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BackgroundGuidelines are contradictory regarding the use of alginate in infants with persisting gastroesophageal reflux (GER). While The British National Institute for Health and Care (NICE) guidelines consider alginate as a treatment option, the guidelines of the European and North-American Societies for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN, NASPGHAN) do not recommend alginates.AimsWe assessed the efficacy of alginate to reduce GER episodes in infants.MethodsIn a prospective, observational study, we consecutively enrolled all infants referred for pH-multiple intraluminal impedance (pH-MII) recording because of persisting GER symptoms not responsive to behavior and dietetic modifications. A 48-h pH-MII was performed in all infants; a baseline recording was performed during the first 24 h while magnesium or sodium alginate was administered during the second 24 h. The primary endpoint was the difference in the total number of GER episodes per 24 h between the baseline day and the second day during which the alginate was administered. The secondary outcome was the difference in symptoms between each period. We also compared other pH-MII data from before and during alginate administration.ResultsWe recruited 43 infants (median age 68 days, range 25–306); three pH-MII tracings were excluded because of artifacts. The median number of all MII reflux episodes was significantly reduced during alginate administration (76.0 vs 69.5; p < 0.001). Crying-fussiness, cough and regurgitation episodes all significantly improved during alginate administration (p = 0.00012; p = 0.005 and p = 0.04, respectively). The following MII parameters also decreased during the alginate administration: acid (19.0 vs 14.5; p < 0.04), non-acid (52.0 vs 49.5; p < 0.004), proximal GER episodes (46.0 vs 41.4; p < 0.007), and bolus exposure index (1.9 vs 1.6; p = 0.002). At least three out of seven pH-MII parameters decreased by > 10% during the alginate period in 31/40 infants (77.5%), without a significant difference between magnesium and sodium alginate.ConclusionThese results suggest that alginate significantly decreases the number and extension of both acid and non-acid reflux episodes and associated symptoms in infants.Electronic supplementary materialThe online version of this article (10.1007/s40272-018-0314-0) contains supplementary material, which is available to authorized users.

Background/Aims Combined multichannel intraluminal impedance and pH monitoring (MII/pH) is considered the most accurate test to detect gastroesophageal reflux (GER), however lacking reference values. We aim to determine reference values for the pediatric population and to correlate these values with age and postprandial/fasting period. Methods We evaluated MII/pH traces from patients (newborns, infants, and children) admitted to 3 Italian hospitals and who underwent MII/ pH for suspected GER disease. Patients with MII/pH traces that showed significant symptom-reflux associations and/or a pathological reflux index (> 6% for newborns and infants, > 3% for children) were excluded. Traces were analysed in their entirety, and in the postprandial period (first hour after a meal) and the fasting period (the following hours before the next meal) separately. Results A total of 195 patients (46 newborns, 83 infants, and 66 children) were included. Age positively correlated with frequency of acidic GER events (r = 0.37, P < 0.05) and negatively associated with weakly acidic GER events (r = 0.46, P < 0.05). Conclusions This study describes the distribution of MII/pH values in a pediatric population with normally acidic GER exposure and no significant association between GER events and symptoms. These MII/pH values may be used as reference values in clinical practice for a corrected GER disease diagnosis in the pediatric population.

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Signal transducer and activator of transcription 3 (STAT3) plays an important role in cancer cell proliferation. HO-3867, a STAT3 inhibitor, has shown preclinical efficacy in ovarian cancer, but there is limited data in Hepatocellular carcinoma (HCC), a lethal disease with limited systemic therapy options. This project hypothesizes HO-3867 inhibits HCC cellular proliferation through STAT3 inhibition. Methods: Effects of increasing concentrations of HO-3867 on three HCC cell lines were assessed via calorimetric assay. Cell lysates were examined via Western blot for cell cycle arrest, pro-and anti-apoptotic markers, and traditional oncogenic pathways Notch, STAT3, and Phosphatidylinositol-3 Kinase (PI3-K)/Akt. Results: Concentrations of 2 mM HO-3867 led to a significant reduction in cellular proliferation (p = 0.001). Upon Western analysis, HO-3867 was associated with increased expression of cell cycle markers p21 and p27 and reduction in cyclin D1. Furthermore, an increase in pro-apoptotic cleaved poly ADP ribose polymerase (PARP) and reduction in anti-apoptotic Bcl2, BclXL, XIAP, and Survivin was observed. HO-3867 also demonstrated a reduction in pSTAT3 and concomitant inhibition of Notch and PI3-K/ AKT pathways as evidenced by reduction in Notch1-3, Hes1, and pAKT. However, higher concentrations of HO-3867 were associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), a cell survival protein. Conclusion: HO-3867, STAT3 inhibitor, mitigates HCC cell proliferation through cell cycle arrest and apoptosis through STAT3 inhibition. HO-3867 also reduces oncogenic targets Notch and Akt but at higher concentration increases phospho ERK1/2. This is the first study demonstrating HO-3867 effectiveness in HCC cells, providing a strong rationale for further preclinical analysis of HO-3867.