Pediatric testicular torsion management practices: A survey of Canadian urologists.

INTRODUCTION: Pediatric testicular torsion (TT) is a urologic emergency that may result in testicular loss if left untreated. Testicular salvage is dependent on prompt intervention, and thus delays in diagnosis and management may threaten testicular viability. Knowledge of real-world Canadian practice patterns for pediatric TT will allow optimization of practices based on resource availability and geographic limitations to improve care. METHODS: An electronic survey on pediatric TT management was distributed to Canadian urologists. Descriptive statistics were performed on respondent demographic factors, hospital policies and barriers to care, surgical approaches, and transfer practices. Respondent practice patterns were analyzed based on geographic location and training. RESULTS: Thirty-four urologists responded, with the majority of respondents operating a community practice. Ultrasonography (US) was frequently used to support TT diagnosis. Despite this, poor US access was often cited as a barrier to care, with particular impact on rural urologists. Neonatal patients and <10 years old were commonly transferred to a pediatric hospital for definitive management due to surgeon discomfort and hospital policies. Reported transport methods commonly included use of the patient's own vehicle or ambulance based on availability and timing. CONCLUSIONS: Neonatal patients and patients under 10 years old are most commonly reported to be transferred to pediatric hospitals for TT management. Patients located in rural locations and at centers with limited US access may be at risk for delayed diagnosis and treatment. Pathways for prompt management of suspected TT may better serve these younger pediatric patients.

Shared decision-making for pediatric elective penile surgery.

INTRODUCTION: In pediatric surgery, proxy decision-makers are frequently involved in treatment planning and may experience decisional conflict (DC). Shared decision-making (SDM) approaches may be effective to remedy DC. This study investigates DC and SDM involvement in elective pediatric penile surgery. METHODS: Forty-four parents of children aged <8 years undergoing elective penile surgery consultations at a tertiary pediatric hospital were prospectively enrolled. Patient and physician questionnaires were used to assess the SDM process and the SURE (Sure of myself; Understand information; Risk-benefit ratio; Encouragement) screening test was used to assess DC. RESULTS: Thirty-seven (84.1%) mothers and seven (15.9%) fathers were enrolled for circumcision (n=33, 75.0%) and distal hypospadias repair (n=11, 25.0%) consultations, with 21 (47.7%) choosing to proceed with surgery. Seven (15.9%) participants experienced clinically significant DC. Participant gender was not associated with higher levels of DC (p=0.318). The average patient and physician SDM scores were 88.2±10.0 and 85.3±7.4, respectively, with no correlation found between participant and physician perception of SDM involvement (p=0.168, p=0.276). DC was significantly associated with lower participant and physician ratings of SDM. CONCLUSIONS: There was a high perception of SDM involvement by both parents and pediatric urologists regarding elective penile surgery. Of the 15% of parents experiencing DC, there was an association with lower participant and physician levels of SDM involvement. Despite high SDM scores overall, discrepancies exist between the perceived physician and participant SDM involvement.

Concurrent Multicystic Dysplastic Kidney, Posterior Urethral Valves, and Obstructive Ureterocele in a Male Pediatric Patient: A Case Report.

Congenital anomalies of the kidney and urinary tract (CAKUT) are diagnosed in approximately 3-6 per 1000 live births and represent a spectrum of urologic conditions impacting the kidneys, ureter, bladder, and urethra.1 Although both are considered under the classification of CAKUT, there is no known unifying pathophysiologic mechanism for ureteroceles and posterior urethral valves with only 1 case report noted in the literature. Herein we report the only documented case of a patient with CAKUT related to posterior urethral valves, ureterocele, and multicystic dysplastic kidney.

A survey of management preferences for bladder exstrophy and cloacal anomalies among Canadian pediatric surgeons and urologists.

