Electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): A single-arm, open-label, single-assignment trial.

AIMS: To investigate changes in subjective and objective sleep quality after desmopressin administration in patients with nocturia due to nocturnal polyuria (NP) using electroencephalography (EEG) and the Pittsburgh sleep quality index (PSQI). METHODS: Twenty male patients (≥65 years old) with NP participated in this study. The inclusion criteria were nocturnal frequency ≥ 2, NP index (NPi) ≥ 0.33, first uninterrupted sleep period (FUSP) ≤ 2.5 h, serum sodium concentration ≥ 135 mEq/L, and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2. Participants were given 50 µg of desmopressin to be taken orally once daily before bed. The primary endpoint was the change in the duration of slow-wave sleep (nonrapid eye movement sleep stages 3 and 4), as evaluated by EEG 28 days from the baseline. The visual analog scale (VAS) was used as an additional indicator of sleep quality. RESULTS: Analysis of data from 15 participants (median age: 74.0 [70.5, 76.0] years) revealed that from before to after desmopressin administration, significant decreases occurred in the median nocturnal frequency (3.0 [2.0, 4.0] to 1.5 [1.0, 2.0]) and NPi (0.445 [0.380, 0.475] to 0.360 [0.250, 0.430]). Furthermore, FUSP was significantly prolonged from 120.0 (94.0, 150.0) min to 210.0 (203.8, 311.3) min. Although the VAS scores improved, slow-wave sleep duration and the PSQI global score showed no significant differences (68.50 [47.50, 75.50] and 48.00 [38.00, 66.50]; 5.0 [5.0, 10.0] and 7.0 [5.0, 9.0] min, respectively). CONCLUSION: Oral administration of 50 µg desmopressin improved nocturnal frequency and FUSP in older individuals with NP but did not significantly enhance sleep quality. In older adults, decreased nighttime urinary frequency may enhance quality of life; however, its influence on objective sleep quality may be limited.

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.

Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Prognostic role of nutritional and inflammatory indicators for patient survival and death with functional graft in living kidney transplant recipients.

BACKGROUND: The clinical importance of nutrition and inflammation in patients with end-stage renal disease is well established. In this study, we investigated the role of nutritional and inflammatory indicators in the patient outcomes of living donor kidney transplant recipients. METHODS: We included 204 consecutive patients who underwent kidney transplantation at our institute between 2003 and 2022. We retrospectively reviewed medical charts to obtain clinical information. Six nutritional indicators and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median patient age and follow-up period were 48 years and 99 months, respectively. The cohort included patients with preoperative malnutrition and microinflammation. No significant differences in graft survival were identified according to nutritional and inflammatory indicators, whereas the survival index, controlled nutritional status, and C-reactive protein levels were associated with patient survival. The survival index was an independent indicator of survival and death in patients with functioning grafts (P = 0.047 and P = 0.013, respectively). Furthermore, the C-reactive protein level could distinguish between low and high mortality risks in patients with good nutrition (P = 0.019). CONCLUSIONS: Our findings suggest that nutrition and inflammation indicators play important roles in predicting outcomes in living donor kidney transplantation recipients. Further research is warranted to establish optimal management strategies.

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.

Difference of oncological efficacy between two immune checkpoint inhibitors following first-line platinum-based chemotherapy in patients with unresectable, metastatic, advanced urothelial carcinoma: a multicenter real-world Japanese cohort.

BACKGROUND: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab. METHODS: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup. RESULTS: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT. CONCLUSIONS: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT.

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.

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.

Post-Disaster Community Transition of Psychiatric Inpatients: Lessons from the Fukushima Nuclear Accident.

This study sought to explore factors related to community transition after the mandatory evacuation of psychiatric inpatients to other hospitals owing to the Fukushima Daiichi Nuclear Power Plant accident. A retrospective cohort design was adopted and 391 psychiatric patients were examined. Univariate and multivariate analyses were conducted to confirm the association between the achievement or non-achievement of discharge to community living and their backgrounds (age, gender, evacuation destination, psychiatric diagnoses, and physical complications). Multivariate analysis indicated that patients with psychiatric diagnoses of schizophrenia, schizotypal, and delusional disorders (International Statistical Classification of Diseases and Related Health Problems 10th revision, F20-29), and those with physical diagnoses of the circulatory (I00-95) and digestive (K00-93) systems showed a significant association with the non-attainment of community transition. From these results, we hypothesized that difficulties in the management of medication during and immediately after the extremely chaotic settings of evacuation could have negative effects on the community transitions. Furthermore, another possible concern was that individuals' persistent psychotic status before the accident had been carried over to the destination hospitals. Therefore, pre-disaster daily cooperation across hospitals and challenges for vulnerable psychiatric patients' future community lives are also essential.

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.

Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer.

Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti-tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor-bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC-treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short-change fatty acid-related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer-associated fibroblasts and regulatory T cells, and activation of CD8+ T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti-tumor effects through the gut-tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.

The Japanese health care system-based cost-effectiveness of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer.

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor reduces the risk of intravesical recurrence compared with conventional white light-transurethral resection of bladder tumor. However, the patient burden of costs for photodynamic diagnosis-transurethral resection of bladder tumor is higher than that for white light-transurethral resection of bladder tumor per installment, and the impact of the medical economics of photodynamic diagnosis-transurethral resection of bladder tumor is unclear. Therefore, we evaluated the Japanese health care system-based cost-effectiveness of photodynamic diagnosis-transurethral resection of bladder tumor compared with that of white light-transurethral resection of bladder tumor. METHODS: We conducted a retrospective chart review of 100 patients who underwent initial white light- or photodynamic diagnosis-transurethral resection of bladder tumor for non-muscle invasive bladder cancer from February 2012 to August 2019. Cumulative intravesical recurrences during 1000 post-operative days after the initial transurethral resection of bladder tumor were counted. Furthermore, the cumulative costs were calculated using the Diagnostic Procedure Combination and Per-Diem Payment System unique to Japan. The costs/year/person calculated using the person-year method was compared between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. RESULTS: Among the 100 patients, 40 (40%) and 60 (60%) underwent the initial white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cumulative incidence of bladder recurrence requiring hospitalization and transurethral resection of bladder tumor was 20 and 5% for the white light-transurethral resection of bladder tumor and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The costs for hospitalization and surgical procedures per white light- or photodynamic diagnosis-transurethral resection of bladder tumor were 348 228 and 481 820 Japanese yen, respectively. The cost/year/person by the person-year method was 8073 and 8557 Japanese yen for the white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. CONCLUSIONS: The cost/year/person for hospitalization and surgical procedures was slightly different between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Furthermore, photodynamic diagnosis-transurethral resection of bladder tumor can reduce intravesical recurrence and is more cost-effective than white light-transurethral resection of bladder tumor.

Clinical practice of UroVysion® urine test in patients with bladder carcinoma in situ treated with intravesical Bacillus Calmette-Guerin.

In January 2019, the use of the UroVysion® urine test for surveillance of non-muscle invasive bladder cancer with carcinoma in situ (CIS) was approved in Japan. Clinical evidence of its use remains limited. Herein, we report the real-world clinical practice of the UroVysion test. Of 29 patients underwent at least one UroVysion test at our hospital from 2019 to 2022, only two (6.9%) tested positive without any visible tumor on the cystoscopy after the initial transurethral resection: a 77-year-old man with T1 high-grade tumor and concomitant CIS and a 76-year-old woman with CIS. The remaining 27 patients (93.1%) tested negative post-transurethral resection. This study was the first to report the Japanese real-world practice of the UroVysion test, demonstrating relatively low positive rate as compared to the previous reports from other countries. Further clinical evidence from other Japanese institutes needs to be accumulated to update the true value of this test.

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study.

OBJECTIVE: To develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC). METHODS: A multicenter-derived database registered 505 patients diagnosed with aUC between 2008 and 2021. Of these, 204 patients (40%) were selected and stratified according to the type of therapy used: maintenance avelumab group (27 [5.3%]), second-line (2 L) pembrolizumab group (103 [20%]) and 2 L cytotoxic chemotherapy group (74 [15%]). The progression-free survival and overall survival from the initiation of following therapy were compared. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors guideline v1.1 during the treatment period. A detailed analysis was performed in the maintenance avelumab group to investigate possible factors associated with response to avelumab therapy. RESULTS: The maintenance avelumab group had a longer overall survival, not progression-free survival, compared with the other two treatment groups. The median treatment-free interval between the last dose of first-line (1 L) chemotherapy and the initiation of avelumab therapy was 6 weeks (range, 3-22). Disease control rate of maintenance avelumab therapy in patients with a treatment-free interval of ≤6 weeks was higher than that in patients with a treatment-free interval of >6 weeks (77 vs 40%, P = 0.029). The patients showing objective response to 1 L chemotherapy were less likely to experience tumor relapse (4 of 19) after the initiation of avelumab therapy compared with those showing stable disease (7 of 8). CONCLUSIONS: Objective response to 1 L chemotherapy and early induction of maintenance avelumab therapy may be associated with increased benefit from maintenance avelumab therapy.

Clinical impact of catheter insertion for peritoneal dialysis on patient survival and catheter-related complications.

OBJECTIVES: The stepwise initiation of peritoneal dialysis (PD) using Moncrief and Popovich's technique (SMAP) for catheter insertion is recommended for the systemic introduction of PD and prevention of catheter-related infections. In this study, we investigated patient outcomes in patients who underwent insertion of a PD catheter with a direct method versus the SMAP method. METHODS: We enrolled 295 consecutive patients who underwent PD as a primary renal replacement therapy and underwent insertion of a PD catheter at our institute between 2006 and 2021. We retrospectively reviewed their data and investigated patient outcomes, including mortality and PD catheter-related complications. RESULTS: Median age at PD induction was 65 years in the direct insertion group and 65 years in the SMAP group (P = 0.80). The rate of PD introduction after emergency hemodialysis was significantly higher in the direct insertion group than in the SMAP group (P < 0.001). There was no significant difference in survival between the direct insertion and SMAP groups during the median follow-up period of 54 months (P = 0.12). Additionally, patients who transitioned to hemodialysis or kidney transplantation after PD showed significantly longer survival (P < 0.001). The incidence of PD catheter-related complications was not significantly different between the two groups. A body mass index ≥ 23 kg/m2 was an independent risk factor for peritonitis and exit-site infection (P = 0.006 and P = 0.011, respectively). CONCLUSIONS: Planned sequential renal replacement therapy including hybrid hemodialysis, complete hemodialysis, and kidney transplantation after PD is important for improving patient outcomes. PD catheter insertion by SMAP may not be mandatory in our clinical practice.

Clinical significance of limited and extended pelvic lymph node dissection during robot-assisted radical prostatectomy for patients with localized prostate cancer: A retrospective, propensity score matching analysis.

OBJECTIVES: We investigated the diagnostic and therapeutic benefits of limited or extended pelvic lymph node dissection during a robot-assisted radical prostatectomy for localized prostate cancer. METHODS: Diagnostic and therapeutic benefits were assessed according to the rates of pN1 and biochemical recurrence, respectively. The primary outcome was the biochemical recurrence-free rate, and secondary outcomes included the diagnostic and therapeutic benefits of pelvic lymph node dissection. RESULTS: A total of 534 patients were analyzed. Out of the 534 patients, 207 (38.8%) received limited pelvic lymph node dissection while 134 (25.1%) received extended dissection. There were 297 patients with a Briganti index ≥5%. Extended dissections yielded significantly more resected lymph nodes (p < 0.0001), and 72.2% of cases of pN1 were located outside the obturator. The incidence rate of pN1 was 6.1%, and performance of extended lymph node dissection was an independent predictor for pN1 (odds ratio 9.0, 95% confidence interval 2.5-33.1). The rate of biochemical recurrence was 14.9%, and Cox proportional hazards regression analysis of the propensity score matched population revealed that patients with high or very-high risk tended to benefit from limited lymph node dissection (hazard ratio 8.4, 95% confidence interval 0.8-82.3) while the therapeutic benefit of extended dissection was unclear by comparison. CONCLUSIONS: Extended pelvic lymph node dissection significantly improves diagnostic accuracy; however, the therapeutic benefit of pelvic lymph node dissection was not observed in this study.

Therapeutic effects of a soluble guanylate cyclase activator, BAY 60-2770, on lower urinary tract dysfunction in mice with spinal cord injury.

We aimed to evaluate the effects of a soluble guanylate cyclase (sGC) activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury (SCI). Mice were divided into the following three groups: spinal cord intact (group A), SCI + vehicle (group B), and SCI + BAY 60-2770 (group C). SCI mice underwent Th8-Th9 spinal cord transection and treatment with BAY 60-2770 (10 mg/kg/day) once daily for 2-4 wk after SCI. We evaluated urodynamic parameters using awake cystometry and external urethral sphincter electromyograms (EMG); mRNA levels of mechanosensory channels, nitric oxide (NO)-, ischemia-, and inflammation-related markers in L6-S1 dorsal root ganglia, the urethra, and bladder tissues; and protein levels of cGMP in the urethra at 4 wk after SCI. With awake cystometry, nonvoiding contractions, postvoid residual, and bladder capacity were significantly larger in group B than in group C. Voiding efficiency (VE) was significantly higher in group C than in group B. In external urethral sphincter EMGs, the duration of notch-like reductions in intravesical pressure and reduced EMG activity time were significantly longer in group C than in group B. mRNA expression levels of transient receptor potential ankyrin 1, transient receptor potential vanilloid 1, acid-sensing ion channel (ASIC)1, ASIC2, ASIC3, and Piezo2 in the dorsal root ganglia, and hypoxia-inducible factor-1α, VEGF, and transforming growth factor-ß1 in the bladder were significantly higher in group B than in groups A and C. mRNA levels of neuronal NO synthase, endothelial NO synthase, and sGCα1 and protein levels of cGMP in the urethra were significantly lower in group B than in groups A and C. sGC modulation might be useful for the treatment of SCI-related neurogenic lower urinary tract dysfunction.NEW & NOTEWORTHY This is the first report to evaluate the effects of a soluble guanylate cyclase activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury.

Association between urine 6-sulfatoxy-melatonin level and intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer.

PURPOSE: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG). METHODS: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively. RESULTS: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration. CONCLUSIONS: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making.

Intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer: functional outcome assessment based on a questionnaire survey and actigraphy.

PURPOSE: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer. METHODS: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation. RESULTS: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03). CONCLUSIONS: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy.

A new nomogram of urinary flow rate and volume based on multiple measurements per healthy adult Japanese men using a portable uroflowmeter (P-Flowdiary®).

BACKGROUND: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear. METHODS: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created. RESULTS: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively. CONCLUSIONS: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms.