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Background: The onabotulinumtoxinA detrusor injection (OnabotA DI) was approved a decade ago for the treatment of patients with idiopathic overactive bladder (iOAB) or neurogenic detrusor overactivity (nDO) dysfunction who had not been treated successfully otherwise. The procedure is usually performed under local anesthesia (LA), and various approaches have been investigated to make the procedure as painless as possible. We examined the level of anxiety and pain experienced by patients who wanted to have the procedure performed under LA or general anesthesia (GA). Material and Methods: Patients scheduled for OnabotA DI were able to choose the anesthesia procedure (LA or GA). The Amsterdam Preoperative Anxiety and Information Scale (APAIS) was used to grade anxiety before anesthesia or before the procedure itself. Intra- and postoperative pain was determined using the Visual Analogue Scale (VAS). Various established questionnaires (including the Urinary Distress Inventory UDI-6), as well as a postoperative satisfaction questionnaire, were used to evaluate the success of the therapy. Results: In total, 104 patients (93 F, 11 M; age 64.0 (22–89) years; 80× iOAB, 24× nDO) were evaluated. OnabotA-DI was performed with LA in 72 patients and GA in 32. Stratified by first versus repeat injection in the LA group, there was a significant decrease in the Anxiety Score in the first vs. repeat injection group (p = 0.038). The LA group showed higher concerns in the anesthesia questions of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) than the GA group (OR: 0.29, 95%CI: 0.02–1.74). The VAS Pain Score during the procedure was significantly lower in the GA group compared to the LA group (LA: 3.3 ± 2.2, GA group 1.5 ± 1.5; p < 0.001). There were no differences in the success of therapy. Despite the fear and pain, patients preferred LA to GA. Conclusions: This study shows that the anxiety and pain burden of patients undergoing OnabotA-DI under LA is significant in comparison to GA during the first injection, but insignificant for following injections. Overall, LA is favored over GA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate neurogenic bladder and bowel dysfunction (NBBD) in children with cerebral palsy (CP) and acquired brain injury (ABI), a condition considered less frequent in those patients than in children with spinal cord injury (SCI), and to study the relationship between NBBD and disability grade in this population. Study Design: We retrospectively reviewed the clinical data of all patients (aged 3–18 years old) admitted during a three-month observation in our neurorehabilitation department. Data collected were as follows: demographic parameters; disability status (Wee-FIM Scale, Gross Motor Function Classification System (GMFCS) and the Communication Function Classification System); and gastrointestinal and urological symptoms (diaries, Bristol scale, Pad Test and International Consultation on Incontinence Modular Questionnaire). Results: Sixty patients were enrolled (31 females, 29 males): 30 CP, 17 ABI, 3 SCI, and 10 others with neurological diseases. All presented urinary incontinence without gender differences. CP and ABI had major incidences of bowel dysfunction (50% and 64.7%, respectively) and SCI of urinary tract infections (66.6%) and enuresis (100%). A major incidence of symptoms was recorded in patients with higher GMFCS levels (level 3-4-5). Conclusions: NBBD has a high frequency in children with CP and ABI, as in SCI. More attention is needed from pediatricians and pediatric urologists for this clinical entity. Further studies are needed to better understand clinical relevance and, therefore, to establish specific management. [ABSTRACT FROM AUTHOR]

Introduction: Botulinum neurotoxin A (BoNT-A) is a treatment option for neurogenic lower urinary tract dysfunctions (NLUTD) and idiopathic overactive bladder (OAB) in adults. Recently, its use has gained popularity in paediatric urology. Transitional urology deals with adolescents affected by congenital urological issues, who mature into adulthood. The aim of this systematic review was to update the current knowledge on the use of BoNT-A in children and adolescents. Methods: A comprehensive search in PubMed, Scopus, and Web of Science databases was performed from articles published up to September 2024. Both prospective and retrospective single-cohort or comparative studies evaluating outcomes of interest were included. These consisted of the amelioration of urinary incontinence (UI), continence rates, improvement of urodynamic parameters (maximum detrusor pressure during voiding, maximum bladder capacity, and bladder compliance), and type and prevalence of adverse/side effects. Qualitative and quantitative data syntheses were provided. Moderators and meta-regression analyses were carried out as well. Results: Forty-one full-text manuscripts were selected of which 26 focused on children with NLUTD, 13 on idiopathic OAB, and two on both conditions. Overall, 1521 patients were included of whom 715 were male, 646 female, and 160 of unknown sex. Mean age varied between 5.6 and 15.6 years. No studies specifically focused on transitional urology, despite patients up to at least 17 years of age being included. Several differences existed in design, type, dose, way of administration, outcomes measured and follow-up time; however, all studies independently showed an improvement of UI and urodynamic parameters with no major side/adverse events. Pooled analysis showed a mean rate of improvement in UI scores/episodes of 75.87% within a period of 3–6 months following BoNT-A treatment. Meta-regression analyses demonstrated a significant correlation between dryness rate and both patients' age (negative) and bladder compliance (positive). Conclusions: Several uncontrolled or comparative studies provided significative evidence of the clinical benefit and safety of BoNT-A administration in children in terms of UI relief and improvement of urodynamic parameters, with neurogenic aetiologies being the most investigated conditions. A reduced bladder compliance was identified as one of the potential predictors of poor response to BoNT-A. Moreover, the earlier the treatment was started the higher the success rate that was reached in terms of dryness/urinary continence achievement. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bladder outlet obstruction (BOO) resulting from benign prostate enlargement (BPE) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with central nervous system (CNS) diseases, such as spinal cord injury (SCI), Parkinson's disease (PD), cerebrovascular accident (CVA) and multiple systemic atrophy (MSA), commonly experience lower urinary tract dysfunction. Men who suffer from CNS diseases may also experience symptoms related to BPE and BOO, which pose an additional burden to their overall clinical status and result in the need for catheter use and a deterioration in quality of life. The aim of this study was to identify if prostate surgery will benefit men with CNS diseases who have been diagnosed with BPE-related BOO. Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EMBASE, MEDLINE, Cochrane systematic reviews, Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov were searched from 1946 up to July 2023 for peer-reviewed publications addressing the primary outcome (success rate) and the secondary outcomes (postoperative changes in incontinence episodes, urodynamic parameters, questionnaire scores, and quality of life). In addition, the perioperative outcomes (adverse events and the need for further medical or surgical therapy) were reported. Results: A total of 1572 abstracts were screened, and 13 studies involving 1144 patients were eligible for inclusion. Six studies assessed the effect of prostate surgery for BPE-related BOO in SCI, four studies in CVA, two studies in PD, and one study in the MSA population. All studies were considered to have a high risk of bias. Transurethral resection of the prostate (TURP) was the most common de-obstruction procedure, followed by prostatic artery embolism and open prostatectomy. The overall pooled success rate was calculated as 81.4% (65–100%) in SCI, 27.1% (9–70%) in PD, and 66.7% (50–79%) in CVA populations. The risk of de novo incontinence was 24.7–50% in SCI, 20% in PD, 21–50% in CVA, and 60% in MSA population. In patients with SCI with BPE-related BOO, prostate surgery improved mean bladder compliance and detrusor filling pressure and resolved detrusor overactivity in up to 50% of patients. Improvement of free flow rate, voided volume, and post-void residual was observed in all patients. Patients with CVA had an increased risk of perioperative mortality compared to non-CVA patients, and the risk of postoperative complications was inversely proportional to the timing of the CVA insult since surgery. Conclusions: This systematic review provides an overview of the available evidence on the outcome of prostate surgery in patients with neurologic diseases and BPE-related BOO. Identifying the optimal practice was challenging due to the limited availability of high-quality studies and the high variability of the reported outcomes. Properly selected patients with neurological diseases may benefit from prostate surgery, provided that preoperative investigations indicate BPE-related BOO. [ABSTRACT FROM AUTHOR]

Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic and genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI to better understand the disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation and SSCI groups. The SSCI group underwent sacral spinal cord injury, while the sham group did not. Urodynamic and histological assessments were conducted at various intervals (1, 2, 3, 4, and 6 weeks) post-injury to elucidate the disease process. Urodynamic examinations revealed significant bladder dysfunction in the SSCI group compared to the sham group, stabilizing around 3–4 weeks post-injury. Histological examination, including hematoxylin–eosin and Masson's trichrome staining, correlated these functional changes with bladder microstructural alterations. RNA-seq was performed on bladder tissues from the sham group and SSCI group at 6 weeks to identify differentially expressed genes and pathways. Selected genes were further analyzed using polymerase chain reaction (PCR). The findings indicated a pronounced inflammatory response in the first 2 weeks post-SSCI, progressing to bladder fibrosis at 3–4 weeks. In conclusion, this study presents a reliable, reproducible, and straightforward SSCI model, providing insights into bladder functional and morphological alterations post-SSCI and laying the groundwork for future therapeutic research. [ABSTRACT FROM AUTHOR]

Background/Objectives: Data on the long-term effects of oxybutynin in patients with neurogenic bladder (NGB) due to spinal cord injury (SCI) are limited. This study aimed to evaluate the long-term effects of oxybutynin and the combination of oxybutynin with trospium in these patients, under real-world medical conditions. Methods: A total of 107 patients with NGB due to SCI were included. The mean treatment duration was 2.8 years ± 0.8 years. The patients were categorized into three groups: (1) low-dose oxybutynin (5–15 mg/day), (2) high-dose oxybutynin (20–40 mg/day), and (3) oxybutynin combined with trospium. The main outcomes were maximal detrusor pressure (MDP) and cystometric bladder capacity (CBC). Both were assessed at baseline and at three subsequent follow-up visits. Generalized estimation equation models were used to estimate the overall mean reduction in MDP and CBC for each group. Results: The overall adjusted mean reduction from baseline of MDP in groups 1, 2, and 3 were 2.5 (95% CI: −5.4 to 10.4; p = 0.540), 16.9 (95% CI: 4.4 to 29.4; p = 0.008), and 21.9 (95% CI: 4.1 to 39.8; p = 0.016) cmH2O, respectively. For the CBC, the mean reduction was not significant in any group at any visit, nor were the overall mean reductions. Conclusions: These findings suggest that high-dose oxybutynin and oxybutynin–trospium combination achieve a significant long-term reduction in MDP in patients with NGB after SCI. The effects were sustained across all three follow-up periods. [ABSTRACT FROM AUTHOR]

Neurogenic bladder dysfunction (NB) represents a challenge in pediatric urology. Intravesical botulin toxin-A (BTX-A) bladder injection is part of the armamentarium for the treatment of this condition, usually after failed first-line medical strategies and before the escalation to more invasive options such as neuromodulation or augmented cystoplasty in severe cases. However, there is still a lack of consensus about the appropriate treatment modality for the pediatric population. A review of the last 10 years' research was performed on the PubMed database by two authors. Articles doubly selected and meeting the inclusion criteria were collected and analyzed for their study type, demographics, neurological disease(s) at diagnosis, BTX-A treatment modality and duration, previous treatment, clinical and urodynamic parameters, adverse events, outcomes, and follow-ups. A total of 285 studies were initially selected, 16 of which matched the inclusion criteria. A cohort of 630 patients was treated with BTX-A at a median age of 9.7 years, 40% of which had a diagnosis of myelomeningocele. The results of the selected publications show the overall efficacy and safety of BTX-A injections in children and confirmed BTX-A as a valuable strategy for NB treatment in pediatric population. Nevertheless, up to now, the literature on this topic offers scarce uniformity among the published series and poor protocol standardization. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) often leads to neurogenic lower urinary tract dysfunction, causing dysuria and affecting patients' well-being. This study aimed to evaluate the efficacy of a urethral sphincter botulinum toxin A (BoNT-A) injection in patients with SCI and dysuria. This was a retrospective study including 118 patients with SCI who underwent a urethral BoNT-A injection following a standardized protocol for refractory voiding dysfunction. The protocol involved injecting BoNT-A into the urethral sphincter under cystoscopic guidance. Patient demographics, bladder condition parameters, and treatment outcomes were analyzed. Logistic regression and receiver operating characteristic curve analyses were performed to identify predictors of treatment success. Of the 118 patients, 71 (60.1%) showed satisfactory treatment outcomes after the injection. Post-injection status, bladder management, and injection frequency varied significantly among patients with satisfactory and unsatisfactory treatment outcomes. Age, bladder compliance, intravesical pressure, and bladder contractility were indicators of satisfactory outcomes. The first sensation of bladder filling of ≤263 mL, intravesical pressure of ≤28, and bladder contractility index of ≥14 were highly correlated with satisfactory outcomes. A urethral sphincter BoNT-A injection shows promise in managing dysuria in patients with SCI. Understanding bladder condition parameters and patient demographics helps optimize patient selection for this intervention. Further studies are needed to validate these findings and refine treatment protocols. [ABSTRACT FROM AUTHOR]

One of the most common complications of neurogenic bladder secondary to spinal cord injury (SCI) is urinary incontinence, which is possibly related to bladder-emptying methods and changes in quality of life. This study aimed to identify the occurrence of this complication in adults with SCI and analyze its relationship with bladder-emptying methods, satisfaction, and lifestyle. This is a quantitative, exploratory, and cross-sectional study. The variables were collected using the Bowel and Bladder Treatment Index during a telephone interview with 290 participants from February to November 2021. According to the results, 70% of the participants were male and 74.1% performed clean intermediate catheterization (CIC) as the main bladder-emptying method. Moreover, 55.6% were considered incontinent in the last year. Emptying by normal urination and bladder reflex triggering had a statistically significant relationship with urinary incontinence. A statistical association was observed between all the variables of satisfaction and lifestyle with urinary incontinence. Although CIC reduced urine leakage, a considerable number of participants still presented with frequent urine leakage. Urinary incontinence had a negative impact on satisfaction with the bladder-emptying method, effectiveness of bladder management, quality of life, and personal and social relationships. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to identify the unique characteristics of neurogenic bladders and associated symptoms in patients with cervical or thoracic myelopathy using clinical surveys and urodynamic studies (UDSs). Methods: Patients with degenerative cervical (DCM) or thoracic (DTM) myelopathy and lower urinary tract symptoms (LUTSs) scheduled for decompressive surgery were prospectively enrolled. A UDS was performed one day preceding surgery to evaluate the preoperative urological function. Subjective symptoms were evaluated using the International Prostate Symptom Score (IPSS) and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire before surgery and one year postoperatively. Results: Sixty-two patients (DCM: 50, DTM: 12) with a mean age of 63.2 years (men: 30, women: 32) were enrolled. The UDS revealed that 5 (8.1%) patients, all with DCM, exhibited completely normal UDS results, and the remaining 57 had at least one abnormal finding. Based on the International Continence Society classification, an underactive bladder was significantly more common in patients with DTM compared to patients with DCM (75.0% vs. 18.0%, p < 0.001). The results of the questionnaire showed that the voiding symptom IPSS were significantly worse, preoperatively, in patients with DTM (5.0 ± 4.4 [DCM] vs. 8.7 ± 4.5 [DTM]; p = 0.013). One year postoperatively, the IPSS grade of 24.0% of patients with DCM improved, whereas only one (8.3%) patient with DTM showed improvement. Conclusions: Patients with DTM reported worse voiding symptoms and exhibited more underactive bladders on UDS than patients with DCM before decompression. One year postoperatively, more patients with DCM showed subjective improvements in urinary function than those with DTM. [ABSTRACT FROM AUTHOR]

