Early pyloric stenosis: a case control study

Pyloric stenosis (PS) is rare in the first 2 weeks of life, often leading to delays in diagnosis and treatment. We conducted a case control study to delineate the characteristics of patients with early PS (EPS). In addition, we tested the hypothesis that patients with EPS present with a smaller pylorus than older patients. A database of all patients presenting with PS to a children’s hospital over a 5-year period (2002–2006) was obtained. Each patient admitted during the first 2 weeks of life (subject) was matched to a patient admitted after 4 weeks of age (control), with the same gender, electrolyte status, and treating surgeon. A single pediatric radiologist, blinded to patient age, reviewed all available ultrasounds retrospectively. Demographic, clinical, diagnostic, therapeutic, and outcome data were compared. During the study period, 278 pyloromyotomies were performed for PS. Sixteen patients (5.8%) presented with EPS between 2 and 14 days of life. EPS patients had a higher prevalence of positive family history (31 vs. 0%, P = 0.043), and breast milk feeding (75 vs. 31%, P = 0.045). Sonographic measurements showed a pylorus that was of significantly less length (17.1 ± 0.6 vs. 20.5 ± 0.9 mm, P = 0.006) and muscle thickness (3.5 ± 0.2 vs. 4.9 ± 0.2 mm, P < 0.001) in patients with EPS. Hospital stay was significantly longer for EPS patients (4.3 ± 0.9 vs. 2.0 ± 0.1 days, P = 0.19) Babies presenting with EPS are more likely to be breast fed and to have a positive family history. EPS is associated with a longer hospital stay. Use of sonographic diagnostic measurements specific to this age group may prevent delays in diagnosis and treatment, and improve outcomes

Rapid induction of inflammatory lipid mediators by the inflammasome in vivo

Detection of microbial products by host inflammasomes is critical for innate immune surveillance. Inflammasomes activate the CASPASE-1 (CASP1) protease, which processes the cytokines interleukin(IL)-1β and -18, and initiates a lytic host cell death called pyroptosis(1). To identify novel CASP1 functions in vivo, we devised a strategy for cytosolic delivery of bacterial flagellin, a specific ligand for the NAIP5 (NLR family, apoptosis inhibitory protein 5)/NLRC4 (NLR family, CARD domain containing 4) inflammasome(2–4). Here we show that systemic inflammasome activation by flagellin leads to loss of vascular fluid into the intestine and peritoneal cavity, resulting in rapid (< 30 minutes) death in mice. This unexpected response depends on the inflammasome components NAIP5, NLRC4, and CASP1, but is independent of IL-1β/-18 production. Instead, inflammasome activation results, within minutes, in an ‘eicosanoid storm’ – a pathological release of signaling lipids that rapidly initiate inflammation and vascular fluid loss. Mice deficient in cyclooxygenase-1 (COX-1), a critical enzyme in prostaglandin biosynthesis, are resistant to these rapid pathological effects of systemic inflammasome activation by either flagellin or anthrax lethal toxin. Inflammasome-dependent biosynthesis of eicosanoids is mediated by activation of cPLA2 (cytosolic phospholipase A2) in resident peritoneal macrophages, which are specifically primed for production of eicosanoids by high expression of eicosanoid biosynthetic enzymes. Thus, our results identify eicosanoids as a novel cell type-specific signaling output of the inflammasome with dramatic physiological consequences in vivo