Urinary biomarkers in children with neurogenic and non-neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

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.

Safety and efficacy of an α1 -blocker plus mirabegron compared with an α1 -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis.

AIM: Antimuscarinics and the ß3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -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 α1 -blocker plus mirabegron with an α1 -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 α1 -blocker plus OAB agent with an α1 -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 (Qmax ). 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 α1 -blocker plus mirabegron and α1 -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 α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -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 α1 -blocker plus mirabegron and an α1 -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.

Can we predict whether a man with acute or chronic urinary retention will void after bladder outflow resistance reduction surgery? ICI-RS 2023.

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.

Can we predict and manage persistent storage and voiding LUTS following bladder outflow resistance reduction surgery in men? ICI-RS 2023.

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.

Is it Possible to Regenerate the Underactive Detrusor? Part 2 Electrical Stimulation Therapies, Treatment of Bladder Outlet Obstruction, Constipation, and Pelvic Floor Disorders ICI-RS 2024.

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.

Is It Possible to Regenerate the Underactive Detrusor? Part 1 Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis ICI-RS 2024.

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.

How do we make progress in phenotyping patients with LUT such as OAB and underactive detrusor, including using urine markers and microbiome data, in order to personalize therapy? ICI-RS 2023: Part 1.

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.

How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023-Part 2.

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.

How Can We Show That Artificial Intelligence May Improve Our Assessment and Management of Lower Urinary Tract Dysfunctions?-ICI-RS 2024.

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.

Does Sexual Intercourse Position Have a Role in Occurrence of Coital Urinary Incontinence?

INTRODUCTION AND HYPOTHESIS: This study was aimed at investigating the hypothesis that sexual intercourse positions may have an impact on the occurrence of coital urinary incontinence (CUI) in women. METHODS: This case-control observational study enrolled 360 married, heterosexual, sexually active female participants with CUI. Each patient was evaluated using medical and sexual histories, questionnaires, physical examinations, and laboratory tests, including urodynamics. Participants were asked whether or not their intercourse positions had an impact on the occurrence of their CUI. Patients with intercourse position-dependent CUI were included in group 1, and those independent of it were allocated to group 2. The clinic and laboratory findings of the patient groups were compared. RESULTS: The patients' mean age was 47.24 ± 0.57 years. Of these women, 28.9% (n = 104) were in group 1, and 71.1% (n = 256) were in group 2. Group 1 had a lower mean age, body mass index, Charlson comorbidity index, number of urinary incontinence episodes, severity of CUI and incontinence, and pad weight than group 2 (p < 0.05). The rates of detrusor overactivity and penetration type of CUI were higher in group 1 than in group 2 (p < 0.0009, p = 0.009 respectively). According to logistic regression analysis, the likelihood of sexual position-related CUI was 3.5 times higher in women with detrusor overactivity. CONCLUSIONS: In certain patients, intercourse position is associated with the occurrence of CUI. This condition seems to be related to detrusor overactivity and is inversely associated with incontinence severity. However, further studies are necessary to explain this phenomenon.

Evaluation of new treatments for benign prostatic obstruction: ICI-RS 2023.

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.

Consistency of uroflowmetry analysis in children among observers.

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.

The association of urinary BDNF, ATP, and MMP-2 with bladder compliance in children with myelodysplasia.

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.

How should prospective research be designed to legitimately assess the value of urodynamic studies in female urinary incontinence?

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.

The results of three times repeated filling cystometry and pressure flow studies in children with non-neurogenic lower urinary tract dysfunction.

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 (Pdet.first.sens ), maximum detrusor pressure during filling (Pdet.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%). Pdet.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, Pdet.fill.max, and compliance at the third test.

Molecular Regulation of Concomitant Lower Urinary Tract Symptoms and Erectile Dysfunction in Pelvic Ischemia.

Aging correlates with greater incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the male population where the pathophysiological link remains elusive. The incidence of LUTS and ED correlates with the prevalence of vascular risk factors, implying potential role of arterial disorders in concomitant development of the two conditions. Human studies have revealed lower bladder and prostate blood flow in patients with LUTS suggesting that the severity of LUTS and ED correlates with the severity of vascular disorders. A close link between increased prostatic vascular resistance and greater incidence of LUTS and ED has been documented. Experimental models of atherosclerosis-induced chronic pelvic ischemia (CPI) showed increased contractile reactivity of prostatic and bladder tissues, impairment of penile erectile tissue relaxation, and simultaneous development of detrusor overactivity and ED. In the bladder, short-term ischemia caused overactive contractions while prolonged ischemia provoked degenerative responses and led to underactivity. CPI compromised structural integrity of the bladder, prostatic, and penile erectile tissues. Downstream molecular mechanisms appear to involve cellular stress and survival signaling, receptor modifications, upregulation of cytokines, and impairment of the nitric oxide pathway in cavernosal tissue. These observations may suggest pelvic ischemia as an important contributing factor in LUTS-associated ED. The aim of this narrative review is to discuss the current evidence on CPI as a possible etiologic mechanism underlying LUTS-associated ED.

Is coexistent overactive-underactive bladder (with or without detrusor overactivity and underactivity) a real clinical syndrome? ICI-RS 2019.

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.

Psychological comorbidities and functional neurological disorders in women with idiopathic urinary retention: International Consultation on Incontinence Research Society (ICI-RS) 2019.

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.

Hyperbaric oxygen therapy prevents subarachnoid hemorrhage-induced apoptosis and impaired contractility of the rabbit bladder.

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: Isometric 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.

Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019.

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.