Onabotulinum Toxin-A (BTX-A) is a second-line treatment for neurogenic bladder (NB). It requires repeated injections over time, which is a possible limit for long-term adherence, especially in children, as general anesthesia is required. Almost 50% of adults discontinue therapy; few data on pediatric patients are present. The aim of this study is to share our long-term experience of BTX-A adherence in children. This study is a retrospective review of 230 refractory NB patients treated with BTX-A. The inclusion criteria were ≥3 treatments and the first injection performed ≥10 years before the study endpoint. Fifty-four patients were included. Mean follow-up was 10.2 years; mean treatment number was 6.4 for each patient. During follow-up, 7% did not need BTX-A anymore; 76% discontinued therapy, with a prevalence of acquired NB (64% acquired vs. 34% congenital; p = 0.03); sex-based and urodynamic findings did not influence the discontinuation rate (p = 0.6, p = 0.2, respectively). Considering those who withdrew from the therapy, 43% were lost to follow-up/died after a mean of 7.5 years (although 33% still experienced clinical efficacy); 33% changed therapy after a mean of 5.8 years (with reduced efficacy in 22%, persistent efficacy in 11%). BTX-A is a safe and effective therapy for pediatric patients. The treatment abandonment rate is higher for children than for adults; no specific reasons were highlighted. It is necessary to evaluate any age-specific factors to explain these data. [ABSTRACT FROM AUTHOR]

Introduction: Transurethral injections into the bladder wall with botulinum toxin are an established treatment for refractory overactive bladder or detrusor overactivity. With the current injection technique, an average of approx. 18% and up to 40% of botulinum toxin is injected next to the bladder wall, potentially causing reduced efficacy or non-response. The article aims to evaluate the reasons for incorrect injections and propose strategies for complete delivery of the entire botulinum toxin fluid into the bladder wall. Material and Methods: Unstructured literature search and narrative review of the literature. Results: Incorrect injection of botulinum toxin fluid next to the bladder wall is caused by pushing the injection needle too deep and through the bladder wall. Bladder wall thickness decreases with increasing bladder filling and has a thickness of less than 2 mm beyond 100 mL in healthy individuals. Ultrasound imaging of the bladder wall before botulinum toxin injection can verify bladder wall thickness in individual patients. Patient movements during the injection therapy increase the chance of incorrect placement of the needle tip. Conclusions: Based on the literature search, it is helpful and recommended to (1) perform pretreatment ultrasound imaging of the bladder to estimate bladder wall thickness and to adjust the injection depth accordingly, (2) fill the bladder as low as possible, ideally below 100 mL, (3) use short needles, ideally 2 mm, and (4) provide sufficient anesthesia and pain management to avoid patient movements during the injection therapy. [ABSTRACT FROM AUTHOR]

Considerable research efforts have been directed towards investigating neurogenic bladder dysfunction over the preceding decade. This condition stands as the most prevalent and incapacitating pelvic floor disorder amidst patients afflicted with specific upper motor neuron syndromes, including multiple sclerosis, stroke, and spinal cord injury. The current study aims to bring up-to-date findings on rehabilitation methods for treating neurogenic bladder. The Web of Science database (MEDLINE, PsychINFO, EMBASE, CENTRAL, ISRCTN, and ICTRP) was screened for randomized controlled studies and clinical studies using combinations of keywords including "neurogenic bladder", "stroke", "multiple sclerosis", and "spinal cord injury". The PEDro scale was used to assess the quality of the articles included in this study. After a thorough examination, eleven articles met the criteria for inclusion in our research. The outcome measures showed a variety of forms of electrostimulation that can be combined with or without PFMT. These interventions significantly enhance health-related quality of life, as evidenced by various assessment methods. The physical approach constitutes an effective therapeutic method that can reduce the severity of urinary incontinence. [ABSTRACT FROM AUTHOR]

DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARβ, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-β was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients. [ABSTRACT FROM AUTHOR]

Lower urinary tract dysfunction is clinically important because it may cause urinary tract infections, mainly due to accumulation of residual urine, and adversely affect renal function. In addition, it may cause urinary incontinence, strongly affecting the child's quality of life. The function of the lower urinary tract is closely associated with function of the bowel because constipation is commonly present with bladder dysfunction. The interplay between the lower urinary tract and bowel function, coupled with common conditions such as detrusor overactivity and voiding dysfunction, requires a nuanced diagnostic approach. Detrusor overactivity, a benign but socially harmful condition, is the principal cause of daytime urinary incontinence in childhood. It needs to be differentiated from more serious conditions such as neurogenic bladder dysfunction or urethral obstruction. Voiding dysfunction, a habitual sphincter contraction during voiding, is common in children with detrusor overactivity and may be self limiting but may also result in residual urine and urinary tract infections. It may resemble, in severe cases, neurogenic bladder dysfunction, most often caused by spinal dysraphism, which very often leads to recurrent urinary tract infections and high intravesical pressures, jeopardizing renal function. A voiding diary is crucial in the initial evaluation of lower urinary tract function in children. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is increasing in the pediatric population and, as in adults, symptoms vary among patients. In children the first manifestations can sometimes overlap with acute neurological symptoms. Urological symptoms have not been much studied in childhood. We shared our experience with MS urological manifestation in children. Methods: This article is a retrospective evaluation of all children with MS, according to the Krupp criteria, who also present with urological symptoms. We collected demographic and clinical history, the MR localization of demyelinating lesions, urological symptoms, and exams. Results: We report on six MS pediatric cases with urological manifestation. Urinary symptoms, characterized by urinary incontinence in five patients and urinary retention in one patient, appeared in a different time frame from MS diagnosis. Urodynamic exams showed both overactive and underactive bladder patterns. Treatment was defined according to lower urinary tract dysfunction, using clean intermittent catheterization, oxybutynin, and intradetrusor Onabotulinum Toxin-A injection. A low acceptance rate of invasive evaluation and urological management was observed. Conclusions: The MS diagnosis was traumatic for all our patients. We believe it is important to address urological care in young people from the time of diagnosis for prompt management; it could be useful to include a pediatric urologist in multidisciplinary teams. [ABSTRACT FROM AUTHOR]

