Surgery for female urethral stricture.

BACKGROUND: Female urethral stricture (FUS) is a rare entity that causes great morbidity and suffering in those affected. As the available scientific data is sparce, there are no formal guidelines or standard of care for this disease. METHODS: This is a narrative review of the surgical management for female urethral stricture. The literature review was performed on PubMed. Articles were limited to English, but there was no limitation in terms of date. RESULTS: Management of FUS is divided between endoscopic and open surgical repair. Urethral dilation with or without urethrectomy can be offered as a first-line treatment. However, the rate of success of this procedure remains inferior to open surgical repair, and its efficacy decreases with the number of previous dilations. For distal urethral strictures, distal urethrectomy and advancement meatoplasty may be considered. Vaginal flaps are readily available, easy to harvest, well-vascularized, and allow for a dorsal or ventral orientation urethroplasty. The results of this procedure are promising, but most studies are small and retrospective. Labia flaps are easily accessible, wet, hairless, and elastic. The main limitations with the use of vaginal or labial tissues are co-existing conditions such as lichen sclerosis or vaginal atrophy, which may affect future results. Vaginal and labial graft urethroplasty can be used when it is not possible to mobilize an adequate flap. Stricture-free rates of this technique are variable. In cases of more severe stricture, an augmentation urethroplasty using buccal mucosa graft may be necessary. The techniques used in FUS replicate those for male urethral strictures, where both ventral and dorsal approaches can be utilized. CONCLUSIONS: Although there is growing interest in the field, the optimal management of FUS remains to be determined.

Synthesis and secretion of Nerve Growth Factor is regulated by Nitric Oxide in bladder cells in vitro under a hyperglycemic environment.

Urine samples of female patients with overactive bladder (OAB) are characterized by low levels of nerve growth factor (NGF) and elevated concentrations of nitric oxide (NO) compared to healthy controls. We therefore examined how NO might regulate NGF synthesis using rat bladder smooth muscle (SMCs) and urothelial (UROs) cells in culture. In UROs, incubation in hyperglycemic conditions to mimic insulin insensitivity present in the OAB cohort increased secretion of NO and concomitantly decreased NGF, except when the NO synthase inhibitor, l-NAME (1 mM) was present. Sodium nitroprusside (SNP) (300 µM, 24 h), a NO generator, decreased NGF levels and decreased cyclic GMP (cGMP) content, a process validated by the cGMP synthase inhibitor ODQ (100 µM). Alternatively, SNP increased mRNA of both NGF and matrix metalloproteinase-9 (MMP-9). MMP-9 knockout of UROs by Crispr-Cas9 potently decreased the effect of SNP on NGF, implying a dependent role of NO on MMP-9. On the other hand, matrix metalloproteinase-7 (MMP-7) activity was increased by SNP, which taken together with increase in NGF mRNA, suggests a compensatory mechanism. In SMCs, hyperglycemic conditions had the same effect on extracellular content of NO and NGF than in UROs. SNP also decreased NGF secretion but increased cGMP content. Stable permeable analogs of cGMP 8-(4-Chlorophenylthio)-cGMP (1 mM) and N2,2'-O-Dibutyryl-cGMP (3 mM) inhibited NGF release. NGF and MMP-9 mRNA expression was unchanged by SNP. Deletion of MMP-9 in SMCs by Crispr-Cas9 did not alter the effect of SNP. Finally, SNP decreased MMP-7 activity, diminishing the conversion of proNGF to NGF. These results demonstrate that enhanced NO secretion triggered by high glucose decreases NGF secretion through pathways unique for each cell type that involve cGMP and proteases MMP-7 and MMP-9. These results might help to explain our observations from the urine from patients with OAB associated with metabolic syndrome.

Bladder outlet obstruction in women: Scope of the problem and differential diagnosis.

