The different elements of the Urinary Tract Dilation (UTD) Classification System and their capacity to predict findings on mercaptoacetyltriglycine (MAG3) diuretic renography.

INTRODUCTION: The UTD Classification System risk stratifies postnatal UTD into three groups: low risk (UTD P1), intermediate risk (UTD P2), and high risk (UTD P3). In the original consensus document, a functional scan is not recommended for UTD P1 and is left to the discretion of the clinician for UTD P2 and P3. OBJECTIVE: This study aims to understand which patients with postnatal urinary tract dilation would benefit from a functional study. We investigated how different elements of the UTD classification system predict differential renal function (DRF) and diuretic half-life (T½) on MAG3 scan in infants undergoing evaluation for prenatally detected UTD. STUDY DESIGN: This is a multicenter retrospective chart review of infants 6 months of age or younger evaluated for prenatal UTD, correlating their first MAG3 scan and first postnatal renal ultrasound (RUS). Multivariable logistic regression was used to find UTD elements predictive of DRF < 40% and/or T½ > 20 min. RESULTS: A total of 517 patients met study criteria. Median age at time of RUS and MAG3 renal scan was 48 days (IGR 31-81) and 63 days (IQR 45-98), respectively. DRF < 40% was found in 6% of kidneys with UTD P2 and 35% of kidneys with UTD P3. T½ > 20 min was found in 31% of kidneys with UTD P2 and 79% of kidneys with UTD P3. An abnormal ureter (OR 2.7, 95% CI 1.2-6.0) and parenchymal thinning (OR 16, 95% CI 5.8-41.4) were significant at predicting DRF < 40%. Parenchymal thinning (OR 3.0, 95% CI 1.5-6.1) also predicted T½ > 20 min, as did each cm increase in the anterior-posterior renal pelvic diameter (APRPD) (OR 4.8, 95% CI 3.0-7.7). DISCUSSION: The UTD system discriminates well and correlates with the likelihood of finding adverse features on diuretic renography. Patients in the UTD P3 high-risk category had a significantly higher incidence of decreased differential renal function and delayed drainage than those in UTD P1 and P2. Of the individual components of the UTD Classification system, the presence of parenchymal thinning was the most important factor in predicting both decreased differential renal function and delayed drainage. CONCLUSION: Given the high incidence of poor function and delayed drainage seen in the UTD P3 group, we believe a functional study should be recommended in the evaluation of these patients. Our findings support leaving the performance of a functional study at the discretion of the physician for UTD P2.

Chemoradiotherapy-induced Cytodifferentiation in Bladder/Prostate Rhabdomyosarcoma With Genetic Downregulation of Myogenin and MyoD1 Gene Expression: A Case Study and Review of the Literature.

Rhabdomyosarcoma is the most common sarcoma diagnosed in childhood and adolescence, arising from the bladder/prostate in only 5%-10% of cases. Treatment-induced cytodifferention of tumor cells into mature rhabdomyoblasts has been reported following chemoradiation and is thought to suggest a more favorable outcome. We report a case of embryonal rhabdomyosarcoma of the bladder/prostate that exhibited extensive cytodifferentiation with downregulation of myogenin and MyoD1 gene expression in rhabdomyoblasts following treatment with chemoradiation therapy. The downregulation of myogenin and MyoD1 expression in rhabdomyoblasts following chemoradiation treatment has not previously been described in the literature and its significant remains uncertain.

Effect of active versus passive void trials on time to patient discharge, urinary tract infection, and urinary retention: a randomized clinical trial.

PURPOSE: We sought to determine the effect of active versus passive voiding trials on time to hospital discharge and rates of urinary tract infection (UTI) and urinary retention (UR). METHODS: We performed a prospective, randomized trial comparing active (AVT) versus passive (PVT) void trials of inpatients requiring urethral catheter removal. Of 329 eligible patients, 274 were randomized to AVT (bladder filled with saline before catheter removal) or PVT (spontaneous bladder filling after catheter removal). Primary outcome was time to hospital discharge. Secondary outcomes were UTI (NSQIP criteria) and UR (requiring repeat catheterization) within 2 weeks of void trial. RESULTS: The median time to void was 18 (5-115) versus 236 (136-360) min in the AVT and PVT groups, respectively (p < 0.0001). However, no difference was seen in comparison of the median time to hospital discharge between AVT [28.4 (13.6-69.3) h] and PVT [30.0 (10.4-75.6) h] cohorts, respectively (p = 0.93). Six (4.8%) and 13 (12.9%) patients developed UTI in the AVT and PVT groups, respectively (p = 0.03). Eleven (8.8%) and 12 (11.9%) patients developed UR in the AVT and PVT groups, respectively (p = 0.36). CONCLUSION: Our study comparing AVT versus PVT demonstrated no difference in time to discharge despite a 3.6 h reduction in time to void associated with AVT. AVT was associated with a 63% reduction in UTI, with no difference seen in UR rates across cohorts. Given the reduction in UTI and technical advantages, our data suggest that AVT should be considered as a recommended technique for void trial protocol. TRIAL REGISTRATION: NCT02886143 (clinicaltrials.gov).

Intermediate Follow-up and Management of Previously Reported Malignant Peripheral Nerve Sheath Tumor of the Penis.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerve fibers and primarily occur in the setting of neurofibromatosis (NF1). MPNST arising from the penis is very rare and may require mutilating surgery to achieve surgical cure. We previously reported a case of MPNST involving the penis in a 14-month-old boy treated with neoadjuvant chemotherapy, total penectomy, and adjuvant radiation. Here we report intermediate follow-up of the same patient, describe his subsequent genitourinary reconstruction, and discuss management dilemmas that arise following treatment of penile MPNST.

Management of Bilateral Undescended Bilobed Testes and Review of the Literature.

Polyorchidism is a rare anomaly of testicular development. Particularly, a bilobed testis is an extremely rare congenital malformation, which is thought to be a variant expression of polyorchidism. Only 5 cases of bilobed testis have been reported in the literature to date. This report is of bilateral, undescended, bilobed testes in a 15-month-old boy who has multiple other malformations of possible genetic etiology.

Increases in Sex Hormones during Anti-Tumor Necrosis Factor α Therapy in Adolescents with Crohn's Disease.

OBJECTIVE: To evaluate children with Crohn's disease for inverse relationships between systemic inflammatory cytokines and sex hormone regulation in the context of anti-tumor necrosis factor α (TNF-α) therapy. STUDY DESIGN: An observational study design was used to assess sex hormone and gonadotropin levels at the time of initiation of anti-TNF-α therapy and 10 weeks and 12 months later in 72 adolescents (Tanner stage 2-5) with Crohn's disease. Mixed-model linear regression was used to evaluate relationships between hormone levels, systemic inflammation, and dual-energy x-ray absorptiometry whole-body fat mass Z scores over the study interval. RESULTS: Sex hormone Z scores increased significantly during the 10-week induction interval: testosterone Z scores in male patients increased from a median of -0.36 to 0.40 (P < .05) and estradiol Z scores in females increased from -0.35 to -0.02 (P < .01). In mixed model regression, the pediatric Crohn's disease activity index score, cytokine levels, and measures of inflammation were significantly and negatively associated with sex hormone Z scores and with luteinizing hormone and follicle-stimulating hormone levels, adjusted for sex and Tanner stage. Sex hormone and gonadotropin levels were not associated with body mass index or fat mass Z-scores. CONCLUSIONS: Crohn's disease is associated with delayed maturation, and initiation of anti-TNF-α therapy was associated with significant and rapid increases in sex hormone and gonadotropin levels, in association with improvements in disease activity and measures of inflammation. These data are consistent with preclinical studies of the effects of inflammation on sex hormone regulation.

Milk intake, height and body mass index in preschool children.

OBJECTIVES: To evaluate links between the volume of milk consumed and weight and height status in children aged 4 and 5 years. DESIGN: We analysed data from 8950 children followed up as part of the Early Childhood Longitudinal Survey, Birth cohort, a nationally representative cohort of children. We used linear and logistic regression to assess associations of daily servings of milk intake at age 4 years with z-scores of body mass index (BMI), height and weight-for-height at 4 and 5 years, adjusted for sex, race/ethnicity, socioeconomic status and type of milk consumed. RESULTS: Among children who drank milk at age 4 years, higher milk consumption was associated with higher z-scores of BMI, height and weight-for-height at 4 years (all p<0.05). This corresponded to differences between children drinking <1 and ≥4 milk servings daily of approximately 1 cm in height and 0.15 kg in weight. By age 5 years, only the association with height remained significant (p<0.001). At 4 years, children drinking ≥3 servings of milk daily were more likely to be overweight/obese (BMI≥85th percentile) than those drinking 0.5-2 servings of milk daily (adjusted OR 1.16 (95% CI 1.02 to 1.32) p=0.02). CONCLUSIONS: In a cohort of children at age 4 years, the volume of milk consumed was associated with higher weight status and taller stature, while at 5 years, higher milk consumption continued to be associated with taller stature. Given higher odds of overweight/obesity with milk consumption ≥3 servings daily, this study supports current American Academy of Pediatrics recommendations that pre-school children consume two milk servings daily.

Development of a new class of aromatase inhibitors: design, synthesis and inhibitory activity of 3-phenylchroman-4-one (isoflavanone) derivatives.

Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC(50) values of 2.4 µM, 0.26 µM and 5.8 µM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors.