Intradetrusor botox injection and augmentation cystoplasty trends among spina bifida patients at US freestanding children's hospitals.

INTRODUCTION: Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. OBJECTIVE: We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. STUDY DESIGN: We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. RESULTS: In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend. DISCUSSION: Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. CONCLUSIONS: Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

Accuracy of contrast-enhanced voiding urosonography using Optison™ for diagnosis of vesicoureteral reflux in children.

BACKGROUND: There is limited quality of evidence regarding the accuracy of contrast-enhanced voiding urosonography (ceVUS) for diagnosis of vesicoureteral reflux (VUR) compared to fluoroscopic voiding cystourethrography (VCUG), and minimal data on the use of the ultrasound contrast agent Optison™ for this purpose. OBJECTIVE: To compare the accuracy of ceVUS using Optison™ to VCUG, and to assess inter-rater agreement regarding presence and grading of VUR. STUDY DESIGN: In this retrospective investigation, all sequential ceVUS with Optison™ and VCUG studies performed in children between 2014 and 2017 were reviewed. Two raters independently graded all ceVUS studies using a 5-point scale. CeVUS sensitivity and specificity were estimated separately for each rater using the VCUG report as the ground truth for presence and degree of VUR. Logistic and ordinary linear regression models assessed rater-report agreement and inter-rater agreement for each kidney, Optison™ dose, and referral diagnosis. RESULTS: 97 children (51 females) with 101 paired studies were included. Sensitivity and specificity of ceVUS for VUR detection were identical for both raters: right kidney 75%/90.9%; left kidney 85.7%/78.9% (Figure). There was no statistically significant difference in disagreement between raters and the VCUG report for the right or left kidney. Inter-rater agreement on ceVUS grading was 90% and 88% for right and left kidneys, respectively. There was a significant negative association between fetal hydronephrosis vs urinary tract infection and disagreement between Rater 2 and the VCUG report for the left kidney. There were no other significant associations with respect to either kidney, Optison™ dose, or referral diagnosis. DISCUSSION: Our study showed that detection of VUR with ceVUS and Optison™ is comparable to fluoroscopic VCUG. Based on the VCUG reports, the incidence of VUR in our patient population was substantially lower than in the meta-analysis of Chua et al. and in the study of Kim et al. The explanation for the large discrepancy in VUR incidence may reflect differences in the patient populations, and in our reporting of VUR with respect to kidney number rather than to pelviureteral units. Study limitations include its retrospective nature and potential bias in terms of patient selection. Since VUR is an intermittent phenomenon, sequential rather than simultaneous performance of the ceVUS and fluoroscopic studies might have influenced VUR detection. CONCLUSION: A blinded comparison of ceVUS performed with Optison™ to fluoroscopic VCUG showed moderate-good sensitivity and specificity for diagnosis of VUR.

The surface topography of silicone breast implants mediates the foreign body response in mice, rabbits and humans.

Silicone is widely used in chronic implants and is generally perceived to be safe. However, textured breast implants have been associated with immune-related complications, including malignancies. Here, by examining for up to one year the foreign body response and capsular fibrosis triggered by miniaturized or full-scale clinically approved breast implants with different surface topography (average roughness, 0-90 µm) placed in the mammary fat pads of mice or rabbits, respectively, we show that surface topography mediates immune responses to the implants. We also show that the surface surrounding human breast implants collected during revision surgeries also differentially alters the individual's immune responses to the implant. Moreover, miniaturized implants with an average roughness of 4 µm can largely suppress the foreign body response and fibrosis (but not in T-cell-deficient mice), and that tissue surrounding these implants displayed higher levels of immunosuppressive FOXP3+ regulatory T cells. Our findings suggest that, amongst the topographies investigated, implants with an average roughness of 4 µm provoke the least amount of inflammation and foreign body response.

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder.

AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.

ICS educational module: Cystometry in children.

AIMS: To introduce the standard procedure of cystometry and interpretation of the results in children. METHODS: The literature on cystometry in children in PubMed for the last 20 years was reviewed. The updated knowledge regarding indication, preparation, technique, and interpretation of cystometry in children were summarized. RESULTS: Filling cystometry is the core content of a paediatric urodynamic study. In this section, the technique for performing cystometry is introduced in details. Emphasis is placed on correctly setting up the equipment according to ICS and ICCS guidelines, using appropriate terminology, providing indications for its performance with specific considerations for children, and proper interpretation of results. CONCLUSIONS: Cystometry can be used in children including newborn to evaluate lower urinary tract dysfunction.

Antibiotic Exposure and Reduced Short Chain Fatty Acid Production after Hematopoietic Stem Cell Transplant.

Human studies have shown loss of diversity of the gut microbiome following hematopoietic stem cell transplantation (HSCT) in association with significant gut injury caused by the preparative regimen. Prolonged antibiotic use worsens loss of microbiome diversity and increases risk of complications such as graft-versus-host disease (GVHD). Our data support the hypothesis that loss of intestinal commensals that produce short-chain fatty acids (SCFAs) may increase dysbiosis. Here, we report an extensive longitudinal examination of changes in the luminal SCFAs in children undergoing allogeneic HSCT, and the relationship of those changes to the microbiota and antibiotic exposure. We found significant and progressive alterations in butyrate, and in additional SCFAs in stool in the first 14 days after transplant, a finding not observed in published mouse studies. SCFA levels were lower in children receiving antibiotics with activity against anaerobic organisms. Moreover, day 14 post-HSCT butyrate and propionate levels are lower in children who went on to develop GVHD, although our disease population was small. These data provide insight into the mechanism of prior observations that loss of diversity and increased antibiotic use are associated with GVHD following HSCT. Our findings offer potential modifiable targets to reduce risk of GVHD and improve survival after HSCT.

Pelvic floor laxity: A not so rare but unrecognized form of daytime urinary incontinence in peripubertal and adolescent girls.

INTRODUCTION: Stress urinary incontinence (SUI) is common among older multiparous females but rarely reported in active, young girls. OBJECTIVES: Our hypothesis is: physically active adolescent females develop pelvic floor laxity demonstrable on upright VCUG. Our objectives are to (1) increase awareness of SUI in young females, (2) test our hypothesis with an upright VCUG, and (3) report effectiveness of step-wise management. STUDY DESIGN: A retrospective review was performed of nulliparous girls with only SUI seen from 2000 to 2015, who were evaluated with upright voiding cystourethrography (VCUG) (bladder descent defined as ≥2 cm drop of bladder neck below pubic ramus at capacity). Data collection included level of physical activity, physical examination, BMI and Z-scores, urodynamics, management, and treatment response. Standard urotherapy (SUT) (timed voiding, proper diet, adequate fluids, bowel management) and biofeedback therapy (BFT) was initiated. Fisher exact test was used to calculate 'p' values. RESULTS: Thirty-three females (median age 15.1 years, range 5.5-20.3) were identified who underwent an upright VCUG; 20 had bladder neck descent (Fig.). Of these 20, 15 (75%) were involved in strenuous activity, whereas only three of 13 (23%) without descent engaged in intense athletics. No differences were noted in median BMI and Z-score with strenuous activity (21.1 (15.2-26.7) and 0.31 (-0.9-1.94)), respectively, versus patients without (21.3 (15.8-33.5) and 0.62 (-0.0-2.38)). Average follow-up for all was 16.6 months (range 0.4-102.2). Of 20 demonstrating bladder neck descent, three did not complete therapy and were lost to follow-up. Only six of these 17 became dry. Of the remaining 11, eight underwent surgery: Burch colposuspension (5), fascial sling (2), Coaptite to the bladder neck (1), and an artificial urinary sphincter (1). This latter girl had a failed Burch colposuspension 1 year previously. All surgical patients are dry. Of 13 without bladder descent on VCUG, five did not complete therapy and were lost to follow-up. The remaining eight were managed non-surgically; seven were fully dry at last follow-up. Overall, 13 of 25 (52%) achieved dryness. SUT and BFT were more effective in those without, than in those with bladder descent (87.5% vs. 35.3%, p = 0.0302, Fisher exact test). DISCUSSION AND CONCLUSIONS: Physically active, nulligravid girls with SUI can be efficaciously diagnosed on upright VCUG. They should be considered for non-surgical therapy but will likely require bladder neck elevating surgery. Non-surgical therapy works for those with minimal bladder descent on cystography.

ICS educational module: Pressure flow study in children.

AIMS: To introduce the standard procedure and results interpretation of pressure/flow study (PFS) in children. METHODS: The literature on PFS in children in PubMed for the last 20 years was reviewed. The updated knowledge on PFS in children in children regarding indication, preparation, technique, and interpretation were summarized. RESULTS: This educational module explains when and how to do a PFS and how to analyze the results. All requirements and instructions for the PFS in children described in this document follow ICS reports on Good Urodynamic Practice and urodynamic equipment performance as well as guidelines from the ICCS. PFS can be obtained subsequent to filling cystometry with no specific additional equipment (apart from a flowmeter) or patient preparation needed. It requires both vesical and intra-abdominal pressures being recorded. Information from clinical history, physical examination, voiding diaries, and free uroflowmetry with or without perineal patch EMG and pertinent imaging results should be available before undertaking urodynamic testing. CONCLUSIONS: Following ICS and ICCS guidelines, PFS is an easy procedure and a useful tool to provide information on voiding function in children.

A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity mapping (HM) in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c.1336C>T, p.Arg446Cys) in the gene Von Willebrand factor A domain containing 2 (VWA2). With immunohistochemistry studies on kidneys of newborn (P1) mice, we show that Vwa2 and Fraser extracellular matrix complex subunit 1 (Fras1) co-localize in the nephrogenic zone of the renal cortex. We identified a pronounced expression of Vwa2 in the basement membrane of the ureteric bud (UB) and derivatives of the metanephric mesenchyme (MM). By applying in vitro assays, we demonstrate that the Arg446Cys mutation decreases translocation of monomeric VWA2 protein and increases translocation of aggregated VWA2 protein into the extracellular space. This is potentially due to the additional, unpaired cysteine residue in the mutated protein that is used for intermolecular disulfide bond formation. VWA2 is a known, direct interactor of FRAS1 of the Fraser-Complex (FC). FC-encoding genes and interacting proteins have previously been implicated in the pathogenesis of syndromic and/or isolated CAKUT phenotypes in humans. VWA2 therefore constitutes a very strong candidate in the search for novel CAKUT-causing genes. Our results from in vitro experiments indicate a dose-dependent neomorphic effect of the Arg446Cys homozygous mutation in VWA2.

The value of synchro-cystourethrometry for evaluating the relationship between urethral instability and overactive bladder.

PURPOSE: To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. METHODS: We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG). The effectiveness of treatment was evaluated. Average voided volume (AVV), maximum voided volume (MVV), and number of voids per day (NV) were collected and analyzed. RESULTS: In OAB children, the prevalence of DO and URI was 51.6 and 32.5%, respectively. The prevalence of URI was 5.6% in controls. The prevalence of URI was significantly higher in OAB children. The diagnostic sensitivity and Youden index of DO combined with URI were higher than DO alone. In SG, 45.7% of children were cured, with a ≥ 50% improvement rate of 82.9%, while no child was cured, with a ≥ 50% improvement rate of 36.8% in NSG. A significant increase in AVV and MVV together, with a decrease in NV, was seen in SG. There was a significant difference in visual analogue scale values between SG and NSG (P < 0.01). CONCLUSIONS: Urethral instability plays an essential role in the pathogenesis and progression of OAB in children. Synchro-cystourethrometry is a useful urodynamic technology to precisely diagnose OAB, and transcutaneous electrical pudendal nerve stimulation may be an effective treatment for OAB children induced by URI.

Evaluation and management of tethered cord syndrome in occult spinal dysraphism: Recommendations from the international children's continence society.

AIMS: As awareness and frequency of tethered spinal cord (TSC) related to occult spinal dysraphism (OSD) has increased with magnetic resonance imaging (MRI), variability exists in its evaluation and management. Due to no published level I data, we summarize the current International Children's Continence Society (ICCS) recommendations for diagnosis and treatment of OSD. METHODS: Guidelines were formulated based on analysis of pertinent literature and consensus among authors. This document was vetted by the multidisciplinary members of the ICCS via its website before submission for peer review publication. RESULTS: The more frequent diagnosis of OSD is associated with increased operative intervention. Spinal cord untethering (SCU) has a highly variable risk profile, largely dependent on the specific form of OSD. Progressive neurological deterioration attributed to "tethered cord" may occur, with or without surgery, in selected forms of OSD whereas other cohorts do well. CONCLUSION: Infants with classic cutaneous markers of OSD, with progressive neurologic, skeletal, and/or urologic findings, present no diagnostic or therapeutic dilemma: they routinely undergo MRI and SCU. Conversely, in asymptomatic patients or those with fixed, minor abnormalities, the risk profile of these OSD cohorts should be carefully considered before SCU is performed. Irrespective of whether or not SCU is performed, patients at risk for progression should be followed carefully throughout childhood and adolescence by a multidisciplinary team.

