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Lower urinary tract dysfunction (LUTD) can manifest as a spectrum of voiding symptoms in childhood, including urinary urgency, frequency, hesitancy, and incontinence. In severe cases, it can lead to frequent urinary tract infections, hydronephrosis, kidney scarring, and chronic kidney disease. Non-neurogenic neurogenic bladder (NNNB) is a diagnosis of exclusion in which children develop discoordination between the detrusor smooth muscle and external urethral sphincter in the absence of neurological or obstructive lesions, resulting in severe LUTD. Historically, such disorders of voiding were thought to result from behavioral maladaptation. However, it is now increasingly recognized that some individuals may have an underlying genetic etiology for their symptoms. Here, we performed exome sequencing for five probands with NNNB or other forms of severe LUTD, and we identified two individuals with monogenic etiologies for their symptoms. One individual had a homozygous exon 9 deletion in HPSE2 and another had a homozygous single amino acid deletion (p.Gly167del) in ARL6. We performed PCR experiments to identify the breakpoints of the HPSE2 exon 9 deletion and implicate microhomology-mediated end joining as a potential mechanism by which the deletion arose. These findings suggest that genetic testing should be considered for children with severe LUTD.

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Bladder dysfunction represents a frequent and important clinical problem in stroke patients. The aim of this narrative review was to explore the currently available information regarding the diagnosis and management of bladder dysfunction following stroke. The most common symptoms of bladder dysfunction following stroke are urinary incontinence, urgency, increased frequency, and difficulty voiding. Medical history, including voiding diary, physical examination, and urodynamic studies are useful in establishing diagnosis. Bladder pressure in stroke patients with detrusor overactivity is rarely high enough to damage the upper urinary tract. In neurogenic bladder, however, there is always a risk for transmission of intravesical pressure to the upper tract. In incontinent patients, urodynamic studies can reveal bladder hyper- or hyporeflexia, detrusor overactivity with impaired contractility or detrusor-sphincter dyssynergia, or even no abnormalities at all. With stroke patients with urinary dysfunction, establishing a proper diagnosis is of paramount importance to start appropriate treatment, prevent upper tract damage, maintain continence, and ensure complete emptying. After diagnosis, an individually tailored treatment plan is mandatory, including behavioral techniques, lifestyle interventions, and anticholinergic medication. Other therapeutic choices include alternative drugs, intradetrusor injection of botulinum toxin, and spinal neuromodulation. A bladder rehabilitation program is essential for improving post-stroke lower urinary symptoms and depends on the patient's awareness, cooperation, and independence. Bladder dysfunction after stroke, as a strong prognostic factor of disability, exerts an enormous impact on health and economy. Therefore, every single effort toward a proper diagnosis and effective rehabilitation is crucial.

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BACKGROUND: Clean intermittent self-catheterisation (CISC) with conventional eyelet catheters (CECs) is associated with urine flow-stops, which require the catheter to be repositioned so flow can resume. Flow-stops often occur because bladder mucosa is sucked into the eyelets. AIMS: This investigation aimed to compare the bladder-emptying performance of the micro-hole zone catheter (MHZC) with the CEC. METHODS: This was a multi-centre, randomised, open-label, controlled cross-over study with 82 women comparing the MHZC to the CEC. The endpoints relating to bladder-emptying performance included the residual volume at first flow-stop, the number of flow-stops and the proportion of successful treatment responses. The women's perception of the catheters was assessed as well as device discomfort. FINDINGS: Catheterisations with MHZC significantly reduced the risk of flow-stops, with relative risk results showing a 2.74 times lower risk of flow-stops with a health professional-led catheterisation and a 2.52 times lower risk during self-catheterisation. There was no statistical difference in residual urine volume at first flow-stop between the two catheters. Catheterisations with the MHZC were significantly more likely to achieve zero flow-stops and a residual urine volume of <10 ml at first flow-stop. The women had a significantly more positive perception of the MHZC than the CEC in areas including handling, confidence, sensation and satisfaction. CONCLUSION: The MHZC enabled effective bladder emptying without catheters needing to be repositioned, supporting the women by simplifying the procedure and making them feel confident that their bladders were empty.

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INTRODUCTION: Clean Intermittent Catheterization (CIC) is considered as a gold standard of treatment for bladder emptying disorders. A large amount of literature on CIC for patients suffering from neurological disorders is available, but there is a lack of research specifically concerning multiple sclerosis (MS) patients. Our primary outcome was to determine the characteristics of our population (sex, EDSS and age when CIC was introduced). Our secondary outcomes were to determine adherence of CIC. METHOD: As part of a multicenter, observational, retro-prospective study, data was collected from neuro-urologist consultation reports, and extracted from bladder diaries between 01/01/2000 and 31/03/24. MS patients, over 18 years, with the indication of CIC were included. RESULT: 195 patients (72.3% women) were included, with a mean age of 49 years old. The median of follow-up was 9 years. Median EDSS at the start of the study was 5.5. There was an adherence rate of 65.1%. Urinary leakage was present in 74,2% of patients prior to CIC and 31.6% following CIC. CONCLUSION: Catheterization is mainly offered to patients with an EDSS between 0 and 7. Rate of adhesion is encouraging, with most patients still continuing to use CIC by the end of follow-up. During the follow-up, we observed a reduced leakage rate but CIC alone can not explain this improvement. Following studies should include a list of constraints and reasons of halted CIC.

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Urinary tract infections (UTIs) are frequently associated with lower urinary tract dysfunction (LUTD). Urodynamic investigation (UDI) is the gold standard for assessing LUTD, but its value in identifying UTI risk factors remains underexplored. Studies have shown high rates of storage and voiding dysfunction in patients with recurrent UTIs, suggesting a causal link between LUTD and UTIs. Specific UDI findings, such as low bladder capacity, high detrusor pressures, and detrusor overactivity, have been associated with greater UTI risk, especially in kidney transplant recipients and infants. However, the current evidence is limited by the lack of control groups and therapeutic interventions, making it difficult to draw definitive conclusions. Further well-designed studies are needed to determine if UDI-guided therapies can improve UTI management outcomes. PATIENT SUMMARY: Urinary infections are often linked to problems with the lower urinary tract. Tests that measure lower urinary tract function can help in identifying these issues. More research is needed to see if treating bladder problems can prevent urinary infections.

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BACKGROUND: Neurogenic bladder (NB) is a prevalent urologic condition significantly impacting the health and quality of life of affected individuals. The condition, often resulting from various etiologies such as spinal cord injuries and multiple sclerosis, leads to severe life problems, including pain and impaired physical, mental, social, and emotional functioning. This study aims to explore the medical practices of urologists in the diagnosis, management, and care of NB patients within the Palestinian healthcare context, highlighting the absence of a unified treatment protocol and the reliance on private clinics for care. METHODS: An exploratory qualitative study design was employed, adhering to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Structured interviews were conducted with 14 urologists and two urology residents across eight different cities in Palestine, including 10 governmental hospitals, two private hospitals, one university hospital, and one charity hospital. Fourteen doctors had private outpatient clinics alongside their work in hospitals. A questionnaire developed by the authors was delivered to specialists and residents to understand the evaluation, management, follow-up practices, and challenges faced in treating NB patients. The study focused on the diagnostic processes, treatment modalities, complications management, and the impact of the lack of standardized protocols on patient care. Our qualitative study consists of six major themes, each theme consisting of multiple sub-themes and different participant responses: (1) diagnosis and follow-up of NB patients; (2) general issues in the management of NB; (3) evaluation and follow-up of upper and lower urinary system function in NB patients; (4) urinary tract infections associated with NB disease and how to deal with it; (5) opinions and future attitudes in the treatment of NB patients; (6) NB in patients with multiple sclerosis. RESULTS: The study found that urodynamic studies are crucial in NB diagnosis, yet there is no unified management protocol, leading to varied practices. Most participants preferred the American Urological Association (AUA) guidelines in the absence of Palestinian protocols. Six major themes emerged, including diagnosis and follow-up challenges, general issues in NB management, evaluation and follow-up of urinary system function, urinary tract infections management, opinions on future treatment directions, and specific considerations for NB patients with multiple sclerosis. CONCLUSIONS: The study highlights the need for a unified, standardized protocol for the management of NB patients in Palestine. The reliance on international guidelines, primarily the AUA protocols, underscores the gap in local healthcare policies. The findings call for the establishment of national guidelines and enhanced resources for the effective management of NB, aiming to improve patient outcomes and quality of life.

