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Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable. © 2020, The Author(s).

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future. © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ‡60 months’ follow-up). Patients were randomized to Rd continuous (n 5 535), Rd18 (n 5 541), or MPT (n 5 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P 5 .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an 30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. © 2018 by The American Society of Hematology.

In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib or lenalidomide, MM remains incurable. The FIRST study demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of lenalidomide and low-dose dexamethasone (Rd) until progression vs. MPT in transplant-ineligible ndMM patients. However, to date no head-to-head randomized controlled trials (RCTs) have compared Rd or MPT versus VMP. We conducted a network meta-analysis using RCTs identified through a systematic literature review to evaluate the relative efficacy of Rd versus other regimens on survival endpoints in previously untreated MM patients ineligible for ASCT. In this analysis, Rd was associated with a significant PFS and survival advantage versus other first-line treatments (VMP, MPT, MP), challenging the role of alkylators in this setting. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core–shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core–shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79–9.75 s–1 mM–1; r2 = 7.98–14.22 s–1 mM–1) compared with fresh Gd(DTPA) (r1 = 4.13 s–1 mM–1 and r2 = 4.40 s–1 mM–1), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon.

Currently, the restoration materials used to fill gaps in architectural historic azulejos (e.g. lime or organic resin pastes) present relevant drawbacks in terms of compatibility, efficacy or durability. The current solutions are not able to fully protect the azulejos resulting in further deterioration. Geopolymers can be a potential solution for azulejo lacunae infill given the chemical-mineralogical similitude, durability and versatile range of physical properties that may be obtained through the manipulation of their formulation and curing conditions. This communication presents and discusses the viability of the use of geopolymeric pastes to fill lacunae in azulejos or to act as “cold” cast ceramic tile surrogates reproducing missing azulejo fragments. The formulation of geopolymers (type and concentration of activators, aluminosilicate source and water content) and curing conditions was optimized. The need for post-curing treatments (desalination) was also taken into consideration in view of the purpose of their application: the restoration of outdoor architectural historic azulejos, which are exposed to adverse environmental conditions. The possible advantages and disadvantages of the use of geopolymers in the conservation of azulejos is also discussed. 279-282pp. Project CerAzul: Research and development of materials and methods for the conservation of historic azulejos (PTDC/CTM-CER/119085/2010). LNEC own financing under Proc. 0202/111719014 (RI. IPERION-CH.pt). DM/NBPC Proceedings of the International Conference Glazed Ceramics in Architectural Heritage (GlazeArch 2015)

Submitted by Marta Frade (marta.diogo@ess.ips.pt) on 2018-03-22T14:59:34Z No. of bitstreams: 1 Artigo 11-J. Organomet. Chem. 792 (2015), 154-166.pdf: 1882517 bytes, checksum: 5d5c625edc1d3d89af8d86ab4141fef1 (MD5) Approved for entry into archive by Isabel Nunes (isabel.nunes@estsetubal.ips.pt) on 2018-03-22T15:30:44Z (GMT) No. of bitstreams: 1 Artigo 11-J. Organomet. Chem. 792 (2015), 154-166.pdf: 1882517 bytes, checksum: 5d5c625edc1d3d89af8d86ab4141fef1 (MD5) Made available in DSpace on 2018-03-22T15:30:44Z (GMT). No. of bitstreams: 1 Artigo 11-J. Organomet. Chem. 792 (2015), 154-166.pdf: 1882517 bytes, checksum: 5d5c625edc1d3d89af8d86ab4141fef1 (MD5) Previous issue date: 2015 A series of allyl complexes of the general formula [Cp'Mo(η3-C3H5)(CO)2], where Cp' = Cp, CpMe, Cp*, Ind, IndMe, IndMe2, Flu, and three tungsten analogues, has been prepared and characterized by 1H, 13C, and 95Mo NMR, cyclic voltammetry, and the structure of [IndMo(η3-C3H5)(CO)2] was determined by X-ray single crystal analysis. Two conformers, corresponding to the two extreme orientations of the allyl ligand (endo and exo), have been identified in solution by 1H and 95Mo NMR for all the complexes, except for [FluMo(η3-C3H5)(CO)2], which only presents an exo conformation in solution. A 95Mo NMR investigation also shows the influence of electron donor capability of the Cp' ligands on the 95Mo chemical shifts of the Mo center. He I and He II photoelectron spectra probe the electron richness of the metal center and the electronic structure of the complexes. Cyclic voltammetry studies show one oxidation process, which is only reversible for the Cp derivatives. DFT calculations provided a reliable way to determine ionization energies, and reflected very well the trends of the other properties, from the 95Mo NMR chemical shifts, to vibration frequencies, and oxidation potentials. info:eu-repo/semantics/publishedVersion

BACKGROUND: Plerixafor with granulocyte-colony-stimulating factor (G-CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty-three patients with germ cell tumor (n=11), Ewing sarcoma (n=6), Wiscott-Aldrich disease (n=5), neuroblastoma (n=4), and other nonhematologic diseases (n=7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G-CSF (n=21) or after chemotherapy and G-CSF (n=12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2×10(6)/kg body weight (b.w.) CD34+ cells (median, 5.0×10(6)/kg b.w. CD34+ cells; range, 2.0×10(6)-29.5×10(6)/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5×10(6)/kg b.w. CD34+ cells (range, 0.9×10(6)-1.8×10(6)/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3×10(6)/kg b.w. (range, 2.3×10(6)-6.7×10(6)/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9-12) and 15 (range, 10-25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G-CSF or chemotherapy and G-CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients.

Dual modality contrast agents, such as radiolabelle d magnetic nanoparticles, are promising candidates for a number of diagnostic applications, since they combine two complementing imaging modalities, namely photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). The benefit of such combin ation lies on the ability to interpret more accurately abnormalities in vivo , by integrating the high sensitivity of SPECT with the superb spatial resolution and anatomical information provi ded by MRI [1]. Superparamagnetic iron oxide nanoparticles (SPION) have been extensively s tudied as MRI contrast agents [2]. SPIONs need to be coated in order to allow formulation in aqueous solutions and to increase in vivo stability [3]. Dextrin nanomagnetogels consists on superparamagnet ic iron oxide nanoparticles ( γ -Fe 2 O 3 ) stabilized within hydrophobized-dextrin nanogel (sc heme 1). The nanomagnetogel formulation, with about 4 mM of iron and a diameter of 100 nm, p resents relevant features such as superparamagnetic behaviour, high stability, narrow size distribution and potential for magnetic guidance to target areas by means of an external ma gnetic field [4]. The functionalization of the dextrin nanomagnetogel with a DOTA-monoamide ω -thiol metal chelator and radiolabelling with 111 In were used to ascertain its in vivo stability and behavior (blood clearance rate and o rgan distribution) after intravenous administration in m ice model. The surface modification of the nanomagnetogel with PEG 5,000 was accomplished in a n attempt to escape the phagocytic system. The unloaded radiolabeled dextrin nanogel ( around 30 nm) showed lower uptake in the liver, spleen and kidneys than the nanomagnetogel l oaded with SPIONs (around 110 nm). This difference in biodistribution profile can be ascrib ed to the differences in the particle size. Nanomagnetogel pegylation resulted in lower liver a nd spleen accumulation. The blood half-life obtained was approximately 4 hours for all formulat ions. A good correlation between the amount of polymer (quantified through radioactivity) and t he amount of iron (ICP measurement) in the spleen was observed, indicating that leakage of iro n from the nanomagnetogels after intravenous administration was negligible. The pilo t imaging study demonstrated good performance of dextrin nanomagnetogels as dual moda lity imaging (MRI and SPECT) bioprobes as expected by the high transverse relaxi vity (215-248 mM -1 s -1 ) obtained in vitro , higher than those of commercial available formulati ons (160-177 mM -1 s -1 ). The production of the nanomagnetogel is simple and easy to scale up, thus offering great technological potential.

Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P