INTRODUCTION: The prevalence, formal definition, and diagnostic criteria of bladder outlet obstruction in owmen have not been clearly defined. METHODS: This is a literature review of the definition of BOO in women, its prevalence, as well as its differential diagnosis. RESULTS: The main causes of BOO in women are divided into functional and anatomic conditions. Functional etiologies include detrusor external sphincter dyssynergia, dysfunctional voiding, Fowler's syndrome, and primary bladder neck obstruction. Anatomic causes can be further divided into extrinsinc and intrinsic conditions. Intrinsic etiologies include urethral stricture and urethral diverticula, whereas extrinsic causes comprise pelvic organ prolapse, post anti-incontinence surgery, and Skene's gland cyst or abscess. CONCLUSIONS: There are multiple etiologies to BOO in women, and this condition is most probably underdiagnosed, owing to a lack of consensus for a standard definition.

A cost-effectiveness analysis of bladder management strategies in neurogenic lower urinary tract dysfunction after spinal cord injury: A publicly funded health care perspective.

STUDY DESIGN: Economic evaluation study. OBJECTIVES: To investigate the long-term cost-effectiveness of clean intermittent catheterization (CIC) compared with suprapubic catheters (SPC) and indwelling urethral catheters (UC) among individuals with neurogenic lower urinary tract dysfunction (NLUTD) related to spinal cord injury (SCI) from a public healthcare perspective. SETTING: University affiliated hospital in Montreal, Canada. METHODS: A Markov model with Monte Carlo simulation was developed with a cycle length of 1 year and lifetime horizon to estimate the incremental cost per quality-adjusted life years (QALYs). Participants were assigned to treatment with either CIC or SPC or UC. Transition probabilities, efficacy data, and utility values were derived from literature and expert opinion. Costs were obtained from provincial health system and hospital data in Canadian Dollars. The primary outcome was cost per QALY. Probabilistic and one-way deterministic sensitivity analyses were performed. RESULTS: CIC had a lifetime mean total cost of $ 29,161 for 20.91 QALYs. The model predicted that a 40-year-old person with SCI would gain an additional 1.77 QALYs and 1.72 discounted life-years gained if CIC were utilized instead of SPC at an incremental cost savings of $330. CIC confer 1.96 QALYs and 3 discounted life-years gained compared to UC with an incremental cost savings of $2496. A limitation of our analysis is the lack of direct long-term comparisons between different catheter modalities. CONCLUSIONS: CIC appears to be a dominant and more economically attractive bladder management strategy for NLUTD compared with SPC and/or UC from the public payer perspective over a lifetime horizon.

Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome.

PURPOSE: Given the disputable link between nerve growth factor (NGF) and overactive bladder syndrome (OAB) and the lack of studies on its precursor (proNGF) in OAB, the aim of the study was to identify changes in the urinary levels of NGF and its proteolytic enzymes in aging women with OAB. METHODS: We examined the urinary proNGF/NGF ratio and its processing enzymes in aging women (50-80 years), comparing 20 controls and 20 subjects with OAB. RESULTS: In contrast to previous reports correlating NGF to OAB symptoms, we found that proNGF/NGF ratio in the OAB group was twice as high compared to controls (p = 0.009) with a lower NGF levels in women with OAB without statistical significance [1.36 (Q1, Q3: 0.668, 2.39) vs. 1.7 (Q1, Q3: 1.27, 3.045) pg/mg creatinine in control group, p = 0.05]. Enzymatic activity of MMP-7, the main enzyme for extracellular proNGF maturation, was significantly increased in the OAB group and correlated positively with scores of OAB symptoms questionnaires. However, this was counteracted by several-folds increase in the MMP-9 enzyme responsible for NGF proteolysis. While these findings highlight the importance of changes in the proteolytic enzymes to maintain proNGF/NGF balance in OAB, analysis of covariates showed that these changes were attributed to age, insulin resistance and renal function. CONCLUSION: NGF proteolysis imbalance can be clinically meaningful in OAB related to aging, rendering it as a potential therapeutic target. However, other age-related factors such as insulin resistance and renal function may contribute to the relationship between NGF and aging-related OAB phenotype.

