Robot-assisted Foley Tie Ureteric Tapering and Reimplantation.

Objective: This study aimed to introduce and evaluate the feasibility and outcomes of a novel surgical technique, robot-assisted Foley tie ureteric tapering (RAFUT) and reimplantation, specifically designed for intravesical ureteral tapering during pediatric robotic-assisted ureteric reimplantation. Materials and Methods: A retrospective analysis was conducted on pediatric patients diagnosed with primary vesicoureteric reflux (VUR), who underwent RAFUT between January 2019 and July 2021. Patient records were reviewed to assess preoperative characteristics, operative details, and postoperative outcomes. RAFUT involved meticulous patient positioning, precise port placement with a 6 mm separation, and bladder anchoring to maintain pneumovesicum. Ureteric tapering was performed with the Foley tie technique to enhance surgical precision. The primary outcome measures included operative time, complications, and postoperative VUR resolution. Results: All four patients underwent successful intravesical RAFUT without any intraoperative or postoperative complications. The age of the patients ranged from 3 to 12 years, with varying bladder capacities (range: 210-550 mL). The operating times ranged from 180 to 210 min, and the estimated blood loss was 35-50 mL. None of the patients required conversion to open surgery. Patients demonstrated resolution of VUR on postoperative imaging, and none experienced recurrent urinary tract infections during follow-up, which ranged from 1.5 to nearly 4 years. Conclusion: RAFUT represents a safe and effective surgical technique for intravesical ureteral tapering during pediatric robotic-assisted ureteric reimplantation. This innovative approach addresses the challenges posed by intravesical surgery for dilated ureters, maintains anatomical orientation, and offers precise excision and suturing capabilities.

A scoping review on chordee correction in boys with ventral congenital penile curvature and hypospadias.

Introduction: Congenital penile curvature (PC), often concomitant with hypospadias, poses challenges in urology. Surgical correction techniques, including plication and corporotomy, lack standardized guidelines. This study aims to address the paucity of high-level evidence by comprehensively reviewing the outcomes of PC correction procedures in patients with and without hypospadias. This will inform clinical decision-making and provide insights for future research and meta-analyses. Methods: We conducted this scoping review in accordance with the JBI Manual for Evidence Synthesis and PRISMA-ScR guidelines. An extensive literature search was performed and comparative studies published in English up to June 2023 were included. The studies were divided into three categories: PC without hypospadias, PC with hypospadias, and studies comparing two or more materials for covering the ventral corporotomy. Data extraction comprised author details, patient characteristics, study design, interventions, outcomes, and complications. Methodological quality was assessed using the Newcastle-Ottawa Scale. Results: Forty-two studies were included in the review, which collectively comprised 3180 patients. Thirteen comparative studies reported the outcomes of surgery for congenital PC without hypospadias, 22 studies compared different techniques of PC correction in patients with hypospadias and 7 studies compared the type of materials for coverage following ventral corporotomy. In cases of PC without hypospadias, the most commonly reported surgery was the Nesbit's plication. For PC with hypospadias correction, the results of ventral corporotomy were superior to that of dorsal plication in most of the studies. The two-stage repair had better results when compared to the one-stage repair for patients with perineo-scrotal hypospadias. In studies comparing materials for coverage of ventral corporotomy, the tunica vaginalis flap or graft was utilized most commonly. The majority of the studies reported a success rate ranging from 85% to 100%. The methodological quality was high in all but four studies. Conclusion: Plication procedures are generally preferred for PC without hypospadias, but they result in penile shortening. For those with hypospadias, corporotomy is associated with superior outcomes than plication, especially for those with severe curvature and redo procedures. For ventral corporotomy coverage, the tunica vaginalis flap or graft is the most commonly reported tissue in the literature.

Predicting obstruction risk using common ultrasonography parameters in paediatric hydronephrosis with machine learning.

OBJECTIVE: To sensitively predict the risk of renal obstruction on diuretic renography using routine reported ultrasonography (US) findings, coupled with machine learning approaches, and determine safe criteria for deferral of diuretic renography. PATIENTS AND METHODS: Patients from two institutions with isolated hydronephrosis who underwent a diuretic renogram within 3 months following renal US were included. Age, sex, and routinely reported US findings (laterality, kidney length, anteroposterior diameter, Society for Fetal Urology [SFU] grade) were abstracted. The drainage half-times were collected from renography and stratified as low risk (<20 min, primary outcome), intermediate risk (20-60 min), and high risk of obstruction (>60 min). A random Forest model was trained to classify obstruction risk, here named the 'Artificial intelligence Evaluation of Renogram Obstruction' (AERO). Model performance was determined by measuring area under the receiver-operating-characteristic curve (AUROC) and decision curve analysis. RESULTS: A total of 304 patients met the inclusion criteria, with a median (interquartile range) age of diuretic renogram at 4 (2-7) months. Of all patients, 48 (16%) were low risk, 102 (33%) were intermediate risk, 156 (51%) were high risk of obstruction based on diuretic renogram. The AERO achieved a binary AUROC of 0.84, multi-class AUROC of 0.74 that was superior to the SFU grade, and external validation (n = 64) binary AUROC of 0.76. The most important features for prediction included age, anteroposterior diameter, and SFU grade. We deployed our application in an easy-to-use application (https://sickkidsurology.shinyapps.io/AERO/). At a threshold probability of 30%, the AERO would allow 66 more patients per 1000 to safely avoid a renogram without missing significant obstruction compared to a strategy in which a renogram is routinely performed for SFU Grade ≥3. CONCLUSIONS: Coupled with machine learning, routine US findings can improve the criteria to determine in which children with isolated hydronephrosis a diuretic renogram can be safely avoided. Further optimisation and validation are required prior to implementation into clinical practice.

Mini-versus standard percutaneous nephrolithotomy in pediatric population: A randomized controlled trial.

INTRODUCTION: Mini PCNL has gained popularity in adult patients due to reduction in the complication rate with comparable stone free rate. There is paucity of level 1 evidence regarding the benefit of mini PCNL in the pediatric group. OBJECTIVE: We performed a randomised study to compare mini PCNL (mPCNL) with standard PCNL (sPCNL) for the management of renal calculi in patients less than 18 years of age in terms of safety, efficacy, and stone-free rate (SFR). MATERIALS AND METHODS: A randomised controlled trial was performed on 50 children who underwent PCNL from June 2015 to March 2021, who were divided into two groups. Group I had 25 patients managed with mPCNL (sheath size 16.5 Fr) and Group II had 25 patients who underwent sPCNL (sheath size 26 Fr). Primary outcomes including stone free rates (SFR) and hemoglobin drop and secondary outcomes like operative time, complications, pain score, need of analgesia, incidence of nephrostomy site leak, hospital stay in days were compared between the two groups. RESULTS: The mean age of patients in groups I and II was 9.4 ± 2.6 and 10.4 ± 2.26 years, respectively (p = 0.15). The mean stone sizes in both groups I and II were 18.6 ± 2.56 and 20.2 ± 3.58 mm, respectively (p > 0.05). The stone free rate for group I was 88% and for group II, 92% (p = 0.64). The average drop in hemoglobin was higher in group II compared to group I (1.1 ± 0.31 g/dl and 1.7 ± 0.23 g/dl respectively; p < 0.0001), however the mean blood transfusion rate was not significantly different in both groups. The operating time was shorter in group II compared to group I (p-value - 0.0030). The pain scores were lesser for the group I. Grade I complications were higher in group II as compared to group I (p-0.047); however, grade II complications were comparable in both groups. The mean hospital stay was not significantly different in both groups. DISCUSSION: This study confirms the role of mini PCNL in pediatric patients with renal stones. The stone clearance rate of mini PCNL is equivalent to standard PCNL, with lesser blood loss and postoperative complications, however with longer operative time during mPCNL. The small number of the participants in both arms is a limitation of this study and may also reflect fewer children with urolithiasis being treated surgically even in a tertiary care referral centre. CONCLUSIONS: Mini-PCNL offers equivalent stone free outcome with lower complications rate compared to the standard PCNL for all types of renal stones.

