SPLUNC1 as a biomarker of pulmonary exacerbations in children with cystic fibrosis.

BACKGROUND: Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is an innate defence protein that acts as an anti-microbial agent and regulates airway surface liquid volume through inhibition of the epithelial sodium channel (ENaC). SPLUNC1 levels were found to be reduced in airway secretions of adults with cystic fibrosis (CF). The potential of SPLUNC1 as a biomarker in children with CF is unknown. METHODS: We quantified SPLUNC1, interleukin-8 (IL-8) and neutrophil elastase (NE) in sputum of CF children treated with either intravenous antibiotics or oral antibiotics for a pulmonary exacerbation (PEx)s, and in participants of a prospective cohort of CF children with preserved lung function on spirometry, followed over a period of two years. RESULTS: Sputum SPLUNC1 levels were significantly lower before compared to after intravenous and oral antibiotic therapy for PEx. In the longitudinal cohort, SPLUNC1 levels were found to be decreased at PEx visits compared to both previous and subsequent stable visits. Higher SPLUNC1 levels at stable visits were associated with longer PEx-free time (hazard ratio 0.85, p = 0.04). SPLUNC1 at PEx visits did not correlate with IL-8 or NE levels in sputum or forced expiratory volume in one second (FEV1) but did correlate with the lung clearance index (LCI) (r=-0.53, p < 0.001). CONCLUSION: SPLUNC1 demonstrates promising clinometric properties as a biomarker of PEx in children with CF.

Low molecular weight heparin therapy during pregnancy is associated with elevated circulatory levels of placental growth factor.

INTRODUCTION: Low molecular weight heparin (LMWH) has been shown to be effective in decreasing the recurrence of placenta-mediated complications of pregnant women. The aim of this study was to determine the effect of LMWH on circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PLGF) in pregnant women who required anticoagulation therapy. METHODS: A longitudinal prospective cohort study was performed including pregnant women in whom anticoagulation therapy by LMWH during pregnancy was clinically indicated (n = 33). Healthy pregnant women, matched for gestational age, who did not require thromboprophylaxis served as controls (n = 29). Maternal plasma samples were obtained throughout gestation every 4 weeks and stored at -70 °C. Maternal plasma concentrations of sFlt-1, sEng and PLGF were determined by ELISA and compared between the two groups. RESULTS: Patients treated with LMWH had significantly increased circulatory levels of PLGF during the third trimester compared with controls (28-34 weeks: 719.2 pg/ml vs 558.6 pg/ml at, p < 0.01; 35-40 weeks: 975.6 pg/ml vs 511.2 pg/ml, p < 0.01, respectively). In contrast, circulatory levels of sFlt-1 and sEng were similar between the LMWH treatment group and controls throughout gestation. Consistent with these findings, the ratio of sFlt-1/PLGF was lower in patients treated with LMWH compared to controls (28-34 weeks: 1.9 vs 7.2, p < 0.05; 35-40 weeks: 5 vs 12.9, p < 0.05, respectively). DISCUSSION: Anticoagulation treatment of pregnant women with LMWH is associated with a pro-angiogenic state. These findings may explain the effectiveness of LMWH in the prevention of placenta-mediated complications of pregnancy.

Late diagnosis of fetal central nervous system anomalies following a normal second trimester anatomy scan.

OBJECTIVE: The aim of this study was to describe the nature of central nervous system (CNS) anomalies diagnosed during the third trimester following a normal anatomy scan at 21-24 weeks of gestation. METHODS: Retrospective cohort study of all pregnant women referred to the fetal medicine unit at Sheba Medical Center between 2005 and 2011 due to fetal CNS anomalies detected at the late second and third trimesters following a normal anatomy scan at 21-24 weeks of gestation. RESULTS: During the study period, 47 patients were diagnosed with fetal CNS anomalies at a median gestational age of 31.1 weeks (range 24-38). The four most common anomalies found included intracranial cysts (19%), mild ventriculomegaly (15%), absence or dysgenesis of the corpus callosum (10%), and intracerebral hemorrhage (10%). Other CNS anomalies detected in this group of patients included hydrocephalus, Dandy walker malformation, large cysterna magna, microcephalus with lissencephaly, craniosynestosis, periventricular pseudocysts, global brain ischemia, cerebellar hypoplasia, and sub-ependymal nodule. CONCLUSIONS: Fetal brain continues to evolve throughout gestation, and therefore, some of the CNS anomalies can be diagnosed only during late second and third trimesters of pregnancy. Consequently, in patients who have a third trimester scan for any reason, assessment of the fetal CNS should be considered.