Technical aspects of percutaneous endovascular arteriovenous fistula creation with the Ellipsys® Vascular Access System. Preliminary results after 16 patients.

PURPOSE: Technical aspects are crucial for planning and performing endovascular arteriovenous fistula (AVF) creation. The Ellipsys® Vascular Access System represents a minimal invasive method for the creation of a proximal forearm fistula. This report summarizes the essential elements for AVF creation with the Ellipsys® Vascular Access System and investigates feasibility, efficacy, and safety procedures conducted on 16 patients. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent endovascular AVF creation with the Ellipsys® Vascular Access System between May 2020 and March 2022 at a tertiary referral center. RESULTS: The median age was 67.5 years (47-86 years). The mean BMI was 31.4 kg/m2. AV fistula was created on 15/16 patients on their left arm. The technical success was 100%. The mean operation time was 24.2 min. There were no complications associated with the procedure. All patients were examined after 30 days (± 5 days). Primary patency after 30 days was 94% (15/16). The mean fistula flow was 681.1 mL/min and the mean AVF diameter was 6.1 mm. Thirteen out of 15 patients met the criteria for potential hemodialysis. CONCLUSION: With the Ellipsys Vascular Access System exist an additional possibility of an AV fistula creation. Based on above findings, the Ellipsys® Vascular Access System represents a feasible, safe, and effective method for AVF creation.

Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1.

The poor survival rate of pancreatic cancer is still a major challenge for the clinicians and their patients. In this study, we evaluated the efficacy of metformin, an inhibitor of oxidative phosphorylation, in combination with LW6, which impairs malate dehydrogenase 2 activities, in treating pancreatic cancer cells. We observed that this combinational therapy significantly reduced cell proliferation, migration, and significantly induced cell death when compared to cells treated by each monotherapy or Sham. In addition, we found that the combination of metformin and LW6 increased the phosphorylation of yes-associated protein 1 at serine 127 and attenuated the nuclear localization of this transcription factor. This combinatorial treatment also decreased the level of cellular yes-associated protein 1. This suggests that metformin in combination with LW6 impairs pancreatic cancer cells and reduces nuclear localization of yes-associated protein 1.

Grading Distress of Different Animal Models for Gastrointestinal Diseases Based on Plasma Corticosterone Kinetics.

Comparative studies for evaluating distress in established animal models are still rare. However, this issue is becoming more important as a consequence of worldwide appreciation of animal welfare. One good parameter for evaluating distress is the quantification of corticosterone. We hypothesized that not just the absolute value but also the duration of increased corticosterone concentration in the blood is an important aspect for evaluating animal distress. Therefore, we analyzed plasma corticosterone concentrations 30, 60, 120, and 240 min after induction of pancreatitis by cerulein, liver damage by carbon tetrachloride, liver damage by bile duct ligation, and after orthotopic injection of pancreatic cancer cells. We also evaluated corticosterone kinetics after injection of distinct carrier substances. Compared to phosphate buffered saline, dimethyl sulfoxide leads to dose-dependent higher and longer-lasting circulating corticosterone concentrations. In all disease models, we observed significantly increased corticosterone concentration 30 min after stress induction. However, the corticosterone kinetics differed among the animal models. Both the absolute value of corticosterone concentration and the duration correlated positively with the quantification of animal distress by a score sheet. This suggests that both variables of corticosterone kinetics might provide a solid basis for comparing and grading distress of different animal models.

α-cyano-4-hydroxycinnamate impairs pancreatic cancer cells by stimulating the p38 signaling pathway.

Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death. α-cyano-4-hydroxycinnamate in combination with metformin reduced the export of lactate significantly, whereas α-cyano-4-hydroxycinnamate monotherapy only modestly influenced lactate export. None of these two drugs inhibited the expression of distinct glycolytic enzymes. Interestingly, α-cyano-4-hydroxycinnamate rather inhibited the ERK and very strongly stimulated the p38 signaling pathway in 6606PDA as well as in 7265PDA cells. In addition, the inhibition of the p38 signaling pathway by PH-797804 partially reversed the effect of α-cyano-4-hydroxycinnamate on cell apoptosis in both cell lines. We conclude that α-cyano-4-hydroxycinnamate monotherapy and especially the combinatorial therapy with metformin has strong anti-cancerous effects. α-cyano-4-hydroxycinnamate causes cancer cell apoptosis by a novel mechanism for this drug, namely the stimulation of the p38 signaling pathway.