The European Reference Network eUROGEN, an interview by the Journal of Pediatric Urology.

The European Reference Networks (ERNs) initiative was started by the European Commission. The initiative was launched in 2017 in response to the 2011 EU Directive on Cross-Border Healthcare (Directive 2011/24/EU), which emphasized the need to improve healthcare for patients with rare diseases and complex conditions across the European Union. Currently, 24 ERNs are available for rare diseases.

Complement-Mediated Two-Step NETosis: Serum-Induced Complement Activation and Calcium Influx Generate NADPH Oxidase-Dependent NETs in Serum-Free Conditions.

The complement system and neutrophils play crucial roles in innate immunity. Neutrophils release neutrophil extracellular traps (NETs), which are composed of decondensed DNA entangled with granular contents, as part of their innate immune function. Mechanisms governing complement-mediated NET formation remain unclear.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel.

Shiga Toxin 2a Induces NETosis via NOX-Dependent Pathway.

Shiga toxin (Stx)-producing (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS), one of the main causes of acute kidney injury in children. Stx plays an important role in endothelium damage and pathogenesis of STEC-HUS. However, the effects of Stx on neutrophils and neutrophil extracellular trap (NET) formation are not well understood.

The Shiga Toxin Receptor Globotriaosylceramide as Therapeutic Target in Shiga Toxin Mediated HUS.

In 90% of the cases, childhood hemolytic uremic syndrome (HUS) is caused by an infection with the Shiga toxin (Stx) producing bacteria (STEC-HUS). Stx preferentially binds to its receptor, the glycosphingolipid, globotriaosylceramide (Gb3), present on the surface of human kidney cells and various organs. In this study, the glycosphingolipid pathway in endothelial cells was explored as therapeutic target for STEC-HUS.

Cell Biological Responses after Shiga Toxin-1 Exposure to Primary Human Glomerular Microvascular Endothelial Cells from Pediatric and Adult Origin.

Hemolytic uremic syndrome (HUS) is characterized by a triad of symptoms consisting of hemolytic anemia, thrombocytopenia and acute renal failure. The most common form of HUS is caused by an infection with Shiga toxin (Stx) producing bacteria (STEC-HUS), and the kidneys are the major organs affected. The development of HUS after an infection with Stx occurs most frequently in children under the age of 5 years.

Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium.

Hemolytic uremic syndrome (HUS) is a severe renal disease that is often preceded by infection with Shiga toxin (Stx)-producing (STEC). The exact mechanism of Stx-mediated inflammation on human glomerular microvascular endothelial cells (HGMVECs) during HUS is still not well understood. In this study, we investigated the effect of Stx1 on the gene expression of proteins involved in leucocyte-mediated and complement-mediated inflammation.

Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction.

Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause.

The genetics of atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia due to endothelial injury. aHUS is felt to be caused by defective complement regulation due to underlying genetic mutations in complement regulators or activators, most often of the alternative pathway. Mutations causing aHUS can be subdivided into two groups, loss of function mutations (affecting factor H, factor H-related proteins, membrane co-factor protein, and factor I), and gain of function mutations (affecting factor B and C3).

CNV analysis in 169 patients with bladder exstrophy-epispadias complex.

Background: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology.

Predictors for a positive outcome of adapted clinical dry bed training in adolescents and adults with enuresis.

Aims: Adapted Dry Bed Training (Adapted DBT) has been shown to be effective in therapy-resistant adolescents and adults with enuresis. Given the substantial impact of enuresis and the time-consuming nature of Adapted DBT, we investigated which patients benefited most from Adapted DBT. Therefore, we identified predictors for a successful treatment response to Adapted DBT in this population.

Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.

Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE.

Seamless vascularized large-diameter tubular collagen scaffolds reinforced with polymer knittings for esophageal regenerative medicine.

A clinical demand exists for alternatives to repair the esophagus in case of congenital defects, cancer, or trauma. A seamless biocompatible off-the-shelf large-diameter tubular scaffold, which is accessible for vascularization, could set the stage for regenerative medicine of the esophagus. The use of seamless scaffolds eliminates the error-prone tubularization step, which is necessary when emanating from flat scaffolds.

Regenerative urology clinical trials: an ethical assessment of road blocks and solutions.

Tissue engineering--part of regenerative medicine--is a promising technology that could potentially offer elegant solutions to urogenital defects, but so far, it has fallen short of its potential. Within experimental studies for bladder and urethra reconstructions, two clinical applications have been described, but extension of these techniques to the broader urological patient population has not happened so far. In this article, we aim to identify the ethical road blocks in the clinical evaluation of tissue-engineered products under the European Medicines Agency and Food and Drug Administration regulations for pediatric urological conditions and, ultimately, to recommend strategies to overcome them.

Treatment response of an outpatient training for children with enuresis in a tertiary health care setting.

Purpose: To evaluate treatment effectiveness for children with enuresis, according to the definitions of the International Children's Continence Society (ICCS, 2006).

Material And Methods: Children ≥6 years of age followed a 4-month outpatient treatment consisted of a visit during which history regarding enuresis was taken, causes were explained and therapeutic tips & tricks were discussed. All children received a booklet about enuresis and were trained with an alarm and/or pharmacological therapy.

Genes in the ureteric budding pathway: association study on vesico-ureteral reflux patients.

Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis.

Surgical treatment of uterine prolapse in women with bladder exstrophy: report of two cases with modified Prolift procedure.

The incidence of pelvic organ prolapse is 18% in women with bladder exstrophy. A vaginal technique to correct the prolapse may be preferable in these women with multiple abdominal operations in their histories. We have performed a modified Prolift procedure for the repair of severe uterine prolapse in two young women.

Risk factors for undescended testis.

Objective: To contribute to the understanding of the etiology of undescended testis (UDT), by exploring a wide range of potential risk factors in a case-referent study.

Patients And Methods: Cases and referents were recruited at five hospitals and included 200 boys with surgically corrected UDT and 629 boys with persistent middle ear effusion. Risk factor data were obtained by postal questionnaires to both parents.

Longer than expected-duration of caudal analgesia with two different doses of levobupivacaine in children undergoing hypospadias repair.

Objective: To assess our study design and to obtain preliminary data for a dose-effect study on levobupivacaine for caudal analgesia in patients undergoing hypospadias repair.

Study Design: non randomised, non-blinded pilot study.

Method: For this non-randomized, non-blinded pilot study, 20 patients (median age 17 months, median weight 10.

Teaching children clean intermittent self-catheterization (CISC) in a group setting.

Objective: To teach children to perform clean intermittent self-catheterization (CISC) at our institution, the nurse practitioner uses a step-by-step approach in combination with an instruction model in an outpatient setting. For a small group of children the procedure remains difficult to learn. For them, we developed a multidisciplinary, group-wise training program.

Hypospadias: risk factor patterns and different phenotypes.

Objective: To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes.

Patients And Methods: Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43).

Bladder augmentation: Review of the literature and recent advances.

Bladder augmentation is an important tool in the management of children requiring reconstructions for urinary incontinence or preserving of the upper urinary tract in congenital malformations. We reviewed the literature and evaluated the long-term results of enterocystoplasty in the pediatric age group and summarized techniques, experimental options and future perspectives for the treatment of these patients. For this purpose, a directed Medline literature review for the assessment of enterocystoplasty was performed.