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

BACKGROUND: 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. AIM: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427.

[Gingival hyperplasia and visual reduction]. / Zahnfleischschwellung und Visusreduktion.

This case report describes the unilateral acute reduction of vision in the right eye of a 48-year-old woman. The patient was otherwise healthy but 2 days previously had suffered from dizziness and blurred vision. Secondary to this, the patient had already been under dental treatment for 1 week due to gingival swelling. At the first examination a macular branch retinal vein occlusion and Roth spots were found in the right eye by indirect ophthalmoscopy. The immediate diagnostic procedure identified aute amyeloid leukemia (AML) as the cause of the vascular pathology. The AML can be manifested in different ways and the retina is involved in approximately 50% of cases. Due to a secondary hyperviscosity syndrome, which is found in approx. 20% of acute leukaemias, symptomatic central vein occlusion or macular branch vein occlusion can occur. Ophthalmic symptoms can be the first and only signs to be detected. Therefore, ophthalmologists should also consider a systemic disease and initiate a clarification. A differential blood count is indispensable. The results usually improve by a rapidly arranged and suitable therapy. Ophthalmological follow-up examinations are imperative as an initiated chemotherapy can also produce ophthalmological side-effects.

Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study.

Dendritic cells (DC) are professional antigen-presenting cells that are widely used in the experimental immunotherapy of cancer. For clinical use GMP-like protocols for the preparation of functionally active dendritic cells (DC) in large numbers and at high purity are needed. However, the currently available protocols have certain disadvantages. In this study we tested the generation and clinical applicability of DC from monocyte preparations produced by immunomagnetic CD14(+) selection using a semiautomated clinical scale immunomagnetic column. Peripheral blood mononuclear cells (PBMC) of 10 patients with metastatic solid tumors were used. With the immunomagnetic separation, we obtained a cell suspension of high CD14(+) purity (median 97.4%, range 94.9-99.0) with a high monocyte yield (median 82.3%, range 63.9-100.0). Differentiation of CD14(+) cells into mature monocyte-derived DC was induced by incubation with IL-4, GM-CSF, TNF-alpha, PGE(2), IL-1 beta, and IL-6. Mature DC showed a high expression of CD83, HLA-DR, and the co-stimulatory molecules CD80 and CD86. Overall CD83(+) yield was 12.1% (range 4.0-29.4). Allogeneic T stimulatory capacity could be demonstrated for all DC preparations in proliferation assays. No significant differences in marker expression or T cell stimulation was detected between fresh DC and those derived from cryopreserved immature DC. Clinical administration of autologous DC by three different parenteral routes was tolerated by all 10 patients without systemic signs of toxicity. Our results indicate that immunomagnetic isolation of CD14(+) monocytes using the CliniMACS device is a suitable method for clinical-scale generation of functional DC under GMP-grade conditions. The selection can be performed in a closed system. Therefore, immunomagnetic CD14(+) selection can be seen as an alternative way to generate DC for clinical tumor vaccination protocols.

Thawing of cryopreserved mobilized peripheral blood--comparison between waterbath and dry warming device.

BACKGROUND: Thawing of cryopreserved mobilized peripheral blood (MPB) is routinely performed for autologous and allogeneic MPB transplantation. Usually thawing is achieved by submerging the cell bag in a waterbath (37 degrees C temperature). We compared the effectiveness of thawing cryopreserved MPB in a waterbath with an electric dry-warming device containing warmed gel pads (Sahara, Transmed). METHODS: Two cryopreserved bags from each of 31 apheresis procedures were thawed in a waterbath and under dry conditions in parallel. Viability (dye exclusion), apoptosis/necrosis (annexin/propidiumiodide staining) and clonogenic potential (CFU-E plus BFU-E, CFU-GM) of the cells were tested after thawing. RESULTS: Statistical analysis by Wilcoxon matched-pair test showed no significant difference between the thawing procedures in terms of the in vitro parameters tested. DISCUSSION: Our results indicate that thawing of cryopreserved MPB using dry warming and water bath give similar viability, apoptosis/necrosis rate and clonogenic potential. Both procedures take about the same amount of time and are easy to perform. Nevertheless, the potentially decreased risk of bacterial contamination of either the cell product or the patient room, and guidelines of good clinical practice (GCP), favor the use of the dry warming procedure.