Clinical features and sequelae of detrusor underactivity: a study of possible cause and effect.

PURPOSE: To describe the clinical presentation and urodynamic findings in detrusor underactivity (DU) patients and investigate the association between DU and straining related complications such as pelvic organ prolapse (POP), inguinal hernia, and hemorrhoids. METHODS: We retrospectively reviewed all consecutive patients who underwent urodynamic studies (UDS) from 2012 to 2023, divided into two groups: those with evidence of DU (n = 573), and control subjects with normal voiding parameters (n = 522). Exclusion criteria were patients who lacked sufficient data, those with obstructive voiding parameters, and those who had received intravesical botulinum toxin injections within the previous nine months. Demographic information, clinical presentation, straining related complications, and UDS findings were compared between the two groups using univariate statistical analysis. RESULTS: The male DU group had a statistically significant higher prevalence of spinal disease and previous cerebrovascular accidents, while the female DU group had a statistically significant higher prevalence of spinal disease, multiple sclerosis, diabetes, previous colorectal surgery, previous transabdominal gynecological surgery, POP surgery, and recurrent UTIs. Female DU patients had a higher prevalence of pronounced vaginal bulging symptoms, recurrent POP, inguinal hernia, and hemorrhoids. The predominant LUTS were voiding symptoms (81.2% in males and 77.9% in females), followed closely by storage symptoms (66.2% in males and 74.7% in females). The median Qmax, PdetQmax, and PVR were 6 ml/sec, 18 cmH2O, 190 ml for male DU patients, and 8 ml/sec, 11 cmH2O, and 200 ml for female DU patients, respectively. CONCLUSION: Risk factors for DU that were identified include age, neurological diseases (spinal disease, CVA in men, MS in women), diabetes and transabdominal surgery (colorectal, gynecological) that can cause pelvic denervation in women. DU patients commonly present with both voiding and storage symptoms. There is approximately twice the risk of having POP surgery and inguinal hernia, an eight-fold risk of hemorrhoids, and a three-fold risk of recurrent UTIs for females. This is thought to be secondary to increased intra-abdominal pressure during urinary straining.

Is detrusor underactivity the urodynamic characteristic of long-COVID in patients with benign prostate hyperplasia?

Although coronavirus disease 19 (COVID-19) was reported to involve with multiple organs, COVID-19 reports focusing on urinary system mostly evaluated the association between lower urinary tract symptoms and COVID-19 using questionnaire score. In this study, sonography video urodynamic studies was first conducted to explore the effects of COVID-19 on contractility of bladder detrusor of patients with benign prostate hyperplasia (BPH). Clinical data was respectively reviewed and compared between BPH patients with previous COVID-19 infection (COVID-19 group) and without previous COVID-19 (non-COVID-19 group). The incidence of detrusor underactivity (DU) was compared between 2 groups. Comparison of age and noninvasive parameters was conducted between BPH patients with DU and without DU in COVID-19 group. Correlation coefficient between noninvasive parameters and detrusor contractility was determined and receiver operating characteristic curve of noninvasive parameters was used to choose the most appropriate cutoff for detection of DU in COVID-19 group. Beside a significant increase in the incidence of DU in BPH patients of COVID-19 group, a lower detrusor contractility and a greater bladder wall thick was detected compared to that of patients in non-COVID-19 group. Post-voiding residual urine was found to have a linear correlation with detrusor contractility in COVID-19 group. It was suggested that COVID-19 infection would further exacerbate impairment of detrusor previously resulted from bladder outlet obstruction in BPH patients. DU may be a urodynamic characteristic of long-COVID.

Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats.

Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.

