Reduced microvascular density in omental biopsies of children with chronic kidney disease

Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD.Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease

Online collaboration and cooperation : the recurring importance of evidence, rationale and viability

This paper investigates collaboration in teaching and learning and draws out implications for the promotion of collaboration within online environments. It is divided into four sections. First the case for collaboration, including specifically cooperative approaches, is explored. This case revolves around the impact of collaboration on the quality of learning and on learning outcomes. Collaboration is seen as constrained by context but, if structured and rewarded, it will bring important motivational and cognitive benefits. Next, the case for online collaboration is examined. This is based on longstanding arguments about the benefits of working together albeit in an environment which offers greater reach; a mix of media; and archives of interaction. The third section of the paper compares perspectives on online collaboration with a longer tradition of research into collaboration in general; it critiques the idea that online mediation offers a paradigm change in teaching and learning. The fourth section of the paper considers future directions for promoting online collaboration

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort

Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective:To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance:Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.The research received funding from grant agreement 259882 from the European Union Seventh Framework Program (2007-2013). Additional funding in France was provided by the French Institute of Public Health Research/Institute of Public Health and its partners, including the French Health Ministry, the National Institute of Health and Medical Research, the National Institute of Cancer, and the National Solidarity Fund for Autonomy, by grant ANR-11-EQPX-0038 from the National Research Agency through the French Equipex Program of Investments in the Future, and by the PremUp Foundation; in Poland, by 2012-2015 allocation of funds for international projects from the Polish Ministry of Science and HigherEducation; and in Sweden, by regional agreementon medical training and clinical research betweenStockholm County Council and Karolinska Institutetand by the Department of Neonat al Medicine at theKarolinska University Hospital

O-066 Admission Hypothermia In Very Preterm Infants Is Associated With Mortality – Results From The Epice Cohort

Strategies to prevent heat loss in the delivery room after very preterm birth have been proven effective in randomised controlled trials. Nevertheless, we hypothesise that hypothermia at admission to neonatal care is still common and contributes to mortality after very preterm birth. The EPICE cohort included all births between 22+0 and 31+6 weeks of gestation in 19 regions from11 European countries in 2011–2012. We studied infants surviving to admission to neonatal care (n = 7577). The association between temperature at admission and in-hospital mortality was analysed using logistic regression. The final model adjusted for gestational age, small for gestational age (SGA), Apgarscore <7 at 5 min, infant sex and region of birth. Of 6639 infants with data on body temperature at admission, 1670 infants (25%) were hypothermic (<36.0° C); 6% had temperatures <35°C, 7% between 35.0 and 35.4°and 12% between 35.5 and 35.9°. Body temperature at admission was inversely related to mortality. The crude odds ratio (OR) (95% confidence interval [CI]) for mortality was 5.81(4.27–7.92) when temperature was <35°C; 3.32 (2.35–4.69) at 35.0–35.4°; and 1.61 (1.18–2.19) at 35.5–35.9°compared to normothermic infants (36.5–37.5°C). After adjustment, temperatures below 35.5°C remained significantly associated with mortality, 1.94 (1.32–2.83) at <35°C and 1.91(1.30–2.82) at 35–35.4°C compared to normothermic infants. Hypothermia after very preterm birth contributes to mortality in modern perinatal care settings in Europe. Further studies should investigate if evidence-based heat loss prevention strategies have been implemented