Genome-wide analysis identifies MYH11 compound heterozygous variants leading to visceral myopathy corresponding to late-onset form of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Megacystis-microcolon-hypoperistalsis-syndrome (MMIHS) is a rare and early-onset congenital disease characterized by massive abdominal distension due to a large non-obstructive bladder, a microcolon and decreased or absent intestinal peristalsis. While in most cases inheritance is autosomal dominant and associated with heterozygous variant in ACTG2 gene, an autosomal recessive transmission has also been described including pathogenic bialellic loss-of-function variants in MYH11. We report here a novel family with visceral myopathy related to MYH11 gene, confirmed by whole genome sequencing (WGS). WGS was performed in two siblings with unusual presentation of MMIHS and their two healthy parents. The 38 years-old brother had severe bladder dysfunction and intestinal obstruction, whereas the 30 years-old sister suffered from end-stage kidney disease with neurogenic bladder and recurrent sigmoid volvulus. WGS was completed by retrospective digestive pathological analyses. Compound heterozygous variants of MYH11 gene were identified, associating a deletion of 1.2 Mb encompassing MYH11 inherited from the father and an in-frame variant c.2578_2580del, p.Glu860del inherited from the mother. Pathology analyses of the colon and the rectum revealed structural changes which significance of which is discussed. Cardiac and vascular assessment of the mother was normal. This is the second report of a visceral myopathy corresponding to late-onset form of MMIHS related to compound heterozygosity in MYH11; with complete gene deletion and a hypomorphic allele in trans. The hypomorphic allele harbored by the mother raised the question of the risk of aortic disease in adults. This case shows the interest of WGS in deciphering complex phenotypes, allowing adapted diagnosis and genetic counselling.

Isolated Hydronephrosis and Urinary Tract Infection by Two Years of Age: A Population-Based Study.

OBJECTIVE: To evaluate the risk for urinary tract infection (UTI) in infants with isolated hydronephrosis (IH). STUDY DESIGN: A retrospective, population-based study including all infants insured by Clalit Health Services and followed from birth to age 2 years in 3 regions of central Israel. Infants were divided into 3 groups based on electronic medical record diagnoses by age 6 months: (1) control: no urological diagnosis; (2) IH; and (3) complicated urological diagnosis (CUD): any additional nephrological/urological diagnosis with/without HN. The primary outcome was a diagnosis of UTI in the first 2 years of life. RESULTS: The cohort included 340 619 infants (52% male): 333 920 controls, 4369 with IH, and 2331 with CUD. Infants with IH were associated with a greater risk for UTI than control patients (17% vs 4%, P < .001). UTI risk for a male infant with IH was greater than for a female infant in the control group (12.6% vs 6.5%, P < .001). In a multivariable logistic regression analysis, both IH (OR 7.04; 95% CI 6.46-7.66) and CUD (OR 14.9; 95% CI 13.6-16.4) were independently associated with UTI. CONCLUSION: Infants with IH are at a greater risk for UTI in the first 2 years of life, supporting the recommendation for a high index of suspicion for UTI in this population.

Novel anti-reflux ureteral skirt: proof of concept in a Yorkshire-Landrace pig model.

INTRODUCTION: Stents with anti-reflux properties have been previously described in various studies but not widely adopted. We designed, constructed and tested a novel umbrella-looking anti-reflux skirt on a double J stent at the level of the ureteral orifice in a previous ex-vivo study. This study serves as a proof of concept of testing this prototype in a porcine model. METHODS: 3 Yorkshire-Landrace pigs were put under general anaesthesia. Conventional bilateral retrograde stenting with white-colored double-J stents were performed. Deployment of anti-reflux skirt was performed unilaterally. Capsaicin mixed with methylene blue and saline were instilled in the bladder. Both stents were removed and methylene blue stain were inspected to assess the level of reflux. Bilateral stenting was performed again and stents/skirt prototype were left in-situ for 1 week. The procedure was repeated on Day 7 to re-test the anti-reflux property of the prototype after ureteral dilatation. RESULTS: Intraluminal reflux was evident, with methylene blue stain seen on the inner surface of the stents. Extraluminal reflux was proved with blue stain seen on the outer surface of the stents, both in undilated and dilated ureters. Study also proved the anti-reflux property of the skirt as the blue stain didn't go beyond the skirt, whereas the contralateral stent was stained up to proximal ureter. CONCLUSION: In this porcine in-vivo study, we elucidated that reflux occurred were both intraluminal and extraluminally. As a proof of concept, it also showed the anti-reflux property of a novel ureteral skirt.