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Purpose: The primary aim of this study was to evaluate the indications and additional information provided by videourodynamic study (VUDS) over urodynamic studies (UDS) in men with spinal cord injury (SCI) and neurogenic lower urinary tract dysfunction (NLUTD). The secondary aim was to determine the added value of VUDS and its impact on bladder management. Materials and Methods: Single-centre retrospective study of all men with SCI who underwent VUDS between 2011 and 2021. Participant characteristics, clinical data and indications for UDS and VUDS as well as bladder management were recorded. The added value of VUDS was defined as additional information not provided by standard UDS that impacted on bladder management (choice of voiding mode, surgical indication or type of surgery). Results: Eighty-eight men with a median age of 52 years were included. In 20 men who were unable to perform self-catheterisation, the VUDS clarified the nature and extent of the obstruction and enabled targeted surgery to achieve reflex bladder emptying in all of them. VUDS also clarified the type and level of obstruction in 28 patients, enabling targeted surgery in 24. In 11 men, VUDS was performed as part of the preoperative assessment for a Brindley procedure or after this operation if a complication occurred during follow-up to confirm the need for further surgery or to target surgical revision. Overall, VUDS had added value in 59 patients (67%). Conclusions: VUDS had added value over UDS in specific situations; the additional information provided impacted on bladder management in men with SCI and NLUTD.

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Neuronal intranuclear inclusion disease is an uncommon neurodegenerative disorder. The diagnosis of this condition has become more definitive based on current research. However, treatment options remain limited. Neurogenic lower urinary tract dysfunction is one of the prevalent and significant complications, which is the result of its multi-system effects. Here, we present the case of a 48-year-old man diagnosed with neuronal intranuclear inclusion disease based on existing evidence and was complicated by neurogenic lower urinary tract dysfunction. Despite undergoing some medical treatments, his lower urinary tract symptoms, including urinary incontinence, incomplete or intermittent voiding, etc, continued to worsen while upper urinary tract injury developed. Based on careful consideration of the patient's condition and the available findings, we performed an unprecedented sacral neuromodulation on him. Implementation of sacral neuromodulation led to significant improvement in his urination function and alleviate kidney function damage. Our case suggests a potential therapeutic role for sacral neuromodulation in the treatment of neurogenic lower urinary tract dysfunction associated with neuronal intranuclear inclusion disease. Additional research is required to determine the effectiveness of sacral neuromodulation in managing neurogenic lower urinary tract dysfunction caused by various etiologies.

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Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with central nervous system (CNS) lesions. Cases of cerebrovascular accidents (CVA), Parkinson's disease, dementia, and other intracranial lesions develop poor bladder control with or without urinary difficulty due to loss of cortical perception of bladder filling sensation and poor coordination of urethral sphincter relaxation during reflex micturition. Patients with CNS lesions usually have overactive bladder (OAB) symptoms, including urgency, frequency, incontinence, voiding symptoms of dysuria, large postvoid residual volume, and retention. In elderly patients with severe CNS disease the OAB symptoms are usually difficult to adequately relieve by medical treatment, and thus, their quality of life is greatly. Botulinum toxin A (BoNT-A) is currently licensed and has been applied in patients with idiopathic and neurogenic OAB due to spinal cord injury or multiple sclerosis. However, the application of BoNT-A in the treatment of urinary incontinence due to NLUTD in chronic CNS lesions has not been well-documented. Although cohort studies and case series support BoNT-A treatment for neurogenic OAB, chronic urine retention after intravesical BoNT-A injection for OAB and exacerbated urinary incontinence after urethral BoNT-A injection for voiding dysfunction have greatly limited its application among patients with NLUTD due to CNS lesions. This article reviews the pathophysiology and clinical characteristics of NLUTD in patients with CNS lesions and the clinical effects and adverse events of BoNT-A injection for patients with NLUTD. A flowchart was created to outline the patient selection and treatment strategy for neurogenic OAB.

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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.

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AIMS: To discuss the role of autocrine/paracrine signaling of urothelial arginine vasopressin (AVP) on mammalian bladder capacities and micturition thresholds, impact of distension on water/urea reabsorption from the bladder, review of the literature to better characterize the central/peripheral effects of AVP, desmopressin (dAVP) toxicity, and urine biomarkers of nocturia. METHODS: This review summarizes discussions during an International Consultation on Incontinence-Research Society 2024 think tank with respect to the role of urothelial AVP in aged individuals with nocturnal polyuria, impact of solute and water reabsorption by the bladder on uninterrupted sleep, central effects of AVP, pharmacological basis of dAVP toxicity, and biomarkers in nocturia/lower urinary tract dysfunction (LUTD) with neurological diseases. RESULTS: Consensus recognized AVP function and pathways in the central nervous system (CNS), pre-proAVP localized using immunohistochemistry in bladder sections from adult/aged noncancerous human punch biopsies and rodent bladder sections is likely to accelerate the systemic uptake of water and urea from the bladder of anesthetized mice instilled with 3H-water and 14C-urea. Mechanisms for charged and uncharged solutes and water transport across the bladder, mechanism of dAVP toxicity, and utility of urine biomarkers in those with neurological diseases/nocturia were determined from literature reviews. CONCLUSION: Pre-proAVP is present in human/rodent bladders and may be involved in water reabsorption from bladder that prevents the sensation of fullness for uninterrupted sleep in healthy adults. The mechanism of action of AVP in the CNS was discussed, as was electrolyte/water transport across the bladder, the basis for dAVP toxicity, and feasibility of urine biomarkers to identify nocturia/LUTD with neurological diseases.

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Introduction: Lower urinary tract dysfunction (LUTD) in cerebral palsy (CP) and other neuromuscular diseases can present with chronic retention that leads to hydronephrosis, recurrent urinary tract infections (UTI), and stone formation. Whenever the conservative treatment of LUTD fails for any reason, it is considered to be complicated LUTD, in which a surgical approach is warranted. Cutaneous vesicostomy (CV) is a simple, well-tolerated, and potentially reversible procedure that protects the upper tracts. We describe our experience using CV for this complex population. Materials and methods: Children with CP and other neuromuscular diseases admitted to pediatric long-term care units for palliative care between 2015 and 2019 were included in the study. They present multi-system involvement, polypharmacy, and Gross Motor Function Classification System levels of 4 or 5. We retrospectively studied this population's indications and results of CV. Results: Of the 52 admitted patients, 18 presented LUTD with UTI (n:18; 100%), stones (n:5; 28%), progressive hydroureteronephrosis (n:3; 17%), or stones (n:2; 11%). Conservative initial management (catheterizations, prophylaxis antibiotics) was effective in half the cases. The remaining nine were defined as complicated LUTD and underwent CV. After a mean follow-up of 11.3 months, the follow-up showed improved hydronephrosis in all nine (100%) patients. Recurrent UTIs were no longer seen in eight of nine patients, although three patients required bladder irrigations; bladder stones did not recur after CV; the kidney stones needed further intervention. Revision of the CV was required in two (11%) cases at 12 and 24 months postoperatively due to stoma stenosis. Conclusion: CV is a relatively simple and effective procedure representing a pragmatic solution for managing complicated LUTD in complex long-term institutionalized pediatric palliative care patients with neuropathic bladders.

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PURPOSE: The management of bowel bladder disorder (BBD) has only been indicated for subjective constipation without objective evidence. We attempted to highlight the radiological findings in patients with BBD and construct a scoring system to identify patients with BBD prior to treatment. MATERIALS AND METHODS: Forty-five patients with lower urinary tract dysfunction (LUTD) received polyethylene glycol for 2 months before bladder medication for LUTD. Based on partial response to LUTD following treatment, we divided the patients into LUTD-fecal impaction (FI) and LUTD not attributed to FI (LUTD-NFI) groups. Pre/post-treatment kidney, ureter, and bladder (KUB) were compared with respect to several radiographic parameters. Items with significant changes after treatment were included in the scoring system. The accuracy and inter-rater agreement were also evaluated. RESULTS: Cecal dilation, descending colon dilation, fecal quality, and overall haziness were found to undergo significant changes after laxative treatment. We assigned 0 to 2 points for each item, with a total score of 8. Receiver operating characteristic curve analysis revealed a cutoff value of 5 between LUTD-FI and LUTD-NFI, with 79% sensitivity and 88% specificity. The scoring system was instructed to six doctors who were unaware of it and was then tested on previous patients, which showed a substantial concordance rate (κ=0.79, p<0.05). CONCLUSIONS: Fecal scoring system based on KUB was beneficial in identifying children with LUTD attributed to FI. This may provide an opportunity to obtain objective FI data as an alternative to subjective assessment of constipation.

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AIMS: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls. METHODS: This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies. RESULTS: This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population. CONCLUSIONS: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency.

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AIMS: To investigate the risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS), and develop an internally validated predictive nomogram. The study aims to offer insights for preventing AIS-NLUTD. METHODS: We conducted a retrospective study on AIS patients in a Shenzhen Hospital from June 2021 to February 2023, categorizing them into non-NLUTD and NLUTD groups. The bivariate analysis identified factors for AIS-NLUTD (p < 0.05), integrated into a least absolute shrinkage and selection operator (LASSO) regression model. Significant variables from LASSO were used in a multivariate logistic regression for the predictive model, resulting in a nomogram. Nomogram performance and clinical utility were evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC). Internal validation used 1000 bootstrap resamplings. RESULTS: A total of 373 participants were included in this study, with an NLUTD incidence rate of 17.7% (66/373). NIHSS score (OR = 1.254), pneumonia (OR = 6.631), GLU (OR = 1.240), HGB (OR = 0.970), and hCRP (OR = 1.021) were used to construct a predictive model for NLUTD in AIS patients. The model exhibited good performance (AUC = 0.899, calibration curve p = 0.953). Internal validation of the model demonstrated strong discrimination and calibration abilities (AUC = 0.898). Results from DCA and CIC curves indicated that the prediction model had high clinical utility. CONCLUSIONS: We developed a predictive model for AIS-NLUTD and created a nomogram with strong predictive capabilities, assisting healthcare professionals in evaluating NLUTD risk among AIS patients and facilitating early intervention.

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OBJECTIVE: Guanyuan (CV4), Zhongji (CV3) and Sanyinjiao (SP6) are the most frequently used acupoints for treating neurogenic bladder after spinal cord injury (SCI). However, there has been no investigation to clarify the differences in effects of these acupoints in different types of neurogenic bladder. METHODS: The study was structured with a randomized, two-phase cross over design with a washout period. A routine urodynamic examination was performed first, then, in the order of grouping, electroacupuncture was performed on CV4, CV3, and SP6, respectively，and urodynamic examination was performed to observe the changes of urodynamic indexes in real time. RESULTS: When undergoing electroacupuncture at CV4, CV3, and SP6 in patients with neurogenic detrusor overactivity (DO), the bladder volume at the first occurrence of DO and maximum cystometric capacity increased (p < 0.05), but maximum detrusor pressure (Pdetmax) at DO decreased (p < 0.05), and the changes using CV4 and CV3 was more significantly than using SP6 (p < 0.05). And in patients with in neurogenic detrusor underactivity, there were no significant changes in maximum urinary flow rate and Pdetmax during urination (p > 0.05). CONCLUSION: The immediate relief effect of electroacupuncture at CV4, CV3 on DO was greater than at SP6.

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To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

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INTRODUCTION: Despite advancements in the treatment of benign prostatic hyperplasia (BPH), the mechanisms underlying BPH development and progression remain elusive and lacks a one-size-fits-all therapeutic solution. Prostatic inflammation contributes to BPH and lower urinary tract symptoms (LUTS), but the initial trigger remains unknown. Current research suggests dysbiosis of the urinary microbiome as a potential culprit. This systematic review explores the emerging field of the male urinary and prostatic microbiome and its relationship with BPH/LUTS. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A systematic search in the Pubmed and Scopus databases was performed using specific terms. Inclusion criteria considered male non-neurogenic patients with LUTS due to BPH with analyses of urinary microbiome, concerning evaluation of English-language publications with relevance. RESULTS: Among seven articles involving 542 patients, there was an association between male LUTS/BPH and the urinary microbiome. Findings indicate a correlation between urinary microbiome dysbiosis and LUTS severity, with specific bacterial genera such as Streptococcus and Haemophilus linked to higher International Prostate Symptom Score (IPSS) scores and PSA levels. The fecal microbiome may be associated with LUTS, although contradictory findings are reported. The review also highlights methodological inconsistencies, small sample sizes, few negative controls and a lack of comprehensive clinical data as major limitations. CONCLUSIONS: While there is an undeniable correlation between the microbiome and LUTS/BPH, future research should aim to standardize sampling techniques and expand the score to include functional microbiome characterization, potentially leading to novel, microbiome-targeted therapeutic strategies for BPH.

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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, RARß, 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-ß 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.

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INTRODUCTION: Bladder dysfunction, or more specifically lower urinary tract dysfunction (LUTD), remains a common reason for pediatric urology consultation, and the management of these patients is time consuming and frustrating for patients, families and providers alike. But what happens when the patient proves refractory to current treatment modalities? Is there a role for the use of videourodynamics (VUDS) to help guide therapy in the patient with refractory voiding dysfunction, and if so how might we select patients for this invasive study in order to increase the yield of useful information? OBJECTIVES: To determine the role, if any, for VUDS in the evaluation of pediatric patients with refractory LUTD and to identify parameters that might be used to select patients for this invasive study in order to increase the yield of useful information. STUDY DESIGN: Through our IRB-approved prospectively maintained urodynamics database, we retrospectively identified 110 patients with non-neurogenic LUTD over a period from 2015 to 2022 who underwent VUDS. We excluded patients with known neurologic or anatomic lesions and developmental delay. RESULTS: There were 76 females and 34 males (69%/31%) and their average age at the time of the study was 10.5 years ± 4 with a median age of 7.3 years. Patients had been followed for a mean of 5.9 ± 3.5 office visits prior to obtaining the VUDS and reported a mean Dysfunction Voiding and Incontinence Symptom Score (DVISS) of 15.6 ± 6.7 before the VUDS. VUDS resulted in a change in management in 86 of these 110 patients (78%). Management changes included a change in medication (53/110), consideration of CIC (11/110), PTENS (1/110) and surgery (14/110). As shown in the Figure, the DVISS score was significantly higher and the number of office visits prior to VUDS was significantly higher in the 86 patients whose management was changed versus the 24 patients in whom management did not change (P < 0.02). CONCLUSION: This retrospective analysis suggests that criteria for selecting these patients include: 1) long standing urinary incontinence that is refractory to biofeedback and medications, 2) ≥6 visits to LUTD clinic with no improvement, and 3) LUT symptom score of ≥16. Our findings suggest these criteria identify a cohort of patients in which a VUDS evaluation for the child with refractory LUTD can offer a more exact diagnosis that can shape management.