Assessment of urinary tract dilation grading amongst pediatric urologists.

INTRODUCTION: The Urinary Tract Dilation (UTD) system was created to address variability in hydronephrosis grading. It is unknown if or how pediatric urologists are integrating this newer system into practice. OBJECTIVE: We sought to evaluate the current use of hydronephrosis grading systems, inter-rater reliability (IRR) for individual systems, and management preferences based on degree of hydronephrosis. STUDY DESIGN: A survey was emailed to the Societies for Pediatric Urology listserv. Questions addressed familiarity/preference for various grading systems and respondent confidence in interpretation of hydronephrosis. Three clinical vignettes asked respondents to grade hydronephrosis using their system of choice and report further imaging they would obtain. Descriptive statistics were calculated, and IRR was calculated using a linear-weighted modified Fleiss' kappa test. RESULTS: Response rate was 43% (n = 138). The majority of respondents used Society for Fetal Urology (SFU) (70%) or UTD (19%) systems. Most favored SFU (58%) or UTD (34%) systems for a unified system. Confidence in own interpretation was higher than confidence in radiologists' reads (median 4.4 vs 3.6, p < 0.001). IRR was substantial for UTD (κ0.68 [0.64-0.71]) and moderate for SFU (κ0.60 [0.52-0.76]). There was notable heterogeneity regarding follow-up imaging for cases. There was no difference in requested follow-up studies between SFU and UTD systems, except for fewer voiding cystourethrogram (VCUG) requests for Case 3 with UTD (28% vs 4%, p = 0.02). CONCLUSION: Most pediatric urologists still use SFU rather than the UTD system. There was slightly higher IRR with the UTD system. There was substantial variability in follow-up imaging not related to grading system, except with low grade hydronephrosis.

Impact of environmental toxin exposure on male fertility potential.

Idiopathic infertility is the most common individual diagnosis in male infertility, representing nearly 44% of cases. Research studies dating over the last half-century consistently demonstrate a decline in male fertility that is incompletely explained by obesity, known genetic causes, or diet and lifestyle changes alone. Human exposures have changed dramatically over the same time course as this fertility decline. Synthetic chemicals surround us. Some are benevolent; however, many are known to cause disruption of the hypothalamic-pituitary-gonadal axis and impair spermatogenesis. More than 80,000 chemicals are registered with the United States National Toxicology Program and nearly 2,000 new chemicals are introduced each year. Many of these are known toxins, such as phthalates, polycyclic aromatic hydrocarbons, aromatic amines, and organophosphate esters, and have been banned or significantly restricted by other countries as they carry known carcinogenic effects and are reproductively toxic. In the United States, many of these chemicals are still permissible in exposure levels known to cause reproductive harm. This contrasts to other chemical regulatory legislature, such as the European Union's REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) regulations which are more comprehensive and restrictive. Quantification of these diverse exposures on an individual level has proven challenging, although forthcoming technologies may soon make this data available to consumers. Establishing causality and the proportion of idiopathic infertility attributable to environmental toxin exposures remains elusive, however, continued investigation, avoidance of exposure, and mitigation of risk is essential to our reproductive health. The aim of this review is to examine the literature linking changes in male fertility to some of the most common environmental exposures. Specifically, pesticides and herbicides such as dichlorodiphenyltrichloroethane (DDT), dibromochloropropane (DBCP), organophosphates and atrazine, endocrine disrupting compounds including plastic compounds phthalates and bisphenol A (BPA), heavy metals, natural gas/oil, non-ionizing radiation, air and noise pollution, lifestyle factors including diet, obesity, caffeine use, smoking, alcohol and drug use, as well as commonly prescribed medications will be discussed.

Contemporary management of ejaculatory dysfunction.