Simple Summary: Among the various options for urinary diversion following radical cystectomy, the orthotopic neobladder most closely resembles the original bladder both in location and function. However, a significant number of patients with these reservoirs have dysfunctional voiding. Our objective here is to provide the first systematic review focusing on the urodynamic and continence outcomes of ileal orthotopic neobladders. By summarising these important outcomes, the current paper may represent the reference manuscript for outcome comparison in future papers. The manuscript also describes the methodology of the urodynamic evaluation of the neobladders, highlighting the frequent lack of precise indications, accurate guidelines (at the state of the art, the same parameters used for the native bladder are also used for the ileal neobladders), standardised definitions, and standard values for outcome comparison. By underlining these gaps, our systematic review may aid future studies in having more adequate designs and will allow for a more accurate functional evaluation of the patients harbouring an ileal neobladder. Introduction: The orthotopic neobladder is the type of urinary diversion (UD) that most closely resembles the original bladder. However, in the literature the urodynamic aspects are scarcely analysed. Objective: To provide the first systematic review (SR) on the urodynamic (UDS) outcomes of the ileal orthotopic neobladders (ONB). Continence outcomes are also presented. Methods: A PubMed, Embase and Cochrane CENTRAL search for peer-reviewed studies on ONB published between January 2001–December 2022 was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Results and Conclusion: Fifty-nine manuscripts were eligible for inclusion in this SR. A great heterogeneity of data was encountered. Concerning UDS parameters, the pooled mean was 406.2 mL (95% CI: 378.9–433.4 mL) for maximal (entero)cystometric capacity (MCC) and 21.4 cmH2O (95% CI: 17.5–25.4 cmH2O) for Pressure ONB at MCC. Postvoid-residual ranged between 4.9 and 101.6 mL. The 12-mo rates of day and night-time continence were 84.2% (95% CI: 78.7–89.1%) and 61.7% (95% CI: 51.9–71.1%), respectively.Despite data heterogeneity, the ileal ONB seems to guarantee UDS parameters that resemble those of the native bladder. Although acceptable rates of daytime continence are reported the issue of high rates of night-time incontinence remains unsolved. Adequately designed prospective trials adopting standardised postoperative care, terminology and methods of outcome evaluation as well as of conduction of the UDS in the setting of ONB are necessary to obtain homogeneous follow-up data and to establish UDS guidelines for this setting. [ABSTRACT FROM AUTHOR]

Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with neurological lesions in the central nervous system (CNS). Medical treatment usually cannot adequately relieve NLUTD. This study reported the real-life treatment outcome of botulinum toxin A (BoNT-A) for overactive bladders (OAB) and voiding dysfunction in patients with CNS lesions. Methods: We retrospectively analyzed the first-time treatment outcome of 74 patients who received detrusor 100 U BoNT-A for OAB and 45 patients who received a urethral sphincter 100 U BoNT-A injection for voiding dysfunction. The treatment outcome, therapeutic duration, and adverse events (AE) after BoNT-A were compared among different CNS lesions and among patients with different urodynamic characteristics. Results: The study included 74 patients receiving detrusor injections for OAB (36 with cerebrovascular accidents, 13 with Parkinson's disease, and 25 with dementia) and 45 patients receiving a urethral sphincter injection for voiding dysfunction (26 with cerebrovascular accidents, 7 with Parkinson's disease, and 12 with dementia). After detrusor BoNT-A treatment, urinary continence was achieved in 28.4% of patients with neurogenic OAB, postoperative difficult urination in 59.5%, acute urinary retention (AUR) in 9.5%, and urinary tract infection (UTI) in 14.9%, with a therapeutic duration of 6.43 months. There were no differences among subgroups or between patients with detrusor overactivity (DO) and DO with detrusor underactivity (DU) in terms of treatment outcomes and AEs. The improvement rate of urethral sphincter BoNT-A injections was 75.6% without any difference among subgroups. After treatment, 24.4% of the patients had exacerbated urinary incontinence, 33.3% had persistent difficult urination, and 15.6% had UTI. Patients with dementia had higher rates of difficult urination and UTI, higher postvoid residual volume, and a shorter therapeutic duration. Patients with DU and those without urethral sphincter dyssynergia had less favorable outcomes after their urethral sphincter BoNT-A injection. Conclusions: The therapeutic efficacy of detrusor BoNT-A injection for OAB due to CNS lesions is limited, with high rates of difficult urination, AUR, and UTI. Although urethral sphincter BoNT-A injection is effective in treating voiding dysfunction; however, exacerbated urinary incontinence and persistent difficult urination remain a problem, particularly in patients with dementia. [ABSTRACT FROM AUTHOR]

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The medical charts of the children were examined to determine age, sex, anthropometric measurements, activity assessment using Hoffer's scale, and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the study group compared with the reference group, but the difference was not statistically significant (p = 0.52, p > 0.05). However, the uL-FABP/creatinine ratio exhibited a wider range in NB patients compared to the reference group. NB children with proteinuria and the history of high-grade vesicoureteral reflux (VUR) tended to have the highest uL-FABP concentrations. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and the history of VUR may be the factors influencing the uL-FABP. [ABSTRACT FROM AUTHOR]

Neurogenic bladder is a dysfunction in the lower urinary tract due to damage to the nervous system. One of the treatments that has shown important results is transcutaneous neuromodulation. The neuromodulation equipment available on the market does not allow remote activation or offer many resources for adjusting the parameters of the generated stimulus, as most devices operate with pre-established parameters in closed packages. For this reason, customizing therapy for each individual can be difficult. Therefore, the objective was to develop and validate a neuromodulation device capable of being remotely programmed and properly monitored. Materials and methods for validating devices were used according to the Brazilian Regulatory Standard (NBR), which deals with general requirements for the basic safety and essential performance of electromedical devices. After verifying the reliability of the device, which was capable of generating a biphasic and symmetrical wave, measured by an oscilloscope, considered safe by the technical requirements, it was tested in a real application. Users reported feeling a comfortable stimulus, similar to other previously used devices, and considered the device easy to use. In this way, it was possible to demonstrate the reliability and validity of the developed device. [ABSTRACT FROM AUTHOR]

Neurogenic bowel dysfunction (NBD) is a common condition in individuals with spinal cord injury (SCI) or multiple sclerosis (MS). It usually entails constipation, difficult evacuation of the rectum, and fecal incontinence (FI); often in combination. It is highly burdensome for affected patients and is correlated with poor quality of life. The current treatment algorithm, or treatment pyramid, does not completely correspond to actual clinical practice, and the known and classical pyramid contains both treatments still in their experimental stage as well as several treatments which are not available at all treatment centers. Thus, an updated treatment algorithm is called upon, and the authors of this paper therefore propose a simplified version of the treatment pyramid, aiming to guide clinicians in treating NBD. [ABSTRACT FROM AUTHOR]

