Analysis of serum inflammatory mediators identifies unique dynamic networks associated with death and spontaneous survival in pediatric acute liver failure

Background: Tools to predict death or spontaneous survival are necessary to inform liver transplantation (LTx) decisions in pediatric acute liver failure (PALF), but such tools are not available. Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure. We hypothesized that specific, dynamic, and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF. Methods: We assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group (PALFSG) collected within 7 days after enrollment. Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors, non-survivors, and LTx recipients. Data were subjected to statistical analysis, patient-specific Principal Component Analysis (PCA), and Dynamic Bayesian Network (DBN) inference. Findings: Raw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes. However, DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died. The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died, a finding supported by PCA. Interpretation: The application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF. Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died. DBN-based analyses might lead to a better prediction of outcome in PALF, and could also have more general utility in other complex diseases with an inflammatory etiology. Copyright: © 2013 Azhar et al

Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study

<p>Abstract</p> <p>Background</p> <p>Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.</p> <p>Methods</p> <p>Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.</p> <p>Results</p> <p>Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.</p> <p>Conclusions</p> <p>Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.</p> <p>Trial Registration</p> <p>D9614C00097; ClinicalTrials.gov identifier NCT00228527.</p

Gravitational Lensing in Astronomy

Deflection of light by gravity was predicted by General Relativity and observationaly confirmed in 1919. In the following decades various aspects of the gravitational lens effect were explored theoretically, among them the possibility of multiple or ring-like images of background sources, the use of lensing as a gravitational telescope on very faint and distant objects, and the possibility to determine Hubble's constant with lensing. Only relatively recently gravitational lensing became an observational science after the discovery of the first doubly imaged quasar in 1979. Today lensing is a booming part of astrophysics. In addition to multiply-imaged quasars, a number of other aspects of lensing have been discovered since, e.g. giant luminous arcs, quasar microlensing, Einstein rings, galactic microlensing events, arclets, or weak gravitational lensing. By now literally hundreds of individual gravitational lens phenomena are known. Although still in its childhood, lensing has established itself as a very useful astrophysical tool with some remarkable successes. It has contributed significant new results in areas as different as the cosmological distance scale, the large scale matter distribution in the universe, mass and mass distribution of galaxy clusters, physics of quasars, dark matter in galaxy halos, or galaxy structure.Comment: Review article for "Living Reviews in Relativity", see http://www.livingreviews.org . 41 pages, latex, 22 figures (partly in GIF format due to size constraints). High quality postscript files can be obtained electronically at http://www.aip.de:8080/~jkw/review_figures.htm