FDA approval summary for lonafarnib (Zokinvy) for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies.

The U.S. Food and Drug Administration recently approved lonafarnib as the first treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies. This approval was primarily based on a comparison of patients with HGPS treated with lonafarnib in 2 open-label trials with an untreated patient cohort. With up to 11 years of follow-up, it was found that the lonafarnib treated patients with HGPS had a survival benefit of 2.5 years compared with the untreated patients with HGPS. This large treatment effect on the objective endpoint of mortality using a well-matched comparator group mitigated potential sources of bias and together with other evidence, established compelling evidence of a drug effect with benefits that outweighed the risks. This approval is an example of U.S. Food and Drug Administration's regulatory flexibility for a rare disease while ensuring that standards for drug approval are met.

Incidence of Urinary Tract Infections in Newborns with Spina Bifida-Is Antibiotic Prophylaxis Necessary?

PURPOSE: Urinary tract infections commonly occur in patients with spina bifida and pose a risk of renal scarring. Routine antibiotic prophylaxis has been utilized in newborns with spina bifida to prevent urinary tract infections. We hypothesized that prophylaxis can safely be withheld in newborns with spina bifida until clinical assessment allows for risk stratification. MATERIALS AND METHODS: Newborns with myelomeningocele at 9 institutions were prospectively enrolled in the UMPIRE study and managed by a standardized protocol with a strict definition of urinary tract infection. Patient data were collected regarding details of reported urinary tract infection, baseline renal ultrasound findings, vesicoureteral reflux, use of clean intermittent catheterization and circumcision status in boys. Risk ratios and corresponding 95% confidence intervals were calculated using log-binomial models. RESULTS: From February 2015 through August 2019 data were available on 299 newborns (50.5% male). During the first 4 months of life, 48 newborns (16.1%) were treated for urinary tract infection with 23 (7.7%) having positive cultures; however, only 12 (4.0%) met the strict definition of urinary tract infection. Infants with grade 3-4 hydronephrosis had an increased risk of urinary tract infection compared to infants with no hydronephrosis (RR=10.1; 95% CI=2.8, 36.3). Infants on clean intermittent catheterization also had an increased risk of urinary tract infection (RR=3.3; 95% CI=1.0, 10.5). CONCLUSIONS: The incidence of a culture positive, symptomatic urinary tract infection among newborns with spina bifida in the first 4 months of life was low. Patients with high grades of hydronephrosis or those on clean intermittent catheterization had a significantly greater incidence of urinary tract infection. Our findings suggest that routine antibiotic prophylaxis may not be necessary for most newborns with spina bifida.

Baseline Urinary Tract Imaging in Infants Enrolled in the UMPIRE Protocol for Children with Spina Bifida.

PURPOSE: The lifetime risk of renal damage in children with spina bifida is high but only limited baseline imaging data are available for this population. We evaluated a large prospective cohort of infants with spina bifida to define their baseline imaging characteristics. MATERIALS AND METHODS: The UMPIRE Protocol for Young Children with Spina Bifida is an iterative quality improvement protocol that follows a cohort of newborns at 9 United States centers. Using descriptive statistics, we report the initial baseline imaging characteristics, specifically regarding renal bladder ultrasound, cystogram and dimercaptosuccinic acid nuclear medicine scan. RESULTS: Data on 193 infants from 2015 to 2018 were analyzed. Renal-bladder ultrasound was normal in 55.9% of infants, while 40.4% had Society for Fetal Urology grade 1 to 2 hydronephrosis in at least 1 kidney, 3.7% had grade 3 to 4 hydronephrosis in either kidney and 21.8% had grade 1 or higher bilateral hydronephrosis. There was no vesicoureteral reflux in 84.6% of infants. A third of enrolled infants underwent dimercaptosuccinic acid nuclear medicine renal scan, of whom 92.4% had no renal defects and 93.9% had a difference in differential function of less than 15%. CONCLUSIONS: The majority of infants born with spina bifida have normal baseline imaging characteristics and normal urinary tract anatomy at birth. This proactive protocol offers careful scheduled surveillance of the urinary tract with the goal of lifelong maintenance of normal renal function and healthy genitourinary development.

Bladder Management and Continence Outcomes in Adults with Spina Bifida: Results from the National Spina Bifida Patient Registry, 2009 to 2015.

PURPOSE: Most children with spina bifida now survive into adulthood, although most have neuropathic bladder with potential complications of incontinence, infection, renal damage and diminished quality of life. In this study we sought to 1) describe contemporary bladder management and continence outcomes of adults with spina bifida, 2) describe differences from younger individuals and 3) assess for association with socioeconomic factors. MATERIALS AND METHODS: We analyzed data on bladder management and outcomes in adults with spina bifida from the National Spina Bifida Patient Registry. A strict definition of continence was used. Results were compared to young children (age 5 to 11 years) and adolescents (12 to 19). Statistical analysis compared cohorts by gender, ethnicity, spina bifida type, lesion level, insurance status, educational attainment, employment status and continence. RESULTS: A total of 5,250 patients with spina bifida were included, of whom 1,372 (26.1%) were adults. Of the adult patients 45.8% did not take medication, but 76.8% performed clean intermittent catheterization. Continence was decreased in adults with myelomeningocele (45.8%) vs those with nonmyelomeningocele spina bifida (63.1%, p <0.0001). Continence rates were higher in the older cohorts with myelomeningocele (p <0.0001) but not in those with nonmyelomeningocele spina bifida (p = 0.1192). Bladder management and history of urological surgery varied among age groups. On univariate analysis with spina bifida related or socioeconomic variables continence was significantly associated with educational level but on multivariable logistic regression analysis bladder continence was significantly associated with employment status only. CONCLUSIONS: Bladder management techniques differ between adults and children with spina bifida. Bladder continence outcomes were better in adults, with nearly half reporting continence. Continence was significantly associated with employment status in patients age 25 years or older.

Bladder Reconstruction Rates Differ among Centers Participating in National Spina Bifida Patient Registry.

PURPOSE: We performed an exploratory analysis of data from the NSBPR (National Spina Bifida Patient Registry) to assess variation in the frequency of bladder reconstruction surgeries among NSBPR centers. MATERIALS AND METHODS: We queried the 2009-2014 NSBPR to identify patients who had ever undergone bladder reconstruction surgeries. We evaluated demographic characteristics, spina bifida type, functional level, mobility and NSBPR center to determine whether any of these factors were associated with reconstructive surgery rates. Multivariable logistic regression was used to simultaneously adjust for the impact of these factors. RESULTS: We identified 5,528 patients with spina bifida enrolled in the NSBPR. Of these patients 1,129 (20.4%) underwent bladder reconstruction (703 augmentation, 382 continent catheterizable channel, 189 bladder outlet procedure). Surgical patients were more likely older, female, nonHispanic white, with a higher lesion level, myelomeningocele diagnosis, nonambulators (all p <0.001) and nonprivately insured (p=0.018). Bladder reconstruction surgery rates varied among NSBPR centers (range 12.1% to 37.9%, p <0.001). After correcting for known confounders NSBPR center, spina bifida type, mobility, gender and age (all p <0.001) were significant predictors of surgical intervention. Race (p=0.19) and insurance status (p=0.11) were not associated with surgical intervention. CONCLUSIONS: There is significant variation in rates of bladder reconstruction surgery among NSBPR centers. In addition to clinical factors such as mobility status, lesion type and lesion level, nonclinical factors such as patient age, gender and treating center are also associated with the likelihood of an individual undergoing bladder reconstruction.

Interrater Reliability in Interpretation of Neuropathic Pediatric Urodynamic Tracings: An Expanded Multicenter Study.

PURPOSE: Urodynamic findings often guide treatment for neuropathic bladder and are reported as objective data points in multi-institutional trials. However, urodynamic interpretation can be variable. In a pilot study pediatric urologists interpreting videourodynamics exhibited only moderate agreement despite similar training and practice patterns. We hypothesized the pilot study variability would be replicated in a multi-institutional study. MATERIALS AND METHODS: We developed an anonymous electronic survey that contained 20 scenarios, each with a brief patient history, 1 urodynamic tracing and fluoroscopic imagery. All videourodynamics were completed during routine care of patients with neuropathic bladder at a single institution. Pediatric urologists from Centers for Disease Control and Prevention Urologic Protocol sites were invited to complete an interpretation instrument for each scenario. Fleiss kappa and 95% confidence limits were reported, with Fleiss kappa 1.00 corresponding to perfect agreement. RESULTS: The survey was completed by 14 pediatric urologists at 7 institutions. Substantial agreement was seen for assessment of fluoroscopic bladder shape (Fleiss kappa 0.73), while moderate agreement was observed for assessment of bladder safety, end filling detrusor pressure and bladder capacity (Fleiss kappa 0.50, 0.56 and 0.54, respectively). Fair agreement was seen for electromyographic synergy and presence of detrusor overactivity (Fleiss kappa 0.21 and 0.35, respectively). CONCLUSIONS: Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida.

PURPOSE: Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. MATERIALS AND METHODS: In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. RESULTS: An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. CONCLUSIONS: The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements.

Utility of urodynamics in the management of asymptomatic tethered cord in children.

BACKGROUND: We have noted a recent increase in neurosurgical requests at our institution for urodynamics (UDS) prior to release of asymptomatic tethered cord. Our aim was to determine how preoperative UDS results are used in the clinical management of asymptomatic tethered cord. METHODS: A retrospective review was performed of 120 patients diagnosed with primary tethered cord from 2007 to 2010. Inclusion criteria included MRI diagnosis of tethered cord and UDS performed by three pediatric urologists. Excluded were any neurologic or urologic dysfunction or associated syndromes, as well as other significant comorbidities. RESULTS: Thirty-eight patients (female 26; male 12), mean age of 3 years (0.2-16.3) were diagnosed with an asymptomatic tethered cord. The majority of the patients had normal preoperative renal ultrasounds. Thirty-one (82 %) of the children had normal baseline UDS, yet twenty-one (68 %) of these patients still underwent neurosurgical intervention. Of the 27 patients untethered, 15 patients (55 %) had follow-up UDS performed. Three patients had improved UDS parameters and one had worsening UDS parameters, including high PVR and DSD. Of the seven patients with abnormal baseline UDS, all had normal renal ultrasound findings and had no other significant differences in presentation from the patients with normal UDS. CONCLUSION: In children with asymptomatic tethered cord, abnormal preoperative UDS may prompt intervention, while normal UDS do not appear to prevent intervention. There is no significant correlation between abnormal preoperative UDS and abnormal preoperative imaging. Further study is needed to evaluate the utility of this procedure in the preoperative setting in this asymptomatic patient population.

Autologous cell seeded biodegradable scaffold for augmentation cystoplasty: phase II study in children and adolescents with spina bifida.

PURPOSE: Augmentation cystoplasty using gastrointestinal segments in children/adolescents with medically refractory neurogenic bladder is associated with significant complications. We evaluated an autologous cell seeded biodegradable scaffold (Tengion®) for bladder augmentation as an alternative to traditional enterocystoplasty in this population. MATERIALS AND METHODS: A phase II prospective study was performed in children with neurogenic bladder due to spina bifida requiring enterocystoplasty for detrusor pressure 40 cm H2O or greater despite maximum antimuscarinic medication. Following open bladder biopsy, urothelial and smooth muscle cells were grown ex vivo and seeded onto a biodegradable scaffold to form a regenerative augment as the foundation for bladder tissue regeneration. Bladder neck sling was the only concomitant surgical procedure permitted. Bladders were cycled postoperatively to promote regeneration. Primary and secondary outcomes at 12 months included change in bladder compliance, bladder capacity and safety. Long-term assessment was done with similar outcomes at 36 months. RESULTS: Compliance improved in 4 patients at 12 months and in 5 patients at 36 months, although the difference was not clinically or statistically significant. There was no clinical or statistical improvement in bladder capacity at 12 or 36 months in any patient. Adverse events occurred in all patients, and most were easily treated. Two patients had low cell growth following bladder biopsy, of whom 1 withdrew from the study and 1 underwent a second biopsy. Serious adverse events of bowel obstruction and/or bladder rupture occurred in 4 patients. CONCLUSIONS: Our autologous cell seeded biodegradable scaffold did not improve bladder compliance or capacity, and our serious adverse events surpassed an acceptable safety standard.

Radiation exposure in pediatric videourodynamics: An evaluation of safety in comparison to voiding cystourethrogram.

INTRODUCTION: Children with spina bifida (SB) undergo a videourodynamic study (VUDS) or urodynamic study and voiding cystourethrogram (VCUG). A standardized protocol for imaging during a pediatric VUDS has not been established. Our aim is to quantify radiation exposure and establish a baseline for children with spina bifida (SB) undergoing VUDS in current practice at our institution. METHODS: This is a retrospective study from 2013 to 2020 of consecutive pediatric SB patients undergoing VUDS by a single provider. Patients were categorized into three groups based on age; group 1 (0-2 YR), group 2 (2-10 YR), group 3 (>10 YR). Radiation data was reported as mean air kerma (AK), dose area product (DAP) and exposure time (seconds). Effective dose (ED) was calculated based on radiation quantity (Air Kerma, AK) and organ sensitivity. The lifetime attributable risk (LAR) was calculated based on AK and a risk coefficient. Data points calculated for patients undergoing VUDS were then compared to age matched institutional VCUG data in the same age groups. RESULTS: 398 patients undergoing VUDS met inclusion criteria and 262 independent patients underwent VCUG. ED increased with age in both VUDS and VCUG. All VCUG groups were found to have a higher ED than VUDS. The LAR for VUDS groups 1-3 was 0.001, 0.002, and 0.006, respectively. Reported in percentages, there is a 0.1%, 0.2%, and 0.6% chance, respectively, of age groups 1, 2 and 3 developing cancer as a result of the radiation exposure from a VUDS. DISCUSSION: Our study found that ED was low across all age groups for VUDS, comparing favorably to the VCUG groups. VCUG was selected as a benchmark comparison for its diagnostic similarities and, at times, overlapping indications. Few studies have described ED with respect to VUDS or extrapolate the ED of VUDS into LAR in the pediatric population. We recognize that we have not determined the true ED of the gonads and bladder, rather we have overestimated, as the data is based on an international reference point proximal to the exposed individual. However, LAR was calculated for each age group and revealed that patients are at a negligible increased risk of developing malignancy secondary to exposure compared to the general population. CONCLUSION: Our current practice for pediatric VUDS has exhibited consistently low radiation exposure amongst all age groups. Moving forward, we have the foundation and flexibility to create an imaging protocol for pediatric VUDS, while taking more calculated steps toward incorporating ALARA, as low as reasonably achievable, principles. A protocol adhering to the ALARA principle could provide consistency across institutions and aid in multi-institutional studies.

Effect of the American Urological Association Annual Review course on the results of the urology qualifying examination.

PURPOSE: In this study we assess the impact of a urology dedicated review course on the scores of the corresponding board qualifying examination for attendees of the urology review course. MATERIALS AND METHODS: The ABU (American Board of Urology) Qualifying Examination scores from 2009, 2010 and 2011 were categorized into group 1 candidates who attended the AUA (American Urological Association) Annual Review Course the same year, and group 2 candidates who did not attend the AUA Annual Review Course that same year, and were compared. The scores of the preceding year's In-Service Examination were also compared for the same groups of candidates and compared to their subsequent first time taken Qualifying Examination scores. RESULTS: There was no difference in Qualifying Examination scores of resident candidates attending vs not attending the AUA Annual Review Course in all 3 years. The overall failure rate was low, and essentially the same for all candidates in all years regardless of attendance at the AUA Annual Review Course at 2% in 2009, 2% in 2010 and 4% in 2011. Of group 1 candidates the majority (80% to 98%) considered the Annual Review Course helpful or very helpful in preparation for the Qualifying Examination. CONCLUSIONS: The majority of candidates are adequately prepared to pass their Qualifying Examination at the conclusion of their residency training program regardless of their attendance of the AUA Annual Review Course. This course may help bolster the confidence of the candidate preparing for their Qualifying Examination.

Do chief resident scores on the in-service examination predict their performance on the American Board of Urology Qualifying Examination?

PURPOSE: The American Urological Association In-Service Examination and the American Board of Urology Qualifying Examination are written multiple choice tests that cover all domains in urology. We investigated whether In-Service Examination performance could identify chief residents who scored in the lowest quartile on the Qualifying Examination. MATERIALS AND METHODS: All urology chief residents in the United States and Canada in 2008 and 2009 were eligible to participate in this study. In-Service Examination 2008 and Qualifying Examination 2009 performance data were obtained from the American Urological Association and American Board of Urology, respectively. Data were analyzed with the Pearson correlation and descriptive statistics. RESULTS: Of the 257 American and Canadian chief residents who completed the Qualifying Examination 2009, 194 (75%) enrolled in this study and were included in analysis. Overall In-Service Examination 2008 scores correlated significantly with Qualifying Examination 2009 scores (r=0.55, p<0.001), accounting for 30% of score variance. Substantial variability in In-Service Examination-Qualifying Examination rankings was notable among individual residents. An In-Service Examination 2008 cutoff percentile rank of 40% identified chief residents in the lowest quartile on the Qualifying Examination 2009 with 71% sensitivity, 77% specificity, and a likelihood ratio of 3.1 and 0.4 (positive and negative likelihood ratios, respectively). CONCLUSIONS: The substantial variability of In-Service Examination-Qualifying Examination performance among individual chief residents limits In-Service Examination predictive utility. A single In-Service Examination score should not be used to make a high stakes judgment about an individual resident. In-Service Examination scores should be used as 1 part of an overall evaluation program to prospectively identify residents who could benefit from additional educational support.

Urodynamic utilization in the adult spina bifida patient: An institutional review.

PURPOSE: To characterize common clinical indications for urodynamic, a bladder function test, in adults with spina bifida. METHODS: A retrospective chart review was performed for 215 patients seen in an adult multidisciplinary spina bifida clinic who were registered with the National Spina Bifida Patient Registry from October 2011 to October 2018. Descriptive statistics were used for statistical comparisons. RESULTS: A total of 52 of 215 patients developed a clinical indication for urodynamics. Of these, 71 (33%) patients (8 of whom underwent testing twice) had urodynamics performed, resulting in a total of 79 urodynamic study encounters that were analyzed. Thirty-four (43%) urodynamic testing cases were performed due to a symptomatic change in lower urinary tract function; 14 (18%) were due to declining renal function or concern for upper tract deterioration based on imaging. The data obtained from urodynamic investigation led to new recommendations for urinary tract management in 59 (75%) of the urodynamic studies performed. A total of 32 of the 90 (35%) recommendations made were surgical interventions and 30 (33%) were for a change in medical management. Interestingly, 8 of the 18 (44%) routine or baseline urodynamic tests performed led to new recommendations in urinary tract management. CONCLUSION: A total of 24%of patients in the multidisciplinary spina bifida clinic developed an indication for urodynamic testing over a 7-year period which resulted in new recommendations for urinary tract management in most. As more patients with spina bifida enter adulthood, the indications for urodynamic evaluation may become more defined, since the results often lead to alterations in bladder management.

Translating pediatric urodynamics from clinic into collaborative research: Lessons and recommendations from the UMPIRE study group.

Pediatric patients present unique challenges in the performance and interpretation of urodynamic studies. Interpretation of urodynamics to guide clinical management at an institutional level is accepted as reliable. Challenges arise however when multi-site collaborations incorporate urodynamics into study design to determine primary or secondary outcomes or to direct decision-making. Although standardized terminology has been established by ICCS, the application of this shared language to performance and interpretation of pediatric urodynamics to across multiple sites may not be intuitive or reliable. With a primary goal of defining the care necessary to protect future renal function, the UMPIRE protocol (Urologic Management to Preserve Initial REnal function) utilizes a urodynamics-based risk stratification to determine medical management for infants with myelomeningocele. Iterative changes in the protocol are based upon the clinical progress of the enrolled children. Despite a team experienced in subtleties of urodynamics and despite efforts to minimize variability across sites, the UMPIRE study group identified several areas in which the language of urodynamics required additional clarification or creation of more explicit definitions to standardize performance and interpretation across sites. This article reviews the foundations of current urodynamics practice, describes limitations and challenges unique to pediatric studies, and the shares the humble lessons learned by the UMPIRE study group on their journey toward standardized urodynamic language for management of infants and children with myelomeningocele.

Urodynamic characteristics of neurogenic bladder in newborns with myelomeningocele and refinement of the definition of bladder hostility: Findings from the UMPIRE multi-center study.

INTRODUCTION: Infants with myelomeningocele are at risk for chronic kidney disease caused by neurogenic bladder dysfunction. Urodynamic evaluation plays a key role to risk stratify individuals for renal deterioration. OBJECTIVE: To present baseline urodynamic findings from the Urologic Management to Preserve Initial Renal function for young children with spina bifida (UMPIRE) protocol, to present the process that showed inadequacies of our original classification scheme, and to propose a refined definition of bladder hostility and categorization. STUDY DESIGN: The UMPIRE protocol follows a cohort of newborns with myelomeningocele at nine children's hospitals in the United States. Infants are started on clean intermittent catheterization shortly after birth. If residual volumes are low and there is no or mild hydronephrosis, catheterization is discontinued. Baseline urodynamics are obtained at or before 3 months of age to determine further management. Based on protocol-specific definitions, urodynamic studies were reviewed by the clinical site in addition to a central review team; and if necessary, by all site urologists to achieve 100% concurrence. RESULTS: We reviewed 157 newborn urodynamic studies performed between May 2015 and September 2017. Of these 157 infants, 54.8% were boys (86/157). Myelomeningocele closure was performed in-utero in 18.4% (29/157) and postnatally in 81.5% (128/157) of newborns. After primary review, reviewers agreed on overall bladder categorization in 50% (79/157) of studies. Concurrence ultimately reached 100% with further standardization of interpretation. We found that it was not possible to reliably differentiate a bladder contraction due to detrusor overactivity from a volitional voiding contraction in an infant. We revised our categorization system to group the "normal" and "safe" categories together as "low risk". Additionally, diagnosis of detrusor sphincter dyssynergia (DSD) with surface patch electrodes could not be supported by other elements of the urodynamics study. We excluded DSD from our revised high risk category. The final categorizations were high risk in 15% (23/157); intermediate risk in 61% (96/157); and low risk in 24% (38/157). CONCLUSION: We found pitfalls with our original categorization for bladder hostility. Notably, DSD could not be reliably measured with surface patch of electrodes. The effect of this change on future renal outcomes remains to be defined.

Outcome after discontinuing prophylactic antibiotics in children with persistent vesicoureteral reflux.

PURPOSE: Treatment for vesicoureteral reflux remains controversial. Lacking an evidence-based treatment protocol, we offered the option of terminating prophylactic antibiotics in otherwise healthy patients with persistent vesicoureteral reflux at age 5 years or greater. We report outcomes with respect to the urinary tract infection incidence and to whether surgical intervention was eventually done. MATERIALS AND METHODS: We obtained institutional review board approval to retrospectively review the records of all children with vesicoureteral reflux from December 1999 to February 2009. Of this group we selected children 5 years old or older who had been taken off prophylactic antibiotics. We assessed children with primary vesicoureteral reflux in detail. RESULTS: The records of 1,217 that we reviewed showed that antibiotics were discontinued in 185 patients, including 160 girls (89%) and 25 boys (11%), at an average age of 6.2 years. Average followup was 2.0 years with recorded followup up to 8 years off prophylaxis. In 50 girls (91%) and 5 boys (9%), urinary tract infection developed after discontinuing prophylaxis. Correction was done in 57 patients, including open repair in 34 and endoscopic injection in 23. Two patients underwent intervention at parent request after an average of 0.7 years of uneventful observation. We identified no parameter predicting patients at risk for urinary tract infection. CONCLUSIONS: Urinary tract infection develops in 29% of patients 5 years old or older with persistent vesicoureteral reflux within 2 years after the cessation of prophylaxis. Most of these cases are febrile. Discontinuing antibiotics is reasonable but a prospective, randomized, long-term, multi-institutional trial is required to determine whether this approach is beneficial.

Sirolimus therapy for fibromatosis and multifocal renal cell carcinoma in a child with tuberous sclerosis complex.

A male with tuberous sclerosis complex (TSC) developed a chest wall fibromatosis and bilateral multifocal renal cell carcinoma (RCC). The fibromatosis tumor was initially resected during infancy but recurred 5 years later. At that time, bilateral RCC was also detected, leading to the resection of the more extensively affected right kidney. In an attempt to avoid bilateral nephrectomies, the patient was treated with the mTOR inhibitor sirolimus. Within 6 months of therapy, the fibromatosis and remaining RCC tumors responded substantially with minimal adverse effects.