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Aims: The integration of artificial intelligence (AI) into functional urology management must be assessed for its clinical utility, but hopefully will change, perhaps to revolutionize the way LUTD and other conditions are assessed, the aim being to offer patients more rapid and effective management which enhances patient outcomes. The aim of this proposal, discussed at the ICI-RS annual meeting, is to evaluate the available evidence on AI and the way it might change the approach to urodynamic (UDS) diagnoses, including overactive bladder syndrome (OAB), and perhaps other LUTDs such as bladder outflow obstruction., Methods: A compendium of discussion based on the current evidence related to AI and its potential applications in UDS and OAB., Results: AI-powered diagnostic tools are being developed to analyze complex datasets from urodynamic studies, imaging, and other diagnostic tests. AI systems can leverage large volumes of clinical data to recommend personalized treatment plans based on individual patient profiles to optimize surgical procedures, enhance diagnostic precision, tailor the therapy, reduce the risk of complications, and improve outcomes. In the future, AI will be able to provide tailored counseling regarding the outcomes and potential side effects of drugs and procedures to a given patient., Conclusion: AI's role in functional urology has been poorly investigated, and its implementation across several areas may improve clinical care and the pathophysiological understanding of functional urologic conditions., (© 2024 Wiley Periodicals LLC.)

Introduction: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No approved therapies have been proven to augment the strength of a detrusor voiding contraction., Methods: This subject was discussed by a think-tank at the International Consultation on Incontinence- Research Society (ICI-RS) meeting held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This first part discusses molecular and stem cell therapies targeting the urinary bladder and the neural axis., Results: Senescence of the urothelium and extracellular ATP acting through P2X3 receptors might be important in detrusor underactivity. Several molecules such as parasympathomimetics, acotiamide, ASP8302, neurokinin-2 agonists have been explored but none has shown unequivocal clinical benefit. Different stem cell therapy approaches have been used, chiefly in neurogenic dysfunction, with some studies showing benefit. Molecular targets for the neural axis have included TRPV-4, Bombesin, and serotoninergic receptors and TAC-302 which induces neurite growth., Conclusions: Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive., Clinical Trial Registration: Not necessary. Not a clinical trial., (© 2024 Wiley Periodicals LLC.)

Introduction: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No clinical therapy has been proven to augment the strength of a detrusor contraction., Methods: This subject was discussed at a think-tank at the International Consultation on Incontinence-Research Society (ICI-RS) held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This second part discusses the role of electrical stimulation therapies, treatment of bladder outlet obstruction, constipation, and pelvic floor disorders, in the enhancement of strength of a detrusor contraction., Results: Electrical stimulation therapies, specifically sacral neuromodulation, have long been used in the salvage of patients with refractory nonobstructive voiding dysfunction. Clinical improvements can be noted in men following bladder outlet resistance reduction surgery especially, though not limited to those with demonstrable obstruction. Some patients may also show improvement with pelvic floor relaxation therapies and constipation care. However, there is a lack of high-quality urodynamic data to demonstrate an improvement in the strength of a detrusor contraction with these therapies. The think-tank recommends standards for future clinical studies examining treatments aimed at improving an underactive detrusor., Conclusions: Studies need to examine whether clinical improvement following treatment of patients with an underactive detrusor is associated with improvement in strength of the detrusor contraction. New therapeutic options should apply specified standards for assessing and reporting the impact on detrusor contraction., (© 2024 Wiley Periodicals LLC.)

Aims: To address the predictive factors of a successful voiding after bladder outflow resistance reduction surgery (BORRS) in men presenting with acute or chronic urinary retention (UR)., Methods: A think tank (TT) of ICI-RS was gathered in 2023, Bristol, UK, to discuss several aspects of the problem, such as the pathophysiology of UR, the clinical and urodynamic evaluation of men with UR and whether it is possible to predict which men will be able to successfully void after treatment with contemporary surgical options., Results: The TT agreed that successful voiding after BORRS depends on several factors but that a strong recommendation cannot be made regarding preoperative evaluation and whether there are predictive factors of success because of the heterogeneity of patients and methodology in published trials. The diagnosis of obstruction in men with UR may be challenging when there is apparent reduced detrusor contraction during urodynamic studies. Even in the absence of bladder contractility there is documentation of such cases that have voided adequately after BORRS. Still, detrusor underactivity and inadequate relief of prostatic obstruction are the main causes of an unsuccessful voiding after BORRS. Conventional resection and enucleation methods remain the most successful surgeries in relieving UR in men, whereas the efficacy of minimally invasive surgical treatments needs to be assessed further., Conclusion: Research is needed to understand the pathophysiology of UR and the predictors of successful voiding after different types of BORRS in men with UR., (© 2024 Wiley Periodicals LLC.)

Aims: Lower urinary tract symptoms (LUTS) persist in up to 50% of patients after bladder outflow resistance reduction surgery (BORRS) in men. Our think tank aims to address the predictive factors for persistent LUTS after BORRS and to propose the recommendations for future research to enable improved better patient counseling and selection by more accurate prediction of treatment outcome., Methods: A think tank of ICI-RS gathered in 2023, Bristol, UK, to discuss the pre and postsurgical clinical and urodynamic evaluation of men undergoing BORRS and whether it is possible to predict which men will have persistent LUTS after BORRS., Results: Our think tank agrees that due to the multifactorial, and still not fully understood, etiology of male LUTS it is not possible to precisely predict in many men who will have persistent LUTS after BORRS. However, severe storage symptoms (overactive bladder, OAB) in association with low volume and high amplitude detrusor overactivity and low bladder capacity in preoperative urodynamics, increase the likelihood of persistent OAB/storage symptoms after BORRS. Furthermore, patients who are clearly obstructed and have good bladder contractility on preoperative pressure flow studies do better postoperatively compared to their counterparts. However, the benefit of pressure flow studies is decreased in patients who do not acceptably void during the study. Poor voiding after BORRS may occur due to persistent obstruction or detrusor underactivity., Conclusion: Future research is needed to increase our understanding of why male LUTS persist after surgery, and to enable better patient selection and more precise patient counseling before BORRS., (© 2024 Wiley Periodicals LLC.)