Summary Paper on Underactive Bladder from the European Association of Urology Guidelines on Non-neurogenic Male Lower Urinary Tract Symptoms.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU) Guidelines Panel on non-neurogenic male lower urinary tract symptoms (LUTS) aimed to develop a new subchapter on underactive bladder (UAB) in non-neurogenic men to inform health care providers of current best evidence and practice. Here, we present a summary of the UAB subchapter that is incorporated into the 2024 version of the EAU guidelines on non-neurogenic male LUTS. METHODS: A systematic literature search was conducted from 2002 to 2022, and articles with the highest certainty evidence were selected. A strength rating has been provided for each recommendation according to the EAU Guideline Office methodology. KEY FINDINGS AND LIMITATIONS: Detrusor underactivity (DU) is a urodynamic diagnosis defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is a terminology that should be reserved for describing symptoms and clinical features related to DU. Invasive urodynamics is the only widely accepted method for diagnosing DU. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred to indwelling catheters. Alpha-adrenergic blockers are recommended before more invasive techniques, but the level of evidence is low. In men with DU and concomitant benign prostatic obstruction (BPO), benign prostatic surgery should be considered only after appropriate counseling. In men with DU and no BPO, a test phase of sacral neuromodulation may be considered. CONCLUSIONS AND CLINICAL IMPLICATIONS: The current text represents a summary of the new subchapter on UAB. For more detailed information, refer to the full-text version available on the EAU website (https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts).

Is detrusor underactivity associated with voiding dysfunction after single incision sling surgery?

BACKGROUND: Some women experience voiding dysfunction after stress urinary incontinence (SUI) surgery. We explore if detrusor underactivity (DU) found in urodynamic study (UDS) prior to SUI surgery using an adjustable single incision sling (SIS) may be related to voiding dysfunction after surgery. METHODS: This is a prospective, diagnostic, transversal, single center study comparing voiding dysfunction after SUI surgery with a SIS (Altis®; Coloplast, Humlebæk, Denmark) between women with DU (cases) or normal detrusor (controls). Inclusion criterium was women ≥18 years with SUI/mixed UI (stress predominant) operated between June 2013 and December 2020. Exclusion criteria were: women without UDS prior to surgery or without voiding phase in the P/Q, previous incontinence surgery, POP stage ≥2, neurogenic conditions, other pelvic floor surgery. Urinary symptoms were assessed using structured questions evaluating storage/voiding symptoms. Patients were divided into two groups according to projected Isovolumetric Pressure Index (PIP1) with 30-75 cmH2O indicating normal contractility. RESULTS: A total of 139 women were included, 29 (20.9%) in DU group and 110 (79.1%) in control group. Control and DU groups have shown similar objective (75.5% vs. 71.4% P=0.66) and subjective (85.4% vs. 96.1% P=0.22) success rates, respectively, without statistical differences. Voiding symptoms increased after surgery in both groups (+20.7% DU group vs. +8.1% normal group, P=0.29). More voiding symptoms (persistent/de novo) were found in DU group vs. normal group, but without statistically significant differences. CONCLUSIONS: According to our results, the presence of DU previous to SUI surgery with a SIS (Altis®, Coloplast) has no impact on objective and subjective success rates. On the other hand, patients with preoperative DU showed higher proportion of voiding dysfunction but no statistical difference.

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8 ± 10.9% of control and a significant reduction in bladder contraction amplitude to 56.0 ± 5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4 ± 10.7% and 132.4 ± 14.2% of control, respectively, and increased contraction amplitude to 85.3 ± 6.2% and 75.8 ± 4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

Bladder underactivity induced by prolonged pudendal afferent activity in cats.