Purple urine bag syndrome (PUBS) is an uncommon, but usually benign, underrecognized clinical condition with the distressing presentation of purple, blue or reddish discoloration of a patient's catheter bag and tubing in the setting of catheter-associated urinary tract infections (UTIs). PUBS is the result of the complex metabolic pathway of the dietary essential amino acid tryptophan. Its urinary metabolite, indoxyl sulfate, is converted into red and blue byproducts (indirubin and indigo) in the presence of the bacterial enzymes indoxyl sulfatase and phosphatase. The typical predisposing factors are numerous and include the following: female gender, advanced age, long-term catheterization and immobilization, constipation, institutionalization, dementia, increased dietary intake of tryptophan, chronic kidney disease, alkaline urine, and spinal cord injury (SCI). Here, we present a case of PUBS in a home-dwelling elderly female patient with a history of long-term immobility after a pathological spinal fracture, long-term catheterization, constipation, and malignant disease in remission. Urine culture was positive for Proteus mirabilis. This state can be alarming to both patients and physicians, even if the patient is asymptomatic. Healthcare professionals and caregivers need to be aware of this unusual syndrome as an indicator of bacteriuria in order to initiate proper diagnostics and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: As patients with neurogenic bladders are at higher risk for advanced-stage bladder cancer, it is important to develop non-invasive screening methods for bladder cancer other than cystoscopy in this patient population. We conducted a study to explore changes in five bladder cancer-associated genes in the urine of such patients in comparison with healthy controls, and found that changes in certain tumor-suppressing genes associated with bladder cancer were significantly more frequent in the neurogenic group. Apart from a neurogenic bladder, male gender was another risk factor for such gene changes. Bladder biopsies taken from these patients revealed a high percentage of chronic inflammation. We need larger long-term studies to establish the value of this non-invasive method in the screening and diagnosis of bladder cancer, but also to explore possible associations between gene changes in the urine, chronic bladder inflammation and bladder cancer in the neurogenic population. Background: Bladder cancer (BCa) in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) is a significant concern due to its advanced stage at diagnosis and high mortality rate. Currently, there is a scarcity of specific guidelines for BCa screening in these patients. The development of urine biomarkers for BCa seems to be an attractive non-invasive method of screening or risk stratification in this patient population. DNA methylation is an epigenetic modification, resulting in the transcriptional silencing of tumor suppression genes, that is frequently detected in the urine of BCa patients. Objectives: We aimed to investigate DNA hypermethylation in five gene promoters, previously associated with BCa, in the urine of NLUTD patients, and in comparison with healthy controls. Design, setting and participants: This was a prospective case–control study that recruited neurourology outpatients from a public teaching hospital who had suffered from NLUTD for at least 5 years. They all underwent cystoscopy combined with biopsy for BCa screening following written informed consent. DNA was extracted and DNA methylation was assessed for the RASSF1, RARβ, DAPK, TERT and APC gene promoters via quantitative methylation-specific PCR in urine specimens from the patients and controls. Results: Forty-one patients of mixed NLUTD etiology and 35 controls were enrolled. DNA was detected in 36 patients' urine specimens and in those of 22 controls. In the urine specimens, DNA was hypermethylated in at least one of five gene promoters in 17/36 patients and in 3/22 controls (47.22% vs. 13.64%, respectively, p = 0.009). RASSF1 was hypermethylated in 10/17 (58.82%) specimens with detected methylation, APC in 7/17 (41.18%), DAPK in 4/17 (23.53%), RAR-β2 in 3/17 (17.56%) and TERT in none. According to a multivariate logistic regression analysis, NLUTD and male gender were significantly associated with hypermethylation (OR = 7.43, p = 0.007 and OR = 4.21; p = 0.04, respectively). In the tissue specimens, histology revealed TaLG BCa in two patients and urothelial squamous metaplasia in five patients. Chronic bladder inflammation was present in 35/41 bladder biopsies. Conclusions: DNA hypermethylation in a panel of five BCa-associated genes in the urine was significantly more frequent in NLUTD patients than in the controls. Our results warrant further evaluation in longitudinal studies assessing the clinical implications and possible associations between DNA hypermethylation, chronic inflammation and BCa in the NLUTD population. [ABSTRACT FROM AUTHOR]

Tissue engineering (TE) is a rapidly evolving biomedical discipline that can play an important role in treating neurogenic bladder dysfunction and compensating for current conventional options' shortcomings. This review aims to analyze the current status of preclinical and clinical trials and discuss what could be expected in the future based on the current state of the art. Although most preclinical studies provide promising results on the effectiveness of TE and stem cell therapies, the main limitations are mainly the very slow translation of preclinical trials to clinical trials, lack of quality research on neurogenic preconditions of neurogenic bladder dysfunction outside of the spinal cord injury and varying therapeutic methods of the existing research that lacks a standardized approach. [ABSTRACT FROM AUTHOR]

Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-β1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-β1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-β1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-β1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk. [ABSTRACT FROM AUTHOR]

We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, 6, and 12 months after acute SCI, within the framework of a population-based longitudinal study at a single university SCI center. Candidate predictors included demographic characteristics and neurological and functional statuses 1 month after SCI. Outcomes included urodynamic risk factors for UUT damage: detrusor overactivity combined with detrusor sphincter dyssynergia, maximum storage detrusor pressure (pDetmax) ≥ 40 cmH2O, bladder compliance < 20 mL/cmH2O, and vesicoureteral reflux. Multivariable logistic regression was used for the prediction model development and internal validation, using the area under the receiver operating curve (aROC) to assess model discrimination. Two models showed fair discrimination for pDetmax ≥ 40 cmH2O: (i) upper extremity motor score and sex, aROC 0.79 (95% CI: 0.69–0.89), C-statistic 0.78 (95% CI: 0.69–0.87), and (ii) neurological level, American Spinal Injury Association Impairment Scale grade, and sex, aROC 0.78 (95% CI: 0.68–0.89), C-statistic 0.76 (95% CI: 0.68–0.85). We identified two models that provided fair predictive values for urodynamic risk factors of UUT damage during the first year after SCI. Pending external validation, these models may be useful for clinical trial planning, although less so for individual-level patient management. Therefore, urodynamics remains essential for reliably identifying patients at risk of UUT damage. [ABSTRACT FROM AUTHOR]

Neurogenic bladder dysfunction is a condition that affects both bladder storage and voiding function and remains one of the leading causes of morbidity after spinal cord injury (SCI). The vast majority of individuals with severe SCI develop neurogenic lower urinary tract dysfunction (NLUTD), with symptoms ranging from neurogenic detrusor overactivity, detrusor sphincter dyssynergia, or sphincter underactivity depending on the location and extent of the spinal lesion. Animal models are critical to our fundamental understanding of lower urinary tract function and its dysfunction after SCI, in addition to providing a platform for the assessment of potential therapies. Given the need to develop and evaluate novel assessment tools, as well as therapeutic approaches in animal models of SCI prior to human translation, urodynamics assessment techniques have been implemented to measure NLUTD function in a variety of animals, including rats, mice, cats, dogs and pigs. In this narrative review, we summarize the literature on the use of animal models for cystometry testing in the assessment of SCI-related NLUTD. We also discuss the advantages and disadvantages of various animal models, and opportunities for future research. [ABSTRACT FROM AUTHOR]

In pediatric patients with neurogenic bladder (NGB), urinary tract evaluation, early diagnosis, and individualized management are important. We aimed to clarify the current status of diagnosis and treatment of NGB in Japanese children. This descriptive, observational, retrospective cohort study using the JMDC claims database included NGB patients aged ≤17 years over a 12-month follow-up period. Of the 1065 pediatric NGB patients, 38.9% had spina bifida. Dermatological and gastrointestinal comorbidities were common in the baseline period. Renal/bladder ultrasound was a commonly performed investigation (38.3%), but urodynamics was infrequently used (3.0%). Of all the overactive bladder medications, anticholinergics were used commonly (17.9% patients), and most patients used anticholinergics alone (without combination therapy). Clean intermittent catheterization (CIC; alone or in combination with medications) was performed in 9.3% of patients, and 3.9% of patients were concomitantly treated with medications. The most common incident complication was lower urinary tract infection (18.1%), which was especially common in patients with open spina bifida (54.1%). Despite guideline recommendations, lower urinary tract dysfunction is not thoroughly evaluated. Adequate understanding of patient status is critical to optimal patient management (behavioral therapy, CIC, and medication) in clinical practice. [ABSTRACT FROM AUTHOR]

The human bladder has been long thought to be sterile until that, only in the last decade, advances in molecular biology have shown that the human urinary tract is populated with microorganisms. The relationship between the urobiota and the development of urinary tract disorders is now of great interest. Patients with spina bifida (SB) can be born with (or develop over time) neurological deficits due to damaged nerves that originate in the lower part of the spinal cord, including the neurogenic bladder. This condition represents a predisposing factor for urinary tract infections so that the most frequently used approach to treat patients with neurogenic bladder is based on clean intermittent catheterization (CIC). In this study, we analyzed the urobiota composition in a pediatric cohort of patients with SB compared to healthy controls, as well as the urobiota characteristics based on whether patients received CIC or not. [ABSTRACT FROM AUTHOR]

Background: In the last twenty-five years, Onabotulinum Toxin A (BTX-A) has gained increasing popularity for neurogenic lower urinary tract dysfunction (NLUTD) treatment. To maintain its efficacy, repeated BTX-A intradetrusor injections are required over time, with unknown effects on the bladder wall in children. The aim of this paper is to report long-term effects on the bladder wall in children treated with BTX-A. Methods: Children with NLUTD not responsive to anticholinergics were treated with BTX-A, according to our protocol, with bladder wall control using endoscopic cold-cup biopsy. Specimens were evaluated considering edema, chronic inflammation, and fibrosis. Results: Of the 230 patients treated from 1997 to 2022, we considered only specimens obtained in patients who had received ≥5 treatments (36 children), considered as the threshold to evaluate clinical effectiveness on long-term treatment with BTX-A. Most of them had congenital NLUTD (25 patients) and detrusor overactivity (27 patients). In all, increased edema and chronic inflammation with reduced fibrosis over time was reported; these data were not statistically significant. No difference was observed between patients with congenital and acquired diseases. Conclusions: Repeated intradetrusor BTX-A injections are not related to significant histological alterations in children, similarly with adults, and repeated injections could be considered safe. [ABSTRACT FROM AUTHOR]

This document is a special issue of the Journal of Clinical Medicine focusing on the latest advances in urinary incontinence (UI). The issue includes contributions from experts in functional and neuro-urology, providing new scientific evidence on the diagnosis and management of UI. Topics covered include strategies to reduce catheter-associated infections, treatment options for neurogenic urinary incontinence, the impact of UI on patients' quality of life, UI after robot-assisted radical prostatectomy, treatment options for female stress and mixed urinary incontinence, and patients' preferences and expectations for overactive bladder treatment. The authors believe that the papers included in this special issue will be a valuable resource for researchers and inspire further research in the field. [Extracted from the article]

Introduction: The utility of a clinical tool lies in its clinical performance evaluation and describes the relevance and usefulness of that tool in a medical setting. The utility of urodynamic and video-urodynamic studies in the management of specific urodynamic profiles in the diagnosis, treatment, and prognostic approach in neuro-urological patients is the focus of the current review. Methods: For this narrative review, a PubMed® search was performed by cross-referencing the keywords "urodynamics", "neurogenic bladder", "utility", "clinical utility" and "clinical performance" with various terms related to the management of neurogenic lower urinary tract dysfunction. Clinical practice guidelines and landmark reviews from the most renowned experts in the field were also used. Analysis: Assessment of the utility of urodynamic study was performed during the diagnostic, therapeutic and prognostic steps of the neuro-urological patients' management. We focused on its clinical performance in the identification and evaluation of several unfavorable events, such as neurogenic detrusor overactivity, detrusor-sphincter dyssynergia, elevated detrusor leak point pressure and the presence of vesico-ureteral reflux, which may be indicators for a higher risk for the development of urological comorbidities. Conclusion: Despite the paucity of existing literature assessing the utility of urodynamic study—specifically video-urodynamic study—in neuro-urological patients, it does remain the gold standard to assess lower urinary tract function precisely in this patient category. With regard to its utility, it is associated with high clinical performance at every step of management. The feedback on possible unfavorable events allows for prognostic assessment and may lead us to question current recommendations. [ABSTRACT FROM AUTHOR]

To review the available data on non-surgical management for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI) and provide the most updated knowledge for readers. We categorized the bladder management approaches into storage and voiding dysfunction separately; both are minimally invasive, safe, and efficacious procedures. The main goals for NLUTD management are to achieve urinary continence; improve quality of life; prevent urinary tract infections and, last but not least, preserve upper urinary tract function. Annual renal sonography workups and regular video urodynamics examinations are crucial for early detection and further urological management. Despite the extensive data on NLUTD, there are still relatively few novel publications and there is a lack of high-quality evidence. There is a paucity of new minimally invasive and prolonged efficacy treatments for NLUTD, and a partnership between urologists, nephrologists and physiatrists is required to promote and ensure the health of SCI patients in the future. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of urinary biomarkers in discriminating different bladder and bladder outlet dysfunctions in women with frequency–urgency syndrome. Materials and Methods: Urine samples collected from 146 women with frequency–urgency syndrome and 34 controls were investigated. All patients were included in previous clinical trials of functional urology studies and underwent a videourodynamic study. Patients with frequency–urgency syndrome were subdivided into idiopathic detrusor overactivity (IDO), neurogenic detrusor overactivity (NDO), dysfunctional voiding (DV), and hypersensitive bladder (HSB) subgroups. Urine samples were collected before any treatment, and urinary inflammatory proteins (interleukin- (IL-) 1β, IL-2, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)), neurogenic proteins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin E2 (PGE2)), and oxidative stress biomarkers (8-isoprostane, total antioxidant capacity (TAC), and 8-hydroxydeoxyguanosine (8-OHdG)) were measured and compared between the different OAB subgroups and controls. Results: Of the 146 patients, 31 had IDO, 41 had NDO, 45 had DV, and 29 had HSB. The control group included 34 women. The patients with HSB had lower urinary TAC and IL-2 levels than the controls. The patients with IDO, NDO, and DV had significantly higher urinary TNF-α levels than those with HSB. The patients with IDO and NDO showed an increase in the urinary 8-isoprostane levels, whereas the patients with IDO had higher urinary IL-2, NGF, and BDNF levels than those with NDO. The other urinary inflammatory biomarkers did not show enough significant differences to discriminate between the different bladder and bladder outlet dysfunctions. Conclusions: The urinary levels of inflammatory, neurogenic, and oxidative stress biomarkers varied widely among the patients with bladder and bladder outlet dysfunction. This study's results provide evidence that women with frequency–urgency syndrome and different urodynamic subtypes have varying bladder inflammation and oxidative stress conditions, which might have an impact on treatment outcomes. [ABSTRACT FROM AUTHOR]

Spinal cord injuries (SCI) have a profound impact on autonomic systems, sometimes resulting in multi-organ dysfunction, including of the neurogenic bladder. Autonomic dysreflexia (AD) is commonly seen in patients with SCI above T6 when the injured cord develops a deregulated sympathetic reflex, which can be induced by bladder sensation and can cause hypertensive crisis. While intravesical injection of botulinum toxin A (Botox) is a standard therapy for neurogenic detrusor overactivity, the role of Botox for AD has rarely been described. This study reviewed the medical records of SCI patients who reported AD and received either detrusor or urethral sphincter injection with Botox. The primary endpoint is the subjective improvement of AD. The secondary endpoint is a change in videourodynamic parameters before and after Botox injection. A total of 200 patients were enrolled for analysis. There were 125 (62.5%) patients in the detrusor injection group, and 75 (37.5%) in the urethral sphincter injection group. There were 79 (63.2%) patients in the detrusor injection group and 43 (57.3%) in the urethral sphincter injection group reporting moderate or marked improvement. Detrusor injection leads to a greater improvement in AD, probably because of decreased detrusor pressure and increased compliance after Botox injection. Urethral sphincter injection appears to have a modest effect on AD, despite general improvements in the voiding parameters of videourodynamic study. [ABSTRACT FROM AUTHOR]

Background: Neurogenic lower urinary tract dysfunction requires lifelong surveillance and management for the perseveration of patients' quality of life and the prevention of significant morbidity and mortality. Urine biomarkers are an attractive noninvasive method of surveillance for these patients. The aim of this systematic review is to search for and critically appraise studies that investigate the clinical usefulness of urine biomarkers in the management of neurogenic lower urinary tract dysfunction (NLUTD) in adults. Methods: This review was conducted according to PRISMA and MOOSE guidelines. Search strategy included PubMed, CENTRAL, and Scopus (until October 2022). Studies investigating potential urine biomarkers for the management of adults with NLUTD were included. Results: Fifteen studies fulfilled the criteria. To date, a variety of different urine molecules have been investigated for the diagnosis and management of neurogenic overactive bladder and detrusor overactivity (nerve growth factor, brain-derived neurotrophic factor, prostaglandin E2, prostaglandin F2α, transformation growth factor β-1, tissue inhibitor metalloproteinase-2, matrix metalloproteinase-2, substance P, microRNA), diagnosis of vesicoureteral reflux (exosomal vitronectin), urinary tract infection (neutrophil gelatinase-associated lipocalin, interleukin 6) and bladder cancer screening (cytology, BTA stat, survivin) in neurological patients. Conclusion: Further studies are needed to specify the utility of each molecule in the management algorithm of adult NLUTD. [ABSTRACT FROM AUTHOR]

Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines. [ABSTRACT FROM AUTHOR]

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe–metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection. [ABSTRACT FROM AUTHOR]

Bladder dysfunction is a common complication after chronic spinal cord injury (SCI). Patients may experience renal function loss, urinary tract infection (UTI), urolithiasis, bladder cancer, and even life-threatening events such as severe sepsis or renal failure. Suitable patient care may prevent UTI and urinary incontinence, decrease medication use, and preserve renal function. As the primary goal is to preserve renal function, management should be focused on facilitating bladder drainage, the avoidance of UTI, and the maintenance of a low intravesical pressure for continence and complete bladder emptying. Currently, several bladder management options are available to SCI patients: (1) reflex voiding; (2) clean intermittent catheterization; (3) indwelling catheterization. The target organ may be the bladder or the bladder outlet. The purposes of intervention include the following: (1) increasing bladder capacity and/or decreasing intravesical pressure; (2) increasing bladder outlet resistance; (3) decreasing bladder outlet resistance; (4) producing detrusor contractility; (5) urinary diversion. Different bladder management methods and interventions may have different results depending on the patient's lower urinary tract dysfunction. This review aims to report the current management options for long-term bladder dysfunction in chronic SCI patients. Furthermore, we summarize the most suitable care plans for improving the clinical outcome of SCI patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Several central and peripheral nervous system disorders are responsible for neurogenic bladder (NB) in dogs and cats. In this review, the authors summarized the neurological diseases causing neurogenic bladder comparable with human medicine. For the first time, the authors provided an overview of the epidemiology, prevalence, clinical findings, diagnosis and prognosis of the NB in dogs and cats compared with humans. Lower urinary tract disease (LUTD) includes abnormalities in the structure and function of the bladder and the urethra. LUTD caused by neurological disease is defined neurogenic bladder (NB). The integrity of the central nervous system (CNS) and peripheral nervous system (PNS) is required to explicate normal micturition, maintaining the proper function of bladder and urethra. The location and type of neurological lesions influence the pattern of clinical manifestations, potential treatment, and prognosis. Though, in dogs and cats, spinal cord injury is considered mainly responsible for bladder and/or urethra incompetence, other disorders, congenital or acquired, involving CNS or PNS, could play a role in NB. In veterinary medicine, the information about the epidemiology, prevalence, etiopathogenesis, diagnosis and treatment of NB are scattered. The aim of this study is to provide an overview of the epidemiology, prevalence, clinical findings, diagnosis and prognosis for NB in dogs and cats compared with humans. [ABSTRACT FROM AUTHOR]

Background: Neurogenic bladder (NB) patients exhibit varying degrees of bladder fibrosis, and the thickening and hardening of the bladder wall induced by fibrosis will further affect bladder function and cause renal failure. Our study aimed to investigate the mechanism of bladder fibrosis caused by a spinal cord injury (SCI). Methods: NB rat models were created by cutting the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves. RNA-seq, Western blotting, immunofluorescence, cell viability and ELISA were performed to assess the inflammation and fibrosis levels. Results: The rats showed bladder dysfunction, upper urinary tract damage and bladder fibrosis after SCI. RNA-seq results indicated that hypoxia, EMT and pyroptosis might be involved in bladder fibrosis induced by SCI. Subsequent Western blot, ELISA and cell viability assays and immunofluorescence of bladder tissue confirmed the RNA-seq findings. Hypoxic exposure increased the expression of HIF-1α and induced EMT and pyroptosis in bladder epithelial cells. Furthermore, HIF-1α knockdown rescued hypoxia-induced pyroptosis, EMT and fibrosis. Conclusion: EMT and pyroptosis were involved in the development of SCI-induced bladder fibrosis via the HIF-1α pathway. Inhibition of the HIF-1α pathway may serve as a potential target to alleviate bladder fibrosis caused by SCI. [ABSTRACT FROM AUTHOR]

In 50% of typical (nonneurogenic) women, at least one urinary tract infection (UTI) will occur, with cystitis being the most common UTI, with about 25% of patients experiencing recurrence. A factor not currently included in UTI risk models is egress of urine from the bladder into the urethra during bladder filling and activities of daily living. Urinary egress, if it occurs, would shorten the distance that bacteria need to travel to gain access to the bladder. Video urodynamics with contrast medium can demonstrate urinary egress; however, the observations can be difficult to conduct. Egress can be expected to be more likely in women with lower urinary tract conditions such as urge and stress incontinence. Treatment of the incontinence also reduces UTI rates and the reduction could, in part, be due to reduced urine egress. If UTI risk remains after incontinence management, then further treatment with pelvic floor exercises and pessaries could be considered to reduce the risk from potential residual urine egress. In summary, urine egress as a risk factor for UTI needs further research and clinical consideration. [ABSTRACT FROM AUTHOR]

Introduction: traumatic brain injury (TBI) is very often associated with spasticity. Medical interventions may include medications such as baclofen, a Gamma-Aminobutyric Acid (GABA) -receptor agonist of poor lipid solubility. Intrathecal baclofen (ITB) administration is a contemporary treatment option which minimizes adverse effects in contrast with the oral form of the drug. Regarding low urinary tract dysfunction, TBI, as a suprapontine lesion, results in neurogenic detrusor overactivity. Frequency, urgency and urge incontinence are the predominant signs and symptoms of this condition. Our study aims to report the potential changes in bladder function in patients with spasticity, due to TBI, after the implantation of the baclofen pump and the control of spasticity. Material and Methods: We report three cases of TBI whose spasticity responded well to ITB. We evaluated our medical reports regarding bladder function retrospectively, before and after baclofen pump implantation. We compared the data of bladder diaries and urodynamic parameters. Results: Bladder function was improved in all patients. Regarding bladder diaries; the number of incontinence and micturition episodes was decreased and the volume per void was slightly increased. Regarding urodynamic parameters; bladder capacity and reflex volume increased, Pdetmax decreased, PVR was the same and DLPP was slightly decreased. Conclusions: Although the baclofen pump is implanted to treat spasticity, detrusor activity may be also affected. Therefore, patients' urologic profiles should also be reevaluated after ITB. Further prospective studies are required to investigate the effect of ITB on bladder function in the clinical field and also at the basic science level. [ABSTRACT FROM AUTHOR]

Neurogenic lower urinary tract dysfunction (NLUTD) in asymptomatic patients with MS has been described in preliminary studies, but specific investigations of this topic are rare. Many authors advise early diagnosis and treatment of NLUTD in patients with MS. In contrast, clinical practice and different guidelines recommend neuro-urological diagnostics only in the presence of symptoms. Our aim was to investigate the characteristics of NLUTD and the correlations of clinical parameters with NLUTD in asymptomatic patients with MS. We evaluated bladder diaries, urodynamic findings, and therapy proposals. Correlations of the voided volume, voiding frequency, urinary tract infections, and uroflowmetry including post-void residual with the urodynamic findings were determined. In our study, 26% of the patients were asymptomatic. Of these, 73.7% had urodynamic findings indicative of NLUTD, 21.1% had detrusor overactivity, 13.2% had detrusor underactivity, 13.2% detrusor overactivity and detrusor sphincter dyssynergia, and 57.9% had radiologically abnormal findings of the bladder. No patients presented low bladder compliance or renal reflux. Clinical parameters from the bladder diary and urinary tract infections were found to be correlated with NLUTD, and the absence of symptoms did not exclude NLUTD in patients with MS. We observed that urinary tract damage is already present in a relevant proportion. Based on our results, we recommend that patients with MS be screened for NLUTD regardless of the subjective presence of urinary symptoms or the disease stage. [ABSTRACT FROM AUTHOR]

Neurogenic lower urinary tract dysfunction, common in patients with chronic spinal cord injury, inevitably results in urological complications. To address neurogenic lower urinary tract dysfunction after spinal cord injury, proper and adequate bladder management is important in spinal cord injury rehabilitation, with the goal and priorities of the protection of upper urinary tract function, maintaining continence, preserving lower urinary tract function, improvement of SCI patients' quality of life, achieving compatibility with patients' lifestyles, and decreasing urological complications. This concise review aims to help urologists address neurogenic lower urinary tract dysfunction by focusing on the risks of long-term urological complications and the effects of different bladder management strategies on these complications based on scientifically supported knowledge. [ABSTRACT FROM AUTHOR]

The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a traumatic spinal cord injury (SCI), supraspinal influences on the peripheral nervous system and autonomic nervous system (ANS) are disrupted, leading to spastic paralysis, sympathetic blunting, and parasympathetic dominance, resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions, and uncontrolled bowel, bladder, and sexual dysfunction. This article outlines the pathophysiology of the less reported nontraumatic SCI (NTSCI), its classification, its influence on sensory/motor function, and introduces the probable comorbidities associated with SCI that will be discussed in more detail in the accompanying manuscripts of this special issue. Finally, management strategies for NTSCI will be provided. [ABSTRACT FROM AUTHOR]

This is a retrospective study of our experience with Gentamicin intravesical instillation as therapy and prophylaxis in patients with lower urinary tract infections (UTIs) undergoing clean intermittent catheterization because of a neurogenic bladder. It is an alternative therapy when all other systemic treatments have failed as it is still an off-label prescription. [ABSTRACT FROM AUTHOR]

Capsaicin acts on sensory nerves via vanilloid receptors. TRPV1 has been extensively studied with respect to functional lower urinary tract (LUT) conditions in rodents and humans. We aimed to (1) provide background information on capsaicin and TRPV1 and its mechanisms of action and basis for clinical use, (2) review the use of acute intravesical capsaicin instillation (AICI) in rodents to mimic various LUT disorders in which capsaicin sensitive C-fibers are involved and (3) discuss future innovative treatments. A comprehensive search of the major literature databases until June 2022 was conducted. Both capsaicin-sensitive and resistant unmyelinated bladder afferent C-fibers are involved in non-neurogenic overactive bladder/detrusor overactivity (OAB/DO). AICI is a suitable model to study afferent hyperactivity mimicking human OAB. Capsaicin-sensitive C-fibers are also involved in neurogenic DO (NDO) and potential targets for NDO treatment. AICI has been successfully tested for NDO treatment in humans. Capsaicin-sensitive bladder afferents are targets for NDO treatment. TRPV1-immunoreactive nerve fibers are involved in the pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS). The AICI experimental model appears relevant for the preclinical study of treatments targeting bladder afferents for refractory IC/BPS. The activity of capsaicin-sensitive bladder afferents is increased in experimental bladder outlet obstruction (BOO). The AICI model may also be relevant for bladder disorders resulting from C-fiber hyperexcitabilities related to BOO. In conclusion, there is a rationale for the selective blockade of TRPV1 channels for various bladder disorders. The AICI model is clinically relevant for the investigation of pathophysiological conditions in which bladder C-fiber afferents are overexcited and for assessing innovative treatments for bladder disorders based on their pathophysiology. [ABSTRACT FROM AUTHOR]

New, contextualized modern solutions must be found to solve the dilemma of catheter-associated urinary infection (CAUTI) in long-term care settings. In this paper, we describe the etiology, risk factors, and complications of CAUTI, explore different preventive strategies proposed in literature from the past to the present, and offer new insights on therapeutic opportunities. A care bundle to prevent CAUTI mainly consists of multiple interventions to improve clinical indications, identifying a timeline for catheter removal, or whether any alternatives may be offered in elderly and frail patients suffering from chronic urinary retention and/or untreatable urinary incontinence. Among the various approaches used to prevent CAUTI, specific urinary catheter coatings according to their antifouling and/or biocidal properties have been widely investigated. Nonetheless, an ideal catheter offering holistic antimicrobial effectiveness is still far from being available. After pioneering research in favor of bladder irrigations or endovesical instillations was initially published more than 50 years ago, only recently has it been made clear that evidence supporting their use to treat symptomatic CAUTI and prevent complications is needed. [ABSTRACT FROM AUTHOR]