Receptor GPR91 contributes to voiding function and detrusor relaxation mediated by succinate.

AIM: Succinate activates the receptor GPR91 identified in the bladder. The present study aims to unravel the mechanisms of bladder relaxation by succinate and how the receptor is involved in structural and functional changes of the bladder. METHODS: Physiological recordings of bladder function were carried out by cystometry and organ bath from C57BL/6 mice, homozygous GPR91-/- mice, and Sprague-Dawley (SD) rats. GPR91 expression was confirmed by polymerase chain reaction and tissue morphology was examined by light (Masson trichrome) and fluorescence microscopy. Nitric oxide (NO) and ATP secretion were measured. RESULTS: Bladders of GPR91 KO mice had a greater mass to body weight ratio with a thicker bladder wall compared to C57BL/6 mice. They also displayed increased basal and maximal bladder pressures, and decreased intercontraction intervals, bladder capacity, micturition volume, and compliance. During cystometry, bladders of SD rats and C57BL/6 mice instilled with succinate (10 mM) showed signs of relaxation while bladders of GPR91 KO mice were unresponsive. Similarly, in organ bath, succinate relaxed bladder strips preincubated with carbachol, except GPR91 KO ones. Relaxation was stronger in the presence of urothelium and independent of NO synthesis. Bladder strips from all mice groups showed similar responses to KCl, carbachol, and electrical stimulation. In vitro, succinate increased NO secretion in urothelial cell culture of both C57BL6 and GPR91 KO mice while ATP secretion was potently decreased by succinate in C57BL6 culture only. CONCLUSION: Succinate through GPR91 is essential to bladder structure and contraction. GPR91 relaxes the detrusor partially by decreasing urothelial ATP secretion.

Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder.

The extracellular matrix of the bladder consists mostly of type I and III collagen, which are required during loading. During bladder injury, there is an accumulation of collagen that impairs bladder function. Little is known about the genes that regulate production of collagens in the bladder. We demonstrate that the transcription factor Odd-skipped related 1 (Osr1) is expressed in the bladder mesenchyme and epithelium at the onset of development. As development proceeds, Osr1 is mainly expressed in mesenchymal progenitors and their derivatives. We hypothesized that Osr1 regulates mesenchymal cell differentiation and production of collagens in the bladder. To test this hypothesis, we examined newborn and adult mice heterozygous for Osr1, Osr1+/-. The bladders of newborn Osr1+/- mice had a decrease in collagen I by western blot analysis and a global decrease in collagens using Sirius red staining. There was also a decrease in the cellularity of the lamina propria, where most collagen is synthesized. This was not due to decreased proliferation or increased apoptosis in this cell population. Surprisingly, the bladders of adult Osr1+/- mice had an increase in collagen that was associated with abnormal bladder function; they also had a decrease in bladder capacity and voided more frequently. The results suggest that Osr1 is important for the differentiation of mesenchymal cells that give rise to collagen-producing cells.

Is Early Surgical Treatment for Benign Prostatic Hyperplasia Preferable to Prolonged Medical Therapy: Pros and Cons.

Background and objectives: Treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) has shifted over the last decades, with medical therapy becoming the primary treatment modality while surgery is being reserved mostly to patients who are not responding to medical treatment or presenting with complications from BPH. Here, we aim to explore the evidence supporting or not early surgical treatment of BPH as opposed to prolonged medical therapy course. Materials and Methods: The debate was presented with a "pro and con" structure. The "pro" side supported the early surgical management of BPH. The "con" side successively refuted the "pro" side arguments. Results: The "pro" side highlighted the superior efficacy and cost-effectiveness of surgery over medical treatment for BPH, as well as the possibility of worse postoperative outcomes for delayed surgical treatment. The "con" side considered that medical therapy is efficient in well selected patients and can avoid the serious risks inherent to surgical treatment of BPH including important sexual side effects. Conclusions: Randomized clinical trials comparing the outcomes for prolonged medical therapy versus early surgical treatment could determine which approach is more beneficial in the long-term in context of the aging population. Until then, both approaches have their advantages and patients should be involve in the treatment decision.

Antagonism of proNGF or its receptor p75NTR reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction.

AIMS/HYPOTHESIS: Although 80% of diabetic patients will suffer from voiding difficulties and urinary symptoms, defined as diabetic voiding dysfunction (DVD), therapeutic targets and treatment options are limited. We hypothesise that the blockade of the pro-nerve growth factor (NGF)/p75 neurotrophin receptor (p75NTR) axis by an anti-proNGF monoclonal antibody or by a small molecule p75NTR antagonist (THX-B) can restore bladder remodelling (represented by bladder weight) in an animal model of DVD. Secondary outcomes of the study include improvements in bladder compliance, contractility and morphology, as well as in voiding behaviour, proNGF/NGF balance and TNF-α expression. METHODS: In a streptozotocin-induced mouse model of diabetes, diabetic mice received either a blocking anti-proNGF monoclonal antibody or a p75NTR antagonist small molecule as weekly systemic injections for 4 weeks. Animals were tested at baseline (at 2 weeks of diabetes induction), and after 2 and 4 weeks of treatment. Outcomes measured were voiding function with voiding spot assays and cystometry. Bladders were assessed by histological, contractility and protein expression assays. RESULTS: Diabetic mice showed features of DVD as early as 2 weeks after diabetes diagnosis (baseline) presented by hypertrophy, reduced contractility and abnormal cystometric parameters. Following treatment initiation, a twofold increase (p < 0.05) in untreated diabetic mouse bladder weight and thickness compared with non-diabetic controls was observed, and this change was reversed by p75NTR antagonism (37% reduction in bladder weight compared with untreated diabetic mice [95% CI 14%, 60%]) after 4 weeks of treatment. However, blocking proNGF did not help to reverse bladder hypertrophy. While diabetic mice had significantly worse cystometric parameters and contractile responses than non-diabetic controls, proNGF antagonism normalised bladder compliance (0.007 [Q1-Q3; 0.006-0.009] vs 0.015 [Q1-Q3; 0.014-0.029] ml/cmH2O in untreated diabetic mice, representing 62% reduction [95% CI 8%, 110%], p < 0.05) and contractility to KCl, carbachol and electrical field stimulation (p < 0.05 compared with the diabetic group) after 2 weeks of treatment. These effects were not observed after 4 weeks of treatment with proNGF antagonist. p75NTR antagonism did not show important improvements in cystometric parameters after 2 weeks of treatment. Slightly improved bladder compliance (0.01 [Q1-Q3; 0.009-0.012] vs 0.013 [Q1-Q3; 0.011-0.016] ml/cmH2O for untreated diabetic mice) was seen in the p75NTR antagonist-treated group after 4 weeks of treatment with significantly stabilised contractile responses to KCl, carbachol and electric field stimulation (p < 0.05 for each) compared with diabetic mice. Bladder dysfunction observed in diabetic mice was associated with a significant increase in bladder proNGF/NGF ratio (3.1 [±1.2] vs 0.26 [±0.04] ng/pg in control group, p < 0.05 at week 2 of treatment) and TNF-α (p < 0.05). The proNGF/NGF ratio was partially reduced (about 60% reduction) with both treatments (1.03 [±0.6] ng/pg for proNGF antibody-treated group and 1.4 [±0.76] ng/pg for p75NTR blocker-treated group after 2 weeks of treatment), concomitant with a significant decrease in the bladder levels of TNF-α (p < 0.05), despite persistent hyperglycaemia. CONCLUSIONS/INTERPRETATION: Our findings indicate that blockade of proNGF and the p75NTR receptor in diabetes can impede the development and progression of DVD. The reported improvements in morphological and functional features in our DVD model validates the proNGF/p75NTR axis as a potential therapeutic target in this pathology. Graphical abstract.