The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve. After determination of the threshold intensity (T) for PNS to induce an anal twitch, PNS (5 Hz, 0.2 ms, 2 T or 4 T) was applied during cystometrograms (CMGs). PNS (4-6 T) of 30-min duration was then applied repeatedly until bladder underactivity was produced. Following stimulation, control CMGs were performed over 1.5-2 h to determine the duration of bladder underactivity. When applied during CMGs, PNS (2 T and 4 T) significantly (P < 0.05) increased bladder capacity while PNS at 4 T also significantly (P < 0.05) reduced bladder contraction amplitude, duration, and area under contraction curve. Repeated application of 30-min PNS for a cumulative period of 3-8 h produced bladder underactivity exhibiting a significantly (P < 0.05) increased bladder capacity (173 ± 14% of control) and a significantly (P < 0.05) reduced contraction amplitude (50 ± 7% of control). The bladder underactivity lasted more than 1.5-2 h after termination of the prolonged PNS. These results provide basic science evidence supporting the proposal that abnormal afferent activity from external urethral/anal sphincter could produce central inhibition that underlies nonobstructive urinary retention (NOUR) in Fowler's syndrome. This cat model of UAB may be useful to investigate the mechanism by which sacral neuromodulation reverses NOUR in Fowler's syndrome.

Detrusor Underactivity Model in Rats by Conus Medullaris Transection.

The goal of the presented protocol was to establish a detrusor underactivity (DU) model in the rat through conus medullaris transection. Laminectomy was performed in a total of 40 female Wistar rats (control group: 10 rats; test group: 30 rats) weighing 200-220 g, and the conus medullaris was transected at the L4‒L5 level in the test group. All the rats were housed and fed under the same environmental conditions for six weeks. In the test group, urine voiding was performed twice daily for six weeks, and mean residual urine volume was recorded. A cystometrogram was performed in both groups. Maximum cystometric capacity (MCC), detrusor opening pressure (DOP), and compliance of the bladder were recorded and calculated. The test group showed significant urinary retention after the surgery, both during and after the spinal shock. However, no abnormality was observed in the control group. When compared to the control group, the MCC and compliance of bladder in the test group was significantly higher than that of the test group (3.24 ± 2.261 mL versus 1.04 ± 0.571 mL; 0.43 ± 0.578 mL/cmH2O versus 0.032 ± 0.016 mL/cmH2O), whereas DOP in the test group was lower than control (20.28 ± 14.022 cmH2O versus 35 ± 13.258 cmH2O). This method of establishing an animal model of DU by the conus medullaris transection offers an excellent opportunity to understand DU's pathophysiology in a better manner.

EP2 and EP3 receptors as therapeutic targets for underactive bladder/detrusor underactivity due to diabetic cystopathy in a type 1 diabetic rat model.

OBJECTIVES: Diabetic cystopathy (DC) is recognized as one of the major etiologies of underactive bladder (UAB)/detrusor underactivity (DU). Although DC was first reported about three decades ago, there is a distinct lack of effective pharmacological management methods for UAB/DU due to DC with a robust certainty of evidence. In this study, we investigated whether EP2 and EP3 receptors are promising targets of pharmacological management of UAB/DU due to DC. METHODS: We used streptozotocin (STZ)-induced diabetic Sprague-Dawley rats with postvoid residual urine (PVR) greater than 0.1 mL. Sixteen weeks after induction of diabetes, we performed awake single cystometry after oral administration of the vehicle, an α-blocker (tamsulosin [TAM], 0.1 and 0.3 mg/kg), a cholinesterase inhibitor (distigmine [DIS], 0.3 and 1.0 mg/kg), or an EP2/3 dual agonist (ONO-8055, 0.01 and 0.03 mg/kg). We compared cystometric parameters after administration of the vehicle and drugs using a paired t test. P < .05 was considered to be statistically significant. RESULTS: Compared with the vehicle, TAM significantly decreased maximum intravesical pressure during voiding (Pmax), while DIS significantly increased it. However, neither drug significantly affected PVR or the residual urine rate (RUR). On the other hand, ONO-8055 significantly decreased PVR and tended to decrease RUR, although it did not significantly affect Pmax. CONCLUSION: The present study was unable to demonstrate that stimulation of EP2 and EP3 receptors caused major improvements in UAB/DU due to DC. However, this equivocal result could arise from inherent limitations of the STZ-induced diabetic rat as a UAB/DU model.

Feasibility, Complications, and Recurrence after Discoid Resection for Colorectal Endometriosis: A Series of 93 Cases.

Laparoscopic discoid colorectal resection is a surgical option for bowel endometriosis, 1 of the most severe forms of endometriosis. However, no study has clearly analyzed the feasibility or the complication and recurrence rates of the procedure in a homogeneous population with specific criteria for discoid resection. The aims of this study were to evaluate the rate of conversion to segmental resection, the need for double discoid resection, and the complication and recurrence rates. We conducted a prospective study of 93 consecutive patients who underwent discoid resection in Tenon University Hospital, Paris, France. The median follow-up was 20 months. We included patients with colorectal endometriosis (≤3 cm long and <90° of bowel circumference) experiencing failure of medical treatment or associated infertility. All the patients underwent a discoid colorectal resection using a transanal circular stapler. The primary end point was the rate of conversion to segmental resection (3.2%). The secondary end point was the rate of double discoid resection (6.5%). The overall complication rate was 24%, and the severe complication rate (i.e., Clavien-Dindo IIIB) was 3% (n = 4). Postoperative voiding dysfunction requiring bladder self-catheterization was observed in 16% (n = 15). The mean duration of bladder self-catherization was 30 days (range, 15-90) including 11 cases (74%) lasting less than 30 days and 4 cases lasting more than 30 days. No patients required bladder self-catheterization over 3 months. No difference in the complication rate or in voiding dysfunction was observed between double and single discoid resection. The low rate of conversion to radical resection confirms the satisfactory preoperative evaluation of bowel endometriosis. Few publications report the rate of conversion to radical surgery. This raises the crucial issue of the right indications for discoid resection. The present study confirms that discoid resection is probably the best option for small lesions because of its high feasibility and low complication rate. Further studies are required to evaluate the technique for larger colorectal endometriotic lesions.

Detrusor contractility to parasympathetic mediators is differentially altered in the compensated and decompensated states of diabetic bladder dysfunction.

Diabetic bladder dysfunction (DBD) affects up to 50% of all patients with diabetes, characterized by symptoms of both overactive and underactive bladder. Although most diabetic bladder dysfunction studies have been performed using models with type 1 diabetes, few have been performed in models of type 2 diabetes, which accounts for ~90% of all diabetic cases. In a type 2 rat model using a high-fat diet (HFD) and two low doses of streptozotocin (STZ), we examined voiding measurements and functional experiments in urothelium-denuded bladder strips to establish a timeline of disease progression. We hypothesized that overactive bladder symptoms (compensated state) would develop and progress into symptoms characterized by underactive bladder (decompensated state). Our results indicated that this model developed the compensated state at 1 wk after STZ and the decompensated state at 4 mo after STZ administration. Diabetic bladders were hypertrophied compared with control bladders. Increased volume per void and detrusor muscle contractility to exogenous addition of carbachol and ATP confirmed the development of the compensated state. This enhanced contractility to carbachol was not due to increased levels of M3 receptor expression. Decompensation was characterized by increased volume per void, number of voids, and contractility to ATP but not carbachol. Thus, progression from the compensated to decompensated state may involve decreased contractility to muscarinic stimulation. These data suggest that the compensated state of DBD progresses temporally into the decompensated state in the male HFD/STZ model of diabetes; therefore, this male HFD/STZ model can be used to study the progression of DBD.

Medical evaluation and management of male and female voiding dysfunction: a review.

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients suffer. Despite this high prevalence and its negative impact on quality of life, however, few seek or receive treatment, as many do not readily disclose these impactful yet personal symptoms. We sought to summarize the typical presentation, evaluation, assessment and therapeutic options for both male and female patients presenting with voiding dysfunction.

Urodynamic analysis of the impact of diabetes mellitus on bladder function.

