Safety and Efficacy of Robot-Assisted Laparoscopic Pyeloplasty Compared to Open Repair in Infants under 1 Year of Age.

PURPOSE: Robot-assisted laparoscopic pyeloplasty (RALP) use in children has increased, though many centers still favor open pyeloplasty (OP) in infants. This study aims to compare safety and efficacy of RALP and OP in infants. MATERIALS AND METHODS: A single-institution, retrospective cohort study of infants <1 year of age who underwent primary RALP or OP between January 2009 and June 2020 was performed. Primary outcomes were intraoperative and 30-day complications, postoperative radiographic improvement at last clinic visit, and operative failure leading to redo pyeloplasty. Multivariable logistic regression was performed for 30-day complications to adjust for demographic variation between groups. Survival analysis was performed to compare time to diagnosis of operative failure leading to redo pyeloplasty. RESULTS: Among 204 patients, 121 underwent OP and 83 underwent RALP (74.5% male). RALP patients were older (median 7.2 vs 2.9 months, p <0.001) and larger (median 8.2 vs 5.9 kg, p <0.001) than OP patients. Radiographic improvement was seen in 91.1% of RALP patients and 88.8% of OP patients at last visit. Median (interquartile range) followup in months was 24.4 (10.8-50.3) for the full cohort. In adjusted analysis, the odds of a 30-day complication (OR 0.40, 95% CI 0.08-2.00) was lower for RALP compared to OP, though not statistically significant. In survival analysis, there was no difference in time to diagnosis of operative failure and redo pyeloplasty between groups (p=0.65). CONCLUSIONS: RALP is a safe and effective alternative to OP for infants, with comparable intraoperative and 30-day complications, radiographic improvement at last followup, and risk of pyeloplasty failure.

Stem cell antigen/Ly6a protects against bladder fibrosis in mice.

We have defined a population of stem cell antigen (Sca)-1+/CD34+/lin- mesenchymal stem cells in the mouse urinary bladder. These cells are reduced after partial bladder outlet obstruction (PO). To test the role of Sca-1 expressed by these cells, we analyzed bladders from Sca-1 knockout (KO) mice in both uninjured male mice and male mice subjected to PO. We found that loss of Sca-1 alone had little effect on bladder development or function but reduced the total number of mesenchymal stem cells by 30%. After PO, bladders from Sca-1-null KO male mice were larger, with more collagen and less muscle, than obstructed wild-type mice. Steady-state levels of caldesmon were significantly reduced and levels of fibroblast-specific protein 1 were significantly increased in Sca-1 KO mice compared with wild-type mice after PO. In investigating the effects of PO on cell proliferation, we found that loss of Sca-1 changed the timing of cell division in CD34+/lin-, collagen-producing, and smooth muscle cells. PO in combination with loss of Sca-1 drastically reduced the ability of CD34+/lin- cells to form colonies in vitro. Our findings therefore support the hypothesis that Sca-1 protects the bladder from fibrotic remodeling after obstruction, in part by influencing the proliferation of cells responding to the injury.

Ureteral Complications of Pediatric Renal Transplantation.

PURPOSE: Ureteral complications following renal transplantation are more common in children than in adults. We identify potential risk factors for ureteral complications in pediatric patients. MATERIALS AND METHODS: We retrospectively studied a cohort of patients who underwent renal transplantation at Lurie Children's Hospital between 2004 and 2016. We analyzed the associations between patient characteristics, operative factors, graft characteristics and postoperative complications. RESULTS: A total of 224 renal transplantations in 219 patients were identified. Preexisting bladder pathology was present in 25% of cases. Overall rate of ureteral complications was 16%, with symptomatic vesicoureteral reflux being the most common. Ureteral complications were seen significantly more frequently in patients with underlying bladder pathology (26% vs 12%, p = 0.01). Rate of postoperative vesicoureteral reflux in patients with bladder pathology was lower when a urologist performed the reimplantation but the difference was not statistically significant (15% vs 27%, p = 0.35). Urologists were significantly more likely to perform the ureteral anastomosis in patients on clean intermittent catheterization (85% vs 43%, p = 0.004) and in patients with a history of complex bladder reconstruction (75% vs 28%, p <0.001). CONCLUSIONS: Patients with existing bladder pathology are at increased risk for ureteral complications, particularly vesicoureteral reflux. Since pediatric urologists routinely perform ureteral reimplantation in patients with existing bladder pathology, these patients may benefit from a multidisciplinary approach between urology and transplant surgery at renal transplantation.

Robot-Assisted Laparoscopic Reoperative Repair for Failed Pyeloplasty in Children: An Updated Series.

PURPOSE: Reoperative pyeloplasty is commonly used in children with recurrent obstruction after pyeloplasty. We previously reported on reoperative robot-assisted laparoscopic repair for failed pyeloplasty in 16 children and concluded that short-term and intermediate outcomes were comparable to open reoperative repair. In this updated series we describe longer term outcomes from an extended study. MATERIALS AND METHODS: We retrospectively reviewed outcomes of consecutive children with prior failed primary pyeloplasty who underwent robot-assisted laparoscopic reoperative repair at a single institution from January 2008 to June 2018. RESULTS: Overall, 36 children 0.6 to 15.2 years old (median 3.7) underwent robot-assisted laparoscopic reoperative repair (pyeloplasty in 31, ureterocalicostomy in 5) at a median of 24.3 months (range 3.9 to 136.7) after primary repair. Median reoperative time was 285.0 minutes (range 207 to 556) and median length of stay was 1 day (1 to 8). Crossing vessels were present in 8 of 30 children (26.7%) with prior open repair and in 0 of 6 with prior minimally invasive repair. Clavien-Dindo grade 1 to 2 perioperative complications occurred in 4 children (11.1%) and grade 3 to 5 complications in 2 (5.6%). Median followup was 35.3 months (range 1.4 to 108.3), with 18 children (50.0%) being followed for more than 3 years. Postoperative ultrasound in 34 children revealed improvement in 31 (91.2%), stability in 2 (5.9%) and worsening hydronephrosis in 1 (2.9%). All 11 children undergoing preoperative and postoperative diuretic renography demonstrated stable or improved differential renal function. All children were symptom-free at last followup. CONCLUSIONS: To our knowledge, this is the largest series of robot-assisted laparoscopic reoperative repair for failed pyeloplasty in children. Our results indicate the feasibility, efficacy, safety and durability of this procedure.

The Correlation between Serial Ultrasound and Diuretic Renography in Children with Severe Unilateral Hydronephrosis.

PURPOSE: While serial renal ultrasound is often used as an alternative to functional renal imaging in children followed for hydronephrosis, it is unclear whether a lack of hydronephrosis progression safeguards against loss of renal function. In this study we characterize the association between findings on serial renal ultrasound and diuretic renography in children with severe unilateral hydronephrosis. MATERIALS AND METHODS: We retrospectively reviewed imaging among patients younger than 18 years old with a history of severe unilateral hydronephrosis, 2 renal ultrasounds and 2 diuretic renograms. Each pair of renal ultrasounds was interpreted by an independent blinded diagnostic radiologist and compared to a contemporaneous diuretic renogram. Change in hydronephrosis was considered as 1) a change in hydronephrosis grade or 2) any change by radiologist interpretation. A 5% or greater change in split differential function was considered significant. Chi-square and Spearman correlation analyses were performed. RESULTS: A total of 85 children were evaluated. Increased hydronephrosis was noted in 11.8% of children by grade and 32.9% by radiologist interpretation. Split differential renal function worsened by 5% or more in 17.6% of children. Overall, 13.3% of children with stable or decreased hydronephrosis demonstrated worsening split differential function at an average of 11.8 months. When renal ultrasound and diuretic renograms were directly compared, the Spearman correlation was poor (r = 0.24, 95% CI 0.03 to 0.43). CONCLUSIONS: The overall correlation between imaging modalities was poor, and 13.3% of children with stable or decreased hydronephrosis had worsening of split differential renal function. These findings are important to consider when counseling nonoperatively managed children followed without diuretic renography.

Use of Pediatric Open, Laparoscopic and Robot-Assisted Laparoscopic Ureteral Reimplantation in the United States: 2000 to 2012.

PURPOSE: We characterize the use of pediatric open, laparoscopic and robot-assisted laparoscopic ureteral reimplantation in the United States from 2000 to 2012. MATERIALS AND METHODS: We used the Kids' Inpatient Database to identify patients who underwent ureteral reimplantation for primary vesicoureteral reflux. Before 2009 laparoscopic ureteral reimplantion and robot-assisted laparoscopic ureteral reimplantation were referred to together as minimally invasive ureteral reimplantation. A detailed analysis of open vs robot-assisted laparoscopic ureteral reimplantation was performed for 2009 and 2012. RESULTS: A total of 14,581 ureteral reimplantations were performed. The number of ureteral reimplantations yearly decreased by 14.3%. However, the proportion of minimally invasive ureteral reimplantations increased from 0.3% to 6.3%. A total of 125 robot-assisted laparoscopic ureteral reimplantations were performed in 2012 (81.2% of minimally invasive ureteral reimplantations), representing 5.1% of all ureteral reimplantations, compared to 3.8% in 2009. In 2009 and 2012 mean ± SD patient age was 5.7 ± 3.6 years for robot-assisted laparoscopic ureteral reimplantation and 4.3 ± 3.3 years for open reimplantation (p <0.0001). Mean ± SD length of hospitalization was 1.6 ± 1.3 days for robot-assisted laparoscopic ureteral reimplantation and 2.4 ± 2.6 for open reimplantation (p <0.0001). Median charges were $22,703 for open and $32,409 for robot-assisted laparoscopic ureteral reimplantation (p <0.0001). These relationships maintained significance on multivariate analyses. On multivariate analysis robot-assisted laparoscopic ureteral reimplantation use was associated with public insurance status (p = 0.04) and geographic region outside of the southern United States (p = 0.02). Only 50 of 456 hospitals used both approaches (open and robotic), and only 6 hospitals reported 5 or more robot-assisted laparoscopic ureteral reimplantations during 2012. CONCLUSIONS: Treatment of primary vesicoureteral reflux with ureteral reimplantation is decreasing. Robot-assisted laparoscopic ureteral reimplantation is becoming more prevalent but remains relatively uncommon. Length of stay is shorter for the robotic approach but the costs are higher. Nationally robot-assisted laparoscopic ureteral reimplantation appears to still be in the early phase of adoption and is clustered at a small number of hospitals.

Growth in Newborn Circumcisions Performed by Pediatric Urologists and Advanced Practice Providers Between 2010 and 2021 in the United States.

OBJECTIVE: To characterize changes in the proportion of newborn circumcisions performed by pediatric urologists and advanced practiced providers (APPs) in the United States over the last decade. METHODS: The Merative MarketScan Commercial Database was queried for newborn circumcision private health insurance claims (Common Procedural Terminology 54150) between 2010 and 2021. Setting (inpatient/outpatient), US Census Bureau region, clinician specialty, and patient age (days) were determined for the full study time period, and by study year. Simple linear regression assessed growth in proportion of newborn circumcisions performed by pediatric urologists and APPs (nurse practitioner/physician assistant/midwife), over time. RESULTS: In total, 1,006,748 newborn circumcisions (59% inpatient) were identified; while most were performed by obstetricians (45%) or pediatricians (33%); APPs performed 0.9%, and pediatric urologists performed 0.7%. From 2010-2021, the proportion of newborn circumcisions performed by pediatric urologists increased from 0.3% to 2.0% and by APPs in from 0.5% to 2.9% (P < .001 for both). Growth for both pediatric urologists and APPs occurred APPs predominantly from 2016 to 2021. Trends in proportion of newborn circumcision performed by pediatricians was stable [31.5% (2010) and 32.5% (2021)], but decreased for obstetricians [48.8% (2014) and 38.1% (2021)]. CONCLUSION: The proportion of newborn circumcisions performed by pediatric urologists and APPs increased more than 6-fold between 2010 and 2021, though both specialties still perform a minority of newborn circumcisions. These data provide important baseline information for newborn circumcision workforce planning, including evaluating collaborative care models where pediatric urologists train APPs to perform circumcision.

Exploring the Landscape of Aptamers: From Cross-Reactive to Selective to Specific, High-Affinity Receptors for Cocaine.

We reported over 20 years ago MNS-4.1, the first DNA aptamer with a micromolar affinity for cocaine. MNS-4.1 is based on a structural motif that is very common in any random pool of oligonucleotides, and it is actually a nonspecific hydrophobic receptor with wide cross-reactivity with alkaloids and steroids. Despite such weaknesses preventing broad applications, this aptamer became widely used in proof-of-concept demonstrations of new formats of biosensors. We now report a series of progressively improved DNA aptamers recognizing cocaine, with the final optimized receptors having low nanomolar affinity and over a thousand-fold selectivity over the initial cross-reactants. In the process of optimization, we tested different methods to eliminate cross-reactivities and improve affinity, eventually achieving properties that are comparable to those of the reported monoclonal antibody candidates for the therapy of overdose. Multiple aptamers that we now report share structural motifs with the previously reported receptor for serotonin. Further mutagenesis studies revealed a palindromic, highly adaptable, broadly cross-reactive hydrophobic motif that could be rebuilt through mutagenesis, expansion of linker regions, and selections into receptors with exceptional affinities and varying specificities.