Faculty Bibliography

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

Historically nephrolithiasis was considered a disease of dehydration and abnormal urine composition. However, over the past several decades, much has been learned about the epidemiology of this disease and its relation to patient demographic characteristics and common systemic diseases. Here we review the latest epidemiologic studies in the field.

Cystinuria is a genetic disease marked by recurrent kidney stone formation, usually at a young age. It frequently leads to chronic kidney disease. Treatment options for cystinuria have been limited despite comprehensive understanding of its genetic pathophysiology. Currently available therapies suffer from either poor clinical adherence to the regimen or potentially serious adverse effects. Recently, we employed atomic force miscopy (AFM) to identify L-cystine dimethylester (CDME) as an effective molecular imposter of L-cystine, capable of inhibiting crystal growth in vitro. More recently, we demonstrated CDME's efficacy in inhibiting L-cystine crystal growth in vivo utilizing a murine model of cystinuria. The application of AFM to discover inhibitors of crystal growth through structural mimicry suggests a novel approach to preventing and treating crystal diseases.

PURPOSE: Delivering the recommended care is an important quality measure that has been insufficiently studied in urology. Obstructive pyelonephritis is a suitable case study for this focus because many patients do not receive such care, although guidelines advocate decompression. We determined the influence of hospital factors, particularly familiarity with urolithiasis, on the likelihood of decompression in such patients. MATERIALS AND METHODS: We used the NIS from 2002 to 2011 to retrospectively identify patients admitted to community hospitals with severe infection and ureteral calculi. Hospital familiarity with nephrolithiasis was estimated by calculating hospital stone volume (divided into quartiles) and hospital treatment intensity (the decompression rate in patients with ureteral calculi and no infection). After calculating national estimates we performed logistic regression to determine the association between the receipt of decompression and hospital stone volume, controlling for treatment intensity and other covariates thought to be associated with receiving recommended care. RESULTS: Of an estimated 107,848 patients with obstructive pyelonephritis 27.4% failed to undergo decompression. Discrepancies were greatest between hospitals with the highest and lowest stone volumes (76% vs 25%, OR 2.77, 95% CI 1.94-3.96, p <0.01) as well as high and low treatment intensity (78% vs 37%, p <0.01). CONCLUSIONS: High hospital stone volume and treatment intensity were associated with an increased likelihood of receiving decompression. Such findings might be useful to identify hospitals and regions where access to quality urological care should be augmented.