Introduction: Overactive bladder (OAB) and underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction., Objectives: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment., Methods: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU using urodynamic tests, functional neuro-imaging, urinary markers, and microbiome., Results and Conclusions: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract (LUT) symptoms, such as OAB and UAB. The intricate interplay between the LUT and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach., (© 2024 Wiley Periodicals LLC.)

Aims: To address how invasive therapies for benign prostatic obstruction (BPO) have been evaluated, what their effect is on BPO, if they can prevent progression to BPO and how new therapies need to be evaluated before implementation into clinical practice., Methods: The think tank conducted a literature review and looked at the previous and current American Urological Association, European Association of Urology and the International Consultation on Urological Diseases guidelines to see what procedures have been used to treat BPO. They then assessed whether trials have been conducted before implementation of the procedures and whether they have been compared to a "gold" standard treatment. The use of urodynamics has also been addressed in the think tank in relation the clinical trials as well as terminology., Results: Guidelines vary in the use of terminology when it comes to BPO with some continuing to use the term benign prostatic hyperplasia (BPH). There are several procedures for example, TUNA, which have become obsolete although continues to be mentioned in the guidelines until recently. Majority of procedures have been introduced without comparing to "gold" standard treatment and without any long-term data. There continues to be many unknowns with regard to the success of some of the BPO procedures and why some of the adverse events develop., Conclusion: There needs to be more robust long-term clinical trials conducted of new BPO therapies, with men who have both lower urinary tract symptoms and urinary retention, before introduction into clinical practice., (© 2023 Wiley Periodicals LLC.)

Introduction: Overactive bladder (OAB) and Underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction., Objectives: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment., Methods: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU investigating metabolic, neurogical, psychological and gastrointestinal aspects with the aim to personalize the treatment., Results and Conclusions: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract symptoms, such as OAB and UAB. The intricate interplay between the lower urinary tract and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach., (© 2024 Wiley Periodicals LLC.)

Aim: The aim of this systematic review is to assess urinary biomarkers studied in children with neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD)., Materials and Methods: The systematic review was conducted in accordance with the PRISMA guidelines. The screening was performed on PUBMED without any publication date limitation. Only original articles were included. Parameters related to the following topics were obtained: study design, characteristics of participants, number of participants, age, control group, types of biomarkers, measurement technique in urine, subgroup analysis, urodynamic findings, and outcome. Dutch Cochrane Checklist (DCC) and level of evidence by EBRO platform were used for quality assessment. Meta-analysis was performed with the Comprehensive Meta-Analysis Version 4 program., Results: A total of 494 studies were screened and 16 studies were included. 11 (68.75%) were conducted in children with non-neurogenic LUTD and 5 (31.25%) neurogenic LUTD. Nerve growth factor (NGF) was evaluated in 12 studies, brain-derived neurotrophic factor (BDNF) in 5, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in 2, transforming growth factor beta-1 (TGF Beta-1) in 2, neutrophil gelatinase-associated lipocalin (NGAL) in 1, and Aquaporin-2 in 1. According to DCC, 10 (62.5%) articles were evaluated on 4 (37.5%) items and 4 articles on 5 items. The average score was 3.91+/-0.56. The level of evidence was found as B for 13 (81.25%) articles and C for 3 (18.75%). In meta-analysis, urinary NGF levels in children with non-neurogenic LUTS were significantly higher than in the healthy control group (Hedges's g = 1.867, standard error = 0.344, variance = 0.119, p = 0.0001)., Conclusion: Urinary biomarkers are promising for the future with their noninvasive features. However, prospective studies with larger sample sizes are needed to better understand the potential of urinary biomarkers to reflect urodynamic and clinical findings in children with LUTD., (© 2024 Wiley Periodicals LLC.)

Aim: Antimuscarinics and the β3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α 1 -adrenoreceptor antagonists (α 1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α 1 -blocker plus mirabegron with an α 1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations., Methods: Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α 1 -blocker plus OAB agent with an α 1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Q max ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis., Results: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α 1 -blocker plus mirabegron and α 1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α 1 -blocker plus mirabegron group compared with the α 1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Q max . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α 1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation., Conclusion: This systematic review and meta-analysis showed that an α 1 -blocker plus mirabegron and an α 1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Aim: The purpose of our study was to evaluate the relationship of urinary brain-derived neurotrophic factor (BDNF), adenosine triphosphate (ATP), matrix metallopreteinase-2 (MMP-2) with urodynamic findings and upper urinary tract deterioration (UUTD) in children with myelodysplasia., Materials and Methods: Children with myelodysplasia evaluated in outpatient clinic between 2022 and 2023 were included. All patients underwent urinary ultrasonography, voiding cystourethrography, urodynamics, and DMSA scintigraphy. Urine samples were collected before urodynamics. Control urine was collected from 10 healthy children. Urinary biomarker values of patients and controls were compared, and subgroup analysis was performed., Results: The median age of 40 children (26 girls) included in the study was 108 (8-216) months, and the control group (six girls) was 120 (60-154) (p = 0.981). Urinary BDNF, MMP-2, and ATP were found to be significantly higher in children with myelodysplasia compared to the control (p = 0.007, p = 0.027, p = 0.014, respectively). The three biomarker values were similar in children with bladder compliance below or above 10 cmH2O/mL (p = 0.750, p = 0.844, p = 0.575). No difference was found in terms of UUTD in all three biomarkers (p = 0.387, p = 0.892, p = 0.705). A negative correlation was found between urinary ATP and compliance (p < 0.05)., Conclusion: In this study, all three biomarkers were found to be higher in children with myelodysplasia than in controls. There was a negative correlation between urinary ATP and compliance. Urinary biomarkers may contribute the follow-up of children with neurogenic lower urinary tract deterioration in future with their noninvasive features. However, the lack of standardization and the inability to reliably predict risky groups are important shortcomings of urinary biomarkers., (© 2023 Wiley Periodicals LLC.)

