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Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour

Mon, 11/28/2016 - 11:32am

Astrocytes associate with synapses throughout the brain and express receptors for neurotransmitters that can increase intracellular calcium (Ca2+). Astrocytic Ca2+ signalling has been proposed to modulate neural circuit activity, but the pathways that regulate these events are poorly defined and in vivo evidence linking changes in astrocyte Ca2+ levels to alterations in neurotransmission or behaviour is limited. Here we show that Drosophila astrocytes exhibit activity-regulated Ca2+ signalling in vivo. Tyramine and octopamine released from neurons expressing tyrosine decarboxylase 2 (Tdc2) signal directly to astrocytes to stimulate Ca2+ increases through the octopamine/tyramine receptor (Oct-TyrR) and the transient receptor potential (TRP) channel Water witch (Wtrw), and astrocytes in turn modulate downstream dopaminergic neurons. Application of tyramine or octopamine to live preparations silenced dopaminergic neurons and this inhibition required astrocytic Oct-TyrR and Wtrw. Increasing astrocyte Ca2+ signalling was sufficient to silence dopaminergic neuron activity, which was mediated by astrocyte endocytic function and adenosine receptors. Selective disruption of Oct-TyrR or Wtrw expression in astrocytes blocked astrocytic Ca2+ signalling and profoundly altered olfactory-driven chemotaxis and touch-induced startle responses. Our work identifies Oct-TyrR and Wtrw as key components of the astrocytic Ca2+ signalling machinery, provides direct evidence that octopamine- and tyramine-based neuromodulation can be mediated by astrocytes, and demonstrates that astrocytes are essential for multiple sensory-driven behaviours in Drosophila.

Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter

Mon, 11/28/2016 - 11:32am

Circadian rhythms are based on endogenous clocks that allow organisms to adjust their physiology and behavior by entrainment to the solar day and, in turn, to select the optimal times for most biological variables. Diverse model systems-including mice, flies, fungi, plants, and bacteria-have provided important insights into the mechanisms of circadian rhythmicity. However, the general principles that govern the circadian clock of Caenorhabditis elegans have remained largely elusive. Here we report robust molecular circadian rhythms in C elegans recorded with a bioluminescence assay in vivo and demonstrate the main features of the circadian system of the nematode. By constructing a luciferase-based reporter coupled to the promoter of the suppressor of activated let-60 Ras (sur-5) gene, we show in both population and single-nematode assays that C elegans expresses approximately 24-h rhythms that can be entrained by light/dark and temperature cycles. We provide evidence that these rhythms are temperature-compensated and can be re-entrained after phase changes of the synchronizing agents. In addition, we demonstrate that light and temperature sensing requires the photoreceptors LITE and GUR-3, and the cyclic nucleotide-gated channel subunit TAX-2. Our results shed light on C elegans circadian biology and demonstrate evolutionarily conserved features in the circadian system of the nematode.

Obesity, health-care utilization, and health-related quality of life after fracture in postmenopausal women: Global Longitudinal Study of Osteoporosis in Women (GLOW)

Tue, 11/22/2016 - 2:21pm

Fractures may be associated with higher morbidity in obese postmenopausal women than in nonobese women. We compared health-care utilization, functional status, and health-related quality of life (HRQL) in obese, nonobese, and underweight women with fractures. Information from the GLOW study, started in 2006, was collected at baseline and at 1, 2, and 3 years. In this subanalysis, self-reported incident clinical fractures, health-care utilization, HRQL, and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 nonobese, and 941 obese women with one or more incident clinical fractures during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities, and fracture type, was significantly greater in obese than nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score were significantly worse in obese than in nonobese women, both before and after fracture; but changes after fracture were similar across groups. Use of antiosteoporosis medication was significantly lower in obese than in nonobese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than nonobese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.

Biomedical Research Data Management Open Online Education: Challenges & Lessons Learned

Sun, 11/20/2016 - 7:52pm

The Best Practices for Biomedical Big Data project is a two year collaboration between Harvard Medical School and University of Massachusetts Medical School, funded by the NIH Big Data to Knowledge (BD2K) Initiative for Resource Development. The Best Practices for Biomedical Research Data Management Massive Open Online Course (MOOC) provides training to librarians, biomedical researchers, undergraduate and graduate biomedical students, and other interested individuals on recommended practices facilitating the discoverability, access, integrity, reuse value, privacy, security, and long term preservation of biomedical research data. This poster highlights lessons learned from the first year of this project.

Built upon the New England Collaborative Data Management Curriculum, the development team sought to use existing curricular materials to create a fully online course. The course is designed with an open course platform, WordPress Learning Management System (WPLMS), in order to facilitate broad access. Each of the MOOC’s nine modules is dedicated to a specific component of data management best practices and includes video lectures, presentation slides, research teaching cases, readings, activities, and interactive quizzes.

The project team overcame multiple challenges related to creating an open online course: curriculum, audience and software.

Working towards overcoming these, the Best Practices for Biomedical Research Data Management MOOC development team has moved slowly and deliberately, created additional content, and added content experts to provide guidance. These lessons learned will assist course development beyond this project, adding to best practices for creating massive open online courseware. Lessons learned include: teaching method influences the curriculum and content should not be developed in isolation from the teaching method; content is dependent on audience and supplementary content can be used to bridge audience gaps; and implementing new or unfamiliar technologies is challenging so allow more time in the timeline for project team to work with open source platform.

Gallbladder opacification on gadoxetate disodium-enhanced CT scan

Fri, 11/18/2016 - 8:23am

This study aimed to evaluate the radiologist's ability to identify excreted gadoxetate disodium within the gallbladder on CT scan. Thirty three healthy adults underwent imaging of the liver during work-up for potential liver donation. Three patients had undergone prior cholecystectomy and therefore were excluded. Imaging consisted of gadoxetate disodium-enhanced magnetic resonance cholangiography (MRC) and multiphase contrast-enhanced CT scan of the abdomen and pelvis. Two fellowship-trained abdominal imaging radiologists, who were blinded to the MRC images and the contrast agent used during MRC, independently reviewed the CT scans of the 30 patients that were included. The scans were evaluated for the presence or absence of abnormal hyperdensity within the gallbladder. Three patients did not receive intravenous gadoxetate disodium, 4 patients had their MRC after the CT scan, and 1 patient had the CT scans 5 days following the MRC. Twenty two patients had the CT scan within 24 h following the gadoxetate disodium-enhanced MRC. Of the 22 patients expected to have gadolinium in the gallbladder, both reviewers identified hyperdensity in the same 20 patients (90%). Both reviewers reported no abnormal hyperdensity within the gallbladder in the remaining 10 patients. CT scan can reveal excreted gadoxetate disodium within the gallbladder lumen and therefore gadoxetate disodium-enhanced CT scan can potentially play a role in the evaluation of cystic duct patency and work-up of acute cholecystitis.

Transfusion practices in evolution, not revolution*

Thu, 11/17/2016 - 12:31pm

Comment on: Survey on stated transfusion practices in PICUs*. [Pediatr Crit Care Med. 2014]

Determinants of red blood cell transfusion in pediatric trauma patients admitted to the intensive care unit

Thu, 11/17/2016 - 12:31pm

BACKGROUND: There are no well-designed prospective studies evaluating transfusion practices in pediatric trauma. We sought to describe red blood cell (RBC) transfusion practices in trauma patients who were admitted to a pediatric intensive care unit (PICU).

STUDY DESIGN AND METHODS: This study is a post-hoc analysis of a prospective, 6-month observational study in 30 PICUs. We studied a total of 580 patients aged less than 18 years who had been admitted to a PICU for more than 48 hours, including 95 who were trauma patients.

RESULTS: Trauma patients more frequently received transfusion before PICU admission (p < 0.001), were older (p < 0.0001), and more frequently were mechanically ventilated (p = 0.05). In the PICU, trauma patients received more transfusions (55% vs. 37%; p < 0.001), although admission hemoglobin levels were similar in both groups (p = 0.86). The mean (+/- standard deviation) pretransfusion hemoglobin level in the PICU was 9.0 +/- 2.4 g/dL for trauma patients compared with 8.3 +/- 2.4 g/dL for nontrauma patients (p = 0.09). Among the trauma patients, transfusion was associated with younger age, higher Pediatric Logistic Organ Regression scores, mechanical ventilation, bleeding, and transfusion before PICU admission. Multivariate regression demonstrated that receiving an RBC transfusion before admission was strongly associated with receiving a blood transfusion in the PICU (p = 0.008).

CONCLUSION: Trauma patients are at high risk for receiving an RBC transfusion both before and during their PICU stay, despite a similar transfusion threshold compared with nontrauma patients. Transfusion before PICU admission is a strong determinant, suggesting ongoing bleeding that will require re-transfusion. Further studies are needed to evaluate whether a restrictive transfusion strategy can safely be considered in these patients.

1274: Pediatric Critical Care Transfusion and Anemia Expertise Initiative

Thu, 11/17/2016 - 12:31pm

Abstract no. 1974 for the Critical Care Congress, Research Snapshot Theater: Quality and Safety XXV.

