Folic acid supplementation rescues bladder injury in fetal rats with myelomeningocele.

BACKGROUND: Bladder dysfunction has been linked to the progression of renal failure in children with neurogenic bladder (NB) dysfunction. The purpose of this study was to determine whether bladder injuries in fetal rats with myelomeningocele (MMC) may be treated with folic acid. METHODS: Pregnant Sprague-Dawley rats were randomly divided into three groups. On the 10th day of gestation, pregnant rats were intragastrically injected with all-trans retinoic acid (ATRA) (60 mg/kg) to induce MMC fetal rats. The same amount of olive oil was put into the control group to create normal fetal rats. The rats in the rescue group were given folic acid (40 mg/kg) by gavage 0.5 and 12 hr after ATRA therapy. Bladders were obtained via cesarean section on embryonic day E20.5 and examined for MMC. The histology of the fetuses was examined using hematoxylin and eosin staining, and immunohistochemistry (IHC) was utilized to determine the expression of α-smooth muscle actin (α-SMA) and neuron-specific nuclear-binding protein (NeuN). Furthermore, the levels of neuromuscular development-related and apoptotic proteins were determined by western blotting. RESULTS: The incidence of MMC in the model group was 60.6% (20/33) while it was much lower in the rescue group (21.4%). In comparison to the model group, the weight and crown-rump length of the fetal rats in the rescue group were significantly improved. IHC revealed that there was no significant difference in the expression of α-SMA and NeuN between the control and ATRA groups, while the expression levels decreased significantly in the MMC group. Western blot analysis showed that there was no significant difference between the model and ATRA groups, but the expression of the α-SMA protein and the ß3-tubulin was much lower in the MMC group than in the control group. After the administration of folic acid, the α-SMA and ß3-tubulin proteins considerably increased in the folic acid-rescued MMC group and folic acid-rescued ATRA group. Meanwhile, in the control group, the expression of cleaved caspase-3 in the bladder tissue was significantly higher, and the expression of poly (ADP-ribose) polymerase (PARP) protein was significantly lower compared to the control group. Folic acid therapy reduced cleaved caspase-3 expression while increasing PARP expression in comparison to the MMC group. CONCLUSIONS: NB in MMC fetal rats is associated with the reduction of bladder nerve and smooth muscle-related protein synthesis. However, folic acid therapy can help improve these functional deficiencies. Folic acid also exhibits strong anti-apoptotic properties against NB in MMC fetal rats.

Survival and Analysis of Prognostic Factors for Bladder Malignancies in Children and Adolescents: A Population-based Study.

OBJECTIVE: To explore the clinicopathological features and prognosis of pediatric patients with malignant bladder tumors in a population-based cohort. METHODS: The database Surveillance, Epidemiology, and End Results was used to evaluate all pediatric patients diagnosed with malignant bladder tumors between 1975 and 2018. The log-rank test was used to compare survival curves. Kaplan-Meier estimations were used to create survival curves based on various parameters. The Cox proportional hazards model was utilized to determine the factors that were independently related to mortality. RESULTS: A total of 263 children and adolescents with bladder malignancies were assessed. Papillary urothelial neoplasms of low malignant potential were the most frequent histologic subtype (35.1%), while embryonal rhabdomyosarcoma was more common during the first decade of life. Survival rates varied significantly by age at diagnosis, with older patients showing better outcomes. When compared to other subtypes, papillary urothelial neoplasms of low malignant potential had the highest overall survival rates (3- and 5-year were 99.2% and 98.3%, respectively). Multivariate analysis of the entire cohort showed that Surveillance, Epidemiology, and End Results stage and surgery were significant independent predictors of progression to disease-specific death in this model. CONCLUSION: Bladder malignancies are rare in children and adolescents. The prognosis for them varies. The localized stage was independently associated with superior survival and surgery could extend survival time.

Minimally Invasive versus Open Ureteral Reimplantation in Children: A Systematic Review and Meta-Analysis.

PURPOSE: We performed a systematic review and meta-analysis to compare the safety and efficacy of minimally invasive surgery (MIS) versus open ureteral reimplantation (OUR) in children. METHODS: Literature searches were conducted to identify studies that compared MIS (laparoscopic ureteral reimplantation or robot-assisted laparoscopic ureteral replantation) and OUR in children. Parameters such as operative time, blood loss, length of hospital stay, success rate, postoperative urinary tract infection (UTI), urinary retention, postoperative hematuria, wound infection, and overall postoperative complications were pooled and compared by meta-analysis. RESULTS: Among the 7,882 pediatric participants in the 14 studies, 852 received MIS, and 7,030 received OUR. When compared with the OUR, the MIS approach resulted in shorter hospital stays (I 2 = 99%, weighted mean difference [WMD] -2.82, 95% confidence interval [CI] -4.22 to -1.41; p < 0.001), less blood loss (I 2 = 100%, WMD -12.65, 95% CI -24.82 to -0.48; p = 0.04), and less wound infection (I 2 = 0%, odds ratio 0.23, 95% CI 0.06-0.78; p = 0.02). However, no significant difference was found in operative time and secondary outcomes such as postoperative UTI, urinary retention, postoperative hematuria, and overall postoperative complications. CONCLUSION: MIS is a safe, feasible, and effective surgical procedure in children when compared with OUR. Compared with OUR, MIS has a shorter hospital stay, less blood loss, and less wound infection. Furthermore, MIS is equivalent to OUR in terms of success rate and secondary outcomes such as postoperative UTI, urinary retention, postoperative hematuria, and overall postoperative complications. We conclude that MIS should be considered an acceptable option for pediatric ureteral reimplantation.

Spongioplasty with Buck's fascia covering dorsal inlay graft urethroplasty for primary hypospadias repair.

INTRODUCTION: Neourethral covering is an essential technique for preventing complications such as fistula and glans dehiscence in hypospadias repairs. The spongioplasty has been reported for neourethral coverage about 20 years ago. However, reports of the outcome are limited. OBJECTIVE: This study aimed to retrospectively evaluate the short-term outcome of spongioplasty with Buck's fascia covering dorsal inlay graft urethroplasty (DIGU). METHODS: From December 2019 to December 2020, 50 patients with primary hypospadias (median age at surgery, 37 months; range, 10 months-12 years) were treated by a single pediatric urologist. The patients underwent spongioplasty with Buck's fascia covering dorsal inlay graft urethroplasty in single stage. The penile length, glans width, urethral plate width and length, and the location of the meatus of the patients were recorded preoperatively. The patients were followed up,complications noted, and postoperative uroflowmetries at the one-year follow-up time were evaluated. RESULTS: The average width of glans was 12.92 ± 1.86 mm. A minor penile curvature was observed in all patients (≤30°). The patients were followed up for 12-24 months, and 47 patients (94%) were free from complications. A neourethra formed with a slit-like meatus at the tip of the glans, and the urinary stream was straight. Three patients had coronal fistulae (3/50) and no glans dehiscence, and the mean ± SD Qmax of postoperative uroflowmetry was 8.13 ± 3.8 ml/s. DISCUSSION: This study estimated the short-term outcome of the DIGU covered using spongioplasty with Buck's fascia as the second layer in patients diagnosed with primary hypospadias with a relatively small glans (average width <14 mm). However, only a few reports emphasize spongioplasty with Buck's fascia as the second layer and the DIGU procedure performed on a relatively small glans. The major limitations of this study were its short follow-up time and the retrospective data collection. CONCLUSIONS: Dorsal inlay graft urethroplasty combined with spongioplasty with Buck's fascia as coverage is an effective procedure. In our study, this combination had good short-term outcomes for primary hypospadias repair.

Glutathione metabolism rewiring protects renal tubule cells against cisplatin-induced apoptosis and ferroptosis.

Renal proximal tubular cells are highly vulnerable to different types of assaults during filtration and reabsorption, leading to acute renal dysfunction and eventual chronic kidney diseases (CKD). The chemotherapeutic drug cisplatin elicits cytotoxicity causing renal tubular cell death, but its executing mechanisms of action are versatile and elusive. Here, we show that cisplatin induces renal tubular cell apoptosis and ferroptosis by disrupting glutathione (GSH) metabolism. Upon cisplatin treatment, GSH metabolism is impaired leading to GSH depletion as well as the execution of mitochondria-mediated apoptosis and lipid oxidation-related ferroptosis through activating IL6/JAK/STAT3 signaling. Inhibition of JAK/STAT3 signaling reversed cell apoptosis and ferroptosis in response to cisplatin induction. Using a cisplatin-induced acute kidney injury (CAKI) mouse model, we found that inhibition of JAK/STAT3 significantly mitigates cisplatin nephrotoxicity with a reduced level of serum BUN and creatinine as well as proximal tubular distortion. In addition, the GSH booster baicalein also reclaims cisplatin-induced renal tubular cell apoptosis and ferroptosis as well as the in vivo nephrotoxicity. In conclusion, cisplatin disrupts glutathione metabolism, leading to renal tubular cell apoptosis and ferroptosis. Rewiring glutathione metabolism represents a promising strategy for combating cisplatin nephrotoxicity.

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

BACKGROUND: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

Intrauterine neuromuscular and stromal dysplasia of the bladder in retinoic acid-induced myelomeningocele fetal rats.

OBJECTIVES: To observe the changes in the bladder of fetal rats with myelomeningocele (MMC) induced by all-trans retinoic acid (atRA) during the embryonic development stages. METHODS: The fetal rat model of MMC was induced by intragastric administration of atRA to pregnant rats on embryonic day 10 (E10). Fetal rats were harvested at E16, E18, E20, and E21 for observation and further testing. Those with MMC were classified as the MMC group, while those without MMC as the RA group. The areas of MMC skin defect, the crown-rump length (CRL), and body weight in different groups were compared. The histopathological changes in the bladder were compared. The expression levels of alpha-smooth muscle actin (αSMA), smooth muscle myosin heavy chain (SMMHC), connexin 43 (Cx43), desmin, ß3 tubulin, and vesicular acetylcholine transporter (VAChT) in the bladder were investigated by immunohistochemical staining and Western blotting. Pregnant rats given intragastric administration with olive oil (OIL group) at E10 were set as the blank control group. RESULTS: A total of 415 fetal rats of different gestational ages were harvested with an MMC incidence of 56.05 % (139/248). The incidence rate increased with embryonic days (p < 0.001). Compared with the other two control groups, the CRL and bodyweight of MMC fetal rats were significantly delayed at E21 (p < 0.001). The expression levels of αSMA, SMMHC, Cx43, desmin, ß3 tubulin and VAChT in the bladder of MMC fetal rats were significantly decreased at E21 (p < 0.05). CONCLUSIONS: In atRA-induced MMC fetal rats, there is neural, muscular, and stromal dysplasia in the bladder at an early gestational age. Further investigations on neurogenic bladder secondary to MMC are applicable using this animal model.

The Mechanism of Bladder Injury in Fetal Rats With Myelomeningocele.

Background: Bladder dysfunction has been implicated as a major cause of progressive renal failure in children with neurogenic bladder. However, its pathogenesis remains unclear. This study aimed to compare the expression of proliferation, apoptosis, and neuromuscular-related proteins during the development of the bladder in myelomeningocele fetal rats, and to explore the characteristics of its abnormal development. Methods: For the myelomeningocele group, Sprague Dawley pregnant rats were intragastrically injected with retinoic acid on the 10th day of gestation to induce myelomeningocele fetal rats. For the control group, the same amount of olive oil was injected to induce normal fetal rats. Bladders were harvested at embryonic days E16, E18, E20, and E22. Real-time quantitative polymerase chain reaction and western blotting were used to detect the protein levels of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, neuron-specific nuclear-binding protein (NeuN), α-smooth muscle actin (α-SMA), and mRNA at E16-E22; immunohistochemistry was used to detect the expression of cleaved caspase-3 at E22. Results: The proliferation of bladder tissue cells was inhibited, with suppressed PCNA expression in myelomeningocele bladder tissue compared with that in control tissue at the early stage (E16). Myelomeningocele bladders showed increased tissue apoptosis in the late embryonic stage, with significantly higher cleaved caspase-3 protein expression than in the control bladders at E20 and E22. NeuN protein expression increased along with embryonic stage, although the expression at E20 and E22 was significantly lower in myelomeningocele bladders than in control bladders. α-SMA protein expression in myelomeningocele bladders increased gradually with the progression of pregnancy, although its expression was lower than that for control bladders at E22. Immunohistochemistry showed abundant positive staining for cleaved caspase-3 in the bladder mucosa and muscle layer of myelomeningocele bladders, and the expression of cleaved caspase-3 was significantly higher in myelomeningocele bladders than in control bladders. Conclusions: Bladder dysfunction in myelomeningocele fetal rats is related to the inhibition of proliferation, promotion of apoptosis, and reduction of bladder nerve and smooth muscle-related protein synthesis.

Tumor Suppressive Role of MUC6 in Wilms Tumor via Autophagy-Dependent ß-Catenin Degradation.

Wilms tumor is the most common renal malignancy in children. Known gene mutations account for about 40% of all wilms tumor cases, but the full map of genetic mutations in wilms tumor is far from clear. Whole genome sequencing and RNA sequencing were performed in 5 pairs of wilms tumor tissues and adjacent normal tissues to figure out important genetic mutations. Gene knock-down, CRISPR-induced mutations were used to investigate their potential effects in cell lines and in-vivo xenografted model. Mutations in seven novel genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) occurred in more than one patient. The most prevalent mutation was found in MUC6, which had 7 somatic exonic variants in 4 patients. In addition, TaqMan assay and immunoblot confirmed that MUC6 expression was reduced in WT tissues when compared with control tissues. Moreover, the results of MUC6 knock-down assay and CRISPR-induced MUC6 mutations showed that MUC6 inhibited tumor aggression via autophagy-dependent ß-catenin degradation while its mutations attenuated tumor-suppressive effects of MUC6. Seven novel mutated genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) were found in WT, among which MUC6 was the most prevalent one. MUC6 acted as a tumor suppressive gene through autophagy dependent ß-catenin pathway.

Value of sufficient clean intermittent catheterization in urinary tract infection and upper urinary tract protection in children with neurogenic bladder.

INTRODUCTION: Clean intermittent catheterization (CIC) is a mainstay in the management of neurogenic bladder. OBJECTIVE: To assess the effect of CIC on urinary tract infection and upper renal tract function in pediatric patients with neurogenic bladder, and the influence of duration of CIC on these variables. STUDY DESIGN: A retrospective study was performed in 67 pediatric patients with neurogenic bladder who started CIC between 2014 and 2019 at our institution. The febrile urinary tract infection (fUTI) rate, renal pelvis diameter (measured by antero-posterior renal pelvis diameter, APPD), bladder wall thickness (BWT) on ultrasound, and creatinine level at 6 months and 12 months of CIC were compared with baseline in all patients. The grade of vesicoureteral reflux (VUR) at 12 months of CIC were also compared with baseline. RESULTS: There were no significant differences compared with baseline after 6 months of CIC in the rate of fUTI, APPD, and BWT (p > 0.05); however, all of these parameters significantly improved after 12 months of CIC (p < 0.05). The VUR grade was significantly reduced after 12 months of CIC(p = 0.03). There was no significant change in serum creatinine level with any duration of CIC (both p > 0.05). DISCUSSION: Continuing CIC for more than 6 months had a beneficial influence on protecting the upper urinary tract. Complications of CIC, such as recurrent fUTI and lower urinary tract trauma, are more likely to occur in the early stage of CIC due to poor technique by the caregivers and poor patient compliance underscoring the importance of caregiver education. Study limitations include the retrospective nature and small sample size. CONCLUSION: CIC for less than 6 months may have limited influence on renal protection; however, a longer duration of CIC (12 months) resulted in significant improvement in outcomes. This study demonstrates the importance of proper caregiver education to establish standardized CIC techniques and to improve CIC quality.

Phenotypic spectrum and genetics of PAX2-related disorder in the Chinese cohort.

BACKGROUND: Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype. METHODS: We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants. RESULTS: Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p < 0.05). A system review of 234 reported cases to date indicated a clear association of RCS to heterozygous loss-of-function PAX2 variants (LGD variants). Furthermore, we identified a subset of PAX2 missense variants in DNA-binding domain predicted to affect the protein structure or protein-DNA interaction associated with the phenotype of RCS. CONCLUSION: Defining the phenotypic spectrum combined with genotype in PAX2-related disorder allows us to predict the pathogenic variants associated with renal and ophthalmological development. It highlighted the approach of structure-based analysis can be applied to diagnostic strategy aiding precise and timely diagnosis.

Responsible genes in children with primary vesicoureteral reflux: findings from the Chinese Children Genetic Kidney Disease Database.

BACKGROUND: Primary vesicoureteral reflux (VUR) is a common congenital anomaly of the kidney and urinary tract (CAKUT) in childhood. The present study identified the possible genetic contributions to primary VUR in children. METHODS: Patients with primary VUR were enrolled and analysed based on a national multi-center registration network (Chinese Children Genetic Kidney Disease Database, CCGKDD) that covered 23 different provinces/regions in China from 2014 to 2019. Genetic causes were sought using whole-exome sequencing (WES) or targeted-exome sequencing. RESULTS: A total of 379 unrelated patients (male: female 219:160) with primary VUR were recruited. Sixty-four (16.9%) children had extrarenal manifestations, and 165 (43.5%) patients showed the coexistence of other CAKUT phenotypes. Eighty-eight patient (23.2%) exhibited impaired renal function at their last visit, and 18 of them (20.5%) developed ESRD at the median age of 7.0 (IQR 0.9-11.4) years. A monogenic cause was identified in 28 patients (7.39%). These genes included PAX2 (n = 4), TNXB (n = 3), GATA3 (n = 3), SLIT2 (n = 3), ROBO2 (n = 2), TBX18 (n = 2), and the other 11 genes (one gene for each patient). There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications (14.1% vs. 6%, P = 0.035). The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT (9.6% vs. 5.6%, P = 0.139, Chi-square test) and the grade of reflux (9.4% vs. 6.7%, P = 0.429). Kaplan-Meier survival curve showed that the presence of genetic mutations did affect renal survival (Log-rank test, P = 0.01). PAX2 mutation carriers (HR 5.1, 95% CI 1.3-20.0; P = 0.02) and TNXB mutation carriers (HR 20.3, 95% CI 2.4-168.7; P = 0.01) were associated with increased risk of progression to ESRD. CONCLUSIONS: PAX2, TNXB, GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4% of monogenic VUR. Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR. Like other types of CAKUT, several genes may be responsible for isolated VUR.

Urethral plate in tubularized incised plate urethroplasty: how wide is enough?

BACKGROUND: Previous reports found that a preincision urethral plate (UP) width <8 mm increased the occurrence of urethroplasty complications (UCs) in tubularized incised plate (TIP) hypospadias repair. However, is the classification of the UP width based on an 8 mm cut-off value to predict the outcome of TIP urethroplasty objective enough or universally applicable? The purpose of our study was to assess the effect of the UP width on the outcomes of TIP hypospadias repair in the Eastern population we served. METHODS: We retrospectively reviewed the records of patients who underwent TIP hypospadias repair by the same surgeon between August 2013 and December 2019 in our hospital. Data were collected, including demographics, intrinsic parameters of the penis, surgical parameters and subsequent surgical outcomes. The data were analyzed and the cut-off value of the UP width was calculated using a receiving-operator curve. RESULTS: Primary TIP urethroplasty was carried out in 116 patients with a mean age of 35.89±29.40 months. The meatal location was distal in 49 patients, midshaft in 56 patients and proximal in 11 patients. The mean glans width was 12.28±1.36 mm, the mean UP width was 5.74±1.37 mm, the mean neourethral length was 1.96±1.32 cm, and the mean operation duration was 87.52±11.47 min. During a median follow-up of 42 (range: 6 to 80) months, UCs developed in 12 patients, and the UP width was significantly related to the occurrence of UCs (P=0.014). According to the 6 mm cut-off value of the UP width by the receiver operating characteristic curve, patients were divided into two groups. Group A (UP width ≥6 mm) included 69 patients, and Group B (UP width <6 mm), 47 patients. UCs occurred in 3 patients in Group A vs. 9 patients in Group B, P=0.010. CONCLUSIONS: UP width is a potential risk factor for UCs after TIP hypospadias repair. Using this technique with an UP width ≥6 mm is sufficient to result in a good outcome of hypospadias repair.

Cryptorchid testicular torsion in children: characteristics and treatment outcomes.

This study aimed to review and compare the characteristics and treatment outcomes of cryptorchid testicular torsion in pre- and postpubertal children. We reviewed the clinical data of 22 patients with testicular torsion complicated by cryptorchidism who were treated between January 2010 and December 2019. Patients were categorized into prepubertal (1 month to 9 years; n = 12) and postpubertal groups (10-16 years; n = 10). The age at presentation, clinical presentations, physical examination, and operation outcomes were assessed. The common clinical presentations in both groups were inguinal pain and a tender inguinal mass. Patients in the prepubertal group were significantly more likely to present with restlessness (33.3%) than those in the postpubertal group (0%; P = 0.044). After detorsion, testicular blood flow recovered during surgery in 25.0% of the prepubertal and 80.0% of the postpubertal patients (P = 0.010). Orchiectomy was required in 50.0% of the prepubertal and 20.0% of the postpubertal patients (P = 0.145). Of the 22 patients with follow-up data, the rates of testicular salvage were significantly different, at 16.7% in the prepubertal patients and 60.0% in the postpubertal patients (P = 0.035). Cryptorchid testicular torsion has various manifestations. Although an empty hemiscrotum and a painful groin mass were common in both groups, restlessness was more prevalent in the prepubertal patients during early testicular torsion onset than that in the postpubertal patients. Notably, the testicular salvage rate was significantly lower in the prepubertal patients than that in the postpubertal patients.

Pediatric Trauma-Induced Testicular Torsion: A Surgical Emergency.

OBJECTIVE: To evaluate the features of testicular torsion (TT) resulting from minor groin trauma and to raise the awareness of trauma-induced testicular torsion (TITT). METHODS: This is a retrospective chart review of patients presenting with TT resulting from minor genital trauma that was performed from January 2010 to December 2018 at a single tertiary care institution. The demographic, clinical, and perioperative characteristics, as well as data on follow-up and complications, were analyzed. RESULTS: Of the 155 patients treated for TT, 15 were included in this study. The average age of the patients was 10.3 years (range: 3.2-13.3 years). All patients experienced a direct scrotal trauma and subsequently presented with an ipsilateral scrotal or testicular pain secondary to the twisted testicle. Six patients were misdiagnosed as having scrotal inflammation or hematoma, and all were initially treated at local hospitals. The mean duration of symptoms before hospitalization was 138 h (range: 5-504 h). The mean degree of torsion was 390° (range: 180-720°). The testicular salvation rate, at 33%, was poor. No serious postoperative complications or recurrences of TT was observed. CONCLUSIONS: TITT is a rare entity and still has delayed diagnosis. This may subsequently lead to a low testicular salvation rate. Emergency surgeons, especially in local hospitals, should be aware of the possibility of TT following testicular trauma in pediatric patients. Improving the parents' awareness regarding TT is also important.

Exploration of postnatal integrated management for prenatal renal and urinary tract anomalies in China.

Objective: The aim of this prospective observational study was to establish a suitable model for the postnatal follow-up and management of prenatal renal and urinary tract anomalies in Shanghai, China.Methods: Minhang and Changning maternal child health care hospitals were selected to establish the integrated management model. Newborns with prenatal renal and urinary tract anomalies in these two centers were eligible to participate in the study from 2015 to 2017. All newborns were classified into three groups based on prenatal findings: (1) severe/complex urinary tract dilatation (UTD) with ureterectasia, (2) other renal and urinary tract abnormalities, and (3) isolated mild to moderate UTD. The newborns underwent their first postnatal ultrasound and follow-up according to the presumed management strategy. Demographic and clinical data were collected from all institutes.Results: A total of 129 newborns fulfilled the study criteria, and 121 completed the postnatal evaluation. Ten newborns in group 1 (n = 13) were diagnosed with obstructive uropathy, including 9 with ureteropelvic junction obstruction (UPJO) and one with megaureter. All 13 newborns in group 2 had consistent postnatal results and were followed under previously established procedures. Sixty-seven cases in group 3 (n = 95) had a UTD at their first scan at 42 postnatal days, and two were diagnosed with UPJO. A total of 2 infants with UPJO underwent surgery, and 71 (65.7%, 71/108) of the UTD cases were resolved.Conclusions: The majority of the patients had a favorable outcome. Close multidisciplinary collaboration among obstetricians, neonatologists, pediatricians, and pediatric nephrologists and urologists is mandatory.

Posterior Urethral Valves with Lower Urinary Tract Symptoms: Perspective on Urodynamics.

BACKGROUND: Lower urinary tract symptoms (LUTs) are common in young boys with posterior urethral valves (PUVs). It is crucial to investigate the characteristics of PUV patients with and without LUTs after valve ablation. METHODS: Between January 2017 and December 2019, PUV patients visited Children's Hospital, Fudan University for following up were enrolled. Medical records and information from the patients' urodynamic studies (UDS) were reviewed. RESULTS: A total of 54 enrolled PUV patients were divided into symptomatic PUV group (28 cases) and non-symptomatic PUV group (26 cases) according to daytime incontinence or not, and 21 OAB cases without structural abnormalities were set as UDS control group. The non-symptomatic PUV patients had lager filling volume (135 ± 46% of EBC) than the symptomatic PUV patients and OAB patients (106.1 ± 44.4% of EBC, p = 0.0255 and 88.1 ± 39.6% of EBC, p = 0.0007, respectively). The detrusor pressure at 1/4 and 3/4 of full filling was higher in PUV groups than the control group, but no significant difference was found between the PUV groups. PUV patients with LUTs had a higher rate (19/28, 67.9%) of impaired bladder compliance than non-symptomatic PUV patients (11/26, 42.3%, p = 0.0489). The PUV patients with LUTs had a trend of worse kidney functions in lower GFR, higher serum creatinine and lower estimated GFR. CONCLUSION: PUV patients have higher detrusor pressure regardless of the presence or absence of LUT symptoms. Bladder function assessments are needed in boys with PUV, even without incontinence symptoms after valve ablation.

Application and efficacy of reconstructing forked corpus spongiosum in distal/midshaft hypospadias repair.

We reviewed our experience in reconstructing forked corpus spongiosum (FCS) in distal/midshaft hypospadias repair and analyzed the efficacy of this surgical technique. From August 2013 to December 2018, 137 consecutive cases of distal/midshaft hypospadias operated by the same surgeon in Urology Department, Children's Hospital of Fudan University (Shanghai, China), were retrospectively analyzed. Sixty-four patients who underwent routine tubularized incised plate (TIP) or onlay island flap (ONLAY) surgery were included in the nonreconstructing group, and 73 patients who underwent reconstructing FCS during TIP or ONLAY surgery were included as the reconstructing group. Thirty-eight cases underwent TIP, and 26 underwent ONLAY in the nonreconstructing group, with a median follow-up of 44 (range: 30-70) months. Twenty-seven cases underwent TIP, and 46 underwent ONLAY in the reconstructing group, with a median follow-up of 15 (range: 6-27) months. In the nonreconstructing/reconstructing groups, the mean age at the time of surgery was 37.55 (standard deviation [s.d.]: 29.65)/35.23 (s.d.: 31.27) months, the mean operation duration was 91.95 (s.d.: 12.17)/93.84 (s.d.: 14.91) min, the mean neourethral length was 1.88 (s.d.: 0.53)/1.94 (s.d.: 0.53) cm, and the mean glans width was 11.83 (s.d.: 1.32)/11.56 (s.d.: 1.83) mm. Twelve (18.8%)/5 (6.8%) postoperative complications occurred in the nonreconstructing/reconstructing groups. These included fistula (5/2), glans dehiscence (3/0), diverticulum (1/2), residual chordee (3/0), and meatus stenosis (0/1) in each group. There was a significant difference in the overall rate of complications (P= 0.035). These results indicate that the technique of reconstructing FCS provides excellent outcomes with fewer complications in distal/midshaft hypospadias repair.

Genetic Architecture of Childhood Kidney and Urological Diseases in China.

Kidney disease is manifested in a wide variety of phenotypes, many of which have an important hereditary component. To delineate the genotypic and phenotypic spectrum of pediatric nephropathy, a multicenter registration system is being implemented based on the Chinese Children Genetic Kidney Disease Database (CCGKDD). In this study, all the patients with kidney and urological diseases were recruited from 2014 to 2020. Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features. The genetic diagnosis was confirmed in 883 of 2256 (39.1%) patients from 23 provinces in China. Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome (SRNS, 23.5%), glomerulonephritis (GN, 32.2%), congenital anomalies of the kidney and urinary tract (CAKUT, 21.2%), cystic renal disease (3.9%), renal calcinosis/stone (3.6%), tubulopathy (9.7%), and chronic kidney disease of unknown etiology (CKDu, 5.8%). The pathogenic variants of 105 monogenetic disorders were identified. Ten distinct genomic disorders were identified as pathogenic copy number variants (CNVs) in 11 patients. The diagnostic yield differed by subgroups, and was highest in those with cystic renal disease (66.3%), followed by tubulopathy (58.4%), GN (57.7%), CKDu (43.5%), SRNS (29.2%), renal calcinosis /stone (29.3%) and CAKUT (8.6%). Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions. We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed. Our data demonstrate the utility of family-based exome sequencing, and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-021-00014-1.