Pediatric Urology Providers' Perceptions and Attitudes on Transitional Urologic Care in a Single-Payer Healthcare System.

INTRODUCTION: Advances in healthcare have improved outcomes for pediatric patients with congenital neuro-urological conditions, highlighting the need for an effective transition from pediatric to adult care. This study investigates Canada's transitional urologic care within its single-payer healthcare system, focusing on the active members of Pediatric Urologists of Canada's (PUC) practices, perceptions, and attitudes towards transitional urologic care. METHODS: A survey was distributed to 35 Pediatric Urologists of Canada (PUC) members from July 2023 to January 2024, which collected data on transitional care practices and available Transitional Urology (TU) clinics. It also focused on a service overview, covering aspects such as the responder's geographic and institutional affiliations, clinical practice characteristics involving transitional care, perceived challenges, and strategies for care enhancement. RESULTS: Nationwide engagement emphasized a commitment to improving transitional care, with a significant proportion of respondents (64%) having over 10 years of practice, reflecting substantial experience in addressing transitional care challenges. The survey identified 4 dedicated transitional care clinics, 3 of which are active, pointing to concerted efforts towards specialized service provision. The major challenges identified include the lack of adult transitional care initiatives and governmental support. Recommendations for improvement should focus on standardizing transition protocols and boosting patient education. The survey also underscored the necessity of protocolized care for Spina Bifida-Neurogenic Bladder and complex urogenital conditions. CONCLUSION: This study highlights the active efforts and existing challenges within Canada's transitional urologic care system, particularly emphasizing operational transitional care clinics as a crucial step forward in catering to transitioning patients' needs.

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.

The importance of animal specificity in animal experimentation, part I: Anatomy in relation to pediatric urology.

Why and when is animal experimentation relevant? The answer to this question depends on the research question. In this short educational article we aim to raise awareness of the importance of formulating a very specific research question before choosing an animal species. An awareness of anatomical and physiological differences vis-a-vis similarities between species, will increase the potential for obtaining data that is relevant for translation to human conditions.

The importance of animal specificity in animal experimentation, part II: Physiological challenges and opportunities in relation to pediatric urology.

When performing animal experimentation in Pediatric Urology studies, it is important to be aware of physiological differences between species and to understand when relevant disease models are available. Diseased animal models may be more relevant in many cases, rather than performing studies in healthy and normally developed animals. For example, they may be more appropriate for the study of congenital malformations, to investigate the secondary effects of prenatal urinary obstruction, to study the effect of prenatal exposure to endogenous or exogenous factors which may lead to disease, or in testing bioengineered structures. In this short educational article, we aim to describe some disease models that have been used to simulate human pathologies and how, if properly designed, these studies can lead to important new knowledge for human translation. In addition, we also highlight the importance of formulating a research question(s) before deciding on the animal experimental model and species to choose.

Combining Oxygenated Cold Perfusion With Normothermic Ex Vivo Perfusion Improves the Outcome of Donation After Circulatory Death Porcine Kidney Transplantation.

BACKGROUND: Ex vivo machine perfusion is a novel preservation technique for storing and assessing marginal kidney grafts. All ex vivo perfusion techniques have advantages and shortcomings. The current study analyzed whether a combination of oxygenated hypothermic machine perfusion (oxHMP) followed by a short period of normothermic ex vivo kidney perfusion (NEVKP) could combine the advantages of both techniques. METHODS: Porcine kidneys were exposed to 30 min of warm ischemia followed by perfusion. Kidneys underwent either 16-h NEVKP or 16-h oxHMP. The third group was exposed to 16-h oxHMP followed by 3-h NEVKP (oxHMP + NEVKP group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed up for 8 d. RESULTS: All animals survived the follow-up period. Grafts preserved by continuous NEVKP showed improved function with lower peak serum creatinine and more rapid recovery compared with the other 2 groups. Urine neutrophil gelatinase-associated lipocalin, a marker of kidney injury, was found to be significantly lowered on postoperative day 3 in the oxHMP + NEVKP group compared with the other 2 groups. CONCLUSIONS: A short period of NEVKP after oxHMP provides comparable short-term outcomes to prolonged NEVKP and is superior to oxHMP alone. A combination of oxHMP with end-ischemic NEVKP could be an attractive, practical strategy to combine the advantages of both preservation techniques.

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.

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.

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.

Translational and linguistic validation of the Arabic version of dysfunctional voiding symptom score questionnaire.

INTRODUCTION: Dysfunctional voiding is a multifactorial condition that encompasses a wide variety of symptoms rendering its diagnosis a challenging process. In this setting, several tools have been proposed to aid the diagnosis of this disease among which is the Dysfunctional Voiding Symptom Score (DVSS). The DVSS has been translated and validated to different languages including Japanese, Thai, Chinese, Serbian, and Portuguese. The aim of the current study is to translate and cross-culturally validate the DVSS into the Arabic language. MATERIAL AND METHODS: The DVSS was translated and culturally adapted to the Arabic language following the standards of the ISPOR for the translation and cultural adaptation process for patient-reported outcomes measures. Subsequently, the translated version underwent a pre-test on 15 patients with dysfunctional voiding. Afterwards, the translated version was filled by 82 pediatric patients and/or their parents with dysfunctional voiding and then the same questionnaire was refilled by the patients and their families one week later at home. Finally, a group of healthy children and/or their parents were recruited to fill the questionnaire as a control group. Cronbach's alpha, Pearson's correlation, and Interclass correlation were used to assess for internal consistency and reliability between test-retest of the Arabic version. RESULTS: The mean total score of DVSS for the case and control groups was 16.66 ± 6.07 and 6.11 ± 3.36, respectively (P < 0.001). The Arabic-DVSS showed excellent internal consistency (Cronbach's α > 0.9) for all the questions except Q1, Q3, Q6, and Q7 that showed good internal consistency. DISCUSSION: Translational and linguistic validation of the DVSS questionnaire into Arabic language is an important step toward its introduction in the clinical practice in Arabic countries; however, this step has also to consider the cultural variations between countries and not just linguistic translation. Generally, the Arabic-DVSS showed a satisfactory test-retest internal consistency and reliability with an excellent Cronbach's α (0.982) and ICC (0.962) for the total score of the Arabic-DVSS. Yet, the main limitation of this study was that it was only advocated for the translation and validation of the Arabic-DVSS and did not assess its value in patients' follow-up. CONCLUSION: The Arabic version of the DVSS is reliable and valid to help in the evaluation of DV in children of Arabic countries.

Neural network non-linear modeling to predict hypospadias genotype-phenotype correlation.

INTRODUCTION: Hypospadias is an abnormal development of the urethral, ventral skin and corporeal bodies. Urethral meatus and ventral curvature have been historically the landmarks to define clinical severity. Genotyping has never been explored as a clinical predictor. Available reports have demonstrated a correlation between genetic mutations and syndromic hypospadias with poor surgical outcomes. We hypothesize that inclusion of genotyping can serve at classifying all types of hypospadias. We present the use of neural network algorithm to evaluate phenotype/genotype correlations and propose its potential clinical applicability. METHODS: A systematic review was performed from January 1974 to June 2022. Literature was retrieved from Medline, Embase, Web of Science and Google Scholar. Included manuscripts were those that had an explicit anatomical description of hypospadias phenotype (urethral meatus location following an anatomical description) and a defined genotype (genetic mutation) description. Cases with more than one variant/mutation were excluded. A comprehensive phenotype-genotype statistical analysis using neural network non-linear data modeling SPSS™ was performed. RESULTS: Genotype-Phenotype analysis was performed on 1731 subjects. Of those, 959 (55%) were distal and 772 (45%) proximal. 49 genes with mutations were identified. Neural network clustering predicted better for coronal (90%) and glanular (80%), and lowest for midshaft (22%) and perineal (45%). Using genes as predictor factor only, the model was able to highly and more accurately predict the phenotype for coronal and glanular hypospadias. The following genotypes showed association to a specific phenotype: AR gene n.2058G > A for glanular (p<0.0001), n.480C  >  T for coronal (p = 0.034), R840C for perineal (p = 0.002), MAMLD1 gene c.2960C > T for coronal (p< 0.0001), p. G289S for glanular (p<0.0001), gene SRD5A2 607G > A for scrotal (p<0.0001), c16C > T for penoscrotal (p<0.0001), c59 T  >  c for perineal (p = 0.042), V89L for midshaft and scrotal (p<0.0001, p = 0.041; respectively). DISCUSSION: Hypospadias phenotype has always been described from a purely anatomical perspective. Our results demonstrate that current phenotyping has poor correlation to the genotype. Higher genotype/phenotype correlation for distal hypospadias proves the clinical applicability of genotyping these cases. The concept and classification of differences in sexual development needs to be reconsidered given high positive yield reported for distal hypospadias. Given the better predictive value of genotyping in correlation to the phenotype, future efforts should be directed towards using the genotype. CONCLUSION: Hypospadias has poor phenotype/genotype correlation. Sequencing all hypospadias phenotypes may add clinical value if used in association to other predictive variables. Neural network analysis may have the ability to combine all these variables for clinical prediction.

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.

Scoping review of neurogenic bladder patient-reported readiness and experience following care in a transitional urology clinic.

OBJECTIVE: To generate a scoping review that summarizes thematically on all reported patient perceptions on readiness and experiences during transitional urologic care for patients with neurogenic bladder and or congenital genitourinary conditions that require continuity of care into adulthood. METHODS: A systematic literature search was performed in October 2021. Records were screened and identified for studies relevant to reported readiness and experience in urologic transitional care among patients needing life-long urologic care. The methodological quality of the cross-sectional studies was assessed using AXIS. The included studies were clustered according to patient readiness in transition and patient experience-satisfaction in the urologic transition process. This scoping review was part of a systematic review registered on PROSPERO CRD42022306229 and was conducted in compliance with the PRISMA extension for scoping reviews. RESULTS: A total of 12 articles were included that assessed patients with neurogenic bladder that reported either readiness or patient experience following the transitional care process. The patient readiness was assessed in six studies, determined using the TRAQ score with a range of 3-4/5. Older age, high health literacy, and parental or families' transition process awareness were associated with readiness. Generally, patients experience better satisfaction with pediatric care than with adult care facilities. Most patients felt that sexuality and fertility were not adequately tackled during the transition. The reported barriers to successful transition were patient, provider, and system factors, including lack of insurance coverage/financial management, patient preference, long-term bond with the pediatric providers, and communication by the adult provider. Based on AXIS, all of the studies identified for this scoping review did not determine the sample size, and most of the studies did not categorize the responders, which could introduce bias to the interpretation of their results. CONCLUSION: This scoping review summarizes the readiness and experience of neurogenic bladder patients who underwent the urologic transitional process. Overall, understanding the patient, provider, and system factors associated with better readiness and enhancing the patient experience will ensure a better transition process.

The utilization of hyperbaric oxygenation therapy in hypospadias repair: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to evaluate the efficacy and safety of Hyperbaric Oxygen Therapy (HBOT) use in hypospadias repair through systematic review and meta-analysis of comparative studies. METHODS: A systematic literature search was performed in May 2021. Comparative studies assessing the surgical outcome of hypospadias repair between control versus HBOT utilization were identified and evaluated according to Cochrane collaboration recommendations. The assessed outcome includes hypospadias repair failures and graft failure for staged repair using a buccal graft. Relative risk with corresponding 95% confidence intervals (CI) were extrapolated. A random-effect model was used to generate pooled effect estimates. Heterogeneity and inter-study variability were assessed using Chi-square and I-square. Subgroup analysis was performed according to primary repair versus redo-hypospadias with buccal graft. PROSPERO registration (CRD42021251423). RESULTS: Five comparative studies with 576 cases (301 HBOT versus 275 controls) were included. Overall pooled effect estimates showed that the HBOT group has significantly lesser hypospadias repair failure (RR 0.52, 95%CI 0.37, 0.72). Subgroup analysis on the use of HBOT for graft take showed lesser graft failure compared to the control group (RR 0.20, 95% CI 0.05, 0.75), while the use of HBOT for primary and redo single staged hypospadias repair showed lesser complication rate (RR 0.56, 95%CI 0.40, 0.78). Based on ROBINS-I assessment, all included comparative studies are determined to be of serious risk of bias mainly due to presence of confounding. CONCLUSION: The currently available low-quality of evidence suggests that compared to control groups, HBOT as an adjunctive intervention to complicated hypospadias repair was able to reduce surgical outcome failure and graft failure rates.

Perinatal testicular torsion: The clear cut, the controversial, and the "quiet" scenarios.

BACKGROUND: Perinatal testicular torsion (PTT) is a catastrophic event that occurs in utero or up to 30 days postnatally, with testicular loss being the most common outcome. OBJECTIVE: To assess clinical evaluation, surgical management and clinical outcomes in patients with PTT in a quaternary referral pediatric center, to determine testicular salvageability and propose future management options. METHODS: We retrospectively reviewed a cohort of males born outside the quaternary center with a diagnosis of PTT, from May 2000 to July 2020. Data collection included mode of delivery, gestational age, birth weight, testicular examination at birth, clinical presentation, ultrasound results at diagnosis, surgical management and findings, perioperative complications, and follow-up. RESULTS: 62 patients, including 2 patients with bilateral asynchronous PTT, were identified. Median (IQR) gestational age and birth weight were 39 (38-39.4) weeks and 3.4 (3.1-3.72) kg, respectively. Abnormal testicular examination at birth was found in 69% (Table 1). Doppler ultrasound was performed in all but 1 patient. 59 patients underwent surgery, 21 within 4 h, with bilateral exploration in 44 cases. Affected and non-affected testicles were explored in 76% and 98% of cases, respectively. 3 "nubbins" were found, of which 2 were excised. 3 nonsurgical complications were identified. During a median (IQR) follow-up of 3 (3-3) months, 63 testicles were removed or found to be non-functional, with compensatory hypertrophy in 38% of patients. CONCLUSION: Given that 3% of our patients presented with asynchronous bilateral PTT, as well as the safety of general anesthesia in a referral pediatric hospital, early bilateral scrotal exploration of PTT is recommended. LEVEL OF EVIDENCE: IV.