Impact of Novel Agents on Patient Characteristics, Treatment Patterns, and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: The therapeutic landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the introduction of several novel agents. However, limited data are available to determine whether the introduction of novel agents affected patient characteristics, treatment patterns, and outcomes compared with the period when these agents were not available. The objective of this study was to evaluate the impact of the introduction of novel mCRPC agents on patient characteristics, treatment patterns, and outcomes. PATIENTS AND METHODS: Two cohorts of Japanese patients diagnosed with mCRPC between 2009 and 2014 (Epoch 1) and 2015 and 2019 (Epoch 2) were retrospectively analyzed. RESULTS: A total of 125 treatment-naïve mCRPC patients, consisting of 42 patients in Epoch 1 and 83 patients in Epoch 2, were evaluated. We obtained the following results: (i) a dramatic shift in the first-line treatment from docetaxel to androgen receptor axis-targeted agents (ARATs), (ii) an age range expansion for first-line treatment, and (iii) an overall survival (OS) advantage in Eopch 2 compared to Epoch 1. Multivariate analysis in the overall population showed that Epoch 2 and low prostate-specific antigen (PSA) levels at the start of first-line treatment were independent prognostic factors for OS. CONCLUSION: In real-world mCRPC practice, the introduction of novel agents has improved the prognosis of mCRPC while allowing more patients to receive mCRPC treatment across a broad age range. In addition, low PSA levels at the start of first-line treatment were associated with improved OS, indicating the importance of starting mCRPC treatment while PSA levels are low.

Sex differences in lower urinary tract function in mice with or without spinal cord injury.

OBJECTIVES: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). METHODS: SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. CONCLUSIONS: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.

Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab.

INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. METHODS: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. CONCLUSIONS: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.

Prognosis of Patients Receiving Chemotherapy for Metastatic Upper Tract Urothelial Carcinoma Compared With Metastatic Urinary Bladder Cancer.

BACKGROUND/AIM: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. RESULTS: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. CONCLUSION: Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.

The pressure flow study investigation of pathophysiology of post-micturition dribble in male patients.

PURPOSE: In this study, we aimed to elucidate the pathophysiology of post-micturition dribble (PMD) through analyzing several variables including pressure flow study (PFS) findings and symptoms questionnaire. METHODS: We retrospectively analyzed male patients who visited our department between 2010 and 2020. We used modified international prostate symptom score (m-IPSS), which consists of eight sub-score related to lower urinary tract symptoms (Incomplete Emptying, Frequency, Intermittency, Urgency, Weak Stream, Straining, Nocturia, and PMD) and one question related to quality of life (QOL). Multivariate regression analysis was conducted to evaluate the relationship between PMD and the variables, including age, prostate volume (PV), body mass index, bladder outlet obstruction index (BOOI), bladder contractility index, and bladder voiding efficiency, which were obtained by PFS. RESULTS: A total of 143 male patients were analyzed. The patients with PMD showed significantly larger PV and higher BOOI, and worse IPSS total and QOL score than those without PMD. Multivariate regression analysis showed that large PV and BOOI were significantly associated with PMD. In Spearman's correlation analysis, PMD and each m-IPSS sub-score except nocturia had significant positive correlation. Furthermore, Spearman's correlation analysis showed that PMD and QOL had significant strong positive correlation. CONCLUSION: PMD was significantly associated with large PV and BOO evaluated by PFS. Furthermore, PMD significantly exacerbated QOL. The severity of PMD and the other m-IPSS sub-score except nocturia could have intercorrelation with each other.

Prognostic factors in Japanese men with high-Gleason metastatic castration-resistant prostate cancer.

Background: Several therapeutic agents are available for metastatic castration-resistant prostate cancer (CRPC). However, prognosis is still not well developed. The Gleason score (GS) is a prognostic factor available for patients with metastatic CRPC. GSs ranging from 6 to 10 and GSs ≥8 are usually categorized as single prognostic factors. In this study, we evaluated the prognosis of high-GS metastatic CRPC in Japanese men. Methods: Overall, 105 patients with metastatic CRPC with a GS ≥8 were retrospectively analyzed. Multivariate analyses of patient age, GS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) were performed using Cox proportional hazards analysis to predict overall survival (OS). Results: GS 8 had all Gleason patterns of 4+4. Thirty patients (28.6%) had GS of 8, and 75 (71.4%) had GS of 9 or 10. As a first-line treatment for metastatic CRPC, 42 patients (40%) received abiraterone, 35 (33.3%) received enzalutamide, and 26 (24.8%) received docetaxel. The 5-year OS in patients with GS of 8 was 65.0% [95% confidence interval (CI): 43.07-86.82%], while the 5-year OS in patients with GS of 9 or 10 was 37.0% (95% CI: 24.41-56.11%). There was a significant difference in OS between the GS 8 and GS 9-10 groups (log-rank test, P=0.038). Multivariate analysis showed that GS and ECOG-PS were significant prognostic factors for OS. Conclusions: Patients with metastatic CRPC with GS 9-10 had poor prognoses, suggesting the need for additional treatment options.

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.

Outcome of primary androgen deprivation therapy in super-elderly men with localized high-risk prostate cancer.

The purpose of this study is to provide certain data on clinical outcome of primary androgen deprivation therapy in men over 80 years of age with localized high-risk prostate cancer. This study included 54 Japanese super-elderly men with high-risk prostate cancer treated with primary androgen deprivation therapy between 2005 and 2015. The median overall survival was 9.1 years (95% confidence interval, 8.1-10.1) and no patient died from prostate cancer. Overall, 51.9% of patients experienced any grade of adverse events following androgen deprivation therapy. Associations between clinicopathological factors including comorbidity count at initial diagnosis and overall survival were investigated. On multivariate analysis, only comorbidity count at initial diagnosis [≥2 vs. ≤1; hazard ratio, 5.34 (95% confidence interval, 1.55-18.49); P = 0.003] was an independent risk factor for overall survival. Our findings suggest that comorbidity count at initial diagnosis is robustly prognostic for overall survival. For super-elderly men with localized high-risk prostate cancer, comorbidity count at initial diagnosis should be emphasized when deciding whether primary androgen deprivation therapy is necessary or not.

Identification of diagnostic serum biomarkers for Hunner-type interstitial cystitis.

OBJECTIVES: Diagnosis of Hunner-type interstitial cystitis (HIC) relies on the ability to identify Hunner lesions endoscopically, which can lead to storage symptom misdiagnosis. Here, we examined serum biomarkers for HIC and verified their utility. METHODS: Based on the previous definition of the Japanese guidelines, which did not distinguish HIC and non-HIC diseases, we searched for serum biomarkers in 25 patients with interstitial cystitis (IC) and 25 control participants using metabolomics during 2013-2014. In 2019, we conducted a validation study in HIC and control groups. Serum samples were analyzed using liquid chromatography-tandem mass spectrometry, and candidate biomarker concentrations were compared between the groups using Mann-Whitney test. RESULTS: Metabolomics targeted 678 metabolites and revealed that the levels of 14 lysolipids, seven γ-glutamyl amino acids, and two monoacylglycerols were significantly different between the IC and control groups. The following metabolites were selected from each metabolite category as candidates: 1-linoleoylglycerophosphocholine (1-linoleloyl-GPC [18:2]), γ-glutamylisoleucine (γ-Glu-Ile), and 1-arachidonylglycerol (1-AG). The serum concentrations of 1-linoleoyl-GPC (18:2) in the HIC and control groups were 27 920 ± 6261 and 40 360 ± 1514 ng/mL (P = 0.0003), respectively. The serum concentrations of γ-Glu-Ile and 1-AG were not significantly different between the groups. When the cut-off value of 1-linoleoyl-GPC (18:2) was set at 28 400 ng/mL, the sensitivity and specificity were 68% and 84%, respectively. CONCLUSIONS: Serum 1-linoleoyl-GPC (18:2) is a candidate diagnostic biomarker for HIC. Additional studies on whether this biomarker can distinguish HIC from other diseases with high urination frequency are required for its clinical use.

Clinical features of detrusor underactivity in elderly men without neurological disorders.

