) and 169 (80%) of 210 kidneys with grade I to II hydronephrosis showed resolution at a median of 14 months (interquartile range: 6-23 months). Of 76 kidneys with grade III to IV hydronephrosis, 24 (32%) showed resolution at a median of 29 months (interquartile range: 24-41 months), and 56 (74%) showed improvement to grade II or less at a median of 12 months (interquartile range: 5-23 months). Of the 76 kidneys with grade III to IV hydronephrosis, five required delayed pyeloplasty at a median of 66 months (interquartile range: 42-89 months). One patient was asymptomatic, with a marked worsening of hydronephrosis and decreased renal function 6 years after the resolution of hydronephrosis. CONCLUSIONS: None of the patients with grade I to II hydronephrosis required surgical treatment, and a shorter follow-up may be sufficient. Grade III to IV severe hydronephrosis should be considered for a longer and more careful follow-up, given the possibility of asymptomatic exacerbation of hydronephrosis.

Detailed Cause of Donor Ineligibility in Living Donor Kidney Transplants: A Retrospective, Single-Center Cohort Study.

BACKGROUND: Living kidney donors are evaluated to determine their physical and psychological suitability for transplantation and ensure their safety. During this process, we frequently encounter cases where a donor is found to be ineligible. In this study, we surveyed donors who are ineligible for transplantation at our hospital to educate patients, their families, and medical staff regarding transplantation in the future. METHODS: We examined the proportion of ineligible donors among 237 potential donors who visited our hospital between January 2002 and March 2022. Data were collected retrospectively from electronic medical records and evaluated from various aspects such as age, body mass index, medical history, medications, and renal function. RESULTS: The mean age at presentation was 55.5 years, the male-to-female ratio was 1:1.6, and no significant difference was found between the ineligible and eligible donor groups. The transplant ineligibility rate was 23.6%, and the categories were for medical, backout, immunologic, and recipient-related reasons, in descending order. Furthermore, a low glomerular filtration rate (GFR) was the most common cause of medical cases. CONCLUSIONS: Many patients were judged ineligible because of lifestyle-related diseases such as low GFR, diabetes mellitus, and obesity. Therefore, thorough patient education should be conducted using these data as a reference to reduce the number of donors ineligible because of lifestyle-related diseases.

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort.

OBJECTIVE: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. METHODS: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. RESULTS: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). CONCLUSIONS: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

Quality of life after non-nerve-sparing, robot-assisted radical prostatectomy.

OBJECTIVE: To evaluate quality of life (QOL) after non-nerve-sparing, robot-assisted radical prostatectomy (RARP) and factors associated with worsened QOL. METHODS: Patients who underwent non-nerve-sparing RARP (n = 115) were enrolled. The Expanded Prostate Cancer Index Composite and 8-item Short Form Health Survey were used to evaluate QOL at baseline and postoperative 1, 3, 6, 12, and 24 months. Preoperative factors were evaluated by multivariate analysis for worsened QOL. RESULTS: Postoperative 24-month urinary QOL worsened in 68 of 115 (59%) patients. In multivariate analysis, membranous urethral length ≥10.8 mm [odds ratio (OR): .26, 95% confidence interval (CI): .07-.96] and intravesical prostatic protrusion ≥12 mm (OR: .14, 95% CI .06-.35) were significantly associated with maintaining postoperative 24-month urinary QOL. Significantly more patients with intravesical prostatic protrusion ≥12 mm than < 12 mm had improved urinary QOL. At postoperative 24 months, 43 of 115 (38%) patients had worsened sexual QOL. In multivariate analysis, higher Sexual Health Inventory for Men score (OR: 8.39, 95% CI 2.28-30.9), sexual activity (OR: 6.94, 95% CI: 2.27-21.2), and intercourse activity (OR: 6.81, 95% CI: 1.64-28.3) preoperatively were significantly associated with worsened postoperative 24-month sexual QOL. More patients with high preoperative intercourse activity (12/23,53%) had significantly worsened (p = .009) QOL regarding sexual bother than those who had no preoperative intercourse activity (21/92, 23%). CONCLUSION: After non-nerve-sparing RARP, patients with long membranous urethral length and/or intravesical prostatic protrusion maintain urinary QOL. Patients with high intercourse activity presented with impairment of sexual QOL after non-nerve-sparing RARP.

Clinical impact of the intensity of follow-up cystoscopy in patients with high-risk non-muscle-invasive bladder cancer.

PURPOSE: There is significant lack on evidence regarding the effect of non-adherence to a recommended protocol in follow-up of high-risk non-muscle-invasive bladder cancer (NMIBC), or the impact of delaying detection of recurrent lesion. Here, we aimed to investigate the optimal frequency of follow-up cystoscopy of high-risk NMIBC with respect to oncological safety in the Japanese real-world clinical practice. METHODS: This retrospective single-center study included 206 patients with primary high-risk NMIBC. The intensity (%) of follow-up cystoscopy was calculated based on actual visits for cystoscopy and guideline-recommended frequency in the first 24-month follow-up period. Inverse probability of treatment weighting analyses was used to reduce the risk of bias between groups. We performed a restricted cubic spline analysis with knots at intensity of follow-up cystoscopy ≤ 100% group to examine the possible association of progression risk with the intensity of follow-up as a continuous exposure. RESULTS: The median intensity was 87.5% (interquartile range, 75-100). Adjusted multivariate analysis for MIBC-free and progression-free survival demonstrated no significant difference between adjusted ≤ 75% and > 75% intensity groups. A restricted cubic spline analysis suggested no significant effect of the intensity of follow-up on progression risk, and hazard ratios of patients of < 100% intensity were equivalent to those of patients of 100% intensity. CONCLUSION: Our finding suggested decreased intensity of follow-up cystoscopy did not affect oncological outcomes in patients with high-risk NMIBC. Further prospective trials directly aimed at investigating optimized follow-up schedules for NMIBC are mandatory before substantial changes to existing clinical guidelines.

Impact of nutrition and inflammation indicators on peritoneal dialysis initiation and management.

BACKGROUND: The clinical significance of nutrition and inflammation in dialysis patients is well established. This study aimed to evaluate the association between prognosis and indicators of nutrition and inflammation. METHODS: A total of 253 consecutive patients who underwent peritoneal dialysis (PD) as primary renal replacement therapy at our institute between 2006 and 2021 were included. We retrospectively reviewed the patient's medical charts and obtained their clinical information. Nine nutritional and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median age and follow-up period were 65 years and 54 months, respectively. Most nutritional indicators and C-reactive protein (CRP) levels showed a significant correlation with residual renal function. Multivariate analysis revealed that the survival index, nutritional risk index for Japanese hemodialysis patients, and CRP levels were independent indicators of patient survival (P < 0.001, P = 0.034, and P = 0.005, respectively) and cardiovascular disease-free survival (P = 0.009, P = 0.04, and P = 0.017, respectively). Patients with a survival index < 19 and CRP ≥ 0.5 had a high risk of mortality and cardiovascular death (P < 0.0001 and P = 0.0002, respectively). CONCLUSIONS: Our findings suggest that indicators of nutrition and inflammation play important roles in predicting patient outcomes. Further research is warranted to establish optimal management strategies for patients on PD.

Assessment of diagnostic accuracy for cryptorchidism and risk factors for delayed orchidopexy.

OBJECTIVES: Cryptorchidism (CO) diagnosis by palpation is challenging. Patients with suspected CO are primarily referred to pediatric urologists by general pediatricians and urologists. Currently, surgical treatment for CO is recommended earlier than in previous guidelines. In this study, we evaluated factors that lead to diagnosis discordance and delayed orchidopexy in patients referred with suspected CO in addition to timing of initial screening. METHODS: In total, 731 patients (1052 testes) with suspected CO were included. Risk factors for diagnostic discrepancy in CO diagnosis by pediatric urologists and risk of delayed orchiopexy were evaluated. RESULTS: Herein, 659 (90%) patients were diagnosed during routine public health checkups for infants and young children, and 419 (57%) patients were referred by pediatric practitioners. Of 1052 testes, 374 (36%) were diagnosed with CO by pediatric urologists. In multivariate analysis, risk factors of diagnostic discrepancy for CO diagnosis by pediatric urologists were bilateral testis (odds ratio [OR] = 9.17, p < 0.0001), >6 months old at initial diagnosis (OR = 1.036, p < 0.0001), and pediatric referral (OR = 4.60, p < 0.0001). In total, 296 patients underwent orchiopexy for CO. In multivariate analysis, risk factors for delayed orchiopexy were presence of comorbidities (OR = 3.43, p = 0.003) and >10 months old at referral (OR = 12.62, p < 0.0001). CONCLUSIONS: Pediatric referral is a risk factor for discordant CO diagnostics, and late age at referral brings a risk of delayed orchiopexy. It is necessary to enlighten pediatricians, who are mainly responsible for routine health checkups, in teaching CO diagnostic techniques to ensure early referral.

[The Relationship Between Prognosis and Duration of Drug Holidays after Docetaxel Therapy for Castration-Resistant Prostate Cancer].

The next treatment strategy after drug holidays following docetaxel (DTX) therapy for patients with castration-resistant prostate cancer (CRPC) is unclear. This study investigated the relationship between the duration of drug holidays and prognosis after DTX therapy. This study retrospectively assessed 26 patients treated with DTX in our hospital. Overall survival duration was significantly longer in the long-term withdrawal group (duration of drug holidays ≥6 months) than in the short-term withdrawal group (duration of drug holidays ＜6 months) (P＝0.015). Similarly, progression-free survival duration was significantly longer in the long-term withdrawal group than in the short-term withdrawal group (P＝0.008). The short-term withdrawal group had a significantly lower body mass index (P＝0.009) and higher prostate-specific antigen (PSA) (P＝0.017) at the initiation of DTX therapy, higher PSA nadir during DTX therapy (P＝0.009), and higher PSA at the end of DTX therapy (P＝0.022), compared to the long-term withdrawal group. This study suggests that the optimal opportunity to introduce DXT therapy is when the patients with CRPC are physically able to tolerate chemotherapy and their tumor volume remains a lower burden. This may provide a clinical benefit, longer drug holidays, and a better prognosis.

Depth of invasion to the bladder wall as a prognostic factor and its association with circulating cell-free DNA levels in patients with muscle-invasive bladder cancer.

Background: Radical cystectomy (RC) is the standard surgical treatment for patients with muscle-invasive bladder cancer, but the prognosis is not favorable, and new prognostic factors need to be discovered. We investigated the potential of depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer who underwent RC. Furthermore, we examined the association between preoperative levels of circulating cell-free DNA and DOI. Materials and methods: We retrospectively reviewed patients who underwent RC between January 2007 and December 2017; those who received neoadjuvant chemotherapy were excluded. Depth of invasion was measured using hematoxylin-eosin-stained RC specimens. Results: Of the 121 patients selected, 41 (33.9%) were eligible for analysis. The median follow-up period was 14 months and mean DOI was 17 mm (range, 2-75 mm). Long DOI (>17 mm) was significantly associated with shorter progression-free survival (hazard ratio, 14.5; 95% confidence interval, 3.9-53.97, p < 0.0001) and cancer-specific survival (hazard ratio, 18.97; 95% confidence interval, 4.04-88.99, p = 0.0002) compared with short DOI. Multivariate analysis revealed that DOI was an independent risk factor for cancer-specific survival. The levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI (65 vs. 20 ng/mL, respectively; p = 0.028). Conclusions: Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.

Utility of a penile compression device for the quality of life in male patients with urinary incontinence after prostatectomy (the MORE study): a randomized prospective study.

OBJECTIVES: To verify the effects of penile clamping on the degree of stress urinary incontinence and quality of life in post-radical prostatectomy patients. RESULTS: Thirty-seven patients suffering from stress urinary incontinence after undergoing radical prostatectomy were enrolled. A total of 19 and 18 patients were analyzed in the non-clamp and clamp groups, respectively. The mean ages of the patients in non-clamp and clamp groups were 68.3 ± 7.1 years and 71.2 ± 4.8 years, respectively; the mean time after radical prostatectomy was 28.9 ± 44.0 months and 26.2 ± 39.0 months, respectively. The penile clamp used was the CLAMPMED® (URINE CONTROL CLAMP) size M (MURANAKA MEDICAL INSTRUMENTS Co., Ltd.). Specific urinary care pads (Sawayaka Pad for Men, Small Quantity®, Unicharm Corporation), were provided; the average daily usage was monitored for four weeks. The quality of life was evaluated using the King's Health Questionnaire. The average daily use of urinary care pads was significantly reduced in the clamp group than in the non-clamp group (-0.83 ± 1.51 vs. -0.16 ± 0.69, P = 0.0071). King's Health Questionnaire scores did not change significantly in either group. Wearing the CLAMPMED® reduced the amount of urinary incontinence but did not improve the quality of life. TRIAL REGISTRATION: The Japan Registry of Clinical Trials (jRCT1052230083). Registered 2 August, 2023.

Chronological Changes in Emotional Status and Vaccine Implementation Rate Among Patients on the Waiting List for Deceased-Donor Kidney Transplantation During the Prolonged COVID-19 Pandemic.

BACKGROUND: To investigate the emotional attributes and vaccine implementation rate of patients waiting for kidney transplants during the prolonged COVID-19 pandemic. METHODS: We included 145 patients who were on the waiting list at our institution. Clinical information was obtained from medical charts, and emotional changes were assessed using a telephone questionnaire comprising 13 questions, including vaccine implementation. We also investigated factors affecting the decision to accept or decline deceased-donor kidney transplantation during the COVID-19 pandemic. RESULTS: Of the 145 patients, 121 (83.4%) provided informed consent and completed the questionnaire. The median age at registration on the waiting list for deceased-donor kidney transplantation and the median waiting period was 45.5 years and 103 months, respectively. This cohort comprised 84 males and 37 females. Twenty patients (16.5%) were diagnosed with COVID-19, and 15 (12.4%) were more curious about deceased-donor kidney transplantation. One hundred patients (82.6%) were vaccinated against COVID-19 more than thrice. Thirty patients (24.8%) declined, and 91 patients (75.2%) accepted an organ transplant offer during the COVID-19 pandemic. Multivariate analysis revealed that the long-term waiting period (P = .038) and anxiety about COVID-19, such as visiting the transplant facility (P < .0001) and prudence over time (P < .0001), were independent factors influencing the decline of a kidney transplant offer. CONCLUSIONS: Our findings suggest that some patients hesitated to undergo deceased-donor kidney transplantation during the pandemic. There is a need to develop an appropriate system to ensure safe and secure kidney transplantation during prolonged pandemics.

Impaired nitric oxide mechanisms underlying lower urinary tract dysfunction in aging rats.

The study aimed to investigate the bladder and urethral activity and nitric oxide (NO)-related molecular changes in aging rats. Rats were divided into two groups: Group Y (young rats; 12 wk) and Group A (aging rats; 15 mo). A 24-h voiding assay was performed, and the urodynamic parameters were evaluated using awake cystometry (CMG) and urethral perfusion pressure (UPP) recordings under urethane anesthesia. The mRNA expression levels of NO-, ischemia-, and inflammation-related markers in urethra and bladder tissues and cGMP levels in the urethra were assessed. Body weight was significantly higher in Group A than in Group Y. Voiding assay results (24 h) were insignificant. In the CMG, the number of non-voiding contractions per voiding cycle and post-void residual volume were significantly higher in Group A than in Group Y; voiding efficiency was significantly lower in Group A than in Group Y. In the UPP recordings, the urethral pressure reduction and high-frequency oscillation (HFO) amplitude were significantly lower in Group A than in Group Y. The mRNA expression levels of Hif-1α, Vegf-a, and Tgf-ß1 in the bladder were significantly higher in Group A than in Group Y. The mRNA expression levels of Nos1 and Prkg1 and the cGMP concentrations in the urethra were significantly lower in Group A than in Group Y. Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired NO-mediated transmitter function is likely to be an important mechanism.NEW & NOTEWORTHY Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired nitric oxide-mediated transmitter function is likely to be an important mechanism.

Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis/bladder pain syndrome from overactive bladder: An exploratory study.

OBJECTIVES: Diagnosing interstitial cystitis/bladder pain syndrome presents a major challenge because it relies on subjective symptoms and empirical cystoscopic findings. A practical biomarker should discriminate diseases that cause increased urinary frequency, particularly overactive bladder. Therefore, we aimed to identify blood biomarkers that can discriminate between interstitial cystitis/bladder pain syndrome and overactive bladder. METHODS: We enrolled patients with Hunner-type interstitial cystitis (n = 20), bladder pain syndrome (n = 20), and overactive bladder (n = 20) and without lower urinary tract symptoms (controls, n = 15) at Ueda Clinic and Nara Medical University Hospital from February 2020 to August 2021. The degree of interstitial cystitis/bladder pain syndrome symptoms was evaluated using the interstitial cystitis symptom and problem indices. Metabolomics analysis was performed on 323 serum metabolites using liquid chromatography time-of-flight mass spectrometry. RESULTS: In the Hunner-type interstitial cystitis or bladder pain syndrome group, we observed smaller relative areas, including anandamide, acylcarnitine (18:2), linoleoyl ethanolamide, and arachidonic acid, compared to those in the overactive bladder or control group. Notably, the differences in the relative areas of anandamide were statistically significant (median: 3.950e-005 and 4.150e-005 vs. 8.300e-005 and 9.800e-005), with an area under the curve of 0.9321, demonstrating its ability to discriminate interstitial cystitis/bladder pain syndrome. CONCLUSIONS: Serum anandamide may be a feasible diagnostic biomarker for interstitial cystitis/bladder pain syndrome. Reduced serum anandamide levels may be associated with pain and inflammation initiation, reflecting the pathology of interstitial cystitis/bladder pain syndrome. Furthermore, our findings suggest that abnormal linoleic acid metabolism may be involved in the pathogenesis of interstitial cystitis/bladder pain syndrome.