What do we really know about the role of caffeine on urinary tract symptoms? A scoping review on caffeine consumption and lower urinary tract symptoms in adults.

AIMS: The purpose of this scoping review was to map out the existing literature on caffeine intake and lower urinary tract symptoms (LUTS) in adults. METHODS: In this scoping review, we searched for all studies available until June 2019 in MEDLINE, Embase, CINAHL, Cochrane Central Register, PsycINFO, LILACS, LiSSa, Web of Science, and Joanna Briggs Institute electronic databases, in addition to a hand search of the bibliographies of all relevant articles and a gray literature search. Both intervention studies on the effects of caffeine reduction in adults with LUTS and observational studies on the association between caffeine intake and LUTS-related outcomes in adults were included and assessed for methodological quality by two independent reviewers. RESULTS: Fourteen intervention and 12 observational studies were included. Overall, there was a decrease in urgency episodes (level of evidence 2, grade of recommendation B) and nocturnal enuresis episodes (4, C) with caffeine reduction. Observational studies reported an unclear association between caffeine intake and LUTS-related outcomes. Most importantly, this present review highlighted high heterogeneity in the studied populations, caffeine measures, and reported outcomes. There was also unknown or high risk of bias in most identified studies. CONCLUSIONS: Caffeine reduction appears to reduce LUTS. Future studies on caffeine reduction interventions should target populations with urgency and urge urinary incontinence, which show the most promising results, and include valid and reliable measures of caffeine intake and LUTS. Finally, future studies should also use reporting guidelines to ensure lower risk of bias.

Best practices for cystometric evaluation of lower urinary tract function in muriform rodents.

AIMS: Rodent cystometry has provided valuable insights into the impact of the disease, injury, and aging on the cellular and molecular pathways, neurologic processes, and biomechanics of lower urinary tract function. The purpose of this white paper is to highlight the benefits and shortcomings of different experimental methods and strategies and to provide guidance on the proper interpretation of results. METHODS: Literature search, selection of articles, and conclusions based on discussions among a panel of workers in the field. RESULTS: A range of cystometric tests and techniques used to explore biological phenomena relevant to the lower urinary tract are described, the advantages and disadvantages of various experimental conditions are discussed, and guidance on the practical aspects of experimental execution and proper interpretation of results are provided. CONCLUSIONS: Cystometric evaluation of rodents comprises an extensive collection of functional tests that can be performed under a variety of experimental conditions. Decisions regarding which approaches to choose should be determined by the specific questions to be addressed and implementation of the test should follow standardized procedures.

Urinary metabolomics predict the severity of overactive bladder syndrome in an aging female population.

INTRODUCTION AND HYPOTHESIS: To identify urinary metabolites that can facilitate the diagnosis and the characterization of the underlying pathophysiology of the association between the overactive bladder syndrome (OAB) and metabolic syndrome. METHODS: We used gas chromatography-mass spectrometry to compare the urinary metabolome of 20 females of 50-80 years of age with OAB to that of 20 controls of the same age group. We performed urinary metabolomic analysis and obtained serum markers of metabolic syndrome for each subject. Participants completed a clinical evaluation and validated self-reported questionnaires of lower urinary tract symptoms as well as a one-day voiding diary. RESULTS: In the OAB subjects, we identified increased urinary levels of markers of mitochondrial dysfunction (itaconate, malate and fumarate), oxidative stress (L-pyroglutamate and α-hydroxyglutarate) and ketosis (α-hydroxybutyrate and α-hydroxyisobutyrate). The increased levels of these markers correlated significantly with the OAB symptoms score on questionnaires. We found, using a multiple linear regression model, that age, blood glucose and urine metabolites (malate, fumarate and α-hydroxyisobutyrate) were significant predictive factors of OAB severity. Fumarate had high sensitivity as a biomarker of OAB due to metabolic syndrome, based on a statistically significant receiver-operating characteristic (ROC) curve, indicating its potential as a diagnostic tool. CONCLUSIONS: Altogether, these findings establish that urinary metabolites of mitochondrial dysfunction, ketosis and oxidative stress can be potential biomarkers of OAB severity and diagnosis.

