Effect of detrusor underactivity on surgical outcomes of holmium laser enucleation of the prostate.

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.

Emerging drugs for the treatment of benign prostatic hyperplasia: a 2023 update.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a condition that affects over 50% of men as they enter their fifth decade of life, often leading to lower urinary tract symptoms (LUTS). Primary treatment options include alpha blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors. However, these medications can have some side effects, and there is a noticeable dearth of information addressing the long-term use of these medications. Thus, the exploration of all treatment modalities helps ensure patients receive personalized and effective care. Consequently, the primary objective of this review is to identify potential emerging medications for the treatment of BPH. AREAS COVERED: We conducted an extensive review of articles discussing pharmacotherapy for BPH spanning the last 15 years. Our information gathering process involved Scopus, PubMed-MEDLINE, Cochrane, Wiley Online Library Google Scholar, ClinicalTrials.gov, and the PharmaProjects database. This approach ensures that readers gain an in-depth knowledge of the existing therapeutic agents as well as promising avenues for managing BPH. EXPERT OPINION: BPH treatment targets a patient's specific constellation of symptoms. Therefore, a broad knowledge base encompassing various treatment options is paramount in ensuring optimal treatment. Looking forward, the emphasis on personalization promises to reshape the landscape of BPH treatment and improve patient outcomes.

Bicentric retrospective study comparing the postoperative outcomes of patients treated surgically for bladder stones with or without concomitant surgery for BPH.

PURPOSE: To compare the postoperative outcomes of male patients who underwent bladder stone (BS) removal, with or without concomitant benign prostatic hyperplasia (BPH) surgery. PATIENTS AND METHODS: All men aged > 50 years who underwent BS removal at two French university hospitals between 2009 and 2018 were retrospectively reviewed. Four binary outcome criteria were identified during the follow-up: early postoperative complications, stone recurrence, subsequent surgery for BS or BPH, and late surgical complications. A composite score ranging from 0 to 4 was calculated by combining the four criteria. RESULTS: A median follow-up period of 42 months was observed in 179 patients. Of these, 107 patients were in the "concomitant surgical treatment" (CST) group and 72 in the bladder "stone removal alone" (SRA) group. The CST group presented higher baseline post-void residual volume (105 vs. 30 ml, p = 0.005). Patients who underwent CST had a significantly lower rate of BS recurrence (12% vs. 39%; p = 0,001) and underwent fewer subsequent surgeries (14% vs. 44%; p < 0.001). There was no significant difference in the early (51% vs. 35%, p = 0,168) and late (26% vs. 17%, p = 0,229) complications rates between the two groups. A better composite score was observed in the CST than in the SRA, but the difference was not significant (3.07 vs. 2.72, p = 0.078). CONCLUSION: As CST increases morbidity and decreases the risk of reoperation, each situation should be considered, taking into account patient choice and comorbidities.

Bladder outlet obstruction in women: Advanced evaluation.

INTRODUCTION: Herein, we provide a review of the indications, practical considerations, and interpretation of urodynamics (UDS) with or without fluoroscopy, as well as cystourethroscopy, for women with suspected bladder outlet obstruction (BOO). METHODS AND RESULTS: A narrative review was performed focusing on the current primary literature and society guidelines around advanced diagnostic modalities for female BOO patients. UDS studies help diagnose BOO by identifying high-pressure low-flow voiding patterns and/or the characteristic radiographic appearance of the bladder neck and urethra during micturition. Cystourethroscopy aids in evaluating structural aberrations of the bladder outlet, and in surgical planning. CONCLUSIONS: UDS studies and cystourethroscopy are useful adjuncts in carefully-selected female patients with suspected BOO.

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p-FGFR3 pathway.

BACKGROUND: Partial bladder outlet obstruction (pBOO) may lead to bladder remodeling, including fibrosis and extracellular matrix (ECM) deposition. Despite the extensive research on the mechanisms underlying pBOO, potential therapeutic targets for the treatment of pBOO require further research. Dysregulated expression of thrombospondin-1 (Thbs1) has been reported in various human fibrotic diseases; however, its relationship with pBOO remains unclear. AIMS: Investigate the effects of Thbs1 on bladder remodeling caused by pBOO. METHODS: We established a pBOO model in Sprague-Dawley rats and performed urodynamic analyses to estimate functional changes in the bladder, validated the histopathological changes in the bladder by using haematoxylin-eosin and Masson's trichrome staining, identified key target genes by integrating RNA sequencing (RNA-seq) and bioinformatics analyses, validated the expression of related factors using Western blot analysis and RT-qPCR, and used immunofluorescence staining to probe the potential interaction factors of Thbs1. RESULTS: Urodynamic results showed that pressure-related parameters were significantly increased in rats with pBOO. Compared with the sham group, the pBOO group demonstrated significant increases in bladder morphology, bladder weight, and collagen deposition. Thbs1 was significantly upregulated in the bladder tissues of rats with pBOO, consistent with the RNA-seq data. Thbs1 upregulation led to increased expression of matrix metalloproteinase (MMP) 2, MMP9, and fibronectin (Fn) in normal human urinary tract epithelial cells (SV-HUC-1), whereas anti-Thbs1 treatment inhibited the production of these cytokines in TGF-ß1-treated SV-HUC-1. Further experiments indicated that Thbs1 affected bladder remodeling in pBOO via the fibroblast growth factor receptor 3 (FGFR3) pathway. CONCLUSIONS: Thbs1 plays a crucial role in bladder remodeling caused by pBOO. Targeting Thbs1 might alleviate ECM damage. Mechanistically, Thbs1 may function via the FGFR signaling pathway by regulating the FGFR3 receptor, identified as the most relevant disease target of pBOO, and FGF2 may be a mediator. These findings suggest that Thbs1 plays a role in BOO development and is a therapeutic target for this condition.

Primary bladder neck obstruction in men: The importance of urodynamic assessment and cystourethrography in measuring its severity.

OBJECTIVE: Primary bladder neck obstruction (PBNO) is a condition primarily affecting young men, characterized by obstruction at the bladder neck, leading to lower urinary tract symptoms. The aim of this study was to identify a correlation between the severity of bladder neck opening impairment and urinary symptoms by means of urodynamic studies. MATERIALS AND METHODS: A retrospective analysis was conducted in adult males diagnosed with PBNO at a university neurourology department between 2015 and 2022 who underwent voiding cystourethrography (VCUG) and pressure-flow studies. The cohort was divided into two groups: absence of bladder neck opening on VCUG (Group A) and incomplete bladder neck opening (Group B). RESULTS: Out of the 82 patients with PBNO screened, 53 were included in the analysis. Nocturia was the only symptom more prevalent in Group A (65% in Group A vs. 30% in Group B, p = 0.02) but scores and subscores of the Urinary Symptom Profile questionnaire were not different between groups. In addition, the detrusor pressure at a maximum flow rate (PdetQmax), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI) were higher in Group A than in Group B [PdetQmax (A = 93.7 ± 53.7 cmH2O vs. B = 65.7 ± 26.4 cmH2O; p = 0.01)-BOOI (A = 77 ± 58.3 vs. B = 48 ± 25.7; p = 0.03)-BCI (A = 136 ± 51.3 vs. B = 110 ± 41.7; p = 0.04)]. CONCLUSION: This study demonstrates a significant association between the extent of bladder neck opening impairment observed on VCUG and obstruction and contraction urodynamic parameters, but no association with the severity of urinary symptoms. Future studies should evaluate the predictive value of treatment response and the occurrence of complications based on clinical and urodynamic parameters.

Is there evidence for pelvic floor muscle relaxation training in nonneurogenic female bladder outlet obstruction?-A narrative review.

INTRODUCTION: Functional bladder outlet obstruction (BOO) in women is postulated to be caused by pelvic floor muscle (PFM) dyssynergia or increased tone. The aim of the present review was to investigate the effect of PFM relaxation training on PFM tone and female BOO symptoms. MATERIALS AND METHODS: This was a narrative review using an open search strategy on PubMed with the search terms "Bladder outlet obstruction" AND "female" AND ("pelvic floor muscles" OR "Kegel"). The risk of bias of the randomized controlled trials (RCTs) was scored with the Physiotherapy Evidence Database (PEDro) scale (0-10). RESULTS: Only three RCTs were found. All three RCTs compared different types of exercise, and no trial compared relaxation training with no or sham treatment. None of the trials reported the effect between groups on the reduction of PFM tone. There was a tendency toward positive effect of PFM relaxation training to improve BOO symptoms in women. PEDro score varied between 4 and 7. Few studies yielded information on the immediate effect of any type of PFM relaxation technique on PFM tone. CONCLUSION: Few RCTs have been conducted on the effect of PFM relaxation training on PFM tone and functional female BOO symptoms. There is an urgent need for RCTs with high methodological and interventional quality in addition to basic research on mechanisms of different relaxation techniques on PFM activity.

A new nomogram for the evaluation of detrusor underactivity and bladder outlet obstruction in nonneurogenic female patients with lower urinary tract symptoms who undergo urodynamic studies.

INTRODUCTION: Micturition physiology differs in men and women. However, the results in standard urodynamic studies in women with lower urinary tract symptoms (LUTS) were extrapolated from studies in men. Nowadays, the only validated nomogram for females is Solomon-Greenwell's. However, it only evaluated bladder outlet obstruction (BOO) without considering detrusor underactivity (DU). This study aims to create a nomogram that includes an evaluation of DU and BOO in nonneurogenic women and validate it against videourodynamic studies along with other nomograms. MATERIALS AND METHODS: For the first analysis (creation cohort), we included 183 women with LUTS who underwent videourodynamic study between 2022 and 2023. Exclusion criteria were females with neurologic diseases, renal transplantation, and trouble performing the flow-pressure study. Baseline characteristics of the patients, urodynamic parameters, and classifications on different nomograms and indexes were evaluated. A logistic regression found Qmax and PdetQmax as predictors for DU and BOO. The Barco-Castillo nomogram was created by clustering analysis and adjusted by the results of the logistic regression. A second (test) cohort was evaluated from 2023 to 2024, including 142 patients for the validation of the nomogram. A p < 0.05 was considered significant. RESULTS: All urodynamic parameters were compared between both cohorts, with no significant differences. The median age of the creation cohort was 50 years old (interquartile range [IQR] 39-63). All patients had LUTS and a previous standard urodynamic study without a clear diagnosis. The cluster analysis had a p < 0.05 for two groups of BOO (yes/no) and two of DU (yes/no). We created the graph based on the logistic regression results and adjusted it according to the data. The median age of the test cohort was 44 years old (IQR 33.75-59) and had the same indication for the videourodynamic study. The receiver operating characteristic (ROC) curve for BOO showed an accuracy of 85.4% for Barco-Castillo nomogram, 68.5% for Blaivas-Groutz, 58.1% for Solomon-Greenwell, 57.1% for BOOI, and 50% for LinPURR. For DU, accuracy was 80.5% for PIP-1, 80.2% for Barco-Castillo, 76.6% for BCI, and 70.1% for LinPURR. CONCLUSIONS: When evaluating women's urodynamic studies, it is important to focus on female physiology and discourage the use of parameters previously standardized in men. We encourage using the new Barco-Castillo nomogram to determine BOO and DU in women as the currently easiest and more accurate tool.

Post-obstructive diuresis after posterior urethral valve treatment in neonates: a retrospective cohort study.

BACKGROUND: The management of posterior urethral valve (PUV) in neonates requires close monitoring in the intensive care unit because of the risk of post-obstructive diuresis (POD). Our aim was to describe the incidence and factors associated with POD in newborns treated for PUV. METHODS: Retrospective analysis of the medical records of all neonates who underwent surgical intervention for PUV in our neonatal intensive care unit between January 2014 and April 2021. RESULTS: Of the 40 patients included, 15 (37.5%) had POD defined by urine output > 6 ml.kg-1.h-1 during the first 24 h following urinary tract obstruction relief. At prenatal ultrasound examinations, oligohydramnios was more common in the group with POD than in the group without (53.3% vs. 8%, p = 0.002). Preterm birth was more frequent in neonates with POD (66.7% vs. 8%; p < 0.001). Median serum creatinine (212 [137-246] vs. 95 [77-125] µmol.l-1; p < 0.001) and urea (8.5 [5.2-12.2] vs. 4.1 [3.5-4.7] mmol.l-1; p < 0.001) concentrations on the day of obstruction relief were significantly higher in the group with POD than in the group without. After adjustment for prematurity, logistic regression models confirmed correlation between the occurrence of POD and the severity of the consequences of urethral obstruction (i.e., oligohydramnios and serum creatinine levels; ß = 2.90 [0.88; 5.36], p = 0.013 and ß = 0.014 [0.003; 0.031], p = 0.034, respectively). CONCLUSIONS: In neonates, POD is common after the relief of PUV-related obstruction. Our findings may help to identify patients at highest risk. A higher resolution version of the Graphical abstract is available as Supplementary information.

Management of the Devastated Bladder Outlet after Prostate CANCER Treatment.

PURPOSE OF REVIEW: Devastating complications of the bladder outlet resulting from prostate cancer treatments are relatively uncommon. However, the combination of the high incidence of prostate cancer and patient longevity after treatment have raised awareness of adverse outcomes deteriorating patients' quality of life. This narrative review discusses the diagnostic work-up and management options for bladder outlet obstruction resulting from prostate cancer treatments, including those that require urinary diversion. RECENT FINDINGS: The devastated bladder outlet can be a consequence of the treatment of benign conditions, but more frequently from complications of pelvic cancer treatments. Regardless of etiology, the initial treatment ladder involves endoluminal options such as dilation and direct vision internal urethrotomy, with or without intralesional injection of anti-fibrotic agents. If these conservative strategies fail, surgical reconstruction should be considered. Although surgical reconstruction provides the best prospect of durable success, reconstructive procedures are also associated with serious complications. In the worst circumstances, such as prior radiotherapy, failed reconstruction, devastated bladder outlet with end-stage bladders, or patient's severe comorbidities, reconstruction may neither be realistic nor justified. Urinary diversion with or without cystectomy may be the best option for these patients. Thorough patient counseling before treatment selection is of utmost importance. Outcomes and repercussions on quality of life vary extensively with management options. Meticulous preoperative diagnostic evaluation is paramount in selecting the right treatment strategy for each individual patient. The risk of bladder outlet obstruction, and its severest form, devastated bladder outlet, after treatment of prostate cancer is not negligible, especially following radiation. Management includes endoluminal treatment, open or robot-assisted laparoscopic reconstruction, and urinary diversion in the worst circumstances, with varying success rates.

Voiding Dysfunction in Patients With Advanced Pelvic Organ Prolapse and Bladder Outlet Obstruction Following Pelvic Reconstructive Surgery: Urodynamic Profile and Predictive Risk Factors.

STUDY OBJECTIVE: To determine the outcome of voiding function 1 year after pelvic reconstructive surgery (PRS) in women with bladder outlet obstruction (BOO). DESIGN: Retrospective cohort study. SETTING: Tertiary referral hospital. PATIENTS: A total of 1894 women underwent PRS for advanced pelvic organ prolapse (POP) stages 3 to 4 with urodynamic findings of BOO. INTERVENTIONS: PRS. MEASUREMENTS: The primary outcome measured was the resumption of normal voiding function, defined clinically with multichannel urodynamic testing at 1 year postoperatively. The secondary outcomes were to identify the different risk factors for persistence voiding dysfunction (VD) 1 year after PRS. MAIN RESULTS: A total of 431 women with Pelvic Organ Prolapse Quantification stages 3 and 4, urodynamic study of maximum urinary flow rate ≤15 mL/s, and detrusor pressure at maximum flow ≥20 cm H2O were included. Resumption of normal voiding function was found in 91% (n = 392 of 431), whereas 9% (n = 39 of 431) remained to have VD 1 year postoperatively. Those with persistent VD, 20.5% (n = 8 of 39) remained having urodynamic diagnosis of BOO. Univariate and multivariate logistic regression revealed factors associated with postoperative VD were pre-operative maximal cystometric capacity ≥500 mL and postvoid residual volume ≥200 mL. CONCLUSION: VD may persist in women with BOO after PRS, particularly in those with preoperative maximal cystometric capacity of >500 mL and postvoid residual volume >200 mL.

Building Dual AI Models and Nomograms Using Noninvasive Parameters for Aiding Male Bladder Outlet Obstruction Diagnosis and Minimizing the Need for Invasive Video-Urodynamic Studies: Development and Validation Study.

BACKGROUND: Diagnosing underlying causes of nonneurogenic male lower urinary tract symptoms associated with bladder outlet obstruction (BOO) is challenging. Video-urodynamic studies (VUDS) and pressure-flow studies (PFS) are both invasive diagnostic methods for BOO. VUDS can more precisely differentiate etiologies of male BOO, such as benign prostatic obstruction, primary bladder neck obstruction, and dysfunctional voiding, potentially outperforming PFS. OBJECTIVE: These examinations' invasive nature highlights the need for developing noninvasive predictive models to facilitate BOO diagnosis and reduce the necessity for invasive procedures. METHODS: We conducted a retrospective study with a cohort of men with medication-refractory, nonneurogenic lower urinary tract symptoms suspected of BOO who underwent VUDS from 2001 to 2022. In total, 2 BOO predictive models were developed-1 based on the International Continence Society's definition (International Continence Society-defined bladder outlet obstruction; ICS-BOO) and the other on video-urodynamic studies-diagnosed bladder outlet obstruction (VBOO). The patient cohort was randomly split into training and test sets for analysis. A total of 6 machine learning algorithms, including logistic regression, were used for model development. During model development, we first performed development validation using repeated 5-fold cross-validation on the training set and then test validation to assess the model's performance on an independent test set. Both models were implemented as paper-based nomograms and integrated into a web-based artificial intelligence prediction tool to aid clinical decision-making. RESULTS: Among 307 patients, 26.7% (n=82) met the ICS-BOO criteria, while 82.1% (n=252) were diagnosed with VBOO. The ICS-BOO prediction model had a mean area under the receiver operating characteristic curve (AUC) of 0.74 (SD 0.09) and mean accuracy of 0.76 (SD 0.04) in development validation and AUC and accuracy of 0.86 and 0.77, respectively, in test validation. The VBOO prediction model yielded a mean AUC of 0.71 (SD 0.06) and mean accuracy of 0.77 (SD 0.06) internally, with AUC and accuracy of 0.72 and 0.76, respectively, externally. When both models' predictions are applied to the same patient, their combined insights can significantly enhance clinical decision-making and simplify the diagnostic pathway. By the dual-model prediction approach, if both models positively predict BOO, suggesting all cases actually resulted from medication-refractory primary bladder neck obstruction or benign prostatic obstruction, surgical intervention may be considered. Thus, VUDS might be unnecessary for 100 (32.6%) patients. Conversely, when ICS-BOO predictions are negative but VBOO predictions are positive, indicating varied etiology, VUDS rather than PFS is advised for precise diagnosis and guiding subsequent therapy, accurately identifying 51.1% (47/92) of patients for VUDS. CONCLUSIONS: The 2 machine learning models predicting ICS-BOO and VBOO, based on 6 noninvasive clinical parameters, demonstrate commendable discrimination performance. Using the dual-model prediction approach, when both models predict positively, VUDS may be avoided, assisting in male BOO diagnosis and reducing the need for such invasive procedures.

Local Injection of Stem Cells Can Be a Potential Strategy to Improve Bladder Dysfunction after Outlet Obstruction in Rats.

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-ß1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFß-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.

The role of transurethral resection of prostate (TURP) in patients with underactive bladder: 12 months follow-up in different grades of detrusor contractility.

INTRODUCTION AND OBJECTIVE: Male detrusor underactivity (DUA) definition remains controversial and no effective treatment is consolidated. Transurethral resection of the prostate (TURP) is one of the cornerstones surgical treatments recommended in bladder outlet obstruction (BOO). However, the role of prostatic surgery in male DUA is not clear. The primary endpoint was the clinical and voiding improvement based on IPSS and the maximum flow rate in uroflowmetry (Qmax) within 12 months. MATERIALS AND METHODS: We analyzed an ongoing prospective database that embraces benign prostata hyperplasia (BPH) male patients with lower urinary tract symptoms who have undergone to TURP. All patients were evaluated pre and postoperatively based on IPSS questionnaires, prostate volume measured by ultrasound, postvoid residual urine volume (PVR), Prostate Specific Antigen measurement and urodynamic study (UDS) before the procedure. After surgery, all patients were evaluated at 1-, 3-, 6- and 12-months. Patients were categorized in 3 groups: Group 1-Detrusor Underactive (Bladder Contractility Index (BCI) [BCI] < 100 and BOO index [BOOI] < 40); Group 2-Detrusor Underactive and BOO (BCI < 100 and BOOI ≥ 40); Group 3-BOO (BCI ≥ 100 and BOOI ≥ 0). RESULTS: It was included 158 patients underwent monopolar or bipolar TURP since November 2015 to March 2021. According to UDS, patients were categorized in: group 1 (n = 39 patients); group 2 (n = 41 patients); group 3 (n = 77 patients). Preoperative IPSS was similar between groups (group 1-24.9 ± 6.33; group 2-24.8 ± 7.33; group 3-24.5 ± 6.23). Qmax was statistically lower in the group 2 (group 1-5.43 ± 3.69; group 2-3.91 ± 2.08; group 3-6.3 ± 3.18) as well as greater PVR. The 3 groups presented similar outcomes regard to IPSS score during the follow-up. There was a significant increase in Qmax in the 3 groups. However, group 1 presented the lowest Qmax improvement. CONCLUSION: There were different objective outcomes depending on the degree of DUA at 12 months follow-up. Patients with DUA had similar IPSS improvement. However, DUA patients had worst Qmax improvement than men with normal bladder contraction.

Exosomes from human urine-derived stem cells carry NRF1 to alleviate bladder fibrosis via regulating miR-301b-3p/TGFßR1 pathway.

Bladder outlet obstruction (BOO) is a common disease that always make the bladder develops from inflammation to fibrosis. This study was to investigate the effect of exosomes from human urine-derived stem cells (hUSCs) on bladder fibrosis after BOO and the underlying mechanism. The BOO mouse model was established by inserting a transurethral catheter, ligation of periurethral wire, and removal of the catheter. Mouse primary bladder smooth muscle cells (BSMCs) were isolated and treated with TGFß1 to mimic the bladder fibrosis model in vitro. Exosomes from hUSCs (hUSC-Exos) were injected into the bladder of BOO mice and added into the culture of TGFß1-induced BSMCs. The associated factors in mouse bladder tissues and BSMCs were detected. It was confirmed that the treatment of hUSC-Exos alleviated mouse bladder fibrosis and down-regulated fibrotic markers (a-SMA and collagen III) in bladder tissues and TGFß1-induced BSMCs. Overexpression of NRF1 in hUSC-Exos further improved the effects of hUSC-Exos on bladder fibrosis both in vivo and in vitro. TGFßR1 was a target of NRF1 and miR-301b-3p, and miR-301b-3p was a target of NRF1. It was next characterized that hUSC-Exos carried NRF1 to up-regulate miR-301B-3p, thereby reducing TGFßR1level. Our results illustrated that hUSC-Exos carried NRF1 to alleviate bladder fibrosis through regulating miR-301b-3p/TGFßR1 pathway.

Comparison of traditional outcome measures and self-assessed goal achievement in patients treated surgically for benign prostatic hyperplasia.

PURPOSE: To determine self-assessed goal achievement (SAGA) outcomes in men treated surgically for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) and compare them to the traditional outcome measures. METHODS: Single-center analysis of prospective database of men undergoing surgical treatment of LUTS/BPO at a single institution between July 2019 and March 2021. We assessed individual goals, traditional questionnaires, and functional outcomes prior to treatment, and at first follow-up after 6-12 weeks. We compared SAGA outcomes 'overall goal achievement' and 'satisfaction with treatment' to subjective and objective outcomes using Spearman's rank correlations (rho). RESULTS: A total of sixty-eight patients completed the individual goal formulation prior to surgery. Preoperative goals varied between different treatments and individuals. IPSS correlated with 'overall goal achievement' (rho = - 0.78, p < 0.001) and 'satisfaction with treatment' (rho = - 0.59, p < 0.001). Similarly, the IPSS-QoL was correlated with overall goal achievement (rho = - 0.79, p < 0.001) and satisfaction with treatment (rho = - 0.65, p < 0.001). No correlation was seen between SAGA outcomes and functional outcomes Qmax and PVR. CONCLUSIONS: SAGA represents a uniquely patient-specific outcome measure. Our study is, to our knowledge, the first to assess patient-specific goals prior to surgery and examine SAGA outcomes following treatment in men suffering from LUTS/BPO. The correlation of SAGA outcomes with IPSS and IPSS-QoL highlight the importance of this well-established questionnaire. Functional outcomes do not necessarily reflect patient's goals and may rather be considered physician-directed outcomes.

Benign prostatic hyperplasia/obstruction ameliorated using a soluble guanylate cyclase activator.

Benign prostatic hyperplasia (BPH) is a feature of ageing males. Up to half demonstrate bladder outlet obstruction (BOO) with associated lower urinary tract symptoms (LUTS) including bladder overactivity. Current therapies to reduce obstruction, such as α1-adrenoceptor antagonists and 5α-reductase inhibitors, are not effective in all patients. The phosphodiesterase-5 inhibitor (PDE5I) tadalafil is also approved to treat BPH and LUTS, suggesting a role for nitric oxide (NO• ), soluble guanylate cyclase (sGC), and cGMP signalling pathways. However, PDE5I refractoriness can develop for reasons including nitrergic nerve damage and decreased NO• production, or inflammation-related oxidation of the sGC haem group, normally maintained in a reduced state by the cofactor cytochrome-b5-reductase 3 (CYB5R3). sGC activators, such as cinaciguat (BAY 58-2667), have been developed to enhance sGC activity in the absence of NO• or when sGC is oxidised. Accordingly, their effects on the prostate and LUT function of aged mice were evaluated. Aged mice (≥24 months) demonstrated a functional BPH/BOO phenotype, compared with adult animals (2-12 months), with low, delayed voiding responses and elevated intravesical pressures as measured by telemetric cystometry. This was consistent with outflow tract histological and molecular data that showed urethral constriction, increased prostate weight, greater collagen deposition, and cellular hyperplasia. All changes in aged animals were attenuated by daily oral treatment with cinaciguat for 2 weeks, without effect on serum testosterone levels. Cinaciguat had only transient (1 h) cardiovascular effects with oral gavage, suggesting a positive safety profile. The benefit of cinaciguat was suggested by its reversal of an overactive cystometric profile in CYB5R3 smooth muscle knockout mice that mirrors a profile of oxidative dysfunction where PDE5I may not be effective. Thus, the aged male mouse is a suitable model for BPH-induced BOO and cinaciguat has a demonstrated ability to reduce prostate-induced obstruction and consequent effects on bladder function. © 2021 The Pathological Society of Great Britain and Ireland.

METTL3-dependent m6A modification mediates bladder remodeling after partial bladder outlet obstruction through CCN2 activation.

AIMS: N6-methyladenosine (m6A) modification is a critical posttranscriptional event in gene regulation. Thus, identifying methyltransferase, demethylase, or m6A binding protein-mediated m6A modifications in cancer or noncancer transcriptomes has become a promising novel strategy for disease therapy development. However, novel insights into m6A modification in partial bladder outlet obstruction (pBOO) and detailed information about the drivers of bladder remodeling remain to be elucidated. Here, we first characterized the m6A modification landscape in pBOO and investigated potential actionable pharmaceutical targets for future therapies. METHODS: We generated an improved animal model of pBOO in SD rats with urethral meatus stricture induced by suturing. Urodynamic investigations and cystometry were carried out to evaluate the physiologic changes elicited by pBOO. Whole-transcriptome sequencing (RNA-seq) and m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) were subsequently performed to analyze the expression pattern associated with bladder remodeling in pBOO. RESULTS: The cystometric evaluation of bladder function demonstrated obvious increases in pressure-related parameters in the pBOO group. Hematoxylin and eosin staining and Masson's trichrome staining validated the occurrence of bladder remodeling. A global elevation in m6A RNA methylation levels was observed in parallel to a increased expression of METTL3 in the pBOO group. High-throughput sequencing revealed the differences in expression patterns between the pBOO and sham-operated groups. Furthermore, potential m6A-modified genes, including CCN2, may serve as new pharmaceutical targets to reverse bladder remodeling. CONCLUSIONS: Exploring the roles of m6A-modified genes identified as associated with bladder remodeling by integrating RNA-seq and MeRIP-seq data can offer new insights for developing promising treatments for pBOO patients.

The bladder contractility and bladder outlet obstruction indices in children. Results of a global Delphi consensus study.

AIMS: This Delphi study was planned to examine global expert consensus with regard to utility, accuracy, and categorization of Bladder Contractility Index (BCI), Bladder Outlet Obstruction Index (BOOI), and the related evidence. This manuscript deals with children and follows previous manuscripts reporting on adult men and women. METHODS: Eighteen experts were invited to answer the two-round survey including three foundation questions and four survey questions. Consensus was defined as ≥75% agreement. The ordinal scale (0-10) in Round 1 was classified into "strongly agree," "agree," "neutral," "disagree," and "strongly disagree" for the final round. A systematic search for evidence was conducted for therapeutic studies that have examined outcome stratified by the indices in children. RESULTS: Eleven experts participated in the survey with 100% completion. Consensus was not noted with regard to any of the questions. There was a general trend toward disagreement with the utility of the BCI and BOOI in children. Systematic search yielded one publication pertaining the value of the indices in predicting long-term outcome in boys treated for posterior urethral valves. CONCLUSIONS: This global Delphi survey of experts showed a general disinclination to use numerical indices for bladder contractility and bladder outflow obstruction in children. There is very little data on the use of the BCI and BOOI indices in children. The establishment of urodynamic indices in children might help refine the treatment of functional urological disorders in children.

Defining bladder outlet obstruction and detrusor underactivity in females with overactive bladder: Are we forgetting about the free uroflowmetry?

INTRODUCTION: Both detrusor underactivity (DU) and bladder outlet obstruction (BOO) can coexist in patients with overactive bladder. Definitions of both DU and BOO are based on pressure-flow study (PFS) data. However, invasive urodynamics study can differ from a natural micturition, in fact, discrepancies between free uroflowmetry (UFM) and PFS have been largely described. Our goal is to assess the correlation of free-flowmetry and PFS among patients with OAB and to evaluate how different definitions of DU/BOO are able to discriminate patients with different free UFMs. METHODS: A retrospective review of urodynamics performed at a single institution was conducted. Females with OAB who voided more than 150 mL in both UFM and PFS were included. Parameters from both voiding episodes were compared with nonparametric test. Two definitions of DU were applied; PIP1: Pdet@Qmax+Qmax < 30 and Gammie: Pdet@Qmax < 20 cmH2 O, Qmax < 15 mL/s, and BVE < 90% (Bladder voiding efficiency). Also, two definitions of obstruction were chosen; Defretias: Pdet@Qmax ≥25 cmH2 O and Qmax ≤ 12 mL/s and Solomon-Greenwell female BOO index ≥ 18. Patients who matched with each definition were compared to those who did not, to assess if any definitions were able to discriminate different noninvasive uroflowmetries. RESULTS: A total of 195 patients were included. Overall, mean age was 55 ± 12 years, 90.8% had mixed urinary incontinence, and 39% complained of at least one voiding symptom. Globally, Qmax and BVE correlated poorly between UFM and PFS, showing that most of the variation corresponded to a systematic error. Twenty-two individuals were found to have DU, they had a difference of 13 mL/s on both maximum flows. Fifty-four patients showed BOO, with a difference between their Qmax of 19 mL/s. Among the four definitions analyzed, only PIP1 and Defreitas were able to discriminate patients with actually a lower Qmax on the free UFM. CONCLUSIONS: Patients with overactive bladder seem to have a systematic discordance between the urine flow of the free and invasive studies. Current definitions of DU and BOO, which are based on the PFS parameters, are not consistently able to discriminate patients who actually void deficiently on the free UFM.