EZH2 and matrix co-regulate phenotype and KCNB2 expression in bladder smooth muscle cells.

BACKGROUND: Partial bladder outlet obstruction (PBO) is a widespread cause of urinary dysfunction and patient discomfort, resulting in immense health care costs. Previously, we found that obstruction is associated with altered regulation of epigenetic machinery and altered function. Here we examined if PBO and chronic bladder obstructive disease (COBD) affect epigenetic marks in a proof of principle gene and explored mechanisms of its epigenetic regulation using in vitro models. METHODS: Archival obstruction tissues from COBD had been created in 200-250 g female Sprague-Dawley rats by surgical ligation of the urethra for 6 weeks, followed by removal of the suture and following animals for 6 more weeks. Obstruction (PBO) is the 6-week ligation only. Sham ligations comprise passing the suture behind the urethra. Histone3 lysine27 trimethylation (H3K27me3) was studied by immunostaining and Chromatin immunoprecipitation (ChIP)/PCR. The interaction of matrix with KCNB2 regulation was studied in human bladder SMC plated on damaged matrix and native collagen and treated with vehicle or UNC1999. Cells were analyzed by immunostaining for cell phenotype, and western blotting for KCNB2, H3K27me3 and EZH2. Effects of conditioned media from these cells were also examined on cell phenotype. siRNA against KCNB2 was examined for effects on cell phenotype and gene expression by RT-qPCR. RESULTS: H3K27me3 increased by immunofluorescence during PBO, and by ChIP/PCR during COBD in the CpG Island (CGI) as well as 350 bp upstream. Obstruction vs. sham also showed an increase in H3K27me3 deposition. In SMC in vitro, EZH2 inhibition restored KCNB2 expression and partially restored SMC phenotype. CONCLUSIONS: Regulation of KCNB2 at the promoter demonstrated dynamic changes in H3K27me3 during COBD and obstruction. In vitro models suggest that matrix plays a role in regulation of EZH2, H3K27me3 and KCNB2, which may play a role in the regulation of smooth muscle phenotype in vivo.

A quantitative analysis of voiding cystourethrogram features confirms the association between high-grade vesicoureteral reflux with male sex, younger age, and hydronephrosis.

INTRODUCTION: Vesicoureteral reflux (VUR) is commonly diagnosed in the workup of urinary tract infections or hydronephrosis in children. Traditionally, VUR severity is graded subjectively based on voiding cystourethrogram (VCUG) imaging. Herein, we characterized the association between age, sex, and indication for VCUG, by employing standardized quantitative features. METHODS: We included renal units with a high certainty in VUR grade (>80% consensus) from the qVUR model validation study at our institution between 2013 and 2019. We abstracted the following variables: age, sex, laterality, indication for VCUG, and qVUR parameters (tortuosity, ureter widths on VCUG). High-grade VUR was defined as grade 4 or 5 The association between each variable and VUR grade was assessed. RESULTS: A total of 443 patients (523 renal units) were included, consisting of a 48:52 male/female ratio. The median age at VCUG was 13 months. Younger age at VCUG (<6 months) was associated with greater odds of severe VUR (odds ratio [OR] 2.0), and there was a weak correlation between age and VUR grade (ρ=-0.17). Male sex was associated with increased odds of high-grade VUR (OR 2.7). VCUGs indicated for hydronephrosis were associated with high-grade VUR (OR 4.1) compared to those indicated for UTI only. Ureter tortuosity and width were significantly associated with each clinical variable and VUR severity. CONCLUSIONS: Male sex, younger age (<6 months), and history of hydronephrosis are associated with both high-grade VUR and standardized quantitative measures, including greater ureter tortuosity and increased ureteral width. This lends support to quantitative assessment to improve reliability in VUR grading.

Spontaneous urinary bladder regeneration after subtotal cystectomy increases YAP/WWTR1 signaling and downstream BDNF expression: Implications for smooth muscle injury responses.

Rodents have the capacity for spontaneous bladder regeneration and bladder smooth muscle cell (BSMC) migration following a subtotal cystectomy (STC). YAP/WWTR1 and BDNF (Brain-derived neurotrophic factor) play crucial roles in development and regeneration. During partial bladder outlet obstruction (PBO), excessive YAP/WWTR1 signaling and BDNF expression increases BSMC hypertrophy and dysfunction. YAP/WWTR1 and expression of BDNF and CYR61 were examined in models of regeneration and wound repair. Live cell microscopy was utilized in an ex vivo model of STC to visualize cell movement and division. In Sprague-Dawley female rats, STC was performed by resection of the bladder dome sparing the trigone, followed by closure of the bladder. Smooth muscle migration and downstream effects on signaling and expression were also examined after scratch wound of BSMC with inhibitors of YAP and BDNF signaling. Sham, PBO and incision (cystotomy) were comparators for the STC model. Scratch wound in vitro increased SMC migration and expression of BDNF, CTGF and CYR61 in a YAP/WWTR1-dependent manner. Inhibition of YAP/WWTR1 and BDNF signaling reduced scratch-induced migration. BDNF and CYR61 expression was elevated during STC and PBO. STC induces discrete genes associated with endogenous de novo cell regeneration downstream of YAP/WWTR1 activation.

Long term outcomes of Cohen's cross trigonal reimplantation for primary vesicoureteral reflux in poorly functioning kidney.

BACKGROUND: Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux (VUR). There is a lack of evidence in literature though for what happens to such kidneys, in the long run, particularly those which are poorly functioning. AIM: To assess the long-term outcomes of ureteric reimplantation in poorly functioning kidneys in children with unilateral primary VUR. METHODS: Children with unilateral primary VUR and a relative renal function of less than 35% who underwent open or laparoscopic ureteric reimplantation between January 2005 and January 2017 were included in the study. Patients who had a follow up of less than five years were excluded. Preoperative evaluation consisted of a voiding cystourethrogram and Dimercaptosuccinic acid (DMSA) scan. In the follow-up period, patients underwent a diuretic scan at 6 weeks and 6 months. Follow up ultrasound was done for change in grade of hydronephrosis and retrovesical ureteric diameter. Subsequent follow up was done at 6 monthly intervals with evaluation for proteinuria and hypertension and any recurrent urinary tract infection (UTI). For assessment of cortical function, DMSA was repeated annually for 5 years after surgery. A paired-samples t-test was used to test the mean difference of DMSA between pre-post observations. RESULTS: During this period, 36 children underwent ureteric reimplantation for unilateral primary VUR. After excluding those with insufficient follow-up, 31 were included in the analysis. Most of the patients were males (n = 26/31, 83.8%). Patient's age (mean ± SD, range) was 5.21 ± 3.71, 1-18 years. The grades of VUR were grade II (1 patient), grade III (8 patients), grade IV (10 patients), and grade V (12 patients). The pre and postoperative DMSA was 24.064 ± 12.02 and 24.06 ± 10.93, which was almost the same (statistically equal, paired-samples t-test: P = 0.873). The median (range) follow-up duration was 82 (60-120) mo. One patient had persistent reflux after surgery (preoperative: grade IV, postoperative: grade III), and the very same patient developed recurrent UTI. The difference in the preoperative and postoperative DRF was less than 10% in 29 patients. In one patient, the DRF decreased by 17% (22% to 05%) while in another patient, the DRF increased by 12% (25% to 37%) after surgery. None of the patients had an increase in scarring after surgery. 15% of patients were hypertensive before surgery and all of them continued to be hypertensive after surgery while none developed hypertension after surgery. None of the patients had significant proteinuria (> 150 mg/d) during the follow-up period. CONCLUSION: Children with unilateral primary VUR and poorly functioning kidney maintain the renal function over the long term in most cases. Hypertension and proteinuria do not progress over time in these patients.

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Posterior urethral valves, pressure pop-offs, and kidney function: systematic review and meta-analysis.