Are Beta 3 Adrenergic Agonists Now the Preferred Pharmacologic Management of Overactive Bladder?

PURPOSE OF THE REVIEW: This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome. RECENT FINDINGS: Mirabegron has a similar efficacy profile to first-line antimuscarinics with favorable adverse effects profile. Treatment of OAB with beta-3 adrenergic agonist should be favored in patients at higher risk of anticholinergic adverse events. The efficacy and tolerability of beta-3 adrenergic agonists are consistently reported in older OAB patients, whether used alone or with other antimuscarinics. Mirabegron is cost-effective in treating OAB unless the symptoms were severe or refractory. Combination therapy of mirabegron and other pharmacotherapy has proven to be efficient in controlling OAB symptoms without inducing serious add-on adverse effects. While beta-3 adrenergic agonists bear favorable advantages in OAB treatment, physicians should perform a thorough and careful pre-treatment planning to optimize treatment benefits and adherence.

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects.

PURPOSE: Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS: Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 µg and 0.12 µg desmopressin subcutaneous (SC) bolus injection. RESULTS: AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 µg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS: AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Beta-3 Adrenoceptor Signaling Pathways in Urothelial and Smooth Muscle Cells in the Presence of Succinate.

Succinate, an intermediate metabolite of the Krebs cycle, can alter the metabolomics response to certain drugs and controls an array of molecular responses in the urothelium through activation of its receptor, G-protein coupled receptor 91 (GPR91). Mirabegron, a ß3-adrenergic receptor (ß3-AR) agonist used to treat overactive bladder syndrome (OAB), increases intracellular cAMP in the detrusor smooth muscle cells (SMC), leading to relaxation. We have previously shown that succinate inhibits forskolin-stimulated cAMP production in urothelium. To determine whether succinate interferes with mirabegron-mediated bladder relaxation, we examined their individual and synergistic effect in urothelial-cell and SMC signaling. We first confirmed ß3-AR involvement in the mirabegron response by quantifying receptor abundance by immunoblotting in cultured urothelial cells and SMC and cellular localization by immunohistochemistry in rat bladder tissue. Mirabegron increased cAMP levels in SMC but not in urothelial cells, an increase that was inhibited by succinate, suggesting that it impairs cAMP-mediated bladder relaxation by mirabegron. Succinate and mirabegron increased inducible nitric oxide synthesis and nitric oxide secretion only in urothelial cells, suggesting that its release can indirectly induces SMC relaxation. Succinate exposure decreased the expression of ß3-AR protein in whole bladder in vivo and in SMC in vitro, indicating that this metabolite may lead to impaired pharmacodynamics of the bladder. Together, our results demonstrate that increased levels of succinate in settings of metabolic stress (e.g., the metabolic syndrome) may lead to impaired mirabegron and ß3-AR interaction, inhibition of cAMP production, and ultimately requiring mirabegron dose adjustment for its treatment of OAB related to these conditions.

Bladder overdistension with polyuria in a hypertensive rat model.

AIMS: Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. MATERIALS AND METHODS: Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. RESULTS: Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. CONCLUSIONS: Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology.

A cost-utility analysis of artificial urinary sphincter versus AdVance male sling in post prostatectomy stress urinary incontinence: A publicly funded health care perspective.

