Isatuximab plus Pomalidomide and Dexamethasone in a Patient with Dialysis-Dependent Multiple Myeloma

The phase 3 ICARIA-MM trial showed that the addition of isatuximab improved the progression-free survival compared with pomalidomide/dexamethasone. However, the safety and efficacy of isatuximab for end-stage renal failure remains unclear. A 67-year-old man who started hemodialysis 5 years ago for diabetic nephropathy was diagnosed with International Staging System stage III multiple myeloma (MM) of IgD-λ type 3 years ago. After receiving a total of 7 treatment regimens, his free light chain (FLC) λ level increased from 419 to 2,070 mg/L, indicating progressive disease. Twelve days after starting isatuximab plus pomalidomide (3 mg daily) and dexamethasone (IsaPd), his FLC λ level rapidly decreased to 412 mg/L. The patient has now completed 7 courses of IsaPd with no adverse events, including infusion reactions and neutropenia. Isatuximab requires a lower dilution volume than daratumumab and can be safely and effectively administered to hemodialysis-dependent MM patients.

CUSTOM DESIGN PERSPECTIVE IN THE PROCESS PARAMETER OPTIMIZATION OF NANO LIPID CARRIERS

Objective: Nanostructured lipid carrier is an emerging lipid-derived delivery system that is rapidly gaining popularity due to the simplicity of the manufacturing technique. The primary task in formulating nanoparticles is to optimize the parameters that are involved in the process. The rationale behind this study is to optimize the process parameters for the preparation of nanostructured lipid carriers. Methods: The optimization of selected techniques hot homogenization with ultra-sonication and melt dispersion technique, was carried out via statistical analysis software JMP version 13 Pro using custom design approaches. Sonication time, homogenization speed, stirring rate, and cooling temperature were selected as factors for hot homogenization. Stirring speed, stirring time, and dilution volume were the factors deliberated for melt dispersion. The impact of these factors on the responses, particle size, and polydispersity index were studied. The nanoparticles were prepared according to the ten experimental runs generated by the design. Based on the responses, the design space and optimum framework were selected. Results: The prediction profiler indicated maximum desirability at 81% and 80% for hot homogenization and melt dispersion respectively. The actual versus predicted plot of particle size indicated a regression coefficient (R2) of 0.98, and a p-value of 0.0001 for hot homogenization and for melt dispersion the corresponding values were 0.95 and 0.0003. For the response polydispersity index, these values were 0.92 and 0.0052 for hot homogenization and 0.90 and 0.0024 for melt dispersion. Conclusion: The endorsing results indicated the authenticity of the model in predicting the significant processing parameters for NLC.

Core and margin in warm convective clouds – Part 2: Aerosol effects on core properties

The effects of aerosol on warm convective cloud cores are evaluated using single cloud and cloud field simulations. Three core definitions are examined: positive vertical velocity (Wcore), supersaturation (RHcore), and positive buoyancy (Bcore). As presented in Part 1 (Heiblum et al., 2019), the property Bcore⊆RHcore⊆Wcore is seen during growth of warm convective clouds. We show that this property is kept irrespective of aerosol concentration. During dissipation core fractions generally decrease with less overlap between cores. However, for clouds that develop in low aerosol concentrations capable of producing precipitation, Bcore and subsequently Wcore volume fractions may increase during dissipation (i.e., loss of cloud mass). The RHcore volume fraction decreases during cloud lifetime and shows minor sensitivity to aerosol concentration. It is shown that a Bcore forms due to two processes: (i) convective updrafts – condensation within supersaturated updrafts and release of latent heat – and (ii) dissipative downdrafts – subsaturated cloudy downdrafts that warm during descent and “undershoot” the level of neutral buoyancy. The former process occurs during cloud growth for all aerosol concentrations. The latter process only occurs for low aerosol concentrations during dissipation and precipitation stages where large mean drop sizes permit slow evaporation rates and subsaturation during descent. The aerosol effect on the diffusion efficiencies plays a crucial role in the development of the cloud and its partition to core and margin. Using the RHcore definition, it is shown that the total cloud mass is mostly dictated by core processes, while the total cloud volume is mostly dictated by margin processes. Increase in aerosol concentration increases the core (mass and volume) due to enhanced condensation but also decreases the margin due to evaporation. In clean clouds larger droplets evaporate much slower, enabling preservation of cloud size, and even increase by detrainment and dilution (volume increases while losing mass). This explains how despite having smaller cores and less mass, cleaner clouds may live longer and grow to larger sizes.

Investigation of Space Charge Distribution of MgO/XLPE Composites Depending on Particle Size of MgO as Inorganic Filler

MgO/XLPE composites, composed of micro-and nanosized MgO material having different particle size as inorganic filler and cross linked polyethylene (XLPE), were prepared and investigated to the space charge dynamics of these composites for high voltage DC insulation. Added MgO material, having 50nm to 1μm in size, were synthesized from the calcination of Mg (OH)2nanoplatelets which was controlled by potassium content in Mg (OH)2, varying the dilution volume ratio of distilled water/ Mg (OH)2suspension. MgO/XLPE composites were obtained by thoroughly mixing LDPE and dicumyl peroxide (DCP) as the cross-linking agent and silane modified MgO before kneading to enhance the dispersion degree of the composites. The space charge distributions of the composites were observed by controlling the particle size and content of a dispersed MgO in XLPE matrix. To prevent the breakdown under high DC stress, it was found that the reduction of space charge of MgO/XLPE composite depends upon the smaller size of MgO particle and the its content above 0.5 phr (per hundred part of resin, wt%). MgO material and MgO/ XLPE composites were characterized with TEM, XRD, BET, ICP, and the space charge properties of the composites were measured by a pulsed electro-acoustic method (PEA).