Quantitation and localization of beta-blockers and SSRIs accumulation in fathead minnows by complementary mass spectrometry analyses.

Beta-blockers and selective serotonin reuptake inhibitors (SSRIs) enter the environment through the improper disposal of drugs in garbage, sinks, or toilets as well as via excretion after their intended use. Beta-blockers and SSRIs are resistant to biodegradation and highly water soluble, leading to limited removal capabilities by wastewater treatment plants. As a result, these compounds can easily enter the aquatic environment in a biologically active state, posing risks to the behavior, anatomy, and physiology of aquatic organisms through exposure. However, there is insufficient research on the effects of beta-blockers on aquatic vertebrates to have a complete understanding of the impact of beta-blocker pollution on aquatic organisms. Exposing fathead minnows at environmentally-relevant concentrations allows for an accurate representation of how beta-blockers and SSRIs affect and accumulate in aquatic vertebrates. Singular exposures to two beta-blockers and two selective serotonin reuptake inhibitors (SSRIs) at seven days modeled how pollution affects aquatic wildlife during acute exposure events. After exposure, the entire organism was analyzed quantitatively by liquid chromatography mass spectrometry and qualitatively by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Imaging allowed for the determination of the part of the organism in which the drugs were accumulating. Results showed that after seven days of exposure there was accumulation of both the beta-blockers and SSRIs in the fathead minnows. This data represents the first application of LC-MS quantitation guided by MALDI-MSI in aquatic toxicology-type research in environmental analytical chemistry.

Contemporary practice patterns in the treatment of pediatric stone disease.

INTRODUCTION: To compare endourology versus pediatric urology exposure to pediatric stone cases during fellowship, comfortability in treating pediatric stone cases, and access to pediatric surgical equipment. MATERIALS AND METHODS: A survey was distributed to all pediatric urology fellowship programs and the Endourological Society. Age was stratified into < 12 months old, 12 months-4 years, 5-12 years, and 13-18 years. Exposure and comfortability performing extracorporeal shock wave lithotripsy (SWL), ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) were assessed across age groups. Exposure was assessed as 'yes/no' and comfortability was scaled from 1-5 ('would not do' to 'very comfortable'). RESULTS: Seventy-two surveys met inclusion criteria, with 23 (31.9%) from pediatric urologists and 49 (68.1%) by endourologists. During fellowship, pediatric urologists had more exposure to SWL in toddlers (p = 0.03) and school age children (p = 0.045), URS in toddlers (p = 0.012) and school age children (p = 0.002), and PCNL in infants (p = 0.031) and school age children (p = 0.025) compared to endourologists. Pediatric urologists were significantly more comfortable performing SWL in toddlers (p = 0.04), URS in toddlers (p = 0.04) and school age children (p = 0.04), and PCNL in school age children (p = 0.02) compared to endourologists. Endourologists were significantly more uncomfortable than pediatric urologists in performing URS in toddlers (p = 0.03) and PCNL in infants (p = 0.04) and school age children (p = 0.03). There were no differences in availability of pediatric equipment. CONCLUSIONS: Pediatric urologists, have significantly more exposure than endourologists during fellowship and are more comfortable performing surgical treatment for urolithiasis in most pediatric ages. Endourology fellowships may benefit from greater exposure to pediatric patients with stones.

Pediatric hospitalizations for upper urinary tract calculi: Epidemiological and treatment trends in the United States, 2001-2014.

INTRODUCTION: The incidence of urolithiasis in the pediatric population in the United States has steadily been increasing over the past few decades. Few studies to date have examined trends in the hospitalization and inpatient surgical treatment of urolithiasis in the pediatric population using nationally representative data. OBJECTIVE: The aim was to evaluate nationwide trends in the rates of pediatric hospitalization and inpatient surgical activity for upper urinary tract calculi (UUTC) in the United States from 2001 to 2014. PATIENTS AND METHODS: The National Inpatient Sample (NIS) databases for 2001-2014 were queried. Hospitalizations for patients younger than age 18 (excluding newborns), with principal discharge diagnoses of kidney or ureteral calculi were selected. Surgical procedures during hospitalization were identified. Hospitalization and surgical activity data were analyzed using trends tests, chi-square statistics, and multivariable logistic regression as appropriate. RESULTS: Of an estimated 30.2 million pediatric hospitalizations during the study period, 44,369 overall (147 per 100,000) were for UUTC. The total number and proportion of UUTC hospitalizations per 100,000 all-cause admissions significantly decreased between 2001 and 2014 (p < 0.0001) (figure). Surgical intervention was undertaken in 19,946 (45%) of UUTC hospitalizations, with significantly increasing frequency over the study interval (p < 0.0001). Urinary tract drainage was the most frequently performed surgical intervention. On multivariable analysis, significant predictors of a higher likelihood of undergoing inpatient surgical intervention during hospitalization for UUTC included older age, female gender, deficiency anemias, hypertension, neurologic disorders, paralysis, and hospitalization after 2001. DISCUSSION: The declining trend in hospitalization for UUTC likely reflects a shift toward outpatient care for routine cases, reserving hospitalization for sicker patients or those with complications of urolithiasis. Similar to previous studies, we also observed that girls were significantly more likely than boys to be hospitalized for stone disease, and that majority of the stone activity in the pediatric population was in children aged 15-17 years. We also observed a sharp increase in the proportion of hospitalized patients who underwent surgical intervention between 2001 and 2014, but the primary driver of this trend remains uncertain. CONCLUSION: Pediatric hospitalizations for UUTC in US children significantly decreased between 2001 and 2014, while of those hospitalized the proportion who underwent stone-related surgical intervention significantly increased over the same period. A shift towards outpatient care, reserving hospitalization and inpatient surgical care for sicker patients, those with urolithiasis-related complications, or those who fail conservative management, is a possible explanation for these observed trends.

Bowel preparation prior to reconstructive urologic surgery in pediatric myelomeningocele patients.

INTRODUCTION: Mechanical bowel preparation (MBP) has historically been the standard of care for patients undergoing reconstructive urologic surgery, including urinary diversion. To date, several studies have examined the role of mechanical bowel preparation in postoperative outcomes in pediatric patients undergoing augmentation cystoplasty. However, these patient populations have been heterogeneous in nature, with no studies dedicated to examining the role of MBP prior to reconstructive urologic surgery in pediatric patients with myelomenginoceles. Thus, our objective was to retrospectively assess perioperative measures and postoperative complications after reconstructive urologic surgery with or without mechanical bowel preparation in pediatric myelomeningocele patients. MATERIALS AND METHODS: From 2008 to 2013, 80 patients with myelomeningocele underwent reconstructive urologic surgery involving the use of bowel. Seventy patients underwent a preoperative MBP while 10 did not. Perioperative measures and postoperative complications for these two cohorts were assessed. RESULTS: Eighty patients with myelomeningocele were identified; 70 patients underwent MBP while 10 patients did not. There were no statistically significant differences in demographics or operative time. There were no statistically significant differences in postoperative outcomes including time to first bowel movement and time to tolerating diet. There was also no significant difference in overall complication rate; patients with MBP had 31/70 (44%) complications while 2/10 (20%) of those without MBP had complications (p = 0.18). CONCLUSION: There was no significant difference in perioperative measures and postoperative complications for patients who did not receive a mechanical bowel preparation. Our findings indicate that it is safe and warranted to perform a prospective, randomized study to better characterize the risks and benefits of preoperative bowel preparation for patients with myelomeningocele.

Open versus robotic cystectomy: Comparison of outcomes.

Open radical cystectomy (ORC) is the current gold standard treatment for muscle invasive bladder cancer. As surgeons become more proficient in minimally invasive and robotic surgical techniques, the number of patients undergoing robotic-assisted radical cystectomy (RARC) is increasing. Although minimally invasive methods are on the rise, research that critically compares open surgery with robotic methods is limited. In this review, we surveyed and appraised the current literature comparing ORC and RARC with regards to perioperative, functional, and oncologic outcomes in order to distinguish the benefits and disadvantages of each method. Here we report that RARC is associated with several perioperative advantages over ORC such as lower estimated blood loss and transfusion rate, and possibly faster gastrointestinal recovery, lower narcotic requirement, and shorter length of stay. ORC is less costly and permits less time in the operating room. Recent data suggests that there is no difference between ORC and RARC when comparing urinary continence and postoperative quality of life. Moreover, ORC and RARC are both associated with similar rates of obtaining positive surgical margins, lymph node yield, and recurrence. However, RARC patients had an increased likelihood of having distant metastases to extrapelvic lymph nodes and the peritoneum. At this point, it is unclear if ORC or RARC has superior patient outcomes, and more research is needed to ascertain management-altering conclusions.

VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature.

Unlike during development, blood vessels in the adult are generally thought not to require VEGF for normal function. However, VEGF is a survival factor for many tumor vessels, and there are clues that some normal blood vessels may also depend on VEGF. In this study, we sought to identify which, if any, vascular beds in adult mice depend on VEGF for survival. Mice were treated with a small-molecule VEGF receptor (VEGFR) tyrosine kinase inhibitor or soluble VEGFRs for 1-3 wk. Blood vessels were assessed using immunohistochemistry or scanning or transmission electron microscopy. In a study of 17 normal organs after VEGF inhibition, we found significant capillary regression in pancreatic islets, thyroid, adrenal cortex, pituitary, choroid plexus, small-intestinal villi, and epididymal adipose tissue. The amount of regression was dose dependent and varied from organ to organ, with a maximum of 68% in thyroid, but was less in normal organs than in tumors in RIP-Tag2-transgenic mice or in Lewis lung carcinoma. VEGF-dependent capillaries were fenestrated, expressed high levels of both VEGFR-2 and VEGFR-3, and had normal pericyte coverage. Surviving capillaries in affected organs had fewer fenestrations and less VEGFR expression. All mice appeared healthy, but distinct physiological changes, including more efficient blood glucose handling, accompanied some regimens of VEGF inhibition. Strikingly, most capillaries in the thyroid grew back within 2 wk after cessation of treatment for 1 wk. Our findings of VEGF dependency of normal fenestrated capillaries and rapid regrowth after regression demonstrate the plasticity of the adult microvasculature.