PURPOSE: To determine the role of pressure pop-off mechanisms, including vesicoureteral reflux and renal dysplasia (VURD) syndrome, in determining long-term kidney outcomes in boys with posterior urethral valves (PUV). METHODS: A systematic search was performed in December 2022. Descriptive and comparative studies with a defined pressure pop-off group were included. Assessed outcomes included end-stage renal disease (ESRD), kidney insufficiency (defined as chronic kidney disease [CKD] stage 3 + or SCr > 1.5 mg/dL), and kidney function. Pooled proportions and relative risks (RR) with 95% confidence intervals (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analyses were performed according to the study design and techniques. The risk of bias was assessed with the QUIPS tool and GRADE quality of evidence. The systematic review was prospectively registered on PROSPERO (CRD42022372352). RESULTS: A total of 15 studies describing 185 patients with a median follow-up of 6.8 years were included. By the last follow-up, overall effect estimates demonstrate the prevalence of CKD and ESRD to be 15.2% and 4.1%, respectively. There was no significant difference in the risk of ESRD in patients with pop-off compared to no pop-off patients [RR 0.34, 95%CI 0.12, 1.10; p = 0.07]. There was a significantly reduced risk for kidney insufficiency in boys with pop-off [RR 0.57, 95%CI 0.34, 0.97; p = 0.04], but this protective effect was not re-demonstrated after excluding studies with inadequate reporting of CKD outcomes [RR 0.63, 95%CI 0.36, 1.10; p = 0.10]. Included study quality was low, with 6 studies having moderate risk and 9 having a high risk of bias. CONCLUSIONS: Pop-off mechanisms may be associated with reducing the risk of kidney insufficiency, but current certainty in the evidence is low. Further research is warranted to investigate sources of heterogeneity and long-term sequelae in pressure pop-offs.

Clinical and Urodynamic Predictors for Failure of Medical Management with Alpha Blockers in PBNO: A Retrospective Cohort Analysis.

OBJECTIVE: To evaluate the clinical and urodynamic variables that may predict the failure of alpha-blockers in primary bladder neck obstruction (PBNO) patients. Alpha-blockers are useful as a treatment option in patients with PBNO. Nonresponders need to undergo bladder neck incision (BNI). Little is known about the predictive factors determining the success of treatment. MATERIALS AND METHODS: This was a retrospective study, spanning over a period of 8 years. PBNO was diagnosed in the presence of a bladder outlet obstruction index (BOOI) >40 with video-urodynamic evidence of obstruction at the bladder neck. The patients were initially managed with alpha-blockers (alfuzosin and tamsulosin) for 3-6 months, and BNI contemplated when pharmacotherapy failed. The patients with upper tract changes managed with upfront BNI or clean intermittent catheterization were excluded. The data for the international prostate symptom score (IPSS), uroflowmetry, urodynamic studies, and ultrasonography of pre and post-treatment periods were reviewed. Treatment outcomes were defined as complete response (>50% improvement in Qmax and IPSS score) and partial response (30%-50% improvement in Qmax and IPSS score) at 3 or 6 months. RESULTS: Ninety-nine patients were analyzed. 21 patients underwent BNI for the failure of medical management and 31 for recurrence of symptoms at a mean follow-up of 18.8 ± 3.5 months (12-70 months). Independent predictors of failure of pharmacotherapy with alpha-blockers were age (P = .021), Pdet@Qmax (P = .015), and BOOI (P = .019). CONCLUSION: Alpha-blockers are more likely to fail in PBNO in younger patients generating higher voiding pressures and BOOI > 60.

Does VURD syndrome impact voiding efficiency in posterior urethral valves?

INTRODUCTION: There is debate regarding the effect of VURD syndrome, consisting of vesicoureteral reflux (VUR) and ipsilateral kidney dysplasia, on long-term outcomes in boys with posterior urethral valve (PUV). Here, we assessed whether VURD syndrome played a "protective" role on long-term bladder outcomes and voiding efficiency in boys with PUV. MATERIALS AND METHOD: A retrospective chart review was conducted for toilet-trained children with PUV managed at our institution between 2000 and 2022, only excluding cases without recorded uroflowmetry studies. Patients were stratified by VUR status and by the presence of VURD syndrome (high-grade VUR + ipsilateral kidney dysplasia). Outcomes included initial and final uroflowmetry parameters, and initiation of clean-intermittent catheterization (CIC). RESULTS: We identified a total of 101 patients who met study inclusion criteria, with an overall median follow-up of 114 months (IQR 67, 169). The median age of first and last uroflowmetry was 57 months (IQR 48, 82) and 120 months (IQR 89, 160), respectively. Patients with VURD syndrome had similar flow velocity, post-void residuals, and bladder voiding efficiency to other PUV patients at last follow-up uroflowmetry. On survival analysis, patients with VURD syndrome had no significant difference in risk of requiring CIC compared to patients without pop-offs (p = 0.06). DISCUSSION: Like more contemporary studies on pressure pop-offs, we show that this population is not at higher risk of poorer voiding and intermittent catheterization than others. VURD syndrome does not confer protection against poorer bladder function. Instead, our study suggests an independent association between kidney dysplasia and bladder outcomes which requires further attention. CONCLUSIONS: Among boys with PUV, VURD syndrome was not associated with significantly different uroflowmetry findings or rates of CIC by last follow-up.

Dorsal shortening vs. ventral lengthening for congenital ventral curvature in patients with/without severe hypospadias A meta-analysis of comparative studies.

INTRODUCTION: Herein, we compared surgical outcome of dorsal shortening (DS) vs. ventral lengthening (VL) for correcting congenital ventral curvatures. METHODS: A systematic literature search was performed in September 2021 using the PubMed, EMBASE, Scopus, CENTRAL, ProQuest, and Clinicaltrials.gov databases. Comparative studies were identified and evaluated according to Cochrane Collaboration recommendations. Assessed outcomes included success and complication rates, which were extrapolated for the respective odds ratios (OR) with 95% confidence intervals (CIs). Subgroup analyses were performed according to congenital curvature, with or without severe hypospadias or recurrent curvatures (PROSPERO: CRD42021276193). RESULTS: Based on pooled effect estimates from 12 studies with 430 (DS 253, VL 177) cases of ventral curvature repair, VL rendered a better success rate for curvature correction (OR 4.20, 95% CI 2.11, 8.33) than DS, with comparable composite surgical complication rates (OR 0.77, 95% CI 0.27, 2.18). Subgroup analysis showed that the success rate remained significantly better for VL among patients with associated severe hypospadias (OR 3.59, 95% CI 1.25, 10.26) and recurrent penile curvatures (OR 5.70, 95% CI 1.69, 19.21) but not among those with congenital curvature without hypospadias or those with mild hypospadias (OR 2.99, 95% CI 0.32, 27.57). CONCLUSIONS: For congenital curvature associated with severe hypospadias and recurrent curvatures, VL renders a modestly better success rate; however, careful selection of patients is key for best outcome.

Primary ablation versus urinary diversion in posterior urethral valve: Systematic review and meta-analysis.

PURPOSE: To determine differences in long-term kidney and bladder outcomes in boys with posterior urethral valves (PUV) managed by a primary valve ablation or primary urinary diversion. MATERIALS AND METHODS: A systematic search was performed in March 2021. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included kidney outcomes (chronic kidney disease, end-stage renal disease, kidney function) and bladder outcomes. Odds ratios (OR) and mean difference (MD) with 95% confidence interval (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design, and potential covariates were assessed with subgroup analysis. The systematic review was prospectively registered on PROSPERO (CRD42021243967). RESULTS: Thirty unique studies describing 1547 boys with PUV were included in this synthesis. Overall effect estimates demonstrate that patients undergoing primary diversion have significantly increased odds of developing renal insufficiency [OR 0.60, 95% CI 0.44, 0.80; p < 0.001]. However, when adjusting for baseline kidney function between intervention groups, there was no significant difference in long term kidney outcomes [p = 0.09, 0.35], or the development of bladder dysfunction or requiring clean-intermittent catheterization with primary ablation rather than diversion [OR 0.89, 95% CI 0.49, 1.59; p = 0.68]. CONCLUSIONS: Current low-quality evidence suggests that medium-term kidney outcomes in children are similar between primary ablation and primary diversion after adjusting for baseline kidney function, while bladder outcomes are highly heterogenous. Further research with covariate control is warranted to investigate sources of heterogeneity. LEVEL OF EVIDENCE: Level III.

Assessing the role of upside-down (inverted) renal allografts in pediatric kidney transplantation: a propensity-score matched analysis.

OBJECTIVE: To evaluate the implications of inverted (upside-down) kidney configuration in pediatric renal transplantation employing a comparative analysis with at least 1-year follow-up. METHODS: Patients who underwent kidney transplantation at our institution between January 2011 and June 2021 were reviewed. Patients who had an inverted renal transplant were propensity-score matched (PSM) in 1:2 ratio with those who had traditional orientation transplant. The outcomes assessed included delayed graft function (DGF), urine leak, lymphocele, rejection, allograft calculus, ureteric stricture, and nadir creatinine. RESULTS: A total of 24 patients with inverted orientation were identified. Following PSM, 41 patients were matched, with exclusions due to incompatible propensity scores. Baseline characteristics were appropriately matched, and no significant differences were noted between the two groups. There were no differences in: delayed graft function (0/24 vs. 3/41, p = 0.290), urine leak (3/24 vs. 2/41, p = 0.350), lymphocele (2/24 vs. 4/41, p = 1.000), rejection (3/24 vs. 5/41, p = 1.000), graft calculus (2/24 vs. 0/41, p = 0.133), and ureteric stricture (0/24 vs. 2/41, p = 0.527). The two cases of renal calculus seen in the inverted transplant group occurred on post-operative day 13 and 1584, both were managed without complications. There was no difference in nadir creatinine (median 34umol/L IQR23-57 vs. 35 umol/L IQR 20-50, p = 0.624) or time to nadir creatinine (8 days IQR 6-12 vs. 8 days IQR 7-28, p = 0.315). CONCLUSION: Inverting a renal allograft does not appear to significantly contribute to increased risk of post-operative adverse outcomes. When aiming to achieve the best anatomical placement to secure a comfortable vascular anastomosis, inverting the allograft should be considered.

A study on etiology of incontinence in double knockout mouse model.

INTRODUCTION AND OBJECTIVE: Stress urinary incontinence is of concern in both pediatric and adult population. Double mutant GLI family zinc finger Gli2+/-; Gli3Δ699/+ murine model of stress incontinence has been recently developed as a reliable model which does not require surgical manipulation to create incontinence and is shown to survive to adulthood. The aim of this study was to establish the etiology of incontinence in the double mutant Gli2+/-; Gli3Δ699/+ mice. STUDY DESIGN: We used 13 cluster of differentiation 1 (CD-1) mice (7-9 weeks) for demonstration of histology of the bladder and urethra. There were 3 Wild Gli2+/- females, 2 Wild Gli2+/- males, 4 Gli2+/-;Gli3Δ699/+ females and 4 Gli2+/-;Gli3Δ699/+ males. The Wild Gli2+/- mice served as the control group and Gli2+/-;Gli3Δ699/+ mice served as the test group. Additionally, eight 16.5 days mice (2 each of Wild Gli2+/- females, Wild Gli2+/- males, double knockout (DKO) Gli2+/-;Gli3Δ699/+ females and Gli2+/-;Gli3Δ699/+ males) were used to assess the histology of the spinal cord. The gross appearance of bladder and urethra was studied using ink injection assays. Immunohistochemistry was done for smooth muscle actin and cytokeratin. RESULTS: Gross and histologic appearance confirmed the previously reported widening of bladder outlet and hypoplasia of smooth muscles in female urethra and also established them in the male urethra of Gli2+/-;Gli3Δ699/+ mice compared to Gli2+/- mice. The double knockout mice were smaller than the Gli2 mice (5.2 vs 6.1 cm, p = 0.002). Immunohistochemistry demonstrated epithelial hyperplasia and smooth muscle hypoplasia. Additionally, there was prostatic hypoplasia in the Gli2+/-;Gli3Δ699/+ male mice. The spinal cord length for body size appeared comparable between the Gli2+/- and Gli2+/-;Gli3Δ699/+ mice but histological evaluation revealed abnormal development of the caudal end of the vertebral body with premature termination of the spinal cord (Figure). DISCUSSION: The histological changes in the bladder neck and urethra were consistent to those previously reported. While previous report described the findings in female mice only, we confirmed that these findings are also present in males as well as prostatic hypoplasia, a possible additional factor leading to stress incontinence. The most important finding in the present study however, was the detection of premature termination of spinal cord in the DKO Gli2+/-; Gli3Δ699/+ mice which has not been reported previously and is likely a major contributor to incontinence in this model. CONCLUSION: The incontinence in male as well as female Gli2+/-; Gli3Δ699/+ mice is due to both myogenic and neurogenic involvement. These double knockout mice are a valuable model of stress incontinence related to neurogenic bladder due to low outlet resistance.

A systematic review of paediatric neurogenic lower urinary tract dysfunction guidelines using the Appraisal of Guidelines and Research Evaluation (AGREE) II instrument.

OBJECTIVE: To examine and critique current international clinical practice guidelines (CPGs) on management of paediatric neurogenic lower urinary tract dysfunction (NLUTD) and assess the applicability of these guidelines to clinical practice. MATERIALS AND METHODS: We conducted a systematic review of all CPGs on NLUTD published in English from the year 2010 to 2022. Six reviewers independently used the Appraisal of Guidelines and Research Evaluation (AGREE) II instrument to appraise all eligible CPGs. This instrument is comprised of 23 items organised into six quality domains. The scores for each item and domain were tabulated for each reviewer and interrater reliability was assessed for each domain using the intraclass correlation coefficient (ICC). RESULTS: Six CPGs were appraised and these included: National Institute for Health and Care Excellence (NICE), European Society for Paediatric Urology, International Children's Continence Society, Irish, Spina Bifida Association (SBA), and International Brazilian Journal of Urology guidelines. They had high mean standardised scores in the domain on 'scope and purpose' and 'clarity of presentation' but had low scores in the domain of 'applicability'. The top three CPGs based on overall score were the NICE, Irish and SBA guidelines and the reviewers had high degree of interrater reliability (ICC 0.912, P < 0.001). The mean scores in various domains for the top three guidelines were 95.8 (scope and purpose), 87.5 (stakeholder involvement), 69.1 (rigour of development), 94.0 (clarity of presentation), 68.4 (applicability), and 59.7 (editorial independence). The diagnostic and treatment recommendations of the top three guidelines were presented. CONCLUSION: The existing CPGs on paediatric NLUTD provide high-quality evidence based recommendations. The NICE, Irish and SBA guidelines were the top three CPGs identified. They scored high on most domains except applicability and editorial independence. These domains need to be considered for future updates to improve the utility.

The effect of primary urinary diversion on kidney function in posterior urethral valve: A matched comparison.

OBJECTIVE: To determine long-term kidney outcomes in boys with posterior urethral valve (PUV) undergoing either primary valve ablation or urinary diversion with matched baseline kidney function. METHODS: After retrospective review of patients managed for PUV at our institution, propensity score matched analysis was conducted using nadir serum creatinine with logistic regression analysis. Nearest neighbor matching was used to allocate boys to primary urinary diversion and primary ablation groups. Primary outcomes included kidney function by creatinine or estimated glomerular filtration rate, chronic kidney disease, and end-stage renal disease. Comparative statistics by odds ratio (OR) and hazard ratios on survival analysis were calculated. RESULTS: A total of 21 boys undergoing primary diversion were matched with 42 boys undergoing ablation using nadir serum creatinine and follow-up time with a median follow-up of 4.8 years. After matching, there was no significant difference in last follow-up kidney function by creatinine (P = .99) or estimated glomerular filtration rate (P = .98). Primary diversion was not associated with increased likelihood of developing chronic kidney disease stage 3 (OR 1.33; P = .31) or end-stage renal disease (OR 1.88; P = .35 and hazard ratios 1.85; P = .30) compared to primary ablation. CONCLUSIONS: Our propensity matched study suggests that long-term kidney function and kidney outcomes are similar between primary ablation and primary diversion after adjusting for baseline kidney function in boys with PUV.