Aims: Since formal evidence demonstrating the value of urodynamic studies (UDS) in functional urology remains elusive, we aimed to consider how best to design robust research for this purpose in female urinary incontinence., Methods: An expert group was convened to debate the following considerations: (a) precedents for formally proving the value of a gold standard diagnostic test, (b) key research principles, (c) defining a study population, (d) selecting endpoints, (e) defining interventional and controls arms, (f) blinding, (g) powering the study, and (h) duration of follow-up. In each case, we considered the strengths and weaknesses of different approaches in terms of scientific validity, ethical acceptability, practicality, and likelihood of bias., Results: We agreed that unlike evaluating therapies, attempting to judge the value of a diagnostic test based on eventual treatment success is conceptually flawed. Nonetheless, we explored the design of a hypothetical randomized controlled trial for this purpose, agreeing that: (1) the study population must sufficiently reflect its real-world counterpart; (2) clinical endpoints should include not only continence status but also other lower urinary tract symptoms and risks of management; (3) participants in the interventional arm should receive individualized management based on their UDS findings; (4) the most scientifically valid approach to the control arm-empiric treatment-is ethically problematic; (5) sufficient statistical power is imperative; and (6) ≥ 2 years' follow-up is needed to assess the long-term impact of management., Conclusions: Although a perfect protocol does not exist, we recommend careful consideration of our observations when reflecting on past studies or planning new prospective research., (© 2023 Wiley Periodicals LLC.)

Aim: The aim of the study is to compare the intra- and inter-observer interpretations of the same uroflowmetry study at two different times., Materials and Methods: Two-hundred children with a voided volume of 50% above the expected bladder capacity were included. All traces were asked to be evaluated by 11 observers two times in a time span of 1 month. These observers consist of pediatric urologists (n = 2), pediatric urology fellows (n = 2), urology residents (n = 5), and certified urodynamics nurses (n = 2). Each uroflowmetry was asked to be assessed for three domains: voided volume (VV), detrusor sphincter dyssynergia (DSD), and flow curve pattern (FCP)., Results: Of the 200 patients with a median age of 10 (4-18) years, 128 (64%) were girls and 72 (36%) boys. The maximum flow rate and the median voided volume were found to be 20 (4-61) mL/s and 232 (116-781) mL. The Fleiss' kappa coefficient of VV, DSD, and FCP in the first assessment was 0.510, 0.501, and 0.346. In the second assessment, κ values were 0.530, 0.422, and 0.373. The best-agreed findings were similar at both times. These were found to be low VV (0.602 and 0.626) and intermittent pattern (0.500 and 0.553). Interpreters were found to have a statistically significant difference in agreement with their own interpretation at different times., Conclusion: Both inter- and intra-observer reliability of the agreement point out the problem in the standardization of uroflowmetry. Inter- and intra-observer reliability of uroflowmetry interpretation can be increased by defining precise numbers and numerical algorithms., (© 2023 Wiley Periodicals LLC.)

Aim: We previously reported that some urodynamic parameters change with repetitive filling in children with neurogenic lower urinary tract dysfunction (LUTD). In this study, we aimed to search if three-times repeated filling cystometries (FC) and pressure-flow studies (PFS) would change the urodynamics parameters in children with non-neurogenic LUTD., Materials and Methods: All children with three repeated FC and PFS between June 2017 and December 2018 were included in the study. Urodynamic reports and charts were evaluated retrospectively. The first sensation of bladder filling (FSBF), maximum cystometric capacity (MCC), detrusor pressure at the FSBF (P det.first.sens ), maximum detrusor pressure during filling (P det.fill.max ), presence of detrusor over activity, compliance, maximum urine flow (Qmax), detrusor pressure at the maximum urine flow (PdetQmax), residual urine and presence of detrusor sphincter dyssynergy (DSD) were compared among three-times repeated urodynamic studies., Results: Forty children were included in the study. 27 (67.5%) were girls and 13 (32.5%) were boys. Median age was 9 (3.4-17) years. Indications were LUTD with low grade vesicoureteral reflux in 19 (47.5%), LUTD refractory to conservative management in 13 (32.5%), urinary tract infection with LUTD in 6 (15%) and secondary enuresis in 2 (5%). P det.first.sens , presence of DO, MCC, Qmax, PdetQmax, residual urine, flow pattern, and presence of DSD were comparable in all three repeated tests. The third FC may show decreased filling detrusor pressures and increased compliance with no change on capacity., Conclusion: In children with non-neurogenic LUTD, three-times repeated FC and PFS present comparable results except FSBF, P det.fill.max, and compliance at the third test., (© 2022 Wiley Periodicals LLC.)

Aims: Psychological morbidities play a major role in idiopathic lower urinary tract dysfunction (iLUTD). The aim of the Think Tank (TT) was to discuss the relevance of psychological morbidities in idiopathic LUTD over the life span, including overactive bladder (OAB) or dysfunctional voiding (DV) and methods of assessment., Methods: The paper is based on a selective review of the literature and in-depth discussions, leading to research recommendations regarding the assessment of psychological morbidities in iLUTD on children and adults held during the TT of the International Consultation on Incontinence Research Society in 2019., Results: Psychological comorbidities affect the health behaviors and treatment outcomes in patients with iLUTD. Both clinically relevant comorbid mental disorders, as well as subclinical psychological symptoms have a major impact and negatively influence incontinence treatment. Research is needed to elucidate mechanisms underlying iLUTD and psychological comorbidities. Clinical studies are needed to determine how perception generation and cognition impacts on the relationship of urinary perceptions, symptoms, and objective urodynamic function. Due to high psychological comorbidity rates, screening with validated, generic questionnaires for emotional and behavioral disorders in children with nocturnal enuresis, daytime urinary incontinence, and fecal incontinence is recommended. Brief screening is recommended for all adults with iLUTD, especially with OAB and DV, who are refractory to treatment., Conclusions: Due to the high rate and relevance in clinical practice, screening for psychological comorbidities is recommended for all age groups. The research recommendations of this TT may be followed to improve the assessment of psychological morbidities in iLUTD., (© 2020 Wiley Periodicals, Inc.)

