Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.     

Trait modality distribution of aquatic macrofauna communities as explained by pesticides and water chemistry

Analyzing functional species’ characteristics (species traits) that represent physiological, life history and morphological characteristics of species help understanding the impacts of various stressors on aquatic communities at field conditions. This research aimed to study the combined effects of pesticides and other environmental factors (temperature, dissolved oxygen, dissolved organic carbon, floating macrophytes cover, phosphate, nitrite, and nitrate) on the trait modality distribution of aquatic macrofauna communities. To this purpose, a field inventory was performed in a flower bulb growing area of the Netherlands with significant variation in pesticides pressures. Macrofauna community composition, water chemistry parameters and pesticide concentrations in ditches next to flower bulb fields were determined. Trait modalities of nine traits (feeding mode, respiration mode, locomotion type, resistance form, reproduction mode, life stage, voltinism, saprobity, maximum body size) likely to indicate pesticides impacts were analyzed. According to a redundancy analysis, phosphate -and not pesticides- constituted the main factor structuring the trait modality distribution of aquatic macrofauna. The functional composition could be ascribed for 2–4 % to pesticides, and for 3–11 % to phosphate. The lack of trait responses to pesticides may indicate that species may have used alternative strategies to adapt to ambient pesticides stress. Biomass of animals exhibiting trait modalities related to feeding by predation and grazing, presence of diapause form or dormancy, reproduction by free clutches and ovoviviparity, life stage of larvae and pupa, was negatively correlated to the concentration of phosphate. Hence, despite the high pesticide pollution in the area, variation in nutrient-related stressors seems to be the dominant driver of the functional composition of aquatic macrofauna assembly in agricultural ditches.