PURPOSE: This study examined the current referral patterns and preferences of Canadian Association of Paediatric Surgeons (CAPS) and Pediatric Urologists of Canada (PUC) members for management of bladder exstrophy and cloacal anomalies (BECA). METHODS: We invited CAPS and PUC members to participate in an online survey using RedCap. Demographic variables, years in practice, current referral patterns and local expertise at the participants' institution were collected. Participants' preferences towards three distinct referral models were assessed using Likert scales: no centralization of care, centralization in one or two national centres of excellence, or a consortium-based approach. RESULTS: There were 82 survey respondents (2/3 were CAPS members, 35.4% female, 72% in practice for >10 years). Although >90% of participants agreed/somewhat agreed that surgical volumes impact outcomes, 58% reported not referring out BECA patients for treatment; about 50% recognized the existence of a local dedicated expert. In terms of referral preferences, 84% of participants favoured identification of a few centres with expertise based on geographic location (a consortium-based approach), while only 7% chose a one or two national centres of excellence model. Over half of participants agreed/somewhat agreed with participating in trials of a consortium-based approach in Canada. CONCLUSION: Most CAPS and PUC members do not refer BECA patients elsewhere for treatment. Nonetheless, most surgeons recognize the importance of volume to improve outcomes and show willingness to participate in trials to concentrate experience; most participants favour a consortium-based approach through identification of a few centres of excellence based on geographic location.

Psychosocial Distress in Parents with Children Awaiting Surgery during the COVID-19 Pandemic.

Due to resource restrictions related to the COVID-19 pandemic, many pediatric patients are facing substantial delays for surgery, potentially resulting in additional distress for caregivers. We aimed to assess the experiences and psychosocial distress of parents during COVID-19 as they relate to the pandemic, waiting for surgery, and the combined effects of both events. The was a cross-sectional qualitative study. Parents with children who faced treatment delays during the initial wave of the COVID-19 pandemic for elective, non-emergent procedures across a variety of surgical specialties were recruited. Semi-structured telephone interviews and thematic analysis were utilized. Thematic saturation was reached with eighteen participants. Four themes were identified: coping with COVID-19, distress levels, quality and nature of communication with the surgical team, and the experience of COVID-19 related hospital restrictions. Participants reported varying levels of distress due to the delay in surgery, such as the fear of developmental delay or disease progression for their child. They also indicated their own physical and mental health had been impacted by emotional distress related to both COVID-19 and delays in treatment. Most participants experienced the COVID-19-related hospital restrictions as distressing. This related predominantly to limiting in-hospital caregivers to only one caregiver. Participants were found to have substantial levels of psychosocial distress. Targeted social and emotional support may be helpful in reducing parental distress as the pandemic timeframe continues. Within the limits of individual health systems, reducing restrictions to the number of allowed care givers may help allay distress felt by parents.

Association of vesicoureteral reflux and gastroesophageal reflux disease in children: A population-based study.

INTRODUCTION: Practitioners have anecdotally hinted at a possible association between gastroesophageal reflux disease (GERD) and vesicoureteral reflux (VUR). We sought to identify an association in diagnosis between GERD and VUR using a population-based dataset in a well-defined geographic area covered by a single-payer healthcare system. METHODS: A retrospective review of individuals aged 0-16 years registered in the Nova Scotia Medical Service Insurance database from January 1997 to December 2012 was completed. Presence of GERD and VUR were ascertained based on billing codes. The baseline prevalence of GERD and VUR was calculated for this population for the same time period. Proportions of VUR patients with and without GERD were compared. The risk of being diagnosed with VUR in patients with GERD controlling for sex was calculated. RESULTS: Of 404 300 patients identified, 6.6% had a diagnosis of GERD (n=27 092), 0.33% had a diagnosis of VUR (n=1348), and 0.08% were diagnosed with both (n=327). Among patients with VUR, the prevalence of GERD was 24.3% compared to 6.6% in patients without VUR (p<0.0001). Among patients with GERD, the prevalence of VUR was 1.2% compared to 0.27% in patients without (p<0.0001). The risk of being diagnosed with VUR was higher in the presence of GERD (odds ratio [OR] 4.49; 95% confidence interval [CI] 3.96-5.09; p<0.0001), irrespective of sex. CONCLUSIONS: The odds of being diagnosed with VUR is more than 4.5 times higher in an individual with GERD. The clinical significance of this association remains to be explored.

Urological Follow-up in Adult Spina Bifida Patients: Is There an Ideal Interval?

OBJECTIVE: To establish the time to development of urological issues over time in adult spina bifida (SB) patients. MATERIALS AND METHODS: This is a retrospective study of adult patients attending a multidisciplinary adult SB clinic from 2000 to 2013. Patient age, sex, number of clinic visits, and length of follow-up were recorded. For each unique visit, presence of symptoms, type of urological issue (if any), and time lapsed since last appointment were obtained. The interval between the development of urological issues was assessed using a time-to-event analysis. RESULTS: One hundred twenty-three patients (46% male, 54% female, median age 26.8years) were followed for a median of 48 months, contributing to 586 unique clinic visits. Urological issues were identified in 109 patients (88.5%) during 267 visits (46%), and of those 21% were asymptomatic. In symptomatic patients, the median time to present with a urological issue was 12 months. Among the asymptomatic cases, 12%, 23%, and 34% had developed a urological issue at 12, 24, and 36 months of follow-up, respectively. Eighty-one percent of the urological issues seen in the clinic required some form of treatment or intervention. The treatment or intervention in 56% of asymptomatic urological issues was surgery. CONCLUSION: Most adult SB patients with urological issues are symptomatic by 2 years of follow-up; however, over time the proportion of asymptomatic patients with urological issues rises steadily, reaching a worrisome 34% at 3 years. Closer follow-up seems warranted.

A two-stage spin cartridge for integrated protein precipitation, digestion and SDS removal in a comparative bottom-up proteomics workflow.

Protein precipitation with organic solvent is an effective means of depleting contaminants such as sodium dodecyl sulfate (SDS), while maintaining high analyte recovery. Here, we report the use of a disposable two-stage spin cartridge to facilitate isolation of the precipitated protein, with subsequent enzyme digestion and peptide cleanup in the cartridge. An upper filtration cartridge retains over 95% of the protein (10 µg BSA), with 99.75% detergent depleted from a sample initially containing 2% SDS. Following precipitation, a plug attached to the base of the filtration cartridge retains the solution to enable tryptic digestion in the vial, while a solid phase extraction cartridge attached to the base of the filter facilitates peptide cleanup post-digestion. A GELFrEE fractionated Escherichia coli proteome extract processed with the spin cartridge yields similar protein identifications compared to controls (226 vs 216 for control), and with an increased number of unique peptides (1753 vs 1554 for control). The device is applied to proteome characterization of rat kidneys experiencing a surgically induced ureteral tract obstruction, revealing several statistically altered proteins, consistent with the morphology and expected pathophysiology of the disease. BIOLOGICAL SIGNIFICANCE: Conventionally, protein precipitation involves extended centrifugation to pellet the sample, with careful pipetting to remove the supernatant without disturbing the pellet. The method is not only time consuming but is highly subject to the skill of the individual, particularly at lower protein concentrations where the pellet may not be visible. As such, protein precipitation is often overlooked in proteomics, favoring column-based approaches to concentrate or purify samples. Here, all aspects of sample manipulation are integrated into a simple disposable cartridge. The device enables SDS depletion, sample preconcentration, resolubilization, derivatization, digestion, and peptide cleanup in a highly repeatable and easily multiplexed format. The device is ideally suited for comparative proteome studies. Antenatal hydronephrosis is a congenital disorder affecting 1-5% of all pregnancies, and can require surgical intervention to avoid loss of renal function. Using our device, we investigated the impact of hydronephrosis on the kidneys in a surgically induced animal model of the disease. Proteome analysis points to decreased metabolic activity in the obstructed kidney, with upregulation of proteins involved in cytoskeletal organization. This article is part of a Special Issue entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault and Anne-Claude Gingras.

Proteomic analysis of rat proximal tubule cells following stretch-induced apoptosis in an in vitro model of kidney obstruction.

Urinary tract obstruction (UTO) is a commonly noted disorder on prenatal ultrasound that has the potential to lead to permanent loss of renal function. To study the molecular processes of the disease, an in vitro model has been developed which involves mechanical stretch of proximal tubule cells grown on flexible plates which mimics the physiological conditions during UTO. This study employs a one dimensional SDS-PAGE fractionation procedure, followed by in-gel digest and LC-MS/MS analysis in a semi-quantitative experiment using spectral counting to relatively quantify changes in protein expression following the established model of UTO. Quantitative analysis shows 317 of the 1630 identified proteins express altered abundance, with 135 increased and 182 decreased in abundance as a result of stretch. Gene ontology (GO) and KEGG annotations implicate a number of physiological processes that have been previously shown in addition to some potentially novel processes in UTO. The quantitative proteomic analysis we performed here provides a more complete characterization of changes in protein abundance as a result of stretch than previous studies, and provides a number of previously undescribed proteins in proximal tubule cells that may play a role in UTO. BIOLOGICAL SIGNIFICANCE: Urinary tract obstruction (UTO) is a commonly noted abnormality on prenatal ultrasound that can either resolve spontaneously or require surgical intervention to prevent permanent renal damage or loss of function. While targeted studies of UTO have shown a number of pathological responses in proximal tubule cells, there are currently no large-scale quantitative studies that aim to elucidate a global cellular response. This study uses a semi-quantitative approach and applies a well characterized model of UTO to determine a number of cellular processes affected by UTO simulation and identifies a number of proteins with altered abundance that have not been noted previously in UTO. This article is part of a Special Issue entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes?

Transition of care to an adult spina bifida clinic: patient perspectives and medical outcomes.

PURPOSE: Transitioning care of patients with spina bifida to adult centers poses a challenge. We sought patient and parent perspectives on the transition process at our center and correlated these perspectives with medical outcomes. MATERIALS AND METHODS: Patients who attended the adult spina bifida clinic at our institution were invited to complete SF-36®, the Ambulatory Care Experience Survey and a Transition of Care Survey. Urological and neurosurgical medical outcomes were correlated with health status, clinic experience and perspectives on the transition process. Statistical analysis was done using SPSS®, version 16.0. RESULTS: Of 105 patients with spina bifida 24 participated in the study. SF-36 results showed that the physical health domain correlated with lack of employment (p = 0.006). Patients whose parents completed the surveys on their behalf were more likely to have physical limitations than the patients who completed surveys (p = 0.011). Urological and neurosurgical outcomes did not significantly affect SF-36, Ambulatory Care Experience Survey or Transition of Care Survey scores in this patient population. Patients and caregivers identified similar key elements and barriers in the transition process. Satisfaction with care at the pediatric center was higher than at the adult center. CONCLUSIONS: Transitioning care of patients with spina bifida from pediatric to adult care poses challenges for the health care system. Medical outcomes do not impact the patient perspective of the transition process. To optimize the transition of care we must address the barriers identified by patients and their caregivers.

Alterations in urinary metabolites due to unilateral ureteral obstruction in a rodent model.

Urinary tract obstruction (UTO) results in renal compensatory mechanisms and may progress to irrecoverable functional loss and histologic alterations. The pathophysiology of this progression is poorly understood. We identified urinary metabolite alterations in a rodent model of partial and complete UTO using (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy. Principal component analysis (PCA) was used for classification and discovery of differentiating metabolites. UTO was associated with elevated urinary levels of alanine, succinate, dimethylglycine (DMG), creatinine, taurine, choline-like compounds, hippurate, and lactate. Decreased urinary levels of 2-oxoglutarate and citrate were noted. The patterns of alteration in partial and complete UTO were similar except that an absence of elevated urinary osmolytes (DMG and hippurate) was noted in complete UTO. This pattern of metabolite alteration indicates impaired oxidative metabolism of the mitochondria in renal proximal tubules and production of renal protective osmolytes by the medulla. Decreased production of osmolytes in complete obstruction better elucidates the pathophysiology of progression from renal compensatory mechanisms to irrecoverable changes. Further confirmation of these potential biomarkers in children with UTO is necessary.

Management of pediatric neurogenic bladder.

PURPOSE OF REVIEW: To review the most current literature regarding the management of neurogenic bladder in children. RECENT FINDINGS: Several recent papers have addressed the investigation and management of children with neurogenic bladder. Bladder wall thickness as measured by ultrasound may identify the children with urodynamic risk factors for upper urinary tract deterioration. Strategies such as maximal anticholinergic therapy, total endoscopic management, conservative management throughout puberty, and isolated bladder neck procedures to avoid bladder augmentation show promise. However, at present, there is inadequate long-term follow-up to recommend widespread application of all of these approaches. As children with neurogenic bladder enjoy longer life spans, issues including risks of malignancy related to augmentation and transition to adult-centered care will continue to gain significance. SUMMARY: Pediatric urologists continue to face many challenges in the management of children with neurogenic bladder. This includes identifying predictors of upper urinary tract deterioration, finding efficacious strategies to avoid bladder augmentation, and long-term care. The most recent literature attempts to address these issues. Further prospective studies with adequate follow-up will benefit our understanding of this disease process and help to choose the best strategies to achieve continence and preserve renal function in this population.

Maternal and fetal risk factors associated with severity of hypospadias: a comparison of mild and severe cases.

OBJECTIVE: To determine maternal and fetal demographic factors which predict the risk of increasing severity of hypospadias. PATIENTS AND METHODS: A population-based study using the Nova Scotia Atlee Perinatal Database was performed. Demographic variables of mothers and boys with hypospadias were obtained from 1980 to 2007 inclusive. Hypospadias was graded by the position of the urinary meatus as glanular, coronal, shaft, or proximal to shaft. Maternal and fetal risk factors for hypospadias severity were compared using logistic regression. RESULTS: The total number of male pregnancy and birth records during the study period was 130,796. The total number of cases of hypospadias was 995, yielding an incidence of 0.76%. The severity of hypospadias was graded as glanular in 428 (77.8%); coronal in 77 (14%); penile shaft in 34 (6.2%); and proximal to the penile shaft in 12 (2.2%). The severity of hypospadias was not graded in 445 cases. Low birth weight, low gestational age and maternal age were associated with increased severity of hypospadias, but only maternal age (P<0.03) when logistic regression was performed. Limitations included self-reporting for some parameters, such as smoking, and lack of data, such as for the use of assisted reproductive technologies. CONCLUSIONS: Advanced maternal age was associated with increased severity of hypospadias in our population.

A qualitative proteome investigation of the sediment portion of human urine: Implications in the biomarker discovery process.

Inherent to the biomarker discovery process is a comparative analysis of physiological states. It is therefore critical that the proteome detection protocol does not bias the analysis. With urine, the sediment portion, obtained upon thawing frozen urine, is routinely discarded prior to proteome analysis. However, our results demonstrate that such a practice inadvertently induces bias, having significant implications in the biomarker discovery process. We present the first proteome investigation of human urinary sediments, identifying 60 proteins in this phase by MS. Many sediment proteins were also detected in the urinary supernatant, indicating that several proteins partition between the two phases. This partitioning is dependant on the pH of the sample, as well as the degree of sample agitation. As a consequence of discarding the sediment portion of urine, the concentration of potential candidate biomarkers in the supernatant phase will be altered or, in other instances, may be completely removed from the sample. To minimize this, the pH of all samples should first be normalized, and the samples vigorously vortexed prior to discarding the sediments. For more comprehensive biomarker investigations, we suggest that urinary sediments be analyzed along with the supernatant proteins.

Recent advances in external genitalia.

In the last decade, significant progress in the knowledge and management of external genital anomalies has been achieved, including an improved understanding of epidemiology and pathophysiology of these anomalies, the identification of etiologic genetic defects, and significant improvements in surgical approaches that have decreased complications and improved cosmetic outcomes. We highlight the most clinically important advances of the commonly encountered external genital anomalies.

A quantitative proteomic analysis of growth factor-induced compositional changes in lipid rafts of human smooth muscle cells.

Signals that promote proliferation and migration of smooth muscle cells (SMC) have been implicated in pathologic growth of hollow organs. Members of the platelet-derived growth factor (PDGF) family, potent mitogens and motility factors for SMC, have been shown to signal through cholesterol-enriched lipid rafts. We recently demonstrated that PDGF-stimulated DNA synthesis in urinary tract SMC was dependent on the integrity of lipid rafts. Despite its known ability to rapidly alter discrete proteins within rafts, the effect of PDGF on overall raft protein composition is unknown. In this study, we employed isotope coded affinity tag (ICAT) analysis to evaluate PDGF-induced protein changes in lipid rafts of primary culture human SMC. Following acute (i.e., 15 min) exposure of SMC to PDGF, 23 proteins increased in rafts >20%. In contrast, raft localization of only three proteins increased after 12 h of PDGF treatment. Among the proteins that increased at 15 min were the glycophosphatidylinositol-anchored proteins Thy-1, 5'-nucleotidase, and CD55, the cytoskeletal proteins actin, actinin, tropomyosin-3 and -4, and the endocytosis-related proteins clathrin and beta-adaptin. In addition, eight Rho family members were localized to rafts by ICAT analysis. Collectively, these observations suggest a role for lipid rafts in regulation of PDGF-stimulated changes in the cytoskeleton.