Minor procedure, major impact: Patient-reported outcomes following urethral meatotomy.

INTRODUCTION: Urethral meatotomy as treatment for meatal stenosis is a common pediatric urology procedure; however, little is known about the patient experience following this procedure. OBJECTIVE: We aim to evaluate clinical factors associated with patient-reported symptom improvement after urethral meatotomy. STUDY DESIGN: The families of boys undergoing urethral meatotomy between 2/2013 and 8/2016 received a survey by mail 6 weeks after surgery. Families were queried on changes in symptoms using a Likert-type scale (5 = much improved, 4 = somewhat improved, 3 = no change, 2 = somewhat worse, and 1 = much worse). Patient and procedure characteristics of the respondents were obtained via chart review. These included surgical indication(s) (abnormal stream, dysuria, or storage symptoms), postoperative complications, reoperation, and unplanned postoperative communications. Patients who had procedures other than simple urethral meatotomy were excluded. Descriptive statistics were compiled, and generalized estimating equations used to determine the associations of patient and procedure characteristics with symptom improvement. RESULTS: We sent 629 surveys and received 194 responses (30.4%). Twelve respondents were excluded for complex procedures or miscoding. The majority of respondents were privately insured (74%) and were between 5 and 12 years old (45%) or 1 and 4 years old (42%). The most frequent surgical indication was abnormal stream (72%) followed by pain (21%) and storage symptoms (15.5%). Nine respondents had minor complications (4.9%). Four patients had restenosis requiring repeat urethral meatotomy. After surgery, a majority (79%) were "much improved," 16% were "somewhat improved," 3% had "no change," and 1% were "somewhat worse." No family reported "much worse." Those patients who had "abnormal stream" as a surgical indication were significantly more likely to report "much improved" (OR 1.83, p = 0.014) than those without. Patient-reported improvement was not associated with suture use, patient age, insurance, surgeon, or location of the procedure (Table). DISCUSSION: Little has been written about patient-reported outcomes following urethral meatotomy. Our study affirms that the majority of boys improve following this procedure. However, improvement is significantly more likely if the child has a preoperative indication of an abnormal stream, such as deflection or spraying. Boys with symptoms of dysuria, frequency, or incontinence may be experiencing sequelae of meatal stenosis that simply take longer to improve. Alternatively, the meatal stenosis may be incidental to the primary symptoms. CONCLUSIONS: A majority of families report substantial symptomatic improvement after urethral meatotomy. However, boys undergoing urethral meatotomy for reasons other than a urinary stream abnormality are less likely to experience improvement.

Advances in paediatric urology.

Paediatric urological surgery is often required for managing congenital and acquired disorders of the genitourinary system. In this Series paper, we highlight advances in the surgical management of six paediatric urological disorders. The management of vesicoureteral reflux is evolving, with advocacy ranging from a less interventional assessment and antimicrobial prophylaxis to surgery including endoscopic injection of a bulking agent and minimally invasive ureteric reimplantation. Evidence supports early orchidopexy to improve fertility and reduce malignancy in boys with undescended testes. A variety of surgical techniques have been developed for hypospadias, with excellent outcomes for distal but not proximal hypospadias. Pelvi-ureteric junction obstruction is mostly detected prenatally; indications for surgery have been refined with evidence, and minimally invasive pyeloplasty is now standard. The outlook for patients with neurogenic bladder has been transformed by a combination of clean intermittent catheterisation, algorithms of diagnostic investigations, and innovative medical and surgical therapies. Posterior urethral valves are associated with considerable mortality; fetal diagnosis allows stratification of candidates for intervention, but ongoing bladder dysfunction in patients after valve ablation remains a cause of long-term morbidity.

Establishing a standard protocol for the voiding cystourethrography.

The voiding cystourethrogram (VCUG) is a frequently performed test to diagnose a variety of urologic conditions, such as vesicoureteral reflux (VUR). The test results determine whether continued observation or an interventional procedure is indicated. VCUGs are ordered by many specialists and primary care providers, including pediatricians, family practitioners, nephrologists, hospitalists, emergency room physicians, and urologists. Current protocols for performing and interpreting a VCUG are based on the International Reflux Study in 1985. However, more recent information provided by many national and international institutions suggests a need to refine those recommendations. The lead author of the 1985 study, R.L. Lebowitz, agreed to and participated in the current protocol. In addition, a recent survey directed to the chairpersons of pediatric radiology of 65 children's hospitals throughout the United States and Canada showed that VCUG protocols vary substantially. Recent guidelines from the American Academy of Pediatrics (AAP) recommend a VCUG for children between 2 and 24 months of age with urinary tract infections but did not specify how this test should be performed. To improve patient safety and to standardize the data obtained when a VCUG is performed, the AAP Section on Radiology and the AAP Section on Urology initiated the current VCUG protocol to create a consensus on how to perform this test.

Feasibility Study of NMR Based Serum Metabolomic Profiling to Animal Health Monitoring: A Case Study on Iron Storage Disease in Captive Sumatran Rhinoceros (Dicerorhinus sumatrensis).

A variety of wildlife species maintained in captivity are susceptible to iron storage disease (ISD), or hemochromatosis, a disease resulting from the deposition of excess iron into insoluble iron clusters in soft tissue. Sumatran rhinoceros (Dicerorhinus sumatrensis) is one of the rhinoceros species that has evolutionarily adapted to a low-iron diet and is susceptible to iron overload. Hemosiderosis is reported at necropsy in many African black and Sumatran rhinoceroses but only a small number of animals reportedly die from hemochromatosis. The underlying cause and reasons for differences in susceptibility to hemochromatosis within the taxon remains unclear. Although serum ferritin concentrations have been useful in monitoring the progression of ISD in many species, there is some question regarding their value in diagnosing hemochromatosis in the Sumatran rhino. To investigate the metabolic changes during the development of hemochromatosis and possibly increase our understanding of its progression and individual susceptibility differences, the serum metabolome from a Sumatran rhinoceros was investigated by nuclear magnetic resonance (NMR)-based metabolomics. The study involved samples from female rhinoceros at the Cincinnati Zoo (n = 3), including two animals that died from liver failure caused by ISD, and the Sungai Dusun Rhinoceros Conservation Centre in Peninsular Malaysia (n = 4). Principal component analysis was performed to visually and statistically compare the metabolic profiles of the healthy animals. The results indicated that significant differences were present between the animals at the zoo and the animals in the conservation center. A comparison of the 43 serum metabolomes of three zoo rhinoceros showed two distinct groupings, healthy (n = 30) and unhealthy (n = 13). A total of eighteen altered metabolites were identified in healthy versus unhealthy samples. Results strongly suggest that NMR-based metabolomics is a valuable tool for animal health monitoring and may provide insight into the progression of this and other insidious diseases.

Validation of a bowel dysfunction instrument for adolescents with spina bifida.

INTRODUCTION: Existing survey instruments for bowel dysfunction in the pediatric population are either parent-reported or focus on non-neurogenic bowel dysfunction. OBJECTIVE: The purpose of this study was to develop and validate an adolescent-reported survey to assess the severity of bowel dysfunction in spina bifida patients and examine its impact on quality of life (QOL). STUDY DESIGN: We performed a cross-sectional study of patients in our Myelodysplasia Program, aged 11-17 years, with a history of constipation and/or fecal incontinence (FI) from November 2010 to June 2013. Control patients, aged 11-17 years, were recruited from the stone clinic. Exclusion criteria were lack of English fluency, insufficient reading skills, or an incontinent fecal diversion. A 29-item version of the Adolescent Fecal Incontinence and Constipation Symptom Index (A-FICSI) was developed with five domains (Figure). Test re-test reliability and correlation with the total global health-related QOL score from the Parkin survey were measured using the Pearson correlation coefficient. A factor analysis model with four-fold correlations was tested. RESULTS: Of the 65 study-eligible individuals approached, 25 (11 boys) completed the A-FICSI (median age 12.6 years, IQR 11.8-14.7 years) and 17 completed another survey on urinary incontinence (64.6% response rate). Twenty-one control patients with nephrolithiasis completed the A-FICSI. Nine of the 25 completed a second administration of the survey. The mean correlation between repeated administrations of the survey was r = 0.43. There was a significant negative correlation between severity of constipation (r = -0.299, p < 0.05) and severity of FI (r = -0.316, p < 0.05) with the total Parkin QOL score. The Comparative Fit Index (CFI) was 0.864. Most items loaded significantly on their respective factors. Between-factor correlations were all significant (>0.30) in the predicted direction. Unstandardized residuals were 8.7% (95% CI 6.4-10.9%). Item reduction was performed on the 29-item instrument based on results of the factor analysis. The finalized instrument contained 21 items. DISCUSSION: This is the first adolescent-reported bowel dysfunction instrument to undergo formal psychometric assessment in the spina bifida population. The instrument demonstrated adequate reliability and the five-factor structure fit the data well. This study highlights the negative impact of bowel dysfunction on the QOL of spina bifida patients. It is limited by the moderate sample size that is a common issue in relatively rare diseases. CONCLUSION: The A-FICSI possesses desirable psychometric properties for the measurement of bowel dysfunction in the spina bifida population.

Semen parameters in adolescents with varicocele: association with testis volume differential and total testis volume.

PURPOSE: We evaluated the relationship between testicular volume differential, total testis volume and total motile sperm count in adolescents with varicocele. Prior reports have been inconclusive regarding the association of testis volume with semen analysis parameters. MATERIALS AND METHODS: We retrospectively reviewed a single institution database of Tanner 5 adolescents with nonoperated left varicocele with at least 1 semen analysis available. Patients were included in analysis if they had clinical left varicocele, ultrasound measurement of testis volume and no prior inguinal or scrotal surgery. RESULTS: We analyzed the records of 100 patients. Mean ± SD age at presentation was 15.2 ± 3.5 years. The mean testicular volume differential was 8% ± 23% and 31 patients (31%) had a greater than 20% testicular volume differential. Mean total testis volume was 30.4 ± 13.3 cc. Varicocele was grade 3 in 39 patients, grade 2 in 50, grade 1 in 8 and ungraded in 3. Median total motile sperm count in the cohort was 42.0 (IQR 9.2, 105.8). ROC analysis with the Youden index indicated an optimal total testis volume cutoff of 30 cc to predict the total motile sperm count. In a multivariable logistic model accounting for age and varicocele grade a testicular volume differential of greater than 20% was associated with twice the odds of a total motile sperm count of less than 20 million per cc (OR 2.1, 95% CI 1.02-4.12, p = 0.04). Total testis volume less than 30 cc more than quadrupled the odds of a total motile sperm count of less than 20 million per cc (OR 4.2, 95% CI 1.8-9.7, p <0.001). CONCLUSIONS: Total testis volume and the testicular volume differential are associated with semen analysis outcomes in adolescents with varicocele. A testicular volume differential of greater than 20% doubles the odds of a low total motile sperm count. A total testis volume of less than 30 cc quadruples the odds of a low total motile sperm count.

Combined cystometrography and electromyography of the external urethral sphincter following complete primary repair of bladder exstrophy.

PURPOSE: Concern in patients with bladder exstrophy after reconstruction regarding potential injury to pelvic neurourological anatomy and a resultant functional deficit prompted combined (simultaneous) cystometrography and electromyography after complete primary repair of bladder exstrophy. We determined whether complete primary repair of bladder exstrophy would adversely affect the innervation controlling bladder and external urethral sphincter function. MATERIALS AND METHODS: Complete primary repair of bladder exstrophy was performed via a modified Mitchell technique in newborns without osteotomy. Postoperative evaluation included combined cystometrography and needle electrode electromyography via the perineum, approximating the external urethral sphincter muscle complex. Electromyography was done to evaluate the external urethral sphincter response to sacral reflex stimulation and during voiding. RESULTS: Nine boys and 4 girls underwent combined cystometrography/electromyography after complete primary repair of bladder exstrophy. Age at study and time after complete primary repair of bladder exstrophy was 3 months to 10 years (median 11.5 months). Cystometrography revealed absent detrusor overactivity and the presence of a sustained detrusor voiding contraction in all cases. Electromyography showed universally normal individual motor unit action potentials of biphasic pattern, amplitude and duration. The external urethral sphincter sacral reflex response was intact with a normal caliber with respect to Valsalva, Credé, bulbocavernosus and anocutaneous (bilateral) stimulation. Synergy was documented by abrupt silencing of external urethral sphincter electromyography activity during voiding. CONCLUSIONS: After complete primary repair of bladder exstrophy combined cystometrography/electromyography in patients with bladder exstrophy showed normal neurourological findings, including sacral reflex responses, sustained detrusor voiding contraction and synergic voiding, in all patients postoperatively. These findings confirm the safety of complete primary repair of bladder exstrophy. Based on our results we have discontinued routine electromyography in these patients.