OBJECTIVES: To analyze sequential changes of diabetic cystopathy based on urodynamic data in patients with diabetes mellitus. METHODS: Participants included male diabetes patients who underwent a pressure flow study at Nagoya University Graduate School of Medicine, Nagoya, Japan, from April 2005 to October 2016. Patients with a previous history of lower urinary tract dysfunction were excluded. Bladder dysfunction was categorized into four urodynamic patterns: (i) normal; (ii) detrusor overactivity with normal detrusor contractility; (iii) detrusor hyperreflexia/impaired contractility; and (iv) detrusor underactivity. The urodynamic patterns were evaluated according to the presence of diabetic retinopathy and nephropathy, which was correlated to diabetes mellitus duration. Furthermore, the association of clinical factors with voiding function, as well as sensory function, was investigated. RESULTS: A total of 57 patients were enrolled. Detrusor overactivity with normal detrusor contractility patterns was seen only in cases with neither diabetic retinopathy nor diabetic nephropathy, whereas the prevalence of detrusor hyperreflexia/impaired contractility pattern was highest in cases with diabetic retinopathy. Detrusor underactivity pattern was found with the highest frequency in cases with both diabetic retinopathy and diabetic nephropathy. On multivariate analysis, the existence of diabetic retinopathy was only significantly correlated with bladder contractility index. Furthermore, multivariate analysis showed that first desire volume and maximum cystometric capacity were significantly positively correlated with post-void residual urine volume, and also negatively correlated with voiding efficiency independent of bladder contractility index. CONCLUSIONS: Diabetes patients have diverse progressive bladder dysfunction according to the diabetes stage. An optimal screening program is necessary to detect and manage diabetic cystopathy at an early stage.

Long-term functional change of cryoinjury-induced detrusor underactivity and effects of extracorporeal shock wave therapy in a rat model.

PURPOSE: To investigate the long-term functional change of cryoinjury-induced detrusor underactivity (DU) and the therapeutic potential of repeated low-energy shock wave therapy (LESW). METHODS: Fifty-six female Sprague-Dawley rats were assigned into sham and cryoinjury of bladder with or without LESW (0.05 or 0.12 mJ/mm2; 200 pulses; twice a week for 2 weeks after cryoinjury). Under halothane anesthesia, an incision was made in lower abdomen, and cryoinjury was provoked by bilateral placement of a chilled aluminum rod on the bladder filled with 1 ml saline. Measurement of contractile responses to KCl and carbachol in vitro, conscious voiding, and histological and protein changes were performed on week 1, 2, and 4 after cryoinjury. RESULTS: Cryoinjury of bladder induced a significant decrease in the detrusor contraction amplitude at week 1 (55.0%) and week 2 (57.2%), but the decrease in the contractile response to KCl and carbachol was only noted at week 1. At week 1, significantly increased COX-2 and TGF-ß1 expression accompanied a decrease of VEGF and CGRP expression. At week 4, there was a partial recovery of voiding function and a significant increase in the Ki-67 staining. LESW treatment at higher energy level further amplified the Ki-67 staining and improved the recovery of contraction amplitude and the expression of TGF-ß1 and VEGF. CONCLUSIONS: Cryoinjury of detrusor induces DU/UAB with functional impairment lasting for up to 4 weeks, but the associated molecular changes are restored by 2 weeks. LESW improved bladder wall composition, and hastened functional recovery from cryoinjury.

Urodynamic findings and functional outcomes after laparoscopic sacrocolpopexy for symptomatic pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the functional outcomes and urodynamic findings after laparoscopic sacrocolpopexy (LSC) in patients with stages II-IV pelvic organ prolapse (POP). METHODS: In this single-center prospective study, we evaluated 63 women (mean age 62.5 ± 7.5 years) women with symptomatic and advanced POP (stage II-IV) who underwent LSC without concomitant anti-incontinence surgery. The preoperative evaluation incuded history, clinical examination, and urodynamic testing. Women were followed up at 1, 3, 6, and 12 months after surgery and then annually using history, examination, and uroflowmetry. At 6 months, we performed urodynamic testing. To evaluate urinary symptoms, we used the Urogenital Distress Inventory (UDI)-6 questionnaire before and 6 months after surgery. RESULTS: Median follow- up was 22 months (range 8-48). After surgery, maximum flow (Qmax) significantly improved compared with baseline (14.17 ± 2.3 vs 27 ± 8.4 ml/s; p = 0.02), and the percentage of patients with elevated postvoid residual (PVR) significantly decreased (33.3% vs 11.1%; p = 0.001). Detrusor overactivity and bladder outlet obstruction disappeared in 73.6% and 85.7% of patients, respectively, while detrusor underactivity persisted in 66.6% of women. Twenty women (31.7%) reported stress urinary incontinence (SUI) before surgery (14 clinically evident and 6 as occult form), which persisted in only 7/20 (11%) patients following LSC, with no de novo cases. The most common preoperative symptoms were voiding symptoms, present in 42/63 (66.6%) patients, which resolved in 36 (85.7%). The overactive bladder syndrome disappeared in 60% of women, with no de novo cases. Results were reflected by a significant decrease in UDI-6 score from a median of 16 (0-45) at baseline to 5.5 (0-17) at the final follow-up (p = 0.001). The domain on storage symptoms (median 3 vs 1) and voiding symptoms (median 3 vs 1) of UDI-6 showed an improvement after surgery (p = 0.001). CONCLUSIONS: The urodynamic finding showed that LSC in women with advanced POP provides good functional outcomes.

Elevated post-void residual volume in a geriatric post-hip fracture assessment in women-associated factors and risk of mortality.

BACKGROUND AND AIM: Multiple factors contribute to elevated post-void residual urine volumes (PVR), but they may indicate detrusor underactivity (DU), especially in older women. The aim here was to examine factors associated with and prognostic significance of elevated PVR in a geriatric post-hip fracture assessment in a female population. METHODS: Consecutive female hip fracture patients (n = 409) aged 65 years and older were included. PVR was measured by bladder scanner. PVR of 160 ml or more was deemed elevated. Age-adjusted univariate logistic regression analyses were conducted to examine the association of the domains of the comprehensive geriatric assessment (CGA) with elevated PVR. Cox proportional hazards model was used to determine the age-adjusted association of an elevated PVR with 1-year mortality. RESULTS: Of the patients, 64 (15.6%) had elevated PVR. Having urinary or fecal incontinence, difficulties in physical activities of daily living, malnutrition, poor performance on Timed Up and Go and Elderly Mobility Scale were significantly associated with elevated PVR. Difficulties in instrumental activities of daily living, renal dysfunction, constipation, polypharmacy, nocturia, cognitive impairment and depressive mood were not associated with elevated PVR. Elevated PVR significantly increased the risk of mortality 1 year post hip fracture. CONCLUSIONS: Elevated PVR is relatively common in older female hip fracture patients and associated with physical functioning, malnutrition and risk of mortality. Even though a causal relationship cannot be confirmed, the findings may suggest a relationship between DU and physical frailty. PVR deserves to be included in the CGA of frail older patients including women.

Functional and molecular characterisation of the bilateral pelvic nerve crush injury rat model for neurogenic detrusor underactivity.

OBJECTIVES: To create a rat model for neurogenic detrusor underactivity (DU) by bilateral pelvic nerve crush injury (BPNI) and to study temporal changes in detrusor contractility and morphology. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to BPNI or sham surgery and evaluated at 1, 3 and 9 weeks after surgery. Bladder function was determined in vivo by awake cystometry, micturition pattern analysis, and 24-h urine collection. Bladders were harvested for in vitro pharmacological investigation by isometric tension recording. Bladders and major pelvic ganglia were investigated by quantitative reverse transcription-polymerase chain reaction and histochemistry. RESULTS: Overflow incontinence was observed at 1 week after BPNI. At 3 and 9 weeks after BPNI, rats showed a bladder phenotype characteristic for DU with increased post-void residual urine volumes, reduced voiding efficiencies, and lower maximum pressures. In isolated bladder strips, contractile responses to KCl, carbachol, and α,ß-methylene adenosine 5'-triphosphate (α,ß-mATP) were preserved. On the other hand, neural-induced contractility was reduced after BPNI, in line with reduced expression of protein gene product 9.5 and choline acetyltransferase in the major pelvic ganglion at 1 week after BPNI. The bladder-to-body weight ratio and detrusor thickness increased after BPNI, indicating detrusor hypertrophy to compensate for the reduced neural input. CONCLUSIONS: BPNI induces a rat model for neurogenic DU. In this model, the detrusor maintains its contractility but denervation of the detrusor was observed.

Effect of TRPV4 activation in a rat model of detrusor underactivity induced by bilateral pelvic nerve crush injury.

AIMS: To produce an animal model of peripheral neurogenic detrusor underactivity (DU) and to evaluate the effect of TRPV4 receptor activation in this DU model. METHODS: In female Sprague-Dawley rats, bilateral pelvic nerve crush (PNC) was performed by using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham and PNC rats. A TRPV4 agonist (GSK 1016790A) with or without a TRPV4 antagonist (RN1734) were administered intravesically and CMG parameters were compared before and after drug administration in each group. The TRPV4 transcript level in the bladder mucosa and histological changes were also evaluated. RESULTS: In CMG, PNC rats showed significant increases in intercontraction intervals (ICI), number of non-voiding contractions (NVCs), baseline pressure, threshold pressure, bladder capacity, voided volumes, and post-void residual (PVR) compared to sham rats. Contraction amplitude and voiding efficiency were significantly decreased in PNC rats. In PNC rats, intravesical application of GSK1016790A (1.5 µM) significantly decreased ICI, bladder capacity, voided volume, and PVR without increasing NVCs, and these effects were blocked by RN1734 (5.0 µM). In contrast, 1.5 µM GSK1016790A had no significant effects on CMG parameters in normal rats. TRPV4 expression within the bladder mucosa of PNC rats was increased in association with urothelial thickening. CONCLUSIONS: Rats with bilateral PNC showed characteristics of DU, and this model seems appropriate for further evaluation of peripheral neurogenic mechanisms of DU. Also, TRPV4 receptors, the activation of which reduced bladder capacity and PVR, could be a target for DU treatment.

Development of stress-induced bladder insufficiency requires functional TRPV1 channels.

Social stress causes profound urinary bladder dysfunction in children that often continues into adulthood. We previously discovered that the intensity and duration of social stress influences whether bladder dysfunction presents as overactivity or underactivity. The transient receptor potential vanilloid type 1 (TRPV1) channel is integral in causing stress-induced bladder overactivity by increasing bladder sensory outflow, but little is known about the development of stress-induced bladder underactivity. We sought to determine if TRPV1 channels are involved in bladder underactivity caused by stress. Voiding function, sensory nerve activity, and bladder wall remodeling were assessed in C57BL/6 and TRPV1 knockout mice exposed to intensified social stress using conscious cystometry, ex vivo afferent nerve recordings, and histology. Intensified social stress increased void volume, intermicturition interval, bladder volume, and bladder wall collagen content in C57BL/6 mice, indicative of bladder wall remodeling and underactive bladder. However, afferent nerve activity was unchanged and unaffected by the TRPV1 antagonist capsazepine. Interestingly, all indices of bladder function were unchanged in TRPV1 knockout mice in response to social stress, even though corticotrophin-releasing hormone expression in Barrington's Nucleus still increased. These results suggest that TRPV1 channels in the periphery are a linchpin in the development of stress-induced bladder dysfunction, both with regard to increased sensory outflow that leads to overactive bladder and bladder wall decompensation that leads to underactive bladder. TRPV1 channels represent an intriguing target to prevent the development of stress-induced bladder dysfunction in children.