Colon polyps in patients with short bowel syndrome before and after teduglutide: post hoc analysis of the STEPS study series

Background & aims: Teduglutide promotes intestinal growth and is approved for the treatment of short bowel syndrome and intestinal failure (SBS-IF). Based on the pharmacologic activity and preclinical findings, teduglutide can potentially induce proliferative colonic mucosal changes. The aim of this study is to report the occurrence of colorectal polyps in adult patients with SBS-IF who received teduglutide in clinical studies conducted to date. Methods: A post hoc analysis of the completed Study of Teduglutide Effectiveness in Parenteral Nutrition-Dependent Short Bowel Syndrome Subjects (STEPS) clinical study series (NCT00798967, EudraCT 2008-006193-15; NCT00930644, EudraCT 2009-011679-65; NCT01560403) evaluated electronic case report form data for baseline colonoscopies (performed before treatment) and for surveillance or end-of-study (performed after treatment with teduglutide 0.05 mg/kg/day for 24 and 36 months) post-exposure procedures. Results: In the STEPS studies, 73 patients treated with teduglutide had a baseline colonoscopy. No post-exposure colonoscopy was scheduled in STEPS. In STEPS-2/3, 50 of 65 patients with remnant colon (77%) underwent a protocol-mandated post-exposure colonoscopy. Colon polyps were reported at baseline in 12% (9/73) of patients and post-exposure in 18% (9/50) of patients. Two had polyps both at baseline and post-exposure. On histology, available for 7 patients, 5 had adenomas (1 serrated, 4 tubular) and none had malignancy or high-grade dysplasia. Conclusion: These data support recommendations for colonoscopic screening before teduglutide therapy and subsequent on-therapy colonoscopic surveillance for patients with SBS-IF. Further studies are required to assess the risk of polyp formation in patients with SBS-IF and the most appropriate colon polyp surveillance strategies

Prospective Multi-Center Trial for the Efficacy of Ecabet Sodium on the Relief of Dyspepsia in Korean Patients with Chronic Gastritis

Anti-peptic and anti-inflammatory actions of ecabet sodium might be beneficial in either improving gastritis or relieving dyspeptic symptoms. This study was designed to evaluate the clinical efficacy of ecabet sodium on dyspeptic symptoms and to elucidate the molecular mechanism attributable to symptom relief in patients with chronic gastritis. Two hundred and sixty eight chronic gastritis patients with persistent dyspepsia received ecabet sodium 1 g b.i.d. for 2 weeks, after which dyspeptic symptoms were reassessed with a questionnaires as before. The changes of interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), and vascular endothelial growth factor (VEGF) levels in gastric juices were measured by ELISA. The changes of nitrotyrosine in gastric mucosa were measured by immunohistochemical staining. The most common dyspeptic symptom in Korean patients with chronic gastritis was epigastric soreness (76.8%), which was improved significantly after ecabet sodium treatment (81.7%, p<0.001). Ecabet sodium was more effective in patients with epigastric pain than vague abdominal discomfort (p = 0.02), especially in patients with old age. Complete relief of discomfort was more highly achieved in patients with positive Helicobacter pylori than without (p = 0.01). In spite of clear tendency that the decreased levels of IL-8, iNOS, and PGE2 and increased levels of VEGF were measured in gastric juices after ecabet sodium treatment, no statistical significance was noted, which might be due to high inter-individual variations. The nitrotyrosine expressions were significantly decreased after ecabet sodium treatment than before (p<0.01). In conclusion, ecabet sodium treatment was very useful for the relief of dyspeptic symptoms in chronic gastritis, to which both attenuated inflammatory and enhanced regenerative mechanisms were contributive

Stretchable and recoverable acrylate-based pressure sensitive adhesives with high adhesion performance, optical clarity, and metal corrosion resistance

In the era of the Internet of Things, digital displays play a critical role in human-machine interfaces. In particular, displays applied to contemporary devices such as flexible smart watches and foldable/rollable electronics underline the need for pertinent materials and device technologies to fulfill their designed functions. However, despite the technical advancements of electronic components such as stretchable/flexible electrodes and flexible backplanes, their proper assembly remains a challenge. Herein, we report the compositional effect of acrylic acid (AA) on the physical properties of as-synthesized pressure sensitive adhesives (PSAs), especially on their adhesion performance in terms of wettability and peel adhesion. Accordingly, an empirical criterion for intimate wetting is proposed based on the storage modulus of the PSAs. In this study, the PSA with the best adhesion performance was evaluated for its viscoelastic properties and suitability for specific applications. The results demonstrated the strain-dependent conformational recovery of the adhesive; the implementation of the prestrain strategy enables rapid strain reversibility at 25% of the total strain. Furthermore, the AA-incorporated PSAs exhibited remarkable metal corrosion resistance as well as high optical clarity. Thus, this fundamental study of stretchable PSAs can provide useful guidance for the development of advanced PSAs that can be used in a wide range of applications involving display devices

Long-Term Velaglucerase Alfa Treatment in Children with Gaucher Disease Type 1 Naïve to Enzyme Replacement Therapy or Previously Treated with Imiglucerase

Background Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427). Methods Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30–60 U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty. Results The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for \u3e 30 months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8 years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24 months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients. Conclusion The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults