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Radical nephrectomy combined with contemporary chemotherapeutic and radiation therapy protocols has drastically improved outcomes for children with Wilms tumor. Patients with bilateral disease and a syndrome predisposing to tumor development have necessitated the use of nephron-sparing surgery in select cases. Success in managing these patients has increased the indication for partial nephrectomy, although current guidelines for unilateral Wilms tumor are limited. Given that children are being cured with increasing success, recent focus has shifted to long-term health outcomes in addition to tumor treatment. Specifically, renal function has an impact on long-term cardiovascular health and events. Adult outcomes with partial nephrectomy provide a guideline for a paradigm shift in the management of children with Wilms tumor, particularly with advances in imaging and adjuvant therapy. The data are limited for children undergoing partial nephrectomy for unilateral Wilms tumor and outcomes for larger tumors will need to be studied closely in future trials. Increased utilization of neoadjuvant chemotherapy could further expand the number of patients eligible for partial nephrectomy.

Summary The maturation and functional characteristics of human induced pluripotent stem cell (hiPSC)-cortical neurons has not been fully documented. This study developed a phenotypic model of hiPSC-derived cortical neurons, characterized their maturation process, and investigated its application for disease modeling with the integration of multi-electrode array (MEA) technology. Immunocytochemistry analysis indicated early-stage neurons (day 21) were simultaneously positive for both excitatory (vesicular glutamate transporter 1 [VGlut1]) and inhibitory (GABA) markers, while late-stage cultures (day 40) expressed solely VGlut1, indicating a purely excitatory phenotype without containing glial cells. This maturation process was further validated utilizing patch clamp and MEA analysis. Particularly, induced long-term potentiation (LTP) successfully persisted for 1 h in day 40 cultures, but only achieved LTP in the presence of the GABAA receptor antagonist picrotoxin in day 21 cultures. This system was also applied to epilepsy modeling utilizing bicuculline and its correction utilizing the anti-epileptic drug valproic acid., Graphical abstract, Highlights • Characterization of human cortical neuronal differentiation to a mature phenotype • Microelectrode evaluation of development from a mixed to pure excitatory population • Utilization of defined culture stage to create an epilepsy model • Manipulation of immaturity with inhibitors for maintaining long-term potentiation, In this article, Hickman and colleagues used controlled hiPSC-cortical neuron maturation to develop models capable of evaluating functional deficits in long-term potentiation, which is the basis for many neurodegenerative diseases. This model has the potential for patient-specific personalized medicine and can be used for both the investigation of pathogenesis and subsequent preclinical assaying of potential drug treatments.

Early kidney and anatomic features may be predictive of future progression and need for additional procedures in patients with posterior urethral valve (PUV). The objective of this study was to use machine learning (ML) to predict clinically relevant outcomes in these patients. Patients diagnosed with PUV with kidney function measurements at our institution between 2000 and 2020 were included. Pertinent clinical measures were abstracted, including estimated glomerular filtration rate (eGFR) at each visit, initial vesicoureteral reflux grade, and renal dysplasia at presentation. ML models were developed to predict clinically relevant outcomes: progression in CKD stage, initiation of kidney replacement therapy (KRT), and need for clean-intermittent catheterization (CIC). Model performance was assessed by concordance index (c-index) and the model was externally validated. A total of 103 patients were included with a median follow-up of 5.7 years. Of these patients, 26 (25%) had CKD progression, 18 (17%) required KRT, and 32 (31%) were prescribed CIC. Additionally, 22 patients were included for external validation. The ML model predicted CKD progression (c-index = 0.77; external C-index = 0.78), KRT (c-index = 0.95; external C-index = 0.89) and indicated CIC (c-index = 0.70; external C-index = 0.64), and all performed better than Cox proportional-hazards regression. The models have been packaged into a simple easy-to-use tool, available at https://share.streamlit.io/jcckwong/puvop/main/app.py ML-based approaches for predicting clinically relevant outcomes in PUV are feasible. Further validation is warranted, but this implementable model can act as a decision-making aid. A higher resolution version of the Graphical abstract is available as Supplementary information

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic factors that contribute to liver disease development and progression, and evaluation of the therapeutic metformin. This model uses a serum-free, recirculating medium tailored to represent different human metabolic conditions over a 14-day period. The system validated the indirect influence of adipocyte physiology on hepatocytes that modeled important aspects of NAFLD progression, including insulin resistant biomarkers, differential adipokine signaling in different media and increased TNF-α-induced steatosis observed only in the two-tissue model. This model provides a simple but unique platform to evaluate aspects of an individual factor’s contribution to NAFLD development and mechanisms as well as evaluate preclinical drug efficacy and reassess human dosing regimens.

Telemedicine utilization rapidly expanded throughout the coronavirus disease 2019 (COVID-19) pandemic and yielded numerous patient benefits. However, its future remains uncertain, limiting further institutional investments in telemedicine. We aimed to evaluate trends in the volume of telemedicine visits throughout the pandemic and patient factors associated with telemedicine usage to inform the future role of telemedicine in pediatric urology. An Institutional Review Board (IRB)-approved registry of pediatric urology outpatient visits was queried from June 2019 to November 2021 at a single institution. Variables of interest included patient demographics, travel distance for care, insurance status, primary visit diagnosis, and visit type (in-person visits, IPVs; or video visits, VVs). IPVs and VVs were further categorized as new patient visits (NPVs), return patient visits (RPVs), and post-operative visits (post-ops). Monthly trends in descriptive variables were summarized. A total of 51,605 pediatric urology outpatient visits occurred during the study period. Patients had a median age of 5 years [interquartile range (IQR), 1–11] and were predominantly male (71.6%), white (61.6%), and held private insurance (69%). VVs increased substantially from 0% in February 2020 to 100% in April 2020 and then subsequently declined through November 2021, although total visit volumes were increasing throughout the period. As the pandemic progressed, compared to IPVs, VVs were more likely to have an RPV visit type (80% vs. 50%–60%) and longer median travel distance (30+ vs. 14 miles). VVs were less frequently covered by subsidized insurance (20%–30% vs. 50%–70%). In summary, this study found that telemedicine usage has declined since the peak of the COVID-19 pandemic, although its use remains higher than pre-pandemic levels and appears to be associated with RPVs, longer travel distance, and private insurance coverage. Utilization has stabilized as we have emerged from peak pandemic restrictions. Further work is required to elucidate the optimal role of telemedicine and its effects on access to care in pediatric urology.

We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone.We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years.Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone.Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

Purpose:Controversy remains within the pediatric urology community regarding adequate duration of followup after hypospadias repair. Some have suggested that minimal long-term followup is necessary...

Myelination and node of Ranvier formation play an important role in the rapid conduction of nerve impulses, referred to as saltatory conduction, along axons in the peripheral nervous system. We report a human-human myelination model using human primary Schwann cells (SCs) and human-induced pluripotent stem-cell-derived motoneurons utilizing a serum-free medium supplemented with ascorbate to induce myelination, where 41.6% of SCs expressed the master transcription factor for myelination, early growth response protein 2. After 30 days in coculture, myelin segments were visualized using immunocytochemistry for myelin basic protein surrounding neurofilament-stained motor neuron axons, which was confirmed via 3D confocal Raman microscopy, a viable alternative for transmission electron microscopy analysis. The myelination efficiency was 65%, and clusters of voltage-gated sodium channels and the paranodal protein contactin-associated protein 1 indicated node of Ranvier formation. This model has applications to study remyelination and demyelinating diseases, including Charcot-Marie Tooth disorder, Guillian-Barre syndrome, and anti-myelin-associated glycoprotein peripheral neuropathy.

Chronic autoimmune demyelinating neuropathies are a group of rare neuromuscular disorders with complex, poorly characterized etiology. Here we describe a phenotypic, human-on-a-chip (HoaC) electrical conduction model of two rare autoimmune demyelinating neuropathies, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), and explore the efficacy of TNT005, a monoclonal antibody inhibitor of the classical complement pathway. Patient sera was shown to contain anti-GM1 IgM and IgG antibodies capable of binding to human primary Schwann cells and induced pluripotent stem cell derived motoneurons. Patient autoantibody binding was sufficient to activate the classical complement pathway resulting in detection of C3b and C5b-9 deposits. A HoaC model, using a microelectrode array with directed axonal outgrowth over the electrodes treated with patient sera, exhibited reductions in motoneuron action potential frequency and conduction velocity. TNT005 rescued the serum-induced complement deposition and functional deficits while treatment with an isotype control antibody had no rescue effect. These data indicate that complement activation by CIDP and MMN patient serum is sufficient to mimic neurophysiological features of each disease and that complement inhibition with TNT005 was sufficient to rescue these pathological effects and provide efficacy data included in an investigational new drug application, demonstrating the model's translational potential.

Testosterone (T) administration prior to hypospadias surgery to increase glans size remains controversial. Understanding T's effect on glans width (GW) is essential to understanding its potential impact on surgical outcomes. We hypothesized that preoperative T in prepubertal boys significantly increases GW at the time of hypospadias surgery.Our single institutional database was queried to identify patients who underwent hypospadias surgery from 2016 to 2020, in which data for T administration and GW were available. Descriptive, nonparametric and categorical statistics were performed as indicated.A total of 579 patients were eligible for analysis. Median age at surgery was 0.9 years (IQR 0.6-1.6). A total of 247/579 patients (42.7%) received T. The median GW at surgery was 15 mm (IQR 13-17). When comparing patients who had T administered to those who did not, we found a significant difference in GW at surgery (16 mm vs 14 mm, p0.001). The median change in GW from the office to surgery was 4 mm for those receiving T vs 0 mm for those not receiving T (p0.001). We identified a greater change in GW from preoperative to intraoperative measurements in patients who received 2 doses of T vs 1 dose (4 mm vs 2 mm, p0.001). A histogram plot revealed the distribution of GW change at surgery.In our prospectively collected cohort of patients undergoing hypospadias surgery, we were able to quantitate the change in GW from preoperative T. Two doses of T resulted in a significant increase in GW vs 1 dose.

With the advent of robot-assisted laparoscopic ureteral reimplantation (RALUR) for primary vesicoureteral reflux (VUR), understanding and minimizing its complications continues to be critical. Incidence of de novo hydronephrosis after RALUR could be indicative of an outcome that needs further study or could be a benign transient finding.In the present study, we hypothesized that the incidence of de novo hydronephrosis after RALUR is low and resolves spontaneously.An IRB-approved prospective single-institutional registry was utilized to identify all patients undergoing RALUR via an extravesical approach from 2012 to 2020. Patients with primary VUR and minimal (Grade I SFU) or no hydronephrosis prior to surgery were included. Patients who had other associated pathology or underwent concomitant procedures were excluded. Preoperative characteristics including VUR and hydronephrosis grades as well as post-operative clinical details and hydronephrosis grades were aggregated and analyzed.86/172 (50%) patients (133 ureters), with median reflux grade of 3 (IQR: G2, G3) met the inclusion criteria. Patients underwent RALUR at a median age of 5.7 years (IQR: 3.4, 8.7) with median 36.2 months (IQR: 19.6, 63.6) follow-up. Renal ultrasound at 4-6 weeks post-op showed de novo hydronephrosis in 18 (13.5%) ureters; the complete resolution was seen in 13 ureters (72%) at a median of 4.5 months from surgery. Among the 5 with non-resolved hydronephrosis (SFU G2:4, G3:1), 2 patients (3 ureters) underwent subsequent interventions.The present study evaluating the natural history of de novo hydronephrosis after RALUR-EV performed for primary VUR, is to our knowledge the largest cohort of patients undergoing RALUR that this has been studied in. In our cohort, the incidence of de novo hydronephrosis after RALUR was 13.5%, similar to rates reported in two OUR cohorts, and significantly lower than reported incidence rates of 22-26% in several OUR cohorts, and 30% in a RALUR cohort. In the present cohort, hydronephrosis resolved spontaneously in more than 72% of cases. The median time from surgery until resolution of hydronephrosis was 4.5 (1.6, 10.5) months, which is shorter in comparison to the average time to resolution of 7.6 months, reported by Kim et al. in an earlier study.De novo hydronephrosis after RALUR can be followed with serial renal ultrasounds. The majority of de novo hydronephrosis post-RALUR is transient and resolves spontaneously within a year of surgery with a very low re-intervention rate.