Aims: Chronic urinary retention occurring in young women is poorly understood and a cause may not be found in a majority of cases. Different psychological comorbidities and functional neurological symptom disorders (FNDs) have been reported; however, these have been poorly explored., Methods: At the International Consultation on Incontinence Research Society meeting in 2019, a panel of clinicians generated a proposal to explore the relationship between psychological comorbidities, FNDs, and urinary retention in women with chronic idiopathic urinary retention., Results: Psychological comorbidities such as depression and anxiety, and FNDs such as leg weakness and loss of consciousness, have been reported in women with idiopathic urinary retention. Individuals react differently to physical and emotional stressors, and experimental models have demonstrated a relationship between the stress response and developing urinary retention. Trauma, particularly sexual trauma, may be a shared risk factor for developing psychological comorbidities and urinary retention. Children with voiding postponement often suffer from psychological comorbidities and behavioral disturbances; however, there is no evidence to suggest that this progresses to urinary retention in adulthood. "Psychogenic urinary retention" has been described in the urology and psychiatry literature in the past, and anecdotal cases of successful voiding following psychotherapy have been reported, though the true pathophysiology of this entity is uncertain., Conclusion: Psychological and functional disorder comorbidities are reported in women with chronic urinary retention. The nature of the association between urinary retention and functional neurological disorder comorbidities needs to be further explored in terms of a disorder of bladder-brain interaction., (© 2019 Wiley Periodicals, Inc.)

Aims: To assess the state of technologies for urodynamics that are less invasive than standard cystometry and pressure-flow studies and to suggest areas needing research to improve this., Methods: A summary of a Think Tank debate held at the 2019 meeting of the International Consultation on Incontinence Research Society is provided, with subsequent analysis by the authors. Less-invasive techniques were summarized, classified by method, and possible developments considered. Discussions and recommendations were summarized by the co-chairs and edited into the form of this paper by all authors., Results: There is a full spectrum of technologies available for less-invasive assessment, ranging from simple uroflowmetry through imaging techniques to emerging complex technologies. Less-invasive diagnostics will not necessarily need to replace diagnosis by, or even provide the same level of diagnostic accuracy as, invasive urodynamics. Rather than aiming for a technique that is merely less invasive, the priority is to develop methods that are either as accurate as current invasive methods, or spare patients from the necessity of invasive methods by improving early triaging., Conclusions: Technologies offering less-invasive urodynamic measurement of specific elements of function can be potentially beneficial. Less-invasive techniques may sometimes be useful as an adjunct to invasive urodynamics. The potential for current less-invasive tests to completely replace invasive urodynamic testing is considered, however, to be low. Less-invasive techniques must, therefore, be tested as screening/triaging tools, with the aim to spare some patients from invasive urodynamics early in the treatment pathway., (© 2020 Wiley Periodicals, Inc.)

Several studies indicate that pelvic ischemia and oxidative stress may play a significant role in lower urinary tract dysfunction (LUTD), including detrusor overactivity (DO)/overactive bladder (OAB) and detrusor underactivity (DU)/underactive bladder (UAB). The present article addresses proposal 1: "Are oxidative stress and ischemia significant causes of bladder damage leading to LUTD?" from the 2019 International Consultation on Incontinence-Research Society (ICI-RS) meeting. Bladder ischemia in animals and humans is briefly described, along with the proposed progression from ischemia to LUTD. Bladder ischemia is compared with ischemia of other organs, and the ongoing development of pelvic ischemia animal models is discussed. In addition, the distribution of blood within the bladder during filling and voiding and the challenges of quantification of blood flow in vivo are described. Furthermore, oxidative stress, including potential biomarkers and treatments, and challenges regarding antioxidant therapy for the treatment of LUTD are discussed. Finally, seven critical research questions and proposed studies to answer those questions were identified as priorities that would lead to major advances in the understanding and treatment of lower urinary tract symptoms (LUTS)/LUTD associated with pelvic ischemia and oxidative stress., (© 2020 Wiley Periodicals, Inc.)

Aims: Lower urinary tract symptoms (LUTS) can be classified into symptom syndromes based on which symptoms are predominant. Overactive bladder (OAB) syndrome, a storage dysfunction, and underactive bladder (UAB) syndrome, a voiding dysfunction, are common syndromes, which urodynamic tests may show to be caused by detrusor overactivity (DO) and detrusor underactivity (DU), but can also be associated with other urethro-vesical dysfunctions. Sometimes OAB and UAB can coexist in the same patient and, if so, need a specific approach beyond treatment of the single and apparently opposing syndromes., Methods: During its 2019 meeting in Bristol, the International Consultation on Incontinence Research Society held a literature review and expert consensus discussion focused on the emerging awareness of the coexisting overactive-underactive bladder (COUB)., Results: The consensus considered whether COUB is the combination of OAB and UAB syndromes, or a real unique clinical syndrome in the same patient, possibly with a common etiology. Definitions, pathophysiology, diagnosis, and treatment were discussed, and high-priority research questions were identified., Conclusions: COUB (with or without urodynamic evidence of DO and DU) may be considered a real clinical syndrome, because it differs from single OAB and UAB, and may not be the combination of both syndromes. Urodynamic tests may be necessary in unclear cases or in cases not responding to initial treatment of the most troublesome symptoms. It is pivotal to define the evolution of the syndrome and the characteristic population, and to recognize predictive or phenotyping factors to develop a specific approach and adequate outcome measures., (© 2020 Wiley Periodicals, Inc.)

Aim: To explore the effects of experimental subarachnoid hemorrhage (SAH) on rabbit urinary bladder and to assess the potential protective effects of hyperbaric oxygen therapy (HBOT)., Methods: A total of 15 male New Zealand white rabbits were divided randomly to one of three groups: group I was spared as the control group (n = 5), group II was exposed to SAH, received no treatment, and acted as the SAH group (n = 5) and group III was exposed to SAH and received five sessions of HBOT (started 12 hours after SAH induction and was given twice daily for the first 2 days and once on the third day) and acted as the treatment group (n = 5). At 72 hours after the SAH induction, bladders from all animals were removed for in vitro organ bath experiments and biochemical analyses., Results: İsometric tension studies revealed that compared to group I, the contractile responses of the strips to carbachol in group II were significantly decreased whereas HBOT restored the contractile responses (P < .05). Caspase-3 and nitric oxide synthase (NOS) activities of bladder tissues were significantly increased in group II when compared with group I, whereas caspase-3 and NOS activities were significantly decreased in the tissues of group III (P < .01)., Conclusions: Subarachnoid hemorrhage stimulates apoptosis of the rabbit bladder and impairs the contractile response of the rabbit bladder to carbachol. HBOT creates a protective effect in rabbit bladder tissues and restores SAH-induced changes., (© 2020 Wiley Periodicals LLC.)

Background: This paper summarises the discussion in a think tank at the International Consultation on Incontinence-Research Society (ICI-RS) 2018 about the treatment of bladder pain syndrome., Aims: To review the treatments of bladder pain syndrome from behavioural treatments to surgical interventions., Materials and Methods: Review the literature in the light of the think tank discussions., Results: All guidelines recommend different levels of treatment starting with conservative behavioral treatments then introducing oral treatments followed by intravesical instillations. If these treatments fail then more invasive treatments such as botulinum toxin injections, neuromodulation, or surgery could be suggested., Conclusion: Unfortunately for all treatments, the numbers are limited and, therefore, the evidence base is not strong. Further suggestions for research are suggested., (© 2019 Wiley Periodicals, Inc.)

Background: This paper summarizes the discussion in a think tank at the ICI-RS 2018 about the diagnosis of bladder pain syndrome (BPS)., Aims: To review the guidelines, investigations and subtypes of BPS., Materials and Methods: Review of literature in the light of the think tank discussion., Results: All guidelines recommend completing history, physical examination, urine analysis, urine culture, and urine cytology to define the BPS phenotype but there are differences on further investigations. In those guidelines which recommend cystoscopy, the identification of Hunner's lesions (HLs) is recommended as this changes the treatment plan and outcome., Conclusion: We propose that the differentiation of Hunner's ulcers is an important step in the assessment of these patients. Further suggestions for research are suggested., (© 2019 Wiley Periodicals, Inc.)

Aims: Dysfunctional voiding (DV) remains a poorly understood and a poorly managed problem, both in children and adults. The Think Tank (TT) discussed how to improve the management of DV in these two different age groups and in transitional care., Methods: During the 2018 International Consultation on Incontinence Research Society held in Bristol, a multidisciplinary TT on DV was created. The presentations and subsequent discussion, leading to research recommendations intended to improve the management of DV in children and adults are summarized., Results: To improve the management of DV in children and adults, the TT panel proposed: (1) to conduct reliable prevalence studies of DV; (2) to perform longitudinal studies to prospectively test the sequence hypothesis by answering the following questions: (a) Which, if any children show a progression from overactive bladder or voiding postponement to DV?; (b) Which children develop each disorder without precursors?; and (c) Is there a continuation of DV from childhood to adulthood, or are adult cases new-onset presentations?; (3) to obtain detailed information regarding psychopathology to understand which comorbid psychological disorders prevail and at which rate, in those suffering DV; (4) to develop and validate diagnostic tools specifically for DV; (5) to better establish urodynamic correlates of DV specific for different age groups; and (6) to generate prospective long-term data regarding the efficacy of different treatment options and management strategies., Conclusions: The future research recommendations of this TT may improve our management of DV in children and adults., (© 2019 Wiley Periodicals, Inc.)

Introduction: Turkish Continence Society aimed to analyze how overactive bladder (OAB) is being managed in routine practice by the urologists in Turkey., Material and Methods: Fourteen urology departments were randomly selected to represent the whole population in this multicenter study. An online data entry and storage software was created for patient recruitment and data assessment. A survey including demographic data, daily habits, lower urinary tract symptoms, and Turkish-validated OAB-V8 and ICIQ-SF questionnaires were completed by all patients. Second part of the survey, including the questions about clinical evaluation and management of the patient, was completed by the treating physician., Results: A total of 507 patients (394 female and 113 male) were included. Behavioral therapy was recommended to 73.2% of female and 81.4% of male patients although bladder diary was requested for 59.5% and 52.7% of the female and male patients, respectively. In the first visit, 86.1% of the female and 89.3% of the male patients were given antimuscarinics (P = .431). Antimuscarinic-related side effects occurred in 94.9% and 88.9% of the female and male patients, respectively (P = .937). However, the rate of medical treatment change due to antimuscarinic-related side effects was only 1.7% in female and 4.8% in male patients at the end of 4 months., Conclusions: Behavioral therapy and antimuscarinics were the preferred initial treatment modalities of OAB in concordance with the guidelines. Despite guideline recommendations, bladder diaries were not utilized in half of the patients. Insufficient efficacy appeared to be the main reason for treatment modification., (© 2019 Wiley Periodicals, Inc.)

Aims: Energy-based devices using radiofrequency and laser technologies have gained popularity as therapies for vaginal atrophy, urinary incontinence, and vaginal prolapse. They have been promoted by cosmetic and aesthetic industries for vaginal "laxity" and vaginal "rejuvenation," both of which are undefined conditions and terms. This article aims to review the current available literature and its quality on this emerging technology., Methods: An international panel of gynaecologists, urogynaecologists, and urologists undertook a review of the available published literature, identifying articles, guidance, and society statements on the use vaginal energy-based devices., Results: There is currently no formal guidance for the use of vaginal energy based therapies. No randomized controlled trials have been published. No comparative studies to existing treatment has been carried out. Studies suggest that vaginal laser can be used in the treatment of vaginal prolapse or "vaginal laxity" and stress urinary incontinence with no quality evidence supporting the use of the therapy for vaginal atrophy or lichen sclerosis., Conclusions: This international group propose that whilst there remains a paucity of good quality data describing the safety, benefits, and appropriate use of vaginal radiofrequency or laser treatments in gynaecology and urogynaecology, a consensus best practice document by an established scientific community needs to be developed., (© 2019 Wiley Periodicals, Inc.)

Background: The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology is controversial., Aims: In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review., Materials & Methods: This project was developed between January and September 2018. The development of this document followed the ICS White Paper Standard Operating Procedures., Results: Most of the available studies are limited by their design; for example they lack a control group, patients are not randomized, follow up is short term, series are small, LASER is not compared with standard treatments, and studies are industry sponsored. Due to these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration following LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women., Discussion: The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, while short-term complications seem to be uncommon, data concerning long-term outcomes are lacking., Conclusion: At this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit., (© 2019 Wiley Periodicals, Inc.)

Aims: The Think Tank aimed to discuss the pitfalls and advantages of current definitions in terms of research and management of underactive bladder (UAB). UAB broadly defines a symptom complex of bladder emptying problems and does not indicate a specific pathology. Detrusor underactivity (DU) is a urodynamic diagnosis from pressure-flow studies. The correlation of UAB with DU remains to be precisely determined., Methods: The presentations and subsequent discussion, leading to research recommendations during the Think Tank of the International Consultation on Incontinence Research Society in Bristol, 2017, are summarized., Results: To develop more specific individualized management strategies, the Think Tank panel proposed (i) that, since defining a single type of index patient to represent all UAB will not fulfill all clinical research needs, several index patients should be defined by phenotyping of patients with UAB, including, children, young men and women, elderly male and female patients with co-existing DU and detrusor overactivity, and neurological patients with UAB; (ii) prospective longitudinal studies to assess the natural history of UAB, in the different target populations, based on different UAB phenotypes, should be initiated; (iii) DU should be precisely defined by urodynamic parameters; and (iv) work to develop validated specific questionnaires combined with non-invasive tests for screening, diagnosis and follow up, needs to be continued., Conclusions: The precise relationship of UAB to DU remains to be defined. Phenotyping patients with UAB/DU, performing prospective trials of natural history, and developing symptom questionnaires and diagnostic investigations will improve our ability to identify and treat UAB/DU., (© 2018 Wiley Periodicals, Inc.)

Aims: This article focuses on how, and if, urodynamics can help to identify which kidneys are in danger of deteriorating in function and also gives recommendations for future research., Methods: At the International Consultation on Incontinence-Research Society (ICI-RS) in 2017, a multi-disciplinary group presented a literature search of what is known about the utility of Urodynamics, including ambulatory, and 24 h monitoring, in predicting upper urinary tract damage in neuro-urological patients and other lower urinary tract dysfunctions. Wider discussions regarding knowledge gaps, and ideas for future research ensued and are presented in this paper along with a review of the evidence., Results: The current treatment strategy both in congenital and acquired neurogenic bladder is rather aggressive and successful when addressing hazards to kidney function. This article has highlighted uncertainties concerning the use of 40 cmH2O DLPP and even the lower value of 20. The current literature suggests that patients with spina bifida and those with spinal cord injury have a higher risk of developing upper urinary tract damage and kidney function impairment than those with multiple sclerosis., Conclusions: Future research should focus on less invasive methods to assess the risk to the upper and lower urinary tract such as urine and serum measurements of cytokines that are involved in the pathophysiology of urinary tract impairment., (© 2018 Wiley Periodicals, Inc.)

Introduction: A cough stress test (CST) is recommended in the evaluation of the uncomplicated female patient with the complaint of stress urinary incontinence (SUI) to identify the sign of SUI, and is often used as an outcome measure following SUI treatment. However, there has been no standardization of the performance or reporting of CST. A working group of the International Continence Society (ICS) has developed an educational module, comprising a Powerpoint™ presentation and evidence base manuscript, to instruct on the performance, interpretation, and reporting of the CST in a standardized manner: the ICS-Uniform Cough Stress Test (ICS-UCST)., Methods: The working group performed a PUBMED literature search of articles (observational/experimental and reviews) published prior to 2017 that mentioned a CST. The evidence base examined various variables in performing a CST as well as sensitivity/specificity and positive/negative predictive values of CST., Results: The variables involved in performing/interpreting an ICS-UCST include: patient positioning, degree of bladder filling, number, and forcefulness of coughs, and method of SUI detection. For the ICS-UCST it is recommended that the patient be in a supine/lithotomy position with 200-400 mL of fluid in the bladder. She coughs forcefully 1-4 times and the examiner directly visualizes the urethral meatus for the presence of leakage. Leakage of fluid from the urethral meatus coincident with/simultaneous to the cough(s) is considered a positive test., Conclusion: This module provides instructions to educate a uniform CST (the ICS-UCST), with the aim of improving the clinical practice of cough stress testing in female patients with urinary incontinence., (© 2018 Wiley Periodicals, Inc.)

Aims: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia., Methods: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA). Urine samples of each child were collected before and after BoNT-A injections, specifically at the first and third postoperative months. Urine samples were analyzed with ELISA method and NGF, TGF-Beta-1, and TIMP-2 levels were measured. Urine marker levels and clinical findings were assessed for statistical significance with Wilcoxon Signed Ranks Test and Friedman Test., Results: A total of 15 children (5 boys and 10 girls) were assigned as the study group. Mean age of the patients was 7.1 ± 2.5 years (range 2.5-11). A statistically significantly decline was observed in urinary TGF-Beta-1 and NGF levels following BoNT-A injections, compared to the preoperative levels (P < 0.05). TIMP-2 levels also tend to decrease following BoNT-A injections but this was not statistically significant compared to the preoperative levels., Conclusion: This preliminary study, suggests urinary TGF-Beta-1 and NGF as a potent marker in children with NDOA, as they decline following BoNT-A injection. Further studies are needed in identifying their special role in assessing treatment success after invasive interventions., (© 2017 Wiley Periodicals, Inc.)

Aims: Our aim was to investigate the effects of doxazosin, sildenafil, and their combination on bladder tissue contractility and adrenergic receptor (AR) and inducible nitric oxide synthase (iNOS) expression utilizing a male rat model of partial urethral obstruction (PUO)., Methods: Thirty male Sprague Dawley rats were divided into five groups. Except the SHAM group, all animals in remaining four groups underwent surgery for PUO. No further treatment was given to the first group (NT group). Remaining three groups received 6 weeks of treatment with 20 mg/kg doxazosin (D group), 20 mg/kg sildenafil (S group), 20 mg/kg doxazosin, and 20 mg/kg sildenafil combination (DS group), respectively via oral gavage. Then, bladder strips were harvested from each animal for isometric tension studies and for real time polymerase chain reaction studies of both AR subtypes and iNOS mRNA., Results: Contractile responses to carbachol and electrical field stimulation at various concentrations/frequencies showed a significant increase after PUO. Any treatment helped to normalize these increased responses. Alpha 1a and 1d AR subtype expressions were found to be down- and up-regulated, respectively, in every group with PUO, compared to SHAM group. iNOS expression was similar in D and NT groups and significantly increased in S and DS groups., Conclusions: Contractile changes of rat bladder tissue due to PUO were prevented by sildenafil or doxazosin alone or in combination where combination treatment did not provide any additional advantage. Further studies are needed to clarify the role of phosphodiesterase inhibitors and combination treatment in the treatment of LUTS., (© 2016 Wiley Periodicals, Inc.)

Purpose: The purpose of this study, is to find out the most accurate cut-off level for the detrusor leak point pressure (DLPP) in terms of upper urinary tract (UUT) protection in a cohort of children with myelodysplasia., Materials and Methods: One hundred and ninety-three children with myelodysplasia were included in the study based on the availability of urological evaluation at age of 3 years. Children were assigned to one of two groups-those who had UUT damage at age 3 (group 1, n: 70) and those without UUT changes (group 2, n: 123), and compared., Results: Urological follow-up data revealed higher incidences of febrile urinary tract infections and secondary tethering of the spinal cord in group 1. No statistically significant difference was determined between group 1 and group 2 in terms of DLPP values (median 42.5 vs. 39.5 cm H 2 O, respectively, P = 0.087). Analysis of different cut-off values showed that DLPP above 20 cm H 2 O had a higher sensitivity for UUT damage (91.4%). A normal UUT was found in 56.5% and 62.2% of children with DLPP between 20 and 40 cm H 2 O, and with DLPP over 40 cm H 2 O, respectively., Conclusions: Present study showed that more than half of the children with myelodysplasia had normal UUT function even with a DLPP of 40 cm H 2 O and over. Thus, DLPP, is not the sole decision making parameter to rely for more invasive therapies in children with myelodysplasia. On the other hand, a DLPP cut-off value of 20 cm H 2 O showed a higher sensitivity to predict UUT damage instead of 40 cm H 2 O. Neurourol. Urodynam. 36:759-763, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Aims: This manuscript serves as a scientific background review; the evidence base, for the presentation made available on ICS website to summarize current knowledge and recommendations for the measurement and use of the DLPP., Methods: This review has been prepared by a Working Group of The ICS Urodynamics Committee. The methodology used included comprehensive literature review, consensus formation by the members of the Working Group, and review by members of the ICS Urodynamics Committee core panel., Results: DLPP has been recommended and utilized in the urodynamic evaluation of N-LUTD for many years, but it lacks standardization and there are numerous pitfalls in its measurement. EFP and LPP associated with N-DO are frequently and mistakenly reported as DLPP. The information that high DLPP predicts UUTD originates from retrospective cohort studies of a low level of evidence (LoE 3). Existing data confirm that patients with lower DLPP do better than patients with higher DLPP in terms of their upper urinary tract. However, there appears to be no reliable 'safe/no safe' cut-off for DLPP since there are other urodynamic factors that influence UUTD such as bladder compliance and more., Conclusion: Although higher DLPP is associated with a greater risk of UUTD, there is no reliable cut-off level to undoubtedly discriminate the risky group, including the traditional cut-off level of 40 cm H 2 O. Therefore, DLPP should not be used as the sole urodynamic parameter. Future research should be directed to standardization of the technique and better classification of DLPP cut-offs in N-LUTD. Neurourol. Urodynam. 36:259-262, 2017. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Aims: Since lower urinary tract dysfunction (LUTD) related to multiple sclerosis (MS) has a different behavior pattern than other types of neurogenic voiding dysfunction, we aimed to prepare a national consensus report for the management of LUTD due to multiple sclerosis in light of available literature., Methods: A search of available databases yielded an evidence base of 125 articles after the application of inclusion/exclusion criteria. When sufficient evidence existed, recommendations A (high), B (moderate), or C (low) were made according to the strength of evidence; recommendation D was provided when insufficient evidence existed., Results: Available data did not support the use of invasive urodynamics in the initial evaluation of patients with MS and LUTD. Clinical studies on the safety and efficacy of antimuscarinics and alpha-blockers in these patients were scarce and low quality. Desmopressin could be used in MS-related overactive bladder symptoms owing to its short-term effects as an adjunctive treatment. Intravesical botulinum toxin type A treatment in patients with MS and detrusor overactivity was recommended in cases of medical treatment failure or severe side effects due to antimuscarinics. Pelvic floor rehabilitation together with neuromuscular electrical stimulation was also recommended as it increased symptomatic treatment success. This systematic review was not able to find any evidence-based cut off post-void residual value for the recommendation to start clean intermittent catheterization in MS-related LUTD., Conclusions: Patients with MS and LUTD could be best managed through the use of this consensus report., (© 2013 Wiley Periodicals, Inc.)

Aims: We evaluated effects of BoNT-A injections on bladder function and histomorphology in a male-rat-overactive-bladder model, created by partial urethral obstruction., Methods: A total of 45 male Sprague-Dawley rats were separated into 5 groups. Partial urethral obstruction (PUO) was created in all rats except the control group. At the 6th week after PUO, intradetrusor injections of 50 µl of saline (2 sham groups) or 50 µl BoNT-A (2 treatment groups) was performed. Treatment and sham groups were studied 5 and 30 days after injection and neuropharmacological and histomorphological findings on bladder tissues were compared to the control group., Results: Bladder muscle hypertrophy and connective tissue increase were detected at 5th and more prominent at 30th day after saline injection. Intradetrusor BoNT-A injection significantly reduced PUO-induced histological changes in the bladder tissue both at 5th and 30th day after injection. At 5th day after saline injection, a significantly increased contractile response to electrical field stimulation (EFS) and carbachol were recorded in the saline group and this effect disappeared at 30th day. There was no statistically significant difference between BoNT-A and control groups in terms of contractile responses to EFS and carbachol, both at 5th and 30th days., Conclusion: Partial urethral obstruction induces increased bladder tissue contractile responses to neurogenic and pharmacological stimulation and intradetrusor BoNT-A injections decrease these responses at 5th days after injection. As the unique finding of this study, intradetrusor BoNT-A injections appear to decrease bladder fibrosis secondary to PUO in the male rat model., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims: Abdominal leak point pressure (ALPP) measurements in female SUI may show variability because of the variations in measurement protocols. The aim of this study is to investigate the effect of cystometry catheter on ALPP measurement and compare the sensitivity of Valsalva and cough maneuvers in demonstrating urinary leakage in women complaining of SUI., Methods: In this prospective study, 194 female patients complaining of SUI underwent urodynamic studies using a 8-fr urethral cystometry and 10-fr rectal catheter. At the cystometric capacity, Valsalva and then cough ALPP was measured in semi-supine position. The same procedure was repeated after removing the cystometry catheter. The results were analyzed with Chi-square and student's t-test where appropriate., Results: In the whole study group, more patients lost urine when coughing than with Valsalva (122 vs. 93, P = 0.0013). One hundred thirty-seven (71%) women revealed a positive stress test both with and without catheter where the presence of the catheter was associated with significantly higher cough and Valsalva ALPP. In this subgroup of 137 patients, cough-induced ALPP values were significantly higher than Valsalva ALPP. Another 29 (15%) women leaked only after the removal of the catheter. Urine leakage could not be demonstrated in the rest of 28 patients (14%) with any maneuver even without catheter in the semi-supine position., Conclusion: Cough-induced stress test is significantly more sensitive than Valsalva to demonstrate urinary leakage. Cystometry catheter significantly increases cough and Valsalva ALPP whereas stress test can be false negative due obstructive effect of cystometry catheter in a group of patients. Stress test may be negative in the semi-supine position in about 14% of women complaining of SUI., ((c) 2009 Wiley-Liss, Inc.)

Aims: To investigate the effects of cold-induced stress on bladder tissue histomorphology and contractility in a rat model., Methods: Eighteen male Sprague-Dawley rats were divided into three groups: Control group (Group 1), acute cold-stress group (Group 2, kept at +4 degrees C for 8 hr), and chronic cold-stress group (Group 3, kept at +4 degrees C for 4 hr/day for 21 days). At the end of protocols, histological examination of general bladder tissue morphology and determination of mast cells was performed. Organ bath studies were conducted at basal tone where contractile responses to 120 mM potassium, electrical field stimulation (EFS), and carbachol (10(-9)-10(-4) M) were assessed. Relaxation responses to EFS, isoproterenol (10(-9)-10(-4) M), papaverine plus sodium nitroprusside (10(-4) M each) were recorded in carbachol pre-contracted strips. All data were compared by one-way ANOVA test., Results: Group 1 revealed regular bladder mucosa with intact urothelium. Groups 2 and 3 showed degeneration of urothelium with accumulation of neutrophils and significantly increased number of mast cells in both mucosa and muscularis. Mast cell counts were significantly higher in Group 3 compared to Group 2. Contractile responses to 120 mM potassium and EFS were significantly greater in the control group compared to other groups. Carbachol caused dose-dependent contractions that were significantly higher in the control group (at 10(-5), 3 x 10(-5), and 10(-4) M doses). There was no statistical difference between the groups in terms of relaxation responses., Conclusions: In vivo cold exposure induces significant bladder injury and decreased tissue contractility. Mechanistic pathways involved in the response of the urinary bladder to cold-induced stress need further investigation., ((c) 2006 Wiley-Liss, Inc.)

Aims: Previously we showed that ischemia alters bladder smooth muscle contractility in the rabbit. This study investigates the role of urothelium and eicosanoid-release in ischemic bladder smooth muscle instability., Materials and Methods: Male New Zealand white rabbits were divided into treated (n = 12) and age-matched control (n = 10) groups. The treated group underwent balloon endothelial injury of the iliac arteries, and then received 4 weeks of cholesterol diet, followed by 4 weeks of regular diet. The control group received a regular diet for 8 weeks. After 8 weeks, blood flow for both the iliac arteries and the bladder as well as bladder oxygen tension were recorded. In one-half of each ischemic and control bladder, the urothelium was removed. Bladder tissues were processed for organ bath and enzyme-immunoassay (EIA) of prostaglandins (PGs) and leukotrienes (LTs)., Results: A significant decrease in iliac arterial blood flow, bladder wall blood flow, and bladder oxygen tension was found in the treated group. Bladder ischemia increased the frequency and amplitude of baseline spontaneous smooth muscle contractility. Ischemic tissues with urothelium (Uro+) demonstrated significant increases in the contractile response to electrical field stimulation (EFS) and carbachol relative to control Uro+ tissues. Urothelial removal increased smooth muscle contraction in the control tissues but had no significant effect in the ischemic/hypoxic tissues. Contraction of control tissues without urothelium (Uro-) was similar to contraction of ischemic Uro+ tissues. Contractions of ischemic Uro+ and control Uro- tissues were unchanged after treatment with the cyclooxygenase (COX) inhibitor indomethacin, while they were significantly reduced by the 5-lipoxygenase (5-LO) inhibitor NDGA. EIA showed no change in PGs release from the ischemic urothelium, but significant increase in PGF(2-alpha) and thromboxane A(2) release from the ischemic suburothelial tissue. Ischemia increased the release of LTB(4), LTC(4), and LTE(4) from both urothelium and suburothelial tissue., Conclusions: Our studies suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder.