Resolution of post-circumcision penile adhesions in newborns.

INTRODUCTION: Penile adhesions are a common complication of neonatal circumcision and can cause significant distress to families. Although prior studies have suggested adhesions resolve with conservative measures, the information on the likelihood and time frame is not known. Alternatively, a lysis of adhesions (LOA) procedure can be performed in the office. The aim of the study was to determine the likelihood of spontaneous resolution with conservative measures at home. METHODS: A retrospective review of patients with post circumcision penile adhesions that were referred to a pediatric urologist was conducted. Data regarding patient age, extent and severity of adhesions, chosen treatment modality (home-care with daily retraction versus LOA), improvement in subsequent visits, and final outcome of adhesions was obtained from chart review. Contingency tables, chi-square tests, or t-tests were used to assess statistical significance. RESULTS: 429 patients were reviewed. The mean age was 28.2 months (range 1-152) and mean follow-up was 7.4 months (range 1-70). Adhesions were circumferential in 81% of patients and incomplete in 19%. Additionally, 64% of patients had adhesions that covered less than 50% of the glans penis, compared to adhesions that covered 50% or more in 36% of patients. After the initial visit, 66% of patients elected the home-care regimen, 89% of which were seen in follow-up visits. Only 36% of patients treated with the home-care regimen had completely or substantially resolved adhesions after a median of 6 months. Results showed a significant difference in success with home care depending on the circumferential extent of adhesions (p < 0.05), with patients whose adhesions covered less than 25% of the glans penis having the greatest likelihood of improvement. Effectiveness of home therapy also varied depending on the severity of adhesions (p < 0.05), with patients whose adhesions covered less than 50% of the glans having a higher chance of success. Most patients that initially chose the home-care regimen (65%) eventually elected to undergo LOA in the office. This study is limited by the retrospective nature, failure to control for potential confounders such as weight and the degree of participation at home, and the time frame after initiation of home therapy, which might have been insufficient for complete resolution of adhesions. DISCUSSION: The conservative management of post-circumcision adhesions is not effective over a 6 month time frame, with the great majority of the patients eventually undergoing LOA. Physicians can classify the severity and extent of adhesions to predict what patients might have more success with conservative management. LOA might be better suited for patients with more severe adhesions.

Histologic evaluation of therapeutic responses in ischemic myocardium elicited by dual growth factor delivery from composite glycosaminoglycan hydrogels.

In this project, the ability of dual growth factor-preloaded, silk-reinforced, composite hyaluronic acid-based hydrogels to elicit advantageous histologic responses when secured to ischemic myocardium was evaluated in vivo. Reinforced hydrogels containing both Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF) were prepared by crosslinking chemically modified hyaluronic acid and heparin with poly(ethylene glycol)-diacrylate around a reinforcing silk mesh. Composite patches were sutured to the ventricular surface of ischemic myocardium in Sprague-Dawley rats, and the resulting angiogenic response was followed for 28 days. The gross appearance of treated hearts showed significantly reduced ischemic area and fibrous deposition compared to untreated control hearts. Histologic evaluation showed growth factor delivery to restore myofiber orientation to pre-surgical levels and to significantly increase elicited microvessel density and maturity by day 28 in infarcted myocardial tissue (p < 0.05). In addition, growth factor delivery reduced cell apoptosis and decreased the density of elicited mast cells and both CD68+ and anti-inflammatory CD163+ macrophages. These findings suggest that HA-based, dual growth factor-loaded hydrogels can successfully induce a series of beneficial responses in ischemic myocardium, and offer the potential for therapeutic improvement of ischemic myocardial remodeling.

Unusual cause of Fournier's gangrene: colorectal-genitourinary tract fistulae status post brachytherapy.

There are few reports of radiation associated colorectal-genitourinary tract (CRGU) fistulae causing Fournier's gangrene (FG). We describe a case of FG in a patient with possibly two CRGU fistulae in the context of previous high-dose brachytherapy and external beam radiation therapy for prostate cancer. Unfortunately, CRGU fistulae are not well classified as significant risk factors for the development of FG. Our case demonstrates the rationale for maintaining a broad differential in patients presenting with recurrent urinary tract symptoms or necrotising soft tissue infections to include undiagnosed fistulae.

Review of the comparative effectiveness of radical prostatectomy, radiation therapy, or expectant management of localized prostate cancer in registry data.

Evidence regarding the effectiveness of treatment for prostate cancer is primarily based on randomized controlled trials. Long-term outcomes are generally difficult to evaluate within experimental studies and may benefit from large pools of observational data. We conducted a systematic review of administrative and registry studies to evaluate the comparative effectiveness of treatment for clinically localized prostate cancer on overall and prostate-cancer specific mortality. MATERIALS AND METHODS: In accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P, 2015), we conducted a systematic search of Ovid Medline and Embase (1946-February 2017) and identified studies that evaluated the relationship between types of treatment for localized prostate cancer and mortality. Additional articles were identified through manual search. Randomized, prospective, and single institution studies were excluded. The risk of bias for each study was evaluated with the Newcastle Ottawa scale. Multivariable adjusted hazard ratios were reported to evaluate overall and cancer-specific mortality. RESULTS: We screened 4,721 studies and included for review, 19 that were published between 2001 and 2015. The pooled population included 228,444 patients. Countries of origin included the United States, Canada, China, Switzerland, the Netherlands, and Sweden, and the sources included administrative (n = 6) and cancer registry or prostate databases (n = 11). Overall and cancer-specific mortality were lowest among definitive treatment arms as compared to conservative therapy with no treatment, observation, or active surveillance. Radiotherapy was associated with worse overall and cancer-specific mortality than radical prostatectomy. CONCLUSION: Although observational studies using large, population-based cohorts have the potential for bias, we found consistent evidence that high-quality observational studies may be used to evaluate the comparative effectiveness of prostate cancer treatment. Methodologic limitations of observational data should be considered.

Healthcare policy and urologic practice.

PURPOSE OF REVIEW: Healthcare policy is currently a topic of national debate, with numerous implications for the practice of urology. RECENT FINDINGS: Healthcare policy has broad reaching effects, both predicted and unforeseen. The effects of healthcare policy are manifested through clinical practice guidelines, payment reform and the overall structure of the healthcare system. This review describes each of these topics and their impact on clinical practice, with a specific focus on urology and urologic practice. SUMMARY: Guidelines are useful for guiding and determining what is considered appropriate clinical practice, but there are drawbacks including poor implementation and overabundance. Payment reform is constantly evolving, with multiple efforts being implemented to move away from a fee-for-service model of reimbursement. The structure of healthcare delivery is moving toward more outpatient procedures, with varying amount of physician ownership of facilities and equipment, which is itself a controversial topic.

Symptomatic infundibulopelvic dysgenesis in an adolescent.

Infundibulopelvic dysgenesis is a rare condition characterized by congenital malformation of the pelvicalyceal system. We present the case of an 18-year-old boy with chronic intermittent right flank pain and cystic dilation with parenchymal thinning on ultrasonography. The left kidney was normal. The patient denied dysuria, constipation, and history of UTIs or renal calculi. Cystoscopy with retrograde pyelogram showed marked stenosis of the right pelvicalyceal system and anatomy unfavorable to stenting. The patient's symptoms were unresponsive to conservative management. Reconstruction of the right collecting system was unsuccessful and a simple nephrectomy was performed, which led to complete resolution of his symptoms.

Porous microspheres of MgO-patched TiO2 for CO2 photoreduction with H2O vapor: temperature-dependent activity and stability.

A novel MgO-patched TiO2 microsphere photocatalyst demonstrated 10 times higher activity toward CO production from CO2 photoreduction with H2O vapor, when the reaction temperature increased from 50 to 150 °C. The catalytic performance of hybrid MgO-TiO2 was much more stable than TiO2, particularly at a higher temperature, likely due to easier desorption of reaction intermediates and the enhanced CO2 adsorption by MgO.

Discovery of a selective allosteric M1 receptor modulator with suitable development properties based on a quinolizidinone carboxylic acid scaffold.

One approach to ameliorate the cognitive decline in Alzheimer's disease (AD) has been to restore neuronal signaling from the basal forebrain cholinergic system via the activation of the M(1) muscarinic receptor. A number of nonselective M(1) muscarinic agonists have previously shown positive effects on cognitive behaviors in AD patients, but were limited due to cholinergic adverse events thought to be mediated by the activation of the M(2) to M(5) subtypes. One strategy to confer selectivity for M(1) is the identification of positive allosteric modulators, which would target an allosteric site on the M(1) receptor rather than the highly conserved orthosteric acetylcholine binding site. Quinoline carboxylic acids have been previously identified as highly selective M(1) positive allosteric modulators with good pharmacokinetic and in vivo properties. Herein is described the optimization of a novel quinolizidinone carboxylic acid scaffold with 4-cyanopiperidines being a key discovery in terms of enhanced activity. In particular, modulator 4i gave high plasma free fractions, enhanced central nervous system (CNS) exposure, was efficacious in a rodent in vivo model of cognition, and afforded good physicochemical properties suitable for further preclinical evaluation.

N-heterocyclic derived M1 positive allosteric modulators.

Replacement of a phenyl ring with N-linked heterocycles in a series of quinolone carboxylic acid M1 positive allosteric modulators was investigated. In particular, a pyrazole derivative exhibited improvements in potency, free fraction, and CNS exposure.

Pyridine containing M(1) positive allosteric modulators with reduced plasma protein binding.

Incorporation of pyridines and diazines into the biphenyl region of quinolone carboxylic acid derived M(1) positive allosteric modulators was investigated as a means of lowering plasma protein binding to enhance CNS exposure.

Insecticidal activity of N-arylalkylbenzhydrolpiperidines.

Benzhydrolpiperidine (BZP) insecticides represent a novel class of chemistry. Their specificity and efficacy as well as their low mammalian toxicity give them excellent potential for commercialization. Several N-arylalkylbenzhydrolpiperidines were tested for activity against a variety of insects in the laboratory and greenhouse. These tests were used to select compounds for field trials and determine rates of application for field tests. The BZP compounds have good activity against Lepidoptera, with modest Coleoptera activity. They are toxic by oral administration and have about 100-fold lower activity by topical exposure. A methyl carbamate BZP, F4265, was the most active compound, with LC50 values of 6 mg litre(-1) or less for most Lepidopteran species tested. F4265 was active in a variety of field trials at 112-224gAI ha(-1). Whole-plant testing methods conducted in the greenhouse were effective in determining field test rates.