Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO.

The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.

Responses of Diversity and Productivity to Organo-Mineral Fertilizer Inputs in a High-Natural-Value Grassland, Transylvanian Plain, Romania.

Ecosystems with high natural value (HNV) have generally been maintained by agricultural practices and are increasingly important for the ecosystem services that they provide and for their socio-economic impact in the ever-changing context. Biodiversity conservation is one of the main objectives of the European Green Deal, which aims to address biodiversity loss, including the potential extinction of one million species. The aim of this research was to trace the effects of organic and mineral fertilizers on the floristic composition, but also on the number of species, of the grasslands with high biodiversity (HNV) from the Transylvanian Plain, Romania. The experiments were established in 2018 on the nemoral area and analyzed the effect of a gradient of five organic and mineral treatments. Fertilization with 10 t ha-1 manure or N50 P25K25 ensures an increase in yield and has a small influence on diversity, and it could be a potential strategy for the maintenance and sustainable use of HNV grasslands. Each fertilization treatment determined species with indicator value that are very useful in the identification and management of HNV grasslands. The dry matter biomass increases proportionally as the amounts of fertilizer applied increase and the number of species decreases.

Exploration of Soil Functional Microbiomes-A Concept Proposal for Long-Term Fertilized Grasslands.

Exploring grassland microbiomes is a challenge in the current context of linking soil microorganism activity with the balance of these ecosystems. Microbiologists are constantly attempting to develop faster and lower-cost methods, and propose new and best-fitted indicators that will provide a more complex data analysis. A different concept was proposed for assessing functional microbiomes by splitting the functional ecological niche into complementary segments. The comparison with the upper and lower limits of the ecological niche provides a clearer image of community alterations due to long-term applied treatments. The method allows the extraction of the most sensitive and stable functional guilds, with the extraction of the most critical dominant-codominant functional groups in every segment of the functional niche. The resulting microbial functional-sociological model is ready to use on community-level physiological profile databases and also can be applied backward for vegetation analysis.

Changes in Diversity Due to Long-Term Management in a High Natural Value Grassland.

High nature value (HNV) grassland systems are increasingly important for the ecosystem services they provide and for their socio-economic impact in the current constant-changing context. The aim of our paper is to evaluate the long-term effect of organic fertilizers on HNV systems in the Apuseni Mountains, Romania. As an objective we want to identify the optimal intensity of conservation management and its recognition based on indicator value plant species. The experiments were established in 2001 on the boreal floor and analyze the effect of a gradient of four organic treatments with manure. Fertilization with 10 t ha-1 manure ensures an increase in yield and has a small influence on diversity, and could be a real possibility for the maintenance and sustainable use of HNV. Each fertilization treatment determined species with indicator value that are very useful in the identification and management of HNV. The indicator species are useful in forecasting the fluctuations and successions in grasslands, determined by the modification of the dominance-codominance ratio and the real coverage of each species.

Mycorrhizal Patterns in the Roots of Dominant Festuca rubra in a High-Natural-Value Grassland.

Grassland ecosystems occupy significant areas worldwide and represent a reservoir for biodiversity. These areas are characterized by oligotrophic conditions that stimulate mycorrhizal symbiotic partnerships to meet nutritional requirements. In this study, we selected Festuca rubra for its dominance in the studied mountain grassland, based on the fact that grasses more easily accept a symbiotic partner. Quantification of the entire symbiosis process, both the degree of colonization and the presence of a fungal structure, was performed using the root mycorrhizal pattern method. Analysis of data normality indicated colonization frequency as the best parameter for assessing the entire mycorrhizal mechanism, with five equal levels, each of 20%. Most of the root samples showed an intensity of colonization between 0 and 20% and a maximum of arbuscules of about 5%. The colonization degree had an average value of 35%, which indicated a medium permissiveness of roots for mycorrhizal partners. Based on frequency regression models, the intensity of colonization presented high fluctuations at 50% frequency, while the arbuscule development potential was set to a maximum of 5% in mycorrhized areas. Arbuscules were limited due to the unbalanced and unequal root development and their colonizing hyphal networks. The general regression model indicated that only 20% of intra-radicular hyphae have the potential to form arbuscules. The colonization patterns of dominant species in mountain grasslands represent a necessary step for improved understanding of the symbiont strategies that sustain the stability and persistence of these species.

Sensitive approach and future perspectives in microscopic patterns of mycorrhizal roots.

The harmonization of methodologies for the assessment of radicular endophytic colonization is a current necessity, especially for the arbuscular mycorrhizas. The functionality of mycorrhizal symbionts for plants can be described only by indicators obtained based on microscopic analysis. That is the reason for which a unifying methodology will lead to the achievement of highly correlated indicators comparable from one research to another. Our proposed methodology can further digitize the microscopic observations of colonization. The MycoPatt system is developed as a methodological framework for obtaining objective and comparable microscopic observations. The horizontal, vertical and transversal indicators are highly adaptable and allow the tracking of mycorrhizal colonization in root length. All structures developed by symbionts can be traced and the obtained metadata can be compared without any transformation. Mycorrhizal maps have a high degree of applicability in evaluating soil inoculum efficiency. In the future, the application of this method will lead to digital maps with a high degree of accuracy. MycoPatt allows the mathematical expression of colonization patterns, being a complex model that converts biological data into statistically comparable indicators. This will further allow obtaining inferences with applicative importance and similarity spectra for the colonizing fungi and host plants.

Thrombocytopenia after aortic valve replacement with freedom solo bioprosthesis: a propensity study.

BACKGROUND: The incidence of postoperative thrombocytopenia after aortic valve replacement with the Freedom Solo bioprosthesis remains unclear. This propensity-matched study was carried out to evaluate the incidence and clinical impact of thrombocytopenia in patients receiving the Freedom Solo bioprosthesis. METHODS: Patients who underwent aortic valve replacement with a Freedom Solo or Carpentier-Edwards Perimount pericardial prosthesis at our institution between 2006 and 2008 were screened retrospectively. Exclusion criteria included double valve replacement, redo surgery, and active endocarditis. Two hundred six patients were considered eligible for this analysis. Using propensity scores 36 matched pairs of patients with a Freedom Solo or Perimount bioprosthesis were obtained. The primary end point was the occurrence of postoperative thrombocytopenia. Secondary end points were postoperative thromboembolic or hemorrhagic events and 30-day mortality. RESULTS: Before matching, severe thrombocytopenia (<30 x 10(9) platelets/L) occurred in 22% of patients with a Freedom Solo bioprosthesis and 1% with a Perimount bioprosthesis (p < 0.0001), thromboembolic or hemorrhagic events occurred in 3% and 2%, respectively (p = 0.37), and 30-day mortality was 4% and 6%, respectively (p = 0.48). Multivariate analysis identified preoperative platelet count (p = 0.01) and Freedom Solo (p < 0.0001) as independent risk factors for severe postoperative thrombocytopenia. After matching, severe thrombocytopenia occurred in 25% and 3% of patients with Freedom Solo and Perimount bioprostheses, respectively (p < 0.0001), thromboembolic or hemorrhagic events occurred in 0%, and 30-day mortality was 3% and 6%, respectively (p = 0.99). CONCLUSIONS: The risk of thrombocytopenia was high after Freedom Solo implantation. However, this complication was not related to any deleterious events in our study population.