Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage

Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ?5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.Funding: This work has been supported in part by grants from the Instituto de Salud Carlos III, Spanish Ministry of Health (FIS PI19/00669), Fondo Europeo de Desarrollo Regional (FEDER) and 2017SGR00792 (AGAUR; Generalitat de Catalunya)

Characterization of the Cell-Sensor Contact with Total Internal Reflection Fluorescence Microscopy

Electrically active cells are specialized cells, responsible for a vast variety of functions. Among others, information processing in the central nervous system, motor functions of organs and muscles, and sensory input recognition in highly complex organs like the eye or the ear are based on evolutionary optimized networks of electrically active cells. A deeper understanding of their basic properties may lead to a better insight into memory formation in the brain or diseases of the nervous system like Parkinson’s disease. One possible method to analyze electric properties of cells is the Patch-Clamp Technique [Hamill et al., 1981; Neher and Sakmann, 1976]. A patch-pipette with a diameter of several micrometers is used to open the cell membrane at a specific point to form an electric connection to the cell. Although huge progress in understanding of electrically cells was achieved with this method, it comes with two main limitations. Since every cell has to be contacted by a separate patch pipette, the number of cells that can be analyzed simultaneously is limited by spatial restrictions. Furthermore, the patch pipette inflicts irreversible damage to the cell membrane, which leads to an exchange of intra- and extracellular liquids, as well as to the death of the cell after typically a few hours. These limitations make it difficult to analyze huge neuronal networks, or to do longterm measurements, both of which are important for the understanding of central brain functions like memory formation. As an alternative to the Patch-Clamp Technique, electrical sensing devices, such as Multi-Electrode-Arrays [Gross et al., 1985; Jimbo et al., 1993; Pancrazio et al., 1998; Pine, 1980; Stett et al., 2000; Thomas et al., 1972] or Field Effect Transistors [Bergveld et al., 1976; Fromherz et al., 1991] were introduced. These devices use the change in [...

The voxel onset time as an in situ method to evaluate focal position effects on two-photon-induced lithography

Two-photon-induced lithography is a versatile method to generate arbitrary three-dimensional microstructures. Although the lithographic result sensitively depends on the experimental conditions, there is a lack of in situ methods to measure process conditions prior to structuring. Current methods rely on determining the size of cross-linked structures, such as single-volume pixels (voxels), as a result of a set of parameters. This procedure is time consuming and possesses several inherent drawbacks, since results are not easily interpretable. Therefore, we established an in situ method, called the voxel onset time (VOT) method, which is easy to integrate in an existing two-photon lithographic setup and is based on determining the time that a voxel necessitates to form by measuring the transmitted laser intensity. In this study, we demonstrate how the VOT method can be used to determine the influence of the axial focal position on voxel formation for different experimental conditions. We find that the voxel onset time is strongly linked to the maximum intensity that is influenced by specimen-induced spherical aberration, especially for a high-numerical-aperture objective

New method for scaffold fabrication for tissue engineering by combination of inkjet-printing and multiphoton

Additive manufacturing is a promising technology for applications in medical engineering. With the aid of 3D-CAD-Tools it is possible to design implants patient-specific which then are manufactured with additive manufacturing technologies. This abstract introduces a new additive manufacturing method for the generation of scaffolds for tissue engineering which combines Inkjet-Printing and Multiphoton Polymerization (MPP)

Advantages and drawbacks of Thiol-ene based resins for 3D-printing

The technology of 3D printing is conquering the world and awakens the interest of many users in the most varying of applications. New formulation approaches for photo-sensitive thiol-ene resins in combination with various printing technologies, like stereolithography (SLA), projection based printing/digital light processing (DLP) or two-photon polymerization (TPP) are presented. Thiol-ene polymerizations are known for its fast and quantitative reaction and to form highly homogeneous polymer networks. As the resins are locally and temporally photo-curable the polymerization type is very promising for 3D-printing. By using suitable wavelengths, photoinitiator-free fabrication is feasible for single- and two photon induced polymerization. In this paper divinyl ethers of polyethylene glycols in combination with star-shaped tetrathiols were used to design a simple test-system for photo-curable thiol-ene resins. In order to control and improve curing depth and lateral resolution in 3D-polymerization processes, either additives in chemical formulation or process parameters can be changed. The achieved curing depth and resolution limits depend on the applied fabrication method. While two-/multiphoton induced lithography offers the possibility of micron- to sub-micron resolution it lacks in built-up speed. Hence single- photon polymerization is a fast alternative with optimization potential in sub-10-micron resolution. Absorber- and initiator free compositions were developed in order to avoid aging, yellowing and toxicity of resulting products. They can be cured with UV-laser radiation below 300 nm. The development at Fraunhofer ILT is focusing on new applications in the field of medical products and implants, technical products with respect to mechanical properties or optical properties of 3D-printed objects. Recent process results with model system (polyethylene glycol divinylether/Pentaerithrytol tetrakis (3-mercaptopropionat), Raman measurements of polymer conversion and surface modifications using bifunctional crosslinkers are presented with advantages, drawbacks and a general outlook

Soft polymers for building up small and smallest blood supplying systems by stereolithography

Synthesis of a homologous series of photo-polymerizable α,w-polytetrahydrofuranether-diacrylate (PTHF-DA) resins is described with characterization by NMR, GPC, DSC, soaking and rheometrical measurements. The curing speeds of the resins are determined under UV light exposure. Young’s modulus and tensile strength of fully cured resins show flexible to soft material attributes dependent on the molar mass of the used linear PTHF-diacrylates. Structuring the materials by stereo lithography (SL) and multiphoton polymerization (MPP) leads to tubes and bifurcated tube systems with a diameter smaller than 2 mm aimed at small to smallest supplying systems with capillary dimensions. WST-1 biocompatibility tests ofm polymer extracts show nontoxic characteristics of the adapted polymers after a washing process. Some polymers show shape memory effect (SME)