BackgroundSingle-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database.MethodsAll neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition —i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7.FindingsIncidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5–8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1–11·5); p<0·0001].InterpretationNeonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients.FundingUS National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children’s, University of New Mexico.

Background-House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent T H 2-mediated responses, are unknown.

Allergic diseases, which have reached epidemic proportions, are driven by inappropriate immune responses to a relatively small number of environmental proteins. The molecular basis for the propensity of specific proteins to drive maladaptive, allergic responses has been difficult to define. Recent data suggest that the ability of such proteins to drive allergic responses in susceptible hosts is a function of their ability to interact with diverse pathways of innate immune recognition and activation at mucosal surfaces. This review highlights recent insights into innate immune activation by allergens—via proteolytic activity, engagement of pattern recognition receptors, molecular mimicry of TLR signaling complex molecules, lipid binding activity, and oxidant potential—and the role of such activation in inducing allergic disease. A greater understanding of the fundamental origins of allergenicity should help define new preventive and therapeutic targets in allergic disease.

Caffeine, a nonspecific adenosine receptor (AR) antagonist is widely used to treat apnea of prematurity. Because adenosine modulates multiple biologic processes including inflammation, we hypothesized that AR blockade by caffeine would increase cytokine release from neonatal monocytes. Using cord blood monocytes (CBM), we investigated 1) the changes in AR mRNA profile by real time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and protein expression (western blot) after in vitro culture, caffeine or lipopolysaccharide (LPS) exposure, and 2) the modulation of cytokine release and cyclic adenosine monophosphate (cAMP) production by enzyme-linked immunosorbent assay (ELISA) induced by caffeine and specific AR antagonists: DPCPX(A 1 R), ZM241385(A 2a R), MRS1754(A 2b R), and MRS1220(A 3 R). After 48 h in culture, A 2a R and A 2b R gene expression increased 1.9 (p ϭ 0.04) and 2.5-fold (p ϭ 0.003), respectively. A 1 R protein expression directly correlated with increasing LPS concentrations (p ϭ 0.01), with minimal expression preexposure. Only caffeine (50 M) and DPCPX (10 nM) decreased tumor necrosis factor-alpha (TNF-␣) release from LPS activated-CBM by 20 and 25% (p ϭ 0.01) and TNF-␣ gene expression by 30 and 50%, respectively, in conjunction with a Ն2-fold increase in cAMP (p Ͻ 0.05). AR blockade did not modulate other measured cytokines. The induction of A 1 R after LPS exposure suggests an important role of this receptor in the control of inflammation in neonates. Our findings also suggest that caffeine, via A 1 R blockade, increases cAMP production and inhibits pretranscriptional TNF-␣ production by CBM. (Pediatr Res 65: 203-208, 2009) C affeine (1,3,11 trimethylxantine) is a stimulant widely used in neonatology to treat apnea of prematurity (1). At therapeutic range (5 to 15 g/mL), caffeine blocks A 1 and A 2a adenosine receptors (ARs) stimulating ventilation (2-4). Recently, caffeine has also been linked to a decrease in the incidence of bronchopulmonary dysplasia and cerebral palsy in extremely premature infants (5,6), although the mechanisms explaining these findings have not been elucidated.The natural ligand for ARs, adenosine, has a crucial role in multiple biologic processes including inflammation (7,8). The increase in tumor necrosis factor-alpha (TNF-␣) release by adult peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) exposure can be abolished by pretreatment with A 2a R agonists (9,10). Adenosine binding to A 1 R (11,12) and A 3 R (13,14) also modulates TNF-␣ release from adult monocytes, whereas A 2b R appears to have little effect (10).Little is known about AR expression on neonatal monocytes and the role of caffeine in modulating cytokine release. We hypothesized that caffeine blockade of ARs on neonatal monocytes would increase the release of cytokines in response to LPS. To test this hypothesis, we used cord blood monocytes (CBM) from full-term infants to 1) characterize the changes in AR mRNA profile and protein expression after 48 h in ...