AIMS: To investigate the long-term cost-utility of the artificial urinary sphincter (AUS) compared with Transobturator Retroluminal Sling (AdVance) in the treatment of patients with severe post prostatectomy stress urinary incontinence (PPSUI) from a Canadian provincial health perspective. METHODS: A Markov model with Monte Carlo simulation was developed with a cycle length of 1 year and time horizon up to 10 years to estimate the incremental cost per quality-adjusted life years (QALYs). Patients were assigned to treatment with either AUS or an AdVance sling. Transition probabilities, efficacy data, and utility indices were derived from published literature and expert opinion. Cost data were obtained from provincial health care system and hospital data in 2016-Canadian dollars. The primary outcome was cost per quality-adjusted life year. A standard discount rate of 1.5% was applied annually. Probabilistic and one way deterministic sensitivity analyses were performed. RESULTS: AUS implantation had a 10-year mean total cost of $14 228 (SD ± 3,509) for 7.58 QALYs. AdVance sling had a mean total cost $18 938 (SD ± 12,435) for 6.43 QALYs. The incremental cost savings of AUS over 10-years was -$ 4710 with an added effectiveness of 1.15 QALYs. At a willingness to pay threshold of $50 000, AUS remained the most cost-effective option. A limitation of our analysis is the lack of direct long-term comparisons between both scenarios along with standard success definition. CONCLUSIONS: AUS implantation appears to be more economical treatment strategy for severe PPSUI compared with AdVance sling for a publicly funded health care system over a 5- and 10-year time horizon.

Succinate decreases bladder function in a rat model associated with metabolic syndrome.

AIMS: Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function. MATERIALS AND METHODS: Healthy Sprague-Dawley (SD) rats and hypertensive Dahl rats received an intraperitoneal injection of either saline or succinate (50 mg/kg) daily for a period of 4 weeks. Conscious cystometry was performed at the end of this period. Bladders were collected and used for contractility studies and morphological assessment. Two-way ANOVA was performed to compare between the two strains and student t-tests to compare treatment groups within each strain. RESULTS: Compared to SD rats, Dahl rats showed signs of bladder dysfunction. Succinate treatment led to higher urinary succinate levels and lower bladder capacities compared to saline-treated animals. In SD rats, this was associated with higher collagen content, lower GPR91 expression and an altered bladder nerve profile in the bladder. In succinate-treated Dahl rats, detrusor contractility was reduced and associated with decreased cholinergic innervation and increased collagen content. CONCLUSIONS: It is suggested that succinate negatively affects bladder function via effects through its receptor, GPR91, and that its effects are enhanced in the presence of metabolic disturbance. These findings contribute to our understanding of the pathophysiology of bladder dysfunction, specifically in a metabolic syndrome setting.

Teaching and evaluation of basic urodynamic skills in urology residency programs: Randomized controlled study.

AIMS: Considering the growing role of urodynamic studies (UDS) in urology, we aimed to determine the most effective teaching method with objective evaluation for urodynamic skills, to improve training and patient care. METHODS: Urology residents (n = 20) post-graduate years 3-5 were randomized to receive either a UDS video training module or a standard UDS teaching document one week prior to an objective structured clinical examination (OSCE). The OSCE was a validated visual recognition exam with interpretation of 12 UDS tracing scenarios. Participants rated their proficiency to interpret UDS tracings before doing the OSCE. Total interpretation score was determined by the accuracy of their response to each question ranging from 0 to 2. RESULTS: The mean total interpretation score was 13.3 of 24 (55%). The video group achieved significantly higher interpretation scores (15.1 ± 2.08 vs 11.4 ± 2.41, P = 0.0017), and cumulative certainty scores (P = 0.0341). Overall interpretation scores significantly correlated with self-reported proficiency scores prior to the exam (r = 0.502, P < 0.05), and total certainty scores (r = 0.531, P < 0.05). CONCLUSIONS: Reviewing a UDS video training module resulted in significantly better scores on objective assessment of urology residents' UDS interpretation skills when compared with a standard teaching document. These findings must be interpreted with caution in light of sample size and short knowledge retention required for the assessment within a week. Therefore, using a UDS video training module could be more effective review tool for urology residents. These findings highlight the need to incorporate multimedia teaching into urology training curriculum.