Although erectile dysfunction is the most common disorder of male sexual health, ejaculatory dysfunction is the most common form of sexual dysfunction experienced by men. Ejaculatory dysfunction covers a broad range of disorders that we have divided into four main categories: premature ejaculation, delayed ejaculation (DE)/anorgasmia, unsatisfactory sensation of ejaculation (including painful ejaculation and ejaculatory anhedonia), and absent ejaculate (including retrograde ejaculation and aspermia). We also cover several special scenarios including hematospermia, spinal cord injury and fertility with anejaculation. In this paper, we will review the anatomy and pathophysiology of normal ejaculation to establish the baseline knowledge of how this pathway can go awry. We will then briefly review the critical diagnostic criteria, pertinent steps in evaluation, risk factors, and causes (if known) for each of the ejaculatory disorders. Finally, the bulk of the paper will discuss current management strategies of each disorder.

Associations between Patient Characteristics and a New, Early Do-Not-Attempt Resuscitation Order after Intracerebral Hemorrhage.

BACKGROUND: Decisions to limit care, including use of a do-not-resuscitate (DNR) order, are associated with increased risk of death after intracerebral hemorrhage (ICH). Given the value that patient surrogates place on the physician's perception of prognosis, understanding prognostic indicators that influence clinical judgment of outcomes is critical. OBJECTIVE: The purpose of this study was to understand the patient variables and comorbid illnesses associated with DNR orders placed on patients within 72 hours after ICH. DESIGN: Single-center, retrospective review of medical records of 198 consecutive patients with an admission diagnosis of primary supratentorial ICH between July 2007 and December 2010. SUBJECTS: Patients who did not experience a DNR order placement during their primary admission for ICH (non-DNR group) were compared to patients who received a new DNR order in the first 72 hours of admission (DNR group). MEASUREMENTS: Patient characteristics obtained include demographic data, past medical history, clinical data pertaining to the admission for the ICH, and radiographic images. Demographic, medical, and ICH injury data during the first three days of admission were collected. RESULTS: Multiple differences in patient and hospital factors were found between patients receiving a new, early DNR order and those who did not receive a DNR order after ICH. In regression modeling, Caucasian race, direct admission, and higher ICH score were associated with placement of a new DNR order early in the course of injury. CONCLUSIONS: Race, transfer procedures, and injury severity may be important factors associated with placement of new, early DNR orders in patients after ICH.

Survey of anesthesiologists practicing in American neurointensive care units as neurointensivists.

BACKGROUND: A group of anesthesiologists practice as intensivists in neurointensive care units (NeuroICU). The current nature and implications of the role of anesthesiology-based neurointensivist remain unclear. The purpose of this survey was to assess today's practice environment of anesthesiology-based neurointensivists as a framework for future study. METHODS: During the period between January 2011 and March 2011, we identified anesthesiologists who provide patient care in specialized NeuroICUs in the United States. We used an online, 15-question survey to gauge the environment and their role in the delivery of care to critically ill patients admitted to NeuroICUs. RESULTS: Of the 104 NeuroICUs in the United States, 22 institutions include anesthesiology-based neurointensivists (n=41). With a response from 33 of 41 requested surveys, anesthesiology-based neurointensivists reported that background training and roles for providing patient care in the NeuroICU setting varied widely between institutions. In contrast, these practices were similar in providing 24-hour coverage (76%), working with neurosurgical (88%) and anesthesiology residents (85%), and having critical-care fellowship training (97%). Almost all surveyed individuals practice both neurocritical care and anesthesia in the operating room, and 76% reported satisfaction with their working environment in the NeuroICU relative to other responsibilities. CONCLUSIONS: Anesthesiology-based neurointensivists currently represent a small subgroup within the rapidly growing neurointensivist workforce in the United States and consider neurocritical care a valuable aspect of their career. Promoting subspecialty training in neurocritical care among anesthesiologists may provide an opportunity for new patient-care frontiers and address the increasing need for NeuroICU physicians.

Predictors of extraventricular drain-associated bacterial ventriculitis.

PURPOSE: Bacterial ventriculitis (BV) may develop in patients requiring external ventricular drains (EVDs). The purpose of this study was to determine predictors of EVD-associated BV onset. MATERIALS AND METHODS: A retrospective review of Duke University Hospital patients with EVD device placement between January 2005 and May 2010 was conducted. Subject data were captured for predefined variables. Outcomes included in-hospital mortality, length of stay, and neurologic status at discharge. RESULTS: In 410 subjects with 420 EVDs, the BV rate was 10.2%. Univariate analysis indicated that age, sex, positive blood culture, duration of EVD placement, and the number of cerebrospinal fluid (CSF) samples taken were associated with BV. Of these, the number of CSF samples and sex retained significance in multivariable modeling (female: odds ratio, 0.47 [confidence interval, 0.23-0.97]; CSF samples: odds ratio, 1.08 [confidence interval 1.01-1.17]; P = .04; c index = 0.69). In this model, each CSF sample taken expanded the likelihood of BV by 8.3%. The most common pathogens were Staphylococcus or proprioniobacter (n = 26). Bacterial ventriculitis was associated with an increase in hospital length of stay (33 ± 22.9 days vs 24.6 ± 20.4 days; P = .04) but not mortality. CONCLUSION: An association exists between CSF sampling frequency and the development of EVD-associated BV. Larger prospective studies should be aimed at identifying causal relationships between these variables.

Gender and age interact to affect early outcome after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common and devastating form of cerebrovascular disease. In ICH, gender differences in outcomes remain relatively understudied but have been examined in other neurological emergencies. Further, a potential effect of age and gender on outcomes after ICH has not been explored. This study was designed to test the hypothesis that age and gender interact to modify neurological outcomes after ICH. METHODS: Adult patients admitted with spontaneous primary supratentorial ICH from July 2007 through April 2010 were assessed via retrospective analysis of an existing stroke database at Duke University. Univariate analysis of collected variables was used to compare gender and outcome. Unfavorable outcome was defined as discharge to hospice or death. Using multivariate regression, the combined effect of age and gender on outcome after ICH was analyzed. RESULTS: In this study population, women were younger (61.1+14.5 versus 65.8+17.3 years, p=0.03) and more likely to have a history of substance abuse (35% versus 8.9%, p<0.0001) compared to men. Multivariable models demonstrated that advancing age had a greater effect on predicting discharge outcome in women compared to men (p=0.02). For younger patients, female sex was protective; however, at ages greater than 60 years, female sex was a risk factor for discharge to hospice or death. CONCLUSION: While independently associated with discharge to hospice or death after ICH, the interaction effect between gender and age demonstrated significantly stronger correlation with early outcome after ICH in a single center cohort. Prospective study is required to verify these findings.

In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation.

Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene product (FMRP), is the most common heritable cause of intellectual disability and autism spectrum disorders. It has been long hypothesized that the phosphorylation of serine 500 (S500) in human FMRP controls its function as an RNA-binding translational repressor. To test this hypothesis in vivo, we employed neuronally targeted expression of three human FMR1 transgenes, including wild-type (hFMR1), dephosphomimetic (S500A-hFMR1) and phosphomimetic (S500D-hFMR1), in the Drosophila FXS disease model to investigate phosphorylation requirements. At the molecular level, dfmr1 null mutants exhibit elevated brain protein levels due to loss of translational repressor activity. This defect is rescued for an individual target protein and across the population of brain proteins by the phosphomimetic, whereas the dephosphomimetic phenocopies the null condition. At the cellular level, dfmr1 null synapse architecture exhibits increased area, branching and bouton number. The phosphomimetic fully rescues these synaptogenesis defects, whereas the dephosphomimetic provides no rescue. The presence of Futsch-positive (microtubule-associated protein 1B) supernumerary microtubule loops is elevated in dfmr1 null synapses. The human phosphomimetic restores normal Futsch loops, whereas the dephosphomimetic provides no activity. At the behavioral level, dfmr1 null mutants exhibit strongly impaired olfactory associative learning. The human phosphomimetic targeted only to the brain-learning center restores normal learning ability, whereas the dephosphomimetic provides absolutely no rescue. We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior.