Search

Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, cell surface and external environmental factors. UTI89 filamentation and macrophage engulfment efficiency was also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM in both in vivo and in vitro models of infection. Compared to filaments formed via antibiotic inhibition of division, the infection-derived filaments were preferentially targeted by macrophages. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial physiological and morphological states during infection. Author summary: Urinary tract infections (UTIs) are one of the most common bacterial infections worldwide with 50% of women suffering from a UTI during their lifetime. Escherichia coli is the primary bacteria responsible for UTIs and is usually found in short rod forms. However, during UTIs E. coli can elongate into extremely long thin shapes called 'filaments'. Filaments are thought to be advantageous during infections because they are too long to be engulfed and killed by immune cells called macrophages. Due to increasing antibiotic resistance in bacteria there is a strong need for the discovery of new ways to treat infections and this is only possible once we thoroughly understand the mechanisms bacteria employ to overcome our immune response. Therefore, we investigated the effect of E. coli filamentation on macrophage engulfment along with other aspects of bacteria reported to influence engulfment. We found that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, surface and external environmental factors. Our research has highlighted the importance of bacterial shape changes during infections and provided a foundational understanding of macrophage engulfment of filaments. Eventually, this knowledge may reveal new targets for treatment of infections. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes is highly prevalent worldwide, with an estimated 536 million living with diabetes in 2021, and that number projected to increase to 783 million by 2045. Diabetic bladder dysfunction is thought to affect up to 60%–90% of individuals with diabetes and can significantly impact quality of life. Despite the prevalence of diabetic bladder dysfunction, the exact pathophysiological mechanism, and resulting clinical presentation, remains debated. Our objective was to compare urodynamic parameters between diabetic and nondiabetic women, assessing the impact of various markers of diabetes severity on bladder function. Methods: A retrospective chart review was conducted on female patients aged 18 and above who underwent urodynamic studies at a single tertiary care university hospital system from 2014 to 2020. Patients were categorized based on diabetes status, and diabetes severity including duration of disease, hemoglobin A1c levels, insulin dependence, and markers of end‐organ dysfunction. Urodynamic variables, including compliance, bladder voided efficiency, bladder contractility index, postvoid residual, maximum flow rate, capacity, voided volume, and detrusor overactivity, were assessed by two independent reviewers. Statistical analyses were performed to assess the impact of diabetes and diabetic severity on urodynamic parameters. Results: A total of 652 female patients were included in the study, of which, 152 (23.3%) had diabetes, with an average duration of diagnosis of 82.3 months. Diabetic women were older and had higher body mass index compared to nondiabetic women. Diabetic retinopathy and neuropathy were present in 18% and 54.6% of diabetic patients, respectively. Significant differences in urodynamic parameters were observed between diabetic and nondiabetic women, with diabetic women showing higher rates of detrusor overactivity (p = 0.01), particularly associated with increasing BMI (p = 0.03). However, classic markers of diabetes severity including duration, as well as markers of end‐organ damage, showed mixed associations with urodynamic changes. Conclusions: Despite the prevalence of diabetic bladder dysfunction and its impact on patient quality of life, the exact mechanisms and clinical presentation remain elusive. Our study highlights the significant differences in urodynamic parameters between diabetic and nondiabetic women, emphasizing the need for further research into the relationship between diabetes and diabetic bladder dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Detrusor overactivity with detrusor underactivity (DO‐DU) is classically described in frail institutionalized elderly patients, but we have also observed this diagnosis in younger populations. This research aims to identify the differences between two age groups of DO‐DU patients. Materials and Methods: This study included DO‐DU patients from a single center from 2012 to 2023. Patients were divided into two groups: the "Younger" group (aged less than 70 years) and the "Older" group (aged 70 years or older). We separately compared demographics, the number of risk factors considered to affect bladder function, clinical presentations, and urodynamic findings between these two groups in each gender. Results: There were 210 patients included in the analysis, with 50.48% in the younger group and 49.52% in the older group. The median ages of males and females in the younger group were 57 and 62 years, whereas the median ages of males and females in the older group were 76.5 and 76 years. Multiple sclerosis exhibited statistically significant prevalence in the younger patients (7.7% vs. 0%, p = 0.03 in males and 19.9% vs. 4.6% in females). While diabetes mellitus (DM) was more prevalent in the older males (20.0% vs. 4.6%, p = 0.01), transabdominal hysterectomy was more common in the younger females (46.3% vs. 25%, p = 0.04). 69.8% of the younger group and 71.2% of the older group have at least one risk factor that impact their bladder function. There was no statistically significant difference between the two groups across various risk factor categories. The older males reported a higher incidence of urgency (78.3% vs. 58.5%, p = 0.02) and urge incontinence (61.7% vs. 32.3%, p < 0.01), while the younger females reported a higher incidence of straining during voiding on history (46.3% vs. 20.5%, p = 0.01). The younger males exhibited a greater volume of strong desire to void (385 vs. 300 mL, p = 0.01), maximal cystometric capacity (410 vs. 300 mL, p < 0.01), and a lower highest detrusor overactivity (DO) pressure (37 vs. 50.5 cmH2O, p = 0.02). The younger group had a higher postvoid residual (170 vs. 85 mL in males, p < 0.01 and 180 vs. 120 mL in females, p = 0.02). The voiding efficiency was lower in younger females (40% vs. 60%, p = 0.02). In both ages, the ICS detrusor contraction index and projected isovolumetric pressure 1 were similar. However, without considering risk factors, the older males had the highest DO pressure (57 vs. 29 cmH2O, p < 0.01), and the younger males had a higher voiding pressure (PdetQmax) than the older males (28 vs. 20 cmH2O, p = 0.02). Conclusion: DO‐DU is not exclusive to elderly patients. It can also be diagnosed in individuals with risk factors regardless of age; therefore, clinicians need a high degree of suspicion, especially in patients who have risk factor(s) for DO and DU. A notable clinical differentiation is that older males diagnosed with DO‐DU have a higher incidence of urgency and urge urinary incontinence, while younger females have a higher incidence of straining. [ABSTRACT FROM AUTHOR]

Background: Machine learning algorithms as a research tool, including traditional machine learning and deep learning, are increasingly applied to the field of urodynamics. However, no studies have evaluated how to select appropriate algorithm models for different urodynamic research tasks. Methods: We undertook a narrative review evaluating how the published literature reports the applications of machine learning in urodynamics. We searched PubMed up to December 2023, limited to the English language. We selected the following search terms: artificial intelligence, machine learning, deep learning, urodynamics, and lower urinary tract symptoms. We identified three domains for assessment in advance of commencing the review. These were the applications of urodynamic studies examination, applications of diagnoses of dysfunction related to urodynamics, and applications of prognosis prediction. Results: The machine learning algorithm applied in the field of urodynamics can be mainly divided into three aspects, which are urodynamic examination, diagnosis of urinary tract dysfunction and prediction of the efficacy of various treatment methods. Most of these studies were single‐center retrospective studies, lacking external validation, requiring further validation of model generalization ability, and insufficient sample size. The relevant research in this field is still in the preliminary exploration stage; there are few high‐quality multi‐center clinical studies, and the performance of various models still needs to be further optimized, and there is still a distance from clinical application. Conclusions: At present, there is no research to summarize and analyze the machine learning algorithms applied in the field of urodynamics. The purpose of this review is to summarize and classify the machine learning algorithms applied in this field and to guide researchers to select the appropriate algorithm model for different task requirements to achieve the best results. [ABSTRACT FROM AUTHOR]

Purpose of Review: Invasive urodynamics are currently used to diagnose disorders of bladder function. However, due to patient discomfort as well as artifacts induced by catheters and non-physiologic filling, less invasive screening tools that can improve diagnostic information, such as ultrasound are required. The purpose of this review is to assess different modalities of ultrasound as applied to functional bladder imaging. This information will help guide future studies in the use of ultrasound during urodynamics. Recent Findings: Recently, multiple studies have employed ultrasound to evaluate bladder volume, wall thickness, shape, vibrometry, elastography, compliance, biomechanics, and micromotion during urodynamics. These new techniques have used both 2D and 3D ultrasound techniques to evaluate bladder changes during filling. Continued research is needed to confirm ongoing findings prior to widespread incorporation into clinical practice. Summary: This review demonstrates the potential use of ultrasound as an adjunct to urodynamics for the diagnostic evaluation of functional bladder disorders. [ABSTRACT FROM AUTHOR]

Objectives: To provide guidance in the form of consensus statement in the management of ketamine uropathy. Methods: A literature review of ketamine uropathy was performed. The consensus method was of a modified nominal group technique and has been use in the previous British Association of Urological Surgeons (BAUS) consensus documents and was led by the Female, Neurological and Urodynamic Urology Section of the BAUS. Results: A number of consensus statements detailing the assessment and management of urological complications relate to the recreational use of ketamine (ketamine uropathy) in both elective and emergency urology settings. Conclusion: Comprehensive management pathway for ketamine‐related urinary tract dysfunction and uropathy has been detailed. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aims to assess the outcomes of detrusorectomy in children with neurogenic bladder (NB). A search was performed in PUBMED, EMBASE and the Cochrane Library database in August 2023. The following search terms were used: "detrusorectomy", "detrusorotomy", "auto-augmentation". The two main primary outcomes were improvement in bladder capacity and bladder compliance after intervention. Outcomes were dichotomized into favorable and unfavorable. The secondary outcomes were the effect of postoperative bladder cycling on bladder compliance and bladder capacity and complications. 258 references were screened for inclusion, of these 242 were excluded. 8 of the remaining 16 studies were included for the qualitative and quantitative analysis. All studies were retrospective case series studies (165 patients). Median follow-up time varied between studies (1.75–11.1 years), while two studies reported a mean follow-up time of 8.1 years. Using a random effects meta-analysis, the overall rate for unchanged or improved bladder capacity was 95% (Proportion[CI]: 0.95 [0.61; 1.00]). The overall rate for improved bladder compliance after detrusorectomy was 67% (Proportion[CI]: 0.67 [0.26; 0.92)) (Summary Fig). In the bladder cycling group improved compliance was found in 89% of patients (Proportion[CI]: 0.89 [0.41; 0.99]), whereas it was 21% in the non-cycling group (Proportion[CI]: 0.21 [0.04; 0.61]) (p = 0.0552). Bladder cycling did not affect bladder capacity as the overall rate for unchanged or improved bladder capacity was 98% (Proportion[CI]: 0.98 [0.35; 0.92]) in the cycling and 73% (Proportion[CI]: 0.73 [0.46; 0.90]) in the non-cycling group (p > 0.05). Overall complications were encountered in 16 (9.7%) patients, with major complications (stones, bladder perforations) detected only in 5(3%) patients. Detrusorectomy leads to an improved bladder compliance in 67% of children. As such, detrusorectomy proves to be a viable procedure to enhance bladder compliance or to cure overactivity. Importantly, the beneficial effect of detrusorectomy on bladder compliance seems to be long-lasting. Bladder capacity remained unchanged or improved in almost all patients undergoing detrusorectomy. Postoperative bladder cycling was effective in improving bladder compliance outcome compared to the non-cycling group. Proper patient selection is the key to good postoperative outcomes. Detrusorectomy enhances bladder compliance in pediatric neurogenic bladders. Postoperative bladder cycling improves bladder compliance and the overall complication rate of the procedure is low. Therefore, detrusorectomy should be considered a valuable therapeutic option in the comprehensive management of neurogenic bladders in children. [ABSTRACT FROM AUTHOR]

The storage and periodic voiding of urine in the lower urinary tract are regulated by a complex neural control system that includes the brain, spinal cord, and peripheral autonomic ganglia. Investigating the neuromodulation mechanisms of the lower urinary tract helps to deepen our understanding of urine storage and voiding processes, reveal the mechanisms underlying lower urinary tract dysfunction, and provide new strategies and insights for the treatment and management of related diseases. However, the current understanding of the neuromodulation mechanisms of the lower urinary tract is still limited, and further research methods are needed to elucidate its mechanisms and potential pathological mechanisms. This article provides an overview of the research progress in the functional study of the lower urinary tract system, as well as the key neural regulatory mechanisms during the micturition process. In addition, the commonly used research methods for studying the regulatory mechanisms of the lower urinary tract and the methods for evaluating lower urinary tract function in rodents are discussed. Finally, the latest advances and prospects of artificial intelligence in the research of neuromodulation mechanisms of the lower urinary tract are discussed. This includes the potential roles of machine learning in the diagnosis of lower urinary tract diseases and intelligent-assisted surgical systems, as well as the application of data mining and pattern recognition techniques in advancing lower urinary tract research. Our aim is to provide researchers with novel strategies and insights for the treatment and management of lower urinary tract dysfunction by conducting in-depth research and gaining a comprehensive understanding of the latest advancements in the neural regulation mechanisms of the lower urinary tract. [ABSTRACT FROM AUTHOR]

Aims: The postvoid residual (PVR) volume of urine in the bladder is widely used in clinical practice as a guide to initiate treatment, including clean‐intermittent self‐catheterization (CISC). It is often believed that an elevated PVR causes complications such as recurrent urinary tract infections (UTI) and renal failure. However, evidence for this is limited and identifying alternative measures to guide treatment decisions may optimize patient care. At the International Consultation on Incontinence Research Society (ICI‐RS) meeting in 2023 a Think Tank addressed the question of whether we can define the optimal PVR at which CISC should be recommended, and whether there are other measures that could guide a CISC protocol. Methods: The Think Tank conducted a literature review and expert consensus meeting focusing on current limitations in defining and measuring PVR, and highlighting other measures that may optimize selection for, and persistence with, CISC. Results: There is no consensus on the threshold value of PVR that is considered "elevated" or "significant." There is a lack of standardization on terminology, and the normal range of PVR in different populations of different ages remains to be well‐studied. The measurement of PVR is influenced by several factors, including intraindividual variation, timing and method of measurement. Furthermore, the evidence linking an elevated PVR with complications such as UTI and renal failure is mixed. Other measures, such as bladder voiding efficiency or urodynamic parameters, may be better at predicting such complications, and therefore may be more relevant at guiding a CISC protocol. Conclusions: There is a lack of high quality evidence to support PVR as a predictor for complications of UTI or renal failure. Threshold values for normal PVR in different populations are unknow, and so threshold values for "elevated" or "significant" PVR cannot be determined. Other factors, such as urodynamic findings, may be better at predicting complications and therefore guiding management decisions, and this remains to be studied. Areas for further research are proposed. [ABSTRACT FROM AUTHOR]

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

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

Introduction: The evidence basis for therapy selection in women who have failed primary stress urinary incontinence (SUI) surgery is limited. The ICI‐RS group discussed the available data at its meeting in June 2023, particularly the anatomical characteristics as assessed using magnetic resonance imaging (MRI) and ultrasound (US) modalities, functional characteristics associated with storage and voiding urodynamic assessment, as well as the patient characteristics that might influence outcomes. This paper summarizes the evidence base that supported these discussions and offers the basis for research proposals for future groups. Methods: A literature search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed, and the data is presented. Research questions are based on the knowledge gaps highlighted. Results: Possible MRI parameters that may influence outcomes were striated urethral sphincter volume, bladder and proximal urethral funneling, pubo‐urethral ligament integrity, distance of the bladder neck below the pubococcygeal line, posterior urethra‐vesical angle, and bladder neck to levator ani distance. US parameters included sling distance to the urethral lumen and pubis, sling position, bladder neck mobility, and lateral arm asymmetry, twisting, or curling. Urodynamic parameters included detrusor overactivity, Valsalva leak point pressure, maximum urethral closure pressure, and bladder outlet obstruction. Important patient parameters included body mass index, age, and previous interventions. Conclusions: Identifying and quantifying causative factors in patients with recurrent SUI, that allow clinicians to modify subsequent treatment choices and techniques may help reduce treatment failure and complications. Formulating algorithms is the next step in optimizing patient counseling, surgical selection, and healthcare allocation. [ABSTRACT FROM AUTHOR]

Introduction: A session at the 2023 International Consultation on Incontinence – Research Society (ICI‐RS) held in Bristol, UK, focused on the question: Is the time right for a new initiative in mathematical modeling of the lower urinary tract (LUT)? The LUT is a complex system, comprising various synergetic components (i.e., bladder, urethra, neural control), each with its own dynamic functioning and high interindividual variability. This has led to a variety of different types of models for different purposes, each with advantages and disadvantages. Methods: When addressing the LUT, the modeling approach should be selected and sized according to the specific purpose, the targeted level of detail, and the available computational resources. Four areas were selected as examples to discuss: utility of nomograms in clinical use, value of fluid mechanical modeling, applications of models to simplify urodynamics, and utility of statistical models. Results: A brief literature review is provided along with discussion of the merits of different types of models for different applications. Remaining research questions are provided. Conclusions: Inadequacies in current (outdated) models of the LUT as well as recent advances in computing power (e.g., quantum computing) and methods (e.g., artificial intelligence/machine learning), would dictate that the answer is an emphatic "Yes, the time is right for a new initiative in mathematical modeling of the LUT." [ABSTRACT FROM AUTHOR]

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

Introduction: The underlying pathophysiology behind a diagnosis of acontractile or underactive detrusor at invasive urodynamics is very heterogeneous. Lack of etiological classification currently limits the possibility of stratifying therapy. Methods: This subject was discussed at a think‐tank on the subject at the International Consultation on Incontinence‐Research Society held in Bristol, June 2023. This manuscript is a result of those deliberations and the subsequent discussions of the think‐tank. Results: There are challenges in defining abnormalities of detrusor contraction with resultant implications for available evidence. Pathology at any level of the neuromuscular pathway can impair or prevent a detrusor voiding contraction. Attempts have been made to identify clinical markers that might predict an underactive detrusor but strong supporting evidence is lacking. Hence, a holistic approach to phenotyping requires specialized neuro‐imaging as well as physiological investigations. Several general measures can help individuals with an abnormal detrusor contraction. The search for a molecule to enhance the detrusor voiding contraction remains elusive but there are promising new candidates. Neuromodulation can help select individuals but data is not well stratified by underlying etiology. Manipulation of central neurotransmitters might offer an alternate therapeutic option. Conclusions: A better understanding of the underlying pathophysiologies behind an abnormality of the detrusor voiding contraction is needed for improving management. Towards this goal, the think‐tank proposes a classification of the underactive detrusor that might help in selecting and reporting more well‐defined patient cohorts. [ABSTRACT FROM AUTHOR]

Introduction: A "Think Tank" at the International Consultation on Incontinence‐Research Society meeting held in Bristol, United Kingdom in June 2023 considered the progress and promise of machine learning (ML) applied to urodynamic data. Methods: Examples of the use of ML applied to data from uroflowmetry, pressure flow studies and imaging were presented. The advantages and limitations of ML were considered. Recommendations made during the subsequent debate for research studies were recorded. Results: ML analysis holds great promise for the kind of data generated in urodynamic studies. To date, ML techniques have not yet achieved sufficient accuracy for routine diagnostic application. Potential approaches that can improve the use of ML were agreed and research questions were proposed. Conclusions: ML is well suited to the analysis of urodynamic data, but results to date have not achieved clinical utility. It is considered likely that further research can improve the analysis of the large, multifactorial data sets generated by urodynamic clinics, and improve to some extent data pattern recognition that is currently subject to observer error and artefactual noise. [ABSTRACT FROM AUTHOR]

Over the last couple of decades, image‐based computational fluid dynamics (CFD) has revolutionized cardiovascular research by uncovering hidden features of wall strain, impact of vortices, and its use in treatment planning, as examples, that were simply not evident in the gold‐standard catheterization studies done previously. In the work presented here, we have applied magnetic resonance imaging (MRI)‐based CFD to study bladder voiding and to demonstrate the feasibility and potential of this approach. We used 3D dynamic MRI to image the bladder and urethra during voiding. A surface mesh processing tool was developed to process the bladder wall prior to executing a wall‐motion driven CFD simulation of the bladder and urethra. The obtained flow rate and pressure were used to calculate urodynamic nomograms, which are currently used in the clinical setting to assess bladder voiding dysfunction. These nomograms concluded that our healthy volunteer has an unobstructed bladder and normal contractility. We calculated the work done to void the bladder and propose this as an additional quantitative metric to comprehensively assess bladder function. Further, we discuss the areas that would improve this relatively new methodology of image‐based CFD in urodynamics. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to reveal the relationship between AMIGO2 and proliferation, migration and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. Methods: The expression level of AMIGO2 is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell Counting Kit (CCK-8 assay) was produced to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was applied to explore the underlying mechanisms. The expression level of PPAR-γ was measured by Western Blot. Results: AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration. Low AMIGO2 expression inhibited tumorigenicity of 5637 in nude mice. According to RNA-Seq and bioinformatics analysis, 917 DEGs were identified. The DEGs were mainly enriched in cell–cell adhesion, peroxisome proliferators-activated receptors (PPARs) signaling pathway and some other pathways. PPAR-γ is highly expressed in bladder cancer cell lines T24 and 5637, but when AMIGO2 is knocked down in T24 and 5637, the expression level of PPAR-γ is also decreased, and overexpression of PPAR-γ could reverse the suppression effect of cell proliferation and migration caused by the inhibition of AMIGO2. Conclusion: AMIGO2 is overexpressed in bladder cancer cells and tissues. Knockdown of AMIGO2 suppresses bladder cancer cell proliferation and migration. These processes might be regulated by PPAR-γ signaling pathway. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Detrusor underactivity (DU) is a common cause of lower urinary tract symptoms (LUTS). To date, no consensus has been reached on the urodynamic criteria for defining DU. We previously proposed the area under the curve of the Watts factor (WF‐AUC) as a new parameter for diagnosing DU. By comparing previously reported five criteria for DU and WF‐AUC, we analyzed whether the WF‐AUC could assess detrusor contraction in women with LUTS.Using urodynamic data of consecutive 77 women with LUTS, first, we classified DU based on previously reported five criteria. Second, we assessed the potential correlation between multiple parameters and WF‐AUC. Third, receiver operating characteristic curve analysis was performed to determine the cutoff value of WF‐AUC for diagnosing DU based on previously reported five criteria. Fourth, a linear regression analysis was conducted and compared using multiple criteria and female bladder outlet obstruction index (BOOIf).WF‐AUC was positively correlated with the maximum values of WF, bladder contractility index (BCI), and projected isovolumetric pressure 1 (PIP1) with correlation coefficients of 0.63, 0.57, and 0.34, respectively. AUC for diagnosing DU based on previously reported five criteria ranging from 0.773 to 0.896 with different cutoff values of AUC‐WF. The Spearman's correlation test revealed that BOOIf was significantly correlated with BCI, but not Wmax, PIP1 and WF‐AUC.This study demonstrated the non‐inferiority of the WF‐AUC compared to previously reported criteria for defining DU. Depending on the cutoff value, the WF‐AUC could appropriately evaluate women with DU, regardless of the presence of BOO. [ABSTRACT FROM AUTHOR]

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C‐Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM‐affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14–16, embryos from both normal and ARM groups underwent spatial transcriptome sequencing, which identified key genes and signalling pathways. Rack1 exhibited significant interactions among differentially expressed genes on GDs 15 and 16. Reduced Rack1 expression in the ARM‐affected hindgut, verified by Rack1 silencing in intestinal epithelial cells, led to increased P38 phosphorylation and activation of the MAPK signalling pathway. The suppression of this pathway downregulated Nqo1 and Gpx4 expression, resulting in elevated intracellular levels of ferrous ions, reactive oxygen species (ROS) and lipid peroxides. Downregulation of Gpx4 expression in the ARM hindgut, coupled with Rack1 co‐localisation and consistent mitochondrial morphology, indicated ferroptosis. In summary, Rack1, acting as a hub gene, modulates ferrous ions, lipid peroxides, and ROS via the P38‐MAPK/Nqo1/Gpx4 axis. This modulation induces ferroptosis in intestinal epithelial cells, potentially influencing hindgut development during ARM onset. [ABSTRACT FROM AUTHOR]

A crucial aspect of bladder function is the maintenance of a normo-active detrusor during bladder filling. The physiological mechanisms and pathways underlying this function are yet to be fully elucidated. Premature detrusor contractions are a key phenotype in detrusor overactivity, a common pathophysiological condition of the urinary bladder. Recent literature has identified PDFGRα+ cells as mediators in transducing inhibitory signals to detrusor smooth muscle cells via gap junctions. We employ computational modeling to study transduction pathways via which inhibitory signals are generated in PDFGRα+ cells in response to purinergic, nitrergic and mechanical stimuli. The key focus of our study here is to explore the effect of ATP, stretch and NO on the membrane potential of PDFGRα+ cells, which is driven to hyperpolarized potentials via the activation of SK3 channels. Our results indicate that purinergic, mechanical and nitrergic inputs can induce significant membrane hyperpolarizations of 20–35 mV relative to the resting membrane potential. Given the interconnections between PDFGRα+ cells and detrusor SMCs through gap junctions, these hyperpolarizations can have significant functional implications in the maintenance of a normo-active detrusor as also in departures from this state as seen in detrusor overactivity. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the therapeutic potential of cationic liposomal neostigmine bromide (NB), a novel drug delivery system, for the treatment of detrusor underactivity. By comparing the characteristics of NB‐liposomes (NLP), NB‐β‐cyclodextrin inclusion complex liposomes (NCLP), and NB‐mesoporous silica nanoparticle@CaCO3 liposomes (NMCLP), NMCLP is selected as the main research subject. It has an average particle size and zeta potential of 100 nm and +50 mV, and its encapsulation efficiency and loading capacity of NB are 14.75% and 12.8%, respectively. Most importantly, NMCLP shows the best in vitro release performance among the three liposomes, demonstrating its ability in sustained release of NB. During cell and animal assays, efficient cellular uptake of liposomes through liposome‐specific pathways is observed, facilitating targeted drug delivery, and in vivo experiments demonstrate the efficacy of NMCLP in improving bladder function in mice. Urodynamic measurements show increased bladder capacity and reduced voiding pressure, indicating enhanced bladder muscle activity. Histological analysis reveals the distribution and deep penetration of NMCLP within bladder tissues, supporting its localized drug effect. Therefore, NMCLP holds promise as a targeted and effective therapeutic strategy for detrusor underactivity. [ABSTRACT FROM AUTHOR]

The European Association of Urology and the International Incontinence Society recommend uroflowmetry (UF) as the first objective assessment tool for patients with signs and symptoms of lower urinary tract dysfunction. In addition, the American Urological Association stated that "clinicians should be aware that the UF may be affected by the voided volume (VV) and the conditions of the test" and that "consistent, similar and comparable serial UF measurements provide the most valuable results." This study aimed to investigate the impact of psychological factors and anxiety on UF results. The study comprised 42 patients (20 men and 22 women) who presented to our clinic, reported lower urinary tract symptoms, and were scheduled to undergo UF between the 1st of February 2020 and the 1st of March 2022. We evaluated the generalized anxiety disorder‐7 form (GAD‐7) to determine the general and baseline anxiety level of the patients and the state–trait anxiety inventory scale (STAI‐S) to determine the current anxiety level of the patients. A non‐significant increase in post‐voiding residual urine was observed in the second UF compared to the first one (p > 0.05). However, there was a significant increase in the VV, peak flow rate and average flow rate and a significant decrease in the time to peak flow rate for all patients (p < 0.05). Consistent with the GAD‐7, all patients had moderate general anxiety before the first UF. However, men's anxiety levels decreased to a mild level on the second session (p < 0.05), while women's remained at a moderate level (p > 0.05). There was a non‐significant decrease in STAI‐S scores before the second uroflowmetry compared to the first in both genders (p > 0.05). In addition, women's STAI‐S scores were higher than men's in both sessions (p < 0.01). No significant correlation was found between the percentage change in STAI‐S scores and all uroflowmetry parameters (p > 0.05). We determined that patients of both genders experienced moderate general anxiety before UF, which decreased in men on the second session and remained in women. In addition, we found that the women had a higher momentary anxiety compared to men before both UF sessions. Patients' sense of privacy and embarrassment can lead to tension, anxiety and stress, which may have an impact on the results of UF. Reducing patient anxiety during the UF test can contribute to more accurate diagnoses and appropriate treatment by clinicians. [ABSTRACT FROM AUTHOR]