A Longitudinal Study of Peripubertal Serum Organochlorine Concentrations and Semen Parameters in Young Men: The Russian Children's Study

Wed, 11/16/2016 - 9:02pm

BACKGROUND: Exposures to endocrine disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.

OBJECTIVE: We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.

METHODS: From 2003 to 2005, 516 boys were enrolled at age 8-9 years and followed for up to ten years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At age 18-19 years, 133 young men provided one or two semen samples (256 samples) collected approximately one week apart, which were analyzed for volume, sperm concentration and motility. Unadjusted and adjusted linear mixed models were used to examine the associations of quartiles of lipid-standardized concentrations of dioxins [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs)], furans, polychlorinated biphenyls (PCBs) and corresponding toxic equivalents (TEQs) with semen parameters.

RESULTS: The median (range) for TCDD was 2.9 (0.4, 12.1) pg/g lipid and PCDD TEQs was 8.7 (1.0, 36.0) pg TEQ/g lipid. Higher quartiles of TCDD and PCDD TEQs were associated with lower sperm concentration, total sperm count and total motile sperm count (p-trends < /=0.05). The highest quartile of peripubertal serum TCDD concentrations was associated with a decrease (95% Confidence Interval) of 40% (18, 66%), 29% (3, 64%) and 30% (2, 70%) in sperm concentration, total sperm count, and total motile sperm count, respectively, compared with the lowest quartile. Similar associations were observed for serum PCDD TEQs with semen parameters. Serum PCBs, furans and total TEQs were not associated with semen parameters.

CONCLUSION: Higher peripubertal serum TCDD concentrations and PCDD TEQs were associated with poorer semen parameters.

WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects

Wed, 11/16/2016 - 9:02pm

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis

Wed, 11/16/2016 - 9:02pm

The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa-induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice that are typically resistant to P. aeruginosa-induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found to be dependent on both eye and gut microbiota with the eye microbiota having a moderate, but significant impact on the resistance to infection. These events were IL-1ss-dependent as corneal IL-1ss levels were decreased in the infected GF and antibiotic-treated mice when compared to the SPF controls, and neutralization of IL-1ss increased the ocular bacterial burden in the SPF mice. Monocolonizing GF mice with Coagulase Negative Staphylococcus sp. isolated from the conjunctival swabs was sufficient to restore resistance to infection. Cumulatively, these data underline a previously unappreciated role for microbiota in regulating susceptibility to ocular keratitis. We predict that these results will have significant implications for contact lens wearers, where alterations in the ocular commensal communities may render the ocular surface vulnerable to infections.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations

Wed, 11/16/2016 - 9:02pm

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

And the survey said.... evaluating rationale for participation in gun buybacks as a tool to encourage higher yields

Wed, 11/16/2016 - 9:02pm

BACKGROUND: Gun buyback programs represent one arm of a multipronged approach to raise awareness and education about gun safety.

METHODS: The city of Worcester, MA has conducted an annual gun buyback at the Police Department Headquarters since 2002. We analyzed survey responses from a voluntary, 18-question, face-to-face structured interview from December 2009 to June 2015 using descriptive statistics to determine participant demographics and motivations for participation.

RESULTS: A total of 943 guns were collected, and 273 individuals completed surveys. The majority of participants were white males older than 55years (42.4%). Participants represented 61 zip codes across Worcester County, with 68% having prior gun safety training and 61% with weapons remaining in the home (27% of which children could potentially access). The top reasons for turning in guns were "no longer needed" (48%) and "fear of children accessing the gun" (14%). About 1 in 3 respondents knew someone injured/killed by gun violence. Almost all (96%) respondents claimed the program raised community awareness of firearm risk.

CONCLUSION: The Worcester Goods for Guns Buyback has collected more than 900 guns between 2009 and 2015. The buyback removes unwanted guns from homes and raises community awareness about firearm safety.

Differences in the Quality of Pediatric Resuscitative Care Across a Spectrum of Emergency Departments

Wed, 11/16/2016 - 9:02pm

Importance: The quality of pediatric resuscitative care delivered across the spectrum of emergency departments (EDs) in the United States is poorly described. In a recent study, more than 4000 EDs completed the Pediatric Readiness Survey (PRS); however, the correlation of PRS scores with the quality of simulated or real patient care has not been described.

Objective: To measure and compare the quality of resuscitative care delivered to simulated pediatric patients across a spectrum of EDs and to examine the correlation of PRS scores with quality measures.

Design, Setting, and Participants: This prospective multicenter cohort study evaluated 58 interprofessional teams in their native pediatric or general ED resuscitation bays caring for a series of 3 simulated critically ill patients (sepsis, seizure, and cardiac arrest).

Main Outcomes and Measures: A composite quality score (CQS) was measured as the sum of 4 domains: (1) adherence to sepsis guidelines, (2) adherence to cardiac arrest guidelines, (3) performance on seizure resuscitation, and (4) teamwork. Pediatric Readiness Survey scores and health care professional demographics were collected as independent data. Correlations were explored between CQS and individual domain scores with PRS.

Results: Overall, 58 teams from 30 hospitals participated (8 pediatric EDs [PEDs], 22 general EDs [GEDs]). The mean CQS was 71 (95% CI, 68-75); PEDs had a higher mean CQS (82; 95% CI, 79-85) vs GEDs (66; 95% CI, 63-69) and outperformed GEDs in all domains. However, when using generalized estimating equations to estimate CQS controlling for clustering of the data, PED status did not explain a higher CQS (beta = 4.28; 95% CI, -4.58 to 13.13) while the log of pediatric patient volume did explain a higher CQS (beta = 9.57; 95% CI, 2.64-16.49). The correlation of CQS to PRS was moderate (r = 0.51; P < .001). The correlation was weak for cardiac arrest (r = 0.24; P = .07), weak for sepsis (rho = 0.45; P < .001) and seizure (rho = 0.43; P = .001), and strong for teamwork (rho = 0.71; P < .001).

Conclusions and Relevance: This multicenter study noted significant differences in the quality of simulated pediatric resuscitative care across a spectrum of EDs. The CQS was higher in PEDs compared with GEDs. However, when controlling for pediatric patient volume and other variables in a multivariable model, PED status does not explain a higher CQS while pediatric patient volume does. The correlation of the PRS was moderate for simulation-based measures of quality.

Medicare Facility Diagnosis Related Groups Have Outpaced Individual Physician Payment

Wed, 11/16/2016 - 9:01pm

INTRODUCTION: We set out to compare the rates of Medicare reimbursement to physicians versus hospitals for several major vascular procedures over a period of five years.

METHODS: We queried the Wolters Luwer MediRegs database to collect Medicare reimbursement data from fiscal years 2011 to 2015. We surveyed reimbursements for carotid endarterectomy (CEA), carotid angioplasty and stenting (CAS), femoropopliteal bypass, and lower extremity fem-pop revascularization with stenting. Based on data availability, we surveyed physician reimbursement data on the national level and in both medically over-served and underserved areas. Hospital reimbursement rates were examined on a national level and by hospitals' teaching and wage index statuses.

RESULTS: We found that for all four vascular procedures, Medicare reimbursements to hospitals increased by a greater percentage than to physicians. By region, underserved areas had lower physician reimbursements than the national average, while the opposite was true for overserved areas. Additionally, for hospital Medicare reimbursements, location in a high wage index accounted for a significant increase in reimbursement over the national average, with teaching status contributing to this increase to a smaller extent.

CONCLUSIONS: This data on Medicare reimbursements indicate that payments to hospitals are increasing more significantly than to physicians. This disparity in pay changes affects both independent and academic vascular surgeons. Medicare should consider pay increases to independent providers in accordance to the hospital pay increase.

Poor Adherence to Lung-Protective Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome

Wed, 11/16/2016 - 9:01pm

OBJECTIVES: To determine the frequency of low-tidal volume ventilation in pediatric acute respiratory distress syndrome and assess if any demographic or clinical factors improve low-tidal volume ventilation adherence.

DESIGN: Descriptive post hoc analysis of four multicenter pediatric acute respiratory distress syndrome studies.

SETTING: Twenty-six academic PICU.

PATIENTS: Three hundred fifteen pediatric acute respiratory distress syndrome patients.

MEASUREMENTS AND MAIN RESULTS: All patients who received conventional mechanical ventilation at hours 0 and 24 of pediatric acute respiratory distress syndrome who had data to calculate ideal body weight were included. Two cutoff points for low-tidal volume ventilation were assessed: less than or equal to 6.5 mL/kg of ideal body weight and less than or equal to 8 mL/kg of ideal body weight. Of 555 patients, we excluded 240 for other respiratory support modes or missing data. The remaining 315 patients had a median PaO2-to-FIO2 ratio of 140 (interquartile range, 90-201), and there were no differences in demographics between those who did and did not receive low-tidal volume ventilation. With tidal volume cutoff of less than or equal to 6.5 mL/kg of ideal body weight, the adherence rate was 32% at hour 0 and 33% at hour 24. A low-tidal volume ventilation cutoff of tidal volume less than or equal to 8 mL/kg of ideal body weight resulted in an adherence rate of 58% at hour 0 and 60% at hour 24. Low-tidal volume ventilation use was no different by severity of pediatric acute respiratory distress syndrome nor did adherence improve over time. At hour 0, overweight children were less likely to receive low-tidal volume ventilation less than or equal to 6.5 mL/kg ideal body weight (11% overweight vs 38% nonoverweight; p = 0.02); no difference was noted by hour 24. Furthermore, in the overweight group, using admission weight instead of ideal body weight resulted in misclassification of up to 14% of patients as receiving low-tidal volume ventilation when they actually were not.

CONCLUSIONS: Low-tidal volume ventilation is underused in the first 24 hours of pediatric acute respiratory distress syndrome. Age, Pediatric Risk of Mortality-III, and pediatric acute respiratory distress syndrome severity were not associated with improved low-tidal volume ventilation adherence nor did adherence improve over time. Overweight children were less likely to receive low-tidal volume ventilation strategies in the first day of illness.

Barriers to Care Coordination and Medical Home Implementation

Wed, 11/16/2016 - 9:01pm

BACKGROUND: Pediatricians are central in leading the family-centered medical home (FCMH), yet little is known about how provider-perceived barriers to and attitudes toward the FCMH affect implementation. This study aims to assess the relationship between pediatrician-perceived barriers to and attitudes toward FCMH and reported care coordination.

METHODS: Pediatricians working in ambulatory care responded to the American Academy of Pediatrics Periodic Survey of Fellows #79 (N = 572, response rate, 59%). Our primary care coordination outcomes were whether pediatricians were: (1) leading a multidisciplinary team; (2) developing care plans; and (3) connecting with support services. Independent variables included barriers to FCMH implementation (lack of communication skills, support services, and time). Associations between outcomes and barriers were assessed by multivariate logistic regression, controlling for pediatrician and practice characteristics.

RESULTS: Lack of sufficient personnel was significantly associated with fewer care coordination activities: leading a multidisciplinary team (odds ratio [OR], 0.53), developing care plans (OR, 0.51), and connecting with support services (OR, 0.42). Lacking communication skills was significantly associated with lower odds of development of care plans (OR, 0.56) and assistance with support services (OR, 0.64). Lack of time was significantly associated with lower odds of leading a multidisciplinary team (OR, 0.53). A pediatrician's belief that the FCMH encourages the use of preventive services was significantly associated with increased support services (OR, 2.06).

CONCLUSIONS: Pediatricians report a need for sufficient personnel and communication skills to provide care coordination, a core component of the FCMH. Interventions to boost FCMH implementation should focus on providing resources to develop these characteristics.

Multiple Cafe au Lait Spots in a Group of Fair-Skinned Children without Signs or Symptoms of Neurofibromatosis Type 1

Wed, 11/16/2016 - 9:01pm

BACKGROUND: The presence of six or more cafe au lait (CAL) spots is a criterion for the diagnosis of neurofibromatosis type 1 (NF-1). Children with multiple CAL spots are often referred to dermatologists for NF-1 screening. The objective of this case series is to characterize a subset of fair-complected children with red or blond hair and multiple feathery CAL spots who did not meet the criteria for NF-1 at the time of their last evaluation.

METHODS: We conducted a chart review of eight patients seen in our pediatric dermatology clinic who were previously identified as having multiple CAL spots and no other signs or symptoms of NF-1.

RESULTS: We describe eight patients ages 2 to 9 years old with multiple, irregular CAL spots with feathery borders and no other signs or symptoms of NF-1. Most of these patients had red or blond hair and were fair complected. All patients were evaluated in our pediatric dermatology clinic, some with a geneticist. The number of CAL spots per patient ranged from 5 to 15 (mean 9.4, median 9).

CONCLUSION: A subset of children, many with fair complexions and red or blond hair, has an increased number of feathery CAL spots and appears unlikely to develop NF-1, although genetic testing was not conducted. It is important to recognize the benign nature of CAL spots in these patients so that appropriate screening and follow-up recommendations may be made.

Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence

Wed, 11/16/2016 - 9:01pm

BACKGROUND: Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels.

METHODS: Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays.

RESULTS: A predictor of recurrence was age > /=65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI.

CONCLUSIONS: Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI.

CLINICAL TRIALS REGISTRATION: NCT00350298.