Faculty of 1000 evaluations

Journal of Pediatric Urology (2012) 8, 214e217

Faculty of 1000 evaluations* Antibiotic prophylaxis for urinary tract infections in children with spina bifida on intermittent catheterization Zegers B, Uiterwaal C, Kimpen J, van Gool J, de Jong T, Winkler-Seinstra P, Houterman S, Verpoorten C, de Jongde Vos van Steenwijk C (J Urol. 2011 Dec; 186(6):2365e70) PURPOSE: Antibiotic prophylaxis (low dose chemoprophylaxis) has been prescribed since the introduction of clean intermittent catheterization in children with spina bifida. We hypothesized that stopping low dose chemoprophylaxis does not increase the number of urinary tract infections in these patients. MATERIALS AND METHODS: A total of 176 patients with spina bifida participated in a randomized controlled trial (ISRCTN trial number 56278131) of either continuation or discontinuation of low dose chemoprophylaxis. During the 18-month study period biweekly urine samples were evaluated for leukocyturia and bacteriuria with dipsticks and cultures. Asymptomatic significant bacteriuria (positive culture results without clinical symptoms) and urinary tract infections (significant bacteriuria with clinical symptoms and leukocyturia) were analyzed. RESULTS: Discontinuation of low dose chemoprophylaxis resulted in higher rates of asymptomatic significant * Faculty of 1000: Post-publication peer review. The core service of Faculty of 1000 (F1000) identifies and evaluates the most important articles in biology and medical research publications. The selection process comprises a peer-nominated global ’Faculty’ of the world’s leading scientists and clinicians who rate the best of the articles they read and explain their importance. For more details, visit http://f1000.com

1477-5131/$36 doi:10.1016/j.jpurol.2012.01.003

bacteriuria (incidence rate ratio 1.23, 95% CI 1.08e1.40, p Z 0.002) and urinary tract infection (IRR 1.44, 95% CI 1.13e1.83, p Z 0.003). For urinary tract infection the number needed to harm was 2.2, that is if 2 patients discontinued low dose chemoprophylaxis for a year, 1 extra urinary tract infection would result. Febrile urinary tract infection occurred once in every 30 patient-years and slightly more often in the discontinuation group (relative risk 2.0, 95% CI 0.38e10.6, p Z 0.4). Of 88 patients allocated to discontinuation of low dose chemoprophylaxis 38 (43%) switched back to chemoprophylaxis. The urinary tract infection rate was nonsignificantly higher in the presence of vesicoureteral reflux. Male gender and a low pre-study rate of urinary tract infection predicted successful discontinuation. CONCLUSIONS: Patients with spina bifida on clean intermittent catheterization and antibiotic prophylaxis for urinary tract infections can safely discontinue this prophylaxis, in particular males, patients with low urinary tract infection rates and patients without vesicoureteral reflux. F1000 evaluation by Rosalia Misseri, USA With increasing rates of bacterial resistance to antibiotics, the decision to use antibiotic prophylaxis is sometimes challenging, particularly in patients at long-term (lifelong) risk of infections such as individuals with spina bifida. The authors hypothesized that stopping low-dose chemoprophylaxis in patients with spina bifida who catheterize intermittently does not increase the number of urinary tract infections (UTIs) in these patients and found that males and those with low UTI rates can safely discontinue antibiotic prophylaxis. A total of 176 patients were randomized to either continuation or discontinuation of low-dose