Clinical efficacy of laparoscopic Lich-Gregoir versus transvesicoscopic Cohen reimplantation for ureterobladder junction malformations in children.

OBJECTIVE: To assess the clinical efficacy of laparoscopic Lich-Gregoir (LLG) and transvesicoscopic Cohen reimplantation (TCR) in the treatment of vesicoureteral junction obstruction (VUJO) and vesicoureteral reflux (VUR). METHODS: This study retrospectively analyzed the clinical data of 66 pediatric patients with VUJO and VUR. They were classified into two groups, undergoing either the laparoscopic Lich-Gregoir operation (LLGO) (n = 35) or transvesicoscopic Cohen reimplantation operation (TCRO) (n = 31). The surgeries were performed between April 2018 and September 2022 at the First Affiliated Hospital of Guangxi Medical University, China. General characteristics, preoperative attributes, postoperative complications, renal function recovery, and improvement of hydronephrosis were compared between the two groups. RESULTS: All surgical procedures were successful with no requirement for reoperation. Both groups were comparable with respect to gender, affected side, weight, and postoperative complications. Nonetheless, the LLGO group contained a greater number of children younger than 12 months. The LLGO group demonstrated superiority over the TCRO group regarding the duration of the operation, intraoperative blood loss, and length of postoperative hospital stay. In contrast, postoperative complications, recovery of renal function, and hydronephrosis improvement did not exhibit statistically significant differences between the two groups. CONCLUSION: Both LLGO and TCRO were demonstrated to be precise, safe, and reliable surgical methods for treating pediatric VUJO and VUR. LLGO ureteral reimplantation offers particular advantages in selecting cases and appears more suitable for children younger than 12 months who have a small bladder capacity.

Contrast media viscosity and its potential effect on the diagnosis of vesicoureteral reflux in children.

OBJECTIVE: To confirm that contrast-enhanced voiding cystourosonography (ceVUS) diagnoses more vesicoureteral reflux (VUR) than voiding cystourethrography (VCUG) and assess whether this could be explained by contrast agent viscosity differences. MATERIALS AND METHODS: Children addressed for a VCUG for suspected or known VUR between April 2021 and June 2023 were prospectively included. CeVUS and VCUG were consecutively performed during the same procedure by two operators; for each pelviureteric unit (PUU), VUR presence was assessed and scored (I-V scale). At least 6 months later, three radiologists reassessed VUR grading on all ceVUS static images. The viscosity of the two contrast agents and of the urine were measured at 25 °C and 37 °C. Wilcoxon tests were used for comparisons and linear Cohen's Kappa coefficient for Interobserver and Intraobserver agreement. RESULTS: Eighty-nine children, representing 192 PUU, were included. VUR was detected in 54 PUUs by at least one technique, by both in 30/54, by ceVUS only in 21/54 (38.8%), and by VCUG only in 3/54 (5.5%). VUR grade was higher with ceVUS in 19/30 (63.3%, p < 0.0008) PUUs. The ceVUS agent viscosity at 25 °C/37 °C (1.13 cP/1.03 cP) was almost identical to urine viscosity (1.14 cP/1.02 cP) and it was respectively 8 and 6 times lower than VCUG contrast agent viscosity (9.44 cP/6.03 cP). The Cohen's kappa for ceVUS grading was between 0.75-0.97 (interobserver) and 0.93-0.98 (intraobserver). CONCLUSION: Our study confirms that ceVUS detects more VUR and grades them higher in comparison to VCUG in children. This could be explained by the lower viscosity of the US contrast agent. KEY POINTS: Question Why are there differences in detecting and grading VUR between ceVUS and VCUG? Finding VUR was detected by ceVUS or VCUG only in, respectively 38.8% and 5.5% of PUUs. VUR grade was higher with ceVUS in 63.3%. Clinical relevance The higher detection rate and grading of vesicoureteral reflux in children by ceVUS might be explained by the lower viscosity of its sonographic contrast agent. CeVUS might reproduce the urine movement in the urinary tract.

Clinical implications of primary "occult" vesicoureteral reflux in male children.

OBJECTIVES: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR. MATERIALS AND METHODS: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria. RESULTS: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI. CONCLUSION: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR. CLINICAL RELEVANCE STATEMENT: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention.

Current management of symptomatic vesicoureteral reflux in pediatric kidney transplantation-A European survey among surgical transplant professionals.

BACKGROUND: Vesicoureteral reflux (VUR) is common in children and adolescents undergoing kidney transplantation (KTx) and may adversely affect allograft kidney function. METHODS: To explore the current management of symptomatic native and allograft VUR in pediatric KTx recipients, an online survey was distributed to European surgical transplant professionals. RESULTS: Surgeons from 40 pediatric KTx centers in 18 countries participated in this survey. Symptomatic native kidney VUR was treated before or during KTx by 68% of the centers (all/selected patients: 33%/67%; before/during KTx: 89%/11%), with a preference for endoscopic treatment (59%). At KTx, 90% favored an anti-reflux ureteral reimplantation procedure (extravesical/transvesical approach: 92%/8%; preferred extravesical technique: Lich-Gregoir [85%]). Management strategies for symptomatic allograft VUR included surgical repair (90%), continuous antibiotic prophylaxis (51%), bladder training (49%), or noninterventional surveillance (21%). Redo ureteral implantation and endoscopic intervention for allograft VUR were equally reported (51%/49%). CONCLUSIONS: This survey shows uniformity in some surgical aspects of the pediatric KTx procedure. However, with regard to VUR, there is a significant variation in practice patterns that need to be addressed by future well-designed and prospective studies. In this way, more robust data could be translated into consensus guidelines for a more standardized and evidence-based management of this common condition in pediatric KTx.

Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux.

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7-10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3-5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis.

Role of vesicoureteral reflux on pediatric kidney allograft function.

BACKGROUND: Vesicoureteral reflux (VUR) is a common urologic complication of pediatric kidney transplant, though there is little data on the effect of VUR on histologic graft changes or graft survival. METHODS: All pediatric patients who received a kidney transplant from 2007 to 2020 were selected for retrospective chart review. All participants underwent a voiding cystourethrogram (VCUG) at a 6-month post-transplant. Patients were then categorized into two groups based on vesicoureteral reflux grade: no/low-grade VUR (grades 0-2) and high-grade VUR (grades 3-5). Outcomes collected included graft failure rates, graft function, urinary tract infections (UTIs), proteinuria, and Banff scores at 3- and 12-month post-transplant surveillance kidney biopsies. RESULTS: There were 74 pediatric patients who received a kidney transplant in the designated time-period, and of those 39 had no/low-grade VUR and 35 had high-grade VUR. There was no difference in graft failure among the two groups over time when stratified for age (p = 0.389, CI 0.53-5.08). Patients with high grade VUR had a higher risk of UTI development overall (RR 1.89, 95%CI 1-3.6, p = 0.041), mostly accounted for from increased development of febrile UTI (RR 1.66, 95%CI 1.1-2.6, p = 0.038). CONCLUSIONS: Unselected pediatric kidney transplant recipients with high-grade vesicoureteral reflux on VCUG at a 6-month post-kidney transplant are more likely to have febrile UTI compared to those in the low-grade VUR group. There is no difference in graft survival among the two groups.

Infant urinary tract infection in Sweden - A national study of current diagnostic procedures, imaging and treatment.

BACKGROUND: Urinary tract infection (UTI) in infants is a common, potentially life-threatening bacterial infection, and must be managed carefully through the entire chain of care from diagnosis, choice of treatment, follow-up and risk stratification of future complications. This Swedish nationwide study of infant UTI was conducted to evaluate the current management of infant UTI, yield of investigations and the Swedish UTI guidelines' ability to detect abnormalities of importance in the urinary tract. METHODS: Infants < 1 year with a first episode of UTI were included in a prospective multicenter study. Treatment and follow-up were provided by local pediatricians. Clinical and laboratory findings and imaging results were reported to the coordinating center. The current management and results were compared with a previous Swedish study. RESULTS: One thousand three hundred six infants were included. Urine sampling was performed with clean catch technique in 93% of patients. Initial oral antibiotic treatment was used in 63%, predominantly third generation cephalosporines. Permanent kidney abnormalities were found in 10% and dilating vesicoureteral reflux (VUR) in 8%. Higher rates of male gender, non-E. coli infection and ultrasound dilatation were seen in infants < 1 month. UTI recurrences were reported in 18%. CONCLUSIONS: Infant UTI is still generating a considerable amount of follow-up examinations. There is a significant shift towards clean catch as the main urine sampling method. Voiding cystourethrography is performed less frequently reducing the findings of low grade VUR. The incidence of renal scarring is comparable with earlier studies which suggests that the Swedish guidelines are able to identify individuals with risk for long-term complications.

Validation of A 3D-printed simulator for training in endoscopic injection of bulking agent for vesicoureteral reflux: a pilot study.

BACKGROUND: Simulation-based training plays a significant role in surgical education, especially in minimally invasive pediatric surgery and urology. This study aimed to evaluate a novel 3D-printed model as training tool for endoscopic injection of bulking agent. METHODS: Forty-three attendees and ten teaching faculty members were invited to complete a post hoc questionnaire after completing training sessions using the Fish Tank Simulation Model (FTSM). The survey consisted of a 7-question 5-point Likert scale to assess the model's realism (face validity) and its effectiveness as training tool (content validity). RESULTS: Regarding the training status, 20/53 (37.7%) participants were fellow and/or specialist in pediatric surgery and 33/53 (62.3%) were surgeons in training. Their level of confidence in endoscopic injection procedure was defined as novice (< 10 procedures per year) in 33/53 (62.3%), intermediate (10-20 procedures per year) in 10/53 (18.9%), and expert (> 20 procedures per year) in 10/53 (18.9%). Regarding both face validity and content validity assessments, no statistically significant differences were found between scores given by novice vs intermediate/expert groups. Similarly, no statistically significant differences emerged between scores given by participant vs faculty groups assessing the content validity of the FTSM. The FTSM was considered a good teaching tool for beginners by 44/53 (83%) and for pediatric surgeons/urologists by 38/53 (71.7%). CONCLUSIONS: The 3D-printed Fish Tank Simulation Model proved to be a valuable, high-fidelity, easily accessible, cost-effective, hygienic, and domestic-use training tool for pediatric surgeons/urologists conducting the procedure. The model's user-friendly design and realistic environment enhanced learning opportunities for trainees, regardless of their experience level or training status. Nevertheless, further development is necessary, particularly in enhancing the realism of the ureteral hiatus and reproducing more complex anatomy, to make it beneficial for the training of advanced surgeons.

Advancements in Surgical Management of Megaureters.

PURPOSE OF REVIEW: To review and describe the recent evolution of surgery for the various types of pediatric megaureter. RECENT FINDINGS: Megaureter management first relies on determining the underlying cause, whether by obstruction, reflux, or a combination, and then setting appropriate surgical indications because many cases do not require surgery as shown by observation studies. Endoscopic balloon dilation has been on the rise as a major treatment option for obstructive megaureter, while refluxing megaureters can also be treated by laparoscopic and robotic techniques, whether extravesically or transvesicoscopically. During ureteral reimplantation, tapering is sometimes necessary to address the enlarged ureter, but there are also considerations for not tapering or for tapering alternatives. Endoscopic and minimally invasive surgeries for megaureter have been the predominant focus of recent megaureter literature. These techniques still need collaborative prospective studies to better define which surgeries are best for patients needing megaureter interventions.

Single-port plus one in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux, a comparative analysis with short-term outcomes.

OBJECTIVE: To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. METHODS: The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients' characteristics as well as their perioperative and follow-up data were collected and evaluated. RESULTS: There was no significant difference in the data regarding patients' characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups. CONCLUSION: The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.

Effects of Intrarenal Reflux on Renal Growth in Children With Grades III-V Primary Vesicoureteral Reflux.

The phenomenon of intrarenal reflux (IRR) has been considered a crucial link between vesicoureteral reflux (VUR) and segmental scarring. We conducted a study on renal length in 104 children diagnosed with Grades III-V VUR, with or without IRR, using contrast-enhanced voiding urosonography (ceVUS). The patients were divided into two treatment groups: the conservative antibiotic prophylaxis (CAP) group and the operation group, which were further categorized into two subgroups: the IRR group and the non-IRR group. Our findings revealed an incidence rate of 35.96% (41/114) for IRR occurrence, with 43.42% (33/76) occurring in upper renal segments, 32.89% (25/76) in lower segments, and 23.68% (18/76) in middle segments. In the CAP group where the effects of IRR persisted, the renal growth observed was as follows: IRR group-0.19 ± 0.13 cm; non-IRR group-0.39 ± 0.23 cm; contralateral negative group-0.66 ± 0.35 cm; control group-0.46 ± 0 .25 cm respectively (P < .05). In the operation group, where the effects of IRR were eliminated, the renal growth for the IRR group, non-IRR group, contralateral negative group, and control group was 0.46 ± 0.22 cm, 0.54 ± 0.31 cm, 0.67 ± 0 .42 cm, and 0.36 ± 0.17 cm respectively (P < .005). In conclusion, the presence of IRR can impact renal growth in children diagnosed with Grades III-V primary VUR. Following surgical intervention, the IRR kidney does not exhibit catch-up growth; however, it demonstrates parallel growth alongside the unaffected kidney. Conversely, the non-IRR kidney experiences catch-up growth. Therefore, for children presenting with Grades III-V primary VUR combined with IRR, a more aggressive treatment approach such as surgery is recommended.

Update on imaging recommendations in paediatric uroradiology: the European Society of Paediatric Radiology workgroup session on voiding cystourethrography.

Voiding cystourethrography (VCUG) is a fluoroscopic technique that allows the assessment of the urinary tract, including the urethra, bladder, and-if vesicoureteral reflux (VUR) is present-the ureters and the pelvicalyceal systems. The technique also allows for the assessment of bladder filling and emptying, providing information on anatomical and functional aspects. VCUG is, together with contrast-enhanced voiding urosonography (VUS), still the gold standard test to diagnose VUR and it is one of the most performed fluoroscopic examinations in pediatric radiology departments. VCUG is also considered a follow-up examination after urinary tract surgery, and one of the most sensitive techniques for studying anatomy of the lower genitourinary tract in suspected anatomical malformations. The international reflux study in 1985 published the first reflux-protocol and graded VUR into five classes; over the following years, other papers have been published on this topic. In 2008, the European Society of Paediatric Radiology (ESPR) Uroradiology Task Force published the first proposed VCUG Guidelines with internal scientific society agreement. The purpose of our work is to create a detailed overview of VCUG indications, procedural recommendations, and to provide a structured final report, with the aim of updating the 2008 VCUG paper proposed by the European Society of Paediatric Radiology (ESPR). We have also compared VCUG with contrast-enhanced VUS as an emergent alternative. As a result of this work, the ESPR Urogenital Task Force strongly recommends the use of contrast-enhanced VUS as a non-radiating imaging technique whenever indicated and possible.

Ultrasound-based predictive indicators for treatment outcomes in pediatric vesicoureteral reflux.

PURPOSE: To evaluate the effectiveness of preoperative ultrasound (US) measurements in predicting pediatric vesicoureteral reflux (VUR) treatment outcomes. METHODS: This prospective study enrolled 35 patients (53 renal units) aged 1-16 years who underwent subureteric injection therapy for primary VUR between July 2020 and June 2022. Preoperative ultrasound examinations measured the bladder wall thickness at the ureteral orifice, ureteral submucosal tunnel length, distal ureteral diameter, patient demographics, VUR grade, presenting complaints, bladder-bowel dysfunction, and renal scarring, and the impact of these variables on treatment success was analyzed. RESULTS: Among the patients, 91.4% were female, with a mean age of 6.83 ± 3.84 years. A comparison between the treatment success and failure groups revealed no significant differences in the age, sex, VUR grade, laterality, bilaterality, presenting complaints, bladder-bowel dysfunction, bladder wall thickness, or distal ureteral diameter (p > 0.05). However, renal scarring occurred in 16 (38.1%) patients in the treatment success group and 10 (90.9%) in the treatment failure group (p = 0.002). The treatment failure group had shorter detrusor-to-ureteral orifice distances and smaller detrusor-ureteral orifice distance-to-distal ureteral diameter (D/U) ratios than that of the success group (p = 0.004 and p = 0.006, respectively). Patients with a detrusor-to-ureteral orifice distance < 7.4 mm had an 81.82% likelihood of treatment failure. CONCLUSION: Ultrasound measurements of the detrusor-to-ureteral orifice distance and D/U ratio proved reliable in predicting the success of endoscopic subureteric injection therapy for VUR.

Comparison and clinical analysis of antibiotics and endoscopic injection for vesicoureteral reflux in children.

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.

Mitochondrial viability in neurogenic bladder urothelium after sigmoidocolocystoplasty. Implications for persistent vesicoureteral reflux.

PURPOSE: We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP). METHODS: Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson's trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity. RESULTS: Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively). CONCLUSION: Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.

Voiding cystourethrography in patients undergoing endoscopic decompression of duplex system ureteroceles: to do or not to do?

OBJECTIVE: To assess the role of voiding cystourethrography (VCUG) in patients with duplex system ureterocele (DSU) undergoing endoscopic decompression (ED). MATERIALS AND METHODS: This is a retrospective study of 75 consecutive patients with DSU undergoing ED [median (range) age, 6 (1-148) months]. Patients were divided into 3 groups, 33 with a VCUG showing vesicoureteral reflux (VUR) before ED (VUR-group), 22 with a VCUG negative for VUR (No-VUR-group), and 20 who did not undergo a VCUG (No-VCUG-group). Secondary surgery (SS) rate was compared among groups. RESULTS: Groups were comparable for baseline characteristics. SS rate was 82% (27/33) in VUR-group vs. 32% (7/22) in the No-VUR-group (p = 0.0001), and 25% (5/20) in the No-VCUG-group (p = 0.001 vs. VUR-group, and 1 vs. No-VUR-group). In the VUR-group, 9 patients underwent preemptive endoscopic treatment of VUR during ED and SS rate was 44% (4/9) vs. 96% (23/24) in the remainder, p= 0.003. In the No-VCUG-group, a VCUG was performed during follow-up in 9/15 patients and showed reflux in all, although only 2 of these developed a (single) urinary tract infections. CONCLUSIONS: SS rate was significantly higher in patients with preoperative VUR. Instead, it was not significantly different between patients without VUR and those who did not undergo a VCUG before ED, despite all the latter who underwent a VCUG during follow-up had evidence of VUR generally in the absence of symptoms. In our opinion, a VCUG could be limited to patients developing symptoms after ED. If a VCUG is performed before ED, a preemptive treatment of VUR should be taken into consideration.

A novel homozygous missense variant in TBC1D31 in a consanguineous family with congenital anomalies of the kidney and urinary tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of chronic kidney disease in the first three decades of life. Until now, more than 180 monogenic causes of isolated or syndromic CAKUT have been described. In addition, copy number variants (CNV) have also been implicated, however, all of these causative factors only explain a small fraction of patients with CAKUT, suggesting that additional yet-to-be-discovered novel genes are present. Herein, we report three siblings (two of them are monozygotic twin) of a consanguineous family with CAKUT. Whole-exome sequencing identified a homozygous variant in TBC1D31. Three dimensional protein modeling as well as molecular dynamics simulations predicted it as pathogenic. We therefore showed for the first time an association between a homozygous TBC1D31 variant with CAKUT in humans, expanding its genetic spectrum.