Federico Storni

Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis.

Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low‐flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.

Automated low-flow ascites pump for the treatment of cirrhotic patients with refractory ascites.

Cirrhotic patients with refractory ascites (RA) can be treated with repeated large volume paracentesis (LVP), with the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) or with liver transplantation. However, side effects and complications of these therapeutic options, as well as organ shortage, warrant the development of novel treatments. The automated low-flow ascites pump (alfapump®) is a subcutaneously-implanted novel battery-driven device that pumps ascitic fluid from the peritoneal cavity into the urinary bladder. Ascites can therefore be aspirated in a time- and volume-controlled mode and evacuated by urination. Here we review the currently available data about patient selection, efficacy and safety of the alfapump and provide recommendations for the management of patients treated with this new method.

Allergens displayed on Virus-Like Particles are highly immunogenic but fail to activate human mast cells

The goal of allergen‐specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus‐like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased protective IgG responses compared to free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity.

P523 SAFETY AND EFFICACY OF AN AUTOMATED LOW FLOW ASCITES (ALFA) PUMP IN CIRRHOTIC PATIENTS WITH REFRACTORY ASCITES

P522 TOTAL SERUM BILE ACIDS IN PATIENTS WITH HEPATOPULMONARY SYNDROME T. Horvatits, A. Drolz, C. Muller, G. Fauler, P. Schenk, M. Trauner, V. Fuhrmann. Dep. Internal Medicine, Div. of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria E-mail: thomas.horvatits@meduniwien.ac.at

An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor FcγRIIb

Background: Induction of allergen‐specific IgG antibodies is a critical parameter for successful allergen‐specific immunotherapy. IgG antibodies can inhibit IgE‐mediated mast cell activation through direct allergen neutralization or through the inhibitory receptor Fc&ggr;RIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation. Objective: Here we addressed the question of affinity thresholds of allergen‐specific IgG antibodies for inhibition of mast cell activation using 2 different mAbs against the major cat allergen Fel d 1 both in vitro and in vivo in mice. Methods: Sequences of the 2 high‐affinity mAbs were back‐mutated to germline, resulting in low‐affinity (10−7 mol/L) antibodies of the exact same specificity. Results: Using these newly generated recombinant antibodies, we demonstrate that low‐affinity antibodies are still able to inhibit mast cell activation through Fc&ggr;RIIb but do not neutralize the allergen. Conclusion: Antibody affinity dictates the mechanism of mast cell inhibition, and IgG antibodies triggering the inhibitory Fc&ggr;RIIb pathway can show a broader cross‐reactivity pattern than previously thought. This indicates that allergen‐specific immunotherapy generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated. Graphical abstract: Figure. No caption available.

Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis.

Pleiotrophin (PTN) is a secreted cytokine that is expressed in various cancer cell lines and human tumor such as colon cancer, lung cancer, gastric cancer and melanoma. It plays significant roles in angiogenesis, metastasis, differentiation and cell growth. The expression of PTN in the adult is limited to the hippocampus in an activity-dependent manner, making it a very attractive target for cancer therapy. RNA interference (RNAi) offers great potential as a new powerful therapeutic strategy based on its highly specific and efficient silencing of a target gene. However, efficient delivery of small interfering RNA (siRNA) in vivo remains a significant hurdle for its successful therapeutic application. In this study, we first identified, on a cell-based experiment, applying a 1:1 mixture of two PTN specific siRNA engenders a higher silencing efficiency on both mRNA and protein level than using any of them discretely at the same dose. As a consequence, slower melanoma cells growth was also observed for using two specific siRNA combinatorially. To establish a robust way for siRNA delivery in vivo and further investigate how silence of PTN affects tumor growth, we tested three different methods to deliver siRNA in vivo: first non-targeted in-vivo delivery of siRNA via jetPEI; second lung targeted delivery of siRNA via microbubble coated jetPEI; third tumor cell targeted delivery of siRNA via transferrin-polyethylenimine (Tf-PEI). As a result, we found that all three in-vivo siRNAs delivery methods led to an evident inhibition of melanoma growth in non-immune deficiency C57BL/6 mice without a measureable change of ALT and AST activities. Both targeted delivery methods showed more significant curative effect than jetPEI. The lung targeted delivery by microbubble coated jetPEI revealed a comparable therapeutic effect with Tf-PEI, indicating its potential application for target delivery of siRNA in vivo.

Treatment of Malignant Ascites Using an Automated Pump Device

Fig. 1 A micro-forceps is passed through a 19-gauge needle under endoscopic ultrasound guidance to sample the cystic wall (a). The sample consists of multiple specimens of hypercellular stroma lined by a monolayer epithelium (b). At higher magnification, the mucinous epithelium differentiation is appreciable (c). Alcian-PAS reaction positivity for mucine heavily depicts epithelial cells (d). On immunohistochemistry, the diffuse positivity of stromal cells for Estrogen receptors is consistent with the ovarian-like differentiation (e). On surgical histology, the inner surface of the fibrous wall of the cyst is covered by a mucinous epithelium and ovarian-like stroma is consistent with mucinous cystic neoplasia, low-grade atypia (f)