Background: Urinary stress incontinence (USI) is defined as involuntary leakage of urine. Two times as many women as men experience incontinence. To assess urinary incontinence and its subtypes, many investigations are used. The primary diagnostic imaging modality used for examining the lower urinary tract in cases diagnosed with urine leakage is transperineal ultrasonography. It has been demonstrated that it helps to increase the precision of morphological and functional abnormality when combined with the history, clinical examination, and urodynamics. Patients and methods: This case control study included two groups; 17 female complaining of USI and 17 healthy females examined by trans-perineal ultrasonography. The difference of both α and β angles at rest and at stress as well as other urethral parameters. Results: The alpha and beta angles at stress and the difference between rest and stress (R alpha and R beta) were significantly higher in cases than controls. No detectable significant difference between both groups regarding alpha angle at rest & beta angle at rest. No appreciable significant difference between the study groups as regards the bladder wall, urethral length, width, Pubourethral distance at rest and at stress. Conclusion: Transperineal ultrasonography can assess stress incontinence by measuring different angles and other parameters. There were no difference between cases and controls during rest for both alpha and beta angles while a significant value showed up during stress. The other parameters showed no significant value between two groups. [ABSTRACT FROM AUTHOR]

Background and objective: A urodynamic study (UDS) is a routine clinic procedure that can cause significant discomfort for certain patients, with no satisfactory analgesic alternatives currently available. Our aim was to evaluate the effectiveness of low-dose self-adjusted nitrous oxide (SANO), titrated to the patient’s desired effect, on standard metrics for bladder function and on patient-reported pain and anxiety. Methods: We conducted a single-institution, double-blind, randomized crossover trial in adults undergoing UDS. Each patient underwent two consecutive UDS runs, randomized to receive oxygen during the first run followed by SANO during the second run, or vice versa. UDS outcomes (capacity, detrusor strength, residual volume) and patient subjective outcomes (Visual Analog Scale for pain and anxiety, operator assessment of verbal feedback) were compared between the two runs. Secondary analyses were performed to compare outcomes during the first UDS run and adjust for treatment order. A paired Wilcoxon signed rank-sum test and McNemar’s χ2 test were used to compare continuous and categorical variables, respectively. Adverse events were recorded. Key findings and limitations: Nineteen patients were randomized (10 to oxygen for the first run, 9 to SANO for the first run). UDS outcomes did not differ between the two arms. Patients reported significantly less pain during the SANO run than during the oxygen run (p = 0.046). Verbal feedback was significantly better with SANO (p = 0.001). Most patients (15/19, 79%) stated that they would prefer to receive SANO during future UDS. There were no significant complications. Conclusions and clinical implications: SANO oxide is a safe and effective means of preserving standard adult UDS metrics while significantly reducing patient-reported pain. Patient summary: Urodynamic tests (UDS) for evaluation of lower urinary tract symptoms can cause discomfort and pain. Our study shows that nitrous oxide gas self-adjusted by patients had no effect on UDS test outcomes or on verbal feedback during the procedure, and reduced discomfort and pain in comparison to oxygen. Nitrous oxide may an attractive option for patients who are reluctant to undergo UDS.

An overview of the analytical process in this study: ①Resting-state networks (RSNs) were extracted using group independent component analysis (ICA).②Static functional connectivity differences within and between networks were compared.③The sliding window method and k-means cluster analysis were combined to identify seven stable repetitive states and compare the differences in dynamic functional network connectivity (dFNC) and dynamic temporal metrics between the two groups.④Support vector machine (SVM) models based on functional connectivity (FC) and functional network connectivity (FNC) were utilized to distinguish primary angle-closure glaucoma (PACG) patients from healthy controls (HCs). [Display omitted] • We investigated static and dynamic brain networks alterations in PACG patients. • PACG patients showed low-level and higher-order networks changes. • These results offer insights into the neural mechanisms of visual loss in PACG. Primary angle-closure glaucoma (PACG) is a severe and irreversible blinding eye disease characterized by progressive retinal ganglion cell death. However, prior research has predominantly focused on static brain activity changes, neglecting the exploration of how PACG impacts the dynamic characteristics of functional brain networks. This study enrolled forty-four patients diagnosed with PACG and forty-four age, gender, and education level-matched healthy controls (HCs). The study employed Independent Component Analysis (ICA) techniques to extract resting-state networks (RSNs) from resting-state functional magnetic resonance imaging (rs-fMRI) data. Subsequently, the RSNs was utilized as the basis for examining and comparing the functional connectivity variations within and between the two groups of resting-state networks. To further explore, a combination of sliding time window and k-means cluster analyses identified seven stable and repetitive dynamic functional network connectivity (dFNC) states. This approach facilitated the comparison of dynamic functional network connectivity and temporal metrics between PACG patients and HCs for each state. Subsequently, a support vector machine (SVM) model leveraging functional connectivity (FC) and FNC was applied to differentiate PACG patients from HCs. Our study underscores the presence of modified functional connectivity within large-scale brain networks and abnormalities in dynamic temporal metrics among PACG patients. By elucidating the impact of changes in large-scale brain networks on disease evolution, researchers may enhance the development of targeted therapies and interventions to preserve vision and cognitive function in PACG. [ABSTRACT FROM AUTHOR]

[Display omitted] • Different models of SCI produced distinct patterns of urinary impairment. • There is a correlation between the severity of SCI and bladder dysfunction. • Post-SCI changes in bladder and urethra nerve fibres are independent of the model. • In contrast, different SCI models produce diverse neuroplastic lumbosacral changes. • This data is important for advancing treatment of neurogenic bladder dysfunction. Spinal cord injury (SCI) above the lumbosacral spinal cord induces loss of voluntary control over micturition. Spinal cord transection (SCT) was the gold standard method to reproduce SCI in rodents, but its translational value is arguable and other experimental SCI methods need to be better investigated, including spinal cord contusion (SCC). At present, it is not fully investigated if urinary impairments arising after transection and contusion are comparable. To explore this, we studied bladder-reflex activity and lower urinary tract (LUT) and spinal cord innervation after SCT and different severities of SCC. Severe-contusion animals presented a longer spinal shock period and the tendency for higher residual volumes, followed by SCT and mild-contusion animals. Urodynamics showed that SCT animals presented higher basal and peak bladder pressures. Immunostaining against growth-associated protein-43 (GAP43) and calcitonin gene-related peptide (CGRP) at the lumbosacral spinal cord demonstrated that afferent sprouting is dependent on the injury model, reflecting the severity of the lesion, with a higher expression in SCT animals. In LUT organs, the expression of GAP43, CGRP cholinergic (vesicular acetylcholine transporter (VAChT)) and noradrenergic (tyrosine hydroxylase (TH)) markers was reduced after SCI in the LUT and lumbosacral cord, but only the lumbosacral expression of VAChT was dependent on the injury model. Overall, our findings demonstrate that changes in LUT innervation and function after contusion and transection are similar but result from distinct neuroplastic processes at the lumbosacral spinal cord. This may impact the development of new therapeutic options for urinary impairment arising after spinal cord insult. [ABSTRACT FROM AUTHOR]

[Display omitted] The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB–saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE. [ABSTRACT FROM AUTHOR]

Objectives: Benign prostatic hyperplasia is one of the most common urological diseases. Among these patients, the presence of detrusor underactivity or acontractility represents a challenging condition since no medical treatment is available. Our objective is to evaluate early term outcomes following transurethral anatomical enucleation of the prostate with Tm:YAG support. Methods: In a retrospective analysis of 115 patients who underwent this procedure between January 2019 and March 2022 due to lower urinary tract symptoms, 8 patients with urodynamic evidence of detrusor underactivity secondary to a non-neurogenic aetiology were identified. Detrusor underactivity was defined as a bladder contractility index of Results: Median age, prostate volume and bladder contractility index were 73.2 years, 78.5 cm3 and 63.9, respectively. Median International Prostate Symptom Score/quality of life, Qmax and post-void residual volume were 15/3.5 points, 4.4 mL/s and 189 mL, respectively. Postoperatively, immediate catheter-removal success rate was 87.5% (7/8), at 2 months all patients were catheter-free and remained so at 1-year follow-up. Significant improvements for quality of life, Qmax and post-void residual volume were detected. Median postoperative International Prostate Symptom Score/Quality of life, Qmax and post-void residual volume were 7/2, 21.6 mL/s and 0 mL, respectively. Conclusions: This surgical approach offers high catheter-free rates, significantly improves functional voiding parameters and increases patient satisfaction in patients with benign prostatic hyperplasia and concomitant detrusor underactivity. Therefore, it can be regarded as an effective approach for such patients.

Abstract This study explores 15-year urological complications in chronic spinal cord injury (SCI) patients and investigates the predictive factors from video-urodynamic study (VUDS) and bladder management. Analyzing 864 SCI patients with a mean 15.6-year follow-up, we assessed complications and utilized multivariate logistic regression for risk evaluation. VUDS factors such as autonomic dysreflexia, detrusor sphincter dyssynergia, vesicourethral reflux (VUR), contracted bladder, and high voiding detrusor pressure significantly increased the likelihood of recurrent urinary tract infections (rUTI). Low bladder compliance, VUR, and contracted bladder notably raised the risk of hydronephrosis, while contracted bladder and detrusor overactivity with detrusor underactivity heightened chronic kidney disease risk. Volitional voiding reduced rUTI and VUR risk, whereas Valsalva maneuver-assisted voiding increased hydronephrosis risk. In conclusion, a contracted bladder identified in VUDS is associated with long-term urological complications in SCI, we propose that patients already experiencing a contracted bladder should prioritize volitional voiding as their preferred bladder management strategy to minimize the risk of additional complications such as rUTI and VUR. These findings unveil previously unexplored aspects in research, emphasizing the need for proactive management strategies in this patient population.

Testicular cancer is the most common solid malignancy among men aged 15–35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1 cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease. To assess patient outcomes and complications considering different treatment regimens and clinical characteristics. In a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed. Standard 3–4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5–6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases. The study suggests no significant benefit from exceeding 3–4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical. • No benefit from more than 3–4 courses of chemotherapy in metastatic germ cell cancer. • Viable disease in residual mass indicated lower survival. • High rate of viable disease in patients receiving 5–6 courses of chemotherapy. • Heidenreich criteria is used for salvage retroperitoneal resection if feasible. • Perform retroperitoneal dissection in high volume centers for optimal outcomes. [ABSTRACT FROM AUTHOR]

Background: Upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BLCA) both originate from uroepithelial tissue, sharing remarkably similar clinical manifestations and therapeutic modalities. However, emerging evidence suggests that identical treatment regimens may lead to less favorable outcomes in UTUC compared to BLCA. Therefore, it is imperative to explore molecular processes of UTUC and identify biological differences between UTUC and BLCA. Methods: In this study, we performed a comprehensive analysis using single-cell RNA sequencing (scRNA-seq) on three UTUC cases and four normal ureteral tissues. These data were combined with publicly available datasets from previous BLCA studies and RNA sequencing (RNA-seq) data for both cancer types. This pooled analysis allowed us to delineate the transcriptional differences among distinct cell subsets within the microenvironment, thus identifying critical factors contributing to UTUC progression and phenotypic differences between UTUC and BLCA. Results: scRNA-seq analysis revealed seemingly similar but transcriptionally distinct cellular identities within the UTUC and BLCA ecosystems. Notably, we observed striking differences in acquired immunological landscapes and varied cellular functional phenotypes between these two cancers. In addition, we uncovered the immunomodulatory functions of vein endothelial cells (ECs) in UTUC, and intercellular network analysis demonstrated that fibroblasts play important roles in the microenvironment. Further intersection analysis showed that MARCKS promote UTUC progression, and immunohistochemistry (IHC) staining revealed that the diverse expression patterns of MARCKS in UTUC, BLCA and normal ureter tissues. Conclusion: This study expands our multidimensional understanding of the similarities and distinctions between UTUC and BLCA. Our findings lay the foundation for further investigations to develop diagnostic and therapeutic targets for UTUC. [ABSTRACT FROM AUTHOR]

Introduction/background: Bladder exstrophy epispadias complex (BEEC) is a rare congenital anomaly of unknown etiology, although, genetic and environmental factors have been associated with its development. Variants in several genes expressed in the urogenital pathway have been reported as causative for bladder exstrophy in human and murine models. The expansion of next-generation sequencing and molecular genomics has improved our ability to identify the underlying genetic causes of similarly complex diseases and could thus assist with the investigation of the molecular basis of BEEC. Objective: The objective was to identify the presence of rare heterozygous variants in genes previously implicated in bladder exstrophy and correlate them with the presence or absence of bladder regeneration in our study population. Patients and Methods: We present a case series of 12 patients with BEEC who had bladder biopsies performed by pediatric urology during bladder neck reconstruction or bladder augmentation. Cases were classified as "sufficient" or "insufficient" (n = 5 and 7, respectively) based on a bladder volume of greater than or less than 40% of expected bladder size. Control bladder tissue specimens were obtained from patients (n = 6) undergoing biopsies for conditions other than bladder exstrophy. Whole exome sequencing was performed on DNA isolated from the bladder specimens. Based on the hypothesis of de novo mutations, as well as the potential implications of autosomal dominant conditions with incomplete penetrance, each case was evaluated for autosomal dominant variants in a set of genes previously implicated in BEEC. Results: Our review of the literature identified 44 genes that have been implicated in human models of bladder exstrophy. Our whole exome sequencing data analysis identified rare variants in two of these genes among the cases classified as sufficient, and seven variants in five of these genes among the cases classified as insufficient. Conclusion: We identified rare variants in seven previously implicated genes in our BEEC specimens. Additional research is needed to further understand the cellular signaling underlying this potentially genetically heterogeneous embryological condition. [ABSTRACT FROM AUTHOR]

The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette–Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of detrusor underactivity (DUA) on the postoperative outcomes of holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic hyperplasia (BPH). Patients and Methods: Patients with BPH who underwent HoLEP between January 2018 and December 2022 were enrolled in this prospective database study. Patients were divided into DUA (bladder contractility index [BCI] <100) and non‐DUA (BCI ≥100) groups. Objective (maximum urinary flow rate [Qmax], post‐void residual urine volume [PVR]) and subjective outcomes (International Prostate Symptom Score [IPSS], Overactive Bladder Symptom Score [OABSS], satisfaction with treatment question [STQ], overall response assessment [ORA], and willingness to undergo surgery question [WUSQ]) were compared between the two groups before surgery, and at 3 and 6 months after HoLEP. Results: A total of 689 patients, with a mean (standard deviation [SD]) age of 69.8 (7.1) years, were enrolled. The mean (SD) BCI in the non‐DUA (325 [47.2%]) and DUA (364 [52.8%]) groups was 123.4 (21.4) and 78.6 (14.2), respectively. Both objective (Qmax and PVR) and subjective (IPSS, IPSS‐quality of life, and OABSS) outcomes after surgery significantly improved in both groups. The Qmax was lower in the DUA than in the non‐DUA group postoperatively. At 6 months postoperatively, the total IPSS was higher in the DUA than in the non‐DUA group. There were no significant differences in surgical complications between the two groups. Responses to the STQ, ORA, and WUSQ at 6 months postoperatively demonstrated that the patients were satisfied with the surgery (90.5% in the DUA group; 95.2% in the non‐DUA group), their symptoms improved with surgery (95.9% in the DUA group; 100.0% in the non‐DUA group), and they were willing to undergo surgery again (95.9% in the DUA group; 97.9% in the non‐DUA group). There were no significant differences in the responses to the STQ and WUSQ between the two groups. Conclusion: Our midterm results demonstrated that patients with BPH and DUA showed minimal differences in clinical outcomes after HoLEP compared to those without DUA. The overall satisfaction was high in the DUA group. [ABSTRACT FROM AUTHOR]

This study explores 15-year urological complications in chronic spinal cord injury (SCI) patients and investigates the predictive factors from video-urodynamic study (VUDS) and bladder management. Analyzing 864 SCI patients with a mean 15.6-year follow-up, we assessed complications and utilized multivariate logistic regression for risk evaluation. VUDS factors such as autonomic dysreflexia, detrusor sphincter dyssynergia, vesicourethral reflux (VUR), contracted bladder, and high voiding detrusor pressure significantly increased the likelihood of recurrent urinary tract infections (rUTI). Low bladder compliance, VUR, and contracted bladder notably raised the risk of hydronephrosis, while contracted bladder and detrusor overactivity with detrusor underactivity heightened chronic kidney disease risk. Volitional voiding reduced rUTI and VUR risk, whereas Valsalva maneuver-assisted voiding increased hydronephrosis risk. In conclusion, a contracted bladder identified in VUDS is associated with long-term urological complications in SCI, we propose that patients already experiencing a contracted bladder should prioritize volitional voiding as their preferred bladder management strategy to minimize the risk of additional complications such as rUTI and VUR. These findings unveil previously unexplored aspects in research, emphasizing the need for proactive management strategies in this patient population. [ABSTRACT FROM AUTHOR]

This text is a preface for a special issue of Neurochemical Research dedicated to Dr. Vicente Felipo, who has dedicated his career to researching hepatic encephalopathy (HE) and general neuropathological mechanisms. HE is a neuropsychiatric syndrome that impairs cerebral function due to liver failure, leading to a range of cognitive and motor abnormalities. Dr. Felipo has made significant contributions to understanding the molecular bases and mechanisms of HE, including the role of hyperammonemia and inflammation. His research has also explored potential therapeutic targets and evaluated pharmacologic therapies in preclinical animal models. The issue includes original research articles and reviews on HE and other neurological diseases with a neuroinflammatory component, such as Alzheimer's and Parkinson's diseases. [Extracted from the article]

Objective: This study aimed to evaluate the effectiveness of parasacral transcutaneous electrical nerve stimulation (p-TENS) in children with detrusor overactivity (DO) who were subjected to standard medical treatment, urotherapy, and/or biofeedback. Materials and Methods: Thirty-two children (female: 17, male: 15) underwent p-TENS because of refractory lower urinary tract dysfunction symptoms between 2017 and 2019. Children with neurogenic bladder (n=7) and dysfunctional voiding (n=13) were excluded. The data of 12 children diagnosed with DO after the urodynamic study (boys: 8, girls: 4), were evaluated for treatment response 6 months after the last session. p-TENS was performed using S2-3 dermatome 2 days a week for 3 months. Each session lasted 20 min with a frequency of 10 Hz and generated a pulse of 250 µs. Results: The median age of 12 children was 11 years (interquartile range 25-75, range: 9.5-12.5). Incontinence is the main complaint. Significant improvement in uroflow parameters was detected in all children. Urgency, urge incontinence (p=0.016), and constipation (p=0.031) rates were significantly decreased. Voiding dynamics revealed improved voiding patterns (pre/post tower shaped pattern; n=7 vs. n=2), and incontinence was completely resolved in nine children (75%). Conclusion: P-TENS has emerged as a therapeutic alternative in children with DO refractory to standard treatment protocol and medication. [ABSTRACT FROM AUTHOR]

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformations in recent years. The introduction of novel combination therapies involving tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors has resulted in improved oncological outcomes compared to traditional TKI monotherapy. In this evolving paradigm, the pivotal role of the multidisciplinary tumor board is underscored, particularly in shaping the therapeutic trajectory for patients eligible for locoregional interventions like cytoreductive nephrectomy and metastasectomy. In cases where systemic treatment is deemed appropriate, the absence of direct comparisons among the various combination therapies complicates the selection of a first-line approach. The clinician is faced with the challenge of making decisions based on patient-specific factors such as performance status, risk classification according to the International Metastatic Renal Cell Carcinoma Database Consortium, comorbidities, and disease characteristics, including the number and location of metastases and tumor histology. Considering these concerns, we propose, as a member of a Tuscany Interdisciplinary Uro-Oncologic Group, an algorithm to streamline the decision-making process for mRCC patients, offering guidance to clinicians in their day-to-day clinical practice. [ABSTRACT FROM AUTHOR]

• Evidence does not support the systematic preoperative use of UDS for uncomplicated cases. • In case of complicated SUI, preoperative UDS can be beneficial in anticipating postoperative outcomes. • UDS should be performed considering the patient's specific clinical situation and the surgeon's judgment. Stress urinary incontinence (SUI) is defined as a condition characterized by the involuntary leakage of urine during activities that increase intra-abdominal pressure which may decrease quality of life with a significant economic impact on health systems, necessitating the implementation of cost-effective management plans. Urodynamics (UDS) has been considered during the last decades as the gold standard for assessment of lower urinary tract symptoms (LUTS) due to their high reproducibility. At the same time, concerns about the systematic use of UDS before SUI surgery were raised due to a limited evidenced base to recommend their routine use. In uncomplicated female patients with SUI, UDS can offer further insights into LUTS, potentially assisting the physician in determining the appropriate therapeutic approach. However, it has not been shown that preoperative UDS can directly impact the surgical outcome for continence. Indeed, evidence supports the conclusion that pre-operative UDS in women with uncomplicated, clinically demonstrable, SUI does not improve the outcome of surgery for SUI. Nevertheless, asymptomatic detrusor overactivity (DO) identified by urodynamic testing or pre-existing voiding dysfunction are associated with an increased occurrence of postoperative overactive bladder (OAB) and voiding dysfunction, respectively. The EUGA Working Group concluded that the evidence does not support the systematic preoperative use of UDS for uncomplicated cases. However, in cases where mixed symptoms, voiding dysfunction, previous surgery, or concomitant prolapse are present, preoperative UDS are advised as they can be beneficial in anticipating postoperative outcomes. This aids in conducting comprehensive and thorough preoperative counseling. The Group recommend performing preoperative UDS considering the patient's specific clinical situation and the surgeon's judgment, with consideration given to the potential benefits, risks, and impact on treatment decisions and patient outcomes. [ABSTRACT FROM AUTHOR]

The updated 2024 European Association of Urology neurourology guidelines highlight the importance of a tailored, comprehensive approach for management of neurourological disorders. Patient outcomes can be improved by addressing individual needs, including urodynamics and lifestyle considerations via a multidisciplinary strategy. The guidelines cover the latest evidence and treatments to support patients in maintaining their quality of life across all facets of neurological impact. Most patients with neurourological disorders require lifelong medical care. The European Association of Urology (EAU) regularly updates guidelines for diagnosis and treatment of these patients. The objective of this review is to provide a summary of the 2024 updated EAU guidelines on neurourology. A structured literature review covering the timeframe 2021–2023 was conducted for the guideline update. A level of evidence and a strength rating were assigned for each recommendation on the basis of the literature data. Neurological conditions significantly affect urinary, sexual, and bowel function, and lifelong management is required for neurourological patients to maintain their quality of life and prevent urinary tract deterioration. Early diagnosis and effective treatment are key, and comprehensive clinical assessments, including urodynamics, are crucial. Management should be customised to individual needs and should involve a multidisciplinary approach and address sexuality and fertility. Lifelong monitoring and follow-up highlight the importance of continuous care for neurourological patients. The 2024 EAU guidelines on neurourology provide an up-to-date overview of available evidence on diagnosis, treatment, and follow-up for neurourological patients. Neurological disorders very frequently affect the lower urinary tract and sexual and bowel function and patients need lifelong management. We summarise the updated European Association of Urology guidelines on neurourology to provide patients and caregivers with the latest insights for optimal health care support. [ABSTRACT FROM AUTHOR]

Revue de littérature sur les facteurs pronostics cliniques et urodynamiques de complications urinaires chez les patients blessés médullaires (BM). Les articles traitant des complications urinaires du BM et de leurs facteurs pronostics cliniques et urodynamiques ont été recherchés dans la base de données Pubmed jusqu'en mars 2024, les articles en anglais ou en français ont été inclus et analysés. Trente-huit articles publiés entre 1965 et 2024 ont été inclus dans cette revue, l'incidence des complications urinaires a considérablement diminué depuis les années soixante. Les facteurs pronostics cliniques de complications urinaires sont une lésion médullaire cervicale, une lésion complète, l'âge ou le mode mictionnel, la sonde urinaire à demeure étant le plus à risque. Les facteurs urodynamiques sont un trouble de la compliance (< 20), de hautes pressions détrusoriennes (>40 cm d'eau), une dyssynergie vésico-sphinctérienne et un résidu post-mictionnel. Les complications urinaires chez le BM sont fréquentes, il est nécessaire de connaître leurs facteurs pronostics afin de les dépister et les prendre en charge précocement pour les limiter. Literature review on the prognostic clinical and urodynamic factors of urinary complications in spinal cord injury (SCI) patients. Articles dealing with SCI urinary complications and their prognostic clinical and urodynamic factors have been searched in the Pubmed database until march 2024, articles in english or in french were included and analysed. Thirty-eight articles published between 1965 and 2024 were included in this review, the incidence of urinary complications has decreased considerably since the 60s. Clinical prognostic factors are a cervical or complete SCI, age, voiding mode, the indwelling catheter most at risk. Urodynamics factors are compliance disorder (< 20), high detrusor pressure (> 40 cm of water), detrusor sphincter dyssynergia and a postvoid residual volume. Urinary complications in SCI patients are frequents, it is necessary to know the prognostic factors in order to have an early detection and management to limit them. [ABSTRACT FROM AUTHOR]

Introduction: Although antibiotic prophylaxis (AB) demonstrated a statistically significant reduction in bacteriuria after invasive urodynamics (UDS), no significant decrease in the incidence of urinary tract infections (UTI) has been confirmed. No absolute recommendations on the use of AB in case of relevant potential risk of UTI have been reported, though some categories of patients at increased infective probability after UDS have been recognized. The aim of this study is to report the experts' consensus on the best practice for the use of AB before UDS in the main categories of patients at potential risk of developing UTI. Materials and Methods: A systematic literature review was performed on AB before UDS in males and females. A panel of experts from the Italian Society of Urodynamics, Continence, Neuro‐Urology, and Pelvic Floor (SIUD) assessed the review data and decided by a modified Delphi method on 16 statements proposed and discussed by the panel. The cut‐off percentage for the consensus was a ≥70% of positive responses to the survey. The study was a Delphi consensus with experts' opinions, not a clinical trial involving directly patients. Results: The panel group was composed of 57 experts in functional urology and UDS, mainly urologists, likewise gynaecologists, physiatrists, infectivologists, pediatric urologists, and nurses. A positive consensus was achieved on 9/16 (56.25%) of the statements, especially on the need for performing AB before UD in patients with neurogenic bladder and immunosuppression. Urine analysis and urine culture before UDS are mandatory, and in the event of their positivity, UDS should be postponed. A consensus was reached on avoiding AB in menopausal status, diabetes, age, gender, bladder outlet obstruction, high postvoid residual, chronic catheterization, previous urological surgery, lack of urological abnormalities, pelvic organ prolapse, and negative urine analysis. Conclusions: Antibiotic prophylaxis is not recommended for patients without notable risk factors and with a negative urine test due to the potential morbidities that may result from antibiotic administration. However, AB can be used for risk categories such as neurogenic bladder and immunosuppression. The evaluation of urine analysis and urine culture and postponing UDS in cases of positive tests were considered good practices, as well as performing AB in the neurogenic bladder and immunosuppression. [ABSTRACT FROM AUTHOR]