OBJECTIVES: To investigate the clinical features of detrusor underactivity (DU) in elderly men without neurological disorders. METHODS: A total of 336 men aged ≥50 years without neurogenic disorders who underwent pressure flow studies and who had DU or bladder outlet obstruction (BOO) were reviewed retrospectively. According to the bladder contractility index (BCI) and the BOO index (BOOI), the subjects were classified into the following three groups: (a) pure DU group, BCI < 100 and BOOI < 40; (b) DU + BOO group, BCI < 100 and BOOI ≥ 40; and (c) pure BOO group, BCI ≥ 100 and BOOI ≥ 40. Subjective and objective parameters were compared among the three groups, and the predictors for pure DU were evaluated by multivariate analysis. RESULTS: Of the 336 patients, 205 who met the study criteria were included in the analysis: 63 (30.7%) with pure DU, 48 (23.4%) with DU + BOO, and 94 (45.9%) with pure BOO. The proportion of the pure DU group increased with increasing age. Prostate volume was the lowest in the pure DU group. Frequency, urgency on the International Prostate Symptom Score (IPSS), and the IPSS storage subscore were the lowest in the pure DU group. Multivariate analysis showed that age (odds ratio [OR] 1.114 [95% CI, 1.032-1.203], P = .005), prostate volume (OR 0.968 [95% CI, 0.949-0.987], P = .001), and urgency (OR 0.623 [95% CI, 0.431-0.900], P = .012) were predictors of pure DU. CONCLUSION: Older age, smaller prostate volume, and less urgency may be clinical features of pure DU.

Sarcopenia and Visceral Obesity are Significantly Related to Severe Storage Symptoms in Geriatric Female Patients.

PURPOSE: This study aimed to elucidate the relationship of psoas muscle atrophy and visceral obesity with lower urinary tract symptoms in geriatric female patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of female patients aged ≥65 years. The psoas muscle index was defined, using computed tomography, as the cross-sectional area of the psoas muscle at the third lumbar vertebral level divided by the body surface area. We also measured visceral fat area at the umbilical level using computed tomography. We used logistic regression analysis to examine the relationships between the International Prostate Symptom Score (total score, voiding subscore, and storage subscore) and variables, such as age, body mass index, psoas muscle index, and visceral fat area. The International Prostate Symptom Score was categorized as mild, moderate, or severe. RESULTS: One hundred thirty-nine patients were included in our study. In the logistic regression analysis, we found statistically significant relationships between severe (versus mild-to-moderate) International Prostate Symptom Score storage subscore and variables, including low and high levels of psoas muscle index and visceral fat area, respectively. We could not find any significant relationships between the International Prostate Symptom Score total score and voiding subscore and the variables. CONCLUSION: Psoas muscle atrophy and visceral fat accumulation are potential risk factors for severe storage symptoms in female patients aged ≥65 years.

Efficacy of vibegron, a novel ß3-adrenoreceptor agonist, for lower urinary tract dysfunction in mice with spinal cord injury.

OBJECTIVES: To investigate the effect of vibegron, a new clinically approved ß3-adrenoceptor agonist in lower urinary tract dysfunction in mice with spinal cord injury. METHODS: Investigators performed cystometry under awake conditions in 4-week spinal cord injury female mice. Two weeks after spinal cord injury, saline or vibegron (30 mg/kg) was orally administered for 2 weeks prior to the urodynamic study. Investigators removed L6-S1 dorsal root ganglia from the saline- or vibegron-treated spinal cord injury mice as well as from saline-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase transcripts using real-time polymerase chain reaction. RESULTS: In vibegron-treated spinal cord injury mice, nonvoiding contractions during bladder filling, which were increased in spinal cord injury compared to spinal intact mice, were significantly decreased. Micturition pressure or voiding efficiency was not significantly increased in comparison to measurements in saline-treated spinal cord injury mice. The expression of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase messenger RNA was increased in spinal cord injury mice compared to spinal intact mice, but significantly decreased after vibegron treatment. CONCLUSIONS: Vibegron improves spinal cord injury-induced detrusor overactivity in addition to significantly reducing C-fiber afferent receptors such as transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, and inflammatory cytokines/markers, such as activating transcription factor 3 and inducible nitric oxide synthase, in spinal cord injury mice. Thus, vibegron might be effective in the treatment of storage lower urinary tract dysfunction induced by C-fiber afferent activation after spinal cord injury.

Sodium plays an important role in the absorption of intravesical fluid.

OBJECTIVES: To investigate the role of sodium in intravesical absorption of water in the bladder and the sodium pathway in the urothelium. METHODS: Adult female Sprague-Dawley rats received either saline or a 5% glucose solution injection into their bladders. The changes in intravesical fluid volume; concentrations of sodium and chlorine and osmolality; and expression of aquaporin-2, epithelial sodium channel, and claudins were compared after 3 hours. RESULTS: Intravesical volume decreased significantly in the saline group compared to that in the 5% glucose solution group. The expression of claudin-3 and -6 was higher in the saline group than in the glucose group. There was a significant correlation between changes in the intravesical saline volume and the concentration of sodium and chlorine. Intravesical administration of amiloride did not affect changes in the fluid volume and concentration of sodium. CONCLUSIONS: The presence of sodium is important for the absorption of intravesical fluid through aquaporin-2 in the urinary bladders of rats. Claudin-3 and -6 may be associated with the transport of sodium through the bladder urothelium.

Comparison of Abiraterone and Combined Androgen Blockade Therapy for High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Propensity Score-Matched Analysis.

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score-matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2-89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

Comparison of the Safety and Efficacy of Photoselective Vaporization of the Prostate (PVP) and Transurethral Enucleation with a Bipolar System (TUEB): A Single-Center Retrospective Study.

PURPOSE: The aim of this study was to compare the safety and efficacy of photoselective vaporization of the prostate (PVP) and transurethral enucleation with a bipolar system (TUEB). PATIENTS AND METHODS: Patients who underwent PVP or TUEB surgery for lower urinary tract symptoms due to bladder outlet obstruction at our institution from September 2015 to May 2019 were retrospectively reviewed. A total of 83 patients (PVP: n=45, TUEB: n=38) who were available for follow-up at least 12 months after surgery were included. Preoperative characteristics, perioperative parameters, and postoperative outcomes-such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications-at 3, 6, and 12 months after surgery were compared between the two groups. RESULTS: Although differences in age, IPSS, and QoL were not significant, a significantly greater prostate volume, lower Qmax, and greater PVR were noted in the TUEB group. In perioperative parameters, a significantly shorter operation time, less change in serum hemoglobin, fewer days of catheterization, and shorter length of stay were observed in the PVP group. As for postoperative outcomes, the IPSS storage subscore and PVR were significantly improved in the TUEB group. As complications, stress urinary incontinence was more frequently observed in the TUEB group, and urethral stricture was more common in the PVP group. CONCLUSION: The present data suggest that PVP and TUEB are efficient and safe surgical treatment options. Management of patients undergoing PVP in the perioperative period appears easy. Improvements of subjective and objective parameters were superior after TUEB than after PVP.

Daily salt intake is associated with leg edema and nocturnal urinary volume in elderly men.

AIMS: There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria. METHODS: A total of 56 men aged ≥60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated. RESULTS: The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria. CONCLUSIONS: Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria.

Cognitive burden and polypharmacy in elderly Japanese patients treated with anticholinergics for an overactive bladder.

This study aimed to investigate the cognitive burden and polypharmacy in elderly patients treated with anticholinergics for an overactive bladder. We conducted a retrospective study of patients with an overactive bladder receiving treatment at two hospitals in Japan (Nara Medical University Hospital and Saiseikai Nara Hospital). Prescription data were collected from the medical records of the patients registered between January 2013 and April 2014. The Anticholinergic Cognitive Burden Scale was used to estimate the severity of the anticholinergic effects on the cognition of each patient. We collected the prescription data of 584 and 246 patients from the Nara Medical University Hospital and Saiseikai Nara Hospital, respectively. The mean daily total Anticholinergic Cognitive Burden score ranged between 3 and 4 (3.59 ± 1.16 at Nara Medical University Hospital vs 3.32 ± 0.78 at Saiseikai Nara Hospital, P < 0.01). At both hospitals, the mean number of prescriptions was >5 in patients ≥75 years (5.95 ± 4.43 and 5.64 ± 3.90 at Nara Medical University Hospital and Saiseikai Nara Hospitals, respectively). Our findings suggest that 10%-20% of elderly patients (≥65 years) receiving treatment with anticholinergics for an overactive bladder are in a state of polypharmacy. The total anticholinergic cognitive burden of each patient mainly depends on the anticholinergics being used for treating the overactive bladder. Especially for elderly patients with a high risk of adverse effects, including cognitive impairment, careful attention needs to be paid during selection of drugs for treating patients with an overactive bladder.

Role of p38 MAP kinase signaling pathways in storage and voiding dysfunction in mice with spinal cord injury.

AIM: To investigate the role of p38 MAP kinase in lower urinary tract dysfunction in mice with spinal cord injury (SCI). METHODS: Cystometry and external urethral sphincter-electromyography were performed under an awake condition in 4-week SCI female mice. Two weeks after SCI, a catheter connected to an osmotic pump filled with a p38 mitogen-activated protein kinase (MAPK) inhibitor or artificial cerebrospinal fluid (CSF) was implanted into the intrathecal space of L6-S1 spinal cord for continuous intrathecal instillation at infusion rate of 0.51 µL/h for 2 weeks before the urodynamic study. L6 dorsal root ganglia were then removed from CSF and p38 MAPK inhibitor-treated SCI mice as well as from CSF-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) transcripts by real-time polymerase chain reaction. RESULTS: In p38 MAPK inhibitor-treated SCI mice, nonvoiding contractions during bladder filling, bladder capacity, and post-void residual volume were significantly reduced while micturition pressure and voiding efficiency were significantly increased in comparison to these measurements in CSF-treated SCI mice. The expression of TRPV1, TNF-α, and iNOS messenger RNA was increased in SCI mice compared with expression in spinal intact mice and significantly decreased after p38 MAPK inhibitor treatment. CONCLUSIONS: The p38 MAPK signaling pathway in bladder sensory neurons or in the spinal cord plays an important role in storage and voiding problems such as detrusor overactivity and inefficient voiding after SCI.

Tadalafil, a phosphodiesterase type 5 inhibitor, restores urethra and detrusor function in the initial phase of diabetes in rats.

OBJECTIVE: This study investigated the effects of tadalafil on the urethra and detrusor in the initial phase of diabetes in rats. METHODS: Thirty-six female Sprague-Dawley rats were assigned to a non-diabetes (ND), diabetes (D), or tadalafil-treated diabetes (DT) group (n = 12 per group), with the DT group receiving oral tadalafil (2 mg/kg/d) for 7 days before the experiments. Seven weeks after diabetes induction (by a single intraperitoneal injection of streptozotocin), urethral and intravesical pressure were simultaneously recorded in vivo, whereas responses of detrusor strips to potassium chloride (30 mM), electrical field stimulation (EFS) and carbachol were measured in vitro. RESULTS: The intravesical pressure at which the urethra started to relax was significantly lower in the DT than D group (mean [± s.d.] 18.9 ± 2.9 vs 29.1 ± 6.6 cm H2 O; P < .05). In addition, the reduction in urethral pressure was significantly larger in the DT than D group (-10.9 ± 4.0 vs -4.0 ± 2.9 cm H2 O; P < .05). Detrusor stimulation revealed that the mean contractile responses to EFS and carbachol were significantly lower in the ND and DT groups than in the D group (120.7 ± 26.5% and 130.8 ± 15.8% vs 200.1 ± 47.9% of the 30 mM KCl-induced contraction, respectively, in response to 50 Hz EFS [P < .05]; 211.1 ± 35.4% and 208.4 ± 25.3% vs 425.7 ± 125.0% of the 30 mM KCl-induced contraction, respectively, in response to 10-3 M carbachol [P < .05]). CONCLUSIONS: Tadalafil restored urethral relaxation function and detrusor responses to EFS and carbachol during the initial phase of diabetes.