Faculty of 1000 evaluations chemoprophylaxis and were studied for 18 months. Rates of asymptomatic significant bacteriuria and UTI increased in the discontinued group. Febrile urinary tract infection occurred once in every 30 patient-years and only slightly more in the discontinuation group. Despite this, 43% of patients in whom antibiotics were discontinued were switched back to chemoprophylaxis. They did find that male gender and a low pre-study rate of UTI predicted successful discontinuation. This study allows us to be more selective in our use of chemoprophylaxis, possibly decreasing antimicrobial resistance in this high-risk group. Trial registration: 56278131 http://f1000.com/13404964 (c) Faculty of 1000 Ltd. Long-term urological impact of fetal myelomeningocele closure Clayton DB, Tanaka ST, Trusler L, Thomas JC, Pope JC, Adams MC, Brock JW (J Urol. 2011 Oct; 186(4 Suppl):1581e5) PURPOSE: Between 1997 and 2002 a large number of fetal myelomeningocele closures were performed at our institution. Previously early reports showed little improvement in neonatal bladder function after fetal back closure. We evaluated the long-term urological impact of this procedure. MATERIALS AND METHODS: Using a combination of retrospective review and survey questionnaire we reviewed the records of 28 patients in whom fetal myelomeningocele closure was done at our institution between 1997 and 2002. The areas addressed included medical management for neurogenic bladder and bowel, need for lower urinary tract reconstruction and functional bladder assessment by videourodynamics. Parameters after fetal myelomeningocele closure were compared to those of 33 age and sex matched patients with myelomeningocele who underwent standard postnatal closure. RESULTS: We reviewed the records of 28 patients after fetal myelomeningocele closure. At a mean age of 9.6 years 23 used clean intermittent catheterization to manage the bladder, 24 required a bowel regimen to manage constipation and 6 underwent lower urinary tract reconstruction with enterocystoplasty and a catheterizable bladder channel. Videourodynamics performed in 14 patients at a mean age of 7.4 years revealed decreased bladder capacity in 71%, detrusor overactivity in 35% and increased detrusor pressure in 25%. Compared to age and sex matched children who underwent postnatal closure we noted no significant differences in bladder management, urinary tract surgery or urodynamics. CONCLUSIONS: Neurogenic bowel and bladder management continues to be a significant issue for patients after fetal myelomeningocele closure. After fetal surgery patients should be followed closely, similar to patients who undergo postnatal closure. F1000 evaluation by Earl Cheng, USA This is an important article that is very timely in light of the recent article from the Management of Myelomeningocele Study (MOMS), which has demonstrated that there are definable neurologic benefits with prenatal closure. The urologic data that truly define outcome with regard to bladder function and continence from the MOMS

215 trial will not likely be out for many years. However, this study allows us to look at the preliminary data from a patient cohort that had prenatal closure (that predates the MOMS trial) at one of the centers that is participating in the MOMS trial. These data suggest that there are no major benefits for bladder function from prenatal closure. While the data from the MOMS trial will be more definitive in defining the urologic differences that may result in prenatal closure, these data are important to know when counseling expectant mothers with a fetus with myelomeningocele (MM) on the pros and cons of prenatal closure. References: {1} Adzick et al. N Engl J Med 2011, 364:993e1004 [PMID:21306277]. http://f1000.com/13372966 (c) Faculty of 1000 Ltd. Gender assignment for newborns with 46XY cloacal exstrophy: a 6-year followup survey of pediatric urologists Diamond DA, Burns JP, Huang L, Rosoklija I, Retik AB (J Urol. 2011 Oct; 186(4 Suppl):1642e8) PURPOSE: Gender assignment for newborns with ambiguous genitalia remains a challenge. An initial survey of colleagues on this subject was performed in 2004. Our objective was to understand the basis for the attitudes and practices of pediatric urologists in regard to gender assignment for 46XY cloacal exstrophy in a 6-year followup survey. MATERIALS AND METHODS: A survey on a case of 46XY cloacal exstrophy was completed by 191 of the 263 fellows (73%) in the Urology Section, American Academy of Pediatrics. Questions referred to gender assignment, surgery timing, clinical outcomes and respondent demographics. RESULTS: Of the fellows 79% favored male gender assignment. The most important factor in male assignment remained androgen brain imprinting (97%) while in female assignment it was surgical success in creating functional genitalia (96%). Respondent characteristics associated with assigning female gender were longer practice duration (greater than 15 years) (p < 0.03), having trained in programs where female gender was always or usually assigned (p < 0.02) and not being a fellowship program director (0 of 27 respondents, p < 0.03). There was an evolution among respondents from female gender assignment earlier in the career to male assignment currently (p < 0.0001). CONCLUSIONS: Most pediatric urologists favor male gender assignment for 46XY cloacal exstrophy, which is a significant increase in 6 years. This change represents an evolution from female to male gender assignment and virtual unanimity among fellowship directors to gender assign male. Longer practicing clinicians perceived better outcomes for female gender assignment. If this reflects true clinical outcomes, the trend toward the eventual disappearance of female gender assignment for 46XY cloacal exstrophy is concerning. F1000 evaluation by Earl Cheng, USA This article reports the interesting results of a repeat survey of pediatric urologists; it demonstrates that views

216 are changing with regard to gender assignment in patients with cloacal exstrophy. Based upon the landmark work of Reiner et al. and subsequent discussions of this topic at major meetings, the results of this survey show that there is now a strong trend towards male gender assignment in these patients. This represents a paradigm shift in thinking from decades ago. However, some more experienced and ’seasoned’ pediatric urologists still favor a female gender assignment. Whether this represents a view that is based on valuable objective observations over the years and should be looked upon as ’words of wisdom’ or whether this represents a subjective bias that is based on a different era of training is not clear. The results of this survey highlight the changing views on an extremely controversial topic with significant clinical implications. It also demonstrates the critical need for long-term objective studies that better define the factors that are most important in helping to make a gender assignment in this unique patient population. http://f1000.com/13372967 (c) Faculty of 1000 Ltd. Pediatric testicular torsion epidemiology using a national database: incidence, risk of orchiectomy and possible measures toward improving the quality of care Zhao LC, Lautz TB, Meeks JJ, Maizels M (J Urol. 2011 Nov; 186(5):2009-13) PURPOSE: Testicular torsion causes considerable morbidity in the pediatric population but the societal burden is poorly quantified. We determined the modern incidence of testicular torsion as well as the current rates of orchiectomy and attempted testicular salvage, and identified the risk factors for testicular loss. MATERIALS AND METHODS: A cohort analysis was performed of 2,443 boys (age 1 month to less than 18 years) and 152 newborns who underwent surgery for testicular torsion in the 2000, 2003 and 2006 Healthcare Cost and Utilization Project Kids’ Inpatient Database. Patient and hospital characteristics predictive of orchiectomy vs attempted testicular salvage were analyzed. RESULTS: There was a bimodal distribution of testicular torsion with peaks in the first year of life and in early adolescence. The overall mean age  SD at presentation was 10.6  5.8 years. The estimated yearly incidence of testicular torsion for males younger than 18 years old was 3.8 per 100,000. Orchiectomy was performed in 41.9% of boys undergoing surgery for torsion. The adjusted odds ratio for orchiectomy was highest for children in the youngest age quartile (younger than 10 years old, OR 1.58, 95% CI 1.252.00). Additional independent predictors of orchiectomy included Medicaid insurance (OR 1.39, 95% CI 1.14-1.69), black race (OR 1.33, 95% CI 1.04-1.71), nonemergency room admission source (OR 1.97, 95% CI 1.60-2.42) and surgery at a children’s hospital or unit (OR 1.64, 95% CI 1.36-1.98). CONCLUSIONS: Testicular torsion is uncommon but the rate of orchiectomy is high, especially in the youngest patients. F1000 Evaluation by Michael Ost and Janelle Fox, USA This article caught my attention for the finding of higher orchiectomy rates with testicular torsion in younger children, <1 year of age, after excluding all cases of presumed

Faculty of 1000 evaluations extravaginal torsion by limiting data to children >1 month of age. This is in contrast to prior reports of higher orchiectomy rates in older children {1}, although a mechanism for the spike in presumed intravaginal torsion in infants is not well defined. One could theorize whether these are indeed not extravaginal torsions occurring outside the expected first month of life window, perhaps underlying early bellclapper deformities, or whether the testosterone surge and testicular growth in the infant may impact higher torsion rates. It would make sense that orchiectomy rates may be higher in children unable to articulate their pain. The authors showed an estimate yearly incidence of testicular torsion in children of 3.8 per 100,000 boys aged <18, using the Kids’ Inpatient Database (KID). In addition, children <10 years old, predominantly represented by children >1 month of age but <1 year old, had higher orchiectomy rates than older children. Multivariate analysis found statistically higher orchiectomy rates among patients with Medicaid insurance, patients not presenting through an emergency room (ER), those seen in Southern or Midwestern US hospitals and African American children. I would like to see future investigations include the following: 1) The mechanism of testicular torsion in the population of infants aged >1 month but <1 year old that account for the majority of orchiectomies, i.e. is there a greater incidence of bell-clapper deformity or are extravaginal torsions occurring beyond the expected <1 month of age window? 2) Why does the type of insurance affect testicular torsion outcomes, i.e. what are the triage times, modes of presentation (ER, clinic, hospital transfer requirement) and ability to access prompt healthcare? 3) What is the ‘time to treatment’ in different areas of the country? Is this related to geographic hospital or urologist concentration? 4) What is the average ‘time to treatment’ at children’s vs. non-children’s hospitals? What is the average time to an urologist’s arrival and what is the ER waiting time? Is the use of preoperative ultrasound delaying surgery? Acknowledgements: I would like to thank Steven Docimo (Children’s Hospital of Pittsburgh) for his assistance in the preparation of this evaluation. References: {1} Mansbach et al. Arch Pediatr Adolesc Med 2005, 159:1167-71 [PMID:16330742]. http://f1000.com/13372969 (c) Faculty of 1000 Ltd. Safety, efficacy and health related quality of life of autologous myoblast transplantation for treatment of urinary incontinence in children with bladder exstrophyepispadias complex Elmi A, Kajbafzadeh AM, Tourchi A, Talab SS, Esfahani SA (J Urol. 2011 Nov; 186(5):2021e6) PURPOSE: Children with bladder exstrophyeepispadias complex undergoing endourethral autologous myoblast transplantation to treat urinary incontinence were evaluated

Faculty of 1000 evaluations at 4 years of followup regarding the safety, efficacy and durability of the procedure, and health related quality of life. MATERIALS AND METHODS: Seven boys underwent autologous myoblast transplantation between May and December 2006. All patients had persistent urinary incontinence after bladder neck reconstruction and bulking agent injection. Patients were followed for 4 years after autologous myoblast transplantation regarding clinical outcomes and cystometric, urodynamic, uroflowmetric and urethrocystoscopic evaluations. Health related quality of life was also measured before treatment and at final followup. RESULTS: No evidence of urinary obstruction was observed. Five children (71%) were completely continent and 2 (29%) were socially dry with complete daytime dryness at final followup. Health related quality of life was improved significantly. Urodynamic studies revealed a progressive increase in bladder capacity (p < 0.001). Mean detrusor leak point pressure showed a 27 cm H(2)O (158%) increase during 4-year followup. Uroflowmetry parameters of voided volume and average maximum flow rate were improved significantly (p < 0.001). CONCLUSIONS: The 4-year outcomes demonstrate that autologous myoblast transplantation for urinary incontinence in children with bladder exstrophyeepispadias complex is relatively reliable, reproducible, safe and effective with minimal morbidity. This novel treatment represents a promising therapeutic approach in patients with urinary incontinence. Further randomized trials with larger numbers of patients and longer followup are needed. F1000 evaluation by Bassem Wadie, Egypt This study is an extended followup of a previous study on an important subject by the same group of authors. Treatment of post-exstrophy repair incontinence is very tricky. Many techniques are out there, while cure is still a long way off. In this interesting report, autologous myoblast injection was shown to be effective and durable. The authors followed a group of children with previous exstrophy repair (seven boys and one girl) were subjected to autologous transurethral myoblast injection at the site

217 of the rhabdosphincter. The average number of myoblasts injected was 7e40 million cells. The girl did not show clinical improvement, while all boys did. At 15 months after injection, four boys were socially dry, while three were completely dry (being socially dry was defined according the authors as having dry intervals of 3 h or more during the day with or without nocturnal enuresis). At 4 years, five boys were considered completely dry and two were socially dry. A positive point about the study was the use of a selfreported questionnaire to evaluate the quality of life of the children and their parents. However, when reading this manuscript, one should be cautious about two points: the first is the urodynamics definition of ’bladder stability’ the authors adopted. Absence of uninhibited contractions of 15cmH2O or greater is an old definition. Since 2002, the International Continence Society (ICS) has recommended that any increase of detrusor pressure during voiding should be classified as instability. Therefore, the authors might have underestimated the presence of detrusor overactivity in their patients. In table 3, the authors depict detrusor leak point pressure in all patients at different intervals. This means that their patients are not as ’completely dry’ as stated in their results. A child leaking at a pressure of 40 or 45cmH2O could not be truly dry at different daily activities. The second point is the effect of time, especially in boys with exstrophy. Children followed over 5 years might have some improvement, especially with the growth of prostatic tissue. Although the long-term followup is quite admirable, the effect of time on the outcome measured (continence) can not be ignored. It is noteworthy that myoblast injection for sphincteric incompetence needs some time in order to give rise to solid improvement. This has been shown before in the work of Mitterberger et al. {1}. Despite these limitations, this is nevertheless an important study in an area where effective treatments are hard to come by. References: {1} Mitterberger et al. J Urol 2008, 179:226e31 [PMID:18001790]. http://f1000.com/13364976 (c) Faculty of 1000 Ltd.