Predicting the Risk of Breakthrough Urinary Tract Infections: Primary Vesicoureteral Reflux.

PURPOSE: We constructed a risk prediction instrument stratifying patients with primary vesicoureteral reflux into groups according to their 2-year probability of breakthrough urinary tract infection. MATERIALS AND METHODS: Demographic and clinical information was retrospectively collected in children diagnosed with primary vesicoureteral reflux and followed for 2 years. Bivariate and binary logistic regression analyses were performed to identify factors associated with breakthrough urinary tract infection. The final regression model was used to compute an estimation of the 2-year probability of breakthrough urinary tract infection for each subject. Accuracy of the binary classifier for breakthrough urinary tract infection was evaluated using receiver operator curve analysis. Three distinct risk groups were identified. The model was then validated in a prospective cohort. RESULTS: A total of 252 bivariate analyses showed that high grade (IV or V) vesicoureteral reflux (OR 9.4, 95% CI 3.8-23.5, p <0.001), presentation after urinary tract infection (OR 5.3, 95% CI 1.1-24.7, p = 0.034) and female gender (OR 2.6, 95% CI 0.097-7.11, p <0.054) were important risk factors for breakthrough urinary tract infection. Subgroup analysis revealed bladder and bowel dysfunction was a significant risk factor more pronounced in low grade (I to III) vesicoureteral reflux (OR 2.8, p = 0.018). The estimation model was applied for prospective validation, which demonstrated predicted vs actual 2-year breakthrough urinary tract infection rates of 19% vs 21%. Stratifying the patients into 3 risk groups based on parameters in the risk model showed 2-year risk for breakthrough urinary tract infection was 8.6%, 26.0% and 62.5% in the low, intermediate and high risk groups, respectively. CONCLUSIONS: This proposed risk stratification and probability model allows prediction of 2-year risk of patient breakthrough urinary tract infection to better inform parents of possible outcomes and treatment strategies.

Extension of Drosophila lifespan by Rhodiola rosea through a mechanism independent from dietary restriction.

Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR) that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2) proteins, insulin and insulin-like growth factor signaling (IIS), and the target of rapamycin (TOR). In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.

Primary vesico-ureteric reflux: The need for individualised risk stratification.

The management of paediatric primary vesico-ureteric reflux (VUR) has undergone serial changes over the last decade. As this disorder is extremely heterogeneous, and high-quality prospective data are limited, the treatment strategies vary among centres. Current treatment options include observation only, continuous antibiotic prophylaxis, and surgery. Surgical intervention is indicated if a child has a breakthrough urinary tract infection (UTI) while on continuous antibiotic prophylaxis or if there are renal scars present. After excluding a secondary cause of VUR the physician should consider the risk factors affecting the severity of VUR and manage the child accordingly. Those factors include demographic factors (age at presentation, gender, ethnicity) and clinical factors (VUR grade, unilateral vs. bilateral, presence of renal scars, initial presentation, the number of UTIs, and presence of any voiding or bowel dysfunction). In this review we summarise the major controversial issues in current reports on VUR and highlight the importance of individualised patient management according to their risk stratification.