Use of Nebulized Amphotericin B in the Treatment of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis

Background. Systemic steroids and adjunctive antifungal therapy are the cornerstone in treating allergic bronchopulmonary aspergillosis (ABPA) in the context of CF. Aim. Evaluate the use of inhaled amphotericin B (iAMB) as antifungal agent in this context. Methods. Report of 7 CF patients with recurrent or difficult to treat ABPA and failure to taper systemic corticosteroids treated with AMB deoxycholate (AMB-d) (Fungizone 25 mg 3× a week) or AMB lipid complex (ABLC) (Abelcet 50 mg twice weekly). Successful therapy was defined as steroid withdrawal without ABPA relapse within 12 months. Results. Therapy was successful in 6 of 7 patients treated with iAMB. In 5/6, lung function improved. The patient with treatment failure has concomitant MAC lung infection. Conclusion. Inhaled AMB may be an alternative to commonly used adjunctive antifungal therapy in the treatment of ABPA. More data are needed on safety and efficacy

Heparanase Levels Are Elevated in the Urine and Plasma of Type 2 Diabetes Patients and Associate with Blood Glucose Levels

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. Utilizing an ELISA method capable of detection and quantification of heparanase, we examined heparanase levels in the plasma and urine of a cohort of 29 patients diagnosed with type 2 diabetes mellitus (T2DM), 14 T2DM patients who underwent kidney transplantation, and 47 healthy volunteers. We provide evidence that heparanase levels in the urine of T2DM patients are markedly elevated compared to healthy controls (1162±181 vs. 156±29.6 pg/ml for T2DM and healthy controls, respectively), increase that is statistically highly significant (P<0.0001). Notably, heparanase levels were appreciably decreased in the urine of T2DM patients who underwent kidney transplantation, albeit remained still higher than healthy individuals (P<0.0001). Increased heparanase levels were also found in the plasma of T2DM patients. Importantly, urine heparanase was associated with elevated blood glucose levels, implying that glucose mediates heparanase upregulation and secretion into the urine and blood. Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions. These results provide evidence for a significant involvement of heparanase in diabetic complications

Clinical Study Use of Nebulized Amphotericin B in the Treatment of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis

Background. Systemic steroids and adjunctive antifungal therapy are the cornerstone in treating allergic bronchopulmonary aspergillosis (ABPA) in the context of CF. Aim. Evaluate the use of inhaled amphotericin B (iAMB) as antifungal agent in this context. Methods. Report of 7 CF patients with recurrent or difficult to treat ABPA and failure to taper systemic corticosteroids treated with AMB deoxycholate (AMB-d) (Fungizone 25 mg 3× a week) or AMB lipid complex (ABLC) (Abelcet 50 mg twice weekly). Successful therapy was defined as steroid withdrawal without ABPA relapse within 12 months. Results. Therapy was successful in 6 of 7 patients treated with iAMB. In 5/6, lung function improved. The patient with treatment failure has concomitant MAC lung infection. Conclusion. Inhaled AMB may be an alternative to commonly used adjunctive antifungal therapy in the treatment of ABPA. More data are needed on safety and efficacy

Exploring the future of carbon capture and utilisation by combining an international Delphi study with local scenario development

This article identifies the factors that, according to international experts, will have substantial effects on the future development and commercialisation of carbon capture and utilisation (CCU) technologies. A two-round online Delphi study with 15 international experts in the field of CCU enabled us to explore the main items within five impact categories: (1) benefits, (2) risks, (3) future developments, (4) demand, and (5) supply constraints. Based on the results of the Delphi study, we constructed 4 future scenarios that represent how the CCU sector could develop within 10 years, using a local scenario development workshop with 9 experts from within Flanders (Belgium) and the Netherlands. We used a deductive, explorative scenario development method, which resulted in a two-by-two scenario matrix. We find that the local experts consider the role of the government and the development of CCU costs to be the most uncertain factors and could have the highest impact on the development of the sector within the next 10 years. Our insights can be instructive for facilitating the process of scenario planning for CCU development activities. Finally, although we work with a regionally specific case study, the same method could be implemented in other regions, using the general findings from our Delphi study as a starting point for the scenario development. © 2019 Elsevier B.V